{"input": "Models to predict intestinal absorption of therapeutic peptides and proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Prediction of human intestinal absorption is a major goal in the design, optimization, and selection of drugs intended for oral delivery, in particular proteins, which possess intrinsic poor transport across intestinal epithelium.", "output": {"entities": {}}, "schema": []}
{"input": "There are various techniques currently employed to evaluate the extension of protein absorption in the different phases of drug discovery and development.", "output": {"entities": {}}, "schema": []}
{"input": "Screening protocols to evaluate protein absorption include a range of preclinical methodologies like in silico, in vitro, in situ, ex vivo and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "It is the careful and critical use of these techniques that can help to identify drug candidates, which most probably will be well absorbed from the human intestinal tract.", "output": {"entities": {}}, "schema": []}
{"input": "It is well recognized that the human intestinal permeability cannot be accurately predicted based on a single preclinical method.", "output": {"entities": {}}, "schema": []}
{"input": "However, the present social and scientific concerns about the animal well care as well as the pharmaceutical industries need for rapid, cheap and reliable models predicting bioavailability give reasons for using methods providing an appropriate correlation between results of in vivo and in vitro drug absorption.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this review is to describe and compare in silico, in vitro, in situ, ex vivo and in vivo methods used to predict human intestinal absorption, giving a special attention to the intestinal absorption of therapeutic peptides and proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder.", "output": {"entities": {"chemical": [{"text": "Serotonin", "start": 0, "end": 9}, {"text": "venlafaxine XR", "start": 79, "end": 93}]}}, "schema": []}
{"input": "Generalized anxiety disorder (GAD) is a chronic psychiatric disorder with significant morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Antidepressant drugs are the preferred choice for treatment; however, treatment response is often variable.", "output": {"entities": {}}, "schema": []}
{"input": "Several studies in major depression have implicated a role of the serotonin receptor gene (HTR2A) in treatment response to antidepressants.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 66, "end": 75}]}}, "schema": []}
{"input": "We tested the hypothesis that the genetic polymorphism rs7997012 in the HTR2A gene predicts treatment outcome in GAD patients treated with venlafaxine XR.", "output": {"entities": {"chemical": [{"text": "venlafaxine XR", "start": 139, "end": 153}]}}, "schema": []}
{"input": "Treatment response was assessed in 156 patients that participated in a 6-month open-label clinical trial of venlafaxine XR for GAD.", "output": {"entities": {"chemical": [{"text": "venlafaxine XR", "start": 108, "end": 122}]}}, "schema": []}
{"input": "Primary analysis included Hamilton Anxiety Scale (HAM-A) reduction at 6 months.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary outcome measure was the Clinical Global Impression of Improvement (CGI-I) score at 6 months.", "output": {"entities": {}}, "schema": []}
{"input": "Genotype and allele frequencies were compared between groups using chi (2) contingency analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The frequency of the G-allele differed significantly between responders (70%) and nonresponders (56%) at 6 months (P = 0. 05) using the HAM-A scale as outcome measure.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, using the CGI-I as outcome, the G-allele was significantly associated with improvement (P = 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "Assuming a dominant effect of the G-allele, improvement differed significantly between groups (P = 0. 001, odds ratio = 4. 72).", "output": {"entities": {}}, "schema": []}
{"input": "Similar trends were observed for remission although not statistically significant.", "output": {"entities": {}}, "schema": []}
{"input": "We show for the first time a pharmacogenetic effect of the HTR2A rs7997012 variant in anxiety disorders, suggesting that pharmacogenetic effects cross diagnostic categories.", "output": {"entities": {}}, "schema": []}
{"input": "Our data document that individuals with the HTR2A rs7997012 single nucleotide polymorphism G-allele have better treatment outcome over time.", "output": {"entities": {}}, "schema": []}
{"input": "Future studies with larger sample sizes are necessary to further characterize this effect in treatment response to antidepressants in GAD.", "output": {"entities": {}}, "schema": []}
{"input": "Pollutant concentrations in placenta.", "output": {"entities": {}}, "schema": []}
{"input": "Unborn children are exposed to environmental pollutants via the placenta, and there is a causal relationship between maternal intake of pollutants and fetal exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Placental examination is an effective way for acquiring data for estimating fetal exposure.", "output": {"entities": {}}, "schema": []}
{"input": "We analyzed the concentrations of 104 congeners of persistent organic pollutants, seven organotin compounds, five heavy metals, and methylmercury in 130 randomly selected placentas.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 132, "end": 145}]}}, "schema": []}
{"input": "Additionally, we examined similarities between pollutant concentrations by analyzing correlations between their placental concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "Our results yield new information for conducting contaminant risk assessments for the prenatal period.", "output": {"entities": {}}, "schema": []}
{"input": "Out of the 117 individual persistent organic pollutants or metals assayed, 46 could be detected in more than half of the placentas.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, dichlorodiphenyldichloroethylene (p, p'-DDE) was found in all placentas.", "output": {"entities": {"chemical": [{"text": "dichlorodiphenyldichloroethylene", "start": 10, "end": 42}, {"text": "p, p'-DDE", "start": 44, "end": 53}]}}, "schema": []}
{"input": "The data indicates that fetal exposure to dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs), p, p'-DDE, and methylmercury depends on the mother' s parity, and age.", "output": {"entities": {"chemical": [{"text": "dioxins", "start": 42, "end": 49}, {"text": "furans", "start": 54, "end": 60}, {"text": "PCDD", "start": 62, "end": 66}, {"text": "polychlorinated biphenyls", "start": 72, "end": 97}, {"text": "PCBs", "start": 99, "end": 103}, {"text": "p, p'-DDE", "start": 106, "end": 115}, {"text": "methylmercury", "start": 121, "end": 134}]}}, "schema": []}
{"input": "We also conclude that sources of the above four pollutants are similar but differ from the sources of polybrominated diphenyl ethers.", "output": {"entities": {"chemical": [{"text": "polybrominated diphenyl ethers", "start": 102, "end": 132}]}}, "schema": []}
{"input": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment.", "output": {"entities": {}}, "schema": []}
{"input": "The fish ingredient N3-docosahexaenoic acid 22: 6 n-3 (DHA) stimulates brain development.", "output": {"entities": {"chemical": [{"text": "N3-docosahexaenoic acid", "start": 20, "end": 43}, {"text": "DHA", "start": 55, "end": 58}]}}, "schema": []}
{"input": "On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 18, "end": 31}, {"text": "MeHg", "start": 33, "end": 37}]}}, "schema": []}
{"input": "In this Context the IQ score in children is considered as an aggregate measure of in utero brain development.", "output": {"entities": {}}, "schema": []}
{"input": "To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children.", "output": {"entities": {"chemical": [{"text": "DHA", "start": 27, "end": 30}, {"text": "DHA", "start": 82, "end": 85}]}}, "schema": []}
{"input": "For MeHg the maternal intake was converted into its accumulation in the maternal body.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 4, "end": 8}]}}, "schema": []}
{"input": "The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score.", "output": {"entities": {}}, "schema": []}
{"input": "Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 11, "end": 15}, {"text": "DHA", "start": 20, "end": 23}]}}, "schema": []}
{"input": "For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 44, "end": 48}, {"text": "DHA", "start": 99, "end": 102}]}}, "schema": []}
{"input": "In the case of long-living predators a negative effect up to 10 points on the IQ score was found.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content.", "output": {"entities": {"chemical": [{"text": "DHA", "start": 153, "end": 156}, {"text": "MeHg", "start": 206, "end": 210}]}}, "schema": []}
{"input": "Tissues distribution of heavy metals and erythrocytes antioxidant status in rats exposed to Nigerian bonny light crude oil.", "output": {"entities": {}}, "schema": []}
{"input": "The harmful effects of folkloric uses of Nigerian bonny light crude oil (BLCO) in ailments management may outweigh the expected beneficial effects.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the levels of heavy metal concentrations in the tissues as well as the effect of BLCO on the antioxidant status of erythrocytes of rats after oral exposure to 0, 200 and 800 mg/kg BLCO for 7 days.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of heavy metal concentrations in BLCO showed that Zn > Fe > Pb > Cu > Ni.", "output": {"entities": {"chemical": [{"text": "Zn", "start": 59, "end": 61}, {"text": "Fe", "start": 64, "end": 66}, {"text": "Pb", "start": 69, "end": 71}, {"text": "Cu", "start": 74, "end": 76}, {"text": "Ni", "start": 79, "end": 81}]}}, "schema": []}
{"input": "The trend of accumulation of the metals in the tissues is blood-Fe > Pb > Zn whereas Cu and Ni levels were not affected; Liver-Ni > Zn > Fe > Cu > Pb and Testes-Ni > Cu > Pb > Zn > Fe.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 64, "end": 66}, {"text": "Pb", "start": 69, "end": 71}, {"text": "Zn", "start": 74, "end": 76}, {"text": "Cu", "start": 85, "end": 87}, {"text": "Ni", "start": 92, "end": 94}, {"text": "Ni", "start": 127, "end": 129}, {"text": "Zn", "start": 132, "end": 134}, {"text": "Fe", "start": 137, "end": 139}, {"text": "Cu", "start": 142, "end": 144}, {"text": "Pb", "start": 147, "end": 149}, {"text": "Ni", "start": 161, "end": 163}, {"text": "Cu", "start": 166, "end": 168}, {"text": "Pb", "start": 171, "end": 173}, {"text": "Zn", "start": 176, "end": 178}, {"text": "Fe", "start": 181, "end": 183}]}}, "schema": []}
{"input": "The order of concentration of the metals in the tissues is as follows: iron-blood > liver > testes; zinc-liver > blood > testes; lead-blood > liver > testes; copper-testes > liver > blood; nickel-liver > testes > blood.", "output": {"entities": {"chemical": [{"text": "iron", "start": 71, "end": 75}, {"text": "zinc", "start": 100, "end": 104}, {"text": "copper", "start": 158, "end": 164}, {"text": "nickel", "start": 189, "end": 195}]}}, "schema": []}
{"input": "Activities of the antioxidant enzymes of erythrocytes such as superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase increased significantly in a dose-dependent manner with significant elevation in hydrogen peroxide and malondialdehyde levels, whereas glutathione level was not significantly decreased in BLCO-treated animals.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 62, "end": 72}, {"text": "glutathione S", "start": 94, "end": 107}, {"text": "glutathione", "start": 124, "end": 135}, {"text": "hydrogen peroxide", "start": 228, "end": 245}, {"text": "malondialdehyde", "start": 250, "end": 265}, {"text": "glutathione", "start": 282, "end": 293}]}}, "schema": []}
{"input": "Collectively, the results showed that BLCO induces oxidative damage to erythrocytes of rats.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to investigate pharmacogenetic determinants of skin rash associated with epidermal growth factor receptor (EGFR) inhibitor treatment.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 109 prospectively sampled cancer patients, receiving the first treatment with an EGFR inhibitor, were genotyped for functional EGFR polymorphisms and tagging variants in genes involved in receptor downstream signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Skin rash was absent in 26 (23. 9%) patients and associated with shorter overall survival compared with patients presenting skin rash (P = 0. 005).", "output": {"entities": {}}, "schema": []}
{"input": "The EGFR polymorphisms, 497G/A (P = 0. 008), and the haplotypes of the promoter variants, EGFR-216G/T and-191C/A (P = 0. 029), were associated with the appearance of skin rash.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, a common haplotype in the PIK3CA gene was associated with skin rash (P = 0. 045) and overall survival (P = 0. 009).", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, genetic variation within the EGFR gene and its downstream signaling partner PIK3CA might predict EGFR-inhibitor-related skin rash.", "output": {"entities": {}}, "schema": []}
{"input": "Volatile compound in cut and un-cut flowers of tetraploid Freesia hybrida.", "output": {"entities": {}}, "schema": []}
{"input": "The flower volatile compounds (FVCs) of two tetraploid Freesia hybrida (pink-yellow and yellow) cultivars and their cut flowers were analysed by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Twelve FVCs were identified in the pink-yellow cultivar, with linalool as the major compound; 30 FVCs were identified in the yellow cultivar, with linalool and terpineol as the two major compounds.", "output": {"entities": {"chemical": [{"text": "linalool", "start": 62, "end": 70}, {"text": "linalool", "start": 147, "end": 155}, {"text": "terpineol", "start": 160, "end": 169}]}}, "schema": []}
{"input": "The FVCs (> 1%) of the two cut flower cultivars were very similar to that of the un-cut flowers, and no significant difference was observed.", "output": {"entities": {}}, "schema": []}
{"input": "Volatile organic compounds of Schenella pityophilus.", "output": {"entities": {}}, "schema": []}
{"input": "Volatile organic compounds of Schenella pityophilus have been identified via solid-phase microextraction-gas chromatography-mass spectrometry analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Ten compounds have been identified, in which 3-methylthio-1-propene was the most significant component.", "output": {"entities": {"chemical": [{"text": "3-methylthio-1-propene", "start": 45, "end": 67}]}}, "schema": []}
{"input": "Some other components were previously identified in Tuber aestivum and Tuber melanosporum.", "output": {"entities": {}}, "schema": []}
{"input": "Diclavatol and tetronic acids from Penicillium griseoroseum.", "output": {"entities": {"chemical": [{"text": "Diclavatol", "start": 0, "end": 10}, {"text": "tetronic acids", "start": 15, "end": 29}]}}, "schema": []}
{"input": "In our continuous studies on the chemistry of the endophytic fungus Penicillium griseoroseum, an endophyte isolated from fruits of Coffea arabica, we isolated clavatol, a dimethylated tetraketide, and its dimer which appears to be a novel natural compound.", "output": {"entities": {"chemical": [{"text": "clavatol", "start": 159, "end": 167}, {"text": "dimethylated tetraketide", "start": 171, "end": 195}]}}, "schema": []}
{"input": "The studies also resulted in the identification of two known tetronic acids, viridicatic acid and terrestric acid, found in ethyl acetate and n-butanol extracts.", "output": {"entities": {"chemical": [{"text": "tetronic acids", "start": 61, "end": 75}, {"text": "viridicatic acid", "start": 77, "end": 93}, {"text": "terrestric acid", "start": 98, "end": 113}, {"text": "ethyl acetate", "start": 124, "end": 137}, {"text": "n-butanol", "start": 142, "end": 151}]}}, "schema": []}
{"input": "Spectroscopic studies using 1-D and 2-D NMR and MS/MS analysis were performed to determine the structures of these compounds, first reported by this Penicillium.", "output": {"entities": {}}, "schema": []}
{"input": "Two other tetronic acids congeners were identified through HPLC/MS/MS studies, based on fragmentation pattern of ions produced from ionised tetronic acids, and UV light absorptions.", "output": {"entities": {"chemical": [{"text": "tetronic acids", "start": 10, "end": 24}, {"text": "tetronic acids", "start": 140, "end": 154}]}}, "schema": []}
{"input": "A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus.", "output": {"entities": {}}, "schema": []}
{"input": "Adenovirus serotype 5 (Ad5) is frequently used as an effective vector for induction of therapeutic transgenes in cancer gene therapy or of tumor cell lysis in oncolytic virotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "Ad5 can infect target cells through binding with the coxsackie and adenovirus receptor (CAR).", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the infectious ability of Ad5-based vectors depends on the CAR expression level in target cells.", "output": {"entities": {}}, "schema": []}
{"input": "There are conventional methods to evaluate the CAR expression level in human target cells, including flow cytometry, western blotting and immunohistochemistry.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show a simple system for detection and assessment of functional CAR expression in human tumor cells, using the green fluorescent protein (GFP)-expressing telomerase-specific replication-competent adenovirus OBP-401.", "output": {"entities": {}}, "schema": []}
{"input": "OBP-401 infection induced detectable GFP expression in CAR-expressing tumor cells, but not in CAR-negative tumor cells, nor in CAR-positive normal fibroblasts, 24 h after infection.", "output": {"entities": {}}, "schema": []}
{"input": "OBP-401-mediated GFP expression was significantly associated with CAR expression in tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "OBP-401 infection detected tumor cells with low CAR expression more efficiently than conventional methods.", "output": {"entities": {}}, "schema": []}
{"input": "OBP-401 also distinguished CAR-positive tumor tissues from CAR-negative tumor and normal tissues in biopsy samples.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that GFP-expressing telomerase-specific replication-competent adenovirus is a very potent diagnostic tool for assessment of functional CAR expression in tumor cells for Ad5-based antitumor therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical composition and antioxidant activity of the essential oil of Tabernaemontana catharinensis A.", "output": {"entities": {}}, "schema": []}
{"input": "DC. leaves.", "output": {"entities": {}}, "schema": []}
{"input": "The essential oils obtained by hydrodistillation from the leaves of Tabernaemontana catharinensis had their composition analysed by GC-MS.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 18 substances were identified, consisting of a complex mixture of sesquiterpenes (83. 52%), monoterpenes (5. 46%) and triterpenes (4. 56%).", "output": {"entities": {"chemical": [{"text": "sesquiterpenes", "start": 77, "end": 91}, {"text": "monoterpenes", "start": 103, "end": 115}, {"text": "triterpenes", "start": 129, "end": 140}]}}, "schema": []}
{"input": "The main components in the oil were beta-caryophyllene (56. 87%), alpha-cadinol (12. 52%), 8S, 13-cedran-diol (5. 41%), alpha-terpineol (3. 99%), beta-eudesmol (2. 54%), caryophyllene oxide (2. 51%) and ethyl iso-allocholate (2. 03%) along with beta-cubebene, gamma-cadinene, cubenol, 1, 8-cineol, o-cymene, curcumenol, spathulenol, friedeline and beta-sitosterol as minor constituents.", "output": {"entities": {"chemical": [{"text": "beta-caryophyllene", "start": 36, "end": 54}, {"text": "alpha-cadinol", "start": 66, "end": 79}, {"text": "8S, 13-cedran-diol", "start": 91, "end": 109}, {"text": "alpha-terpineol", "start": 120, "end": 135}, {"text": "beta-eudesmol", "start": 146, "end": 159}, {"text": "caryophyllene oxide", "start": 170, "end": 189}, {"text": "ethyl iso-allocholate", "start": 203, "end": 224}, {"text": "beta-cubebene", "start": 245, "end": 258}, {"text": "gamma-cadinene", "start": 260, "end": 274}, {"text": "cubenol", "start": 276, "end": 283}, {"text": "1, 8-cineol", "start": 285, "end": 296}, {"text": "o-cymene", "start": 298, "end": 306}, {"text": "curcumenol", "start": 308, "end": 318}, {"text": "spathulenol", "start": 320, "end": 331}, {"text": "friedeline", "start": 333, "end": 343}, {"text": "beta-sitosterol", "start": 348, "end": 363}]}}, "schema": []}
{"input": "An antioxidant property was tested with the oil obtained by means of 1, 1-diphenyl-2-picrylhydrazyl assay; the oil presented interesting radical scavenging activity.", "output": {"entities": {"chemical": [{"text": "1, 1-diphenyl-2-picrylhydrazyl", "start": 69, "end": 99}]}}, "schema": []}
{"input": "To the best of our knowledge, this is the first study of the composition and antioxidant activity of essential oil from the T. catharinensis collected from Brazil.", "output": {"entities": {}}, "schema": []}
{"input": "Green tea extract alleviates arsenic-induced biochemical toxicity and lipid peroxidation in rats.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 29, "end": 36}]}}, "schema": []}
{"input": "The present work was undertaken to evaluate the protective effect of an aqueous extract of green tea (GT, Camellia sinensis) leaves against arsenic (NaAsO2)-induced biochemical toxicity and lipid peroxidation production in experimental rats.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 140, "end": 147}, {"text": "NaAsO2", "start": 149, "end": 155}]}}, "schema": []}
{"input": "The treatment with arsenic exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 19, "end": 26}, {"text": "alanine", "start": 116, "end": 123}, {"text": "aspartate", "start": 142, "end": 151}, {"text": "bilirubin", "start": 216, "end": 225}, {"text": "cholesterol", "start": 227, "end": 238}, {"text": "urea", "start": 240, "end": 244}, {"text": "creatinine", "start": 249, "end": 259}]}}, "schema": []}
{"input": "But the co-administration of GT has increased the level of plasmatic concentration of biochemical parameters.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure of rats to arsenic caused also a significant increase in liver, kidney and testicular thiobarbituric acid reactive substances compared to control.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 20, "end": 27}, {"text": "thiobarbituric acid", "start": 95, "end": 114}]}}, "schema": []}
{"input": "However, the co-administration of GT was effective in reducing its level.", "output": {"entities": {}}, "schema": []}
{"input": "To conclude, our data suggest that arsenic exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the GT co-administration alleviates the toxicity induced by arsenic exposure.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 35, "end": 42}, {"text": "arsenic", "start": 198, "end": 205}]}}, "schema": []}
{"input": "Changes in carbohydrate metabolism, oxidative stress and loss of cortisol secretion in adrenocortica l cells of Oreochromis niloticus exposed in vitro to endosulfan.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 11, "end": 23}, {"text": "cortisol", "start": 65, "end": 73}, {"text": "endosulfan", "start": 154, "end": 164}]}}, "schema": []}
{"input": "The effects of endosulfan, an organochlorine pesticide regularly used in Niger Delta ecological zone, were examined and also its effects on various biochemical parameters in the serum of Oreochromis niloticus, a dominant fish species in Nigeria.", "output": {"entities": {"chemical": [{"text": "endosulfan", "start": 15, "end": 25}, {"text": "organochlorine", "start": 30, "end": 44}]}}, "schema": []}
{"input": "One hundred and fifty juveniles of O. niloticus were used for the toxicity study.", "output": {"entities": {}}, "schema": []}
{"input": "Lethal concentration of 50% mortality of sample (LC50) was determined using semi-static method.", "output": {"entities": {}}, "schema": []}
{"input": "From the result of the LC50 determination, lower concentrations of endosulfan were prepared for sublethal test.", "output": {"entities": {"chemical": [{"text": "endosulfan", "start": 67, "end": 77}]}}, "schema": []}
{"input": "Five fish per test concentration in three replicates were exposed to varying concentrations of endosulfan.", "output": {"entities": {"chemical": [{"text": "endosulfan", "start": 95, "end": 105}]}}, "schema": []}
{"input": "Glucose level and the enzyme activities were measured spectrophotometrically at the end of 28 days of exposure.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Glucose levels and glutathione-S-transferase activities were significantly (p < 0. 05) higher than the control and the concentrations increased with increasing concentration of the toxicant and exposure duration.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}, {"text": "glutathione", "start": 19, "end": 30}, {"text": "S", "start": 31, "end": 32}]}}, "schema": []}
{"input": "Cortisol secretion was significantly (p = 0. 05) lower in the treated fish than the control.", "output": {"entities": {"chemical": [{"text": "Cortisol", "start": 0, "end": 8}]}}, "schema": []}
{"input": "These findings indicated that endosulfan altered all the investigated parameters, which is an indication of their suitability as markers for fish and other aquatic organism toxicity study.", "output": {"entities": {"chemical": [{"text": "endosulfan", "start": 30, "end": 40}]}}, "schema": []}
{"input": "Determination of aflatoxin M1 in milk by high-performance liquid chromatography in Mashhad (north east of Iran).", "output": {"entities": {"chemical": [{"text": "aflatoxin M1", "start": 17, "end": 29}]}}, "schema": []}
{"input": "The aim of this study was to evaluate aflatoxin M1 (AFM1) contamination in milk samples in Mashhad in Iran.", "output": {"entities": {"chemical": [{"text": "aflatoxin M1", "start": 38, "end": 50}, {"text": "AFM1", "start": 52, "end": 56}]}}, "schema": []}
{"input": "A total of 60 milk samples were collected from retail stores of five regions in June 2011.", "output": {"entities": {}}, "schema": []}
{"input": "The occurrence and concentration range of AFM1 in the samples were investigated by high-performance liquid chromatography method.", "output": {"entities": {"chemical": [{"text": "AFM1", "start": 42, "end": 46}]}}, "schema": []}
{"input": "AFM1 was found in 100% of the examined milk samples by average concentration of 16. 16 ng/L and the contamination level ranging between 2 and 64 ng/L.", "output": {"entities": {"chemical": [{"text": "AFM1", "start": 0, "end": 4}]}}, "schema": []}
{"input": "The concentration of AFM1 in all the samples was lower than the Iranian national standard and Food and Drug Administration limit (500 ng/L), and only in one (1. 6%) of the samples, the concentration of AFM1 was greater than the maximum tolerance limit (50 ng/L) accepted by European Union and Codex Alimentarius Commission.", "output": {"entities": {"chemical": [{"text": "AFM1", "start": 21, "end": 25}, {"text": "AFM1", "start": 202, "end": 206}]}}, "schema": []}
{"input": "Statistical evaluation showed no significant difference between the mean concentrations of AFM1 in milk samples taken from different regions (p > 0. 05).", "output": {"entities": {"chemical": [{"text": "AFM1", "start": 91, "end": 95}]}}, "schema": []}
{"input": "CNS distribution of metabotropic glutamate 2 and 3 receptors: transgenic mice and [(3) H] LY459477 autoradiography.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 33, "end": 42}, {"text": "[(3) H] LY459477", "start": 82, "end": 98}]}}, "schema": []}
{"input": "Group II metabotropic glutamate (mGlu) receptor agonists were efficacious in randomized clinical research trials for schizophrenia and generalized anxiety disorder.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 22, "end": 31}]}}, "schema": []}
{"input": "The regional quantification of mGlu (2) and mGlu (3) receptors remains unknown.", "output": {"entities": {}}, "schema": []}
{"input": "A selective and structurally novel mGlu (2/3) receptor agonist, 2-amino-4-fluorobicyclo [3. 1. 0] hexane-2, 6-dicarboxylic acid (LY459477) was tritiated and the distribution of mGlu (2) and mGlu (3) receptors was studied in transgenic mice lacking either mGlu (2), mGlu (3) or both receptors.", "output": {"entities": {"chemical": [{"text": "2-amino-4-fluorobicyclo [3. 1. 0] hexane-2, 6-dicarboxylic acid", "start": 64, "end": 127}, {"text": "LY459477", "start": 129, "end": 137}]}}, "schema": []}
{"input": "LY459477 is an agonist with 1-2 nM potency for rodent and human mGlu (2) and mGlu (3) receptors.", "output": {"entities": {"chemical": [{"text": "LY459477", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The functional selectivity of LY459477 was demonstrated by over 640-fold selectivity and the displacement binding selectivity was greater than 320-fold for all glutamate receptors except mGlu (6) (~ 230-fold).", "output": {"entities": {"chemical": [{"text": "LY459477", "start": 30, "end": 38}, {"text": "glutamate", "start": 160, "end": 169}]}}, "schema": []}
{"input": "More than 1000-fold selectivity was demonstrated for all non-glutamate receptors known to be targeted by antipsychotic drugs.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 61, "end": 70}]}}, "schema": []}
{"input": "Like atypical antipsychotic drugs, LY459477 reversed in vitro electrophysiological effects of a serotonergic hallucinogen and behavioral effects of phencyclidine or amphetamine.", "output": {"entities": {"chemical": [{"text": "LY459477", "start": 35, "end": 43}, {"text": "phencyclidine", "start": 148, "end": 161}, {"text": "amphetamine", "start": 165, "end": 176}]}}, "schema": []}
{"input": "There was virtually no binding of [(3) H] LY459477 to any brain region in mice with a deletion of both mGlu (2) and mGlu (3) receptors.", "output": {"entities": {"chemical": [{"text": "[(3) H] LY459477", "start": 34, "end": 50}]}}, "schema": []}
{"input": "Regions enriched in mGlu (2) receptors included the medial prefrontal cortex, select hippocampal regions, the medial mammillary nucleus, the medial habenula, and the cerebellar granular cell layer.", "output": {"entities": {}}, "schema": []}
{"input": "Regions enriched in mGlu (3) receptors were the dorsolateral entorhinal cortex, the hippocampal CA1 field, the piriform cortex, the substantia nigra, the thalamic reticular nucleus, and primary sensory thalamic nuclei.", "output": {"entities": {}}, "schema": []}
{"input": "These findings suggest [(3) H] LY459477 should be a useful tool to further define the role of mGlu (2) and mGlu (3) receptors throughout the brain with respect to major neuropsychiatric syndromes.", "output": {"entities": {"chemical": [{"text": "[(3) H] LY459477", "start": 23, "end": 39}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 79, "end": 90}]}}, "schema": []}
{"input": "The efficacy of oral risperidone treatment in prevention of schizophrenia is well known.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 21, "end": 32}]}}, "schema": []}
{"input": "However, oral side effects and patient compliance is always a problem for schizophrenics.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, risperidone was formulated into matrix transdermal patches to overcome these problems.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 15, "end": 26}]}}, "schema": []}
{"input": "The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated.", "output": {"entities": {"chemical": [{"text": "eudragit RL 100", "start": 52, "end": 67}, {"text": "eudragit RS 100", "start": 72, "end": 87}]}}, "schema": []}
{"input": "The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 35, "end": 46}]}}, "schema": []}
{"input": "Among the tested preparations, formulations with 20% risperidone, 3: 2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1. 87 +/- 0. 09 mg/cm (2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 53, "end": 64}, {"text": "ERL 100", "start": 71, "end": 78}, {"text": "ERS 100", "start": 83, "end": 90}]}}, "schema": []}
{"input": "The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 53, "end": 64}, {"text": "risperidone", "start": 128, "end": 139}]}}, "schema": []}
{"input": "The calculated relative bioavailability of risperidone transdermal patch was 115. 20% with prolonged release of drug.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 43, "end": 54}]}}, "schema": []}
{"input": "Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation.", "output": {"entities": {}}, "schema": []}
{"input": "This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 45, "end": 56}]}}, "schema": []}
{"input": "Defining \" epileptogenesis \" and identifying \" antiepileptogenic targets \" in animal models of acquired temporal lobe epilepsy is not as simple as it might seem.", "output": {"entities": {}}, "schema": []}
{"input": "The \" latent period \" between brain injury and clinical epilepsy is widely regarded to be a seizure-free, pre-epileptic state during which a time-consuming cascade of molecular events and structural changes gradually mediates the process of \" epileptogenesis. \" The concept of the \" latent period \" as the duration of \" epileptogenesis \" implies that epilepsy is not an immediate result of brain injury, and that anti-epileptogenic strategies need to target delayed secondary mechanisms that develop sometime after an initial injury.", "output": {"entities": {}}, "schema": []}
{"input": "However, depth recordings made directly from the dentate granule cell layers in awake rats after convulsive status epilepticus-induced injury have now shown that whenever perforant pathway stimulation-induced status epilepticus produces extensive hilar neuron loss and entorhinal cortical injury, hyperexcitable granule cells immediately generate spontaneous epileptiform discharges and focal or generalized behavioral seizures.", "output": {"entities": {}}, "schema": []}
{"input": "This indicates that hippocampal injury caused by convulsive status epilepticus is immediately epileptogenic and that hippocampal epileptogenesis requires no delayed secondary mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "When latent periods do exist after injury, we hypothesize that less extensive cell loss causes an extended period during which initially subclinical focal seizures gradually increase in duration to produce the first clinical seizure.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the \" latent period \" is suggested to be a state of \" epileptic maturation, \" rather than a prolonged period of \" epileptogenesis, \" and therefore the antiepileptogenic therapeutic window may only remain open during the first week after injury, when some delayed cell death may still be preventable.", "output": {"entities": {}}, "schema": []}
{"input": "Following the perhaps unavoidable development of the first focal seizures (\" epileptogenesis \"), the most fruitful therapeutic strategy may be to interrupt the process of \" epileptic maturation, \" thereby keeping focal seizures focal.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' New Targets and Approaches to the Treatment of Epilepsy'.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical composition and antibacterial activity of the volatile oil from seeds of Artemisia annua L. from Iran.", "output": {"entities": {}}, "schema": []}
{"input": "The composition of essential oil of the seeds of Artemisia annua L. was analysed by GC-MS.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, 16 volatile components were identified on the basis of their mass spectra characteristics and retention indices representing 95. 5% of the total oil.", "output": {"entities": {}}, "schema": []}
{"input": "Trans-3 (10)-caren-4-ol (22. 3%), artemisia ketone (18. 6%), 1, 8-cineole (14. 9%), delta-selinene (13. 0%) and alpha-pinene (8. 2%) were the major compounds.", "output": {"entities": {"chemical": [{"text": "Trans-3 (10)-caren-4-ol", "start": 0, "end": 23}, {"text": "artemisia ketone", "start": 34, "end": 50}, {"text": "1, 8-cineole", "start": 61, "end": 73}, {"text": "delta-selinene", "start": 84, "end": 98}, {"text": "alpha-pinene", "start": 112, "end": 124}]}}, "schema": []}
{"input": "Oxygenated monoterpenes were the main compounds with 51. 6% followed by sesquiterpene hydrocarbons (13. 3%), monoterpene hydrocarbons (9. 9%) and other compounds (8. 3%).", "output": {"entities": {"chemical": [{"text": "monoterpenes", "start": 11, "end": 23}, {"text": "sesquiterpene hydrocarbons", "start": 72, "end": 98}, {"text": "monoterpene hydrocarbons", "start": 109, "end": 133}]}}, "schema": []}
{"input": "The essential oil was highly active against Escherichia coli and Enterococcus faecalis.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to contaminants exacerbates oxidative stress in amphipod Monoporeia affinis subjected to fluctuating hypoxia.", "output": {"entities": {}}, "schema": []}
{"input": "Fitness and survival of an organism depend on its ability to mount a successful stress response when challenged by exposure to damaging agents.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that co-exposure to contaminants may exacerbate oxidative stress in hypoxia-challenged benthic animals compromising their ability to recover upon reoxygenation.", "output": {"entities": {}}, "schema": []}
{"input": "This was tested using the amphipod Monoporeia affinis exposed to hypoxia followed by reoxygenation in sediments collected in polluted and pristine areas.", "output": {"entities": {}}, "schema": []}
{"input": "In both sediment types, oxygen radical absorbance capacity (ORAC) and antioxidant enzyme activities [superoxide dismutase (SOD) and catalase (CAT)] increased during hypoxia, suggesting that M. affinis has a strategy of preparation for oxidative stress that facilitates recovery after a hypoxic episode.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 24, "end": 30}, {"text": "superoxide", "start": 101, "end": 111}]}}, "schema": []}
{"input": "Exposure to contaminants altered this anticipatory response as indicated by higher baselines of ORAC and SOD during hypoxia and no response upon reoxygenation.", "output": {"entities": {}}, "schema": []}
{"input": "This coincided with significantly elevated oxidative damage evidenced by a marked reduction in glutathione redox status (ratio of reduced GSH/oxidized GSSG) and an increase in lipid peroxidation (TBARS levels).", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 95, "end": 106}, {"text": "reduced GSH", "start": 130, "end": 141}, {"text": "oxidized GSSG", "start": 142, "end": 155}]}}, "schema": []}
{"input": "Moreover, RNA: DNA ratio, a proxy for protein synthetic activity, decreased in concert with increased TBARS, indicating a linkage between oxidative damage and fitness.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, inhibited acetylcholinesterase (AChE) activity in animals exposed to contaminated sediments suggested a neurotoxic impact, whereas significant correlations between AChE and oxidative biomarkers may indicate connections with redox state regulation.", "output": {"entities": {}}, "schema": []}
{"input": "The oxidative responses in pristine sediments suggested a typical scenario of ROS production and removal, with no apparent oxidative damage.", "output": {"entities": {}}, "schema": []}
{"input": "By contrast, co-exposure to contaminants caused greater increase in antioxidants, lipid peroxidation, and slowed recovery from hypoxia as indicated by CAT, GSH/GSSG, TBARS and AChE responses.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 156, "end": 159}, {"text": "GSSG", "start": 160, "end": 164}]}}, "schema": []}
{"input": "These results support the hypothesized potential of xenobiotics to hamper ability of animals to cope with fluctuating hypoxia.", "output": {"entities": {}}, "schema": []}
{"input": "They also emphasize the importance of understanding interactions between antioxidant responses to different stressors and physiological mechanisms of oxidative damage.", "output": {"entities": {}}, "schema": []}
{"input": "Simultaneous determination of glucoraphanin and sulforaphane in Brassica oleracea seeds by high-performance liquid chromatography with evaporative light-scattering detector.", "output": {"entities": {"chemical": [{"text": "glucoraphanin", "start": 30, "end": 43}, {"text": "sulforaphane", "start": 48, "end": 60}]}}, "schema": []}
{"input": "In this article, a novel and efficient analysis method is described to simultaneously and quantitatively determine glucoraphanin and its major degradation product sulforaphane by reversed-phase high-performance liquid chromatography (HPLC) coupled with an evaporative light-scattering detector (ELSD).", "output": {"entities": {"chemical": [{"text": "glucoraphanin", "start": 115, "end": 128}, {"text": "sulforaphane", "start": 163, "end": 175}]}}, "schema": []}
{"input": "This method was validated according to the regulatory guidelines with respect to precision, accuracy and linearity.", "output": {"entities": {}}, "schema": []}
{"input": "The HPLC-ELSD method was successfully used to assess the contents of glucoraphanin and sulforaphane in varieties of Brassica oleracea seeds.", "output": {"entities": {"chemical": [{"text": "glucoraphanin", "start": 69, "end": 82}, {"text": "sulforaphane", "start": 87, "end": 99}]}}, "schema": []}
{"input": "The developed analytical method not only avoids the underestimation of total glucoraphanin content, but also provides a reduction in analysis time and good efficiency and sensitivity compared to with conventional HPLC methods.", "output": {"entities": {"chemical": [{"text": "glucoraphanin", "start": 77, "end": 90}]}}, "schema": []}
{"input": "RETRACTED: Detection of acute toxicity test of crude diesel oil on Beluga, Huso huso.", "output": {"entities": {}}, "schema": []}
{"input": "RETRACTED.", "output": {"entities": {}}, "schema": []}
{"input": "The PP1 binding code: a molecular-lego strategy that governs specificity.", "output": {"entities": {}}, "schema": []}
{"input": "Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly 200 validated interactors in vertebrates.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 0, "end": 3}, {"text": "Thr", "start": 4, "end": 7}]}}, "schema": []}
{"input": "PP1-interacting proteins (PIPs) are ubiquitously expressed but show an exceptional diversity in brain, testis and white blood cells.", "output": {"entities": {}}, "schema": []}
{"input": "The binding of PIPs is mainly mediated by short motifs that dock to surface grooves of PP1.", "output": {"entities": {}}, "schema": []}
{"input": "Although PIPs often contain variants of the same PP1 binding motifs, they differ in the number and combination of docking sites.", "output": {"entities": {}}, "schema": []}
{"input": "This molecular-lego strategy for binding to PP1 creates holoenzymes with unique properties.", "output": {"entities": {}}, "schema": []}
{"input": "The PP1 binding code can be described as specific, universal, degenerate, nonexclusive and dynamic.", "output": {"entities": {}}, "schema": []}
{"input": "PIPs control associated PP1 by interference with substrate recruitment or access to the active site.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, some PIPs have a subcellular targeting domain that promotes dephosphorylation by increasing the local concentration of PP1.", "output": {"entities": {}}, "schema": []}
{"input": "The diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Serratin a new metabolite obtained from Serratia marcescens, a bacterium isolated from the microflora associated with banana plantations.", "output": {"entities": {"chemical": [{"text": "Serratin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "When cultures of Serratia marcescens, an enterobacteria isolated from the microflora associated with banana plantations incubated at 27 degrees C in a yeast-calcium carbonate-dextrose solid medium (10 g of yeast extract, 20 g dextrose, 15 g bacteriological agar, 20 g calcium carbonate and 1000 mL distilled water) were extracted with chloroform and purified by column chromatography, we obtained a new colourless bacterial metabolite which according to spectroscopic data proved to be serratin.", "output": {"entities": {"chemical": [{"text": "calcium carbonate", "start": 157, "end": 174}, {"text": "dextrose", "start": 175, "end": 183}, {"text": "dextrose", "start": 226, "end": 234}, {"text": "calcium carbonate", "start": 268, "end": 285}, {"text": "chloroform", "start": 335, "end": 345}, {"text": "serratin", "start": 486, "end": 494}]}}, "schema": []}
{"input": "MTBP suppresses cell migration and filopodia formation by inhibiting ACTN4.", "output": {"entities": {}}, "schema": []}
{"input": "Murine double minute (MDM2) binding protein (MTBP) has been implicated in cancer progression.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate one mechanism by which MTBP inhibits cancer metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "Overexpression of MTBP in human osteosarcoma cell lines lacking wild-type p53 did not alter primary tumor growth in mice, but significantly inhibited metastases.", "output": {"entities": {}}, "schema": []}
{"input": "MTBP downregulation increased the migratory potential of MDM2 (-/-) p53 (-/-) mouse embryonic fibroblasts, suggesting that MTBP inhibited cell migration independently of the Mdm2-p53 pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Co-immunoprecipitation and mass spectrometric analysis identified alpha-actinin-4 (ACTN4) as an MTBP-interacting protein.", "output": {"entities": {}}, "schema": []}
{"input": "Endogenous MTBP interacted with and partially colocalized with ACTN4.", "output": {"entities": {}}, "schema": []}
{"input": "MTBP overexpression inhibited cell migration and filopodia formation mediated by ACTN4.", "output": {"entities": {}}, "schema": []}
{"input": "Increased cell migration by MTBP downregulation was inhibited by concomitant downregulation of ACTN4.", "output": {"entities": {}}, "schema": []}
{"input": "MTBP also inhibited ACTN4-mediated F-actin bundling.", "output": {"entities": {}}, "schema": []}
{"input": "We furthermore demonstrated that nuclear localization of MTBP was dispensable for inhibiting ACTN4-mediated cell migration and filopodia formation.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, MTBP suppresses cell migration, at least partially, by inhibiting ACTN4 function.", "output": {"entities": {}}, "schema": []}
{"input": "Our study not only provides a mechanism of metastasis suppression by MTBP, but also suggests MTBP as a potential biomarker for cancer progression.", "output": {"entities": {}}, "schema": []}
{"input": "Phytochemical composition of polar fraction of Stachys germanica L. subsp.", "output": {"entities": {}}, "schema": []}
{"input": "salviifolia (Ten.) Gams, a typical plant of Majella National Park.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we report the isolation and identification of several compounds present in the polar fraction of Stachys germanica L. subsp.", "output": {"entities": {}}, "schema": []}
{"input": "salviifolia (Ten.) Gams, collected in the protected area of Majella National Park.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, we have isolated and identified harpagide, 7-beta-hydroxy-harpagide, ajugol, 5-allosyloxy-aucubin, verbascoside and, for the first time in this genus, arbutin.", "output": {"entities": {"chemical": [{"text": "harpagide", "start": 47, "end": 56}, {"text": "7-beta-hydroxy-harpagide", "start": 58, "end": 82}, {"text": "ajugol", "start": 84, "end": 90}, {"text": "5-allosyloxy-aucubin", "start": 92, "end": 112}, {"text": "verbascoside", "start": 114, "end": 126}, {"text": "arbutin", "start": 166, "end": 173}]}}, "schema": []}
{"input": "Pharmacokinetic and pharmacodynamic evaluation of floating microspheres of metformin hydrochloride.", "output": {"entities": {"chemical": [{"text": "metformin hydrochloride", "start": 75, "end": 98}]}}, "schema": []}
{"input": "Metformin hydrochloride (MH), a biguanide antidiabetic, is the drug of choice in obese patients.", "output": {"entities": {"chemical": [{"text": "Metformin hydrochloride", "start": 0, "end": 23}, {"text": "biguanide", "start": 32, "end": 41}]}}, "schema": []}
{"input": "It is well absorbed from the upper part of gastrointestinal tract and has oral bioavailability of 50% to 60%.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to formulate MH into floating microspheres in order to increase its residence time at the site of absorption and thus improve its bioavailability; and to extend the duration of action along with possibilities of dose reduction.", "output": {"entities": {}}, "schema": []}
{"input": "Microspheres were prepared by emulsion solvent evaporation method and evaluated for particle size, entrapment efficiency, buoyancy, and in vitro release; and further characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacokinetic and pharmacodynamic evaluation of selected formulation was carried out in male Wistar diabetic rats.", "output": {"entities": {}}, "schema": []}
{"input": "The data was statistically analyzed by unpaired t-test.", "output": {"entities": {}}, "schema": []}
{"input": "A 3. 5-fold increase in relative bioavailability was observed.", "output": {"entities": {}}, "schema": []}
{"input": "The prolongation of half-life (t (1/2)) from 4. 5 +/- 2. 41 h to 14. 12 +/- 4. 81 h indicated extended duration of action.", "output": {"entities": {}}, "schema": []}
{"input": "Oral glucose tolerance test (OGTT) was analyzed by one-way analysis of variance followed by Dunnet multiple comparison test, a significant decrease (p < 0. 05) in the blood glucose levels was observed when formulations were compared with control rats.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 5, "end": 12}, {"text": "glucose", "start": 173, "end": 180}]}}, "schema": []}
{"input": "Hence, MH floating microspheres were tested at 50 mg/kg and 100 mg/kg body weight, OGTT data showed nonsignificant difference (p > 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, an effective oral antidiabetics treatment can be achieved by formulating MH into floating microspheres which results in increase in bioavailability along with extended duration of action resulting in possible reduction in dose.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacological evidence of functional inhibitory metabotrophic glutamate receptors on mouse arousal-related cholinergic laterodorsal tegmental neurons.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 64, "end": 73}]}}, "schema": []}
{"input": "Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) are importantly involved in neurobiological mechanisms governing states of arousal such as sleep and wakefulness as well as other appetitive behaviors, such as drug-seeking.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, mechanisms controlling their excitability are important to elucidate if we are to understand how these LDT neurons generate arousal states.", "output": {"entities": {}}, "schema": []}
{"input": "Glutamate mediates the vast majority of excitatory synaptic transmission in the vertebrate CNS and while presence of glutamate input in the LDT has been shown and ionotropic responses to glutamate have been reported in the LDT, characterization of metabotropic responses is lacking.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 0, "end": 9}, {"text": "glutamate", "start": 117, "end": 126}, {"text": "glutamate", "start": 187, "end": 196}]}}, "schema": []}
{"input": "Therefore, electrophysiological responses and changes in levels of intracellular Ca (2 +) in mouse cholinergic LDT neurons following application of specific mGluR agonists and antagonists were examined.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Unexpectedly, both the mGluR (5) specific agonist, CHPG, and the group II mGluR (mGlu (2/3)) agonist, LY379268 (LY), induced a TTX-insensitive outward current/hyperpolarization.", "output": {"entities": {"chemical": [{"text": "CHPG", "start": 51, "end": 55}, {"text": "LY379268", "start": 102, "end": 110}, {"text": "TTX", "start": 127, "end": 130}]}}, "schema": []}
{"input": "Both outward currents were significantly reduced by the mGluR antagonist MCPG and the CHPG-induced current was blocked by the specific mGluR (5) antagonist MTEP.", "output": {"entities": {"chemical": [{"text": "MCPG", "start": 73, "end": 77}, {"text": "CHPG", "start": 86, "end": 90}, {"text": "MTEP", "start": 156, "end": 160}]}}, "schema": []}
{"input": "Concurrent Ca (2 +) imaging revealed that while CHPG actions did include release of Ca (2 +) from CPA/thapsigargin-sensitive intracellular stores, actions of LY did not.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 11, "end": 19}, {"text": "CHPG", "start": 48, "end": 52}, {"text": "Ca (2 +)", "start": 84, "end": 92}, {"text": "CPA", "start": 98, "end": 101}, {"text": "thapsigargin", "start": 102, "end": 114}]}}, "schema": []}
{"input": "Both CHPG-and LY-induced outward currents were mediated by a TEA-sensitive potassium conductance.", "output": {"entities": {"chemical": [{"text": "CHPG", "start": 5, "end": 9}, {"text": "TEA", "start": 61, "end": 64}, {"text": "potassium", "start": 75, "end": 84}]}}, "schema": []}
{"input": "The large-conductance, Ca (2 +)-dependent potassium (BK) channel blocker, iberiotoxin, attenuated CHPG actions.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 23, "end": 31}, {"text": "potassium", "start": 42, "end": 51}, {"text": "CHPG", "start": 98, "end": 102}]}}, "schema": []}
{"input": "Consistent with actions on the BK conductance, CHPG enhanced the amplitude of the fast component of the after hyperpolarizing potential, concurrent with a reduction in the firing rate.", "output": {"entities": {"chemical": [{"text": "CHPG", "start": 47, "end": 51}]}}, "schema": []}
{"input": "We conclude that stimulation of mGluR (5) and group II (mGluR (2/3)) elicits postsynaptically-mediated outward currents/hyperpolarizations in cholinergic LDT neurons.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of glutamatergic input would be, thus, expected not only to be excitation via stimulation of ionotropic glutamate receptors and mGluR (1), but also inhibition via actions at mGluR (5) and mGluR (2/3) on these neurons.", "output": {"entities": {"chemical": [{"text": "glutamatergic", "start": 11, "end": 24}]}}, "schema": []}
{"input": "As these two processes counteract each other, these surprising findings necessitate revision of predictions regarding the net level of excitation generated by glutamate input to cholinergic LDT cells and, by extension, the functional outcome of glutamate transmission on processes which these neurons regulate.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 159, "end": 168}, {"text": "glutamate", "start": 245, "end": 254}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "A potent Chk1 inhibitor is selectively cytotoxic in melanomas with high levels of replicative stress.", "output": {"entities": {}}, "schema": []}
{"input": "There are few effective treatments for metastatic melanoma.", "output": {"entities": {}}, "schema": []}
{"input": "Checkpoint kinase 1 (Chk1) inhibitors are being trialled for their efficacy in enhancing conventional chemotherapeutic agents, but their effectiveness as single agents is not known.", "output": {"entities": {}}, "schema": []}
{"input": "We have examined the effectiveness of two novel Chk1 selective inhibitors, AR323 and AR678, in a panel of melanoma cell lines and normal cell types.", "output": {"entities": {"chemical": [{"text": "AR323", "start": 75, "end": 80}, {"text": "AR678", "start": 85, "end": 90}]}}, "schema": []}
{"input": "We demonstrate that these drugs display single-agent activity, with IC50s in the low nanomolar range.", "output": {"entities": {}}, "schema": []}
{"input": "The drugs produce cytotoxic effects in cell lines that are most sensitive to these drugs, whereas normal cells are only sensitive to these drugs at the higher concentrations where they have cytostatic activity.", "output": {"entities": {}}, "schema": []}
{"input": "The cytotoxic effect is the consequence of inhibition of S-phase Chk1, which drives cells prematurely from late S phase into an aberrant mitosis and results in either failure of cytokinesis or cell death through an apoptotic mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "The sensitivity to the Chk1 inhibitors was correlated with the level of endogenous DNA damage indicating replicative stress.", "output": {"entities": {}}, "schema": []}
{"input": "Chk1 inhibitors are viable single-agent therapies that target melanoma cells with high levels of endogenous DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "This sensitivity suggests that Chk1 is a critical component of an adaptation to replicative stress in these cells.", "output": {"entities": {}}, "schema": []}
{"input": "It also suggests that markers of DNA damage may be useful in identifying the melanomas and potentially other tumour types that are more likely to be sensitive to Chk1 inhibitors as single agents.", "output": {"entities": {}}, "schema": []}
{"input": "Development and characterization of coated-microparticles based on whey protein/alginate using the Encapsulator device.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study is to prepare whey protein (WP)-based microparticles (MP) using the Encapsulator ((R)) device.", "output": {"entities": {}}, "schema": []}
{"input": "The viscosity dependence of the extrusion device required to mix WP with a food-grade and less viscous polymer.", "output": {"entities": {}}, "schema": []}
{"input": "Mixed WP/ALG MP were obtained with the optimized WP/alginate (ALG) ratio (62/38).", "output": {"entities": {}}, "schema": []}
{"input": "These particles were further coated with WP or ALG using non-traumatic and solvent-free coating process developed in this study.", "output": {"entities": {}}, "schema": []}
{"input": "Size and morphology of coated and uncoated MP were determined.", "output": {"entities": {}}, "schema": []}
{"input": "Then, swelling and degradation (WP release) of formulations were investigated in pH 1. 2 and 7. 5 buffers and in simulated gastric and intestinal fluids (SGF, SIF) and compared to pure ALG and pure WP particle behaviours.", "output": {"entities": {}}, "schema": []}
{"input": "At pH 1. 2, pure ALG shrank and pure WP swelled, whereas the sizes of mixed WP/ALG matrix were stable.", "output": {"entities": {}}, "schema": []}
{"input": "In SGF, WP/ALG MP resisted to pepsin degradation compare to pure WP particles due to ALG shrinkage which limited pepsin diffusion within particles.", "output": {"entities": {}}, "schema": []}
{"input": "Coating addition with WP or ALG slowed down pepsin degradation.", "output": {"entities": {}}, "schema": []}
{"input": "At pH 7. 5, WP/ALG particles were rapidly degraded due to ALG sensitivity but the addition of a WP coating limited effectively the swelling and the degradation of MP.", "output": {"entities": {}}, "schema": []}
{"input": "In SIF, pancreatin accelerated MP degradation but ALG-coated MP exhibited interesting robustness.", "output": {"entities": {}}, "schema": []}
{"input": "These results confirmed the interest and the feasibility to produce coated WP-based MP which could be a potential orally controlled release drug delivery system.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary metabolites from Marchantia paleacea calluses and their allelopathic effects on Arabidopsis seed growth.", "output": {"entities": {}}, "schema": []}
{"input": "Rapid-growth Marchantia paleacea calluses were induced on MSK2 medium through surface sterilisation of the capsula.", "output": {"entities": {}}, "schema": []}
{"input": "Ten known compounds including two steroids (1-2), six bibenzyls (3, 5-9), a flavonoid (10), and a terpenoid (4) were isolated from these calluses.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 34, "end": 42}, {"text": "bibenzyls", "start": 54, "end": 63}, {"text": "flavonoid", "start": 76, "end": 85}, {"text": "terpenoid", "start": 98, "end": 107}]}}, "schema": []}
{"input": "The allelopathic effect of the six bibenzyls was assessed in Arabidopsis thaliana.", "output": {"entities": {"chemical": [{"text": "bibenzyls", "start": 35, "end": 44}]}}, "schema": []}
{"input": "Results revealed that bibenzyls could inhibit seedling growth in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "bibenzyls", "start": 22, "end": 31}]}}, "schema": []}
{"input": "Preparation and in vitro/in vivo evaluation of a ketoprofen orally disintegrating/sustained release tablet.", "output": {"entities": {"chemical": [{"text": "ketoprofen", "start": 49, "end": 59}]}}, "schema": []}
{"input": "Context: Orally disintegrating tablets (ODTs) with sustained release profiles are a new generation of ODTs called orally disintegrating/sustained release tablets (ODSRTs), which are convenient in use and able to slowly release drugs to maintain effective blood concentrations over a prolonged period of time.", "output": {"entities": {}}, "schema": []}
{"input": "Ketoprofen, one of non-steroidal anti-inflammatory drugs, is an ideal model drug for ODSRTs.", "output": {"entities": {"chemical": [{"text": "Ketoprofen", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Methods: We designed a simple two-step process to develop novel ketoprofen orally disintegrating/sustained release tablets (KODSRTs).", "output": {"entities": {"chemical": [{"text": "ketoprofen", "start": 64, "end": 74}]}}, "schema": []}
{"input": "Firstly, sustained release ketoprofen fine granules were developed by spray drying the aqueous dispersions composed of Eudragit RS-30D, Starch 1500 and PEG 6000.", "output": {"entities": {"chemical": [{"text": "ketoprofen", "start": 27, "end": 37}, {"text": "Eudragit RS-30D", "start": 119, "end": 134}, {"text": "PEG 6000", "start": 152, "end": 160}]}}, "schema": []}
{"input": "The optimal parameters of spray drying were 100 degrees C for inlet air temperature and 1. 5 mL/min for feed rate.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, the obtained granules were directly compressed into KODSRTs after mixing with lactose, mannitol and a superdisintegrant, crosslinked polyvinylpyrrolidone (PVPP).", "output": {"entities": {"chemical": [{"text": "lactose", "start": 92, "end": 99}, {"text": "mannitol", "start": 101, "end": 109}, {"text": "polyvinylpyrrolidone", "start": 147, "end": 167}, {"text": "PVPP", "start": 169, "end": 173}]}}, "schema": []}
{"input": "The characteristics of KODSRTs, especially their potential for extended drug release, were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Results: Results of an in vitro release test demonstrated that KODSRTs could slowly release ketoprofen for 24 h after disintegrating within 30 s.", "output": {"entities": {"chemical": [{"text": "ketoprofen", "start": 92, "end": 102}]}}, "schema": []}
{"input": "Extended release properties of KODSRTs were decided by the ketoprofen sustained release fine granules in tablets.", "output": {"entities": {"chemical": [{"text": "ketoprofen", "start": 59, "end": 69}]}}, "schema": []}
{"input": "Besides, the disintegration time of KODSRTs depended on the percentage of PVPP in tablets.", "output": {"entities": {"chemical": [{"text": "PVPP", "start": 74, "end": 78}]}}, "schema": []}
{"input": "In vivo pharmacokinetic studies in beagles also showed that KODSRTs possessed a significantly extended release profile compared with ketoprofen normal capsules.", "output": {"entities": {"chemical": [{"text": "ketoprofen", "start": 133, "end": 143}]}}, "schema": []}
{"input": "Conclusion: KODSRTs were successfully prepared using a simple two-step process: spray drying and direct compression.", "output": {"entities": {}}, "schema": []}
{"input": "The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 29, "end": 37}]}}, "schema": []}
{"input": "However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested.", "output": {"entities": {}}, "schema": []}
{"input": "In this report we identified Axl as a new therapeutic target for prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Axl is consistently overexpressed in prostate cancer cell lines and human prostate tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, the blockage of Axl gene expression strongly inhibits proliferation, migration, invasion and tumor growth.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, inhibition of Axl expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the nuclear factor-kappa B pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, blockage of Axl expression leads to inhibition of Akt, IKK alpha and I kappa B alpha phosphorylation, increasing I kappa B alpha expression and stability.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, induction of Akt phosphorylation by insulin-like growth factor 1 in Axl knockdown cells restores Akt activity and proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our results establish an unambiguous role for Axl in prostate cancer tumorigenesis with implications for prostate cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Oncogenic K-ras expression is associated with derangement of the cAMP/PKA pathway and forskolin-reversible alterations of mitochondrial dynamics and respiration.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 65, "end": 69}, {"text": "forskolin", "start": 86, "end": 95}]}}, "schema": []}
{"input": "The Warburg effect in cancer cells has been proposed to involve several mechanisms, including adaptation to hypoxia, oncogenes activation or loss of oncosuppressors and impaired mitochondrial function.", "output": {"entities": {}}, "schema": []}
{"input": "In previous papers, it has been shown that K-ras transformed mouse cells are much more sensitive as compared with normal cells to glucose withdrawal (undergoing apoptosis) and present a high glycolytic rate and a strong reduction of mitochondrial complex I.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 130, "end": 137}]}}, "schema": []}
{"input": "Recent observations suggest that transformed cells have a derangement in the cyclic adenosine monophosphate/cAMP-dependent protein kinase (cAMP/PKA) pathway, which is known to regulate several mitochondrial functions.", "output": {"entities": {"chemical": [{"text": "cyclic adenosine monophosphate", "start": 77, "end": 107}, {"text": "cAMP", "start": 108, "end": 112}, {"text": "cAMP", "start": 139, "end": 143}]}}, "schema": []}
{"input": "Herein, the derangement of the cAMP/PKA pathway and its impact on transformation-linked changes of mitochondrial functions is investigated.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 31, "end": 35}]}}, "schema": []}
{"input": "Exogenous stimulation of PKA activity, achieved by forskolin treatment, protected K-ras-transformed cells from apoptosis induced by glucose deprivation, enhanced complex I activity, intracellular adenosine triphosphate (ATP) levels, mitochondrial fusion and decreased intracellular reactive oxygen species (ROS) levels.", "output": {"entities": {"chemical": [{"text": "forskolin", "start": 51, "end": 60}, {"text": "glucose", "start": 132, "end": 139}, {"text": "adenosine triphosphate", "start": 196, "end": 218}, {"text": "ATP", "start": 220, "end": 223}, {"text": "oxygen", "start": 291, "end": 297}]}}, "schema": []}
{"input": "Several of these effects were almost completely prevented by inhibiting the PKA activity.", "output": {"entities": {}}, "schema": []}
{"input": "Short-time treatment with compounds favoring mitochondrial fusion strongly decreased the cellular ROS levels especially in transformed cells.", "output": {"entities": {}}, "schema": []}
{"input": "These findings support the notion that glucose shortage-induced apoptosis, specific of K-ras-transformed cells, is associated to a derangement of PKA signaling that leads to mitochondrial complex I decrease, reduction of ATP formation, prevalence of mitochondrial fission over fusion, and thereby opening new approaches for development of anticancer drugs.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 39, "end": 46}, {"text": "ATP", "start": 221, "end": 224}]}}, "schema": []}
{"input": "A new chromone from the leaves of Melaleuca cajuputi Powell.", "output": {"entities": {"chemical": [{"text": "chromone", "start": 6, "end": 14}]}}, "schema": []}
{"input": "A new chromone, 5, 7-dihydroxy-2-(hydroxymethyl)-6, 8-dimethyl-chromen-4-one, named melachromone, together with 12 known compounds, including chromones, anthraquinone, flavonoids, flavonoid glycosides, benzene derivatives, ellagic acids and terpenes, were isolated from the leaves of Melaleuca cajuputi Powell.", "output": {"entities": {"chemical": [{"text": "chromone", "start": 6, "end": 14}, {"text": "5, 7-dihydroxy-2-(hydroxymethyl)-6, 8-dimethyl-chromen-4-one", "start": 16, "end": 76}, {"text": "melachromone", "start": 84, "end": 96}, {"text": "chromones", "start": 142, "end": 151}, {"text": "anthraquinone", "start": 153, "end": 166}, {"text": "flavonoids", "start": 168, "end": 178}, {"text": "flavonoid glycosides", "start": 180, "end": 200}, {"text": "benzene", "start": 202, "end": 209}, {"text": "ellagic acids", "start": 223, "end": 236}, {"text": "terpenes", "start": 241, "end": 249}]}}, "schema": []}
{"input": "Their structures were characterised by spectroscopic methods.", "output": {"entities": {}}, "schema": []}
{"input": "Functional selectivity induced by mGlu 4 receptor positive allosteric modulation and concomitant activation of Gq coupled receptors.", "output": {"entities": {}}, "schema": []}
{"input": "Metabotropic glutamate receptors (mGlus) are a group of Family C Seven Transmembrane Spanning Receptors (7TMRs) that play important roles in modulating signaling transduction, particularly within the central nervous system.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 13, "end": 22}]}}, "schema": []}
{"input": "mGlu (4) belongs to a subfamily of mGlus that is predominantly coupled to G (i/o) G proteins.", "output": {"entities": {}}, "schema": []}
{"input": "We now report that the ubiquitous autacoid and neuromodulator, histamine, induces substantial glutamate-activated calcium mobilization in mGlu (4)-expressing cells, an effect which is observed in the absence of co-expressed chimeric G proteins.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 63, "end": 72}, {"text": "glutamate", "start": 94, "end": 103}, {"text": "calcium", "start": 114, "end": 121}]}}, "schema": []}
{"input": "This strong induction of calcium signaling downstream of glutamate activation of mGlu (4) depends upon the presence of H (1) histamine receptors.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 25, "end": 32}, {"text": "glutamate", "start": 57, "end": 66}, {"text": "histamine", "start": 125, "end": 134}]}}, "schema": []}
{"input": "Interestingly, the potentiating effect of histamine activation does not extend to other mGlu (4)-mediated signaling events downstream of G (i/o) G proteins, such as cAMP inhibition, suggesting that the presence of G (q) coupled receptors such as H (1) may bias normal mGlu (4)-mediated G (i/o) signaling events.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 42, "end": 51}, {"text": "cAMP", "start": 165, "end": 169}]}}, "schema": []}
{"input": "When the activity induced by small molecule positive allosteric modulators of mGlu (4) is assessed, the potentiated signaling of mGlu (4) is further biased by histamine toward calcium-dependent pathways.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 159, "end": 168}, {"text": "calcium", "start": 176, "end": 183}]}}, "schema": []}
{"input": "These results suggest that G (i/o)-coupled mGlus may induce substantial, and potentially unexpected, calcium-mediated signaling events if stimulation occurs concomitantly with activation of G (q) receptors.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 101, "end": 108}]}}, "schema": []}
{"input": "Additionally, our results suggest that signaling induced by small molecule positive allosteric modulators may be substantially biased when G (q) receptors are co-activated.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Two new triterpenoid saponins from the husks of Xanthoceras sorbifolia.", "output": {"entities": {"chemical": [{"text": "triterpenoid saponins", "start": 8, "end": 29}]}}, "schema": []}
{"input": "Two new oleanane triterpenoid saponins, xanthohuskisides A (1) and B (2), were isolated from the husks of Xanthoceras sorbifolia.", "output": {"entities": {"chemical": [{"text": "oleanane triterpenoid saponins", "start": 8, "end": 38}, {"text": "xanthohuskisides", "start": 40, "end": 56}]}}, "schema": []}
{"input": "The structures of these two compounds were established as 3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-glucopyranosyl 16-deoxybarringtogenol C (1) and 3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl 16-deoxybarringtogenol C (2), respectively, based on the analysis on their spectral data including NMR and HR-ESI-MS.", "output": {"entities": {"chemical": [{"text": "3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-glucopyranosyl 16-deoxybarringtogenol C", "start": 58, "end": 270}, {"text": "3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl 16-deoxybarringtogenol C", "start": 279, "end": 455}]}}, "schema": []}
{"input": "The growth inhibitory activities of compounds 1 and 2 were assayed, and 2 showed moderate activity against U937 cell line with the IG (50) value of 82. 85 +/- 1. 58 micro M.", "output": {"entities": {}}, "schema": []}
{"input": "Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor.", "output": {"entities": {}}, "schema": []}
{"input": "The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers.", "output": {"entities": {}}, "schema": []}
{"input": "Cetuximab is an anti-EGFR antibody that has been approved for use in oncology.", "output": {"entities": {}}, "schema": []}
{"input": "Previously we investigated mechanisms of resistance to cetuximab using a model derived from the non-small cell lung cancer line NCI-H226.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrated that cetuximab-resistant clones (Ctx (R)) had increased nuclear localization of the EGFR.", "output": {"entities": {}}, "schema": []}
{"input": "This process was mediated by Src family kinases (SFKs), and nuclear EGFR had a role in resistance to cetuximab.", "output": {"entities": {}}, "schema": []}
{"input": "To better understand SFK-mediated nuclear translocation of EGFR, we investigated which SFK member (s) controlled this process as well as the EGFR tyrosine residues that are involved.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 146, "end": 154}]}}, "schema": []}
{"input": "Analyses of mRNA and protein expression indicated upregulation of the SFK members Yes (v-Yes-1 yamaguchi sarcoma viral oncogene) and Lyn (v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog) in all Ctx (R) clones.", "output": {"entities": {}}, "schema": []}
{"input": "Further, immunoprecipitation analysis revealed that EGFR interacts with Yes and Lyn in Ctx (R) clones, but not in cetuximab-sensitive (Ctx (S)) parental cells.", "output": {"entities": {}}, "schema": []}
{"input": "Using RNAi interference, we found that knockdown of either Yes or Lyn led to loss of EGFR translocation to the nucleus.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, overexpression of Yes or Lyn in low nuclear EGFR-expressing Ctx (S) parental cells led to increased nuclear EGFR.", "output": {"entities": {}}, "schema": []}
{"input": "Chromatin immunoprecipitation (ChIP) assays confirmed nuclear EGFR complexes associated with the promoter of the known EGFR target genes B-Myb and iNOS.", "output": {"entities": {}}, "schema": []}
{"input": "Further, all Ctx (R) clones exhibited upregulation of B-Myb and iNOS at the mRNA and protein levels.", "output": {"entities": {}}, "schema": []}
{"input": "siRNAs directed at Yes or Lyn led to decreased binding of EGFR complexes to the B-Myb and iNOS promoters based on ChIP analyses.", "output": {"entities": {}}, "schema": []}
{"input": "SFKs have been shown to phosphorylate EGFR on tyrosines 845 and 1101 (Y845 and Y1101), and mutation of Y1101, but not Y845, impaired nuclear entry of the EGFR.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR nuclear translocation in this model of cetuximab resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "sinensetin", "start": 11, "end": 21}]}}, "schema": []}
{"input": "Sinensetin is a rare polymethoxylated flavone found in certain citrus fruits.", "output": {"entities": {"chemical": [{"text": "Sinensetin", "start": 0, "end": 10}, {"text": "polymethoxylated flavone", "start": 21, "end": 45}]}}, "schema": []}
{"input": "In this study, we investigated the effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "sinensetin", "start": 46, "end": 56}]}}, "schema": []}
{"input": "Sinensetin decreased the expression of sterol regulatory element-binding protein 1c (SREBP1c), suggesting its antiadipogeneic property via downreguation of SREBP1c.", "output": {"entities": {"chemical": [{"text": "Sinensetin", "start": 0, "end": 10}, {"text": "sterol", "start": 39, "end": 45}]}}, "schema": []}
{"input": "Also, sinensetin increased the phosphorylation of protein kinase A and hormone-sensitive lipase, indicating its lipolytic property via a cAMP-mediated signaling pathway.", "output": {"entities": {"chemical": [{"text": "sinensetin", "start": 6, "end": 16}, {"text": "cAMP", "start": 137, "end": 141}]}}, "schema": []}
{"input": "Moreover, sinensetin inhibited insulin-stimulated glucose uptake by decreasing the phosphorylation of insulin receptor substrate and Akt.", "output": {"entities": {"chemical": [{"text": "sinensetin", "start": 10, "end": 20}, {"text": "glucose", "start": 50, "end": 57}]}}, "schema": []}
{"input": "Furthermore, sinensetin increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase.", "output": {"entities": {"chemical": [{"text": "sinensetin", "start": 13, "end": 23}, {"text": "AMP", "start": 57, "end": 60}, {"text": "acetyl-CoA", "start": 97, "end": 107}]}}, "schema": []}
{"input": "It also upregulated mRNA expression of carnitine palmitoyltransferase-1a, suggesting that sinensetin enhances fatty acid beta-oxidation through the AMPK pathway.", "output": {"entities": {"chemical": [{"text": "carnitine", "start": 39, "end": 48}, {"text": "sinensetin", "start": 90, "end": 100}]}}, "schema": []}
{"input": "Taken together, these results suggest that sinensetin may have potential as a natural agent for prevention/improvement of obesity.", "output": {"entities": {"chemical": [{"text": "sinensetin", "start": 43, "end": 53}]}}, "schema": []}
{"input": "The marine alga Gelidium amansii promotes the development and complexity of neuronal cytoarchitecture.", "output": {"entities": {}}, "schema": []}
{"input": "Neurotrophic factors are vital not only to support neuronal development but also to protect mature neurons from atrophy in neurodegenerative diseases.", "output": {"entities": {}}, "schema": []}
{"input": "As an effort to explore natural sources that possess neurotrophic activity, we screened common marine algae for their neuritogenic activity in the developing rat hippocampal neurons in culture.", "output": {"entities": {}}, "schema": []}
{"input": "Of the 22 seaweed species examined, ethanol extracts of Gelidium amansii (GAE) exhibited potent neuritogenic activity, followed by Undaria pinnatifida and Sargassum fulvellum extracts.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 36, "end": 43}]}}, "schema": []}
{"input": "The effects of GAE were dose dependent with an optimum concentration of 15 micro g/mL.", "output": {"entities": {}}, "schema": []}
{"input": "The GAE significantly promoted the initial neuronal differentiation from the stage I into the stage II and increased the indices of axonal and dendritic development such as the length, the numbers of primary processes, and branching frequencies by a minimum of twofold compared with the vehicle control.", "output": {"entities": {}}, "schema": []}
{"input": "These results show that marine algae are promising candidates for neurotrophic potentials.", "output": {"entities": {}}, "schema": []}
{"input": "New immunosuppressive cyclomyrsinol diterpenes from Euphorbia kopetdaghi Prokh.", "output": {"entities": {"chemical": [{"text": "cyclomyrsinol diterpenes", "start": 22, "end": 46}]}}, "schema": []}
{"input": "Aceton: chloroform (1: 2) extracts of the aerial parts of Euphorbia kopetdaghi Prokh.", "output": {"entities": {"chemical": [{"text": "Aceton", "start": 0, "end": 6}, {"text": "chloroform", "start": 8, "end": 18}]}}, "schema": []}
{"input": "(Euphorbiaceae) were investigated for its diterpenoids and afforded three new five-membered ring, pentacyclic myrisinane polyester comprised of 3, 5, 10-O-triacetyl-8-O-isobutanoyl-14-O-benzoylcyclomyrsinol (1), 3, 5, 10, 14-O-tetraacetyl-8-O-(2'-methyl butanoyl)-cyclomyrsinol (2) and 3, 5, 10, 14-O-tetracetyl-8-O-isobutanoylcyclomyrsinol (3).", "output": {"entities": {"chemical": [{"text": "diterpenoids", "start": 42, "end": 54}, {"text": "pentacyclic myrisinane polyester", "start": 98, "end": 130}, {"text": "3, 5, 10-O-triacetyl-8-O-isobutanoyl-14-O-benzoylcyclomyrsinol", "start": 144, "end": 206}, {"text": "3, 5, 10, 14-O-tetraacetyl-8-O-(2'-methyl butanoyl)-cyclomyrsinol", "start": 212, "end": 277}, {"text": "3, 5, 10, 14-O-tetracetyl-8-O-isobutanoylcyclomyrsinol", "start": 286, "end": 340}]}}, "schema": []}
{"input": "The structures were elucidated based on (13) C-and (1) H-NMR as well as 2D-NMR, IR and different MS spectra and the immunomodulation activity for compound 1 was evaluated through lymphocyte proliferation assay, IL-2 assay, oxidative burst of phagocytic leukocytes and through their cytotoxicity on two cell lines.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 40, "end": 46}, {"text": "(1) H", "start": 51, "end": 56}]}}, "schema": []}
{"input": "Compound 1 showed significant suppressive activity against phytohemagglutinin-activated T-cell proliferation with an IC (50) of 1. 83 micro g mL (-1), IL-2 suppressive activity with an IC (50) of 19. 0 micro g mL (-1) and oxidative burst suppressive activity with an IC (50) of 1. 6 micro g mL (-1) and ignorable cytotoxic effect on the CC-1 rat hepatocyte and 3T3-L1 mouse fibroblast cell-lines.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular crosstalk between a chemical and a biological stressor and consequences on disease manifestation in rainbow trout.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to examine the molecular and organism reaction of rainbow trout, Oncorhynchus mykiss, to the combined impact of two environmental stressors.", "output": {"entities": {}}, "schema": []}
{"input": "The two stressors were the myxozoan parasite, Tetracapsuloides bryosalmonae, which is the etiological agent of proliferative kidney disease (PKD) and a natural stressor to salmonid populations, and 17 beta-estradiol (E2) as prototype of estrogen-active chemical stressors in the aquatic environment.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 198, "end": 215}, {"text": "estrogen", "start": 237, "end": 245}]}}, "schema": []}
{"input": "Both stressors, the parasite and estrogenic contaminants, co-exist in Swiss rivers and are discussed as factors contributing to the decline of Swiss brown trout populations over the last decades.", "output": {"entities": {}}, "schema": []}
{"input": "Using a microarray approach contrasting parasite-infected and non-infected rainbow trout at low or high estrogen levels, it was observed that molecular response patterns under joint exposure differed from those to the single stressors.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 104, "end": 112}]}}, "schema": []}
{"input": "More specifically, three major response patterns were present: (i) expression responses of gene transcripts to one stressor are weakened by the presence of the second stressor; (ii) expression responses of gene transcripts to one stressor are enhanced by the presence of the second stressor; (iii) expression responses of gene transcripts at joint treatment are dominated by one of the two stressors.", "output": {"entities": {}}, "schema": []}
{"input": "Organism-level responses to concurrent E2 and parasite treatment-assessed through measuring parasite loads in the fish host and cumulative mortalities of trout-were dominated by the pathogen, with no modulating influence of E2.", "output": {"entities": {}}, "schema": []}
{"input": "The findings reveal function-and level-specific responses of rainbow trout to stressor combinations, which are only partly predictable from the response to the single stressors.", "output": {"entities": {}}, "schema": []}
{"input": "Intraspecific chemical variability of essential oil from leaves of Cupressus atlantica Gaussen, an endemic and endangered coniferous species in Morocco.", "output": {"entities": {}}, "schema": []}
{"input": "The composition of essential oils isolated from leaves of 11 natural populations of Cupressus atlantica, an endemic and endangered coniferous species from Morocco, was investigated by GC-MS.", "output": {"entities": {}}, "schema": []}
{"input": "In total, 42 essential oil components were identified, accounting for 73. 1-97. 7% of the total oil.", "output": {"entities": {}}, "schema": []}
{"input": "Monoterpene (25. 2-84. 9%) and sesquiterpene hydrocarbons (12. 2-46. 8%) were the principal subclasses of compounds, with alpha-pinene (15-65. 4%), germacrene D (5. 9-30. 5%), delta-3-carene (2-16. 6%) and gamma-cadinene (1. 3-9. 8%) as the main constituents.", "output": {"entities": {"chemical": [{"text": "Monoterpene", "start": 0, "end": 11}, {"text": "sesquiterpene hydrocarbons", "start": 31, "end": 57}, {"text": "alpha-pinene", "start": 122, "end": 134}, {"text": "germacrene D", "start": 148, "end": 160}, {"text": "delta-3-carene", "start": 176, "end": 190}, {"text": "gamma-cadinene", "start": 206, "end": 220}]}}, "schema": []}
{"input": "The results of the oil composition were analysed by hierarchical cluster and principal component analysis that established three main groups of essential oils.", "output": {"entities": {}}, "schema": []}
{"input": "These oils were differentiated by the content of the major constituents (alpha-pinene, germacrene D, delta-3-carene and gamma-cadinene), geographical location and climatic characteristics.", "output": {"entities": {"chemical": [{"text": "alpha-pinene", "start": 73, "end": 85}, {"text": "germacrene D", "start": 87, "end": 99}, {"text": "delta-3-carene", "start": 101, "end": 115}, {"text": "gamma-cadinene", "start": 120, "end": 134}]}}, "schema": []}
{"input": "The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity.", "output": {"entities": {}}, "schema": []}
{"input": "Protein phosphatase type 2A (PP2A) enzymes constitute a large family of Ser/Thr phosphatases with multiple functions in cellular signaling and physiology.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 72, "end": 75}, {"text": "Thr", "start": 76, "end": 79}]}}, "schema": []}
{"input": "The composition of heterotrimeric PP2A holoenzymes, resulting from the combinatorial assembly of a catalytic C subunit, a structural A subunit, and regulatory B-type subunit, provides the essential determinants for substrate specificity, subcellular targeting, and fine-tuning of phosphatase activity, largely explaining why PP2A is functionally involved in so many diverse physiological processes, sometimes in seemingly opposing ways.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we highlight how PP2A holoenzyme biogenesis and enzymatic activity are controlled by a sophisticatedly coordinated network of five PP2A modulators, consisting of alpha 4, phosphatase 2A phosphatase activator (PTPA), leucine carboxyl methyl transferase 1 (LCMT1), PP2A methyl esterase 1 (PME-1) and, potentially, target of rapamycin signaling pathway regulator-like 1 (TIPRL1), which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled.", "output": {"entities": {"chemical": [{"text": "leucine carboxyl methyl", "start": 232, "end": 255}, {"text": "methyl", "start": 284, "end": 290}, {"text": "rapamycin", "start": 338, "end": 347}]}}, "schema": []}
{"input": "Likewise, these modulators may come into play when PP2A holoenzymes are disassembled following particular cellular stresses.", "output": {"entities": {}}, "schema": []}
{"input": "Malfunctioning of these cellular control mechanisms contributes to human disease.", "output": {"entities": {}}, "schema": []}
{"input": "The potential therapeutic benefits or pitfalls of interfering with these regulatory mechanisms will be briefly discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of the total alkaloidal extract of Murraya koenigii leaf on oxidative stress and cholinergic transmission in aged mice.", "output": {"entities": {}}, "schema": []}
{"input": "Alzheimer' s disease (AD) is characterized by signs of major oxidative stress and the loss of cholinergic cells.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was designed to investigate the role of the total alkaloidal extract from Murraya koenigii (MKA) leaves on age related oxidative stress and the cholinergic pathway in aged mice.", "output": {"entities": {}}, "schema": []}
{"input": "Ascorbic acid (100 mg/kg, p. o.) was used as a standard drug.", "output": {"entities": {"chemical": [{"text": "Ascorbic acid", "start": 0, "end": 13}]}}, "schema": []}
{"input": "The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p. o.).", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 62, "end": 73}, {"text": "reduced glutathione", "start": 92, "end": 111}, {"text": "GSH", "start": 113, "end": 116}, {"text": "glutathione", "start": 119, "end": 130}, {"text": "superoxide", "start": 148, "end": 158}]}}, "schema": []}
{"input": "Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p. o.).", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 81, "end": 93}]}}, "schema": []}
{"input": "Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 103, "end": 116}, {"text": "ACh", "start": 118, "end": 121}]}}, "schema": []}
{"input": "In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 90, "end": 97}, {"text": "aspartate", "start": 118, "end": 127}, {"text": "creatinine", "start": 189, "end": 199}, {"text": "cholesterol", "start": 207, "end": 218}, {"text": "urea nitrogen", "start": 220, "end": 233}, {"text": "glucose", "start": 238, "end": 245}]}}, "schema": []}
{"input": "The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "To understand the molecular mechanisms underlying the influence of quercetin on the physiological effects of hyperlipidemia, we investigated its role in the prevention of high-fat diet (HFD)-induced obesity and found that it regulated hepatic gene expression related to lipid metabolism.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 67, "end": 76}]}}, "schema": []}
{"input": "Quercetin supplementation in mice significantly reduced the HFD-induced gains in body weight, liver weight, and white adipose tissue weight compared with the mice fed only with HFD.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "It also significantly reduced HFD-induced increases in serum lipids, including cholesterol, triglyceride, and thiobarbituric acid-reactive substance (TBARS).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 79, "end": 90}, {"text": "triglyceride", "start": 92, "end": 104}, {"text": "thiobarbituric acid", "start": 110, "end": 129}]}}, "schema": []}
{"input": "Consistent with the reduced liver weight and white adipose tissue weight, hepatic lipid accumulation and the size of lipid droplets in the epididymal fat pads were also reduced by quercetin supplementation.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 180, "end": 189}]}}, "schema": []}
{"input": "To further investigate how quercetin may reduce obesity, we analyzed lipid metabolism-related genes in the liver.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Quercetin supplementation altered expression profiles of several lipid metabolism-related genes, including Fnta, Pon1, Pparg, Aldh1b1, Apoa4, Abcg5, Gpam, Acaca, Cd36, Fdft1, and Fasn, relative to those in HFD control mice.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The expression patterns of these genes observed by quantitative reverse transcriptase-polymerase chain reaction were confirmed by immunoblot assays.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, our results indicate that quercetin prevents HFD-induced obesity in C57B1/6 mice, and its anti-obesity effects may be related to the regulation of lipogenesis at the level of transcription.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 40, "end": 49}]}}, "schema": []}
{"input": "Effects of Bixa orellana L. seeds on hyperlipidemia.", "output": {"entities": {}}, "schema": []}
{"input": "Bixa orellana L., urucum, or urucu, a native tropical tree of Central and South American rain forests is used to treat various diseases in popular medicine.", "output": {"entities": {}}, "schema": []}
{"input": "In Cear a, Northeast of Brazil, the seeds of urucum have been used for the treatment of high lipid blood levels.", "output": {"entities": {}}, "schema": []}
{"input": "The present study investigated the effects of the aqueous extract from Bixa orellana seeds (AEBO) in mice with hyperlipidemia induced by tyloxapol, fructose and ethanol.", "output": {"entities": {"chemical": [{"text": "tyloxapol", "start": 137, "end": 146}, {"text": "fructose", "start": 148, "end": 156}, {"text": "ethanol", "start": 161, "end": 168}]}}, "schema": []}
{"input": "In hyperlipidemia induced by Triton WR1339, 400 and 800 mg/kg AEBO reduced triglycerides (TG) serum levels at 24 h and 48 h.", "output": {"entities": {"chemical": [{"text": "Triton WR1339", "start": 29, "end": 42}, {"text": "triglycerides", "start": 75, "end": 88}]}}, "schema": []}
{"input": "In the study of hypertriglyceridemia induced by fructose, AEBO in doses of 400 mg/kg and 800 mg/kg reduced TG levels by 48. 2% and 48. 7%, respectively.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Finally, the ethanol experimental model with 400 mg/kg AEBO promoted a reduction of 33. 6% of TG levels, while the 800 mg/kg concentration reduced hypertriglyceridemia in 62. 2%.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 13, "end": 20}]}}, "schema": []}
{"input": "In conclusion, the aqueous extract of the seeds of Bixa orellana was capable of reversing the hypertriglyceridemia induced by Triton, fructose and ethanol, demonstrating a hypolipidemic effect.", "output": {"entities": {"chemical": [{"text": "Triton", "start": 126, "end": 132}, {"text": "fructose", "start": 134, "end": 142}, {"text": "ethanol", "start": 147, "end": 154}]}}, "schema": []}
{"input": "However, further studies are necessary to discover the precise mechanism of action.", "output": {"entities": {}}, "schema": []}
{"input": "Sarmentosamide, a novel hexadienamide from Thai soil actinomycetes.", "output": {"entities": {"chemical": [{"text": "Sarmentosamide", "start": 0, "end": 14}, {"text": "hexadienamide", "start": 24, "end": 37}]}}, "schema": []}
{"input": "A new hexadienamide derivative named sarmentosamide (1) was identified from the culture of Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "sarmentosamide", "start": 37, "end": 51}]}}, "schema": []}
{"input": "SBI108 isolated from Thai soil under an herb.", "output": {"entities": {}}, "schema": []}
{"input": "The structure was elucidated on the basis of spectroscopic data, and the absolute configuration was determined by chemical degradation.", "output": {"entities": {}}, "schema": []}
{"input": "A comparative study of phytochemical composition of genetically and non-genetically modified soybean (Glycine max L.) and evaluation of antitumor activity.", "output": {"entities": {}}, "schema": []}
{"input": "Colon cancer is one of the major causes of cancer mortality worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "The analysed feeds, containing non-genetically modified (GM) soybean and Roundup Ready soybean, showed a different polyphenolic content and lipophilic composition.", "output": {"entities": {"chemical": [{"text": "polyphenolic", "start": 115, "end": 127}]}}, "schema": []}
{"input": "Non-GM soybean extract possessed twice the polyphenolic content of GM soybean and the highest number of sterols.", "output": {"entities": {"chemical": [{"text": "polyphenolic", "start": 43, "end": 55}, {"text": "sterols", "start": 104, "end": 111}]}}, "schema": []}
{"input": "Among them, gamma-sitosterol was found to be the major constituent.", "output": {"entities": {"chemical": [{"text": "gamma-sitosterol", "start": 12, "end": 28}]}}, "schema": []}
{"input": "Methanolic extract of non-GM soybean extract was more potent than GM soybean extract against colon carcinoma cell line LoVo using MTT assay, while the second one showed a slightly higher anti-inflammatory activity.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 130, "end": 133}]}}, "schema": []}
{"input": "The findings add to epidemiological evidence for the therapeutic effects of soy foods in colorectal carcinoma.", "output": {"entities": {}}, "schema": []}
{"input": "Isolation of a p-hydroxyphenyl anhydride from the leaves of Diphysa carthagenensisw.", "output": {"entities": {"chemical": [{"text": "p-hydroxyphenyl anhydride", "start": 15, "end": 40}]}}, "schema": []}
{"input": "Diphysidione (1), a new p-hydroxyphenyl anhydride, and vitexin (2) were isolated from the leaves of Diphysa carthagenensis.", "output": {"entities": {"chemical": [{"text": "Diphysidione", "start": 0, "end": 12}, {"text": "p-hydroxyphenyl anhydride", "start": 24, "end": 49}, {"text": "vitexin", "start": 55, "end": 62}]}}, "schema": []}
{"input": "The structure of the new metabolite was characterised as 4-(4-hydroxy-phenyl)-3H-pyran-2, 6-dione using 1D and 2D NMR spectroscopy.", "output": {"entities": {"chemical": [{"text": "4-(4-hydroxy-phenyl)-3H-pyran-2, 6-dione", "start": 57, "end": 97}]}}, "schema": []}
{"input": "Electroporation-mediated gene transfer directly to the swine heart.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease.", "output": {"entities": {}}, "schema": []}
{"input": "In the current study, we investigated the use of in vivo electroporation for gene transfer using three different penetrating electrodes and one non-penetrating electrode.", "output": {"entities": {}}, "schema": []}
{"input": "The hearts of adult male swine were exposed through a sternotomy.", "output": {"entities": {}}, "schema": []}
{"input": "Eight electric pulses synchronized to the rising phase of the R wave of the electrocardiogram were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein.", "output": {"entities": {}}, "schema": []}
{"input": "Four sites on the anterior wall of the left ventricle were treated.", "output": {"entities": {}}, "schema": []}
{"input": "Animals were killed 48 h after injection and electroporation and gene expression was determined.", "output": {"entities": {}}, "schema": []}
{"input": "Results were compared with sites in the heart that received plasmid injection but no electric pulses or were not treated.", "output": {"entities": {}}, "schema": []}
{"input": "Gene expression was higher in all electroporated sites when compared with injection only sites demonstrating the robustness of this approach.", "output": {"entities": {}}, "schema": []}
{"input": "Our results provide evidence that in vivo electroporation can be a safe and effective non-viral method for delivering genes to the heart, in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Combination of group I mGlu receptors antagonist with dopaminergic agonists strengthens the synaptic transmission at corticostriatal synapses in culture.", "output": {"entities": {}}, "schema": []}
{"input": "Restoring synaptic plasticity in neurodegenerative diseases could prevent neuronal degeneration, as well as motor and cognitive disorders.", "output": {"entities": {}}, "schema": []}
{"input": "In Parkinson' s disease, synaptic plasticity at corticostriatal synapses is altered.", "output": {"entities": {}}, "schema": []}
{"input": "Dendrites of striatal medium spiny neurons (MSNs) receive dopaminergic inputs from the substantia nigra and glutamatergic cortical afferents.", "output": {"entities": {}}, "schema": []}
{"input": "Because both glutamate and dopamine are required to induce and sustain MSNs plasticity, the particular molecular mechanisms involved at this synaptic triad are difficult to understand.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 13, "end": 22}, {"text": "dopamine", "start": 27, "end": 35}]}}, "schema": []}
{"input": "In the present work, we established a convenient in vitro model of the corticostriatal synapse to study synaptic plasticity.", "output": {"entities": {}}, "schema": []}
{"input": "We focused on long-term depression involving group I metabotropic glutamate (mGlu) receptors.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 66, "end": 75}]}}, "schema": []}
{"input": "We found that in striatal neurons co-cultured with cortical neurons, the absence of dopaminergic stimuli favored the excess of glutamatergic drive from cortical neuron terminals, thus resulting in a constitutive depression of the corticostriatal glutamatergic transmission.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, concomitant blockade of group I mGlu receptors and activation of dopaminergic receptors stably reduced the depression of the synaptic transmission.", "output": {"entities": {}}, "schema": []}
{"input": "Thus the dependence on glutamate and dopamine balance of the corticostriatal synapse responsiveness validates the accuracy of this manageable in vitro model to depict the molecular pathways involved in the plasticity at corticostriatal synapses and to test restorative therapeutic approaches in Parkinson' s disease.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 23, "end": 32}, {"text": "dopamine", "start": 37, "end": 45}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Heavy metals content by ICP-OES in Sarda sarda, Sardinella aurita and Lepidopus caudatus from the Strait of Messina (Sicily, Italy).", "output": {"entities": {}}, "schema": []}
{"input": "In this study copper, nickel, lead, cadmium, arsenic, chromium and vanadium content was measured in the muscles and gills of 24 fishes (Sarda sarda, Sardinella aurita and Lepidopus caudatus) caught in the Strait of Messina, by inductively coupled plasma-optical emission spectroscopy with microwave digestion techniques.", "output": {"entities": {"chemical": [{"text": "copper", "start": 14, "end": 20}, {"text": "nickel", "start": 22, "end": 28}, {"text": "cadmium", "start": 36, "end": 43}, {"text": "arsenic", "start": 45, "end": 52}, {"text": "chromium", "start": 54, "end": 62}, {"text": "vanadium", "start": 67, "end": 75}]}}, "schema": []}
{"input": "In general, it was found that arsenic was higher than other analytes in all fish species, particularly its content was much higher in S. aurita than in the other two exemplary species.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 30, "end": 37}]}}, "schema": []}
{"input": "Lead and cadmium were always detected with values below the legal limits (CE no. 1881/2006 and subsequent modification CE no. 629/2008).", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 9, "end": 16}]}}, "schema": []}
{"input": "A new abietane diterpenoid from Salvia xanthocheila Boiss.", "output": {"entities": {"chemical": [{"text": "abietane diterpenoid", "start": 6, "end": 26}]}}, "schema": []}
{"input": "From the chloroform extract of aerial part of Salvia xanthocheila Boiss. one new abietane diterpenoid, xantoquinone (5 alpha, 6 alpha-dimethoxy-7, 11, 14-trioxoabieta-8, 12-diene) and one known oleanene triterpenoid namely 1 beta, 3 beta-dihydroxy-12-oleanene were isolated.", "output": {"entities": {"chemical": [{"text": "chloroform", "start": 9, "end": 19}, {"text": "abietane diterpenoid", "start": 81, "end": 101}, {"text": "xantoquinone", "start": 103, "end": 115}, {"text": "5 alpha, 6 alpha-dimethoxy-7, 11, 14-trioxoabieta-8, 12-diene", "start": 117, "end": 178}, {"text": "oleanene triterpenoid", "start": 194, "end": 215}, {"text": "1 beta, 3 beta-dihydroxy-12-oleanene", "start": 223, "end": 259}]}}, "schema": []}
{"input": "The structure of the new terpenoid was elucidated by comprehensive spectroscopic analysis including electron ionisation-mass spectra, (1) H NMR, (13) C NMR, distortionless enchancement by polarisation transfer, H, H correlation spectroscopy, heteronuclear multiple-quantum coherence and heteronuclear multiple-bond correlation.", "output": {"entities": {"chemical": [{"text": "terpenoid", "start": 25, "end": 34}, {"text": "(1) H", "start": 134, "end": 139}, {"text": "(13) C", "start": 145, "end": 151}, {"text": "H", "start": 211, "end": 212}, {"text": "H", "start": 214, "end": 215}]}}, "schema": []}
{"input": "A new amide and a new monoterpene from the seeds of Clausena lansium.", "output": {"entities": {"chemical": [{"text": "amide", "start": 6, "end": 11}, {"text": "monoterpene", "start": 22, "end": 33}]}}, "schema": []}
{"input": "A new amide (2) and a new monoterpene (6) were isolated from the seeds of Clausena lansium together with four known ones (1, 3-5).", "output": {"entities": {"chemical": [{"text": "amide", "start": 6, "end": 11}, {"text": "monoterpene", "start": 26, "end": 37}]}}, "schema": []}
{"input": "The structures of the new compounds were elucidated by extensive spectroscopic analyses.", "output": {"entities": {}}, "schema": []}
{"input": "The absolute configurations of 1, 2 and 6 were determined by optical rotation and the modified Mosher' s method.", "output": {"entities": {}}, "schema": []}
{"input": "New triterpenoids from Morus alba L. stem bark.", "output": {"entities": {"chemical": [{"text": "triterpenoids", "start": 4, "end": 17}]}}, "schema": []}
{"input": "Two lupeol-type pentacyclic triterpenoids characterised as lup-20 (29)-en-3 beta-ol-27-oic acid (moruslupenoic acid A) and lup-12, 20 (29)-dien-3 beta-ol-26-oic acid (moruslupenoic acid B) and lanst-5, 24-dien-3 beta-yl acetate (moruslanosteryl acetate) along with the known triterpenoidal phytoconstituents alpha-amyrin acetate, beta-amyrin-beta-D-glucopyranoside and betulinic acid have been isolated from the stem bark of Morus alba L.", "output": {"entities": {"chemical": [{"text": "lupeol", "start": 4, "end": 10}, {"text": "pentacyclic triterpenoids", "start": 16, "end": 41}, {"text": "lup-20 (29)-en-3 beta-ol-27-oic acid", "start": 59, "end": 95}, {"text": "moruslupenoic acid A", "start": 97, "end": 117}, {"text": "lup-12, 20 (29)-dien-3 beta-ol-26-oic acid", "start": 123, "end": 165}, {"text": "moruslupenoic acid B", "start": 167, "end": 187}, {"text": "lanst-5, 24-dien-3 beta-yl acetate", "start": 193, "end": 227}, {"text": "moruslanosteryl acetate", "start": 229, "end": 252}, {"text": "alpha-amyrin acetate", "start": 308, "end": 328}, {"text": "beta-amyrin-beta-D-glucopyranoside", "start": 330, "end": 364}, {"text": "betulinic acid", "start": 369, "end": 383}]}}, "schema": []}
{"input": "(Moraceae).", "output": {"entities": {}}, "schema": []}
{"input": "The structures of the isolated phytoconstituents were established on the basis of spectral data analysis and chemical means.", "output": {"entities": {}}, "schema": []}
{"input": "Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: implications for Parkinson' s disease treatment and dyskinesia.", "output": {"entities": {"chemical": [{"text": "L-DOPA", "start": 16, "end": 22}, {"text": "glutamate", "start": 81, "end": 90}]}}, "schema": []}
{"input": "Group III metabotropic glutamate (mGlu) receptors are localized in presynaptic terminals within basal ganglia (BG) circuitry that become hyperactive due to dopamine depletion in Parkinson' s disease (PD).", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 23, "end": 32}, {"text": "dopamine", "start": 156, "end": 164}]}}, "schema": []}
{"input": "For this reason, group III mGlu receptors, in particular mGlu4, have been considered as key strategic targets for non-dopaminergic pharmacological treatments aimed at modulating these synapses, without producing the well known side-effects of l-DOPA, in particular the highly disabling l-DOPA-induced dyskinesia (LID).", "output": {"entities": {"chemical": [{"text": "l-DOPA", "start": 243, "end": 249}, {"text": "l-DOPA", "start": 286, "end": 292}]}}, "schema": []}
{"input": "Herein we add physiological and functional support to this hypothesis using Lu AF21934, a novel selective and brain-penetrant mGlu4 receptor positive allosteric modulator (PAM) tool compound.", "output": {"entities": {"chemical": [{"text": "Lu AF21934", "start": 76, "end": 86}]}}, "schema": []}
{"input": "By in vitro electrophysiological recordings we demonstrate that Lu AF21934 inhibits corticostriatal synaptic transmission and enhances the effect of the orthosteric mGlu4 receptor-preferred agonist LSP1-2111.", "output": {"entities": {"chemical": [{"text": "Lu AF21934", "start": 64, "end": 74}, {"text": "LSP1-2111", "start": 198, "end": 207}]}}, "schema": []}
{"input": "In na i ve rats, Lu AF21934 dose-dependently (10 and 30 mg/kg) alleviated haloperidol-induced catalepsy.", "output": {"entities": {"chemical": [{"text": "Lu AF21934", "start": 17, "end": 27}, {"text": "haloperidol", "start": 74, "end": 85}]}}, "schema": []}
{"input": "In hemiparkinsonian rats (unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta), Lu AF21934 alone did not affect akinesia at the doses tested (10 and 30 mg/kg).", "output": {"entities": {"chemical": [{"text": "6-hydroxydopamine", "start": 37, "end": 54}, {"text": "Lu AF21934", "start": 102, "end": 112}]}}, "schema": []}
{"input": "However, when Lu AF21934 was combined with sub-threshold doses of l-DOPA (1 and 5 mg/kg), it acted synergistically in alleviating akinesia in a dose-dependent manner and, notably, also reduced the incidence of LID but not its severity.", "output": {"entities": {"chemical": [{"text": "Lu AF21934", "start": 14, "end": 24}, {"text": "l-DOPA", "start": 66, "end": 72}]}}, "schema": []}
{"input": "Interestingly, these effects occurred at Lu AF21934 brain free concentrations that showed functional activity in in vitro screens (calcium flux and electrophysiology assays).", "output": {"entities": {"chemical": [{"text": "Lu AF21934", "start": 41, "end": 51}, {"text": "calcium", "start": 131, "end": 138}]}}, "schema": []}
{"input": "These results support the potential for antiparkinsonian clinical use of a combined treatment consisting in l-DOPA and a mGlu4 receptor PAM to reduce efficacious l-DOPA doses (generally known as l-DOPA sparing), while maintaining the same benefit on PD motor troubles, and at the same time minimizing the development of LID.", "output": {"entities": {"chemical": [{"text": "l-DOPA", "start": 108, "end": 114}, {"text": "l-DOPA", "start": 162, "end": 168}, {"text": "l-DOPA", "start": 195, "end": 201}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "New triterpenoids from the stem bark of Hypodaphnis zenkeri.", "output": {"entities": {"chemical": [{"text": "triterpenoids", "start": 4, "end": 17}]}}, "schema": []}
{"input": "A new pentacyclic triterpenoid and three new derivatives based on the taraxer-14-ene skeleton with a C-28 attached a carboxylic acid group have been isolated from the stem bark of Hypodaphnis zenkeri, together with six known compounds.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenoid", "start": 6, "end": 30}, {"text": "taraxer-14-ene", "start": 70, "end": 84}, {"text": "carboxylic acid", "start": 117, "end": 132}]}}, "schema": []}
{"input": "The new product was identified as 2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid (1).", "output": {"entities": {"chemical": [{"text": "2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid", "start": 34, "end": 85}]}}, "schema": []}
{"input": "Its derivatives, 2 alpha, 3 alpha-diacetyltaraxer-14-en-28-oic acid (2), 2 alpha, 3 alpha-di-O-carbonyl-2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid (3) and 2 alpha, 3 alpha-dipropionyltaraxer-14-en-28-oic acid (4) were obtained by semisynthesis.", "output": {"entities": {"chemical": [{"text": "2 alpha, 3 alpha-diacetyltaraxer-14-en-28-oic acid", "start": 17, "end": 67}, {"text": "2 alpha, 3 alpha-di-O-carbonyl-2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid", "start": 73, "end": 155}, {"text": "2 alpha, 3 alpha-dipropionyltaraxer-14-en-28-oic acid", "start": 164, "end": 217}]}}, "schema": []}
{"input": "The known compounds were identified as 3 beta-hydroxytaraxer-14-en-28-oic acid or aleuritolic acid (5) (McPhail, A. T., McPhail, D. R., Wani, M. C., Wall, M. E. & A. W., Nicholas, A. W. (1989). Identity of maprounic acid with aleuritolic acid. Revision of the structure of maprounic acid: X-ray crystal structure of p-bromobenzyl acetylmaprounate. Journal Natural Products, 52, 212), 3 alpha-hydroxytaraxer-14-en-28-oic acid or isoaleuritolic acid (6), 3 alpha-acetyltaraxer-14-en-28-oic acid acetate or aleuritolic acid acetate (7) (Chaudhuri, S. K., Fullas, F., Brown, D. M., Wani, M. C., Wall, M. E., Cai, L., ... Kinghorn, A. D. (1995). Isolation and structural elucidation of pentacyclic triterpenoids from Maprounea africana. Journal of Natural Products, 58, 1-9), 3-oxo-taraxer-14-ene or taraxerone (8) beta-sitosterol (9) and stigmasterol (10) (Kamboj & Saluja, 2011), together with fatty acids.", "output": {"entities": {"chemical": [{"text": "3 beta-hydroxytaraxer-14-en-28-oic acid", "start": 39, "end": 78}, {"text": "aleuritolic acid", "start": 82, "end": 98}, {"text": "maprounic acid", "start": 206, "end": 220}, {"text": "aleuritolic acid", "start": 226, "end": 242}, {"text": "maprounic acid", "start": 273, "end": 287}, {"text": "p-bromobenzyl acetylmaprounate", "start": 316, "end": 346}, {"text": "3 alpha-hydroxytaraxer-14-en-28-oic acid", "start": 384, "end": 424}, {"text": "isoaleuritolic acid", "start": 428, "end": 447}, {"text": "3 alpha-acetyltaraxer-14-en-28-oic acid acetate", "start": 453, "end": 500}, {"text": "aleuritolic acid acetate", "start": 504, "end": 528}, {"text": "3-oxo-taraxer-14-ene", "start": 771, "end": 791}, {"text": "taraxerone", "start": 795, "end": 805}, {"text": "beta-sitosterol", "start": 810, "end": 825}, {"text": "stigmasterol", "start": 834, "end": 846}]}}, "schema": []}
{"input": "Their structures were established on the basis of spectroscopic studies and chemical transformations.", "output": {"entities": {}}, "schema": []}
{"input": "A new flavonol from Oxytropis ochrocephala Bunge.", "output": {"entities": {"chemical": [{"text": "flavonol", "start": 6, "end": 14}]}}, "schema": []}
{"input": "A new acylated flavonoid, 3-O-rhamnocitrin-6-O-benzoyl-beta-D-glucopyranoside (1), together with five known flavonoids, rhamnocitrin (2), pratensein (3), (3R)-7, 3'-dihydroxy-2', 4'-dimethoxyisoflavan (4), (3R)-7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan (5) and isoliquiritigenin (6), was isolated from Oxytropis ochrocephala Bunge.", "output": {"entities": {"chemical": [{"text": "acylated flavonoid", "start": 6, "end": 24}, {"text": "3-O-rhamnocitrin-6-O-benzoyl-beta-D-glucopyranoside", "start": 26, "end": 77}, {"text": "flavonoids", "start": 108, "end": 118}, {"text": "rhamnocitrin", "start": 120, "end": 132}, {"text": "pratensein", "start": 138, "end": 148}, {"text": "(3R)-7, 3'-dihydroxy-2', 4'-dimethoxyisoflavan", "start": 154, "end": 200}, {"text": "(3R)-7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan", "start": 206, "end": 252}, {"text": "isoliquiritigenin", "start": 261, "end": 278}]}}, "schema": []}
{"input": "The structural elucidation of the isolated compounds was primarily based on HRESIMS, IR and 1-D-and 2-D-NMR analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Continuous infusion of 20-hydroxyecdysone increased mass of triceps brachii in C57BL/6 mice.", "output": {"entities": {"chemical": [{"text": "20-hydroxyecdysone", "start": 23, "end": 41}]}}, "schema": []}
{"input": "Phytoecdysteroids have been attributed with numerous pharmacological properties in animals, including increasing muscle mass, and 20-hydroxyecdysone (20E) is one of the most abundant phytoecdysteroids produced by plants.", "output": {"entities": {"chemical": [{"text": "Phytoecdysteroids", "start": 0, "end": 17}, {"text": "20-hydroxyecdysone", "start": 130, "end": 148}, {"text": "phytoecdysteroids", "start": 183, "end": 200}]}}, "schema": []}
{"input": "In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 days using subcutaneously implanted Alzet (R) osmotic pumps.", "output": {"entities": {}}, "schema": []}
{"input": "The masses of the total body, muscle groups and organs were determined.", "output": {"entities": {}}, "schema": []}
{"input": "There was a significant increase (p = 0. 01) in the mass of triceps brachii in mice treated with 20E for 5 days (115 +/- 8 mg) compared with mice treated with saline for 5 days (88 +/- 3 mg), however, there were no differences in the other measured parameters.", "output": {"entities": {}}, "schema": []}
{"input": "To determine potential mechanisms of 20E in skeletal muscle, Illumina' s Mouse Whole Genome-6 v2. 0 Expression BeadChips were used to evaluate changes in gene expression of the triceps brachii after 20E infusion.", "output": {"entities": {}}, "schema": []}
{"input": "Ingenuity Pathways Analysis was used to identify genes with the most evidence for differential expression, of which, 16 genes involved in the skeletal and muscular system were identified.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, the data suggest that 20E does not have potent anabolic properties, however, a muscle-specific increase was observed and genes were identified to provide an explanation for the muscle accretion.", "output": {"entities": {}}, "schema": []}
{"input": "Antihyperglycemic and antihyperlipidemic activities of ethanolic extract of Zygophyllum album in streptozotocin-induced diabetic mice.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 97, "end": 111}]}}, "schema": []}
{"input": "Zygophyllum album has been mentioned in Tunisian system of folk medicine to be of value in the treatment of diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was designed to investigate the possible antihyperglycemic effects of ethanolic extracts of the whole plant of Z. album on blood glucose, plasma insulin, serum lipids and hepatic glycogen and metabolism enzymes of carbohydrate in streptozotocin (STZ)-induced diabetic mice.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 147, "end": 154}, {"text": "carbohydrate", "start": 232, "end": 244}, {"text": "streptozotocin", "start": 248, "end": 262}, {"text": "STZ", "start": 264, "end": 267}]}}, "schema": []}
{"input": "Administration of the ethanolic extract from plant (100 and 300 mg/kg body weight) for 14 days resulted in significant reduction in plasma glucose, cholesterol, triglycerides, low-density lipoprotein, very-low-density liprotein, hepatic glucokinase and glycogen in STZ diabetic mice.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 139, "end": 146}, {"text": "cholesterol", "start": 148, "end": 159}, {"text": "triglycerides", "start": 161, "end": 174}, {"text": "STZ", "start": 265, "end": 268}]}}, "schema": []}
{"input": "In addition to that, significant increase in plasma high-density lipoprotein, hepatic phosphofructokinase and glucose-6 phosphate dehydrogenase was observed in STZ diabetic mice.", "output": {"entities": {"chemical": [{"text": "glucose-6 phosphate", "start": 110, "end": 129}, {"text": "STZ", "start": 160, "end": 163}]}}, "schema": []}
{"input": "After administration of the ethanolic extract, the increased level of plasma insulin is not significant in diabetic mice.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the present results showed that the ethanolic extract of Z. album possesses significant antihyperglycemic and antihyperlipidemic effects in experimental model of diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Continuous production of drug nanoparticle suspensions via wet stirred media milling: a fresh look at the Rehbinder effect.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticles of BCS Class II drugs are produced in wet stirred media mills operating in batch or recirculation mode with the goal of resolving the poor water-solubility issue.", "output": {"entities": {}}, "schema": []}
{"input": "Scant information is available regarding the continuous production of drug nanoparticles via wet media milling.", "output": {"entities": {}}, "schema": []}
{"input": "Griseofulvin and Naproxen were milled in both recirculation mode and multi-pass continuous mode to study the breakage dynamics and to determine the effects of suspension flow rate.", "output": {"entities": {"chemical": [{"text": "Griseofulvin", "start": 0, "end": 12}, {"text": "Naproxen", "start": 17, "end": 25}]}}, "schema": []}
{"input": "The evolution of the median particle size was measured and described by an empirical breakage model.", "output": {"entities": {}}, "schema": []}
{"input": "We found that these two operation modes could produce drug nanosuspensions with similar particle size distributions (PSDs).", "output": {"entities": {}}, "schema": []}
{"input": "A reduced suspension flow rate slowed the breakage rate and led to a wider PSD and more differentiation between the two operation modes.", "output": {"entities": {}}, "schema": []}
{"input": "The latter part of this study focused on the roles of stabilizers (hydroxypropyl cellulose and sodium lauryl sulfate) and elucidation of the so-called Rehbinder effect (reduction in particle strength due to adsorbed stabilizers such as polymers and surfactants).", "output": {"entities": {"chemical": [{"text": "hydroxypropyl", "start": 67, "end": 80}, {"text": "sodium lauryl sulfate", "start": 95, "end": 116}]}}, "schema": []}
{"input": "Milling the drugs in the absence of the stabilizers produced primary nanoparticles and their aggregates, while milling with the stabilizers produced smaller primary nanoparticles with minimal aggregation.", "output": {"entities": {}}, "schema": []}
{"input": "Using laser diffraction, BET nitrogen adsorption, scanning electron microscopy imaging, and a microhydrodynamic analysis of milling, this study, for the first time, provides sufficient evidence for the existence of the Rehbinder effect during the milling of drugs.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Not only do the polymers and surfactants allow proper stabilization of the nanoparticles in the suspensions, but they also do facilitate drug particle breakage.", "output": {"entities": {}}, "schema": []}
{"input": "Egr-1 mediates epidermal growth factor-induced downregulation of E-cadherin expression via Slug in human ovarian cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Loss of the cell adhesion protein E-cadherin increases the invasive capability of ovarian cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "We have previously shown that epidermal growth factor (EGF) downregulates E-cadherin and induces ovarian cancer cell invasion through the H (2) O (2)/p38 MAPK-mediated upregulation of the E-cadherin transcriptional repressor Snail.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 138, "end": 149}]}}, "schema": []}
{"input": "However, the molecular mechanisms underlying the EGF-induced downregulation of E-cadherin are not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "In the current study, we demonstrated that treatment of two ovarian cancer cell lines, SKOV3 and OVCAR5, with EGF induced the expression of the transcription factor Egr-1, and this induction was abolished by small interfering RNA (siRNA)-mediated depletion of the EGF receptor.", "output": {"entities": {}}, "schema": []}
{"input": "EGF-induced Egr-1 expression required the activation of the ERK1/2 and PI3K/Akt signaling pathways and was unrelated to EGF-induced H (2) O (2) production and activation of the p38 MAPK pathway.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 132, "end": 143}]}}, "schema": []}
{"input": "Moreover, depletion of Egr-1 with siRNA abolished the EGF-induced downregulation of E-cadherin and increased cell invasion.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, siRNA depletion of Egr-1 attenuated the EGF-induced expression of Slug, but not that of Snail.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, chromatin immunoprecipitation (ChIP) analysis showed that Slug is a target gene of Egr-1.", "output": {"entities": {}}, "schema": []}
{"input": "These results provide evidence that Egr-1 is a mediator that is involved in the EGF-induced downregulation of E-cadherin and increased cell invasion.", "output": {"entities": {}}, "schema": []}
{"input": "Our results also demonstrate that EGF activates two independent signaling pathways, which are the H (2) O (2)/p38 MAPK-mediated upregulation of Snail expression and the Egr-1-mediated upregulation of Slug expression.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 98, "end": 109}]}}, "schema": []}
{"input": "These two signaling pathways contribute to the EGF-induced downregulation of E-cadherin, which subsequently increases the invasive capability of ovarian cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-oncogenic potential of the eIF4E-binding proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The eIF4E-binding proteins (4E-BPs) are inhibitors of protein synthesis that sequester the mRNA cap-binding protein eIF4E and consequently block cell growth and proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "In most tumors however, their inhibitory function is compromised by major oncogenic signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, thanks to the generation of mouse genetic models, considerable progress has been made in elucidating the involvement of 4E-BPs and their unique target, eIF4E, in the process of carcinogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Increasing evidence indicates that an' addiction' to protein synthesis emerges in cancer cells, highlighting the potential that 4E-BPs have as targets for therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we summarize the biochemical function, regulation and anti-oncogenic activity of the 4E-BPs.", "output": {"entities": {}}, "schema": []}
{"input": "Macrophage immunomodulatory activity of a purified polysaccharide isolated from Ganoderma atrum.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to evaluate the immunomodulatory effects of the purified Ganoderma atrum polysaccharide (PSG-1) on murine macrophage cell line RAW264. 7.", "output": {"entities": {}}, "schema": []}
{"input": "Phagocytotic assay by fluorescein isothiocyanate-dextran internalization showed that PSG-1 stimulated the phagocytosis of macrophages.", "output": {"entities": {"chemical": [{"text": "fluorescein isothiocyanate", "start": 22, "end": 48}]}}, "schema": []}
{"input": "G. atrum polysaccharide increased the production of NO, and the level of mRNA expression of inducible nitric oxide synthase in a dose-response manner.", "output": {"entities": {"chemical": [{"text": "NO", "start": 52, "end": 54}, {"text": "nitric oxide", "start": 102, "end": 114}]}}, "schema": []}
{"input": "G. atrum polysaccharide also dose-dependently induced the release of TNF-alpha and interleukin-1 beta.", "output": {"entities": {}}, "schema": []}
{"input": "Generation of reactive oxygen species was promoted by PSG-1, as determined by flow cytometry.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 23, "end": 29}]}}, "schema": []}
{"input": "Moreover, PSG-1 induced nuclear factor-kappa B activation by elevation of p65 nuclear translocation, suggesting that PSG-1 probably stimulated macrophage activities by activating the nuclear factor-kappa B pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Prevention of hydrogen peroxide-induced red blood cells lysis by Ilex paraguariensis aqueous extract: participation of phenolic and xanthine compounds.", "output": {"entities": {"chemical": [{"text": "hydrogen peroxide", "start": 14, "end": 31}, {"text": "phenolic", "start": 119, "end": 127}, {"text": "xanthine", "start": 132, "end": 140}]}}, "schema": []}
{"input": "The fresh leaves and stems of Ilex paraguariensis (Aquifoliaceae) are employed to prepare the commercial product used in North-eastern Argentina, Southern Brazil and Eastern Paraguay named yerba mat e.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of polyphenols and xanthines, which present antioxidant activity, has been described in I. paraguariensis.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 16, "end": 27}, {"text": "xanthines", "start": 32, "end": 41}]}}, "schema": []}
{"input": "In living organism, reactive oxygen species can cause tissue damage affecting erythrocyte membranes leading to hemolysis.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 29, "end": 35}]}}, "schema": []}
{"input": "The aim of this work was to evaluate the protective effect of an aqueous extract of I. paraguariensis (green leaves) on the hemolysis of red blood cells induced by hydrogen peroxide and to correlate this activity with the enzymatic activity related to hydrogen peroxide metabolism.", "output": {"entities": {"chemical": [{"text": "hydrogen peroxide", "start": 164, "end": 181}, {"text": "hydrogen peroxide", "start": 252, "end": 269}]}}, "schema": []}
{"input": "The antioxidant activity of chlorogenic acid and caffeine was also analysed to evaluate their contribution to the activity of the crude extract.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 28, "end": 44}, {"text": "caffeine", "start": 49, "end": 57}]}}, "schema": []}
{"input": "The extract as well as the isolated compounds protected red blood cells from hemolysis.", "output": {"entities": {}}, "schema": []}
{"input": "This effect was related to a catalase-like activity.", "output": {"entities": {}}, "schema": []}
{"input": "This study could contribute to the knowledge of the antioxidant activity of I. paraguariensis in view of the great quantities of yerba mat e consumed by the population.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-hyperglycemic effect of fermented ginseng in type 2 diabetes mellitus mouse model.", "output": {"entities": {}}, "schema": []}
{"input": "Ginseng has shown an efficacy in preventing and managing various health conditions.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to evaluate the effect of the fermented ginseng extract (FGE) in type 2 diabetes mellitus murine model.", "output": {"entities": {}}, "schema": []}
{"input": "FGE was provided to male C57BL/ksJ-db/db mice for 8 weeks at 0. 1% (w/w) dose in contrast to water for the control group.", "output": {"entities": {}}, "schema": []}
{"input": "Potential anti-diabetic mechanisms were investigated with blood glucose, serum insulin, serum adiponectin, hemoglobin A1c (HbA1c), glucose tolerance, insulin secretion assay, quantitative real-time polymerase chain reaction, and hematoxylin-eosin staining.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 64, "end": 71}, {"text": "hematoxylin", "start": 229, "end": 240}, {"text": "eosin", "start": 241, "end": 246}]}}, "schema": []}
{"input": "Compared with the control group, the FGE group had lower levels of blood glucose after 6 and 9 h fasting, HbA1c, and the area under the curve in an oral glucose tolerance test and higher levels of adiponectin and serum insulin (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 73, "end": 80}, {"text": "glucose", "start": 153, "end": 160}]}}, "schema": []}
{"input": "The FGE group had higher levels of peroxisome proliferator-activated receptor gamma 2 and glucose transporter protein 2 mRNAs, a lower level of tumor necrosis factor-alpha (TNF-alpha) (p < 0. 05), and less lymphocytes in pancreas than the control group had.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 90, "end": 97}]}}, "schema": []}
{"input": "The FGE exerted anti-diabetic effects in type 2 diabetic mice.", "output": {"entities": {}}, "schema": []}
{"input": "A simple method of microneedle array fabrication for transdermal drug delivery.", "output": {"entities": {}}, "schema": []}
{"input": "The outermost layer of skin, stratum corneum, being lipophilic limits the passive transport of hydrophilic and large molecular weight drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Microfabrication technology has been adapted to fabricate micron scale needles, which are minimally invasive, yet able to deliver the drugs across this barrier layer.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we fabricated microneedles from a biocompatible polymer, namely, poly (ethylene glycol) diacrylate.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol) diacrylate", "start": 80, "end": 113}]}}, "schema": []}
{"input": "A simple lithographical approach was developed for microneedle array fabrication.", "output": {"entities": {}}, "schema": []}
{"input": "Several factors including polymerization time, ultraviolet light intensity and distance from light source were studied for their effects on microneedle formation.", "output": {"entities": {}}, "schema": []}
{"input": "The microneedle length and tip diameter can be controlled by varying these factors.", "output": {"entities": {}}, "schema": []}
{"input": "The microneedles were shown to be able to penetrate cadaver pig skin.", "output": {"entities": {}}, "schema": []}
{"input": "Model drug rhodamine B was encapsulated in the range of 50 micro g to 450 micro g per microneedle array.", "output": {"entities": {"chemical": [{"text": "rhodamine B", "start": 11, "end": 22}]}}, "schema": []}
{"input": "The fabricated microneedles containing rhodamine B increased the permeability by four times than the control.", "output": {"entities": {"chemical": [{"text": "rhodamine B", "start": 39, "end": 50}]}}, "schema": []}
{"input": "Altogether, we demonstrated that the microneedle arrays can be fabricated through a simple single-step process and needles were mechanically strong to penetrate skin, increasing the permeability of encapsulated drug through skin.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of estradiol in adult neurogenesis and brain repair in zebrafish.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 11, "end": 20}]}}, "schema": []}
{"input": "The brain of the adult teleost fish exhibits intense neurogenic activity and an outstanding capability for brain repair.", "output": {"entities": {}}, "schema": []}
{"input": "Remarkably, the brain estrogen-synthesizing enzyme, aromatase B, is strongly expressed, particularly in adult fishes, in radial glial cells, which act as progenitors.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 22, "end": 30}]}}, "schema": []}
{"input": "Using zebrafish, we tested the hypothesis that estrogens affect adult neurogenesis and brain regeneration by modulating the neurogenic activity of radial glial cells.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 47, "end": 56}]}}, "schema": []}
{"input": "To investigate this, the estrogenic environment was modified through inhibition of aromatase activity, blockade of nuclear estrogen receptors, or estrogenic treatments.", "output": {"entities": {"chemical": [{"text": "estrogenic", "start": 25, "end": 35}]}}, "schema": []}
{"input": "Estrogens significantly decreased cell proliferation and migration at the olfactory bulbs/telencephalon junction and in the mediobasal hypothalamus.", "output": {"entities": {}}, "schema": []}
{"input": "It also appears that cell survival is reduced at the olfactory bulbs/telencephalon junction.", "output": {"entities": {}}, "schema": []}
{"input": "We also developed a model of telencephalic lesion to assess the role of aromatase and estrogens in brain repair.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 86, "end": 95}]}}, "schema": []}
{"input": "Proliferation increased rapidly immediately after the lesion in the parenchyma of the injured telencephalon, while proliferation at the ventricular surface appeared after 48 h and peaked at 7 days.", "output": {"entities": {}}, "schema": []}
{"input": "At this time, most proliferative cells express Sox2, however, none of these Sox2 positive cells correspond to aromatase B-positive radial glial cells.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, aromatase B expression was significantly reduced 48 h and 7 days after the injury, but surprisingly, at 72 h after lesion, aromatase B expression appeared de novo expressed in parenchyma cells, suggesting a role for this ectopic expression of aromatase in brain repair mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Altogether these data suggest that estrogens modulate adult, but not reparative neurogenesis, in zebrafish.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 35, "end": 44}]}}, "schema": []}
{"input": "Stabilization of fenofibrate in low molecular weight hydroxypropylcellulose matrices produced by hot-melt extrusion.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to improve the dissolution rate and to enhance the stability of a poorly water-soluble and low glass-trasition temperature (T (g)) model drug, fenofibrate, in low molecular weight grades of hydroxypropylcellulose matrices produced by hot-melt extrusion (HME).", "output": {"entities": {"chemical": [{"text": "fenofibrate", "start": 175, "end": 186}]}}, "schema": []}
{"input": "Percent drug loading had a significant effect on the extrudability of the formulations.", "output": {"entities": {}}, "schema": []}
{"input": "Dissolution rate of fenofibrate from melt extruded pellets was faster than that of the pure drug (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "fenofibrate", "start": 20, "end": 31}]}}, "schema": []}
{"input": "Incorporation of sugars within the formulation further increased the fenofibrate release rates.", "output": {"entities": {"chemical": [{"text": "sugars", "start": 17, "end": 23}, {"text": "fenofibrate", "start": 69, "end": 80}]}}, "schema": []}
{"input": "Differential scanning calorimetry results revealed that the crystalline drug was converted into an amorphous form during the HME process.", "output": {"entities": {}}, "schema": []}
{"input": "Fenofibrate is prone to recrystallization due to its low T (g).", "output": {"entities": {"chemical": [{"text": "Fenofibrate", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Various polymers were evaluated as stabilizing agents among which polyvinylpyrrolidone 17PF and amino methacrylate copolymer exhibited a significant inhibitory effect on fenofibrate recrystallization in the hot-melt extrudates.", "output": {"entities": {"chemical": [{"text": "polyvinylpyrrolidone", "start": 66, "end": 86}, {"text": "amino methacrylate", "start": 96, "end": 114}, {"text": "fenofibrate", "start": 170, "end": 181}]}}, "schema": []}
{"input": "Subsequently immediate-release fenofibrate tablets were successfully developed and complete drug release was achieved within 5 min.", "output": {"entities": {"chemical": [{"text": "fenofibrate", "start": 31, "end": 42}]}}, "schema": []}
{"input": "The dissolution profile was comparable to that of a currently marketed formulation.", "output": {"entities": {}}, "schema": []}
{"input": "The hot-melt extruded fenofibrate tablets were stable, and exhibited an unchanged drug release profile after 3-month storage at 40 degrees C/75% RH.", "output": {"entities": {"chemical": [{"text": "fenofibrate", "start": 22, "end": 33}]}}, "schema": []}
{"input": "PTPN14 interacts with and negatively regulates the oncogenic function of YAP.", "output": {"entities": {}}, "schema": []}
{"input": "The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis.", "output": {"entities": {}}, "schema": []}
{"input": "The pivotal effector of this pathway is YAP, a transcriptional co-activator amplified in mouse and human cancers where it promotes epithelial-to-mesenchymal transition and malignant transformation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report a novel regulatory mechanism for the YAP oncogenic function via direct interaction with non-receptor tyrosine phosphatase 14 (PTPN14) through the WW domain of YAP and the PPxY domain of PTPN14.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 117, "end": 125}]}}, "schema": []}
{"input": "We also found that YAP is a direct substrate of PTPN14.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, luciferase reporter assay showed that the inhibition of the YAP transcriptional co-activator function by PTPN14 is mediated through their protein interactions and may result from an increase in the inactive cytoplasmic form of YAP.", "output": {"entities": {}}, "schema": []}
{"input": "Last, knockdown of PTPN14 induces the nuclear retention of YAP and increases the YAP-dependent cell migration.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, our results indicate a potential regulatory role of PTPN14 on YAP and demonstrate a novel mechanism in YAP regulation.", "output": {"entities": {}}, "schema": []}
{"input": "The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells.", "output": {"entities": {}}, "schema": []}
{"input": "The aggressiveness of glioblastoma multiforme (GBM) is defined by local invasion and resistance to therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Within established GBM, a subpopulation of tumor-initiating cells with stem-like properties (GBM stem cells, GSCs) is believed to underlie resistance to therapy.", "output": {"entities": {}}, "schema": []}
{"input": "The metabolic pathway autophagy has been implicated in the regulation of survival in GBM.", "output": {"entities": {}}, "schema": []}
{"input": "However, the status of autophagy in GBM and its role in the cancer stem cell fraction is currently unclear.", "output": {"entities": {}}, "schema": []}
{"input": "We found that a number of autophagy regulators are highly expressed in GBM tumors carrying a mesenchymal signature, which defines aggressiveness and invasion, and are associated with components of the MAPK pathway.", "output": {"entities": {}}, "schema": []}
{"input": "This autophagy signature included the autophagy-associated genes DRAM1 and SQSTM1, which encode a key regulator of selective autophagy, p62.", "output": {"entities": {}}, "schema": []}
{"input": "High levels of DRAM1 were associated with shorter overall survival in GBM patients.", "output": {"entities": {}}, "schema": []}
{"input": "In GSCs, DRAM1 and SQSTM1 expression correlated with activation of MAPK and expression of the mesenchymal marker c-MET.", "output": {"entities": {}}, "schema": []}
{"input": "DRAM1 knockdown decreased p62 localization to autophagosomes and its autophagy-mediated degradation, thus suggesting a role for DRAM1 in p62-mediated autophagy.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, autophagy induced by starvation or inhibition of mTOR/PI-3K was not affected by either DRAM1 or p62 downregulation.", "output": {"entities": {}}, "schema": []}
{"input": "Functionally, DRAM1 and p62 regulate cell motility and invasion in GSCs.", "output": {"entities": {}}, "schema": []}
{"input": "This was associated with alterations of energy metabolism, in particular reduced ATP and lactate levels.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 81, "end": 84}, {"text": "lactate", "start": 89, "end": 96}]}}, "schema": []}
{"input": "Taken together, these findings shed new light on the role of autophagy in GBM and reveal a novel function of the autophagy regulators DRAM1 and p62 in control of migration/invasion in cancer stem cells.", "output": {"entities": {}}, "schema": []}
{"input": "Selective activation of either mGlu2 or mGlu3 receptors can induce LTD in the amygdala.", "output": {"entities": {}}, "schema": []}
{"input": "Group II metabotropic glutamate (mGlu) receptors are known to induce a long-term depression (LTD) of synaptic transmission in many brain regions including the amygdala.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 22, "end": 31}]}}, "schema": []}
{"input": "However the roles of the individual receptor subtypes, mGlu2 and mGlu3, in LTD are not well understood.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, it is unclear whether activation of mGlu3 receptors is sufficient to induce LTD at synapses in the CNS.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, advantage was taken of a Wistar rat strain not expressing mGlu2 receptors (Ceolin et al., 2011) to investigate the function of mGlu3 receptors in the amygdala.", "output": {"entities": {}}, "schema": []}
{"input": "In this preparation, the group II agonist, DCG-IV induced an LTD of the cortical, but not the intra-nuclear, synaptic input to the lateral amygdala.", "output": {"entities": {}}, "schema": []}
{"input": "This LTD was concentration dependent and was blocked by the group II mGlu receptor antagonist, LY341495.", "output": {"entities": {"chemical": [{"text": "LY341495", "start": 95, "end": 103}]}}, "schema": []}
{"input": "To investigate further the role of mGlu3 receptors, we used LY395756 (an mGlu2 agonist and mGlu3 antagonist), which acts as a pure mGlu3 receptor antagonist in this rat strain.", "output": {"entities": {"chemical": [{"text": "LY395756", "start": 60, "end": 68}]}}, "schema": []}
{"input": "This compound alone had no effect on basal synaptic transmission, but blocked the LTD induced by DCG-IV.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we found that DCG-IV also induces LTD in mGlu2 receptor knock-out (KO) mice to a similar extent as in wild-type mice.", "output": {"entities": {}}, "schema": []}
{"input": "This confirms that the activation of mGlu3 receptors alone is sufficient to induce LTD at this amygdala synapse.", "output": {"entities": {}}, "schema": []}
{"input": "To address whether mGlu2 activation alone is also sufficient to induce LTD at this synapse we used LY541850 (the active enantiomer of LY395756) in wild-type mice.", "output": {"entities": {"chemical": [{"text": "LY541850", "start": 99, "end": 107}, {"text": "LY395756", "start": 134, "end": 142}]}}, "schema": []}
{"input": "LY541850 induced a substantial LTD showing that either receptor alone is capable of inducing LTD in this pathway.", "output": {"entities": {"chemical": [{"text": "LY541850", "start": 0, "end": 8}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Effect of water extracts from edible myrtaceae plants on uptake of 2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose in TNF-alpha-treated FL83B mouse hepatocytes.", "output": {"entities": {"chemical": [{"text": "2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose", "start": 67, "end": 130}]}}, "schema": []}
{"input": "This study investigated the glucose uptake activity of the water extracts from the leaves and fruit of edible Myrtaceae plants, including guava (Psidium guajava Linn.), wax apples [Syzygium samarangense (Blume) Merr. and L. M. Perry], Pu-Tau [Syzygium jambo (L.) Alston], and Kan-Shi Pu-Tau (Syzygium cumini Linn.) in FL83B mouse hepatocytes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 28, "end": 35}]}}, "schema": []}
{"input": "The fluorescent dye 2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose was used to estimate the uptake ability of the cells.", "output": {"entities": {"chemical": [{"text": "2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose", "start": 20, "end": 83}]}}, "schema": []}
{"input": "Glucose uptake test showed that pink wax apple fruit extract (PWFE) exhibits the highest glucose uptake activity, at an increment of 21% in the insulin-resistant FL83B mouse hepatocytes as compared with the TNF-alpha-treated control group.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}, {"text": "glucose", "start": 89, "end": 96}]}}, "schema": []}
{"input": "Vescalagin was isolated using column chromatography of PWFE.", "output": {"entities": {"chemical": [{"text": "Vescalagin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "This compound, at the concentration of 6. 25 micro g/mL, exhibits the same glucose uptake improvement in insulin-resistant cells as PWFE at a 100-micro g/mL dose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 75, "end": 82}]}}, "schema": []}
{"input": "We postulate that vescalagin is an active component in PWFE that may alleviate the insulin resistance in mouse hepatocytes.", "output": {"entities": {"chemical": [{"text": "vescalagin", "start": 18, "end": 28}]}}, "schema": []}
{"input": "Two new C-15 enolic acyl phragmalin-type limonoids from Chukrasia tabularis var. velutina.", "output": {"entities": {"chemical": [{"text": "enolic acyl phragmalin", "start": 13, "end": 35}, {"text": "limonoids", "start": 41, "end": 50}]}}, "schema": []}
{"input": "Two new C-15 enolic acyl phragmalin-type limonoid orthoesters, chukvelutilide G (1) and chukrasine F (2), were isolated from the stem barks of Chukrasia tabularis var. velutina.", "output": {"entities": {"chemical": [{"text": "enolic acyl phragmalin", "start": 13, "end": 35}, {"text": "limonoid orthoesters", "start": 41, "end": 61}, {"text": "chukvelutilide G", "start": 63, "end": 79}, {"text": "chukrasine F", "start": 88, "end": 100}]}}, "schema": []}
{"input": "Their structures were elucidated by their extensive high resolution-electrospray ionization mass spectrometry (HR-ESI-MS), one-and two-dimensional spectroscopic analysis, including heteronuclear single quantum coherence (HSQC), HMBC and NOESY experiments.", "output": {"entities": {}}, "schema": []}
{"input": "A new xanthone from the bark of Calophyllum thorelii.", "output": {"entities": {"chemical": [{"text": "xanthone", "start": 6, "end": 14}]}}, "schema": []}
{"input": "A new xanthone, calothorexanthone, together with five known compounds, garbogiol, 1, 4, 8-trihydroxyxanthone, delta-tocotrienol, 1, 7-dihydroxyxanthone and globuxanthone, was isolated from a petroleum ether extract of the bark of Calophyllum thorelii.", "output": {"entities": {"chemical": [{"text": "xanthone", "start": 6, "end": 14}, {"text": "calothorexanthone", "start": 16, "end": 33}, {"text": "garbogiol", "start": 71, "end": 80}, {"text": "1, 4, 8-trihydroxyxanthone", "start": 82, "end": 108}, {"text": "delta-tocotrienol", "start": 110, "end": 127}, {"text": "1, 7-dihydroxyxanthone", "start": 129, "end": 151}, {"text": "globuxanthone", "start": 156, "end": 169}]}}, "schema": []}
{"input": "Their structures were established on the basis of spectroscopic methods, mainly one-and two-dimensional NMR.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activity of the isolated compounds was tested using DPPH free radical scavenging assay and some exhibited remarkable effects with IC50 of 13. 63-17. 46 micro g mL (-1).", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 64, "end": 68}]}}, "schema": []}
{"input": "TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "Intellectual disability (ID) with autosomal recessive (AR) inheritance is believed to be common; however, very little is known about causative genes and genotype-phenotype correlations.", "output": {"entities": {}}, "schema": []}
{"input": "The broad genetic heterogeneity of AR-ID, and its usually nonsyndromic nature make it difficult to pool multiple pedigrees with the same underlying genetic defect to achieve consistent nosology.", "output": {"entities": {}}, "schema": []}
{"input": "Nearly all autosomal genes responsible for recessive cognitive disorders have been identified in large consanguineous families from the Middle East, and nonsense mutations in TRAPPC9 have been reported in a total of 5.", "output": {"entities": {}}, "schema": []}
{"input": "Although several recurrent phenotypic abnormalities are described in some of these patients, the associated phenotype is usually referred to as nonsyndromic.", "output": {"entities": {}}, "schema": []}
{"input": "By means of single-nucleotide polymorphism-array first and then by exome sequencing, we identified a new pathogenic mutation in TRAPPC9 in two Italian sisters born to healthy and apparently nonconsanguineous parents.", "output": {"entities": {}}, "schema": []}
{"input": "It consists of a homozygous splice site mutation causing exon skipping with frameshift and premature termination, as confirmed by mRNA sequencing.", "output": {"entities": {}}, "schema": []}
{"input": "By detailed phenotypic analysis of our patients, and by critical literature review, we found that homozygous TRAPPC9 loss-of-function mutations cause a distinctive phenotype, characterized by peculiar facial appearance, obesity, hypotonia (all signs resembling a Prader-Willi-like phenotype), moderate-to-severe ID, and consistent brain abnormalities.", "output": {"entities": {}}, "schema": []}
{"input": "MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.", "output": {"entities": {}}, "schema": []}
{"input": "Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options.", "output": {"entities": {}}, "schema": []}
{"input": "We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals.", "output": {"entities": {}}, "schema": []}
{"input": "Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein.", "output": {"entities": {}}, "schema": []}
{"input": "To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route.", "output": {"entities": {}}, "schema": []}
{"input": "Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps.", "output": {"entities": {}}, "schema": []}
{"input": "Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30 +/- 10 non-overlapping injections per animal.", "output": {"entities": {}}, "schema": []}
{"input": "Vector DNA was detectable in all samples tested and ranged from < 1 to > 3000 vector genome copies per cell.", "output": {"entities": {}}, "schema": []}
{"input": "RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium.", "output": {"entities": {}}, "schema": []}
{"input": "Left ventricular function remained unchanged over a 3-month follow-up.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM.", "output": {"entities": {}}, "schema": []}
{"input": "This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.", "output": {"entities": {}}, "schema": []}
{"input": "Preparation and cyclodextrin assisted dissolution rate enhancement of itraconazolium dinitrate salt.", "output": {"entities": {"chemical": [{"text": "itraconazolium dinitrate", "start": 70, "end": 94}]}}, "schema": []}
{"input": "The poor solubility of itraconazole (ITR) results in its variable oral absorption and bioavailability and has also proven to be a major setback in developing an efficient oral delivery system.", "output": {"entities": {"chemical": [{"text": "itraconazole", "start": 23, "end": 35}, {"text": "ITR", "start": 37, "end": 40}]}}, "schema": []}
{"input": "To improve its solubility and dissolution profile, itraconazolium dinitrate salt (ITRDNT) was prepared and characterized using various spectral and thermal techniques.", "output": {"entities": {"chemical": [{"text": "itraconazolium dinitrate", "start": 51, "end": 75}, {"text": "ITRDNT", "start": 82, "end": 88}]}}, "schema": []}
{"input": "The morphology of the salt was studied using optical and scanning electron microscopy (SEM).", "output": {"entities": {}}, "schema": []}
{"input": "Broth microdilution assay demonstrated antifungal efficacy of ITRDNT similar to ITR against four different fungal strains namely, Asparagillus fumigatus, Microsporum canis, Microsporum gypsum and Trichophyton rubrum.", "output": {"entities": {"chemical": [{"text": "ITRDNT", "start": 62, "end": 68}, {"text": "ITR", "start": 80, "end": 83}]}}, "schema": []}
{"input": "The salt exhibited better solubility profile than ITR in water and a number of pharmaceutical solvents.", "output": {"entities": {"chemical": [{"text": "ITR", "start": 50, "end": 53}]}}, "schema": []}
{"input": "Dissolution studies revealed the total amount of drug released from ITRDNT in 3 h was four times greater than that of ITR.", "output": {"entities": {"chemical": [{"text": "ITRDNT", "start": 68, "end": 74}, {"text": "ITR", "start": 118, "end": 121}]}}, "schema": []}
{"input": "To further improve dissolution characteristics, the physical mixtures of ITR and ITRDNT with two cyclodextrins, beta-cyclodextrin (beta-CD) and HP-beta-cyclodextrin (HP-beta-CD) were prepared and their molar ratios were optimized.", "output": {"entities": {"chemical": [{"text": "ITR", "start": 73, "end": 76}, {"text": "ITRDNT", "start": 81, "end": 87}, {"text": "beta-cyclodextrin", "start": 112, "end": 129}, {"text": "beta-CD", "start": 131, "end": 138}, {"text": "HP-beta-cyclodextrin", "start": 144, "end": 164}, {"text": "HP-beta-CD", "start": 166, "end": 176}]}}, "schema": []}
{"input": "It was observed that about 75% of drug was released in 30 min from 1: 3 molar ratio of ITRDNT and HP-beta-CD physical mixture, which was distinctly higher than ITR commercial capsules (70%).", "output": {"entities": {"chemical": [{"text": "ITRDNT", "start": 87, "end": 93}, {"text": "HP-beta-CD", "start": 98, "end": 108}, {"text": "ITR", "start": 160, "end": 163}]}}, "schema": []}
{"input": "Owing to its facile and economical preparation and substantially better in vitro release profile, the ITRDNT and its CD physical mixtures could be better and cost effective alternatives to ITR and commercial ITR capsules.", "output": {"entities": {"chemical": [{"text": "ITRDNT", "start": 102, "end": 108}, {"text": "ITR", "start": 189, "end": 192}, {"text": "ITR", "start": 208, "end": 211}]}}, "schema": []}
{"input": "\" Vitamin E \" fortified parenteral lipid emulsions: Plackett-Burman screening of primary process and composition parameters.", "output": {"entities": {"chemical": [{"text": "Vitamin E", "start": 2, "end": 11}]}}, "schema": []}
{"input": "The objective of this study was to screen the effect of eight formulations and process parameters on the physical attributes and stability of \" Vitamin E \"-rich parenteral lipid emulsions.", "output": {"entities": {"chemical": [{"text": "Vitamin E", "start": 144, "end": 153}]}}, "schema": []}
{"input": "Screening was performed using a 12-run, 8-factor, 2-level Plackett-Burman design.", "output": {"entities": {}}, "schema": []}
{"input": "This design was employed to construct polynomial equations that identified the magnitude and direction of the linear effect of homogenization pressure, number of homogenization cycles, primary and secondary emulsifiers, pre-homogenization temperature, oil loading, and ratio of vitamin E to medium-chain triglycerides (MCT) in the oil phase on particle size, polydispersity index, short-term stability, and outlet temperature of manufactured emulsions.", "output": {"entities": {"chemical": [{"text": "vitamin E", "start": 278, "end": 287}, {"text": "triglycerides", "start": 304, "end": 317}]}}, "schema": []}
{"input": "The viscosity of vitamin E was reduced from 3700 (100%) to 64 mPa. s (30%) by MCT addition.", "output": {"entities": {"chemical": [{"text": "vitamin E", "start": 17, "end": 26}]}}, "schema": []}
{"input": "As viscosity is critical for efficient emulsification, vitamin/MCT ratio was the most significant contributor for the stability of emulsions.", "output": {"entities": {}}, "schema": []}
{"input": "Particle size increased from 236 to 388 nm, and percentage vitamin remaining emulsified after 48 h dropped from 100 to 73% with increase in vitamin/MCT ratio from 30/70 to 70/30.", "output": {"entities": {}}, "schema": []}
{"input": "Significant decrease in particle size and PI, and an increase in outlet temperature were also observed with increase in homogenization pressure and number of homogenization cycles.", "output": {"entities": {}}, "schema": []}
{"input": "Emulsifiers and oil loading, however, had insignificant effect on the responses.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, stable submicron emulsions at vitamin/MCT ratio of 30/70 could be prepared at 25, 000 psi and 25 cycles in ambient conditions.", "output": {"entities": {}}, "schema": []}
{"input": "The identification of these parameters by a well-constructed design demonstrated the utility of screening studies in the \" Quality by Design \" approach to pharmaceutical product development.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of process parameters on audible acoustic emissions from high-shear granulation.", "output": {"entities": {}}, "schema": []}
{"input": "Product quality in high-shear granulation is easily compromised by minor changes in raw material properties or process conditions.", "output": {"entities": {}}, "schema": []}
{"input": "It is desired to develop a process analytical technology (PAT) that can monitor the process in real-time and provide feedback for quality control.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, the application of audible acoustic emissions (AAEs) as a PAT tool was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "A condenser microphone was placed at the top of the air exhaust on a PMA-10 high-shear granulator to collect AAEs for a design of experiment (DOE) varying impeller speed, total binder volume and spray rate.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed the 10 Hz total power spectral densities (TPSDs) between 20 and 250 Hz were significantly affected by the changes in process conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Impeller speed and spray rate were shown to have statistically significant effects on granulation wetting, and impeller speed and total binder volume were significant in terms of process end-point.", "output": {"entities": {}}, "schema": []}
{"input": "The DOE results were confirmed by a multivariate PLS model of the TPSDs.", "output": {"entities": {}}, "schema": []}
{"input": "The scores plot showed separation based on impeller speed in the first component and spray rate in the second component.", "output": {"entities": {}}, "schema": []}
{"input": "The findings support the use of AAEs to monitor changes in process conditions in real-time and achieve consistent product quality.", "output": {"entities": {}}, "schema": []}
{"input": "mGlu3 receptor and astrocytes: partners in neuroprotection.", "output": {"entities": {}}, "schema": []}
{"input": "Astrocytes are currently studied intensively because of their now highlighted relevance as key players with neurons that modulate a wide range of central functions, from synaptic plasticity and synaptogenesis to regulation of metabolic and neuroinflammatory processes.", "output": {"entities": {}}, "schema": []}
{"input": "Since the discovery of mGlu3 receptors on astrocytes, accumulating evidence supports a role of these receptors not only in maintaining synaptic homeostasis and treating psychiatric disorders but also in promoting astrocyte survival in several pathologic conditions.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on providing up-to-date knowledge regarding effects of activating astroglial mGlu3 receptors on psychiatric disorders, astrocyte and neuronal survival, and neurodegenerative diseases.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {}}, "schema": []}
{"input": "Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Human studies suggest that a variety of prenatal stressors are related to high risk for cognitive and behavioral abnormalities associated with psychiatric illness (Markham and Koenig, 2011).", "output": {"entities": {}}, "schema": []}
{"input": "Recently, a downregulation in the expression of GABAergic genes (i. e., glutamic acid decarboxylase 67 and reelin) associated with DNA methyltransferase (DNMT) overexpression in GABAergic neurons has been regarded as a characteristic phenotypic component of the neuropathology of psychotic disorders (Guidotti et al., 2011).", "output": {"entities": {"chemical": [{"text": "glutamic acid", "start": 72, "end": 85}]}}, "schema": []}
{"input": "Here, we characterized mice exposed to prenatal restraint stress (PRS) in order to study neurochemical and behavioral abnormalities related to development of schizophrenia in the adult.", "output": {"entities": {}}, "schema": []}
{"input": "Offspring born from non-stressed mothers (control mice) showed high levels of DNMT1 and 3a mRNA expression in the frontal cortex at birth, but these levels progressively decreased at post-natal days (PND) 7, 14, and 60.", "output": {"entities": {}}, "schema": []}
{"input": "Offspring born from stressed mothers (PRS mice) showed increased levels of DNMTs compared to controls at all time-points studied including at birth and at PND 60.", "output": {"entities": {}}, "schema": []}
{"input": "Using GAD67-GFP transgenic mice, we established that, in both control and PRS mice, high levels of DNMT1 and 3a were preferentially expressed in GABAergic neurons of frontal cortex and hippocampus.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, the overexpression of DNMT in GABAergic neurons was associated with a decrease in reelin and GAD67 expression in PRS mice in early and adult life.", "output": {"entities": {}}, "schema": []}
{"input": "PRS mice also showed an increased binding of DNMT1 and MeCP2, and an increase in 5-methylcytosine and 5-hydroxymethylcytosine in specific CpG-rich regions of the reelin and GAD67 promoters.", "output": {"entities": {"chemical": [{"text": "5-methylcytosine", "start": 81, "end": 97}, {"text": "5-hydroxymethylcytosine", "start": 102, "end": 125}, {"text": "CpG", "start": 138, "end": 141}]}}, "schema": []}
{"input": "Thus, the epigenetic changes in PRS mice are similar to changes observed in the post-mortem brains of psychiatric patients.", "output": {"entities": {}}, "schema": []}
{"input": "Behaviorally, adult PRS mice showed hyperactivity and deficits in social interaction, prepulse inhibition, and fear conditioning that were corrected by administration of valproic acid (a histone deacetylase inhibitor) or clozapine (an atypical antipsychotic with DNA-demethylation activity).", "output": {"entities": {"chemical": [{"text": "valproic acid", "start": 170, "end": 183}, {"text": "clozapine", "start": 221, "end": 230}]}}, "schema": []}
{"input": "Taken together, these data show that prenatal stress in mice induces abnormalities in the DNA methylation network and in behaviors indicative of a schizophrenia-like phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, PRS mice may be a valid model for the investigation of new drugs for schizophrenia treatment targeting DNA methylation.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.", "output": {"entities": {}}, "schema": []}
{"input": "Presynaptic mGlu7 receptors control GABA release in mouse hippocampus.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 36, "end": 40}]}}, "schema": []}
{"input": "The functional role of presynaptic release-regulating metabotropic glutamate type 7 (mGlu7) receptors in hippocampal GABAergic terminals was investigated.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 67, "end": 76}]}}, "schema": []}
{"input": "Mouse hippocampal synaptosomes were preloaded with [(3) H] D-gamma-aminobutyric acid ([(3) H] GABA) and then exposed in superfusion to 12 mM KCl.", "output": {"entities": {"chemical": [{"text": "[(3) H] D-gamma-aminobutyric acid", "start": 51, "end": 84}, {"text": "[(3) H] GABA", "start": 86, "end": 98}, {"text": "KCl", "start": 141, "end": 144}]}}, "schema": []}
{"input": "The K (+)-evoked [(3) H] GABA release was inhibited by the mGlu7 allosteric agonist N, N'-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride (AMN082, 0. 001-10 mu M), as well as by the group III mGlu receptor agonist l-(+)-2-amino-4-phosphonobutyric acid [(l)-AP4, 0. 01-1 mM].", "output": {"entities": {"chemical": [{"text": "K (+)", "start": 4, "end": 9}, {"text": "[(3) H] GABA", "start": 17, "end": 29}, {"text": "N, N'-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride", "start": 84, "end": 139}, {"text": "AMN082", "start": 141, "end": 147}, {"text": "l-(+)-2-amino-4-phosphonobutyric acid", "start": 216, "end": 253}, {"text": "(l)-AP4", "start": 255, "end": 262}]}}, "schema": []}
{"input": "The mGlu8 receptor agonist (S)-3, 4-dicarboxyphenylglycine [(S)-3, 4-DCPG, 10-100 nM] was ineffective.", "output": {"entities": {"chemical": [{"text": "(S)-3, 4-dicarboxyphenylglycine", "start": 27, "end": 58}, {"text": "(S)-3, 4-DCPG", "start": 60, "end": 73}]}}, "schema": []}
{"input": "AMN082 and (l)-AP4-induced effects were recovered by the mGlu7 negative allosteric modulator (NAM) 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo [4, 5-c] pyridin-4 (5H)-one hydrochloride (MMPIP).", "output": {"entities": {"chemical": [{"text": "AMN082", "start": 0, "end": 6}, {"text": "(l)-AP4", "start": 11, "end": 18}, {"text": "6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo [4, 5-c] pyridin-4 (5H)-one hydrochloride", "start": 99, "end": 195}, {"text": "MMPIP", "start": 197, "end": 202}]}}, "schema": []}
{"input": "AMN082 also inhibited in a MMPIP-sensitive manner the K (+)-evoked release of endogenous GABA.", "output": {"entities": {"chemical": [{"text": "AMN082", "start": 0, "end": 6}, {"text": "MMPIP", "start": 27, "end": 32}, {"text": "K (+)", "start": 54, "end": 59}, {"text": "GABA", "start": 89, "end": 93}]}}, "schema": []}
{"input": "AMN082 and the adenylyl cyclase (AC) inhibitor MDL-12, 330A reduced [(3) H] GABA exocytosis in a 8-Br-cAMP-sensitive.", "output": {"entities": {"chemical": [{"text": "AMN082", "start": 0, "end": 6}, {"text": "MDL-12, 330A", "start": 47, "end": 59}, {"text": "[(3) H] GABA", "start": 68, "end": 80}, {"text": "8-Br-cAMP", "start": 97, "end": 106}]}}, "schema": []}
{"input": "AMN082-inhibitory effect was additive to that caused by (-) baclofen, but insensitive to the GABA (B) antagonist 3-[[(3, 4-Dichlorophenyl) methyl] amino] propyl] diethoxymethyl) phosphinic acid (CGP52432).", "output": {"entities": {"chemical": [{"text": "AMN082", "start": 0, "end": 6}, {"text": "(-) baclofen", "start": 56, "end": 68}, {"text": "GABA", "start": 93, "end": 97}, {"text": "3-[[(3, 4-Dichlorophenyl) methyl] amino] propyl] diethoxymethyl) phosphinic acid", "start": 113, "end": 193}, {"text": "CGP52432", "start": 195, "end": 203}]}}, "schema": []}
{"input": "Conversely, (-) baclofen-induced inhibition of GABA exocytosis was insensitive to MMPIP.", "output": {"entities": {"chemical": [{"text": "(-) baclofen", "start": 12, "end": 24}, {"text": "GABA", "start": 47, "end": 51}, {"text": "MMPIP", "start": 82, "end": 87}]}}, "schema": []}
{"input": "Finally, the forskolin-evoked [(3) H] GABA release was reduced by AMN082 or (-) baclofen but abolished when the two agonists were added concomitantly.", "output": {"entities": {"chemical": [{"text": "forskolin", "start": 13, "end": 22}, {"text": "[(3) H] GABA", "start": 30, "end": 42}, {"text": "AMN082", "start": 66, "end": 72}, {"text": "(-) baclofen", "start": 76, "end": 88}]}}, "schema": []}
{"input": "Mouse hippocampal synaptosomal plasmamembranes posses mGlu7 receptor proteins; confocal microscopy analysis unveiled that mGlu7 proteins colocalize with syntaxin-1A (Stx-1A), with vesicular GABA transporter (VGAT)-proteins and with GABA (B) receptor subunit proteins.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 190, "end": 194}, {"text": "GABA", "start": 232, "end": 236}]}}, "schema": []}
{"input": "We propose that presynaptic inhibitory mGlu7 heteroreceptors, negatively coupled to AC-dependent intraterminal pathway, exist in mouse hippocampal GABA-containing terminals, where they colocalize, but do not functionally cross-talk, with GABA (B) autoreceptors.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 147, "end": 151}, {"text": "GABA", "start": 238, "end": 242}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {}}, "schema": []}
{"input": "RETRACTED: Effects of crude diesel oil on the enzymatic defenses of the Great sturgeon, Huso huso.", "output": {"entities": {}}, "schema": []}
{"input": "RETRACTED.", "output": {"entities": {}}, "schema": []}
{"input": "A new method for preparing pentacyclic triterpene rich Centella asiatica extracts.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpene", "start": 27, "end": 49}]}}, "schema": []}
{"input": "This study evaluated microwave-assisted extraction (MAE) for four pentacyclic triterpenes as well as developed a method for preparing a pentacyclic triterpenene rich extract from Centella asiatica.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenes", "start": 66, "end": 89}, {"text": "pentacyclic triterpenene", "start": 136, "end": 160}]}}, "schema": []}
{"input": "MAE was capable of increasing the yield of the pentacyclic triterpenes up to twice that produced by the heat reflux method, and it was also much less time consuming.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenes", "start": 47, "end": 70}]}}, "schema": []}
{"input": "The optimal conditions of MAE employed were extraction with absolute ethanol as solvent, an irradiation power of 600 W, at 75 degrees C, four irradiation cycles and four extraction times.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 69, "end": 76}]}}, "schema": []}
{"input": "Here, we provide a simple method for the preparation of the pentacyclic triterpene rich C. asiatica extracts, which contained not less than 65% w/w total pentacyclic triterpenes.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpene", "start": 60, "end": 82}, {"text": "pentacyclic triterpenes", "start": 154, "end": 177}]}}, "schema": []}
{"input": "The method involved a macroporous resin (Diaion (R) HP-20) column eluted with ethanol and a decolourisation step with activated charcoal.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 78, "end": 85}]}}, "schema": []}
{"input": "Discovery and structural characterization of a phospholamban-binding cyclic peptide and design of novel inhibitors of phospholamban.", "output": {"entities": {}}, "schema": []}
{"input": "The interplay between cardiac sarcoplasmic Ca (2 +) ATPase and phospholamban is a key regulating factor of contraction and relaxation in the cardiac muscle.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 43, "end": 51}]}}, "schema": []}
{"input": "In heart failure, aberrations in the inhibition of sarcoplasmic Ca (2 +) ATPase by phospholamban are associated with anomalies in cardiac functions.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 64, "end": 72}]}}, "schema": []}
{"input": "In experimental heart failure models, modulation of the interaction between these two proteins has been shown to be a potential therapeutic approach.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of our research was to find molecules able to interfere with the inhibitory activity of phospholamban on sarcoplasmic Ca (2 +) ATPase.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 126, "end": 134}]}}, "schema": []}
{"input": "For this purpose, a portion of phospholamban was synthesized and used as target for a phage-display peptide library screening.", "output": {"entities": {}}, "schema": []}
{"input": "The cyclic peptide C-Y-W-E-L-E-W-L-P-C-A was found to bind to phospholamban (1-36) with high specificity.", "output": {"entities": {}}, "schema": []}
{"input": "Its functional activity was tested in Ca (2 +) uptake assays utilizing preparations from cardiac sarcoplasmic reticulum.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 38, "end": 46}]}}, "schema": []}
{"input": "By synthesizing and testing a series of alanine point-mutated cyclic peptides, we identified which amino acid was important for the inhibition of the phospholamban function.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 40, "end": 47}, {"text": "amino acid", "start": 99, "end": 109}]}}, "schema": []}
{"input": "The structures of active and inactive alanine-mutated cyclic peptides, and of phospholamban (1-36), were determined by NMR.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 38, "end": 45}]}}, "schema": []}
{"input": "This structure-activity analysis allowed building a model of phospholamban-cyclic peptide complex.", "output": {"entities": {}}, "schema": []}
{"input": "Thereafter, a simple pharmacophore was defined and used for the design of small molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, examples of such molecules were synthesized and characterized as phospholamban inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "A possible explanation for the population size discrepancy in tuna (genus Thunnus) estimated from mitochondrial DNA and microsatellite data.", "output": {"entities": {}}, "schema": []}
{"input": "A recent study using both mitochondrial DNA (mtDNA) and microsatellite data reported on a population size discrepancy in the eastern tiger salamander where the effective population size (N (e)) estimate of the former exceeded that of the latter.", "output": {"entities": {}}, "schema": []}
{"input": "That study suggested, among other hypotheses, that homoplasy of microsatellite alleles is responsible for the discrepancy.", "output": {"entities": {}}, "schema": []}
{"input": "In this investigation, we report 10 new cases of a similar discrepancy in five species of tuna.", "output": {"entities": {}}, "schema": []}
{"input": "These cases derive from our Bayesian inferences using data from Pacific Bluefin Tuna (Thunnus orientalis) and Yellowfin Tuna (Thunnus albacares), as well as from published estimates of genetic diversity for additional populations of Yellowfin Tuna and three other tuna species.", "output": {"entities": {}}, "schema": []}
{"input": "Phylogenetic character analyses of inferred genealogies of Pacific Bluefin and Yellowfin Tuna reveal similar reduced levels of mtDNA and microsatellite homoplasy.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the discrepancy between inferred population sizes from mtDNA and microsatellite data in tuna is most likely not an artifact of the chosen mutation models used in the microsatellite analyses, but may reflect behavioral differences between the sexes such as female-biased philopatry and male-biased dispersal.", "output": {"entities": {}}, "schema": []}
{"input": "This explanation now warrants critical testing with more local populations of tuna and with other animal and plant groups that have different life histories.", "output": {"entities": {}}, "schema": []}
{"input": "Organ accumulation in mice after inhalation of single or mixed essential oil compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Essential oils are composed of multiple components.", "output": {"entities": {}}, "schema": []}
{"input": "It is thought that the effect of essential oils is due to specific component ratios, which may differ from the original ratio when the essential oil is absorbed.", "output": {"entities": {}}, "schema": []}
{"input": "However, very little detailed research exists in this area.", "output": {"entities": {}}, "schema": []}
{"input": "We studied the distribution of essential oil components after inhalation of single and mixed components in mice.", "output": {"entities": {}}, "schema": []}
{"input": "This research was done using four main components of Alpinia zerumbet (Pers.) B.", "output": {"entities": {}}, "schema": []}
{"input": "L.", "output": {"entities": {}}, "schema": []}
{"input": "Burtt. and R.", "output": {"entities": {}}, "schema": []}
{"input": "M.", "output": {"entities": {}}, "schema": []}
{"input": "Sm.: alpha-pinene, p-cymene, 1, 8-cineole, and limonene.", "output": {"entities": {"chemical": [{"text": "alpha-pinene", "start": 5, "end": 17}, {"text": "p-cymene", "start": 19, "end": 27}, {"text": "1, 8-cineole", "start": 29, "end": 41}, {"text": "limonene", "start": 47, "end": 55}]}}, "schema": []}
{"input": "After inhalation of single or mixed components for 90 min, component levels in the brain and liver of mice were measured.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicated that the amount of alpha-pinene in the brain and liver was twofold greater after mixed-component inhalation than that after single-component inhalation.", "output": {"entities": {"chemical": [{"text": "alpha-pinene", "start": 41, "end": 53}]}}, "schema": []}
{"input": "In a comparison of the components of the mixed inhalation, the ratio of alpha-pinene increased to about three times that of 1, 8-cineole.", "output": {"entities": {"chemical": [{"text": "alpha-pinene", "start": 72, "end": 84}, {"text": "1, 8-cineole", "start": 124, "end": 136}]}}, "schema": []}
{"input": "It is thought that the absorption via the nasal mucus greatly influences this phenomenon.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this investigation of the bodily distribution of essential oil volatile components may provide clues for elucidating their action.", "output": {"entities": {}}, "schema": []}
{"input": "Antiangiogenic effects of p-coumaric acid in human endothelial cells.", "output": {"entities": {"chemical": [{"text": "p-coumaric acid", "start": 26, "end": 41}]}}, "schema": []}
{"input": "p-Coumaric acid, a hydroxy derivative of cinnamic acid, has been known to possess antioxidant and anticancer activities.", "output": {"entities": {"chemical": [{"text": "p-Coumaric acid", "start": 0, "end": 15}, {"text": "hydroxy", "start": 19, "end": 26}, {"text": "cinnamic acid", "start": 41, "end": 54}]}}, "schema": []}
{"input": "Despite its potential contribution to chemopreventive effects, the mechanism by which p-coumaric acid exerts its antiangiogenic actions remains elusive.", "output": {"entities": {"chemical": [{"text": "p-coumaric acid", "start": 86, "end": 101}]}}, "schema": []}
{"input": "In this study, we revealed that p-coumaric acid inhibited the sprouting of endothelial cells in rat aortic rings and inhibited the tube formation and migration of endothelial cells.", "output": {"entities": {"chemical": [{"text": "p-coumaric acid", "start": 32, "end": 47}]}}, "schema": []}
{"input": "We observed that p-coumaric acid could downregulate mRNA expression levels of the key angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor.", "output": {"entities": {"chemical": [{"text": "p-coumaric acid", "start": 17, "end": 32}]}}, "schema": []}
{"input": "Also, we demonstrated that p-coumaric acid inhibited both the AKT and ERK signaling pathways, which are known to be crucial for angiogenesis.", "output": {"entities": {"chemical": [{"text": "p-coumaric acid", "start": 27, "end": 42}]}}, "schema": []}
{"input": "Using a mouse model, we also showed that p-coumaric acid effectively suppressed tumor growth in vivo by lowering hemoglobin contents.", "output": {"entities": {"chemical": [{"text": "p-coumaric acid", "start": 41, "end": 56}]}}, "schema": []}
{"input": "Collectively, these findings indicate that p-coumaric acid possesses potent anticancer properties due to the inhibition of angiogenesis in vivo.", "output": {"entities": {"chemical": [{"text": "p-coumaric acid", "start": 43, "end": 58}]}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Fatty acid composition of selected macrophytes.", "output": {"entities": {"chemical": [{"text": "Fatty acid", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The content of total lipids and the fatty acid (FA) profile were determined for eight macroalgae (Cystoseira abies-marina, Fucus spiralis, Chaetomorpha pachynema, Codium elisabethae, Porphyra sp., Osmundea pinnatifida, Pterocladiella capillacea and Sphaeroccoccus coronopifolius).", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 36, "end": 46}]}}, "schema": []}
{"input": "Total lipids were extracted using a solvent mixture of methanol/chloroform (2/1, v/v) and further derivatised to FA methyl esters (FAME).", "output": {"entities": {"chemical": [{"text": "methanol", "start": 55, "end": 63}, {"text": "chloroform", "start": 64, "end": 74}, {"text": "FA methyl esters", "start": 113, "end": 129}, {"text": "FAME", "start": 131, "end": 135}]}}, "schema": []}
{"input": "The analyses of FAME samples were performed by gas chromatography coupled to a flame ionisation detector.", "output": {"entities": {"chemical": [{"text": "FAME", "start": 16, "end": 20}]}}, "schema": []}
{"input": "The total lipid content ranged from 0. 06 to 3. 54 g (per 100 g).", "output": {"entities": {}}, "schema": []}
{"input": "The most abundant saturated FA were palmitic (C16: 0) and myristic (C14: 0), while oleic (C18: 1 n-9) was the dominant monounsaturated acid.", "output": {"entities": {"chemical": [{"text": "palmitic", "start": 36, "end": 44}, {"text": "C16: 0", "start": 46, "end": 52}, {"text": "myristic", "start": 58, "end": 66}, {"text": "C14: 0", "start": 68, "end": 74}, {"text": "oleic", "start": 83, "end": 88}, {"text": "C18: 1", "start": 90, "end": 96}, {"text": "monounsaturated acid", "start": 119, "end": 139}]}}, "schema": []}
{"input": "All seaweeds contained linoleic FA (C18: 2 n-6).", "output": {"entities": {"chemical": [{"text": "linoleic FA", "start": 23, "end": 34}, {"text": "C18: 2", "start": 36, "end": 42}]}}, "schema": []}
{"input": "The alpha-linolenic (C18: 3 n-3) and eicosapentaenoic (20: 5 n-3) acids were present only in Porphyra sp.", "output": {"entities": {"chemical": [{"text": "alpha-linolenic", "start": 4, "end": 19}, {"text": "C18: 3", "start": 21, "end": 27}, {"text": "eicosapentaenoic", "start": 37, "end": 53}]}}, "schema": []}
{"input": "(3. 34% +/- 0. 13) and C. pachynema (0. 47% +/- 0. 12), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The n-6/n-3 and h/H ratios were low, suggesting a high nutritional value of the algae studied.", "output": {"entities": {"chemical": [{"text": "H", "start": 18, "end": 19}]}}, "schema": []}
{"input": "Improvement in solubility and bioavailability of puerarin by mechanochemical preparation.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 49, "end": 57}]}}, "schema": []}
{"input": "An efficient and solvent-free procedure was developed to improve the solubility and bioavailability of the poorly water-soluble drug puerarin by mechanochemical technology.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 133, "end": 141}]}}, "schema": []}
{"input": "The stable inclusion complex of puerarin and 2-hydroxypropyl-beta-cyclodextrin (HPCD) was prepared by a ball mill under the following conditions: equimolar ratio of puerarin to HPCD; rotational speed of 250 rpm; milling time of 90 min; steel balls of 22 mm diameter.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 32, "end": 40}, {"text": "2-hydroxypropyl-beta-cyclodextrin", "start": 45, "end": 78}, {"text": "HPCD", "start": 80, "end": 84}, {"text": "HPCD", "start": 177, "end": 181}]}}, "schema": []}
{"input": "The solid complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometry (XRD), and fourier transformation-infrared spectroscopy (FT-IR).", "output": {"entities": {}}, "schema": []}
{"input": "Mechanochemical action could result in enhanced molecular encapsulation, homogeneous distribution and amorphization of the drug.", "output": {"entities": {}}, "schema": []}
{"input": "In comparison to puerarin, a 1. 64-fold increase in absolute bioavailability was obtained.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 17, "end": 25}]}}, "schema": []}
{"input": "The solubility of the inclusion complex was 25. 33-fold higher and the drug release amount reached 79. 44% at 15 min, 2. 76-fold higher.", "output": {"entities": {}}, "schema": []}
{"input": "Design and evaluation of a self-microemulsifying drug delivery system for apigenin.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 74, "end": 82}]}}, "schema": []}
{"input": "Objective of this study was to prepare, characterize and evaluate a self-microemulsifying drug delivery system (SMEDDS) with the aim to improve the solubility and dissolution of apigenin.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 178, "end": 186}]}}, "schema": []}
{"input": "Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of apigenin loaded SMEDDS was optimized by a simplex lattice experiment design.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 129, "end": 137}]}}, "schema": []}
{"input": "The optimal formulation of SMEDDS obtained was comprised of 60% Cremophor ((R)) EL, 30% Transcutol ((R)) HP and 10% Capryol (TM) 90.", "output": {"entities": {"chemical": [{"text": "Transcutol", "start": 88, "end": 98}, {"text": "Capryol", "start": 116, "end": 123}]}}, "schema": []}
{"input": "The equilibrium solubility of apigenin in SMEDDS was about 15 mg/g, and it could increase the solubility of apigenin in water for about 7500 folds.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 30, "end": 38}, {"text": "apigenin", "start": 108, "end": 116}]}}, "schema": []}
{"input": "Apigenin loaded SMEDDS could turn into microemulsion when diluted with distilled water and the droplets were spherical under transmission electron microscope (TEM), the average particle size was 17. 1 nm and zeta potential-5. 18 mV.", "output": {"entities": {"chemical": [{"text": "Apigenin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "In vitro dissolution studies showed about 95% of apigenin was released within 10 min.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 49, "end": 57}]}}, "schema": []}
{"input": "All of the results showed that SMEDDS could enhance the solubility and dissolution of apigenin, and would be a potential carrier to improve the oral absorption of apigenin, a poorly water soluble drug.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 86, "end": 94}, {"text": "apigenin", "start": 163, "end": 171}]}}, "schema": []}
{"input": "Improvement of liver function in humans using a mixture of schisandra fruit extract and sesamin.", "output": {"entities": {"chemical": [{"text": "sesamin", "start": 88, "end": 95}]}}, "schema": []}
{"input": "This was a randomized, parallel, and placebo-controlled study.", "output": {"entities": {}}, "schema": []}
{"input": "Forty subjects were divided into a test group and a placebo group.", "output": {"entities": {}}, "schema": []}
{"input": "The study was focused on the potential effects of a mixture of Schisandra fruit extract and sesamin (hereinafter called' SCH') in the subjects with borderline high levels (40-60 U/L) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST).", "output": {"entities": {"chemical": [{"text": "sesamin", "start": 92, "end": 99}, {"text": "SCH", "start": 121, "end": 124}, {"text": "alanine", "start": 186, "end": 193}, {"text": "aspartate", "start": 220, "end": 229}]}}, "schema": []}
{"input": "Twenty subjects taking SCH (four tablets per day) and 20 subjects taking a placebo (four tablets per day) were studied.", "output": {"entities": {"chemical": [{"text": "SCH", "start": 23, "end": 26}]}}, "schema": []}
{"input": "The effects of SCH on ALT, AST, total bilirubin, direct bilirubin, free radical levels, total antioxidant status, glutathione peroxidase, glutathione reductase, and the lag time for low-density lipoprotein oxidation were determined.", "output": {"entities": {"chemical": [{"text": "SCH", "start": 15, "end": 18}, {"text": "bilirubin", "start": 38, "end": 47}, {"text": "bilirubin", "start": 56, "end": 65}, {"text": "glutathione", "start": 114, "end": 125}, {"text": "glutathione", "start": 138, "end": 149}]}}, "schema": []}
{"input": "The total test period was 5 months.", "output": {"entities": {}}, "schema": []}
{"input": "Intervention of SCH clearly reduced the levels of ALT and AST, but it made no change in the total bilirubin and direct bilirubin.", "output": {"entities": {"chemical": [{"text": "SCH", "start": 16, "end": 19}, {"text": "bilirubin", "start": 98, "end": 107}, {"text": "bilirubin", "start": 119, "end": 128}]}}, "schema": []}
{"input": "Intake of SCH also greatly increased the antioxidant capacity and decreased the values of thiobarbituric acid reactive substances, total free radicals, and superoxide anion radicals in the plasma.", "output": {"entities": {"chemical": [{"text": "SCH", "start": 10, "end": 13}, {"text": "thiobarbituric acid", "start": 90, "end": 109}, {"text": "superoxide", "start": 156, "end": 166}]}}, "schema": []}
{"input": "The activities of glutathione peroxidase and reductase in the erythrocytes were significantly increased.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 18, "end": 29}]}}, "schema": []}
{"input": "In addition, the lag time for low-density lipoprotein oxidation, an inflammatory marker, was evidently increased.", "output": {"entities": {}}, "schema": []}
{"input": "Fatty liver was found to have been significantly improved in this study.", "output": {"entities": {}}, "schema": []}
{"input": "SCH proved to have the effects of antioxidation and improving liver function.", "output": {"entities": {"chemical": [{"text": "SCH", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Most solid tumors are characterized by a metabolic shift from glucose oxidation to glycolysis, in part due to actively suppressed mitochondrial function, a state that favors resistance to apoptosis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 62, "end": 69}]}}, "schema": []}
{"input": "Suppressed mitochondrial function may also contribute to the activation of hypoxia-inducible factor 1 alpha (HIF1 alpha) and angiogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "We have previously shown that the inhibitor of pyruvate dehydrogenase kinase (PDK) dichloroacetate (DCA) activates glucose oxidation and induces apoptosis in cancer cells in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "pyruvate", "start": 47, "end": 55}, {"text": "dichloroacetate", "start": 83, "end": 98}, {"text": "DCA", "start": 100, "end": 103}, {"text": "glucose", "start": 115, "end": 122}]}}, "schema": []}
{"input": "We hypothesized that DCA will also reverse the' pseudohypoxic' mitochondrial signals that lead to HIF1 alpha activation in cancer, even in the absence of hypoxia and inhibit cancer angiogenesis.", "output": {"entities": {"chemical": [{"text": "DCA", "start": 21, "end": 24}]}}, "schema": []}
{"input": "We show that inhibition of PDKII inhibits HIF1 alpha in cancer cells using several techniques, including HIF1 alpha luciferase reporter assays.", "output": {"entities": {}}, "schema": []}
{"input": "Using pharmacologic and molecular approaches that suppress the prolyl-hydroxylase (PHD)-mediated inhibition of HIF1 alpha, we show that DCA inhibits HIF1 alpha by both a PHD-dependent mechanism (that involves a DCA-induced increase in the production of mitochondria-derived alpha-ketoglutarate) and a PHD-independent mechanism, involving activation of p53 via mitochondrial-derived H (2) O (2), as well as activation of GSK3 beta.", "output": {"entities": {"chemical": [{"text": "prolyl", "start": 63, "end": 69}, {"text": "DCA", "start": 136, "end": 139}, {"text": "DCA", "start": 211, "end": 214}, {"text": "alpha-ketoglutarate", "start": 274, "end": 293}, {"text": "H (2) O (2)", "start": 382, "end": 393}]}}, "schema": []}
{"input": "Effective inhibition of HIF1 alpha is shown by a decrease in the expression of several HIF1 alpha regulated gene products as well as inhibition of angiogenesis in vitro in matrigel assays.", "output": {"entities": {}}, "schema": []}
{"input": "More importantly, in rat xenotransplant models of non-small cell lung cancer and breast cancer, we show effective inhibition of angiogenesis and tumor perfusion in vivo, assessed by contrast-enhanced ultrasonography, nuclear imaging techniques and histology.", "output": {"entities": {}}, "schema": []}
{"input": "This work suggests that mitochondria-targeting metabolic modulators that increase pyruvate dehydrogenase activity, in addition to the recently described pro-apoptotic and anti-proliferative effects, suppress angiogenesis as well, normalizing the pseudo-hypoxic signals that lead to normoxic HIF1 alpha activation in solid tumors.", "output": {"entities": {"chemical": [{"text": "pyruvate", "start": 82, "end": 90}]}}, "schema": []}
{"input": "Macrophage cathepsin K promotes prostate tumor progression in bone.", "output": {"entities": {}}, "schema": []}
{"input": "Bone marrow macrophages (BMMs) share common progenitors with osteoclasts and are critical components of bone-tumor microenvironment; however, their function in prostate tumor growth in the skeleton has not been explored.", "output": {"entities": {}}, "schema": []}
{"input": "BMMs are the major source of inflammatory factors and proteases, including cysteine protease cathepsin K (CTSK).", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 75, "end": 83}]}}, "schema": []}
{"input": "In this study, utilizing mice deficient in CTSK, we demonstrate the critical involvement of this potent collagenase in tumor progression in bone.", "output": {"entities": {}}, "schema": []}
{"input": "We present the evidence that tumor growth and progression in the bone are impaired in the absence of CTSK.", "output": {"entities": {}}, "schema": []}
{"input": "Most importantly, we show for the first time that BMM-supplied CTSK may be involved in CCL2-and COX-2-driven pathways that contribute to tumor progression in bone.", "output": {"entities": {}}, "schema": []}
{"input": "Together, our data unravel novel roles for CTSK in macrophage-regulated processes, and provide evidence for close interplay between inflammatory, osteolytic and tumor cell-driven events in the bone-tumor microenvironment.", "output": {"entities": {}}, "schema": []}
{"input": "Single non-ionic surfactant based self-nanoemulsifying drug delivery systems: formulation, characterization, cytotoxicity and permeability enhancement study.", "output": {"entities": {}}, "schema": []}
{"input": "Single non-ionic surfactant based self-nanoemulsifying drug delivery system (SNEDDS) was formulated and characterised for poor water soluble drug, Atorvastatin calcium.", "output": {"entities": {"chemical": [{"text": "Atorvastatin calcium", "start": 147, "end": 167}]}}, "schema": []}
{"input": "Capmul MCM oil showing highest solubility for Atorvastatin calcium was selected as oil phase.", "output": {"entities": {"chemical": [{"text": "Atorvastatin calcium", "start": 46, "end": 66}]}}, "schema": []}
{"input": "Self-nanoemulsifying capacity of Cremophor RH 40, Cremophor EL, Tween 20, Tween 60, Tween 80 and Labrasol were tested for the selected oil.", "output": {"entities": {"chemical": [{"text": "Tween 20", "start": 64, "end": 72}, {"text": "Tween 60", "start": 74, "end": 82}, {"text": "Tween 80", "start": 84, "end": 92}]}}, "schema": []}
{"input": "In vitro dissolution studies were performed and were characterized by t85% and dissolution efficiency (DE).", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxicity of the formulations and permeation enhancement of the drug across caco-2 cell monolayer was assessed.", "output": {"entities": {}}, "schema": []}
{"input": "Capmul MCM was found to be better nanoemulsified in decreasing order of Cremophor RH 40 > Cremophor EL > Tween 20 > Tween 60 > Tween 80.", "output": {"entities": {"chemical": [{"text": "Tween 20", "start": 105, "end": 113}, {"text": "Tween 60", "start": 116, "end": 124}, {"text": "Tween 80", "start": 127, "end": 135}]}}, "schema": []}
{"input": "Values of droplet size (range 11-83 nm), polydispersity index (range 0. 07-0. 65); zeta potential (range-3. 97 to-19. 0) and cloud point (60-85 degrees C) before and after drug loading proves the uniformity and stability of the formulations.", "output": {"entities": {}}, "schema": []}
{"input": "SNEDDS formulated with Tween 20 surfactant showed enhanced dissolution with t85% and DE values at 10 min and 78. 70, respectively.", "output": {"entities": {"chemical": [{"text": "Tween 20", "start": 23, "end": 31}]}}, "schema": []}
{"input": "None of the formulation showed cytotoxicity at the concentration tested.", "output": {"entities": {}}, "schema": []}
{"input": "Tween 20 based SNEDDS enhanced permeation of the drug as compared with pure drug across cell lines.", "output": {"entities": {"chemical": [{"text": "Tween 20", "start": 0, "end": 8}]}}, "schema": []}
{"input": "It can be concluded that SNEDDS can be formulated by using single non-ionic surfactant system for enhance dissolution and absorption of poorly soluble drug, Atorvastatin calcium.", "output": {"entities": {"chemical": [{"text": "Atorvastatin calcium", "start": 157, "end": 177}]}}, "schema": []}
{"input": "Does the light influence astaxanthin production in Xanthophyllomyces dendrorhous?", "output": {"entities": {"chemical": [{"text": "astaxanthin", "start": 25, "end": 36}]}}, "schema": []}
{"input": "Astaxanthin (C40H52O4) is an important natural pigment that has considerable promising applications in human health.", "output": {"entities": {"chemical": [{"text": "Astaxanthin", "start": 0, "end": 11}, {"text": "C40H52O4", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Until now, many efforts were made aimed to develop economically sustainable bioprocesses alternative to the chemical synthesis, to satisfy the increasing demand of this ketocarotenoid from feed, food and cosmetic industries.", "output": {"entities": {}}, "schema": []}
{"input": "The extraction of natural astaxanthin from the yeast Xanthophyllomyces dendrorhous till now seems to be rather expensive if compared with chemically synthesized astaxanthin.", "output": {"entities": {"chemical": [{"text": "astaxanthin", "start": 26, "end": 37}, {"text": "astaxanthin", "start": 161, "end": 172}]}}, "schema": []}
{"input": "In this article, astaxanthin production by Xanthophyllomyces dendrorhous under two different conditions was studied: a first effort was made using a conventional reactor while a second using an enlightened one.", "output": {"entities": {"chemical": [{"text": "astaxanthin", "start": 17, "end": 28}]}}, "schema": []}
{"input": "This research was aimed also to optimise astaxanthin production by testing the influence of the light and of some nutrient sources.", "output": {"entities": {"chemical": [{"text": "astaxanthin", "start": 41, "end": 52}]}}, "schema": []}
{"input": "From fermentation tests, an astaxanthin yield ranging about 970 micro g g (-1) was obtained after fed batch cultivation in the conventional reactor.", "output": {"entities": {"chemical": [{"text": "astaxanthin", "start": 28, "end": 39}]}}, "schema": []}
{"input": "In the enlightened reactor lower values, about 930 micro g g (-1), were found.", "output": {"entities": {}}, "schema": []}
{"input": "Silibinin triggers apoptosis and cell-cycle arrest of SGC7901 cells.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Silibinin, a flavonoid compound, has shown to be of chemopreventive potential against many cancers.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 0, "end": 9}, {"text": "flavonoid", "start": 13, "end": 22}]}}, "schema": []}
{"input": "However, its efficacy against gastric cancer has not been well elucidated.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we assessed the activity of Silibinin on apoptosis and cell-cycle arrest in human gastric cells culture system using SGC-7901 as the model.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 34, "end": 43}]}}, "schema": []}
{"input": "Silibinin treatment could inhibit the cell growth and cause a prominent G2 phase arrest and apoptosis in dose-and time-dependent manner.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In mechanistic studies, Silibinin decreased the protein level of p34cdc2, which might be the possible molecular mechanism of Silibinin efficacy on the growth inhibition in SGC-7901 cells.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 24, "end": 33}, {"text": "Silibinin", "start": 125, "end": 134}]}}, "schema": []}
{"input": "In addition, Silibinin caused an increase in p53 and p21 protein level as well as mRNA levels.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 13, "end": 22}]}}, "schema": []}
{"input": "Interestingly, Silibinin-induced apoptosis in SGC-7901 cells was independent of caspases activation.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 15, "end": 24}]}}, "schema": []}
{"input": "These results indicated that Silibinin is a cell-cycle regulator and apoptosis inducer in human gastric carcinoma SGC-7901 cells and might be used as a candidate chemopreventive agent for gastric carcinoma prevention and intervention.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 29, "end": 38}]}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Acetylation and deacetylation--novel factors in muscle wasting.", "output": {"entities": {}}, "schema": []}
{"input": "We review recent evidence that acetylation and deacetylation of cellular proteins, including transcription factors and nuclear cofactors, may be involved in the regulation of muscle mass.", "output": {"entities": {}}, "schema": []}
{"input": "The level of protein acetylation is balanced by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and studies suggest that this balance is perturbed in muscle wasting.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperacetylation of transcription factors and nuclear cofactors regulating gene transcription in muscle wasting may influence muscle mass.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, hyperacetylation may render proteins susceptible to degradation by different mechanisms, including intrinsic ubiquitin ligase activity exerted by HATs and by dissociation of proteins from cellular chaperones.", "output": {"entities": {}}, "schema": []}
{"input": "In recent studies, inhibition of p300/HAT expression and activity and stimulation of SIRT1-dependent HDAC activity reduced glucocorticoid-induced catabolic response in skeletal muscle, providing further evidence that hyperacetylation plays a role in muscle wasting.", "output": {"entities": {}}, "schema": []}
{"input": "It should be noted, however, that although several studies advocate a role of hyperacetylation in muscle wasting, apparently contradictory results have also been reported.", "output": {"entities": {}}, "schema": []}
{"input": "For example, muscle atrophy caused by denervation or immobilization may be associated with reduced, rather than increased, protein acetylation.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, whereas hyperacetylation results in increased degradation of certain proteins, other proteins may be stabilized by increased acetylation.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the role of acetylation and deacetylation in the regulation of muscle mass may be both condition-and protein-specific.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of HATs and HDACs on the regulation of muscle mass, as well as methods to modulate protein acetylation, is an important area for continued research aimed at preventing and treating muscle wasting.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of an antiosteoporosis herbal formula containing epimedii herba, ligustri lucidi fructus and psoraleae fructus on density and structure of rat long bones under tail-suspension, and its mechanisms of action.", "output": {"entities": {}}, "schema": []}
{"input": "An innovative anti-osteoporosis herbal formula containing Epimedii Herba, Ligustri Lucidi Fructus and Psoraleae Fructus (ELP) has been previously shown its bone protecting effects in ovariectomized osteoporotic rats and also in post-menopausal osteopenic women.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to investigate the efficacy of ELP against bone loss during physical inactivity or weightlessness.", "output": {"entities": {}}, "schema": []}
{"input": "A hindlimb unloading tail-suspended rat model was used for studying the effects of ELP on bone mineral density (BMD) and bone micro-architecture.", "output": {"entities": {}}, "schema": []}
{"input": "For in vitro mechanistic studies, rat mesenchymal stem cells (MSCs) and mouse macrophage cells (RAW264. 7) were used for studying the effects of ELP on osteogenic/adipogenic differentiations and osteoclastogenesis, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Our data illustrated that ELP had a significant preventive effect against bone loss induced by tail-suspension (TS) at day 28 (p < 0. 01) as indicated in the reduction in BMD loss and the preservation of bone micro-architecture.", "output": {"entities": {}}, "schema": []}
{"input": "ELP could significantly promote the osteogenesis and suppress the adipogenesis (p < 0. 05) in MSCs.", "output": {"entities": {}}, "schema": []}
{"input": "Besides, significant inhibition of osteoclast formation (p < 0. 01) was found in ELP-treated RAW264. 7 cells upon receptor activator of nuclear factor kappa-B ligand induction.", "output": {"entities": {}}, "schema": []}
{"input": "Our study presents the first scientific evidence that ELP had a significant preventive effect against bone loss induced by TS through the actions of enhancing osteogenesis, suppressing adipogenesis and osteoclastogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Two new alkaloid galactosides from the kernel of Prinsepia uniflora.", "output": {"entities": {"chemical": [{"text": "alkaloid galactosides", "start": 8, "end": 29}]}}, "schema": []}
{"input": "Two new alkaloid galactosides have been isolated from the kernel of Prinsepia uniflora.", "output": {"entities": {"chemical": [{"text": "alkaloid galactosides", "start": 8, "end": 29}]}}, "schema": []}
{"input": "Their structures were elucidated as 5-[(alpha-D-galactopyranosyloxy) methyl]-1H-pyrrole-2-carbaldehyde (1) and 6-[(alpha-D-galactopyranosyloxy) methyl]-3-pyridinol (2) by various spectroscopic means including HR-ESI-MS, IR, 1D and 2D NMR.", "output": {"entities": {"chemical": [{"text": "5-[(alpha-D-galactopyranosyloxy) methyl]-1H-pyrrole-2-carbaldehyde", "start": 36, "end": 102}, {"text": "6-[(alpha-D-galactopyranosyloxy) methyl]-3-pyridinol", "start": 111, "end": 163}]}}, "schema": []}
{"input": "The determined structures were characterized with a unit of galactose which is rarely seen in the previously isolated pyrrole and pyridinol compounds.", "output": {"entities": {"chemical": [{"text": "galactose", "start": 60, "end": 69}, {"text": "pyrrole", "start": 118, "end": 125}, {"text": "pyridinol", "start": 130, "end": 139}]}}, "schema": []}
{"input": "mGlu2/3 and mGlu5 receptors: potential targets for novel antidepressants.", "output": {"entities": {}}, "schema": []}
{"input": "Major depressive disorder is among the most prevalent forms of mental illness.", "output": {"entities": {}}, "schema": []}
{"input": "All currently available antidepressant medications have stemmed from study of the mechanisms of serendipitously discovered drugs, and only 30-50% of patients exhibit remission and frequently at least 3-4 weeks are required for manifestation of significant therapeutic effects.", "output": {"entities": {}}, "schema": []}
{"input": "To overcome these drawbacks, discovering novel neuronal mechanisms of pathophysiology of depression as well as more effective treatments are necessary.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on the metabotropic glutamate (mGlu) receptors and their potential for drug targets for the treatment of depression.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 40, "end": 49}]}}, "schema": []}
{"input": "In particular, accumulating evidence has indicated the potential importance and usefulness of agents acting on mGlu2/3 and mGlu5 receptors.", "output": {"entities": {}}, "schema": []}
{"input": "Preclinical and clinical evidence of mGlu2/3 receptor ligands and mGlu5 receptor antagonists are described.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, their potential in clinic will be discussed in the context of neuronal mechanisms of ketamine, an agent recently demonstrated a robust effect for patients with treatment-resistant depression.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 95, "end": 103}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Combining GLP-1 receptor agonists with insulin: therapeutic rationales and clinical findings.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control.", "output": {"entities": {}}, "schema": []}
{"input": "However, there is a degree of inertia among physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia.", "output": {"entities": {}}, "schema": []}
{"input": "Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose-dependent manner, thus conferring glycaemic control with a low incidence of hypoglycaemia.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 115, "end": 122}]}}, "schema": []}
{"input": "GLP-1RAs also promote weight loss, and have beneficial effects on markers of beta cell function, lipid levels, blood pressure and cardiovascular risk markers.", "output": {"entities": {}}, "schema": []}
{"input": "However, the durability of their effectiveness is unknown and, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited.", "output": {"entities": {}}, "schema": []}
{"input": "The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 84, "end": 91}]}}, "schema": []}
{"input": "Data from clinical studies support the therapeutic potential of GLP-1RA-insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, the physiological and pharmacological rationale for using GLP-1RA and insulin therapies in combination is discussed, and data from clinical studies that have assessed the efficacy and safety of this treatment strategy are outlined.", "output": {"entities": {}}, "schema": []}
{"input": "Metabonomic Study of Genkwa Flos-induced Hepatotoxicity and Effect of Herb-Processing Procedure on Toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "A urinary metabonomic approach based on ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) was developed to study the metabolic disturbances caused by the administration of Genkwa Flos (GF) to rats.", "output": {"entities": {}}, "schema": []}
{"input": "Potential biomarkers of GF-induced toxic effects were screened out and identified, and the underlying toxicological mechanism as well as the detoxification of vinegar-processing procedure on this herb was discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Urine samples were analyzed by the established UPLC-MS method.", "output": {"entities": {}}, "schema": []}
{"input": "With the help of serum biochemistry and histopathology results, metabolic disturbances induced by the exposure to GF and the detoxification of processing procedure were confirmed.", "output": {"entities": {}}, "schema": []}
{"input": "The differences in the metabolic profiles of healthy and treated rats were clearly discriminated with the principal component analysis of the chromatographic data.", "output": {"entities": {}}, "schema": []}
{"input": "Eight significantly changed metabolites were identified and interpreted as biomarkers for the hepatotoxicity and detoxification of processing procedure.", "output": {"entities": {}}, "schema": []}
{"input": "This study indicated that a UPLC-MS-based metabonomic analysis of urine samples could be considered as a promising tool to predict the hepatotoxicity induced by the GF and the detoxification of traditional vinegar-processing procedure on this herb.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Group III and subtype 4 metabotropic glutamate receptor agonists: discovery and pathophysiological applications in Parkinson' s disease.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 37, "end": 46}]}}, "schema": []}
{"input": "Restoring the balance between excitatory and inhibitory circuits in the basal ganglia, following the loss of dopaminergic (DA) neurons of the substantia nigra pars compacta, represents a major challenge to treat patients affected by Parkinson' s disease (PD).", "output": {"entities": {}}, "schema": []}
{"input": "The imbalanced situation in favor of excitation in the disease state may also accelerate excitotoxic processes, thereby representing a potential target for neuroprotective therapies.", "output": {"entities": {}}, "schema": []}
{"input": "Reducing the excitatory action of glutamate, the major excitatory neurotransmitter in the basal ganglia, should lead to symptomatic improvement for PD patients and may promote the survival of DA neurons.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 34, "end": 43}]}}, "schema": []}
{"input": "Recent studies have focused on the modulatory action of metabotropic glutamate (mGlu) receptors on neurodegenerative diseases including PD.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 69, "end": 78}]}}, "schema": []}
{"input": "Group III mGlu receptors, including subtypes 4, 7 and 8, are largely expressed in the basal ganglia.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies highlight the use of selective mGlu4 receptor positive allosteric modulators (PAMs) for the treatment of PD.", "output": {"entities": {}}, "schema": []}
{"input": "Here we review the effects of newly-designed group-III orthosteric agonists on neuroprotection, neurorestoration and reduction of l-DOPA induced dyskinesia in animal models of PD.", "output": {"entities": {"chemical": [{"text": "l-DOPA", "start": 130, "end": 136}]}}, "schema": []}
{"input": "The combination of orthosteric mGlu4 receptor selective agonists with PAMs may open new avenues for the symptomatic treatment of PD.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated rDNA transcription.", "output": {"entities": {}}, "schema": []}
{"input": "The transcription factor c-Myc has a critical role in cell proliferation and growth.", "output": {"entities": {}}, "schema": []}
{"input": "The control of ribosome biogenesis by c-Myc through the regulation of transcription mediated by all three RNA polymerases is essential for c-Myc-driven proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, in the nucleolus, c-Myc has been shown to be recruited to ribosomal DNA and activate RNA polymerase (pol) I-mediated transcription of ribosomal RNA (rRNA) genes.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, c-Myc accumulates in nucleoli upon inhibition of the proteasome, suggesting nucleolar localization also has a role in c-Myc proteolysis.", "output": {"entities": {}}, "schema": []}
{"input": "Nucleophosmin (NPM), a predominantly nucleolar protein, is also critical in ribosome biogenesis and, like c-Myc, is found overexpressed in many types of tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, we demonstrated that NPM directly interacts with c-Myc and controls c-Myc-induced hyperproliferation and transformation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that NPM is necessary for the localization of c-Myc protein to nucleoli, whereas c-Myc nucleolar localization is independent of p53, Mdm2 and ARF.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, high transient NPM expression enhances c-Myc nucleolar localization, leading to increased c-Myc proteolysis.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, NPM is necessary for the ability of c-Myc to induce rRNA synthesis in the nucleolus, and constitutive NPM overexpression stimulates c-Myc-mediated rRNA synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these results demonstrate an essential role for NPM in c-Myc nucleolar localization and c-Myc-mediated rDNA transcription.", "output": {"entities": {}}, "schema": []}
{"input": "Opposing functions of Fbxw7 in keratinocyte growth, differentiation and skin tumorigenesis mediated through negative regulation of c-Myc and Notch.", "output": {"entities": {}}, "schema": []}
{"input": "The tumor suppressor Fbxw7 (also known as Sel-10, hCdc4, hAgo, or Fbw7) is an F-box protein that functions as the substrate-recognition subunit of an SCF ubiquitin ligase complex and targets a group of oncoproteins for degradation.", "output": {"entities": {}}, "schema": []}
{"input": "We now show that Fbxw7 regulates the proliferation and differentiation of keratinocytes by mediating the degradation of c-Myc and Notch proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Fbxw7-deficient keratinocytes showed an increased proliferative capacity that was dependent on the accumulation of c-Myc but not on that of Notch.", "output": {"entities": {}}, "schema": []}
{"input": "Fbxw7 deficiency also resulted in the premature differentiation of keratinocytes in a manner dependent on both c-Myc and Notch.", "output": {"entities": {}}, "schema": []}
{"input": "Although Fbxw7-deficient keratinocytes proliferated excessively in vitro, loss of Fbxw7 did not predispose keratinocytes to the formation of squamous cell carcinoma in vivo induced by the expression of oncogenic Ras, possibly because the stem cell population of keratinocytes becomes exhausted as a result of enhanced Notch activity.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, suppression of Notch signaling by additional ablation of RBP-J in Fbxw7-deficient keratinocytes conferred a more aggressive tumorigenic capacity.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these results indicate that Fbxw7 controls the proliferation and differentiation of keratinocytes, and that it exerts both inhibitory and stimulatory actions in skin carcinogenesis by counteracting the proliferation-promoting effect of c-Myc and the tumor-suppressive effect of Notch, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Risk factors for Parkinson' s disease may differ in men and women: an exploratory study.", "output": {"entities": {}}, "schema": []}
{"input": "Although several environmental and genetic risk or protective factors have been associated with Parkinson' s disease (PD), their interactions overall and in men and women separately remain unknown.", "output": {"entities": {}}, "schema": []}
{"input": "We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995.", "output": {"entities": {}}, "schema": []}
{"input": "Each incident case was matched by age (+/- 1 year) and sex to a general population control.", "output": {"entities": {}}, "schema": []}
{"input": "We considered the following 12 risk or protective factors: personal history of head trauma, pesticide use, immunologic diseases, anemia, hysterectomy (in women only), cigarette smoking, coffee consumption, and education; and family history of parkinsonism, essential tremor, dementia, or psychiatric disorders.", "output": {"entities": {}}, "schema": []}
{"input": "We used recursive partitioning analyses to explore interactions overall and in men and women separately and used logistic regression analyses to test for interactions.", "output": {"entities": {}}, "schema": []}
{"input": "In the overall group, we observed the independent effects of anemia, lack of coffee consumption (never vs. ever), and head trauma; however, the findings were different in men and women.", "output": {"entities": {}}, "schema": []}
{"input": "In men, we observed the independent effects of lack of coffee consumption (never vs. ever), head trauma, and pesticide use, and a suggestive synergistic interaction between immunologic diseases and family history of dementia.", "output": {"entities": {}}, "schema": []}
{"input": "By contrast, in women, anemia was the most important factor and we observed a suggestive synergistic interaction between anemia and higher education.", "output": {"entities": {}}, "schema": []}
{"input": "Risk factors for PD and their interactions may differ in men and women.", "output": {"entities": {}}, "schema": []}
{"input": "Solid lipid nanoparticles and nanosuspension of adefovir dipivoxil for bioavailability improvement: formulation, characterization, pharmacokinetic and biodistribution studies.", "output": {"entities": {"chemical": [{"text": "adefovir dipivoxil", "start": 48, "end": 66}]}}, "schema": []}
{"input": "The present study was aimed at developing colloidal formulations like solid lipid nanoparticles (SLN) and nanosuspension (NS) for improving bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor which displays poor oral bioavailability.", "output": {"entities": {"chemical": [{"text": "adefovir dipivoxil", "start": 159, "end": 177}, {"text": "nucleoside", "start": 186, "end": 196}]}}, "schema": []}
{"input": "SLNs were prepared by solvent injection method while NS was prepared by pearl milling method.", "output": {"entities": {}}, "schema": []}
{"input": "The prepared formulations were characterized for physicochemical parameters such as particle size, zeta potential, drug content, X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC).", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetic and biodistribution studies were performed in mice to evaluate in vivo fate of the formulations.", "output": {"entities": {}}, "schema": []}
{"input": "The SLNs showed particle size of 267 +/- 18 nm and entrapment efficiency of 73. 5 +/- 2. 12%.", "output": {"entities": {}}, "schema": []}
{"input": "The particle size obtained for NS was 393 +/- 13 nm against 710 +/- 70 mu m for bulk drug, which led to significant improvement in saturation solubility.", "output": {"entities": {}}, "schema": []}
{"input": "DSC and XRD studies of NS and SLN showed reduction in crystallinity while in vitro studies showed improved dissolution rate in both cases.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetics studies of orally administered formulations in mice exhibited higher plasma concentration compared to plain drug.", "output": {"entities": {}}, "schema": []}
{"input": "Biodistribution studies showed higher accumulation of drug in liver, kidneys, intestine and stomach.", "output": {"entities": {}}, "schema": []}
{"input": "The higher concentration of AD in liver after 24 hr highlights its potential advantage for effective treatment of chronic hepatitis infection.", "output": {"entities": {}}, "schema": []}
{"input": "The relative bioavailability for adefovir NS and SLN were 52. 46% and 78. 23% respectively compared to 34. 34% bioavailability obtained after administration of adefovir micro suspension (AMS), indicating suitability of both nanoparticulate formulations for improving bioavailability.", "output": {"entities": {"chemical": [{"text": "adefovir", "start": 33, "end": 41}, {"text": "adefovir", "start": 160, "end": 168}]}}, "schema": []}
{"input": "SLNs were found to performed better as compared to NS for improving the bioavailability of AD.", "output": {"entities": {}}, "schema": []}
{"input": "A new bromobenzyl methyl sulphoxide from marine red alga Symphyocladia latiuscula.", "output": {"entities": {"chemical": [{"text": "bromobenzyl methyl sulphoxide", "start": 6, "end": 35}]}}, "schema": []}
{"input": "A new bromophenol, 2, 3, 6-tribromo-4, 5-dihydroxybenzyl methyl sulphoxide, was isolated from the EtOH extract of the marine alga Symphyocladia latiuscula.", "output": {"entities": {"chemical": [{"text": "bromophenol", "start": 6, "end": 17}, {"text": "2, 3, 6-tribromo-4, 5-dihydroxybenzyl methyl sulphoxide", "start": 19, "end": 74}, {"text": "EtOH", "start": 98, "end": 102}]}}, "schema": []}
{"input": "Its structure was confirmed by spectroscopic methods (1D-and 2D-NMR, HR-ESI-MS).", "output": {"entities": {}}, "schema": []}
{"input": "This new bromophenol showed moderate antifungal activity against Candida albicans with MIC value of 37. 5 micro g mL (-1).", "output": {"entities": {"chemical": [{"text": "bromophenol", "start": 9, "end": 20}]}}, "schema": []}
{"input": "Aromadendrine, a new component of the flavonoid pattern of Olea europaea L. and its anti-inflammatory activity.", "output": {"entities": {"chemical": [{"text": "Aromadendrine", "start": 0, "end": 13}, {"text": "flavonoid", "start": 38, "end": 47}]}}, "schema": []}
{"input": "Leaves of Olea europaea, cultivar Nocellara del Belice, were examined with respect to the medium-polar fraction, obtained by an ethyl acetate extraction of the whole extract.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 128, "end": 141}]}}, "schema": []}
{"input": "In the medium polar fraction, we isolated the two hydroxy-phenyl-ethyl alcohols (hydroxyl-tyrosol and tyrosol) that are the main component of olives.", "output": {"entities": {"chemical": [{"text": "hydroxy-phenyl-ethyl alcohols", "start": 50, "end": 79}, {"text": "hydroxyl-tyrosol", "start": 81, "end": 97}, {"text": "tyrosol", "start": 102, "end": 109}]}}, "schema": []}
{"input": "In addition, we isolated a flavonoidic compound, aromadendrine, a dihydroflavonol yet known but quite rare in nature.", "output": {"entities": {"chemical": [{"text": "flavonoidic", "start": 27, "end": 38}, {"text": "aromadendrine", "start": 49, "end": 62}, {"text": "dihydroflavonol", "start": 66, "end": 81}]}}, "schema": []}
{"input": "It is the first time that aromadendrine is isolated in O. europaea and we studied the aromadendrine biological activity.", "output": {"entities": {"chemical": [{"text": "aromadendrine", "start": 26, "end": 39}, {"text": "aromadendrine", "start": 86, "end": 99}]}}, "schema": []}
{"input": "In particular, the ability of aromadendrine to reduce the inflammation induced in normal keratinocytes using an in vitro cell model was evaluated.", "output": {"entities": {"chemical": [{"text": "aromadendrine", "start": 30, "end": 43}]}}, "schema": []}
{"input": "The results of the present research indicate aromadendrine as a novel component in O. europaea with effective activity against skin inflammation.", "output": {"entities": {"chemical": [{"text": "aromadendrine", "start": 45, "end": 58}]}}, "schema": []}
{"input": "Ibuprofen ion-exchange fiber complex: improved dissolution and gastric tolerance based on ion exchange.", "output": {"entities": {"chemical": [{"text": "Ibuprofen", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The purpose of the present study is to develop a novel method to improve the dissolution of water-insoluble drug ibuprofen and the gastric tolerance of this non-steroidal anti-inflammatory drug which has potentially serious gastrointestinal side effects.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 113, "end": 122}]}}, "schema": []}
{"input": "This method is based on ion exchange of ion-exchange fibers.", "output": {"entities": {}}, "schema": []}
{"input": "Water-insoluble drug ibuprofen was dispersed in deionized water, and then the ion-exchange fibers in OH (-) type was immersed in it.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 21, "end": 30}, {"text": "OH (-)", "start": 101, "end": 107}]}}, "schema": []}
{"input": "Ibuprofen and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction.", "output": {"entities": {"chemical": [{"text": "Ibuprofen", "start": 0, "end": 9}]}}, "schema": []}
{"input": "This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange.", "output": {"entities": {}}, "schema": []}
{"input": "Confirmed by the X-ray diffraction and the scanning electron microscopy, the ibuprofen combined onto the ion-exchange fibers was in a highly molecular level dispersed state.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 77, "end": 86}]}}, "schema": []}
{"input": "The improved dissolution of ibuprofen ion-exchange fiber complexes is likely to originate from this ibuprofen' s highly dispersed state.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 28, "end": 37}, {"text": "ibuprofen", "start": 100, "end": 109}]}}, "schema": []}
{"input": "Due to this, ibuprofen' s highly dispersed state, ibuprofen ion-exchange fiber complexes significantly decreases the gastrointestinal side effects of ibuprofen by avoiding the solid ibuprofen' s educing.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 13, "end": 22}, {"text": "ibuprofen", "start": 50, "end": 59}, {"text": "ibuprofen", "start": 150, "end": 159}, {"text": "ibuprofen", "start": 182, "end": 191}]}}, "schema": []}
{"input": "The present study showed that ibuprofen ion-exchange fiber complexes have the two-fold advantages.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 30, "end": 39}]}}, "schema": []}
{"input": "One is to improve the dissolution of ibuprofen.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 37, "end": 46}]}}, "schema": []}
{"input": "The other is to decrease the ibuprofen' s gastrointestinal toxicity.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 29, "end": 38}]}}, "schema": []}
{"input": "A modern approach for controlled transdermal delivery of diflunisal: optimization and in vivo evaluation.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 57, "end": 67}]}}, "schema": []}
{"input": "The purpose of the present work was to elaborate an optimized transdermal therapeutic system for diflunisal.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 97, "end": 107}]}}, "schema": []}
{"input": "Selection of suitable ingredients was done via solubility and phase behavior studies.", "output": {"entities": {}}, "schema": []}
{"input": "Composition of microemulsion (ME) systems consisting of butyl lactate, Brij ((R)) 97, Transcutol ((R)) and water was optimized using augmented simplex lattice mixture design.", "output": {"entities": {"chemical": [{"text": "butyl lactate", "start": 56, "end": 69}, {"text": "Brij", "start": 71, "end": 75}, {"text": "Transcutol", "start": 86, "end": 96}]}}, "schema": []}
{"input": "The independent variables selected were the percentages of butyl lactate, surfactant mixture and water.", "output": {"entities": {"chemical": [{"text": "butyl lactate", "start": 59, "end": 72}]}}, "schema": []}
{"input": "The dependent variables were refractive index, pH, conductivity, viscosity, drug solubility in the ME formulation and the ex vivo skin permeation flux.", "output": {"entities": {}}, "schema": []}
{"input": "Mathematical equations and response surface plots were used to relate the dependent and independent variables.", "output": {"entities": {}}, "schema": []}
{"input": "The statistical validity of the polynomials was established.", "output": {"entities": {}}, "schema": []}
{"input": "Optimized formulation factors were selected by desirability approach.", "output": {"entities": {}}, "schema": []}
{"input": "The optimized ME formulation was converted into gel using Carbomer ((R)) 934.", "output": {"entities": {"chemical": [{"text": "Carbomer", "start": 58, "end": 66}]}}, "schema": []}
{"input": "The microemulsion based gel (MBG) showed better spreadability and 5. 07-fold increase in the transdermal flux than Carbomer ((R)) 934 gel.", "output": {"entities": {"chemical": [{"text": "Carbomer", "start": 115, "end": 123}]}}, "schema": []}
{"input": "The in vivo antihyperalgesia assay performed on mice showed significant reduction of the licking time in the treated group compared to the control group.", "output": {"entities": {}}, "schema": []}
{"input": "This demonstrated the reliability of the simplex lattice statistical design for predicting optimum ME formulation.", "output": {"entities": {}}, "schema": []}
{"input": "The developed MBG proved its in vivo efficiency for transdermal delivery of diflunisal.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 76, "end": 86}]}}, "schema": []}
{"input": "Antimicrobial and antioxidant properties of Betula aetnensis Rafin.", "output": {"entities": {}}, "schema": []}
{"input": "(Betulaceae) leaves extract.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to evaluate the antimicrobial effects, the radical scavenging activity (by DPPH and ABTS tests) and the antioxidant capacity (by beta-carotene bleaching test) of Betula aetnensis leaves extract.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 92, "end": 96}, {"text": "ABTS", "start": 101, "end": 105}, {"text": "beta-carotene", "start": 146, "end": 159}]}}, "schema": []}
{"input": "The antimicrobial activity was tested against 14 Gram-positive clinical strains, 2 ATCC Gram-positive strains, 10 Gram-negative clinical strains and 4 Gram-negative ATCC strains.", "output": {"entities": {}}, "schema": []}
{"input": "Streptococcus pyogenes Ery-S and Ery-R1 were the most sensitive.", "output": {"entities": {}}, "schema": []}
{"input": "Betula aetnensis was considerably active against three bacterial strains, namely Haemophilus influenzae ATCC 49247, Amp-R1 and Moraxella catarrhalis ATCC 25238.", "output": {"entities": {}}, "schema": []}
{"input": "Standard ATCC strains of Gram-positive bacteria were more sensitive than Gram-negative.", "output": {"entities": {}}, "schema": []}
{"input": "Betula aetnensis showed also an interesting reducing power with TEAC values of 9. 7 and a good inhibition of linoleic acid oxidation with an IC50 value of 22. 0 micro g mL (-1) after 30 min of incubation.", "output": {"entities": {"chemical": [{"text": "linoleic acid", "start": 109, "end": 122}]}}, "schema": []}
{"input": "The total phenol and flavonoid contents were determined with the purpose to evaluate the relationship with the observed bioactivities.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 10, "end": 16}, {"text": "flavonoid", "start": 21, "end": 30}]}}, "schema": []}
{"input": "Feroniellides C-E, new apotirucallane triterpenoids from the stem bark of Feroniella lucida.", "output": {"entities": {"chemical": [{"text": "Feroniellides C-E", "start": 0, "end": 17}, {"text": "apotirucallane triterpenoids", "start": 23, "end": 51}]}}, "schema": []}
{"input": "Bioassay-directed isolation of Feroniella lucida stem bark yielded three new apotirucallane triterpenoids named feroniellides C-E.", "output": {"entities": {"chemical": [{"text": "apotirucallane triterpenoids", "start": 77, "end": 105}, {"text": "feroniellides C-E", "start": 112, "end": 129}]}}, "schema": []}
{"input": "The structures of the new compounds were established by extensive analysis of spectroscopic data.", "output": {"entities": {}}, "schema": []}
{"input": "Of triterpenoids examined, feroniellides D and E revealed anticancer activity against KB and HeLa cells with IC50 values in range of 3. 4-14. 2 micro g mL (-1), which are significantly more potent than feroniellides A-C (IC50 25. 5-60. 0 micro g mL (-1)).", "output": {"entities": {"chemical": [{"text": "triterpenoids", "start": 3, "end": 16}, {"text": "feroniellides D and E", "start": 27, "end": 48}, {"text": "feroniellides A-C", "start": 202, "end": 219}]}}, "schema": []}
{"input": "The present investigation suggests that an isovalerate moiety in feroniellides D and E is possibly associated with exerting cytotoxicity against cancer cells.", "output": {"entities": {"chemical": [{"text": "isovalerate", "start": 43, "end": 54}, {"text": "feroniellides D and E", "start": 65, "end": 86}]}}, "schema": []}
{"input": "Nanostructural difference of water-soluble pectin and chelate-soluble pectin among ripening stages and cultivars of Chinese cherry.", "output": {"entities": {}}, "schema": []}
{"input": "Nanostructure of water-soluble pectin (WSP) and chelate-soluble pectin (CSP) of two Chinese cherry (Prunus pseudocerasus L.) cultivars (soft cultivar' Caode' and crisp cultivar' Bende') with two different ripening stages were characterised using atomic force microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Both cultivars shared some common values of chain widths for WSP or CSP, and both pectins shared several values of chain widths including 37, 55 and 61 nm.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that different cultivars shared similar components of pectin, and cultivar textural difference might be related to the interaction between pectin and other cherry components or the dissociation of pectin.", "output": {"entities": {}}, "schema": []}
{"input": "During ripening, the wide WSP and CSP gradually dissociate in width.", "output": {"entities": {}}, "schema": []}
{"input": "The results demonstrated that the changes of WSP and CSP of Chinese cherry in widths were a dissociation process.", "output": {"entities": {}}, "schema": []}
{"input": "Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments.", "output": {"entities": {"chemical": [{"text": "chloride", "start": 7, "end": 15}]}}, "schema": []}
{"input": "In cortical and hippocampal neurons, cation-chloride cotransporters (CCCs) control the reversal potential (EGABA) of GABAA receptor-mediated current and voltage responses and, consequently, they modulate the efficacy of GABAergic inhibition.", "output": {"entities": {"chemical": [{"text": "chloride", "start": 44, "end": 52}]}}, "schema": []}
{"input": "Two members of the CCC family, KCC2 (the major neuron-specific K-Cl cotransporter; KCC isoform 2) and NKCC1 (the Na-K-2Cl cotransporter isoform 1 which is expressed in both neurons and glial cells) have attracted much interest in studies on GABAergic signaling under both normal and pathophysiological conditions, such as epilepsy.", "output": {"entities": {}}, "schema": []}
{"input": "There is tentative evidence that loop diuretic compounds such as furosemide and bumetanide may have clinically relevant antiepileptic actions, especially when administered in combination with conventional GABA-mimetic drugs such as phenobarbital.", "output": {"entities": {}}, "schema": []}
{"input": "Furosemide is a non-selective inhibitor of CCCs while at low concentrations bumetanide is selective for NKCCs.", "output": {"entities": {}}, "schema": []}
{"input": "Search for novel antiepileptic drugs (AEDs) is highly motivated especially for the treatment of neonatal seizures which are often resistant to, or even aggravated by conventional AEDs. This review shows that the antiepileptic effects of loop diuretics described in the pertinent literature are based on widely heterogeneous mechanisms ranging from actions on both neuronal NKCC1 and KCC2 to modulation of the brain extracellular volume fraction.", "output": {"entities": {}}, "schema": []}
{"input": "A promising strategy for the development of novel CCC-blocking AEDs is based on prodrugs that are activated following their passage across the blood-brain barrier.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' New Targets and Approaches to the Treatment of Epilepsy'.", "output": {"entities": {}}, "schema": []}
{"input": "Celiac disease in subjects with type 1 diabetes mellitus: a prevalence study in western Sicily (Italy).", "output": {"entities": {}}, "schema": []}
{"input": "The association between celiac disease and type 1 diabetes mellitus is well known.", "output": {"entities": {}}, "schema": []}
{"input": "Up to now, celiac disease prevalence in children and adults with type 1 diabetes in Sicily has not been reported.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to assess the prevalence of celiac disease in patients with type 1 diabetes mellitus who come from a defined geographical area in western Sicily and to investigate the clinical features of these subjects.", "output": {"entities": {}}, "schema": []}
{"input": "The records of 492 consecutive patients with type 1 diabetes mellitus referred in a period of 5 years were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "During the period of the survey, out of 492 patients with type 1 diabetes, 22 (4. 5%) had a previous diagnosis of celiac disease.", "output": {"entities": {}}, "schema": []}
{"input": "There were 14 females and 8 males; these patients showed a mean age of 13 years at diabetes onset.", "output": {"entities": {}}, "schema": []}
{"input": "Diagnosis of celiac disease was often simultaneous or subsequent to that of diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Autoimmune thyroiditis was coexisting in 8 patients (36%).", "output": {"entities": {}}, "schema": []}
{"input": "Our data confirm, in a Sicilian population, the not unusual association between celiac disease and type 1 diabetes, although prevalence rate is lower than in others Italian studies.", "output": {"entities": {}}, "schema": []}
{"input": "Autoimmune thyroiditis is present with high prevalence in these patients.", "output": {"entities": {}}, "schema": []}
{"input": "Celiac disease diagnosis often followed onset of type 1 diabetes, particularly in female subjects with a young age at diabetes onset; therefore, in these subjects, an active search for the presence of celiac disease is warranted for many years after appearance of diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxic and leishmanicidal properties of garcinielliptone FC, a prenylated benzophenone from Platonia insignis.", "output": {"entities": {}}, "schema": []}
{"input": "Garcinielliptone FC (GFC), a natural prenylated benzophenone, was extracted from Platonia insignis Mart.", "output": {"entities": {"chemical": [{"text": "Garcinielliptone FC", "start": 0, "end": 19}, {"text": "GFC", "start": 21, "end": 24}, {"text": "prenylated benzophenone", "start": 37, "end": 60}]}}, "schema": []}
{"input": "(Clusiaceae), a native plant commonly known as bacuri and used in traditional Brazilian medicine for the treatment of skin diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to evaluate the cytotoxic and leishmanicidal effects of GFC using in vitro models.", "output": {"entities": {"chemical": [{"text": "GFC", "start": 82, "end": 85}]}}, "schema": []}
{"input": "The experimental data demonstrated that the polyisoprenylated benzophenone GFC possesses cytotoxic and leishmanicidal activities.", "output": {"entities": {"chemical": [{"text": "polyisoprenylated benzophenone GFC", "start": 44, "end": 78}]}}, "schema": []}
{"input": "A new acylated flavone glycoside with antioxidant and radical scavenging activities from Teucrium polium leaves.", "output": {"entities": {"chemical": [{"text": "acylated flavone glycoside", "start": 6, "end": 32}]}}, "schema": []}
{"input": "The antioxidant properties of six flavones from Teucrium polium L., one of them isolated for the first time, have been established through the determination of their abilities to inhibit free radicals using DPPH, ABTS radicals and ORAC test.", "output": {"entities": {"chemical": [{"text": "flavones", "start": 34, "end": 42}, {"text": "DPPH", "start": 207, "end": 211}, {"text": "ABTS", "start": 213, "end": 217}]}}, "schema": []}
{"input": "The structure of the new metabolite has been elucidated by 1-D (1H, 13C and DEPT) and 2-D (COSY, TOCSY, HSQC, CIGAR) NMR experiments and by ESI Q-TOF HRMS analysis.", "output": {"entities": {"chemical": [{"text": "1H", "start": 64, "end": 66}, {"text": "13C", "start": 68, "end": 71}]}}, "schema": []}
{"input": "Flavones 1-3 presented an efficacious activity towards the stable DPPH radical.", "output": {"entities": {"chemical": [{"text": "Flavones", "start": 0, "end": 8}, {"text": "DPPH", "start": 66, "end": 70}]}}, "schema": []}
{"input": "Analogously, compounds 2 and 3 resulted significantly active also versus ABTS cation radical.", "output": {"entities": {"chemical": [{"text": "ABTS", "start": 73, "end": 77}]}}, "schema": []}
{"input": "On the basis of the comparable bioactivity of luteolin-based compounds, the presence of an ortho-dihydroxy substitution in the flavone B-ring is supposed to be the structural feature responsible for the antioxidant activity.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 46, "end": 54}, {"text": "ortho-dihydroxy", "start": 91, "end": 106}, {"text": "flavone", "start": 127, "end": 134}]}}, "schema": []}
{"input": "Composition and antioxidant capacity of the essential oil of leaves of Vitex megapotamica (Sprengel) Moldenke.", "output": {"entities": {}}, "schema": []}
{"input": "This study is designed to examine the chemical composition and antioxidant activity of the essential oil of Vitex megapotamica.", "output": {"entities": {}}, "schema": []}
{"input": "Gas chromatography-mass spectrometry analysis resulted in the detection of 27 components, representing 92. 36% of the total oil composition.", "output": {"entities": {}}, "schema": []}
{"input": "The main components in the oil were butylated hydroxytoluene (BHT) (34. 17%), phytol (12. 66%), alpha-caryophyllene (11. 84%), delta-elemene (10. 65%), beta-caryophyllene (7. 82%), gamma-elemene (4. 24%) and germacrene D (2. 82%).", "output": {"entities": {"chemical": [{"text": "butylated hydroxytoluene", "start": 36, "end": 60}, {"text": "BHT", "start": 62, "end": 65}, {"text": "phytol", "start": 78, "end": 84}, {"text": "alpha-caryophyllene", "start": 96, "end": 115}, {"text": "delta-elemene", "start": 127, "end": 140}, {"text": "beta-caryophyllene", "start": 152, "end": 170}, {"text": "gamma-elemene", "start": 181, "end": 194}, {"text": "germacrene D", "start": 208, "end": 220}]}}, "schema": []}
{"input": "The antioxidant activity of the oil was evaluated in terms of their free-radical scavenging activity against 1, 1-diphenyl-2-picrylhydrazyl.", "output": {"entities": {"chemical": [{"text": "1, 1-diphenyl-2-picrylhydrazyl", "start": 109, "end": 139}]}}, "schema": []}
{"input": "The oil showed percentage inhibition of 35. 62% and 75. 25% at concentrations of 76 and 101. 6 mg mL (-1), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "BHT (36. 30%) was also determined by HPLC-DAD in the hexane fraction from the leaves.", "output": {"entities": {"chemical": [{"text": "BHT", "start": 0, "end": 3}, {"text": "hexane", "start": 53, "end": 59}]}}, "schema": []}
{"input": "To the best of our knowledge, this is the first study of the composition and antioxidant activity of the essential oil of the species V. megapotamica.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitory action on rat uterine muscle contraction in vitro and acute toxicity in rats of the Thai traditional preparation Prasaplai.", "output": {"entities": {}}, "schema": []}
{"input": "The activity of an aqueous extract of Prasaplai, a Thai traditional medicine, was studied on the isolated rat uterus in the oestrus stage.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that the extract inhibited the contraction induced by a submaximal dose of acetylcholine (2. 04 x 10 (-4) mg mL (-1)), oxytocin (1. 54 x 10 (-4) mg mL (-1)) and prostaglandin E2 (PGE2) (6. 00 x 10 (-4) mg mL (-1)).", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 94, "end": 107}, {"text": "oxytocin", "start": 138, "end": 146}, {"text": "prostaglandin E2", "start": 180, "end": 196}, {"text": "PGE2", "start": 198, "end": 202}]}}, "schema": []}
{"input": "The inhibition was concentration-dependent and reversible by tissue washing.", "output": {"entities": {}}, "schema": []}
{"input": "The IC50 of Prasaplai extracts expressed as milligram of powdered preparation per millilitre of perfusion solution for acetylcholine, oxytocin and PGE2 were 11. 70, 10. 00 and 5. 75 mg mL (-1), respectively.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 119, "end": 132}, {"text": "oxytocin", "start": 134, "end": 142}, {"text": "PGE2", "start": 147, "end": 151}]}}, "schema": []}
{"input": "These data reveal that Prasaplai has an antispasmodic effect against uterine contraction by different mechanisms and corroborate the traditional use in the treatment of dysmenorrhoea.", "output": {"entities": {}}, "schema": []}
{"input": "Oral administration of single dose of the water extract, calculated as powdered Prasaplai up to 20 g kg (-1) in rats, showed no sign and symptom of acute toxicity, and no rat died even at the maximum dose.", "output": {"entities": {}}, "schema": []}
{"input": "A new caryolane sesquiterpene from Heteropappus altaicus (Willd.) Novopokr.", "output": {"entities": {"chemical": [{"text": "caryolane sesquiterpene", "start": 6, "end": 29}]}}, "schema": []}
{"input": "A new caryolane sesquiterpene, 1 beta-methoxycaryol-9-one (1), along with eight known compounds (2-9), was isolated from the whole plant of Heteropappus altaicus.", "output": {"entities": {"chemical": [{"text": "caryolane sesquiterpene", "start": 6, "end": 29}, {"text": "1 beta-methoxycaryol-9-one", "start": 31, "end": 57}]}}, "schema": []}
{"input": "The structures were elucidated on the basis of comprehensive 1D-and 2D-NMR analysis and high-resolution mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The 13C-NMR data of compound 2 are reported for the first time.", "output": {"entities": {"chemical": [{"text": "13C", "start": 4, "end": 7}]}}, "schema": []}
{"input": "An antileishmanial prenyloxy-naphthoquinone from roots of Plumbago zeylanica.", "output": {"entities": {"chemical": [{"text": "prenyloxy-naphthoquinone", "start": 19, "end": 43}]}}, "schema": []}
{"input": "Leishmania donovani, an obligate intracellular parasite of genus Leishmania causes visceral leishmaniasis that affects millions of people worldwide, especially in the Indian subcontinent and East Africa.", "output": {"entities": {}}, "schema": []}
{"input": "Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness but the growing incidence of their resistance has seriously hampered their use.", "output": {"entities": {}}, "schema": []}
{"input": "This study discloses strong in vitro antileishmanial activity of 2-methyl-5-(3'-methyl-but-2'-enyloxy)-[1, 4] naphthoquinone (1), a prenyloxy-naphthoquinone isolated and characterised from roots of the plant Plumbago zeylanica (family-Plumbaginaceae).", "output": {"entities": {"chemical": [{"text": "2-methyl-5-(3'-methyl-but-2'-enyloxy)-[1, 4] naphthoquinone", "start": 65, "end": 124}, {"text": "prenyloxy-naphthoquinone", "start": 132, "end": 156}]}}, "schema": []}
{"input": "The observed EC50 for the compound 1 against promastigote and amastigote forms of L. donovani was significantly (p < 0. 001) lower than miltefosine, a reference drug.", "output": {"entities": {"chemical": [{"text": "miltefosine", "start": 136, "end": 147}]}}, "schema": []}
{"input": "In context to limited treatment options and growing resistance for available drugs, compound 1 offers a greater prospect towards antileishmanial drug discovery and development.", "output": {"entities": {}}, "schema": []}
{"input": "Isolation and structure determination of new siderophore tsukubachelin B from Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "tsukubachelin B", "start": 57, "end": 72}]}}, "schema": []}
{"input": "TM-74.", "output": {"entities": {}}, "schema": []}
{"input": "The new siderophore tsukubachelin B (1) was isolated from the iron-deficient culture medium of the newly isolated strain Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "tsukubachelin B", "start": 20, "end": 35}, {"text": "iron", "start": 62, "end": 66}]}}, "schema": []}
{"input": "TM-74.", "output": {"entities": {}}, "schema": []}
{"input": "The chemical structure of tsukubachelin B (1) was established via interpretation of 2D nuclear magnetic resonance and electrospray ionization-mass spectroscopic data.", "output": {"entities": {"chemical": [{"text": "tsukubachelin B", "start": 26, "end": 41}]}}, "schema": []}
{"input": "The structure of tsukubachelin B (1) comprises 6 mol of amino acids, including 2 mol of serine and 1 mol each of ornithine, N-alpha-methyl-N-delta-hydroxy-N-delta-formylornithine, N-alpha-methyl-N-delta-hydroxyornithine, and cyclic N-hydroxyornithine.", "output": {"entities": {"chemical": [{"text": "tsukubachelin B", "start": 17, "end": 32}, {"text": "amino acids", "start": 56, "end": 67}, {"text": "serine", "start": 88, "end": 94}, {"text": "ornithine", "start": 113, "end": 122}, {"text": "N-alpha-methyl-N-delta-hydroxy-N-delta-formylornithine", "start": 124, "end": 178}, {"text": "N-alpha-methyl-N-delta-hydroxyornithine", "start": 180, "end": 219}, {"text": "cyclic N-hydroxyornithine", "start": 225, "end": 250}]}}, "schema": []}
{"input": "Hierarchical clustering analysis of blood plasma lipidomics profiles from mono-and dizygotic twin families.", "output": {"entities": {}}, "schema": []}
{"input": "Twin and family studies are typically used to elucidate the relative contribution of genetic and environmental variation to phenotypic variation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we apply a quantitative genetic method based on hierarchical clustering, to blood plasma lipidomics data obtained in a healthy cohort consisting of 37 monozygotic and 28 dizygotic twin pairs, and 52 of their biological nontwin siblings.", "output": {"entities": {}}, "schema": []}
{"input": "Such data are informative of the concentrations of a wide range of lipids in the studied blood samples.", "output": {"entities": {}}, "schema": []}
{"input": "An important advantage of hierarchical clustering is that it can be applied to a high-dimensional' omics' type data, whereas the use of many other quantitative genetic methods for analysis of such data is hampered by the large number of correlated variables.", "output": {"entities": {}}, "schema": []}
{"input": "For this study we combined two lipidomics data sets, originating from two different measurement blocks, which we corrected for block effects by' quantile equating'.", "output": {"entities": {}}, "schema": []}
{"input": "In the analysis of the combined data, average similarities of lipidomics profiles were highest between monozygotic (MZ) cotwins, and became progressively lower between dizygotic (DZ) cotwins, among sex-matched nontwin siblings and among sex-matched unrelated participants, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Our results suggest that (1) shared genetic background, shared environment, and similar age contribute to similarities in blood plasma lipidomics profiles among individuals; and (2) that the power of quantitative genetic analyses is enhanced by quantile equating and combination of data sets obtained in different measurement blocks.", "output": {"entities": {}}, "schema": []}
{"input": "Measles virus selectively blind to signaling lymphocyte activation molecule as a novel oncolytic virus for breast cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Oncolytic viruses hold much promise as novel therapeutic agents that can be combined with conventional therapeutic modalities.", "output": {"entities": {}}, "schema": []}
{"input": "Measles virus (MV) is known to enter cells using the signaling lymphocyte activation molecule (SLAM), which is expressed on cells of the immune system.", "output": {"entities": {}}, "schema": []}
{"input": "Although human breast cancer cell lines do not express SLAM, we found that a wild-type MV (HL strain) efficiently infected various breast cancer cell lines, causing cell death.", "output": {"entities": {}}, "schema": []}
{"input": "Based on this finding, we used reverse genetics to generate a recombinant MV selectively unable to use SLAM (rMV-SLAMblind).", "output": {"entities": {}}, "schema": []}
{"input": "The rMV-SLAMblind lacked infectivity for SLAM-positive lymphoid cells, while retaining oncolytic activity against breast cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "We showed that, unlike the MV vaccine strains, rMV-SLAMblind used PVRL4 (polio virus receptor-related 4) as a receptor to infect breast cancer cells and not the ubiquitously expressed CD46.", "output": {"entities": {}}, "schema": []}
{"input": "Consistent with this, rMV-SLAMblind infected CD46-positive primary normal human cells at a much-reduced level, whereas a vaccine strain of the Edmonston lineage (rMV-Edmonston) efficiently infected and killed them.", "output": {"entities": {}}, "schema": []}
{"input": "The rMV-SLAMblind showed antitumor activity against human breast cancer xenografts in immunodeficient mice.", "output": {"entities": {}}, "schema": []}
{"input": "The oncolytic activity of rMV-SLAMblind was significantly greater than that of rMV-Edmonston.", "output": {"entities": {}}, "schema": []}
{"input": "To assess the in vivo safety, three monkeys seronegative for MV were inoculated with rMV-SLAMblind, and no clinical symptoms were documented.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of these results, rMV-SLAMblind could be a promising candidate as a novel oncolytic virus for breast cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPL (S447X)) gene therapy for lipoprotein lipase deficiency: an open-label trial.", "output": {"entities": {}}, "schema": []}
{"input": "We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPL (S447X) gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis.", "output": {"entities": {}}, "schema": []}
{"input": "The LPL (S447X) gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis.", "output": {"entities": {}}, "schema": []}
{"input": "Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a <E2F6> 40% reduction in fasting median plasma triglyceride (TG) at 3-12 weeks compared with baseline.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 139, "end": 151}]}}, "schema": []}
{"input": "Cohorts 1 (n = 2) and 2 (n = 4) received 3 x 10 (11) gc kg (-1), and cohort 3 (n = 8) received 1 x 10 (12) gc kg (-1).", "output": {"entities": {}}, "schema": []}
{"input": "Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years.", "output": {"entities": {}}, "schema": []}
{"input": "Half of the patients demonstrated a <E2F6> 40% reduction in fasting TG between 3 and 12 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "TG subsequently returned to baseline, although sustained LPL (S447X) expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-diabetic Activity of Swertiamarin is due to an Active Metabolite, Gentianine, that Upregulates PPAR-gamma Gene Expression in 3T3-L1 cells.", "output": {"entities": {"chemical": [{"text": "Swertiamarin", "start": 26, "end": 38}, {"text": "Gentianine", "start": 71, "end": 81}]}}, "schema": []}
{"input": "We have previously shown the anti-diabetic effects of swertiamarin; however, pharmacokinetic analysis showed that swertiamarin had a plasma half-life of 1. 3 h.", "output": {"entities": {"chemical": [{"text": "swertiamarin", "start": 54, "end": 66}, {"text": "swertiamarin", "start": 114, "end": 126}]}}, "schema": []}
{"input": "Gentianine is an active metabolite of swertiamarin that possesses a pharmacophoric moiety.", "output": {"entities": {"chemical": [{"text": "Gentianine", "start": 0, "end": 10}, {"text": "swertiamarin", "start": 38, "end": 50}]}}, "schema": []}
{"input": "The aim of this study was to explore the possibility whether the anti-diabetic effect of swertiamarin is due to gentianine.", "output": {"entities": {"chemical": [{"text": "swertiamarin", "start": 89, "end": 101}, {"text": "gentianine", "start": 112, "end": 122}]}}, "schema": []}
{"input": "Swertiamarin treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-gamma and GLUT-4; however, there was a significant increase in the mRNA expression of adiponectin.", "output": {"entities": {"chemical": [{"text": "Swertiamarin", "start": 0, "end": 12}]}}, "schema": []}
{"input": "On the other hand, treatment with gentianine significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-gamma, GLUT-4 and adiponectin.", "output": {"entities": {"chemical": [{"text": "gentianine", "start": 34, "end": 44}]}}, "schema": []}
{"input": "These findings suggest, for the first time, that the anti-diabetic effect of swertiamarin is due to gentianine, an active metabolite of swertiamarin.", "output": {"entities": {"chemical": [{"text": "swertiamarin", "start": 77, "end": 89}, {"text": "gentianine", "start": 100, "end": 110}, {"text": "swertiamarin", "start": 136, "end": 148}]}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic treatment with selective I2-imidazoline receptor ligands decreases the content of pro-apoptotic markers in rat brain.", "output": {"entities": {"chemical": [{"text": "imidazoline", "start": 36, "end": 47}]}}, "schema": []}
{"input": "Selective I (2)-imidazoline receptor ligands induce neuroprotection through various molecular mechanisms including blockade of N-methyl-D-aspartate (NMDA) receptors.", "output": {"entities": {"chemical": [{"text": "imidazoline", "start": 16, "end": 27}, {"text": "N-methyl-D-aspartate", "start": 127, "end": 147}, {"text": "NMDA", "start": 149, "end": 153}]}}, "schema": []}
{"input": "To investigate new neuroprotective mechanisms associated with I (2)-imidazoline receptors, the effects of selective (2-styryl-2-imidazoline (LSL 61122), 2-(2-benzofuranyl)-2-imidazoline (2-BFI), 2-(4, 5-dihydroimidazol-2-yl) quinoline hydrochloride (BU-224)) and non-selective (idazoxan) I (2)-drugs on canonical apoptotic pathways were assessed in rat brain cortex.", "output": {"entities": {"chemical": [{"text": "imidazoline", "start": 68, "end": 79}, {"text": "2-styryl-2-imidazoline", "start": 117, "end": 139}, {"text": "LSL 61122", "start": 141, "end": 150}, {"text": "2-(2-benzofuranyl)-2-imidazoline", "start": 153, "end": 185}, {"text": "2-BFI", "start": 187, "end": 192}, {"text": "2-(4, 5-dihydroimidazol-2-yl) quinoline hydrochloride", "start": 195, "end": 248}, {"text": "BU-224", "start": 250, "end": 256}, {"text": "idazoxan", "start": 278, "end": 286}]}}, "schema": []}
{"input": "The acute treatment with LSL 61122 (10 mg/kg) reduced the content of mitochondrial (pro-apoptotic) Bax (-33%) and cytochrome c (-31%), which was prevented by idazoxan, an I (2)-receptor antagonist.", "output": {"entities": {"chemical": [{"text": "LSL 61122", "start": 25, "end": 34}, {"text": "idazoxan", "start": 158, "end": 166}]}}, "schema": []}
{"input": "The sustained stimulation of I (2)-imidazoline receptors with selective drugs (10 mg/kg, every 12 h for seven days) was associated with down-regulation of key components of the extrinsic (Fas receptor:-20%; Fas associated protein with death domain (FADD) adaptor:-47-54%) and/or intrinsic (Bax:-20-23%; cytochrome c:-22-28%) apoptotic signalling and/or up-regulation of survival anti-apoptotic factors (p-Ser194 FADD/FADD ratio: + 1. 6-2. 5-fold; and/or Bcl-2/Bax ratio: + 1. 5-fold), which in the long-term could dampen cell death in the brain.", "output": {"entities": {"chemical": [{"text": "imidazoline", "start": 35, "end": 46}, {"text": "Ser194", "start": 405, "end": 411}]}}, "schema": []}
{"input": "Similar chronic treatments with LSL 60101 (the imidazole analogue of 2-BFI) and idazoxan (a mixed I (2)/alpha (2)-ligand) did not induce significant alterations of pro-or anti-apoptotic proteins.", "output": {"entities": {"chemical": [{"text": "LSL 60101", "start": 32, "end": 41}, {"text": "imidazole", "start": 47, "end": 56}, {"text": "2-BFI", "start": 69, "end": 74}, {"text": "idazoxan", "start": 80, "end": 88}]}}, "schema": []}
{"input": "The disclosed anti-apoptotic mechanisms of selective I (2)-imidazoline drugs may work in concert with other molecular mechanisms of neuroprotection (e. g. blockade of NMDA receptors) that are engaged by I (2)-ligands.", "output": {"entities": {"chemical": [{"text": "imidazoline", "start": 59, "end": 70}]}}, "schema": []}
{"input": "A new furolactone-type lignan from Lycium chinense.", "output": {"entities": {"chemical": [{"text": "furolactone", "start": 6, "end": 17}, {"text": "lignan", "start": 23, "end": 29}]}}, "schema": []}
{"input": "The phytochemical investigation of extracts from the root barks of Lycium chinense yielded a new furolactone-type lignan, lyciumin (1).", "output": {"entities": {"chemical": [{"text": "lyciumin", "start": 122, "end": 130}]}}, "schema": []}
{"input": "Its structure and absolute configurations were established on the basis of spectral data, particularly by the use of 1D NMR, 2D shift-correlated NMR pulse sequences ((1) H-(1) H COSY, HSQC, HMBC and ROESY) and CD spectra.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 166, "end": 171}, {"text": "(1) H", "start": 172, "end": 177}]}}, "schema": []}
{"input": "How inhibition influences seizure propagation.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitory neuron behaviour is of fundamental importance to epileptic pathophysiology.", "output": {"entities": {}}, "schema": []}
{"input": "When inhibition is compromised, such as by GABAergic blockade (Curtis et al., 1970; Connors, 1984; Traub and Miles, 1991) or by shifts in GABAergic reversal potential (Huberfeld et al., 2007), epileptiform discharges occur far more readily.", "output": {"entities": {}}, "schema": []}
{"input": "Other studies have shown enhanced inhibition in vivo in the surrounding cortical territories associated with both focal pathological and physiological activity (Prince and Wilder, 1967; Dichter and Spencer, 1969a, b; Goldensohn and Salazar, 1986; Traub and Miles, 1991; Liang and Jones, 1997; Liang et al., 1998; Schwartz and Bonhoeffer, 2001).", "output": {"entities": {}}, "schema": []}
{"input": "This gave rise to the concept of an \" inhibitory restraint \".", "output": {"entities": {}}, "schema": []}
{"input": "This concept can explain the often confusing anatomical reorganizations seen in chronically epileptic brains (Sloviter, 1987; Cossart et al., 2001), indicating which changes might be pro-epileptic, and which oppose the epileptic state.", "output": {"entities": {}}, "schema": []}
{"input": "It also may explain key electrophysiological features of epileptic seizures.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe current knowledge about the restraint, gleaned mainly from acute pharmacological experiments in animals, both in vivo and in vitro, and speculate how this may alter our understanding of human seizure activity in clinical practice.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' New Targets and Approaches to the Treatment of Epilepsy'.", "output": {"entities": {}}, "schema": []}
{"input": "Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 15, "end": 24}]}}, "schema": []}
{"input": "Excessive fear is a hallmark of several emotional and mental disorders such as phobias and panic disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Considerable attention is focused on defining the neurobiological mechanisms of the extinction of conditioned fear memory in an effort to identify mechanisms that may hold clinical significance for remediating aberrant fear memory.", "output": {"entities": {}}, "schema": []}
{"input": "Serotonin modulates the acquisition and retention of conditioned emotional memory, and the serotonin 2A receptor (5HT2AR) may be one of the postsynaptic targets mediating such effects.", "output": {"entities": {"chemical": [{"text": "Serotonin", "start": 0, "end": 9}, {"text": "serotonin", "start": 91, "end": 100}]}}, "schema": []}
{"input": "Here we tested the hypothesis that the 5HT2AR regulates the consolidation and extinction of fear memory in male C57BL/6J mice.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of 5HT2ARs on memory consolidation was further confirmed with a novel object recognition task.", "output": {"entities": {}}, "schema": []}
{"input": "With a trace fear conditioning paradigm, administration of the 5HT2AR agonist TCB-2 (1. 0 mg/kg, i. p.) before the extinction test facilitated the acquisition of extinction of fear memory as compared to vehicle treatment.", "output": {"entities": {"chemical": [{"text": "TCB-2", "start": 78, "end": 83}]}}, "schema": []}
{"input": "In contrast, administration of the 5HT2AR antagonist MDL 11, 939 (0. 5 mg/kg, i. p.) delayed the acquisition of extinction of fear memory.", "output": {"entities": {"chemical": [{"text": "MDL 11, 939", "start": 53, "end": 64}]}}, "schema": []}
{"input": "Further, the post-conditioning administration of TCB-2 enhanced contextual and cued fear memory, possibly by facilitating the consolidation of fear memory.", "output": {"entities": {"chemical": [{"text": "TCB-2", "start": 49, "end": 54}]}}, "schema": []}
{"input": "Administration of TCB-2 also facilitated the acquisition of extinction of fear memory in delay fear conditioned mice.", "output": {"entities": {"chemical": [{"text": "TCB-2", "start": 18, "end": 23}]}}, "schema": []}
{"input": "Stimulation or blockade of 5HT2ARs did not affect the encoding or retrieval of conditioned fear memory.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, administration of TCB-2 right after training in an object recognition task enhanced the consolidation of object memory.", "output": {"entities": {"chemical": [{"text": "TCB-2", "start": 27, "end": 32}]}}, "schema": []}
{"input": "These results suggest that stimulation of 5HT2ARs facilitates the consolidation and extinction of trace and delay cued fear memory and the consolidation of object memory.", "output": {"entities": {}}, "schema": []}
{"input": "Blocking the 5HT2AR impairs the acquisition of fear memory extinction.", "output": {"entities": {}}, "schema": []}
{"input": "The results support the view that serotonergic activation of the 5HT2AR provides an important modulatory influence on circuits engaged during extinction learning.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together these results suggest that the 5HT2AR may be a potential therapeutic target for enhancing hippocampal and amygdala-dependent memory.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model.", "output": {"entities": {}}, "schema": []}
{"input": "Anxiety disorders are characterized by persistent, excessive fear.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders.", "output": {"entities": {}}, "schema": []}
{"input": "We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning.", "output": {"entities": {}}, "schema": []}
{"input": "We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval.", "output": {"entities": {}}, "schema": []}
{"input": "Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training.", "output": {"entities": {"chemical": [{"text": "d-cycloserine", "start": 77, "end": 90}, {"text": "N-methly-d-aspartate", "start": 92, "end": 112}, {"text": "MS-275", "start": 133, "end": 139}]}}, "schema": []}
{"input": "We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests.", "output": {"entities": {}}, "schema": []}
{"input": "Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls.", "output": {"entities": {}}, "schema": []}
{"input": "Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice.", "output": {"entities": {"chemical": [{"text": "valproic acid", "start": 158, "end": 171}, {"text": "AMN082", "start": 217, "end": 223}, {"text": "glutamate", "start": 238, "end": 247}, {"text": "MS-275", "start": 283, "end": 289}, {"text": "PEPA", "start": 293, "end": 297}, {"text": "AMPA", "start": 299, "end": 303}]}}, "schema": []}
{"input": "Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Alleviation of high salt toxicity-induced oxidative damage by salicylic acid pretreatment in two wheat cultivars.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 62, "end": 76}]}}, "schema": []}
{"input": "Role of exogenous salicylic acid (SA) in the antioxidative response to salt toxicity of two wheat (Triticum aestivum) cultivars (Gerek-79 and Bezostaya) was investigated.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 18, "end": 32}]}}, "schema": []}
{"input": "Hydroponic growth environment of 10-day wheat seedlings grown under normal conditions (22/20 degrees C) was adjusted to 0. 0, 0. 25, 0. 50 and 0. 75 M of salt (NaCl), and then freshly prepared SA solutions (0. 0, 0. 01 and 0. 1 mM) were once sprayed on leaves of the same seedlings.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 160, "end": 164}]}}, "schema": []}
{"input": "Activities of superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT) were determined in fresh leaves obtained from 15-day seedlings.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 14, "end": 24}]}}, "schema": []}
{"input": "Treatment with SA alone increased all the antioxidant activities in Gerek-79.", "output": {"entities": {}}, "schema": []}
{"input": "However, the same treatments with SA decreased the activities of CAT and SOD in Bezostaya, while increased that of POX.", "output": {"entities": {}}, "schema": []}
{"input": "Salt applications alone increased the activities of POX and SOD, while decreased that of CAT in Bezostaya.", "output": {"entities": {}}, "schema": []}
{"input": "The same salt applications increased the POX activity, while decreased the activities of CAT and SOD in Gerek-79.", "output": {"entities": {}}, "schema": []}
{"input": "In plants under saline conditions, except 0. 75 M NaCl, treatments with SA increased the activities of CAT, POX and SOD in both the varieties compared with plants applied salt alone.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 50, "end": 54}]}}, "schema": []}
{"input": "In plants applied with 0. 75 M NaCl, however, treatments with SA decreased CAT activity.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 31, "end": 35}]}}, "schema": []}
{"input": "Results showed that salt toxicity caused a derangement in the regulation of antioxidant enzyme activities by decreasing CAT activity especially in both the varieties, but treatments with SA could turn back the derangement in the antioxidative enzymes caused by salt toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "SA can involve in increasing salt tolerance by regulating the activities of antioxidant enzymes in wheat cultivars exposed to salt toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Possibility for the development of cosmetics with PLGA nanospheres.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 50, "end": 54}]}}, "schema": []}
{"input": "The optimized preparation of Poly-(lactide-co-glycolic acid) (PLGA) nanospheres containing ubiquinone (UQ) for cosmetic products was pursued.", "output": {"entities": {"chemical": [{"text": "Poly-(lactide-co-glycolic acid)", "start": 29, "end": 60}, {"text": "PLGA", "start": 62, "end": 66}]}}, "schema": []}
{"input": "By investigating various conditions for the preparation of UQ/PLGA nanospheres such as the molecular weight of PLGA, PLGA concentration, and UQ concentration, UQ/PLGA nanospheres with increased stability and slower drug release at a higher drug loading efficiency were prepared.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 62, "end": 66}, {"text": "PLGA", "start": 111, "end": 115}, {"text": "PLGA", "start": 117, "end": 121}, {"text": "PLGA", "start": 162, "end": 166}]}}, "schema": []}
{"input": "Permeation tests on the prepared nanospheres using iontophoresis via electric dermal administration on membrane filters (200 nm pore size) and hairless mouse skin samples were also carried out.", "output": {"entities": {}}, "schema": []}
{"input": "After iontophoresis, the nanospheres choked the membrane filter and remained on the horny layer of the hairless mouse skin, even after washing.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the prepared UQ/PLGA nanospheres and the established iontophoresis technique with the PLGA nanospheres in the present study can be applied to the future development of cosmetics.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 27, "end": 31}, {"text": "PLGA", "start": 97, "end": 101}]}}, "schema": []}
{"input": "Melamine in prenatal and postnatal organs in rats.", "output": {"entities": {"chemical": [{"text": "Melamine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Melamine can be transferred to fetus in utero through placenta and to infant ex utero by breast feeding.", "output": {"entities": {"chemical": [{"text": "Melamine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "In this study, we characterized the pharmacokinetics of melamine in prenatal and postnatal organs in rats.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 56, "end": 64}]}}, "schema": []}
{"input": "Single bolus of melamine was administered to pregnant rats at different gestational stages and to infants at different postnatal stages.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 16, "end": 24}]}}, "schema": []}
{"input": "Distribution of melamine in maternal serum was about 30% higher in late pregnancy than that in early pregnancy; and it was 2 folds higher in postnatal serum in early infants in young adulthood.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 16, "end": 24}]}}, "schema": []}
{"input": "Distribution of melamine in all postnatal organs was higher than that in prenatal organs.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 16, "end": 24}]}}, "schema": []}
{"input": "Postnatal kidneys in early infants had the highest maximum concentration and the lowest clearance of melamine than the other postnatal organs.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 101, "end": 109}]}}, "schema": []}
{"input": "It may relate to the high vulnerability to the toxicity of melamine in this population.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 59, "end": 67}]}}, "schema": []}
{"input": "Selective GABA (A) alpha 5 positive allosteric modulators improve cognitive function in aged rats with memory impairment.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 10, "end": 14}]}}, "schema": []}
{"input": "A condition of excess activity in the hippocampal formation is observed in the aging brain and in conditions that confer additional risk during aging for Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds that act as positive allosteric modulators at GABA (A) alpha 5 receptors might be useful in targeting this condition because GABA (A) alpha 5 receptors mediate tonic inhibition of principal neurons in the affected network.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 56, "end": 60}, {"text": "GABA", "start": 135, "end": 139}]}}, "schema": []}
{"input": "While agents to improve cognitive function in the past focused on inverse agonists, which are negative allosteric modulators at GABA (A) alpha 5 receptors, research supporting that approach used only young animals and predated current evidence for excessive hippocampal activity in age-related conditions of cognitive impairment.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 128, "end": 132}]}}, "schema": []}
{"input": "Here, we used two compounds, Compound 44 [6, 6-dimethyl-3-(3-hydroxypropyl) thio-1-(thiazol-2-yl)-6, 7-dihydro-2-benzothiophen-4 (5H)-one] and Compound 6 [methyl 3, 5-diphenylpyridazine-4-carboxylate], with functional activity as potentiators of gamma-aminobutyric acid at GABA (A) alpha 5 receptors, to test their ability to improve hippocampal-dependent memory in aged rats with identified cognitive impairment.", "output": {"entities": {"chemical": [{"text": "6, 6-dimethyl-3-(3-hydroxypropyl) thio-1-(thiazol-2-yl)-6, 7-dihydro-2-benzothiophen-4 (5H)-one", "start": 42, "end": 137}, {"text": "methyl 3, 5-diphenylpyridazine-4-carboxylate", "start": 155, "end": 199}, {"text": "gamma-aminobutyric acid", "start": 246, "end": 269}, {"text": "GABA", "start": 273, "end": 277}]}}, "schema": []}
{"input": "Improvement was obtained in aged rats across protocols differing in motivational and performance demands and across varying retention intervals.", "output": {"entities": {}}, "schema": []}
{"input": "Significant memory improvement occurred after either intracereboventricular infusion with Compound 44 (100 mu g) in a water maze task or systemic administration with Compound 6 (3 mg/kg) in a radial arm maze task.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, systemic administration improved behavioral performance at dosing shown to provide drug exposure in the brain and in vivo receptor occupancy in the hippocampus.", "output": {"entities": {}}, "schema": []}
{"input": "These data suggest a novel approach to improve neural network function in clinical conditions of excess hippocampal activity.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "A Safety Assessment of the Antimalarial Herb Artemisia annua During Pregnancy in Wistar Rats.", "output": {"entities": {}}, "schema": []}
{"input": "Artemisia annua is a Chinese antimalarial herb that has been used for more than 2000 years.", "output": {"entities": {}}, "schema": []}
{"input": "The maternal and foetal safety of the ethanolic leaf extract of therapeutically active Artemisia annua (EAA), with previously determined artemisinin yield of 1. 098% was evaluated in Wistar rats.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty pregnant rats, divided into four study groups of saline treated (control), and test groups administered orally with 100, 200 and 300 mg/kg body weights of EAA, respectively, from gestation days (GD) 8 to 19.", "output": {"entities": {}}, "schema": []}
{"input": "Following overnight fast, animals were sacrificed on GD 20, and maternal blood was collected to evaluate biochemical and haematological markers.", "output": {"entities": {}}, "schema": []}
{"input": "Foetuses were carefully removed, weighed, and observed for any possible malformation.", "output": {"entities": {}}, "schema": []}
{"input": "Biochemical and haematological studies revealed that EAA did not result in maternal hepatotoxicity, haematotoxicity, and hyperlipidemia.", "output": {"entities": {}}, "schema": []}
{"input": "While litter size significantly decreased (p < 0. 05) at 100 mg/kg EAA, maternal estrogen levels decreased in all the EAA-treated groups.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Non-viable (21%) and malformed (31%) foetuses were observed at the 300 mg/kg dose of EAA, which implies that although consumption of the leaf extract may not predispose users to hepatotoxicity, haematotoxicity, and hyperlipidemia, it should be taken with caution during pregnancy due to possible risk of embryotoxicity at concentrations higher than the therapeutic dose.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Up-regulation of cytochrome P450 and phase II enzymes by xenobiotics in precision-cut tissue slices.", "output": {"entities": {}}, "schema": []}
{"input": "1. Induction of the drug-metabolising enzyme systems is a major cause of clinically relevant drug interactions.", "output": {"entities": {}}, "schema": []}
{"input": "The potential of a drug to engage in such interactions may be assessed in in vitro systems such as precision-cut tissue slices.", "output": {"entities": {}}, "schema": []}
{"input": "2. Precision-cut tissue slices have a number of important advantages compared with the use of cells in culture, especially when tissues with a heterogeneous cellular population are concerned.", "output": {"entities": {}}, "schema": []}
{"input": "3. Extensive studies concerned with the induction of cytochrome P450 and Phase II enzymes in precision-cut tissue slices from various animal and human tissues, such as liver, lung and intestine, using established inducing agents have revealed that slices mimic the in vivo situation.", "output": {"entities": {}}, "schema": []}
{"input": "4. Precision-cut tissue slices is a reliable, informative and cost-effective technique for assessing the potential of chemicals to up-regulate drug-metabolising enzyme systems.", "output": {"entities": {}}, "schema": []}
{"input": "The pathways of mitophagy for quality control and clearance of mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "Selective autophagy of mitochondria, known as mitophagy, is an important mitochondrial quality control mechanism that eliminates damaged mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "Mitophagy also mediates removal of mitochondria from developing erythrocytes, and contributes to maternal inheritance of mitochondrial DNA through the elimination of sperm-derived mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies have identified specific regulators of mitophagy that ensure selective sequestration of mitochondria as cargo.", "output": {"entities": {}}, "schema": []}
{"input": "In yeast, the mitochondrial outer membrane protein autophagy-related gene 32 (ATG32) recruits the autophagic machinery to mitochondria, while mammalian Nix is required for degradation of erythrocyte mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "The elimination of damaged mitochondria in mammals is mediated by a pathway comprised of PTEN-induced putative protein kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin.", "output": {"entities": {}}, "schema": []}
{"input": "PINK1 and Parkin accumulate on damaged mitochondria, promote their segregation from the mitochondrial network, and target these organelles for autophagic degradation in a process that requires Parkin-dependent ubiquitination of mitochondrial proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Here we will review recent advances in our understanding of the different pathways of mitophagy.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we will discuss the relevance of these pathways in neurons where defects in mitophagy have been implicated in neurodegeneration.", "output": {"entities": {}}, "schema": []}
{"input": "Nicotine facilitates memory consolidation in perceptual learning.", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices.", "output": {"entities": {}}, "schema": []}
{"input": "The cholinergic system is known to modulate declarative learning.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 66, "end": 79}]}}, "schema": []}
{"input": "However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning.", "output": {"entities": {}}, "schema": []}
{"input": "Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT).", "output": {"entities": {}}, "schema": []}
{"input": "One group received chewing tobacco containing nicotine for 1 h directly following the TDT training.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 46, "end": 54}]}}, "schema": []}
{"input": "The other group received a similar tasting control substance without nicotine.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 69, "end": 77}]}}, "schema": []}
{"input": "Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 120, "end": 128}]}}, "schema": []}
{"input": "When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training.", "output": {"entities": {}}, "schema": []}
{"input": "These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex.", "output": {"entities": {}}, "schema": []}
{"input": "A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 76, "end": 84}]}}, "schema": []}
{"input": "These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 48, "end": 56}, {"text": "acetylcholine", "start": 92, "end": 105}]}}, "schema": []}
{"input": "Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning).", "output": {"entities": {}}, "schema": []}
{"input": "In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 15, "end": 28}]}}, "schema": []}
{"input": "Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Gene therapy and neurodevelopmental disorders.", "output": {"entities": {}}, "schema": []}
{"input": "With a number of recent clinical successes, gene therapy is quickly becoming a realistic treatment option for neurological disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Advancements in global central nervous system (CNS) gene delivery, in particular, have accelerated to the point that treatments for neurological disorders such as lysosomal storage diseases seem within reach.", "output": {"entities": {}}, "schema": []}
{"input": "Other neurodevelopmental disorders, such as Rett Syndrome, Fragile X, and autism still face significant obstacles to overcome before a viable human gene therapy can be considered.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on the most common CNS gene delivery vehicle, adeno-associated virus (AAV), and the current state of AAV vector design and delivery for CNS gene therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Relevant examples of gene therapy studies for neurodevelopmental disorders, as well as outstanding challenges, are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.", "output": {"entities": {}}, "schema": []}
{"input": "Phytochemical analysis of the essential oils of 10 endemic Cephalaria species from Turkey.", "output": {"entities": {}}, "schema": []}
{"input": "The volatile composition of 10 endemic Cephalaria (Dipsacaceae) species (Cephalaria gazipashensis, Cephalaria lycica, Cephalaria paphlagonica, Cephalaria elmaliensis, Cephalaria stellipilis, Cephalaria scoparia, Cephalaria isaurica, Cephalaria cilicica, Cephalaria elazigensis var. purpurea and Cephalaria davisiana) was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The essential oil mixtures were obtained by steam distillation in a Clevenger-type apparatus.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-eight components were identified by GC-FID and GC-MS techniques.", "output": {"entities": {}}, "schema": []}
{"input": "While total volatile percentages ranged from 68. 99% to 84. 57%, the total essential oil yields ranged between 38. 15% and 64. 05%.", "output": {"entities": {}}, "schema": []}
{"input": "Geraniol, alpha-cedrene and p-cymene were determined as the main components.", "output": {"entities": {"chemical": [{"text": "Geraniol", "start": 0, "end": 8}, {"text": "alpha-cedrene", "start": 10, "end": 23}, {"text": "p-cymene", "start": 28, "end": 36}]}}, "schema": []}
{"input": "Geraniol was detected as a major component in C. cilicica (14. 64%), and alpha-cedrene was detected as a major component with 26. 03% for C. lycica, 16. 93% for C. scoparia, 13. 01% for C. davisiana and 10. 94% for C. paphlagonica.", "output": {"entities": {"chemical": [{"text": "Geraniol", "start": 0, "end": 8}, {"text": "alpha-cedrene", "start": 73, "end": 86}]}}, "schema": []}
{"input": "Cephalaria scoparia, C. davisiana and C. gazipashensis have considerable amount of p-cymene as 12. 86%, 12. 70% and 11. 16%, respectively.", "output": {"entities": {"chemical": [{"text": "p-cymene", "start": 83, "end": 91}]}}, "schema": []}
{"input": "This was the first essential oil report concerning the Cephalaria genus.", "output": {"entities": {}}, "schema": []}
{"input": "Auraptene and its Effects on the Re-emergence of Colon Cancer Stem Cells.", "output": {"entities": {"chemical": [{"text": "Auraptene", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Recent studies indicate that auraptene (7-geranyloxycoumarin, AUR), a geranyloxycoumarin extracted from fruits of edible plants belonging to the Rutaceae family, may represent a novel lead compound for dietary colon cancer chemoprevention in rodents.", "output": {"entities": {"chemical": [{"text": "auraptene", "start": 29, "end": 38}, {"text": "7-geranyloxycoumarin", "start": 40, "end": 60}, {"text": "AUR", "start": 62, "end": 65}, {"text": "geranyloxycoumarin", "start": 70, "end": 88}]}}, "schema": []}
{"input": "As a continuation of studies aimed to better depict the pharmacological effects and mechanism of action of the title natural compound, the current investigation was undertaken to determine whether AUR would be able to prevent the growth and sphere (surrogate tumors) formation of FOLFOX-resistant colon cancer cells that are highly enriched in cancer stem cells (CSCs).", "output": {"entities": {"chemical": [{"text": "AUR", "start": 197, "end": 200}]}}, "schema": []}
{"input": "Our results demonstrate that AUR at a concentration of 10 mu M was able to inhibit the growth and formation of colonospheres of FOLFOX-resistant colon cancer HT-29 cells in vitro.", "output": {"entities": {"chemical": [{"text": "AUR", "start": 29, "end": 32}]}}, "schema": []}
{"input": "The corresponding parental cells were also similarly affected by AUR at the same concentration level.", "output": {"entities": {"chemical": [{"text": "AUR", "start": 65, "end": 68}]}}, "schema": []}
{"input": "The reduction in the growth and colonospheres formation in FOLFOX-resistant HT-29 was also associated with a concomitant decrease in phospho-epidermal growth factor receptor.", "output": {"entities": {"chemical": [{"text": "phospho", "start": 133, "end": 140}]}}, "schema": []}
{"input": "These findings suggest that AUR could prevent the re-emergence of CSCs.", "output": {"entities": {"chemical": [{"text": "AUR", "start": 28, "end": 31}]}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) Extracts Inhibit the Growth of the Breast Cancer Cell Lines MDA-MB-231 and MCF-7, But Not the Brain Tumour Cell Line U251 In Vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Zanthoxylum usambarense (Engl.) Kokwaro has traditionally been used for the treatment of malaria, upper respiratory tract infections, cough, rheumatism, tooth decay and sore gums in Kenya and other African countries.", "output": {"entities": {}}, "schema": []}
{"input": "Dried ground parts of Z. usambarense were extracted by maceration using methanol (MeOH) at room temperature, extract was dried and reconstituted in 70% aq.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 72, "end": 80}, {"text": "MeOH", "start": 82, "end": 86}]}}, "schema": []}
{"input": "MeOH and partitioned against n-hexane and chloroform (CHCl3) to obtain MeOH, n-hexane and CHCl3 extracts.", "output": {"entities": {"chemical": [{"text": "MeOH", "start": 0, "end": 4}, {"text": "n-hexane", "start": 29, "end": 37}, {"text": "chloroform", "start": 42, "end": 52}, {"text": "CHCl3", "start": 54, "end": 59}, {"text": "MeOH", "start": 71, "end": 75}, {"text": "n-hexane", "start": 77, "end": 85}, {"text": "CHCl3", "start": 90, "end": 95}]}}, "schema": []}
{"input": "All extracts were assessed for cytotoxicity against two breast cancer cell lines, MDA-MB-231 and MCF-7, and the brain tumour cell line U251 by the MTT assay.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 147, "end": 150}]}}, "schema": []}
{"input": "The free-radical scavenging activity of the extracts was also determined by the 2, 2-diphenyl-1-picryhydrazyl (DPPH) assay.", "output": {"entities": {"chemical": [{"text": "2, 2-diphenyl-1-picryhydrazyl", "start": 80, "end": 109}, {"text": "DPPH", "start": 111, "end": 115}]}}, "schema": []}
{"input": "In the DPPH assay, the MeOH extract was found to be the most active free-radical scavenger with a RC50 value of 41. 1 x 10 (-3) mg/mL.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 7, "end": 11}, {"text": "MeOH", "start": 23, "end": 27}]}}, "schema": []}
{"input": "It also displayed significant cytotoxicity against the MCF-7 cell line (IC50 42. 9 micro g/mL) and appeared to have induced cell death through apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "None of the test extracts showed any activity against the U251 cell line at test concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "The present findings demonstrated that Z. usambarense could be a potential source for new cytotoxic compounds for possible anticancer drug development.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Perturbing peptide cation-radical electronic states by thioxoamide groups: formation, dissociations, and energetics of thioxopeptide cation-radicals.", "output": {"entities": {"chemical": [{"text": "thioxoamide", "start": 55, "end": 66}]}}, "schema": []}
{"input": "Thioxodipeptides Gly-thio-Lys (GtK), Ala-thio-Lys (AtK), and Ala-thio-Arg (AtR) in which the amide group has been modified to a thioxoamide were made into dications by electrospray ionization and converted to cation-radicals, (GtK + 2H) (+ *), (AtK + 2H) (+ *), and (AtR + 2H) (+ *), by electron transfer dissociation (ETD) tandem mass spectrometry using fluoranthene anion-radical as an electron donor.", "output": {"entities": {"chemical": [{"text": "Thioxodipeptides Gly-thio-Lys", "start": 0, "end": 29}, {"text": "GtK", "start": 31, "end": 34}, {"text": "Ala-thio-Lys", "start": 37, "end": 49}, {"text": "AtK", "start": 51, "end": 54}, {"text": "Ala-thio-Arg", "start": 61, "end": 73}, {"text": "AtR", "start": 75, "end": 78}, {"text": "amide", "start": 93, "end": 98}, {"text": "thioxoamide", "start": 128, "end": 139}, {"text": "GtK", "start": 227, "end": 230}, {"text": "2H", "start": 233, "end": 235}, {"text": "AtK", "start": 245, "end": 248}, {"text": "2H", "start": 251, "end": 253}, {"text": "AtR", "start": 267, "end": 270}, {"text": "2H", "start": 273, "end": 275}, {"text": "fluoranthene anion-radical", "start": 355, "end": 381}]}}, "schema": []}
{"input": "The common and dominant dissociation of these cation-radicals was the loss of a hydrogen atom.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 80, "end": 88}]}}, "schema": []}
{"input": "The dissociation products were characterized by collision-induced dissociation (CID) multistage tandem mass spectrometry up to CID-MS (5).", "output": {"entities": {}}, "schema": []}
{"input": "The ground electronic states of several (GtK + 2H) (+ *), (AtK + 2H) (+ *), and (AtR + 2H) (+ *) conformers were explored by extensive ab initio and density functional theory calculations of the potential energy surface.", "output": {"entities": {"chemical": [{"text": "GtK", "start": 41, "end": 44}, {"text": "2H", "start": 47, "end": 49}, {"text": "AtK", "start": 59, "end": 62}, {"text": "2H", "start": 65, "end": 67}, {"text": "AtR", "start": 81, "end": 84}, {"text": "2H", "start": 87, "end": 89}]}}, "schema": []}
{"input": "In silico electron transfer to the precursor dications, (GtK + 2H) (2 +), (AtK + 2H) (2 +), and (AtR + 2H) (2 +), formed zwitterionic intermediates containing thioenol anion-radical and ammonium cation groups that were local energy minima on the potential energy surface of the ground electronic state.", "output": {"entities": {"chemical": [{"text": "GtK", "start": 57, "end": 60}, {"text": "2H", "start": 63, "end": 65}, {"text": "AtK", "start": 75, "end": 78}, {"text": "2H", "start": 81, "end": 83}, {"text": "AtR", "start": 97, "end": 100}, {"text": "2H", "start": 103, "end": 105}, {"text": "thioenol anion-radical", "start": 159, "end": 181}, {"text": "ammonium cation", "start": 186, "end": 201}]}}, "schema": []}
{"input": "The zwitterions underwent facile isomerization by N-terminal ammonium proton migration to the thioenol anion-radical group forming aminothioketyl intermediates.", "output": {"entities": {"chemical": [{"text": "N", "start": 50, "end": 51}, {"text": "ammonium", "start": 61, "end": 69}, {"text": "thioenol anion-radical", "start": 94, "end": 116}, {"text": "aminothioketyl", "start": 131, "end": 145}]}}, "schema": []}
{"input": "Combined potential energy mapping and RRKM calculations of dissociation rate constants identified N-C (alpha) bond cleavages as the most favorable dissociation pathways, in a stark contrast to the experimental results.", "output": {"entities": {"chemical": [{"text": "N-C (alpha)", "start": 98, "end": 109}]}}, "schema": []}
{"input": "This discrepancy is interpreted as being due to the population upon electron transfer of low-lying excited electronic states that promote loss of hydrogen atoms.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 146, "end": 154}]}}, "schema": []}
{"input": "For (GtK + 2H) (+ *), these excited states were characterized by time-dependent density functional theory as A-C states that had large components of Rydberg-like 3s molecular orbitals at the N-terminal and lysine ammonium groups that are conducive to hydrogen atom loss.", "output": {"entities": {"chemical": [{"text": "GtK", "start": 5, "end": 8}, {"text": "2H", "start": 11, "end": 13}, {"text": "N", "start": 191, "end": 192}, {"text": "lysine ammonium", "start": 206, "end": 221}, {"text": "hydrogen", "start": 251, "end": 259}]}}, "schema": []}
{"input": "Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study.", "output": {"entities": {}}, "schema": []}
{"input": "In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric alpha 7 nicotinic acetylcholine receptor (nAChR) modulator JNJ-39393406 in a key translational assay (sensory P50 gating) in 39 regularly smoking male patients with schizophrenia.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 179, "end": 192}, {"text": "JNJ-39393406", "start": 220, "end": 232}]}}, "schema": []}
{"input": "All patients were clinically stable and JNJ-39393406 was administered as an adjunct treatment to antipsychotics.", "output": {"entities": {"chemical": [{"text": "JNJ-39393406", "start": 40, "end": 52}]}}, "schema": []}
{"input": "No indication was found that JNJ-39393406 has the potential to reverse basic deficits of information processing in schizophrenia (sensory P50 gating) or has a significant effect on other tested electrophysiological markers (MMN, P300 and quantitative resting EEG).", "output": {"entities": {"chemical": [{"text": "JNJ-39393406", "start": 29, "end": 41}]}}, "schema": []}
{"input": "Sensitivity analyses including severity of disease, baseline P50 gating, medication and gene variants of the CHRNA7 gene did not reveal any subgroups with consistent significant effects.", "output": {"entities": {}}, "schema": []}
{"input": "It is discussed that potential positive effects in subgroups not present or not large enough in the current study or upon chronic dosing are possible, but unlikely to be developed.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Terminal differentiation and loss of tumorigenicity of human cancers via pluripotency-based reprogramming.", "output": {"entities": {}}, "schema": []}
{"input": "Pluripotent cells can be derived from various types of somatic cells by nuclear reprogramming using defined transcription factors.", "output": {"entities": {}}, "schema": []}
{"input": "It is, however, unclear whether human cancer cells can be similarly reprogrammed and subsequently terminally differentiated with abrogation of tumorigenicity.", "output": {"entities": {}}, "schema": []}
{"input": "Here, using sarcomas we show that human-derived complex karyotype solid tumors: (1) can be reprogrammed into a pluripotent-like state as defined by all in vitro criteria used to define pluripotent stem cells generated from somatic cells; (2) can be terminally differentiated into mature connective tissue and red blood cells; and (3) terminal differentiation is accompanied with loss of both proliferation and tumorigenicity.", "output": {"entities": {}}, "schema": []}
{"input": "We go on to perform the first global DNA promoter methylation and gene expression analyses comparing human cancers to their reprogrammed counterparts and report that reprogramming/differentiation results in significant epigenetic remodeling of oncogenes and tumor suppressors, while not significantly altering the differentiation status of the reprogrammed cancer cells, in essence dedifferentiating them to a state slightly before the mesenchymal stem cell differentiation stage.", "output": {"entities": {}}, "schema": []}
{"input": "Our data demonstrate that direct nuclear reprogramming can restore terminal differentiation potential to human-derived cancer cells, with simultaneous loss of tumorigenicity, without the need to revert to an embryonic state.", "output": {"entities": {}}, "schema": []}
{"input": "We anticipate that our models would serve as a starting point to more fully assess how nuclear reprogramming overcomes the multitude of genetic and epigenetic aberrancies inherent in human cancers to restore normal terminal differentiation pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, these findings suggest that nuclear reprogramming may be a broadly applicable therapeutic strategy for the treatment of cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of collisional and vibrational velocity on proton and deuteron transfer in the reaction of HOD + with CO.", "output": {"entities": {"chemical": [{"text": "deuteron", "start": 62, "end": 70}, {"text": "HOD +", "start": 99, "end": 104}, {"text": "CO", "start": 110, "end": 112}]}}, "schema": []}
{"input": "Reaction of HOD (+) with CO was studied over the collision energy (E (col)) range between 0. 18 and 2. 87 eV, for HOD (+) in its ground state and with one quantum in each of its vibrational modes: (001)--predominantly OH stretch; (010)--bend, and (100)--predominately OD stretch.", "output": {"entities": {"chemical": [{"text": "HOD (+)", "start": 12, "end": 19}, {"text": "CO", "start": 25, "end": 27}, {"text": "HOD (+)", "start": 114, "end": 121}, {"text": "OH", "start": 218, "end": 220}, {"text": "OD", "start": 268, "end": 270}]}}, "schema": []}
{"input": "In addition to integral cross sections, product recoil velocity distributions were also measured for each initial condition.", "output": {"entities": {}}, "schema": []}
{"input": "The dominant reactions are near-thermoneutral proton and deuteron transfer, generating HCO (+) and DCO (+) product ions by a predominantly direct mechanism.", "output": {"entities": {"chemical": [{"text": "deuteron", "start": 57, "end": 65}, {"text": "HCO (+)", "start": 87, "end": 94}, {"text": "DCO (+)", "start": 99, "end": 106}]}}, "schema": []}
{"input": "The HCO (+) and DCO (+) channels occur with a combined efficiency of 76% for ground state HOD (+) at our lowest E (col), increasing to 94% for E (col) around 0. 33 eV, then falling at high E (col) to ~ 40%.", "output": {"entities": {"chemical": [{"text": "HCO (+)", "start": 4, "end": 11}, {"text": "DCO (+)", "start": 16, "end": 23}, {"text": "HOD (+)", "start": 90, "end": 97}]}}, "schema": []}
{"input": "The HCO (+) and DCO (+) channels have a complicated dependence on the HOD (+) vibrational state.", "output": {"entities": {"chemical": [{"text": "HCO (+)", "start": 4, "end": 11}, {"text": "DCO (+)", "start": 16, "end": 23}, {"text": "HOD (+)", "start": 70, "end": 77}]}}, "schema": []}
{"input": "Excitation of the OH or OD stretch modes enhances H (+) or D (+) transfer, respectively, and inhibits D (+) or H (+) transfer.", "output": {"entities": {"chemical": [{"text": "OH", "start": 18, "end": 20}, {"text": "OD", "start": 24, "end": 26}, {"text": "H (+)", "start": 50, "end": 55}, {"text": "D (+)", "start": 59, "end": 64}, {"text": "D (+)", "start": 102, "end": 107}, {"text": "H (+)", "start": 111, "end": 116}]}}, "schema": []}
{"input": "Bend excitation preferentially enhances H (+) transfer, with no effect on D (+) transfer.", "output": {"entities": {"chemical": [{"text": "H (+)", "start": 40, "end": 45}, {"text": "D (+)", "start": 74, "end": 79}]}}, "schema": []}
{"input": "There is no coupling of energy initially in any HOD (+) vibrational mode to recoil velocity of either of the product ions, even at low E (col) where vibrational excitation doubles or triples the energy available to products.", "output": {"entities": {"chemical": [{"text": "HOD (+)", "start": 48, "end": 55}]}}, "schema": []}
{"input": "The results suggest that transfer of H or D atoms is enhanced if the atom in question has a high vibrational velocity, and that this effect offsets what is otherwise a general inhibition of reactivity by added energy.", "output": {"entities": {"chemical": [{"text": "H", "start": 37, "end": 38}, {"text": "D", "start": 42, "end": 43}]}}, "schema": []}
{"input": "HOCO (+) + D and DOCO (+) + H products are also observed, but as minor channels despite being barrierless and exoergic.", "output": {"entities": {"chemical": [{"text": "HOCO (+)", "start": 0, "end": 8}, {"text": "D", "start": 11, "end": 12}, {"text": "DOCO (+)", "start": 17, "end": 25}, {"text": "H", "start": 28, "end": 29}]}}, "schema": []}
{"input": "These channels appear to be complex mediated at low E (col), essentially vanish at intermediate E (col), then reappear with a direct reaction mechanism at high E (col).", "output": {"entities": {}}, "schema": []}
{"input": "Density functional theory study on the reaction mechanism of synthesizing 1, 3-dimethyl-2-imidazolidinone by urea method.", "output": {"entities": {"chemical": [{"text": "1, 3-dimethyl-2-imidazolidinone", "start": 74, "end": 105}, {"text": "urea", "start": 109, "end": 113}]}}, "schema": []}
{"input": "We report a first-principles density functional theory investigation on tailoring the fundamental reaction mechanism of synthesizing 1, 3-dimethyl-2-imidazolidinone (DMI) through the urea method with water serving as both solvent and catalyst.", "output": {"entities": {"chemical": [{"text": "1, 3-dimethyl-2-imidazolidinone", "start": 133, "end": 164}, {"text": "DMI", "start": 166, "end": 169}, {"text": "urea", "start": 183, "end": 187}]}}, "schema": []}
{"input": "The nucleophilic cyclization reaction is implemented by two ammonia removal steps.", "output": {"entities": {"chemical": [{"text": "ammonia", "start": 60, "end": 67}]}}, "schema": []}
{"input": "One-NH group of dimethylethylenediamine (DMEDA) first attacks the carbon atom of urea, eliminating one-NH3 group and forming an intermediate state CH3NHC2H4N (CH3) CONH2 (IMI).", "output": {"entities": {"chemical": [{"text": "NH", "start": 4, "end": 6}, {"text": "dimethylethylenediamine", "start": 16, "end": 39}, {"text": "DMEDA", "start": 41, "end": 46}, {"text": "carbon", "start": 66, "end": 72}, {"text": "urea", "start": 81, "end": 85}, {"text": "NH3", "start": 103, "end": 106}, {"text": "CH3NHC2H4N (CH3) CONH2", "start": 147, "end": 169}]}}, "schema": []}
{"input": "IMI subsequently undergoes the cyclization process through a secondary ammonia removal via similar manner.", "output": {"entities": {"chemical": [{"text": "secondary ammonia", "start": 61, "end": 78}]}}, "schema": []}
{"input": "Without water, the two ammonia removal steps are both slightly exothermic with high activation barriers (~ 50 kcal mol (-1)).", "output": {"entities": {"chemical": [{"text": "ammonia", "start": 23, "end": 30}]}}, "schema": []}
{"input": "As water participated in the reaction, the kinetics of the two steps can be significantly improved, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The role that water plays, beside as solvent, more importantly, is to serve as a proton exchange bridge.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the spatial configuration, the direct proton migration from the N atoms of ethylenediamine to urea is difficult to occur.", "output": {"entities": {"chemical": [{"text": "N", "start": 71, "end": 72}, {"text": "ethylenediamine", "start": 82, "end": 97}, {"text": "urea", "start": 101, "end": 105}]}}, "schema": []}
{"input": "The water bridge facilitates the proton migration by shortening the migration distance.", "output": {"entities": {}}, "schema": []}
{"input": "As a consequence, the activation barriers are considerably lowered down to ~ 30 kcal mol (-1), indicating a strong catalytic effect from water.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the three possible side reactions of IM (I), even catalyzed by water, have higher activation barriers due to strong steric inhibitive effect and consequently become difficult to occur at the same condition.", "output": {"entities": {}}, "schema": []}
{"input": "The current computational understanding on the prototypical reaction to DMI can be extended to guide developing more efficient routes to synthesize imidazolidinone derivatives through the urea method.", "output": {"entities": {"chemical": [{"text": "DMI", "start": 72, "end": 75}, {"text": "imidazolidinone", "start": 148, "end": 163}, {"text": "urea", "start": 188, "end": 192}]}}, "schema": []}
{"input": "Leveraging the cortical cholinergic system to enhance attention.", "output": {"entities": {}}, "schema": []}
{"input": "Attentional impairments are found in a range of neurodegenerative and neuropsychiatric disorders.", "output": {"entities": {}}, "schema": []}
{"input": "However, the development of procognitive enhancers to alleviate these impairments has been hindered by a lack of comprehensive hypotheses regarding the circuitry mediating the targeted attentional functions.", "output": {"entities": {}}, "schema": []}
{"input": "Here we discuss the role of the cortical cholinergic system in mediating cue detection and attentional control and propose two target mechanisms for cognition enhancers: stimulation of prefrontal alpha 4 beta 2 * nicotinic acetylcholine receptors (nAChR) for the enhancement of cue detection and augmentation of tonic acetylcholine levels for the enhancement of attentional control.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 223, "end": 236}, {"text": "acetylcholine", "start": 318, "end": 331}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "A selective dopamine reuptake inhibitor improves prefrontal cortex-dependent cognitive function: potential relevance to attention deficit hyperactivity disorder.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 12, "end": 20}]}}, "schema": []}
{"input": "Drugs used to treat attention deficit hyperactivity disorder (ADHD) improve prefrontal cortex (PFC)-dependent cognitive function.", "output": {"entities": {}}, "schema": []}
{"input": "The majority of ADHD-related treatments act either as dual norepinephrine (NE) and dopamine (DA) reuptake inhibitors (psychostimulants) or selective NE reuptake inhibitors (SNRIs).", "output": {"entities": {"chemical": [{"text": "norepinephrine", "start": 59, "end": 73}, {"text": "dopamine", "start": 83, "end": 91}]}}, "schema": []}
{"input": "Certain benztropine analogs act as highly selective DA reuptake inhibitors while lacking the reinforcing actions, and thus abuse potential, of psychostimulants.", "output": {"entities": {"chemical": [{"text": "benztropine", "start": 8, "end": 19}]}}, "schema": []}
{"input": "To assess the potential use of these compounds in the treatment of ADHD, we examined the effects of a well-characterized benztropine analog, AHN 2-005, on performance of rats in a PFC-dependent delayed-alternation task of spatial working memory.", "output": {"entities": {"chemical": [{"text": "benztropine", "start": 121, "end": 132}, {"text": "AHN 2-005", "start": 141, "end": 150}]}}, "schema": []}
{"input": "Similar to that seen with all drugs currently approved for ADHD, AHN 2-005 dose-dependently improved performance in this task.", "output": {"entities": {"chemical": [{"text": "AHN 2-005", "start": 65, "end": 74}]}}, "schema": []}
{"input": "Clinically-relevant doses of psychostimulants and SNRIs elevate NE and DA preferentially in the PFC.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the selectivity of this compound for the DA transporter, additional microdialysis studies demonstrated that a cognition-enhancing dose of AHN 2-005 that lacked locomotor activating effects increased extracellular levels of both DA and NE in the PFC.", "output": {"entities": {"chemical": [{"text": "AHN 2-005", "start": 146, "end": 155}]}}, "schema": []}
{"input": "AHN 2-005 produced a larger increase in extracellular DA in the nucleus accumbens, although the magnitude of this was well below that seen with motor activating doses of psychostimulants.", "output": {"entities": {"chemical": [{"text": "AHN 2-005", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Collectively, these observations suggest that benztropine analogs may be efficacious in the treatment of ADHD or other disorders associated with PFC dysfunction.", "output": {"entities": {"chemical": [{"text": "benztropine", "start": 46, "end": 57}]}}, "schema": []}
{"input": "These studies provide a strong rationale for future research focused on the neural mechanisms contributing to the cognition-enhancing actions and the potential clinical utility of AHN 2-005 and related compounds.", "output": {"entities": {"chemical": [{"text": "AHN 2-005", "start": 180, "end": 189}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "The NMDA receptor as a target for cognitive enhancement.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 4, "end": 8}]}}, "schema": []}
{"input": "NMDA receptors (NMDARs) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development.", "output": {"entities": {}}, "schema": []}
{"input": "Enhancement of NMDAR function is a core strategy toward this goal.", "output": {"entities": {}}, "schema": []}
{"input": "In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation.", "output": {"entities": {}}, "schema": []}
{"input": "There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required.", "output": {"entities": {}}, "schema": []}
{"input": "Excessive activation and the resultant deleterious effects will need to be carefully avoided.", "output": {"entities": {}}, "schema": []}
{"input": "Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Correlation of high urinary Smad1 level with glomerular hyperfiltration in type 2 diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to assess the relationship between urinary Smad1 and glomerular hyperfiltration (GHF) in type 2 diabetes mellitus (T2DM), and to explore the factors related to the urinary Smad1 in T2DM.", "output": {"entities": {}}, "schema": []}
{"input": "The reference value of the estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals.", "output": {"entities": {}}, "schema": []}
{"input": "30 patients with GHF, 58 patients with norm-GFR T2DM, and 24 healthy patients who served as controls were recruited.", "output": {"entities": {}}, "schema": []}
{"input": "Urinary Smad1, fasting plasma glucose (FPG), fasting serum C-Peptide (C-P), hemoglobin A1C (HbA1c), cystatin C, and other chemistry laboratory parameters of T2DM participants and controls were measured.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 30, "end": 37}]}}, "schema": []}
{"input": "Patients with GHF had higher levels of urinary Smad1 than the control group, and those with norm-GFR.", "output": {"entities": {}}, "schema": []}
{"input": "For T2DM patients with body mass index, age, and gender adjustments, urinary Smad1 was positively correlated with FPG, HbA1C, and eGFR, but negatively correlated with fasting serum C-P.", "output": {"entities": {}}, "schema": []}
{"input": "Multivariate linear regression analysis demonstrated that eGFR, HbA1C, and fasting serum C-P were independently associated with urinary Smad1.", "output": {"entities": {}}, "schema": []}
{"input": "High levels of urinary Smad1 were found in GHF patients with T2DM, which may be another potential mechanism of GHF in relation to diabetic nephropathy.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of antifungal activities of Vietnamese citrus essential oils.", "output": {"entities": {}}, "schema": []}
{"input": "Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method.", "output": {"entities": {}}, "schema": []}
{"input": "The results show that the EOs had significant antifungal activity.", "output": {"entities": {}}, "schema": []}
{"input": "Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries.", "output": {"entities": {}}, "schema": []}
{"input": "Metastability in Pressure-Induced Structural Transformations of CdSe/ZnS Core/Shell Nanocrystals.", "output": {"entities": {"chemical": [{"text": "CdSe", "start": 64, "end": 68}, {"text": "ZnS", "start": 69, "end": 72}]}}, "schema": []}
{"input": "The kinetics and thermodynamics of structural transformations under pressure depend strongly on particle size due to the influence of surface free energy.", "output": {"entities": {}}, "schema": []}
{"input": "By suitable design of surface structure, composition, and passivation it is possible, in principle, to prepare nanocrystals in structures inaccessible to bulk materials.", "output": {"entities": {}}, "schema": []}
{"input": "However, few realizations of such extreme size-dependent behavior exist.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show with molecular dynamics computer simulation that in a model of CdSe/ZnS core/shell nanocrystals the core high-pressure structure can be made metastable under ambient conditions by tuning the thickness of the shell.", "output": {"entities": {"chemical": [{"text": "CdSe", "start": 77, "end": 81}, {"text": "ZnS", "start": 82, "end": 85}]}}, "schema": []}
{"input": "In nanocrystals with thick shells, we furthermore observe a wurtzite to NiAs transformation, which does not occur in the pure bulk materials.", "output": {"entities": {"chemical": [{"text": "wurtzite", "start": 60, "end": 68}, {"text": "NiAs", "start": 72, "end": 76}]}}, "schema": []}
{"input": "These phenomena are linked to a fundamental change in the atomistic transformation mechanism from heterogeneous nucleation at the surface to homogeneous nucleation in the crystal core.", "output": {"entities": {}}, "schema": []}
{"input": "Radiolabeled mass-balance excretion and metabolism studies in laboratory animals: a commentary on why they are still necessary.", "output": {"entities": {}}, "schema": []}
{"input": "The necessity of conducting traditional radiolabeled absorption, distribution, metabolism and excretion (ADME) studies in animals during development of new investigative agents has been questioned in a recent review.", "output": {"entities": {}}, "schema": []}
{"input": "We present a compilation of the benefits of such studies in the understanding of the in vivo pharmacological activity and disposition of new drug candidates, including interpretation of preclinical toxicology findings, characterization of circulating metabolites, and determination of principal pathways of clearance.", "output": {"entities": {}}, "schema": []}
{"input": "This understanding is valuable in anticipating the human disposition of the drugs and the planning of the clinical development program.", "output": {"entities": {}}, "schema": []}
{"input": "Because of new technologies, evolving regulatory expectations, and increased scientific understanding of the disposition of drugs, the traditional design and timing of both animal and human ADME studies should be reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "Innovative \" fit-for-purpose \" studies may well be a better choice in a particular drug development program than a standard animal ADME \" package \".", "output": {"entities": {}}, "schema": []}
{"input": "However, we submit that, at this time, radiolabeled animal ADME studies still provide a definitive and irreplaceable component of our understanding of the in vivo actions and behaviors of drugs and should continue to be performed prior to the exposure of large numbers of human subjects to investigative drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Serotonergic involvement in the amelioration of behavioral abnormalities in dopamine transporter knockout mice by nicotine.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 76, "end": 84}, {"text": "nicotine", "start": 114, "end": 122}]}}, "schema": []}
{"input": "Dopamine transporter knockout (DAT KO) mice exhibit elevated extracellular dopamine levels in brain regions that include the striatum and the nucleus accumbens, but not the prefrontal cortex.", "output": {"entities": {"chemical": [{"text": "Dopamine", "start": 0, "end": 8}, {"text": "dopamine", "start": 75, "end": 83}]}}, "schema": []}
{"input": "DAT KO mice model some aspects of psychiatric disorders, including schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "Smoking is more common in patients with schizophrenia, suggesting that nicotine might ameliorate aspects of the behavioral abnormalities and/or treatment side effects seen in these individuals.", "output": {"entities": {}}, "schema": []}
{"input": "We report nicotine-induced normalization of effects on locomotion and prepulse inhibition of acoustic startle (PPI) in DAT KO mice that require intact serotonin 5-HT1A systems.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 10, "end": 18}, {"text": "serotonin", "start": 151, "end": 160}]}}, "schema": []}
{"input": "First, we observed that the marked hyperactivity displayed by DAT KO mice was reduced by administration of nicotine.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 107, "end": 115}]}}, "schema": []}
{"input": "This nicotine effect was blocked by pretreatment with the non-specific nicotinic acetylcholine (nACh) receptor antagonist mecamylamine, or the 5-HT1A antagonist WAY100635.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 5, "end": 13}, {"text": "acetylcholine", "start": 81, "end": 94}, {"text": "mecamylamine", "start": 122, "end": 134}, {"text": "WAY100635", "start": 161, "end": 170}]}}, "schema": []}
{"input": "Secondly, we examined the effects of nicotine on PPI in DAT KO mice.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Treatment with nicotine significantly ameliorated the PPI deficits observed in DAT KO mice.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 15, "end": 23}]}}, "schema": []}
{"input": "The ameliorating action of nicotine on PPI deficits in DAT KO mice was blocked by mecamylamine, the alpha 7 nACh receptor antagonist methyllycaconitine or WAY100635, while the alpha 4 beta 2 nACh receptor antagonist dihydro-beta-erythroidinehydrobromide (DH beta E) produced only a non-significant trend toward attenuation of nicotine effects.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 27, "end": 35}, {"text": "mecamylamine", "start": 82, "end": 94}, {"text": "methyllycaconitine", "start": 133, "end": 151}, {"text": "WAY100635", "start": 155, "end": 164}, {"text": "dihydro-beta-erythroidinehydrobromide", "start": 216, "end": 253}, {"text": "DH beta E", "start": 255, "end": 264}, {"text": "nicotine", "start": 326, "end": 334}]}}, "schema": []}
{"input": "Finally, we observed that administration of the 5-HT1A receptor agonist 8-OH-DPAT also ameliorated the deficit in PPI observed in DAT KO mice.", "output": {"entities": {"chemical": [{"text": "8-OH-DPAT", "start": 72, "end": 81}]}}, "schema": []}
{"input": "This amelioration was antagonized by pretreatment with WAY100635.", "output": {"entities": {"chemical": [{"text": "WAY100635", "start": 55, "end": 64}]}}, "schema": []}
{"input": "These data support the idea that nicotine might ameliorate some of the cognitive dysfunctions found in schizophrenia in a 5-HT1A-dependent fashion.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 33, "end": 41}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Two new diterpenes from Caesalpinia minax Hance.", "output": {"entities": {"chemical": [{"text": "diterpenes", "start": 8, "end": 18}]}}, "schema": []}
{"input": "Two new cassane-type diterpenes, Caesalpinolide F (1) and Caesalpinolide G (2) were isolated from Caesalpinia minax Hance.", "output": {"entities": {"chemical": [{"text": "cassane", "start": 8, "end": 15}, {"text": "diterpenes", "start": 21, "end": 31}, {"text": "Caesalpinolide F", "start": 33, "end": 49}, {"text": "Caesalpinolide G", "start": 58, "end": 74}]}}, "schema": []}
{"input": "Their structures were elucidated on the basis of 1D and 2D NMR, MS and CD analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1 and 2 were tested against colon carcinoma (HCT-8) and breast cancer (MCF-7) human cancer cell lines, and showed mild cytotoxicity activities.", "output": {"entities": {}}, "schema": []}
{"input": "Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats.", "output": {"entities": {"chemical": [{"text": "diiosononyl phthalate", "start": 15, "end": 36}]}}, "schema": []}
{"input": "Pregnant Sprague-Dawley rats received 50, 250, and 500 mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus.", "output": {"entities": {"chemical": [{"text": "diisononyl phthalate", "start": 65, "end": 85}, {"text": "DiNP", "start": 87, "end": 91}]}}, "schema": []}
{"input": "Monoisononyl phthalate (MiNP), mono (carboxy-isooctyl) phthalate (MCiOP), mono (hydroxyl-isononyl) phthalate (MHiNP), mono (oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues.", "output": {"entities": {"chemical": [{"text": "Monoisononyl phthalate", "start": 0, "end": 22}, {"text": "MiNP", "start": 24, "end": 28}, {"text": "mono (carboxy-isooctyl) phthalate", "start": 31, "end": 64}, {"text": "MCiOP", "start": 66, "end": 71}, {"text": "mono (hydroxyl-isononyl) phthalate", "start": 74, "end": 108}, {"text": "MHiNP", "start": 110, "end": 115}, {"text": "mono (oxo-isononyl) phthalate", "start": 118, "end": 147}, {"text": "MOiNP", "start": 149, "end": 154}, {"text": "monoisononyl phthalate glucuronide", "start": 161, "end": 195}, {"text": "MiNP-G", "start": 197, "end": 203}]}}, "schema": []}
{"input": "MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G.", "output": {"entities": {"chemical": [{"text": "MCiOP", "start": 0, "end": 5}, {"text": "MiNP", "start": 64, "end": 68}, {"text": "MHiNP", "start": 70, "end": 75}, {"text": "MOiNP", "start": 77, "end": 82}, {"text": "MiNP-G", "start": 88, "end": 94}]}}, "schema": []}
{"input": "Percentage of dose absorbed decreased at 750 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "Testosterone concentration in the fetal testes was reduced at 250 and 750 mg/kg/day.", "output": {"entities": {"chemical": [{"text": "Testosterone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Multinucleated germ cells were increased in the testes of rats at 250 and 750 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 111, "end": 123}]}}, "schema": []}
{"input": "Quantitative prediction of CYP2B6 induction by estradiol during pregnancy: potential explanation for increased methadone clearance during pregnancy.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 47, "end": 56}, {"text": "methadone", "start": 111, "end": 120}]}}, "schema": []}
{"input": "There is considerable evidence that pregnancy changes the disposition of drugs in an enzyme-and gestational stage-specific manner.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of probe drug studies, the activity of CYP3A4 and CYP2D6 increases and CYP1A2 decreases during human pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "However, no studies of CYP2B6 activity during human pregnancy have been conducted.", "output": {"entities": {}}, "schema": []}
{"input": "In rodent models and in HepG2 cells, CYP2B enzymes have been shown to be regulated by estradiol.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 86, "end": 95}]}}, "schema": []}
{"input": "Because estradiol concentrations increase by ~ 50-fold during human pregnancy, it was hypothesized that the increasing estradiol concentrations during human pregnancy would result in induction of CYP2B6 activity.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 8, "end": 17}, {"text": "estradiol", "start": 119, "end": 128}]}}, "schema": []}
{"input": "Hepatocytes from three female donors were treated with estradiol, and the EC (50) and E (max) were measured for CYP2B6 mRNA and bupropion hydroxylation activity.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 55, "end": 64}, {"text": "bupropion", "start": 128, "end": 137}]}}, "schema": []}
{"input": "The measured values were used to predict the magnitude of CYP2B6 induction during human pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "At 100 nM total estradiol, a concentration achievable during the third trimester of pregnancy, CYP2B6 activity was predicted to increase by 1. 5-3-fold, based on increased CYP2B6 activity and mRNA.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 16, "end": 25}]}}, "schema": []}
{"input": "When the E (max) and EC (50) values were compared with those for carbamazepine and rifampin, estradiol was found to be as potent an inducer of CYP2B6 as rifampin and carbamazepine.", "output": {"entities": {"chemical": [{"text": "carbamazepine", "start": 65, "end": 78}, {"text": "rifampin", "start": 83, "end": 91}, {"text": "estradiol", "start": 93, "end": 102}, {"text": "rifampin", "start": 153, "end": 161}, {"text": "carbamazepine", "start": 166, "end": 179}]}}, "schema": []}
{"input": "These data suggest that, during human pregnancy, the increasing estradiol concentrations will result in increased clearance of drugs that have CYP2B6-mediated clearance pathways.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 64, "end": 73}]}}, "schema": []}
{"input": "This could in part explain the observed increase in methadone clearance during pregnancy.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 52, "end": 61}]}}, "schema": []}
{"input": "Lipid rafts, synaptic transmission and plasticity: impact in age-related neurodegenerative diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The synapse is a crowded area.", "output": {"entities": {}}, "schema": []}
{"input": "In the last years, the concept that proteins can be organized in different membrane domains according to their structure has emerged.", "output": {"entities": {}}, "schema": []}
{"input": "Cholesterol-rich membrane domains, or lipid rafts, form an organized portion of the membrane that is thought to concentrate signaling molecules.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Accumulating evidence has shown that both the pre-synaptic and post-synaptic sites are highly enriched in lipid rafts, which are likely to organize and maintain synaptic proteins in their precise localization.", "output": {"entities": {}}, "schema": []}
{"input": "Here we review recent studies highlighting the importance of lipid rafts for synaptic function and plasticity, as well as their relevance for age or disease-related cognitive impairment.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6 * 6 polymorphism.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 11, "end": 22}, {"text": "clarithromycin", "start": 27, "end": 41}, {"text": "sibutramine", "start": 64, "end": 75}]}}, "schema": []}
{"input": "Plasma concentrations of sibutramine and its two active metabolites after single oral dose of sibutramine were determined in Korean healthy male subjects with different CYP2B6 genotypes (CYP2B6 * 1/* 1, * 1/* 6 and * 6/* 6), either alone or after four-day pretreatment with clopidogrel or clarithromycin.", "output": {"entities": {"chemical": [{"text": "sibutramine", "start": 25, "end": 36}, {"text": "sibutramine", "start": 94, "end": 105}, {"text": "clopidogrel", "start": 274, "end": 285}, {"text": "clarithromycin", "start": 289, "end": 303}]}}, "schema": []}
{"input": "The pretreatment with clopidogrel and clarithromycin raised the mean area under the concentration-time curve (AUC) of sibutramine by 163% and 255%, respectively.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 22, "end": 33}, {"text": "clarithromycin", "start": 38, "end": 52}, {"text": "sibutramine", "start": 118, "end": 129}]}}, "schema": []}
{"input": "Co-administration of clarithromycin, combined with CYP2B6 * 6/* 6 genotype, led to highest concentration of sibutramine.", "output": {"entities": {"chemical": [{"text": "clarithromycin", "start": 21, "end": 35}, {"text": "sibutramine", "start": 108, "end": 119}]}}, "schema": []}
{"input": "The molar sum AUC (M1 + M2) was raised by 35% in the clopidogrel phase but not significantly affected by clarithromycin or CYP2B6 genotype.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 53, "end": 64}, {"text": "clarithromycin", "start": 105, "end": 119}]}}, "schema": []}
{"input": "The CYP2B6 * 6/* 6 subjects in the clopidogrel phase showed the highest molar AUC (M1 + M2) among three genotype groups throughout the three phases.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 35, "end": 46}]}}, "schema": []}
{"input": "The exposure of sibutramine and its metabolites seemed to be associated with the CYP2B6 genotype.", "output": {"entities": {"chemical": [{"text": "sibutramine", "start": 16, "end": 27}]}}, "schema": []}
{"input": "The treatment of clopidogrel significantly altered the disposition of active metabolites as well as sibutramine, but clarithromycin only affects the disposition of sibutramine.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 17, "end": 28}, {"text": "sibutramine", "start": 100, "end": 111}, {"text": "clarithromycin", "start": 117, "end": 131}, {"text": "sibutramine", "start": 164, "end": 175}]}}, "schema": []}
{"input": "These results suggest that the perturbation of CYP2B6 activity may contribute to the inter-individual variation of sibutramine drug responses although the clinical relevance is remained to be established.", "output": {"entities": {"chemical": [{"text": "sibutramine", "start": 115, "end": 126}]}}, "schema": []}
{"input": "Leydig cell hyperplasia and Leydig cell tumour in postmenopausal women: report of two cases.", "output": {"entities": {}}, "schema": []}
{"input": "Leydig cell hyperplasia and Leydig cell tumours of the ovary are rare.", "output": {"entities": {}}, "schema": []}
{"input": "We present two cases in which patients had increased blood levels of testosterone and frank hirsutism.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 69, "end": 81}]}}, "schema": []}
{"input": "Imaging showed minimal abnormalities.", "output": {"entities": {}}, "schema": []}
{"input": "After adrenal disease had been ruled out, they underwent a bilateral oophorectomy.", "output": {"entities": {}}, "schema": []}
{"input": "One case showed a Leydig cell hyperplasia, the other a Leydig cell tumour.", "output": {"entities": {}}, "schema": []}
{"input": "An androgen producing tumour should be excluded in every woman with evidence of hirsutism or frank virilization and markedly elevated testosterone levels.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 3, "end": 11}, {"text": "testosterone", "start": 134, "end": 146}]}}, "schema": []}
{"input": "Adrenal disease with androgen hypersecretion can be suspected by detailed clinical, laboratory and radiologic imaging.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 21, "end": 29}]}}, "schema": []}
{"input": "Although DHEAS has a good sensitivity in the detection of adrenal origin of hyperandrogenism (and hence a good negative predictive value) it is not specific (specificity ranging from 85 to 98%).", "output": {"entities": {"chemical": [{"text": "DHEAS", "start": 9, "end": 14}]}}, "schema": []}
{"input": "Imaging of the ovaries can be helpful but does not rule out ovarian disease if normal.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, diffuse stromal Leydig cell hyperplasia and Leydig cell tumours (usually small) may escape imaging and in some cases diagnosis can only be made on pathology.", "output": {"entities": {}}, "schema": []}
{"input": "As these clinical entities represent a diagnostic and therapeutic challenge, oophorectomy should be considered in postmenopausal women with hirsutism and elevated testosterone levels, after the exclusion of adrenal causes.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 163, "end": 175}]}}, "schema": []}
{"input": "The procedure is relatively safe and effective.", "output": {"entities": {}}, "schema": []}
{"input": "Follow-up remains indicated.", "output": {"entities": {}}, "schema": []}
{"input": "Drug repurposing in pediatrics and pediatric hematology oncology.", "output": {"entities": {}}, "schema": []}
{"input": "Drug' repurposing', that is, using old drugs for new indications, has been proposed as a more efficient strategy for drug development than the current standard of beginning with novel agents.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we explore the scope of drug repurposing in pediatric hematology oncology and in pediatrics in general.", "output": {"entities": {}}, "schema": []}
{"input": "Drugs commonly used in children were identified using the Harriet Lane Handbook (HLH) and searched in PubMed for different uses.", "output": {"entities": {}}, "schema": []}
{"input": "Additional drugs were identified by searching PubMed and Google. com for' drug repurposing' or' drug repositioning'.", "output": {"entities": {}}, "schema": []}
{"input": "Almost 10% of drugs with primary uses in pediatrics have been repurposed in pediatric hematology oncology or pediatrics.", "output": {"entities": {}}, "schema": []}
{"input": "The observant clinician, pharmacologist and translational bioinformatician, as well as structural targeting, will have a role in discovering new repurposing opportunities.", "output": {"entities": {}}, "schema": []}
{"input": "Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 62, "end": 71}, {"text": "progesterone", "start": 76, "end": 88}]}}, "schema": []}
{"input": "Results from clinical studies suggest that pregnancy alters hepatic drug metabolism in a cytochrome P450 (P450) isoform-specific manner, and rising concentrations of female hormones are potentially responsible for the changes.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to comprehensively characterize the effects of estrogen and progesterone on the expression and activity of major drug-metabolizing P450s.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 79, "end": 87}, {"text": "progesterone", "start": 92, "end": 104}]}}, "schema": []}
{"input": "To this end, primary human hepatocytes were treated with estradiol and progesterone, and mRNA expression and activity levels of 10 different P450 isoforms were determined.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 57, "end": 66}, {"text": "progesterone", "start": 71, "end": 83}]}}, "schema": []}
{"input": "The results showed that estradiol enhances CYP2A6, CYP2B6, and CYP3A4 expression, whereas progesterone induces CYP2A6, CYP2B6, CYP2C8, CYP3A4, and CYP3A5 expression.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 24, "end": 33}, {"text": "progesterone", "start": 90, "end": 102}]}}, "schema": []}
{"input": "The induction was mainly observed when the average hormone concentrations were at the levels reached during pregnancy, suggesting that these effects are likely pregnancy-specific.", "output": {"entities": {}}, "schema": []}
{"input": "Estradiol also increased enzyme activities of CYP2C9 and CYP2E1 without affecting the mRNA expression levels by unknown mechanisms.", "output": {"entities": {"chemical": [{"text": "Estradiol", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Taken together, our results show differential effects of estrogen and progesterone on P450 expression, suggesting involvement of different regulatory mechanisms in female hormone-mediated P450 regulation.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 57, "end": 65}, {"text": "progesterone", "start": 70, "end": 82}]}}, "schema": []}
{"input": "Our findings potentially provide a basis in mechanistic understanding for altered drug metabolism during pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Towards the use of hydrogels in the treatment of limbal stem cell deficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i. e. biocompatibility, inertness and a biodegradable structure) but unlike AM, they are structurally uniform and can be easily manipulated to alter mechanical and physical properties.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrogels can be delivered with minimum trauma to the ocular surface and do not require extensive serological screening before clinical application.", "output": {"entities": {}}, "schema": []}
{"input": "The hydrogel structure is also amenable to modifications which direct stem cell fate.", "output": {"entities": {}}, "schema": []}
{"input": "In this focussed review we highlight hydrogels as biomaterial substrates which may replace and/or complement AM in the treatment of LSCD.", "output": {"entities": {}}, "schema": []}
{"input": "Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells.", "output": {"entities": {"chemical": [{"text": "Naringin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Cervical cancer is the second most common female cancer worldwide, and it remains a challenge to manage preinvasive and invasive lesions.", "output": {"entities": {}}, "schema": []}
{"input": "Fruit-based cancer prevention entities, such as flavonoid and their derivatives, have demonstrated a marked ability to inhibit preclinical models of epithelial cancer cell growth and tumor formation.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 48, "end": 57}]}}, "schema": []}
{"input": "Here, we extend the role of naringin-mediated chemoprevention to that of cervical carcinogenesis.", "output": {"entities": {"chemical": [{"text": "naringin", "start": 28, "end": 36}]}}, "schema": []}
{"input": "The present study sought to investigate the therapeutic potential effect of naringin on apoptosis in human cervical SiHa cancer cells.", "output": {"entities": {"chemical": [{"text": "naringin", "start": 76, "end": 84}]}}, "schema": []}
{"input": "Viability of SiHa cells was evaluated by the MTT assay, apoptosis and mitochondrial transmembrane potential by flow cytometry, and pro-apoptotic related genes by Real-time quantitative PCR.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 45, "end": 48}]}}, "schema": []}
{"input": "Naringin showed a 50% inhibition of SiHa human cervical cancer cells at a concentration of 750 mu M.", "output": {"entities": {"chemical": [{"text": "Naringin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "SiHa cells exhibited apoptotic cell death, intranucleosomal DNA fragmentation, morphological changes and decline in the mitochondrial transmembrane potential.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, administration of naringin increased the expression of caspases, p53 and Bax, Fas death receptor and its adaptor protein FADD.", "output": {"entities": {"chemical": [{"text": "naringin", "start": 31, "end": 39}]}}, "schema": []}
{"input": "These results suggest that the induction of apoptosis by naringin is through both death-receptor and mitochondrial pathways.", "output": {"entities": {"chemical": [{"text": "naringin", "start": 57, "end": 65}]}}, "schema": []}
{"input": "Taken together, our results suggest that naringin might be an effective agent to treat human cervical cancer.", "output": {"entities": {"chemical": [{"text": "naringin", "start": 41, "end": 49}]}}, "schema": []}
{"input": "Localisation and role of activin receptor-interacting protein 1 in mouse brain.", "output": {"entities": {}}, "schema": []}
{"input": "Activin A, a stimulator of follicle-stimulating hormone secretion from the pituitary, acts as a neurotrophic and neuroprotective factor in the central nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "Activin receptor-interacting protein 1 (ARIP1) has been identified as a cytoplasmic protein that interacts with the type II receptor of activin (ActRII).", "output": {"entities": {}}, "schema": []}
{"input": "However, the distribution pattern and function of ARIP1 are not well characterised in the brain.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we confirmed the existence of mRNA and protein of ARIP1 in the mouse brain, and found that ARIP1 was mainly localised at the hippocampus and hypothalamus in the cerebrum, granular layers in the cerebellum (especially in Purkinje cells of the cerebellum) and choroid epithelial cells by immunohistochemical staining.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, in contrast to the significant increase of activin A mRNA, ARIP1 mRNA and protein expression decreased in the mechanically lesioned brain of the mouse.", "output": {"entities": {}}, "schema": []}
{"input": "Using neuroblastoma-derived Neuro-2a cells to investigate the function of ARIP1, we found that overexpression of ARIP1 down-regulated the activin A-induced signal transduction and significantly decreased the voltage-gated Na (+) current (I (Na)).", "output": {"entities": {"chemical": [{"text": "Na (+)", "start": 222, "end": 228}, {"text": "Na", "start": 241, "end": 243}]}}, "schema": []}
{"input": "These data indicate that ARIP1 is a key molecule for the regulation of the action of activin in neurones, and also that decreased ARIP1 expression in the lesioned brain may be beneficial to the neurotrophic and neuroprotective roles of activin A in recovery after brain injury.", "output": {"entities": {}}, "schema": []}
{"input": "Powering the future of molecular artificial photosynthesis with light-harvesting metallosupramolecular dye assemblies.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical ingenuity will play a significant role in solving the greatest challenge currently facing society: providing clean and carbon neutral energy for all of humanity.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular artificial photosynthesis is an emerging technology based on principles learned from Nature where individual components perform the essential light-harvesting, charge-separation, and water splitting functions to store solar energy in the form of chemical bonds.", "output": {"entities": {}}, "schema": []}
{"input": "This tutorial review focuses specifically on the application of metallosupramolecular self-assembly strategies to interface solar fuel catalysts with photosensitizers and construct light-harvesting antennae capable of achieving panchromatic absorption and directional energy concentration.", "output": {"entities": {}}, "schema": []}
{"input": "Coronary microvascular function in patients with Cushing' s syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the study was to evaluate patients with Cushing' s syndrome the coronary flow reserve (CFR), an index of coronary microvascular function.", "output": {"entities": {}}, "schema": []}
{"input": "Fifteen newly diagnosed patients with Cushing' s syndrome (1 male/14 females; mean age 45 +/- 11 years), were selected for having no clinical evidence of ischemic heart disease.", "output": {"entities": {}}, "schema": []}
{"input": "Twelve patients had pituitary-dependent Cushing' s disease and three had an adrenal adenoma.", "output": {"entities": {}}, "schema": []}
{"input": "Fifteen subjects matched for age, sex, and major cardiovascular risk factors were used as controls.", "output": {"entities": {}}, "schema": []}
{"input": "Coronary flow velocity in the left anterior descending coronary artery was investigated by transthoracic Doppler echocardiography at rest and during adenosine infusion.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 149, "end": 158}]}}, "schema": []}
{"input": "CFR was obtained as the ratio hyperemic/resting diastolic flow velocity.", "output": {"entities": {}}, "schema": []}
{"input": "A reduced coronary reserve (hyperemic/resting ratio <= 2. 5) was found in 5/15 Cushing patients and 4/15 controls.", "output": {"entities": {}}, "schema": []}
{"input": "In all patients with abnormal CFR, epicardial coronary stenosis was excluded by multi-slice computed tomographic coronary angiography.", "output": {"entities": {}}, "schema": []}
{"input": "CFR was inversely related to urinary cortisol in patients with endogenous hypercortisolism (Spearman' s rho =-0. 57, P = 0. 03), while no correlation was found in controls.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Coronary microvascular function, as assessed by CFR, is pathologically reduced in a considerable number of patients with Cushing' s syndrome without clinical symptoms of ischemic heart disease and in the absence of epicardial coronary artery lesions, as well as in controls matched for cardiovascular risk factors.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of comorbidities can explain this early coronary abnormality in both patients and controls.", "output": {"entities": {}}, "schema": []}
{"input": "Whether urinary cortisol may be a predictor of coronary microvascular function in the setting of patients with Cushing' s syndrome, needs further investigation.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 16, "end": 24}]}}, "schema": []}
{"input": "A rosette cooling cell: more effective container for solubilization of single-walled carbon nanotubes under probe-type ultrasonic irradiation.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 85, "end": 91}]}}, "schema": []}
{"input": "Probe-type ultrasonication has been employed for surfactant-aided solubilization, or individualization, of single-walled carbon nanotubes (SWNTs).", "output": {"entities": {"chemical": [{"text": "carbon", "start": 121, "end": 127}]}}, "schema": []}
{"input": "The resulting solution can be used not only for spectroscopic analyses such as absorption, photoluminescence, and circular dichroism, but also for separation by density gradient ultracentrifugation, dielectrophoresis, chromatography, and polymer wrapping.", "output": {"entities": {}}, "schema": []}
{"input": "In spite of its importance, the sonochemical processing of SWNTs has not been considered seriously.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we report on a more efficient cooling cell for probe-type ultrasonication.", "output": {"entities": {}}, "schema": []}
{"input": "As compared with a conventional cylindrical cell, the concentration of the SWNTs solubilized in water was found to be almost double in a rosette cooling cell after ultracentrifugation.", "output": {"entities": {}}, "schema": []}
{"input": "The efficiency of a rosette cell can be attributed to the higher efficiency in circulation and cooling of the SWNT dispersion as well as enhancement of the cavitation process.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembled monolayers with dynamicity stemming from (bio) chemical conversions: from construction to application.", "output": {"entities": {}}, "schema": []}
{"input": "Surfaces with \" dynamicity \" whereby surface properties can be modulated by an external stimulus on user demand have been actively exploited for the past decade.", "output": {"entities": {}}, "schema": []}
{"input": "These switchable surfaces with dynamic properties are widely used for a number of applications such as micro/nanoarrays, biomolecule immobilization, basic cell studies, and tissue engineering on a variety of materials.", "output": {"entities": {}}, "schema": []}
{"input": "This minireview highlights the dynamic control of surface properties on self-assembled monolayers and focuses on dynamicity that stems from (bio) chemical conversions achieved by electrical potentials, photoillumination, chemical reagents, enzymes, and pH.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetic characterization of the novel TAZ modulator TM-25659 using a multicompartment kinetic model in rats and a possibility of its drug-drug interactions in humans.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 60, "end": 68}]}}, "schema": []}
{"input": "This study evaluated the pharmacokinetics of the novel TAZ modulator TM-25659 in rats following intravenous and oral administration at dose ranges of 0. 5-5 mg/kg and 2-10 mg/kg, respectively.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 69, "end": 77}]}}, "schema": []}
{"input": "Plasma protein binding, plasma stability, liver microsomal stability, CYP inhibition, and transport in Caco-2 cells were also evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "After intravenous injection, systemic clearance, steady-state volumes of distribution, and half-life were dose-independent, with values ranging from 0. 434-0. 890 mL. h (-1). kg (-1), 2. 02-4. 22 mL/kg, and 4. 60-7. 40 h, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Mean absolute oral bioavailability was 50. 9% and was not dose dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Recovery of TM-25659 was 43. 6% in bile and < 1% in urine.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 12, "end": 20}]}}, "schema": []}
{"input": "In pharmacokinetic modeling studies, the three-compartment (3C) model was appropriate for understanding these parameters in rats.", "output": {"entities": {}}, "schema": []}
{"input": "TM-25659 was stable in plasma.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Plasma protein binding was approximately 99. 2%, and was concentration-independent.", "output": {"entities": {}}, "schema": []}
{"input": "TM-25659 showed high permeation of Caco-2 cells and did not appear to inhibit CYP450.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 0, "end": 8}]}}, "schema": []}
{"input": "TM-25659 was metabolized in phase I and II steps in rat liver microsomes.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 0, "end": 8}]}}, "schema": []}
{"input": "In conclusion, the pharmacokinetics of TM-25659 was characterized for intravenous and oral administration at doses of 0. 5-5 and 2-10 mg/kg, respectively.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 39, "end": 47}]}}, "schema": []}
{"input": "TM-25659 was eliminated primarily by hepatic metabolism and urinary excretion.", "output": {"entities": {"chemical": [{"text": "TM-25659", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Inhibitory function of the dorsomedial hypothalamic nucleus on the hypothalamic-pituitary-adrenal axis response to an emotional stressor but not immune challenge.", "output": {"entities": {}}, "schema": []}
{"input": "Accumulating evidence implicates the dorsomedial hypothalamic nucleus (DMH) in the regulation of autonomic and neuroendocrine stress responses.", "output": {"entities": {}}, "schema": []}
{"input": "However, although projections from the DMH to the paraventricular hypothalamic nucleus (PVN), which is the critical site of the neuroendocrine stress axis, have been described, the impact of DMH neurones in the modulation of hypothalamic-pituitary-adrenal (HPA) axis activation during stress is not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "The present study aimed to investigate the role of the DMH in HPA axis responses to different types of stimuli.", "output": {"entities": {}}, "schema": []}
{"input": "Male Sprague-Dawley rats fitted with a chronic jugular venous catheter were exposed to either an emotional stressor (elevated platform-exposure) or immune challenge (systemic interleukin-1 beta administration).", "output": {"entities": {}}, "schema": []}
{"input": "Bilateral electrolytic lesions of the DMH disinhibited HPA axis responses to the emotional stressor, as indicated by higher plasma adrenocorticotrophic hormone levels during and after elevated platform exposure in lesioned animals compared to sham-lesioned controls.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, DMH-lesioned animals showed increased neuronal activation in the PVN, as indicated by a higher c-Fos expression after elevated-platform exposure compared to controls.", "output": {"entities": {}}, "schema": []}
{"input": "By contrast, DMH-lesions had no effects on HPA axis responses to immune challenge.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our data suggest an inhibitory role of DMH neurones on stress-induced HPA axis activation that is dependent upon the nature of the stimulus being important in response to an emotional stressor but not to immune challenge.", "output": {"entities": {}}, "schema": []}
{"input": "The interaction of amylin with other hormones in the control of eating.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty years of research established amylin as an important control of energy homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Amylin controls nutrient and energy fluxes by reducing energy intake, by modulating nutrient utilization via an inhibition of postprandial glucagon secretion and by increasing energy disposal via a prevention of compensatory decreases of energy expenditure in weight reduced individuals.", "output": {"entities": {}}, "schema": []}
{"input": "Like many other gastrointestinal hormones, amylin is secreted in response to meals and it reduces eating by promoting meal-ending satiation.", "output": {"entities": {}}, "schema": []}
{"input": "Not surprisingly, amylin interacts with many of these hormones to control eating.", "output": {"entities": {}}, "schema": []}
{"input": "These interactions seem to occur at different levels because amylin seems to mediate the eating inhibitory effect of some of these gastrointestinal hormones, and the combination of some of these hormones seems to lead to a stronger reduction in eating than single hormones alone.", "output": {"entities": {}}, "schema": []}
{"input": "Amylin' s effect on eating is thought to be mediated by a stimulation of specific amylin receptors in the area postrema.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary brain sites that were defined to mediate amylin action-and hence potential additional sites of interaction with other hormones-include the nucleus of the solitary tract, the lateral parabrachial nucleus, the lateral hypothalamic area and other hypothalamic nuclei.", "output": {"entities": {}}, "schema": []}
{"input": "The focus of this review is to summarize the current knowledge of amylin interactions in the control of eating.", "output": {"entities": {}}, "schema": []}
{"input": "In most cases, these interactions have only been studied at a descriptive rather than a mechanistic level and despite the clear knowledge on primary sites of amylin action, the interaction sites between amylin and other hormones are often unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Density functional study on the adsorption of the drug isoniazid onto pristine and B-doped single wall carbon nanotubes.", "output": {"entities": {"chemical": [{"text": "isoniazid", "start": 55, "end": 64}, {"text": "B", "start": 83, "end": 84}, {"text": "carbon", "start": 103, "end": 109}]}}, "schema": []}
{"input": "The current study explores a new strategy to incorporate single wall carbon nanotubes (SWNTs)/doped SWNTs as carrier modules in target-specific administration of antitubercular chemotherapeutics through covalent and noncovalent functionalization onto the nanotube sidewall.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 69, "end": 75}]}}, "schema": []}
{"input": "Density functional studies illustrate that noncovalent functionalization of isoniazid (INH) is preferred over covalent attachment, exhibiting low adsorption energy values, HOMO-LUMO gap and comparison of quantum molecular descriptors performed in (5, 5) and (9, 0) SWNT systems.", "output": {"entities": {"chemical": [{"text": "isoniazid", "start": 76, "end": 85}, {"text": "INH", "start": 87, "end": 90}]}}, "schema": []}
{"input": "Substitution doping of boron facilitates the adsorption of INH onto the otherwise inert nanotube.", "output": {"entities": {"chemical": [{"text": "boron", "start": 23, "end": 28}, {"text": "INH", "start": 59, "end": 62}]}}, "schema": []}
{"input": "Frontier orbital analysis reveals reorientation of electronic charge in the nanotubes after functionalization, the effect being more pronounced in the case of doped nanotubes.", "output": {"entities": {}}, "schema": []}
{"input": "The charge transfer is significant in covalent functionalization of INH via the B-dopant atom, whereas in noncovalent functionalization a small amount of charge transfer is noted.", "output": {"entities": {"chemical": [{"text": "INH", "start": 68, "end": 71}, {"text": "B", "start": 80, "end": 81}]}}, "schema": []}
{"input": "Solvation studies demonstrate the dissolution of INH in B-doped (5, 5) and (9, 0) SWNTs to be higher compared to pristine nanotube-INH complexes.", "output": {"entities": {"chemical": [{"text": "INH", "start": 49, "end": 52}, {"text": "B", "start": 56, "end": 57}, {"text": "INH", "start": 131, "end": 134}]}}, "schema": []}
{"input": "Functionalization of nanotubes via covalent and noncovalent means can foster pioneering prospects especially for experimental studies in this area of research.", "output": {"entities": {}}, "schema": []}
{"input": "Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 14, "end": 21}, {"text": "apigenin", "start": 23, "end": 31}, {"text": "luteolin", "start": 37, "end": 45}, {"text": "heme", "start": 122, "end": 126}, {"text": "glutamate cysteine", "start": 143, "end": 161}]}}, "schema": []}
{"input": "Chrysin, apigenin, and luteolin are flavones that differ in their number of hydroxyl groups in the B ring.", "output": {"entities": {"chemical": [{"text": "Chrysin", "start": 0, "end": 7}, {"text": "apigenin", "start": 9, "end": 17}, {"text": "luteolin", "start": 23, "end": 31}, {"text": "flavones", "start": 36, "end": 44}, {"text": "hydroxyl", "start": 76, "end": 84}]}}, "schema": []}
{"input": "In this study, we investigated the protection by chrysin, apigenin, and luteolin against tert-butyl hydroperoxide (tBHP)-induced oxidative stress and the possible mechanisms involved in rat primary hepatocytes.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 49, "end": 56}, {"text": "apigenin", "start": 58, "end": 66}, {"text": "luteolin", "start": 72, "end": 80}, {"text": "tert-butyl hydroperoxide", "start": 89, "end": 113}, {"text": "tBHP", "start": 115, "end": 119}]}}, "schema": []}
{"input": "Chrysin, apigenin, and luteolin dose-dependently up-regulated the protein expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase (GCL) catalytic (GCLC) and modifier subunit (GCLM) and increased the intracellular glutathione (GSH) content and the ratio of GSH to oxidized GSH.", "output": {"entities": {"chemical": [{"text": "Chrysin", "start": 0, "end": 7}, {"text": "apigenin", "start": 9, "end": 17}, {"text": "luteolin", "start": 23, "end": 31}, {"text": "heme", "start": 88, "end": 92}, {"text": "glutamate cysteine", "start": 116, "end": 134}, {"text": "glutathione", "start": 225, "end": 236}, {"text": "GSH", "start": 238, "end": 241}, {"text": "GSH", "start": 268, "end": 271}, {"text": "oxidized GSH", "start": 275, "end": 287}]}}, "schema": []}
{"input": "Among the flavones studied, chrysin showed the greatest induction of HO-1, GCLC, and GCLM protein expression and GSH content.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 28, "end": 35}, {"text": "GSH", "start": 113, "end": 116}]}}, "schema": []}
{"input": "Cellular reactive oxygen species production induced by tBHP was attenuated by pretreatment with chrysin, apigenin, and luteolin (P <. 05), and this protection was reversed by the GCL inhibitor l-buthionine-S-sulfoximine and the HO-1 inhibitor zinc protoporphyrin.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 18, "end": 24}, {"text": "tBHP", "start": 55, "end": 59}, {"text": "chrysin", "start": 96, "end": 103}, {"text": "apigenin", "start": 105, "end": 113}, {"text": "luteolin", "start": 119, "end": 127}, {"text": "l-buthionine-S-sulfoximine", "start": 193, "end": 219}, {"text": "zinc protoporphyrin", "start": 243, "end": 262}]}}, "schema": []}
{"input": "Chrysin, apigenin, and luteolin activated extracellular signal-regulated protein kinase 2 (ERK2), nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, nuclear Nrf2-antioxidant responsive element (ARE) binding activity, and ARE-dependent luciferase activity.", "output": {"entities": {"chemical": [{"text": "Chrysin", "start": 0, "end": 7}, {"text": "apigenin", "start": 9, "end": 17}, {"text": "luteolin", "start": 23, "end": 31}]}}, "schema": []}
{"input": "Both ERK2 and Nrf2 siRNAs attenuated chrysin-induced HO-1, GCLC, and GCLM protein expression.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 37, "end": 44}]}}, "schema": []}
{"input": "Taken together, these results suggest that chrysin, apigenin, and luteolin inhibit tBHP-induced oxidative stress by up-regulating HO-1, GCLC, and GCLM gene transcription via the ERK2/Nrf2/ARE signaling pathways in rat primary hepatocytes.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 43, "end": 50}, {"text": "apigenin", "start": 52, "end": 60}, {"text": "luteolin", "start": 66, "end": 74}, {"text": "tBHP", "start": 83, "end": 87}]}}, "schema": []}
{"input": "Alteration in plasma protein binding properties of propranolol and flurbiprofen during development of adjuvant-induced arthritis in rats.", "output": {"entities": {"chemical": [{"text": "propranolol", "start": 51, "end": 62}, {"text": "flurbiprofen", "start": 67, "end": 79}]}}, "schema": []}
{"input": "Adjuvant-induced arthritis (AA) in the rat is used as a model for rheumatoid arthritis.", "output": {"entities": {}}, "schema": []}
{"input": "In AA rats, the pharmacokinetics of various drugs is affected due to the alterations of plasma protein binding of drugs.", "output": {"entities": {}}, "schema": []}
{"input": "We choose propranolol (PL) and flurbiprofen (FP) as model basic and acidic drugs, respectively, and investigated the effect of AA induction on their plasma protein binding at each developing stage of inflammation.", "output": {"entities": {"chemical": [{"text": "propranolol", "start": 10, "end": 21}, {"text": "flurbiprofen", "start": 31, "end": 43}]}}, "schema": []}
{"input": "The plasma protein binding of PL and FP was dramatically changed due to reduced albumin and increased alpha 1-acid glycoprotein levels for at least 21 days after adjuvant treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, we illustrated the differences in protein binding in AA between both the drugs in each developing stage of inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that the changed plasma protein levels in AA rats accompanying the altered protein binding of drugs affect the pharmacokinetics of drugs which extensively bind to plasma protein under inflammatory condition.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of 10 ginsenosides in Panax ginseng of different harvest times based on HPLC fingerprints and principal component analysis.", "output": {"entities": {"chemical": [{"text": "ginsenosides", "start": 20, "end": 32}]}}, "schema": []}
{"input": "A combinative method of HPLC fingerprinting and quantitative determination was successfully applied to monitor dynamic accumulation of ginsenosides in five-year-old Panax ginseng roots from different harvest times.", "output": {"entities": {"chemical": [{"text": "ginsenosides", "start": 135, "end": 147}]}}, "schema": []}
{"input": "The optimal chromatographic conditions were achieved on a C18 column with gradient elution using acetonitrile and 1 mmol. L (-1) KH2PO4 buffer solution at 203 nm.", "output": {"entities": {"chemical": [{"text": "KH2PO4", "start": 129, "end": 135}]}}, "schema": []}
{"input": "The result indicated that the contents of total ginsenosides showed significant variations, and a decrease tendency appeared in the growth period of the fifth year.", "output": {"entities": {"chemical": [{"text": "ginsenosides", "start": 48, "end": 60}]}}, "schema": []}
{"input": "Genotoxic damage in the oral mucosa cells of subjects carrying restorative dental fillings.", "output": {"entities": {}}, "schema": []}
{"input": "A large proportion of the population carries restorative dental fillings containing either classic Hg-based amalgams and/or the more frequently used methacrylates.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 99, "end": 101}, {"text": "amalgams", "start": 108, "end": 116}, {"text": "methacrylates", "start": 149, "end": 162}]}}, "schema": []}
{"input": "Both Hg-and resin-based materials have been shown to be released into the buccal cavity and to be spread systemically.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 5, "end": 7}]}}, "schema": []}
{"input": "In addition, they induce toxic and genotoxic alterations in experimental test systems.", "output": {"entities": {}}, "schema": []}
{"input": "Using the comet assay, we previously demonstrated that circulating lymphocytes of subjects with dental fillings have an increased DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we analyzed the oral mucosa cells of 63 young subjects of both genders, by using both the comet assay and the micronucleus (MN) test and by monitoring cell death markers.", "output": {"entities": {}}, "schema": []}
{"input": "The results obtained show that both amalgams and resin-based composite fillings can induce genotoxic damage in human oral mucosa cells, as convincingly and dose-dependently inferred from the results of the MN test and, more marginally, from comet assay data.", "output": {"entities": {"chemical": [{"text": "amalgams", "start": 36, "end": 44}]}}, "schema": []}
{"input": "Lifestyle variables, also including alcohol intake and smoking habits, did not affect the genotoxic response and did not act as confounding factors.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 36, "end": 43}]}}, "schema": []}
{"input": "Thus, we provide unequivocal evidence for the genotoxicity of both amalgams and resin-based dental fillings in humans not only by testing circulating lymphocytes but also by analyzing oral mucosa cells.", "output": {"entities": {"chemical": [{"text": "amalgams", "start": 67, "end": 75}]}}, "schema": []}
{"input": "These findings are of particular relevance due to the circumstance that subjects with restorative materials are exposed continuously and for long periods of time.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis.", "output": {"entities": {"chemical": [{"text": "thymoquinone", "start": 46, "end": 58}]}}, "schema": []}
{"input": "Prostatitis plays a major role in morbidity and mortality related to prostate diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to detect whether thymoquinone (TQ) could ameliorate oxidative damage and the proliferative response induced by Escherichia coli (E. coli) in rats.", "output": {"entities": {"chemical": [{"text": "thymoquinone", "start": 44, "end": 56}]}}, "schema": []}
{"input": "A total of 42 adult male Wistar rats were used.", "output": {"entities": {}}, "schema": []}
{"input": "The rats were randomly divided into seven groups (three treatment groups, three infected groups and one control group).", "output": {"entities": {}}, "schema": []}
{"input": "Control group received saline and was killed 24 h after saline administration.", "output": {"entities": {}}, "schema": []}
{"input": "Infected rats were killed after 24, 48 and 72 h following direct injection of E. coli into the prostate.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment groups were administered with 10 mg/kg dose of TQ intraperitoneally following E. coli injection and after 24 and 48 h following E. coli injection.", "output": {"entities": {}}, "schema": []}
{"input": "The rats were killed at 24, 48 and 72 h after the first drug administration.", "output": {"entities": {}}, "schema": []}
{"input": "Each group was compared with each other and with the control group.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, infected groups were compared with treatment groups.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings show that the treatment with TQ has a protective effect against bacterial prostatitis-induced tissue injury.", "output": {"entities": {}}, "schema": []}
{"input": "Increase in malondialdehyde levels and histological damage caused by E. coli were improved markedly with TQ treatment.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 12, "end": 27}]}}, "schema": []}
{"input": "TQ treatment particularly increased the activity of glutathione peroxidase and decreased the activities of catalase and superoxide dismutase.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 52, "end": 63}, {"text": "superoxide", "start": 120, "end": 130}]}}, "schema": []}
{"input": "These observations might be attributed, at least in part, to the antioxidant effect of TQ and suggest that it could be a clinically valuable agent in the prevention of acute prostatitis caused by E. coli.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicokinetics of methyleugenol in F344 rats and B6C3F 1 mice.", "output": {"entities": {"chemical": [{"text": "methyleugenol", "start": 18, "end": 31}]}}, "schema": []}
{"input": "1. Methyleugenol (MEG) has been used as a flavouring agent in food, as a fragrance in cosmetic products, and as an insect attractant.", "output": {"entities": {"chemical": [{"text": "Methyleugenol", "start": 3, "end": 16}, {"text": "MEG", "start": 18, "end": 21}]}}, "schema": []}
{"input": "MEG was carcinogenic in both rats and mice following gavage administration.", "output": {"entities": {"chemical": [{"text": "MEG", "start": 0, "end": 3}]}}, "schema": []}
{"input": "In this study we investigated plasma toxicokinetics of MEG in F344 rats and B6C3F 1 mice of both sexes following single gavage (37, 75, or 150 mg/kg) and intravenous (IV) (37 mg/kg) administration.", "output": {"entities": {"chemical": [{"text": "MEG", "start": 55, "end": 58}]}}, "schema": []}
{"input": "2. Following IV administration, MEG was rapidly distributed and cleared from the systemic circulation in both species and sexes.", "output": {"entities": {"chemical": [{"text": "MEG", "start": 32, "end": 35}]}}, "schema": []}
{"input": "Absorption of MEG was rapid following gavage administration with secondary peaks in the plasma MEG concentration-versus-time profiles.", "output": {"entities": {"chemical": [{"text": "MEG", "start": 14, "end": 17}, {"text": "MEG", "start": 95, "end": 98}]}}, "schema": []}
{"input": "C (max) and AUC (T) increased and the clearance decreased greater than proportional to the dose in rats and mice of both sexes.", "output": {"entities": {}}, "schema": []}
{"input": "In general, rats had higher internal exposure to MEG than mice.", "output": {"entities": {"chemical": [{"text": "MEG", "start": 49, "end": 52}]}}, "schema": []}
{"input": "3. The results for AUC (T) and clearance suggest that perhaps the metabolism of MEG is saturated at higher doses tested in this study.", "output": {"entities": {"chemical": [{"text": "MEG", "start": 80, "end": 83}]}}, "schema": []}
{"input": "Absolute bioavailability following gavage administration of 37 mg/kg was low in both rats (~ 4%) and mice (7-9%) of both sexes indicating extensive first-pass metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "There was no sex difference in plasma toxicokinetics of MEG following gavage administration both in rats and mice.", "output": {"entities": {"chemical": [{"text": "MEG", "start": 56, "end": 59}]}}, "schema": []}
{"input": "Anti-inflammatory trends of 1, 3-diphenyl-2-propen-1-one derivatives.", "output": {"entities": {"chemical": [{"text": "1, 3-diphenyl-2-propen-1-one", "start": 28, "end": 56}]}}, "schema": []}
{"input": "Chalcones (1, 3-Diphenyl-2-propen-1-one) are constituted by a three carbon alpha, beta-unsaturated carbonyl system.", "output": {"entities": {"chemical": [{"text": "Chalcones", "start": 0, "end": 9}, {"text": "1, 3-Diphenyl-2-propen-1-one", "start": 11, "end": 39}, {"text": "carbon alpha, beta-unsaturated carbonyl", "start": 68, "end": 107}]}}, "schema": []}
{"input": "The biosynthesis of flavonoids and isoflavonoids is initiated by chalcones.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 20, "end": 30}, {"text": "isoflavonoids", "start": 35, "end": 48}, {"text": "chalcones", "start": 65, "end": 74}]}}, "schema": []}
{"input": "Notable pharmacological activities of chalcones and its derivatives include anti-inflammatory, antifungal, antibacterial, antimalarial, antituberculosis, antitumor, antimicrobial and antiviral effects respectively.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 38, "end": 47}]}}, "schema": []}
{"input": "Owing to simplicity of the chemical structures and a huge variety of pharmacological actions exhibited, the entities derived from chalcones are subjected to extensive consideration.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 130, "end": 139}]}}, "schema": []}
{"input": "This review article is an effort to sum up the anti-inflammatory activities of chalcone derived chemical entities.", "output": {"entities": {"chemical": [{"text": "chalcone", "start": 79, "end": 87}]}}, "schema": []}
{"input": "Effect of chalcones on lipid peroxidation, heme oxygenase 1 (HO-1), cyclooxygenase (COX), interleukin 5 (IL-5), nitric oxide (NO) and expression of cell adhesion molecules (CAM) is summarized stepwise.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 10, "end": 19}, {"text": "heme", "start": 43, "end": 47}, {"text": "nitric oxide", "start": 112, "end": 124}, {"text": "NO", "start": 126, "end": 128}]}}, "schema": []}
{"input": "Chalcones in Cancer: Understanding their Role in Terms of QSAR.", "output": {"entities": {"chemical": [{"text": "Chalcones", "start": 0, "end": 9}]}}, "schema": []}
{"input": "II Part.", "output": {"entities": {}}, "schema": []}
{"input": "Chalcones are a group of plant-derived polyphenolic compounds belonging to the flavonoids family and possess a wide variety of cytoprotective and modulatory functions.", "output": {"entities": {"chemical": [{"text": "Chalcones", "start": 0, "end": 9}, {"text": "polyphenolic", "start": 39, "end": 51}, {"text": "flavonoids", "start": 79, "end": 89}]}}, "schema": []}
{"input": "In this research we tried to review the anticancer effect of chalcones derivatives and to evaluate new QSARs which will help in the understanding of the role of chalcones and of their analogs on cancer.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 61, "end": 70}, {"text": "chalcones", "start": 161, "end": 170}]}}, "schema": []}
{"input": "Simultaneously a comparative study will be presented.", "output": {"entities": {}}, "schema": []}
{"input": "Our QSAR results reveal that: 1) the clog P (hydrophobicity/hydrophilicity) parameter plays an important part in three QSAR relationships (linear model), 2) the steric factors such as molar volume MgVol, molar refractivity CMR or the substituents molar refractivity MR (linear) are important.", "output": {"entities": {}}, "schema": []}
{"input": "Electronic effects are comparatively unimportant.", "output": {"entities": {}}, "schema": []}
{"input": "These results compared to our previous findings on the QSAR of anti-proliferative chalcones support primarily the role of bulk.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 82, "end": 91}]}}, "schema": []}
{"input": "Snake venom induced local toxicities: plant secondary metabolites as an auxiliary therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Snakebite is a serious medical and socio-economic problem affecting the rural and agricultural laborers of tropical and sub-tropical region across the world leading to high morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "In most of the snakebite incidences, victims usually end up with permanent tissue damage and sequelae with high socioeconomic and psychological impacts.", "output": {"entities": {}}, "schema": []}
{"input": "Although, mortality has been reduced markedly due to anti-venom regimen, it is associated with several limitations.", "output": {"entities": {}}, "schema": []}
{"input": "Snake venom metalloprotease, hyaluronidase and myotoxic phospholipase A2 are the kingpins of tissue necrosis and extracellular matrix degradation.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, inhibition of these enzymes is considered to be the rate limiting step in the management of snakebite.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, tissue necrosis and extracellular matrix degradation persists even after the administration of anti-venom.", "output": {"entities": {}}, "schema": []}
{"input": "At present, inhibitors from snake serum and plasma, several synthetic compounds and their analogs have been demonstrated to possess anti-snake venom activities, but the use of plant metabolites for this purpose has an added advantage of traditional knowledge and will make the treatment cheaper and more accessible to the affected population.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the clinical and research forums are highly oriented towards plant metabolites and interestingly, certain phytochemicals are implicated as the antibody elicitors against venom toxicity that can be exploited in designing effective anti-venoms.", "output": {"entities": {}}, "schema": []}
{"input": "Based on these facts, we have made an effort to enlist plant based secondary metabolites with antiophidian abilities and their mechanism of action against locally acting enzymes/toxins in particular.", "output": {"entities": {}}, "schema": []}
{"input": "The review also describes their functional groups responsible for therapeutic beneficial and certainly oblige in designing potent inhibitors against venom toxins.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanism-based modulator discovery for sirtuin-catalyzed deacetylation reaction.", "output": {"entities": {}}, "schema": []}
{"input": "Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of evolutionarily conserved intracellular protein deacetylases that can catalyze the acetyl group removal from the specific N epsilon-acetyl-lysine (AcK) side chains on a variety of proteins from all kingdoms of life.", "output": {"entities": {"chemical": [{"text": "N epsilon-acetyl-lysine", "start": 195, "end": 218}]}}, "schema": []}
{"input": "Yeast Sir2 was the first sirtuin identified, and so far seven sirtuins (i. e. SIRT1-7) have been found in mammals including humans.", "output": {"entities": {}}, "schema": []}
{"input": "The sirtuin-catalyzed deacetylation reaction has captured tremendous interest during the past a few years because of (i) its increasingly demonstrated importance in many crucial biological processes such as gene transcription, metabolism, and aging, and thus its therapeutic potential for metabolic and age-related diseases and cancer, and (ii) its unique deacetylation chemistry.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, the sirtuin-catalyzed AcK side chain deacetylation is not merely an amide hydrolysis reaction, instead is coupled to the nicotinamide cleavage from beta-nicotinamide adenine dinucleotide (beta-NAD + or NAD +) with the generation of three enzymatic products, i. e. the deacetylated protein species, nicotinamide, and 2'-O-acetyl-ADP-ribose (2'-O-AADPR).", "output": {"entities": {"chemical": [{"text": "amide", "start": 82, "end": 87}, {"text": "nicotinamide", "start": 135, "end": 147}, {"text": "beta-nicotinamide adenine dinucleotide", "start": 162, "end": 200}, {"text": "beta-NAD", "start": 202, "end": 210}, {"text": "NAD", "start": 216, "end": 219}, {"text": "2'-O-acetyl-ADP-ribose", "start": 330, "end": 352}, {"text": "2'-O-AADPR", "start": 354, "end": 364}]}}, "schema": []}
{"input": "Here the author would like to review the past endeavors on developing mechanism-based sirtuin modulators (inhibitors and activators).", "output": {"entities": {}}, "schema": []}
{"input": "The first part of this article will provide an updated mechanistic picture of the sirtuin-catalyzed deacetylation reaction.", "output": {"entities": {}}, "schema": []}
{"input": "The second part will be focused on how the mechanistic knowledge has been exploited for the design of effective sirtuin modulators.", "output": {"entities": {}}, "schema": []}
{"input": "Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers independently of the TZD effects on aromatase.", "output": {"entities": {"chemical": [{"text": "Thiazolidinediones", "start": 0, "end": 18}, {"text": "TZDs", "start": 20, "end": 24}, {"text": "TZD", "start": 90, "end": 93}]}}, "schema": []}
{"input": "Thiazolidinediones (TZDs) are insulin sensitizers used for treatment of diabetes.", "output": {"entities": {"chemical": [{"text": "Thiazolidinediones", "start": 0, "end": 18}, {"text": "TZDs", "start": 20, "end": 24}]}}, "schema": []}
{"input": "We have previously reported that TZDs reduce estrogen synthesis by inhibiting aromatase activity in human granulosa cells (HGC).", "output": {"entities": {"chemical": [{"text": "TZDs", "start": 33, "end": 37}, {"text": "estrogen", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Multiple clinical trials demonstrated that TZDs increase the risk of fractures in postmenopausal women with type 2 diabetes.", "output": {"entities": {"chemical": [{"text": "TZDs", "start": 43, "end": 47}]}}, "schema": []}
{"input": "We studied mouse osteoblasts alone or in a co-culture with HGC to determine whether TZD inhibition of aromatase plays a role in their effects on bone metabolism.", "output": {"entities": {"chemical": [{"text": "TZD", "start": 84, "end": 87}]}}, "schema": []}
{"input": "Mouse osteoblasts were cultured with and without HGC, and incubated in a medium with or without testosterone, pioglitazone or rosiglitazone.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 96, "end": 108}, {"text": "pioglitazone", "start": 110, "end": 122}, {"text": "rosiglitazone", "start": 126, "end": 139}]}}, "schema": []}
{"input": "Cell growth, oleic acid uptake, alkaline phosphatase activity, and osteocalcin production were measured.", "output": {"entities": {}}, "schema": []}
{"input": "TZDs inhibited estradiol production by up to 84% in HGC/mouse osteoblast co-cultures.", "output": {"entities": {"chemical": [{"text": "TZDs", "start": 0, "end": 4}, {"text": "estradiol", "start": 15, "end": 24}]}}, "schema": []}
{"input": "TZDs induced mouse osteoblast death and increased oleic acid uptake.", "output": {"entities": {"chemical": [{"text": "TZDs", "start": 0, "end": 4}, {"text": "oleic acid", "start": 50, "end": 60}]}}, "schema": []}
{"input": "TZDs also inhibited alkaline phosphatase activity (58-75%, p < 0. 046) and osteocalcin production (52-75%, p < 0. 031).", "output": {"entities": {"chemical": [{"text": "TZDs", "start": 0, "end": 4}]}}, "schema": []}
{"input": "For all the parameters, there were no significant differences between the osteoblast cultures alone and the HCG/osteoblast co-cultures.", "output": {"entities": {}}, "schema": []}
{"input": "TZD effects on osteoblast viability, oleic acid uptake, alkaline phosphatase and osteocalcin production are independent of their effects on aromatase.", "output": {"entities": {"chemical": [{"text": "TZD", "start": 0, "end": 3}]}}, "schema": []}
{"input": "New alloferon analogues: synthesis and antiviral properties.", "output": {"entities": {"chemical": [{"text": "alloferon", "start": 4, "end": 13}]}}, "schema": []}
{"input": "We have extended our study on structure/activity relationship studies of insect peptide alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) by evaluating the antiviral effects of new alloferon analogues.", "output": {"entities": {"chemical": [{"text": "alloferon", "start": 88, "end": 97}, {"text": "H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH", "start": 99, "end": 155}, {"text": "alloferon", "start": 200, "end": 209}]}}, "schema": []}
{"input": "We synthesized 18 alloferon analogues: 12 peptides with sequences shortened from N-or C-terminus and 6 N-terminally modified analogues H-X (1)-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH, where X (1) = Phe (13), Tyr (14), Trp (15), Phg (16), Phe (p-Cl) (17), and Phe (p-OMe) (18).", "output": {"entities": {"chemical": [{"text": "alloferon", "start": 18, "end": 27}, {"text": "N", "start": 81, "end": 82}, {"text": "C", "start": 86, "end": 87}, {"text": "N", "start": 103, "end": 104}, {"text": "Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH", "start": 143, "end": 193}, {"text": "Phe", "start": 209, "end": 212}, {"text": "Tyr", "start": 219, "end": 222}, {"text": "Trp", "start": 229, "end": 232}, {"text": "Phe (p-Cl)", "start": 249, "end": 259}, {"text": "Phe (p-OMe)", "start": 270, "end": 281}]}}, "schema": []}
{"input": "We found that most of the evaluated peptides inhibit the replication of Human Herpesviruses or Coxsackievirus B2 in Vero, HEp-2 and LLC-MK (2) cells.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that the compound [3-13]-alloferon (1) exhibits the strongest antiviral activity (IC (50) = 38 mu M) among the analyzed compound.", "output": {"entities": {"chemical": [{"text": "[3-13]-alloferon", "start": 39, "end": 55}]}}, "schema": []}
{"input": "Moreover, no cytotoxic activity against the investigated cell lines was observed for all studied peptides at concentration 165 mu M or higher.", "output": {"entities": {}}, "schema": []}
{"input": "Sonochemical synthesis of hierarchical ZnO nanostructures.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 39, "end": 42}]}}, "schema": []}
{"input": "This work is about fabrication of ZnO nanostructures (ZnO-NS) via a simple sonochemical method.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 34, "end": 37}, {"text": "ZnO", "start": 54, "end": 57}]}}, "schema": []}
{"input": "The chemicals used for the synthesis of various shaped ZnO are Zn salt, sodium hydroxide and ammonia solution without other structure directing agent or surfactant needed.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 55, "end": 58}, {"text": "Zn", "start": 63, "end": 65}, {"text": "sodium hydroxide", "start": 72, "end": 88}, {"text": "ammonia solution", "start": 93, "end": 109}]}}, "schema": []}
{"input": "This method is feasible and green, as it does not require high temperature and/or highly toxic chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "The shape of the ZnO-NS can be tuned by adjusting the ultrasound energy dissipated via varying the ultrasonication time from 5 to 60 min.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 17, "end": 20}]}}, "schema": []}
{"input": "It was found that uniform ZnO nanorods with diameter around 50 nm were formed after 15 min of ultrasonication while flowerlike ZnO-NS was formed after 30 min.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 26, "end": 29}, {"text": "ZnO", "start": 127, "end": 130}]}}, "schema": []}
{"input": "This method produces high quality ZnO-NS with controllable shapes, uniformity, and purity.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 34, "end": 37}]}}, "schema": []}
{"input": "Objective and subjective cognitive enhancing effects of mixed amphetamine salts in healthy people.", "output": {"entities": {"chemical": [{"text": "amphetamine", "start": 62, "end": 73}]}}, "schema": []}
{"input": "Psychostimulants such as mixed amphetamine salts (MAS, brand name Adderall) are widely used for cognitive enhancement by healthy young people, yet laboratory research on effectiveness has yielded variable results.", "output": {"entities": {"chemical": [{"text": "amphetamine", "start": 31, "end": 42}, {"text": "Adderall", "start": 66, "end": 74}]}}, "schema": []}
{"input": "The present study assessed the effects of MAS in healthy young adults with an adequately powered double-blind cross-over placebo-controlled trial.", "output": {"entities": {}}, "schema": []}
{"input": "We examined effects in 13 measures of cognitive ability including episodic memory, working memory, inhibitory control, convergent creativity, intelligence and scholastic achievement, with the goals of determining (1) whether the drug is at least moderately enhancing (Cohen' s d > =. 5) to some or all cognitive abilities tested, (2) whether its effects on cognition are moderated by baseline ability or COMT genotype, and (3) whether it induces an illusory perception of cognitive enhancement.", "output": {"entities": {}}, "schema": []}
{"input": "The results did not reveal enhancement of any cognitive abilities by MAS for participants in general.", "output": {"entities": {}}, "schema": []}
{"input": "There was a suggestion of moderation of enhancement by baseline ability and COMT genotype in a minority of tasks, with MAS enhancing lower ability participants on word recall, embedded figures and Raven' s Progressive Matrices.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the lack of enhancement observed for most measures and most participants, participants nevertheless believed their performance was more enhanced by the active capsule than by placebo.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that MAS has no more than small effects on cognition in healthy young adults, although users may perceive the drug as enhancing their cognition.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers.", "output": {"entities": {"chemical": [{"text": "Vitamin D", "start": 0, "end": 9}, {"text": "25-hydroxyvitamin D", "start": 50, "end": 69}]}}, "schema": []}
{"input": "Circulating 25-hydroxyvitamin D (25-OHD) levels vary among human populations.", "output": {"entities": {"chemical": [{"text": "25-hydroxyvitamin D", "start": 12, "end": 31}, {"text": "25-OHD", "start": 33, "end": 39}]}}, "schema": []}
{"input": "Only limited information regarding determinants of these measures is available for infants and children, particularly in minority groups at greatest risk for vitamin D deficiency.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 158, "end": 167}]}}, "schema": []}
{"input": "We identified demographic determinants of circulating 25-OHD in a large cohort of minority children, and now extend our studies to examine potential roles of vitamin D binding protein (DBP) as a determinant of 25-OHD levels.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 54, "end": 60}, {"text": "vitamin D", "start": 158, "end": 167}, {"text": "25-OHD", "start": 210, "end": 216}]}}, "schema": []}
{"input": "Serum DBP level and common single nucleotide polymorphisms (SNPs) at positions 432 and 436 in the GC gene, encoding DBP, were examined.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 34, "end": 44}]}}, "schema": []}
{"input": "We confirmed self-reported ancestry using ancestry informative markers (AIMs), and included quantitative AIMs scores in the analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The multivariate model incorporated previously identified demographic and nutritional determinants of 25-OHD in this cohort, as well as GC SNPs and circulating DBP.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 102, "end": 108}]}}, "schema": []}
{"input": "Genetic variants in GC differed by self-reported ancestry.", "output": {"entities": {}}, "schema": []}
{"input": "The 1f allele (D432/T436) was enriched in African Americans, occurring in 71%.", "output": {"entities": {}}, "schema": []}
{"input": "Homozygosity for the 1f allele (DDTT) occurred in 53% of African Americans but only 6% of Caucasians and 13% of Hispanics.", "output": {"entities": {}}, "schema": []}
{"input": "Circulating DBP was significantly correlated with 25-OHD.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 50, "end": 56}]}}, "schema": []}
{"input": "GC SNPs were associated with both circulating DBP and 25-OHD.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 54, "end": 60}]}}, "schema": []}
{"input": "It appears that progressive substitution of lysine for threonine at the 436 position results in lower circulating 25-OHD.", "output": {"entities": {"chemical": [{"text": "lysine", "start": 44, "end": 50}, {"text": "threonine", "start": 55, "end": 64}, {"text": "25-OHD", "start": 114, "end": 120}]}}, "schema": []}
{"input": "Multivariate analysis revealed that genetic variance in GC significantly contributes to circulating DBP as well as 25-OHD.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 115, "end": 121}]}}, "schema": []}
{"input": "Moreover, the effect of GC SNPs on 25-OHD are evident after adjusting for their effects on circulating DBP.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 35, "end": 41}]}}, "schema": []}
{"input": "Thus in young children genetic variance of the common GC T436K SNP affects circulating levels of the DBP protein, which in turn affects circulating 25-OHD.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 148, "end": 154}]}}, "schema": []}
{"input": "However, the GC genotype also affects circulating 25-OHD independently of its effect on circulating DBP.", "output": {"entities": {"chemical": [{"text": "25-OHD", "start": 50, "end": 56}]}}, "schema": []}
{"input": "These findings provide data that may be important in the interpretation of vitamin D status in children of varying ancestral backgrounds.", "output": {"entities": {}}, "schema": []}
{"input": "The development of better photocatalysts through composition-and structure-engineering.", "output": {"entities": {}}, "schema": []}
{"input": "Semiconductor photocatalysts that can effectively utilize solar irradiation hold great potential for harnessing renewable-energy sources, as well as for environmental protection and-remediation.", "output": {"entities": {}}, "schema": []}
{"input": "Exploring advanced photocatalysts that have improved performance has been a central theme in photocatalysis research.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we review the recent developments in the design-and fabrication of photocatalysts with an emphasis on composition-and structural control over multiple length scales.", "output": {"entities": {}}, "schema": []}
{"input": "This Focus Review will be of value for researchers in the area of photocatalysis, in particular, in the aspects of material design that lead to the synthesis of better photocatalysts.", "output": {"entities": {}}, "schema": []}
{"input": "Can the chemical reactivity of an ultimate carcinogen be related to its carcinogenicity?", "output": {"entities": {}}, "schema": []}
{"input": "An application to propylene oxide.", "output": {"entities": {"chemical": [{"text": "propylene oxide", "start": 18, "end": 33}]}}, "schema": []}
{"input": "In this article we report calculations of the activation free energy for a chemical reaction between propylene oxide and DNA, in particular with the guanine at the N7 position.", "output": {"entities": {"chemical": [{"text": "propylene oxide", "start": 101, "end": 116}, {"text": "guanine", "start": 149, "end": 156}]}}, "schema": []}
{"input": "Calculations were performed using Hartree-Fock and MP2 methods in conjunction with flexible basis sets.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of solvation were considered using the Langevin dipoles and solvent reaction field methods.", "output": {"entities": {}}, "schema": []}
{"input": "The calculated activation free energies are in good agreement with the experimental value of 25. 36 kcal/mol.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the reactivities of a series of ultimate carcinogens of the epoxy type toward DNA are shown to be related to their carcinogenicities.", "output": {"entities": {"chemical": [{"text": "epoxy", "start": 70, "end": 75}]}}, "schema": []}
{"input": "Higher reactivity is generally associated with higher carcinogenicity, although transport properties, reactions with ultimate carcinogen scavengers, and the DNA correction mechanism are also very important.", "output": {"entities": {}}, "schema": []}
{"input": "It is very likely that the window of reactivity rather than a high reactivity value is the relevant measure of carcinogenicity, since highly reactive ultimate carcinogens interact with water and proteins before they reach DNA.", "output": {"entities": {}}, "schema": []}
{"input": "Negative regulation of osteoclast precursor differentiation by CD11b and beta 2 integrin-B-cell lymphoma 6 signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Negative regulation of osteoclastogenesis is important for bone homeostasis and prevention of excessive bone resorption in inflammatory and other diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanisms that directly suppress osteoclastogenesis are not well understood.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we investigated regulation of osteoclast differentiation by the beta 2 integrin CD11b/CD18 that is expressed on myeloid lineage osteoclast precursors.", "output": {"entities": {}}, "schema": []}
{"input": "CD11b-deficient mice exhibited decreased bone mass that was associated with increased osteoclast numbers and decreased bone formation.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, CD11b and beta 2 integrin signaling suppressed osteoclast differentiation by preventing receptor activator of NF-kappa B ligand (RANKL)-induced induction of the master regulator of osteoclastogenesis nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and of downstream osteoclast-related NFATc1 target genes.", "output": {"entities": {}}, "schema": []}
{"input": "CD11b suppressed induction of NFATc1 by the complementary mechanisms of downregulation of RANK expression and induction of recruitment of the transcriptional repressor B-cell lymphoma 6 (BCL6) to the NFATC1 gene.", "output": {"entities": {}}, "schema": []}
{"input": "These findings identify CD11b as a negative regulator of the earliest stages of osteoclast differentiation, and provide an inducible mechanism by which environmental cues suppress osteoclastogenesis by activating a transcriptional repressor that makes genes refractory to osteoclastogenic signaling.", "output": {"entities": {}}, "schema": []}
{"input": "The role of long chain omega-3 polyunsaturated fatty acids in reducing lipid peroxidation among elderly patients with mild cognitive impairment: a case-control study.", "output": {"entities": {"chemical": [{"text": "omega-3 polyunsaturated fatty acids", "start": 23, "end": 58}]}}, "schema": []}
{"input": "The present work explores the effect of dietary omega-3 polyunsaturated fatty acids (PUFAs) intake on lipid peroxidation among mild cognitive impairment (MCI) patients.", "output": {"entities": {"chemical": [{"text": "omega-3 polyunsaturated fatty acids", "start": 48, "end": 83}, {"text": "PUFAs", "start": 85, "end": 90}]}}, "schema": []}
{"input": "The plasma lipid hydroperoxide (LPO) levels in 67 MCI patients were compared to those of 134 healthy elderly controls.", "output": {"entities": {"chemical": [{"text": "hydroperoxide", "start": 17, "end": 30}]}}, "schema": []}
{"input": "Omega-3 PUFA intake was assessed using an interviewer-administered food frequency questionnaire.", "output": {"entities": {"chemical": [{"text": "Omega-3 PUFA", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Apolipoprotein E genotyping was performed using polymerase chain reaction and restriction enzyme digestion.", "output": {"entities": {}}, "schema": []}
{"input": "The association between various confounders and lipid peroxidation was evaluated using regression analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake on LPO level was investigated.", "output": {"entities": {"chemical": [{"text": "docosahexaenoic acid", "start": 17, "end": 37}, {"text": "DHA", "start": 39, "end": 42}, {"text": "eicosapentaenoic acid", "start": 48, "end": 69}, {"text": "EPA", "start": 71, "end": 74}]}}, "schema": []}
{"input": "The results revealed that LPO levels were significantly higher in the MCI group than in the control group.", "output": {"entities": {}}, "schema": []}
{"input": "Inverse correlations were found between DHA and EPA intake and LPO level among the MCI group.", "output": {"entities": {"chemical": [{"text": "DHA", "start": 40, "end": 43}, {"text": "EPA", "start": 48, "end": 51}]}}, "schema": []}
{"input": "LPO levels decreased significantly with increasing DHA and EPA intake.", "output": {"entities": {"chemical": [{"text": "DHA", "start": 51, "end": 54}, {"text": "EPA", "start": 59, "end": 62}]}}, "schema": []}
{"input": "In summary, the findings revealed that DHA and EPA can play a role in alleviating oxidative stress and reducing the risk of neurodegenerative diseases.", "output": {"entities": {"chemical": [{"text": "DHA", "start": 39, "end": 42}, {"text": "EPA", "start": 47, "end": 50}]}}, "schema": []}
{"input": "Multidrug resistance-associated proteins are involved in the transport of the glutathione conjugates of the ultimate carcinogen of benzo [a] pyrene in human Caco-2 cells.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 78, "end": 89}, {"text": "benzo [a] pyrene", "start": 131, "end": 147}]}}, "schema": []}
{"input": "A wide variety of contaminants are ingested through food, among them the pro-carcinogenic polycyclic aromatic hydrocarbon benzo [a] pyrene (BP) that is resorbed and partially metabolized in the enterocytes of the small intestine.", "output": {"entities": {"chemical": [{"text": "benzo [a] pyrene", "start": 122, "end": 138}]}}, "schema": []}
{"input": "Previous in vitro studies have revealed that BP phenols are excreted as Phase II metabolites including glucuronides and sulfates.", "output": {"entities": {"chemical": [{"text": "BP phenols", "start": 45, "end": 55}, {"text": "sulfates", "start": 120, "end": 128}]}}, "schema": []}
{"input": "This export is mediated by the breast cancer resistance protein (ABCG2).", "output": {"entities": {}}, "schema": []}
{"input": "The ultimate carcinogenic Phase I BP metabolite anti-BP-7, 8-dihydrodiol-9, 10-epoxide (BPDE) can be detoxified by glutathione conjugate formation catalyzed by glutathione S-transferases.", "output": {"entities": {"chemical": [{"text": "BP-7, 8-dihydrodiol-9, 10-epoxide", "start": 53, "end": 86}, {"text": "BPDE", "start": 88, "end": 92}, {"text": "glutathione", "start": 115, "end": 126}, {"text": "glutathione S", "start": 160, "end": 173}]}}, "schema": []}
{"input": "In the present study, differentiated human intestinal Caco-2 cells were used as a model for the human small intestine to investigate the detoxification of BPDE and excretion of stereoisomeric glutathione conjugates in the presence of an inhibitor of the glutathione-cleaving enzyme gamma-glutamyl transpeptidase at the cell surface.", "output": {"entities": {"chemical": [{"text": "BPDE", "start": 155, "end": 159}, {"text": "glutathione", "start": 192, "end": 203}, {"text": "glutathione", "start": 254, "end": 265}]}}, "schema": []}
{"input": "The results indicate that the glutathione conjugates of BPDE are formed and excreted mainly to the apical and to a minor extent to the basolateral side of polarized Caco-2 monolayers.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 30, "end": 41}, {"text": "BPDE", "start": 56, "end": 60}]}}, "schema": []}
{"input": "Inhibition studies revealed that the multidrug resistance-associated proteins (ABCCs) are involved in the transport of BPDE glutathione conjugates.", "output": {"entities": {"chemical": [{"text": "BPDE glutathione", "start": 119, "end": 135}]}}, "schema": []}
{"input": "Stable ABCC1, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of BPDE glutathione conjugates.", "output": {"entities": {"chemical": [{"text": "BPDE glutathione", "start": 176, "end": 192}]}}, "schema": []}
{"input": "In conclusion, the ultimate carcinogen BPDE is detoxified via glutathione conjugation and subsequently excreted by Caco-2 cells in both apical and basolateral directions.", "output": {"entities": {"chemical": [{"text": "BPDE", "start": 39, "end": 43}, {"text": "glutathione", "start": 62, "end": 73}]}}, "schema": []}
{"input": "This finding is equivalent to a transport into feces as well as blood system in the in vivo situation.", "output": {"entities": {}}, "schema": []}
{"input": "Oleuropein supplementation increases urinary noradrenaline and testicular testosterone levels and decreases plasma corticosterone level in rats fed high-protein diet.", "output": {"entities": {"chemical": [{"text": "Oleuropein", "start": 0, "end": 10}, {"text": "noradrenaline", "start": 45, "end": 58}, {"text": "testosterone", "start": 74, "end": 86}, {"text": "corticosterone", "start": 115, "end": 129}]}}, "schema": []}
{"input": "The effects of oleuropein, a phenolic compound in extra virgin olive oil, on protein metabolism were investigated by measuring testicular testosterone and plasma corticosterone levels in rats fed diets with different protein levels.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 15, "end": 25}, {"text": "phenolic", "start": 29, "end": 37}, {"text": "testosterone", "start": 138, "end": 150}, {"text": "corticosterone", "start": 162, "end": 176}]}}, "schema": []}
{"input": "In Experiment 1, rats were fed experimental diets with different protein levels (40, 25 and 10 g/100 g casein) with or without 0. 1 g/100 g oleuropein.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 140, "end": 150}]}}, "schema": []}
{"input": "After 28 days of feeding, the testosterone level in the testis was significantly higher and the plasma corticosterone level was significantly lower in rats fed the 40% casein diet with oleuropein than in those fed the same diet without oleuropein.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 30, "end": 42}, {"text": "corticosterone", "start": 103, "end": 117}, {"text": "oleuropein", "start": 185, "end": 195}, {"text": "oleuropein", "start": 236, "end": 246}]}}, "schema": []}
{"input": "The urinary noradrenaline level, nitrogen balance and hepatic arginase activity were significantly higher in rats fed the 40% casein diet with oleuropein supplementation than in those fed the 40% casein diet without oleuropein supplementation.", "output": {"entities": {"chemical": [{"text": "noradrenaline", "start": 12, "end": 25}, {"text": "nitrogen", "start": 33, "end": 41}, {"text": "oleuropein", "start": 143, "end": 153}, {"text": "oleuropein", "start": 216, "end": 226}]}}, "schema": []}
{"input": "In Experiment 2, the effects of oleuropein aglycone (a major phenolic compound in extra virgin olive oil and the absorbed form of oleuropein ingested in the gastrointestinal tracts) on the secretion of luteinizing hormone (LH) from the pituitary gland, which regulates testosterone production in the testis, were investigated in anesthetized rats.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 32, "end": 42}, {"text": "phenolic", "start": 61, "end": 69}, {"text": "oleuropein", "start": 130, "end": 140}, {"text": "testosterone", "start": 269, "end": 281}]}}, "schema": []}
{"input": "Plasma LH level increased dose dependently after the administration of oleuropein aglycone (P <. 001, r = 0. 691).", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 71, "end": 81}]}}, "schema": []}
{"input": "These findings suggest that dietary supplementation with 0. 1 g/100 g oleuropein alters the levels of hormones associated with protein anabolism by increasing urinary noradrenaline and testicular testosterone levels and decreasing plasma corticosterone level in rats fed a high-protein diet.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 70, "end": 80}, {"text": "noradrenaline", "start": 167, "end": 180}, {"text": "testosterone", "start": 196, "end": 208}, {"text": "corticosterone", "start": 238, "end": 252}]}}, "schema": []}
{"input": "The influence of the choice of digestion enzyme used to prepare rat hepatocytes on xenobiotic uptake and efflux.", "output": {"entities": {}}, "schema": []}
{"input": "Isolated rat hepatocytes are widely used to assess the metabolism and toxicity of xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "The choice of digestion enzyme used to prepare the cells has been shown previously to influence their metabolic capability.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigates the effect of the digestion enzyme (collagenase II, collagenase A/trypsin inhibitor, or collagenase plus dispase) on the uptake of xenobiotics into, and efflux from, hepatocytes.", "output": {"entities": {}}, "schema": []}
{"input": "The choice of digestion enzymes used in this study does not affect uptake of either pravastatin (an organic anion probe substrate for Oatp transporter) or metformin (an organic cation probe substrate for Oct transporter).", "output": {"entities": {"chemical": [{"text": "pravastatin", "start": 84, "end": 95}, {"text": "metformin", "start": 155, "end": 164}]}}, "schema": []}
{"input": "With regard to efflux transporters, hepatocyte differentiation was better maintained when cells were isolated using collagenase II alone.", "output": {"entities": {}}, "schema": []}
{"input": "An appeal for the presentation of detailed human derived data for dose-response calculations in nutritional science.", "output": {"entities": {}}, "schema": []}
{"input": "If a diet, food or food constituent is recognised to have both health benefits and health risks, the benefits have to be compared with the risks to develop coherent scientific evidence-based dietary advice.", "output": {"entities": {}}, "schema": []}
{"input": "This means that both risk and benefit assessment should follow a similar paradigm and that benefits and risks are expressed in a common currency.", "output": {"entities": {}}, "schema": []}
{"input": "Dose-response functions are vital for that purpose.", "output": {"entities": {}}, "schema": []}
{"input": "However, the construction of these functions is often of second interest in the currently available (epidemiological) literature.", "output": {"entities": {}}, "schema": []}
{"input": "In order to bring forward the potential of epidemiological studies for the construction of the dose-response functions for benefit-risk purposes, the scientific (nutrition and health) community is asked to expand on their data presentation, either by presenting more detailed data focusing on dose-response necessities, and/or by sharing primary data.", "output": {"entities": {}}, "schema": []}
{"input": "Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms.", "output": {"entities": {}}, "schema": []}
{"input": "Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied.", "output": {"entities": {}}, "schema": []}
{"input": "Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol (R) 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used.", "output": {"entities": {"chemical": [{"text": "aminophylline", "start": 62, "end": 75}, {"text": "Carbopol", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin ((R)) 350, tablets Purdue Frederic, Canada (R-II).", "output": {"entities": {"chemical": [{"text": "Aminofilin", "start": 25, "end": 35}, {"text": "Phyllocontin", "start": 85, "end": 97}]}}, "schema": []}
{"input": "Results: Calculated release rate constants and the f 2 values between R-I/F-I (84. 1) and R-II/F-III (83. 4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport.", "output": {"entities": {}}, "schema": []}
{"input": "Higher Tmax, was found in the rabbits, dosed with F-II (12. 00 h), F-III (10. 50 h), and R-II (15. 00 h) formulation.", "output": {"entities": {}}, "schema": []}
{"input": "The highest Cmax (9. 22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5. 58 mg/L) and R-II (4. 18 mg/L).", "output": {"entities": {}}, "schema": []}
{"input": "Higher AUC values were detected for all three formulations (from 115. 90 to 204. 06 mgh/L) in relation to commercial products (105. 33 and 113. 25 mgh/L).", "output": {"entities": {}}, "schema": []}
{"input": "Discussion and conclusion: The results demonstrated a good correlation of Level A (r (2) = 0. 97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.", "output": {"entities": {}}, "schema": []}
{"input": "Impact of lead and mercuric ions on the interleukin-2-dependent proliferation and survival of T cells.", "output": {"entities": {"chemical": [{"text": "mercuric", "start": 19, "end": 27}]}}, "schema": []}
{"input": "Mercury and lead are widespread in the environment, causing chronic exposure of a large population to low concentrations of these metals.", "output": {"entities": {"chemical": [{"text": "Mercury", "start": 0, "end": 7}]}}, "schema": []}
{"input": "While several studies demonstrated that low levels of both metals affect the immune system, little is known about underlying molecular mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to investigate the impact of mercuric (Hg (2 +)) and lead (Pb (2 +)) ions on T cells.", "output": {"entities": {"chemical": [{"text": "mercuric", "start": 61, "end": 69}, {"text": "Hg (2 +)", "start": 71, "end": 79}, {"text": "Pb (2 +)", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Up to 100 mu M Pb (NO (3)) (2) had no effect on cellular viability and proliferation.", "output": {"entities": {"chemical": [{"text": "Pb (NO (3)) (2)", "start": 15, "end": 30}]}}, "schema": []}
{"input": "In contrast, HgCl (2) caused a concentration-dependent decline of viable leukocytes and especially of activated T cells.", "output": {"entities": {"chemical": [{"text": "HgCl (2)", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Additionally, Hg (2 +) induced reactive oxygen species (ROS) generation accompanied by the loss of mitochondrial transmembrane potential, measured by Dihydrorhodamine and Rhodamine-123, respectively.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 14, "end": 22}, {"text": "oxygen", "start": 40, "end": 46}, {"text": "Dihydrorhodamine", "start": 150, "end": 166}, {"text": "Rhodamine-123", "start": 171, "end": 184}]}}, "schema": []}
{"input": "The antioxidant N-acetylcysteine partially reversed the toxic effects of Hg (2 +), pointing to an involvement of ROS.", "output": {"entities": {"chemical": [{"text": "N-acetylcysteine", "start": 16, "end": 32}, {"text": "Hg (2 +)", "start": 73, "end": 81}]}}, "schema": []}
{"input": "The major cytokine controlling T-cell survival and proliferation is interleukin (IL)-2.", "output": {"entities": {}}, "schema": []}
{"input": "Hg (2 +) had no effect on the secretion of IL-2, but on IL-2 mediated signal transduction pathways, reducing phosphorylation of the downstream kinases ERK1/2 and AKT.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Moreover, Hg (2 +) led to an arrest of the cells in the S phase of the cell cycle.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 10, "end": 18}]}}, "schema": []}
{"input": "Taken together, these data fit a model in which Hg (2 +) disrupts mitochondria, and the resulting release of ROS inhibits IL-2-dependent signal transduction, reducing proliferation and survival of T cells.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Quantitative ultrasound of cortical bone in the femoral neck predicts femur strength: results of a pilot study.", "output": {"entities": {}}, "schema": []}
{"input": "A significant risk of femoral neck (FN) fracture exists for men and women with an areal bone mineral density (aBMD) higher than the osteoporotic range, as measured with dual-energy X-ray absorptiometry (DXA).", "output": {"entities": {}}, "schema": []}
{"input": "Separately measuring the cortical and trabecular FN compartments and combining the results would likely be a critical aspect of enhancing the diagnostic capabilities of a new technique.", "output": {"entities": {}}, "schema": []}
{"input": "Because the cortical shell determines a large part of FN strength a novel quantitative ultrasound (QUS) technique that probes the FN cortical compartment was implemented.", "output": {"entities": {}}, "schema": []}
{"input": "The sensitivity of the method to variations of FN cortical properties and FN strength was tested.", "output": {"entities": {}}, "schema": []}
{"input": "Nine femurs (women, mean age 83 years) were subjected to QUS to measure the through transmission time-of-flight (TOF) at the FN and mechanical tests to assess strength.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative computed tomography (QCT) scans were performed to enable analysis of the dependence of TOF on bone parameters.", "output": {"entities": {}}, "schema": []}
{"input": "DXA was also performed for reference.", "output": {"entities": {}}, "schema": []}
{"input": "An ultrasound wave propagating circumferentially in the cortical shell was measured in all specimens.", "output": {"entities": {}}, "schema": []}
{"input": "Its TOF was not influenced by the properties of the trabecular compartment.", "output": {"entities": {}}, "schema": []}
{"input": "Averaged TOF for nine FN measurement positions/orientations was significantly correlated to strength (R2 = 0. 79) and FN cortical QCT variables: total BMD (R (2) = 0. 54); regional BMD in the inferoanterior (R2 = 0. 90) and superoanterior (R2 = 0. 57) quadrants; and moment of inertia (R2 = 0. 71).", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study demonstrate that QUS can perform a targeted measurement of the FN cortical compartment.", "output": {"entities": {}}, "schema": []}
{"input": "Because the method involves mechanical guided waves, the QUS variable is related to the geometric and material properties of the cortical shell (cortical thickness, tissue elasticity, and porosity).", "output": {"entities": {}}, "schema": []}
{"input": "This work opens the way to a multimodal QUS assessment of the proximal femur, combining our approach targeting the cortical shell with the existing modality sensitive to the trabecular compartment.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo feasibility of our approach has to be confirmed with experimental data in patients.", "output": {"entities": {}}, "schema": []}
{"input": "Isolation and characterization of two new non-hemorrhagic metalloproteinases with fibrinogenolytic activity from the mapanare (Bothrops colombiensis) venom.", "output": {"entities": {}}, "schema": []}
{"input": "Colombienases are acidic, low molecular weight metalloproteinases (Mr of 23, 074. 31 Da colombienase-1 and 23, 078. 80 Da colombienase-2; pI of 6. 0 and 6. 2, respectively) isolated from Bothrops colombiensis snake venom.", "output": {"entities": {}}, "schema": []}
{"input": "The chromatographic profile in RP-HPLC and its partial sequence confirmed its high homogeneity.", "output": {"entities": {}}, "schema": []}
{"input": "Both colombienases present fibrino (geno) lytic activity, but did not show any hemorrhagic, amidolytic, plasminogen activator or coagulant activities, and no effect on platelet aggregation induced by collagen or ADP.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 212, "end": 215}]}}, "schema": []}
{"input": "Both enzymes were strongly active on fibrinogen A alpha chains followed by the B beta chains, and colombienases-2, at high doses, also degraded the gamma chains.", "output": {"entities": {}}, "schema": []}
{"input": "This activity was stable at temperatures ranging between 4 and 37 degrees C, with a maximum activity at 25 degrees C, and at pHs between 7 and 9.", "output": {"entities": {}}, "schema": []}
{"input": "The homology demonstrated by the comparison of sequences, with zinc-dependent metalloproteinases, as well as the metal chelant effects on, confirmed that the colombienases were metalloproteinases, particularly to alpha-fibrinogenases belonging to the P-I class of SVPMs (20-30 kDa), which contain only the single-domain proteins.", "output": {"entities": {"chemical": [{"text": "zinc", "start": 63, "end": 67}]}}, "schema": []}
{"input": "The biological characteristics of the colombienases confer a therapeutic potential, since they contain a high fibrino (geno) lytic activity, devoid of hemorrhagic activity.", "output": {"entities": {}}, "schema": []}
{"input": "These metalloproteinases might be explored as thrombolytic agents given that they dissolve fibrin clots or prevent their formation.", "output": {"entities": {}}, "schema": []}
{"input": "A step toward the reactivation of aged cholinesterases-Crystal structure of ligands binding to aged human butyrylcholinesterase.", "output": {"entities": {}}, "schema": []}
{"input": "Organophosphorus nerve agents irreversibly inhibit cholinesterases.", "output": {"entities": {"chemical": [{"text": "Organophosphorus", "start": 0, "end": 16}]}}, "schema": []}
{"input": "Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes.", "output": {"entities": {"chemical": [{"text": "serine", "start": 31, "end": 37}, {"text": "oximes", "start": 96, "end": 102}]}}, "schema": []}
{"input": "But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i. e., a conjugated enzyme that is no longer reactivable by oximes.", "output": {"entities": {"chemical": [{"text": "oximes", "start": 152, "end": 158}]}}, "schema": []}
{"input": "One strategy to regain reactivability is to alkylate the phosphylic adduct.", "output": {"entities": {}}, "schema": []}
{"input": "Specific alkylating molecules were synthesized and the crystal structures of the complexes they form with soman-aged human butyrylcholinesterase were solved.", "output": {"entities": {"chemical": [{"text": "soman", "start": 106, "end": 111}]}}, "schema": []}
{"input": "Although the compounds bind in the active site gorge of the aged enzyme, the orientation of the alkylating function appears to be unsuitable for efficient alkylation of the phosphylic adduct.", "output": {"entities": {}}, "schema": []}
{"input": "However, these crystal structures provide key information to design efficient alkylators of aged-butyrylcholinesterase and specific reactivators of butyrylcholinesterase.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of cytotoxic T lymphocyte antigen-4 (CTLA-4) promoter-318C/T and + 49A/G gene polymorphisms in Turkish patients with familial Mediterranean fever.", "output": {"entities": {}}, "schema": []}
{"input": "Either the role of the adaptive immune system or the interaction between innate and adaptive immune systems in familial Mediterranean fever (FMF) is not clear so far.", "output": {"entities": {}}, "schema": []}
{"input": "So, we planned to search for the interaction between the innate and adaptive immune systems in the pathogenesis of FMF by investigating polymorphism for CTLA-4 gene, which plays a role in controlling antigen presentation to T cells.", "output": {"entities": {}}, "schema": []}
{"input": "We also aimed to investigate whether there is an association between-318C/T and + 49A/G polymorphisms in the CTLA-4 gene and the main clinical features of the disease.", "output": {"entities": {}}, "schema": []}
{"input": "75 FMF patients and 179 controls were studied.", "output": {"entities": {}}, "schema": []}
{"input": "Polymorphism was detected by the PCR-RFLP technique.", "output": {"entities": {}}, "schema": []}
{"input": "The CT genotype and T allele frequencies of the-318C/T polymorphism and the haplotype frequency for the-318T/+ 49A in the CTLA-4 gene were higher in the FMF (21. 3, 21. 3, and 10. 7%) when compared with the controls (10. 6, 10. 6, and 5. 3%; P = 0. 029, 0. 044, and 0. 029).", "output": {"entities": {}}, "schema": []}
{"input": "However, these differences did not reach a statistically significant level after the Bonferroni correction.", "output": {"entities": {}}, "schema": []}
{"input": "A significant linkage disequilibrium was found between the-318C/T and + 49A/G polymorphisms in the CTLA-4 gene (D' = 0. 997, r (2) = 0. 027, P = 0. 0002).", "output": {"entities": {}}, "schema": []}
{"input": "Genotype and carrier frequencies of the CTLA-4 gene + 49A/G polymorphism were not significantly different between FMF patients and healthy controls.", "output": {"entities": {}}, "schema": []}
{"input": "No association was found between the studied polymorphisms and the main clinical features of the disease.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest that although not statistically significant, higher frequencies of CTLA-4 gene-318CT genotype, T allele, and-318T/+ 49A haplotype in FMF patients may be related to the non-autoimmune pathogenesis of FMF.", "output": {"entities": {}}, "schema": []}
{"input": "Anticholinesterase insecticide retrospective.", "output": {"entities": {}}, "schema": []}
{"input": "The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades.", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 33, "end": 49}, {"text": "methylcarbamate", "start": 59, "end": 74}]}}, "schema": []}
{"input": "About 90 of these compounds are still in use-the largest number for any insecticide chemotype or mode of action.", "output": {"entities": {}}, "schema": []}
{"input": "In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 49, "end": 62}]}}, "schema": []}
{"input": "The cholinergic system of insects is located centrally (where it is protected from ionized OPs and MCs) but not at the neuromuscular junction.", "output": {"entities": {}}, "schema": []}
{"input": "Structural differences between insect and mammalian AChE are also evident in their genomics, amino acid sequences and active site conformations.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 93, "end": 103}]}}, "schema": []}
{"input": "Species selectivity is determined in part by inhibitor and target site specificity.", "output": {"entities": {}}, "schema": []}
{"input": "Pest population selection with OPs and MCs has resulted in a multitude of modified AChEs of altered inhibitor specificity some conferring insecticide resistance and others enhancing sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "Much of the success of antiChE insecticides results from a suitable balance of bioactivation and detoxification by families of CYP450 oxidases, hydrolases, glutathione S-transferases and others.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 156, "end": 169}]}}, "schema": []}
{"input": "Known inhibitors for these enzymes block detoxification and enhance potency which is particularly important in resistant strains.", "output": {"entities": {}}, "schema": []}
{"input": "The current market for OPs and MCs of 19% of worldwide insecticide sales is only half of that of 10years ago for several reasons: there have been no major new compounds for 30years; resistance has eroded their effectiveness; human toxicity problems are still encountered; the patents have expired reducing the incentive to update registration packages; alternative chemotypes or control methods have been developed.", "output": {"entities": {}}, "schema": []}
{"input": "Despite this decline, they still play a major role in pest control and the increasing knowledge on their target sites and metabolism may make it possible to redesign the inhibitors for insensitive AChEs and to target new sites in the cholinergic system.", "output": {"entities": {}}, "schema": []}
{"input": "The OPs and MCs are down but not out.", "output": {"entities": {}}, "schema": []}
{"input": "Disposition and metabolism of [(1) 4 C] PTZ601 in healthy volunteers.", "output": {"entities": {"chemical": [{"text": "[(1) 4 C] PTZ601", "start": 30, "end": 46}]}}, "schema": []}
{"input": "1. Six healthy male subjects were given a single dose of 500 mg of [14C] PTZ601 (mean radioactivity 79. 2 mu Ci) by intravenous (IV) infusion over 1 h, and observed for 5 days post-dose during which pharmacokinetic (PK) samples were collected.", "output": {"entities": {"chemical": [{"text": "[14C] PTZ601", "start": 67, "end": 79}]}}, "schema": []}
{"input": "Plasma PTZ601 concentrations and metabolite identification were determined using LC-MS/MS; PK parameters were estimated by non-compartmental analysis.", "output": {"entities": {"chemical": [{"text": "PTZ601", "start": 7, "end": 13}]}}, "schema": []}
{"input": "Excretion and mass balance were determined with liquid scintillation analysis and metabolites profiling was characterized by HPLC online radiochemical detection.", "output": {"entities": {}}, "schema": []}
{"input": "2. The disposition of PTZ601 was best described by a fast absorption, followed by a biphasic elimination phase.", "output": {"entities": {"chemical": [{"text": "PTZ601", "start": 22, "end": 28}]}}, "schema": []}
{"input": "Peak PTZ601 plasma concentrations were reached within 0. 5-1 h.", "output": {"entities": {"chemical": [{"text": "PTZ601", "start": 5, "end": 11}]}}, "schema": []}
{"input": "The mean elimination half-life was 1. 6 h and clearance was 13 L/h.", "output": {"entities": {}}, "schema": []}
{"input": "3. Recovery of the radioactivity dose was complete (mean 92%).", "output": {"entities": {}}, "schema": []}
{"input": "The main route of excretion (parent and metabolites) was the renal route, as urine accounted for 69-77%, while feces only 13-22%, of the total radioactivity.", "output": {"entities": {}}, "schema": []}
{"input": "4. The majority of the drug was excreted in urine as multiple open ring metabolites: M17. 3 (oxidative ring-opened product) and M22. 2 (di-cysteine conjugate of 17. 3); unchanged PTZ601 in urine contributed to 15% of radioactivity.", "output": {"entities": {"chemical": [{"text": "di-cysteine", "start": 136, "end": 147}, {"text": "PTZ601", "start": 179, "end": 185}]}}, "schema": []}
{"input": "The major metabolites detected in plasma were M17. 3, M12. 8 (acetylated M17. 3), M22. 2, and M41. 4 (methylated M17. 3).", "output": {"entities": {}}, "schema": []}
{"input": "5. PTZ601 was well tolerated.", "output": {"entities": {"chemical": [{"text": "PTZ601", "start": 3, "end": 9}]}}, "schema": []}
{"input": "Cost-effectiveness of hepatitis B vaccination in adults with diagnosed diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE To examine the cost-effectiveness of a hepatitis B vaccination program for unvaccinated adults with diagnosed diabetes in the U. S.", "output": {"entities": {}}, "schema": []}
{"input": "RESEARCH DESIGN AND METHODS We used a cost-effectiveness simulation model to estimate the cost-effectiveness of vaccinating adults 20-59 years of age with diagnosed diabetes not previously vaccinated for or infected by hepatitis B virus (HBV).", "output": {"entities": {}}, "schema": []}
{"input": "The model estimated acute and chronic HBV infections, complications, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.", "output": {"entities": {}}, "schema": []}
{"input": "Data sources included surveillance data, epidemiological studies, and vaccine prices.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS With a 10% uptake rate, the intervention will vaccinate 528, 047 people and prevent 4, 271 acute and 256 chronic hepatitis B infections.", "output": {"entities": {}}, "schema": []}
{"input": "Net health care costs will increase by $91. 4 million, and 1, 218 QALYs will be gained, producing a cost-effectiveness ratio of $75, 094 per QALY gained.", "output": {"entities": {}}, "schema": []}
{"input": "Results are most sensitive to age, the discount rate, the hepatitis B incidence ratio for people with diabetes, and hepatitis B infection rates.", "output": {"entities": {}}, "schema": []}
{"input": "Cost-effectiveness ratios rise with age at vaccination; an alternative intervention that vaccinates adults with diabetes 60 years of age or older had a cost-effectiveness ratio of $2. 7 million per QALY.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS Hepatitis B vaccination for adults with diabetes 20-59 years of age is modestly cost-effective.", "output": {"entities": {}}, "schema": []}
{"input": "Vaccinating older adults with diabetes is not cost-effective.", "output": {"entities": {}}, "schema": []}
{"input": "The study did not consider hepatitis outbreak investigation costs, and limited information exists on hepatitis progression among older adults with diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Partly based on these results, the Advisory Committee on Immunization Practices recently recommended hepatitis B vaccination for people 20-59 years of age with diagnosed diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Postpartum corticosterone administration reduces dendritic complexity and increases the density of mushroom spines of hippocampal CA3 arbours in dams.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 11, "end": 25}]}}, "schema": []}
{"input": "Postpartum depression (PPD) affects approximately 15% of mothers after giving birth.", "output": {"entities": {}}, "schema": []}
{"input": "A complete understanding of depression during the postpartum period has yet to be established, although disruptions in the hypothalamic-pituitary-adrenal axis and stress during the postpartum may be involved.", "output": {"entities": {}}, "schema": []}
{"input": "To model these components in rats, we administered high corticosterone (CORT) postpartum, which increases immobility in the forced swim test (FST), and reduces maternal care, body weight and hippocampal cell proliferation in dams.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 56, "end": 70}, {"text": "CORT", "start": 72, "end": 76}]}}, "schema": []}
{"input": "The hippocampus is altered in response to chronic stress, exposure to high glucocorticoids and in major depression in humans.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we examined whether high CORT reduced dendritic complexity and spines in the CA3 region of the hippocampus.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 47, "end": 51}]}}, "schema": []}
{"input": "Additionally, housing complexity was manipulated so that dams and litters were housed either with tubes (complex) or without tubes (impoverished) to investigate the consequences of new animal care regulations.", "output": {"entities": {}}, "schema": []}
{"input": "Dams received 40 mg/kg/day of CORT or oil starting on day 2 postpartum for 23 days.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 30, "end": 34}]}}, "schema": []}
{"input": "Maternal behaviours were assessed on postpartum days 2-8 and dams were tested using the FST on days 21 and 22.", "output": {"entities": {}}, "schema": []}
{"input": "Dams were killed on day 24 and brains were processed for Golgi impregnation.", "output": {"entities": {}}, "schema": []}
{"input": "Pyramidal cells in the CA3 subfield were traced using a camera lucida and analysed for branch points and dendritic complexity, as well as spine density and type on both basal and apical arbours.", "output": {"entities": {}}, "schema": []}
{"input": "As previously established, high CORT postpartum reduced maternal care and increased immobility in the FST, which is a measure of depressive-like behaviour.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 32, "end": 36}]}}, "schema": []}
{"input": "High CORT postpartum reduced the complexity of basal arbours and increased mushroom spines on both apical and basal dendrites.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 5, "end": 9}]}}, "schema": []}
{"input": "Housing complexity had no effect on spines of CA3 pyramidal cells but modest effects on cell morphology.", "output": {"entities": {}}, "schema": []}
{"input": "These data show that chronic high CORT in postpartum females alters hippocampal morphology and may provide insight regarding the neurobiological consequences of high stress or CORT during the postpartum period, as well as be relevant for postpartum stress or depression.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 34, "end": 38}, {"text": "CORT", "start": 176, "end": 180}]}}, "schema": []}
{"input": "Drug metabolizing enzymes in the perinatal and neonatal period: differences in the expression and activity.", "output": {"entities": {}}, "schema": []}
{"input": "Physiological changes occurring perinatally and in the first month of life can affect the answer to a pharmacological treatment and the individual response to a drug in terms of efficacy and toxicity is highly variable in the neonatal population.", "output": {"entities": {}}, "schema": []}
{"input": "Among potential causes for such variability, differences in drug metabolism may have a great impact.", "output": {"entities": {}}, "schema": []}
{"input": "This article aims to review qualitative and quantitative differences in drug metabolizing enzymes in neonates, since both phase I and phase II metabolic pathways are immature at birth and subject to maturational changes in the first period of extrauterine life.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, clinical implications will be discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 16, "end": 23}, {"text": "cocaine", "start": 59, "end": 66}, {"text": "cocaine", "start": 88, "end": 95}]}}, "schema": []}
{"input": "In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 57, "end": 64}, {"text": "cocaine", "start": 138, "end": 145}, {"text": "cocaine", "start": 179, "end": 186}, {"text": "cocaine", "start": 296, "end": 303}]}}, "schema": []}
{"input": "Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 104, "end": 111}]}}, "schema": []}
{"input": "Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120mg/kg, i. p.).", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 122, "end": 129}]}}, "schema": []}
{"input": "We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1mg/kg; antibody, 8mg/kg), they provided complete protection of liver tissue and motor function.", "output": {"entities": {}}, "schema": []}
{"input": "When the enzyme levels were ~ 400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone.", "output": {"entities": {}}, "schema": []}
{"input": "The prolyl-isomerase Pin1 activates the mitochondrial death program of p53.", "output": {"entities": {"chemical": [{"text": "prolyl", "start": 4, "end": 10}]}}, "schema": []}
{"input": "In response to intense stress, the tumor protein p53 (p53) tumor suppressor rapidly mounts a direct mitochondrial death program that precedes transcription-mediated apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "By eliminating severely damaged cells, this pathway contributes to tumor suppression as well as to cancer cell killing induced by both genotoxic drugs and non-genotoxic p53-reactivating molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Here we have explored the role had in this pathway by the prolyl-isomerase Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1), a crucial transducer of p53' s phosphorylation into conformational changes unleashing its pro-apoptotic activity.", "output": {"entities": {"chemical": [{"text": "prolyl", "start": 58, "end": 64}]}}, "schema": []}
{"input": "We show that Pin1 promotes stress-induced localization of p53 to mitochondria both in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, we demonstrate that upon stress-induced phosphorylation of p53 on Ser46 by homeodomain interacting protein kinase 2, Pin1 stimulates its mitochondrial trafficking signal, that is, monoubiquitination.", "output": {"entities": {"chemical": [{"text": "Ser46", "start": 81, "end": 86}]}}, "schema": []}
{"input": "This pathway is induced also by the p53-activating molecule RITA, and we demonstrate the strong requirement of Pin1 for the induction of mitochondrial apoptosis by this compound.", "output": {"entities": {}}, "schema": []}
{"input": "These findings have significant implications for treatment of p53-expressing tumors and for prospective use of p53-activating compounds in clinics.", "output": {"entities": {}}, "schema": []}
{"input": "Applicability of a keratinocyte gene signature to predict skin sensitizing potential.", "output": {"entities": {}}, "schema": []}
{"input": "There is a need to replace animal tests for the identification of skin sensitizers and currently many alternative assays are being developed that have very promising results.", "output": {"entities": {}}, "schema": []}
{"input": "In this study a gene signature capable of very accurate identification of sensitizers was established in the HaCaT human keratinocyte cell line.", "output": {"entities": {}}, "schema": []}
{"input": "This signature was evaluated in a separate study using six chemicals that are either local lymph node (LLNA) false-positive or false-negative chemicals in addition to nine sensitizers and four non-sensitizers.", "output": {"entities": {}}, "schema": []}
{"input": "Similar studies do not apply these more difficult to classify chemicals, which show the true potential for human predictions of an assay.", "output": {"entities": {}}, "schema": []}
{"input": "Although the gene signature has improved prediction accuracy compared to the LLNA, the misclassified compounds were comparable between the two assays.", "output": {"entities": {}}, "schema": []}
{"input": "Gene profiling also showed a sensitizer specific response of the Nrf2-keap1 and Toll-like receptor signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "After exposure to non-sensitizing chemicals that induce either of the pathways the signature misclassified all Nrf2-inducers, while the Toll-like receptor ligands were correctly classified.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, we confirm that keratinocyte based prediction assays may provide essential information on the properties of compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, chemical selection is critical for assessment of the performance of in vitro alternative assays.", "output": {"entities": {}}, "schema": []}
{"input": "Configuration space partitioning and matrix buildup scaling for the vibrational configuration interaction method.", "output": {"entities": {}}, "schema": []}
{"input": "The accurate computation of anharmonic vibrational states for medium to large molecules is a requirement for the detailed understanding of nonlinear multidimensional infrared spectra and the dynamical information encoded in them.", "output": {"entities": {}}, "schema": []}
{"input": "The vibrational configuration interaction (VCI) method constitutes a particularly promising tool in this respect.", "output": {"entities": {}}, "schema": []}
{"input": "It is generally hampered though by its unfavorable scaling with respect to system size.", "output": {"entities": {}}, "schema": []}
{"input": "We analyze the scaling behavior of several well-known as well as some new approximate VCI schemes in detail, which are complementary to the class of configuration selection schemes developed recently.", "output": {"entities": {}}, "schema": []}
{"input": "We find that the combination of a configuration space partitioning, possibly based on configuration selection, with energetic thresholding and resonance screening provides an efficient scheme for the reduction of computational effort involved in VCI calculations while at the same time maintaining sufficient accuracy for the vibrational energies.", "output": {"entities": {}}, "schema": []}
{"input": "Carbon nanotube functionalization with carboxylic derivatives: a DFT study.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}, {"text": "carboxylic", "start": 39, "end": 49}]}}, "schema": []}
{"input": "Chemical functionalization of a single-walled carbon nanotube (CNT) with different carboxylic derivatives including-COOX (X = H, CH3, CH2NH2, CH3Ph, CH2NO2, and CH2CN) has been theoretically investigated in terms of geometric, energetic, and electronic properties.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 46, "end": 52}, {"text": "carboxylic", "start": 83, "end": 93}, {"text": "COOX", "start": 116, "end": 120}, {"text": "H", "start": 126, "end": 127}, {"text": "CH3", "start": 129, "end": 132}, {"text": "CH2NH2", "start": 134, "end": 140}, {"text": "CH3Ph", "start": 142, "end": 147}, {"text": "CH2NO2", "start": 149, "end": 155}, {"text": "CH2CN", "start": 161, "end": 166}]}}, "schema": []}
{"input": "Reaction energies have been calculated to be in the range of-0. 23 to-7. 07 eV.", "output": {"entities": {}}, "schema": []}
{"input": "The results reveal that the reaction energy is increased by increasing the electron withdrawing character of the functional groups so that the relative magnitude order is-CH2NO2 >-CH2CN >-H >-CH2Ph >-CH3 >-CH2NH2.", "output": {"entities": {"chemical": [{"text": "CH2NO2", "start": 171, "end": 177}, {"text": "CH2CN", "start": 180, "end": 185}, {"text": "H", "start": 188, "end": 189}, {"text": "CH2Ph", "start": 192, "end": 197}, {"text": "CH3", "start": 200, "end": 203}, {"text": "CH2NH2", "start": 206, "end": 212}]}}, "schema": []}
{"input": "The chemical functionalization leads to an increase in HOMO/LUMO energy gap of CNT by about 0. 32 to 0. 35 eV (except for-H).", "output": {"entities": {"chemical": [{"text": "HOMO", "start": 55, "end": 59}]}}, "schema": []}
{"input": "LUMO, HOMO, and Fermi level of the CNT are shifted to lower energies especially in the case of-CH2NO2 and-CH2CN functional groups.", "output": {"entities": {"chemical": [{"text": "CH2NO2", "start": 95, "end": 101}, {"text": "CH2CN", "start": 106, "end": 111}]}}, "schema": []}
{"input": "Therefore, it leads to an increment in work function of the tube, impeding the field electron emission.", "output": {"entities": {}}, "schema": []}
{"input": "Ultrasound promoted one-pot synthesis of 2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile scaffolds in aqueous media: a complementary' green chemistry' tool to organic synthesis.", "output": {"entities": {"chemical": [{"text": "2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile", "start": 41, "end": 97}]}}, "schema": []}
{"input": "A green and simple approach to assembling of 2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile scaffolds via three-component reaction of kojic acid, malononitrile, and aromatic aldehydes in aqueous media under ultrasound irradiation is described.", "output": {"entities": {"chemical": [{"text": "2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile", "start": 45, "end": 101}, {"text": "kojic acid", "start": 144, "end": 154}, {"text": "malononitrile", "start": 156, "end": 169}, {"text": "aromatic aldehydes", "start": 175, "end": 193}]}}, "schema": []}
{"input": "The combinatorial synthesis was achieved for this methodology with applying ultrasound irradiation while making use of water as green solvent.", "output": {"entities": {}}, "schema": []}
{"input": "In comparison to conventional methods, experimental simplicity, good functional group tolerance, excellent yields, short routine, and selectivity without the need for a transition metal or base catalyst are prominent features of this green procedure.", "output": {"entities": {"chemical": [{"text": "transition metal", "start": 169, "end": 185}]}}, "schema": []}
{"input": "Cell transplantation approaches to retinal ganglion cell neuroprotection in glaucoma.", "output": {"entities": {"chemical": [{"text": "retinal", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Glaucoma is a complex neurodegenerative disease that involves interactions among multiple signaling pathways, ultimately leading to progressive retinal ganglion cell (RGC) death.", "output": {"entities": {"chemical": [{"text": "retinal", "start": 144, "end": 151}]}}, "schema": []}
{"input": "The development of neuroprotective approaches to glaucoma therapy could preserve vision by modulating these pathologic pathways or by acting directly on RGCs to attenuate cell death and maintain function.", "output": {"entities": {}}, "schema": []}
{"input": "Intraocular cell transplantation is being evaluated as one approach to achieve sustained RGC neuroprotection.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike traditional pharmacological approaches, transplanted cells might be capable of simultaneously targeting multiple pro-survival pathways via local delivery of secreted factors and/or via modulation of the intraocular microenvironment.", "output": {"entities": {}}, "schema": []}
{"input": "Elucidating the mechanisms by which different cell types attenuate RGC death in models of glaucoma may uncover additional novel mechanisms of neuroprotection.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we will discuss the rationale for transplantation-based approaches to neuroprotection for glaucoma and explore the various mechanisms of action proposed to account for RGC neuroprotection achieved by two distinct cell classes that have been studied most extensively for this purpose: glial cells and mesenchymal stem cells.", "output": {"entities": {}}, "schema": []}
{"input": "Adenosine and autism: a spectrum of opportunities.", "output": {"entities": {"chemical": [{"text": "Adenosine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 25, "end": 34}]}}, "schema": []}
{"input": "In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 54, "end": 63}]}}, "schema": []}
{"input": "Because adenosine is a broad homeostatic regulator of cell function and nervous system activity, increasing adenosine' s influence might be a new therapeutic target for autism with multiple beneficial effects.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 8, "end": 17}, {"text": "adenosine", "start": 108, "end": 117}]}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.", "output": {"entities": {}}, "schema": []}
{"input": "Rett syndrome treatment in mouse models: searching for effective targets and strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Rett syndrome (RTT) is a pervasive developmental disorder, primarily affecting girls with a prevalence of 1 in every 10, 000 births; it represents the second most common cause of intellectual disability in females.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2) have been identified as clear etiological factors in more than 90% of classical RTT cases.", "output": {"entities": {"chemical": [{"text": "methyl", "start": 31, "end": 37}, {"text": "CpG", "start": 38, "end": 41}]}}, "schema": []}
{"input": "Whereas the mechanisms leading to the severe, progressive and specific neurological dysfunctions when this gene is mutated still remain to be elucidated, a series of different mouse models have been generated, bearing different Mecp2 mutation.", "output": {"entities": {}}, "schema": []}
{"input": "Neurobehavioural analysis in these mouse lines have been carried out and phenotyping analysis can be now utilised to preclinically evaluate the effects of potential RTT treatments.", "output": {"entities": {}}, "schema": []}
{"input": "This review summarizes the different results achieved in this research field taking into account different key targets identified to ameliorate RTT phenotype in mouse models, including those not directly downstream of MeCP2 and those limited to the early phases of postnatal development.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.", "output": {"entities": {}}, "schema": []}
{"input": "Rhythm and blues: animal models of epilepsy and depression comorbidity.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical evidence shows a strong, bidirectional comorbidity between depression and epilepsy that is associated with decreased quality of life and responsivity to pharmacotherapies.", "output": {"entities": {}}, "schema": []}
{"input": "At present, the neurobiological underpinnings of this comorbidity remain hazy.", "output": {"entities": {}}, "schema": []}
{"input": "To complicate matters, anticonvulsant drugs can cause mood disturbances, while antidepressant drugs can lower seizure threshold, making it difficult to treat patients suffering from both depression and epilepsy.", "output": {"entities": {}}, "schema": []}
{"input": "Animal models have been created to untangle the mechanisms behind the relationship between these disorders and to serve as screening tools for new therapies targeted to treat both simultaneously.", "output": {"entities": {}}, "schema": []}
{"input": "These animal models are based on chemical interventions (e. g. pentylenetetrazol, kainic acid, pilocarpine), electrical stimulations (e. g. kindling, electroshock), and genetic/selective breeding paradigms (e. g. genetically epilepsy-prone rats (GEPRs), genetic absence epilepsy rat from Strasbourg (GAERS), WAG/Rij rats, swim lo-active rats (SwLo)).", "output": {"entities": {"chemical": [{"text": "pentylenetetrazol", "start": 63, "end": 80}, {"text": "kainic acid", "start": 82, "end": 93}, {"text": "pilocarpine", "start": 95, "end": 106}]}}, "schema": []}
{"input": "Studies on these animal models point to some potential mechanisms that could explain epilepsy and depression comorbidity, such as various components of the dopaminergic, noradrenergic, serotonergic, and GABAergic systems, as well as key brain regions, like the amygdala and hippocampus.", "output": {"entities": {}}, "schema": []}
{"input": "These models have also been used to screen possible therapies.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of the present review is to highlight the importance of animal models in research on comorbid epilepsy and depression and to explore the contributions of these models to our understanding of the mechanisms and potential treatments for these disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Erectile dysfunction as a cardiovascular risk factor in patients with diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Erectile dysfunction (ED) is a highly prevalent disorder among patients with diabetes mellitus (DM).", "output": {"entities": {}}, "schema": []}
{"input": "In most cases, ED is considered a vascular disease and its development is significantly related to the exposure to CVD risk factors.", "output": {"entities": {}}, "schema": []}
{"input": "In this context, ED and coronary artery disease (CAD) have been proposed as different manifestations of the same systemic disease; in nondiabetic patients, ED has progressively emerged as an important sentinel marker of the subsequent onset of CVD events.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this review was to evaluate the association between ED and CAD in diabetic patients and to evaluate the role of ED as an independent CVD risk factor in these patients.", "output": {"entities": {}}, "schema": []}
{"input": "Three large prospective studies confirmed that ED is a powerful predictor of CAD and cardiac mortality in patients with DM.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, diabetic patients with ED had roughly 1. 4-fold higher risk of CAD as compared with those without ED.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, in diabetic patients, CAD is often silent and CAD screening according to the current guidelines can miss up to 40% patients with occult myocardial perfusion abnormalities.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, patients with ED have higher risk of silent myocardial ischemia compared to those without ED, and when ED is added to the risk factors, it can even improve the sensitivity of screening for asymptomatic CAD.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, ED should be considered an independent CVD risk factor, and it could improve the identification of diabetic patients suitable for screening, leading to an early detection of CAD, and thus potentially enhancing the therapeutic effectiveness.", "output": {"entities": {}}, "schema": []}
{"input": "Resistance training decreases serum inflammatory markers in diabetic rats.", "output": {"entities": {}}, "schema": []}
{"input": "Inflammation plays an important role in the genesis and progression of diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to investigate the effect of resistance training on serum levels of some inflammatory markers associated with diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-four male Wistar rats (290 +/- 19 g) were randomly divided into three groups: non-diabetic control (non-DC), diabetic control (DC), and diabetic trained (DT).", "output": {"entities": {}}, "schema": []}
{"input": "Animals in DT group were subjected to a resistance training program with the use of a ladder (3 days/week, for 4 weeks).", "output": {"entities": {}}, "schema": []}
{"input": "Body weight, serum high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, fasting glucose, and insulin were measured.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 128, "end": 135}]}}, "schema": []}
{"input": "Four weeks of resistance training decreased serum levels of TNF-alpha, hs-CRP, and IL-6 in diabetic rats when compared with DC animals.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that resistance training with appropriate intensity, duration, and recovery between exercise bouts has marked anti-inflammatory effects on diabetic rats.", "output": {"entities": {}}, "schema": []}
{"input": "This may be an efficient strategy to protect against some diabetic complications.", "output": {"entities": {}}, "schema": []}
{"input": "Generation of monoclonal antibodies against the Gal beta 1-4Gal epitope: a key tool in studies of species-specific glycans expressed in fish, amphibians and birds.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas the Gal beta 1-4Gal epitope is rarely found in mammalian glycans, it has been found in glycans of various species of non-mammalian vertebrates, such as fish, amphibians and birds.", "output": {"entities": {}}, "schema": []}
{"input": "Although glycans containing Gal beta 1-4Gal in these vertebrates were detected by precise structural analysis of the glycans using mass spectrometry and/or NMR spectrometry, there are no convenient methods to detect Gal beta 1-4Gal from various samples.", "output": {"entities": {}}, "schema": []}
{"input": "To analyze systematically the distribution of Gal beta 1-4Gal in nature, we generated mouse monoclonal antibodies (mAbs) specific for Gal beta 1-4Gal using extracts of medaka eggs as an immunogen.", "output": {"entities": {}}, "schema": []}
{"input": "Four mAbs (two immunoglobulin (Ig) Ms and two IgG1s) were obtained by enzyme-linked immunosorbent assay-based screening.", "output": {"entities": {}}, "schema": []}
{"input": "The specificities of these mAbs were evaluated by frontal affinity chromatography using 142 kinds of 2-aminopyridine (PA)-derivatized oligosaccharides.", "output": {"entities": {"chemical": [{"text": "2-aminopyridine", "start": 101, "end": 116}]}}, "schema": []}
{"input": "While all mAbs interacted with (Gal beta 1-4Gal)-containing oligosaccharides at their non-reducing termini with dissociation constants (K (d)) ranging from 1. 0 x 10-5 to 2. 8 x 10-4 M, no apparent interaction was observed with any other glycans.", "output": {"entities": {}}, "schema": []}
{"input": "The number of branches containing Gal beta 1-4Gal on N-glycans did not significantly affect K (d) of mAbs of IgG1 subclasses, but those of IgM mAbs were decreased by ~ 1 order of magnitude, in increments of the number of branches present.", "output": {"entities": {"chemical": [{"text": "N", "start": 53, "end": 54}]}}, "schema": []}
{"input": "Using the mAbs, we established that Gal beta 1-4Gal is also expressed on glycoproteins in various tissues from the African clawed frog.", "output": {"entities": {}}, "schema": []}
{"input": "Immunohistochemical staining of medaka sections revealed that Gal beta 1-4Gal epitopes were expressed in the endothelium, epithelium and epidermis, which directly contact the external environment or invading organisms.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, these mAbs are useful for systematically investigating the species-specific expression of glycans, which may act as a barrier against infection.", "output": {"entities": {}}, "schema": []}
{"input": "Diethyldithiocarbamate induces apoptosis in neuroblastoma cells by raising the intracellular copper level, triggering cytochrome c release and caspase activation.", "output": {"entities": {"chemical": [{"text": "Diethyldithiocarbamate", "start": 0, "end": 22}, {"text": "copper", "start": 93, "end": 99}]}}, "schema": []}
{"input": "Dithiocarbamates are nitrogen-and sulfur-containing compounds commonly used in pharmacology, medicine and agriculture.", "output": {"entities": {"chemical": [{"text": "Dithiocarbamates", "start": 0, "end": 16}, {"text": "nitrogen", "start": 21, "end": 29}, {"text": "sulfur", "start": 34, "end": 40}]}}, "schema": []}
{"input": "The molecular effects of dithiocarbamates on neuronal cell systems are not fully understood, especially in terms of their ability to accumulate copper ions inside the cell.", "output": {"entities": {"chemical": [{"text": "dithiocarbamates", "start": 25, "end": 41}, {"text": "copper", "start": 144, "end": 150}]}}, "schema": []}
{"input": "In this work, the molecular effects of N, N-diethyldithiocarbamate (DEDTC) were studied in human SH-SY5Y neuroblastoma cells to determine the role of copper in the DEDTC toxicity and the pathway trigged in cell by the complex Cu-DEDTC.", "output": {"entities": {"chemical": [{"text": "N, N-diethyldithiocarbamate", "start": 39, "end": 66}, {"text": "DEDTC", "start": 68, "end": 73}, {"text": "copper", "start": 150, "end": 156}, {"text": "DEDTC", "start": 164, "end": 169}, {"text": "Cu-DEDTC", "start": 226, "end": 234}]}}, "schema": []}
{"input": "From concentration-dependent studies, we found that 5 mu M of this compound induced a drastic decrease in viable cells with a concomitant accumulation in intracellular copper resulted from complexation with DEDTC, measured by atomic absorption spectroscopy.", "output": {"entities": {"chemical": [{"text": "copper", "start": 168, "end": 174}, {"text": "DEDTC", "start": 207, "end": 212}]}}, "schema": []}
{"input": "The mechanism of DEDTC-induced apoptosis in neuronal model cells is thought to occur through the death receptor signaling triggered by DEDTC-copper complex in low concentration that is associated with the activation of caspase 8.", "output": {"entities": {"chemical": [{"text": "DEDTC", "start": 17, "end": 22}, {"text": "DEDTC-copper", "start": 135, "end": 147}]}}, "schema": []}
{"input": "Our results indicated that the mechanism of cell death involves cytochrome c release forming the apoptosome together with Apaf-1 and caspase 9, converting the caspase 9 into its active form, allowing it to activate caspase 3 as observed by immunofluorescence.", "output": {"entities": {}}, "schema": []}
{"input": "This pathway is induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions present in the culture medium and transports them into the cell, suggesting that the DEDTC by itself was not able to cause cell death and the major effect is from its copper-complex in neuroblastoma cells.", "output": {"entities": {"chemical": [{"text": "DEDTC", "start": 65, "end": 70}, {"text": "copper", "start": 96, "end": 102}, {"text": "DEDTC", "start": 193, "end": 198}, {"text": "copper", "start": 275, "end": 281}]}}, "schema": []}
{"input": "The present study suggests a role for the influence of copper by low concentrations of DEDTC in the extracellular media, the absorption and accumulation of copper in the cell and apoptotic events, induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions.", "output": {"entities": {"chemical": [{"text": "copper", "start": 55, "end": 61}, {"text": "DEDTC", "start": 87, "end": 92}, {"text": "copper", "start": 156, "end": 162}, {"text": "DEDTC", "start": 246, "end": 251}, {"text": "copper", "start": 277, "end": 283}]}}, "schema": []}
{"input": "Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "As part of the ACuteTox project aimed at the development of non-animal testing strategies for predicting human acute oral toxicity, aggregating brain cell cultures (AGGR) were examined for their capability to detect organ-specific toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Previous multicenter evaluations of in vitro cytotoxicity showed that some 20% of the tested chemicals exhibited significantly lower in vitro toxicity as expected from in vivo toxicity data.", "output": {"entities": {}}, "schema": []}
{"input": "This was supposed to be due to toxicity at supracellular (organ or system) levels.", "output": {"entities": {}}, "schema": []}
{"input": "To examine the capability of AGGR to alert for potential organ-specific toxicants, concentration-response studies were carried out in AGGR for 86 chemicals, taking as endpoints the mRNA expression levels of four selected genes.", "output": {"entities": {}}, "schema": []}
{"input": "The lowest observed effect concentration (LOEC) determined for each chemical was compared with the IC20 reported for the 3T3/NRU cytotoxicity assay.", "output": {"entities": {}}, "schema": []}
{"input": "A LOEC lower than IC20 by at least a factor of 5 was taken to alert for organ-specific toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that the frequency of alerts increased with the level of toxicity observed in AGGR.", "output": {"entities": {}}, "schema": []}
{"input": "Among the chemicals identified as alert were many compounds known for their organ-specific toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "These findings suggest that AGGR are suitable for the detection of organ-specific toxicity and that they could, in conjunction with the 3T3/NRU cytotoxicity assay, improve the predictive capacity of in vitro toxicity testing.", "output": {"entities": {}}, "schema": []}
{"input": "Silver nanoparticle-induced cytotoxicity in rat brain endothelial cell culture.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Silver nanoparticles (AgNPs) are among the most widely commercialised engineered nanomaterials, because of their antimicrobial properties.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}]}}, "schema": []}
{"input": "They are already commonly used in medical devices, household products and industry.", "output": {"entities": {}}, "schema": []}
{"input": "Concerns have been raised about potential adverse health effects due to increasing dispersion of AgNPs in the environment.", "output": {"entities": {}}, "schema": []}
{"input": "The present study examined the cytotoxic effects of spherical, citrate-coated AgNPs (10, 50 and 100 nm) in rat brain endothelial (RBE4) cells and investigated whether the observed effects can be explained by the intrinsic toxicity of the particles or the silver ions released from the particles.", "output": {"entities": {"chemical": [{"text": "citrate", "start": 63, "end": 70}, {"text": "silver", "start": 255, "end": 261}]}}, "schema": []}
{"input": "The results indicated that exposure of RBE4 cells to AgNPs lead to significant reduction in dye uptake as measured with the Neutral red (NR) assay.", "output": {"entities": {"chemical": [{"text": "Neutral red", "start": 124, "end": 135}]}}, "schema": []}
{"input": "The effect was found to be related to particle size, surface area, dose and exposure time.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, silver ions increased NR uptake (ca. 10%) in RBE4 cells after 1h, while a reduction in NR uptake was observed after 24h exposure at high concentrations (20-30 mu M).", "output": {"entities": {"chemical": [{"text": "silver", "start": 13, "end": 19}]}}, "schema": []}
{"input": "Colony formation, as an indicator of proliferation ability, was completely inhibited by AgNPs at concentrations higher than 1 mu g/ml.", "output": {"entities": {}}, "schema": []}
{"input": "Silver ions had less effect on the colony formation of RBE4 cells than AgNPs.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}]}}, "schema": []}
{"input": "The effects of sonographic and demographic features and needle size on obtaining adequate cytological material in sonography-guided fine-needle aspiration biopsy of thyroid nodules.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study is to investigate the effects of the sonographic characteristics of the nodule, demographic features of patient, and nodule size and needle size used for sampling, on obtaining adequate cytological material (CM) in thyroid fine-needle aspiration biopsy (FNAB).", "output": {"entities": {}}, "schema": []}
{"input": "We performed 270 FNAB between September 2010 and June 2012.", "output": {"entities": {}}, "schema": []}
{"input": "Size, echogenicity, and localization of all nodules were evaluated by ultrasonography (US) before the biopsy.", "output": {"entities": {}}, "schema": []}
{"input": "Nodules were grouped as < 1, 1-3, and > 3 cm according to their size and as hypoechoic, isoechoic, hyperechoic, or heterogeneous according to their US characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "20-, 22-, and 24-G needles were used for the biopsies.", "output": {"entities": {}}, "schema": []}
{"input": "Different sonographic characteristics of the nodules did not affect the needle selection.", "output": {"entities": {}}, "schema": []}
{"input": "All specimens were classified as adequate or inadequate CM by a cytopathologist.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 270 nodules were biopsied, 184 (68. 1%) specimens were considered as adequate CM and 86 (31. 9%) specimens were considered as inadequate CM.", "output": {"entities": {}}, "schema": []}
{"input": "Patient age and the presence of heterogeneous echogenicity were found to have prognostic significance in univariate analysis (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "In a multivariate logistic regression model with forward stepwise method, advanced age (p = 0. 001, OR = 1. 042, 95CI 1. 018-1. 068) and heterogeneous echogenicity (p = 0. 017, OR = 1. 955, 95CI 1. 129-3. 385) remained associated with an increased risk of inadequate CM obtainment after adjustment for other potential confounders (nodule size > 3 cm and needle size 20-G usage) and variables found to be statistically significant in univariate analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Non-diagnostic FNAB remains a significant problem in the evaluation of thyroid nodules and can be as high as 30%.", "output": {"entities": {}}, "schema": []}
{"input": "Inadequate CM rates for elderly patients and heterogeneous nodules were significantly higher than that for other factors.", "output": {"entities": {}}, "schema": []}
{"input": "The nodule size and needle size used for sampling did not affect the adequacy of FNAB.", "output": {"entities": {}}, "schema": []}
{"input": "Delayed temporal increase of hepatic Hsp70 in ApoE knockout mice after prenatal arsenic exposure.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Prenatal arsenic exposure accelerates atherosclerosis in ApoE (-/-) mice by unknown mechanism.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 9, "end": 16}]}}, "schema": []}
{"input": "Arsenic is a hepatotoxicant, and liver disease increases atherosclerosis risk.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Prenatal arsenic exposure may predispose to liver disease by priming for susceptibility to other environmental insults.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 9, "end": 16}]}}, "schema": []}
{"input": "Earlier microarray analyses showed prenatal arsenic exposure increased Hsc70 (HspA8) and Hsp70 (HspA1a) mRNAs in livers of 10-week-old mice.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 44, "end": 51}]}}, "schema": []}
{"input": "We determined effects of prenatal arsenic exposure on hepatic Hsp70 and Hsc70 expression by Western blot and on DNA methylation by methyl acceptance assay during prenatal and postnatal development.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 34, "end": 41}, {"text": "methylation", "start": 116, "end": 127}]}}, "schema": []}
{"input": "Pregnant ApoE (-/-) mice were given drinking water containing 85 mg/l NaAsO (2) (49 ppm arsenic) from gestation day (GD) 8 to 18.", "output": {"entities": {"chemical": [{"text": "NaAsO (2)", "start": 70, "end": 79}, {"text": "arsenic", "start": 88, "end": 95}]}}, "schema": []}
{"input": "Hsp70 and Hsc70 expression and DNA methylation were determined in GD18 fetuses and 3-, 10-, and 24-week-old mice.", "output": {"entities": {}}, "schema": []}
{"input": "Hsc70 expression was unchanged at all ages.", "output": {"entities": {}}, "schema": []}
{"input": "Hsp70 induction was observed at 3 and 10 weeks, but was unchanged in GD18 fetuses and 24-week livers of mice.", "output": {"entities": {}}, "schema": []}
{"input": "Global DNA methylation increased with age; arsenic had no effects.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 43, "end": 50}]}}, "schema": []}
{"input": "Bisulfite sequencing of DNA from livers of 10-week-old mice showed Hsp70 promoter region methylation was unchanged, but methylation was increased within the transcribed region.", "output": {"entities": {"chemical": [{"text": "Bisulfite", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Hsf1 and Nrf2 nuclear translocation were investigated as potential mechanisms of Hsp70 induction and found unaltered.", "output": {"entities": {}}, "schema": []}
{"input": "Putative binding sites were identified in HSP70 for in utero arsenic exposure-suppressed microRNAs suggesting a possible mechanism.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 61, "end": 68}]}}, "schema": []}
{"input": "Thus, prenatal arsenic exposure causes delayed temporal hepatic Hsp70 induction, suggesting a transient state of stress in livers which can predispose the mice to developing liver disease.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 15, "end": 22}]}}, "schema": []}
{"input": "Toxicity profile of small-molecule IAP antagonist GDC-0152 is linked to TNF-alpha pharmacology.", "output": {"entities": {"chemical": [{"text": "GDC-0152", "start": 50, "end": 58}]}}, "schema": []}
{"input": "Inhibitor-of-apoptosis (IAP) proteins suppress apoptosis and are overexpressed in a variety of cancers.", "output": {"entities": {}}, "schema": []}
{"input": "Small-molecule IAP antagonists are currently being tested in clinical trials as novel cancer therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "GDC-0152 is a small-molecule drug that triggers tumor cell apoptosis by selectively antagonizing IAPs.", "output": {"entities": {"chemical": [{"text": "GDC-0152", "start": 0, "end": 8}]}}, "schema": []}
{"input": "GDC-0152 induces NF-kappa B transcriptional activity leading to expression of several chemokines and cytokines, of which tumor necrosis factor alpha (TNF-alpha) is the most important for single-agent tumor activity.", "output": {"entities": {"chemical": [{"text": "GDC-0152", "start": 0, "end": 8}]}}, "schema": []}
{"input": "TNF-alpha is a pleiotropic cytokine that drives a variety of cellular responses, comprising inflammation, proliferation, and cell survival or death depending on the cellular context.", "output": {"entities": {}}, "schema": []}
{"input": "As malignant and normal cells produce TNF-alpha upon IAP antagonism, increased TNF-alpha could drive both efficacy and toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The toxicity profile of GDC-0152 in dogs and rats was characterized after iv dose administration once every 2 weeks for four doses.", "output": {"entities": {"chemical": [{"text": "GDC-0152", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Findings in both species consisted of a dose-related, acute, systemic inflammatory response, and hepatic injury.", "output": {"entities": {}}, "schema": []}
{"input": "Laboratory findings included elevated plasma cytokines, an inflammatory leukogram, and increased liver transaminases with histopathological findings of inflammatory infiltrates and apoptosis/necrosis in multiple tissues; a toxicology profile consistent with TNF-alpha-mediated toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Dogs exhibited more severe findings than rats, and humans did not exhibit these findings, at comparable exposures across species.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, elevations in blood neutrophil count, serum monocyte chemoattractant protein-1, and other markers of inflammation corresponded to GDC-0152 exposure and toxicity and thus may have utility as safety biomarkers.", "output": {"entities": {"chemical": [{"text": "GDC-0152", "start": 143, "end": 151}]}}, "schema": []}
{"input": "Don' t judge a neuron only by its cover: neuronal function in in vitro developmental neurotoxicity testing.", "output": {"entities": {}}, "schema": []}
{"input": "Classical cases of developmental neurotoxicity (DNT) in humans and advances in risk assessment methods did not prevent the emergence of new chemicals with (suspected) DNT potential.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to these chemicals may be related to the increased worldwide incidence of learning and neurodevelopmental disorders in children.", "output": {"entities": {}}, "schema": []}
{"input": "DNT is often investigated in a traditional manner (in vivo using large numbers of experimental animals), whereas development of in vitro methods for DNT reduces animal use and increases insight into cellular and molecular mechanisms of DNT.", "output": {"entities": {}}, "schema": []}
{"input": "Several essential neurodevelopmental processes, including proliferation, migration, differentiation, formation of axons and dendrites, synaptogenesis, and apoptosis, are already being evaluated in vitro using biochemical and morphological endpoints.", "output": {"entities": {}}, "schema": []}
{"input": "Yet, investigation of chemical-induced effects on the development of functional neuronal networks, including network formation, inter-and intracellular signaling and neuronal network function, is underrepresented in DNT testing.", "output": {"entities": {}}, "schema": []}
{"input": "This view therefore focuses on in vitro models and innovative experimental approaches for functional DNT testing, ranging from optical and electrophysiological measurements of intra-and intercellular signaling in neural stem/progenitor cells to measurements of network activity in neuronal networks using multielectrode arrays.", "output": {"entities": {}}, "schema": []}
{"input": "The development of functional DNT assays will strongly support the decision-making process for measures to prevent potential chemical-induced adverse effects on neurodevelopment and cognition in humans.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore argue that for risk assessment, biochemical and morphological approaches should be complemented with investigations of neuronal (network) functionality.", "output": {"entities": {}}, "schema": []}
{"input": "Involvement of interleukin-6-regulated nitric oxide synthase in hemorrhagic cystitis and impaired bladder contractions in young rats induced by acrolein, a urinary metabolite of cyclophosphamide.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 39, "end": 51}, {"text": "acrolein", "start": 144, "end": 152}, {"text": "cyclophosphamide", "start": 178, "end": 194}]}}, "schema": []}
{"input": "Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, a chemotherapeutic alkylating agent.", "output": {"entities": {"chemical": [{"text": "cyclophosphamide", "start": 68, "end": 84}]}}, "schema": []}
{"input": "Acrolein is a urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis.", "output": {"entities": {"chemical": [{"text": "Acrolein", "start": 0, "end": 8}, {"text": "cyclophosphamide", "start": 38, "end": 54}]}}, "schema": []}
{"input": "Here, we investigated the effects and mechanisms of acrolein by intravesical instillation on urinary bladder muscle contractions and pathological alterations in rats.", "output": {"entities": {"chemical": [{"text": "acrolein", "start": 52, "end": 60}]}}, "schema": []}
{"input": "Acrolein instillation significantly increased the muscle contractions of rat bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions after 24 h.", "output": {"entities": {"chemical": [{"text": "Acrolein", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Acrolein increased phosphorylated protein kinase C (pan-PKC) expressions in bladders after 1 and 6 h but inhibited it after 24 h.", "output": {"entities": {"chemical": [{"text": "Acrolein", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Inducible nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in bladders 24 h after acrolein treatment.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 10, "end": 22}, {"text": "NO", "start": 24, "end": 26}, {"text": "acrolein", "start": 109, "end": 117}]}}, "schema": []}
{"input": "Twenty-four-hour acrolein instillation increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary bladder.", "output": {"entities": {"chemical": [{"text": "acrolein", "start": 17, "end": 25}, {"text": "nitrite", "start": 63, "end": 70}, {"text": "nitrate", "start": 71, "end": 78}]}}, "schema": []}
{"input": "The iNOS inhibitors significantly inhibited the acrolein-increased nitrite/nitrate levels, but not IL-6 levels.", "output": {"entities": {"chemical": [{"text": "acrolein", "start": 48, "end": 56}, {"text": "nitrite", "start": 67, "end": 74}, {"text": "nitrate", "start": 75, "end": 82}]}}, "schema": []}
{"input": "IL-6-neutralizing antibodies effectively inhibited the acrolein-increased NOx levels.", "output": {"entities": {"chemical": [{"text": "acrolein", "start": 55, "end": 63}]}}, "schema": []}
{"input": "The increased detrusor contractions by 1-h acrolein treatment were significantly reversed by the PKC inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing antibody.", "output": {"entities": {"chemical": [{"text": "acrolein", "start": 43, "end": 51}, {"text": "RO32-0432", "start": 111, "end": 120}, {"text": "acrolein", "start": 170, "end": 178}]}}, "schema": []}
{"input": "Both the iNOS inhibitor and IL-6-neutralizing antibody effectively reversed the increased iNOS expression, decreased PKC phosphorylation, increased bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment.", "output": {"entities": {"chemical": [{"text": "acrolein", "start": 208, "end": 216}]}}, "schema": []}
{"input": "Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates in the acrolein-triggered detrusor contraction inhibition and hemorrhagic cystitis.", "output": {"entities": {"chemical": [{"text": "acrolein", "start": 107, "end": 115}]}}, "schema": []}
{"input": "These findings may help us to find a new strategy to treat cyclophosphamide-induced hemorrhagic cystitis.", "output": {"entities": {"chemical": [{"text": "cyclophosphamide", "start": 59, "end": 75}]}}, "schema": []}
{"input": "A novel reproductive peptide, phoenixin.", "output": {"entities": {"chemical": [{"text": "phoenixin", "start": 30, "end": 39}]}}, "schema": []}
{"input": "Normal anterior pituitary function is essential for fertility.", "output": {"entities": {}}, "schema": []}
{"input": "Release from the gland of the reproductive hormones luteinising hormone and follicle-stimulating hormone is regulated primarily by hypothalamically-derived gonadotrophin-releasing hormone (GnRH), although other releasing factors (RF) have been postulated to exist.", "output": {"entities": {"chemical": [{"text": "gonadotrophin-releasing hormone", "start": 156, "end": 187}, {"text": "GnRH", "start": 189, "end": 193}]}}, "schema": []}
{"input": "Using a bioinformatic approach, we have identified a novel peptide, phoenixin, that regulates pituitary gonadotrophin secretion by modulating the expression of the GnRH receptor, an action with physiologically relevant consequences.", "output": {"entities": {"chemical": [{"text": "phoenixin", "start": 68, "end": 77}, {"text": "GnRH", "start": 164, "end": 168}]}}, "schema": []}
{"input": "Compromise of phoenixin in vivo using small interfering RNA resulted in the delayed appearance of oestrus and a reduction in GnRH receptor expression in the pituitary.", "output": {"entities": {"chemical": [{"text": "phoenixin", "start": 14, "end": 23}, {"text": "GnRH", "start": 125, "end": 129}]}}, "schema": []}
{"input": "Phoenixin may represent a new class of hypothalamically-derived pituitary priming factors that sensitise the pituitary to the action of other RFs, rather than directly stimulating the fusion of secretary vesicles to pituitary membranes.", "output": {"entities": {"chemical": [{"text": "Phoenixin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells.", "output": {"entities": {}}, "schema": []}
{"input": "Recombinant human IGF-1 currently represents the only available treatment option for the Laron Syndrome, a rare human disorder caused by defects in the gene encoding growth hormone receptor, resulting in irreversibly retarded growth.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in females and 19% in males), while burdening the patients with severe side effects, including hypoglycemia, in association with the unfair chore of taking multiple daily injections that cause local intense pain.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "These findings indicate a novel, simply, safe and successful method for the cell therapy-based cure of the Laron Syndrome, potentially applicable to humans.", "output": {"entities": {}}, "schema": []}
{"input": "Robust and aligned carbon nanotube/titania core/shell films for flexible TCO-free photoelectrodes.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 19, "end": 25}, {"text": "titania", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Carbon nanotube (CNT)/semiconducting oxide hybrids are an ideal architecture for light-harvesting devices, in which the CNTs are expected to not only act as a scaffold but also provide fast transport paths for photogenerated charges in the oxide.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}, {"text": "oxide", "start": 37, "end": 42}, {"text": "oxide", "start": 240, "end": 245}]}}, "schema": []}
{"input": "However, the current potential of CNTs for charge transport is largely suppressed due to the nanotubes not being interconnected but isolated by the low conductive oxide coatings.", "output": {"entities": {"chemical": [{"text": "oxide", "start": 163, "end": 168}]}}, "schema": []}
{"input": "Herein, a flexible and conductive CNT/TiO (2) core/shell heterostructure film is reported, with aligned and interconnected CNTs wrapped in a continuous TiO (2) coating.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 38, "end": 45}, {"text": "TiO (2)", "start": 152, "end": 159}]}}, "schema": []}
{"input": "Without using additional transparent conducting oxide (TCO) substrates, this unique feature of the film boosts the incident photon-to-electron conversion efficiency to 32%, outperforming TiO (2) nanoparticle electrodes fabricated on TCO substrates.", "output": {"entities": {"chemical": [{"text": "oxide", "start": 48, "end": 53}, {"text": "TiO (2)", "start": 187, "end": 194}]}}, "schema": []}
{"input": "Moreover, the film shows high structural stability and can generate a stable photocurrent even after being bent hundreds of times.", "output": {"entities": {}}, "schema": []}
{"input": "The core cysteines, (C909) of islet antigen-2 and (C945) of islet antigen-2 beta, are crucial to autoantibody binding in type 1 diabetes.", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 9, "end": 18}]}}, "schema": []}
{"input": "Cysteines are thought integral to conformational epitopes of islet antigen-2 (IA-2) autoantibodies (IA-2A), possibly through disulfide bond formation.", "output": {"entities": {"chemical": [{"text": "Cysteines", "start": 0, "end": 9}, {"text": "disulfide", "start": 125, "end": 134}]}}, "schema": []}
{"input": "We therefore investigated which cysteines are critical to IA-2A binding in patients with newly diagnosed type 1 diabetes.", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 32, "end": 41}]}}, "schema": []}
{"input": "All 10 cysteines in the intracellular domain of IA-2 were modified to serine by site-directed mutagenesis, and the effects of these changes on autoantibody binding in comparison with wild-type control were investigated by radiobinding assay.", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 7, "end": 16}, {"text": "serine", "start": 70, "end": 76}]}}, "schema": []}
{"input": "Mutation of the protein tyrosine phosphatase (PTP) core cysteine (C909) in IA-2 caused large reductions in autoantibody binding.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 24, "end": 32}, {"text": "cysteine", "start": 56, "end": 64}]}}, "schema": []}
{"input": "In contrast, little or no reduction in binding was seen following substitution of the other cysteines.", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 92, "end": 101}]}}, "schema": []}
{"input": "Modification of the core cysteine (C945) in IA-2 beta also greatly reduced autoantibody binding.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 25, "end": 33}]}}, "schema": []}
{"input": "Lysine substitution of glutamate-836 in IA-2 or glutamate-872 in IA-2 beta resulted in modest reductions in binding and identified a second epitope region.", "output": {"entities": {"chemical": [{"text": "Lysine", "start": 0, "end": 6}, {"text": "glutamate", "start": 23, "end": 32}, {"text": "glutamate", "start": 48, "end": 57}]}}, "schema": []}
{"input": "Binding to IA-2 PTP and IA-2 beta PTP was almost abolished by mutation of both the core cysteine and these glutamates.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 88, "end": 96}, {"text": "glutamates", "start": 107, "end": 117}]}}, "schema": []}
{"input": "The core cysteine is key to the major PTP conformational epitope, but disulfide bonding contributes little to IA-2A epitope integrity.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 9, "end": 17}]}}, "schema": []}
{"input": "In most patients, at disease onset, > 90% of antibodies binding to the PTP domain of IA-2 recognize just two epitope regions.", "output": {"entities": {}}, "schema": []}
{"input": "Role of oestrogen receptors on the modulation of NADPH-diaphorase-positive cell number in supraoptic and paraventricular nuclei of ovariectomised female rats.", "output": {"entities": {"chemical": [{"text": "oestrogen", "start": 8, "end": 17}, {"text": "NADPH", "start": 49, "end": 54}]}}, "schema": []}
{"input": "Modulation of the nitric oxide producing system (demonstrated via the NADPH-diaphorase histochemical reaction) by oestradiol has been established in several structures of the rat brain.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 18, "end": 30}, {"text": "NADPH", "start": 70, "end": 75}, {"text": "oestradiol", "start": 114, "end": 124}]}}, "schema": []}
{"input": "The present study aimed to explore the possible regulation of NADPH-diaphorase activity by oestradiol in neurones of the supraoptic (SON) and paraventricular (PVN) nuclei and the role of oestrogen receptors (ER alpha and ER beta) in this regulation.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 62, "end": 67}, {"text": "oestradiol", "start": 91, "end": 101}, {"text": "oestrogen", "start": 187, "end": 196}]}}, "schema": []}
{"input": "Adult ovariectomised rats were divided into six groups and injected either with vehicle or a single dose of oestradiol, a selective ER alpha agonist-PPT [4, 4', 4''-(4-propyl-[1H]-pyrazole-1, 3, 5-triyl) trisphenol], a selective ER beta agonist-DPN [2, 3-bis (4-hydroxyphenyl)-propionitrile], a selective ER alpha antagonist-MPP [1, 3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride] or a selective ER beta antagonist-PHTPP (4-[2-phenyl-5, 7-bis (trifluoromethyl) pyrazolo [1, 5-a] pyrimidin-3-yl] phenol).", "output": {"entities": {"chemical": [{"text": "oestradiol", "start": 108, "end": 118}, {"text": "PPT", "start": 149, "end": 152}, {"text": "4, 4', 4''-(4-propyl-[1H]-pyrazole-1, 3, 5-triyl) trisphenol", "start": 154, "end": 214}, {"text": "DPN", "start": 245, "end": 248}, {"text": "2, 3-bis (4-hydroxyphenyl)-propionitrile", "start": 250, "end": 290}, {"text": "MPP", "start": 325, "end": 328}, {"text": "1, 3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol", "start": 330, "end": 399}, {"text": "1H-pyrazole dihydrochloride", "start": 401, "end": 428}, {"text": "PHTPP", "start": 464, "end": 469}, {"text": "4-[2-phenyl-5, 7-bis (trifluoromethyl) pyrazolo [1, 5-a] pyrimidin-3-yl] phenol", "start": 471, "end": 550}]}}, "schema": []}
{"input": "The number of NADPH-diaphorase positive elements in the SON and the PVN was modulated by both ERs but, depending on the nucleus, ER alpha and ER beta ligands induced different effects.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 14, "end": 19}]}}, "schema": []}
{"input": "These results suggest that the regulation of nitrergic system by ERs may play a role in the control of oestrogen-dependent physiological mechanisms regulated by the SON and the PVN.", "output": {"entities": {"chemical": [{"text": "oestrogen", "start": 103, "end": 112}]}}, "schema": []}
{"input": "Influence of stimulant-induced hyperactivity on social approach in the BTBR mouse model of autism.", "output": {"entities": {}}, "schema": []}
{"input": "Translational research is needed to discover pharmacological targets and treatments for the diagnostic behavioral domains of autism spectrum disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Animal models with phenotypic relevance to diagnostic criteria offer clear experimental strategies to test the efficacy and safety of novel treatments.", "output": {"entities": {}}, "schema": []}
{"input": "Antagonists of mGluR5 receptors are in clinical trials for Fragile X syndrome and under investigation for the treatment of autism spectrum disorders.", "output": {"entities": {}}, "schema": []}
{"input": "However, in preclinical studies of mGluR5 compounds tested in our laboratory and others, increased locomotion following mGluR5 modulation has been observed.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the influence of general activity on sociability and repetitive behaviors will increase the accuracy of interpretations of positive outcomes measured from pharmacological treatment that produces locomotor activating or sedating effects.", "output": {"entities": {}}, "schema": []}
{"input": "In the present studies, dose-response curves for d-amphetamine (AMPH)-induced hyperlocomotion were similar in standard B6 mice and in the BTBR mouse model of autism.", "output": {"entities": {"chemical": [{"text": "d-amphetamine", "start": 49, "end": 62}, {"text": "AMPH", "start": 64, "end": 68}]}}, "schema": []}
{"input": "AMPH produced significant, robust reductions in the high level of repetitive self-grooming that characterizes BTBR, and also reduced the low baseline grooming in B6, indicating that AMPH-induced hyperlocomotion competes with time spent engaged in self-grooming.", "output": {"entities": {"chemical": [{"text": "AMPH", "start": 0, "end": 4}, {"text": "AMPH", "start": 182, "end": 186}]}}, "schema": []}
{"input": "We then tested AMPH in B6 and BTBR on the 3-chambered social approach task.", "output": {"entities": {"chemical": [{"text": "AMPH", "start": 15, "end": 19}]}}, "schema": []}
{"input": "One component of sociability, the time spent in the chamber with the novel mouse, in B6 mice was reduced, while the sniffing time component of sociability in BTBR mice was enhanced.", "output": {"entities": {}}, "schema": []}
{"input": "This finding replicated across multiple cohorts treated with AMPH and saline vehicle.", "output": {"entities": {"chemical": [{"text": "AMPH", "start": 61, "end": 65}]}}, "schema": []}
{"input": "In-depth analysis revealed that AMPH increased the number and decreased the duration of sniffing bouts in BTBR, suggesting BTBR treated with AMPH mostly engaged in brief sniffs rather than true social interactions with the novel mouse during the social approach task.", "output": {"entities": {"chemical": [{"text": "AMPH", "start": 32, "end": 36}, {"text": "AMPH", "start": 141, "end": 145}]}}, "schema": []}
{"input": "Our data suggest that compounds with stimulant properties may have some direct benefits on reducing repetitive behaviors in autism spectrum disorders, particularly in the subset of autistic individuals with hyperactivity.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.", "output": {"entities": {}}, "schema": []}
{"input": "Estrogen receptor-alpha is required for the osteogenic response to mechanical loading in a ligand-independent manner involving its activation function 1 but not 2.", "output": {"entities": {"chemical": [{"text": "Estrogen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Estrogen receptor-alpha (ER alpha) is crucial for the adaptive response of bone to loading but the role of endogenous estradiol (E2) for this response is unclear.", "output": {"entities": {"chemical": [{"text": "Estrogen", "start": 0, "end": 8}, {"text": "estradiol", "start": 118, "end": 127}]}}, "schema": []}
{"input": "To determine in vivo the ligand dependency and relative roles of different ER alpha domains for the osteogenic response to mechanical loading, gene-targeted mouse models with (1) a complete ER alpha inactivation (ER alpha (-/-)), (2) specific inactivation of activation function 1 (AF-1) in ER alpha (ER alpha AF-1 (0)), or (3) specific inactivation of ER alpha AF-2 (ER alpha AF-2 (0)) were subjected to axial loading of tibia, in the presence or absence (ovariectomy [ovx]) of endogenous E2.", "output": {"entities": {}}, "schema": []}
{"input": "Loading increased the cortical bone area in the tibia mainly as a result of an increased periosteal bone formation rate (BFR) and this osteogenic response was similar in gonadal intact and ovx mice, demonstrating that E2 (ligand) is not required for this response.", "output": {"entities": {}}, "schema": []}
{"input": "Female ER alpha (-/-) mice displayed a severely reduced osteogenic response to loading with changes in cortical area (-78% +/- 15%, p < 0. 01) and periosteal BFR (-81% +/- 9%, p < 0. 01) being significantly lower than in wild-type (WT) mice.", "output": {"entities": {}}, "schema": []}
{"input": "ER alpha AF-1 (0) mice also displayed a reduced response to mechanical loading compared with WT mice (cortical area-40% +/- 11%, p < 0. 05 and periosteal BFR-41% +/- 8%, p < 0. 01), whereas the periosteal osteogenic response to loading was unaffected in ER alpha AF-2 (0) mice.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanical loading of transgenic estrogen response element (ERE)-luciferase reporter mice did not increase luciferase expression in cortical bone, suggesting that the loading response does not involve classical genomic ERE-mediated pathways.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 33, "end": 41}]}}, "schema": []}
{"input": "In conclusion, ER alpha is required for the osteogenic response to mechanical loading in a ligand-independent manner involving AF-1 but not AF-2.", "output": {"entities": {}}, "schema": []}
{"input": "Green tomato extract attenuates high-fat-diet-induced obesity through activation of the AMPK pathway in C57BL/6 mice.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity is a risk factor for numerous metabolic disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, natural compounds that may be beneficial for improving obesity have received increasing attention.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated whether red and green tomato extracts attenuate high-fat-diet-induced obesity in C57BL/6 mice.", "output": {"entities": {}}, "schema": []}
{"input": "The mice were maintained on a normal diet (ND) or high-fat diet (HFD) for 4 weeks and then fed ND, HFD, HFD plus 2% red tomato extract (RTE) or HFD plus 2% green tomato extract (GTE) for 13 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "The weekly food intakes among the groups were not significantly different.", "output": {"entities": {}}, "schema": []}
{"input": "Body weight of mice fed HFD plus GTE was significantly decreased to the level of mice fed ND, but the body weight was only slightly reduced in mice fed HFD plus RTE.", "output": {"entities": {}}, "schema": []}
{"input": "Epididymal adipose tissue and liver weights were significantly decreased in mice fed HFD plus GTE compared to those in HFD.", "output": {"entities": {}}, "schema": []}
{"input": "Serum total cholesterol and low-density lipoprotein cholesterol levels in mice fed GTE were modestly reduced, and liver total cholesterol level was strongly decreased in HFD plus GTE-fed mice compared to that in HFD-fed mice.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 12, "end": 23}, {"text": "cholesterol", "start": 52, "end": 63}, {"text": "cholesterol", "start": 126, "end": 137}]}}, "schema": []}
{"input": "Adenosine-monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase phosphorylation in liver from HFD plus GTE-fed mice was significantly elevated, and HMG-CoA reductase expression was also significantly decreased.", "output": {"entities": {"chemical": [{"text": "Adenosine-monophosphate", "start": 0, "end": 23}, {"text": "acetyl-CoA", "start": 60, "end": 70}, {"text": "HMG-CoA", "start": 167, "end": 174}]}}, "schema": []}
{"input": "GTE strongly decreased the expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha and perilipin in the adipose tissue of mice fed HFD plus GTE.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that the antiobesity effects of GTE may be associated with activation of the AMPK pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Opportunities for functional selectivity in GPCR antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "Monoclonal antibodies (mAbs) have been used for decades as tools to probe the biology and pharmacology of receptors in cells and tissues.", "output": {"entities": {}}, "schema": []}
{"input": "They are also increasingly being developed for clinical purposes against a broad range of targets, albeit to a lesser extent for G-protein-coupled receptors (GPCRs) relative to other therapeutic targets.", "output": {"entities": {}}, "schema": []}
{"input": "Recent pharmacological, structural and biophysical data have provided a great deal of new insight into the molecular details, complexity and regulation of GPCR function.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas GPCRs used to be viewed as having either \" on \" or \" off \" conformational states, it is now recognized that their structures may be finely tuned by ligands and other interacting proteins, leading to the selective activation of specific signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "This information coupled with new technologies for the selection of mAbs targeting GPCRs will be increasingly deployed for the development of highly selective mAbs that recognize conformational determinants leading to novel therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Nephrogenic systemic fibrosis-like effects of magnetic resonance imaging contrast agents in rats with adenine-induced renal failure.", "output": {"entities": {"chemical": [{"text": "adenine", "start": 102, "end": 109}]}}, "schema": []}
{"input": "Nephrogenic systemic fibrosis (NSF) is a scleroderma-like disease associated with prior administration of certain gadolinium chelates (GCs).", "output": {"entities": {"chemical": [{"text": "gadolinium", "start": 114, "end": 124}]}}, "schema": []}
{"input": "NSF occurs in patients with severe renal failure.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to set up a rat model of GC-associated NSF to elucidate the mechanism of this devastating disease.", "output": {"entities": {}}, "schema": []}
{"input": "Firstly, after characterization of the model, male Wistar rats received a 0. 75% adenine-enriched diet for 8, 14, or 16 days to obtain various degrees of renal failure.", "output": {"entities": {"chemical": [{"text": "adenine", "start": 81, "end": 88}]}}, "schema": []}
{"input": "Rats received five consecutive daily iv injections of saline or gadodiamide (2. 5 mmol/kg/day).", "output": {"entities": {"chemical": [{"text": "gadodiamide", "start": 64, "end": 75}]}}, "schema": []}
{"input": "Secondly, the safety profile and in vivo propensity to dissociate of all categories of marketed GCs (gadoterate, gadobutrol, gadobenate, gadopentetate, and gadodiamide) were compared in rats receiving adenine-enriched diet for 16 days.", "output": {"entities": {"chemical": [{"text": "gadoterate", "start": 101, "end": 111}, {"text": "gadobutrol", "start": 113, "end": 123}, {"text": "gadobenate", "start": 125, "end": 135}, {"text": "gadopentetate", "start": 137, "end": 150}, {"text": "gadodiamide", "start": 156, "end": 167}, {"text": "adenine", "start": 201, "end": 208}]}}, "schema": []}
{"input": "Serial skin biopsies were performed for blinded histopathological study.", "output": {"entities": {}}, "schema": []}
{"input": "Total Gd concentration in tissues was measured by Inductively Coupled Plasma Mass Spectrometry.", "output": {"entities": {"chemical": [{"text": "Gd", "start": 6, "end": 8}]}}, "schema": []}
{"input": "Relaxometry was used to evaluate the presence of dissociated Gd in skin and bone.", "output": {"entities": {"chemical": [{"text": "Gd", "start": 61, "end": 63}]}}, "schema": []}
{"input": "Gadodiamide-induced high mortality and skin lesions (dermal fibrosis, calcification, and inflammation) were related to adenine diet duration.", "output": {"entities": {"chemical": [{"text": "Gadodiamide", "start": 0, "end": 11}, {"text": "adenine", "start": 119, "end": 126}]}}, "schema": []}
{"input": "No skin lesions were observed with other molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike macrocyclic GCs, gadodiamide, gadopentetate, and gadobenate gradually increased the r (1) relaxivity value, consistent with in vivo dissociation and release of soluble Gd (or, in the case of gadobenate, the consequence of protein binding).", "output": {"entities": {"chemical": [{"text": "gadodiamide", "start": 24, "end": 35}, {"text": "gadopentetate", "start": 37, "end": 50}, {"text": "gadobenate", "start": 56, "end": 66}, {"text": "Gd", "start": 175, "end": 177}, {"text": "gadobenate", "start": 198, "end": 208}]}}, "schema": []}
{"input": "Gadodiamide-induced cutaneous and systemic toxicity depended on baseline renal function.", "output": {"entities": {"chemical": [{"text": "Gadodiamide", "start": 0, "end": 11}]}}, "schema": []}
{"input": "We demonstrate in vivo dissociation of linear GCs, gadodiamide, and gadopentetate, whereas macrocyclic agents remained stable over the study period.", "output": {"entities": {"chemical": [{"text": "gadodiamide", "start": 51, "end": 62}, {"text": "gadopentetate", "start": 68, "end": 81}]}}, "schema": []}
{"input": "Effects of ozone and particulate matter on cardiac mechanics: role of the atrial natriuretic peptide gene.", "output": {"entities": {"chemical": [{"text": "ozone", "start": 11, "end": 16}]}}, "schema": []}
{"input": "A positive association between air pollution exposure and increased human risk of chronic heart disease progression is well established.", "output": {"entities": {}}, "schema": []}
{"input": "In the current study, we test two hypotheses: (1) the cardiac compensatory changes in response to air pollution are dependent on its composition and (2) specific cardiac adaptations are regulated by atrial natriuretic peptide (ANP).", "output": {"entities": {}}, "schema": []}
{"input": "We address these hypotheses by initially examining the exposure effects of ozone (O (3)) and/or particulate matter (PM) on cardiac function in C57Bl/6J (B6) mice.", "output": {"entities": {"chemical": [{"text": "ozone", "start": 75, "end": 80}, {"text": "O (3)", "start": 82, "end": 87}]}}, "schema": []}
{"input": "Subsequently, the results are compared with cardiac functional changes to the same exposures in Nppa (the precursor gene for ANP) knockout (KO) mice.", "output": {"entities": {}}, "schema": []}
{"input": "Separate groups of mice underwent 3 consecutive days of the same exposure sequence for 3h each consisting of the following: (1) 6h of filtered air (FAFA), (2) O (3) then FA (O (3) FA), (3) FA then carbon black (FACB), or (4) O (3) then CB.", "output": {"entities": {"chemical": [{"text": "O (3)", "start": 159, "end": 164}, {"text": "O (3)", "start": 174, "end": 179}, {"text": "carbon black", "start": 197, "end": 209}, {"text": "O (3)", "start": 225, "end": 230}]}}, "schema": []}
{"input": "Cardiac function was assessed using a conductance catheter to generate cardiac pressure-volume loops 8-10h following each exposure sequence.", "output": {"entities": {}}, "schema": []}
{"input": "As compared with FAFA, each sequence led to a substantial drop (as much as 33%) in stroke volume and cardiac output.", "output": {"entities": {}}, "schema": []}
{"input": "However, these losses of cardiac function occurred by different compensatory mechanisms dependent on the pollutant composition.", "output": {"entities": {}}, "schema": []}
{"input": "For example, O (3) FA exposure led to reductions in both end-systolic and end-diastolic left ventricular (LV) volumes, whereas FACB exposure led an increase in end-diastolic LV volume.", "output": {"entities": {"chemical": [{"text": "O (3)", "start": 13, "end": 18}]}}, "schema": []}
{"input": "These same cardiac compensatory changes were largely abolished in Nppa KO mice following O (3) FA or FACB exposure.", "output": {"entities": {"chemical": [{"text": "O (3)", "start": 89, "end": 94}]}}, "schema": []}
{"input": "These results suggest that cardiac functional changes in response to air pollution exposure are strongly dependent on the pollutant constituents, especially related to O (3) and/or PM.", "output": {"entities": {"chemical": [{"text": "O (3)", "start": 168, "end": 173}]}}, "schema": []}
{"input": "Furthermore, ANP regulation appears to be crucial to these cardiac compensatory mechanisms induced by air pollution.", "output": {"entities": {}}, "schema": []}
{"input": "Solving the lost in translation problem: improving the effectiveness of translational research.", "output": {"entities": {}}, "schema": []}
{"input": "Translational research frequently fails to replicate in the clinic what has been demonstrated in the laboratory.", "output": {"entities": {}}, "schema": []}
{"input": "This has been true for neuroprotection in the central nervous system, neuroprotection in glaucoma, as well as many other areas of medicine.", "output": {"entities": {}}, "schema": []}
{"input": "Two fundamental reasons for this' Lost in Translation' problem are the' Butterfly Effect' (chaotic behavior of many animal models) and the' Two Cultures' problem (differences between the methodologies for preclinical and clinical research).", "output": {"entities": {}}, "schema": []}
{"input": "We propose several strategies to deal with these issues, including the use of ensembles of animal models, adding intraocular pressure lowering to preclinical neuroprotection studies, changing the way in which preclinical research is done, and increasing interactions between the preclinical and clinical teams.", "output": {"entities": {}}, "schema": []}
{"input": "Human plasma-derived BuChE as a stoichiometric bioscavenger for treatment of nerve agent poisoning.", "output": {"entities": {}}, "schema": []}
{"input": "Potent organophosphorous (OP) agents, such as VX, are hazardous by absorption through the skin and are resistant to conventional pharmacological antidotal treatments.", "output": {"entities": {"chemical": [{"text": "organophosphorous", "start": 7, "end": 24}]}}, "schema": []}
{"input": "The residence time of a stoichiometric bioscavenger, human butyrylcholinesterase (huBuChE), in the plasma more closely matches that of VX than do the residence times of conventional therapy drugs (oxime, anti-muscarinic, anticonvulsant).", "output": {"entities": {"chemical": [{"text": "oxime", "start": 197, "end": 202}]}}, "schema": []}
{"input": "Intramuscular (i. m.) huBuChE afforded almost complete protection when administered prior to the onset of observable cholinergic signs of VX poisoning, but once signs of poisoning became evident the efficacy of i. m.", "output": {"entities": {}}, "schema": []}
{"input": "huBuChE decreased.", "output": {"entities": {}}, "schema": []}
{"input": "A combination of nerve agent therapy drugs (oxime, anti-muscarinic, anticonvulsant) with huBuChE (i. m.) protected 100% (8/8) of guinea-pigs from a lethal dose of VX (0. 74mg/kg) to 48h, even when administered on signs of poisoning.", "output": {"entities": {"chemical": [{"text": "oxime", "start": 44, "end": 49}]}}, "schema": []}
{"input": "Survival was presumed to be due to immediate alleviation of the cholinergic crisis by the conventional pharmacological treatment drugs, in conjunction with bioscavenger that prevented further absorbed agent reaching the AChE targets.", "output": {"entities": {}}, "schema": []}
{"input": "Evidence to support this proposed mechanism of action was obtained from PKPD experiments in which multiple blood samples and microdialysate samples were collected from individual conscious ambulatory animals.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma concentrations of intramuscularly-administered atropine, diazepam and HI-6 reached a peak within 15min and were eliminated rapidly within 4h.", "output": {"entities": {"chemical": [{"text": "atropine", "start": 54, "end": 62}, {"text": "diazepam", "start": 64, "end": 72}, {"text": "HI-6", "start": 77, "end": 81}]}}, "schema": []}
{"input": "Plasma concentrations of huBuChE administered by the i. m. route took approximately 24h to reach a peak, but were well-maintained over the subsequent 7days.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the pharmacological therapy rapidly treated the initial signs of poisoning, whilst the bioscavenger provided prolonged protection by neutralising further nerve agent entering the bloodstream and preventing it from reaching the target organs.", "output": {"entities": {}}, "schema": []}
{"input": "Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials.", "output": {"entities": {}}, "schema": []}
{"input": "To overcome the limitations of in vitro exposure of submerged lung cells to nanoparticles (NPs), we validated an integrated low flow system capable of generating and depositing airborne NPs directly onto cells at an air-liquid interface (ALI).", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro exposure system was shown to provide uniform and controlled dosing of particles with 70. 3% efficiency to epithelial cells grown on transwells.", "output": {"entities": {}}, "schema": []}
{"input": "This system delivered a continuous airborne exposure of NPs to lung cells without loss of cell viability in repeated 4h exposure periods.", "output": {"entities": {}}, "schema": []}
{"input": "We sequentially exposed cells to air-delivered copper (Cu) NPs in vitro to compare toxicity results to our prior in vivo inhalation studies.", "output": {"entities": {"chemical": [{"text": "copper", "start": 47, "end": 53}, {"text": "Cu", "start": 55, "end": 57}]}}, "schema": []}
{"input": "The evaluation of cellular dosimetry indicated that a large amount of Cu was taken up, dissolved and released into the basolateral medium (62% of total mass).", "output": {"entities": {"chemical": [{"text": "Cu", "start": 70, "end": 72}]}}, "schema": []}
{"input": "Exposure to Cu NPs decreased cell viability to 73% (p < 0. 01) and significantly (p < 0. 05) elevated levels of lactate dehydrogenase, intracellular reactive oxygen species and interleukin-8 that mirrored our findings from subacute in vivo inhalation studies in mice.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 12, "end": 14}, {"text": "lactate", "start": 112, "end": 119}, {"text": "oxygen", "start": 158, "end": 164}]}}, "schema": []}
{"input": "Our results show that this exposure system is useful for screening of NP toxicity in a manner that represents cellular responses of the pulmonary epithelium in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "The involvement of Reelin in neurodevelopmental disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adulthood (maintenance of synaptic function).", "output": {"entities": {}}, "schema": []}
{"input": "A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer' s disease and lissencephaly share a common feature of abnormal Reelin expression in the brain.", "output": {"entities": {}}, "schema": []}
{"input": "Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanisms for abnormal Reelin expression in some of these disorders are currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP underexpression and Reelin processing abnormalities.", "output": {"entities": {}}, "schema": []}
{"input": "Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.", "output": {"entities": {}}, "schema": []}
{"input": "Ultrasound-assisted coating of silk yarn with sphere-like Mn3O4 nanoparticles.", "output": {"entities": {"chemical": [{"text": "Mn3O4", "start": 58, "end": 63}]}}, "schema": []}
{"input": "The growth of sphere-like trimanganese tetraoxide (Mn (3) O (4)) nanoparticles on silk fiber was achieved by sequential dipping in an alternating bath of potassium hydroxide and manganese (II) nitrate under ultrasound irradiation.", "output": {"entities": {"chemical": [{"text": "trimanganese tetraoxide", "start": 26, "end": 49}, {"text": "Mn (3) O (4)", "start": 51, "end": 63}, {"text": "potassium hydroxide", "start": 154, "end": 173}, {"text": "manganese (II) nitrate", "start": 178, "end": 200}]}}, "schema": []}
{"input": "Some parameters such as the effect of pH, numerous sequential dipping and ultrasonic irradiation on growth of the nanoparticles have been studied.", "output": {"entities": {}}, "schema": []}
{"input": "The samples were characterized with powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and wavelength dispersive X-ray (WDX).", "output": {"entities": {}}, "schema": []}
{"input": "The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines.", "output": {"entities": {"chemical": [{"text": "PJ34", "start": 19, "end": 23}]}}, "schema": []}
{"input": "Since PARP-1 is supposed to be part of a multimeric repressor of sodium iodide symporter (NIS) expression, in this study the effect of the PARP inhibitor PJ34 on several properties of thyroid cancer cell lines was investigated.", "output": {"entities": {"chemical": [{"text": "sodium iodide", "start": 65, "end": 78}, {"text": "PJ34", "start": 154, "end": 158}]}}, "schema": []}
{"input": "In TPC1, BCPAP, FRO, WRO cell lines PJ34 induced a strong increase in NIS mRNA levels.", "output": {"entities": {"chemical": [{"text": "PJ34", "start": 36, "end": 40}]}}, "schema": []}
{"input": "In BCPAP and TPC1 cells also significant increase of radio-iodine uptake was induced.", "output": {"entities": {"chemical": [{"text": "radio-iodine", "start": 53, "end": 65}]}}, "schema": []}
{"input": "Accordingly, in transfection experiments performed in TPC1 cells, treatment with PJ34 increased NIS promoter activity without affecting PARP-1 binding to the promoter sequence.", "output": {"entities": {"chemical": [{"text": "PJ34", "start": 81, "end": 85}]}}, "schema": []}
{"input": "We also investigated the epigenetic status of NIS promoter after PJ34 treatment in TPC1 cell line: in addition to an increase of histone modification activation marks (H3K9K14ac, H3K4me3), surprisingly we observed also an increase of H3K27me3, a classical repressive mark.", "output": {"entities": {"chemical": [{"text": "PJ34", "start": 65, "end": 69}]}}, "schema": []}
{"input": "Our data demonstrate that in various thyroid cancer cell lines PARP inhibition increases NIS gene expression through a particular modulation of transcriptional regulatory mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we suggest that PARP inhibitors may deserve future investigations as tools for medical treatment of thyroid cancer.", "output": {"entities": {}}, "schema": []}
{"input": "NMDA receptor signaling mediates the expression of protein inhibitor of activated STAT1 (PIAS1) in rat hippocampus.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Protein inhibitor of activated STAT1 (PIAS1) was shown to play an important role in inflammation and innate immune response, but how PIAS1 is regulated is not known.", "output": {"entities": {}}, "schema": []}
{"input": "We have recently demonstrated that PIAS1 enhances spatial learning and memory performance in rats.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we examined the signaling pathway and neural mechanism that regulate PIAS1 expression in the brain by using pharmacological and molecular approaches.", "output": {"entities": {}}, "schema": []}
{"input": "Our results revealed that pias1 gene expression is rapidly induced upon NMDA receptor activation in rat hippocampus, but this effect is blocked by transfection of sub-threshold concentrations of ERK1 siRNA/ERK2 siRNA or CREB siRNA.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 72, "end": 76}]}}, "schema": []}
{"input": "Pias1 gene expression is similarly induced by overexpression of the ERK1/ERK2 plasmids in rat hippocampus, and this effect is also blocked by sub-threshold concentration of CREB siRNA transfection.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, transfection of ERK1 siRNA/ERK2 siRNA or CREB siRNA at a higher concentration is sufficient to down-regulate PIAS1 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of PI-3 kinase signaling and CaMKII signaling, which both result in CREB inactivation, similarly decreases PIAS1 expression.", "output": {"entities": {}}, "schema": []}
{"input": "But NMDA and MK-801 do not affect the expression of IL-6 and TNF alpha.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 4, "end": 8}, {"text": "MK-801", "start": 13, "end": 19}]}}, "schema": []}
{"input": "NMDA also did not affect the expression of PIAS2, PIAS3 and PIAS4.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Further, pias1 mRNA has a similar degradation rate to that of the zif268 gene.", "output": {"entities": {}}, "schema": []}
{"input": "These results together suggest that pias1 may function as an immediate early gene in an activity-dependent manner and PIAS1 expression is regulated by the NMDA-MAPK/ERK-CREB signaling pathway implicated in neuronal plasticity.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 155, "end": 159}]}}, "schema": []}
{"input": "Antidepressant-like properties of three new alpha 2-adrenoceptor antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "Evidence suggests that depression is associated with an increase in the high-affinity conformation of the alpha 2-adrenoceptors in human brain.", "output": {"entities": {}}, "schema": []}
{"input": "Such enhanced alpha 2-adrenoceptor activity could explain the deficit in central noradrenergic transmission described in the aetiology of depression.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, administration of alpha 2-adrenoceptor antagonists augments noradrenaline levels and provides an effective therapeutic approach for the treatment of depressive disorders.", "output": {"entities": {"chemical": [{"text": "noradrenaline", "start": 66, "end": 79}]}}, "schema": []}
{"input": "In previous studies, we have characterized three new synthesized guanidine and 2-aminoimidazoline aromatic derivatives (8b, 17b and 20b) as alpha 2-adrenoceptor antagonists that are able to increase extracellular concentration of noradrenaline in rat brain.", "output": {"entities": {"chemical": [{"text": "guanidine", "start": 65, "end": 74}, {"text": "2-aminoimidazoline", "start": 79, "end": 97}, {"text": "noradrenaline", "start": 230, "end": 243}]}}, "schema": []}
{"input": "The purpose of the present study was to evaluate the in vivo antidepressant-like properties of these three new alpha 2-adrenoceptor antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "For that aim, compounds were tested on the tail suspension test (TST) and forced swim test (FST), two classically widely-used behavioural paradigms for the evaluation of antidepressant-like activity.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 8b significantly reduced the immobility time at 10, 20 and 40 mg/kg doses in both TST and FST.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 17b reduced the immobility time at 40 mg/kg in both TST and FST.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 20b showed a significant decrease in the immobility time at 20 mg/kg in the TST.", "output": {"entities": {}}, "schema": []}
{"input": "As drugs of reference, fluoxetine induced a significant antidepressant-like effect in both TST and FST, while mirtazapine induced a significant antidepressant-like effect only in the FST.", "output": {"entities": {"chemical": [{"text": "fluoxetine", "start": 23, "end": 33}, {"text": "mirtazapine", "start": 110, "end": 121}]}}, "schema": []}
{"input": "Additionally, none of the tested compounds increased locomotor activity or displayed anxiolytic-like properties.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that these new synthesized alpha 2-adrenoceptor antagonists may be useful as potential antidepressant drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged leptin action in either region cross-desensitizes.", "output": {"entities": {}}, "schema": []}
{"input": "High-fat feeding or CNS leptin overexpression in chow-fed rats results in a region-specific cellular leptin resistance in medial basal hypothalamic regions and the ventral tegmental area (VTA).", "output": {"entities": {}}, "schema": []}
{"input": "The present investigation examined the effects of targeted chronic leptin overexpression in the VTA as compared with the medial basal hypothalamus on long-term body weight homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "The study also examined if this targeted intervention conserves regional leptin sensitivity or results in localized leptin resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular leptin resistance was assessed by leptin-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3).", "output": {"entities": {}}, "schema": []}
{"input": "Tyrosine hydroxylase was measured in hypothalamus and VTA along with brown adipose tissue uncoupling protein 1.", "output": {"entities": {"chemical": [{"text": "Tyrosine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Leptin overexpression in VTA tempered HF-induced obesity, but to a slightly lesser extent than that with leptin overexpression in the hypothalamus.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the overexpression of leptin in the VTA stimulated cellular STAT3 phosphorylation in several regions of the medial basal hypothalamus, whereas verexpression in the hypothalamus did not activate STAT3 signaling in the VTA.", "output": {"entities": {}}, "schema": []}
{"input": "This unidirectional trans-stimulation did not appear to involve migration of either the vector or the gene product.", "output": {"entities": {}}, "schema": []}
{"input": "Long-term leptin overexpression in either the medial basal hypothalamus or VTA caused desensitization of leptin signaling in the treated region and cross-desensitization of leptin signaling in the untreated region.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate a role of leptin receptors in the VTA in long-term body weight regulation, but the trans-activation of the hypothalamus following VTA leptin stimulation suggests that an integrative response involving both brain regions may account for the observed physiological outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Persistent and high-level expression of human liver prolidase in vivo in mice using adenovirus.", "output": {"entities": {}}, "schema": []}
{"input": "Human liver prolidase, a metal-dependent dipeptidase, is being tested as a potential catalytic bioscavenger against organophosphorus (OP) chemical warfare nerve agents.", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 116, "end": 132}]}}, "schema": []}
{"input": "The purpose of this study was to determine whether persistent and high-levels of biologically active and intact recombinant human (rHu) prolidase could be introduced in vivo in mice using adenovirus (Ad).", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report that a single intravenous injection of Ad containing the prolidase gene with a 6 x histidine-tag (Ad-prolidase) introduced high-levels of rHu prolidase in the circulation of mice which peaked on days 5-7 at 159 +/- 129U/mL.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 99, "end": 108}]}}, "schema": []}
{"input": "This level of prolidase is ~ 120 times greater than that of the enzyme level in mice injected with Ad-null virus.", "output": {"entities": {}}, "schema": []}
{"input": "To determine if all of Ad-prolidase-produced rHu prolidase was exported into the circulation, enzyme activity was measured in a variety of tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Liver contained the highest levels of rHu prolidase on day 7 (5647 +/- 454U/g) compared to blood or any other tissue.", "output": {"entities": {}}, "schema": []}
{"input": "Recombinant Hu prolidase hydrolyzed DFP, a simulant of OP nerve agents, in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo, prolidase overexpression extended the survival of 4 out of 6 mice by 4-8h against exposure to two 1 x LD50 doses of DFP.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, overexpression of mouse butyrylcholinesterase (BChE), a proven stoichiometric bioscavenger of OP compounds, protected 5 out of 6 mice from DFP lethality and surviving mice showed no symptoms of DFP toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the results suggest that gene delivery using Ad is capable of introducing persistent and high levels of human liver prolidase in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "The gene-delivered prolidase hydrolyzed DFP in vitro but provided only modest protection in vivo in mice, delaying the death of the animals by only 4-8h.", "output": {"entities": {}}, "schema": []}
{"input": "Experiences of microsurgical reconstruction for variant hepatic artery in living donor liver transplantation.", "output": {"entities": {}}, "schema": []}
{"input": "There is an emergent need for improving the microsurgical technique of variant arterial anastomosis to reduce the often seen surgery-related complications.", "output": {"entities": {}}, "schema": []}
{"input": "We describe in this article our experience in improving this technique, in 73 living donor liver grafts (64 right lobes, 9 left lobes) in patients with end-stage liver disease during living donor liver transplantation.", "output": {"entities": {}}, "schema": []}
{"input": "The hepatic arteries were evaluated preoperatively with computed tomography and magnetic resonance angiography.", "output": {"entities": {}}, "schema": []}
{"input": "In this series, 13 grafts (17. 80%) with variant hepatic artery were conducted arterioplasty on a back-table under a loupe or a high-power microscope, which included one recipient in situ interposition vessel graft of recipient proper hepatic artery for artery reconstruction.", "output": {"entities": {}}, "schema": []}
{"input": "The back-table reconstruction time was 16 +/- 5. 6 min.", "output": {"entities": {}}, "schema": []}
{"input": "No arterial thrombosis was found in these cases during the 6-month postoperative follow-up.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of our experience, we suggest that back-table microsurgical plasty for graft with arterial variation should be applied to minimize operative difficulties and to avoid arterial complications in living donor liver transplantation.", "output": {"entities": {}}, "schema": []}
{"input": "Information for clinicians: commercially available molecular diagnosis testing in the evaluation of thyroid nodule fine-needle aspiration specimens.", "output": {"entities": {}}, "schema": []}
{"input": "TSH receptor mRNA reverse transcription-polymerase chain reaction, the Veracyte and Asuragen commercial methods, and the noncommercial use of BRAF, RAS, RET/PTC, and PAX8/PPAR gamma testing have promising roles in the diagnosis and treatment of patients with nodular thyroid disease and thyroid cancer.", "output": {"entities": {}}, "schema": []}
{"input": "However, at this time, experience with these molecular methods remains limited, and no test has perfect sensitivity and specificity.", "output": {"entities": {}}, "schema": []}
{"input": "Peer-reviewed data evaluating the diagnostic performance of these tests are increasingly available.", "output": {"entities": {}}, "schema": []}
{"input": "The American Thyroid Association (ATA) feels that until an expert consensus review of existing data (now underway by the ATA Guidelines Task Force) can be completed, no evidence-based recommendation for or against the use of these methods can be made.", "output": {"entities": {}}, "schema": []}
{"input": "Clinicians are therefore advised to consider the use of these genetic diagnosis methods with appropriate caution, and to remain cognizant of the limitations of the data supporting their use.", "output": {"entities": {}}, "schema": []}
{"input": "Patients who are interested in the use of these tests in their own care should discuss them thoroughly with their care providers.", "output": {"entities": {}}, "schema": []}
{"input": "Until evidence-based recommendations are available, determining whether or not the limited data available support the use of these methods should be considered on a case-by-case basis.", "output": {"entities": {}}, "schema": []}
{"input": "Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of rat calvarial osteoblasts--in vitro.", "output": {"entities": {"chemical": [{"text": "Di 2-ethyl hexyl phthalate", "start": 0, "end": 26}]}}, "schema": []}
{"input": "Di-2-ethyl hexyl phthalate (DEHP), an industrial plasticizer and a ubiquitous environmental contaminant, is an established endocrine disruptor (ED).", "output": {"entities": {"chemical": [{"text": "Di-2-ethyl hexyl phthalate", "start": 0, "end": 26}, {"text": "DEHP", "start": 28, "end": 32}]}}, "schema": []}
{"input": "Increasing evidences indicate that some EDs interfere with osteoblast differentiation and function.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we investigated the effects of DEHP on the expression of cell cycle proteins, differentiation markers, Runx2 and its co-activator TAZ in osteoblasts derived from neonatal rat calvaria.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 53, "end": 57}]}}, "schema": []}
{"input": "A significant decrease in protein levels of cyclin D1 and CDK-2 was found at high dosage of DEHP (100 mu M) after 24h treatment.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 92, "end": 96}]}}, "schema": []}
{"input": "DEHP treatment caused a significant decrease in ALP mRNA.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 0, "end": 4}]}}, "schema": []}
{"input": "While DEHP treatment significantly decreased the TAZ at mRNA and protein levels, it decreased only the Runx2protein levels.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 6, "end": 10}]}}, "schema": []}
{"input": "Histochemical localization of ALP, collagen and mineralized nodules studied from cells treated with DEHP (10 and 100 mu M) for 21 days revealed a drastic decrease in collagen, ALP and mineralization.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 100, "end": 104}]}}, "schema": []}
{"input": "In conclusion, DEHP affected differentiation of neonatal rat calvarial osteoblasts and mineralization of matrix secreted by these cells.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 15, "end": 19}]}}, "schema": []}
{"input": "Ultraviolet B activated 1, 25 (OH) (2) D affects the level of fibroblast growth factor-23 in human.", "output": {"entities": {"chemical": [{"text": "1, 25 (OH) (2) D", "start": 24, "end": 40}]}}, "schema": []}
{"input": "Fibroblast growth factor 23 (FGF-23) is known as a phosphaturic factor regulating phosphate homeostasis.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 82, "end": 91}]}}, "schema": []}
{"input": "Several studies suggest that dietary phosphate, serum phosphate and 1, 25-dihydroxyvitamin D [1, 25 (OH) (2) D] are candidate regulators of FGF-23.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 37, "end": 46}, {"text": "phosphate", "start": 54, "end": 63}, {"text": "1, 25-dihydroxyvitamin D", "start": 68, "end": 92}, {"text": "1, 25 (OH) (2) D", "start": 94, "end": 110}]}}, "schema": []}
{"input": "While the human studies, which modulated the dietary or serum phosphate showed in rather controversial results, manipulation of the active vitamin D definitely affected FGF-23 in animals.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 62, "end": 71}, {"text": "vitamin D", "start": 139, "end": 148}]}}, "schema": []}
{"input": "This study was conducted to elucidate the relationship between active vitamin D directly stimulated by ultraviolet B (UVB) exposure and FGF-23 level in human.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 70, "end": 79}]}}, "schema": []}
{"input": "Ten healthy young adults were recruited to get the UVB exposure thrice a week at sub-minimal erythemal dose with gradual increment by 10% only for 4 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Serum calcium, phosphate, mineral-related hormones and bone turnover markers were analyzed before and after the UVB exposure every 4 week for 12 whole weeks.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 6, "end": 13}, {"text": "phosphate", "start": 15, "end": 24}]}}, "schema": []}
{"input": "Twenty five-hydroxyvitamin D [25 (OH) D] increased by 115% (19. 8 ng/mL to 40. 5 ng/mL, p < 0. 001) after 4 weeks of UVB exposure.", "output": {"entities": {"chemical": [{"text": "Twenty five-hydroxyvitamin D", "start": 0, "end": 28}, {"text": "25 (OH) D", "start": 30, "end": 39}]}}, "schema": []}
{"input": "While 1, 25 (OH) (2) D increased by 75% (49. 9 pg/mL to 64. 4 pg/mL, p < 0. 001) then both level decreased after 4 weeks of withdrawal.", "output": {"entities": {"chemical": [{"text": "1, 25 (OH) (2) D", "start": 6, "end": 22}]}}, "schema": []}
{"input": "C-telopeptide peaked at 2nd week then decreased, while osteocalcin increased gradually.", "output": {"entities": {}}, "schema": []}
{"input": "FGF-23 started to increase from the 4th week of UVB exposure then significantly at the 4th week after withdrawal of UVB (27. 8 pg/mL to 41. 4 pg/mL, p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "UVB exposure effectively increased 1, 25 (OH) (2) D with delayed stimulatory effect on FGF-23.", "output": {"entities": {"chemical": [{"text": "1, 25 (OH) (2) D", "start": 35, "end": 51}]}}, "schema": []}
{"input": "This result could support the regulatory loop of 1, 25 (OH) (2) D and FGF-23 in human, FGF-23 regulation by 1, 25 (OH) (2) D.", "output": {"entities": {"chemical": [{"text": "1, 25 (OH) (2) D", "start": 49, "end": 65}, {"text": "1, 25 (OH) (2) D", "start": 108, "end": 124}]}}, "schema": []}
{"input": "Purinergic receptor antagonist a438079 protects against acetaminophen-induced liver injury by inhibiting p450 isoenzymes, not by inflammasome activation.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 56, "end": 69}]}}, "schema": []}
{"input": "Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the western world.", "output": {"entities": {"chemical": [{"text": "Acetaminophen", "start": 0, "end": 13}, {"text": "APAP", "start": 15, "end": 19}]}}, "schema": []}
{"input": "Controversy exists regarding the hypothesis that the hepatocyte injury is amplified by a sterile inflammatory response, rather than being the result of intracellular mechanisms alone.", "output": {"entities": {}}, "schema": []}
{"input": "A recent study suggested that the purinergic receptor antagonist A438079 protects against APAP-induced liver injury by preventing the activation of the Nalp3 inflammasome in Kupffer cells and thereby preventing inflammatory injury.", "output": {"entities": {"chemical": [{"text": "A438079", "start": 65, "end": 72}, {"text": "APAP", "start": 90, "end": 94}]}}, "schema": []}
{"input": "To test the hypothesis that A438079 actually affects the intracellular signaling events in hepatocytes, C57Bl/6 mice were treated with APAP (300 mg/kg) and A438079 (80 mg/kg) or saline and GSH depletion, protein adduct formation, c-jun-N-terminal kinase (JNK) activation, oxidant stress, and liver cell necrosis were determined between 0 and 6 h after APAP administration.", "output": {"entities": {"chemical": [{"text": "A438079", "start": 28, "end": 35}, {"text": "APAP", "start": 135, "end": 139}, {"text": "A438079", "start": 156, "end": 163}, {"text": "GSH", "start": 189, "end": 192}, {"text": "N", "start": 236, "end": 237}, {"text": "APAP", "start": 352, "end": 356}]}}, "schema": []}
{"input": "APAP caused rapid GSH depletion, extensive protein adduct formation in liver homogenates and in mitochondria, JNK phosphorylation and mitochondrial translocation of phospho-JNK within 2 h, oxidant stress, and extensive centrilobular necrosis at 6 h.", "output": {"entities": {"chemical": [{"text": "APAP", "start": 0, "end": 4}, {"text": "GSH", "start": 18, "end": 21}]}}, "schema": []}
{"input": "A438079 significantly attenuated GSH depletion, which resulted in a 50% reduction of total liver and mitochondrial protein adducts and substantial reduction of JNK activation, mitochondrial P-JNK translocation, oxidant stress, and liver injury.", "output": {"entities": {"chemical": [{"text": "A438079", "start": 0, "end": 7}, {"text": "GSH", "start": 33, "end": 36}]}}, "schema": []}
{"input": "The same results were obtained using primary mouse hepatocytes.", "output": {"entities": {}}, "schema": []}
{"input": "A438079 did not directly affect JNK activation induced by tert-butyl hydroperoxide and GSH depletion.", "output": {"entities": {"chemical": [{"text": "A438079", "start": 0, "end": 7}, {"text": "tert-butyl hydroperoxide", "start": 58, "end": 82}, {"text": "GSH", "start": 87, "end": 90}]}}, "schema": []}
{"input": "However, A438079 dose-dependently inhibited hepatic P450 enzyme activity.", "output": {"entities": {"chemical": [{"text": "A438079", "start": 9, "end": 16}]}}, "schema": []}
{"input": "Thus, the protective effect of A438079 against APAP hepatotoxicity in vivo can be explained by its effect on metabolic activation and cell death pathways in hepatocytes without involvement of the Nalp3 inflammasome.", "output": {"entities": {"chemical": [{"text": "A438079", "start": 31, "end": 38}, {"text": "APAP", "start": 47, "end": 51}]}}, "schema": []}
{"input": "Protective roles of single-wall carbon nanotubes in ultrasonication-induced DNA base damage.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 32, "end": 38}]}}, "schema": []}
{"input": "The overall level of ultrasonication-induced DNA damage is reduced in the presence of single-wall carbon nanotubes (SWCNTs), particularly for DNA lesions formed by one-electron reduction of intermediate radicals.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 98, "end": 104}]}}, "schema": []}
{"input": "The protective role of SWCNTs observed in this work suggests a contrary view to the general idea that carbon nanotubes have damaging effects on biomolecules.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 102, "end": 108}]}}, "schema": []}
{"input": "Polymer grafting to single-walled carbon nanotubes: effect of chain length on solubility, graft density and mechanical properties of macroscopic structures.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 34, "end": 40}]}}, "schema": []}
{"input": "Single-walled carbon nanotubes are grafted with polystyrene chains employing a graft-to protocol.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 14, "end": 20}, {"text": "polystyrene", "start": 48, "end": 59}]}}, "schema": []}
{"input": "Thermogravimetric analysis allows calculation of the grafted chain density and average interchain separation on the nanotube surface as a function of molecular weight.", "output": {"entities": {}}, "schema": []}
{"input": "The separation scales with molecular weight as a power law with an exponent of ca.", "output": {"entities": {}}, "schema": []}
{"input": "0. 588, showing the grafted chains to be in a swollen random walk conformation.", "output": {"entities": {}}, "schema": []}
{"input": "This implies that chain packing is controlled by coil size in solution.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the dispersed concentration of functionalized nanotubes scales with the size of the steric potential barrier that prevents aggregation of polymer functionalized nanotubes.", "output": {"entities": {}}, "schema": []}
{"input": "It is also shown that the molecular weight of the grafted chains significantly affects the mechanical properties of nanotube films.", "output": {"entities": {}}, "schema": []}
{"input": "Withaferin A-stimulated Ca2 + entry, ceramide formation and suicidal death of erythrocytes.", "output": {"entities": {"chemical": [{"text": "Withaferin A", "start": 0, "end": 12}, {"text": "Ca2 +", "start": 24, "end": 29}, {"text": "ceramide", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Withaferin A, a triterpenoid component from Withania somnifera, counteracts malignancy, an effect attributed to stimulation of apoptosis.", "output": {"entities": {"chemical": [{"text": "Withaferin A", "start": 0, "end": 12}, {"text": "triterpenoid", "start": 16, "end": 28}]}}, "schema": []}
{"input": "Withaferin A is partially effective through induction of oxidative stress, altered gene expression and mitochondrial depolarization.", "output": {"entities": {"chemical": [{"text": "Withaferin A", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Erythrocytes lack mitochondria and nuclei but may enter apoptosis-like eryptosis, a suicidal cell death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface.", "output": {"entities": {"chemical": [{"text": "phosphatidylserine", "start": 170, "end": 188}]}}, "schema": []}
{"input": "Triggers of eryptosis include increase of cytosolic Ca (2 +)-activity [Ca (2 +)] (i) following activation of oxidant-sensitive Ca (2 +)-permeable cation channels, ceramide formation and/or ATP-depletion.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 52, "end": 60}, {"text": "Ca (2 +)", "start": 71, "end": 79}, {"text": "Ca (2 +)", "start": 127, "end": 135}, {"text": "ceramide", "start": 163, "end": 171}, {"text": "ATP", "start": 189, "end": 192}]}}, "schema": []}
{"input": "The present study explored, whether withaferin A triggers eryptosis.", "output": {"entities": {"chemical": [{"text": "withaferin A", "start": 36, "end": 48}]}}, "schema": []}
{"input": "To this end, [Ca (2 +)] (i) was estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin-V-binding, hemolysis from hemoglobin release, oxidative stress from DCFDA-fluorescence and ceramide abundance utilizing antibodies.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 14, "end": 22}, {"text": "Fluo3", "start": 47, "end": 52}, {"text": "phosphatidylserine", "start": 101, "end": 119}, {"text": "DCFDA", "start": 210, "end": 215}, {"text": "ceramide", "start": 233, "end": 241}]}}, "schema": []}
{"input": "A 48 h exposure to withaferin A significantly decreased forward scatter (at >= 10 mu M withaferin concentration) and increased [Ca (2 +)] (i) (>= 5 mu M), ROS-formation (>= 10 mu M) ceramide-formation (>= 10 mu M) as well as annexin-V-binding (>= 5 mu M).", "output": {"entities": {"chemical": [{"text": "withaferin A", "start": 19, "end": 31}, {"text": "withaferin", "start": 87, "end": 97}, {"text": "Ca (2 +)", "start": 128, "end": 136}, {"text": "ceramide", "start": 182, "end": 190}]}}, "schema": []}
{"input": "Withaferin A treatment was followed by slight but significant increase of hemolysis.", "output": {"entities": {"chemical": [{"text": "Withaferin A", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Extracellular Ca (2 +) removal, amiloride, and the antioxidant N-acetyl-l-cysteine significantly blunted withaferin A-triggered annexin-V-binding.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 14, "end": 22}, {"text": "amiloride", "start": 32, "end": 41}, {"text": "N-acetyl-l-cysteine", "start": 63, "end": 82}, {"text": "withaferin A", "start": 105, "end": 117}]}}, "schema": []}
{"input": "The present observations reveal that withaferin A triggers suicidal erythrocyte death despite the absence of gene expression and key elements of apoptosis such as mitochondria.", "output": {"entities": {"chemical": [{"text": "withaferin A", "start": 37, "end": 49}]}}, "schema": []}
{"input": "Gut microbiota, immune development and function.", "output": {"entities": {}}, "schema": []}
{"input": "The microbiota of Westerners is significantly reduced in comparison to rural individuals living a similar lifestyle to our Paleolithic forefathers but also to that of other free-living primates such as the chimpanzee.", "output": {"entities": {}}, "schema": []}
{"input": "The great majority of ingredients in the industrially produced foods consumed in the West are absorbed in the upper part of small intestine and thus of limited benefit to the microbiota.", "output": {"entities": {}}, "schema": []}
{"input": "Lack of proper nutrition for microbiota is a major factor under-pinning dysfunctional microbiota, dysbiosis, chronically elevated inflammation, and the production and leakage of endotoxins through the various tissue barriers.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the over-comsumption of insulinogenic foods and proteotoxins, such as advanced glycation and lipoxidation molecules, gluten and zein, and a reduced intake of fruit and vegetables, are key factors behind the commonly observed elevated inflammation and the endemic of obesity and chronic diseases, factors which are also likely to be detrimental to microbiota.", "output": {"entities": {}}, "schema": []}
{"input": "As a consequence of this lifestyle and the associated eating habits, most barriers, including the gut, the airways, the skin, the oral cavity, the vagina, the placenta, the blood-brain barrier, etc., are increasingly permeable.", "output": {"entities": {}}, "schema": []}
{"input": "Attempts to recondition these barriers through the use of so called' probiotics', normally applied to the gut, are rarely successful, and sometimes fail, as they are usually applied as adjunctive treatments, e. g. in parallel with heavy pharmaceutical treatment, not rarely consisting in antibiotics and chemotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "It is increasingly observed that the majority of pharmaceutical drugs, even those believed to have minimal adverse effects, such as proton pump inhibitors and anti-hypertensives, in fact adversely affect immune development and functions and are most likely also deleterious to microbiota.", "output": {"entities": {}}, "schema": []}
{"input": "Equally, it appears that probiotic treatment is not compatible with pharmacological treatments.", "output": {"entities": {}}, "schema": []}
{"input": "Eco-biological treatments, with plant-derived substances, or phytochemicals, e. g. curcumin and resveratrol, and pre-, pro-and syn-biotics offers similar effects as use of biologicals, although milder but also free from adverse effects.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 83, "end": 91}, {"text": "resveratrol", "start": 96, "end": 107}]}}, "schema": []}
{"input": "Such treatments should be tried as alternative therapies; mainly, to begin with, for disease prevention but also in early cases of chronic diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmaceutical treatment has, thus far, failed to inhibit the tsunami of endemic diseases spreading around the world, and no new tools are in sight.", "output": {"entities": {}}, "schema": []}
{"input": "Dramatic alterations, in direction of a paleolithic-like lifestyle and food habits, seem to be the only alternatives with the potential to control the present escalating crisis.", "output": {"entities": {}}, "schema": []}
{"input": "The present review focuses on human studies, especially those of clinical relevance.", "output": {"entities": {}}, "schema": []}
{"input": "Aryl methylcarbamates: Potency and selectivity towards wild-type and carbamate-insensitive (G119S) Anopheles gambiae acetylcholinesterase, and toxicity to G3 strain An. gambiae.", "output": {"entities": {"chemical": [{"text": "Aryl methylcarbamates", "start": 0, "end": 21}, {"text": "carbamate", "start": 69, "end": 78}]}}, "schema": []}
{"input": "New carbamates that are highly selective for inhibition of Anopheles gambiae acetylcholinesterase (AChE) over the human enzyme might be useful in continuing efforts to limit malaria transmission.", "output": {"entities": {"chemical": [{"text": "carbamates", "start": 4, "end": 14}]}}, "schema": []}
{"input": "In this report we assessed 34 synthesized and commercial carbamates for their selectivity to inhibit the AChEs found in carbamate-susceptible (G3) and carbamate-resistant (Akron) An. gambiae, relative to human AChE.", "output": {"entities": {"chemical": [{"text": "carbamates", "start": 57, "end": 67}, {"text": "carbamate", "start": 120, "end": 129}, {"text": "carbamate", "start": 151, "end": 160}]}}, "schema": []}
{"input": "Excellent correspondence is seen between inhibition potencies measured with carbamate-susceptible mosquito homogenate and purified recombinant wild-type (WT) An. gambiae AChE (AgAChE).", "output": {"entities": {"chemical": [{"text": "carbamate", "start": 76, "end": 85}]}}, "schema": []}
{"input": "Similarly, excellent correspondence is seen between inhibition potencies measured with carbamate-resistant mosquito homogenate and purified recombinant G119S AgAChE, consistent with our earlier finding that the Akron strain carries the G119S mutation.", "output": {"entities": {"chemical": [{"text": "carbamate", "start": 87, "end": 96}]}}, "schema": []}
{"input": "Although high (100-to 500-fold) WT An. gambiae vs human selectivity is observed for several compounds, none of the carbamates tested potently inhibits the G119S mutant enzyme.", "output": {"entities": {"chemical": [{"text": "carbamates", "start": 115, "end": 125}]}}, "schema": []}
{"input": "Finally, we describe a predictive model for WT An. gambiae tarsal contact toxicity of the carbamates that relies on inhibition potency, molecular volume, and polar surface area.", "output": {"entities": {"chemical": [{"text": "carbamates", "start": 90, "end": 100}]}}, "schema": []}
{"input": "Single molecule sensing with solid-state nanopores: novel materials, methods, and applications.", "output": {"entities": {}}, "schema": []}
{"input": "This tutorial review will introduce and explore the fundamental aspects of nanopore (bio) sensing, fabrication, modification, and the emerging technologies and applications that both intrigue and inspire those working in and around the field.", "output": {"entities": {}}, "schema": []}
{"input": "Although nanopores can be classified into two categories, solid-state and biological, they are essentially two sides of the same coin.", "output": {"entities": {}}, "schema": []}
{"input": "For instance, both garner popularity due to their ability to confine analytes of interest to a nanoscale volume.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the vast diversity of nanopore platforms and applications, no single review can cover the entire landscape of published work in the field.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, in this article focus will be placed on recent advancements and developments taking place in the field of solid-state nanopores.", "output": {"entities": {}}, "schema": []}
{"input": "It should be stated that the intention of this tutorial review is not to cite all articles relating to solid-state nanopores, but rather to highlight recent, select developments that will hopefully benefit the new and seasoned scientist alike.", "output": {"entities": {}}, "schema": []}
{"input": "Initially we begin with the fundamentals of solid-state nanopore sensing.", "output": {"entities": {}}, "schema": []}
{"input": "Then the spotlight is shone on the sophisticated fabrication methods that have their origins in the semiconductor industry.", "output": {"entities": {}}, "schema": []}
{"input": "One inherent advantage of solid-state nanopores is in the ease of functionalizing the surface with a range of molecules carrying functional groups.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, an entire section is devoted to highlighting various chemical and bio-molecular modifications and explores how these permit the development of novel sensors with specific targets and functions.", "output": {"entities": {}}, "schema": []}
{"input": "The review is completed with a discussion on novel detection strategies using nanopores.", "output": {"entities": {}}, "schema": []}
{"input": "Although the most popular mode of nanopore sensing is based upon what has come to be known as ionic-current blockade sensing, there is a vast, growing literature based around exploring alternative detection techniques to further expand on the versatility of the sensors.", "output": {"entities": {}}, "schema": []}
{"input": "Such techniques include optical, electronic, and force based methods.", "output": {"entities": {}}, "schema": []}
{"input": "It is perhaps fair to say that these new frontiers have caused further excitement within the sensing community.", "output": {"entities": {}}, "schema": []}
{"input": "Meta-analysis of vertebral augmentation compared with conservative treatment for osteoporotic spinal fractures.", "output": {"entities": {}}, "schema": []}
{"input": "Cement augmentation is a controversial treatment for painful vertebral compression fractures (VCF).", "output": {"entities": {}}, "schema": []}
{"input": "Our research questions for the meta-analysis were: Is there a clinical and statistical difference in pain relief, functional improvement, and quality of life between conservative care and cement augmentation for VCF and, if so, are they maintained at longer time points?", "output": {"entities": {}}, "schema": []}
{"input": "We conducted a search of MEDLINE from January 1980 to July 2011 using PubMed, Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE.", "output": {"entities": {}}, "schema": []}
{"input": "Searches were performed from medical subject headings.", "output": {"entities": {}}, "schema": []}
{"input": "Terms \" vertebroplasty \" and \" compression fracture \" were used.", "output": {"entities": {}}, "schema": []}
{"input": "The outcome variables of pain, functional measures, health-related quality of life (HRQOL), and new fracture risk were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "A random effects model was chosen.", "output": {"entities": {}}, "schema": []}
{"input": "Continuous variables were calculated using the standardized mean difference comparing improvement from baseline of the experimental group with the control group.", "output": {"entities": {}}, "schema": []}
{"input": "New vertebral fracture risk was calculated using log odds ratio.", "output": {"entities": {}}, "schema": []}
{"input": "Six studies met the criteria.", "output": {"entities": {}}, "schema": []}
{"input": "The pain visual analog scale (VAS) mean difference was 0. 73 (confidence interval [CI] 0. 35, 1. 10) for early (< 12 weeks) and 0. 58 (CI 0. 19, 0. 97) for late time points (6 to 12 months), favoring vertebroplasty (p < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "The functional outcomes at early and late time points were statistically significant with 1. 08 (CI 0. 33, 1. 82) and 1. 16 (CI 0. 14, 2. 18), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The HRQOL showed superior results of vertebroplasty compared with conservative care at early and late time points of 0. 39 (CI 0. 16, 0. 62) and 0. 33 (CI 0. 16, 0. 51), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary fractures were not statistically different between the groups, 0. 065 (CI-0. 57, 0. 70).", "output": {"entities": {}}, "schema": []}
{"input": "This meta-analysis showed greater pain relief, functional recovery, and health-related quality of life with cement augmentation compared with controls.", "output": {"entities": {}}, "schema": []}
{"input": "Cement augmentation results were significant in the early (< 12 weeks) and the late time points (6 to 12 months).", "output": {"entities": {}}, "schema": []}
{"input": "This meta-analysis provides strong evidence in favor of cement augmentation in the treatment of symptomatic VCF fractures.", "output": {"entities": {}}, "schema": []}
{"input": "Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia.", "output": {"entities": {}}, "schema": []}
{"input": "X-linked hypophosphatemia (XLH/HYP)-with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses-is caused by mutations in the zinc-metallopeptidase PHEX gene (phosphate-regulating gene with homologies to endopeptidase on the X chromosome).", "output": {"entities": {"chemical": [{"text": "zinc", "start": 148, "end": 152}, {"text": "phosphate", "start": 181, "end": 190}]}}, "schema": []}
{"input": "PHEX is highly expressed by mineralized tissue cells.", "output": {"entities": {}}, "schema": []}
{"input": "Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization-inhibiting, acidic serine-and aspartate-rich motif (ASARM)-containing peptides, which are proteolytically derived from the mineral-binding matrix proteins of the SIBLING family (small, integrin-binding ligand N-linked glycoproteins).", "output": {"entities": {"chemical": [{"text": "serine", "start": 203, "end": 209}, {"text": "aspartate", "start": 214, "end": 223}]}}, "schema": []}
{"input": "Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein (s) have not been identified.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we investigated two SIBLING proteins containing the ASARM motif-osteopontin (OPN) and bone sialoprotein (BSP)-as potential substrates for PHEX.", "output": {"entities": {}}, "schema": []}
{"input": "Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full-length protein substrate for PHEX.", "output": {"entities": {}}, "schema": []}
{"input": "Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments.", "output": {"entities": {}}, "schema": []}
{"input": "Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ~ 35 kDa OPN fragment that was not present in wild-type mouse bone.", "output": {"entities": {}}, "schema": []}
{"input": "Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild-type bone.", "output": {"entities": {}}, "schema": []}
{"input": "Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, these results identify full-length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization-inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP.", "output": {"entities": {}}, "schema": []}
{"input": "Valproic acid but not D-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans.", "output": {"entities": {"chemical": [{"text": "Valproic acid", "start": 0, "end": 13}, {"text": "D-cycloserine", "start": 22, "end": 35}]}}, "schema": []}
{"input": "The effectiveness of D-cycloserine (DCS), an N-methyl-D-aspartate glutamate receptor partial agonist, and valproic acid (VPA), a histone deacetylase inhibitor, in facilitating the extinction of fear-conditioned memory has been explored in humans and animals.", "output": {"entities": {"chemical": [{"text": "D-cycloserine", "start": 21, "end": 34}, {"text": "DCS", "start": 36, "end": 39}, {"text": "N-methyl-D-aspartate glutamate", "start": 45, "end": 75}, {"text": "valproic acid", "start": 106, "end": 119}, {"text": "VPA", "start": 121, "end": 124}]}}, "schema": []}
{"input": "Here, we confirmed whether DCS (100 mg) and VPA (400 mg) act in off-line learning processes during sleep or waking, for further clinical application to anxiety disorders and posttraumatic stress disorder (PTSD).", "output": {"entities": {"chemical": [{"text": "DCS", "start": 27, "end": 30}, {"text": "VPA", "start": 44, "end": 47}]}}, "schema": []}
{"input": "We performed a randomized, blind, placebo-controlled clinical trial in 90 healthy adults.", "output": {"entities": {}}, "schema": []}
{"input": "Visual cues and electric shocks were used as the conditioned stimulus (CS) and unconditioned stimulus (US), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The extinction effect was observed not in simple recall after the extinction of coupled CS-US, but was observed in the post-re-exposure phase after unexpected re-exposure to reinstatement CS-US coupling.", "output": {"entities": {}}, "schema": []}
{"input": "Newly acquired conditioned fear was also eliminated or habituated by DCS and VPA administration, in line with previous findings.", "output": {"entities": {"chemical": [{"text": "DCS", "start": 69, "end": 72}, {"text": "VPA", "start": 77, "end": 80}]}}, "schema": []}
{"input": "Furthermore, VPA facilitated the off-line learning process of conditioned fear extinction and habituation during sleep, while DCS facilitated this process during waking.", "output": {"entities": {"chemical": [{"text": "VPA", "start": 13, "end": 16}, {"text": "DCS", "start": 126, "end": 129}]}}, "schema": []}
{"input": "These novel findings suggest that DCS and VPA might enhance exposure-based cognitive therapy for anxiety disorders and PTSD by reducing the vulnerability to reinstatement and preventing relapses of fear-conditioned responses, and provide evidence for a peculiarity of the sleep-dependent off-line learning process for conditioned fear extinction.", "output": {"entities": {"chemical": [{"text": "DCS", "start": 34, "end": 37}, {"text": "VPA", "start": 42, "end": 45}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Cognitive Enhancers'.", "output": {"entities": {}}, "schema": []}
{"input": "Acute effects of caffeine on attention: a comparison of non-consumers and withdrawn consumers.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 17, "end": 25}]}}, "schema": []}
{"input": "Despite the large number of studies on caffeine and attention, interpretation is often difficult because of methodological weaknesses.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 39, "end": 47}]}}, "schema": []}
{"input": "In the present study, use of a small battery of tests with four key outcome measures, combined with an appropriate sample size, addresses many of these problems.", "output": {"entities": {}}, "schema": []}
{"input": "This methodology was used to examine whether effects of caffeine (a dose of 2 mg/kg) could be explained in terms of reversal of the effects of caffeine withdrawal.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 56, "end": 64}, {"text": "caffeine", "start": 143, "end": 151}]}}, "schema": []}
{"input": "This was achieved by examining effects in non-consumers (N = 35), who could not be withdrawn, and also in a group of consumers (N = 35) who had undergone withdrawal for a week and no longer reported symptoms of withdrawal.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed no effect of short-term withdrawal on the performance measures, even though subjective reports showed an increase in symptoms after withdrawal.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the caffeine challenge carried out on Day 8 showed that ingestion of caffeine was associated with faster simple reaction time, fewer long responses, greater detection of targets in the cognitive vigilance task, and faster encoding of new information.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 17, "end": 25}, {"text": "caffeine", "start": 82, "end": 90}]}}, "schema": []}
{"input": "These results suggest that it is important to continue to investigate mechanisms underlying these effects of caffeine and to further evaluate the practical implications of such effects.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 109, "end": 117}]}}, "schema": []}
{"input": "Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 24, "end": 34}]}}, "schema": []}
{"input": "It has recently been reported that iron oxide nanoparticles (Fe (3) O (4)-NPs, 30 nm) have the ability to translocate directly from the olfactory nerve to the brain.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 35, "end": 45}, {"text": "Fe (3) O (4)", "start": 61, "end": 73}]}}, "schema": []}
{"input": "The striatum and hippocampus are important structures in the brain and are associated with the development of Parkinson' s and Alzheimer' s diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, it is critical to evaluate Fe (3) O (4)-NPs and their potential to confer striatum and hippocampus neurotoxicity.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 38, "end": 50}]}}, "schema": []}
{"input": "This study focuses on the effects of Fe (3) O (4)-NPs on the striatum and hippocampus, including oxidative injury and the accumulation and retention of Fe (3) O (4)-NPs.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 37, "end": 49}, {"text": "Fe (3) O (4)", "start": 152, "end": 164}]}}, "schema": []}
{"input": "This study also explores the molecular mechanism of oxidative damage in dopaminergic neurons; we were able to assess the neurotoxic effects of Fe (3) O (4)-NPs by incubating dopaminergic neurons with radioactive Fe (3) O (4)-NPs.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 143, "end": 155}, {"text": "Fe (3) O (4)", "start": 212, "end": 224}]}}, "schema": []}
{"input": "A regional distribution of Fe (3) O (4)-NPs was observed in rat brains after the particles were intranasally instilled for seven days.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 27, "end": 39}]}}, "schema": []}
{"input": "The particles were found to be deposited at particularly high concentrations in the rat striata and hippocampi.", "output": {"entities": {}}, "schema": []}
{"input": "Over half of the Fe (3) O (4)-NPs were retained in the striata for a minimum of 14 days, and may have induced oxidative damage to the region.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 17, "end": 29}]}}, "schema": []}
{"input": "However, no injuries were observed in the hippocampi.", "output": {"entities": {}}, "schema": []}
{"input": "These in vitro studies demonstrate that Fe (3) O (4)-NPs may decrease neuron viability, trigger oxidative stress, and activate JNK-and p53-mediated pathways to regulate the cell cycle and apoptosis.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 40, "end": 52}]}}, "schema": []}
{"input": "These results also suggest that environmental exposure to Fe (3) O (4)-NPs may play a role in the development of neurodegenerative diseases.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 58, "end": 70}]}}, "schema": []}
{"input": "Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B.", "output": {"entities": {"chemical": [{"text": "epothilone A and B", "start": 82, "end": 100}]}}, "schema": []}
{"input": "Epothilones are a new group of compounds with action mechanisms similar to taxanes.", "output": {"entities": {"chemical": [{"text": "Epothilones", "start": 0, "end": 11}, {"text": "taxanes", "start": 75, "end": 82}]}}, "schema": []}
{"input": "The aim of this study was to compare the effects of epothilone A (Epo A) and epothilone B (Epo B) on ovarian cancer cell line SKOV-3 with those of paclitaxel (PTX), a classic taxane.", "output": {"entities": {"chemical": [{"text": "epothilone A", "start": 52, "end": 64}, {"text": "Epo A", "start": 66, "end": 71}, {"text": "epothilone B", "start": 77, "end": 89}, {"text": "Epo B", "start": 91, "end": 96}, {"text": "paclitaxel", "start": 147, "end": 157}, {"text": "PTX", "start": 159, "end": 162}, {"text": "taxane", "start": 175, "end": 181}]}}, "schema": []}
{"input": "We evaluate glycoprotein P (P-gp) activity in the ovarian cancer cell line.", "output": {"entities": {}}, "schema": []}
{"input": "Apoptotic and necrotic cell levels were measured by double staining with Hoechst 33258 and propidium iodide (PI) as well as Annexin V staining.", "output": {"entities": {"chemical": [{"text": "Hoechst 33258", "start": 73, "end": 86}, {"text": "propidium iodide", "start": 91, "end": 107}]}}, "schema": []}
{"input": "The production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (Delta Psi m) in cells exposed to Epo A, Epo B and PTX were studied using specific fluorescence probes, DCFH (2)-DA (2', 7'-dichlorodihydrofluorescein diacetate) and JC-1 (5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolcarbocyanine).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 27, "end": 33}, {"text": "Epo A", "start": 130, "end": 135}, {"text": "Epo B", "start": 137, "end": 142}, {"text": "PTX", "start": 147, "end": 150}, {"text": "DCFH (2)-DA", "start": 200, "end": 211}, {"text": "2', 7'-dichlorodihydrofluorescein diacetate", "start": 213, "end": 256}, {"text": "JC-1", "start": 262, "end": 266}, {"text": "5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolcarbocyanine", "start": 268, "end": 340}]}}, "schema": []}
{"input": "The cytotoxic activity of the drugs was determined by the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide) test.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 58, "end": 61}, {"text": "3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide", "start": 63, "end": 125}]}}, "schema": []}
{"input": "All probes were analyzed in both the presence and absence of the antioxidant N-acetylcysteine (NAC).", "output": {"entities": {"chemical": [{"text": "N-acetylcysteine", "start": 77, "end": 93}, {"text": "NAC", "start": 95, "end": 98}]}}, "schema": []}
{"input": "The results obtained demonstrated that the antiproliferative capacity of Epo A and Epo B in SKOV-3 cell line (measured as IC (50) after 72 h continuous treatment) was six and five times greater than that of PTX' s respectively.", "output": {"entities": {"chemical": [{"text": "Epo A", "start": 73, "end": 78}, {"text": "Epo B", "start": 83, "end": 88}, {"text": "PTX", "start": 207, "end": 210}]}}, "schema": []}
{"input": "Epothilones induced timecourse-dependent apoptosis and necrosis.", "output": {"entities": {"chemical": [{"text": "Epothilones", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Apoptotic and necrotic events were partially blocked by NAC, indicating ROS played a substantial role in epothilone-induced apoptosis.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 56, "end": 59}, {"text": "epothilone", "start": 105, "end": 115}]}}, "schema": []}
{"input": "Cell death was also associated with a decrease in mitochondrial membrane potential, which was more pronounced after treatment with epothilones as compared to paclitaxel.", "output": {"entities": {"chemical": [{"text": "epothilones", "start": 131, "end": 142}, {"text": "paclitaxel", "start": 158, "end": 168}]}}, "schema": []}
{"input": "Pitch-tunable size reduction patterning with a temperature-memory polymer.", "output": {"entities": {}}, "schema": []}
{"input": "A scalable and pitch-tunable size reduction patterning method is introduced by exploiting the temperature memory effect of shape memory polymer and replica molding of UV-curable materials.", "output": {"entities": {}}, "schema": []}
{"input": "Enhanced oral bioavailability of isradipine via proniosomal systems.", "output": {"entities": {"chemical": [{"text": "isradipine", "start": 33, "end": 43}]}}, "schema": []}
{"input": "The objective of the present research was to develop a proniosomal formulation of isradipine and to evaluate the influence of proniosomal systems on the oral bioavailability of the drug in albino Wistar rats.", "output": {"entities": {"chemical": [{"text": "isradipine", "start": 82, "end": 92}]}}, "schema": []}
{"input": "Proniosomes were prepared by film deposition on carrier' s method using various molar ratios of nonionic surfactants such as span20, span40, span60, and span80 with cholesterol as membrane stabilizing agent and dicetylphosphate as a charge inducer.", "output": {"entities": {"chemical": [{"text": "span20", "start": 125, "end": 131}, {"text": "span40", "start": 133, "end": 139}, {"text": "span60", "start": 141, "end": 147}, {"text": "span80", "start": 153, "end": 159}, {"text": "cholesterol", "start": 165, "end": 176}, {"text": "dicetylphosphate", "start": 211, "end": 227}]}}, "schema": []}
{"input": "The formation of niosomes and surface morphology of proniosome formulations were studied by optical and scanning electron microscopy (SEM), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The prepared proniosomes have shown higher dissolution of isradipine compared with pure drug powder.", "output": {"entities": {"chemical": [{"text": "isradipine", "start": 58, "end": 68}]}}, "schema": []}
{"input": "Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry studies were performed to understand the solid state properties of the drug.", "output": {"entities": {}}, "schema": []}
{"input": "Ex vivo permeation enhancement assessed from flux, permeability coefficient, and enhancement ratio were significantly higher for proniosomes compared with control.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacokinetic parameters were evaluated in male albino Wistar rats and a significant enhancement in the bioavailability (2. 3-fold) was observed from optimized proniosome formulation compared with control (oral suspension).", "output": {"entities": {}}, "schema": []}
{"input": "The stability study reveals that the proniosome formulations are stable when stored at 4 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "A current opinion on electrophoretic deposition in pulsed and alternating fields.", "output": {"entities": {}}, "schema": []}
{"input": "Electrophoretic deposition (EPD) is a colloidal production process developed in the early 20th century.", "output": {"entities": {}}, "schema": []}
{"input": "Industrial scale EPD for the production of electronic components and phosphorescent screens and in the form of cataphoretic painting has known some success.", "output": {"entities": {}}, "schema": []}
{"input": "Despite its limited practical applications, the inherent versatility of EPD has never ceased to fuel research into this technique.", "output": {"entities": {}}, "schema": []}
{"input": "One of the major drives of this research was to render the method more environmentally friendly by enabling deposition from aqueous suspensions.", "output": {"entities": {}}, "schema": []}
{"input": "One particular route, suggested to circumvent the problems caused by the use of water in EPD, is the use of alternating or pulsed fields.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, the use of alternating fields in EPD has been investigated for the deposition of biological matter in the form of cells and molecules.", "output": {"entities": {}}, "schema": []}
{"input": "With this new avenue of research opening up and coinciding with a rise in biotechnological processes, one can expect a renewed interest in traditional EPD and fundamental research on the use of pulsed and alternating fields in this technique.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, this review attempts to summarize a century' s worth of both fundamental and applied research for scientists venturing into the field of EPD.", "output": {"entities": {}}, "schema": []}
{"input": "Combination of beta-cyclodextrin inclusion complex and self-microemulsifying drug delivery system for photostability and enhanced oral bioavailability of methotrexate: novel technique.", "output": {"entities": {"chemical": [{"text": "beta-cyclodextrin", "start": 15, "end": 32}, {"text": "methotrexate", "start": 154, "end": 166}]}}, "schema": []}
{"input": "In the present study, we prepared an inclusion complex of methotrexate (MTX) with beta-cyclodextrin (beta-CD) in order to decrease its photosensitivity and enhance its aqueous solubility.", "output": {"entities": {"chemical": [{"text": "methotrexate", "start": 58, "end": 70}, {"text": "MTX", "start": 72, "end": 75}, {"text": "beta-cyclodextrin", "start": 82, "end": 99}, {"text": "beta-CD", "start": 101, "end": 108}]}}, "schema": []}
{"input": "Then we incorporated this inclusion complex in a self-microemulsifying drug delivery system (SMEDDS) overall to increase its oral bioavailability.", "output": {"entities": {}}, "schema": []}
{"input": "The inclusion complex has been prepared by freeze drying method and characterized by differential scanning calorimetry (DSC), ultraviolet (UV), and infrared (IR) spectroscopy assays.", "output": {"entities": {}}, "schema": []}
{"input": "The proper molecular ratio of MTX/beta-CD was found to be of 1: 7, and the water-solubility of MTX was increased in an average of 10-fold.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 30, "end": 33}, {"text": "beta-CD", "start": 34, "end": 41}, {"text": "MTX", "start": 95, "end": 98}]}}, "schema": []}
{"input": "The photostability studies showed that the MTX became stable on exposure to light.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 43, "end": 46}]}}, "schema": []}
{"input": "Construction of pseudoternary diagrams were investigated to prepare a MTX/beta-CD inclusion complex loaded SMEDDS which was characterized by measuring the particle size and the zeta-potential.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 70, "end": 73}, {"text": "beta-CD", "start": 74, "end": 81}]}}, "schema": []}
{"input": "The optimum formulation of SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol with a mean droplet size of 39. 42 nm.", "output": {"entities": {"chemical": [{"text": "ethyl oleate", "start": 61, "end": 73}, {"text": "tween 80", "start": 75, "end": 83}, {"text": "propylene glycol", "start": 89, "end": 105}]}}, "schema": []}
{"input": "In vitro drug release in different pH media showed that the release profile of MTX from the MTX/beta-CD loaded SMEDDS was influenced by the pH of the release medium and presented the characteristics of a sustained release profile.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 79, "end": 82}, {"text": "MTX", "start": 92, "end": 95}, {"text": "beta-CD", "start": 96, "end": 103}]}}, "schema": []}
{"input": "Finally, in-vivo studies showed an enhancement of the bioavailability of MTX from the MTX/beta-CD loaded SMEDDS form of 1. 57-fold.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 73, "end": 76}, {"text": "MTX", "start": 86, "end": 89}, {"text": "beta-CD", "start": 90, "end": 97}]}}, "schema": []}
{"input": "We concluded that the beta-CD inclusion complex loaded SMEDDS improved the chemical and physiological properties of MTX and could be a promising means for the delivery of MTX and other unstable and lipophilic drugs by oral route.", "output": {"entities": {"chemical": [{"text": "beta-CD", "start": 22, "end": 29}, {"text": "MTX", "start": 116, "end": 119}, {"text": "MTX", "start": 171, "end": 174}]}}, "schema": []}
{"input": "Prospects of personalized medicine in cardiovascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiovascular diseases remain the dominant cause of death worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "In the last decades, the remarkable advances in human genetic and genomic research, plus the now common use of genome-wide association studies, have led to the identification of numerous genetic variants associated with specific cardiovascular traits and diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Although the clinical applications are limited because the genetic risk of common cardiovascular disease is still unexplained, and the mechanisms of action of the genetic factor (s) are not known, these research advances have, in turn, widely opened the concept of personalized medicine.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, the status and prospects of personalized medicine for cardiovascular disease will be presented.", "output": {"entities": {}}, "schema": []}
{"input": "This will be followed by a discussion of issues regarding the implementation of personalized medicine.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistic systems modeling to guide drug discovery and development.", "output": {"entities": {}}, "schema": []}
{"input": "A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials.", "output": {"entities": {}}, "schema": []}
{"input": "Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli.", "output": {"entities": {}}, "schema": []}
{"input": "Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research.", "output": {"entities": {}}, "schema": []}
{"input": "Snake venom metalloproteinases.", "output": {"entities": {}}, "schema": []}
{"input": "Recent proteomic analyses of snake venoms show that metalloproteinases represent major components in most of the Crotalid and Viperid venoms.", "output": {"entities": {}}, "schema": []}
{"input": "In this chapter we discuss the multiple activities of the SVMPs.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to hemorrhagic activity, members of the SVMP family also have fibrin (ogen) olytic activity, act as prothrombin activators, activate blood coagulation factor X, possess apoptotic activity, inhibit platelet aggregation, are pro-inflammatory and inactivate blood serine proteinase inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Clearly the SVMPs have multiple functions in addition to their well-known hemorrhagic activity.", "output": {"entities": {}}, "schema": []}
{"input": "The realization that there are structural variations in the SVMPs and the early studies that led to their classification represents an important event in our understanding of the structural forms of the SVMPs.", "output": {"entities": {}}, "schema": []}
{"input": "The SVMPs were subdivided into the P-I, P-II and P-III protein classes.", "output": {"entities": {}}, "schema": []}
{"input": "The noticeable characteristic that distinguished the different classes was their size (molecular weight) differences and domain structure: Class I (P-I), the small SVMPs, have molecular masses of 20-30 kDa, contain only a pro domain and the proteinase domain; Class II (P-II), the medium size SVMPs, molecular masses of 30-60 kDa, contain the pro domain, proteinase domain and disintegrin domain; Class III (P-III), the large SVMPs, have molecular masses of 60-100 kDa, contain pro, proteinase, disintegrin-like and cysteine-rich domain structure.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 516, "end": 524}]}}, "schema": []}
{"input": "Another significant advance in the SVMP field was the characterization of the crystal structure of the first P-I class SVMP.", "output": {"entities": {}}, "schema": []}
{"input": "The structures of other P-I SVMPs soon followed and the structures of P-III SVMPs have also been determined.", "output": {"entities": {}}, "schema": []}
{"input": "The active site of the metalloproteinase domain has a consensus HEXXHXXGXXHD sequence and a Met-turn.", "output": {"entities": {"chemical": [{"text": "Met", "start": 92, "end": 95}]}}, "schema": []}
{"input": "The \" Met-turn \" structure contains a conserved Met residue that forms a hydrophobic basement for the three zinc-binding histidines in the consensus sequence.", "output": {"entities": {"chemical": [{"text": "Met", "start": 6, "end": 9}, {"text": "Met", "start": 48, "end": 51}, {"text": "zinc", "start": 108, "end": 112}, {"text": "histidines", "start": 121, "end": 131}]}}, "schema": []}
{"input": "Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway.", "output": {"entities": {"chemical": [{"text": "Wogonoside", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Previous studies have demonstrated that wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Gerogi, has anti-inflammatory and anti-angiogenic activities.", "output": {"entities": {"chemical": [{"text": "wogonoside", "start": 40, "end": 50}, {"text": "flavonoid", "start": 64, "end": 73}]}}, "schema": []}
{"input": "In this study, we evaluated wogonoside-induced autophagy on human breast MDA-MB-231 cells.", "output": {"entities": {"chemical": [{"text": "wogonoside", "start": 28, "end": 38}]}}, "schema": []}
{"input": "We report that wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells.", "output": {"entities": {"chemical": [{"text": "wogonoside", "start": 15, "end": 25}]}}, "schema": []}
{"input": "In addition, cells treated by wogonoside developed autophagosome-like characteristics, including single and double membrane vacuoles containing intact and degraded cellular debris.", "output": {"entities": {"chemical": [{"text": "wogonoside", "start": 30, "end": 40}]}}, "schema": []}
{"input": "The results showed that wogonoside promotes the expression of LC3-II and Beclin-1.", "output": {"entities": {"chemical": [{"text": "wogonoside", "start": 24, "end": 34}]}}, "schema": []}
{"input": "Furthermore, wogonoside inhibited cell growth of MDA-MB-231 cells in a concentration-and time-dependent manner, which was associated with wogonoside-induced autophagy.", "output": {"entities": {"chemical": [{"text": "wogonoside", "start": 13, "end": 23}, {"text": "wogonoside", "start": 138, "end": 148}]}}, "schema": []}
{"input": "Wogonoside also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway.", "output": {"entities": {"chemical": [{"text": "Wogonoside", "start": 0, "end": 10}, {"text": "rapamycin", "start": 65, "end": 74}]}}, "schema": []}
{"input": "Taken together, these results suggest that wogonoside partially inhibits MDA-MB-231 cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a promising anti-tumor agent.", "output": {"entities": {"chemical": [{"text": "wogonoside", "start": 43, "end": 53}]}}, "schema": []}
{"input": "Water extracts of tree Hypericum sps. protect DNA from oxidative and alkylating damage and enhance DNA repair in colon cells.", "output": {"entities": {}}, "schema": []}
{"input": "Diet may induce colon carcinogenesis through oxidative or alkylating DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "However, diet may also contain anticarcinogenic compounds that contribute to cancer prevention.", "output": {"entities": {}}, "schema": []}
{"input": "DNA damage prevention and/or induction of repair are two important mechanisms involved in cancer chemoprevention by dietary compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Hypericum sps. are widely used in traditional medicine to prepare infusions due to their beneficial digestive and neurologic effects.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated the potential of water extracts from three Hypericum sps. and some of their main phenolic compounds to prevent and repair oxidative and alkylating DNA damage in colon cells.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 112, "end": 120}]}}, "schema": []}
{"input": "The results showed that water extracts of Hypericum perforatum, Hypericum androsaemum, Hypericum undulatum, quercetin and rutin have protective effect against oxidative DNA damage in HT29 cells.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 108, "end": 117}, {"text": "rutin", "start": 122, "end": 127}]}}, "schema": []}
{"input": "Protective effect was also observed against alkylating DNA damage induced by methyl-methanesulfonate, except for H. androsaemum.", "output": {"entities": {"chemical": [{"text": "methyl-methanesulfonate", "start": 77, "end": 100}]}}, "schema": []}
{"input": "With regard to alkylating damage repair H. perforatum, H. androsaemum and chlorogenic acid increased repair of alkylating DNA damage by base excision repair pathway.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 74, "end": 90}]}}, "schema": []}
{"input": "No effect was observed on nucleotide excision repair pathway.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 26, "end": 36}]}}, "schema": []}
{"input": "Antigenotoxic effects of Hypericum sps. may contribute to colon cancer prevention and the high amount of phenolic compounds present in Hypericum sps. play an important role in DNA protective effects.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 105, "end": 113}]}}, "schema": []}
{"input": "Ion disturbance and clustering in the NaCl water solutions.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 38, "end": 42}]}}, "schema": []}
{"input": "Ion clustering and the solvation properties in the NaCl solutions are explored by molecular dynamics simulations with several popular force fields.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 51, "end": 55}]}}, "schema": []}
{"input": "The existence of ions has a negligible disturbance to the hydrogen bond structures and rotational mobility of water beyond the first ion solvation shells, which is suggested by the local hydrogen bond structures and the rotation times of water.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 58, "end": 66}, {"text": "hydrogen", "start": 187, "end": 195}]}}, "schema": []}
{"input": "The potential of mean force (PMF) of ion pair in the dilute solution presents a consistent view with the populations of ion clusters in the electrolyte solutions.", "output": {"entities": {}}, "schema": []}
{"input": "The aggregation level of ions is sensitive to the force field used in the simulations.", "output": {"entities": {}}, "schema": []}
{"input": "The ion-ion interaction potential plays an important role in the forming of the contact ion pair.", "output": {"entities": {}}, "schema": []}
{"input": "The entropy of water increases as the ion pair approaches each other and the association of ion pair is driven by the increment of water entropy according to the results from the selected force fields.", "output": {"entities": {}}, "schema": []}
{"input": "The kinetic transition from the single solvent separated state to the contact ion pair is controlled by the enthalpy loss of solution.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of surfactant and solvent on spin-lattice relaxation dynamics of magnetic nanocrystals.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of varying the surfactant and solvent medium on the dynamics of spin-lattice relaxation in photoexcited Fe3O4 nanocrystals has been investigated by measuring the time-dependent magnetization employing pump-probe transient Faraday rotation technique.", "output": {"entities": {"chemical": [{"text": "Fe3O4", "start": 115, "end": 120}]}}, "schema": []}
{"input": "The variation of the surfactants having surface-binding functional groups modified not only the static magnetization but also the dynamics of the recovery of the magnetization occurring via spin-lattice relaxation in the photoexcited Fe3O4 nanocrystals.", "output": {"entities": {"chemical": [{"text": "Fe3O4", "start": 234, "end": 239}]}}, "schema": []}
{"input": "The variation of the polarity and size of the solvent molecules can also influence the spin-lattice relaxation dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "However, the effect is limited to the nanocrystals having sufficiently permeable surfactant layer, where the small solvent molecules (e. g., water) can access the surface and dynamically modify the ligand field on the surface.", "output": {"entities": {}}, "schema": []}
{"input": "Lattice Microbes: high-performance stochastic simulation method for the reaction-diffusion master equation.", "output": {"entities": {}}, "schema": []}
{"input": "Spatial stochastic simulation is a valuable technique for studying reactions in biological systems.", "output": {"entities": {}}, "schema": []}
{"input": "With the availability of high-performance computing (HPC), the method is poised to allow integration of data from structural, single-molecule and biochemical studies into coherent computational models of cells.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we introduce the Lattice Microbes software package for simulating such cell models on HPC systems.", "output": {"entities": {}}, "schema": []}
{"input": "The software performs either well-stirred or spatially resolved stochastic simulations with approximated cytoplasmic crowding in a fast and efficient manner.", "output": {"entities": {}}, "schema": []}
{"input": "Our new algorithm efficiently samples the reaction-diffusion master equation using NVIDIA graphics processing units and is shown to be two orders of magnitude faster than exact sampling for large systems while maintaining an accuracy of! 0. 1%.", "output": {"entities": {}}, "schema": []}
{"input": "Display of cell models and animation of reaction trajectories involving millions of molecules is facilitated using a plug-in to the popular VMD visualization platform.", "output": {"entities": {}}, "schema": []}
{"input": "The Lattice Microbes software is open source and available for download at http://www. scs. illinois. edu/schulten/lm", "output": {"entities": {}}, "schema": []}
{"input": "Pituitary metastasis of thyroid cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Pituitary metastases (PM) from thyroid cancer are rare, but their management can represent a difficult challenge for the endocrinologist.", "output": {"entities": {}}, "schema": []}
{"input": "Our aim was to review all reported cases of PM from thyroid cancer.", "output": {"entities": {}}, "schema": []}
{"input": "PubMed was consulted and 19 papers reporting 20 cases were found.", "output": {"entities": {}}, "schema": []}
{"input": "We moreover discuss two of our own cases, which had come to our attention within a few months of one another.", "output": {"entities": {}}, "schema": []}
{"input": "Eleven cases were follicular cancer, eight cases were papillary cancer, two cases were medullary cancer, and one case was an insular cancer.", "output": {"entities": {}}, "schema": []}
{"input": "In nine cases, PM was the first sign of the disease.", "output": {"entities": {}}, "schema": []}
{"input": "Cranial nerve involvement was the most common sign of its presence, and no neuroradiological imaging could lead to a sure diagnosis of PM.", "output": {"entities": {}}, "schema": []}
{"input": "Neurosurgical intervention was performed in almost all cases, and post-surgical treatment comprised radioiodine, external beam radiotherapy, and radiosurgery.", "output": {"entities": {"chemical": [{"text": "radioiodine", "start": 100, "end": 111}]}}, "schema": []}
{"input": "Prognosis was poor for larger metastases, cranial nerve palsy disappeared in only one case, and in only one case of intrasellar metastasis was the disease cured.", "output": {"entities": {}}, "schema": []}
{"input": "PM from thyroid cancer are rare, but are burdened by a poor prognosis.", "output": {"entities": {}}, "schema": []}
{"input": "An early diagnosis appears important, and a comprehensive strategy for treatment (neurosurgery, radioiodine, external radiotherapy, and radiosurgery) appears advisable.", "output": {"entities": {"chemical": [{"text": "radioiodine", "start": 96, "end": 107}]}}, "schema": []}
{"input": "A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 57, "end": 63}]}}, "schema": []}
{"input": "Inhibition of cardiac late sodium current (late I (Na)) is a strategy to suppress arrhythmias and sodium-dependent calcium overload associated with myocardial ischemia and heart failure.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 27, "end": 33}, {"text": "Na", "start": 51, "end": 53}, {"text": "sodium", "start": 98, "end": 104}, {"text": "calcium", "start": 115, "end": 122}]}}, "schema": []}
{"input": "Current inhibitors of late I (Na) are unselective and can be proarrhythmic.", "output": {"entities": {"chemical": [{"text": "Na", "start": 30, "end": 32}]}}, "schema": []}
{"input": "This study introduces GS967 (6-[4-(trifluoromethoxy) phenyl]-3-(trifluoromethyl)-[1, 2, 4] triazolo [4, 3-a] pyridine), a potent and selective inhibitor of late I (Na), and demonstrates its effectiveness to suppress ventricular arrhythmias.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 22, "end": 27}, {"text": "6-[4-(trifluoromethoxy) phenyl]-3-(trifluoromethyl)-[1, 2, 4] triazolo [4, 3-a] pyridine", "start": 29, "end": 117}, {"text": "Na", "start": 164, "end": 166}]}}, "schema": []}
{"input": "The effects of GS967 on rabbit ventricular myocyte ion channel currents and action potentials were determined.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 15, "end": 20}]}}, "schema": []}
{"input": "Anti-arrhythmic actions of GS967 were characterized in ex vivo and in vivo rabbit models of reduced repolarization reserve and ischemia.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 27, "end": 32}]}}, "schema": []}
{"input": "GS967 inhibited Anemonia sulcata toxin II (ATX-II)-induced late I (Na) in ventricular myocytes and isolated hearts with IC (50) values of 0. 13 and 0. 21 micro M, respectively.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 0, "end": 5}, {"text": "Na", "start": 67, "end": 69}]}}, "schema": []}
{"input": "Reduction of peak I (Na) by GS967 was minimal at a holding potential of-120 mV but increased at-80 mV.", "output": {"entities": {"chemical": [{"text": "Na", "start": 21, "end": 23}, {"text": "GS967", "start": 28, "end": 33}]}}, "schema": []}
{"input": "GS967 did not prolong action potential duration or the QRS interval.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 0, "end": 5}]}}, "schema": []}
{"input": "GS967 prevented and reversed proarrhythmic effects (afterdepolarizations and torsades de pointes) of the late I (Na) enhancer ATX-II and the I (Kr) inhibitor E-4031 in isolated ventricular myocytes and hearts.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 0, "end": 5}, {"text": "Na", "start": 113, "end": 115}, {"text": "Kr", "start": 144, "end": 146}, {"text": "E-4031", "start": 158, "end": 164}]}}, "schema": []}
{"input": "GS967 significantly attenuated the proarrhythmic effects of methoxamine + clofilium and suppressed ischemia-induced arrhythmias.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 0, "end": 5}, {"text": "methoxamine", "start": 60, "end": 71}, {"text": "clofilium", "start": 74, "end": 83}]}}, "schema": []}
{"input": "GS967 was more potent and effective to reduce late I (Na) and arrhythmias than either flecainide or ranolazine.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 0, "end": 5}, {"text": "Na", "start": 54, "end": 56}, {"text": "flecainide", "start": 86, "end": 96}, {"text": "ranolazine", "start": 100, "end": 110}]}}, "schema": []}
{"input": "Results of all studies and assays of binding and activity of GS967 at numerous receptors, transporters, and enzymes indicated that GS967 selectively inhibited late I (Na).", "output": {"entities": {"chemical": [{"text": "GS967", "start": 61, "end": 66}, {"text": "GS967", "start": 131, "end": 136}, {"text": "Na", "start": 167, "end": 169}]}}, "schema": []}
{"input": "In summary, GS967 selectively suppressed late I (Na) and prevented and/or reduced the incidence of experimentally induced arrhythmias in rabbit myocytes and hearts.", "output": {"entities": {"chemical": [{"text": "GS967", "start": 12, "end": 17}, {"text": "Na", "start": 49, "end": 51}]}}, "schema": []}
{"input": "Liquid crystalline phase nanodispersions enable skin delivery of siRNA.", "output": {"entities": {}}, "schema": []}
{"input": "The ability of small interfering RNAs (siRNAs) to potently but reversibly silence genes in vivo has made them particularly well suited as a new class of drugs that interfere with disease-causing or disease-promoting genes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the largest remaining hurdle for the widespread use of this technology in skin is the lack of an effective delivery system.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to evaluate nanodispersed systems in liquid crystalline phases that deliver siRNA into the skin.", "output": {"entities": {}}, "schema": []}
{"input": "The proposed systems present important properties for the delivery of macromolecules in a biological medium, as they are formed by substances that have absorption-enhancing and fusogenic effects; additionally, they facilitate entrapment by cellular membranes due to their nano-scale structure.", "output": {"entities": {}}, "schema": []}
{"input": "The cationic polymer polyethylenimine (PEI) or the cationic lipid oleylamine (OAM) were added to monoolein (MO)-based systems in different concentrations, and after dispersion in aqueous medium, liquid crystalline phase nanodispersions were obtained and characterized by their physicochemical properties.", "output": {"entities": {"chemical": [{"text": "polyethylenimine", "start": 21, "end": 37}, {"text": "PEI", "start": 39, "end": 42}, {"text": "oleylamine", "start": 66, "end": 76}, {"text": "OAM", "start": 78, "end": 81}, {"text": "monoolein", "start": 97, "end": 106}]}}, "schema": []}
{"input": "Then, in vitro penetration studies using diffusion cell and pig ear skin were carried out to evaluate the effect of the nanodispersions on the skin penetration of siRNA; based on these results, the nanodispersions containing MO/OA/PEI/aqueous phase (8: 2: 5: 85, w/w/w/w) and MO/OA/OAM/aqueous phase (8: 2: 2: 88, w/w/w/w) were selected.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 231, "end": 234}, {"text": "OAM", "start": 282, "end": 285}]}}, "schema": []}
{"input": "These systems were investigated in vivo for skin penetration, skin irritation, and the ability to knockdown glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein levels in animal models.", "output": {"entities": {"chemical": [{"text": "glyceraldehyde 3-phosphate", "start": 108, "end": 134}]}}, "schema": []}
{"input": "The results showed that the studied nanodispersions may represent a promising new non-viral vehicle and can be considered highly advantageous in the treatment of skin disorders; they were effective in optimizing the skin penetration of siRNA and reducing the levels of the model protein GAPDH without causing skin irritation.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract.", "output": {"entities": {}}, "schema": []}
{"input": "Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis.", "output": {"entities": {}}, "schema": []}
{"input": "Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate.", "output": {"entities": {"chemical": [{"text": "sodium dichromate", "start": 119, "end": 136}]}}, "schema": []}
{"input": "Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide.", "output": {"entities": {"chemical": [{"text": "ethidium bromide", "start": 74, "end": 90}]}}, "schema": []}
{"input": "The resulting DNA migration trails were obtained using fluorescent microscopy at 400 x magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition.", "output": {"entities": {}}, "schema": []}
{"input": "The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 137, "end": 144}, {"text": "aspartate", "start": 172, "end": 181}]}}, "schema": []}
{"input": "Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue.", "output": {"entities": {"chemical": [{"text": "hematoxylin", "start": 36, "end": 47}, {"text": "eosin", "start": 52, "end": 57}]}}, "schema": []}
{"input": "The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology.", "output": {"entities": {}}, "schema": []}
{"input": "These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds.", "output": {"entities": {"chemical": [{"text": "methylchavicol", "start": 63, "end": 77}]}}, "schema": []}
{"input": "These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications.", "output": {"entities": {}}, "schema": []}
{"input": "Function of the blood-brain barrier and restriction of drug delivery to invasive glioma cells: findings in an orthotopic rat xenograft model of glioma.", "output": {"entities": {}}, "schema": []}
{"input": "Despite aggressive treatment with radiation and chemotherapy, recurrence of glioblastoma multiforme (GBM) is inevitable.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to show that the blood-brain barrier (BBB), through a combination of tight junctions and active efflux transporters in the brain microvasculature, can significantly restrict delivery of molecularly targeted agents to invasive glioma cells.", "output": {"entities": {}}, "schema": []}
{"input": "Transgenic mice lacking P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) were used to study efflux of erlotinib at the BBB.", "output": {"entities": {"chemical": [{"text": "erlotinib", "start": 119, "end": 128}]}}, "schema": []}
{"input": "A U87 rat xenograft model of GBM was used to investigate the regional distribution of erlotinib to the tumor, and brain regions surrounding the tumor.", "output": {"entities": {"chemical": [{"text": "erlotinib", "start": 86, "end": 95}]}}, "schema": []}
{"input": "The effect of concurrent administration of elacridar on regional tumor distribution of erlotinib was evaluated.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 43, "end": 52}, {"text": "erlotinib", "start": 87, "end": 96}]}}, "schema": []}
{"input": "We show that erlotinib transport across an intact BBB is significantly restricted due to P-gp-and Bcrp-mediated efflux transport.", "output": {"entities": {"chemical": [{"text": "erlotinib", "start": 13, "end": 22}]}}, "schema": []}
{"input": "We then show that the BBB is sufficiently intact in areas of brain adjacent to the tumor core to significantly restrict erlotinib delivery.", "output": {"entities": {"chemical": [{"text": "erlotinib", "start": 120, "end": 129}]}}, "schema": []}
{"input": "Inhibition of P-gp and Bcrp by the dual inhibitor elacridar dramatically increased erlotinib delivery to the tumor core, rim, and normal brain.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 50, "end": 59}, {"text": "erlotinib", "start": 83, "end": 92}]}}, "schema": []}
{"input": "These results provide conclusive evidence of the impact that active efflux at the BBB has on the delivery of molecularly targeted therapy to different tumor regions in glioma.", "output": {"entities": {}}, "schema": []}
{"input": "These data also support the possibility that the repeated failure of clinical trials of new drugs for gliomas may be in part due to a failure to achieve effective concentrations in invasive tumor cells that reside behind an intact BBB.", "output": {"entities": {}}, "schema": []}
{"input": "Phenolics profiles of olive fruits (Olea europaea L.) and oils from Ayval i k, Domat and Gemlik varieties at different ripening stages.", "output": {"entities": {"chemical": [{"text": "Phenolics", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Phenolic compounds in olive fruit and oils obtained from Ayval i k, Domat and Gemlik olive varieties collected at different ripening periods were evaluated by High Performance Liquid Chromatography (HPLC).", "output": {"entities": {"chemical": [{"text": "Phenolic", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Gallic acid and p-cumaric acid were identified for Ayval i k and Domat at each period of ripening, respectively.", "output": {"entities": {"chemical": [{"text": "Gallic acid", "start": 0, "end": 11}, {"text": "p-cumaric acid", "start": 16, "end": 30}]}}, "schema": []}
{"input": "In addition, gallic acid, p-cumaric acid, sinapinic and apigenin acids were detected in Gemlik olive fruit.", "output": {"entities": {"chemical": [{"text": "gallic acid", "start": 13, "end": 24}, {"text": "p-cumaric acid", "start": 26, "end": 40}, {"text": "sinapinic and apigenin acids", "start": 42, "end": 70}]}}, "schema": []}
{"input": "Hydroxytyrosol, rutin, oleoropein, luteolin, tyrosol, vanilic acid and gallic acid in Ayval i k olive fruit in all ripening periods were determined.", "output": {"entities": {"chemical": [{"text": "Hydroxytyrosol", "start": 0, "end": 14}, {"text": "rutin", "start": 16, "end": 21}, {"text": "oleoropein", "start": 23, "end": 33}, {"text": "luteolin", "start": 35, "end": 43}, {"text": "tyrosol", "start": 45, "end": 52}, {"text": "vanilic acid", "start": 54, "end": 66}, {"text": "gallic acid", "start": 71, "end": 82}]}}, "schema": []}
{"input": "The tyrasol contents varied between 0. 18 to 1. 57mg/kg.", "output": {"entities": {"chemical": [{"text": "tyrasol", "start": 4, "end": 11}]}}, "schema": []}
{"input": "Luteolin contents of olive oils ranged at the levels between 0. 12 to 2. 28mg/kg.", "output": {"entities": {"chemical": [{"text": "Luteolin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "In contrast, oils had the lowest syringic, p-cumaric, chlorogenic and ferulic acids.", "output": {"entities": {"chemical": [{"text": "syringic, p-cumaric, chlorogenic and ferulic acids", "start": 33, "end": 83}]}}, "schema": []}
{"input": "Vanillic acid contents of oils ranged between 0. 08 to 2. 38mg/kg.", "output": {"entities": {"chemical": [{"text": "Vanillic acid", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Optimization of frozen sour cherries vacuum drying process.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this research was to optimize the vacuum-drying of frozen sour cherries in order to preserve health-beneficial phytochemicals, as well as textural characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "Investigated range of temperature was 46-74 degrees C and, of pressure, 17-583mbar, in a new design of vacuum-dryer equipment.", "output": {"entities": {}}, "schema": []}
{"input": "The total solids, a (w) value, total phenolics, vitamin C, antioxidant activity, anthocyanin content, total colour change and firmness were used as quality indicators of dried sour cherry.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 37, "end": 46}, {"text": "vitamin C", "start": 48, "end": 57}, {"text": "anthocyanin", "start": 81, "end": 92}]}}, "schema": []}
{"input": "Within the experimental range of studied variables, the optimum conditions of 54. 03 degrees C and 148. 16mbar were established for vacuum drying of sour cherry.", "output": {"entities": {}}, "schema": []}
{"input": "Separate validation experiments were conducted, under optimum conditions, to verify predictions and adequacy of the second-order polynomial models.", "output": {"entities": {}}, "schema": []}
{"input": "Under these optimal conditions, the predicted amount of total phenolics was 744mg CAE/100 dw, vitamin C 1. 44mg/100g per dry weight (g dw), anthocyanin content 125mg/100g dw, IC (50) 3. 23mg/ml, total solids 70. 72%, a (w) value 0. 646, total colour change 52. 61 and firmness 3395. 4g.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 62, "end": 71}, {"text": "vitamin C", "start": 94, "end": 103}, {"text": "anthocyanin", "start": 140, "end": 151}]}}, "schema": []}
{"input": "The investigated parameters had a significant effect on the quality of the dried sour cherries.", "output": {"entities": {}}, "schema": []}
{"input": "Occurrence of ochratoxin A in cocoa by-products and determination of its reduction during chocolate manufacture.", "output": {"entities": {"chemical": [{"text": "ochratoxin A", "start": 14, "end": 26}]}}, "schema": []}
{"input": "This work reports an investigation carried out to assess the natural occurrence of ochratoxin A in 168 samples from different fractions obtained during the technological processing of cocoa (shell, nibs, liquor, butter, cake and cocoa powder) and the reduction of ochratoxin A during chocolate manufacture.", "output": {"entities": {"chemical": [{"text": "ochratoxin A", "start": 83, "end": 95}, {"text": "ochratoxin A", "start": 264, "end": 276}]}}, "schema": []}
{"input": "Ochratoxin A analyses were performed with immunoaffinity columns and detection by high performance liquid chromatography.", "output": {"entities": {"chemical": [{"text": "Ochratoxin A", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Concerning the natural ochratoxin A contamination in cocoa by-products, the highest levels of ochratoxin A were found in the shell, cocoa powder and cocoa cake.", "output": {"entities": {"chemical": [{"text": "ochratoxin A", "start": 23, "end": 35}, {"text": "ochratoxin A", "start": 94, "end": 106}]}}, "schema": []}
{"input": "The cocoa butter was the least contaminated, showing that ochratoxin A seems to remain in the defatted cocoa solids.", "output": {"entities": {"chemical": [{"text": "ochratoxin A", "start": 58, "end": 70}]}}, "schema": []}
{"input": "Under the technological conditions applied during the manufacture of chocolate in this study and the level of contamination present in the cocoa beans, this experiment demonstrated that 93. 6% of ochratoxin A present in the beans was reduced during the chocolate producing.", "output": {"entities": {"chemical": [{"text": "ochratoxin A", "start": 196, "end": 208}]}}, "schema": []}
{"input": "Transglutaminase cross-linking effect on sensory characteristics and antioxidant activities of Maillard reaction products from soybean protein hydrolysates.", "output": {"entities": {}}, "schema": []}
{"input": "To improve the yield of Maillard peptides, a microbial transglutaminase (MTGase) was used to increase the content of 1000-5000Da peptides in soybean protein hydrolysates by using a cross-linking reaction.", "output": {"entities": {}}, "schema": []}
{"input": "The sensory characteristics and antioxidant activities of corresponding Maillard Reaction Products (MSPC) was then evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "After cross-linking treatment the content of 1000-5000Da peptides in protein hydrolysates and the yield of Maillard peptides increased by 21. 19% and 8. 71%, respectively, which contributed to the improved mouthfulness of MSPC.", "output": {"entities": {}}, "schema": []}
{"input": "The bitter amino acids were significantly decreased and the umami acids were markedly increased in MSPC.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 11, "end": 22}]}}, "schema": []}
{"input": "Volatile compounds identified by GC-MS analysis showed that the content of the important meaty flavour compounds (such as 2-methyl-3-furanthiol, bis (2-methyl-3-furyl) disulfide) of MSPC were dramatically higher than that of MRPs from uncross-linking peptides.", "output": {"entities": {"chemical": [{"text": "2-methyl-3-furanthiol", "start": 122, "end": 143}, {"text": "bis (2-methyl-3-furyl) disulfide", "start": 145, "end": 177}]}}, "schema": []}
{"input": "Combined with sensory evaluation, it was confirmed that MTGase cross-linking improved the flavour Characteristics and did not affect the antioxidant activity of MSPC.", "output": {"entities": {}}, "schema": []}
{"input": "Green and gold kiwifruit peel ethanol extracts potentiate pentobarbital-induced sleep in mice via a GABAergic mechanism.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 30, "end": 37}, {"text": "pentobarbital", "start": 58, "end": 71}]}}, "schema": []}
{"input": "Kiwifruit is one of the most popular fruits worldwide, and it has various biological properties, including antioxidant, anti-allergic, and cardiovascular protective effects.", "output": {"entities": {}}, "schema": []}
{"input": "The peel of kiwifruit, which is a by-product of processing, is a good source of flavonoids; however, its bioactivity has not been widely investigated.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 80, "end": 90}]}}, "schema": []}
{"input": "In this study, we evaluated the hypnotic effects of green (GRPE, Actinidia deliciosa) and gold (GOPE, Actinidia chinensis) kiwifruit peel ethanol extracts and their solvent fractions, and the possible underlying mechanisms.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 138, "end": 145}]}}, "schema": []}
{"input": "Oral GRPE and GOPE administration (125-1000mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in pentobarbital-treated mice.", "output": {"entities": {"chemical": [{"text": "pentobarbital", "start": 139, "end": 152}]}}, "schema": []}
{"input": "Among three different solvent fractions of GRPE and GOPE, ethyl acetate (EA) fractions had the greatest effect on sleep duration at 250mg/kg.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 58, "end": 71}]}}, "schema": []}
{"input": "The total flavonoid contents of solvent fractions were proportional to sleep duration.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 10, "end": 19}]}}, "schema": []}
{"input": "Like diazepam (a GABA (A)-benzodiazepine (BZD) receptor agonist), the hypnotic effects of GRPE, GOPE, and their EA fractions were fully inhibited by flumazenil (a GABA (A)-BZD receptor antagonist).", "output": {"entities": {"chemical": [{"text": "GABA", "start": 17, "end": 21}, {"text": "benzodiazepine", "start": 26, "end": 40}, {"text": "BZD", "start": 42, "end": 45}, {"text": "flumazenil", "start": 149, "end": 159}, {"text": "GABA", "start": 163, "end": 167}, {"text": "BZD", "start": 172, "end": 175}]}}, "schema": []}
{"input": "These results suggest that potentiation effects of GRPE and GOPE on pentobarbital-induced sleep in mice may be modulated by a GABAergic mechanism.", "output": {"entities": {"chemical": [{"text": "pentobarbital", "start": 68, "end": 81}]}}, "schema": []}
{"input": "An investigation into the supramolecular structure, solubility, stability and antioxidant activity of rutin/cyclodextrin inclusion complex.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 102, "end": 107}]}}, "schema": []}
{"input": "The formation of supramolecular inclusion complexes between rutin and four cyclodextrins, namely beta-cyclodextrin (beta-CD), (2-hydroxypropyl)-alpha-cyclodextrin (HP-alpha-CD), (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) and (2-hydroxypropyl)-gamma-cyclodextrin (HP-gamma-CD), and the effects of the complexation on the stability and antioxidant activity of rutin were investigated.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 60, "end": 65}, {"text": "beta-cyclodextrin", "start": 97, "end": 114}, {"text": "beta-CD", "start": 116, "end": 123}, {"text": "(2-hydroxypropyl)-alpha-cyclodextrin", "start": 126, "end": 162}, {"text": "HP-alpha-CD", "start": 164, "end": 175}, {"text": "(2-hydroxypropyl)-beta-cyclodextrin", "start": 178, "end": 213}, {"text": "HP-beta-CD", "start": 215, "end": 225}, {"text": "(2-hydroxypropyl)-gamma-cyclodextrin", "start": 231, "end": 267}, {"text": "HP-gamma-CD", "start": 269, "end": 280}, {"text": "rutin", "start": 364, "end": 369}]}}, "schema": []}
{"input": "Results from phase-solubility studies showed that rutin formed 1: 1 stoichiometric inclusion complexes with HP-alpha-CD, beta-CD, HP-beta-CD and HP-gamma-CD; the complexes formed with HP-gamma-CD and HP-beta-CD had the greatest stability constants, followed by beta-CD and HP-alpha-CD.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 50, "end": 55}, {"text": "HP-alpha-CD", "start": 108, "end": 119}, {"text": "beta-CD", "start": 121, "end": 128}, {"text": "HP-beta-CD", "start": 130, "end": 140}, {"text": "HP-gamma-CD", "start": 145, "end": 156}, {"text": "HP-gamma-CD", "start": 184, "end": 195}, {"text": "HP-beta-CD", "start": 200, "end": 210}, {"text": "beta-CD", "start": 261, "end": 268}, {"text": "HP-alpha-CD", "start": 273, "end": 284}]}}, "schema": []}
{"input": "Thermodynamic studies demonstrate that the inclusion of rutin into HP-beta-CD was an exothermic process which occurred spontaneously.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 56, "end": 61}, {"text": "HP-beta-CD", "start": 67, "end": 77}]}}, "schema": []}
{"input": "Two-dimensional rotating-frame nuclear Overhauser effect spectroscopy (2D ROESY) (1) H NMR analyses show that the A ring of rutin was the part of the molecule that most likely inserted into the cavity of HP-beta-CD, thus forming a supramolecular inclusion complex.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 81, "end": 86}, {"text": "rutin", "start": 124, "end": 129}, {"text": "HP-beta-CD", "start": 204, "end": 214}]}}, "schema": []}
{"input": "Formation of such an inclusion complex conferred moderate degrees of protection to rutin from degradation by heat and UV radiation during storage, and significantly enhanced its antioxidant capacity as determined by three different procedures.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 83, "end": 88}]}}, "schema": []}
{"input": "A nanosised oxygen scavenger: preparation and antioxidant application to roasted sunflower seeds and walnuts.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 12, "end": 18}]}}, "schema": []}
{"input": "A novel oxygen scavenger using iron nanoparticle was produced and evaluated as a potential oxygen scavenger.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 8, "end": 14}, {"text": "oxygen", "start": 91, "end": 97}]}}, "schema": []}
{"input": "Iron nanoparticle was prepared by liquid phase reduction method in microemulsion systems.", "output": {"entities": {}}, "schema": []}
{"input": "The absorption capacity of different kinds of oxygen scavengers was measured as a function of time, and the absorption rate constant was evaluated at 25 degrees C.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 46, "end": 52}]}}, "schema": []}
{"input": "The absorption kinetic analysis showed that the absorption process followed a first-order reaction.", "output": {"entities": {}}, "schema": []}
{"input": "The absorption rate constant of nanosised and conventional oxygen scavenger were 0. 45 +/- 0. 044h (-1) and 0. 05 +/- 0. 006h (-1), respectively.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 59, "end": 65}]}}, "schema": []}
{"input": "Successful application of the nanosised oxygen scavenger on roasted sunflower seed and walnut demonstrated its ability to inhibit lipid oxidation in lipid-containing food.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 40, "end": 46}]}}, "schema": []}
{"input": "Roasted nut treated with nanosised oxygen scavenger possessed the lowest PV and AnV in all treatments after 120 days of storage.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 35, "end": 41}]}}, "schema": []}
{"input": "Therefore, it has the potential for broad application as an active packaging in a variety of oxygen-sensitive foods.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 93, "end": 99}]}}, "schema": []}
{"input": "Citrus phenylpropanoids and defence against pathogens.", "output": {"entities": {}}, "schema": []}
{"input": "Part II: gene expression and metabolite accumulation in the response of fruits to Penicillium digitatum infection.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of infection of Citrus sinensis (var. Navelina) fruits with Penicillium digitatum was studied at gene expression and metabolite levels.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, expression of genes involved in the phenylpropanoid pathway was studied in the flavedo (outer coloured part of the peel) and albedo (inner white part) in response to pathogen infection.", "output": {"entities": {}}, "schema": []}
{"input": "Results of the time-course experiment showed that maximal expression of 10 out of 17 phenylpropanoid genes analysed occurred at 48h post-inoculation, when decay symptoms started to appear, and mRNA levels either kept constant or decreased after 72h post-inoculation.", "output": {"entities": {}}, "schema": []}
{"input": "To further investigate the putative involvement of the phenylpropanoid pathway in the defence of citrus fruit, changes in the metabolic profile of both tissues infected with P. digitatum was studied by means of HPLC-PDA-FD.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolite accumulation levels along the time course suggest that flavanones, flavones, polymethoxylated flavones and scoparone are induced in citrus fruit in response to P. digitatum infection, although with different trends depending on the tissue.", "output": {"entities": {"chemical": [{"text": "flavanones", "start": 66, "end": 76}, {"text": "flavones", "start": 78, "end": 86}, {"text": "polymethoxylated flavones", "start": 88, "end": 113}, {"text": "scoparone", "start": 118, "end": 127}]}}, "schema": []}
{"input": "Diuretic effects of cannabinoids.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo effects of cannabinoid (CB) agonists are often assessed using four well-established measures: locomotor activity, hypothermia, cataleptic-like effects, and analgesia.", "output": {"entities": {}}, "schema": []}
{"input": "The present studies demonstrate that doses of CB agonists that produce these effects also reliably increase diuresis.", "output": {"entities": {}}, "schema": []}
{"input": "Diuretic effects of several CB agonists were measured in female rats over 2 hours immediately after drug injection, and results were compared with hypothermic effects.", "output": {"entities": {}}, "schema": []}
{"input": "Direct-acting CB1 agonists, including Delta (9)-tetrahydrocannabinol, WIN 55, 212 [R-(1)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate], AM2389 [9 beta-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED (50) values for diuresis than for hypothermia.", "output": {"entities": {"chemical": [{"text": "Delta (9)-tetrahydrocannabinol", "start": 38, "end": 68}, {"text": "WIN 55, 212", "start": 70, "end": 81}, {"text": "R-(1)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate", "start": 83, "end": 212}, {"text": "AM2389", "start": 215, "end": 221}, {"text": "9 beta-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol", "start": 223, "end": 283}, {"text": "AM4054", "start": 290, "end": 296}, {"text": "9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol", "start": 298, "end": 356}]}}, "schema": []}
{"input": "The highest doses of cannabinoid drugs yielded, on average, 26-32 g/kg urine; comparable effects were obtained with 10 mg/kg furosemide and 3. 0 mg/kg trans-(-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide (U50-488).", "output": {"entities": {"chemical": [{"text": "furosemide", "start": 125, "end": 135}, {"text": "trans-(-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide", "start": 151, "end": 234}, {"text": "U50-488", "start": 236, "end": 243}]}}, "schema": []}
{"input": "Methanandamide (10. 0 mg/kg) had lesser effect than other CB agonists, and the CB2 agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl) indole], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects.", "output": {"entities": {"chemical": [{"text": "Methanandamide", "start": 0, "end": 14}, {"text": "AM1241", "start": 91, "end": 97}, {"text": "1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl) indole", "start": 99, "end": 162}, {"text": "anandamide", "start": 169, "end": 179}, {"text": "AM404", "start": 200, "end": 205}, {"text": "rimonabant", "start": 229, "end": 239}]}}, "schema": []}
{"input": "In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55, 212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl) ethyl]-1H-indol-3-yl] (4-methoxyphenyl) methanone)].", "output": {"entities": {"chemical": [{"text": "AM4054", "start": 60, "end": 66}, {"text": "rimonabant", "start": 221, "end": 231}, {"text": "vanilloid", "start": 248, "end": 257}, {"text": "capsazepine", "start": 285, "end": 296}, {"text": "WIN 55, 212", "start": 322, "end": 333}, {"text": "AM630", "start": 368, "end": 373}, {"text": "(6-iodo-2-methyl-1-[2-(4-morpholinyl) ethyl]-1H-indol-3-yl] (4-methoxyphenyl) methanone)", "start": 375, "end": 463}]}}, "schema": []}
{"input": "These data indicate that cannabinoids have robust diuretic effects in rats that are mediated via CB1 receptor mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-breast cancer agents from Chinese herbal medicines.", "output": {"entities": {}}, "schema": []}
{"input": "Chinese Herbal Medicines (CHM) have been used in disease prevention and treatment for centuries in China.", "output": {"entities": {}}, "schema": []}
{"input": "A number of anti-breast cancer agents isolated from CHM recently, showed very interesting structures, although some of the mechanism of action is not quite clear.", "output": {"entities": {}}, "schema": []}
{"input": "These unique chemical structures could be an important information resource for new anti-breast cancer drugs' design and discovery.", "output": {"entities": {}}, "schema": []}
{"input": "This review summarizes these findings on anti-breast cancer agents from CHM.", "output": {"entities": {}}, "schema": []}
{"input": "Role of carbonyl reducing enzymes in the phase I biotransformation of the non-steroidal anti-inflammatory drug nabumetone in vitro.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 8, "end": 16}, {"text": "nabumetone", "start": 111, "end": 121}]}}, "schema": []}
{"input": "1.", "output": {"entities": {}}, "schema": []}
{"input": "Nabumetone is a clinically used non-steroidal anti-inflammatory drug, its biotransformation includes major active metabolite 6-methoxy-2-naphtylacetic acid and another three phase I as well as corresponding phase II metabolites which are regarded as inactive.", "output": {"entities": {"chemical": [{"text": "Nabumetone", "start": 0, "end": 10}, {"text": "6-methoxy-2-naphtylacetic acid", "start": 125, "end": 155}]}}, "schema": []}
{"input": "One important biotransformation pathway is carbonyl reduction, which leads to the phase I metabolite, reduced nabumetone.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 43, "end": 51}, {"text": "nabumetone", "start": 110, "end": 120}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study is the determination of the role of a particular human liver subcellular fraction in the nabumetone reduction and the identification of participating carbonyl reducing enzymes along with their stereospecificities.", "output": {"entities": {"chemical": [{"text": "nabumetone", "start": 111, "end": 121}, {"text": "carbonyl", "start": 172, "end": 180}]}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "Both subcellular fractions take part in the carbonyl reduction of nabumetone and the reduction is at least in vitro the main biotransformation pathway.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 44, "end": 52}, {"text": "nabumetone", "start": 66, "end": 76}]}}, "schema": []}
{"input": "The activities of eight cytosolic carbonyl reducing enzymes--CBR1, CBR3, AKR1B1, AKR1B10, AKR1C1-4--toward nabumetone were tested.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 34, "end": 42}, {"text": "nabumetone", "start": 107, "end": 117}]}}, "schema": []}
{"input": "Except for CBR3, all tested reductases transform nabumetone to its reduced metabolite.", "output": {"entities": {"chemical": [{"text": "nabumetone", "start": 49, "end": 59}]}}, "schema": []}
{"input": "AKR1C4 and AKR1C3 have the highest intrinsic clearances.", "output": {"entities": {}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "The stereospecificity of the majority of the tested enzymes is shifted to the production of an (+)-enantiomer of reduced nabumetone; only AKR1C1 and AKR1C4 produce predominantly an (-)-enantiomer.", "output": {"entities": {"chemical": [{"text": "nabumetone", "start": 121, "end": 131}]}}, "schema": []}
{"input": "This project provides for the first time evidence that seven specific carbonyl reducing enzymes participate in nabumetone metabolism.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 70, "end": 78}, {"text": "nabumetone", "start": 111, "end": 121}]}}, "schema": []}
{"input": "Transport of gemifloxacin, a 4th generation quinolone antibiotic, in the Caco-2 and engineered MDCKII cells, and potential involvement of efflux transporters in the intestinal absorption of the drug.", "output": {"entities": {"chemical": [{"text": "gemifloxacin", "start": 13, "end": 25}, {"text": "quinolone", "start": 44, "end": 53}]}}, "schema": []}
{"input": "The oral (po) bioavailability of gemifloxacin mesylate in rats and its possible association with efflux transporters was investigated.", "output": {"entities": {"chemical": [{"text": "gemifloxacin mesylate", "start": 33, "end": 54}]}}, "schema": []}
{"input": "The apparent permeabilities (Papp) of gemifloxacin across the Caco-2 cell monolayer were 1. 20 +/- 0. 09 x 10 (-5) cm/s for apical to basal (absorptive) transport, and 2. 13 +/- 0. 6 x 10 (-5) cm/s for basal to apical (secretory) transport for a 5-500 mu M concentration range, suggesting the involvement of a carrier-mediated efflux in the secretory transport.", "output": {"entities": {"chemical": [{"text": "gemifloxacin", "start": 38, "end": 50}]}}, "schema": []}
{"input": "The secretory transport in Caco-2 cells was significantly decreased by MRP2 (MK571) and BCRP (Ko143) inhibitors.", "output": {"entities": {"chemical": [{"text": "MK571", "start": 77, "end": 82}, {"text": "Ko143", "start": 94, "end": 99}]}}, "schema": []}
{"input": "The secretory transport was distinct in MDCKII/P-gp, MDCKII/MRP2 and MDCKII/BCRP cells, and the affinity was highest for MRP2, followed by BCRP and P-gp.", "output": {"entities": {}}, "schema": []}
{"input": "The efflux was significantly decreased by verapamil and Ko143, but not significantly by MK571.", "output": {"entities": {"chemical": [{"text": "verapamil", "start": 42, "end": 51}, {"text": "Ko143", "start": 56, "end": 61}, {"text": "MK571", "start": 88, "end": 93}]}}, "schema": []}
{"input": "The comparative po bioavailability in rats was increased by the preadministration of Ko143 (four-fold), MK571 (two-fold) and verapamil (two-fold).", "output": {"entities": {"chemical": [{"text": "Ko143", "start": 85, "end": 90}, {"text": "MK571", "start": 104, "end": 109}, {"text": "verapamil", "start": 125, "end": 134}]}}, "schema": []}
{"input": "Efflux transporters appeared to significantly limit the bioavailability of gemifloxacin in rats, suggesting their possible contribution to the low bioavailability of the drug in the human (70%).", "output": {"entities": {"chemical": [{"text": "gemifloxacin", "start": 75, "end": 87}]}}, "schema": []}
{"input": "A phase I, open-label, single-dose, mass balance study of 14C-labeled abiraterone acetate in healthy male subjects.", "output": {"entities": {"chemical": [{"text": "14C-labeled abiraterone acetate", "start": 58, "end": 89}]}}, "schema": []}
{"input": "1. Metabolic disposition of (14) C-abiraterone acetate (AA), a prodrug of abiraterone was assessed in a phase I, open-label, single-dose (1000 mg, approximately 100 mu Ci) study in healthy males (18-55 years, N = 8).", "output": {"entities": {"chemical": [{"text": "(14) C-abiraterone acetate", "start": 28, "end": 54}, {"text": "abiraterone", "start": 74, "end": 85}]}}, "schema": []}
{"input": "Blood, urine, and faecal samples were obtained at specified timepoints for determination of abiraterone concentrations in the plasma, total radioactivity (TR), and the metabolite profile.", "output": {"entities": {"chemical": [{"text": "abiraterone", "start": 92, "end": 103}]}}, "schema": []}
{"input": "2. Most plasma AA concentrations were below the limit of quantification.", "output": {"entities": {}}, "schema": []}
{"input": "The mean maximum plasma concentration (Cmax) of abiraterone was 10. 4 ng/mL, mean area under the plasma concentration-time curve (AUC) from 0 to the last measurable plasma concentration (AUC0-last) was 74. 8 ng. h/mL.", "output": {"entities": {"chemical": [{"text": "abiraterone", "start": 48, "end": 59}]}}, "schema": []}
{"input": "The exposures for TR in plasma (Cmax = 3429 ng. eq/mL; AUC0-last = 26, 683 ng eq. h/mL) and whole blood (Cmax = 1836 ng. eq/mL; AUC0-last = 12, 162 ng. eq. h/mL) were > 300-fold higher than abiraterone exposure in plasma.", "output": {"entities": {"chemical": [{"text": "abiraterone", "start": 190, "end": 201}]}}, "schema": []}
{"input": "The majority of TR resided in the plasma compartment of blood.", "output": {"entities": {}}, "schema": []}
{"input": "3. Main circulating metabolites were abiraterone sulfate and N-oxide abiraterone sulfate.", "output": {"entities": {"chemical": [{"text": "abiraterone sulfate", "start": 37, "end": 56}, {"text": "N-oxide abiraterone sulfate", "start": 61, "end": 88}]}}, "schema": []}
{"input": "The main metabolite excreted in urine was N-oxide abiraterone sulfate (4. 22% of TR).", "output": {"entities": {"chemical": [{"text": "N-oxide abiraterone sulfate", "start": 42, "end": 69}]}}, "schema": []}
{"input": "Major components of TR in faeces were unchanged AA (55. 3% of TR) and abiraterone (22. 3% of TR).", "output": {"entities": {"chemical": [{"text": "abiraterone", "start": 70, "end": 81}]}}, "schema": []}
{"input": "Mean recovery of TR in faeces was 87. 9%, indicating faeces as primary route of excretion.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 14, "end": 18}]}}, "schema": []}
{"input": "Attention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known.", "output": {"entities": {}}, "schema": []}
{"input": "Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of gamma-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia.", "output": {"entities": {"chemical": [{"text": "gamma-aminobutyric acid", "start": 109, "end": 132}, {"text": "GABA", "start": 134, "end": 138}]}}, "schema": []}
{"input": "Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parvalbumin-containing fast-spiking GABA interneurons.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 53, "end": 57}, {"text": "glutamic acid", "start": 75, "end": 88}, {"text": "GABA", "start": 161, "end": 165}]}}, "schema": []}
{"input": "Thus it is hypothesized that reduced cortical GABA synthesis and release may contribute to the attention deficits in schizophrenia.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 46, "end": 50}]}}, "schema": []}
{"input": "Here the effect of reducing cortical GABA synthesis with l-allylglycine (LAG) on attention was tested using three different versions of the 5-choice serial reaction time task (5CSRTT).", "output": {"entities": {"chemical": [{"text": "GABA", "start": 37, "end": 41}, {"text": "l-allylglycine", "start": 57, "end": 71}, {"text": "LAG", "start": 73, "end": 76}]}}, "schema": []}
{"input": "Because 5CSRTT performance can be affected by locomotor activity, we also measured this behavior in an open field.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, the expression of Fos protein was used as an indirect measure of reduced GABA synthesis.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 82, "end": 86}]}}, "schema": []}
{"input": "Intra-cortical LAG (10 mu g/0. 5 mu l/side) infusions increased Fos expression and resulted in hyperactivity in the open field.", "output": {"entities": {"chemical": [{"text": "LAG", "start": 15, "end": 18}]}}, "schema": []}
{"input": "Intra-cortical LAG infusions did not affect attention in any version of the 5CSRTT.", "output": {"entities": {"chemical": [{"text": "LAG", "start": 15, "end": 18}]}}, "schema": []}
{"input": "These results suggest that a general decrease in GABA synthesis is not sufficient to cause attention deficits.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 49, "end": 53}]}}, "schema": []}
{"input": "It remains to be tested whether a selective decrease in GABA synthesis in parvalbumin-containing GABA neurons could cause attention deficits.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 56, "end": 60}, {"text": "GABA", "start": 97, "end": 101}]}}, "schema": []}
{"input": "Decreased cortical GABA synthesis did increase locomotor activity; this may reflect the positive symptoms of schizophrenia.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 19, "end": 23}]}}, "schema": []}
{"input": "The PNarec method for detection of ancient recombinations through phylogenetic network analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Recombinations are known to disrupt bifurcating tree structure of gene genealogies.", "output": {"entities": {}}, "schema": []}
{"input": "Although recently occurred recombinations are easily detectable by using conventional methods, recombinations may have occurred at any time.", "output": {"entities": {}}, "schema": []}
{"input": "We devised a new method for detecting ancient recombinations through phylogenetic network analysis, and detected five ancient recombinations in gibbon ABO blood group genes [Kitano et al., 2009. Mol. Phylogenet. Evol., 51, 465-471].", "output": {"entities": {}}, "schema": []}
{"input": "We present applications of this method, now named as \" PNarec \", to various virus sequences as well as HLA genes.", "output": {"entities": {}}, "schema": []}
{"input": "Cytisine confers neuronal protection against excitotoxic injury by down-regulating GluN2B-containing NMDA receptors.", "output": {"entities": {"chemical": [{"text": "Cytisine", "start": 0, "end": 8}, {"text": "NMDA", "start": 101, "end": 105}]}}, "schema": []}
{"input": "Cytisine (CYT), one of the principal bioactive components derived from the seeds of Cytisus laborinum L, has been widely used for central nervous system (CNS) diseases treatment.", "output": {"entities": {"chemical": [{"text": "Cytisine", "start": 0, "end": 8}, {"text": "CYT", "start": 10, "end": 13}]}}, "schema": []}
{"input": "The present study investigated the protective effect of CYT on cultured cortical neural injury induced by N-methyl-d-aspartate (NMDA).", "output": {"entities": {"chemical": [{"text": "CYT", "start": 56, "end": 59}, {"text": "N-methyl-d-aspartate", "start": 106, "end": 126}, {"text": "NMDA", "start": 128, "end": 132}]}}, "schema": []}
{"input": "Our data showed that CYT conferred protective effect against loss of cellular viability induced by brief exposure to 200 mu M NMDA in a concentration-dependent manner.", "output": {"entities": {"chemical": [{"text": "CYT", "start": 21, "end": 24}, {"text": "NMDA", "start": 126, "end": 130}]}}, "schema": []}
{"input": "CYT significantly inhibited the neuronal apoptosis induced by NMDA exposure by reversing intracellular Ca (2 +) overload and balancing Bcl-2 and Bax expression levels.", "output": {"entities": {"chemical": [{"text": "CYT", "start": 0, "end": 3}, {"text": "NMDA", "start": 62, "end": 66}, {"text": "Ca (2 +)", "start": 103, "end": 111}]}}, "schema": []}
{"input": "Furthermore, CYT significantly reversed the up-regulation of GluN2B-containing NMDA receptors by exposure to NMDA, but it did not affect the level of GluN2A-containing NMDA receptors.", "output": {"entities": {"chemical": [{"text": "CYT", "start": 13, "end": 16}, {"text": "NMDA", "start": 79, "end": 83}, {"text": "NMDA", "start": 109, "end": 113}, {"text": "NMDA", "start": 168, "end": 172}]}}, "schema": []}
{"input": "These findings suggest that CYT protects cortical neurons, at least partially, by inhibiting the level of GluN2B-containing NMDA receptors and regulating Bcl-2 family.", "output": {"entities": {"chemical": [{"text": "CYT", "start": 28, "end": 31}, {"text": "NMDA", "start": 124, "end": 128}]}}, "schema": []}
{"input": "Inhibition of neurite outgrowth and alteration of cytoskeletal gene expression by sodium arsenite.", "output": {"entities": {"chemical": [{"text": "sodium arsenite", "start": 82, "end": 97}]}}, "schema": []}
{"input": "Arsenic compounds that are often found in drinking water increase the risk of developmental brain disorders.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "In this study, we performed live imaging analyses of Neuro-2a cells expressing SCAT3, a caspase-3 cleavage peptide sequence linking two fluorescent proteins; enhanced cyan fluorescence protein (ECFP) and Venus, to determine whether sodium arsenite (NaAsO (2); 0, 1, 5, or 10 mu M) affects both neurite outgrowth and/or induces apoptosis with the same doses and in the same cell cultures.", "output": {"entities": {"chemical": [{"text": "sodium arsenite", "start": 232, "end": 247}, {"text": "NaAsO (2)", "start": 249, "end": 258}]}}, "schema": []}
{"input": "We observed that the area ratio of neurite to cell body in SCAT3-expressing cells was significantly reduced by 5 and 10 mu M NaAsO (2), but not by 1 mu M, although the emission ratio of ECFP to Venus, an endpoint of caspase-3 activity, was not changed.", "output": {"entities": {"chemical": [{"text": "NaAsO (2)", "start": 125, "end": 134}]}}, "schema": []}
{"input": "However, cytological assay using apoptotic and necrotic markers resulted in that apoptosis, but not necrosis, was significantly induced in Neuro-2a cells when NaAsO (2) exposure continued after the significant effects of NaAsO (2) on neurite outgrowth were found by live imaging.", "output": {"entities": {"chemical": [{"text": "NaAsO (2)", "start": 159, "end": 168}, {"text": "NaAsO (2)", "start": 221, "end": 230}]}}, "schema": []}
{"input": "These results suggested that neurite outgrowth was suppressed by NaAsO (2) prior to NaAsO (2)-induced apoptosis.", "output": {"entities": {"chemical": [{"text": "NaAsO (2)", "start": 65, "end": 74}, {"text": "NaAsO (2)", "start": 84, "end": 93}]}}, "schema": []}
{"input": "Next, we examined the effects of NaAsO (2) on cytoskeletal gene expression in Neuro-2a cells.", "output": {"entities": {"chemical": [{"text": "NaAsO (2)", "start": 33, "end": 42}]}}, "schema": []}
{"input": "NaAsO (2) increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of tau and tubulin in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin.", "output": {"entities": {"chemical": [{"text": "NaAsO (2)", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The changes in cytoskeletal gene expression are likely responsible for the inhibitory effects of NaAsO (2) on neurite outgrowth.", "output": {"entities": {"chemical": [{"text": "NaAsO (2)", "start": 97, "end": 106}]}}, "schema": []}
{"input": "Association analysis between K and-116A variants of butyrylcholinesterase and Alzheimer' s disease in a Brazilian population.", "output": {"entities": {}}, "schema": []}
{"input": "In Alzheimer' s disease (AD) a reduction in acetylcholinesterase (AChE) and an increase in butyrylcholinesterase (BChE) activity are observed.", "output": {"entities": {}}, "schema": []}
{"input": "K variant (539T) is the most common variant of the BCHE gene and, although controversial, several studies reported association between K variant and AD.", "output": {"entities": {}}, "schema": []}
{"input": "Previous results showed that the K variant alone is not capable of diminishing BChE activity, depending on the presence of the-116A variant.", "output": {"entities": {}}, "schema": []}
{"input": "Considering that, we conducted a case-control association study using a clinically well defined group of AD patients (n = 82) and age and sex matched control subjects (EC; n = 78) in order to test the association with these variations of BCHE gene in a Brazilian population.", "output": {"entities": {}}, "schema": []}
{"input": "The allele, genotype and haplotype frequencies of the K and the-116A variants of BCHE gene were not significantly different between cases and controls.", "output": {"entities": {}}, "schema": []}
{"input": "Although not reaching statistical significance, the results suggested that the presence of-116A variant may have a protective effect against AD.", "output": {"entities": {}}, "schema": []}
{"input": "The association of the K variant with AD in a controversial manner in different surveys is probably caused by its linkage disequilibrium with-116A that, by reducing BChE activity, potentially increases cholinergic transmission in comparison with usual genotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism of triethylenetetramine and 1, 12-diamino-3, 6, 9-triazadodecane by the spermidine/spermine-N (1)-acetyltransferase and thialysine acetyltransferase.", "output": {"entities": {"chemical": [{"text": "triethylenetetramine", "start": 14, "end": 34}, {"text": "1, 12-diamino-3, 6, 9-triazadodecane", "start": 39, "end": 75}, {"text": "spermidine", "start": 83, "end": 93}, {"text": "spermine", "start": 94, "end": 102}, {"text": "thialysine", "start": 131, "end": 141}]}}, "schema": []}
{"input": "Triethylenetetramine (TETA; Syprine; Merck Rahway, NJ), a drug for Wilson' s disease, is a copper chelator and a charge-deficient analog of polyamine spermidine.", "output": {"entities": {"chemical": [{"text": "Triethylenetetramine", "start": 0, "end": 20}, {"text": "TETA", "start": 22, "end": 26}, {"text": "Syprine", "start": 28, "end": 35}, {"text": "copper", "start": 91, "end": 97}, {"text": "polyamine spermidine", "start": 140, "end": 160}]}}, "schema": []}
{"input": "We recently showed that TETA is metabolized in vitro by polyamine catabolic enzyme spermidine/spermine-N (1)-acetyltransferase (SSAT1) and by thialysine acetyltransferase (SSAT2) to its monoacetylated derivative (MAT).", "output": {"entities": {"chemical": [{"text": "TETA", "start": 24, "end": 28}, {"text": "polyamine", "start": 56, "end": 65}, {"text": "spermidine", "start": 83, "end": 93}, {"text": "spermine", "start": 94, "end": 102}, {"text": "thialysine", "start": 142, "end": 152}]}}, "schema": []}
{"input": "The acetylation of TETA is increased in SSAT1-overexpressing mice compared with wild-type mice.", "output": {"entities": {"chemical": [{"text": "TETA", "start": 19, "end": 23}]}}, "schema": []}
{"input": "However, SSAT1-deficient mice metabolize TETA at the same rate as the wild-type mice, indicating the existence of another N-acetylase respons 2ible for its metabolism in mice.", "output": {"entities": {"chemical": [{"text": "TETA", "start": 41, "end": 45}]}}, "schema": []}
{"input": "Here, we show that siRNA-mediated knockdown of SSAT2 in HEPG2 cells and in primary hepatocytes from the SSAT1-deficient or wild-type mice reduced the metabolism of TETA to MAT.", "output": {"entities": {"chemical": [{"text": "TETA", "start": 164, "end": 168}]}}, "schema": []}
{"input": "By contrast, 1, 12-diamino-3, 6, 9-triazadodecane (SpmTrien), a charge-deficient spermine analog, was an extremely poor substrate of human recombinant SSAT2 and was metabolized by SSAT1 in HEPG2 cells and in wild-type primary hepatocytes.", "output": {"entities": {"chemical": [{"text": "1, 12-diamino-3, 6, 9-triazadodecane", "start": 13, "end": 49}, {"text": "SpmTrien", "start": 51, "end": 59}, {"text": "spermine", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Thus, despite the similar structures of TETA and SpmTrien, SSAT2 is the main acetylator of TETA, whereas SpmTrien is primarily acetylated by SSAT1.", "output": {"entities": {"chemical": [{"text": "TETA", "start": 40, "end": 44}, {"text": "SpmTrien", "start": 49, "end": 57}, {"text": "TETA", "start": 91, "end": 95}, {"text": "SpmTrien", "start": 105, "end": 113}]}}, "schema": []}
{"input": "Picosecond kinetics of strongly coupled excitons and surface plasmon polaritons.", "output": {"entities": {}}, "schema": []}
{"input": "Coupling between excitons of CdSe nanocrystal quantum dots (NQDs) and surface plasmon polaritons (SPPs) of an Ag film attached to a prism have been studied by steady-state and transient reflectivity measurements in the Kretschmann geometry.", "output": {"entities": {"chemical": [{"text": "CdSe", "start": 29, "end": 33}, {"text": "Ag", "start": 110, "end": 112}]}}, "schema": []}
{"input": "In these experiments, the angle of incidence of the probe beam selects hybrid exciton/SPP states with different wavevectors and exciton/SPP compositions.", "output": {"entities": {}}, "schema": []}
{"input": "The dynamics measured in the transient reflectivity experiments are sensitive to the composition of the hybrid states.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, fast dynamics are observed at probe wavevectors where the lower hybrid state has predominant SPP character.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, at probe wavevectors where the lower hybrid state is predominantly excitonic, the dynamics are similar to that measured for CdSe NQDs on glass.", "output": {"entities": {"chemical": [{"text": "CdSe", "start": 137, "end": 141}]}}, "schema": []}
{"input": "Phospholipases A2: unveiling the secrets of a functionally versatile group of snake venom toxins.", "output": {"entities": {}}, "schema": []}
{"input": "Phospholipases A (2) (PLA (2) s) are abundant components of snake venoms, where they play toxic and digestive roles.", "output": {"entities": {}}, "schema": []}
{"input": "Despite having a similar three-dimensional structure, venom PLA (2) s exert an amazing variety of toxic and pharmacological effects, which include neurotoxic, myotoxic, hemolytic, edematogenic, hyperalgesic, pro-inflammatory, hypotensive, platelet-aggregation inhibitory, anticoagulant, cytotoxic, and bactericidal activities.", "output": {"entities": {}}, "schema": []}
{"input": "Toxinologists have made significant contributions to deciphering the structure, molecular evolution, mechanisms of action, receptors, role of enzymatic activity for toxicity, structural determinants of toxicity and selectivity, and the impact of these enzymes in the overall pathophysiology of snakebite envenoming.", "output": {"entities": {}}, "schema": []}
{"input": "The present work highlights some of the most relevant contributions in the study of venom PLA (2) s, including the personal accounts of the authors of these studies.", "output": {"entities": {}}, "schema": []}
{"input": "Methamphetamine regulation of sulfotransferase 1A1 and 2A1 expression in rat brain sections.", "output": {"entities": {"chemical": [{"text": "Methamphetamine", "start": 0, "end": 15}]}}, "schema": []}
{"input": "Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 90, "end": 98}]}}, "schema": []}
{"input": "rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds.", "output": {"entities": {"chemical": [{"text": "hydroxysteroids", "start": 36, "end": 51}, {"text": "alcoholic", "start": 67, "end": 76}]}}, "schema": []}
{"input": "In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum.", "output": {"entities": {"chemical": [{"text": "methamphetamine", "start": 87, "end": 102}]}}, "schema": []}
{"input": "After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus.", "output": {"entities": {}}, "schema": []}
{"input": "After 7 days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions.", "output": {"entities": {}}, "schema": []}
{"input": "Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level.", "output": {"entities": {}}, "schema": []}
{"input": "Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus.", "output": {"entities": {}}, "schema": []}
{"input": "rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner.", "output": {"entities": {"chemical": [{"text": "methamphetamine", "start": 38, "end": 53}]}}, "schema": []}
{"input": "rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections.", "output": {"entities": {"chemical": [{"text": "methamphetamine", "start": 44, "end": 59}]}}, "schema": []}
{"input": "Induction activity of methamphetamine is in the order of cerebellum > frontal cortex, hippocampus > striatum.", "output": {"entities": {"chemical": [{"text": "methamphetamine", "start": 22, "end": 37}]}}, "schema": []}
{"input": "These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine.", "output": {"entities": {"chemical": [{"text": "methamphetamine", "start": 126, "end": 141}]}}, "schema": []}
{"input": "Nanostructured superhydrophobic substrates trigger the development of 3D neuronal networks.", "output": {"entities": {}}, "schema": []}
{"input": "The generation of 3D networks of primary neurons is a big challenge in neuroscience.", "output": {"entities": {}}, "schema": []}
{"input": "Here, a novel method is presented for a 3D neuronal culture on superhydrophobic (SH) substrates.", "output": {"entities": {}}, "schema": []}
{"input": "How nano-patterned SH devices stimulate neurons to build 3D networks is investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Scanning electron microscopy and confocal imaging show that soon after plating neurites adhere to the nanopatterned pillar sidewalls and they are subsequently pulled between pillars in a suspended position.", "output": {"entities": {}}, "schema": []}
{"input": "These neurons display an enhanced survival rate compared to standard cultures and develop mature networks with physiological excitability.", "output": {"entities": {}}, "schema": []}
{"input": "These findings underline the importance of using nanostructured SH surfaces for directing 3D neuronal growth, as well as for the design of biomaterials for neuronal regeneration.", "output": {"entities": {}}, "schema": []}
{"input": "Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies.", "output": {"entities": {}}, "schema": []}
{"input": "1. We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches.", "output": {"entities": {}}, "schema": []}
{"input": "2. Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology.", "output": {"entities": {}}, "schema": []}
{"input": "3. A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture.", "output": {"entities": {"chemical": [{"text": "polyamine", "start": 114, "end": 123}]}}, "schema": []}
{"input": "They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting.", "output": {"entities": {}}, "schema": []}
{"input": "4. Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.", "output": {"entities": {}}, "schema": []}
{"input": "The GARD assay for assessment of chemical skin sensitizers.", "output": {"entities": {}}, "schema": []}
{"input": "Allergic contact dermatitis is a skin disease caused by an immunologic reaction to low molecular weight compounds, so called haptens.", "output": {"entities": {}}, "schema": []}
{"input": "These substances are commonly present in products used by humans in daily life, such as in cosmetics and fragrances, as well as within chemical industry and in pharmaceuticals.", "output": {"entities": {}}, "schema": []}
{"input": "The frequent usage of these compounds in different applications has led to increasing incidences of allergic contact dermatitis, which has become a substantial economic burden for society.", "output": {"entities": {}}, "schema": []}
{"input": "As a consequence, chemicals are routinely tested for their ability to induce skin sensitization, using animal models such as the murine Local Lymph Node Assay.", "output": {"entities": {}}, "schema": []}
{"input": "However, recent legislations regulate the use of animal models within chemical testing.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, there is an urgent need for in vitro alternatives to replace these assays for safety assessment of chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, we identified a signature of predictive genes, which are differentially regulated in the human myeloid cell-line MUTZ-3 when stimulated with sensitizing compounds compared to non-sensitizing compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Based on these findings, we have formulated a test strategy for assessment of sensitizing compounds, called Genomic Allergen Rapid Detection, GARD.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, we present a detailed method description of how the assay should be performed.", "output": {"entities": {}}, "schema": []}
{"input": "Natural products as sources of new fungicides (I): synthesis and antifungal activity of acetophenone derivatives against phytopathogenic fungi.", "output": {"entities": {"chemical": [{"text": "acetophenone", "start": 88, "end": 100}]}}, "schema": []}
{"input": "Several series of 45 acetophenone derivatives bearing various alkyl or benzyl substituents were conveniently synthesized and their structures characterized by (1) H and (13) C NMR spectroscopy, HRMS and single-crystal X-ray analysis.", "output": {"entities": {"chemical": [{"text": "acetophenone", "start": 21, "end": 33}, {"text": "alkyl", "start": 62, "end": 67}, {"text": "benzyl", "start": 71, "end": 77}, {"text": "(1) H", "start": 159, "end": 164}, {"text": "(13) C", "start": 169, "end": 175}]}}, "schema": []}
{"input": "Their in vitro antifungal activities against a panel of phytopathogenic fungi were evaluated by mycelial growth rate assay.", "output": {"entities": {}}, "schema": []}
{"input": "Of them, 12 derivatives (e. g., 3a-c, 4c and 4e) exhibited more potent antifungal effects on some phytopathogens than a commercial fungicide hymexazol as positive control.", "output": {"entities": {"chemical": [{"text": "hymexazol", "start": 141, "end": 150}]}}, "schema": []}
{"input": "In particular, compound 3b with IC50 values of 10-19 mu g/mL was found to be the most active in this series and might be a potential lead structure for further optimization.", "output": {"entities": {}}, "schema": []}
{"input": "The preliminary structure-activity relationship (SAR) studies of a series of acetophenones are also discussed.", "output": {"entities": {"chemical": [{"text": "acetophenones", "start": 77, "end": 90}]}}, "schema": []}
{"input": "Droplet Digital (TM) PCR quantitation of HER2 expression in FFPE breast cancer samples.", "output": {"entities": {}}, "schema": []}
{"input": "The human epidermal growth factor receptor 2 (HER2, also known as erbB2) gene is involved in signal transduction for cell growth and differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "It is a cell surface receptor tyrosine kinase and a proto-oncogene.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 30, "end": 38}]}}, "schema": []}
{"input": "Overexpression of HER2 is of clinical relevance in breast cancer due to its prognostic value correlating elevated expression with worsening clinical outcome.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, HER2 assessment is also of importance because successful anti-tumor treatment with Herceptin (R) is strongly correlated with HER2 overexpression in the tumor (approximately 30% of all breast tumors overexpress HER2).", "output": {"entities": {}}, "schema": []}
{"input": "In a comprehensive national study, Wolff et al.", "output": {"entities": {}}, "schema": []}
{"input": "[1] state that \" Approximately 20% of current HER2 testing may be inaccurate \" which underscores the importance of developing more accurate methods to determine HER2 status.", "output": {"entities": {}}, "schema": []}
{"input": "Droplet Digital (TM) PCR (ddPCR (TM)) has the potential to improve upon HER2 measurements due to its ability to quantitate DNA and RNA targets with high precision and accuracy.", "output": {"entities": {}}, "schema": []}
{"input": "Here we present a study which investigates whether ddPCR can be used to assess HER2 transcript levels in formalin-fixed paraffin embedded (FFPE) human breast tumors and whether these ddPCR measurements agree with prior assessments of these same samples by pathologists using immunohistochemistry (IHC) and in some cases fluorescence in situ hybridization (FISH).", "output": {"entities": {"chemical": [{"text": "formalin", "start": 105, "end": 113}]}}, "schema": []}
{"input": "We also determined the copy number of HER2 in these samples as compared to the CEP17 reference gene.", "output": {"entities": {}}, "schema": []}
{"input": "Results: Clinical FFPE samples were successfully studied using ddPCR and compared to results from standard FISH and IHC methodology.", "output": {"entities": {}}, "schema": []}
{"input": "The results demonstrate that ddPCR can rank order the samples in complete agreement with the current standard methods and that ddPCR has the added benefit of providing quantitative results, rather than relying on the expert skill of a seasoned pathologist for determination.", "output": {"entities": {}}, "schema": []}
{"input": "Lipoprotein (a) metabolism: potential sites for therapeutic targets.", "output": {"entities": {}}, "schema": []}
{"input": "Lipoprotein (a) [Lp (a)] resembles low-density lipoprotein (LDL), with an LDL lipid core and apolipoprotein B (apoB), but contains a unique apolipoprotein, apo (a).", "output": {"entities": {}}, "schema": []}
{"input": "Elevated Lp (a) is an independent risk factor for coronary and peripheral vascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The size and concentration of plasma Lp (a) are related to the synthetic rate, not the catabolic rate, and are highly variable with small isoforms associated with high concentrations and pathogenic risk.", "output": {"entities": {}}, "schema": []}
{"input": "Apo (a) is synthesized in the liver, although assembly of apo (a) and LDL may occur in the hepatocytes or plasma.", "output": {"entities": {}}, "schema": []}
{"input": "While the uptake and clearance site of Lp (a) is poorly delineated, the kidney is the site of apo (a) fragment excretion.", "output": {"entities": {}}, "schema": []}
{"input": "The structure of apo (a) has high homology to plasminogen, the zymogen for plasmin and the primary clot lysis enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Apo (a) interferes with plasminogen binding to C-terminal lysines of cell surface and extracellular matrix proteins.", "output": {"entities": {"chemical": [{"text": "C", "start": 47, "end": 48}]}}, "schema": []}
{"input": "Lp (a) and apo (a) inhibit fibrinolysis and accumulate in the vascular wall in atherosclerotic lesions.", "output": {"entities": {}}, "schema": []}
{"input": "The pathogenic role of Lp (a) is not known.", "output": {"entities": {}}, "schema": []}
{"input": "Small isoforms and high concentrations of Lp (a) are found in healthy octogenarians that suggest Lp (a) may also have a physiological role.", "output": {"entities": {}}, "schema": []}
{"input": "Studies of Lp (a) function have been limited since it is not found in commonly studied small mammals.", "output": {"entities": {}}, "schema": []}
{"input": "An important aspect of Lp (a) metabolism is the modification of circulating Lp (a), which has the potential to alter the functions of Lp (a).", "output": {"entities": {}}, "schema": []}
{"input": "There are no therapeutic drugs that selectively target elevated Lp (a), but a number of possible agents are being considered.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, new modifiers of apo (a) synthesis have been identified.", "output": {"entities": {}}, "schema": []}
{"input": "This review reports the regulation of Lp (a) metabolism and potential sites for therapeutic targets.", "output": {"entities": {}}, "schema": []}
{"input": "Rational design of apoptosis signal-regulating kinase 1 inhibitors: discovering novel structural scaffold.", "output": {"entities": {}}, "schema": []}
{"input": "Increased activity of apoptosis signal-regulating kinase 1 (ASK1) is associated with a number of human disorders and the inhibitors of ASK1 may become important compounds for pharmaceutical application.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report novel ASK1 inhibitor scaffold, namely 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one, that has been identified using virtual screening and biochemical tests.", "output": {"entities": {"chemical": [{"text": "5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one", "start": 53, "end": 112}]}}, "schema": []}
{"input": "A series of derivatives has been synthesized and evaluated in vitro towards human protein kinase ASK1.", "output": {"entities": {}}, "schema": []}
{"input": "It was revealed that the most active compounds 4-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) butanoic acid and 6-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) hexanoic acid inhibit ASK1 with IC50 of 0. 2 mu M.", "output": {"entities": {"chemical": [{"text": "4-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) butanoic acid", "start": 47, "end": 148}, {"text": "6-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) hexanoic acid", "start": 153, "end": 254}]}}, "schema": []}
{"input": "Structure-activity relationships of 33 derivatives of 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one have been studied and binding mode of this chemical class has been predicted.", "output": {"entities": {"chemical": [{"text": "5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one", "start": 54, "end": 113}]}}, "schema": []}
{"input": "Identification and characterization of novel catalytic bioscavengers of organophosphorus nerve agents.", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 72, "end": 88}]}}, "schema": []}
{"input": "In an effort to discover novel catalytic bioscavengers of organophosphorus (OP) nerve agents, cell lysates from a diverse set of bacterial strains were screened for their capacity to hydrolyze the OP nerve agents VX, VR, and soman (GD).", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 58, "end": 74}, {"text": "soman", "start": 225, "end": 230}]}}, "schema": []}
{"input": "The library of bacterial strains was identified using both random and rational approaches.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, two representative strains from eight categories of extremophiles were chosen at random.", "output": {"entities": {}}, "schema": []}
{"input": "For the rational approach, the protein sequence of organophosphorus hydrolase (OPH) from Brevundimonas diminuta was searched against a non-redundant protein database using the Basic Local Alignment Search Tool to find regions of local similarity between sequences.", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 51, "end": 67}]}}, "schema": []}
{"input": "Over 15 protein sequences with significant sequence similarity to OPH were identified from a variety of bacterial strains.", "output": {"entities": {}}, "schema": []}
{"input": "Some of these matches were based on predicted protein structures derived from bacterial genome sequences rather than from bona fide proteins isolated from bacteria.", "output": {"entities": {}}, "schema": []}
{"input": "Of the 25 strains selected for nerve agent testing, three bacterial strains had measurable levels of OP hydrolase activity.", "output": {"entities": {}}, "schema": []}
{"input": "These strains are Ammoniphilus oxalaticus, Haloarcula sp., and Micromonospora aurantiaca.", "output": {"entities": {}}, "schema": []}
{"input": "Lysates from A. oxalaticus had detectable hydrolysis of VR; Haloarcula sp. had appreciable hydrolysis of VX and VR, whereas lysates from M. aurantiaca had detectable hydrolysis of VR and GD.", "output": {"entities": {}}, "schema": []}
{"input": "Targeting peroxisome proliferator-activated receptor-beta/delta in colon cancer: how to aim?", "output": {"entities": {}}, "schema": []}
{"input": "Peroxisome proliferator-activated receptor-beta/delta (PPAR delta) is a ubiquitously expressed, ligand-activated transcriptional factor that performs diverse critical functions in normal cells (e. g., fatty acid metabolism, obesity, apoptosis, and inflammation).", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 201, "end": 211}]}}, "schema": []}
{"input": "Various studies in humans have found that PPAR delta is upregulated in primary colorectal cancers; however, these findings have been challenged by those of other reports.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, various in vitro and in vivo mechanistic pre-clinical models have yielded data demonstrating that PPAR delta promotes colonic tumorigenesis, but other models have yielded data that contradicts this notion.", "output": {"entities": {}}, "schema": []}
{"input": "Definitive studies are therefore needed to establish the exact role of PPAR delta in human colorectal tumorigenesis and to provide a theoretical basis for PPAR delta therapeutic targeting.", "output": {"entities": {}}, "schema": []}
{"input": "One target-two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1 beta.", "output": {"entities": {}}, "schema": []}
{"input": "Interleukin-1 beta (IL-1 beta) is a key orchestrator in inflammatory and several immune responses.", "output": {"entities": {}}, "schema": []}
{"input": "IL-1 beta exerts its effects through interleukin-1 receptor type I (IL-1RI) and interleukin-1 receptor accessory protein (IL-1RAcP), which together form a heterotrimeric signaling-competent complex.", "output": {"entities": {}}, "schema": []}
{"input": "Canakinumab and gevokizumab are highly specific IL-1 beta monoclonal antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "Canakinumab is known to neutralize IL-1 beta by competing for binding to IL-1R and therefore blocking signaling by the antigen: antibody complex.", "output": {"entities": {}}, "schema": []}
{"input": "Gevokizumab is claimed to be a regulatory therapeutic antibody that modulates IL-1 beta bioactivity by reducing the affinity for its IL-1RI: IL-1RAcP signaling complex.", "output": {"entities": {}}, "schema": []}
{"input": "How IL-1 beta signaling is affected by both canakinumab and gevokizumab was not yet experimentally determined.", "output": {"entities": {}}, "schema": []}
{"input": "We have analyzed the crystal structures of canakinumab and gevokizumab antibody binding fragment (Fab) as well as of their binary complexes with IL-1 beta.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we characterized the epitopes on IL-1 beta employed by the antibodies by NMR epitope mapping studies.", "output": {"entities": {}}, "schema": []}
{"input": "The direct comparison of NMR and X-ray data shows that the epitope defined by the crystal structure encompasses predominantly those residues whose NMR resonances are severely perturbed upon complex formation.", "output": {"entities": {}}, "schema": []}
{"input": "The antigen: Fab co-structures confirm the previously identified key contact residues on IL-1 beta and provide insight into the mechanisms leading to their distinct modulation of IL-1 beta signaling.", "output": {"entities": {}}, "schema": []}
{"input": "A significant steric overlap of the binding interfaces of IL-1R and canakinumab on IL-1 beta causes competitive inhibition of the association of IL-1 beta and its receptor.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, gevokizumab occupies an allosteric site on IL-1 beta and complex formation results in a minor reduction of binding affinity to IL-1RI.", "output": {"entities": {}}, "schema": []}
{"input": "This suggests two different mechanisms of IL-1 beta pathway attenuation.", "output": {"entities": {}}, "schema": []}
{"input": "Establishment of a molecular embryonic stem cell developmental toxicity assay.", "output": {"entities": {}}, "schema": []}
{"input": "The mouse embryonic stem cell test (EST) is a 10-day screen for teratogenic potential developed to reduce animal use for embryotoxicity testing of chemicals (Spielmann, 2005; Spielmann et al., 1997).", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we used the cytotoxicity IC (50) values and transcriptional expression changes as primary endpoints in a shorter 4-day version of the EST, the molecular embryonic stem cell assay.", "output": {"entities": {}}, "schema": []}
{"input": "Mouse D3 embryonic stem cells were used for cytotoxicity assessment (monolayers) or grown as embryoid bodies in low attachment plates for transcriptional profiling.", "output": {"entities": {}}, "schema": []}
{"input": "Sixty-five compounds with known in vivo teratogenicity (33 teratogens and 32 nonteratogens) were evaluated to develop a model for classifying compounds with teratogenic potential.", "output": {"entities": {}}, "schema": []}
{"input": "The expression of 12 developmentally regulated gene targets (nanog, fgf5, gsc, cd34, axin2, apln, chst7, lhx1, fgf8, sox17, foxa2, and cxcr4) was measured following exposure of embryoid bodies to a single compound concentration (0. 1 x the cytotoxicity IC (20)) for 4 days.", "output": {"entities": {}}, "schema": []}
{"input": "In the decision-tree model, compounds with IC (50) values < 22 micro M were categorized as teratogens, whereas compounds in the two groups with IC (50) values between 22-200 micro M and > 200 micro M were categorized as teratogens if >= 8 and 12 genes, respectively, were deregulated by at least 10%.", "output": {"entities": {}}, "schema": []}
{"input": "Forty-seven of 65 compounds of the training set were correctly identified (72% total concordance).", "output": {"entities": {}}, "schema": []}
{"input": "In a test set of 12 additional compounds (5 teratogens, 7 nonteratogens), 10 were correctly classified by this approach (83% concordance).", "output": {"entities": {}}, "schema": []}
{"input": "The false positive rate in the training and test sets was 24 and 0%, respectively, indicating that this assay has potential to identify teratogens.", "output": {"entities": {}}, "schema": []}
{"input": "Differential cell-protective function of two resveratrol (trans-3, 5, 4'-trihydroxystilbene) glucosides against oxidative stress.", "output": {"entities": {"chemical": [{"text": "resveratrol (trans-3, 5, 4'-trihydroxystilbene) glucosides", "start": 45, "end": 103}]}}, "schema": []}
{"input": "Resveratrol (trans-3, 5, 4'-trihydroxystilbene; RSV), a natural polyphenol, exerts a beneficial effect on health and diseases.", "output": {"entities": {"chemical": [{"text": "Resveratrol", "start": 0, "end": 11}, {"text": "trans-3, 5, 4'-trihydroxystilbene", "start": 13, "end": 46}, {"text": "RSV", "start": 48, "end": 51}, {"text": "polyphenol", "start": 64, "end": 74}]}}, "schema": []}
{"input": "RSV targets and activates the NAD (+)-dependent protein deacetylase SIRT1; in turn, SIRT1 induces an intracellular antioxidative mechanism by inducing mitochondrial superoxide dismutase (SOD2).", "output": {"entities": {"chemical": [{"text": "RSV", "start": 0, "end": 3}, {"text": "NAD (+)", "start": 30, "end": 37}, {"text": "superoxide", "start": 165, "end": 175}]}}, "schema": []}
{"input": "Most RSV found in plants is glycosylated, and the effect of these glycosylated forms on SIRT1 has not been studied.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we compared the effects of RSV and two glycosyl RSVs, resveratrol-3-O-beta-d-glucoside (3G-RSV; polydatin/piceid) and resveratrol-4'-O-beta-d-glucoside (4' G-RSV), at the cellular level.", "output": {"entities": {"chemical": [{"text": "RSV", "start": 42, "end": 45}, {"text": "glycosyl RSVs", "start": 54, "end": 67}, {"text": "resveratrol-3-O-beta-d-glucoside", "start": 69, "end": 101}, {"text": "3G-RSV", "start": 103, "end": 109}, {"text": "polydatin", "start": 111, "end": 120}, {"text": "piceid", "start": 121, "end": 127}, {"text": "resveratrol-4'-O-beta-d-glucoside", "start": 133, "end": 166}, {"text": "4' G-RSV", "start": 168, "end": 176}]}}, "schema": []}
{"input": "In oxygen radical absorbance capacity and 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assays, the antioxidant activity of 3G-RSV was comparable to that of RSV, whereas the radical-scavenging efficiency of 4' G-RSV was less than 50% of that of RSV.", "output": {"entities": {"chemical": [{"text": "2, 2-diphenyl-1-picrylhydrazyl", "start": 42, "end": 72}, {"text": "3G-RSV", "start": 128, "end": 134}, {"text": "RSV", "start": 161, "end": 164}, {"text": "4' G-RSV", "start": 211, "end": 219}, {"text": "RSV", "start": 249, "end": 252}]}}, "schema": []}
{"input": "However, 4' G-RSV, but not 3G-RSV, induced SIRT1-dependent histone H3 deacetylation and SOD2 expression in mouse C2C12 skeletal myoblasts; as with RSV, SIRT1 knockdown blunted these effects.", "output": {"entities": {"chemical": [{"text": "4' G-RSV", "start": 9, "end": 17}, {"text": "3G-RSV", "start": 27, "end": 33}, {"text": "RSV", "start": 147, "end": 150}]}}, "schema": []}
{"input": "RSV and 4' G-RSV, but not 3G-RSV, mitigated oxidative stress-induced cell death in C2C12 cells and primary neonatal rat cardiomyocytes.", "output": {"entities": {"chemical": [{"text": "RSV", "start": 0, "end": 3}, {"text": "4' G-RSV", "start": 8, "end": 16}, {"text": "3G-RSV", "start": 26, "end": 32}]}}, "schema": []}
{"input": "RSV and 4' G-RSV inhibited C2C12 cell proliferation, but 3G-RSV did not.", "output": {"entities": {"chemical": [{"text": "RSV", "start": 0, "end": 3}, {"text": "4' G-RSV", "start": 8, "end": 16}, {"text": "3G-RSV", "start": 57, "end": 63}]}}, "schema": []}
{"input": "RSV was found in both the intracellular and extracellular fractions of C2C12 cells that had been incubated with 4' G-RSV, indicating that 4' G-RSV was extracellularly deglycosylated to RSV, which was then taken up by the cells.", "output": {"entities": {"chemical": [{"text": "RSV", "start": 0, "end": 3}, {"text": "4' G-RSV", "start": 112, "end": 120}, {"text": "4' G-RSV", "start": 138, "end": 146}, {"text": "RSV", "start": 185, "end": 188}]}}, "schema": []}
{"input": "C2C12 cells did not deglycosylate 3G-RSV.", "output": {"entities": {"chemical": [{"text": "3G-RSV", "start": 34, "end": 40}]}}, "schema": []}
{"input": "Our results point to 4' G-RSV as a useful RSV prodrug with high water solubility.", "output": {"entities": {"chemical": [{"text": "4' G-RSV", "start": 21, "end": 29}, {"text": "RSV", "start": 42, "end": 45}]}}, "schema": []}
{"input": "These data also show that the in vitro antioxidative activity of these molecules did not correlate with their ability to protect cells from oxidative stress-induced apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism and disposition of vilanterol, a long-acting beta (2)-adrenoceptor agonist for inhalation use in humans.", "output": {"entities": {"chemical": [{"text": "vilanterol", "start": 30, "end": 40}]}}, "schema": []}
{"input": "The metabolism and disposition of vilanterol, a novel long-acting beta (2)-adrenoceptor agonist (LABA) for inhalation use, was investigated after oral administration in humans.", "output": {"entities": {"chemical": [{"text": "vilanterol", "start": 34, "end": 44}]}}, "schema": []}
{"input": "Single oral administrations of up to 500 mu g of vilanterol were shown to be safe and well tolerated in two clinical studies in healthy men.", "output": {"entities": {"chemical": [{"text": "vilanterol", "start": 49, "end": 59}]}}, "schema": []}
{"input": "In a human radiolabel study, six healthy men received a single oral dose of 200 mu g of [(14) C] vilanterol (74 kBq).", "output": {"entities": {"chemical": [{"text": "[(14) C] vilanterol", "start": 88, "end": 107}]}}, "schema": []}
{"input": "Plasma, urine, and feces were collected up to 168 hours after the dose and were analyzed for vilanterol, metabolites, and radioactivity.", "output": {"entities": {"chemical": [{"text": "vilanterol", "start": 93, "end": 103}]}}, "schema": []}
{"input": "At least 50% of the radioactive dose was orally absorbed.", "output": {"entities": {}}, "schema": []}
{"input": "The primary route of excretion of drug-related material was via O-dealkylation to metabolites, which were mainly excreted in urine.", "output": {"entities": {"chemical": [{"text": "O", "start": 64, "end": 65}]}}, "schema": []}
{"input": "Vilanterol represented a very small percentage (< 0. 5%) of the total drug-related material in plasma, indicative of extensive first-pass metabolism.", "output": {"entities": {"chemical": [{"text": "Vilanterol", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Circulating metabolites resulted mainly from O-dealkylation and exhibited negligible pharmacologic activity.", "output": {"entities": {"chemical": [{"text": "O", "start": 45, "end": 46}]}}, "schema": []}
{"input": "The therapeutic dose level for vilanterol is 25 mu g by the inhalation route.", "output": {"entities": {"chemical": [{"text": "vilanterol", "start": 31, "end": 41}]}}, "schema": []}
{"input": "At this low-dose level, the likelihood of pharmacologically inactive metabolites causing unexpected toxicity is negligible.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to providing an assessment of the disposition of vilanterol in human, this work highlights a number of complexities associated with determining human absorption, distribution, metabolism, and excretion (ADME) for inhaled molecules--mainly related to the low chemical doses and complications associated with the inhalation route of administration.", "output": {"entities": {"chemical": [{"text": "vilanterol", "start": 61, "end": 71}]}}, "schema": []}
{"input": "Establishment of an in vitro photoallergy test using NCTC2544 cells and IL-18 production.", "output": {"entities": {}}, "schema": []}
{"input": "Differentiation between photoallergenic and phototoxic reactions induced by low molecular weight compounds represents a current problem.", "output": {"entities": {}}, "schema": []}
{"input": "The use of keratinocytes as a potential tool for the detection of photoallergens as opposed to photoirritants is considered an interesting strategy for developing in vitro methods.", "output": {"entities": {}}, "schema": []}
{"input": "We have previously demonstrated the possibility to use the human keratinocyte cell line NCTC2455 and the production of interleukin-18 (IL-18) to screen low molecular weight sensitizers.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this work was to explore the possibility to use the NCTC2544 assay to identify photoallergens and discriminate from phototoxic chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "First, we identified suitable condition of UV-irradiation (3. 5 J/cm (2)) by investigating the effect of UVA irradiation on intracellular IL-18 on untreated or chloropromazine (a representative phototoxic compound)-treated NCTC2544 cells.", "output": {"entities": {"chemical": [{"text": "chloropromazine", "start": 160, "end": 175}]}}, "schema": []}
{"input": "Then, the effect of UVA-irradiation over NCTC2544 cells treated with increasing concentrations of 15 compounds including photoallergens (benzophenone, 4-ter-butyl-4-methoxy-dibenzoylmethane, 2-ethylexyl-p-methoxycinnamate, ketoprofen, 6-methylcumarin); photoirritant and photoallergen (4-aminobenzoic acid, chlorpromazine, promethazine); photoirritants (acridine, ibuprofen, 8-methoxypsoralen, retinoic acid); and negative compounds (lactic acid, SDS and p-phenilendiamine) was investigated.", "output": {"entities": {"chemical": [{"text": "benzophenone", "start": 137, "end": 149}, {"text": "4-ter-butyl-4-methoxy-dibenzoylmethane, 2-ethylexyl-p-methoxycinnamate", "start": 151, "end": 221}, {"text": "ketoprofen", "start": 223, "end": 233}, {"text": "6-methylcumarin", "start": 235, "end": 250}, {"text": "4-aminobenzoic acid", "start": 286, "end": 305}, {"text": "chlorpromazine", "start": 307, "end": 321}, {"text": "promethazine", "start": 323, "end": 335}, {"text": "acridine", "start": 354, "end": 362}, {"text": "ibuprofen", "start": 364, "end": 373}, {"text": "8-methoxypsoralen", "start": 375, "end": 392}, {"text": "retinoic acid", "start": 394, "end": 407}, {"text": "lactic acid", "start": 434, "end": 445}, {"text": "SDS", "start": 447, "end": 450}, {"text": "p-phenilendiamine", "start": 455, "end": 472}]}}, "schema": []}
{"input": "Twenty-four hours after exposure, cytotoxicity was evaluated by the MTT assay or LDH leakage, while ELISA was used to measure the production of IL-18.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 68, "end": 71}]}}, "schema": []}
{"input": "At the maximal concentration assayed with non-cytotoxic effects (CV80 under irradiated condition), all tested photoallergens induced a significant and a dose-dependent increase of intracellular IL-18 following UVA irratiation, whereas photoirritants failed.", "output": {"entities": {}}, "schema": []}
{"input": "We suggest that this system may be useful for the in vitro evaluation of the photoallergic potential of chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT.", "output": {"entities": {"chemical": [{"text": "zoledronic acid", "start": 45, "end": 60}]}}, "schema": []}
{"input": "Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton.", "output": {"entities": {}}, "schema": []}
{"input": "We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to detail effects on compartmental geometry, density, and microarchitecture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 micro g sc daily, n = 18) or PTH 1-84 (100 micro g sc daily, n = 20) for 18 months in an open-label, nonrandomized study.", "output": {"entities": {}}, "schema": []}
{"input": "A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n = 33) was also included.", "output": {"entities": {"chemical": [{"text": "zoledronic acid", "start": 55, "end": 70}]}}, "schema": []}
{"input": "Anabolic therapy increased cortical porosity in radius (PTH 1-34 32 +/- 37%, PTH 1-84 39 +/- 32%, both p < 0. 001) and tibia (PTH 1-34 13 +/- 27%, PTH 1-84 15 +/- 22%, both p < 0. 001) with corresponding declines in cortical density.", "output": {"entities": {}}, "schema": []}
{"input": "With PTH 1-34, increases in cortical thickness in radius (2. 0 +/- 3. 8%, p < 0. 05) and tibia (3. 8 +/- 10. 4%, p < 0. 01) were found.", "output": {"entities": {}}, "schema": []}
{"input": "Trabecular number increased in tibia with both PTH 1-34 (4. 2 +/- 7. 1%, p < 0. 05) and PTH 1-84 (5. 3 +/- 8. 3%, p < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "Zoledronic acid did not impact cortical porosity at either site but increased cortical thickness (3. 0 +/- 3. 5%, p < 0. 01), total (2. 7 +/- 2. 5%, p < 0. 001) and cortical density (1. 5 +/- 2. 0%, p < 0. 01) in tibia as well as trabecular volume fraction in radius (2. 5 +/- 5. 1%, p < 0. 05) and tibia (2. 2 +/- 2. 2%, p < 0. 01).", "output": {"entities": {"chemical": [{"text": "Zoledronic acid", "start": 0, "end": 15}]}}, "schema": []}
{"input": "FE estimated bone strength was preserved, but not increased, with PTH 1-34 and zoledronic acid at both sites, whereas it decreased with PTH 1-84 in radius (-2. 8 +/- 5. 8%, p < 0. 05) and tibia (-3. 9 +/- 4. 8%, p < 0. 001).", "output": {"entities": {"chemical": [{"text": "zoledronic acid", "start": 79, "end": 94}]}}, "schema": []}
{"input": "Conclusively, divergent treatment-specific effects in cortical and trabecular bone were observed with anabolic and zoledronic acid therapy.", "output": {"entities": {"chemical": [{"text": "zoledronic acid", "start": 115, "end": 130}]}}, "schema": []}
{"input": "The finding of decreased estimated strength with PTH 1-84 treatment was surprising and warrants confirmation.", "output": {"entities": {}}, "schema": []}
{"input": "Deletion of CD74, a putative MIF receptor, in mice enhances osteoclastogenesis and decreases bone mass.", "output": {"entities": {}}, "schema": []}
{"input": "CD74 is a type II transmembrane protein that can act as a receptor for macrophage migration inhibitory factor (MIF) and plays a role in MIF-regulated responses.", "output": {"entities": {}}, "schema": []}
{"input": "We reported that MIF inhibited osteoclast formation and MIF knockout (KO) mice had decreased bone mass.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore examined if CD74 was involved in the ability of MIF to alter osteoclastogenesis in cultured bone marrow (BM) from wild-type (WT) and CD74-deficient (KO) male mice.", "output": {"entities": {}}, "schema": []}
{"input": "We also measured the bone phenotype of CD74 KO male mice.", "output": {"entities": {}}, "schema": []}
{"input": "Bone mass in the femur of 8-week-old mice was measured by micro-computed tomography and histomorphometry.", "output": {"entities": {}}, "schema": []}
{"input": "Bone marrow cells from CD74 KO mice formed 15% more osteoclast-like cells (OCLs) with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappa B ligand (RANKL) (both at 30 ng/mL) compared to WT.", "output": {"entities": {}}, "schema": []}
{"input": "Addition of MIF to WT cultures inhibited OCL formation by 16% but had no effect on CD74KO cultures.", "output": {"entities": {}}, "schema": []}
{"input": "The number of colony forming unit granulocyte-macrophage (CFU-GM) in the bone marrow of CD74 KO mice was 26% greater than in WT controls.", "output": {"entities": {}}, "schema": []}
{"input": "Trabecular bone volume (TBV) in the femurs of CD74 KO male mice was decreased by 26% compared to WT.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, cortical area and thickness were decreased by 14% and 11%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Histomorphometric analysis demonstrated that tartrate-resistant acid phosphatase (TRAP) (+) osteoclast number and area were significantly increased in CD74 KO by 35% and 43%, respectively compared to WT.", "output": {"entities": {"chemical": [{"text": "tartrate", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Finally, we examined the effect of MIF on RANKL-induced-signaling pathways in bone marrow macrophage (BMM) cultures.", "output": {"entities": {}}, "schema": []}
{"input": "MIF treatment decreased RANKL-induced nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and c-Fos protein in BMM cultures by 70% and 41%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Our data demonstrate that CD74 is required for MIF to affect in vitro osteoclastogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Further, the bone phenotype of CD74 KO mice is similar to that of MIF KO mice.", "output": {"entities": {}}, "schema": []}
{"input": "MIF treatment of WT cultures suppressed RANKL-induced activator protein 1 (AP-1) expression, which resulted in decreased osteoclast differentiation in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "We propose that CD74 plays a critical role in the MIF inhibition of osteoclastogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Immune-induced expression of lipocalin-2 in brain endothelial cells: relationship with interleukin-6, cyclooxygenase-2 and the febrile response.", "output": {"entities": {}}, "schema": []}
{"input": "Interleukin (IL)-6 is critical for the febrile response to peripheral immune challenge.", "output": {"entities": {}}, "schema": []}
{"input": "However, the mechanism by which IL-6 enables fever is still unknown.", "output": {"entities": {}}, "schema": []}
{"input": "To characterise the IL-6-dependent fever generating pathway, we used microarray analysis to identify differentially expressed genes in the brain of lipopolysaccharide (LPS)-treated IL-6 wild-type and knockout mice.", "output": {"entities": {}}, "schema": []}
{"input": "Mice lacking IL-6 displayed a two-fold lower expression of the lipocalin-2 gene (lcn2), and this difference was confirmed by real-time reverse transcriptase-polymerase chain reaction.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, the induction of lipocalin-2 protein was observed in brain vascular cells following i. p. administration of recombinant IL-6, suggesting a direct relationship between IL-6 and lipocalin-2.", "output": {"entities": {}}, "schema": []}
{"input": "Immunohistochemical analysis also revealed that LPS-induced lipocalin-2 is expressed by brain endothelial cells and is partly co-localised with cyclooxygenase-2 (Cox-2), the rate-limiting enzyme for the production of inflammatory induced prostaglandin E (2) (PGE (2)), which is the key mediator of fever.", "output": {"entities": {"chemical": [{"text": "prostaglandin E (2)", "start": 238, "end": 257}, {"text": "PGE (2)", "start": 259, "end": 266}]}}, "schema": []}
{"input": "The direct role of lipocalin-2 in fever was examined in LPS-challenged lipocalin-2 knockout mice.", "output": {"entities": {}}, "schema": []}
{"input": "In both male and female mice, normal fever responses were observed at near-thermoneutral conditions (29-30 degrees C) but when recorded at normal room temperature (19-20 degrees C), the body temperature of lipocalin-2 knockout female mice displayed an attenuated fever response compared to their wild-type littermates.", "output": {"entities": {}}, "schema": []}
{"input": "This difference was reflected in significantly attenuated mRNA expression of Cox-2 in the brain of lipocalin-2 knockout female mice, but not of male mice, following challenge with peripheral LPS.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest that IL-6 influences the expression of lipocalin-2, which in turn may be involved in the control of the formation of Cox-2, and hence central PGE (2)-production.", "output": {"entities": {"chemical": [{"text": "PGE (2)", "start": 163, "end": 170}]}}, "schema": []}
{"input": "We have thus identified lipocalin-2 as a new factor in the pathway of inflammatory IL-6 signalling.", "output": {"entities": {}}, "schema": []}
{"input": "However, the effect of lipocalin-2 on fever is small, being sex-dependent and ambient temperature-specific, and thus lipocalin-2 cannot be considered as a major mediator of the IL-6-dependent fever generating pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Interspecies variation in the metabolism of zoniporide by aldehyde oxidase.", "output": {"entities": {"chemical": [{"text": "zoniporide", "start": 44, "end": 54}, {"text": "aldehyde", "start": 58, "end": 66}]}}, "schema": []}
{"input": "1. Aldehyde oxidase (AO) is a cytosolic enzyme that contributes to the Phase I metabolism of xenobiotics in human and preclinical species.", "output": {"entities": {"chemical": [{"text": "Aldehyde", "start": 3, "end": 11}]}}, "schema": []}
{"input": "2. Current studies explored in vitro metabolism of zoniporide in various animal species and humans using S9 fractions.", "output": {"entities": {"chemical": [{"text": "zoniporide", "start": 51, "end": 61}]}}, "schema": []}
{"input": "The animal species included commonly used pharmacology and toxicology models and domestic animals such as the cat, cow or bull, pig and horse.", "output": {"entities": {}}, "schema": []}
{"input": "3. In addition, gender and strain differences in some species were also explored.", "output": {"entities": {}}, "schema": []}
{"input": "4. All animals except the dog and cat converted zoniporide to 2-oxozoniporide (M1).", "output": {"entities": {"chemical": [{"text": "zoniporide", "start": 48, "end": 58}, {"text": "2-oxozoniporide", "start": 62, "end": 77}]}}, "schema": []}
{"input": "5. Michael-Menten kinetic studies were conducted in species that turned over zoniporide to M1.", "output": {"entities": {"chemical": [{"text": "zoniporide", "start": 77, "end": 87}]}}, "schema": []}
{"input": "6. Marked differences in KM, Vmax and Clint were observed in the oxidation of zoniporide.", "output": {"entities": {"chemical": [{"text": "zoniporide", "start": 78, "end": 88}]}}, "schema": []}
{"input": "7. Although the KM and Vmax of zoniporide oxidation in male and female human S9 was similar, some gender difference was observed in animals especially, in Vmax.", "output": {"entities": {"chemical": [{"text": "zoniporide", "start": 31, "end": 41}]}}, "schema": []}
{"input": "8. The domestic animals also showed marked species differences in the AO activity and affinity toward zoniporide.", "output": {"entities": {"chemical": [{"text": "zoniporide", "start": 102, "end": 112}]}}, "schema": []}
{"input": "Adverse outcome pathways during zebrafish embryogenesis: a case study with paraoxon.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 75, "end": 83}]}}, "schema": []}
{"input": "Using paraoxon as a reference acetylcholinesterase (AChE) inhibitor, the objective of this study was to develop an adverse outcome pathway (AOP) that provided quantitative linkages across levels of biological organization during zebrafish embryogenesis.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 6, "end": 14}]}}, "schema": []}
{"input": "Within normal zebrafish embryos, we first demonstrated that ache transcripts and AChE activity increased in a stage-dependent manner following segmentation.", "output": {"entities": {}}, "schema": []}
{"input": "We then showed that static exposure of embryos to paraoxon (31. 2-500 nM) from 5 to 96 hpf resulted in significant stage-and concentration-dependent AChE inhibition, albeit these effects were fully reversible within 48 h following transfer to clean water.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 50, "end": 58}]}}, "schema": []}
{"input": "However, even in the presence of significant AChE inhibition, exposure to non-teratogenic paraoxon concentrations (<= 250 nM) did not adversely impact secondary motoneuron development at 96 hpf.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 90, "end": 98}]}}, "schema": []}
{"input": "Therefore, we investigated the potential effects of paraoxon exposure on spontaneous tail contractions at 26 hpf-an early locomotor behavior that results from innervation of primary (not secondary) motoneuron axons to target axial muscles.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 52, "end": 60}]}}, "schema": []}
{"input": "Based on these studies, the frequency of spontaneous tail contractions at 26 hpf-a developmental stage with minimal AChE expression and activity-was significantly higher following exposure to paraoxon concentrations as low as 31. 2 nM.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 192, "end": 200}]}}, "schema": []}
{"input": "Overall, our data suggest that (1) normal AChE activity is not required for secondary motoneuron development and (2) spontaneous tail contractions at 26 hpf are sensitive to paraoxon exposure, an effect that may be independent of AChE inhibition.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 174, "end": 182}]}}, "schema": []}
{"input": "Using a well-studied reference chemical, this study highlights the potential challenges in developing quantitative AOPs to support chemical screening and prioritization strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Hierarchical rutile TiO2 flower cluster-based high efficiency dye-sensitized solar cells via direct hydrothermal growth on conducting substrates.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 20, "end": 24}]}}, "schema": []}
{"input": "Dye-sensitized solar cells (DSSCs) based on hierarchical rutile TiO (2) flower clusters prepared by a facile, one-pot hydrothermal process exhibit a high efficiency.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 64, "end": 71}]}}, "schema": []}
{"input": "Complex yet appealing rutile TiO (2) flower films are, for the first time, directly hydrothermally grown on a transparent conducting fluorine-doped tin oxide (FTO) substrate.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 29, "end": 36}, {"text": "fluorine-doped tin oxide", "start": 133, "end": 157}, {"text": "FTO", "start": 159, "end": 162}]}}, "schema": []}
{"input": "The thickness and density of as-grown flower clusters can be readily tuned by tailoring growth parameters, such as growth time, the addition of cations of different valence and size, initial concentrations of precursor and cation, growth temperature, and acidity.", "output": {"entities": {}}, "schema": []}
{"input": "Notably, the small lattice mismatch between the FTO substrate and rutile TiO (2) renders the epitaxial growth of a compact rutile TiO (2) layer on the FTO glass.", "output": {"entities": {"chemical": [{"text": "FTO", "start": 48, "end": 51}, {"text": "TiO (2)", "start": 73, "end": 80}, {"text": "TiO (2)", "start": 130, "end": 137}, {"text": "FTO", "start": 151, "end": 154}]}}, "schema": []}
{"input": "Intriguingly, these TiO (2) flower clusters can then be exploited as photoanodes to produce DSSCs, yielding a power conversion efficiency of 2. 94% despite their rutile nature, which is further increased to 4. 07% upon the TiCl (4) treatment.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 20, "end": 27}, {"text": "TiCl (4)", "start": 223, "end": 231}]}}, "schema": []}
{"input": "Circulating very-low-density lipoprotein from subjects with impaired glucose tolerance accelerates adrenocortical cortisol and aldosterone synthesis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 69, "end": 76}, {"text": "cortisol", "start": 114, "end": 122}, {"text": "aldosterone", "start": 127, "end": 138}]}}, "schema": []}
{"input": "Apart from their role in cardiovascular homeostasis and immunomodulation, aldosterone and cortisol are also implicated in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM).", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 74, "end": 85}, {"text": "cortisol", "start": 90, "end": 98}]}}, "schema": []}
{"input": "Furthermore, glycoxidative modifications of lipoproteins are increasingly recognized as an etiological factor for increased cardiovascular morbidity and mortality in prediabetic individuals.", "output": {"entities": {}}, "schema": []}
{"input": "The causative relationship between in vivo lipoprotein modifications and steroidogenesis in subjects with impaired glucose tolerance (IGT), however, is not well defined.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 115, "end": 122}]}}, "schema": []}
{"input": "Therefore, we aimed to investigate the impact of in vivo modified lipoproteins on aldosterone and cortisol release from human adrenocortical H295R cells.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 82, "end": 93}, {"text": "cortisol", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Following an oral glucose tolerance test, 20 individuals with normal glucose tolerance (NGT) and 20 IGT subjects were randomly selected from the ongoing PRAEDIAS prevention study in our department.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 18, "end": 25}, {"text": "glucose", "start": 69, "end": 76}]}}, "schema": []}
{"input": "Cells were incubated for 24 h with lipoproteins isolated from NGT and IGT individuals and aldosterone and cortisol release was measured in the supernatants.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 90, "end": 101}, {"text": "cortisol", "start": 106, "end": 114}]}}, "schema": []}
{"input": "VLDL induced a greater stimulating effect on adrenocortical aldosterone and cortisol release compared to HDL and LDL.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 60, "end": 71}, {"text": "cortisol", "start": 76, "end": 84}]}}, "schema": []}
{"input": "Moreover, IGT-VLDL evoked a significantly higher effect (p < 0. 05) on hormone release than NGT-VLDL.", "output": {"entities": {}}, "schema": []}
{"input": "Incubation of cells with in vitro modified lipoproteins and specific pharmacological inhibitors suggests that VLDL presumably recruits ERK1/2 as one of the downstream effectors of Jak-2.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, in vivo modified VLDL are able to promote prediabetic hormonal dysregulation by modulating adrenocortical steroidogenesis via Jak-2-ERK dependent pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques.", "output": {"entities": {}}, "schema": []}
{"input": "The melanocortin-4 receptor (MC4R) is well recognized as an important mediator of body weight homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of MC4R causes dramatic weight loss in rodent models, and mutations in human are associated with obesity.", "output": {"entities": {}}, "schema": []}
{"input": "This makes MC4R a logical target for pharmacological therapy for the treatment of obesity.", "output": {"entities": {}}, "schema": []}
{"input": "However, previous studies in rodents and humans have observed a broad array of side effects caused by acute treatment with MC4R agonists, including increased heart rate and blood pressure.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that treatment with a highly-selective novel MC4R agonist (BIM-22493 or RM-493) resulted in transient decreases in food intake (35%), with persistent weight loss over 8 weeks of treatment (13. 5%) in a diet-induced obese nonhuman primate model.", "output": {"entities": {"chemical": [{"text": "BIM-22493", "start": 74, "end": 83}, {"text": "RM-493", "start": 87, "end": 93}]}}, "schema": []}
{"input": "Consistent with weight loss, these animals significantly decreased adiposity and improved glucose tolerance.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 90, "end": 97}]}}, "schema": []}
{"input": "Importantly, we observed no increases in blood pressure or heart rate with BIM-22493 treatment.", "output": {"entities": {"chemical": [{"text": "BIM-22493", "start": 75, "end": 84}]}}, "schema": []}
{"input": "In contrast, treatment with LY2112688, an MC4R agonist previously shown to increase blood pressure and heart rate in humans, caused increases in blood pressure and heart rate, while modestly decreasing food intake.", "output": {"entities": {"chemical": [{"text": "LY2112688", "start": 28, "end": 37}]}}, "schema": []}
{"input": "These studies demonstrate that distinct melanocortin peptide drugs can have widely different efficacies and side effects.", "output": {"entities": {}}, "schema": []}
{"input": "Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 10, "end": 20}]}}, "schema": []}
{"input": "Adipocyte fatty acid binding protein (AFABP, also known as aP2 and FABP4) has recently been introduced as a novel fat-derived circulating protein.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 10, "end": 20}]}}, "schema": []}
{"input": "AFABP serum concentrations are positively correlated with markers of the metabolic syndrome and vascular disease in various cross-sectional and interventional studies.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, a small set of prospective studies indicates that high AFABP serum levels at baseline predict the risk for metabolic and vascular morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Studies in Afabp (also known as Fabp4) knockout mice and AFABP inhibitor-treated animals suggest that total AFABP promotes insulin resistance, hypertriacylglycerolaemia and atherosclerosis by ligand/ligand delivery, as well as ligand-independent mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the pathophysiological significance of circulating AFABP and the mechanisms leading to its release remain to be established.", "output": {"entities": {}}, "schema": []}
{"input": "The current review summarises recent findings on the regulation and potential role of AFABP in metabolic and vascular disease.", "output": {"entities": {}}, "schema": []}
{"input": "Magnesium sulfate treatment against sarin poisoning: dissociation between overt convulsions and recorded cortical seizure activity.", "output": {"entities": {"chemical": [{"text": "Magnesium sulfate", "start": 0, "end": 17}, {"text": "sarin", "start": 36, "end": 41}]}}, "schema": []}
{"input": "Sarin, a potent organophosphate cholinesterase inhibitor, induces an array of toxic effects including convulsions.", "output": {"entities": {"chemical": [{"text": "Sarin", "start": 0, "end": 5}, {"text": "organophosphate", "start": 16, "end": 31}]}}, "schema": []}
{"input": "Many antidotal treatments contain anticonvulsants to block seizure activity and the ensuing brain damage.", "output": {"entities": {}}, "schema": []}
{"input": "Magnesium sulfate (MGS) is used to suppress eclamptic seizures in pregnant women with hypertension and was shown to block kainate-induced convulsions.", "output": {"entities": {"chemical": [{"text": "Magnesium sulfate", "start": 0, "end": 17}, {"text": "MGS", "start": 19, "end": 22}, {"text": "kainate", "start": 122, "end": 129}]}}, "schema": []}
{"input": "Magnesium sulfate was evaluated herein as an anticonvulsant against sarin poisoning and its efficacy was compared with the potent anticonvulsants midazolam (MDZ) and caramiphen (CRM).", "output": {"entities": {"chemical": [{"text": "Magnesium sulfate", "start": 0, "end": 17}, {"text": "midazolam", "start": 146, "end": 155}, {"text": "MDZ", "start": 157, "end": 160}, {"text": "caramiphen", "start": 166, "end": 176}, {"text": "CRM", "start": 178, "end": 181}]}}, "schema": []}
{"input": "Rats were exposed to a convulsant dose of sarin (96 mu g/kg, im) and 1 min later treated with the oxime TMB4 and atropine to increase survival.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 42, "end": 47}, {"text": "oxime TMB4", "start": 98, "end": 108}, {"text": "atropine", "start": 113, "end": 121}]}}, "schema": []}
{"input": "Five minutes after initiation of convulsions, MGS, CRM, or MDZ were administered.", "output": {"entities": {"chemical": [{"text": "MGS", "start": 46, "end": 49}, {"text": "CRM", "start": 51, "end": 54}, {"text": "MDZ", "start": 59, "end": 62}]}}, "schema": []}
{"input": "Attenuation of tonic-clonic convulsions was observed following all these treatments.", "output": {"entities": {}}, "schema": []}
{"input": "However, radio-telemetric electro-corticography (ECoG) monitoring demonstrated sustained seizure activity in MGS-injected animals while this activity was completely blocked by MDZ and CRM.", "output": {"entities": {"chemical": [{"text": "MGS", "start": 109, "end": 112}, {"text": "MDZ", "start": 176, "end": 179}, {"text": "CRM", "start": 184, "end": 187}]}}, "schema": []}
{"input": "This disrupted brain activity was associated with marked increase in brain translocator protein levels, a marker for brain damage, measured 1 week following exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, histopathological analyses of MGS-treated group showed typical sarin-induced brain injury excluding the hippocampus that was partially protected.", "output": {"entities": {"chemical": [{"text": "MGS", "start": 44, "end": 47}, {"text": "sarin", "start": 77, "end": 82}]}}, "schema": []}
{"input": "Our results clearly show that MGS demonstrated misleading features as an anticonvulsant against sarin-induced seizures.", "output": {"entities": {"chemical": [{"text": "MGS", "start": 30, "end": 33}, {"text": "sarin", "start": 96, "end": 101}]}}, "schema": []}
{"input": "This stems from the dissociation observed between overt convulsions and seizure activity.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the presence or absence of motor convulsions may be an unreliable indicator in the assessment of clinical status and in directing adequate antidotal treatments following exposure to nerve agents in battle field or terror attacks.", "output": {"entities": {}}, "schema": []}
{"input": "Repeat oral dose toxicity studies of melamine in rats and monkeys.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Melamine is an important and widely used organic industrial chemical.", "output": {"entities": {"chemical": [{"text": "Melamine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Recently, clinical findings of renal failure and kidney stones in infants have been associated with ingestion of melamine-contaminated infant formula.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 113, "end": 121}]}}, "schema": []}
{"input": "To understand the toxicity and clinical outcome of melamine exposure, repeated oral dose studies in rats and monkeys were performed to characterize the subchronic toxicity of melamine.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 51, "end": 59}, {"text": "melamine", "start": 175, "end": 183}]}}, "schema": []}
{"input": "Assessment of toxicity was based on mortality, clinical signs, body weights, ophthalmic findings, clinical pathology, gross pathology, organ weights, and microscopic observations.", "output": {"entities": {}}, "schema": []}
{"input": "The first rat study was intended to be a 14-day oral study followed by an 8-day recovery period.", "output": {"entities": {}}, "schema": []}
{"input": "The dose levels were 140, 700, and 1, 400 mg/kg/day (lowered to 1, 000 mg/kg/day subsequently due to mortality).", "output": {"entities": {}}, "schema": []}
{"input": "Oral administration of melamine at 700 mg/kg/day for 14 consecutive days in rats produced compound-related clinical signs (red urine), decreased body weights, and changes in clinical pathology (increased serum urea nitrogen and creatinine) and anatomical pathology (renal tubular cell debris, crystal deposition, and hyperactive regeneration of renal tubular epithelium).", "output": {"entities": {"chemical": [{"text": "melamine", "start": 23, "end": 31}, {"text": "urea nitrogen", "start": 210, "end": 223}, {"text": "creatinine", "start": 228, "end": 238}]}}, "schema": []}
{"input": "The kidney was identified as the target organ.", "output": {"entities": {}}, "schema": []}
{"input": "Oral administration at 1, 400 mg/kg/day (subsequently lowered to 1, 000 mg/kg/day) resulted in animal death and moribundity.", "output": {"entities": {}}, "schema": []}
{"input": "There were no treatment-related findings in the 140 mg/kg/day group.", "output": {"entities": {}}, "schema": []}
{"input": "There were no compound-related findings in the high-dose recovery animals.", "output": {"entities": {}}, "schema": []}
{"input": "The second rat study was a 5-day oral toxicity study with genomic biomarkers assayed in the kidney tissues.", "output": {"entities": {}}, "schema": []}
{"input": "At the top dose of 1, 050 mg/kg/day, similar clinical and anatomical pathology findings as described above were observed.", "output": {"entities": {}}, "schema": []}
{"input": "The genes measured, Kim-1, Clu, Spp1, A2m, Lcn2, Tcfrsf12a, Gpnmb, and CD44, were significantly up-regulated (fivefold to 550-fold), while Tff3 was significantly down-regulated (fivefold).", "output": {"entities": {}}, "schema": []}
{"input": "These results indicated that genomic markers could sensitively diagnose melamine-induced kidney injury.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 72, "end": 80}]}}, "schema": []}
{"input": "A 3-month oral study with 4-week recovery in monkeys was also conducted.", "output": {"entities": {}}, "schema": []}
{"input": "In this monkey study, the animals were treated with melamine at doses of 60, 200, or 700 mg/kg/day.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 52, "end": 60}]}}, "schema": []}
{"input": "The administration of 700 mg/kg/day melamine by nasal-gastric gavage to monkeys resulted in test article-related clinical signs including turbid and whitish urine, urine crystals, red blood cell changes, increased serum alanine aminotransferase and kidney and/or liver weights, and microscopic findings including nephrotoxicity, pericarditis, and increased hematopoiesis.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 36, "end": 44}, {"text": "alanine", "start": 220, "end": 227}]}}, "schema": []}
{"input": "Nephrotoxicity was also noted at 200 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "It was concluded that the kidney is the primary target organ and the NOAEL was estimated to be 140 mg/kg/day in rats following a 14-day oral administration and 60 mg/kg/day in the monkey study.", "output": {"entities": {}}, "schema": []}
{"input": "Claudin-3 and claudin-4 regulate sensitivity to cisplatin by controlling expression of the copper and cisplatin influx transporter CTR1.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 48, "end": 57}, {"text": "copper", "start": 91, "end": 97}, {"text": "cisplatin", "start": 102, "end": 111}]}}, "schema": []}
{"input": "Claudin-3 (CLDN3) and claudin-4 (CLDN4) are the major structural molecules that form tight junctions (TJs) between epithelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "We found that knockdown of the expression of either CLDN3 or CLDN4 produced marked changes in the phenotype of ovarian cancer cells, including an increase in resistance to cisplatin (cDDP).", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 172, "end": 181}]}}, "schema": []}
{"input": "The effect of CLND3 and CLDN4 on cDDP cytotoxicity, cDDP cellular accumulation, and DNA adduct formation was compared in the CLDN3-and CLDN4-expressing parental human ovarian carcinoma 2008 cells and CLDN3 and CLDN4 knockdown sublines (CLDN3KD and CLDN4KD, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "Knockdown of CLDN3 or CLDN4 rendered human ovarian carcinoma 2008 cells resistant to cDDP in both in vitro culture and in vivo xenograft model.", "output": {"entities": {}}, "schema": []}
{"input": "The net accumulation of platinum (Pt) and the Pt-DNA adduct levels were reduced in CLDN3KD and CLDN4KD cells.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 24, "end": 32}, {"text": "Pt", "start": 34, "end": 36}, {"text": "Pt", "start": 46, "end": 48}]}}, "schema": []}
{"input": "The endogenous mRNA levels of copper influx transporter CTR1 were found to be significantly reduced in the knockdown cells, and exogenous expression of CTR1 restored their sensitivity to cDDP.", "output": {"entities": {"chemical": [{"text": "copper", "start": 30, "end": 36}]}}, "schema": []}
{"input": "Reexpression of an shRNAi-resistant CLDN3 or CLDN4 up-regulated CTR1 levels, reversed the cDDP resistance, and enhanced TJ formation in the knockdown cells.", "output": {"entities": {}}, "schema": []}
{"input": "Baseline copper (Cu) level, Cu uptake, and Cu cytotoxicity were also reduced in CLDN3KD and CLDN4KD cells.", "output": {"entities": {"chemical": [{"text": "copper", "start": 9, "end": 15}, {"text": "Cu", "start": 17, "end": 19}, {"text": "Cu", "start": 28, "end": 30}, {"text": "Cu", "start": 43, "end": 45}]}}, "schema": []}
{"input": "Cu-dependent tyrosinase activity was also markedly reduced in both types of CLDN knockdown cells when incubated with the substrate l-DOPA.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 0, "end": 2}, {"text": "l-DOPA", "start": 131, "end": 137}]}}, "schema": []}
{"input": "These results indicate that CLDN3 and CLDN4 affect sensitivity of the ovarian cancer cells to the cytotoxic effect of cDDP by regulating expression of the Cu transporter CTR1.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 155, "end": 157}]}}, "schema": []}
{"input": "Parallel changes in serotonin levels in brain and blood following acute administration of MDMA.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 20, "end": 29}, {"text": "MDMA", "start": 90, "end": 94}]}}, "schema": []}
{"input": "Recent studies have demonstrated a similar acute effect of 3, 4-methylenedioxymethamphetamine (MDMA) in blood platelets and brain tissue via action on the serotonin transporter.", "output": {"entities": {"chemical": [{"text": "3, 4-methylenedioxymethamphetamine", "start": 59, "end": 93}, {"text": "MDMA", "start": 95, "end": 99}, {"text": "serotonin", "start": 155, "end": 164}]}}, "schema": []}
{"input": "To investigate the validity of blood serotonin as a peripheral marker for central serotonin in this regard, we administered MDMA (20 mg/kg i. p.) to rats and observed a parallel decrease in serotonin levels in the frontal cortex and blood at 2 h (63% and 46% respectively) with some recovery evident at 8 h (42% and 38%) and more so at 18 h (19% and 24% below control levels).", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 37, "end": 46}, {"text": "serotonin", "start": 82, "end": 91}, {"text": "MDMA", "start": 124, "end": 128}, {"text": "serotonin", "start": 190, "end": 199}]}}, "schema": []}
{"input": "Administration of a tryptophan supplement (82. 5 mg/kg p. o.) to na i ve rats produced parallel increases in serotonin levels 2 h later in the frontal cortex (39%) and blood (26%).", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 20, "end": 30}, {"text": "serotonin", "start": 109, "end": 118}]}}, "schema": []}
{"input": "Following MDMA administration, the same dose of tryptophan caused a smaller (26%) rise in brain serotonin whereas in blood it had no effect.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 10, "end": 14}, {"text": "tryptophan", "start": 48, "end": 58}, {"text": "serotonin", "start": 96, "end": 105}]}}, "schema": []}
{"input": "We conclude that blood serotonin is a useful marker for brain serotonin levels in the rat following acute administration of MDMA and this finding highlights the possible use of platelet serotonin as a marker for brain serotonin in human studies involving MDMA.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 23, "end": 32}, {"text": "serotonin", "start": 62, "end": 71}, {"text": "MDMA", "start": 124, "end": 128}, {"text": "serotonin", "start": 186, "end": 195}, {"text": "serotonin", "start": 218, "end": 227}, {"text": "MDMA", "start": 255, "end": 259}]}}, "schema": []}
{"input": "Multi-fuel driven Janus micromotors.", "output": {"entities": {}}, "schema": []}
{"input": "Here the first example of a chemically powered micromotor that harvests its energy from the reactions of three different fuels is presented.", "output": {"entities": {}}, "schema": []}
{"input": "The new Al/Pd Janus microspheres-prepared by depositing a Pd layer on one side of Al microparticles-are propelled efficiently by the thrust of hydrogen bubbles generated from different reactions of Al in strong acidic and alkaline environments, and by an oxygen bubble thrust produced at their partial Pd coating in hydrogen peroxide media.", "output": {"entities": {"chemical": [{"text": "Al", "start": 8, "end": 10}, {"text": "Pd", "start": 11, "end": 13}, {"text": "Pd", "start": 58, "end": 60}, {"text": "Al", "start": 82, "end": 84}, {"text": "hydrogen", "start": 143, "end": 151}, {"text": "Al", "start": 198, "end": 200}, {"text": "oxygen", "start": 255, "end": 261}, {"text": "Pd", "start": 302, "end": 304}, {"text": "hydrogen peroxide", "start": 316, "end": 333}]}}, "schema": []}
{"input": "High speeds and long lifetimes of 200 mu m s (-1) and 8 min are achieved in strong alkaline media and acidic media, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The ability to autonomously adapt to the presence of a new fuel (surrounding environment), without compromising the propulsion behavior is illustrated.", "output": {"entities": {}}, "schema": []}
{"input": "These data also represent the first example of a chemically powered micromotor that propels autonomously and efficiently in alkaline environments (pH > 11) without additional fuels.", "output": {"entities": {}}, "schema": []}
{"input": "The ability to use multiple fuel sources to power the same micromotor offers a broader scope of operation and considerable promise for diverse applications of micromotors in different chemical environments.", "output": {"entities": {}}, "schema": []}
{"input": "INO-8875, a highly selective A1 adenosine receptor agonist: evaluation of chronotropic, dromotropic, and hemodynamic effects in rats.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 0, "end": 8}, {"text": "adenosine", "start": 32, "end": 41}]}}, "schema": []}
{"input": "Selective pharmacological activation of the adenosine 1 receptor (A (1) R) is a promising new approach to achieve a potent block of atrioventricular (A-V)-nodal conduction without significant cardiovascular side effects.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 44, "end": 53}]}}, "schema": []}
{"input": "The purpose of the present study was to evaluate the cardiovascular profile of INO-8875, a highly selective A (1) R agonist, and to compare its properties with N-[3 (R)-tetrahydrofuranyl]-6-aminopurine riboside (CVT-510), which has already been shown to induce negative dromotropic effects with minimal cardiovascular side effects in animals and in clinical studies.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 79, "end": 87}, {"text": "N-[3 (R)-tetrahydrofuranyl]-6-aminopurine riboside", "start": 160, "end": 210}, {"text": "CVT-510", "start": 212, "end": 219}]}}, "schema": []}
{"input": "Dose-response experiments in the isolated hearts of rats were used to evaluate the functional selectivity of INO-8875 for the slowing of A-V-nodal conduction.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 109, "end": 117}]}}, "schema": []}
{"input": "Ventilated adult rats were used to study the effects of INO-8875, in vivo, on arterial blood pressure as well as on supraventricular electrophysiology.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 56, "end": 64}]}}, "schema": []}
{"input": "Ex vivo, INO-8875 (100 nM to 3 mu M) progressively prolonged A-V-nodal conduction without reducing left ventricular function or coronary resistance.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 9, "end": 17}]}}, "schema": []}
{"input": "In vivo, INO-8875 up to a dose of 50 mu g/kg did not reduce the carotid arterial blood pressure (n = 4).", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 9, "end": 17}]}}, "schema": []}
{"input": "INO-8875 (1-50 mu g/kg) and CVT-510 (20 and 50 mu g/kg) both induced a dose-dependent decrease in heart rate and atrial refractoriness, as well as slowing of A-V-nodal conduction.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 0, "end": 8}, {"text": "CVT-510", "start": 28, "end": 35}]}}, "schema": []}
{"input": "However, compared with CVT-510, the activity of INO-8875 was more pronounced in A-V-nodal function.", "output": {"entities": {"chemical": [{"text": "CVT-510", "start": 23, "end": 30}, {"text": "INO-8875", "start": 48, "end": 56}]}}, "schema": []}
{"input": "INO-8875 exhibited a greater duration of action, lasting up to 2. 5 hours post dosing, whereas the effects of CVT-510 dissipated over 1 hour.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 0, "end": 8}, {"text": "CVT-510", "start": 110, "end": 117}]}}, "schema": []}
{"input": "INO-8875 demonstrates functional properties of a highly selective A (1) R agonist.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 0, "end": 8}]}}, "schema": []}
{"input": "INO-8875 exhibits an increased dromotropic effect and greater duration of action compared with CVT-510.", "output": {"entities": {"chemical": [{"text": "INO-8875", "start": 0, "end": 8}, {"text": "CVT-510", "start": 95, "end": 102}]}}, "schema": []}
{"input": "Molecular mechanisms associated with increased tolerance to the neonicotinoid insecticide imidacloprid in the dengue vector Aedes aegypti.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 90, "end": 102}]}}, "schema": []}
{"input": "Mosquitoes are vectors of several major human diseases and their control is mainly based on the use of chemical insecticides.", "output": {"entities": {}}, "schema": []}
{"input": "Resistance of mosquitoes to organochlorines, organophosphates, carbamates and pyrethroids led to a regain of interest for the use of neonicotinoid insecticides in vector control.", "output": {"entities": {"chemical": [{"text": "organochlorines", "start": 28, "end": 43}, {"text": "organophosphates", "start": 45, "end": 61}, {"text": "carbamates", "start": 63, "end": 73}, {"text": "pyrethroids", "start": 78, "end": 89}]}}, "schema": []}
{"input": "The present study investigated the molecular basis of neonicotinoid resistance in the mosquito Aedes aegypti.", "output": {"entities": {}}, "schema": []}
{"input": "A strain susceptible to insecticides was selected at the larval stage with imidacloprid.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 75, "end": 87}]}}, "schema": []}
{"input": "After eight generations of selection, larvae of the selected strain (Imida-R) showed a 5. 4-fold increased tolerance to imidacloprid while adult tolerance level remained low.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 120, "end": 132}]}}, "schema": []}
{"input": "Imida-R larvae showed significant cross-tolerance to other neonicotinoids but not to pyrethroids, organophosphates and carbamates.", "output": {"entities": {"chemical": [{"text": "pyrethroids", "start": 85, "end": 96}, {"text": "organophosphates", "start": 98, "end": 114}, {"text": "carbamates", "start": 119, "end": 129}]}}, "schema": []}
{"input": "Transcriptome profiling identified 344 and 108 genes differentially transcribed in larvae and adults of the Imida-R strain compared to the parental strain.", "output": {"entities": {}}, "schema": []}
{"input": "Most of these genes encode detoxification enzymes, cuticle proteins, hexamerins as well as other proteins involved in cell metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "Among detoxification enzymes, cytochrome P450 monooxygenases (CYPs) and glucosyl/glucuronosyl transferases (UDPGTs) were over-represented.", "output": {"entities": {}}, "schema": []}
{"input": "Bioassays with enzyme inhibitors and biochemical assays confirmed the contribution of P450s with an increased capacity of the Imida-R microsomes to metabolize imidacloprid in presence of NADPH.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 159, "end": 171}, {"text": "NADPH", "start": 187, "end": 192}]}}, "schema": []}
{"input": "Comparison of substrate recognition sites and imidacloprid docking models of six CYP6s over-transcribed in the Imida-R strain together with Bemisia tabaci CYP6CM1vQ and Drosophila melanogaster CYP6G1, both able to metabolize imidacloprid, suggested that CYP6BB2 and CYP6N12 are good candidates for imidacloprid metabolism in Ae. aegypti.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 46, "end": 58}, {"text": "imidacloprid", "start": 225, "end": 237}, {"text": "imidacloprid", "start": 298, "end": 310}]}}, "schema": []}
{"input": "The present study revealed that imidacloprid tolerance in mosquitoes can arise after few generations of selection at the larval stage but does not lead to a significant tolerance of adults.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 32, "end": 44}]}}, "schema": []}
{"input": "As in other insects, P450-mediated insecticide metabolism appears to play a major role in imidacloprid tolerance in mosquitoes.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 90, "end": 102}]}}, "schema": []}
{"input": "Suppressive effect of accumulated aluminum trichloride on the hepatic microsomal cytochrome P450 enzyme system in rats.", "output": {"entities": {"chemical": [{"text": "aluminum trichloride", "start": 34, "end": 54}]}}, "schema": []}
{"input": "Aluminum (Al) is a low toxicological metal and can accumulate in the liver.", "output": {"entities": {"chemical": [{"text": "Aluminum", "start": 0, "end": 8}, {"text": "Al", "start": 10, "end": 12}]}}, "schema": []}
{"input": "The hepatic microsomal cytochrome P450 enzyme system (CYPS) plays important role in the transformation of the toxic materials.", "output": {"entities": {}}, "schema": []}
{"input": "It is not clear if the CYPS is affected by Al exposure.", "output": {"entities": {"chemical": [{"text": "Al", "start": 43, "end": 45}]}}, "schema": []}
{"input": "Thus, the aim of this study is to investigate the effects of aluminum trichloride (AlCl (3)) on CYPS in rats.", "output": {"entities": {"chemical": [{"text": "aluminum trichloride", "start": 61, "end": 81}, {"text": "AlCl (3)", "start": 83, "end": 91}]}}, "schema": []}
{"input": "Forty male Wistar rats (5weeks old) weighing 110-120g were randomly allocated and orally exposed to 0, 64. 18, 128. 36 and 256. 72mg/kg body weight (BW) AlCl (3) in drinking water for 120days.", "output": {"entities": {"chemical": [{"text": "AlCl (3)", "start": 153, "end": 161}]}}, "schema": []}
{"input": "The body weight (BW) of rats, hepatosomatic index (HSI), hepatic Al content, the concentrations of cytochrome P450 (CYP450), cytochrome B5 (B5), microsomal protein and the activities of NADPH-cytochrome c reductase (CR), aminopyrin N-demethylase (AND), erythromycin N-demethylase (ERND) and aniline-4-hydeoxylase (AH) were assessed at the end of the experiment.", "output": {"entities": {"chemical": [{"text": "Al", "start": 65, "end": 67}, {"text": "NADPH", "start": 186, "end": 191}, {"text": "aminopyrin N", "start": 221, "end": 233}, {"text": "aniline", "start": 291, "end": 298}]}}, "schema": []}
{"input": "The results showed that the increase in Al concentration decreased BW, HIS, concentrations of CYP450, B5, microsomal protein and the activity of CR, AND, ERND and AH in hepatic microsomes.", "output": {"entities": {"chemical": [{"text": "Al", "start": 40, "end": 42}]}}, "schema": []}
{"input": "The results revealed that exposure to AlCl (3) inhibited the microsomal CYP450 dependent enzyme system of liver.", "output": {"entities": {"chemical": [{"text": "AlCl (3)", "start": 38, "end": 46}]}}, "schema": []}
{"input": "Our findings suggest that long term daily exposure of AlCl (3) exerts the suppressive effects and thus may cause dysfunction of hepatic CYP450 dependent enzyme system of rat.", "output": {"entities": {"chemical": [{"text": "AlCl (3)", "start": 54, "end": 62}]}}, "schema": []}
{"input": "Metal distribution in tissues of free-range chickens near a lead-zinc mine in Kabwe, Zambia.", "output": {"entities": {"chemical": [{"text": "zinc", "start": 65, "end": 69}]}}, "schema": []}
{"input": "Concentrations of Pb, Cd, and other metals in tissues of 17 free-range and 32 commercial broiler chickens from the Kabwe mining town in Zambia were determined.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 18, "end": 20}, {"text": "Cd", "start": 22, "end": 24}]}}, "schema": []}
{"input": "Mean concentrations of Pb and Cd exceeded maximum levels for human consumption in some organs including muscle (Pb only) in free-range chickens, in contrast to low levels in broiler chickens.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 23, "end": 25}, {"text": "Cd", "start": 30, "end": 32}, {"text": "Pb", "start": 112, "end": 114}]}}, "schema": []}
{"input": "Human consumers in Kabwe could be exposed to Pb and Cd in free-range chickens.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 45, "end": 47}, {"text": "Cd", "start": 52, "end": 54}]}}, "schema": []}
{"input": "The quest for probiotic effector molecules--unraveling strain specificity at the molecular level.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmaceutical agents are widely applied for the treatment of gastrointestinal (and systemic) disorders and their role as modulators of host cell responses is relatively well characterized.", "output": {"entities": {}}, "schema": []}
{"input": "By contrast, we are only beginning to understand the molecular mechanisms by which health-promoting, probiotic bacteria act as host cell modulators.", "output": {"entities": {}}, "schema": []}
{"input": "The last decade has seen a rapid development of the genomics field for the widely applied probiotic genus Lactobacillus, and nowadays dozens of full genome sequences are available, as well as sophisticated post genomic and genetic engineering tools.", "output": {"entities": {}}, "schema": []}
{"input": "This development has enabled comparative (functional) genomics approaches to identify the bacterial effector molecules involved in molecular communication with the host system that may underlie the probiotic effects observed.", "output": {"entities": {}}, "schema": []}
{"input": "These efforts can also be complemented with dedicated mutagenesis approaches to eliminate or alter these effector molecules, followed by assessment of the host interaction consequences thereof, allowing the elucidation of the molecular mechanisms involved in probiotic health effects.", "output": {"entities": {}}, "schema": []}
{"input": "Many of these approaches have pinpointed that the Lactobacillus cell envelope contains several effector molecules that are pivotal in the direct signaling capacity of these bacteria that underlies their immunomodulatory effects, including lipoteichoic acid, peptidoglycan, and (glyco) proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the cell envelope contains several compounds such as wall teichoic acid and capsular polysaccharides that may not be involved in direct signaling to the host cell, but still affect signaling through shielding of other bacterial effector molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Initial structural studies revealed subtle strain-and species-specific biochemical differences in the canonical cell envelope compounds that are involved in these host interactions.", "output": {"entities": {}}, "schema": []}
{"input": "These biochemical variations include the degree and positioning of d-alanyl and glycosyl substitution in lipoteichoic acids, and acetylation of peptidoglycan.", "output": {"entities": {"chemical": [{"text": "d-alanyl", "start": 67, "end": 75}, {"text": "glycosyl", "start": 80, "end": 88}]}}, "schema": []}
{"input": "Furthermore, specific peptides derived from peptidoglycan and envelope associated (glyco) proteins were recently identified as potent immunomodulators.", "output": {"entities": {}}, "schema": []}
{"input": "The latter findings are exciting in the light of the possibility of more pharmacological application of these bioactive probiotic molecules, and especially cost-effective production and targeted delivery of bioactive peptides seems to emerge as a feasible strategy to harness this knowledge.", "output": {"entities": {}}, "schema": []}
{"input": "Nano-graphene in biomedicine: theranostic applications.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 5, "end": 13}]}}, "schema": []}
{"input": "Owing to their unique physical and chemical properties, graphene and its derivatives such as graphene oxide (GO), reduced graphene oxide (RGO) and GO-nanocomposites have attracted tremendous interest in many different fields including biomedicine in recent years.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 56, "end": 64}, {"text": "graphene oxide", "start": 93, "end": 107}, {"text": "reduced graphene oxide", "start": 114, "end": 136}, {"text": "RGO", "start": 138, "end": 141}]}}, "schema": []}
{"input": "With every atom exposed on its surface, single-layered graphene shows ultra-high surface area available for efficient molecular loading and bioconjugation, and has been widely explored as novel nano-carriers for drug and gene delivery.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 55, "end": 63}]}}, "schema": []}
{"input": "Utilizing the intrinsic near-infrared (NIR) optical absorbance, in vivo graphene-based photothermal therapy has been realized, achieving excellent anti-tumor therapeutic efficacy in animal experiments.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 72, "end": 80}]}}, "schema": []}
{"input": "A variety of inorganic nanoparticles can be grown on the surface of nano-graphene, obtaining functional graphene-based nanocomposites with interesting optical and magnetic properties useful for multi-modal imaging and imaging-guided cancer therapy.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 73, "end": 81}, {"text": "graphene", "start": 104, "end": 112}]}}, "schema": []}
{"input": "Moreover, significant efforts have also been devoted to study the behaviors and toxicology of functionalized nano-graphene in animals.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 114, "end": 122}]}}, "schema": []}
{"input": "It has been uncovered that both surface chemistry and sizes play key roles in controlling the biodistribution, excretion, and toxicity of nano-graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 143, "end": 151}]}}, "schema": []}
{"input": "Biocompatibly coated nano-graphene with ultra-small sizes can be cleared out from body after systemic administration, without rendering noticeable toxicity to the treated mice.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 26, "end": 34}]}}, "schema": []}
{"input": "In this review article, we will summarize the latest progress in this rapidly growing field, and discuss future prospects and challenges of using graphene-based materials for theranostic applications.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 146, "end": 154}]}}, "schema": []}
{"input": "Chronic PFOS exposures induce life stage-specific behavioral deficits in adult zebrafish and produce malformation and behavioral deficits in F1 offspring.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 8, "end": 12}]}}, "schema": []}
{"input": "Perfluorooctane sulfonic acid (PFOS) is an organic contaminant that is ubiquitous in the environment.", "output": {"entities": {"chemical": [{"text": "Perfluorooctane sulfonic acid", "start": 0, "end": 29}, {"text": "PFOS", "start": 31, "end": 35}]}}, "schema": []}
{"input": "Few studies have assessed the behavioral effects of chronic PFOS exposure in aquatic organisms.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 60, "end": 64}]}}, "schema": []}
{"input": "The present study defined the behavioral effects of varying life span chronic exposures to PFOS in zebrafish.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 91, "end": 95}]}}, "schema": []}
{"input": "Specifically, zebrafish were exposed to control or 0. 5 micro M PFOS during 1 to 20, 21 to 120, or 1 to 120 d postfertilization (dpf).", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 64, "end": 68}]}}, "schema": []}
{"input": "Exposure to PFOS impaired the adult zebrafish behavior mode under the tapping stimulus.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 12, "end": 16}]}}, "schema": []}
{"input": "The movement speed of male and female fish exposed for 1 to 120 dpf was significantly increased compared with control before and after tapping, whereas in the groups exposed for 1 to 20 and 21 to 120 dpf, only the males exhibited elevated swim speed before tapping.", "output": {"entities": {}}, "schema": []}
{"input": "Residues of PFOS in F1 embryos derived from parental exposure for 1 to 120 and 21 to 120 dpf were significantly higher than control, and F1 embryos in these two groups also showed high malformation and mortality.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 12, "end": 16}]}}, "schema": []}
{"input": "The F1 larvae of parental fish exposed to PFOS for 1 to 20 or 21 to 120 dpf exhibited a higher swimming speed than control larvae in a light-to-dark behavior assessment test.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 42, "end": 46}]}}, "schema": []}
{"input": "The F1 larvae derived from parental fish exposed to PFOS for 1 to 120 dpf showed a significantly lower speed in the light period and a higher speed in the dark period compared with controls.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 52, "end": 56}]}}, "schema": []}
{"input": "Although there was little PFOS residue in embryos derived from the 1-to 20-dpf parental PFOS-exposed group, the adverse behavioral effects on both adult and F1 larvae indicate that exposure during the first 21 dpf induces long-term neurobehaviorial toxicity.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 26, "end": 30}, {"text": "PFOS", "start": 88, "end": 92}]}}, "schema": []}
{"input": "The authors' findings demonstrate that chronic PFOS exposure during different life stages adversely affects adult behavior and F1 offspring morphology, behavior, and survival.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 47, "end": 51}]}}, "schema": []}
{"input": "Defective neural crest migration revealed by a Zebrafish model of Alx1-related frontonasal dysplasia.", "output": {"entities": {}}, "schema": []}
{"input": "Frontonasal dysplasia (FND) refers to a class of midline facial malformations caused by abnormal development of the facial primordia.", "output": {"entities": {}}, "schema": []}
{"input": "The term encompasses a spectrum of severities but characteristic features include combinations of ocular hypertelorism, malformations of the nose and forehead and clefting of the facial midline.", "output": {"entities": {}}, "schema": []}
{"input": "Several recent studies have drawn attention to the importance of Alx homeobox transcription factors during craniofacial development.", "output": {"entities": {}}, "schema": []}
{"input": "Most notably, loss of Alx1 has devastating consequences resulting in severe orofacial clefting and extreme microphthalmia.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, mutations of Alx3 or Alx4 cause milder forms of FND.", "output": {"entities": {}}, "schema": []}
{"input": "Whilst Alx1, Alx3 and Alx4 are all known to be expressed in the facial mesenchyme of vertebrate embryos, little is known about the function of these proteins during development.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report the establishment of a zebrafish model of Alx-related FND.", "output": {"entities": {}}, "schema": []}
{"input": "Morpholino knock-down of zebrafish alx1 expression causes a profound craniofacial phenotype including loss of the facial cartilages and defective ocular development.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate for the first time that Alx1 plays a crucial role in regulating the migration of cranial neural crest (CNC) cells into the frontonasal primordia.", "output": {"entities": {}}, "schema": []}
{"input": "Abnormal neural crest migration is coincident with aberrant expression of foxd3 and sox10, two genes previously suggested to play key roles during neural crest development, including migration, differentiation and the maintenance of progenitor cells.", "output": {"entities": {}}, "schema": []}
{"input": "This novel function is specific to Alx1, and likely explains the marked clinical severity of Alx1 mutation within the spectrum of Alx-related FND.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistic sediment quality guidelines based on contaminant bioavailability: equilibrium partitioning sediment benchmarks.", "output": {"entities": {}}, "schema": []}
{"input": "Globally, estimated costs to manage (i. e., remediate and monitor) contaminated sediments are in the billions of U. S. dollars.", "output": {"entities": {}}, "schema": []}
{"input": "Biologically based approaches for assessing the contaminated sediments which pose the greatest ecological risk range from toxicity testing to benthic community analysis.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, chemically based sediment quality guidelines (SQGs) provide a relatively inexpensive line of evidence for supporting these assessments.", "output": {"entities": {}}, "schema": []}
{"input": "The present study summarizes a mechanistic SQG based on equilibrium partitioning (EqP), which uses the dissolved concentrations of contaminants in sediment interstitial waters as a surrogate for bioavailable contaminant concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "The EqP-based mechanistic SQGs are called equilibrium partitioning sediment benchmarks (ESBs).", "output": {"entities": {}}, "schema": []}
{"input": "Sediment concentrations less than or equal to the ESB values are not expected to result in adverse effects and benthic organisms should be protected, while sediment concentrations above the ESB values may result in adverse effects to benthic organisms.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, ESB values are reported for 34 polycyclic aromatic hydrocarbon, 32 other organic contaminants, and seven metals (cadmium, chromium, copper, nickel, lead, silver, zinc).", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbon", "start": 53, "end": 84}, {"text": "cadmium", "start": 135, "end": 142}, {"text": "chromium", "start": 144, "end": 152}, {"text": "copper", "start": 154, "end": 160}, {"text": "nickel", "start": 162, "end": 168}, {"text": "silver", "start": 176, "end": 182}, {"text": "zinc", "start": 184, "end": 188}]}}, "schema": []}
{"input": "Also included is an overview of EqP theory, ESB derivation, examples of applying ESB values, and considerations when using ESBs.", "output": {"entities": {}}, "schema": []}
{"input": "The ESBs are intended as a complement to existing sediment-assessment tools, to assist in determining the extent of sediment contamination, to help identify chemicals causing toxicity, and to serve as targets for pollutant loading control measures.", "output": {"entities": {}}, "schema": []}
{"input": "Exposures to 1, 3-dimethylamylamine-containing products reported to Texas poison centers.", "output": {"entities": {"chemical": [{"text": "1, 3-dimethylamylamine", "start": 13, "end": 35}]}}, "schema": []}
{"input": "1, 3-Dimethylamylamine (DMAA) is an ingredient in a number of weight loss and exercise performance enhancing products.", "output": {"entities": {"chemical": [{"text": "1, 3-Dimethylamylamine", "start": 0, "end": 22}, {"text": "DMAA", "start": 24, "end": 28}]}}, "schema": []}
{"input": "However, information on the safety of DMAA-containing products is limited.", "output": {"entities": {"chemical": [{"text": "DMAA", "start": 38, "end": 42}]}}, "schema": []}
{"input": "Exposures to DMAA-containing products reported to Texas poison centers during 2010-2011 were identified and selected factors were examined.", "output": {"entities": {"chemical": [{"text": "DMAA", "start": 13, "end": 17}]}}, "schema": []}
{"input": "A total of 56 exposures were found, of which 75. 0% were reported during 2011.", "output": {"entities": {}}, "schema": []}
{"input": "OxyElite Pro (TM) was the reported product in 80. 4% of the exposures.", "output": {"entities": {}}, "schema": []}
{"input": "The patients were 51. 8% male and 55. 4% age <= 5 years.", "output": {"entities": {}}, "schema": []}
{"input": "The patient was managed on site (such as at home) in 57. 1% of the cases, and the exposure was known or expected to result in an outcome that was classified as not serious in 80. 4%.", "output": {"entities": {}}, "schema": []}
{"input": "The most frequently reported clinical effects were tachycardia (28. 6%), nausea (16. 1%), and vomiting (12. 5%).", "output": {"entities": {}}, "schema": []}
{"input": "The most common treatments were dilution (41. 1%), food (19. 6%), and activated charcoal (14. 3%).", "output": {"entities": {"chemical": [{"text": "charcoal", "start": 80, "end": 88}]}}, "schema": []}
{"input": "It should be noted that the adverse clinical effects may be due to other ingredients in the DMAA-containing products, such as caffeine.", "output": {"entities": {"chemical": [{"text": "DMAA", "start": 92, "end": 96}, {"text": "caffeine", "start": 126, "end": 134}]}}, "schema": []}
{"input": "Emergency do not consume/do not use concentrations for blended phosphates in drinking water.", "output": {"entities": {"chemical": [{"text": "phosphates", "start": 63, "end": 73}]}}, "schema": []}
{"input": "The U. S.", "output": {"entities": {}}, "schema": []}
{"input": "Congress [PL 107-188] amended the Safe Drinking Water Act and required each community water system serving more than 3, 000 people to conduct vulnerability assessments.", "output": {"entities": {}}, "schema": []}
{"input": "These assessments address potential circumstances that could compromise the safety and reliability of municipal water.", "output": {"entities": {}}, "schema": []}
{"input": "The present evaluation concerns the concentrations of the blended phosphates (also known as polyphosphates, condensed complex phosphates, polyphosphate glassy balls, and pyrophosphates) intended to aid regulatory agencies in decisions to avoid contact with affected water.", "output": {"entities": {"chemical": [{"text": "phosphates", "start": 66, "end": 76}, {"text": "polyphosphates", "start": 92, "end": 106}, {"text": "phosphates", "start": 126, "end": 136}, {"text": "pyrophosphates", "start": 170, "end": 184}]}}, "schema": []}
{"input": "Polyphosphates are direct food additives and they are used to treat municipal drinking water, but depending upon the concentration and duration of exposure these substances can induce chemical burns.", "output": {"entities": {"chemical": [{"text": "Polyphosphates", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Ingested polyphosphates are degraded by phosphatase enzymes to monophosphates, substances that are over-the-counter bowel purgatives.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 9, "end": 23}, {"text": "monophosphates", "start": 63, "end": 77}]}}, "schema": []}
{"input": "High oral doses of the monophosphates can induce transient hyperphosphatemia in older and susceptible young people, which can lead to acute phosphate nephropathy.", "output": {"entities": {"chemical": [{"text": "monophosphates", "start": 23, "end": 37}]}}, "schema": []}
{"input": "In some patients, the condition is fatal.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the acute diarrhea after the ingestion of a single oral dose of monobasic (NaH2PO (4)) and dibasic (Na2HPO (4)) monophosphates in adults, a do not consume concentration of 600 mg PO (4)/L can be derived.", "output": {"entities": {"chemical": [{"text": "NaH2PO (4)", "start": 84, "end": 94}, {"text": "Na2HPO (4)", "start": 109, "end": 119}, {"text": "monophosphates", "start": 121, "end": 135}, {"text": "PO (4)", "start": 188, "end": 194}]}}, "schema": []}
{"input": "Based on mild local irritation after topical application of 1. 0% sodium metaphosphate [(NaPO (3)) 6 * H2O] to intact skin of sensitive volunteers, a do not use concentration of 8, 000 mg PO4/L can be assigned.", "output": {"entities": {"chemical": [{"text": "sodium metaphosphate", "start": 66, "end": 86}, {"text": "(NaPO (3)) 6 * H2O", "start": 88, "end": 106}, {"text": "PO4", "start": 188, "end": 191}]}}, "schema": []}
{"input": "Given the lack of eye irritation in rabbits after direct instillation of 0. 2% (NaPO (3)) 6 * H2O, an acute ocular contact limit of 50 mg PO4/L serves as the overall do not use level.", "output": {"entities": {"chemical": [{"text": "(NaPO (3)) 6 * H2O", "start": 79, "end": 97}, {"text": "PO4", "start": 138, "end": 141}]}}, "schema": []}
{"input": "TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice.", "output": {"entities": {}}, "schema": []}
{"input": "Although it has been reported that deficiency of toll-like receptor 4 (TLR4) is associated with reduced atherosclerosis in atherosclerosis-prone mice and attenuated pro-inflammatory state in diabetic mice, it remains undetermined whether treatment with a TLR4 antagonist reduces atherosclerosis in nondiabetic or diabetic mice that have TLR4 expression.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we determined the effect of Rhodobacter sphaeroides lipopolysaccharide (Rs-LPS), an established TLR4 antagonist, on early-stage atherosclerosis in nondiabetic and streptozotocin-induced diabetic apolipoprotein E-deficient (Apoe (-/-)) mice.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 178, "end": 192}]}}, "schema": []}
{"input": "Analysis of atherosclerotic lesions of both en face aortas and cross sections of aortic roots showed that administration of Rs-LPS in 14-week-old diabetic Apoe (-/-) mice for 10 weeks significantly reduced atherosclerotic lesions.", "output": {"entities": {}}, "schema": []}
{"input": "Although atherosclerotic lesions in nondiabetic Apoe (-/-) mice appeared to be decreased by Rs-LPS treatment, the difference was not statistically significant.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolic study showed that Rs-LPS significantly lowered serum levels of cholesterol and triglycerides in nondiabetic mice but not in diabetic mice.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 73, "end": 84}, {"text": "triglycerides", "start": 89, "end": 102}]}}, "schema": []}
{"input": "Furthermore, immunohistochemistry studies showed that Rs-LPS inhibited the expression of interleukin 6 and matrix metalloproteinase-9 and reduced the content of monocytes and macrophages in atherosclerotic plaques.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, this study demonstrated for the first time that TLR4 antagonist inhibited vascular inflammation and atherogenesis in diabetic Apoe (-/-) mice and lowered serum cholesterol and triglyceride levels in nondiabetic Apoe (-/-) mice.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 176, "end": 187}, {"text": "triglyceride", "start": 192, "end": 204}]}}, "schema": []}
{"input": "Progress in synthesis and antitumor activities of estradiol-linked platinum complex.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 50, "end": 59}, {"text": "platinum", "start": 67, "end": 75}]}}, "schema": []}
{"input": "Platinum complexes such as cisplatin and caboplatin are widely used in cancer chemotherapy.", "output": {"entities": {"chemical": [{"text": "Platinum", "start": 0, "end": 8}, {"text": "cisplatin", "start": 27, "end": 36}, {"text": "caboplatin", "start": 41, "end": 51}]}}, "schema": []}
{"input": "However, their clinical applications are substantially limited by unexpected toxic side effects.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we discuss the current progress on the design and synthesis of estradiol-linked platinum complexes as the targeted antitumor drugs.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 79, "end": 88}, {"text": "platinum", "start": 96, "end": 104}]}}, "schema": []}
{"input": "Many of them display a high antitumor activity against the growth of breast cancer cell lines in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "The estradiol-linked platinum complexes could be used as target therapeutics for breast cancer.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 4, "end": 13}, {"text": "platinum", "start": 21, "end": 29}]}}, "schema": []}
{"input": "Antioxidant evaluation of heterocyclic compounds by cytokinesis-block micronucleus assay.", "output": {"entities": {}}, "schema": []}
{"input": "This article summarizes the results of using cytokinesis-block micronucleus (CBMN) assay to evaluate the antioxidant potential of heterocyclic compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Most studies were carried out with naturally occurring heterocyclic compounds such as plant polyphenols: flavonoids, xanthones, coumarins, and ellagitannins, or plant derived products (juices, extracts, supplements) rich in bioactive heterocyclic compounds.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 92, "end": 103}, {"text": "flavonoids", "start": 105, "end": 115}, {"text": "xanthones", "start": 117, "end": 126}, {"text": "coumarins", "start": 128, "end": 137}, {"text": "ellagitannins", "start": 143, "end": 156}]}}, "schema": []}
{"input": "There are also some studies dealing with synthetic heterocyclic antioxidants.", "output": {"entities": {}}, "schema": []}
{"input": "CBMN assay is an in vitro study that has been used to evaluate antioxidant and protective effects of heterocyclic compounds on induced chromosome aberration in human lymphocytes.", "output": {"entities": {}}, "schema": []}
{"input": "FoxA1 corrupts the antiandrogenic effect of bicalutamide but only weakly attenuates the effect of MDV3100 (Enzalutamide (TM)).", "output": {"entities": {"chemical": [{"text": "bicalutamide", "start": 44, "end": 56}, {"text": "MDV3100", "start": 98, "end": 105}, {"text": "Enzalutamide", "start": 107, "end": 119}]}}, "schema": []}
{"input": "Prostate cancer growth depends on androgens.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 34, "end": 43}]}}, "schema": []}
{"input": "Synthetic antiandrogens are used in the cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "However, antiandrogens, such as bicalutamide (BIC), have a mixed agonist/antagonist activity.", "output": {"entities": {"chemical": [{"text": "bicalutamide", "start": 32, "end": 44}, {"text": "BIC", "start": 46, "end": 49}]}}, "schema": []}
{"input": "Here we compare the antiandrogenic capacity of BIC to a new antiandrogen, MDV3100 (MDV) or Enzalutamide (TM).", "output": {"entities": {"chemical": [{"text": "BIC", "start": 47, "end": 50}, {"text": "MDV3100", "start": 74, "end": 81}, {"text": "Enzalutamide", "start": 91, "end": 103}]}}, "schema": []}
{"input": "By reconstitution of a hormone-regulated enhancer in Xenopus oocytes we show that both antagonists trigger the androgen receptor (AR) translocation to the nucleus, albeit with a reduced efficiency for MDV.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 111, "end": 119}]}}, "schema": []}
{"input": "Once in the nucleus, both AR-antagonist complexes can bind sequence specifically to DNA in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "The forkhead box transcription factor A (FoxA1) is a negative prognostic indicator for prostate cancer disease.", "output": {"entities": {}}, "schema": []}
{"input": "FoxA1 expression presets the enhancer chromatin and makes the DNA more accessible for AR binding.", "output": {"entities": {}}, "schema": []}
{"input": "In this context the BIC-AR antiandrogenic effect is seriously compromised as demonstrated by a significant chromatin remodeling and induction of a robust MMTV transcription whereas the MDV-AR complex displays a more persistent antagonistic character.", "output": {"entities": {"chemical": [{"text": "BIC", "start": 20, "end": 23}]}}, "schema": []}
{"input": "Global slowing of network oscillations in mouse neocortex by diazepam.", "output": {"entities": {"chemical": [{"text": "diazepam", "start": 61, "end": 69}]}}, "schema": []}
{"input": "Benzodiazepines have a broad spectrum of clinical applications including sedation, anti-anxiety, and anticonvulsive therapy.", "output": {"entities": {"chemical": [{"text": "Benzodiazepines", "start": 0, "end": 15}]}}, "schema": []}
{"input": "At the cellular level, benzodiazepines are allosteric modulators of GABA (A) receptors; they increase the efficacy of inhibition in neuronal networks by prolonging the duration of inhibitory postsynaptic potentials.", "output": {"entities": {"chemical": [{"text": "benzodiazepines", "start": 23, "end": 38}]}}, "schema": []}
{"input": "This mechanism of action predicts that benzodiazepines reduce the frequency of inhibition-driven network oscillations, consistent with observations from human and animal EEG.", "output": {"entities": {"chemical": [{"text": "benzodiazepines", "start": 39, "end": 54}]}}, "schema": []}
{"input": "However, most of existing data are restricted to frequency bands below ~ 30 Hz.", "output": {"entities": {}}, "schema": []}
{"input": "Recent data suggest that faster cortical network rhythms are critically involved in several behavioral and cognitive tasks.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore analyzed diazepam effects on a large range of cortical network oscillations in freely moving mice, including theta (4-12 Hz), gamma (40-100 Hz) and fast gamma (120-160 Hz) oscillations.", "output": {"entities": {"chemical": [{"text": "diazepam", "start": 22, "end": 30}]}}, "schema": []}
{"input": "We also investigated diazepam effects over the coupling between theta phase and the amplitude fast oscillations.", "output": {"entities": {"chemical": [{"text": "diazepam", "start": 21, "end": 29}]}}, "schema": []}
{"input": "We report that diazepam causes a global slowing of oscillatory activity in all frequency domains.", "output": {"entities": {"chemical": [{"text": "diazepam", "start": 15, "end": 23}]}}, "schema": []}
{"input": "Oscillation power was changed differently for each frequency domain, with characteristic differences between active wakefulness, slow-wave sleep and REM sleep.", "output": {"entities": {}}, "schema": []}
{"input": "Cross-frequency coupling strength, in contrast, was mostly unaffected by diazepam.", "output": {"entities": {"chemical": [{"text": "diazepam", "start": 73, "end": 81}]}}, "schema": []}
{"input": "Such state-and frequency-dependent actions of benzodiazepines on cortical network oscillations may be relevant for their specific cognitive effects.", "output": {"entities": {"chemical": [{"text": "benzodiazepines", "start": 46, "end": 61}]}}, "schema": []}
{"input": "They also underline the strong interaction between local network oscillations and global brain states.", "output": {"entities": {}}, "schema": []}
{"input": "The role of oxygen during fracture healing.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 12, "end": 18}]}}, "schema": []}
{"input": "Oxygen affects the activity of multiple skeletogenic cells and is involved in many processes that are important for fracture healing.", "output": {"entities": {"chemical": [{"text": "Oxygen", "start": 0, "end": 6}]}}, "schema": []}
{"input": "However, the role of oxygen in fracture healing has not been fully studied.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 21, "end": 27}]}}, "schema": []}
{"input": "Here we systematically examine the effects of oxygen tension on fracture healing and test the ability of hyperoxia to rescue healing defects in a mouse model of ischemic fracture healing.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 46, "end": 52}]}}, "schema": []}
{"input": "Mice with tibia fracture were housed in custom-built gas chambers and groups breathed a constant atmosphere of 13% oxygen (hypoxia), 21% oxygen (normoxia), or 50% oxygen (hyperoxia).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 115, "end": 121}, {"text": "oxygen", "start": 137, "end": 143}, {"text": "oxygen", "start": 163, "end": 169}]}}, "schema": []}
{"input": "The influx of inflammatory cells to the fracture site, stem cell differentiation, tissue vascularization, and fracture healing were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the efficacy of hyperoxia (50% oxygen) as a treatment regimen for fracture nonunion was tested.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 44, "end": 50}]}}, "schema": []}
{"input": "Hypoxic animals had decreased tissue vascularity, decreased bone formation, and delayed callus remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperoxia increased tissue vascularization, altered fracture healing in un-complicated fractures, and improved bone repair in ischemia-induced delayed fracture union.", "output": {"entities": {}}, "schema": []}
{"input": "However, neither hypoxia nor hyperoxia significantly altered chondrogenesis or osteogenesis during early stages of fracture healing, and infiltration of macrophages and neutrophils was not affected by environmental oxygen after bone injury.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 215, "end": 221}]}}, "schema": []}
{"input": "In conclusion, our results indicate that environmental oxygen levels affect tissue vascularization and fracture healing, and that providing oxygen when fractures are accompanied by ischemia may be beneficial.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 55, "end": 61}, {"text": "oxygen", "start": 140, "end": 146}]}}, "schema": []}
{"input": "Copy number variation in ACHE/EPHB4 (7q22) and in BCHE/MME (3q26) genes in sporadic breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Gene amplifications and deletions are common changes in human cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies indicate that the regions, where the ACHE (7q22) and BCHE (3q26. 1-q26. 2) genes are localized, are suffering such structural modifications in breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the products of these genes, acetylcholinesterase and butyrylcholinesterase, respectively, are related to the process of cell differentiation and proliferation, as well as apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "This study also included two other genes involved in tumorigenesis, the EPHB4 (7q22. 1) and MME (3q21-27).", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to verify amplification and/or deletion in the ACHE, BCHE, EPHB4 and MME genes in 32 samples of sporadic breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The gene alterations were detected using real-time PCR and determined by relative quantification with the standard curve method.", "output": {"entities": {}}, "schema": []}
{"input": "All samples presented genetic alterations, showing a higher tendency for amplification of the ACHE (62. 5% vs. 37. 5%; p > 0. 1) and EPHB4 (53. 13% vs. 46. 88%; p > 0. 5) genes, and for deletions of the BCHE and MME genes (56. 25% vs. 43. 75% for both; p > 0. 5).", "output": {"entities": {}}, "schema": []}
{"input": "A positive correlation was found between alterations in ACHE-EPHB4 and BCHE-MME pairs (rs = 0. 5948; p = 0. 0004; rs = 0. 3581; p = 0. 0478, respectively) indicating that these changes comprise a wide region.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the results suggest that these genomic regions may contain important genes for this pathology, such as the oncogenes MET (7q31) and PIK3CA (3q26), and thus being interesting targets for future studies in breast cancer research.", "output": {"entities": {}}, "schema": []}
{"input": "Delivering the promise of miRNA cancer therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "MicroRNAs (miRNAs) are pivotal post-transcriptional gene expression regulators.", "output": {"entities": {}}, "schema": []}
{"input": "These endogenous small non-coding RNAs aberrantly expressed in cancer have significant roles in tumorigenesis and progression.", "output": {"entities": {}}, "schema": []}
{"input": "Currently, miRNAs are being pursued as diagnostic and prognostic biomarkers, and as therapeutic tools in cancer.", "output": {"entities": {}}, "schema": []}
{"input": "miRNA modulation provides the unique ability to fine-tune multiple genes simultaneously, thereby regulating relevant signaling pathways involved in cell differentiation, proliferation and survival.", "output": {"entities": {}}, "schema": []}
{"input": "This unique miRNA feature shifts the traditional one drug one target paradigm to a novel one drug multiple targets paradigm.", "output": {"entities": {}}, "schema": []}
{"input": "We herein review in vivo strategies of miRNA modulator (mimic and/or inhibitor) delivery in cancer models, a subject that remains the key challenge to the establishment of this novel class of RNA therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Inhalable highly concentrated itraconazole nanosuspension for the treatment of bronchopulmonary aspergillosis.", "output": {"entities": {"chemical": [{"text": "itraconazole", "start": 30, "end": 42}]}}, "schema": []}
{"input": "Cystic fibrosis (CF) patients are suffering from multiple often chronic endobronchial infection.", "output": {"entities": {}}, "schema": []}
{"input": "The stiff mucus in these patients represents a compartment, which cannot easily be reached by systemic treatment.", "output": {"entities": {}}, "schema": []}
{"input": "While bacterial infections are now successfully treated with repeated inhalation of antibiotics such as tobramycine, 57% of CF patients are colonized by Aspergillus species.", "output": {"entities": {"chemical": [{"text": "tobramycine", "start": 104, "end": 115}]}}, "schema": []}
{"input": "About 10-20% of colonized patients develop symptoms of allergic bronchopulmonary aspergillosis (ABPA).", "output": {"entities": {}}, "schema": []}
{"input": "While current standard of treatment of ABPA in CF patients is to suppress the allergy related symptoms by administration of glucocorticoids, itraconazole (ITRA), administered orally at high doses, can alleviate the symptoms of ABPA.", "output": {"entities": {"chemical": [{"text": "itraconazole", "start": 141, "end": 153}, {"text": "ITRA", "start": 155, "end": 159}]}}, "schema": []}
{"input": "However, no inhalable formulation of ITRA is available to enable local treatment of aspergillosis.", "output": {"entities": {"chemical": [{"text": "ITRA", "start": 37, "end": 41}]}}, "schema": []}
{"input": "The aim of this study was to describe an aqueous nanosuspension of ITRA and to characterize the pharmacokinetics after single dose inhalation.", "output": {"entities": {"chemical": [{"text": "ITRA", "start": 67, "end": 71}]}}, "schema": []}
{"input": "Using wet-milling with organic milling beads, a stable nanosuspension with particle size in the range of 200nm and an ITRA concentration of 20% (v/w) could be obtained, using polysorbate 80 at a concentration of 14% relative to ITRA.", "output": {"entities": {"chemical": [{"text": "ITRA", "start": 118, "end": 122}, {"text": "polysorbate 80", "start": 175, "end": 189}, {"text": "ITRA", "start": 228, "end": 232}]}}, "schema": []}
{"input": "The suspension was stable if stored at 8 degrees C for 3 months without particle growth and could be nebulized using standard nebulizer technologies including mesh technology and pressured air nebulizers.", "output": {"entities": {}}, "schema": []}
{"input": "A 10% suspension was well tolerated upon repeated dose inhalation once daily for 7 days at a predicted dose of 45mg/kg in rats.", "output": {"entities": {}}, "schema": []}
{"input": "A single dose inhalation at a predicted dose of 22. 5mg/kg resulted in maximum lung tissue concentration of 21. 4 mu g/g tissue with a terminal half-life of 25. 4h.", "output": {"entities": {}}, "schema": []}
{"input": "Serum concentrations were lower, with a maximum concentration of 104ng/ml at 4h after dosing and a terminal half-life of 10. 5h.", "output": {"entities": {}}, "schema": []}
{"input": "The data indicate that ITRA nanosuspension represents an interesting formulation for inhaled administration in CF patients suffering from ABPA.", "output": {"entities": {"chemical": [{"text": "ITRA", "start": 23, "end": 27}]}}, "schema": []}
{"input": "High and long lasting lung tissue concentrations well above the minimal inhibitory concentration of Aspergillus species enable once daily administration with minimal systemic exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Regulation of adenosine levels during cerebral ischemia.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 14, "end": 23}]}}, "schema": []}
{"input": "Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events, and attenuates the excitotoxic neuronal injury.", "output": {"entities": {"chemical": [{"text": "Adenosine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Adenosine is produced both intracellularly and extracellularly, and nucleoside transport proteins transfer adenosine across plasma membranes.", "output": {"entities": {"chemical": [{"text": "Adenosine", "start": 0, "end": 9}, {"text": "nucleoside", "start": 68, "end": 78}, {"text": "adenosine", "start": 107, "end": 116}]}}, "schema": []}
{"input": "Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption, cellular release of ATP, metabolism of extracellular ATP (and other adenine nucleotides), adenosine influx, adenosine efflux and adenosine metabolism.", "output": {"entities": {"chemical": [{"text": "Adenosine", "start": 0, "end": 9}, {"text": "adenosine", "start": 50, "end": 59}, {"text": "ATP", "start": 91, "end": 94}, {"text": "ATP", "start": 128, "end": 131}, {"text": "ATP", "start": 161, "end": 164}, {"text": "adenine nucleotides", "start": 176, "end": 195}, {"text": "adenosine", "start": 198, "end": 207}, {"text": "adenosine", "start": 216, "end": 225}, {"text": "adenosine", "start": 237, "end": 246}]}}, "schema": []}
{"input": "Recent studies have used genetically modified mice to investigate the relative contributions of intra-and extracellular pathways for adenosine formation.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 133, "end": 142}]}}, "schema": []}
{"input": "The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 75, "end": 84}, {"text": "nucleoside", "start": 209, "end": 219}]}}, "schema": []}
{"input": "From these studies, we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures, but not in hippocampal slices or in vivo mice exposed to ischemic conditions.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 37, "end": 40}, {"text": "adenosine", "start": 93, "end": 102}]}}, "schema": []}
{"input": "The toxicity of the N-hydroxy and 6-hydroxy metabolites of 3, 4-dichloropropionanilide does not depend on calcium release-activated calcium channel inhibition.", "output": {"entities": {"chemical": [{"text": "N-hydroxy", "start": 20, "end": 29}, {"text": "6-hydroxy", "start": 34, "end": 43}, {"text": "3, 4-dichloropropionanilide", "start": 59, "end": 86}, {"text": "calcium", "start": 106, "end": 113}, {"text": "calcium", "start": 132, "end": 139}]}}, "schema": []}
{"input": "Each year ~ 1 billion kg of herbicides are used worldwide to control the unwanted growth of plants.", "output": {"entities": {}}, "schema": []}
{"input": "In the United States, over a quarter of a billion kg of herbicides are used, representing 28% of worldwide use.", "output": {"entities": {}}, "schema": []}
{"input": "(Kiely, T., Donaldson, D., and Grube, A. [2004]. Pesticide Industry Sales and Usage. 2000 and 2001 Market Estimates. Available at: http://www. epa. gov/pesticides/pestsales/01pestsales/market _ estimates2001. pdf. Accessed October 25, 2012.) Propanil (3, 4-dichloropropionanilide [DCPA]) is a commonly used herbicide in the United States, with 2-4 million kg applied annually to 2 million acres of crop land.", "output": {"entities": {"chemical": [{"text": "Propanil", "start": 242, "end": 250}, {"text": "3, 4-dichloropropionanilide", "start": 252, "end": 279}, {"text": "DCPA", "start": 281, "end": 285}]}}, "schema": []}
{"input": "The immunomodulatory effects of DCPA have been well documented, but limited data are available on the effects of its metabolites.", "output": {"entities": {"chemical": [{"text": "DCPA", "start": 32, "end": 36}]}}, "schema": []}
{"input": "(Salazar, K. D., Ustyugova, I. V., Brundage, K. M., Barnett, J. B., and Schafer, R. [2008]. A review of the immunotoxicity of the pesticide 3, 4-dichloropropionanalide. J. Toxicol. Environ. Health B Crit. Rev. 11, 630-645.) In mammals, hepatic enzymes metabolize DCPA, resulting in the production of 3, 4-dichloroaniline (DCA).", "output": {"entities": {"chemical": [{"text": "3, 4-dichloropropionanalide", "start": 140, "end": 167}, {"text": "DCPA", "start": 263, "end": 267}, {"text": "3, 4-dichloroaniline", "start": 300, "end": 320}, {"text": "DCA", "start": 322, "end": 325}]}}, "schema": []}
{"input": "Further biotransformation of DCA leads to the production of 6-hydroxy-3, 4-dichloroaniline (6OH-DCA) and N-hydroxy-3, 4-dichloroaniline (NOH-DCA).", "output": {"entities": {"chemical": [{"text": "DCA", "start": 29, "end": 32}, {"text": "6-hydroxy-3, 4-dichloroaniline", "start": 60, "end": 90}, {"text": "6OH-DCA", "start": 92, "end": 99}, {"text": "N-hydroxy-3, 4-dichloroaniline", "start": 105, "end": 135}, {"text": "NOH-DCA", "start": 137, "end": 144}]}}, "schema": []}
{"input": "We report, for the first time, the immunotoxic effects of DCPA metabolites on T-cell function.", "output": {"entities": {"chemical": [{"text": "DCPA", "start": 58, "end": 62}]}}, "schema": []}
{"input": "Human Jurkat T cells were exposed to varying concentrations of DCPA or its metabolites and assayed for effects on T-cell function.", "output": {"entities": {"chemical": [{"text": "DCPA", "start": 63, "end": 67}]}}, "schema": []}
{"input": "In addition, fluorine analogs of DCPA and DCA were investigated to determine the relative role of chlorine substituents on T-cell immunotoxicity.", "output": {"entities": {"chemical": [{"text": "fluorine", "start": 13, "end": 21}, {"text": "DCPA", "start": 33, "end": 37}, {"text": "DCA", "start": 42, "end": 45}, {"text": "chlorine", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Here we report that exposure of Jurkat T cells to DCPA and DCA alters IL-2 secretion, nuclear factor of activated T cells (NFAT) activity, and calcium influx.", "output": {"entities": {"chemical": [{"text": "DCPA", "start": 50, "end": 54}, {"text": "DCA", "start": 59, "end": 62}, {"text": "calcium", "start": 143, "end": 150}]}}, "schema": []}
{"input": "However, exposure to 6OH-DCA and NOH-DCA reduces IL-2 secretion and NFAT activity but has no effect on calcium flux.", "output": {"entities": {"chemical": [{"text": "6OH-DCA", "start": 21, "end": 28}, {"text": "NOH-DCA", "start": 33, "end": 40}, {"text": "calcium", "start": 103, "end": 110}]}}, "schema": []}
{"input": "When both chlorines in DCPA and DCA were substituted with fluorines all effects were abrogated.", "output": {"entities": {"chemical": [{"text": "chlorines", "start": 10, "end": 19}, {"text": "DCPA", "start": 23, "end": 27}, {"text": "DCA", "start": 32, "end": 35}, {"text": "fluorines", "start": 58, "end": 67}]}}, "schema": []}
{"input": "Our data indicate that metabolites of DCPA have differential effects on T-cell function and the presence of chlorines plays an important role in eliciting these effects.", "output": {"entities": {"chemical": [{"text": "DCPA", "start": 38, "end": 42}, {"text": "chlorines", "start": 108, "end": 117}]}}, "schema": []}
{"input": "Metabolism and quantification of [(18) F] DPA-714, a new TSPO positron emission tomography radioligand.", "output": {"entities": {"chemical": [{"text": "[(18) F] DPA-714", "start": 33, "end": 49}]}}, "schema": []}
{"input": "[(18) F] DPA-714 [N, N-diethyl-2-(2-(4-(2 [(18) F]-fluoroethoxy) phenyl) 5, 7dimethylpyrazolo [1, 5a] pyrimidin-3-yl) acetamide] is a new radioligand currently used for imaging the 18-kDa translocator protein in animal models of neuroinflammation and recently in humans.", "output": {"entities": {"chemical": [{"text": "[(18) F] DPA-714", "start": 0, "end": 16}, {"text": "N, N-diethyl-2-(2-(4-(2 [(18) F]-fluoroethoxy) phenyl) 5, 7dimethylpyrazolo [1, 5a] pyrimidin-3-yl) acetamide", "start": 18, "end": 127}]}}, "schema": []}
{"input": "The biodistribution by positron emission tomography (PET) in baboons and the in vitro and in vivo metabolism of [(18) F] DPA-714 were investigated in rats, baboons, and humans.", "output": {"entities": {"chemical": [{"text": "[(18) F] DPA-714", "start": 112, "end": 128}]}}, "schema": []}
{"input": "Whole-body PET experiments showed a high uptake of radioactivity in the kidneys, heart, liver, and gallbladder.", "output": {"entities": {}}, "schema": []}
{"input": "The liver was a major route of elimination of [(18) F] DPA-714, and urine was a route of excretion for radiometabolites.", "output": {"entities": {"chemical": [{"text": "[(18) F] DPA-714", "start": 46, "end": 62}]}}, "schema": []}
{"input": "In rat and baboon plasma, high-performance liquid chromatography (HPLC) metabolic profiles showed three major radiometabolites accounting for 85% and 89% of total radioactivity at 120 minutes after injection, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Rat microsomal incubations and analyses by liquid chromatography-mass spectrometry (LC-MS) identified seven metabolites, characterized as O-deethyl, hydroxyl, and N-deethyl derivatives of nonradioactive DPA-714, two of them having the same retention times than those detected in rat and baboon plasma.", "output": {"entities": {"chemical": [{"text": "O-deethyl", "start": 138, "end": 147}, {"text": "hydroxyl", "start": 149, "end": 157}, {"text": "N-deethyl", "start": 163, "end": 172}, {"text": "DPA-714", "start": 203, "end": 210}]}}, "schema": []}
{"input": "The third plasma radiometabolite was suggested to be a carboxylic acid compound that accounted for 15% of the rat brain radioactivity.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 55, "end": 70}]}}, "schema": []}
{"input": "O-deethylation led to a nonradioactive compound and [(18) F] fluoroacetic acid.", "output": {"entities": {"chemical": [{"text": "O", "start": 0, "end": 1}, {"text": "[(18) F] fluoroacetic acid", "start": 52, "end": 78}]}}, "schema": []}
{"input": "Human CYP3A4 and CYP2D6 were shown to be involved in the oxidation of the radioligand.", "output": {"entities": {}}, "schema": []}
{"input": "Finally an easy, rapid, and accurate method--indispensable for PET quantitative clinical studies--for quantifying [(18) F] DPA-714 by solid-phase extraction was developed.", "output": {"entities": {"chemical": [{"text": "[(18) F] DPA-714", "start": 114, "end": 130}]}}, "schema": []}
{"input": "In vivo, an extensive metabolism of [(18) F] DPA-714 was observed in rats and baboons, identified as [(18) F] deethyl, [(18) F] hydroxyl, and [(18) F] carboxylic acid derivatives of [(18) F] DPA-714.", "output": {"entities": {"chemical": [{"text": "[(18) F] DPA-714", "start": 36, "end": 52}, {"text": "[(18) F] deethyl", "start": 101, "end": 117}, {"text": "[(18) F] hydroxyl", "start": 119, "end": 136}, {"text": "[(18) F] carboxylic acid", "start": 142, "end": 166}, {"text": "[(18) F] DPA-714", "start": 182, "end": 198}]}}, "schema": []}
{"input": "The main route of excretion of the unchanged radioligand in baboons was hepatobiliary while that of radiometabolites was the urinary system.", "output": {"entities": {}}, "schema": []}
{"input": "Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 21, "end": 30}]}}, "schema": []}
{"input": "Environmental and genetic factors are thought to be involved in the pathogenesis of autoimmune thyroid diseases (AITD), which include Graves' disease, Hashimoto' s thyroiditis.", "output": {"entities": {}}, "schema": []}
{"input": "Polymorphisms of vitamin D receptor (VDR) were implicated in AITDs risk.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 17, "end": 26}]}}, "schema": []}
{"input": "To date, many studies have evaluated the association between a functional polymorphism in the VDR gene and AITDs risk; however, the result is still ambiguous and inconclusive.", "output": {"entities": {}}, "schema": []}
{"input": "To address the association of VDR gene FokI (rs10735810), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) polymorphisms with AITD risk by meta-analysis.", "output": {"entities": {}}, "schema": []}
{"input": "By searching the relevant literature, a total of eight studies were identified and meta-analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "HWE for each study are checked.", "output": {"entities": {}}, "schema": []}
{"input": "Crude odds ratios (OR) with 95% confidence intervals (CIs) were used to assess the strength of association in the allele polymorphism, codominant model, dominant model, and recessive model.", "output": {"entities": {}}, "schema": []}
{"input": "The result indicates that the BsmI or TaqI polymorphisms is significantly associated with AITD risk (OR = 0. 801 95% CI 0. 705, 0. 910, Pz = 0. 001 for B vs. b; OR = 0. 854, 95% CI 0. 757, 0. 963, Pz = 0. 010 for t vs. T), while the ApaI or FokI polymorphism do not.", "output": {"entities": {}}, "schema": []}
{"input": "In the subgroup analysis in Europeans, the decreased risk of AITD remained for the B or t variant.", "output": {"entities": {}}, "schema": []}
{"input": "This gene-based analysis indicates that, based on current evidence from published studies, the cumulative effect of BsmI or TaqI polymorphisms in VDR is significantly associated with AITD.", "output": {"entities": {}}, "schema": []}
{"input": "Optimization of CD4/gp120 inhibitors by thermodynamic-guided alanine-scanning mutagenesis.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 61, "end": 68}]}}, "schema": []}
{"input": "As protein/protein interactions usually trigger signalling processes, inhibitors of those interactions must preclude protein binding without eliciting the signalling process themselves.", "output": {"entities": {}}, "schema": []}
{"input": "To accomplish those goals, small molecules need to target those protein residues that contribute the most to binding (binding hotspots) without disturbing those residues that initiate signalling processes (allosteric hotspots).", "output": {"entities": {}}, "schema": []}
{"input": "The availability of a blueprint identifying binding and allosteric hotspots will significantly aid inhibitor design and optimization.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we show that in some situations the blueprint can be constructed by combining the standard technique of alanine-scanning mutagenesis with isothermal titration calorimetry (ITC).", "output": {"entities": {"chemical": [{"text": "alanine", "start": 119, "end": 126}]}}, "schema": []}
{"input": "We demonstrate the approach by developing the combined binding and allosteric hotspots blueprint for CD4/gp120, the initial interaction leading to HIV-1 cell infection.", "output": {"entities": {}}, "schema": []}
{"input": "A major finding of these studies is that not all binding hotspots are allosteric hotspots opening the possibility for the rational design of inhibitors and antagonist or agonist modulators.", "output": {"entities": {}}, "schema": []}
{"input": "Alanine scan of an immunosuppressive peptide (CP): analysis of structure-function relationships.", "output": {"entities": {"chemical": [{"text": "Alanine", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Core peptide is a hydrophobic peptide, the sequence of which is derived from the T-cell antigen receptor alpha-chain transmembrane region.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies have shown that core peptide can inhibit T-cell-mediated immune responses both in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report the role each constituent amino acid plays within core peptide using an alanine scan and the amino acid effect on function using a biological antigen presentation assay.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 42, "end": 52}, {"text": "alanine", "start": 88, "end": 95}, {"text": "amino acid", "start": 109, "end": 119}]}}, "schema": []}
{"input": "The biophysical behaviour of these analogues in model membranes was analysed using surface plasmon resonance studies and then binding correlated with T-cell function.", "output": {"entities": {}}, "schema": []}
{"input": "Removal of any single hydrophobic amino acid between the two charged amino acids in core peptide (R, K) resulted in lower binding.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 34, "end": 44}, {"text": "amino acids", "start": 69, "end": 80}]}}, "schema": []}
{"input": "Changing the overall net charge of core peptide, by removing either of the positively charged residues (R or K), had varying effects on peptide binding and IL-2 production.", "output": {"entities": {}}, "schema": []}
{"input": "There was a direct correlation (rho = 0. 718) between peptide binding to model membranes and peptide ability to inhibit IL-2.", "output": {"entities": {}}, "schema": []}
{"input": "Except for IL-2 inhibition, production of other T-cell cytokines such as GM-CSF, IFN-gamma, IL-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17 and T-cell antigen receptor alpha-chain was not detected using a fluorescent bead immunoassay.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides important structure-function relationships essential for further drug design.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-tumor necrosis factor treatment in cherubism--clinical, radiological and histological findings in two children.", "output": {"entities": {}}, "schema": []}
{"input": "Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla.", "output": {"entities": {}}, "schema": []}
{"input": "The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha).", "output": {"entities": {}}, "schema": []}
{"input": "Recent findings in the cherubism mouse model suggest that TNF-alpha plays a major role in disease pathogenesis and that removal of TNF-alpha prevents development of the bone phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "We treated two children with cherubism with the TNF-alpha antagonist adalimumab for approximately 2. 5 years and collected extensive clinical, radiological and histological follow-up data during the treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-alpha staining positivity in both patients.", "output": {"entities": {}}, "schema": []}
{"input": "As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla).", "output": {"entities": {}}, "schema": []}
{"input": "In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged.", "output": {"entities": {}}, "schema": []}
{"input": "Bone formation and resorption markers remained unaffected.", "output": {"entities": {}}, "schema": []}
{"input": "The treatment was well tolerated.", "output": {"entities": {}}, "schema": []}
{"input": "Based on our findings, TNF-alpha antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism.", "output": {"entities": {}}, "schema": []}
{"input": "TNF-alpha modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism.", "output": {"entities": {}}, "schema": []}
{"input": "Controlling enzymatic action in living cells with a kinase-inducible bimolecular switch.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular probes designed to monitor or perturb signaling events in living cells rely on engineered molecular switches.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that a kinase-inducible bimolecular switch comprising a kinase-specific substrate and a phosphoamino acid binding domain can be used for acute regulation of cellular events.", "output": {"entities": {"chemical": [{"text": "phosphoamino acid", "start": 102, "end": 119}]}}, "schema": []}
{"input": "As a proof of concept, we employed a Protein Kinase A (PKA)-dependent switch and coupled it to a lipid phosphatase to manipulate the level of phosphatidylinositol 4, 5-bisphosphate (PI (4, 5) P (2)) in living cells.", "output": {"entities": {"chemical": [{"text": "phosphatidylinositol 4, 5-bisphosphate", "start": 142, "end": 180}, {"text": "PI (4, 5) P (2)", "start": 182, "end": 197}]}}, "schema": []}
{"input": "PKA activation results in rapid degradation of PI (4, 5) P (2).", "output": {"entities": {"chemical": [{"text": "PI (4, 5) P (2)", "start": 47, "end": 62}]}}, "schema": []}
{"input": "Conversely, when PKA is inhibited, dephosphorylation of the switch leads to the replenishment of PI (4, 5) P (2).", "output": {"entities": {"chemical": [{"text": "PI (4, 5) P (2)", "start": 97, "end": 112}]}}, "schema": []}
{"input": "Thus, this strategy can be used for reversibly controlling enzymatic action in living cells.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, its genetic encodability and modular design should facilitate the adaptation of this approach to control different cellular activities as a function of phosphorylation-dependent input signals, thereby providing versatile tools for potentially perturbing or rewiring signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis, and in vitro evaluation of new amphiphilic cyclodextrin-based nanoparticles for the incorporation and controlled release of acyclovir.", "output": {"entities": {"chemical": [{"text": "acyclovir", "start": 143, "end": 152}]}}, "schema": []}
{"input": "Acyclovir possesses low solubility in water and in lipid bilayers, so that its dosage forms do not allow suitable drug levels at target sites following oral, local, or parenteral administration.", "output": {"entities": {"chemical": [{"text": "Acyclovir", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In order to improve this lack of solubility, new cyclodextrin-based amphiphilic derivatives have been designed to form nanoparticles, allowing the efficient encapsulation of this hydrophobic antiviral agent.", "output": {"entities": {}}, "schema": []}
{"input": "The present work first describes the synthesis and characterization of five new O-2, O-3 permethylated O-6 alkylthio-and perfluoroalkyl-propanethio-amphiphilic beta-cyclodextrins.", "output": {"entities": {"chemical": [{"text": "O-2, O-3 permethylated O-6 alkylthio-and perfluoroalkyl-propanethio-amphiphilic beta-cyclodextrins", "start": 80, "end": 178}]}}, "schema": []}
{"input": "These derivatives have been obtained with good overall yields.", "output": {"entities": {}}, "schema": []}
{"input": "The capacity of these molecules to form nanoparticles in water and to encapsulate acyclovir has then been studied.", "output": {"entities": {"chemical": [{"text": "acyclovir", "start": 82, "end": 91}]}}, "schema": []}
{"input": "The nanoparticles prepared from the new beta-cyclodextrin derivatives have been characterized by dynamic light scattering and have an average size of 120nm for the fluorinated derivatives and 220nm for the hydrogenated analogs.", "output": {"entities": {"chemical": [{"text": "beta-cyclodextrin", "start": 40, "end": 57}]}}, "schema": []}
{"input": "They all allowed high loading and sustained release of acyclovir.", "output": {"entities": {"chemical": [{"text": "acyclovir", "start": 55, "end": 64}]}}, "schema": []}
{"input": "Fingolimod protects cultured cortical neurons against excitotoxic death.", "output": {"entities": {"chemical": [{"text": "Fingolimod", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Fingolimod (FTY720), a novel drug approved for the treatment of relapsing-remitting multiple sclerosis, activates different sphingosine-1-phosphate receptor (S1PR) subtypes.", "output": {"entities": {"chemical": [{"text": "Fingolimod", "start": 0, "end": 10}, {"text": "FTY720", "start": 12, "end": 18}, {"text": "sphingosine-1-phosphate", "start": 124, "end": 147}]}}, "schema": []}
{"input": "Its primary mechanism of action is to reduce the egress of T lymphocytes from secondary lymphoid organs, thus restraining neuroinflammation and autoimmunity.", "output": {"entities": {}}, "schema": []}
{"input": "However, recent evidence suggests that the action of FTY720 involves S1PRs expressed by cells resident in the CNS, including neurons.", "output": {"entities": {"chemical": [{"text": "FTY720", "start": 53, "end": 59}]}}, "schema": []}
{"input": "Here, we examined the effect of FTY720, its active metabolite, FTY720-P, and sphingosine-1-phosphate (S1P) on neuronal viability using a classical in vitro model of excitotoxic neuronal death.", "output": {"entities": {"chemical": [{"text": "FTY720", "start": 32, "end": 38}, {"text": "FTY720-P", "start": 63, "end": 71}, {"text": "sphingosine-1-phosphate", "start": 77, "end": 100}, {"text": "S1P", "start": 102, "end": 105}]}}, "schema": []}
{"input": "Mixed cultures of mouse cortical cells were challenged with toxic concentrations of N-methyl-d-aspartate (NMDA) for 10 min, and neuronal death was assessed 20 h later.", "output": {"entities": {"chemical": [{"text": "N-methyl-d-aspartate", "start": 84, "end": 104}, {"text": "NMDA", "start": 106, "end": 110}]}}, "schema": []}
{"input": "FTY720, FTY720-P, and S1P were all neuroprotective when applied 18-20 h prior to the NMDA pulse.", "output": {"entities": {"chemical": [{"text": "FTY720", "start": 0, "end": 6}, {"text": "FTY720-P", "start": 8, "end": 16}, {"text": "S1P", "start": 22, "end": 25}, {"text": "NMDA", "start": 85, "end": 89}]}}, "schema": []}
{"input": "Neuroprotection was attenuated by pertussis toxin, and inhibited by the selective type-1 S1PR (S1P1R) antagonist, W146, and by inhibitors of the mitogen associated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PtdIns-3-K) pathways.", "output": {"entities": {"chemical": [{"text": "W146", "start": 114, "end": 118}, {"text": "phosphatidylinositol", "start": 194, "end": 214}]}}, "schema": []}
{"input": "Both FTY720 and FTY720-P retained their protective activity in pure cultures of mouse or rat cortical neurons.", "output": {"entities": {"chemical": [{"text": "FTY720", "start": 5, "end": 11}, {"text": "FTY720-P", "start": 16, "end": 24}]}}, "schema": []}
{"input": "These data offer the first direct demonstration that FTY720 and its active metabolite protect neurons against excitotoxic death.", "output": {"entities": {"chemical": [{"text": "FTY720", "start": 53, "end": 59}]}}, "schema": []}
{"input": "In situ control of cell substrate microtopographies using photolabile hydrogels.", "output": {"entities": {}}, "schema": []}
{"input": "Substratum topography can play a significant role in regulating cellular function and fate.", "output": {"entities": {}}, "schema": []}
{"input": "To study cellular responses to biophysical cues, researchers have developed dynamic methods for controlling cell morphology; however, many of these platforms are limited to one transition between two predefined substratum topographies.", "output": {"entities": {}}, "schema": []}
{"input": "To afford the user additional control over the presentation of microtopographic cues to cell populations, a photolabile, PEG-based hydrogel system is presented in which precisely engineered topographic cues can be formed in situ by controlled erosion.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 121, "end": 124}]}}, "schema": []}
{"input": "Here, the ability to produce precisely engineered static microtopographies in the hydrogel surface is first established.", "output": {"entities": {}}, "schema": []}
{"input": "Human mesenchymal stem cell (hMSC) response to topographies with features of subcellular dimensions (~ 5 to 40 mu m) and with various aspect ratios increasing from 1: 1 to infinity (e. g., channels) are quantified, and the dynamic nature of the culture system is demonstrated by sequentially presenting a series of topographies through in situ modifications and quantifying reversible changes in cell morphology in response to substratum topographies altered in real time.", "output": {"entities": {}}, "schema": []}
{"input": "Treadmill exercise promotes interleukin 15 expression in skeletal muscle and interleukin 15 receptor alpha expression in adipose tissue of high-fat diet rats.", "output": {"entities": {}}, "schema": []}
{"input": "Interleukin 15 (IL-15) has recently been proposed as a myokine involved in regulating lipid metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the effect of exercise training on IL-15 content in skeletal muscle and expression of IL-15 receptor (IL-15R) in adipose tissue of obese rats.", "output": {"entities": {}}, "schema": []}
{"input": "After 12 weeks of a high-fat diet, obese rats underwent treadmill running at 26 m/min (60 min each, 5 days/week for 8 weeks).", "output": {"entities": {}}, "schema": []}
{"input": "High-fat diet induced obesity, with increased body weight, body fat, and lipid profile.", "output": {"entities": {}}, "schema": []}
{"input": "The level of IL-15 immunoreactivity (IL-15-ir) in plasma and gastrocnemius muscle was lower in obese than control rats, and the mRNA level of IL-15 in gastrocnemius muscle was markedly decreased.", "output": {"entities": {}}, "schema": []}
{"input": "The mRNA and protein levels of IL-15R in adipose tissue were markedly lower in obese rats.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with sedentary obese rats, treadmill running showed decreased body weight and elevated mRNA expression of IL-15 in muscle and elevated IL-15-ir level in plasma and muscle.", "output": {"entities": {}}, "schema": []}
{"input": "The mRNA and protein level of IL-15R were increased in adipose tissue in treadmill running obese rats.", "output": {"entities": {}}, "schema": []}
{"input": "Our results showed that exercise training improve obesity and reversed the downregulation of the IL-15 in muscle and IL-15R in adipose tissue induced by high-fat diet.", "output": {"entities": {}}, "schema": []}
{"input": "Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells.", "output": {"entities": {"chemical": [{"text": "silica", "start": 36, "end": 42}]}}, "schema": []}
{"input": "In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs).", "output": {"entities": {"chemical": [{"text": "silica", "start": 116, "end": 122}]}}, "schema": []}
{"input": "HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells).", "output": {"entities": {}}, "schema": []}
{"input": "The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis.", "output": {"entities": {}}, "schema": []}
{"input": "An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles.", "output": {"entities": {"chemical": [{"text": "doxorubicin hydrochloride", "start": 20, "end": 45}, {"text": "Dox", "start": 47, "end": 50}]}}, "schema": []}
{"input": "Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs.", "output": {"entities": {"chemical": [{"text": "Dox", "start": 0, "end": 3}, {"text": "Dox", "start": 72, "end": 75}, {"text": "Dox", "start": 80, "end": 83}]}}, "schema": []}
{"input": "It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.", "output": {"entities": {}}, "schema": []}
{"input": "An in vitro model using the IPEC-J2 cell line for efficacy and drug interaction testing of mycotoxin detoxifying agents.", "output": {"entities": {}}, "schema": []}
{"input": "An in vitro model simulating the intestinal barrier for efficacy and drug interaction testing of mycotoxin detoxifying agents was developed using Transwell (R) cell culture inserts.", "output": {"entities": {}}, "schema": []}
{"input": "Intestinal porcine epithelial cells derived from the jejunum of piglets were exposed to DON and a mycotoxin binder (efficacy testing) or exposed to tylosin and a mycotoxin binder (drug interaction testing).", "output": {"entities": {"chemical": [{"text": "tylosin", "start": 148, "end": 155}]}}, "schema": []}
{"input": "Active carbon and bentonite were used in the efficacy and drug interaction trials, respectively, to validate the developed model.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 7, "end": 13}, {"text": "bentonite", "start": 18, "end": 27}]}}, "schema": []}
{"input": "The evaluated parameters were passage of DON and tylosin through the epithelial monolayer, the integrity of the monolayer by measurements of the trans-epithelial electrical resistance and the viability of the monolayer using the neutral red assay.", "output": {"entities": {"chemical": [{"text": "DON", "start": 41, "end": 44}, {"text": "tylosin", "start": 49, "end": 56}, {"text": "neutral red", "start": 229, "end": 240}]}}, "schema": []}
{"input": "In the efficacy model it was shown that active carbon effectively bound DON at both non-cytotoxic and cytotoxic concentrations of DON, respectively 0. 5 and 1 mu g/mL.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 47, "end": 53}, {"text": "DON", "start": 72, "end": 75}, {"text": "DON", "start": 130, "end": 133}]}}, "schema": []}
{"input": "Moreover, the negative effects of DON at cytotoxic concentrations on cellular viability and integrity were completely offset.", "output": {"entities": {"chemical": [{"text": "DON", "start": 34, "end": 37}]}}, "schema": []}
{"input": "A commercially available modified gluco-mannan binder was also tested and it was able to partly reduce the negative effects on these latter parameter.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, it reduced the transepithelial passage of DON with 37% to 57% compared to active carbon, at both cytotoxic and non-cytotoxic concentrations of DON.", "output": {"entities": {"chemical": [{"text": "DON", "start": 52, "end": 55}, {"text": "carbon", "start": 91, "end": 97}, {"text": "DON", "start": 153, "end": 156}]}}, "schema": []}
{"input": "In our drug interaction model, the interaction between tylosin and mycotoxin binders was investigated as some authors suggest binding of macrolide antibiotics to bentonite clays.", "output": {"entities": {"chemical": [{"text": "tylosin", "start": 55, "end": 62}, {"text": "macrolide", "start": 137, "end": 146}, {"text": "bentonite", "start": 162, "end": 171}]}}, "schema": []}
{"input": "Indeed, a bentonite clay showed decreased passage of tylosin through the epithelial monolayer, indicating binding of tylosin by bentonite.", "output": {"entities": {"chemical": [{"text": "bentonite", "start": 10, "end": 19}, {"text": "tylosin", "start": 53, "end": 60}, {"text": "tylosin", "start": 117, "end": 124}, {"text": "bentonite", "start": 128, "end": 137}]}}, "schema": []}
{"input": "This indicates that the combined use of bentonite and tylosin in the feed could lead to therapy failure.", "output": {"entities": {"chemical": [{"text": "bentonite", "start": 40, "end": 49}, {"text": "tylosin", "start": 54, "end": 61}]}}, "schema": []}
{"input": "The modified gluco-mannan binder did not alter the passage of tylosin significantly, indicating safe combined use.", "output": {"entities": {"chemical": [{"text": "tylosin", "start": 62, "end": 69}]}}, "schema": []}
{"input": "Novel and de novo PHEX mutations in patients with hypophosphatemic rickets.", "output": {"entities": {}}, "schema": []}
{"input": "X-linked hypophosphatemic rickets (XLH) is the most common inherited rickets.", "output": {"entities": {}}, "schema": []}
{"input": "XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated PHEX mutation in 10 patients from 6 unrelated Turkish families by PCR-sequence analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Six different PHEX mutations were detected in the patients.", "output": {"entities": {}}, "schema": []}
{"input": "Four of them were novel: c. 1217G > A (p. C406Y) in exon 11, c. 2078G > T (p. C693F) in exon 21, a splice donor site mutation in intron 13 (IVS13 + 1G > T), and a splice acceptor site mutation in intron 13 (IVS13-2A > G).", "output": {"entities": {}}, "schema": []}
{"input": "De novo PHEX mutations were found exclusively in female patients from 4 families and inherited mutations were detected from remaining two families.", "output": {"entities": {}}, "schema": []}
{"input": "The patients' phenotype was consistent with the loss of PHEX function.", "output": {"entities": {}}, "schema": []}
{"input": "Literature review of 78 sporadic cases shows that de novo mutations are present in 83% female patients and female/male ratio is 5 to 1.", "output": {"entities": {}}, "schema": []}
{"input": "One patient had biallilic PHEX mutations at c. 1735G > A (p. G579R) whereas her mother and two siblings carried a monoallelic mutation.", "output": {"entities": {}}, "schema": []}
{"input": "The clinical and laboratory findings of the patient with biallilic PHEX mutation were similar to those with monoallelic mutation.", "output": {"entities": {}}, "schema": []}
{"input": "The study shows that PHEX mutation is a common cause of either familial or sporadic hypophosphatemic rickets in Turkish population.", "output": {"entities": {}}, "schema": []}
{"input": "Gene dosage effect is not observed.", "output": {"entities": {}}, "schema": []}
{"input": "The frequent de novo mutations found in the female patients are likely resulting from mutagenesis of X chromosome in paternal germ cells.", "output": {"entities": {}}, "schema": []}
{"input": "Ageing and gut microbes: perspectives for health maintenance and longevity.", "output": {"entities": {}}, "schema": []}
{"input": "The ageing process affects the human gut microbiota phylogenetic composition and its interaction with the immune system.", "output": {"entities": {}}, "schema": []}
{"input": "Age-related gut microbiota modifications are associated with immunosenescence and inflamm-ageing in a sort of self-sustaining loop, which allows the placement of gut microbiota unbalances among both the causes and the effects of the inflamm-ageing process.", "output": {"entities": {}}, "schema": []}
{"input": "Even if, up to now, the link between gut microbiota and the ageing process is only partially understood, the gut ecosystem shows the potential to become a promising target for strategies able to contribute to the health status of older people.", "output": {"entities": {}}, "schema": []}
{"input": "In this context, the consumption of pro/prebiotics may be useful in both prevention and treatment of age-related pathophysiological conditions, such as recovery and promotion of immune functions, i. e. adjuvant effect for influenza vaccine, and prevention and/or alleviation of common \" winter diseases \", as well as constipation and Clostridium difficile-associated diarrhoea.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, being involved in different mechanisms which concur in counteracting inflammation, such as down-regulation of inflammation-associated genes and improvement of colonic mucosa conditions, probiotics have the potentiality to be involved in the promotion of longevity.", "output": {"entities": {}}, "schema": []}
{"input": "The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: a comparison.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 4, "end": 12}]}}, "schema": []}
{"input": "The arginine + GHRH test has been established as an alternative to the insulin tolerance test (ITT) for the diagnosis of adult GH deficiency (AGHD).", "output": {"entities": {"chemical": [{"text": "arginine", "start": 4, "end": 12}]}}, "schema": []}
{"input": "However, the glucagon, arginine, and GH releasing peptide-2 (GHRP-2) test are recommended as alternatives in Japan.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 23, "end": 31}]}}, "schema": []}
{"input": "The objective of this study was to evaluate the arginine and GHRP-2 tests as alternatives to the ITT for the diagnosis of AGHD in a Japanese population.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Three stimulation tests (ITT, arginine test, and GHRP-2 test) were conducted in 71 pre-operative adult patients with pituitary tumors (age, 18-65 years).", "output": {"entities": {"chemical": [{"text": "arginine", "start": 30, "end": 38}]}}, "schema": []}
{"input": "The peak GH responses to each test were examined.", "output": {"entities": {}}, "schema": []}
{"input": "The peak GH responses were significantly lower with the ARG test (median 4. 43 mu g/L) (p < 0. 0001) than with the ITT (median 9. 38 mu g/L), and the peak GH responses with the GHRP-2 test (median 28. 88 mu g/L) were higher (p < 0. 0001).", "output": {"entities": {"chemical": [{"text": "ARG", "start": 56, "end": 59}]}}, "schema": []}
{"input": "However, among the AGHD patients, there was no significant difference between the peak GH responses to the ARG test and the ITT.", "output": {"entities": {"chemical": [{"text": "ARG", "start": 107, "end": 110}]}}, "schema": []}
{"input": "The sensitivities and specificities of the ARG/GHRP-2 tests compared to the ITT for the diagnosis of severe AGHD (peak GH responses to ITT <= 1. 8 mu g/L) were 93. 8%/81. 3% and 85. 5%/94. 5%, respectively.", "output": {"entities": {"chemical": [{"text": "ARG", "start": 43, "end": 46}]}}, "schema": []}
{"input": "The arginine and GHRP-2 stimulation tests are acceptable alternatives to the ITT for the diagnosis of AGHD in Japanese patients.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 4, "end": 12}]}}, "schema": []}
{"input": "The method and criterion for the diagnosis of AGHD should be reconsidered and adjusted to each population.", "output": {"entities": {}}, "schema": []}
{"input": "Improved preparation of methyl bis (2, 2, 2-trifluoroethoxy)-bromophosphonoacetate for the stereoselective synthesis of (E)-alpha-bromoacrylates.", "output": {"entities": {"chemical": [{"text": "methyl bis (2, 2, 2-trifluoroethoxy)-bromophosphonoacetate", "start": 24, "end": 82}, {"text": "(E)-alpha-bromoacrylates", "start": 120, "end": 144}]}}, "schema": []}
{"input": "We have established an efficient method for preparing methyl bis (2, 2, 2-trifluoroethoxy) bromophosphonoacetate, which we developed for the stereoselective synthesis of (E)-alpha-bromoacrylates.", "output": {"entities": {"chemical": [{"text": "methyl bis (2, 2, 2-trifluoroethoxy) bromophosphonoacetate", "start": 54, "end": 112}, {"text": "(E)-alpha-bromoacrylates", "start": 170, "end": 194}]}}, "schema": []}
{"input": "This improved method enables the reagent to be prepared reproducibly in one step from methyl bis (2, 2, 2-trifluoroethoxy) phosphonoacetate.", "output": {"entities": {"chemical": [{"text": "methyl bis (2, 2, 2-trifluoroethoxy) phosphonoacetate", "start": 86, "end": 139}]}}, "schema": []}
{"input": "H-TiO (2) @MnO (2)//H-TiO (2) @C core-shell nanowires for high performance and flexible asymmetric supercapacitors.", "output": {"entities": {"chemical": [{"text": "H", "start": 0, "end": 1}, {"text": "TiO (2)", "start": 2, "end": 9}, {"text": "MnO (2)", "start": 11, "end": 18}, {"text": "H", "start": 20, "end": 21}, {"text": "TiO (2)", "start": 22, "end": 29}, {"text": "C", "start": 31, "end": 32}]}}, "schema": []}
{"input": "A flexible solid-state asymmetric supercapacitor device with H-TiO (2) @MnO (2) core-shell NWs as the positive electrode and H-TiO (2) @C core-shell NWs as the negative electrode is developed.", "output": {"entities": {"chemical": [{"text": "H", "start": 61, "end": 62}, {"text": "TiO (2)", "start": 63, "end": 70}, {"text": "MnO (2)", "start": 72, "end": 79}, {"text": "H", "start": 125, "end": 126}, {"text": "TiO (2)", "start": 127, "end": 134}, {"text": "C", "start": 136, "end": 137}]}}, "schema": []}
{"input": "This device operates in a 1. 8 V voltage window and is able to deliver a high specific capacitance of 139. 6 F g (-1) and maximum volumetric energy density of 0. 30 mWh cm (-3) with excellent cycling performance and good flexibility.", "output": {"entities": {}}, "schema": []}
{"input": "Sub-lethal effects of titanium dioxide nanoparticles on the physiology and reproduction of zebrafish.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 22, "end": 38}]}}, "schema": []}
{"input": "There are limited data on the sub-lethal physiological effects of titanium dioxide nanoparticles (TiO (2) NPs) in adult fishes, and the consequences of TiO (2) NP exposure on reproductive success are also unclear.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 66, "end": 82}, {"text": "TiO (2)", "start": 98, "end": 105}, {"text": "TiO (2)", "start": 152, "end": 159}]}}, "schema": []}
{"input": "This study aimed to examine the sub-lethal effects of a 14-d aqueous TiO (2) (TiO (2) NP, 0. 1 or 1. 0 mg l (-1); TiO (2) bulk, 1. 0 mg l (-1)) exposure on the physiology and reproductive health of zebrafish.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 69, "end": 76}, {"text": "TiO (2)", "start": 78, "end": 85}, {"text": "TiO (2)", "start": 114, "end": 121}]}}, "schema": []}
{"input": "After the 14-d exposure, fish were examined for haematology, whole body electrolyte and trace metal profiles, biochemistry, and histopathology.", "output": {"entities": {}}, "schema": []}
{"input": "Then, during a 21-d post exposure recovery period, effects of the TiO (2) exposure on reproductive success were evaluated.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 66, "end": 73}]}}, "schema": []}
{"input": "Whole body Ti concentrations increased significantly in fish exposed to both the 1. 0 mg l (-1) TiO (2) NP and bulk TiO (2) compared to controls, but concentrations returned to control levels by the end of the recovery period.", "output": {"entities": {"chemical": [{"text": "Ti", "start": 11, "end": 13}, {"text": "TiO (2)", "start": 96, "end": 103}, {"text": "TiO (2)", "start": 116, "end": 123}]}}, "schema": []}
{"input": "No change in erythrocyte counts were observed, but there was a two-fold decline in leukocyte counts in all TiO (2) treatment groups relative to time-matched controls.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 107, "end": 114}]}}, "schema": []}
{"input": "Whole body electrolyte and trace metal profiles were not affected by exposure to TiO (2), and there were no changes in Na (+) K (+)-ATPase activity in brain, gill or liver tissues.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 81, "end": 88}, {"text": "Na (+) K (+)", "start": 119, "end": 131}]}}, "schema": []}
{"input": "Total glutathione (GSH) levels in brain, gill and liver tissues were higher in fish exposed to TiO (2) NP (both 0. 1 and 1. 0 mg l (-1)) compared to bulk TiO (2) and control fish.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 6, "end": 17}, {"text": "GSH", "start": 19, "end": 22}, {"text": "TiO (2)", "start": 95, "end": 102}, {"text": "TiO (2)", "start": 154, "end": 161}]}}, "schema": []}
{"input": "Histological examination of gill, liver, brain and gonad tissues showed little evidence of treatment-related morphological change.", "output": {"entities": {}}, "schema": []}
{"input": "At the end of the 14-d exposure adult zebrafish were able to reproduce; however, the cumulative number of viable embryos produced was lower in fish exposed to 1. 0 mg l (-1) TiO (2) (both NP and bulk) by the end of the 21-d recovery period.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 174, "end": 181}]}}, "schema": []}
{"input": "Overall, this study showed limited toxicity of bulk or nano scale TiO (2) during the exposure; however reproduction was affected in both bulk and NP 1. 0 mg l (-1) groups.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 66, "end": 73}]}}, "schema": []}
{"input": "Toxic effects of microcystin-LR on the reproductive system of male Rana nigromaculata in vitro.", "output": {"entities": {"chemical": [{"text": "microcystin-LR", "start": 17, "end": 31}]}}, "schema": []}
{"input": "This study aims to demonstrate that microcystin-LR (MC-LR) has toxic effects on the reproductive system of male Rana nigromaculata in vitro.", "output": {"entities": {"chemical": [{"text": "microcystin-LR", "start": 36, "end": 50}, {"text": "MC-LR", "start": 52, "end": 57}]}}, "schema": []}
{"input": "R. nigromaculata were treated with 0, 0. 1, 1, 10, and 100 nmol/L of MC-LR for 6 h.", "output": {"entities": {}}, "schema": []}
{"input": "Results show that exposure to 1 nmol/L to 100 nmol/L of MC-LR decreased sperm motility and number of sperm cells and increased the sperm abnormality rate, whose values were significantly different from those of the control (P < 0. 01).", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 56, "end": 61}]}}, "schema": []}
{"input": "Moreover, the same dosage of MC-LR increased reactive oxygen species production and malondialdehyde content.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 29, "end": 34}, {"text": "oxygen", "start": 54, "end": 60}, {"text": "malondialdehyde", "start": 84, "end": 99}]}}, "schema": []}
{"input": "At the same time, antioxidant enzyme (catalase and glutathione S-transferase) activity and glutathione reduced content rapidly increased, whereas antioxidant enzyme superoxide dismutase activity significantly decreased.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 51, "end": 64}, {"text": "glutathione", "start": 91, "end": 102}, {"text": "superoxide", "start": 165, "end": 175}]}}, "schema": []}
{"input": "These results imply that the defense system of the testes quickly responds to oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "Ultrastructural observation shows distention of the mitochondria, endoplasmic reticulum, and Golgi apparatus and changes in the mitochondrial matrix color, cristae number, and morphology.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, using real-time PCR, increased relative expressions of P450 aromatase and SF-1 genes were observed.", "output": {"entities": {}}, "schema": []}
{"input": "The results demonstrate for the first time that MC-LR could induce toxicity in the male reproductive system of R. nigromaculata.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 48, "end": 53}]}}, "schema": []}
{"input": "The findings in this research will provide more insights into the relationships between aquatic microcystins and amphibians.", "output": {"entities": {"chemical": [{"text": "microcystins", "start": 96, "end": 108}]}}, "schema": []}
{"input": "Ultrasound-promoted coating of silk yarn with different morphology of magnesium hydroxide nanostructures.", "output": {"entities": {"chemical": [{"text": "magnesium hydroxide", "start": 70, "end": 89}]}}, "schema": []}
{"input": "The growth of magnesium hydroxide nanostructures on silk yarn was achieved by sequential dipping steps in alternating bath of magnesium nitrate and potassium hydroxide under ultrasound irradiation.", "output": {"entities": {"chemical": [{"text": "magnesium hydroxide", "start": 14, "end": 33}, {"text": "magnesium nitrate", "start": 126, "end": 143}, {"text": "potassium hydroxide", "start": 148, "end": 167}]}}, "schema": []}
{"input": "The effects of ultrasound irradiation, concentration, pH and sequential dipping steps on growth of the Mg (OH) (2) nanostructures have been studied.", "output": {"entities": {"chemical": [{"text": "Mg (OH) (2)", "start": 103, "end": 114}]}}, "schema": []}
{"input": "Morphology of the nanostructures, depending on pH and with decreasing pH from 13 to 8, changed from nanoparticle to nanoneedle.", "output": {"entities": {}}, "schema": []}
{"input": "Results show a decrease in the particles size as the concentration and sequential dipping steps increased.", "output": {"entities": {}}, "schema": []}
{"input": "The physicochemical properties of the nanostructures were determined by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and wavelength dispersive X-ray (WDX).", "output": {"entities": {}}, "schema": []}
{"input": "The exposure of highly toxic aconitine does not significantly impact the activity and expression of cytochrome P450 3A in rats determined by a novel ultra performance liquid chromatography-tandem mass spectrometric method of a specific probe buspirone.", "output": {"entities": {"chemical": [{"text": "aconitine", "start": 29, "end": 38}, {"text": "buspirone", "start": 242, "end": 251}]}}, "schema": []}
{"input": "Aconitum species are widely used to treat rheumatism, cardiovascular diseases, and tumors in China and other Asian countries.", "output": {"entities": {}}, "schema": []}
{"input": "The herbs are always used with drugs such as paclitaxel.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 45, "end": 55}]}}, "schema": []}
{"input": "Aconitine (AC) is one of the main bioactive/high-toxic alkaloids of Aconitum roots.", "output": {"entities": {"chemical": [{"text": "Aconitine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "AC is metabolized by cytochrome P450 (CYP) 3A.", "output": {"entities": {}}, "schema": []}
{"input": "However, whether AC inhibits/induces CYP3A, which causes drug-drug interaction (DDI) is unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Our study aims to explore the potent effects of AC, as a marker component of Aconitum, on CYP3A using the probe buspirone in rats.", "output": {"entities": {"chemical": [{"text": "buspirone", "start": 112, "end": 121}]}}, "schema": []}
{"input": "The effects of oral AC on pharmacokinetics of buspirone were evaluated.", "output": {"entities": {"chemical": [{"text": "buspirone", "start": 46, "end": 55}]}}, "schema": []}
{"input": "CYP3A activity and protein levels in rat liver microsomes pretreated with oral AC were also measured using in vitro buspirone metabolism and Western blot.", "output": {"entities": {"chemical": [{"text": "buspirone", "start": 116, "end": 125}]}}, "schema": []}
{"input": "Buspirone and its major metabolites 1-(2-pyrimidinyl) piperazine and 6'-hydroxybuspirone were determined using a newly validated UPLC-MS/MS method.", "output": {"entities": {"chemical": [{"text": "Buspirone", "start": 0, "end": 9}, {"text": "1-(2-pyrimidinyl) piperazine", "start": 36, "end": 64}, {"text": "6'-hydroxybuspirone", "start": 69, "end": 88}]}}, "schema": []}
{"input": "Single dose and 7-day AC administration at 0. 125mg/kg had no effect on CYP3A activity since no change in the formation of 1-(2-pyrimidinyl) piperazine and 6'-hydroxybuspirone.", "output": {"entities": {"chemical": [{"text": "1-(2-pyrimidinyl) piperazine", "start": 123, "end": 151}, {"text": "6'-hydroxybuspirone", "start": 156, "end": 175}]}}, "schema": []}
{"input": "CYP3A activity and protein levels in liver microsomes were also not affected by 7-day AC pretreatment at 0. 125mg/kg.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, AC neither inhibits nor induces CYP3A in rats, indicating AC does not cause CYP3A-related DDI in the liver.", "output": {"entities": {}}, "schema": []}
{"input": "Cholinesterase confabs and cousins: Approaching forty years.", "output": {"entities": {}}, "schema": []}
{"input": "In the past four decades of cholinesterase (ChE) research, we have seen substantive evolution of the field from one centered around substrate and inhibitor kinetic profiles and compound characterizations to the analysis of ChE structure, first through the gene families and then by X-ray crystallographic determinations of the free enzymes and their complexes and conjugates.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, these endeavors have been facilitated by recombinant DNA technologies, structure determinations and parallel studies in related proteins in the alpha/beta-hydrolase fold family.", "output": {"entities": {}}, "schema": []}
{"input": "This approach has not only contributed to a fundamental understanding of structure and function of a large family of hydrolase-like proteins possessing functions other than catalysis, but also has been used to develop new practical strategies for scavenging and antidotal activity in cases of organophosphate insecticide or nerve agent exposure.", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 293, "end": 308}]}}, "schema": []}
{"input": "Timing of decontamination and treatment in case of percutaneous VX poisoning: A mini review.", "output": {"entities": {}}, "schema": []}
{"input": "Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin.", "output": {"entities": {"chemical": [{"text": "organophosphorous", "start": 13, "end": 30}]}}, "schema": []}
{"input": "The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent.", "output": {"entities": {"chemical": [{"text": "oximes", "start": 38, "end": 44}, {"text": "atropine", "start": 46, "end": 54}, {"text": "diazepam", "start": 59, "end": 67}]}}, "schema": []}
{"input": "Repeated administration of these drugs showed to improve treatment efficacy compared to a single injection treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Because of the effectiveness of continuous treatment, it was investigated to what extent a subchronic pretreatment with carbamate (pyridostigmine or physostigmine combined with either procyclidine or scopolamine) would protect against percutaneous VX exposure.", "output": {"entities": {"chemical": [{"text": "carbamate", "start": 120, "end": 129}, {"text": "pyridostigmine", "start": 131, "end": 145}, {"text": "physostigmine", "start": 149, "end": 162}, {"text": "procyclidine", "start": 184, "end": 196}, {"text": "scopolamine", "start": 200, "end": 211}]}}, "schema": []}
{"input": "Inclusion of scopolamine in the pretreatment prevented seizures in all animals, but none of the pretreatments affected survival time or the onset time of cholinergic signs.", "output": {"entities": {"chemical": [{"text": "scopolamine", "start": 13, "end": 24}]}}, "schema": []}
{"input": "These results indicate that percutaneous poisoning with VX requires additional conventional treatment in addition to the current pretreatment regimen.", "output": {"entities": {}}, "schema": []}
{"input": "Decontamination of VX-exposed skin is one of the most important countermeasures to mitigate the effects of the exposure.", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate the window of opportunity for decontamination, the fielded skin decontaminant Reactive Skin Decontaminant Lotion (RSDL) was tested at different times in hairless guinea pigs percutaneously challenged with 4 x LD50 VX in IPA.", "output": {"entities": {"chemical": [{"text": "IPA", "start": 232, "end": 235}]}}, "schema": []}
{"input": "The results showed that RSDL decontamination at 15min after exposure could not prevent progressive blood cholinesterase inhibition and therefore would still require additional treatment.", "output": {"entities": {}}, "schema": []}
{"input": "A similar decontamination regimen with RSDL at 90min showed that it still might effectively increase the time window of opportunity for treatment.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the delay in absorption presents a window of opportunity for decontamination and treatment.", "output": {"entities": {}}, "schema": []}
{"input": "The continuous release of VX from the skin presents a significant challenge for efficacious therapy, which should ideally consist of thorough decontamination and continuous treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular analyses of dinosaur osteocytes support the presence of endogenous molecules.", "output": {"entities": {}}, "schema": []}
{"input": "The discovery of soft, transparent microstructures in dinosaur bone consistent in morphology with osteocytes was controversial.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesize that, if original, these microstructures will have molecular features in common with extant osteocytes.", "output": {"entities": {}}, "schema": []}
{"input": "We present immunological and mass spectrometry evidence for preservation of proteins comprising extant osteocytes (Actin, Tubulin, PHEX, Histone H4) in osteocytes recovered from two non-avian dinosaurs.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, antibodies to DNA show localized binding to these microstructures, which also react positively with DNA intercalating stains propidium iodide (PI) and 4', 6'-diamidino-2-phenylindole dihydrochloride (DAPI).", "output": {"entities": {"chemical": [{"text": "propidium iodide", "start": 138, "end": 154}, {"text": "4', 6'-diamidino-2-phenylindole dihydrochloride", "start": 164, "end": 211}, {"text": "DAPI", "start": 213, "end": 217}]}}, "schema": []}
{"input": "Each antibody binds dinosaur cells in patterns similar to extant cells.", "output": {"entities": {}}, "schema": []}
{"input": "These data are the first to support preservation of multiple proteins and to present multiple lines of evidence for material consistent with DNA in dinosaurs, supporting the hypothesis that these structures were part of the once living animals.", "output": {"entities": {}}, "schema": []}
{"input": "We propose mechanisms for preservation of cells and component molecules, and discuss implications for dinosaurian cellular biology.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of amorphization method on telmisartan solubility and the tableting process.", "output": {"entities": {"chemical": [{"text": "telmisartan", "start": 34, "end": 45}]}}, "schema": []}
{"input": "Telmisartan (TLM), a poorly water-soluble angiotensin II receptor antagonist in crystalline form, was transformed into the amorphous state by the melt quench technique, as well as a cryogenic grinding method, in order to improve its physiochemical properties.", "output": {"entities": {"chemical": [{"text": "Telmisartan", "start": 0, "end": 11}, {"text": "TLM", "start": 13, "end": 16}]}}, "schema": []}
{"input": "The chemical stability of TLM, that is, the tendency of the material to resist change or decomposition due to internal reaction, or due to the effects of air, heat, light, pressure, etc., during formation of the amorphous phase was assessed by monitoring high performance liquid chromatography.", "output": {"entities": {"chemical": [{"text": "TLM", "start": 26, "end": 29}]}}, "schema": []}
{"input": "The existence of the amorphous state was confirmed by differential scanning calorimetry and X-ray powder diffraction.", "output": {"entities": {}}, "schema": []}
{"input": "The glass transition occurred at T (g) = 401K.", "output": {"entities": {}}, "schema": []}
{"input": "In the next stage, the solubility of TLM in 0. 1M HCl, phosphate buffer, pH = 6. 8, and water (25 degrees C and 37 degrees C) was determined.", "output": {"entities": {"chemical": [{"text": "TLM", "start": 37, "end": 40}, {"text": "HCl", "start": 50, "end": 53}]}}, "schema": []}
{"input": "Both amorphous forms of TLM (vitrified and cryogrinded) had a higher solubility (mu g/ml) than their crystalline counterpart.", "output": {"entities": {"chemical": [{"text": "TLM", "start": 24, "end": 27}]}}, "schema": []}
{"input": "An important and interesting problem of the study was to evaluate how the tableting process was affected by the choice of either a crystalline or an amorphous form of TLM.", "output": {"entities": {"chemical": [{"text": "TLM", "start": 167, "end": 170}]}}, "schema": []}
{"input": "Eight different tablet formulations were evaluated using both the crystalline and the amorphous form of TLM.", "output": {"entities": {"chemical": [{"text": "TLM", "start": 104, "end": 107}]}}, "schema": []}
{"input": "Measurements of the physical properties and dissolution tests of G4 formulations tablets with telmisartan in crystalline and amorphous form after different storage periods were also performed.", "output": {"entities": {"chemical": [{"text": "telmisartan", "start": 94, "end": 105}]}}, "schema": []}
{"input": "Binding of Gq protein stabilizes the activated state of the muscarinic receptor type 1.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of G protein coupled receptors (GPCRs) induces various cellular responses through interactions with G proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The key trigger of GPCR activation is agonist binding.", "output": {"entities": {}}, "schema": []}
{"input": "It is reportedly known that the agonist-bound active conformation of the GPCRs, such as the muscarinic acetylcholine receptor type 1 (M (1) R), can be affected by the coupling of G proteins and by depolarization of the membrane potential.", "output": {"entities": {}}, "schema": []}
{"input": "Here we aimed at investigating their effects on the structural rearrangements of the M (1) Rs between the active and quiescent states, using the fluorescence resonance energy transfer (FRET) technique.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, fluorescent M (1) R constructs that maintained intact activation of the Gq pathway and interaction with Gq were used.", "output": {"entities": {}}, "schema": []}
{"input": "We captured the agonist-induced conformational changes of the M (1) R as the FRET decreases and found that the FRET decreases were enhanced by co-expression of the Gq subunits.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, co-expression of the Gq subunits decelerated the recovery of the declined FRET upon removal of the agonists, which was slower than the dissociation of the Gq subunits from the receptor.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggested that Gq binding stabilizes the agonist-induced activated conformation of the M (1) R.", "output": {"entities": {}}, "schema": []}
{"input": "We also found that depolarization of the membrane potential slightly but significantly enhanced the agonist-induced FRET decrease, by accelerating the agonist-induced conformational changes.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, structural rearrangement analyses by FRET revealed that Gq coupling stabilizes the active conformation of the M (1) R and also suggested that depolarization accelerates the transition from quiescent to activation conformation.", "output": {"entities": {}}, "schema": []}
{"input": "What is behind the non-antibiotic properties of minocycline?", "output": {"entities": {"chemical": [{"text": "minocycline", "start": 48, "end": 59}]}}, "schema": []}
{"input": "Minocycline is a second-generation, semi-synthetic tetracycline that has been in use in therapy for over 30 years for its antibiotic properties against both Gram-positive and Gram-negative bacteria.", "output": {"entities": {"chemical": [{"text": "Minocycline", "start": 0, "end": 11}, {"text": "tetracycline", "start": 51, "end": 63}]}}, "schema": []}
{"input": "It displays antibiotic activity due to its ability to bind to the 30S ribosomal subunit of bacteria and thus inhibit protein synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "More recently, it has been described to exert a variety of biological actions beyond its antimicrobial activity, including anti-inflammatory and anti-apoptotic activities, inhibition of proteolysis, as well as suppression of angiogenesis and tumor metastasis, which have been confirmed in different experimental models of non-infectious diseases.", "output": {"entities": {}}, "schema": []}
{"input": "There are also many studies that have focused on the mechanisms involved in these non-antibiotic properties of minocycline, including anti-oxidant activity, inhibition of several enzyme activities, inhibition of apoptosis and regulation of immune cell activation and proliferation.", "output": {"entities": {"chemical": [{"text": "minocycline", "start": 111, "end": 122}]}}, "schema": []}
{"input": "This review summarizes the current findings in this topic, mainly focusing on the mechanisms underlying the immunomodulatory and anti-inflammatory activities of minocycline.", "output": {"entities": {"chemical": [{"text": "minocycline", "start": 161, "end": 172}]}}, "schema": []}
{"input": "Target promiscuity and physicochemical properties contribute to pharmacologically induced ER-stress.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo toxicity of drug candidates remains a major problem in the pharmaceutical industry, and is a significant cause of late stage attrition.", "output": {"entities": {}}, "schema": []}
{"input": "As a consequence predictive in vitro assays are developed and put in place early in the discovery pipeline to aid compound selection.", "output": {"entities": {}}, "schema": []}
{"input": "Endoplasmic reticulum stress (ER-stress) has been implicated in many disease states, as well as compound-induced organ toxicities.", "output": {"entities": {}}, "schema": []}
{"input": "We explored the role of ER-stress as a general mechanism of toxicity by utilizing a high-throughput in vitro assay to screen 316 chemically diverse Pfizer proprietary compounds with known in vivo toxicity outcome for nuclear accumulation of spliced x-box binding protein 1 (XBP1s), a key transcription factor of the unfolded protein response (UPR).", "output": {"entities": {}}, "schema": []}
{"input": "We examined the correlation between physicochemical properties, such as molecular weight, pKA, lipophilicity, topological polar surface area, and passive permeability, as well as target promiscuity, between XBP1s hits and non-hits and found that lipophilicity, target promiscuity and low passive permeability significantly contributed to ER-stress.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we have shown that compounds which cause ER-stress in the form of XBP1s activation at concentrations below 40 mu M have a more than four times greater chance of causing in vivo toxicity at 10 mu M plasma exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical cholecystokinin receptor activation protects against obesity-diabetes in high fat fed mice and has sustainable beneficial effects in genetic ob/ob mice.", "output": {"entities": {}}, "schema": []}
{"input": "The current study has determined the ability of (pGlu-Gln)-CCK-8 to counter the development of diet-induced obesity-diabetes and examined persistence of beneficial metabolic effects in high fat and ob/ob mice, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Twice daily injection of (pGlu-Gln)-CCK-8 in normal mice transferred to a high fat diet reduced energy intake (p < 0. 001), body weight (p < 0. 01), circulating insulin and LDL-cholesterol (p < 0. 001) and improved insulin sensitivity (p < 0. 001) as well as oral and intraperitoneal (p < 0. 001) glucose tolerance.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 177, "end": 188}, {"text": "glucose", "start": 297, "end": 304}]}}, "schema": []}
{"input": "Energy intake, body weight, circulating insulin and glucose tolerance of (pGlu-Gln)-CCK-8 mice were similar to lean controls.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 52, "end": 59}]}}, "schema": []}
{"input": "In addition, (pGlu-Gln)-CCK-8 prevented the effect of high fat feeding on triacylglycerol accumulation in liver and muscle.", "output": {"entities": {"chemical": [{"text": "triacylglycerol", "start": 74, "end": 89}]}}, "schema": []}
{"input": "Interestingly, (pGlu-Gln)-CCK-8 significantly (p < 0. 001) elevated pancreatic glucagon content.", "output": {"entities": {}}, "schema": []}
{"input": "Histological examination of the pancreata of (pGlu-Gln)-CCK-8 mice revealed no changes in islet number or size, but there was increased turnover of beta-cells with significantly (p < 0. 001) increased numbers of peripherally located alpha-cells, co-expressing both glucagon and GLP-1.", "output": {"entities": {}}, "schema": []}
{"input": "Beneficial metabolic effects were observed similarly in ob/ob mice treated twice daily with (pGlu-Gln)-CCK-8 for 18 days, including significantly reduced energy intake (p < 0. 05), body weight (p < 0. 05 to p < 0. 01), circulating glucose (p < 0. 05 to p < 0. 01) and insulin (p < 0. 05 to p < 0. 001) and improved glucose tolerance (p < 0. 05) and insulin sensitivity (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 231, "end": 238}, {"text": "glucose", "start": 315, "end": 322}]}}, "schema": []}
{"input": "Notably, these beneficial effects were still evident 18 days following cessation of treatment.", "output": {"entities": {}}, "schema": []}
{"input": "These studies emphasize the potential of (pGlu-Gln)-CCK-8 for the treatment of obesity-diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluating the neurotoxic effects of lactational exposure to persistent organic pollutants (POPs) in Spanish children.", "output": {"entities": {}}, "schema": []}
{"input": "Although the brain continues developing in the postnatal period, epidemiological studies on the effects of postnatal exposure to neurotoxic POPs through breast-feeding remain mostly inconclusive.", "output": {"entities": {}}, "schema": []}
{"input": "Failure to detect associations between postnatal exposure and health outcomes may stem from the limitations of commonly employed approaches to assess lactational exposure.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to assess whether lactational exposure to polychlorinated biphenyl-153 (PCB-153), dichlorodiphenyldichloroethylene (DDE), or hexachlorobenzene (HCB) as estimated with a physiologically based pharmacokinetic (PBPK) model, is associated with decrements in mental and psychomotor development scores of the Bayley Scales of Infant Development (BSID) test in children aged around 14-months of a subsample (N = 1175) of the Spanish INMA birth cohort, and to compare this with the effects of prenatal exposure.", "output": {"entities": {"chemical": [{"text": "polychlorinated biphenyl-153", "start": 75, "end": 103}, {"text": "PCB-153", "start": 105, "end": 112}, {"text": "dichlorodiphenyldichloroethylene", "start": 115, "end": 147}, {"text": "DDE", "start": 149, "end": 152}, {"text": "hexachlorobenzene", "start": 158, "end": 175}, {"text": "HCB", "start": 177, "end": 180}]}}, "schema": []}
{"input": "Although in the present study population PCB-153, DDE and HCB exposure increased within the first months of postnatal life, no associations were found between different periods of postnatal exposure to these compounds and mental or psychomotor scores.", "output": {"entities": {"chemical": [{"text": "PCB-153", "start": 41, "end": 48}, {"text": "DDE", "start": 50, "end": 53}, {"text": "HCB", "start": 58, "end": 61}]}}, "schema": []}
{"input": "Increasing prenatal PCB-153 concentrations were associated with worse mental and psychomotor scores, although significance was only reached for psychomotor development (beta [95% CI] =-1. 36 [-2. 61,-0. 11]).", "output": {"entities": {"chemical": [{"text": "PCB-153", "start": 20, "end": 27}]}}, "schema": []}
{"input": "Indeed, the association between exposure and effects observed during prenatal life weakened gradually across periods of postnatal life.", "output": {"entities": {}}, "schema": []}
{"input": "Results of the present study suggest that, although breastfeeding increases children' s blood persistent organic pollutants (POPs) levels during postnatal life, deleterious effects of PCB-153 on neuropsychological development are mainly attributable to prenatal exposure.", "output": {"entities": {"chemical": [{"text": "PCB-153", "start": 184, "end": 191}]}}, "schema": []}
{"input": "Identifying the correlation between drug/stabilizer properties and critical quality attributes (CQAs) of nanosuspension formulation prepared by wet media milling technology.", "output": {"entities": {}}, "schema": []}
{"input": "Wet media milling by top down method has proved to be an effective method to prepare nanosuspension of poorly soluble drugs/APIs.", "output": {"entities": {}}, "schema": []}
{"input": "Few or no attempts have been made so far to understand the feasibility of nanosuspension formulation in terms of the mechanism of stabilization as a function of drug properties.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to understand the effect of drug substance and stabilizer properties to form a successful nanosuspension product.", "output": {"entities": {}}, "schema": []}
{"input": "From this study, logP and enthalpy were concluded to have a direct correlation on the feasibility of formation of a stable nanosuspension.", "output": {"entities": {}}, "schema": []}
{"input": "The most likely candidate for media milling was a drug substance with a high enthalpy and hydrophobicity which can be stabilized either electrostatically or sterically.", "output": {"entities": {}}, "schema": []}
{"input": "The least likely candidate will be one that is hydrophilic and having a very low enthalpy value.", "output": {"entities": {}}, "schema": []}
{"input": "Also the choice of an ideal stabilizer/surfactant was found to be influenced by the degree of hydrophobicity of the drug itself.", "output": {"entities": {}}, "schema": []}
{"input": "Finally the morphology of the starting drug was found to significantly affect the milling time required to produce submicron particles.", "output": {"entities": {}}, "schema": []}
{"input": "Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the recent attention focused on the roles of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of type 2 diabetes, little is known about the ex vivo profile of inflammasome activation in type 2 diabetic patients.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 57, "end": 67}]}}, "schema": []}
{"input": "In this study, we investigated patterns of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) from drug-na i ve patients with newly diagnosed type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Type 2 diabetic subjects had significantly increased mRNA and protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and proinflammatory cytokines in MDMs cultured with autologous sera compared with healthy controls.", "output": {"entities": {}}, "schema": []}
{"input": "Upregulated interleukin (IL)-1 beta maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals).", "output": {"entities": {"chemical": [{"text": "ATP", "start": 189, "end": 192}, {"text": "fatty acids", "start": 231, "end": 242}, {"text": "monosodium uric acid", "start": 275, "end": 295}]}}, "schema": []}
{"input": "Mitochondrial reactive oxygen species and NLRP3 were required for IL-1 beta synthesis in MDMs.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 23, "end": 29}]}}, "schema": []}
{"input": "Finally, 2 months of therapy with the antidiabetic drug metformin significantly inhibited the maturation of IL-1 beta in MDMs from patients with type 2 diabetes through AMP-activated protein kinase (AMPK) activation.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 56, "end": 65}, {"text": "AMP", "start": 169, "end": 172}]}}, "schema": []}
{"input": "Taken together, these data suggest that NLRP3 inflammasome activation is elevated in myeloid cells from type 2 diabetic patients and that antidiabetic treatment with metformin contributes to modulation of inflammasome activation in type 2 diabetes.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 166, "end": 175}]}}, "schema": []}
{"input": "Stress-dependent and gender-specific neuroregulatory roles of the apelin receptor in the hypothalamic-pituitary-adrenal axis response to acute stress.", "output": {"entities": {}}, "schema": []}
{"input": "The neuropeptide apelin is expressed in hypothalamic paraventricular and supraoptic nuclei and mediates its effects via activation of the apelin receptor (APJ).", "output": {"entities": {}}, "schema": []}
{"input": "Evidence suggests a role for apelin and APJ in mediating the neuroendocrine response to stress.", "output": {"entities": {}}, "schema": []}
{"input": "To understand the physiological role of APJ in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, we measured ACTH and corticosterone (CORT) plasma levels in male and female mice lacking APJ (APJ knockout, APJ KO) and in wild-type controls, in response to a variety of acute stressors.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 129, "end": 143}, {"text": "CORT", "start": 145, "end": 149}]}}, "schema": []}
{"input": "Exposure to mild restraint, systemic injection of lipopolysaccharide (LPS), insulin-induced hypoglycaemia and forced swim (FS) stressors, elevated plasma ACTH and CORT levels in wild-type mice.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 163, "end": 167}]}}, "schema": []}
{"input": "Acute mild restraint significantly increased plasma ACTH and CORT to a similar level in APJ KO mice as in wild-type mice.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 61, "end": 65}]}}, "schema": []}
{"input": "However, an intact APJ was required for a conventional ACTH, but not CORT, response to LPS administration in male mice and to insulin-induced hypoglycaemia in male and female mice.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 69, "end": 73}]}}, "schema": []}
{"input": "In contrast, APJ KO mice displayed an impaired CORT response to acute FS stress, regardless of gender.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 47, "end": 51}]}}, "schema": []}
{"input": "These data indicate that APJ has a role in regulation of the HPA axis response to some acute stressors and has a gender-specific function in peripheral immune activation of the HPA axis.", "output": {"entities": {}}, "schema": []}
{"input": "Assessing bioavailability and toxicity of permethrin and DDT in sediment using matrix solid phase microextraction.", "output": {"entities": {"chemical": [{"text": "permethrin", "start": 42, "end": 52}, {"text": "DDT", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Matrix solid phase microextraction (matrix-SPME) was evaluated as a surrogate for the absorbed dose in organisms to estimate bioavailability and toxicity of permethrin and dichlorodiphenyltrichloroethane (DDT) in laboratory-spiked sediment.", "output": {"entities": {"chemical": [{"text": "permethrin", "start": 157, "end": 167}, {"text": "dichlorodiphenyltrichloroethane", "start": 172, "end": 203}, {"text": "DDT", "start": 205, "end": 208}]}}, "schema": []}
{"input": "Sediments were incubated for 7, 28, and 90 days at room temperature to characterize the effect of aging on bioavailability and toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Sediment toxicity was assessed using two freshwater invertebrates, the midge Chironomus dilutus and amphipod Hyalella azteca.", "output": {"entities": {}}, "schema": []}
{"input": "Disposable polydimethylsiloxane fibers were used to estimate the absorbed dose in organisms and to examine bioavailability and toxicity.", "output": {"entities": {"chemical": [{"text": "polydimethylsiloxane", "start": 11, "end": 31}]}}, "schema": []}
{"input": "The equilibrium fiber concentrations substantially decreased with an increase in sediment aging time, indicating a reduction in bioavailability.", "output": {"entities": {}}, "schema": []}
{"input": "Based on median lethal fiber concentrations (fiber LC50), toxicity of permethrin was not significantly different among the different aging times.", "output": {"entities": {"chemical": [{"text": "permethrin", "start": 70, "end": 80}]}}, "schema": []}
{"input": "Due to the substantial degradation of DDT to dichlorodiphenyldichloroethane (DDD) in sediment, sediment toxicity to C. dilutus increased, while it decreased for H. azteca with extended aging times.", "output": {"entities": {"chemical": [{"text": "DDT", "start": 38, "end": 41}, {"text": "dichlorodiphenyldichloroethane", "start": 45, "end": 75}, {"text": "DDD", "start": 77, "end": 80}]}}, "schema": []}
{"input": "A toxic unit-based fiber LC50 value represented the DDT mixture (DDT and DDD) toxicity for both species.", "output": {"entities": {"chemical": [{"text": "DDT", "start": 52, "end": 55}, {"text": "DDT", "start": 65, "end": 68}, {"text": "DDD", "start": 73, "end": 76}]}}, "schema": []}
{"input": "Significant linear relationships were found between organism body residues and the equilibrium fiber concentrations for each compound, across aging times.", "output": {"entities": {}}, "schema": []}
{"input": "The study suggested that the matrix-SPME fibers mimicked bioaccumulation in the organisms, and enabled estimation of body residues, and could potentially be used in environmental risk assessment across matrices (e. g. sediment and water) to measure bioavailability and toxicity of hydrophobic pesticides.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of DMSA-coated Fe3O4 nanoparticles on the transcription of genes related to iron and osmosis homeostasis.", "output": {"entities": {"chemical": [{"text": "DMSA", "start": 11, "end": 15}, {"text": "Fe3O4", "start": 23, "end": 28}, {"text": "iron", "start": 84, "end": 88}]}}, "schema": []}
{"input": "In this article, we checked the effect of 2, 3-dimercaptosuccinic acid-coated Fe (3) O (4) nanoparticles on gene expression of mouse macrophage RAW264. 7 cells and found that the transcription of several important genes related to intracellular iron homeostasis were significantly changed.", "output": {"entities": {"chemical": [{"text": "2, 3-dimercaptosuccinic acid", "start": 42, "end": 70}, {"text": "Fe (3) O (4)", "start": 78, "end": 90}, {"text": "iron", "start": 245, "end": 249}]}}, "schema": []}
{"input": "We thus speculated that the cellular iron homeostasis might be disturbed by this nanoparticle through releasing iron ion in cells.", "output": {"entities": {"chemical": [{"text": "iron", "start": 37, "end": 41}, {"text": "iron", "start": 112, "end": 116}]}}, "schema": []}
{"input": "To verify this speculation, we first confirmed the transcriptional changes of several key iron homeostasis-related genes, such as Tfrc, Trf, and Lcn2, using quantitative PCR, and found that an iron ion chelator, desferrioxamine, could alleviate the transcriptional alterations of two typical genes, Tfrc and Lcn2.", "output": {"entities": {"chemical": [{"text": "iron", "start": 90, "end": 94}, {"text": "iron", "start": 193, "end": 197}, {"text": "desferrioxamine", "start": 212, "end": 227}]}}, "schema": []}
{"input": "Then, we designed and validated a method based on centrifugation for assaying intracellular irons in ion and nanoparticle state.", "output": {"entities": {"chemical": [{"text": "irons", "start": 92, "end": 97}]}}, "schema": []}
{"input": "After extensive measures of intracellular iron in two forms and total iron, we found that the intracellular iron ion significantly increased with intracellular total iron and nanoparticle iron, demonstrating degradation of this nanoparticle into iron ion in cells.", "output": {"entities": {"chemical": [{"text": "iron", "start": 42, "end": 46}, {"text": "iron", "start": 70, "end": 74}, {"text": "iron", "start": 108, "end": 112}, {"text": "iron", "start": 166, "end": 170}, {"text": "iron", "start": 188, "end": 192}, {"text": "iron", "start": 246, "end": 250}]}}, "schema": []}
{"input": "We next mimicked the intralysosomal environment in vitro and verified that the internalized iron nanoparticle could release iron ion in lysosome.", "output": {"entities": {}}, "schema": []}
{"input": "We found that as another important compensatory response to intracellular overload of iron ion, cells significantly downregulated the expressions of genes belonging to solute carrier family which are responsible for transferring many organic solutes into cells, such as Slc5a3 and Slc44a1, in order to prevent more organic solutes into cells and thus lower the intracellular osmosis.", "output": {"entities": {"chemical": [{"text": "iron", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Based on these findings, we profiled a map of gene effects after cells were treated with this iron nanoparticle and concluded that the iron nanoparticles might be more detrimental to cell than iron ion due to its intracellular internalization fashion, nonspecific endocytosis.", "output": {"entities": {"chemical": [{"text": "iron", "start": 94, "end": 98}, {"text": "iron", "start": 135, "end": 139}, {"text": "iron", "start": 193, "end": 197}]}}, "schema": []}
{"input": "Developmental consequences of the ColQ/MuSK interactions.", "output": {"entities": {}}, "schema": []}
{"input": "CollagenQ (ColQ) is a specific collagen that anchors acetylcholinesterase (AChE) in the synaptic basal lamina of the neuromuscular junction (NMJ).", "output": {"entities": {}}, "schema": []}
{"input": "Over 30 mutations in the COLQ gene have been identified that are responsible for a congenital myasthenic syndrome with AChE deficiency, highlighting the importance of this collagen in the physiology of the NMJ.", "output": {"entities": {}}, "schema": []}
{"input": "The anchoring of AChE at the synapse requires the interaction of ColQ with MuSK (Muscle-Specific Kinase), a tyrosine kinase expressed on the muscle membrane that is necessary for the formation and the maintenance of the NMJ.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 108, "end": 116}]}}, "schema": []}
{"input": "MuSK forms with its co-receptor LRP4, a member of the Low-density Related Protein family, a receptor complex for agrin and Wnts, representing the core system from which the postsynaptic domain is built, the growth cone attracted and the presynaptic element instructed for some aspects of its differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the discovery that ColQ binds to MuSK prompted us to study a possible regulatory function of ColQ during NMJ development.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, after a brief survey on ColQ, we summarize our recent data demonstrating that ColQ, in addition to its anchoring role, exerts signaling functions and controls some aspects of postsynaptic differentiation such as the clustering of acetylcholine receptors.", "output": {"entities": {}}, "schema": []}
{"input": "Our results also strengthen the hypothesis that the defects observed in synaptic congenital myasthenic syndromes might be linked, at least in part, to alterations of ColQ signaling functions and not only to AChE deficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we discuss future research directions to understand how ColQ may modulate the action of the other ligands of the MuSK/LRP4 complex and cooperate with them to coordinate the different steps of NMJ formation and maintenance.", "output": {"entities": {}}, "schema": []}
{"input": "Redox control of teratogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "A number of human teratogens elicit their deleterious effects through mechanisms involving the generation of reactive oxygen species (ROS) and oxidative stress.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 118, "end": 124}]}}, "schema": []}
{"input": "However, classic definitions of oxidative stress do not fully coincide with basic fundamental principles of teratology.", "output": {"entities": {}}, "schema": []}
{"input": "Newer definitions of oxidative stress focus on the targeted redox modification of cysteine/thiol functional groups found in the regulatory domains of critical signaling pathway proteins, suggesting that the targeted disruption of signaling through specific redox couples may account for the specificity of teratogen-induced malformations which previously could not be rationalized.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 82, "end": 90}, {"text": "thiol", "start": 91, "end": 96}]}}, "schema": []}
{"input": "Here, we review examples of teratogens that induce ROS and oxidative injury, describe oxidative stress-related teratogenic mechanisms, and provide rationale for developmental periods of sensitivity and species susceptibility.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding how chemicals disrupt redox status, induce oxidative stress leading to dysmorphogenesis becomes important to identify potential teratogens and develop therapeutic interventions for attenuation of harmful chemical effects in utero following exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Cholesterol ester droplets and steroidogenesis.", "output": {"entities": {"chemical": [{"text": "Cholesterol ester", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Intracellular lipid droplets (LDs) are dynamic organelles that contain a number of associated proteins including perilipin (Plin) and vimentin.", "output": {"entities": {}}, "schema": []}
{"input": "Cholesteryl ester (CE)-rich LDs normally accumulate in steroidogenic cells and their mobilization is the preferred initial source of cholesterol for steroidogenesis.", "output": {"entities": {"chemical": [{"text": "Cholesteryl ester", "start": 0, "end": 17}, {"text": "cholesterol", "start": 133, "end": 144}]}}, "schema": []}
{"input": "Plin1a, 1b and 5 were found to preferentially associate with triacylglycerol-rich LDs and Plin1c and Plin4 to associate with CE-rich LDs, but the biological significance of this remains unanswered.", "output": {"entities": {"chemical": [{"text": "triacylglycerol", "start": 61, "end": 76}]}}, "schema": []}
{"input": "Vimentin null mice were found to have decreased ACTH-stimulated corticosterone levels, and decreased progesterone levels in females, but normal hCG-stimulated testosterone levels in males.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 64, "end": 78}, {"text": "progesterone", "start": 101, "end": 113}, {"text": "testosterone", "start": 159, "end": 171}]}}, "schema": []}
{"input": "Smaller LDs were seen in null cells.", "output": {"entities": {}}, "schema": []}
{"input": "Lipoprotein cholesterol delivery to adrenals and ovary was normal, as was the expression of steroidogenic genes; however, the movement of cholesterol to mitochondria was reduced in vimentin null mice.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 12, "end": 23}, {"text": "cholesterol", "start": 138, "end": 149}]}}, "schema": []}
{"input": "These results suggest that vimentin is important in the maintenance of CE-rich LDs and in the movement of cholesterol for steroidogenesis.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 106, "end": 117}]}}, "schema": []}
{"input": "The interactive effects of selenomethionine and methylmercury on their absorption, disposition, and elimination in juvenile white sturgeon.", "output": {"entities": {"chemical": [{"text": "selenomethionine", "start": 27, "end": 43}, {"text": "methylmercury", "start": 48, "end": 61}]}}, "schema": []}
{"input": "Selenium (Se) and mercury (Hg) are prevalent pollutants of industrialized watersheds.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 0, "end": 8}, {"text": "Se", "start": 10, "end": 12}, {"text": "mercury", "start": 18, "end": 25}, {"text": "Hg", "start": 27, "end": 29}]}}, "schema": []}
{"input": "However, when co-administered, Se has protective effects on organisms from Hg.", "output": {"entities": {"chemical": [{"text": "Se", "start": 31, "end": 33}, {"text": "Hg", "start": 75, "end": 77}]}}, "schema": []}
{"input": "The mechanism is not fully understood, but it is thought that Se reduces Hg availability, either by forming biologically inert complexes and/or associating with selenoproteins.", "output": {"entities": {"chemical": [{"text": "Se", "start": 62, "end": 64}, {"text": "Hg", "start": 73, "end": 75}]}}, "schema": []}
{"input": "Despite concerns with aquatic contaminations, relatively little information is available on the interaction in aquatic organisms.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, the interactive effects of Se and Hg on their absorption, disposition, and elimination were examined in juvenile white sturgeon, a benthic fish species at high risk to exposures of both contaminants.", "output": {"entities": {"chemical": [{"text": "Se", "start": 49, "end": 51}, {"text": "Hg", "start": 56, "end": 58}]}}, "schema": []}
{"input": "Selenium and Hg were provided as L-selenomethionine (SeMet) and methylmercury (MeHg), respectively.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 0, "end": 8}, {"text": "Hg", "start": 13, "end": 15}, {"text": "L-selenomethionine", "start": 33, "end": 51}, {"text": "SeMet", "start": 53, "end": 58}, {"text": "methylmercury", "start": 64, "end": 77}, {"text": "MeHg", "start": 79, "end": 83}]}}, "schema": []}
{"input": "Groups of 10 sturgeon were orally intubated with a single dose of either 0 (control), SeMet (500 mu g Se/kg body weight; BW), MeHg (850 mu g Hg/kg BW), or their combination (Se/Hg; 500 mu g Se/kg and 850 mu g Hg/kg BW).", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 86, "end": 91}, {"text": "Se", "start": 102, "end": 104}, {"text": "MeHg", "start": 126, "end": 130}, {"text": "Hg", "start": 141, "end": 143}, {"text": "Se", "start": 174, "end": 176}, {"text": "Hg", "start": 177, "end": 179}, {"text": "Se", "start": 190, "end": 192}]}}, "schema": []}
{"input": "The blood was repeatedly sampled and urine collected from the fish, over a 48 h post intubation period.", "output": {"entities": {}}, "schema": []}
{"input": "At 48 h, the fish were sacrificed for Se and Hg tissue concentration and distribution.", "output": {"entities": {"chemical": [{"text": "Se", "start": 38, "end": 40}, {"text": "Hg", "start": 45, "end": 47}]}}, "schema": []}
{"input": "The co-administration of SeMet and MeHg significantly (p < 0. 05) lowered blood concentrations of both Se and Hg and tissue Se concentrations.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 25, "end": 30}, {"text": "MeHg", "start": 35, "end": 39}, {"text": "Se", "start": 103, "end": 105}, {"text": "Hg", "start": 110, "end": 112}, {"text": "Se", "start": 124, "end": 126}]}}, "schema": []}
{"input": "Similarly, assimilation of Se and Hg was also reduced significantly.", "output": {"entities": {"chemical": [{"text": "Se", "start": 27, "end": 29}, {"text": "Hg", "start": 34, "end": 36}]}}, "schema": []}
{"input": "The interaction has a more quantitative effect on Se metabolism because the reduction in the overall tissue Se is a consequence of reduced Se absorption at the gut and not from the metabolic effects after absorption.", "output": {"entities": {"chemical": [{"text": "Se", "start": 50, "end": 52}, {"text": "Se", "start": 108, "end": 110}, {"text": "Se", "start": 139, "end": 141}]}}, "schema": []}
{"input": "In contrast, given the pulse increase in blood Hg concentration, tissue redistribution, and increased urinary elimination, the interactive effect on tissue Hg concentration is likely to be post-absorption.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 47, "end": 49}, {"text": "Hg", "start": 156, "end": 158}]}}, "schema": []}
{"input": "Even in the absence of exogenous SeMet, Se and Hg co-accumulated in tissue at a Se: Hg molar ratio greater than 1.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 33, "end": 38}, {"text": "Se", "start": 40, "end": 42}, {"text": "Hg", "start": 47, "end": 49}, {"text": "Se", "start": 80, "end": 82}, {"text": "Hg", "start": 84, "end": 86}]}}, "schema": []}
{"input": "Thus, similar to mammals, maintaining at least a 1: 1 molar ratio of Se and Hg is of great physiological importance in the white sturgeon.", "output": {"entities": {"chemical": [{"text": "Se", "start": 69, "end": 71}, {"text": "Hg", "start": 76, "end": 78}]}}, "schema": []}
{"input": "Interestingly, SeMet did not divert Hg from the brain.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 15, "end": 20}, {"text": "Hg", "start": 36, "end": 38}]}}, "schema": []}
{"input": "Allocation of Se from the kidneys may have occurred in order to maintain the high Se: Hg molar ratios in the brain of white sturgeon.", "output": {"entities": {"chemical": [{"text": "Se", "start": 14, "end": 16}, {"text": "Se", "start": 82, "end": 84}, {"text": "Hg", "start": 86, "end": 88}]}}, "schema": []}
{"input": "In the current study, the combined use of kinetic analysis and that of the conventional approach of measuring tissue concentration changes provided a comprehensive understanding of the interactive effect of SeMet and MeHg on their respective metabolic processes in juvenile white sturgeon.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 207, "end": 212}, {"text": "MeHg", "start": 217, "end": 221}]}}, "schema": []}
{"input": "Enhanced charge carrier mobility in two-dimensional high dielectric molybdenum oxide.", "output": {"entities": {"chemical": [{"text": "molybdenum oxide", "start": 68, "end": 84}]}}, "schema": []}
{"input": "We demonstrate that the energy bandgap of layered, high-dielectric alpha-MoO (3) can be reduced to values viable for the fabrication of 2D electronic devices.", "output": {"entities": {"chemical": [{"text": "alpha-MoO (3)", "start": 67, "end": 80}]}}, "schema": []}
{"input": "This is achieved through embedding Coulomb charges within the high dielectric media, advantageously limiting charge scattering.", "output": {"entities": {}}, "schema": []}
{"input": "As a result, devices with alpha-MoO (3) of ~ 11 nm thickness and carrier mobilities larger than 1100 cm (2) V (-1) s (-1) are obtained.", "output": {"entities": {"chemical": [{"text": "alpha-MoO (3)", "start": 26, "end": 39}]}}, "schema": []}
{"input": "Adsorption of multimeric T cell antigens on carbon nanotubes: effect on protein structure and antigen-specific T cell stimulation.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 44, "end": 50}]}}, "schema": []}
{"input": "Antigen-specific activation of cytotoxic T cells can be enhanced up to three-fold more than soluble controls when using functionalized bundled carbon nanotube substrates ((b) CNTs).", "output": {"entities": {"chemical": [{"text": "carbon", "start": 143, "end": 149}]}}, "schema": []}
{"input": "To overcome the denaturing effects of direct adsorption on (b) CNTs, a simple but robust method is demonstrated to stabilize the T cell stimulus on carbon nanotube substrates through non-covalent attachment of the linker neutravidin.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 148, "end": 154}]}}, "schema": []}
{"input": "Multiple NSAID-induced hits injure the small intestine: underlying mechanisms and novel strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) injury including jejunal/ileal mucosal ulceration, bleeding, and even perforation in susceptible patients.", "output": {"entities": {}}, "schema": []}
{"input": "The underlying mechanisms are largely unknown, but they are distinct from those related to gastric injury.", "output": {"entities": {}}, "schema": []}
{"input": "Based on recent insights from experimental models, including genetics and pharmacology in rodents typically exposed to diclofenac, indomethacin, or naproxen, we propose a multiple-hit pathogenesis of NSAID enteropathy.", "output": {"entities": {"chemical": [{"text": "diclofenac", "start": 119, "end": 129}, {"text": "indomethacin", "start": 131, "end": 143}, {"text": "naproxen", "start": 148, "end": 156}]}}, "schema": []}
{"input": "The multiple hits start with an initial pharmacokinetic determinant caused by vectorial hepatobiliary excretion and delivery of glucuronidated NSAID or oxidative metabolite conjugates to the distal small intestinal lumen, where bacterial beta-glucuronidase produces critical aglycones.", "output": {"entities": {}}, "schema": []}
{"input": "The released aglycones are then taken up by enterocytes and further metabolized by intestinal cytochrome P450s to potentially reactive intermediates.", "output": {"entities": {}}, "schema": []}
{"input": "The \" first hit \" is caused by the NSAID and/or oxidative metabolites that induce severe endoplasmic reticulum stress or mitochondrial stress and lead to cell death.", "output": {"entities": {}}, "schema": []}
{"input": "The \" second hit \" is created by the significant subsequent inflammatory response that would follow such a first-hit injury.", "output": {"entities": {}}, "schema": []}
{"input": "Based on these putative mechanisms, strategies have been developed to protect the enterocytes from being exposed to the parent NSAID and/or oxidative metabolites.", "output": {"entities": {}}, "schema": []}
{"input": "Among these, a novel strategy already demonstrated in a murine model is the selective disruption of bacteria-specific beta-glucuronidases with a novel small molecule inhibitor that does not harm the bacteria and that alleviates NSAID-induced enteropathy.", "output": {"entities": {}}, "schema": []}
{"input": "Such mechanism-based strategies require further investigation but provide potential avenues for the alleviation of the GI toxicity caused by multiple NSAID hits.", "output": {"entities": {}}, "schema": []}
{"input": "Combination lopinavir and ritonavir alter exogenous and endogenous bile acid disposition in sandwich-cultured rat hepatocytes.", "output": {"entities": {"chemical": [{"text": "lopinavir", "start": 12, "end": 21}, {"text": "ritonavir", "start": 26, "end": 35}, {"text": "bile acid", "start": 67, "end": 76}]}}, "schema": []}
{"input": "Inhibition of the bile salt export pump (BSEP) can cause intracellular accumulation of bile acids and is a risk factor for drug-induced liver injury in humans.", "output": {"entities": {"chemical": [{"text": "bile salt", "start": 18, "end": 27}, {"text": "bile acids", "start": 87, "end": 97}]}}, "schema": []}
{"input": "Antiretroviral protease inhibitors lopinavir (LPV) and ritonavir (RTV) are reported BSEP inhibitors.", "output": {"entities": {"chemical": [{"text": "lopinavir", "start": 35, "end": 44}, {"text": "LPV", "start": 46, "end": 49}, {"text": "ritonavir", "start": 55, "end": 64}, {"text": "RTV", "start": 66, "end": 69}]}}, "schema": []}
{"input": "However, the consequences of LPV and RTV, alone and combined (LPV/r), on hepatocyte viability, bile acid transport, and endogenous bile acid disposition in rat hepatocytes have not been examined.", "output": {"entities": {"chemical": [{"text": "LPV", "start": 29, "end": 32}, {"text": "RTV", "start": 37, "end": 40}, {"text": "LPV", "start": 62, "end": 65}, {"text": "bile acid", "start": 95, "end": 104}, {"text": "bile acid", "start": 131, "end": 140}]}}, "schema": []}
{"input": "The effect of LPV, RTV, and LPV/r on cellular viability and the disposition of [(3) H] taurocholic acid (TCA) and [(14) C] chenodeoxycholic acid (CDCA) was determined in sandwich-cultured rat hepatocytes (SCRH) and suspended rat hepatocytes.", "output": {"entities": {"chemical": [{"text": "LPV", "start": 14, "end": 17}, {"text": "RTV", "start": 19, "end": 22}, {"text": "LPV", "start": 28, "end": 31}, {"text": "[(3) H] taurocholic acid", "start": 79, "end": 103}, {"text": "TCA", "start": 105, "end": 108}, {"text": "[(14) C] chenodeoxycholic acid", "start": 114, "end": 144}, {"text": "CDCA", "start": 146, "end": 150}]}}, "schema": []}
{"input": "Lactate dehydrogenase and ATP assays revealed a concentration-dependent effect of LPV and RTV on cellular viability.", "output": {"entities": {"chemical": [{"text": "Lactate", "start": 0, "end": 7}, {"text": "ATP", "start": 26, "end": 29}, {"text": "LPV", "start": 82, "end": 85}, {"text": "RTV", "start": 90, "end": 93}]}}, "schema": []}
{"input": "LPV (5 micro M), alone and combined with 5 micro M RTV, significantly decreased [(3) H] TCA accumulation in cells + bile of SCRHs compared with control.", "output": {"entities": {"chemical": [{"text": "LPV", "start": 0, "end": 3}, {"text": "RTV", "start": 51, "end": 54}, {"text": "[(3) H] TCA", "start": 80, "end": 91}]}}, "schema": []}
{"input": "LPV/r significantly increased [(3) H] TCA cellular accumulation (7. 7 +/- 0. 1 pmol/mg of protein) compared with vehicle and 5 micro M LPV alone (5. 1 +/- 0. 7 and 5. 0 +/- 0. 5 pmol/mg of protein).", "output": {"entities": {"chemical": [{"text": "LPV", "start": 0, "end": 3}, {"text": "[(3) H] TCA", "start": 30, "end": 41}, {"text": "LPV", "start": 135, "end": 138}]}}, "schema": []}
{"input": "The [(3) H] TCA biliary clearance was reduced significantly by LPV and RTV and further reduced by LPV/r.", "output": {"entities": {"chemical": [{"text": "[(3) H] TCA", "start": 4, "end": 15}, {"text": "LPV", "start": 63, "end": 66}, {"text": "RTV", "start": 71, "end": 74}, {"text": "LPV", "start": 98, "end": 101}]}}, "schema": []}
{"input": "LPV and RTV did not affect the initial uptake rates of [(3) H] TCA or [(14) C] CDCA in suspended rat hepatocytes.", "output": {"entities": {"chemical": [{"text": "LPV", "start": 0, "end": 3}, {"text": "RTV", "start": 8, "end": 11}, {"text": "[(3) H] TCA", "start": 55, "end": 66}, {"text": "[(14) C] CDCA", "start": 70, "end": 83}]}}, "schema": []}
{"input": "LPV (50 micro M), RTV (5 micro M), and LPV/r (5 and 50 micro M/5 micro M) significantly decreased the accumulation of total measured endogenous bile acids (TCA, glycocholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, and alpha/beta-tauromuricholic acid) in SCRH.", "output": {"entities": {"chemical": [{"text": "LPV", "start": 0, "end": 3}, {"text": "RTV", "start": 18, "end": 21}, {"text": "LPV", "start": 39, "end": 42}, {"text": "bile acids", "start": 144, "end": 154}, {"text": "TCA", "start": 156, "end": 159}, {"text": "glycocholic acid", "start": 161, "end": 177}, {"text": "taurochenodeoxycholic acid", "start": 179, "end": 205}, {"text": "glycochenodeoxycholic acid", "start": 207, "end": 233}, {"text": "alpha/beta-tauromuricholic acid", "start": 239, "end": 270}]}}, "schema": []}
{"input": "Quantification of endogenous bile acids in SCRH may reveal important adaptive responses associated with exposure to known BSEP inhibitors.", "output": {"entities": {"chemical": [{"text": "bile acids", "start": 29, "end": 39}]}}, "schema": []}
{"input": "Bimodal surface ligand engineering: the key to tunable nanocomposites.", "output": {"entities": {}}, "schema": []}
{"input": "Tuning the dispersion of inorganic nanoparticles within organic matrices is critical to optimizing polymer nanocomposite properties and is intrinsically difficult due to their strong enthalpic incompatibility.", "output": {"entities": {}}, "schema": []}
{"input": "Conventional attempts to use polymer brushes to control nanoparticle dispersion are challenged by the need for high graft density to reduce particle core-core attractions and the need for low graft density to reduce the entropic penalty for matrix penetration into the brush.", "output": {"entities": {}}, "schema": []}
{"input": "We validated a parametric phase diagram previously reported by Pryamtisyn et al.", "output": {"entities": {}}, "schema": []}
{"input": "(Pryamtisyn, V.; Ganesan, V.; Panagiotopoulos, A. Z.; Liu, H.; Kumar, S. K. Modeling the Anisotropic Self-Assembly of Spherical Polymer-Grafted Nanoparticles. J. Chem. Phys. 2009, 131, 221102) for predicting dispersion of monomodal-polymer-brush-modified nanoparticles in polymer matrices.", "output": {"entities": {}}, "schema": []}
{"input": "The theoretical calculation successfully predicted the experimental observation that the monomodal-poly (dimethyl siloxane) (PDMS)-brush-grafted TiO (2) nanoparticles can only be well dispersed within a small molecular weight silicone matrix.", "output": {"entities": {"chemical": [{"text": "poly (dimethyl siloxane)", "start": 99, "end": 123}, {"text": "PDMS", "start": 125, "end": 129}, {"text": "TiO (2)", "start": 145, "end": 152}, {"text": "silicone", "start": 226, "end": 234}]}}, "schema": []}
{"input": "We further extended the parametric phase diagram to analyze the dispersion behavior of bimodal-PDMS-brush-grafted particles, which is also in good agreement with experimental results.", "output": {"entities": {"chemical": [{"text": "PDMS", "start": 95, "end": 99}]}}, "schema": []}
{"input": "Utilizing a bimodal grafted polymer brush design, with densely grafted short brushes to shield particle surfaces and sparsely grafted long brushes that favor the entanglement with matrix chains, we dispersed TiO (2) nanoparticles in high molecular weight commercial silicone matrices and successfully prepared thick (about 5 mm) transparent high-refractive-index TiO (2)/silicone nanocomposites.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 208, "end": 215}, {"text": "silicone", "start": 266, "end": 274}, {"text": "TiO (2)", "start": 363, "end": 370}, {"text": "silicone", "start": 371, "end": 379}]}}, "schema": []}
{"input": "On the pH-Responsive, Charge-Selective, Polymer-Brush-Mediated Transport Probed by Traditional and Scanning Fluorescence Correlation Spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "The complete and reversible charge-selective sequestration of fluorophores by a weak polyelectrolyte brush, poly (2-(dimethylamino) ethylmethacrylate) (PDMAEMA) was demonstrated using fluorescence correlation spectroscopy (FCS).", "output": {"entities": {"chemical": [{"text": "poly (2-(dimethylamino) ethylmethacrylate)", "start": 108, "end": 150}, {"text": "PDMAEMA", "start": 152, "end": 159}]}}, "schema": []}
{"input": "The chemistry and thickness of the weak polyelectrolyte PDMAEMA was tuned reversibly between neutral and cationic polymer forms.", "output": {"entities": {"chemical": [{"text": "PDMAEMA", "start": 56, "end": 63}]}}, "schema": []}
{"input": "Thus, by switching the pH successively, the brush architecture was tuned to selectively trap and release anionic dye probes while continuously excluding cationic molecules.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, line-scan FCS was implemented and applied for the first time to a synthetic polymer system and used to identify a new, slower diffusion time on the order of seconds for the sequestered anionic probe under acidic conditions.", "output": {"entities": {}}, "schema": []}
{"input": "These results, which quantify the selective sequestration properties of the PDMAEMA brush, are important because they enable a better understanding of transport in polymers and establish a spectroscopic means of evaluating materials with proposed applications in separations science, charge storage/release, and environmental remediation.", "output": {"entities": {"chemical": [{"text": "PDMAEMA", "start": 76, "end": 83}]}}, "schema": []}
{"input": "An exploration of species boundaries in turret-building tarantulas of the Mojave Desert (Araneae, Mygalomorphae, Theraphosidae, Aphonopelma).", "output": {"entities": {}}, "schema": []}
{"input": "Tarantulas in the North American genus Aphonopelma are poorly known due to their challenging patterns of morphological variation and questionable taxonomy; few specimens can be confidently identified using existing keys or comparisons to original descriptions.", "output": {"entities": {}}, "schema": []}
{"input": "In an effort to identify new strategies for resolving what has been characterized as a \" taxonomic and nomenclatural nightmare \", we employed five different approaches for delimiting species in a group of closely related tarantulas from the Mojave Desert in the southwestern United States.", "output": {"entities": {}}, "schema": []}
{"input": "These methods included the application of single techniques (morphology, DNA barcoding, shared genealogical exclusivity among independent loci, and generalized mixed Yule coalescent) and an integrative approach that incorporates genealogical and ecological information.", "output": {"entities": {}}, "schema": []}
{"input": "Results demonstrate that the taxonomy of these spiders as presently defined underestimates actual species-level diversity and the group is in need of revision.", "output": {"entities": {}}, "schema": []}
{"input": "The number of species delimited by each approach, however, was variable and we argue that it is this discordance that emphasizes the importance of incorporating multiple lines of evidence into an integrative taxonomic framework that can be used for constructing robust taxonomic hypotheses for Aphonopelma species.", "output": {"entities": {}}, "schema": []}
{"input": "mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Regulated associated protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (rictor) are two proteins that delineate two different mTOR complexes, mTORC1 and mTORC2 respectively.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 50, "end": 59}]}}, "schema": []}
{"input": "Recent studies demonstrated the role of rictor in the development and function of beta-cells.", "output": {"entities": {}}, "schema": []}
{"input": "mTORC1 has long been known to impact beta-cell function and development.", "output": {"entities": {}}, "schema": []}
{"input": "However, most of the studies evaluating its role used either drug treatment (i. e. rapamycin) or modification of expression of proteins known to modulate its activity, and the direct role of raptor in insulin secretion is unclear.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 83, "end": 92}]}}, "schema": []}
{"input": "In this study, using siRNA, we investigated the role of raptor and rictor in insulin secretion and production in INS-1 cells and the possible cross talk between their respective complexes, mTORC1 and mTORC2.", "output": {"entities": {}}, "schema": []}
{"input": "Reduced expression of raptor is associated with increased glucose-stimulated insulin secretion and intracellular insulin content.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 58, "end": 65}]}}, "schema": []}
{"input": "Downregulation of rictor expression leads to impaired insulin secretion without affecting insulin content and is able to correct the increased insulin secretion mediated by raptor siRNA.", "output": {"entities": {}}, "schema": []}
{"input": "Using dominant-negative or constitutively active forms of Akt, we demonstrate that the effect of both raptor and rictor is mediated through alteration of Akt signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Our finding shed new light on the mechanism of control of insulin secretion and production by the mTOR, and they provide evidence for antagonistic effect of raptor and rictor on insulin secretion in response to glucose by modulating the activity of Akt, whereas only raptor is able to control insulin biosynthesis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 211, "end": 218}]}}, "schema": []}
{"input": "Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers.", "output": {"entities": {}}, "schema": []}
{"input": "Ocular barriers and the poor water solubility of drug candidates present a number of problems for the development of ocular drug delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, the emergence of lipid-based nanocarriers has provided a viable means of enhancing the bioavailability of ophthalmic formulations.", "output": {"entities": {}}, "schema": []}
{"input": "A number of these formulations have been found to be clinically active and several others are currently undergoing clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, the advantages of lipid-based nanocarriers as non-invasive topical ocular drug delivery systems are presented.", "output": {"entities": {}}, "schema": []}
{"input": "Many systems, including emulsions, liposomes, cubosomes, niosomes and other lipid-based nanocarriers, are reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "Phosphoinositide-dependent kinase-1 and protein kinase C delta contribute to endothelin-1 constriction and elevated blood pressure in intermittent hypoxia.", "output": {"entities": {}}, "schema": []}
{"input": "Obstructive sleep apnea (OSA) is associated with cardiovascular complications including hypertension.", "output": {"entities": {}}, "schema": []}
{"input": "Previous findings from our laboratory indicate that exposure to intermittent hypoxia (IH), to mimic sleep apnea, increases blood pressure in rats.", "output": {"entities": {}}, "schema": []}
{"input": "IH also increases endothelin-1 (ET-1) constrictor sensitivity in a protein kinase C (PKC) delta-dependent manner in mesenteric arteries.", "output": {"entities": {}}, "schema": []}
{"input": "Because phosphoinositide-dependent kinase-1 (PDK-1) regulates PKC delta activity, we hypothesized that PDK-1 contributes to the augmented ET-1 constrictor sensitivity and elevated blood pressure following IH.", "output": {"entities": {}}, "schema": []}
{"input": "Male Sprague-Dawley rats were exposed to either sham or IH (cycles between 21% O (2)/0% CO (2) and 5% O (2)/5% CO (2)) conditions for 7 h/day for 14 or 21 days.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 79, "end": 84}, {"text": "CO (2)", "start": 88, "end": 94}, {"text": "O (2)", "start": 102, "end": 107}, {"text": "CO (2)", "start": 111, "end": 117}]}}, "schema": []}
{"input": "The contribution of PKC delta and PDK-1 to ET-1-mediated vasoconstriction was assessed in mesenteric arteries using pharmacological inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Constrictor sensitivity to ET-1 was enhanced in arteries from IH-exposed rats.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of PKC delta or PDK-1 blunted ET-1 constriction in arteries from IH but not sham group rats.", "output": {"entities": {}}, "schema": []}
{"input": "Western analysis revealed similar levels of total and phosphorylated PDK-1 in arteries from sham and IH group rats but decreased protein-protein interaction between PKC delta and PDK-1 in arteries from IH-compared with sham-exposed rats.", "output": {"entities": {}}, "schema": []}
{"input": "Blood pressure was increased in rats exposed to IH, and treatment with the PDK-1 inhibitor OSU-03012 [2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl}-acetamide] (33 mg/day) lowered blood pressure in IH but not sham group rats.", "output": {"entities": {"chemical": [{"text": "OSU-03012", "start": 91, "end": 100}, {"text": "2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl}-acetamide", "start": 102, "end": 190}]}}, "schema": []}
{"input": "Our results suggest that exposure to IH unmasks a role for PDK-1 in regulating ET-1 constrictor sensitivity and blood pressure that is not present under normal conditions.", "output": {"entities": {}}, "schema": []}
{"input": "These novel findings suggest that PDK-1 may be a uniquely effective antihypertensive therapy for OSA patients.", "output": {"entities": {}}, "schema": []}
{"input": "Mouse liver protein sulfhydryl depletion after acetaminophen exposure.", "output": {"entities": {"chemical": [{"text": "sulfhydryl", "start": 20, "end": 30}, {"text": "acetaminophen", "start": 47, "end": 60}]}}, "schema": []}
{"input": "Acetaminophen (APAP)-induced liver injury is the leading cause of acute liver failure in many countries.", "output": {"entities": {"chemical": [{"text": "Acetaminophen", "start": 0, "end": 13}, {"text": "APAP", "start": 15, "end": 19}]}}, "schema": []}
{"input": "This study determined the extent of liver protein sulfhydryl depletion not only in whole liver homogenate but also in the zonal pattern of sulfhydryl depletion within the liver lobule.", "output": {"entities": {"chemical": [{"text": "sulfhydryl", "start": 50, "end": 60}, {"text": "sulfhydryl", "start": 139, "end": 149}]}}, "schema": []}
{"input": "A single oral gavage dose of 150 or 300 mg/kg APAP in B6C3F1 mice produced increased serum alanine aminotransferase levels, liver necrosis, and glutathione depletion in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "APAP", "start": 46, "end": 50}, {"text": "alanine", "start": 91, "end": 98}, {"text": "glutathione", "start": 144, "end": 155}]}}, "schema": []}
{"input": "Free protein sulfhydryls were measured in liver protein homogenates by labeling with maleimide linked to a near infrared fluorescent dye followed by SDS-polyacrylamide gel electrophoresis.", "output": {"entities": {"chemical": [{"text": "sulfhydryls", "start": 13, "end": 24}, {"text": "maleimide", "start": 85, "end": 94}, {"text": "SDS", "start": 149, "end": 152}, {"text": "polyacrylamide", "start": 153, "end": 167}]}}, "schema": []}
{"input": "Global protein sulfhydryl levels were decreased significantly (48. 4%) starting at 1 hour after the APAP dose and maintained at this reduced level through 24 hours.", "output": {"entities": {"chemical": [{"text": "sulfhydryl", "start": 15, "end": 25}, {"text": "APAP", "start": 100, "end": 104}]}}, "schema": []}
{"input": "To visualize the specific hepatocytes that had reduced protein sulfhydryl levels, frozen liver sections were labeled with maleimide linked to horseradish peroxidase.", "output": {"entities": {"chemical": [{"text": "sulfhydryl", "start": 63, "end": 73}, {"text": "maleimide", "start": 122, "end": 131}]}}, "schema": []}
{"input": "The centrilobular areas exhibited dramatic decreases in free protein sulfhydryls while the periportal regions were essentially spared.", "output": {"entities": {"chemical": [{"text": "sulfhydryls", "start": 69, "end": 80}]}}, "schema": []}
{"input": "These protein sulfhydryl-depleted regions correlated with areas exhibiting histopathologic injury and APAP binding to protein.", "output": {"entities": {"chemical": [{"text": "sulfhydryl", "start": 14, "end": 24}, {"text": "APAP", "start": 102, "end": 106}]}}, "schema": []}
{"input": "The majority of protein sulfhydryl depletion was due to reversible oxidation since the global-and lobule-specific effects were essentially reversed when the samples were reduced with tris (2-carboxyethy) phosphine before maleimide labeling.", "output": {"entities": {"chemical": [{"text": "sulfhydryl", "start": 24, "end": 34}, {"text": "tris (2-carboxyethy) phosphine", "start": 183, "end": 213}, {"text": "maleimide", "start": 221, "end": 230}]}}, "schema": []}
{"input": "These temporal and zonal pattern changes in protein sulfhydryl oxidation shed new light on the importance that changes in protein redox status might play in the pathogenesis of APAP hepatotoxicity.", "output": {"entities": {"chemical": [{"text": "sulfhydryl", "start": 52, "end": 62}, {"text": "APAP", "start": 177, "end": 181}]}}, "schema": []}
{"input": "Distinct sensitivity of slo1 channel proteins to ethanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 49, "end": 56}]}}, "schema": []}
{"input": "Ethanol levels reached in circulation during moderate-to-heavy alcohol intoxication (50-100 mM) modify Ca (2 +)-and voltage-gated K (+) (BK) channel steady-state activity, eventually altering both physiology and behavior.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 0, "end": 7}, {"text": "alcohol", "start": 63, "end": 70}, {"text": "Ca (2 +)", "start": 103, "end": 111}, {"text": "K (+)", "start": 130, "end": 135}]}}, "schema": []}
{"input": "Ethanol action on BK steady-state activity solely requires the channel-forming subunit slo1 within a bare lipid environment.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 0, "end": 7}]}}, "schema": []}
{"input": "To identify the protein regions that confer ethanol sensitivity to slo1, we tested the ethanol sensitivity of heterologously expressed slo1 and structurally related channels.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 44, "end": 51}, {"text": "ethanol", "start": 87, "end": 94}]}}, "schema": []}
{"input": "Ethanol (50 mM) increased the steady-state activities of mslo1 and Ca (2 +)-gated MthK, the latter after channel reconstitution into phospholipid bilayers.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 0, "end": 7}, {"text": "Ca (2 +)", "start": 67, "end": 75}]}}, "schema": []}
{"input": "In contrast, 50-100 mM ethanol failed to alter the steady-state activities of Na (+)/Cl (-)-gated rslo2, H (+)-gated mslo3, and an mslo1/3 chimera engineered by joining the mslo1 region encompassing the N terminus to S6 with the mslo3 cytosolic tail domain (CTD).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 23, "end": 30}, {"text": "Na (+)", "start": 78, "end": 84}, {"text": "Cl (-)", "start": 85, "end": 91}, {"text": "H (+)", "start": 105, "end": 110}, {"text": "N", "start": 203, "end": 204}]}}, "schema": []}
{"input": "Collectively, data indicate that the slo family canonical design, which combines a transmembrane 6 (TM6) voltage-gated K (+) channel (K (V)) core with CTDs that empower the channel with ion-sensing, does not necessarily render ethanol sensitivity.", "output": {"entities": {"chemical": [{"text": "K (+)", "start": 119, "end": 124}, {"text": "K", "start": 134, "end": 135}, {"text": "ethanol", "start": 227, "end": 234}]}}, "schema": []}
{"input": "In addition, the region encompassing the N terminus to the S0-S1 cytosolic loop (missing in MthK) is not necessary for ethanol action.", "output": {"entities": {"chemical": [{"text": "N", "start": 41, "end": 42}, {"text": "ethanol", "start": 119, "end": 126}]}}, "schema": []}
{"input": "Moreover, incorporation of both this region and an ion-sensing CTD to TM6 K (V) cores (a design common to mslo1, mslo3, and the mslo1/mslo3 chimera) is not sufficient for ethanol sensitivity.", "output": {"entities": {"chemical": [{"text": "K", "start": 74, "end": 75}, {"text": "ethanol", "start": 171, "end": 178}]}}, "schema": []}
{"input": "Rather, a CTD containing Ca (2 +)-sensing regulator of conductance for K (+) domains seems to be critical to bestow K (V) structures, whether of TM2 (MthK) or TM6 (slo1), with sensitivity to intoxicating ethanol levels.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 25, "end": 33}, {"text": "K (+)", "start": 71, "end": 76}, {"text": "K", "start": 116, "end": 117}, {"text": "ethanol", "start": 204, "end": 211}]}}, "schema": []}
{"input": "Identification of determinants required for agonistic and inverse agonistic ligand properties at the ADP receptor P2Y12.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 101, "end": 104}]}}, "schema": []}
{"input": "The ADP receptor P2Y (12) belongs to the superfamily of G protein-coupled receptors (GPCRs), and its activation triggers platelet aggregation.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 4, "end": 7}]}}, "schema": []}
{"input": "Therefore, potent antagonists, such as clopidogrel, are of high clinical relevance in prophylaxis and treatment of thromboembolic events.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 39, "end": 50}]}}, "schema": []}
{"input": "P2Y (12) displays an elevated basal activity in vitro, and as such, inverse agonists may be therapeutically beneficial compared with antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "Only a few inverse agonists of P2Y (12) have been described.", "output": {"entities": {}}, "schema": []}
{"input": "To expand this limited chemical space and improve understanding of structural determinants of inverse agonist-receptor interaction, this study screened a purine compound library for lead structures using wild-type (WT) human P2Y (12) and 28 constitutively active mutants.", "output": {"entities": {"chemical": [{"text": "purine", "start": 154, "end": 160}]}}, "schema": []}
{"input": "Results showed that ATP and ATP derivatives are agonists at P2Y (12).", "output": {"entities": {"chemical": [{"text": "ATP", "start": 20, "end": 23}, {"text": "ATP", "start": 28, "end": 31}]}}, "schema": []}
{"input": "The potency at P2Y (12) was 2-(methylthio)-ADP > 2-(methylthio)-ATP > ADP > ATP.", "output": {"entities": {"chemical": [{"text": "2-(methylthio)-ADP", "start": 28, "end": 46}, {"text": "2-(methylthio)-ATP", "start": 49, "end": 67}, {"text": "ADP", "start": 70, "end": 73}, {"text": "ATP", "start": 76, "end": 79}]}}, "schema": []}
{"input": "Determinants required for agonistic ligand activity were identified.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular docking studies revealed a binding pocket for the ATP derivatives that is bordered by transmembrane helices 3, 5, 6, and 7 in human P2Y (12,) with Y (105), E (188), R (256), Y (259), and K (280) playing a particularly important role in ligand interaction.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 60, "end": 63}]}}, "schema": []}
{"input": "N-Methyl-anthraniloyl modification at the 3'-OH of the 2'-deoxyribose leads to ligands (mant-deoxy-ATP [dATP], mant-deoxy-ADP) with inverse agonist activity.", "output": {"entities": {"chemical": [{"text": "N-Methyl-anthraniloyl", "start": 0, "end": 21}, {"text": "3'-OH", "start": 42, "end": 47}, {"text": "2'-deoxyribose", "start": 55, "end": 69}, {"text": "ATP", "start": 99, "end": 102}, {"text": "ADP", "start": 122, "end": 125}]}}, "schema": []}
{"input": "Inverse agonist activity of mant-dATP was found at the WT human P2Y (12) and half of the constitutive active P2Y (12) mutants.", "output": {"entities": {}}, "schema": []}
{"input": "This study showed that, in addition to ADP and ATP, other ATP derivatives are not only ligands of P2Y (12) but also agonists.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 39, "end": 42}, {"text": "ATP", "start": 47, "end": 50}, {"text": "ATP", "start": 58, "end": 61}]}}, "schema": []}
{"input": "Modification of the ribose within ATP can result in inverse activity of ATP-derived ligands.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 34, "end": 37}, {"text": "ATP", "start": 72, "end": 75}]}}, "schema": []}
{"input": "Restricted distribution and limited gene flow in the model ciliate Tetrahymena thermophila.", "output": {"entities": {}}, "schema": []}
{"input": "The biogeography of microbial eukaryotes has long been debated, but few phylogeographic data have been available to assess whether protists tend to have ubiquitous or endemic distributions.", "output": {"entities": {}}, "schema": []}
{"input": "We addressed this issue in the ciliate Tetrahymena thermophila, a highly successful model system in cell and molecular biology.", "output": {"entities": {}}, "schema": []}
{"input": "We found that this species has a distribution that is restricted to the Eastern United States, with high diversity in the northeast and low diversity across the rest of its distribution.", "output": {"entities": {}}, "schema": []}
{"input": "We find high levels of population subdivision, low rates of migration and significant isolation by distance, supporting the moderate endemicity model of protist biogeography.", "output": {"entities": {}}, "schema": []}
{"input": "This restricted gene flow may be a result of small population size, which would reduce the probability of migration events, or the inability to establish after migration.", "output": {"entities": {}}, "schema": []}
{"input": "This work lays the foundation for T. thermophila to become a valuable model system for studying population biology.", "output": {"entities": {}}, "schema": []}
{"input": "Differential effects of antipsychotic agents on obsessive-compulsive symptoms in schizophrenia: a longitudinal study.", "output": {"entities": {}}, "schema": []}
{"input": "Indirect evidence supports the assumption that antiserotonergic second-generation antipsychotics (SGA) induce and aggravate obsessive-compulsive symptoms (OCS) in schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "However, multimodal studies assessing the long-term interaction of pharmacotherapy and psychopathology are missing.", "output": {"entities": {}}, "schema": []}
{"input": "Over 12 months, we followed-up 75 schizophrenia patients who were classified into two groups according to antipsychotic treatment: clozapine or olanzapine (group I) versus aripiprazole or amisulpride (group II).", "output": {"entities": {"chemical": [{"text": "clozapine", "start": 131, "end": 140}, {"text": "olanzapine", "start": 144, "end": 154}, {"text": "aripiprazole", "start": 172, "end": 184}, {"text": "amisulpride", "start": 188, "end": 199}]}}, "schema": []}
{"input": "We applied the Yale Brown Obsessive Compulsive Scale (YBOCS) and investigated between-group changes over time as the primary endpoint.", "output": {"entities": {}}, "schema": []}
{"input": "Group I showed markedly higher YBOCS scores at both time points.", "output": {"entities": {}}, "schema": []}
{"input": "Repeated measure analyses of variance (ANOVAs) revealed significant interaction effects of group and time (per protocol sample (PP): p = 0. 006).", "output": {"entities": {}}, "schema": []}
{"input": "This was due to persistently high OCS severity within group I, and decreasing YBOCS scores within group II.", "output": {"entities": {}}, "schema": []}
{"input": "OCS severity correlated significantly with the negative and general psychopathology subscales of the Positive and Negative Syndrome Scale (PANSS), as well as with depressive symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "The progressive differences in OCS severity between our groups support the assumption of differential pharmacodynamic effects on comorbid OCS in schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "Further studies should address the pathogenetic mechanism, define patients at risk and facilitate early detection as well as therapeutic interventions.", "output": {"entities": {}}, "schema": []}
{"input": "Intercellular adhesion molecule-2 is involved in apical ectoplasmic specialization dynamics during spermatogenesis in the rat.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated the role of intercellular adhesion molecule-2 (ICAM2) in the testis.", "output": {"entities": {}}, "schema": []}
{"input": "ICAM2 is a cell adhesion protein having important roles in cell migration, especially during inflammation when leukocytes cross the endothelium.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we showed ICAM2 to be expressed by germ and Sertoli cells in the rat testis.", "output": {"entities": {}}, "schema": []}
{"input": "When a monospecific antibody was used for immunolocalization experiments, ICAM2 was found to surround the heads of elongating/elongated spermatids in all stages of the seminiferous epithelial cycle.", "output": {"entities": {}}, "schema": []}
{"input": "To determine whether ICAM2 is a constituent of apical ectoplasmic specialization (ES), co-immunoprecipitation and dual immunofluorescence staining were performed.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, ICAM2 was found to associate with beta 1-integrin, nectin-3, afadin, Src, proline-rich tyrosine kinase 2, annexin II, and actin.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 102, "end": 110}]}}, "schema": []}
{"input": "Following CdCl 2 treatment, ICAM2 was found to be upregulated during restructuring of the seminiferous epithelium, with round spermatids becoming increasingly immunoreactive for ICAM2 by 6-16 h.", "output": {"entities": {"chemical": [{"text": "CdCl 2", "start": 10, "end": 16}]}}, "schema": []}
{"input": "Interestingly, there was a loss in the binding of ICAM2 to actin during CdCl 2-induced germ cell loss, suggesting that a loss of ICAM2-actin interactions might have facilitated junction restructuring.", "output": {"entities": {"chemical": [{"text": "CdCl 2", "start": 72, "end": 78}]}}, "schema": []}
{"input": "Taken collectively, these results illustrate that ICAM2 plays an important role in apical ES dynamics during spermatogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "A single-device universal logic gate based on a magnetically enhanced memristor.", "output": {"entities": {}}, "schema": []}
{"input": "Memristors are one of the most promising candidates for future information and communications technology (ICT) architectures.", "output": {"entities": {}}, "schema": []}
{"input": "Two experimental proofs of concept are presented based on the intermixing of spintronic and memristive effects into a single device, a magnetically enhanced memristor (MEM).", "output": {"entities": {}}, "schema": []}
{"input": "By exploiting the interaction between the memristance and the giant magnetoresistance (GMR), a universal implication (IMP) logic gate based on a single MEM device is realized.", "output": {"entities": {}}, "schema": []}
{"input": "Novel screening assay for the selective detection of G-protein-coupled receptor heteromer signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Drugs targeting G-protein-coupled receptors (GPCRs) make up more than 25% of all prescribed medicines.", "output": {"entities": {}}, "schema": []}
{"input": "The ability of GPCRs to form heteromers with unique signaling properties suggests an entirely new and unexplored pool of drug targets.", "output": {"entities": {}}, "schema": []}
{"input": "However, current in vitro assays are ill equipped to detect heteromer-selective compounds.", "output": {"entities": {}}, "schema": []}
{"input": "We have successfully adapted an approach, using fusion proteins of GPCRs and chimeric G proteins, to create an in vitro screening assay (in human embryonic kidney cells) in which only activated heteromers are detectable.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that this assay can demonstrate heteromer-selective G-protein bias as well as measure transinhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Using this assay, we reveal that the delta-opioid receptor agonist ADL5859, which is currently in clinical trials, has a 10-fold higher potency against delta-opioid receptor homomers than delta/mu-opioid receptor heteromers (pEC (50) = 6. 7 +/- 0. 1 versus 5. 8 +/- 0. 2).", "output": {"entities": {"chemical": [{"text": "ADL5859", "start": 67, "end": 74}]}}, "schema": []}
{"input": "The assay enables the screening of large compound libraries to identify heteromer-selective compounds that could then be used in vivo to determine the functional role of heteromers and develop potential therapeutic agents.", "output": {"entities": {}}, "schema": []}
{"input": "Two new anthraquinone dimers from the fruit bodies of Bulgaria inquinans.", "output": {"entities": {"chemical": [{"text": "anthraquinone", "start": 8, "end": 21}]}}, "schema": []}
{"input": "Two new dimeric anthraquinone derivatives, bulgareone A (1) and bulgareone B (2), were isolated from the fruit bodies of Bulgaria inquinans.", "output": {"entities": {"chemical": [{"text": "anthraquinone", "start": 16, "end": 29}, {"text": "bulgareone A", "start": 43, "end": 55}, {"text": "bulgareone B", "start": 64, "end": 76}]}}, "schema": []}
{"input": "Their structures were elucidated on the basis of extensive spectroscopic analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro cytotoxic activity of compounds 1 and 2 was assayed.", "output": {"entities": {}}, "schema": []}
{"input": "They displayed inhibitive activities against human cancer cell lines HL60 and K562.", "output": {"entities": {}}, "schema": []}
{"input": "Sex differences in effects of low level domoic acid exposure.", "output": {"entities": {"chemical": [{"text": "domoic acid", "start": 40, "end": 51}]}}, "schema": []}
{"input": "Consumption of seafood containing the phytoplankton-derived toxin domoic acid (DOM) causes neurotoxicity in humans and in animals.", "output": {"entities": {"chemical": [{"text": "domoic acid", "start": 66, "end": 77}, {"text": "DOM", "start": 79, "end": 82}]}}, "schema": []}
{"input": "It has been reported that DOM-induced symptoms may be more severe in men than women, but to date the effect of sex on DOM-induced effects in adults is not known.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 26, "end": 29}, {"text": "DOM", "start": 118, "end": 121}]}}, "schema": []}
{"input": "We investigated sex differences in DOM-induced effects in adult rats.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 35, "end": 38}]}}, "schema": []}
{"input": "Since low level exposure is of greatest relevance to human health (due to DOM regulatory limit), we examined the effects of low level exposure.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 74, "end": 77}]}}, "schema": []}
{"input": "Adult male and female Sprague Dawley rats were administered a single intraperitoneal injection of DOM (0, 1. 0, 1. 8 mg/kg).", "output": {"entities": {"chemical": [{"text": "DOM", "start": 98, "end": 101}]}}, "schema": []}
{"input": "Behaviour was monitored for 3h and immunohistochemistry in the dorsal hippocampus and olfactory bulb was also examined.", "output": {"entities": {}}, "schema": []}
{"input": "DOM increased locomotor and grooming activity, compared to vehicle group.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 0, "end": 3}]}}, "schema": []}
{"input": "DOM exposure also significantly increased stereotypic behaviours and decreased phosphorylated cAMP response element-binding protein immunoreactivity (pCREB-IR).", "output": {"entities": {"chemical": [{"text": "DOM", "start": 0, "end": 3}, {"text": "phosphorylated cAMP", "start": 79, "end": 98}]}}, "schema": []}
{"input": "There was no effect of sex on the magnitude of the behavioural responses, but the onset of DOM-induced locomotor activity and ear scratches was quicker in females than in males.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 91, "end": 94}]}}, "schema": []}
{"input": "Mixed effect modelling revealed the predicted peak in locomotor activity in response to DOM was also quicker in females than in males.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 88, "end": 91}]}}, "schema": []}
{"input": "Severe toxicity was evident in 2/7 male rats and 0/8 female rats dosed with 1. 8 mg/kg DOM.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 87, "end": 90}]}}, "schema": []}
{"input": "These data suggest that males exposed to low level DOM may be more susceptible to severe neurotoxicity, whereas females are affected more quickly.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 51, "end": 54}]}}, "schema": []}
{"input": "Understanding sex differences in DOM-induced neurotoxicity may contribute to future protective strategies and treatments.", "output": {"entities": {"chemical": [{"text": "DOM", "start": 33, "end": 36}]}}, "schema": []}
{"input": "Toxicokinetic study and absolute oral bioavailability of deoxynivalenol, T-2 toxin and zearalenone in broiler chickens.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 57, "end": 71}, {"text": "T-2 toxin", "start": 73, "end": 82}, {"text": "zearalenone", "start": 87, "end": 98}]}}, "schema": []}
{"input": "Mycotoxins lead to economic losses in animal production.", "output": {"entities": {}}, "schema": []}
{"input": "A way to counteract mycotoxicosis is the use of detoxifiers.", "output": {"entities": {}}, "schema": []}
{"input": "The European Food Safety Authority stated that the efficacy of detoxifiers should be investigated based on toxicokinetic studies.", "output": {"entities": {}}, "schema": []}
{"input": "Little information is available on the absolute oral bioavailability and the toxicokinetic parameters of deoxynivalenol, T-2 and zearalenone in broilers.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 105, "end": 119}, {"text": "T-2", "start": 121, "end": 124}, {"text": "zearalenone", "start": 129, "end": 140}]}}, "schema": []}
{"input": "Toxins were administered intravenously and orally in a two-way cross-over design.", "output": {"entities": {}}, "schema": []}
{"input": "For deoxynivalenol a bolus of 0. 75mg/kg BW was administered, for T-2 toxin 0. 02mg/kg BW and for zearalenone 0. 3mg/kg BW.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 4, "end": 18}, {"text": "T-2 toxin", "start": 66, "end": 75}, {"text": "zearalenone", "start": 98, "end": 109}]}}, "schema": []}
{"input": "Blood was collected at several time points.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma levels of the mycotoxins and their metabolite (s) were quantified using LC-MS/MS methods and toxicokinetic parameters were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "Deoxynivalenol has a low absolute oral bioavailability (19. 3%).", "output": {"entities": {"chemical": [{"text": "Deoxynivalenol", "start": 0, "end": 14}]}}, "schema": []}
{"input": "For zearalenone and T-2 no plasma levels above the limit of quantification were observed after an oral bolus.", "output": {"entities": {"chemical": [{"text": "zearalenone", "start": 4, "end": 15}, {"text": "T-2", "start": 20, "end": 23}]}}, "schema": []}
{"input": "Volumes of distribution were recorded, i. e. 4. 99, 0. 14 and 22. 26L/kg for deoxynivalenol, T-2 toxin and zearalenone, respectively.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 77, "end": 91}, {"text": "T-2 toxin", "start": 93, "end": 102}, {"text": "zearalenone", "start": 107, "end": 118}]}}, "schema": []}
{"input": "Total body clearance was 0. 12, 0. 03 and 0. 48L/minkg for deoxynivalenol, T-2 toxin and zearalenone, respectively.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 59, "end": 73}, {"text": "T-2 toxin", "start": 75, "end": 84}, {"text": "zearalenone", "start": 89, "end": 100}]}}, "schema": []}
{"input": "After IV administration, T-2 toxin had the shortest elimination half-life (3. 9min), followed by deoxynivalenol (27. 9min) and zearalenone (31. 8min).", "output": {"entities": {"chemical": [{"text": "T-2 toxin", "start": 25, "end": 34}, {"text": "deoxynivalenol", "start": 97, "end": 111}, {"text": "zearalenone", "start": 127, "end": 138}]}}, "schema": []}
{"input": "Citrus peel polymethoxylated flavones extract modulates liver and heart function parameters in diet induced hypercholesterolemic rats.", "output": {"entities": {"chemical": [{"text": "polymethoxylated flavones", "start": 12, "end": 37}]}}, "schema": []}
{"input": "The primary aim of this study was to investigate the effects of Ortanique peel polymethoxylated flavones extract (PMF (ort)) on organ function parameters in the serum of hypercholesterolemic and normal rats.", "output": {"entities": {"chemical": [{"text": "polymethoxylated flavones", "start": 79, "end": 104}, {"text": "PMF", "start": 114, "end": 117}]}}, "schema": []}
{"input": "Thirty Sprague-Dawley rats were fed high cholesterol diets supplemented with 1. 5% PMF (ort) and niacin respectively for 49days.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 41, "end": 52}, {"text": "PMF", "start": 83, "end": 86}]}}, "schema": []}
{"input": "Hypercholesterolemic rats fed PMF (ort) had significant reductions in the activities of aspartate aminotransferase and alkaline phosphatase (69. 12 +/- 3. 34 and 87. 22 +/- 8. 42U/L respectively) compared to the untreated hypercholesterolemic group (118. 61 +/- 4. 85 and 132. 62 +/- 10. 62U/L respectively, p < 0. 05).", "output": {"entities": {"chemical": [{"text": "PMF", "start": 30, "end": 33}, {"text": "aspartate", "start": 88, "end": 97}]}}, "schema": []}
{"input": "Supplementation of the diet with niacin or PMF (ort) resulted in no significant differences in the serum levels of creatinine or urea in any of the groups.", "output": {"entities": {"chemical": [{"text": "niacin", "start": 33, "end": 39}, {"text": "PMF", "start": 43, "end": 46}, {"text": "creatinine", "start": 115, "end": 125}, {"text": "urea", "start": 129, "end": 133}]}}, "schema": []}
{"input": "Total bilirubin was highest in the untreated hypercholesterolemic group.", "output": {"entities": {"chemical": [{"text": "bilirubin", "start": 6, "end": 15}]}}, "schema": []}
{"input": "Supplementation of the diets of hypercholesterolemic rats with PMF (ort) resulted in significant reductions in the activities of serum creatine kinase and lactate dehydrogenase (119. 3 +/- 25. 3; 222. 5 +/- 50. 3U/L, p < 0. 05) respectively relative to the untreated hypercholesterolemic group (257. 2 +/- 48. 3; 648. 8 +/- 103U/L, p < 0. 05).", "output": {"entities": {"chemical": [{"text": "PMF", "start": 63, "end": 66}, {"text": "creatine", "start": 135, "end": 143}, {"text": "lactate", "start": 155, "end": 162}]}}, "schema": []}
{"input": "The results would suggest that PMF (ort) modulates hypercholesterolemia-associated organ injury in rats.", "output": {"entities": {"chemical": [{"text": "PMF", "start": 31, "end": 34}]}}, "schema": []}
{"input": "PMF (ort) could therefore be a suitable candidate for prophylactic and therapeutic treatment of hypercholesterolemia-associated organ injury.", "output": {"entities": {"chemical": [{"text": "PMF", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Assessment of immunotoxicity and genotoxicity in workers exposed to low concentrations of formaldehyde.", "output": {"entities": {"chemical": [{"text": "formaldehyde", "start": 90, "end": 102}]}}, "schema": []}
{"input": "Formaldehyde (FA), which is an important chemical with a wide commercial use, has been classified as carcinogenic to humans by International Research on Cancer (IARC).", "output": {"entities": {"chemical": [{"text": "Formaldehyde", "start": 0, "end": 12}]}}, "schema": []}
{"input": "The genotoxic and carcinogenic potential of FA has been documented in mammalian cells and in rodents.", "output": {"entities": {}}, "schema": []}
{"input": "A recent evaluation by the E. U.", "output": {"entities": {}}, "schema": []}
{"input": "Scientific Committee for Occupational Exposure Limits (SCOEL) anticipated that an 8-h time-weighted average exposure to 0. 2 ppm FA would not be irritating and not genotoxic in humans.", "output": {"entities": {}}, "schema": []}
{"input": "In order to verify this prediction, a field study was performed that aimed at evaluating immune alterations and genetic damage in peripheral lymphocytes of workers in medium density fiberboard plants exposed to a level of FA equivalent to the OEL recommended by SCOEL (0. 2 ppm).", "output": {"entities": {}}, "schema": []}
{"input": "Subsets of peripheral lymphocytes, immunoglobulins (IgG, IgA, IgM), complement proteins, and tumor necrosis factor-alpha (TNF-alpha) levels were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "DNA damage of the workers was assessed by the Comet assay.", "output": {"entities": {}}, "schema": []}
{"input": "The absolute numbers and the percentages of T lymphocytes and of natural killer cells, and the levels of TNF-alpha were higher than the controls, whereas IgG and IgM levels were found to be lower in workers.", "output": {"entities": {}}, "schema": []}
{"input": "Other examined immunological parameters were not different from those of the controls.", "output": {"entities": {}}, "schema": []}
{"input": "There was no increased DNA damage in the workers compared to controls.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial fusion: a mechanism of cisplatin-induced resistance in neuroblastoma cells?", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 37, "end": 46}]}}, "schema": []}
{"input": "Cisplatin induces apoptosis through different pathways.", "output": {"entities": {"chemical": [{"text": "Cisplatin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The intrinsic apoptotic pathway is mediated by mitochondria, which, as a result of cisplatin treatment, undergo morphological alterations.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 83, "end": 92}]}}, "schema": []}
{"input": "The aim of this study was to investigate cisplatin-induced mitochondrial functional and morphological long-term effects in neuroblastoma B50 rat cells.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 41, "end": 50}]}}, "schema": []}
{"input": "To this purpose, we followed evaluated different several apoptotic markers by means of flow cytometry, confocal and electron microscopy and western blotting techniques.", "output": {"entities": {}}, "schema": []}
{"input": "We applied different treatment protocols based on the incubation of the neuroblastoma B50 rat cells with 40 mu M cisplatin: (i) for 48 h and harvesting of the cells at the end of the treatment; (ii) further recovery in drug-free medium for 7 days post-treatment; (iii) conditions as in (ii) followed by re-seeding in normal medium and growth for a further 4 days.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 113, "end": 122}]}}, "schema": []}
{"input": "We observed apoptosis induction after the first treatment and after the recovery from cell death after long-term culture in drug-free medium.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, the latter phenomenon was characterized by mitochondrial elongation and mitochondrial protein rearrangement.", "output": {"entities": {}}, "schema": []}
{"input": "In recovered and re-seeded cells, mitochondrial equilibrium moved toward fusion, possibly protecting cells from apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "The high bone mass phenotype is characterised by a combined cortical and trabecular bone phenotype: findings from a pQCT case-control study.", "output": {"entities": {}}, "schema": []}
{"input": "High bone mass (HBM), detected in 0. 2% of DXA scans, is characterised by a mild skeletal dysplasia largely unexplained by known genetic mutations.", "output": {"entities": {}}, "schema": []}
{"input": "We conducted the first systematic assessment of the skeletal phenotype in unexplained HBM using pQCT in our unique HBM population identified from screening routine UK NHS DXA scans.", "output": {"entities": {}}, "schema": []}
{"input": "pQCT measurements from the mid and distal tibia and radius in 98 HBM cases were compared with (i) 65 family controls (constituting unaffected relatives and spouses), and (ii) 692 general population controls.", "output": {"entities": {}}, "schema": []}
{"input": "HBM cases had substantially greater trabecular density at the distal tibia (340 [320, 359] mg/cm (3)), compared to both family (294 [276, 312]) and population controls (290 [281, 299]) (p < 0. 001 for both, adjusted for age, gender, weight, height, alcohol, smoking, malignancy, menopause, steroid and estrogen replacement use).", "output": {"entities": {"chemical": [{"text": "steroid", "start": 290, "end": 297}, {"text": "estrogen", "start": 302, "end": 310}]}}, "schema": []}
{"input": "Similar results were obtained at the distal radius.", "output": {"entities": {}}, "schema": []}
{"input": "Greater cortical bone mineral density (cBMD) was observed in HBM cases, both at the midtibia and radius (adjusted p < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "Total bone area (TBA) was higher in HBM cases, at the distal and mid tibia and radius (adjusted p < 0. 05 versus family controls), suggesting greater periosteal apposition.", "output": {"entities": {}}, "schema": []}
{"input": "Cortical thickness was increased at the mid tibia and radius (adjusted p < 0. 001), implying reduced endosteal expansion.", "output": {"entities": {}}, "schema": []}
{"input": "Together, these changes resulted in greater predicted cortical strength (strength strain index [SSI]) in both tibia and radius (p < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "We then examined relationships with age; tibial cBMD remained constant with increasing age amongst HBM cases (adjusted beta-0. 01 [-0. 02, 0. 01], p = 0. 41), but declined in family controls (-0. 05 [-0. 03,-0. 07], p < 0. 001) interaction p = 0. 002; age-related changes in tibial trabecular BMD, CBA and SSI were also divergent.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, at the radius HBM cases and controls showed parallel age-related declines in cBMD and trabecular BMD.", "output": {"entities": {}}, "schema": []}
{"input": "HBM is characterised by increased trabecular BMD and by alterations in cortical bone density and structure, leading to substantial increments in predicted cortical bone strength.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to the radius, neither trabecular nor cortical BMD declined with age in the tibia of HBM cases, suggesting attenuation of age-related bone loss in weight-bearing limbs contributes to the observed bone phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "Comprehensive study on regional human intestinal permeability and prediction of fraction absorbed of drugs using the Ussing chamber technique.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to evaluate the use of human intestinal tissue in Ussing chamber to predict oral and colonic drug absorption and intestinal metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "Data on viability, correlation between apparent permeability coefficients (P (app)) and fraction absorbed (f (a)) after oral and colonic administration, regional permeability, active uptake and efflux of drugs as well as intestinal metabolism were compiled from experiments using 159 human donors.", "output": {"entities": {}}, "schema": []}
{"input": "Permeability coefficients for up to 28 drugs were determined using one or several of four intestinal regions: duodenum, jejunum, ileum and colon and 10 drugs were studied bidirectionally.", "output": {"entities": {}}, "schema": []}
{"input": "Viability was monitored simultaneously with transport experiments by recording potential difference (PD), short-circuit current (SCC) and the resistance (TER).", "output": {"entities": {}}, "schema": []}
{"input": "Intestinal metabolism was studied using testosterone and midazolam as probe substrates.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 40, "end": 52}, {"text": "midazolam", "start": 57, "end": 66}]}}, "schema": []}
{"input": "There was a steep sigmoidal correlation between P (app) in the Ussing chamber, using jejunal segments, and oral f (a) in humans, for a set of 25 drugs (R (2): 0. 85, p < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "A clear sigmoidal relationship was also obtained between P (app) in colonic segments and f (a) after colonic administration in humans for a set of 10 drugs (R (2): 0. 93, p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Regional permeability data showed a tendency for highly permeable compounds to have higher or similar P (app) in colon as in the small intestinal segments, while the colonic regions showed a lower P (app) for more polar compounds as well as for d-glucose and l-leucine.", "output": {"entities": {"chemical": [{"text": "d-glucose", "start": 245, "end": 254}, {"text": "l-leucine", "start": 259, "end": 268}]}}, "schema": []}
{"input": "Bidirectional transport (mucosa to serosa and serosa to mucosa direction) in jejunum showed well functioning efflux-and uptake asymmetry.", "output": {"entities": {}}, "schema": []}
{"input": "Intestinal metabolic extraction during transport across jejunum segments was found for both testosterone and midazolam.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 92, "end": 104}, {"text": "midazolam", "start": 109, "end": 118}]}}, "schema": []}
{"input": "In conclusion, viable excised human intestine mounted in the Ussing chamber, is a powerful technique for predicting regional fraction absorbed (f (a)), transporter-mediated uptake or efflux as well as intestinal metabolism of drug candidates in man.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, a sigmoidal relationship of P (app) vs. f (a) was obtained when permeability data from the present study were merged with data from 2 other independent laboratories (R (2): 0. 83, p < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "The correlation curve reported can be used by any laboratory for predictions of human permeability and f (a) (.) In addition, for the first time a correlation curve between colonic P (app) and human colonic f (a) is reported, which demonstrates the usefulness of this methodology in early assessment of the colonic absorption potential of extended release formulation candidates.", "output": {"entities": {}}, "schema": []}
{"input": "Can P-glycoprotein mediate resistance to nilotinib in human leukaemia cells?", "output": {"entities": {"chemical": [{"text": "nilotinib", "start": 41, "end": 50}]}}, "schema": []}
{"input": "The effect of P-glycoprotein (P-gp, ABCB1, MDR1) expression on cell resistance to nilotinib was studied in human leukaemia cells.", "output": {"entities": {"chemical": [{"text": "nilotinib", "start": 82, "end": 91}]}}, "schema": []}
{"input": "We used K562/Dox cells overexpressing P-gp and their variants (subclones) with a gradually decreased P-gp expression.", "output": {"entities": {"chemical": [{"text": "Dox", "start": 13, "end": 16}]}}, "schema": []}
{"input": "These subclones were established by stable transfection of K562/Dox cells with a plasmid vector expressing shRNA targeting the ABCB1 gene.", "output": {"entities": {"chemical": [{"text": "Dox", "start": 64, "end": 67}]}}, "schema": []}
{"input": "Functional analysis of P-gp using a specific fluorescent probe indicated gradually decreased dye efflux which was proportional to the P-gp expression.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that K562/Dox cells overexpressing P-gp contained a significantly reduced intracellular level of nilotinib when compared to their counter partner K562 cells, which do not express P-gp.", "output": {"entities": {"chemical": [{"text": "Dox", "start": 22, "end": 25}, {"text": "nilotinib", "start": 109, "end": 118}]}}, "schema": []}
{"input": "This effect was accompanied by a decreased sensitivity of the K562/Dox cells to nilotinib.", "output": {"entities": {"chemical": [{"text": "Dox", "start": 67, "end": 70}, {"text": "nilotinib", "start": 80, "end": 89}]}}, "schema": []}
{"input": "Importantly, cells with downregulated expression of P-gp gradually lost their ability to decrease the intracellular level of nilotinib although they still significantly decreased the intracellular level of daunorubicin (DNR).", "output": {"entities": {"chemical": [{"text": "nilotinib", "start": 125, "end": 134}, {"text": "daunorubicin", "start": 206, "end": 218}, {"text": "DNR", "start": 220, "end": 223}]}}, "schema": []}
{"input": "Accordingly, cells with the reduced expression of P-gp concomitantly failed to provide resistance to nilotinib, however, they exhibited a significant resistance to DNR.", "output": {"entities": {"chemical": [{"text": "nilotinib", "start": 101, "end": 110}, {"text": "DNR", "start": 164, "end": 167}]}}, "schema": []}
{"input": "Taken together, we demonstrated that the conclusion as to whether P-gp is involved in nilotinib resistance or not strongly depends on its expression at protein level.", "output": {"entities": {"chemical": [{"text": "nilotinib", "start": 86, "end": 95}]}}, "schema": []}
{"input": "Reversal of the deleterious effects of chronic dietary HFCS-55 intake by PPAR-delta agonism correlates with impaired NLRP3 inflammasome activation.", "output": {"entities": {"chemical": [{"text": "HFCS-55", "start": 55, "end": 62}]}}, "schema": []}
{"input": "Although high-fructose corn syrup (HFCS-55) is the major sweetener in foods and soft-drinks, its potential role in the pathophysiology of diabetes and obesity (\" diabesity \") remains unclear.", "output": {"entities": {"chemical": [{"text": "high-fructose corn syrup", "start": 9, "end": 33}, {"text": "HFCS-55", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Peroxisome-proliferator activated receptor (PPAR)-delta agonists have never been tested in models of sugar-induced metabolic abnormalities.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 101, "end": 106}]}}, "schema": []}
{"input": "This study was designed to evaluate (i) the metabolic and renal consequences of HFCS-55 administration (15% wt/vol in drinking water) for 30 weeks on male C57Bl6/J mice and (ii) the effects of the selective PPAR-delta agonist GW0742 (1 mg/kg/day for 16 weeks) in this condition.", "output": {"entities": {"chemical": [{"text": "HFCS-55", "start": 80, "end": 87}, {"text": "GW0742", "start": 226, "end": 232}]}}, "schema": []}
{"input": "HFCS-55 caused (i) hyperlipidemia, (ii) insulin resistance, and (iii) renal injury/inflammation.", "output": {"entities": {"chemical": [{"text": "HFCS-55", "start": 0, "end": 7}]}}, "schema": []}
{"input": "In the liver, HFCS-55 enhanced the expression of fructokinase resulting in hyperuricemia and caused abnormalities in known insulin-driven signaling events.", "output": {"entities": {"chemical": [{"text": "HFCS-55", "start": 14, "end": 21}]}}, "schema": []}
{"input": "In the kidney, HFCS-55 enhanced the expression of the NLRP3 (nucleotide-binding domain and leucine-rich-repeat-protein 3) inflammasome complex, resulting in caspase-1 activation and interleukin-1 beta production.", "output": {"entities": {"chemical": [{"text": "HFCS-55", "start": 15, "end": 22}, {"text": "nucleotide", "start": 61, "end": 71}, {"text": "leucine", "start": 91, "end": 98}]}}, "schema": []}
{"input": "All of the above effects of HFCS-55 were attenuated by the specific PPAR-delta agonist GW0742.", "output": {"entities": {"chemical": [{"text": "HFCS-55", "start": 28, "end": 35}, {"text": "GW0742", "start": 87, "end": 93}]}}, "schema": []}
{"input": "Thus, we demonstrate for the first time that the specific PPAR-delta agonist GW0742 attenuates the metabolic abnormalities and the renal dysfunction/inflammation caused by chronic HFCS-55 exposure by preventing upregulation of fructokinase (liver) and activation of the NLRP3 inflammasome (kidney).", "output": {"entities": {"chemical": [{"text": "GW0742", "start": 77, "end": 83}, {"text": "HFCS-55", "start": 180, "end": 187}]}}, "schema": []}
{"input": "Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras.", "output": {"entities": {"chemical": [{"text": "hydrogen sulfide", "start": 37, "end": 53}, {"text": "hydrogen sulfide", "start": 58, "end": 74}]}}, "schema": []}
{"input": "Hydrogen sulfide, H2S, is a colorless gas with a strong odor that until recently was only considered to be a toxic environmental pollutant with little or no physiological significance.", "output": {"entities": {"chemical": [{"text": "Hydrogen sulfide", "start": 0, "end": 16}, {"text": "H2S", "start": 18, "end": 21}]}}, "schema": []}
{"input": "However, the past few years have demonstrated its role in many biological systems and it is becoming increasingly clear that H2S is likely to join nitric oxide (NO) and carbon monoxide (CO) as a major player in mammalian biology.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 125, "end": 128}, {"text": "nitric oxide", "start": 147, "end": 159}, {"text": "NO", "start": 161, "end": 163}, {"text": "carbon monoxide", "start": 169, "end": 184}, {"text": "CO", "start": 186, "end": 188}]}}, "schema": []}
{"input": "In this review, we have provided an overview of the chemistry and biology of H2S and have summarized the chemistry and biological activity of some natural and synthetic H2S-donating compounds.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 77, "end": 80}, {"text": "H2S", "start": 169, "end": 172}]}}, "schema": []}
{"input": "The naturally occurring compounds discussed include, garlic, sulforaphane, erucin, and iberin.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 61, "end": 73}, {"text": "erucin", "start": 75, "end": 81}, {"text": "iberin", "start": 87, "end": 93}]}}, "schema": []}
{"input": "The synthetic H2S donors reviewed include, GYY4137; cysteine analogs; S-propyl cysteine, S-allyl cysteine, S-propargyl cysteine, and N-acetyl cysteine.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 14, "end": 17}, {"text": "GYY4137", "start": 43, "end": 50}, {"text": "cysteine", "start": 52, "end": 60}, {"text": "S-propyl cysteine", "start": 70, "end": 87}, {"text": "S-allyl cysteine", "start": 89, "end": 105}, {"text": "S-propargyl cysteine", "start": 107, "end": 127}, {"text": "N-acetyl cysteine", "start": 133, "end": 150}]}}, "schema": []}
{"input": "Dithiolethione and its NSAID and other chimeras such as, L-DOPA, sildenafil, aspirin, diclofenac, naproxen, ibuprofen, indomethacin, and mesalamine have also been reviewed in detail.", "output": {"entities": {"chemical": [{"text": "Dithiolethione", "start": 0, "end": 14}, {"text": "L-DOPA", "start": 57, "end": 63}, {"text": "sildenafil", "start": 65, "end": 75}, {"text": "aspirin", "start": 77, "end": 84}, {"text": "diclofenac", "start": 86, "end": 96}, {"text": "naproxen", "start": 98, "end": 106}, {"text": "ibuprofen", "start": 108, "end": 117}, {"text": "indomethacin", "start": 119, "end": 131}, {"text": "mesalamine", "start": 137, "end": 147}]}}, "schema": []}
{"input": "The newly reported NOSH-aspirin that releases both NO and H2S has also been discussed.", "output": {"entities": {"chemical": [{"text": "NOSH-aspirin", "start": 19, "end": 31}, {"text": "NO", "start": 51, "end": 53}, {"text": "H2S", "start": 58, "end": 61}]}}, "schema": []}
{"input": "The diversity of microbial aldo/keto reductases from Escherichia coli K12.", "output": {"entities": {}}, "schema": []}
{"input": "The genome of Escherichia coli K12 contains 9 open reading frames encoding aldo/keto reductases (AKRs) that are differentially regulated and sequence diverse.", "output": {"entities": {}}, "schema": []}
{"input": "A significant amount of data is available for the E. coli AKRs through the availability of gene knockouts and gene expression studies, which adds to the biochemical and kinetic data.", "output": {"entities": {}}, "schema": []}
{"input": "This together with the availability of crystal structures for nearly half of the E. coli AKRs and homologues of several others provides an opportunity to look at the diversity of these representative bacterial AKRs.", "output": {"entities": {}}, "schema": []}
{"input": "Based around the common AKR fold of (beta/alpha) 8 barrel with two additional alpha-helices, the E. coli AKRs have a loop structure that is more diverse than their mammalian counterparts, creating a variety of active site architectures.", "output": {"entities": {}}, "schema": []}
{"input": "Nearly half of the AKRs are expected to be monomeric, but there are examples of dimeric, trimeric and octameric enzymes, as well as diversity in specificity for NAD as well as NADP as a cofactor.", "output": {"entities": {"chemical": [{"text": "NAD", "start": 161, "end": 164}, {"text": "NADP", "start": 176, "end": 180}]}}, "schema": []}
{"input": "However in functional assignments and characterisation of enzyme activities there is a paucity of data when compared to the mammalian AKR enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary exposure to inorganic arsenic of the Hong Kong population: results of the first Hong Kong total diet study.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 30, "end": 37}]}}, "schema": []}
{"input": "Inorganic arsenic, a human carcinogen, can be found in the environment and food.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 10, "end": 17}]}}, "schema": []}
{"input": "In the first Hong Kong Total Diet Study, the dietary exposure of the Hong Kong people, including various age-gender subgroups, to inorganic arsenic was estimated for assessing the associated health risk.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 140, "end": 147}]}}, "schema": []}
{"input": "Food samples, which represented the Hong Kong people' s diet, were collected and prepared \" as consumed \" for analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Concentrations of inorganic arsenic, as sum of arsenite (As (III)) and arsenate (As (V)) were determined in 600 composite samples by using inductively coupled plasma mass spectrometry.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 28, "end": 35}, {"text": "arsenite", "start": 47, "end": 55}, {"text": "As (III)", "start": 57, "end": 65}, {"text": "arsenate", "start": 71, "end": 79}, {"text": "As (V)", "start": 81, "end": 87}]}}, "schema": []}
{"input": "The dietary exposures were estimated by combining the analytical results with the local food consumption data of the adult population.", "output": {"entities": {}}, "schema": []}
{"input": "The mean and 95th percentile of inorganic arsenic exposures of the Hong Kong people were 0. 22 and 0. 38 mu g/kg body weight (bw)/day, respectively.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 42, "end": 49}]}}, "schema": []}
{"input": "Among the 12 age-gender subgroups, the respective exposures ranged from 0. 19 to 0. 26 mu g/kg bw/day and from 0. 33 to 0. 46 mu g/kg bw/day.", "output": {"entities": {}}, "schema": []}
{"input": "The main food category that contributed inorganic arsenic was \" cereals and their products \" (53. 5% of the total exposure), particularly rice.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 50, "end": 57}]}}, "schema": []}
{"input": "Having considered the carcinogenic risk of inorganic arsenic to humans, it is suggested that efforts should be made to reduce the inorganic arsenic exposure of the Hong Kong population.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 53, "end": 60}, {"text": "arsenic", "start": 140, "end": 147}]}}, "schema": []}
{"input": "Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse.", "output": {"entities": {}}, "schema": []}
{"input": "The lipoprotein receptor ligand Reelin is important for the processes of normal synaptic plasticity, dendritic morphogenesis, and learning and memory.", "output": {"entities": {}}, "schema": []}
{"input": "Heterozygous reeler mice (HRM) show many neuroanatomical, biochemical, and behavioral features that are associated with schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "HRM show subtle morphological defects including reductions in dendritic spine density, altered synaptic plasticity and behavioral deficits in associative learning and memory and pre-pulse inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "The present studies test the hypothesis that in vivo elevation of Reelin levels can rescue synaptic and behavioral phenotypes associated with HRM.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that a single in vivo injection of Reelin increases GAD67 expression and alters dendritic spine morphology.", "output": {"entities": {}}, "schema": []}
{"input": "In parallel we observed enhancement of hippocampal synaptic function and associative learning and memory.", "output": {"entities": {}}, "schema": []}
{"input": "Reelin supplementation also increases pre-pulse inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that characteristics of HRM, similar to those observed in schizophrenia, are sensitive to Reelin levels and can be modified with Reelin supplementation in male and female adults.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of two-component system AfsQ1/Q2 regulon and its cross-regulation with GlnR in Streptomyces coelicolor.", "output": {"entities": {}}, "schema": []}
{"input": "The two-component system AfsQ1/Q2 of Streptomyces coelicolor was identified in our previous work as a pleiotropic regulator for antibiotic biosynthesis and morphological differentiation under the condition of a minimal medium supplemented with 75 mM glutamate.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 250, "end": 259}]}}, "schema": []}
{"input": "In this work, we report the dissection of the mechanism underlying the function of AfsQ1/Q2 on antibiotic production and also the identification of the AfsQ1/Q2 regulon.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that AfsQ1/Q2 stimulated antibiotic ACT, RED and CDA production directly through the pathway-specific activator genes actII-ORF4, redZ and cdaR respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, expression of sigQ that encodes a sigma factor and is divergently transcribed from afsQ1 was also subject to direct regulation by AfsQ1/Q2.", "output": {"entities": {}}, "schema": []}
{"input": "The precise AfsQ1 binding sites in the upstream regions of these target genes were determined by DNase I footprinting assays coupled with site-directed DNA mutagenesis.", "output": {"entities": {}}, "schema": []}
{"input": "By computational prediction and functional analysis, at least 17 new AfsQ1 targets were identified, including pstS gene encoding a high-affinity phosphate-binding protein and two developmental genes whiD, bldM.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 145, "end": 154}]}}, "schema": []}
{"input": "For the AfsQ1/Q2 regulon, an AfsQ1 binding motif comprising the sequence GTnAC-n (6)-GTnAC has been defined.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, we found from electrophoretic mobility shift assays and transcriptional analysis that AfsQ1/Q2 can also function as a repressor for nitrogen assimilation, and AfsQ1 can compete with GlnR for the promoter regions of glnA and nirB, suggesting the cross-regulation between AfsQ1/Q2 and GlnR in nitrogen metabolism.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 147, "end": 155}, {"text": "nitrogen", "start": 306, "end": 314}]}}, "schema": []}
{"input": "These findings suggested that AfsQ1/Q2 is important not only for antibiotic biosynthesis but also in maintaining the metabolic homeostasis of nutrient utilization under the stress of high concentration of glutamate in S. coelicolor.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 205, "end": 214}]}}, "schema": []}
{"input": "Cryopreservation of precision-cut tissue slices.", "output": {"entities": {}}, "schema": []}
{"input": "1. Cryopreservation of precision-cut tissue slices (PCTS) would have many advantages for drug development and would encourage more extensive use of the PCTS preparation.", "output": {"entities": {}}, "schema": []}
{"input": "2. Three methods have been studied to date: slow freezing, fast freezing, and vitrification.", "output": {"entities": {}}, "schema": []}
{"input": "3. Slow freezing can be very effective for some PCTS but is devastating to rat liver PCTS.", "output": {"entities": {}}, "schema": []}
{"input": "Fast freezing can be successful for rat liver PCTS but is devastating to renal PCTS and has given inconsistent results even for rat liver PCTS.", "output": {"entities": {}}, "schema": []}
{"input": "Vitrification has been effective for some slice systems but less effective for rat liver PCTS.", "output": {"entities": {}}, "schema": []}
{"input": "Rat liver PCTS appear to be particularly difficult to cryopreserve well.", "output": {"entities": {}}, "schema": []}
{"input": "4. The general cryobiological principles of slow freezing, rapid freezing, and vitrification are reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "The empirical literature on the cryopreservation of PCTS has not taken sufficient account of these principles, and may, for example, include the effects of easily preventable osmotic injury.", "output": {"entities": {}}, "schema": []}
{"input": "5. More attention is needed to the effects of cryopreservation on specific cell types within PCTS and to the general integrity and viability of cryopreserved PCTS.", "output": {"entities": {}}, "schema": []}
{"input": "Drug metabolism as a sole endpoint of study can be highly misleading.", "output": {"entities": {}}, "schema": []}
{"input": "6. Better application of cryobiological principles may enable improved results in the future.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of the intestinal toxicity and transport of xenobiotics utilizing precision-cut slices.", "output": {"entities": {}}, "schema": []}
{"input": "1. The precision-cut intestinal slice (PCIS) technology is a relatively new addition to the battery of in vitro assays for evaluation of xenobiotic toxicity, metabolism, and transport.", "output": {"entities": {}}, "schema": []}
{"input": "2. The intestine is an important target for drug-induced toxicity due to its high exposure after oral administration.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the prediction of drug-induced intestinal side effects remains a significant safety issue in pharmaceutical development.", "output": {"entities": {}}, "schema": []}
{"input": "Although animal experiments have been proven useful, species differences and the requirement for reduction of animal use warrant the development of in vitro methods which can apply human tissue.", "output": {"entities": {}}, "schema": []}
{"input": "3. The enterocytes lining the villi express high activities of enzymes and transporters involved in drug disposition.", "output": {"entities": {}}, "schema": []}
{"input": "They vary highly in activities: along the length of the intestine and along the villi, gradients of expression levels of the enzymes and proteins exist, which necessitates an in vitro model that can reflect the different regions of the intestine.", "output": {"entities": {}}, "schema": []}
{"input": "4. In this chapter, the application of PCIS in studies on transport and toxicity of xenobiotics is reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "PCIS can be prepared from each region of the intestine and from various species in a similar manner, and the results published so far indicate that they represent a promising model to evaluate intestinal toxicity and transport.", "output": {"entities": {}}, "schema": []}
{"input": "Autophagy upregulation promotes survival and attenuates doxorubicin-induced cardiotoxicity.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 56, "end": 67}]}}, "schema": []}
{"input": "This study evaluated whether the manipulation of autophagy could attenuate the cardiotoxic effects of doxorubicin (DXR) in vitro as well as in a tumour-bearing mouse model of acute doxorubicin-induced cardiotoxicity.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 102, "end": 113}, {"text": "DXR", "start": 115, "end": 118}, {"text": "doxorubicin", "start": 181, "end": 192}]}}, "schema": []}
{"input": "We examined the effect of an increase or inhibition of autophagy in combination with DXR on apoptosis, reactive oxygen species (ROS) production and mitochondrial function.", "output": {"entities": {"chemical": [{"text": "DXR", "start": 85, "end": 88}, {"text": "oxygen", "start": 112, "end": 118}]}}, "schema": []}
{"input": "H9C2 rat cardiac myoblasts were pre-treated with bafilomycin A1 (autophagy inhibitor, 10 nM) or rapamycin (autophagy inducer, 50 mu M) followed by DXR treatment (3 mu M).", "output": {"entities": {"chemical": [{"text": "bafilomycin A1", "start": 49, "end": 63}, {"text": "rapamycin", "start": 96, "end": 105}, {"text": "DXR", "start": 147, "end": 150}]}}, "schema": []}
{"input": "The augmentation of autophagy with rapamycin in the presence of DXR substantially ameliorated the detrimental effects induced by DXR.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 35, "end": 44}, {"text": "DXR", "start": 64, "end": 67}, {"text": "DXR", "start": 129, "end": 132}]}}, "schema": []}
{"input": "This combination treatment demonstrated improved cell viability, decreased apoptosis and ROS production and enhanced mitochondrial function.", "output": {"entities": {}}, "schema": []}
{"input": "To corroborate these findings, GFP-LC3 mice were inoculated with a mouse breast cancer cell line (EO771).", "output": {"entities": {}}, "schema": []}
{"input": "Following the appearance of tumours, animals were either treated with one injection of rapamycin (4 mg/kg) followed by two injections of DXR (10 mg/kg).", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 87, "end": 96}, {"text": "DXR", "start": 137, "end": 140}]}}, "schema": []}
{"input": "Mice were then sacrificed and their hearts rapidly excised and utilized for biochemical and histological analyses.", "output": {"entities": {}}, "schema": []}
{"input": "The combination treatment, rather than the combinants alone, conferred a cardioprotective effect.", "output": {"entities": {}}, "schema": []}
{"input": "These hearts expressed down-regulation of the pro-apoptotic protein caspase-3 and cardiomyocyte cross-sectional area was preserved.", "output": {"entities": {}}, "schema": []}
{"input": "These results strongly indicate that the co-treatment strategy with rapamycin can attenuate the cardiotoxic effects of DXR in a tumour-bearing mouse model.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 68, "end": 77}, {"text": "DXR", "start": 119, "end": 122}]}}, "schema": []}
{"input": "Arsenic inhibits the adipogenic differentiation of mesenchymal stem cells by down-regulating peroxisome proliferator-activated receptor gamma and CCAAT enhancer-binding proteins.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Arsenic remains a top environmental concern in the United States as well as worldwide because of its global existence and serious health impacts.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Apoptotic effect of arsenic in human mesenchymal stem cells (hMSCs) has been identified in our previous study; the effects of arsenic on hMSCs remain largely unknown.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 20, "end": 27}, {"text": "arsenic", "start": 126, "end": 133}]}}, "schema": []}
{"input": "Here, we report that arsenic inhibits the adipogenic differentiation of human mesenchymal stem cells (hMSCs).", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 21, "end": 28}]}}, "schema": []}
{"input": "Arsenic reduced the formation of lipid droplets and the expression of adipogenesis-related proteins, such as CCAAT enhancer binding protein-(C/EBPs), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and adipocyte fatty acid-binding protein aP2 (aP2).", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}, {"text": "fatty acid", "start": 227, "end": 237}]}}, "schema": []}
{"input": "Arsenic mediates this process by sustaining PPAR-gamma activity.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "In addition, inhibition of PPAR-gamma activity with T0070907 and up-regulation with its agonist troglitazone, showed the direct association of PPAR-gamma and arsenic-mediated inhibition of differentiating hMSCs.", "output": {"entities": {"chemical": [{"text": "troglitazone", "start": 96, "end": 108}, {"text": "arsenic", "start": 158, "end": 165}]}}, "schema": []}
{"input": "Taken together, these results indicate that arsenic inhibits adipogenic differentiation through PPAR-gamma pathway and suggest a novel inhibitory effect of arsenic on adipogenic differentiation in hMSCs.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 44, "end": 51}, {"text": "arsenic", "start": 156, "end": 163}]}}, "schema": []}
{"input": "Synthesis and chiral recognition of nickel (II) macrocyclic complex with (R)-naphthylethyleneamine pendant groups and its self-assembled framework.", "output": {"entities": {"chemical": [{"text": "nickel (II)", "start": 36, "end": 47}, {"text": "(R)-naphthylethyleneamine", "start": 73, "end": 98}]}}, "schema": []}
{"input": "A novel nickel (II) hexaaza macrocyclic complex, [Ni (L (R, R))] (ClO (4)) (2) (1), containing chiral pendant groups was synthesized by an efficient one-pot template condensation and characterized (L (R, R) = 1, 8-di ((R)-alpha-methylnaphthyl)-1, 3, 6, 8, 10, 13-hexaazacyclotetradecane).", "output": {"entities": {"chemical": [{"text": "nickel (II) hexaaza", "start": 8, "end": 27}, {"text": "[Ni (L (R, R))] (ClO (4)) (2)", "start": 49, "end": 78}, {"text": "1, 8-di ((R)-alpha-methylnaphthyl)-1, 3, 6, 8, 10, 13-hexaazacyclotetradecane", "start": 209, "end": 286}]}}, "schema": []}
{"input": "The crystal structure of compound 1 was determined by single-crystal X-ray analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The complex was found to have a square-planar coordination environment for the nickel (II) ion.", "output": {"entities": {"chemical": [{"text": "nickel (II)", "start": 79, "end": 90}]}}, "schema": []}
{"input": "Open framework [Ni (L (R, R))] (3) [C (6) H (3) (COO) (3)] (2) (2) was constructed from the self-assembly of compound 1 with deprotonated 1, 3, 5-benzenetricarboxylic acid, BTC (3-).", "output": {"entities": {"chemical": [{"text": "[Ni (L (R, R))] (3) [C (6) H (3) (COO) (3)] (2)", "start": 15, "end": 62}, {"text": "1, 3, 5-benzenetricarboxylic acid", "start": 138, "end": 171}, {"text": "BTC (3-)", "start": 173, "end": 181}]}}, "schema": []}
{"input": "Chiral discrimination of rac-1, 1'-bi-2-naphthol and rac-2, 2, 2-trifluoro-1-(9-anthryl) ethanol was performed to determine the chiral recognition ability of the chiral complex (1) and its self-assembled framework (2).", "output": {"entities": {"chemical": [{"text": "rac-1, 1'-bi-2-naphthol", "start": 25, "end": 48}, {"text": "rac-2, 2, 2-trifluoro-1-(9-anthryl) ethanol", "start": 53, "end": 96}]}}, "schema": []}
{"input": "Binaphthol showed a good chiral discrimination on the framework (2).", "output": {"entities": {"chemical": [{"text": "Binaphthol", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The optimum experimental conditions for the chiral discrimination were examined by changing the weight ratio between the macrocyclic complex 1 or self-assembled framework 2 and racemates.", "output": {"entities": {}}, "schema": []}
{"input": "The detailed synthetic procedures, spectroscopic data including single-crystal X-ray analysis, and the results of the chiral recognition for the compounds are described.", "output": {"entities": {}}, "schema": []}
{"input": "Room-temperature electron spin amplifier based on Ga (In) NAs alloys.", "output": {"entities": {"chemical": [{"text": "Ga (In) NAs", "start": 50, "end": 61}]}}, "schema": []}
{"input": "The first experimental demonstration of a spin amplifier at room temperature is presented.", "output": {"entities": {}}, "schema": []}
{"input": "An efficient, defect-enabled spin amplifier based on a non-magnetic semiconductor, Ga (In) NAs, is proposed and demonstrated, with a large spin gain (up to 2700% at zero field) for conduction electrons and a high cut-off frequency of up to 1 GHz.", "output": {"entities": {"chemical": [{"text": "Ga (In) NAs", "start": 83, "end": 94}]}}, "schema": []}
{"input": "Ethyl acetate: X-ray, solvent and computed structures.", "output": {"entities": {"chemical": [{"text": "Ethyl acetate", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Ethyl acetate (ethyl ethanoate) was crystallized in situ and the crystal structure was determined.", "output": {"entities": {"chemical": [{"text": "Ethyl acetate", "start": 0, "end": 13}, {"text": "ethyl ethanoate", "start": 15, "end": 30}]}}, "schema": []}
{"input": "In the solid, the molecule is flat with trans conformation.", "output": {"entities": {}}, "schema": []}
{"input": "The geometric details of ethyl acetate as a solvate are analyzed statistically using the Cambridge Structural Database, uncovering a high degree of hidden disorder.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 25, "end": 38}]}}, "schema": []}
{"input": "Despite the disorder, they exhibit a preference of the trans over the gauche isomer, with a negligible contribution of the cis isomer.", "output": {"entities": {}}, "schema": []}
{"input": "These results are compared to ab initio calculations on both solid-state and molecular level.", "output": {"entities": {}}, "schema": []}
{"input": "For the molecular structures, the computed energy differences of the isomers match the statistics found as a solvent.", "output": {"entities": {}}, "schema": []}
{"input": "Several DFT-D2 methods used to calculate the solid state yield results that differ significantly from the experiment.", "output": {"entities": {}}, "schema": []}
{"input": "Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Type 2 diabetes mellitus results in increased risk of fracture and delayed fracture healing.", "output": {"entities": {}}, "schema": []}
{"input": "ZDF fa/fa rats are an established model of type 2 diabetes mellitus with low bone mass and delayed bone healing.", "output": {"entities": {}}, "schema": []}
{"input": "We tested whether a sclerostin-neutralizing antibody (Scl-AbVI) would reverse the skeletal deficits of diabetic ZDF rats.", "output": {"entities": {}}, "schema": []}
{"input": "Femoral defects of 3 mm were created in 11-week-old diabetic ZDF fa/fa and nondiabetic ZDF +/+ rats and stabilized by an internal plate.", "output": {"entities": {}}, "schema": []}
{"input": "Saline or 25 mg/kg Scl-AbVI was administered subcutaneously (s. c.) twice weekly for 12 weeks (n = 9-10/group).", "output": {"entities": {}}, "schema": []}
{"input": "Bone mass and strength were assessed using pQCT, micro-computed tomography (micro CT), and biomechanical testing.", "output": {"entities": {}}, "schema": []}
{"input": "Bone histomorphometry was used to assess bone formation, and the filling of the bone defect was analyzed by micro CT.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetic rats displayed lower spinal and femoral bone mass compared to nondiabetic rats, and Scl-AbVI treatment significantly enhanced bone mass of the femur and the spine of diabetic rats (p < 0. 0001).", "output": {"entities": {}}, "schema": []}
{"input": "Scl-AbVI also reversed the deficit in bone strength in the diabetic rats, with 65% and 89% increases in maximum load at the femoral shaft and neck, respectively (p < 0. 0001).", "output": {"entities": {}}, "schema": []}
{"input": "The lower bone mass in diabetic rats was associated with a 65% decrease in vertebral bone formation rate, which Scl-AbVI increased by sixfold, consistent with a pronounced anabolic effect.", "output": {"entities": {}}, "schema": []}
{"input": "Nondiabetic rats filled 57% of the femoral defect, whereas diabetic rats filled only 21% (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Scl-AbVI treatment increased defect regeneration by 47% and 74%, respectively (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Sclerostin antibody treatment reverses the adverse effects of type 2 diabetes mellitus on bone mass and strength, and improves bone defect regeneration in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of repeated pulsed herbicide exposures on the growth of aquatic macrophytes.", "output": {"entities": {}}, "schema": []}
{"input": "Many contaminants are released into aquatic systems intermittently in a series of pulses.", "output": {"entities": {}}, "schema": []}
{"input": "Pulse timing and magnitude can vary according to usage, compound-specific physicochemical properties, and use area characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "Standard laboratory ecotoxicity tests typically employ continuous exposure concentrations over defined durations and thus may not accurately and realistically reflect the effects of certain compounds on aquatic organisms, resulting in potential over-or underestimation.", "output": {"entities": {}}, "schema": []}
{"input": "Consequently, the relative effects of pulsed (2 and 4 d) and continuous exposures of the duckweed Lemna minor to isoproturon, metsulfuron-methyl, and pentachlorophenol over a period of 42 d were explored in the present study.", "output": {"entities": {"chemical": [{"text": "isoproturon", "start": 113, "end": 124}, {"text": "metsulfuron-methyl", "start": 126, "end": 144}, {"text": "pentachlorophenol", "start": 150, "end": 167}]}}, "schema": []}
{"input": "At the highest test concentrations, exposure of L. minor to pulses of metsulfuron-methyl resulted in effects on growth similar to those of an equivalent continuous exposure.", "output": {"entities": {"chemical": [{"text": "metsulfuron-methyl", "start": 70, "end": 88}]}}, "schema": []}
{"input": "For isoproturon, pulsed exposures had a lower impact than a corresponding continuous exposure, whereas the effect of pentachlorophenol delivered in pulses was greater.", "output": {"entities": {"chemical": [{"text": "isoproturon", "start": 4, "end": 15}, {"text": "pentachlorophenol", "start": 117, "end": 134}]}}, "schema": []}
{"input": "These differences may be explained by compound-specific uptake and degradation or dissipation rates in plants and the recovery potential that occurs following pulses for different pesticides.", "output": {"entities": {}}, "schema": []}
{"input": "Given these results, use of a simple time-weighted average approach to estimate effects of intermittent exposures from short-term standard toxicity studies may not provide an accurate prediction that reflects realistic exposure scenarios.", "output": {"entities": {}}, "schema": []}
{"input": "Development of mechanistic modeling approaches may facilitate better estimates of effects from intermittent exposures.", "output": {"entities": {}}, "schema": []}
{"input": "Systematic identification of functional residues in mammalian histone H2AX.", "output": {"entities": {}}, "schema": []}
{"input": "The histone variant H2AX is a principal component of chromatin involved in the detection, signaling, and repair of DNA double-strand breaks (DSBs).", "output": {"entities": {}}, "schema": []}
{"input": "H2AX is thought to operate primarily through its C-terminal S139 phosphorylation, which mediates the recruitment of DNA damage response (DDR) factors to chromatin at DSB sites.", "output": {"entities": {"chemical": [{"text": "C", "start": 49, "end": 50}]}}, "schema": []}
{"input": "Here, we describe a comprehensive screen of 67 residues in H2AX to determine their contributions to H2AX functions.", "output": {"entities": {}}, "schema": []}
{"input": "Our analysis revealed that H2AX is both sumoylated and ubiquitylated.", "output": {"entities": {}}, "schema": []}
{"input": "Individual residues defective for sumoylation, ubiquitylation, and S139 phosphorylation in untreated and damaged cells were identified.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, we identified an acidic triad region in both H2A and H2AX that is required in cis for their ubiquitylation.", "output": {"entities": {}}, "schema": []}
{"input": "We also report the characterization of a human H2AX knockout cell line, which exhibits DDR defects, including p53 activation, following DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, this work constitutes the first genetic complementation system for a histone in human cells.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, our data reveal new roles for several residues in H2AX and define distinct functions for H2AX in human cells.", "output": {"entities": {}}, "schema": []}
{"input": "Aryl-heteroaryl derivatives as novel wake-promoting agents.", "output": {"entities": {}}, "schema": []}
{"input": "In search of a next generation molecule to the novel wake-promoting agent modafinil, a series of aryl-heteroayl-derived wakefulness enhancing agents (in rats) was developed.", "output": {"entities": {"chemical": [{"text": "modafinil", "start": 74, "end": 83}]}}, "schema": []}
{"input": "From this work, compound 16 was separated into its enantiomers to profile them individually.", "output": {"entities": {}}, "schema": []}
{"input": "SPIDIA-RNA: first external quality assessment for the pre-analytical phase of blood samples used for RNA based analyses.", "output": {"entities": {}}, "schema": []}
{"input": "The diagnostic use of in vitro molecular assays can be limited by the lack of guidelines for collection, handling, stabilization and storage of patient specimens.", "output": {"entities": {}}, "schema": []}
{"input": "One of the major goals of the EC funded project SPIDIA (www. spidia. eu) is to develop evidence-based quality guidelines for the pre-analytical phase of blood samples used for molecular testing which requires intracellular RNA analytes.", "output": {"entities": {}}, "schema": []}
{"input": "To this end, a survey and a pan-European external quality assessment (EQA) were implemented.", "output": {"entities": {}}, "schema": []}
{"input": "This report is the summary of the results of that trial.", "output": {"entities": {}}, "schema": []}
{"input": "With the European Federation of Laboratory Medicine (EFLM) support, 124 applications for participation in the trial were received from 27 different European countries, and 102 laboratories actually participated in the trial.", "output": {"entities": {}}, "schema": []}
{"input": "Each participating laboratory described their respective laboratory policies and practices as well as blood collection tubes typically used in performing this type of testing.", "output": {"entities": {}}, "schema": []}
{"input": "The participating laboratories received two identical blood specimens: in an EDTA tubes (unstabilized blood; n = 67) or in tubes designed specifically for the stabilization of intracellular RNA in blood (PAXgene (R) Blood RNA tubes; n = 35).", "output": {"entities": {"chemical": [{"text": "EDTA", "start": 77, "end": 81}]}}, "schema": []}
{"input": "Laboratories were requested to perform RNA extraction according to the laboratory' s own procedure as soon as possible upon receipt of the tubes for one tube and 24h after the first extraction for the second tube.", "output": {"entities": {}}, "schema": []}
{"input": "Participants (n = 93) returned the two extracted RNAs to SPIDIA facility for analysis, and provided details about the reagents and protocols they used for the extraction.", "output": {"entities": {}}, "schema": []}
{"input": "At the SPIDIA facility responsible for coordinating the study, the survey data were classified, and the extracted RNA samples were evaluated for purity, yield, integrity, stability, and the presence of interfering substances affecting RT-qPCR assays.", "output": {"entities": {}}, "schema": []}
{"input": "All participants received a report comparing the performance of the RNA they submitted to that of the other participants.", "output": {"entities": {}}, "schema": []}
{"input": "All the results obtained by participants for each RNA quality parameter were classified as \" in control \", \" warning \", \" out of control \" and \" missing \" by consensus mean analysis.", "output": {"entities": {}}, "schema": []}
{"input": "From the survey data, the most variable parameters were the volume of blood collected and the time and storage temperature between blood collection and RNA extraction.", "output": {"entities": {}}, "schema": []}
{"input": "Analyzing the results of quality testing of submitted RNA samples we observed a data distribution of purity, yield, and presence of assay interference in agreement with expected values.", "output": {"entities": {}}, "schema": []}
{"input": "The RNA Integrity Number (RIN) values distribution was, on the other hand, much wider than the optimal expected value, which led to an \" in control \" classification, even for partly degraded RNA samples.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, RIN values below 5 significantly correlated with a reduction of GAPDH expression levels.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the distribution of the values of the four transcripts investigated (c-fos, IL-1 beta, IL-8, and GAPDH) was wide and the RNA instability between samples separated by 24h were similar.", "output": {"entities": {}}, "schema": []}
{"input": "Assuming the presence of at least two quality parameters \" out of control \" as an indication of a critical performance of the laboratory, 33% of the laboratories were included in this group.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study will be the basis for implementing a second pan-European EQA and the results of both EQAs will be pooled and will provide the basis for the implementation of evidence-based guidelines for the pre-analytical phase of RNA analysis of blood samples.", "output": {"entities": {}}, "schema": []}
{"input": "Reversal of efflux mediated antifungal resistance underlies synergistic activity of two monoterpenes with fluconazole.", "output": {"entities": {"chemical": [{"text": "monoterpenes", "start": 88, "end": 100}, {"text": "fluconazole", "start": 106, "end": 117}]}}, "schema": []}
{"input": "Thymol (THY) and carvacrol (CARV), the principal chemical components of thyme oil have long been known for their wide use in medicine due to antimicrobial and disinfectant properties.", "output": {"entities": {"chemical": [{"text": "Thymol", "start": 0, "end": 6}, {"text": "THY", "start": 8, "end": 11}, {"text": "carvacrol", "start": 17, "end": 26}, {"text": "CARV", "start": 28, "end": 32}]}}, "schema": []}
{"input": "This study, however, draws attention to a possible synergistic antifungal effect of these monoterpenes with azole antimycotic-fluconazole.", "output": {"entities": {"chemical": [{"text": "monoterpenes", "start": 90, "end": 102}, {"text": "azole", "start": 108, "end": 113}, {"text": "fluconazole", "start": 126, "end": 137}]}}, "schema": []}
{"input": "Resistance to azoles in Candida albicans involves over-expression of efflux-pump genes MDR1, CDR1, CDR2 or mutations and over-expression of target gene ERG11.", "output": {"entities": {"chemical": [{"text": "azoles", "start": 14, "end": 20}]}}, "schema": []}
{"input": "The inhibition of drug efflux pumps is considered a feasible strategy to overcome clinical antifungal resistance.", "output": {"entities": {}}, "schema": []}
{"input": "To put forward this approach, we investigated the combination effects of these monoterpenes and FLC against 38 clinically obtained FLC-sensitive, and eleven FLC-resistant Candida isolates.", "output": {"entities": {"chemical": [{"text": "monoterpenes", "start": 79, "end": 91}, {"text": "FLC", "start": 96, "end": 99}, {"text": "FLC", "start": 131, "end": 134}, {"text": "FLC", "start": 157, "end": 160}]}}, "schema": []}
{"input": "Synergism was observed with combinations of THY-FLC and CARV-FLC evaluated by checkerboard microdilution method and nature of the interactions was calculated by FICI.", "output": {"entities": {"chemical": [{"text": "THY", "start": 44, "end": 47}, {"text": "FLC", "start": 48, "end": 51}, {"text": "CARV", "start": 56, "end": 60}, {"text": "FLC", "start": 61, "end": 64}]}}, "schema": []}
{"input": "In addition, antifungal activity was assessed using agar-diffusion and time-kill curves.", "output": {"entities": {}}, "schema": []}
{"input": "The drug efflux activity was determined using two dyes, Rhodamine6G (R6G) and fluorescent Hoechst 33342.", "output": {"entities": {"chemical": [{"text": "Rhodamine6G", "start": 56, "end": 67}, {"text": "R6G", "start": 69, "end": 72}, {"text": "Hoechst 33342", "start": 90, "end": 103}]}}, "schema": []}
{"input": "No significant differences were observed in dye uptakes between FLC-susceptible and resistant isolates, incubated in glucose free buffer.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 117, "end": 124}]}}, "schema": []}
{"input": "However, a significantly higher efflux was recorded in FLC-resistant isolates when glucose was added.", "output": {"entities": {"chemical": [{"text": "FLC", "start": 55, "end": 58}, {"text": "glucose", "start": 83, "end": 90}]}}, "schema": []}
{"input": "Both monoterpenes inhibited efflux by 70-90%, showing their high potency to block drug transporter pumps.", "output": {"entities": {"chemical": [{"text": "monoterpenes", "start": 5, "end": 17}]}}, "schema": []}
{"input": "Significant differences, in the expression levels of CDR1 and MDR1, induced by monoterpenes revealed reversal of FLC-resistance.", "output": {"entities": {"chemical": [{"text": "monoterpenes", "start": 79, "end": 91}, {"text": "FLC", "start": 113, "end": 116}]}}, "schema": []}
{"input": "The selectively fungicidal characteristics and ability to restore FLC susceptibility in resistant isolates signify a promising candidature of THY and CARV as antifungal agents in combinational treatments for candidiasis.", "output": {"entities": {"chemical": [{"text": "FLC", "start": 66, "end": 69}, {"text": "THY", "start": 142, "end": 145}, {"text": "CARV", "start": 150, "end": 154}]}}, "schema": []}
{"input": "Experimental exposure of red-legged partridges (Alectoris rufa) to seeds coated with imidacloprid, thiram and difenoconazole.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 85, "end": 97}, {"text": "thiram", "start": 99, "end": 105}, {"text": "difenoconazole", "start": 110, "end": 124}]}}, "schema": []}
{"input": "Pesticide coated seeds are commonly used in agriculture, and may be an important source of food for some birds in times of scarcity, as well as a route of pesticide ingestion.", "output": {"entities": {}}, "schema": []}
{"input": "We tested the lethal and sub-lethal effects of treated seed ingestion by the red-legged partridge (Alectoris rufa), a game bird of high socio-economic value in Spain.", "output": {"entities": {}}, "schema": []}
{"input": "One year-old partridges (n = 42 pairs) were fed for 10 days in spring (prior to breeding) with wheat treated with difenoconazole (fungicide), thiram (fungicide) or imidacloprid (insecticide), using two doses for each pesticide (the one recommended, and its double to represent potential cases of abuse of pesticides).", "output": {"entities": {"chemical": [{"text": "difenoconazole", "start": 114, "end": 128}, {"text": "thiram", "start": 142, "end": 148}, {"text": "imidacloprid", "start": 164, "end": 176}]}}, "schema": []}
{"input": "We investigated the direct and indirect effects on the body condition, physiology, immunology, coloration and subsequent reproduction of exposed partridges.", "output": {"entities": {}}, "schema": []}
{"input": "For the latter, eggs were collected, measured and incubated and the growth and survival of chicks were monitored.", "output": {"entities": {}}, "schema": []}
{"input": "Thiram and imidacloprid at high exposure doses produced mortalities of 41. 6 and 58. 3%, respectively.", "output": {"entities": {"chemical": [{"text": "Thiram", "start": 0, "end": 6}, {"text": "imidacloprid", "start": 11, "end": 23}]}}, "schema": []}
{"input": "The first death was observed at day 3 for imidacloprid and at day 7 for thiram.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 42, "end": 54}, {"text": "thiram", "start": 72, "end": 78}]}}, "schema": []}
{"input": "Both doses of the three pesticides caused sublethal effects, such as altered biochemical parameters, oxidative stress and reduced carotenoid-based coloration.", "output": {"entities": {}}, "schema": []}
{"input": "The high exposure doses of imidacloprid and thiram also produced a decrease in cellular immune response measured by the phytohemagglutinin test in males.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 27, "end": 39}, {"text": "thiram", "start": 44, "end": 50}]}}, "schema": []}
{"input": "Bearing in mind the limitation of the small number of surviving pairs in some treatments, we found that the three pesticides reduced the size of eggs and imidacloprid and difenoconazole also reduced the fertilization rate.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 154, "end": 166}, {"text": "difenoconazole", "start": 171, "end": 185}]}}, "schema": []}
{"input": "In addition, both thiram and imidacloprid reduced chick survival.", "output": {"entities": {"chemical": [{"text": "thiram", "start": 18, "end": 24}, {"text": "imidacloprid", "start": 29, "end": 41}]}}, "schema": []}
{"input": "These experiments highlight that the toxicity of pesticide-treated seeds is a factor to consider in the decline of birds in agricultural environments.", "output": {"entities": {}}, "schema": []}
{"input": "The role of adenosine receptors on amitriptyline-induced electrophysiological changes on rat atrium.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 12, "end": 21}, {"text": "amitriptyline", "start": 35, "end": 48}]}}, "schema": []}
{"input": "We investigated the role of adenosine receptors in amitriptyline-induced cardiac action potential (AP) changes in isolated rat atria.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 28, "end": 37}, {"text": "amitriptyline", "start": 51, "end": 64}]}}, "schema": []}
{"input": "In the first group, APs were recorded after cumulative addition of amitriptyline (1 mu M, 10 mu M and 50 mu M).", "output": {"entities": {"chemical": [{"text": "amitriptyline", "start": 67, "end": 80}]}}, "schema": []}
{"input": "In other groups, each atrium was incubated with selective adenosine A (1) antagonist (8-cyclopentyl-1, 3-dipropylxanthine (DPCPX), 10 (-4) M) or selective adenosine A (2a) receptor antagonist (8-(3-chlorostyryl) caffeine, 10 (-5) M) before amitriptyline administration.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 58, "end": 67}, {"text": "8-cyclopentyl-1, 3-dipropylxanthine", "start": 86, "end": 121}, {"text": "DPCPX", "start": 123, "end": 128}, {"text": "adenosine", "start": 155, "end": 164}, {"text": "8-(3-chlorostyryl) caffeine", "start": 193, "end": 220}, {"text": "amitriptyline", "start": 240, "end": 253}]}}, "schema": []}
{"input": "Resting membrane potential, AP amplitude (APA), AP duration at 50% and 80% of repolarization (APD (50) and APD (80), respectively), and the maximum rise and decay slopes of AP were recorded.", "output": {"entities": {}}, "schema": []}
{"input": "Amitriptyline (50 mu M) prolonged the APD (50) and APD (80) (p < 0. 001) and the maximum rise slope of AP was reduced by amitriptyline (p < 0. 0001).", "output": {"entities": {"chemical": [{"text": "Amitriptyline", "start": 0, "end": 13}, {"text": "amitriptyline", "start": 121, "end": 134}]}}, "schema": []}
{"input": "Amitriptyline reduced maximum decay slope of AP only at 50 mu M (p < 0. 01).", "output": {"entities": {"chemical": [{"text": "Amitriptyline", "start": 0, "end": 13}]}}, "schema": []}
{"input": "DPCPX significantly decreased the 50-mu M amitriptyline-induced APD (50) and APD (80) prolongation (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "DPCPX", "start": 0, "end": 5}, {"text": "amitriptyline", "start": 42, "end": 55}]}}, "schema": []}
{"input": "DPCPX significantly prevented the effects of amitriptyline (1 mu M and 50 mu M) on maximum rise slope of AP (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "DPCPX", "start": 0, "end": 5}, {"text": "amitriptyline", "start": 45, "end": 58}]}}, "schema": []}
{"input": "DPCPX significantly prevented the amitriptyline-induced (50 mu M) reduction in maximum decay slope of AP (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "DPCPX", "start": 0, "end": 5}, {"text": "amitriptyline", "start": 34, "end": 47}]}}, "schema": []}
{"input": "The selective adenosine A (1) receptor antagonist prevented the electrophysiological effects of amitriptyline on atrial AP.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 14, "end": 23}, {"text": "amitriptyline", "start": 96, "end": 109}]}}, "schema": []}
{"input": "A (1) receptor stimulation may be responsible for the cardiovascular toxic effects produced by amitriptyline.", "output": {"entities": {"chemical": [{"text": "amitriptyline", "start": 95, "end": 108}]}}, "schema": []}
{"input": "Single-agent duloxetine ingestions.", "output": {"entities": {"chemical": [{"text": "duloxetine", "start": 13, "end": 23}]}}, "schema": []}
{"input": "Duloxetine is a serotonin and norepinephrine reuptake inhibitor, which is mainly used to treat depression.", "output": {"entities": {"chemical": [{"text": "Duloxetine", "start": 0, "end": 10}, {"text": "serotonin", "start": 16, "end": 25}, {"text": "norepinephrine", "start": 30, "end": 44}]}}, "schema": []}
{"input": "This retrospective study describes the demographic and clinical effects of duloxetine ingestions reported to the National Poison Data System (NPDS).", "output": {"entities": {"chemical": [{"text": "duloxetine", "start": 75, "end": 85}]}}, "schema": []}
{"input": "NPDS data were searched for duloxetine exposures between 2004 and 2010.", "output": {"entities": {"chemical": [{"text": "duloxetine", "start": 28, "end": 38}]}}, "schema": []}
{"input": "A total of 11, 373 patients were included and exposures were divided into three groups of ages <= 6 years old, 7-12 years and > 12 years.", "output": {"entities": {}}, "schema": []}
{"input": "Neurological clinical effects occurred in 6. 1% of the patients aged <= 6 years, 13. 0% of the patients aged 7-12 years and 24. 6% of the patients aged > 12 years.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiovascular effects occurred in 1. 4% of the patients aged <= 6 years old, 2. 5% of the patients aged 7-12 years and 11. 6% of the patients aged > 12 years.", "output": {"entities": {}}, "schema": []}
{"input": "Gastrointestinal effects occurred in 4. 1% of the patients aged <= 6 years old, 16. 6% of the patients aged 7-12 years and 13. 8% of the patients aged > 12 years.", "output": {"entities": {}}, "schema": []}
{"input": "Tachycardia, nausea, vomiting, agitation/irritability, dizziness/vertigo and drowsiness were among the most common clinical effects in all three groups.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, 61. 4% of the patients aged <= 6 years and 77. 5% of the patients aged 7-12 years were managed in a non-health care facility, while 55. 8% of the patients aged > 12 years were referred to or already in a health care facility.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that the majority of ingestions are benign in both pediatrics and adults.", "output": {"entities": {}}, "schema": []}
{"input": "Most symptomatic patients have neurologic, gastrointestinal and cardiovascular effects.", "output": {"entities": {}}, "schema": []}
{"input": "Most pediatric patients will be able to be managed in a non-health care facility.", "output": {"entities": {}}, "schema": []}
{"input": "Spectral analysis of thioacetamide-induced electroencephalographic changes in rats.", "output": {"entities": {"chemical": [{"text": "thioacetamide", "start": 21, "end": 34}]}}, "schema": []}
{"input": "Thioacetamide (TAA) is widely used as a model of hepatic encephalopathy (HE).", "output": {"entities": {"chemical": [{"text": "Thioacetamide", "start": 0, "end": 13}, {"text": "TAA", "start": 15, "end": 18}]}}, "schema": []}
{"input": "The aim of our study was to investigate the effects of TAA on electroencephalographic (EEG) changes in rats and to compare them with human HE.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 55, "end": 58}]}}, "schema": []}
{"input": "Male Wistar rats were divided into groups: (1) saline-treated group and (2) TAA-treated groups: TAA (300) (300 mg/kg), TAA (600) (600 mg/kg), and TAA (900) (900 mg/kg).", "output": {"entities": {"chemical": [{"text": "TAA", "start": 76, "end": 79}, {"text": "TAA", "start": 96, "end": 99}, {"text": "TAA", "start": 119, "end": 122}, {"text": "TAA", "start": 146, "end": 149}]}}, "schema": []}
{"input": "Daily dose of TAA (300 mg/kg) was administered intraperitoneally once (TAA (300)), twice (TAA (600)), or thrice (TAA (900)) in subsequent days.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 14, "end": 17}, {"text": "TAA", "start": 71, "end": 74}, {"text": "TAA", "start": 90, "end": 93}, {"text": "TAA", "start": 113, "end": 116}]}}, "schema": []}
{"input": "EEG changes were recorded about 24 h after the last dose of TAA.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 60, "end": 63}]}}, "schema": []}
{"input": "Absolute and relative power density in alpha bands were significantly higher in TAA (300) versus control group.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 80, "end": 83}]}}, "schema": []}
{"input": "In TAA (300), absolute beta power density was higher and relative beta power density was lower versus control group.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 3, "end": 6}]}}, "schema": []}
{"input": "Absolute alpha, theta, delta, and relative theta power were significantly lower, while relative power in delta band was significantly higher in TAA (900) versus control group (p < 0. 01).", "output": {"entities": {"chemical": [{"text": "TAA", "start": 144, "end": 147}]}}, "schema": []}
{"input": "In conclusion, decrease in EEG voltage with an increase in delta relative power, which correspond to the EEG manifestations of severe HE in humans, was observed in TAA (900) group.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 164, "end": 167}]}}, "schema": []}
{"input": "Electrical activity in TAA (300) group correlates with mild HE in humans.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 23, "end": 26}]}}, "schema": []}
{"input": "The protective effect of recombinant human erythropoietin against cisplatin-induced renal and hepatic dysfunctions in Wistar rats.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 66, "end": 75}]}}, "schema": []}
{"input": "Cisplatin (Cisp) is one of the most effective chemotherapeutic drugs.", "output": {"entities": {"chemical": [{"text": "Cisplatin", "start": 0, "end": 9}, {"text": "Cisp", "start": 11, "end": 15}]}}, "schema": []}
{"input": "However, the dose of Cisp is greatly limited by its toxicity.", "output": {"entities": {"chemical": [{"text": "Cisp", "start": 21, "end": 25}]}}, "schema": []}
{"input": "Recombinant human erythropoietin (rhEPO), a hormone that regulates hematopoiesis, has also been shown to exert tissue-protective effects.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to explore the protective effect of rhEPO against Cisp-induced renal and liver dysfunctions.", "output": {"entities": {"chemical": [{"text": "Cisp", "start": 80, "end": 84}]}}, "schema": []}
{"input": "Adult male Wistar rats were divided into six groups of six each: control, rhEPO-alone group, Cisp-alone group and rhEPO + Cisp group (pretreatment, cotreatment and posttreatment conditions).", "output": {"entities": {"chemical": [{"text": "Cisp", "start": 93, "end": 97}, {"text": "Cisp", "start": 122, "end": 126}]}}, "schema": []}
{"input": "Our results showed that Cisp-induced a marked renal and liver failure characterized by a significant decrease in body weight, organ weight and organ ratio and a significant increase in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, G-glutamyl transferase, alkaline phosphatase, bilirubin conjugated and bilirubin total levels in serum.", "output": {"entities": {"chemical": [{"text": "Cisp", "start": 24, "end": 28}, {"text": "creatinine", "start": 185, "end": 195}, {"text": "urea nitrogen", "start": 203, "end": 216}, {"text": "alanine", "start": 218, "end": 225}, {"text": "aspartate", "start": 244, "end": 253}, {"text": "bilirubin", "start": 318, "end": 327}, {"text": "bilirubin", "start": 343, "end": 352}]}}, "schema": []}
{"input": "Histological examination showed that Cisp caused kidney alterations.", "output": {"entities": {"chemical": [{"text": "Cisp", "start": 37, "end": 41}]}}, "schema": []}
{"input": "rhEPO treatments restored body weight, organ weight and organ ratio as well as serum biochemical parameters changed due to Cisp exposure.", "output": {"entities": {"chemical": [{"text": "Cisp", "start": 123, "end": 127}]}}, "schema": []}
{"input": "Effects of increasing supplementation of magnesium in diets on productive performance and eggshell quality of aged laying hens.", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 41, "end": 50}]}}, "schema": []}
{"input": "Magnesium (Mg) concentrations in diets have been associated with performance and eggshell quality of laying hens, but the results have been inconclusive.", "output": {"entities": {"chemical": [{"text": "Magnesium", "start": 0, "end": 9}, {"text": "Mg", "start": 11, "end": 13}]}}, "schema": []}
{"input": "In this experiment, the effects of increasing concentrations of dietary Mg on productive performance and eggshell quality of aged laying hens were evaluated.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 72, "end": 74}]}}, "schema": []}
{"input": "A total of 640 Hy-Line Brown laying hens of 72 weeks of age were randomly allotted to one of four dietary treatments with four replicates per treatment.", "output": {"entities": {}}, "schema": []}
{"input": "A commercial-type basal diet containing 1. 6 g/kg Mg was prepared, and three additional diets were prepared to contain 2. 3, 2. 6, or 3. 0 g/kg Mg in diets by adding 1. 0, 1. 5, or 2. 0 g of MgO to the basal diet.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 50, "end": 52}, {"text": "Mg", "start": 144, "end": 146}, {"text": "MgO", "start": 191, "end": 194}]}}, "schema": []}
{"input": "The diets were fed to hens ad libitum for 5 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Results indicated that Mg concentrations in eggshells were increased (linear, P < 0. 01) with increasing concentrations of Mg in diets.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 23, "end": 25}, {"text": "Mg", "start": 123, "end": 125}]}}, "schema": []}
{"input": "Increasing concentrations of Mg in diets decreased (linear and quadratic, P < 0. 01) broken and shell-less egg production, but improved (linear, P < 0. 05) eggshell strength.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 29, "end": 31}]}}, "schema": []}
{"input": "Feed intake was decreased (linear, P < 0. 05) with the concentrations of Mg in diets, but hen-day egg production, egg weight, feed conversion ratio, and Haugh unit were not affected by increasing concentrations of Mg in diets.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 73, "end": 75}, {"text": "Mg", "start": 214, "end": 216}]}}, "schema": []}
{"input": "Hunter L * and a * values of eggshell were decreased (linear, P < 0. 05) as the concentrations of Mg in diets increased.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 98, "end": 100}]}}, "schema": []}
{"input": "In conclusion, feeding aged laying hens with diets containing increasing concentrations of Mg up to 3. 0 g/kg improves eggshell strength, but has no detrimental effects on laying performance.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 91, "end": 93}]}}, "schema": []}
{"input": "Unifying protein inference and peptide identification with feedback to update consistency between peptides.", "output": {"entities": {}}, "schema": []}
{"input": "We first propose a new method to process peptide identification reports from databases search engines.", "output": {"entities": {}}, "schema": []}
{"input": "Then via it we develop a method for unifying protein inference and peptide identification by adding a feedback from protein inference to peptide identification.", "output": {"entities": {}}, "schema": []}
{"input": "The feedback information is a list of high-confidence proteins, which is used to update an adjacency matrix between peptides.", "output": {"entities": {}}, "schema": []}
{"input": "The adjacency matrix is used in the regularization of peptide scores.", "output": {"entities": {}}, "schema": []}
{"input": "Logistic regression (LR) is used to compute the probability of peptide identification with the regularized scores.", "output": {"entities": {}}, "schema": []}
{"input": "Protein scores are then calculated with the LR probability of peptides.", "output": {"entities": {}}, "schema": []}
{"input": "Instead of selecting the best peptide match for each MS/MS, we select multiple peptides.", "output": {"entities": {}}, "schema": []}
{"input": "By testing on two datasets, the results have shown that the proposed method can robustly assign accurate probabilities to peptides, and have a higher discrimination power than PeptideProphet to distinguish correct and incorrect identified peptides.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, not only can our method infer more true positive proteins but also infer less false positive proteins than ProteinProphet at the same false positive rate.", "output": {"entities": {}}, "schema": []}
{"input": "The coverage of inferred proteins is also significantly increased due to the selection of multiple peptides for each MS/MS and the improvement of their scores by the feedback from the inferred proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Novel insights on the effect of nicotine in a murine colitis model.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 32, "end": 40}]}}, "schema": []}
{"input": "Studies showed that nicotine has a positive influence on symptoms of ulcerative colitis.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 20, "end": 28}]}}, "schema": []}
{"input": "In the present study, we explored the effect of nicotine treatment using different routes of administration in the dextran sodium sulfate (DSS) colitis mouse model.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 48, "end": 56}, {"text": "sodium sulfate", "start": 123, "end": 137}]}}, "schema": []}
{"input": "We also investigated the effects of cotinine, a major metabolite of nicotine, in the model.", "output": {"entities": {"chemical": [{"text": "cotinine", "start": 36, "end": 44}, {"text": "nicotine", "start": 68, "end": 76}]}}, "schema": []}
{"input": "C57BL6 adult male mice were given DSS solution freely in the drinking water for seven consecutive days, and tap water was given thereafter.", "output": {"entities": {}}, "schema": []}
{"input": "Disease severity, length of the colon, colon tissue histology, and inflammatory markers, including colonic myeloperoxidase activity and colonic tumor necrosis factor-alpha levels, were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of nicotine and cotinine treatments via various different routes of administration were examined the DSS model.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 14, "end": 22}, {"text": "cotinine", "start": 27, "end": 35}]}}, "schema": []}
{"input": "In addition, we measured the plasma levels of nicotine and cotinine in our treatment protocols.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 46, "end": 54}, {"text": "cotinine", "start": 59, "end": 67}]}}, "schema": []}
{"input": "Administration of low, but not high, doses of oral nicotine in DSS-treated mice resulted in a significant decrease in disease severity, histologic damage scores, as well as colonic level of tumor necrosis factor-alpha.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 51, "end": 59}]}}, "schema": []}
{"input": "However, the anti-inflammatory effect of nicotine was not seen after chronic s. c. or minipump infusion of the drug.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 41, "end": 49}]}}, "schema": []}
{"input": "Differences in plasma levels of nicotine and cotinine do not seem to account for this lack of effect.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 32, "end": 40}, {"text": "cotinine", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Finally, oral cotinine alone failed to show a significant effect in the DSS model of colitis.", "output": {"entities": {"chemical": [{"text": "cotinine", "start": 14, "end": 22}]}}, "schema": []}
{"input": "These results highlight that dose and route of administration play a critical role in the protective effect of nicotine in the DSS mouse colitis model.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 111, "end": 119}]}}, "schema": []}
{"input": "Androgen receptor CAG repeat length modifies the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin on receptor activity in human prostate cells.", "output": {"entities": {"chemical": [{"text": "Androgen", "start": 0, "end": 8}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 59, "end": 97}]}}, "schema": []}
{"input": "Increased incidence of prostate cancer has been reported in men exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 75, "end": 113}, {"text": "TCDD", "start": 115, "end": 119}]}}, "schema": []}
{"input": "TCDD acts through the aryl hydrocarbon receptor (AhR), which interacts with the androgen receptor (AR).", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}, {"text": "aryl hydrocarbon", "start": 22, "end": 38}, {"text": "androgen", "start": 80, "end": 88}]}}, "schema": []}
{"input": "The AR gene contains a polymorphic CAG repeat that influences its transcriptional activity.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the influence of TCDD on prostate cancer cells (PC-3) and non-tumor prostate cells (PNT1A) on 5 alpha-dihydrotestosterone-activated ARs containing CAG repeats within normal length range (16, 22, and 28).", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 33, "end": 37}, {"text": "5 alpha-dihydrotestosterone", "start": 110, "end": 137}]}}, "schema": []}
{"input": "The AhR target gene CYP1A1 mRNA expression was induced by TCDD, but was not affected by the AR CAG length.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 58, "end": 62}]}}, "schema": []}
{"input": "TCDD had no effect on AR activity in PC-3 cells, whereas the shortest AR variant was induced by TCDD in PNT1A cells.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}, {"text": "TCDD", "start": 96, "end": 100}]}}, "schema": []}
{"input": "In conclusion, the CAG length dependent effect of TCDD on AR activity in PNT1A, but not in PC-3 cells, indicates as a cell-specific effect of TCDD on AR activity.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 50, "end": 54}, {"text": "TCDD", "start": 142, "end": 146}]}}, "schema": []}
{"input": "The S349T mutation of SQSTM1 links Keap1/Nrf2 signalling to Paget' s disease of bone.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations affecting the Sequestosome 1 (SQSTM1) gene commonly occur in patients with the skeletal disorder Paget' s disease of bone (PDB), a condition characterised by defective osteoclast differentiation and function.", "output": {"entities": {}}, "schema": []}
{"input": "Whilst most mutations cluster within the ubiquitin-associated (UBA) domain of the SQSTM1 protein, and are associated with dysregulated NF kappa B signalling, several non-UBA domain mutations have also been identified.", "output": {"entities": {}}, "schema": []}
{"input": "Keap1 is a SQSTM1-interacting protein that regulates the levels and activity of the Nrf2 transcription factor.", "output": {"entities": {}}, "schema": []}
{"input": "This in turn controls the expression of numerous cytoprotective genes that contribute to the cell' s capacity to defend itself against chemical and oxidative stress, through binding to the antioxidant response element (ARE).", "output": {"entities": {}}, "schema": []}
{"input": "The PDB-associated S349T mutation maps to the Keap1-interacting region (KIR) of SQSTM1, however the effects of PDB mutant SQSTM1 on Keap1 function have not been investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that unlike other SQSTM1 mutations, the S349T mutation results in neither impaired ubiquitin-binding function in pull-down assays, nor dysregulated NF kappa B signalling in luciferase reporter assays.", "output": {"entities": {}}, "schema": []}
{"input": "Keap1 is expressed in differentiating osteoclast-like cells and the S349T mutation selectively impairs the SQSTM1-Keap1 interaction in co-immunoprecipitations, which molecular modelling indicates results from effects on critical hydrogen bonds required to stabilise the KIR-Keap1 complex.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 229, "end": 237}]}}, "schema": []}
{"input": "Further, S349T mutant SQSTM1, but not other PDB-associated mutants, showed reduced ability to activate Nrf2 signalling as assessed by ARE-luciferase reporter assays.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, SQSTM1-mediated dysregulation of the Keap1-Nrf2 axis, which could potentially lead to aberrant production of oxidative response genes, may contribute to disease aetiology in a subset of PDB patients.", "output": {"entities": {}}, "schema": []}
{"input": "Adaptive radiation-induced epigenetic alterations mitigated by antioxidants.", "output": {"entities": {}}, "schema": []}
{"input": "Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome.", "output": {"entities": {}}, "schema": []}
{"input": "Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (A (vy)) locus in a sex-specific manner (P = 0. 004).", "output": {"entities": {}}, "schema": []}
{"input": "Average DNA methylation was significantly increased in male offspring exposed to doses between 0. 7 and 7. 6 cGy, with maximum effects at 1. 4 and 3. 0 cGy (P < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "Offspring coat color was concomitantly shifted toward pseudoagouti (P < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "These findings provide evidence that in the isogenic A (vy) mouse model, epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful.", "output": {"entities": {}}, "schema": []}
{"input": "Structural asymmetry in the Thermus thermophilus RuvC dimer suggests a basis for sequential strand cleavages during Holliday junction resolution.", "output": {"entities": {}}, "schema": []}
{"input": "Holliday junction (HJ) resolvases are structure-specific endonucleases that cleave four-way DNA junctions (HJs) generated during DNA recombination and repair.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterial RuvC, a prototypical HJ resolvase, functions as homodimer and nicks DNA strands precisely across the junction point.", "output": {"entities": {}}, "schema": []}
{"input": "To gain insights into the mechanisms underlying symmetrical strand cleavages by RuvC, we performed crystallographic and biochemical analyses of RuvC from Thermus thermophilus (T. th. RuvC).", "output": {"entities": {}}, "schema": []}
{"input": "The crystal structure of T. th.", "output": {"entities": {}}, "schema": []}
{"input": "RuvC shows an overall protein fold similar to that of Escherichia coli RuvC, but T. th.", "output": {"entities": {}}, "schema": []}
{"input": "RuvC has a more tightly associated dimer interface possibly reflecting its thermostability.", "output": {"entities": {}}, "schema": []}
{"input": "The binding mode of a HJ-DNA substrate can be inferred from the shape/charge complementarity between the T. th.", "output": {"entities": {}}, "schema": []}
{"input": "RuvC dimer and HJ-DNA, as well as positions of sulfate ions bound on the protein surface.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 47, "end": 54}]}}, "schema": []}
{"input": "Unexpectedly, the structure of T. th.", "output": {"entities": {}}, "schema": []}
{"input": "RuvC homodimer refined at 1. 28 A resolution shows distinct asymmetry near the dimer interface, in the region harboring catalytically important aromatic residues.", "output": {"entities": {}}, "schema": []}
{"input": "The observation suggests that the T. th.", "output": {"entities": {}}, "schema": []}
{"input": "RuvC homodimer interconverts between two asymmetric conformations, with alternating subunits switched on for DNA strand cleavage.", "output": {"entities": {}}, "schema": []}
{"input": "This model provides a structural basis for the' nick-counter-nick' mechanism in HJ resolution, a mode of HJ processing shared by prokaryotic and eukaryotic HJ resolvases.", "output": {"entities": {}}, "schema": []}
{"input": "Metal bioavailability from different natural prey to a marine predator Nassarius siquijorensis.", "output": {"entities": {}}, "schema": []}
{"input": "Gastropods are often the top predators in marine benthic environments, and trophic transfer is the predominant route by which metals are accumulated in these predators.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, the potential influences of prey composition on the trophic transfer, accumulation, subcellular distribution and metallothionein induction of six metals (Ag, As, Cd, Cu, Pb and Zn) in a predator Nassarius siquijorensis were investigated.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 176, "end": 178}, {"text": "As", "start": 180, "end": 182}, {"text": "Cd", "start": 184, "end": 186}, {"text": "Cu", "start": 188, "end": 190}, {"text": "Pb", "start": 192, "end": 194}, {"text": "Zn", "start": 199, "end": 201}]}}, "schema": []}
{"input": "The snails were fed venerid clams Ruditapes philippinarum, mussels Perna viridis, oysters Crassostrea angulata or barnacles Fistulobalanus albicostatus, each differing greatly in their metal accumulation and handling patterns.", "output": {"entities": {}}, "schema": []}
{"input": "N. siquijorensis showed prey-specific bioaccumulation and trophic transfer of the six metals.", "output": {"entities": {}}, "schema": []}
{"input": "In general, the body burdens of metals in the viscera and muscles of N. siquijorensis increased with increasing exposure period and metal concentration in the four prey.", "output": {"entities": {}}, "schema": []}
{"input": "The calculated trophic transfer factors (TTFs) of the metals in different prey varied and were the highest for clams and mussels prey, indicating that metal bioavailability from these prey was higher than that from barnacles and oysters.", "output": {"entities": {}}, "schema": []}
{"input": "All the studied metals except Pb were enriched during transfer to the snails.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 30, "end": 32}]}}, "schema": []}
{"input": "The subcellular metal distribution in the viscera was affected by prey composition.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to the four natural prey induced MTs, which may be used as a better biomarker for muscle than for viscera for metal stress.", "output": {"entities": {}}, "schema": []}
{"input": "Our results imply that metals from different natural prey have different bioavailability and may help better understand the trophic transfer of metals in marine benthic food chain.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitory effect of aqueous spinach extract on degranulation of RBL-2H3 cells.", "output": {"entities": {}}, "schema": []}
{"input": "The inhibitory effect of an aqueous extract from spinach on degranulation of RBL-2H3 cells is herein reported.", "output": {"entities": {}}, "schema": []}
{"input": "The extract significantly suppressed antigen-induced degranulation in a dose-dependent manner without affecting cell viability.", "output": {"entities": {}}, "schema": []}
{"input": "Active substances in the extract were heat-stable and trypsin-resistant with molecular weights ranging from 500 Da to 14 kDa.", "output": {"entities": {}}, "schema": []}
{"input": "The extract inhibited elevation of the intracellular Ca (2 +) concentration caused by stimulation by antigen, while not suppressing degranulation induced by a calcium ionophore A23187.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 53, "end": 61}, {"text": "calcium", "start": 159, "end": 166}, {"text": "A23187", "start": 177, "end": 183}]}}, "schema": []}
{"input": "Immunoblot analysis revealed that the inhibitory effect results from downregulation of phosphorylation of both Syk kinase and phosphatidylinositol 3-kinase in the signalling pathways involved in degranulation caused by the antigen-antibody interaction.", "output": {"entities": {"chemical": [{"text": "phosphatidylinositol", "start": 126, "end": 146}]}}, "schema": []}
{"input": "Taken together, these findings suggest that aqueous spinach extract has an anti-allergic activity that controls degranulation.", "output": {"entities": {}}, "schema": []}
{"input": "Anthraquinone profile, antioxidant and antimicrobial activity of bark extracts of Rhamnus alaternus, R. fallax, R. intermedia and R. pumila.", "output": {"entities": {"chemical": [{"text": "Anthraquinone", "start": 0, "end": 13}]}}, "schema": []}
{"input": "The quantity of phenols, as well as antioxidant and antimicrobial activities, were investigated in bark of Rhamnus alaternus L., R. fallax Boiss., R. intermedia Steud.", "output": {"entities": {"chemical": [{"text": "phenols", "start": 16, "end": 23}]}}, "schema": []}
{"input": "et Hochst., and R. pumila Turra from natural stands in Croatia.", "output": {"entities": {}}, "schema": []}
{"input": "The most abundant anthraquinones in the investigated extracts were chrysophanol in R. alaternus (3. 14 mg/g), emodin in R. pumila (0. 339 mg/g), and physcion in R. fallax (2. 70 mg/g) and R. intermedia (0. 285 mg/g).", "output": {"entities": {"chemical": [{"text": "anthraquinones", "start": 18, "end": 32}, {"text": "chrysophanol", "start": 67, "end": 79}, {"text": "emodin", "start": 110, "end": 116}, {"text": "physcion", "start": 149, "end": 157}]}}, "schema": []}
{"input": "The species exhibiting the highest antioxidant activity were R. fallax and R. pumila.", "output": {"entities": {}}, "schema": []}
{"input": "A positive correlation was observed between total phenolic and flavonoid levels of the extracts and antioxidant activity in some of the assays.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 50, "end": 58}, {"text": "flavonoid", "start": 63, "end": 72}]}}, "schema": []}
{"input": "All species showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Aspergillus niger and Microsporum gypseum with minimal inhibitory concentrations equal to or below 2. 500 mg/mL.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that the investigated Rhamnus species are a source of anthraquinones and other phenols, which act as multifunctional antioxidants with antimicrobial activity.", "output": {"entities": {"chemical": [{"text": "anthraquinones", "start": 75, "end": 89}, {"text": "phenols", "start": 100, "end": 107}]}}, "schema": []}
{"input": "Syzygium aqueum leaf extract and its bioactive compounds enhances pre-adipocyte differentiation and 2-NBDG uptake in 3T3-L1 cells.", "output": {"entities": {"chemical": [{"text": "2-NBDG", "start": 100, "end": 106}]}}, "schema": []}
{"input": "The insulin-like and/or insulin-sensitising effects of Syzygium aqueum leaf extract and its six bioactive compounds; 4-hydroxybenzaldehyde, myricetin-3-O-rhamnoside, europetin-3-O-rhamnoside, phloretin, myrigalone-G and myrigalone-B were investigated in 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "4-hydroxybenzaldehyde", "start": 117, "end": 138}, {"text": "myricetin-3-O-rhamnoside", "start": 140, "end": 164}, {"text": "europetin-3-O-rhamnoside", "start": 166, "end": 190}, {"text": "phloretin", "start": 192, "end": 201}, {"text": "myrigalone-G", "start": 203, "end": 215}, {"text": "myrigalone-B", "start": 220, "end": 232}]}}, "schema": []}
{"input": "We observed that, S. aqueum leaf extract (0. 04-5 mu g/ml) and its six bioactive compounds (0. 08-10 mu M) at non-cytotoxic concentrations were effectively enhance adipogenesis, stimulate glucose uptake and increase adiponectin secretion in 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 188, "end": 195}]}}, "schema": []}
{"input": "Clearly, the compounds myricetin-3-O-rhamnoside and europetin-3-O-rhamnoside showed insulin-like and insulin-sensitising effects on adipocytes from a concentration of 0. 08 mu M.", "output": {"entities": {"chemical": [{"text": "myricetin-3-O-rhamnoside", "start": 23, "end": 47}, {"text": "europetin-3-O-rhamnoside", "start": 52, "end": 76}]}}, "schema": []}
{"input": "These compounds were far better than rosiglitazone and the other isolated compounds in enhancing adipogenesis, stimulating 2-NBDG uptake and increasing adiponectin secretion at all the concentrations tested.", "output": {"entities": {"chemical": [{"text": "rosiglitazone", "start": 37, "end": 50}, {"text": "2-NBDG", "start": 123, "end": 129}]}}, "schema": []}
{"input": "These suggest the antidiabetic potential of S. aqueum leaf extract and its six bioactive compounds.", "output": {"entities": {}}, "schema": []}
{"input": "However, further molecular interaction studies to explain the mechanisms of action are highly warranted.", "output": {"entities": {}}, "schema": []}
{"input": "An improved mass spectrometric method for identification and quantification of phenolic compounds in apple fruits.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 79, "end": 87}]}}, "schema": []}
{"input": "Thirty-nine phenolic compounds were analysed using ultra high performance liquid chromatography (UHPLC) coupled with diode array and accurate mass spectrometry detection using electrospray ionisation (DAD/ESI-am-MS).", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 12, "end": 20}]}}, "schema": []}
{"input": "Instrumental parameters such as scan speed, resolution, and mass accuracy were optimised to establish accurate mass measurements.", "output": {"entities": {}}, "schema": []}
{"input": "The method was fully validated in terms of model deviation (r (2) > 0. 9990), range (typically 10-3500 ngg (-1)), intra/inter-day precision (< 6% and < 8%, respectively) and accuracy (typically 100 +/- 10%).", "output": {"entities": {}}, "schema": []}
{"input": "The mass accuracy of each selected phenolic compound was below 1. 5 ppm.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 35, "end": 43}]}}, "schema": []}
{"input": "The results confirmed that the UHPLC-DAD/ESI-am-MS method developed here was convenient and reliable for the determination of phenolic compounds in apple extracts.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 126, "end": 134}]}}, "schema": []}
{"input": "Identification of active compounds in vegetal extracts based on correlation between activity and HPLC-MS data.", "output": {"entities": {}}, "schema": []}
{"input": "We propose a method identifying candidates for active compounds in vegetal extracts.", "output": {"entities": {}}, "schema": []}
{"input": "From a collection of samples, the method requires, for each sample, a HPLC-MS analysis and a measurement of the activity.", "output": {"entities": {}}, "schema": []}
{"input": "By applying a correlation analysis between the activity and the chromatographic area for each interval of elution time and m/z ratio, the peaks corresponding to candidates for active compounds can be identified.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, when peaks are identified, a model can be estimated to predict the activity in new samples.", "output": {"entities": {}}, "schema": []}
{"input": "Both methods are evaluated in one experiment involving the phenolic extract (PE) from 22 samples of extra virgin olive oil (EVOO) where the activity is a cytotoxicity index against JIMT-1 breast cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "In this experiment, the samples were separated into two disjunct partitions: one was used for training (identification of candidates and estimation of prediction model), while the other was used for validation (by comparing the predicted and the measured activities).", "output": {"entities": {}}, "schema": []}
{"input": "Three compounds were identified as candidates to be responsible for the cytotoxicity of the EVOO-PE against JIMT-1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "The prediction model provided an accurate estimation of the activity.", "output": {"entities": {}}, "schema": []}
{"input": "Phillyrin attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of LKB1/AMP-activated protein kinase-dependent signalling.", "output": {"entities": {"chemical": [{"text": "Phillyrin", "start": 0, "end": 9}, {"text": "glucose", "start": 26, "end": 33}, {"text": "AMP", "start": 119, "end": 122}]}}, "schema": []}
{"input": "Phillyrin, an active constituent found in many medicinal plants and certain functional foods, has anti-obesity activity in vivo.", "output": {"entities": {"chemical": [{"text": "Phillyrin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The aim of our study was to provide new data on the molecular mechanism (s) underlying the role of phillyrin in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes.", "output": {"entities": {"chemical": [{"text": "phillyrin", "start": 99, "end": 108}, {"text": "glucose", "start": 135, "end": 142}]}}, "schema": []}
{"input": "We found that phillyrin suppressed high glucose-induced lipid accumulation in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "phillyrin", "start": 14, "end": 23}, {"text": "glucose", "start": 40, "end": 47}]}}, "schema": []}
{"input": "Phillyrin strongly inhibited high glucose-induced fatty acid synthase (FAS) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation.", "output": {"entities": {"chemical": [{"text": "Phillyrin", "start": 0, "end": 9}, {"text": "glucose", "start": 34, "end": 41}, {"text": "fatty acid", "start": 50, "end": 60}, {"text": "sterol", "start": 101, "end": 107}]}}, "schema": []}
{"input": "Moreover, use of the pharmacological AMP-activated protein kinase (AMPK) inhibitor compound C revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells.", "output": {"entities": {"chemical": [{"text": "AMP", "start": 37, "end": 40}, {"text": "compound C", "start": 83, "end": 93}, {"text": "phillyrin", "start": 165, "end": 174}]}}, "schema": []}
{"input": "Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the phillyrin-enhanced activation of AMPK in HepG2 hepatocytes.", "output": {"entities": {"chemical": [{"text": "phillyrin", "start": 82, "end": 91}]}}, "schema": []}
{"input": "These results indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.", "output": {"entities": {"chemical": [{"text": "phillyrin", "start": 28, "end": 37}, {"text": "phillyrin", "start": 174, "end": 183}]}}, "schema": []}
{"input": "Physicochemical parameters that influence carotenoids bioaccessibility from a tomato juice.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro digestion models have been developed to estimate carotenoid bioavailability but most do not consider that their diffusion from fruit matrix to the lipid phase of the bolus could be a limiting step.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore we designed a model in which tomato juice is mixed with oil or oil/water emulsions, and the carotenoids diffusing to oil are measured by spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Temperature, pH and tomato juice/peanut oil ratio were evaluated for their influence on carotenoid diffusion.", "output": {"entities": {}}, "schema": []}
{"input": "When oil/tomato ratio was between 0. 11 and 1, extraction of lycopene was limited by the saturation of the oil phase.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 61, "end": 69}]}}, "schema": []}
{"input": "With a large excess of oil, diffusion was also limited, as only 31 +/- 1% of lycopene could be extracted from the juice.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 77, "end": 85}]}}, "schema": []}
{"input": "Diffusion did not vary significantly with pH but doubled when temperature rose from 10 degrees C to 37 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "When the juice was mixed in an emulsion stabilised with bovine serum albumin or phospholipids the maximum extraction decreased to 14. 5 +/- 0. 2% and 18. 5 +/- 1. 5% respectively, indicating that in addition to the saturation of the oil phase at low oil/tomato ratio and in addition to intrinsic properties of the tomato juice in non-saturating conditions, lycopene diffusion was limited by the structure of the interface in emulsions.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 357, "end": 365}]}}, "schema": []}
{"input": "Effect of heat treatments on the essential oils of kumquat (Fortunella margarita Swingle).", "output": {"entities": {}}, "schema": []}
{"input": "Kumquats (Fortunella margarita Swingle) cultivated in Taiwan are eaten raw or made into candied fruit or fruit tea.", "output": {"entities": {}}, "schema": []}
{"input": "For the experiments described in this paper, essential oils were obtained from kumquat peels or whole fruit by cold pressing, steam distillation or heating in water at 90 degrees C for 15 min followed by steam distillation.", "output": {"entities": {}}, "schema": []}
{"input": "The volatile components contained in the essential oils were identified by direct injection (DI) or headspace-solid phase microextraction (HS-SPME) coupled with gas chromatography (GC).", "output": {"entities": {}}, "schema": []}
{"input": "A total of 43 compounds were identified, of which 37 were verified by DI/GC and 31 by HS-SPME/GC.", "output": {"entities": {}}, "schema": []}
{"input": "Hot water heating increased the yields of essential oils from both peels and whole fruit.", "output": {"entities": {}}, "schema": []}
{"input": "The principal constituents of the oils were similar except for the minor compounds, including linalool, terpinen-4-ol and alpha-terpineol, the levels of which increased after steam distillation.", "output": {"entities": {"chemical": [{"text": "linalool", "start": 94, "end": 102}, {"text": "terpinen-4-ol", "start": 104, "end": 117}, {"text": "alpha-terpineol", "start": 122, "end": 137}]}}, "schema": []}
{"input": "The whole fruit also contained higher levels of terpene alcohols.", "output": {"entities": {"chemical": [{"text": "terpene alcohols", "start": 48, "end": 64}]}}, "schema": []}
{"input": "Salicylic acid-induced elicitation of folates in coriander (Coriandrum sativum L.) improves bioaccessibility and reduces pro-oxidant status.", "output": {"entities": {"chemical": [{"text": "Salicylic acid", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Foliage of Coriandrum sativum is a rich source of natural folates amenable for enhancement through salicylic acid-mediated elicitation, thereby holding a great promise for natural-mode alleviation of this vitamin (B (9)) deficiency.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 99, "end": 113}, {"text": "vitamin (B (9))", "start": 205, "end": 220}]}}, "schema": []}
{"input": "In the present study we report salicylic acid-mediated differential elicitation of different forms of folates-5-methyltetrahydrofolate, 5-formyltetrahydrofolate and 10-formyltetrahydrofolate-their stabilities during microwave-drying and bioaccessibilities from fresh and dried foliage.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 31, "end": 45}, {"text": "folates", "start": 102, "end": 109}, {"text": "5-methyltetrahydrofolate", "start": 110, "end": 134}, {"text": "5-formyltetrahydrofolate", "start": 136, "end": 160}, {"text": "10-formyltetrahydrofolate", "start": 165, "end": 190}]}}, "schema": []}
{"input": "The first two compounds nearly doubled and the third increased sixfold post-elicitation, with all three showing concomitant increase in bioaccessibilities.", "output": {"entities": {}}, "schema": []}
{"input": "Although a slight decrease in bioaccessibility was observed in dried foliage, over twofold increase of each form of folate upon elicitation would deliver much higher levels of natural folates from this traditional culinary foliage, which is widely used in many cuisines.", "output": {"entities": {}}, "schema": []}
{"input": "Elicitor-mediated folate enhancement also imparted reduction of oxidative status and the enhancement of antioxidant enzyme activities in coriander foliage.", "output": {"entities": {}}, "schema": []}
{"input": "Short-term comparative study of the influence of fried edible oils intake on the metabolism of essential fatty acids in obese individuals.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 105, "end": 116}]}}, "schema": []}
{"input": "The effect of breakfast intake of fried oils containing natural antioxidants or a synthetic autooxidation inhibitor on the metabolism of essential fatty acids focused on obese individuals.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 147, "end": 158}]}}, "schema": []}
{"input": "Serum levels of eicosanoids were compared in individuals before and after intake of different breakfasts.", "output": {"entities": {"chemical": [{"text": "eicosanoids", "start": 16, "end": 27}]}}, "schema": []}
{"input": "Univariate descriptive analysis was used to characterise the cohort selected for this study and multivariate analysis to reveal statistical differences of normalised eicosanoids concentrations (determined by solid-phase extraction coupled to LC-MS/MS) depending on the edible oil used for breakfast preparation.", "output": {"entities": {"chemical": [{"text": "eicosanoids", "start": 166, "end": 177}]}}, "schema": []}
{"input": "The results showed that the intake of breakfast prepared with pure sunflower oil subjected to deep frying causes an effect over the eicosanoids profile that enables discrimination versus the rest of individuals.", "output": {"entities": {"chemical": [{"text": "eicosanoids", "start": 132, "end": 143}]}}, "schema": []}
{"input": "The effect was a significant increase in the concentration of hydroxyoctadecadienoic acid (HODE) metabolites, indicative markers of the intake of fried oils.", "output": {"entities": {"chemical": [{"text": "hydroxyoctadecadienoic acid", "start": 62, "end": 89}, {"text": "HODE", "start": 91, "end": 95}]}}, "schema": []}
{"input": "The concentration of HODE metabolites was lower when the oil contained either natural antioxidants from olive-oil pomace or a synthetic autooxidation inhibitor as dimethylsiloxane.", "output": {"entities": {"chemical": [{"text": "HODE", "start": 21, "end": 25}, {"text": "dimethylsiloxane", "start": 163, "end": 179}]}}, "schema": []}
{"input": "The comparison of the effect of fried sunflower oils with fried extra virgin olive oil shows the benefits associated to the consumption of the latter.", "output": {"entities": {}}, "schema": []}
{"input": "Comprehensive analysis of Phyteuma orbiculare L., a wild Alpine food plant.", "output": {"entities": {}}, "schema": []}
{"input": "Plants which have been traditionally eaten by the alpine population may provide new opportunities for agricultural development in mountain regions.", "output": {"entities": {}}, "schema": []}
{"input": "In this context we have investigated the chemical composition of Phyteuma orbiculare (Campanulaceae), a perennial herb whose leaves have been eaten as salad by rural populations in Valais (Switzerland).", "output": {"entities": {}}, "schema": []}
{"input": "Extracts of different polarities were subjected to comprehensive metabolite profiling using a dereplication platform combining HPLC-PDA-MS, and offline NMR analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-three compounds, including various phenolic glycosides, a new dimeric phenylpropanoid glucoside, saponins, and fatty acids were identified online, or after targeted isolation.", "output": {"entities": {"chemical": [{"text": "phenolic glycosides", "start": 42, "end": 61}, {"text": "phenylpropanoid glucoside", "start": 77, "end": 102}, {"text": "saponins", "start": 104, "end": 112}, {"text": "fatty acids", "start": 118, "end": 129}]}}, "schema": []}
{"input": "Selected phenolic constituents were quantitatively assessed by HPLC-PDA analysis.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, substances relevant for nutrition, such as beta-carotene, fatty acids, ascorbic acid and minerals were quantified in leaves and flowers.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 56, "end": 69}, {"text": "fatty acids", "start": 71, "end": 82}, {"text": "ascorbic acid", "start": 84, "end": 97}]}}, "schema": []}
{"input": "The antioxidant capacity was determined with an ORAC assay, and total phenolic compounds were quantified.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 70, "end": 78}]}}, "schema": []}
{"input": "Finally, the phytochemical profile was compared to that of the related species P. spicatum, P. hemisphaericum and P. ovatum.", "output": {"entities": {}}, "schema": []}
{"input": "Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "Neferine", "start": 0, "end": 8}, {"text": "oxygen", "start": 26, "end": 32}]}}, "schema": []}
{"input": "Evidence has accumulated concerning the medicinal application of Nelumbo nucifera in the treatment of various diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Neferine, an alkaloid from N. nucifera was found to exert cytotoxicity on liver cancer cells HepG2 in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "Neferine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "We evaluated its anticancer potential by studying its effect on mitochondrial membrane potential, intracellular calcium levels [Ca (2 +)] (i), cell membrane integrity, apoptotic body formation and DNA fragmentation in cultured HepG2 cells.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 112, "end": 119}, {"text": "Ca (2 +)", "start": 128, "end": 136}]}}, "schema": []}
{"input": "The reactive oxygen species level has been increased upon neferine treatment with concomitant decrease in reduced glutathione.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 13, "end": 19}, {"text": "neferine", "start": 58, "end": 66}, {"text": "glutathione", "start": 114, "end": 125}]}}, "schema": []}
{"input": "Our data further indicate reduction of Delta psi M and increased [Ca (2 +)] (i) during apoptosis induction by neferine with increased expression of apoptotic proteins such as Bax, Bad, cleaved forms of caspase 3, caspase 9 and PARP, with the downregulation of anti-apoptotic protein Bcl2 in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 66, "end": 74}, {"text": "neferine", "start": 110, "end": 118}]}}, "schema": []}
{"input": "Moreover, the expressions of tumour suppressor proteins p53 and PTEN were upregulated along with the downregulation of P-Akt.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, expression levels of TNF-alpha, p38 and ERK1/2 MAP kinases were increased upon neferine treatment.", "output": {"entities": {"chemical": [{"text": "neferine", "start": 92, "end": 100}]}}, "schema": []}
{"input": "These results imply that mitochondrial-mediated ROS generation induced by neferine leads to caspase-dependent apoptosis in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "neferine", "start": 74, "end": 82}]}}, "schema": []}
{"input": "A sensitive enzyme-linked immunosorbent assay for the determination of fish protein in processed foods.", "output": {"entities": {}}, "schema": []}
{"input": "Fish is one of the most common causes of food allergy and its major allergen is parvalbumin, a 12 kDa muscular protein.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, a sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of fish protein in processed foods was developed using a polyclonal antibody raised against Pacific mackerel parvalbumin.", "output": {"entities": {}}, "schema": []}
{"input": "The developed sandwich ELISA showed 22. 6-99. 0% reactivity (based on the reactivity to Pacific mackerel parvalbumin) to parvalbumins from various species of fish.", "output": {"entities": {}}, "schema": []}
{"input": "The limits of detection and quantitation were estimated to be 0. 23 and 0. 70 mu g protein per g of food, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "When the sandwich ELISA was subjected to inter-laboratory validation, spiked fish protein was recovered from five model processed foods in the range of 69. 4-84. 8% and the repeatability and reproducibility relative standard deviations were satisfactorily low (<= 10. 5%).", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the sandwich ELISA was judged to be a useful tool to determine fish protein in processed foods.", "output": {"entities": {}}, "schema": []}
{"input": "Batch and continuous synthesis of lactulose from whey lactose by immobilized beta-galactosidase.", "output": {"entities": {"chemical": [{"text": "lactulose", "start": 34, "end": 43}, {"text": "lactose", "start": 54, "end": 61}]}}, "schema": []}
{"input": "In this study, lactulose synthesis from whey lactose was investigated in batch and continuous systems using immobilized beta-galactosidase.", "output": {"entities": {"chemical": [{"text": "lactulose", "start": 15, "end": 24}, {"text": "lactose", "start": 45, "end": 52}]}}, "schema": []}
{"input": "In the batch system, the optimal concentration of fructose for lactulose synthesis was 20%, and the effect of galactose, glucose and fructose on beta-galactosidase activity was determined for hydrolysis of whey lactose and the transgalactosylation reaction for lactulose synthesis.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 50, "end": 58}, {"text": "lactulose", "start": 63, "end": 72}, {"text": "galactose", "start": 110, "end": 119}, {"text": "glucose", "start": 121, "end": 128}, {"text": "fructose", "start": 133, "end": 141}, {"text": "lactose", "start": 211, "end": 218}, {"text": "lactulose", "start": 261, "end": 270}]}}, "schema": []}
{"input": "Galactose and fructose were competitive inhibitors, and glucose acted as a noncompetitive inhibitor.", "output": {"entities": {"chemical": [{"text": "Galactose", "start": 0, "end": 9}, {"text": "fructose", "start": 14, "end": 22}, {"text": "glucose", "start": 56, "end": 63}]}}, "schema": []}
{"input": "The inhibitory effects of galactose and glucose were stronger in the transgalactosylation reaction than they were in the hydrolysis reaction.", "output": {"entities": {"chemical": [{"text": "galactose", "start": 26, "end": 35}, {"text": "glucose", "start": 40, "end": 47}]}}, "schema": []}
{"input": "In addition, when immobilized beta-galactosidase was reused for lactulose synthesis, its catalytic activity was retained to the extent of 52. 9% after 10 reuses.", "output": {"entities": {"chemical": [{"text": "lactulose", "start": 64, "end": 73}]}}, "schema": []}
{"input": "Lactulose was synthesized continuously in a packed-bed reactor.", "output": {"entities": {"chemical": [{"text": "Lactulose", "start": 0, "end": 9}]}}, "schema": []}
{"input": "We synthesized 19. 1g/l lactulose during the continuous flow reaction at a flow rate of 0. 5 ml/min.", "output": {"entities": {"chemical": [{"text": "lactulose", "start": 24, "end": 33}]}}, "schema": []}
{"input": "Gangliosides and sialic acid effects upon newborn pathogenic bacteria adhesion: an in vitro study.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 17, "end": 28}]}}, "schema": []}
{"input": "The effect of the main gangliosides (GM (1), GM (3), GD (3)) and free sialic acid (Neu5Ac) upon the adhesion of pathogenic bacteria implicated in infant diarrhoea is assessed in vitro using the Caco-2 cell line.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 70, "end": 81}, {"text": "Neu5Ac", "start": 83, "end": 89}]}}, "schema": []}
{"input": "Concentrations of the bioactive compounds found in the bioaccessible (soluble) fraction of infant formula and human milk are employed.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterial adhesion behaviour included enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli (EPEC), Listeria monocytogenes, Salmonella entericaserovartyphi, Shigella sonnei, Campylobacter jejuni and Helicobacter pylori.", "output": {"entities": {}}, "schema": []}
{"input": "Three different approaches were assayed: pre-incubation of bacteria and compounds before addition to cells (competition); pre-incubation of the cells with compounds (exclusion); and pre-incubation of cells with bacteria (displacement).", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the spatial localization of the most abundant gangliosides, GM (3) and GD (3), in Caco-2 cells has been determined using confocal microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Results show that GM (3), GD (3), GM (1) and Neu5Ac at the assayed concentrations are able to interfere with the adhesion of several pathogenic bacteria involved in neonatal diseases-the greatest effect corresponding to Neu5Ac, followed by GD (3), GM (1) and GM (3).", "output": {"entities": {"chemical": [{"text": "Neu5Ac", "start": 45, "end": 51}, {"text": "Neu5Ac", "start": 220, "end": 226}]}}, "schema": []}
{"input": "Gangliosides GM (3) and GD (3) are located in the apical and basolateral membranes of the Caco-2 cells.", "output": {"entities": {}}, "schema": []}
{"input": "A simple GC-MS method for the screening of betulinic, corosolic, maslinic, oleanolic and ursolic acid contents in commercial botanicals used as food supplement ingredients.", "output": {"entities": {"chemical": [{"text": "betulinic, corosolic, maslinic, oleanolic and ursolic acid", "start": 43, "end": 101}]}}, "schema": []}
{"input": "The occurrence of triterpene pentacyclic acids in plants is extensive, but little is known about their availability in commercial extracts.", "output": {"entities": {"chemical": [{"text": "triterpene pentacyclic acids", "start": 18, "end": 46}]}}, "schema": []}
{"input": "A simple GC-MS method for the simultaneous determination of betulinic, corosolic, maslinic, oleanolic and ursolic acids was developed and applied to 38 different commercial plant extracts sold as ingredients for dietary supplements.", "output": {"entities": {"chemical": [{"text": "betulinic, corosolic, maslinic, oleanolic and ursolic acids", "start": 60, "end": 119}]}}, "schema": []}
{"input": "A suitable protocol was set up to perform routine control of a diverse array of samples with different botanical, chemical and physical characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "Remarkable quantities of corosolic acid were found in dried extracts from aerial parts of Lagerstroemia speciosa and Ortosiphon stamineus (14233 and 1132 mg/kg, respectively), while oleanolic acid was abundant in O. stamineus and Crataegus monogyna flowers (2774 and 2339 mg/kg); ursolic was identified in O. stamineus, C. monogyna, L. speciosa and Arctostaphylos uva-ursi leaves (7773, 4165, 2108 and 1034 mg/kg).", "output": {"entities": {"chemical": [{"text": "corosolic acid", "start": 25, "end": 39}, {"text": "oleanolic acid", "start": 182, "end": 196}, {"text": "ursolic", "start": 280, "end": 287}]}}, "schema": []}
{"input": "Only L. speciosa was rich in maslinic acid (4958 mg/kg), while minor amounts of betulinic acid (257 and 80 mg/kg) were detected in L. speciosa and C. monogyna extracts.", "output": {"entities": {"chemical": [{"text": "maslinic acid", "start": 29, "end": 42}, {"text": "betulinic acid", "start": 80, "end": 94}]}}, "schema": []}
{"input": "Lower quantities of triterpenic acids were identified in dried extracts of Harpagophyton procumbens root, propolis, Punica granatum root, Styrax benzoin, Vaccinium myrtillus fruits and Vitis vinifera seeds.", "output": {"entities": {"chemical": [{"text": "triterpenic acids", "start": 20, "end": 37}]}}, "schema": []}
{"input": "Decoctions and fluid extracts lacked or contained very low amounts of triterpenic acids.", "output": {"entities": {"chemical": [{"text": "triterpenic acids", "start": 70, "end": 87}]}}, "schema": []}
{"input": "Results are discussed in terms of quality and safety of these ingredients.", "output": {"entities": {}}, "schema": []}
{"input": "The importance of amylose and amylopectin fine structures for starch digestibility in cooked rice grains.", "output": {"entities": {}}, "schema": []}
{"input": "Statistically and causally meaningful relationships are established between starch molecular structures (obtained by size-exclusion chromatography, proton NMR and multiple-angle laser light scattering) and digestibility of cooked rice grains (measured by in vitro digestion).", "output": {"entities": {}}, "schema": []}
{"input": "Significant correlations are observed between starch digestion rate and molecular structural characteristics, including fine structures of the distributions of branch (chain) lengths in both amylose and amylopectin.", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro digestion rate tends to increase with longer amylose branches and smaller ratios of long amylopectin and long amylose branches to short amylopectin branches, although the statistical analyses show that further data are needed to establish this unambiguously.", "output": {"entities": {}}, "schema": []}
{"input": "These new relationships between fine starch structural features and digestibility of cooked rice grains are mechanistically reasonable, but suggestive rather than statistically definitive.", "output": {"entities": {}}, "schema": []}
{"input": "Immunoreactivity of hen egg allergens: influence on in vitro gastrointestinal digestion of the presence of other egg white proteins and of egg yolk.", "output": {"entities": {}}, "schema": []}
{"input": "Hen egg white comprises of a complex mixture of proteins, which greatly differ in their physicochemical characteristics and relative abundance.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to identify potential undiscovered egg allergens within the egg white proteome and investigated the existence of matrix effects on the proteolytic stability and resultant IgE-binding of the allergenic proteins.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to the main egg allergens: ovalbumin (OVA), ovomucoid (OM) and lysozyme (LYS), two minor egg white proteins, tentatively identified as ovoinhibitor and clusterin, were found to react with serum IgE from egg-allergic patients.", "output": {"entities": {}}, "schema": []}
{"input": "Egg white exhibited residual immunoreactivity after gastrointestinal digestion due to the presence of intact OVA and LYS, as well as of several IgE-binding peptides derived from OVA.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of egg yolk slightly increased the susceptibility to hydrolysis of egg white proteins and abrogated bile salt-induced precipitation of LYS in the duodenal medium.", "output": {"entities": {"chemical": [{"text": "bile salt", "start": 113, "end": 122}]}}, "schema": []}
{"input": "However, the resultant immunoreactivity against IgE of egg white proteins after in vitro digestion was not significantly modified by the presence of yolk components.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation on the phase behaviour of gelatin/agarose mixture in an environment of reduced solvent quality.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation on the phase behaviour of a biopolymer mixture has been performed using 7. 5% (w/w) gelatin and 1. 5% (w/w) agarose in the presence of variable amounts of polydextrose as the co-solute from low to high levels of total solids.", "output": {"entities": {"chemical": [{"text": "polydextrose", "start": 169, "end": 181}]}}, "schema": []}
{"input": "Mechanical observation of the system was performed using small deformation dynamic oscillation in shear along with thermal studies using modulated differential scanning calorimetry.", "output": {"entities": {}}, "schema": []}
{"input": "Micrographs provided images of the changing morphology of the network with the addition of co-solute.", "output": {"entities": {}}, "schema": []}
{"input": "Agarose and gelatin form non-interactive bicontinuous phases in the aqueous environment.", "output": {"entities": {}}, "schema": []}
{"input": "Systematic increase in the concentration of polydextrose prevents the formation of a stable agarose network, with the polysaccharide chains dispersing in the high solids environment.", "output": {"entities": {"chemical": [{"text": "polydextrose", "start": 44, "end": 56}]}}, "schema": []}
{"input": "Gelatin, on the other hand, retains its conformational stability even at a saturating co-solute environment through enhanced protein structuring.", "output": {"entities": {}}, "schema": []}
{"input": "Vitrification studies on the high solids system at subzero temperatures provides information on the structural and molecular relaxation identified as a glass transition phenomenon.", "output": {"entities": {}}, "schema": []}
{"input": "Fourier transform infrared spectroscopy was used to analyse potential direct interaction between polymers and co-solute.", "output": {"entities": {}}, "schema": []}
{"input": "The extent of amorphicity in the system was confirmed using wide angle X-ray diffraction.", "output": {"entities": {}}, "schema": []}
{"input": "Application of a qualitative and quantitative real-time polymerase chain reaction method for detecting genetically modified papaya line 55-1 in papaya products.", "output": {"entities": {}}, "schema": []}
{"input": "Genetically modified (GM) papaya (Carica papaya L.) line 55-1 (55-1), which is resistant to papaya ringspot virus infection, has been marketed internationally.", "output": {"entities": {}}, "schema": []}
{"input": "Many countries have mandatory labeling regulations for GM foods, and there is a need for specific methods for detecting 55-1.", "output": {"entities": {}}, "schema": []}
{"input": "Here, an event-and construct-specific real-time polymerase chain reaction (PCR) method was developed for detecting 55-1 in papaya products.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative detection was possible for fresh papaya fruit up to dilutions of 0. 001% and 0. 01% (weight per weight [w/w]) for homozygous SunUp and heterozygous Rainbow cultivars, respectively, in non-GM papaya.", "output": {"entities": {}}, "schema": []}
{"input": "The limit of detection and quantification was as low as 250 copies of the haploid genome according to a standard reference plasmid.", "output": {"entities": {}}, "schema": []}
{"input": "The method was applicable to qualitative detection of 55-1 in eight types of processed products (canned papaya, pickled papaya, dried fruit, papaya-leaf tea, jam, puree, juice, and frozen dessert) containing papaya as a main ingredient.", "output": {"entities": {}}, "schema": []}
{"input": "Physico-chemical changes occurring in oil when atmospheric frying is combined with post-frying vacuum application.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to investigate the effect of atmospheric frying followed by drainage under vacuum on the stability of oil, compared to similar frying with drainage at atmospheric pressure.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in the oil were assessed by the free fatty acid (FFA) content, p-anisidine value (AnV), colour, viscosity, fatty acid profile and concentration of tocols.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 45, "end": 55}, {"text": "p-anisidine", "start": 71, "end": 82}, {"text": "fatty acid", "start": 115, "end": 125}]}}, "schema": []}
{"input": "The rate of FFA formation in the case of vacuum drainage was found to be about half that of atmospheric drainage.", "output": {"entities": {}}, "schema": []}
{"input": "Oil deterioration by oxidation and polymerisation was also reduced by the use of vacuum drainage.", "output": {"entities": {}}, "schema": []}
{"input": "The AnV of the oil after vacuum drainage was lower by about 12%, the total colour difference was improved by 14% and viscosity was slightly reduced after 5 days of frying, compared to the values for oil that had been drained at atmospheric pressure.", "output": {"entities": {}}, "schema": []}
{"input": "There was a reduction in the loss of polyunsaturated fatty acids in the case of vacuum drainage after 5 days of frying but differences in retention of tocols were only evident in the first two days of frying.", "output": {"entities": {"chemical": [{"text": "polyunsaturated fatty acids", "start": 37, "end": 64}]}}, "schema": []}
{"input": "Non-targeted metabolomic approach reveals urinary metabolites linked to steroid biosynthesis pathway after ingestion of citrus juice.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 72, "end": 79}]}}, "schema": []}
{"input": "Citrus juice intake has been highlighted because of its health-promoting effects.", "output": {"entities": {}}, "schema": []}
{"input": "LC-MS based metabolomics approaches are applied to obtain a better knowledge on changes in the concentration of metabolites due to its dietary intake and allow a better understanding of involved metabolic pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Eight volunteers daily consumed 400 mL of juice for four consecutive days and urine samples were collected before intake and 24h after each citrus juice intake.", "output": {"entities": {}}, "schema": []}
{"input": "Urine samples were analysed by nanoHPLC-q-TOF, followed by principal component analysis (PCA) and Student' s t-test (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "PCA showed a separation between two groups (before and after citrus juice consumption).", "output": {"entities": {}}, "schema": []}
{"input": "This approach allowed the identification of four endocrine compounds (tetrahydroaldosterone-3-glucuronide, cortolone-3-glucuronide, testosterone-glucuronide and 17-hydroxyprogesterone), which belonged to the steroid biosynthesis pathway as significant metabolites upregulated by citrus juice intake.", "output": {"entities": {"chemical": [{"text": "tetrahydroaldosterone-3-glucuronide", "start": 70, "end": 105}, {"text": "cortolone-3-glucuronide", "start": 107, "end": 130}, {"text": "testosterone-glucuronide", "start": 132, "end": 156}, {"text": "17-hydroxyprogesterone", "start": 161, "end": 183}, {"text": "steroid", "start": 208, "end": 215}]}}, "schema": []}
{"input": "Additionally, these results confirmed the importance of using the non-targeted metabolomics technique to identify new endogenous metabolites, up-or down-regulated as a consequence of food intake.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of flavonoids and flavonoid rhamnosides from Rhododendron mucronulatum for. albiflorum and their inhibitory activities against aldose reductase.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 18, "end": 28}, {"text": "flavonoid rhamnosides", "start": 33, "end": 54}, {"text": "aldose", "start": 142, "end": 148}]}}, "schema": []}
{"input": "To investigate the therapeutic potential of compounds from natural sources, Rhododendron mucronulatum for. albiflorum flowers (RMAF) and R. mucronulatum flowers (RMF) were tested for inhibition of aldose reductase (AR).", "output": {"entities": {"chemical": [{"text": "aldose", "start": 197, "end": 203}]}}, "schema": []}
{"input": "The methanol extracts of RMAF and RMF exhibited AR inhibitory activities (IC (50) values 1. 07 and 1. 29 mu g/mL, respectively).", "output": {"entities": {"chemical": [{"text": "methanol", "start": 4, "end": 12}]}}, "schema": []}
{"input": "The stepwise polarity fractions of RMAF were tested for in vitro inhibition of AR from rat lenses.", "output": {"entities": {}}, "schema": []}
{"input": "Of these, the ethyl acetate (EtOAc) fraction exhibited AR inhibitory activity (IC (50) 0. 15 mu g/mL).", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 14, "end": 27}, {"text": "EtOAc", "start": 29, "end": 34}]}}, "schema": []}
{"input": "A chromatography of the active EtOAc fraction of RMAF led to the isolation of six flavonoids, which were identified by spectroscopic analysis as kaempferol (1), afzelin (2), quercetin (3), quercitrin (4), myricetin (5) and myricitrin (6).", "output": {"entities": {"chemical": [{"text": "EtOAc", "start": 31, "end": 36}, {"text": "flavonoids", "start": 82, "end": 92}, {"text": "kaempferol", "start": 145, "end": 155}, {"text": "afzelin", "start": 161, "end": 168}, {"text": "quercetin", "start": 174, "end": 183}, {"text": "quercitrin", "start": 189, "end": 199}, {"text": "myricetin", "start": 205, "end": 214}, {"text": "myricitrin", "start": 223, "end": 233}]}}, "schema": []}
{"input": "Compounds 1-6 exhibited high AR inhibitory activity, with IC (50) values of 0. 79, 0. 31, 0. 48, 0. 13, 11. 92 and 2. 67 mu g/mL, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "HPLC/UV analysis revealed that the major flavonoids of RMAF and RMF are quercitrin (4) and myricitrin (6).", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 41, "end": 51}, {"text": "quercitrin", "start": 72, "end": 82}, {"text": "myricitrin", "start": 91, "end": 101}]}}, "schema": []}
{"input": "Our results suggest that RMAF containing these six flavonoids could be a useful natural source in the development of a novel AR inhibitory agent against diabetic complications.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 51, "end": 61}]}}, "schema": []}
{"input": "Encapsulation of food grade antioxidant in natural biopolymer by electrospinning technique: a physicochemical study based on zein-gallic acid system.", "output": {"entities": {"chemical": [{"text": "gallic acid", "start": 130, "end": 141}]}}, "schema": []}
{"input": "Gallic acid was successfully incorporated into zein ultra-fine fibres at different loading amount (5%, 10% and 20%) in order to develop an encapsulating technology for functional ingredient delivery using electrospinning.", "output": {"entities": {"chemical": [{"text": "Gallic acid", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The produced fibres exhibit diameters ranging from 327 to 387 nm.", "output": {"entities": {}}, "schema": []}
{"input": "The physical and thermal properties of encapsulated gallic acid were determined by X-ray diffraction (XRD) and differential scanning calorimetry (DSC); and the interaction between gallic acid and zein was attested by attenuated total reflection-Fourier transform infrared (ATR-FTIR).", "output": {"entities": {"chemical": [{"text": "gallic acid", "start": 52, "end": 63}, {"text": "gallic acid", "start": 180, "end": 191}]}}, "schema": []}
{"input": "Thermogravimetric analysis (TGA) demonstrated a different thermal stability of the fabricated complex before and after the gallic acid incorporation.", "output": {"entities": {"chemical": [{"text": "gallic acid", "start": 123, "end": 134}]}}, "schema": []}
{"input": "Lastly, the 1, 1'-diphenyl-2-picrylhydrazyl (DPPH) assay showed that the gallic acid had retained its antioxidant activity after incorporation in zein electrospun fibres.", "output": {"entities": {"chemical": [{"text": "1, 1'-diphenyl-2-picrylhydrazyl", "start": 12, "end": 43}, {"text": "DPPH", "start": 45, "end": 49}, {"text": "gallic acid", "start": 73, "end": 84}]}}, "schema": []}
{"input": "Overall, electrospinning technique had shown promising results as an efficient and effective method for the preparation of sub-micron structured encapsulated functional ingredient that may find uses in food industry.", "output": {"entities": {}}, "schema": []}
{"input": "Suppression of LPS-induced inflammatory activities by Rosmarinus officinalis L.", "output": {"entities": {}}, "schema": []}
{"input": "Rosemary (Rosmarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "However, the mechanisms underlying the anti-inflammatory effects of rosemary need more study to be established.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, in this study, the effects of rosemary on the activation of nuclear factor kappa beta (NF-kB) and mitogen-activated protein kinases (MAPKs), the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of nitric oxide (NO), prostaglandin E (2) (PGE (2)), and cytokine in lipopolysaccharide (LPS)-stimulated RAW 264. 7 cells were investigated.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 180, "end": 192}, {"text": "nitric oxide", "start": 261, "end": 273}, {"text": "NO", "start": 275, "end": 277}, {"text": "prostaglandin E (2)", "start": 280, "end": 299}, {"text": "PGE (2)", "start": 301, "end": 308}]}}, "schema": []}
{"input": "A methanol extract of rosemary and its hexane fraction reduced NO generation with an IC (50) of 2. 75 and 2. 83 mu g/ml, respectively.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 2, "end": 10}, {"text": "hexane", "start": 39, "end": 45}, {"text": "NO", "start": 63, "end": 65}]}}, "schema": []}
{"input": "Also, the methanol extract and the hexane fraction inhibited LPS-induced MAPKs and NF-kB activation associated with the inhibition of iNOS or COX-2 expression.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 10, "end": 18}, {"text": "hexane", "start": 35, "end": 41}]}}, "schema": []}
{"input": "LPS-induced production of PGE (2) and tumour necrosis factor-alpha (TNF-alpha) were blocked by rosemary.", "output": {"entities": {"chemical": [{"text": "PGE (2)", "start": 26, "end": 33}]}}, "schema": []}
{"input": "Rosemary extract and its hexane fraction are important for the prevention of phosphorylation of MAPKs, thereby blocking NF-kB activation, which in turn leads to decreased expression of iNOS and COX-2, thus preventing inflammation.", "output": {"entities": {"chemical": [{"text": "hexane", "start": 25, "end": 31}]}}, "schema": []}
{"input": "Reverse micellar extraction of bovine serum albumin-a comparison between the effects of gemini surfactant and its corresponding monomeric surfactant.", "output": {"entities": {}}, "schema": []}
{"input": "Gemini surfactant displayed distinct advantages over monomeric surfactant in the liquid-liquid reverse micellar extraction process.", "output": {"entities": {}}, "schema": []}
{"input": "First, less amount of gemini surfactant than monomeric surfactant was needed for transferring almost complete bovine serum albumin (BSA) into organic phase from aqueous phase.", "output": {"entities": {}}, "schema": []}
{"input": "Second, the loading capacity of gemini surfactant reverse micelle phase was much higher than that of the corresponding monomeric surfactant reverse micelle.", "output": {"entities": {}}, "schema": []}
{"input": "Third, efficient backward extraction (75-92%) of BSA could be effected in a wide pH range from 4 to 9 with gemini surfactant reverse micelle while a pH of ca.", "output": {"entities": {}}, "schema": []}
{"input": "4. 3 is prerequisite to the recovery of BSA from monomeric surfactant reverse micelle.", "output": {"entities": {}}, "schema": []}
{"input": "So far, the reports about the effect of surfactant structure on protein extraction have been limited.", "output": {"entities": {}}, "schema": []}
{"input": "This study indicates the important role of the spacer of gemini surfactant in protein extraction process and may provide more knowledge on how to optimise surfactant structure.", "output": {"entities": {}}, "schema": []}
{"input": "Reduction of lipid accumulation in white adipose tissues by Cassia tora (Leguminosae) seed extract is associated with AMPK activation.", "output": {"entities": {}}, "schema": []}
{"input": "Natural herbal medications may be one answer to the worldwide epidemic of obesity.", "output": {"entities": {}}, "schema": []}
{"input": "This study examines the effects of Cassia seed ethanol extract (CSEE) upon lipid accumulation in white adipose tissue (WAT).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 47, "end": 54}]}}, "schema": []}
{"input": "CSEE exhibited a significant concentration-dependent decrease in the intracellular accumulation of trigycerides in 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "trigycerides", "start": 99, "end": 111}]}}, "schema": []}
{"input": "After being fed a high-fat diet (HFD) for 2 weeks, rats were fed CSEE (100, 200 or 300 mg/kg) once daily for 8 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "CSEE caused dose-related reductions in body weight gain (as well as plasma lipid levels and epididymal WAT sizes in HFD-fed rats).", "output": {"entities": {}}, "schema": []}
{"input": "CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element-binding protein 1 and fatty acid synthase protein levels in epididymal WAT of HFD-fed rats.", "output": {"entities": {"chemical": [{"text": "AMP", "start": 37, "end": 40}, {"text": "acetyl-CoA", "start": 118, "end": 128}, {"text": "carnitine palmitoyl", "start": 174, "end": 193}, {"text": "fatty acid", "start": 276, "end": 286}]}}, "schema": []}
{"input": "CSEE could attenuate lipid accumulation in WAT via AMPK signaling pathway activation.", "output": {"entities": {}}, "schema": []}
{"input": "NMR structure and dynamics of the C-terminal domain of R-type lectin from the earthworm Lumbricus terrestris.", "output": {"entities": {"chemical": [{"text": "C", "start": 34, "end": 35}]}}, "schema": []}
{"input": "The C-terminal domain (Ch; C-half) of the R-type earthworm 29-kDa lectin (EW29), isolated from the earthworm Lumbricus terrestris, has two sugar-binding sites, in subdomains alpha and gamma, and the protein uses the two sugar-binding sites for its function as a single domain-type haemagglutinin.", "output": {"entities": {"chemical": [{"text": "C", "start": 4, "end": 5}, {"text": "sugar", "start": 139, "end": 144}, {"text": "sugar", "start": 220, "end": 225}]}}, "schema": []}
{"input": "Our previous NMR titration experiments showed that the alpha sugar-binding site is a high-affinity site and the gamma sugar-binding site is a low-affinity site.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 61, "end": 66}, {"text": "sugar", "start": 118, "end": 123}]}}, "schema": []}
{"input": "However, it remains unclear why the alpha sugar-binding site of EW29Ch binds to lactose much more strongly because the crystal structure of lactose-bound EW29Ch showed that the interaction between the alpha sugar-binding site and lactose was almost same as that between the gamma sugar-binding site and lactose.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 42, "end": 47}, {"text": "lactose", "start": 80, "end": 87}, {"text": "sugar", "start": 207, "end": 212}, {"text": "lactose", "start": 230, "end": 237}, {"text": "sugar", "start": 280, "end": 285}, {"text": "lactose", "start": 303, "end": 310}]}}, "schema": []}
{"input": "In the present study, we have determined the NMR structure of EW29Ch in the sugar-free state and performed (15) N relaxation experiments for EW29Ch in both the sugar-free state and the lactose-bound states.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 76, "end": 81}, {"text": "(15) N", "start": 107, "end": 113}, {"text": "sugar", "start": 160, "end": 165}, {"text": "lactose", "start": 185, "end": 192}]}}, "schema": []}
{"input": "The conformation of EW29Ch in the sugar-free state was similar to that of EW29Ch in complex with lactose.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 34, "end": 39}]}}, "schema": []}
{"input": "Conformational changes upon binding of lactose were observed only for the alpha sugar-binding site.", "output": {"entities": {}}, "schema": []}
{"input": "By contrast, the (15) N relaxation experiments revealed a conformational exchange at the alpha sugar-binding site in the sugar-free state, which was suppressed in the lactose-bound state.", "output": {"entities": {"chemical": [{"text": "(15) N", "start": 17, "end": 23}, {"text": "sugar", "start": 95, "end": 100}, {"text": "sugar", "start": 121, "end": 126}, {"text": "lactose", "start": 167, "end": 174}]}}, "schema": []}
{"input": "The conformational exchange phenomenon observed for the alpha sugar-binding site was not observed for the gamma sugar-binding site.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 62, "end": 67}, {"text": "sugar", "start": 112, "end": 117}]}}, "schema": []}
{"input": "Differences in the conformational change and the backbone dynamics between subdomains alpha and gamma may be associated with the difference of the sugar-binding modes between the two sugar-binding sites.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 147, "end": 152}, {"text": "sugar", "start": 183, "end": 188}]}}, "schema": []}
{"input": "DATABASE: Structural data for the NMR structure of EW29Ch in the sugar-free state have been deposited in the Protein Data Bank database under accession number 2RST.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 65, "end": 70}]}}, "schema": []}
{"input": "Comparison the neuropreotective effect of Cortex Phellodendri chinensis and Cortex Phellodendri amurensis against beta-amyloid-induced neurotoxicity in PC12 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Cortex Phellodendron chinensis (CPC) and Cortex Phellodendron amurensis (CPA) derived from the dried bark of Phellodendron chinense Schneid. or Phellodendron amurense Rupr., respectively, are used interchangeably in clinical practice under the name \" Huang Bai \" for centuries in Chinese medicine for the treatment of various inflammatory conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Previous study in our laboratory demonstrated that CPC and CPA had different anti-diarrheal, anti-bacterial and anti-inflammatory effects.", "output": {"entities": {}}, "schema": []}
{"input": "In this present study, we aimed to compare the protective effect of ethanol extract of Cortex Phellodendri chinensis (ECPC) and Cortex Phellodendri Amurensis (ECPA) against beta-amyloid (A beta)-induced neurotoxicity in PC12 cells, a typical model of Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 68, "end": 75}]}}, "schema": []}
{"input": "The results showed that ECPC and ECPA contain four common chemical markers such as berberine, but palmatine and jatrorrhizin were not found in CPC in contrast to the presence in CPA.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 83, "end": 92}, {"text": "palmatine", "start": 98, "end": 107}, {"text": "jatrorrhizin", "start": 112, "end": 124}]}}, "schema": []}
{"input": "In addition, both ECPC and ECPA can significantly increase the cell viability in A beta-treated PC12 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, ECPC and ECPA can markedly elevate the ratio of the protein and mRNA levels of Bcl-2/Bax, while remarkably decrease the release of cytochrome c, and the protein and mRNA expression of caspase-3.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, ECPA has better protective effect than ECPC against A beta-induced neurotoxicity in PC12 cells.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that both ECPC and ECPA have potential protective effect against A beta-induced neurotoxicity in PC12 cells, and ECPA is more potential of the two species to be used in traditional medicine as a neuroprotective agent for the treatment of AD.", "output": {"entities": {}}, "schema": []}
{"input": "The neuroprotective effect of the two species may be mediated, at least in part, via suppressing of the cellular apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "beta-Asarone, an active principle of Acorus calamus rhizome, inhibits morphogenesis, biofilm formation and ergosterol biosynthesis in Candida albicans.", "output": {"entities": {"chemical": [{"text": "beta-Asarone", "start": 0, "end": 12}, {"text": "ergosterol", "start": 107, "end": 117}]}}, "schema": []}
{"input": "Anti-Candida potential of Acorus calamus rhizome and its active principle, beta-asarone, was evaluated against the human fungal pathogen, Candida albicans.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 75, "end": 87}]}}, "schema": []}
{"input": "beta-Asarone exhibited promising growth inhibitory activity at 0. 5mg/ml and it was fungicidal at 8 mg/ml.", "output": {"entities": {"chemical": [{"text": "beta-Asarone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Time dependant kill curve assay showed that MFC of beta-asarone was highly toxic to C. albicans, killing 99. 9% inoculum within 120 min of exposure.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 51, "end": 63}]}}, "schema": []}
{"input": "beta-Asarone caused significant inhibition of C. albicans morphogenesis and biofilm development at sub-inhibitory concentrations.", "output": {"entities": {"chemical": [{"text": "beta-Asarone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Our data indicate that the growth inhibitory activity of beta-asarone might be through inhibition of ergosterol biosynthesis.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 57, "end": 69}, {"text": "ergosterol", "start": 101, "end": 111}]}}, "schema": []}
{"input": "Hemolytic assay showed that beta-asarone is non-toxic, even at concentrations approaching MIC value.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 28, "end": 40}]}}, "schema": []}
{"input": "Our results suggest that beta-asarone may be safe as a topical antifungal agent.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 25, "end": 37}]}}, "schema": []}
{"input": "Testing of novel brain-penetrating oxime reactivators of acetylcholinesterase inhibited by nerve agent surrogates.", "output": {"entities": {"chemical": [{"text": "oxime", "start": 35, "end": 40}]}}, "schema": []}
{"input": "A critical need for combating the effects of organophosphate (OP) anticholinesterases, such as nerve agents, is the current lack of an effective oxime reactivator which can penetrate the blood-brain barrier (BBB), and therefore reactivate inhibited acetylcholinesterase (AChE) in the brain.", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 45, "end": 60}, {"text": "oxime", "start": 145, "end": 150}]}}, "schema": []}
{"input": "Our laboratories have synthesized and have initiated testing of novel phenoxyalkyl pyridinium oximes (patent pending) that are more lipophilic than currently approved oximes.", "output": {"entities": {"chemical": [{"text": "phenoxyalkyl pyridinium oximes", "start": 70, "end": 100}, {"text": "oximes", "start": 167, "end": 173}]}}, "schema": []}
{"input": "This is a preliminary report on these novel oximes which have been tested in vitro in rat brain homogenates with highly relevant surrogates for sarin (phthalimidyl isopropyl methylphosphonate; PIMP) and VX (nitrophenyl ethyl methylphosphonate; NEMP).", "output": {"entities": {"chemical": [{"text": "oximes", "start": 44, "end": 50}, {"text": "sarin", "start": 144, "end": 149}, {"text": "phthalimidyl isopropyl methylphosphonate", "start": 151, "end": 191}, {"text": "PIMP", "start": 193, "end": 197}, {"text": "nitrophenyl ethyl methylphosphonate", "start": 207, "end": 242}, {"text": "NEMP", "start": 244, "end": 248}]}}, "schema": []}
{"input": "The oximes demonstrated a range of 14-76% reactivation of rat brain AChE in vitro.", "output": {"entities": {"chemical": [{"text": "oximes", "start": 4, "end": 10}]}}, "schema": []}
{"input": "An in vivo testing paradigm was developed in which the novel oxime was administered at the time of maximal brain AChE inhibition (about 80%) (1h) elicited by nitrophenyl isopropyl methylphosphonate (NIMP; sarin surrogate).", "output": {"entities": {"chemical": [{"text": "oxime", "start": 61, "end": 66}, {"text": "nitrophenyl isopropyl methylphosphonate", "start": 158, "end": 197}, {"text": "NIMP", "start": 199, "end": 203}, {"text": "sarin", "start": 205, "end": 210}]}}, "schema": []}
{"input": "This paradigm, with delayed administration of oxime to a time when brain AChE was starting to recover, was designed to minimize reactivation/reinhibition of peripheral AChE during the reactivation period which would decrease the availability of the surrogate for entry into the brain; this paradigm will allow proof of concept of BBB penetrability.", "output": {"entities": {"chemical": [{"text": "oxime", "start": 46, "end": 51}]}}, "schema": []}
{"input": "The initial studies of these oximes in vivo with the sarin surrogate NIMP have indicated reactivation of up to about 25% at 30min after oxime administration and substantial attenuation of seizure behavior from some of the oximes.", "output": {"entities": {"chemical": [{"text": "oximes", "start": 29, "end": 35}, {"text": "sarin", "start": 53, "end": 58}, {"text": "NIMP", "start": 69, "end": 73}, {"text": "oxime", "start": 136, "end": 141}, {"text": "oximes", "start": 222, "end": 228}]}}, "schema": []}
{"input": "Therefore these novel oximes have considerable potential as brain-protecting therapeutics for anticholinesterases.", "output": {"entities": {"chemical": [{"text": "oximes", "start": 22, "end": 28}]}}, "schema": []}
{"input": "Contributions of rat Ctr1 to the uptake and toxicity of copper and platinum anticancer drugs in dorsal root ganglion neurons.", "output": {"entities": {"chemical": [{"text": "copper", "start": 56, "end": 62}, {"text": "platinum", "start": 67, "end": 75}]}}, "schema": []}
{"input": "Dorsal root ganglion (DRG) neurons are affected by platinum-induced neurotoxicity and neurodegenerative processes associated with disturbed copper homeostasis and transport.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 51, "end": 59}, {"text": "copper", "start": 140, "end": 146}]}}, "schema": []}
{"input": "This study aimed to understand the role of copper transporter 1 (Ctr1) in the uptake and toxicity of copper and platinum drugs in cultured rat DRG neurons, and the functional activities of rat Ctr1 (rCtr1) as a membrane transporter of copper and platinum drugs.", "output": {"entities": {"chemical": [{"text": "copper", "start": 43, "end": 49}, {"text": "copper", "start": 101, "end": 107}, {"text": "platinum", "start": 112, "end": 120}, {"text": "copper", "start": 235, "end": 241}, {"text": "platinum", "start": 246, "end": 254}]}}, "schema": []}
{"input": "Heterologous expression of rCtr1 in HEK293 cells (HEK/rCtr1 cells) increased the uptake and cytotoxicity of copper, oxaliplatin, cisplatin and carboplatin, in comparison to isogenic vector-transfected control cells.", "output": {"entities": {"chemical": [{"text": "copper", "start": 108, "end": 114}, {"text": "oxaliplatin", "start": 116, "end": 127}, {"text": "cisplatin", "start": 129, "end": 138}, {"text": "carboplatin", "start": 143, "end": 154}]}}, "schema": []}
{"input": "Cultured rat DRG neurons endogenously expressed rCtr1 protein on their neuronal cell body plasma membranes and cytoplasm, and displayed substantial capacity for taking up copper, but were resistant to copper toxicity.", "output": {"entities": {"chemical": [{"text": "copper", "start": 171, "end": 177}, {"text": "copper", "start": 201, "end": 207}]}}, "schema": []}
{"input": "The uptake of copper by both cultured rat DRG neurons and HEK/rCtr1 cells was saturable and inhibited by cold temperature, silver and zinc, consistent with it being mediated by rCtr1.", "output": {"entities": {"chemical": [{"text": "copper", "start": 14, "end": 20}, {"text": "silver", "start": 123, "end": 129}, {"text": "zinc", "start": 134, "end": 138}]}}, "schema": []}
{"input": "Cultured rat DRG neurons accumulated platinum during their exposure to oxaliplatin and were sensitive to oxaliplatin cytotoxicity.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 37, "end": 45}, {"text": "oxaliplatin", "start": 71, "end": 82}, {"text": "oxaliplatin", "start": 105, "end": 116}]}}, "schema": []}
{"input": "The accumulation of platinum by both cultured rat DRG neurons and HEK/rCtr1 cells, during oxaliplatin exposure, was saturable and temperature dependent, but was inhibited by copper only in HEK/rCtr1 cells.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 20, "end": 28}, {"text": "oxaliplatin", "start": 90, "end": 101}, {"text": "copper", "start": 174, "end": 180}]}}, "schema": []}
{"input": "In conclusion, rCtr1 can transport copper and platinum drugs, and sensitizes cells to their cytotoxicities.", "output": {"entities": {"chemical": [{"text": "copper", "start": 35, "end": 41}, {"text": "platinum", "start": 46, "end": 54}]}}, "schema": []}
{"input": "DRG neurons display substantial capacity for accumulating copper via a transport process mediated by rCtr1, but appear able to resist copper toxicity and use alternative mechanisms to take up oxaliplatin.", "output": {"entities": {"chemical": [{"text": "copper", "start": 58, "end": 64}, {"text": "copper", "start": 134, "end": 140}, {"text": "oxaliplatin", "start": 192, "end": 203}]}}, "schema": []}
{"input": "Elevation of cysteine consumption in tamoxifen-resistant MCF-7 cells.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 13, "end": 21}, {"text": "tamoxifen", "start": 37, "end": 46}]}}, "schema": []}
{"input": "Tamoxifen (TAM) resistance is a main cause of therapeutic failure in breast cancers.", "output": {"entities": {"chemical": [{"text": "Tamoxifen", "start": 0, "end": 9}, {"text": "TAM", "start": 11, "end": 14}]}}, "schema": []}
{"input": "Although methionine dependency is a phenotypic characteristic of tumor cells, the role of sulfur amino acid metabolism in chemotherapy resistance remains to be elucidated.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 9, "end": 19}, {"text": "sulfur amino acid", "start": 90, "end": 107}]}}, "schema": []}
{"input": "This study compared metabolite profiles of sulfur amino acid metabolism from methionine to taurine or glutathione (GSH) between normal MCF-7 and TAM-resistant MCF-7 (TAMR-MCF-7) cells.", "output": {"entities": {"chemical": [{"text": "sulfur amino acid", "start": 43, "end": 60}, {"text": "methionine", "start": 77, "end": 87}, {"text": "taurine", "start": 91, "end": 98}, {"text": "glutathione", "start": 102, "end": 113}, {"text": "GSH", "start": 115, "end": 118}, {"text": "TAM", "start": 145, "end": 148}]}}, "schema": []}
{"input": "TAMR-MCF-7 cells showed elevated levels and activities of enzymes involved in both transsulfuration from methionine to cysteine and metabolism of cysteine to GSH and taurine.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 105, "end": 115}, {"text": "cysteine", "start": 119, "end": 127}, {"text": "cysteine", "start": 146, "end": 154}, {"text": "GSH", "start": 158, "end": 161}, {"text": "taurine", "start": 166, "end": 173}]}}, "schema": []}
{"input": "Cysteine concentrations in TAMR-MCF-7 cells and medium conditioned by cell culture for 42h were markedly decreased, while GSH, hypotaurine, and taurine concentrations in the medium were increased.", "output": {"entities": {"chemical": [{"text": "Cysteine", "start": 0, "end": 8}, {"text": "GSH", "start": 122, "end": 125}, {"text": "hypotaurine", "start": 127, "end": 138}, {"text": "taurine", "start": 144, "end": 151}]}}, "schema": []}
{"input": "These results show that TAMR-MCF-7 cells display enhanced cysteine utilization.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 58, "end": 66}]}}, "schema": []}
{"input": "The addition of propargylglycine, a specific cystathionine gamma-lyase inhibitor, and buthionine sulfoximine, a specific gamma-glutamylcysteine ligase inhibitor, to TAMR-MCF-7 cells, but not to MCF-7 cells, resulted in cytotoxicity after sulfur amino acid deprivation.", "output": {"entities": {"chemical": [{"text": "propargylglycine", "start": 16, "end": 32}, {"text": "cystathionine", "start": 45, "end": 58}, {"text": "buthionine sulfoximine", "start": 86, "end": 108}, {"text": "gamma-glutamylcysteine", "start": 121, "end": 143}, {"text": "sulfur amino acid", "start": 238, "end": 255}]}}, "schema": []}
{"input": "These results suggest that cell viability of TAMR-MCF-7 cells is affected by inhibition of sulfur amino acid metabolism, particularly cysteine synthesis from homocysteine and GSH synthesis from cysteine.", "output": {"entities": {"chemical": [{"text": "sulfur amino acid", "start": 91, "end": 108}, {"text": "cysteine", "start": 134, "end": 142}, {"text": "homocysteine", "start": 158, "end": 170}, {"text": "GSH", "start": 175, "end": 178}, {"text": "cysteine", "start": 194, "end": 202}]}}, "schema": []}
{"input": "Additionally, the S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in TAMR-MCF-7 cells increased to ~ 3. 6-fold relative to that in MCF-7 cells, a finding that may result from upregulation of methionine adenosyltransferase IIa and S-adenosylhomocysteine hydrolase.", "output": {"entities": {"chemical": [{"text": "S-adenosylmethionine", "start": 18, "end": 38}, {"text": "S-adenosylhomocysteine", "start": 39, "end": 61}, {"text": "methionine", "start": 234, "end": 244}, {"text": "S-adenosylhomocysteine", "start": 273, "end": 295}]}}, "schema": []}
{"input": "In conclusion, this study suggests that TAMR-MCF-7 cells display enhanced cysteine utilization for synthesis of GSH and taurine, and are sensitive to inhibition of cysteine metabolism.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 74, "end": 82}, {"text": "GSH", "start": 112, "end": 115}, {"text": "taurine", "start": 120, "end": 127}, {"text": "cysteine", "start": 164, "end": 172}]}}, "schema": []}
{"input": "An Indian butyrylcholinesterase variant L307P is not structurally stable: A molecular dynamics simulation study.", "output": {"entities": {}}, "schema": []}
{"input": "The human butyrylcholinesterase (BChE) activity is less than 1% in the serum of silent variant individuals of Vysya community in India.", "output": {"entities": {}}, "schema": []}
{"input": "They are homozygous for a point mutation at codon 307 (CTT --> CCT) resulting in the substitution of leucine 307 by proline.", "output": {"entities": {"chemical": [{"text": "leucine", "start": 101, "end": 108}, {"text": "proline", "start": 116, "end": 123}]}}, "schema": []}
{"input": "The reason for the disappearance of the protein in the serum has not been explicated till date.", "output": {"entities": {}}, "schema": []}
{"input": "Based on this background, we performed molecular dynamics simulation to probe the structural stability of Indian variant (L307P) in comparison with wild and other BChE variants (D70G, E497V, V142M) having differential esterase activity.", "output": {"entities": {}}, "schema": []}
{"input": "The simulation of all the mutants except D70G showed a much larger C alpha root mean square deviation from the wild BChE crystal structure, showing the overall conformational disturbance.", "output": {"entities": {}}, "schema": []}
{"input": "Further analysis revealed that secondary structure of the mutant proteins was not stable.", "output": {"entities": {}}, "schema": []}
{"input": "The orientation of the catalytic triad is also distorted in all the mutants.", "output": {"entities": {}}, "schema": []}
{"input": "The distance between delta nitrogen of His438 to epsilon oxygen of Glu325 and epsilon nitrogen of His438 to gamma oxygen of Ser198 were highly altered in L307P mutant than the wild and other three variants throughout the simulation.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 27, "end": 35}, {"text": "His438", "start": 39, "end": 45}, {"text": "oxygen", "start": 57, "end": 63}, {"text": "Glu325", "start": 67, "end": 73}, {"text": "nitrogen", "start": 86, "end": 94}, {"text": "His438", "start": 98, "end": 104}, {"text": "oxygen", "start": 114, "end": 120}, {"text": "Ser198", "start": 124, "end": 130}]}}, "schema": []}
{"input": "Such disparity of distances between the catalytic residues may be due to the change in the protein conformation attributing to their differential catalytic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Our studies thus prove that the Indian BChE L307P mutant with negligible activity is possibly due to its structural instability when compared to other BChE variants.", "output": {"entities": {}}, "schema": []}
{"input": "Absolute quantitation of stevioside and rebaudioside A in commercial standards by quantitative NMR.", "output": {"entities": {"chemical": [{"text": "stevioside", "start": 25, "end": 35}, {"text": "rebaudioside A", "start": 40, "end": 54}]}}, "schema": []}
{"input": "The extract prepared from the leaves of Stevia rebaudiana BERTONI (Asteraceae) contains sweet steviol glycosides, mainly stevioside and rebaudioside A.", "output": {"entities": {"chemical": [{"text": "steviol glycosides", "start": 94, "end": 112}, {"text": "stevioside", "start": 121, "end": 131}, {"text": "rebaudioside A", "start": 136, "end": 150}]}}, "schema": []}
{"input": "Highly purified stevia extracts have become popular worldwide as a natural, low-calorie sweetener.", "output": {"entities": {}}, "schema": []}
{"input": "They contain various types of steviol glycosides, and their main components are stevioside and rebaudioside A.", "output": {"entities": {"chemical": [{"text": "steviol glycosides", "start": 30, "end": 48}, {"text": "stevioside", "start": 80, "end": 90}, {"text": "rebaudioside A", "start": 95, "end": 109}]}}, "schema": []}
{"input": "The content of each steviol glycoside is quantified by comparing the ratios of the molecular weights and the chromatographic peak areas of the samples to those of stevioside or rebaudioside A standards of the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Joint Expert Committee on Food Additives (JECFA) and other specifications.", "output": {"entities": {"chemical": [{"text": "steviol glycoside", "start": 20, "end": 37}, {"text": "stevioside", "start": 163, "end": 173}, {"text": "rebaudioside A", "start": 177, "end": 191}]}}, "schema": []}
{"input": "However, various commercial standard reagents of stevioside and rebaudioside A are available.", "output": {"entities": {"chemical": [{"text": "stevioside", "start": 49, "end": 59}, {"text": "rebaudioside A", "start": 64, "end": 78}]}}, "schema": []}
{"input": "Their purities are different and their exact purities are not indicated.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the measured values of stevioside and rebaudioside A contained in a sample vary according to the standard used for the quantification.", "output": {"entities": {"chemical": [{"text": "stevioside", "start": 34, "end": 44}, {"text": "rebaudioside A", "start": 49, "end": 63}]}}, "schema": []}
{"input": "In this study, we utilized an accurate method, quantitative NMR (qNMR), for determining the contents of stevioside and rebaudioside A in standards, with traceability to the International System of Units (SI units).", "output": {"entities": {"chemical": [{"text": "stevioside", "start": 104, "end": 114}, {"text": "rebaudioside A", "start": 119, "end": 133}]}}, "schema": []}
{"input": "The purities of several commercial standards were determined to confirm their actual values.", "output": {"entities": {}}, "schema": []}
{"input": "A mutation in the FAM36A gene, the human ortholog of COX20, impairs cytochrome c oxidase assembly and is associated with ataxia and muscle hypotonia.", "output": {"entities": {}}, "schema": []}
{"input": "The mitochondrial respiratory chain complex IV (cytochrome c oxidase) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular oxygen, yielding water.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 152, "end": 158}]}}, "schema": []}
{"input": "Its biogenesis requires concerted expression of mitochondria-and nuclear-encoded subunits and assembly factors.", "output": {"entities": {}}, "schema": []}
{"input": "In this report, we describe a homozygous missense mutation in FAM36A from a patient who displays ataxia and muscle hypotonia.", "output": {"entities": {}}, "schema": []}
{"input": "The FAM36A gene is a remote, putative ortholog of the fungal complex IV assembly factor COX20.", "output": {"entities": {}}, "schema": []}
{"input": "Messenger RNA (mRNA) and protein co-expression analyses support the involvement of FAM36A in complex IV function in mammals.", "output": {"entities": {}}, "schema": []}
{"input": "The c. 154A > C mutation in the FAM36A gene, a mutation that is absent in sequenced exomes, leads to a reduced activity and lower levels of complex IV and its protein subunits.", "output": {"entities": {}}, "schema": []}
{"input": "The FAM36A protein is nearly absent in patient' s fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Cells affected by the mutation accumulate subassemblies of complex IV that contain COX1 but are almost devoid of COX2 protein.", "output": {"entities": {}}, "schema": []}
{"input": "We observe co-purification of FAM36A and COX2 proteins, supporting that the FAM36A defect hampers the early step of complex IV assembly at the incorporation of the COX2 subunit.", "output": {"entities": {}}, "schema": []}
{"input": "Lentiviral complementation of patient' s fibroblasts with wild-type FAM36A increases the complex IV activity as well as the amount of holocomplex IV and of individual subunits.", "output": {"entities": {}}, "schema": []}
{"input": "These results establish the function of the human gene FAM36A/COX20 in complex IV assembly and support a causal role of the gene in complex IV deficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of alpha-tubulin.", "output": {"entities": {}}, "schema": []}
{"input": "Cytoskeleton remodelling is a prerequisite step for the morphological transition from preadipocytes to mature adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Although microtubules play a pivotal role in organizing cellular structure, regulation of microtubule dynamics during adipogenesis remains unclear.", "output": {"entities": {}}, "schema": []}
{"input": "In the present paper we show that acetylation of alpha-tubulin is up-regulated during adipogenesis, and adipocyte development is dependent on alpha-tubulin acetylation, as expression of an acetylation-resistant alpha-tubulin mutant significantly inhibits adipogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, acetylation of alpha-tubulin is under the control of the acetyltransferase MEC-17 and deacetylases SIRT2 (Sirtuin 2) and HDAC6 (histone deacetylase 6).", "output": {"entities": {}}, "schema": []}
{"input": "Adipocyte development is inhibited in MEC-17-knockdown cells, but enhanced in MEC-17-overexpressing cells.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we show that katanin, a microtubule-severing protein with enhanced activity on acetylated alpha-tubulin, is actively involved in adipogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "We propose that co-ordinated up-regulation of alpha-tubulin acetylation initiates cytoskeleton remodelling by promoting alpha-tubulin severing by katanin which, in turn, allows expansion of lipid droplets and accelerates the morphological transition toward mature adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "2-Amino-4-arylthiazole compounds as TRPA1 antagonists (WO 2012085662): a patent evaluation.", "output": {"entities": {"chemical": [{"text": "2-Amino-4-arylthiazole", "start": 0, "end": 22}]}}, "schema": []}
{"input": "The patent claims 2-amino-4-arylthiazole derivative compounds as inhibitors of the TRPA1 (transient receptor potential ankyrin, member 1) receptor.", "output": {"entities": {"chemical": [{"text": "2-amino-4-arylthiazole", "start": 18, "end": 40}]}}, "schema": []}
{"input": "These compounds are potent antagonists on the basis of the results of in vitro assays, and are expected to be useful for treating conditions and disorders associated with TRPA1 function such as pain, chronic pain, neuropathic pain, rheumatoid arthritic pain, osteoarthritic pain, diabetic neuropathy and inflammatory disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Bioactive constituents of Salvia chrysophylla Stapf.", "output": {"entities": {}}, "schema": []}
{"input": "The dichloromethane extract of the aerial parts of Salvia chrysophylla Stapf (Lamiaceae), which is an endemic species to south-western Anatolia, was studied for non-volatile secondary metabolites for the first time in this study.", "output": {"entities": {"chemical": [{"text": "dichloromethane", "start": 4, "end": 19}]}}, "schema": []}
{"input": "Structures of the isolated compounds were elucidated as sclareol, beta-sitosterol, salvigenin, oleanolic acid and ursolic acid.", "output": {"entities": {"chemical": [{"text": "sclareol", "start": 56, "end": 64}, {"text": "beta-sitosterol", "start": 66, "end": 81}, {"text": "salvigenin", "start": 83, "end": 93}, {"text": "oleanolic acid", "start": 95, "end": 109}, {"text": "ursolic acid", "start": 114, "end": 126}]}}, "schema": []}
{"input": "The lipid peroxidation inhibitory activity and the DPPH free radical scavenging activity of the pure isolates were investigated to establish their antioxidant potential.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Their anticholinesterase activity was carried out by the Ellman assay against both enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase, and diterpene sclareol exhibited fairly good activity against both the enzymes while the two triterpenoids oleanolic and ursolic acids exhibited selective activity against AChE.", "output": {"entities": {"chemical": [{"text": "sclareol", "start": 161, "end": 169}, {"text": "oleanolic and ursolic acids", "start": 254, "end": 281}]}}, "schema": []}
{"input": "Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation.", "output": {"entities": {"chemical": [{"text": "8-oxoguanine", "start": 19, "end": 31}]}}, "schema": []}
{"input": "Allergic airway inflammation is characterized by increased expression of pro-inflammatory mediators, inflammatory cell infiltration, mucus hypersecretion, and airway hyperresponsiveness, in parallel with oxidative DNA base and strand damage, whose etiological role is not understood.", "output": {"entities": {}}, "schema": []}
{"input": "Our goal was to establish the role of 8-oxoguanine (8-oxoG), a common oxidatively damaged base, and its repair by 8-oxoguanine DNA glycosylase 1 (Ogg1) in allergic airway inflammatory processes.", "output": {"entities": {"chemical": [{"text": "8-oxoguanine", "start": 38, "end": 50}, {"text": "8-oxoG", "start": 52, "end": 58}, {"text": "8-oxoguanine", "start": 114, "end": 126}]}}, "schema": []}
{"input": "Airway inflammation was induced by intranasally administered ragweed (Ambrosia artemisiifolia) pollen grain extract (RWPE) in sensitized BALB/c mice.", "output": {"entities": {}}, "schema": []}
{"input": "We utilized siRNA technology to deplete Ogg1 from airway epithelium; 8-oxoG and DNA strand break levels were quantified by Comet assays.", "output": {"entities": {"chemical": [{"text": "8-oxoG", "start": 69, "end": 75}]}}, "schema": []}
{"input": "Inflammatory cell infiltration and epithelial methaplasia were determined histologically, mucus and cytokines levels biochemically and enhanced pause was used as the main index of airway hyperresponsiveness.", "output": {"entities": {}}, "schema": []}
{"input": "Decreased Ogg1 expression and thereby 8-oxoG repair in the airway epithelium conveyed a lower inflammatory response after RWPE challenge of sensitized mice, as determined by expression of Th2 cytokines, eosinophilia, epithelial methaplasia, and airway hyperresponsiveness.", "output": {"entities": {"chemical": [{"text": "8-oxoG", "start": 38, "end": 44}]}}, "schema": []}
{"input": "In contrast, 8-oxoG repair in Ogg1-proficient airway epithelium was coupled to an increase in DNA single-strand break (SSB) levels and exacerbation of allergen challenge-dependent inflammation.", "output": {"entities": {"chemical": [{"text": "8-oxoG", "start": 13, "end": 19}]}}, "schema": []}
{"input": "Decreased expression of the Nei-like glycosylases Neil1 and Neil2 that preferentially excise ring-opened purines and 5-hydroxyuracil, respectively, did not alter the above parameters of allergic immune responses to RWPE.", "output": {"entities": {"chemical": [{"text": "5-hydroxyuracil", "start": 117, "end": 132}]}}, "schema": []}
{"input": "These results show that DNA SSBs formed during Ogg1-mediated repair of 8-oxoG augment antigen-driven allergic immune responses.", "output": {"entities": {"chemical": [{"text": "8-oxoG", "start": 71, "end": 77}]}}, "schema": []}
{"input": "A transient modulation of OGG1 expression/activity in airway epithelial cells could have clinical benefits.", "output": {"entities": {}}, "schema": []}
{"input": "Nano-and microscaled particles for drug targeting to inflamed intestinal mucosa: a first in vivo study in human patients.", "output": {"entities": {}}, "schema": []}
{"input": "Most of the drugs used in the treatment of inflammatory bowel disease (IBD) become systemically bioavailable and potentially bear strong adverse effects.", "output": {"entities": {}}, "schema": []}
{"input": "Targeting the inflamed areas of the intestine and keeping the drug localised at its site of action can reduce adverse effects.", "output": {"entities": {}}, "schema": []}
{"input": "In animal studies, luminal uptake into inflamed mucosal areas has been shown to be size dependent.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the potential of nano-and microparticle uptake into the rectal mucosa of human IBD patients.", "output": {"entities": {}}, "schema": []}
{"input": "Fluorescently labelled placebo nanoparticles (NP) 250nm in size and microparticles (MP) 3. 0 mu m in size were prepared.", "output": {"entities": {}}, "schema": []}
{"input": "2h after rectal application to patients with Crohn' s disease (CD) or ulcerative colitis (UC), confocal laser endomicroscopy was performed to visualise the particles in inflamed mucosal areas.", "output": {"entities": {}}, "schema": []}
{"input": "In biopsies, ex vivo mucosal transport processes were investigated in miniaturised Ussing chambers.", "output": {"entities": {}}, "schema": []}
{"input": "We examined 33 patients with IBD (19 patients with CD, 14 patients with UC) and 6 healthy controls.", "output": {"entities": {}}, "schema": []}
{"input": "A significantly enhanced accumulation of MP in ulcerous lesions was observed (covered area = 1. 28% (range 0. 83%-3. 45%) vs. 0% in controls; p = 0. 011), while NP were visible only in traces on mucosal surfaces of all patients.", "output": {"entities": {}}, "schema": []}
{"input": "The Ussing chamber experiments suggest persorption of particles through cellular voids; statistical significance was only reached for NP.", "output": {"entities": {}}, "schema": []}
{"input": "Drug-containing particles may have great potential to more specifically target intestinal lesions to maximise therapeutic efficacy and minimise potential side effects.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticles may not be required for local drug delivery to intestinal lesions in humans, thereby minimising the risk of unintended translocation into the blood system.", "output": {"entities": {}}, "schema": []}
{"input": "Sulfur fumigation, a better or worse choice in preservation of Traditional Chinese Medicine?", "output": {"entities": {"chemical": [{"text": "Sulfur", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Sulfur fumigation (SF) in Traditional Chinese Medicine (TCM) is a highly efficient and important traditional preservation method in China.", "output": {"entities": {"chemical": [{"text": "Sulfur", "start": 0, "end": 6}]}}, "schema": []}
{"input": "This method has generated a great deal of concern and has been disputed in the last few years because of its uncertain safety.", "output": {"entities": {}}, "schema": []}
{"input": "SF can alter the quality of TCMs by damaging the bioactive compounds, changing chemical profiles, and generating detrimental exogenous materials.", "output": {"entities": {}}, "schema": []}
{"input": "However, SF is still widely used in the herbal medicinal industry because of its various benefits, such as its pesticidal and anti-bacterial effects, easy operation, and low-cost.", "output": {"entities": {}}, "schema": []}
{"input": "This review contains the current situation, chemical mechanism and reactions during SF, the pharmacological and pharmacokinetic research, and the influence of quality caused by SF.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, a quantification-operation sulfur fumigation device (QOSFD), which can maintain the quality of TCMs by controlling the SF processing parameters, has been designed and introduced.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 40, "end": 46}]}}, "schema": []}
{"input": "The key technologies of this device involve controlling the O (2) content and the temperature of SO (2) as well as the quantification of sulfur in SF.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 60, "end": 65}, {"text": "SO (2)", "start": 97, "end": 103}, {"text": "sulfur", "start": 137, "end": 143}]}}, "schema": []}
{"input": "This device can reduce the possibility of reaction between bioactive compounds and sulfur/sulfurous acid, as well as control the limitation of SO (2) residues.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 83, "end": 89}, {"text": "sulfurous acid", "start": 90, "end": 104}, {"text": "SO (2)", "start": 143, "end": 149}]}}, "schema": []}
{"input": "The QOSFD is regarded as a promising preservation technique in the field of TCM, medicinal materials, agriculture, and fruit industry.", "output": {"entities": {}}, "schema": []}
{"input": "Nerium oleander derived cardiac glycoside oleandrin is a novel inhibitor of HIV infectivity.", "output": {"entities": {"chemical": [{"text": "oleandrin", "start": 42, "end": 51}]}}, "schema": []}
{"input": "We evaluated the effectiveness of Anvirzel (TM), an aqueous extract of Nerium oleander on HIV infection of human peripheral blood mononuclear cells.", "output": {"entities": {}}, "schema": []}
{"input": "Oleandrin, the principle cardiac glycoside (CG) in Anvirzel (TM) has been shown to exhibit anti-cancer properties but its efficacy against HIV is unknown.", "output": {"entities": {"chemical": [{"text": "Oleandrin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Treatment with Anvirzel (TM) significantly reduced the infectivity of virus produced from infected cells without any change in the total amount of virus produced.", "output": {"entities": {}}, "schema": []}
{"input": "This is in contrast to treatment with AZT, a potent inhibitor of HIV replication that has been shown to significantly reduce virus production.", "output": {"entities": {"chemical": [{"text": "AZT", "start": 38, "end": 41}]}}, "schema": []}
{"input": "Relative to untreated cultures, virus in cultures treated with oleandrin had significantly reduced expression of the envelope protein gp120, the sole determinant of virus infectivity, suggesting a novel mechanism underlying the impaired infectivity.", "output": {"entities": {"chemical": [{"text": "oleandrin", "start": 63, "end": 72}]}}, "schema": []}
{"input": "These results support the potential utility of the Nerium oleander aqueous extract, containing the CG oleandrin as a novel candidate anti-HIV therapeutic.", "output": {"entities": {"chemical": [{"text": "oleandrin", "start": 102, "end": 111}]}}, "schema": []}
{"input": "Protective effect of cinnamon polyphenols against STZ-diabetic mice fed high-sugar, high-fat diet and its underlying mechanism.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 30, "end": 41}, {"text": "STZ", "start": 50, "end": 53}]}}, "schema": []}
{"input": "This study was designed to investigate the potential effects of 14days' intragastrically given of cinnamon polyphenols (CPS) in treating diabetic mice induced by intraperitoneal injection of streptozotocin (150mgkg (-1)) and fed high-sugar, high-fat diet.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 107, "end": 118}, {"text": "streptozotocin", "start": 191, "end": 205}, {"text": "sugar", "start": 234, "end": 239}]}}, "schema": []}
{"input": "The diabetic mice model was successfully established through determining on fasting blood-glucose (FBG) test.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 90, "end": 97}]}}, "schema": []}
{"input": "As revealed by glucose oxidase (GOD) and radioimmunoassay (RIA), both dimethyldiguanide (DC, 0. 6gkg (-1) d (-1)) and CPS (0. 3, 0. 6, 1. 2gkg (-1) d (-1)) treatments significantly resulted in down-regulation of blood glucose and insulin levels in serum, while the levels of oxidative stress markers were markedly lowered through ELISA assay.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 15, "end": 22}, {"text": "dimethyldiguanide", "start": 70, "end": 87}, {"text": "glucose", "start": 218, "end": 225}]}}, "schema": []}
{"input": "Meanwhile, the pathological damage in islet with pancreatic beta cells was ameliorated by treatment of CPS at different doses, as shown in HE stain.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, the treatments also caused notable reduction of iNOS, NF-kappa B expressions showing in Western blot analysis.", "output": {"entities": {}}, "schema": []}
{"input": "These findings demonstrate that cinnamon polyphenols can exert the hypoglycemic and hypolipidemic effects through the mechanisms that may be associated with repairing pancreatic beta cells in diabetic mice and improving its anti-oxidative capacity, as well as attenuating cytotoxicity via inhibition of iNOS, NF-kappa B activation.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 41, "end": 52}]}}, "schema": []}
{"input": "Nine new steroidal glycosides from the roots of Cynanchum stauntonii.", "output": {"entities": {"chemical": [{"text": "steroidal glycosides", "start": 9, "end": 29}]}}, "schema": []}
{"input": "Nine new steroidal glycosides, named as stauntosides C-K (2, 5, 7-10, 13, 14, and 16), along with seven known compounds (1, 3, 4, 6, 11, 12, and 15) were isolated from the 95% ethanol extract of the roots of Cynanchum stauntonii.", "output": {"entities": {"chemical": [{"text": "steroidal glycosides", "start": 9, "end": 29}, {"text": "stauntosides C-K", "start": 40, "end": 56}, {"text": "ethanol", "start": 176, "end": 183}]}}, "schema": []}
{"input": "The structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR, and HRESI-MS, and qualitative chemical methods.", "output": {"entities": {}}, "schema": []}
{"input": "Their significance in terms of the chemotaxonomy of C. stauntonii is discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Polymorphisms in OCTN1 and OCTN2 transporters genes are associated with prolonged time to progression in unresectable gastrointestinal stromal tumours treated with imatinib therapy.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 164, "end": 172}]}}, "schema": []}
{"input": "The two basic mainstays of gastrointestinal stromal tumours (GIST) treatment are surgery and imatinib, a selective tyrosine kinase inhibitor that allows achieving a stable or responding disease in about 80% of patients with unresectable/metastatic GIST.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 93, "end": 101}, {"text": "tyrosine", "start": 115, "end": 123}]}}, "schema": []}
{"input": "Response to imatinib mainly depends from KIT and PDGFR alpha mutational status.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 12, "end": 20}]}}, "schema": []}
{"input": "Nevertheless, some patients with a potentially responsive genotype do not respond, and others develop a pattern of resistance to imatinib which is not associated with secondary mutations.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 129, "end": 137}]}}, "schema": []}
{"input": "This emphasizes the presence of mechanisms of resistance other than the receptor-related genotype, and the need of biological predictors to select the optimal therapeutic strategy, particularly now that other potent inhibitors are available.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated a panel of 31 polymorphisms in 11 genes, potentially associated with the pharmacogenetics of imatinib, in a group of 54 unresectable/metastatic GISTs treated with imatinib 400mg daily as first line therapy.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 109, "end": 117}, {"text": "imatinib", "start": 179, "end": 187}]}}, "schema": []}
{"input": "Included in this analysis were polymorphisms in the transporters' family SLC22, SLCO, ABC, and in the metabolizing genes CYP-3A4 and-3A5.", "output": {"entities": {}}, "schema": []}
{"input": "Time to progression was significantly improved in presence of the C allele in SLC22A4 (OCTN1 rs1050152), and the two minor alleles (G) in SLC22A5 (OCTN2 rs2631367 and rs2631372).", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, multivariate analysis, adjusting for age, gender, KIT/PDGFR alpha mutational status, and tumour size, revealed that all the three genotypes maintained independent predictive significance.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, in this study we showed that SLC22A4 and SLC22A5 genotypes may be an important predictor of time to progression in GIST patients receiving imatinib therapy.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 154, "end": 162}]}}, "schema": []}
{"input": "Further investigations are required in an attempt to further personalize GIST therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Postexposure application of Fas receptor small-interfering RNA to suppress sulfur mustard-induced apoptosis in human airway epithelial cells: implication for a therapeutic approach.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 75, "end": 81}]}}, "schema": []}
{"input": "Sulfur mustard (SM) is a vesicant chemical warfare and terrorism agent.", "output": {"entities": {"chemical": [{"text": "Sulfur", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Besides skin and eye injury, respiratory damage has been mainly responsible for morbidity and mortality after SM exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, it was shown that suppressing the death receptor (DR) response by the dominant-negative Fas-associated death domain protein prior to SM exposure blocked apoptosis and microvesication in skin.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we studied whether antagonizing the Fas receptor (FasR) pathway by small-interfering RNA (siRNA) applied after SM exposure would prevent apoptosis and, thus, airway injury.", "output": {"entities": {}}, "schema": []}
{"input": "Normal human bronchial/tracheal epithelial (NHBE) cells were used as an in vitro model with FasR siRNA, FasR agonistic antibody CH11, and FasR antagonistic antibody ZB4 as investigative tools.", "output": {"entities": {}}, "schema": []}
{"input": "In NHBE cells, both SM (300 micro M) and CH11 (100 ng/ml) induced caspase-3 activation, which was inhibited by FasR siRNA and ZB4, indicating that SM-induced apoptosis was via the Fas response.", "output": {"entities": {}}, "schema": []}
{"input": "FasR siRNA inhibited SM-induced caspase-3 activation when added to NHBE cultures up to 8 hours after SM.", "output": {"entities": {}}, "schema": []}
{"input": "Results using annexin V/propidium iodide-stained cells showed that both apoptosis and necrosis were involved in cell death due to SM; FasR siRNA decreased both apoptotic and necrotic cell populations.", "output": {"entities": {"chemical": [{"text": "propidium iodide", "start": 24, "end": 40}]}}, "schema": []}
{"input": "Bronchoalveolar lavage fluid (BALF) of rats exposed to SM (1 mg/kg, 50 minutes) revealed a significant (P < 0. 05) increase in soluble Fas ligand and active caspase-3 in BALF cells.", "output": {"entities": {}}, "schema": []}
{"input": "These findings suggest an intervention of Fas-mediated apoptosis as a postexposure therapeutic strategy with a therapeutic window for SM inhalation injury and possibly other respiratory diseases involving the Fas response.", "output": {"entities": {}}, "schema": []}
{"input": "Fat body dSir2 regulates muscle mitochondrial physiology and energy homeostasis nonautonomously and mimics the autonomous functions of dSir2 in muscles.", "output": {"entities": {}}, "schema": []}
{"input": "Sir2 is an evolutionarily conserved NAD (+)-dependent deacetylase which has been shown to play a critical role in glucose and fat metabolism.", "output": {"entities": {"chemical": [{"text": "NAD (+)", "start": 36, "end": 43}, {"text": "glucose", "start": 114, "end": 121}]}}, "schema": []}
{"input": "In this study, we have perturbed Drosophila Sir2 (dSir2) expression, bidirectionally, in muscles and the fat body.", "output": {"entities": {}}, "schema": []}
{"input": "We report that dSir2 plays a critical role in insulin signaling, glucose homeostasis, and mitochondrial functions.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 65, "end": 72}]}}, "schema": []}
{"input": "Importantly, we establish the nonautonomous functions of fat body dSir2 in regulating mitochondrial physiology and insulin signaling in muscles.", "output": {"entities": {}}, "schema": []}
{"input": "We have identified a novel interplay between dSir2 and dFOXO at an organismal level, which involves Drosophila insulin-like peptide (dILP)-dependent insulin signaling.", "output": {"entities": {}}, "schema": []}
{"input": "By genetic perturbations and metabolic rescue, we provide evidence to illustrate that fat body dSir2 mediates its effects on the muscles via free fatty acids (FFA) and dILPs (from the insulin-producing cells [IPCs]).", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 146, "end": 157}]}}, "schema": []}
{"input": "In summary, we show that fat body dSir2 is a master regulator of organismal energy homeostasis and is required for maintaining the metabolic regulatory network across tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Steady-state of an enzymatic reaction is dependent on the density of reactant.", "output": {"entities": {}}, "schema": []}
{"input": "The post-translational modification of proteins is controlled by the relative activities of two opposing enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "For example, the extent of phosphorylation of tyrosine residues reflects the balance of a kinase and a phosphatase enzyme.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 46, "end": 54}]}}, "schema": []}
{"input": "The present article uses as a model system a self-assembled monolayer that presents a peptide that can be phosphorylated by Abl kinase and subsequently dephosphorylated by Lambda phosphatase.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment of monolayers with a reaction mixture containing both enzymes reveals that the steady-state level of peptide phosphorylation is dependent on the density of the peptide.", "output": {"entities": {}}, "schema": []}
{"input": "Using identical reaction mixtures, surfaces that presented the substrate at high density led to a phosphorylated peptide at steady-state, whereas surfaces that presented the substrate at low density led to unphosphorylated peptide at steady-state.", "output": {"entities": {}}, "schema": []}
{"input": "This dependence owes to an autocatalytic phosphorylation reaction that operates at high densities of substrate.", "output": {"entities": {}}, "schema": []}
{"input": "This work provides an example of an interfacial reaction that has properties that have no analogue in the corresponding solution phase reaction.", "output": {"entities": {}}, "schema": []}
{"input": "It also provides a model system that is relevant to understanding mechanisms that regulate signaling at the cellular membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Alkaline phosphatase as a treatment of sepsis-associated acute kidney injury.", "output": {"entities": {}}, "schema": []}
{"input": "Currently there are no pharmacological therapies licensed to treat sepsis-associated acute kidney injury (AKI).", "output": {"entities": {}}, "schema": []}
{"input": "Considering the high incidence and mortality of sepsis-associated AKI, there is an urgent medical need to develop effective pharmacological interventions.", "output": {"entities": {}}, "schema": []}
{"input": "Two phase II clinical trials recently demonstrated beneficial effects of the enzyme alkaline phosphatase (AP).", "output": {"entities": {}}, "schema": []}
{"input": "In critically ill patients with sepsis-associated AKI, treatment with AP reduced the urinary excretion of tubular injury biomarkers and plasma markers of inflammation, which was associated with improvement of renal function.", "output": {"entities": {}}, "schema": []}
{"input": "The dephosphorylating enzyme, AP, is endogenously present in the renal proximal tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby possibly contributing to further renal damage.", "output": {"entities": {}}, "schema": []}
{"input": "The exact mechanism of action of AP in AKI is unknown, but might be related to detoxification of circulating lipopolysaccharide and other proinflammatory mediators that lose their proinflammatory effects after dephosphorylation.", "output": {"entities": {}}, "schema": []}
{"input": "Alternatively, tissue damage associated with systemic inflammation might be attenuated by an AP-mediated effect on adenosine metabolism.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 115, "end": 124}]}}, "schema": []}
{"input": "Adenosine is a signaling molecule that has been shown to protect the body from inflammation-induced tissue injury, which is derived through dephosphorylation of ATP.", "output": {"entities": {"chemical": [{"text": "Adenosine", "start": 0, "end": 9}, {"text": "ATP", "start": 161, "end": 164}]}}, "schema": []}
{"input": "In this Perspectives article, we discuss the clinical activity of AP and its putative molecular modes of action, and we speculate on its use to treat and possibly prevent sepsis-associated AKI.", "output": {"entities": {}}, "schema": []}
{"input": "Unambiguous structure elucidation of heterocyclic products from condensation-cyclisation reactions of enaminones by 2D INADEQUATE and 15N NMR.", "output": {"entities": {"chemical": [{"text": "enaminones", "start": 102, "end": 112}, {"text": "15N", "start": 134, "end": 137}]}}, "schema": []}
{"input": "The reaction of enaminones with 3-amino-2-cyanopent-2-enedinitrile can lead to an array of 12 possible products, depending on the reaction pathway and tautomerization.", "output": {"entities": {"chemical": [{"text": "enaminones", "start": 16, "end": 26}, {"text": "3-amino-2-cyanopent-2-enedinitrile", "start": 32, "end": 66}]}}, "schema": []}
{"input": "The use of 2D INADEQUATE and (15) N NMR for the unambiguous structure elucidation of the reaction products is discussed in this manuscript.", "output": {"entities": {"chemical": [{"text": "(15) N", "start": 29, "end": 35}]}}, "schema": []}
{"input": "An ion-induced low-oil-adhesion organic/inorganic hybrid film for stable superoleophobicity in seawater.", "output": {"entities": {}}, "schema": []}
{"input": "Superoleophobicity under seawater: An ion-induced low-oil-adhesion film with underwater superoleophobicity is prepared by a typical layer-by-layer (LBL) method.", "output": {"entities": {}}, "schema": []}
{"input": "Under an artificial marine environment with high ion-strength, the prepared polyelectrolytes/AuNPs hybrid film becomes rougher and possesses a higher water ratio, which in turn endows the film with superoleophobicity and low underwater oil adhesion.", "output": {"entities": {}}, "schema": []}
{"input": "The as-prepared film shows excellent environmental stability in artificial seawater.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides a new strategy for controlling the self-cleaning property and accelerating the development of stable underwater superoleophobic films.", "output": {"entities": {}}, "schema": []}
{"input": "p21-Activated kinase 6 (PAK6) inhibits prostate cancer growth via phosphorylation of androgen receptor and tumorigenic E3 ligase murine double minute-2 (Mdm2).", "output": {"entities": {"chemical": [{"text": "androgen", "start": 85, "end": 93}]}}, "schema": []}
{"input": "The androgen receptor (AR) signaling pathway plays a crucial role in the development and growth of prostate malignancies.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 4, "end": 12}]}}, "schema": []}
{"input": "Regulation of AR homeostasis in prostate tumorigenesis has not yet been fully characterized.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we demonstrate that p21-activated kinase 6 (PAK6) inhibits prostate tumorigenesis by regulating AR homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "First, we demonstrated that in normal prostate epithelium, AR co-localizes with PAK6 in the cytoplasm and translocates into the nucleus in malignant prostate.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, AR phosphorylation at Ser-578 by PAK6 promotes AR-E3 ligase murine double minute-2 (Mdm2) association, causing AR degradation upon androgen stimuli.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 35, "end": 38}, {"text": "androgen", "start": 144, "end": 152}]}}, "schema": []}
{"input": "We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation.", "output": {"entities": {"chemical": [{"text": "Thr", "start": 48, "end": 51}, {"text": "Ser", "start": 60, "end": 63}]}}, "schema": []}
{"input": "Moreover, we found that Thr-158 collaborates with Ser-186 for AR-Mdm2 association and AR ubiquitin-mediated degradation as it facilitates PAK6-mediated AR homeostasis.", "output": {"entities": {"chemical": [{"text": "Thr", "start": 24, "end": 27}, {"text": "Ser", "start": 50, "end": 53}]}}, "schema": []}
{"input": "PAK6 knockdown promotes prostate tumor growth in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, we found a strong inverse correlation between PAK6 and AR expression in the cytoplasm of prostate cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "These observations indicate that PAK6 may be important for the maintenance of androgen-induced AR signaling homeostasis and in prostate malignancy, as well as being a possible new therapeutic target for AR-positive and hormone-sensitive prostate cancer.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 78, "end": 86}]}}, "schema": []}
{"input": "ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to establish the role of apoA-IV, ABCA1, and LCAT in the biogenesis of apoA-IV-containing HDL (HDL-A-IV) using different mouse models.", "output": {"entities": {}}, "schema": []}
{"input": "Adenovirus-mediated gene transfer of apoA-IV in apoA-I (-/-) mice did not change plasma lipid levels.", "output": {"entities": {}}, "schema": []}
{"input": "ApoA-IV floated in the HDL2/HDL3 region, promoted the formation of spherical HDL particles as determined by electron microscopy, and generated mostly alpha-and a few pre-beta-like HDL subpopulations.", "output": {"entities": {}}, "schema": []}
{"input": "Gene transfer of apoA-IV in apoA-I (-/-) x apoE (-/-) mice increased plasma cholesterol and triglyceride levels, and 80% of the protein was distributed in the VLDL/IDL/LDL region.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 76, "end": 87}, {"text": "triglyceride", "start": 92, "end": 104}]}}, "schema": []}
{"input": "This treatment likewise generated alpha-and pre-beta-like HDL subpopulations.", "output": {"entities": {}}, "schema": []}
{"input": "Spherical and alpha-migrating HDL particles were not detectable following gene transfer of apoA-IV in ABCA1 (-/-) or LCAT (-/-) mice.", "output": {"entities": {}}, "schema": []}
{"input": "Coexpression of apoA-IV and LCAT in apoA-I (-/-) mice restored the formation of HDL-A-IV.", "output": {"entities": {}}, "schema": []}
{"input": "Lipid-free apoA-IV and reconstituted HDL-A-IV promoted ABCA1 and scavenger receptor BI (SR-BI)-mediated cholesterol efflux, respectively, as efficiently as apoA-I and apoE.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 104, "end": 115}]}}, "schema": []}
{"input": "Our findings are consistent with a novel function of apoA-IV in the biogenesis of discrete HDL-A-IV particles with the participation of ABCA1 and LCAT, and may explain previously reported anti-inflammatory and atheroprotective properties of apoA-IV.", "output": {"entities": {}}, "schema": []}
{"input": "Efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the prevention of the atypical endometrial hyperplasia and endometrial cancer: retrospective data from selected obese menopausal symptomatic women.", "output": {"entities": {"chemical": [{"text": "levonorgestrel", "start": 16, "end": 30}, {"text": "LNG", "start": 52, "end": 55}]}}, "schema": []}
{"input": "The aim of this retrospective study was to evaluate the efficacy of levonorgestrel intrauterine system-releasing (LNG-IUS) insertion in preventing atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in symptomatic postmenopausal overweight/obese women.", "output": {"entities": {"chemical": [{"text": "levonorgestrel", "start": 68, "end": 82}, {"text": "LNG", "start": 114, "end": 117}]}}, "schema": []}
{"input": "A total of 34 overweight/obese postmenopausal women, presenting abnormal uterine bleeding (AUB) and endometrial hyperplasia (EH), and who were submitted to LNG-IUS insertion, were identified from registry data.", "output": {"entities": {"chemical": [{"text": "LNG", "start": 156, "end": 159}]}}, "schema": []}
{"input": "Endometrial histology at LNG-IUS insertion showed simple EH in 20 cases (58. 8%), complex EH in 14 cases (41. 2%).", "output": {"entities": {"chemical": [{"text": "LNG", "start": 25, "end": 28}]}}, "schema": []}
{"input": "At 36 months, 91% of patients showed no recurrence of AUB and a significant reduction in the mean endometrial thickness (from 8. 2 +/- 2. 2 to 3. 2 +/- 1. 5 mm, p < 0. 05) was observed.", "output": {"entities": {}}, "schema": []}
{"input": "Histologic regression of EH was observed in 27 (79. 4%) and 33 (97. 5%) cases at 12 and 36 months, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "None of the women in which EH persisted, reported cellular atypia or cancer progression at 12 and 36 months of follow-up.", "output": {"entities": {}}, "schema": []}
{"input": "LNG-IUS represents an effective treatment option to manage postmenopausal obese women affected by AUB and EH.", "output": {"entities": {"chemical": [{"text": "LNG", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The device seems to be able to prevent the onset of AH and EC in women at high risk.", "output": {"entities": {}}, "schema": []}
{"input": "Further prospective controlled studies in a well selected group of women are needed.", "output": {"entities": {}}, "schema": []}
{"input": "Investigating the roles of different monoamine transmitters and impulse control using the 5-choice serial reaction time task.", "output": {"entities": {"chemical": [{"text": "monoamine", "start": 37, "end": 46}]}}, "schema": []}
{"input": "Previous studies have shown that drugs which block the reuptake of catecholamine neurotransmitters improve impulse control in diseases such as attention deficit hyperactivity disorder (ADHD).", "output": {"entities": {"chemical": [{"text": "catecholamine", "start": 67, "end": 80}]}}, "schema": []}
{"input": "Serotonin-specific reuptake inhibitors (SSRI) lack efficacy in ADHD and have been linked to increased suicide risk.", "output": {"entities": {"chemical": [{"text": "Serotonin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The present study investigated drugs with affinity for one or more of the monoamine reuptake transporters using the 5-choice serial reaction time task, a model of attention and impulsivity in rodents.", "output": {"entities": {"chemical": [{"text": "monoamine", "start": 74, "end": 83}]}}, "schema": []}
{"input": "We also tested the effects of the alpha (2)-adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which both increase cortical noradrenaline concentrations through non-reuptake mechanisms.", "output": {"entities": {"chemical": [{"text": "idazoxan", "start": 68, "end": 76}, {"text": "agomelatine", "start": 103, "end": 114}, {"text": "noradrenaline", "start": 145, "end": 158}]}}, "schema": []}
{"input": "Improvements in impulse control were observed with venlafaxine, a serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion (dopamine and noradrenaline re-uptake inhibitor).", "output": {"entities": {"chemical": [{"text": "venlafaxine", "start": 51, "end": 62}, {"text": "serotonin", "start": 66, "end": 75}, {"text": "noradrenaline", "start": 80, "end": 93}, {"text": "bupropion", "start": 129, "end": 138}, {"text": "dopamine", "start": 140, "end": 148}, {"text": "noradrenaline", "start": 153, "end": 166}]}}, "schema": []}
{"input": "Sibutramine (SNRI) reduced premature responses by ~ 50% at the highest dose tested but this was not significant.", "output": {"entities": {"chemical": [{"text": "Sibutramine", "start": 0, "end": 11}]}}, "schema": []}
{"input": "All three of the SSRIs tested reduced premature responding in a dose-dependent manner, although also slowed response and collection latencies.", "output": {"entities": {}}, "schema": []}
{"input": "Neither idazoxan nor agomelatine significantly reduced premature responding, suggesting a lack of efficacy at the doses tested.", "output": {"entities": {"chemical": [{"text": "idazoxan", "start": 8, "end": 16}, {"text": "agomelatine", "start": 21, "end": 32}]}}, "schema": []}
{"input": "None of the drugs tested improved attention in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all increased omissions at the highest dose tested.", "output": {"entities": {"chemical": [{"text": "sibutramine", "start": 61, "end": 72}, {"text": "fluoxetine", "start": 81, "end": 91}, {"text": "paroxetine", "start": 103, "end": 113}]}}, "schema": []}
{"input": "These data suggest that the SNRIs and SSRIs reduce premature responding but tend to be less specific than noradrenaline specific reuptake inhibitors in this model.", "output": {"entities": {"chemical": [{"text": "noradrenaline", "start": 106, "end": 119}]}}, "schema": []}
{"input": "SSRIs did not induce any specific impairment in impulse control in this model.", "output": {"entities": {}}, "schema": []}
{"input": "The metallohormone cadmium modulates AhR-associated gene expression in the small intestine of rats similar to ethinyl-estradiol.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 19, "end": 26}, {"text": "ethinyl-estradiol", "start": 110, "end": 127}]}}, "schema": []}
{"input": "Cadmium (Cd) affects the expression of estrogen receptor (ER) and aryl hydrocarbon receptor (AhR)-associated genes in rat uterus and elicits estrogen-like activity in vitro.", "output": {"entities": {"chemical": [{"text": "Cadmium", "start": 0, "end": 7}, {"text": "Cd", "start": 9, "end": 11}, {"text": "estrogen", "start": 39, "end": 47}, {"text": "aryl hydrocarbon", "start": 66, "end": 82}, {"text": "estrogen", "start": 141, "end": 149}]}}, "schema": []}
{"input": "The small intestine is highly exposed to dietary Cd which may mimic or antagonize estrogen action in this tissue.", "output": {"entities": {"chemical": [{"text": "Cd", "start": 49, "end": 51}, {"text": "estrogen", "start": 82, "end": 90}]}}, "schema": []}
{"input": "We investigated the effects of Cd and 17-alpha-ethinylestradiol (EE 2) on AhR-associated gene expression after oral exposure of ovariectomized female Wistar rats, and metallothionein (Mt1a) expression as a typical metal-response marker.", "output": {"entities": {"chemical": [{"text": "Cd", "start": 31, "end": 33}, {"text": "17-alpha-ethinylestradiol", "start": 38, "end": 63}, {"text": "EE 2", "start": 65, "end": 69}]}}, "schema": []}
{"input": "Mt1a in the small intestine was strongly induced by co-treatment with CdCl 2 at 2 mg/kg b. wt (Cd 2) and 0. 1 mg/kg b. wt EE2 than by the single compound (3-day gavage).", "output": {"entities": {"chemical": [{"text": "CdCl 2", "start": 70, "end": 76}, {"text": "Cd", "start": 95, "end": 97}, {"text": "EE2", "start": 122, "end": 125}]}}, "schema": []}
{"input": "The Cd 2-induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was not antagonized by pure anti-estrogen (2. 5 mg/kg b. wt ZK191703 s. c., ZK).", "output": {"entities": {"chemical": [{"text": "Cd", "start": 4, "end": 6}, {"text": "estrogen", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Interestingly, the EE 2-induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was antagonized by Cd 2 in vivo and in colon cancer cell lines (HT-29 and CaCo-2, treated 5 days with Cd 1 micro M and/or E 2 0. 01 micro M) with low or no ER-beta expression.", "output": {"entities": {"chemical": [{"text": "EE 2", "start": 19, "end": 23}, {"text": "Cd", "start": 99, "end": 101}, {"text": "Cd", "start": 182, "end": 184}]}}, "schema": []}
{"input": "Dose dependency was studied after Cd exposure with drinking water (5 and 50 ppm CdCl 2 equivalent to 0. 4 and 4 mg/kg b. wt; Cd 0. 4, Cd 4) for 28 days and EE 2 as reference.", "output": {"entities": {"chemical": [{"text": "Cd", "start": 34, "end": 36}, {"text": "CdCl 2", "start": 80, "end": 86}, {"text": "Cd", "start": 125, "end": 127}, {"text": "Cd", "start": 134, "end": 136}, {"text": "EE 2", "start": 156, "end": 160}]}}, "schema": []}
{"input": "Intestinal Mt1a expression was dose dependently induced, while AhR target genes were down-regulated by Cd 0. 4 similar to EE 2 and more pronounced than by Cd 4.", "output": {"entities": {"chemical": [{"text": "Cd", "start": 103, "end": 105}, {"text": "EE 2", "start": 122, "end": 126}, {"text": "Cd", "start": 155, "end": 157}]}}, "schema": []}
{"input": "We propose that Cd modulates intestinal AhR-associated gene expression similar to estrogens, but (contrary to its effects in uterus) via ER-independent and/or ER-beta-mediated mechanisms.", "output": {"entities": {"chemical": [{"text": "Cd", "start": 16, "end": 18}, {"text": "estrogens", "start": 82, "end": 91}]}}, "schema": []}
{"input": "Our new data suggest interference of Cd with estrogen and AhR signaling in the small intestine.", "output": {"entities": {"chemical": [{"text": "Cd", "start": 37, "end": 39}, {"text": "estrogen", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Interactions between chemical and climate stressors: a role for mechanistic toxicology in assessing climate change risks.", "output": {"entities": {}}, "schema": []}
{"input": "Incorporation of global climate change (GCC) effects into assessments of chemical risk and injury requires integrated examinations of chemical and nonchemical stressors.", "output": {"entities": {}}, "schema": []}
{"input": "Environmental variables altered by GCC (temperature, precipitation, salinity, pH) can influence the toxicokinetics of chemical absorption, distribution, metabolism, and excretion as well as toxicodynamic interactions between chemicals and target molecules.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, GCC challenges processes critical for coping with the external environment (water balance, thermoregulation, nutrition, and the immune, endocrine, and neurological systems), leaving organisms sensitive to even slight perturbations by chemicals when pushed to the limits of their physiological tolerance range.", "output": {"entities": {}}, "schema": []}
{"input": "In simplest terms, GCC can make organisms more sensitive to chemical stressors, while alternatively, exposure to chemicals can make organisms more sensitive to GCC stressors.", "output": {"entities": {}}, "schema": []}
{"input": "One challenge is to identify potential interactions between nonchemical and chemical stressors affecting key physiological processes in an organism.", "output": {"entities": {}}, "schema": []}
{"input": "We employed adverse outcome pathways, constructs depicting linkages between mechanism-based molecular initiating events and impacts on individuals or populations, to assess how chemical-and climate-specific variables interact to lead to adverse outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Case examples are presented for prospective scenarios, hypothesizing potential chemical-GCC interactions, and retrospective scenarios, proposing mechanisms for demonstrated chemical-climate interactions in natural populations.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding GCC interactions along adverse outcome pathways facilitates extrapolation between species or other levels of organization, development of hypotheses and focal areas for further research, and improved inputs for risk and resource injury assessments.", "output": {"entities": {}}, "schema": []}
{"input": "How is (68) Ga labeling of macrocyclic chelators influenced by metal ion contaminants in (68) Ge/(68) Ga generator eluates?", "output": {"entities": {"chemical": [{"text": "(68) Ga", "start": 7, "end": 14}, {"text": "(68) Ge", "start": 89, "end": 96}, {"text": "(68) Ga", "start": 97, "end": 104}]}}, "schema": []}
{"input": "To assess the influence of Zn (2 +), Cu (2 +), Fe (3 +), Al (3 +), Ti (IV), and Sn (IV) on incorporation of (68) Ga (3 +) into pendant-arm macrocyclic chelators, the (68) Ga labeling of 1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA), 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA), 1, 4, 7-triazacyclononane-1, 4, 7-tris [methyl (2-carboxyethyl) phosphinic acid]) (TRAP), and 1, 4, 7-triazacyclononane-1-[methyl (2-carboxyethyl) phosphinic acid]-4, 7-bis [methyl (2-hydroxymethyl) phosphinic acid] (NOPO), as well as their peptide conjugates, was investigated in the presence of varying concentrations of these metal ions.", "output": {"entities": {"chemical": [{"text": "Zn (2 +)", "start": 27, "end": 35}, {"text": "Cu (2 +)", "start": 37, "end": 45}, {"text": "Fe (3 +)", "start": 47, "end": 55}, {"text": "Al (3 +)", "start": 57, "end": 65}, {"text": "Ti (IV)", "start": 67, "end": 74}, {"text": "Sn (IV)", "start": 80, "end": 87}, {"text": "(68) Ga (3 +)", "start": 108, "end": 121}, {"text": "(68) Ga", "start": 166, "end": 173}, {"text": "1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid", "start": 186, "end": 234}, {"text": "NOTA", "start": 236, "end": 240}, {"text": "1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid", "start": 243, "end": 305}, {"text": "DOTA", "start": 307, "end": 311}, {"text": "1, 4, 7-triazacyclononane-1, 4, 7-tris [methyl (2-carboxyethyl) phosphinic acid])", "start": 314, "end": 395}, {"text": "TRAP", "start": 397, "end": 401}, {"text": "1, 4, 7-triazacyclononane-1-[methyl (2-carboxyethyl) phosphinic acid]-4, 7-bis [methyl (2-hydroxymethyl) phosphinic acid]", "start": 408, "end": 529}, {"text": "NOPO", "start": 531, "end": 535}]}}, "schema": []}
{"input": "The (68) Ga labeling yield for carboxylate-type chelators NOTA and DOTA is decreased at lower metal ion contaminant concentrations compared with phosphinate-type chelators TRAP and NOPO.", "output": {"entities": {"chemical": [{"text": "(68) Ga", "start": 4, "end": 11}, {"text": "carboxylate", "start": 31, "end": 42}, {"text": "NOTA", "start": 58, "end": 62}, {"text": "DOTA", "start": 67, "end": 71}, {"text": "phosphinate", "start": 145, "end": 156}, {"text": "TRAP", "start": 172, "end": 176}, {"text": "NOPO", "start": 181, "end": 185}]}}, "schema": []}
{"input": "The latter are able to rapidly exchange coordinated Zn (II) with (68) Ga (3 +), as confirmed by mass spectrometry and (31) P NMR spectroscopy.", "output": {"entities": {"chemical": [{"text": "Zn (II)", "start": 52, "end": 59}, {"text": "(68) Ga (3 +)", "start": 65, "end": 78}, {"text": "(31) P", "start": 118, "end": 124}]}}, "schema": []}
{"input": "(68) Ga labeling of Zn (II) complexes of TRAP and NOPO proceeds as efficient as labeling of neat NOTA; this applies also to the corresponding peptide conjugates of these chelators.", "output": {"entities": {"chemical": [{"text": "(68) Ga", "start": 0, "end": 7}, {"text": "Zn (II)", "start": 20, "end": 27}, {"text": "TRAP", "start": 41, "end": 45}, {"text": "NOPO", "start": 50, "end": 54}, {"text": "NOTA", "start": 97, "end": 101}]}}, "schema": []}
{"input": "This behavior results in substantially improved selectivity for Ga (3 +) and, therefore, in more robust and reliable (68) Ga labeling procedures.", "output": {"entities": {"chemical": [{"text": "Ga (3 +)", "start": 64, "end": 72}, {"text": "(68) Ga", "start": 117, "end": 124}]}}, "schema": []}
{"input": "In addition, none of the investigated chelators binds (68) Ge, rendering post-labeling purification protocols, for example, solid-phase extraction, a reliable means of removal of (68) Ge contamination from (68) Ga radiopharmaceuticals.", "output": {"entities": {"chemical": [{"text": "(68) Ge", "start": 54, "end": 61}, {"text": "(68) Ge", "start": 179, "end": 186}, {"text": "(68) Ga", "start": 206, "end": 213}]}}, "schema": []}
{"input": "Influence of global climate change on chemical fate and bioaccumulation: the role of multimedia models.", "output": {"entities": {}}, "schema": []}
{"input": "Multimedia environmental fate models are valuable tools for investigating potential changes associated with global climate change, particularly because thermodynamic forcing on partitioning behavior as well as diffusive and nondiffusive exchange processes are implicitly considered.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, food-web bioaccumulation models are capable of integrating the net effect of changes associated with factors such as temperature, growth rates, feeding preferences, and partitioning behavior on bioaccumulation potential.", "output": {"entities": {}}, "schema": []}
{"input": "For the climate change scenarios considered in the present study, such tools indicate that alterations to exposure concentrations are typically within a factor of 2 of the baseline output.", "output": {"entities": {}}, "schema": []}
{"input": "Based on an appreciation for the uncertainty in model parameters and baseline output, the authors recommend caution when interpreting or speculating on the relative importance of global climate change with respect to how changes caused by it will influence chemical fate and bioavailability.", "output": {"entities": {}}, "schema": []}
{"input": "The frontotemporal lobar degeneration risk factor, TMEM106B, regulates lysosomal morphology and function.", "output": {"entities": {}}, "schema": []}
{"input": "Haploinsufficiency of Progranulin (PGRN), a gene encoding a secreted glycoprotein, is a major cause of frontotemporal lobar degeneration with ubiquitin (FTLD-U) positive inclusions.", "output": {"entities": {}}, "schema": []}
{"input": "Single nucleotide polymorphisms in the TMEM106B gene were recently discovered as a risk factor for FTLD-U, especially in patients with PGRN mutations.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 7, "end": 17}]}}, "schema": []}
{"input": "TMEM106B is also associated with cognitive impairment in amyotrophic lateral sclerosis patients.", "output": {"entities": {}}, "schema": []}
{"input": "Despite these studies, little is known about TMEM106B at molecular and cellular levels and how TMEM106B contributes to FTLD.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that TMEM106B is localized in the late endosome/lysosome compartments and TMEM106B levels are regulated by lysosomal activities.", "output": {"entities": {}}, "schema": []}
{"input": "Ectopic expression of TMEM106B induces morphologic changes of lysosome compartments and delays the degradation of endocytic cargoes by the endolysosomal pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, overexpression of TMEM106B correlates with elevated levels of PGRN, possibly by attenuating lysosomal degradation of PGRN.", "output": {"entities": {}}, "schema": []}
{"input": "These results shed light on the cellular functions of TMEM106B and the roles of TMEM106B in the pathogenesis of FTLD-U with PGRN mutations.", "output": {"entities": {}}, "schema": []}
{"input": "The binding of multiple nuclear receptors to a single regulatory region is important for the proper expression of EDG84A in Drosophila melanogaster.", "output": {"entities": {}}, "schema": []}
{"input": "Nuclear receptor transcription factor family members share target sequence similarity; however, little is known about how these factors exert their specific regulatory control.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we examine the mechanism regulating the expression of the Drosophila EDG84A gene, a target gene of the orphan nuclear receptor beta FTZ-F1, as a model to study the cooperative behavior among nuclear receptors.", "output": {"entities": {}}, "schema": []}
{"input": "We show that the three nuclear receptors beta FTZ-F1, DHR3, and DHR39 bind to a common element in the EDG84A promoter.", "output": {"entities": {}}, "schema": []}
{"input": "The expression level of the EDG84A promoter-lacZ reporter genes in DHR39-induced and mutant animals, respectively, suggests that DHR39 works as a repressor.", "output": {"entities": {}}, "schema": []}
{"input": "The activity of a reporter gene carrying a mutation preventing DHR3 binding was reduced in ftz-f1 mutants and rescued by the induced expression of beta FTZ-F1, suggesting that DHR3 and beta FTZ-F1 activate the EDG84A gene in a redundant manner.", "output": {"entities": {}}, "schema": []}
{"input": "A reporter gene carrying a mutation that abolishes DHR39 and FTZ-F1 binding was prematurely expressed, and the expression level of the reporter gene carrying a mutation preventing DHR3 binding was reduced.", "output": {"entities": {}}, "schema": []}
{"input": "These findings suggest that the temporal expression of this gene is mainly controlled by beta FTZ-F1 but that the binding of DHR3 is also important.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of the binding site sequence among Drosophila species suggests that DHR3 binding ability was gained after the melanogaster subgroup evolved, and this ability may contribute to the robust expression of this gene.", "output": {"entities": {}}, "schema": []}
{"input": "These results show the complicated regulatory mechanisms utilized by multiple nuclear receptors to properly regulate the expression of their target gene through a single target site.", "output": {"entities": {}}, "schema": []}
{"input": "High-dose sodium selenite toxicity cannot be prevented by the co-administration of pharmacological levels of epigallocatechin-3-gallate which in turn aggravates the toxicity.", "output": {"entities": {"chemical": [{"text": "sodium selenite", "start": 10, "end": 25}, {"text": "epigallocatechin-3-gallate", "start": 109, "end": 135}]}}, "schema": []}
{"input": "Selenium, an essential trace element, can also be toxic at higher levels of exposure.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Several lines of evidence show epigallocatechin-3-gallate (EGCG), a predominant component of green tea catechins with numerous health benefits, can ameliorate the toxicity of many agents.", "output": {"entities": {"chemical": [{"text": "epigallocatechin-3-gallate", "start": 31, "end": 57}, {"text": "EGCG", "start": 59, "end": 63}, {"text": "catechins", "start": 103, "end": 112}]}}, "schema": []}
{"input": "A proof-in-principle experiment was conducted to determine if EGCG would ameliorate sodium selenite-induced growth suppression.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 62, "end": 66}, {"text": "sodium selenite", "start": 84, "end": 99}]}}, "schema": []}
{"input": "Mice were intraperitioneally injected with selenite once daily for five days at a dose of 3 mg Se/kg, which fully suppressed animal growth but did not cause death.", "output": {"entities": {"chemical": [{"text": "selenite", "start": 43, "end": 51}, {"text": "Se", "start": 95, "end": 97}]}}, "schema": []}
{"input": "Surprisingly the co-administration of the selenite and nontoxic doses of EGCG (10, 20 and 40 mg/kg, intraperitioneally) resulted in the mortality of treated mice in a dose and time-dependent manner (33. 3%, 100% and 100%, respectively).", "output": {"entities": {"chemical": [{"text": "selenite", "start": 42, "end": 50}, {"text": "EGCG", "start": 73, "end": 77}]}}, "schema": []}
{"input": "EGCG-selenite induced lethality did not result from enhanced selenium accumulation but appeared to involve the suppression of a selenite-induced adaptive response as evidenced by hepatic glutathione S-transferase activity.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 0, "end": 4}, {"text": "selenite", "start": 5, "end": 13}, {"text": "selenium", "start": 61, "end": 69}, {"text": "selenite", "start": 128, "end": 136}, {"text": "glutathione S", "start": 187, "end": 200}]}}, "schema": []}
{"input": "While EGCG has been reported to ameliorate the toxicity of some agents, the induction of mortality by combined treatment with pharmacological doses of selenium and EGCG is a previously unrecognized synergism that must be considered not only in the remediation of high environmental selenium exposures but also in the development of pharmaceuticals and nutriceuticals.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 6, "end": 10}, {"text": "selenium", "start": 151, "end": 159}, {"text": "EGCG", "start": 164, "end": 168}, {"text": "selenium", "start": 282, "end": 290}]}}, "schema": []}
{"input": "Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice.", "output": {"entities": {}}, "schema": []}
{"input": "Genome-wide association studies recently identified 32 loci that associate with the age at menarche (AAM) in humans.", "output": {"entities": {}}, "schema": []}
{"input": "Because the locus most robustly associated with AAM is in/near LIN28B, the goal of this study was to investigate how the Lin28 pathway might modulate pubertal timing by examining expression of Lin28b, and its homologue, Lin28a, across the pubertal transition in female mice.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative reverse-transcriptase PCR data indicate that, prior to the onset of puberty, expression of both Lin28b and Lin28a decreases in the ovary, while expression of only Lin28a decreases in the hypothalamus; the expression of Lin28a increases after the onset of puberty in the pituitary.", "output": {"entities": {}}, "schema": []}
{"input": "Immunohistochemistry in ovarian tissue verified that Lin28a protein levels decreased in parallel with gene expression.", "output": {"entities": {}}, "schema": []}
{"input": "Although these data do not demonstrate cause and effect, they do suggest that decreased expression of Lin28a/Lin28b may facilitate the transition into puberty, consistent with previous data showing that overexpression of Lin28a in transgenic mice leads to delayed puberty.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, although Lin28b and/or Lin28a expression significantly decreased prior to puberty, neither Let-7a nor Let-7g miRNA levels changed significantly, raising the possibility that some effects of Lin28b and Lin28a within the hypothalamic-pituitary-gonadal (HPG) axis may be Let-7 miRNA independent.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequent studies, such as tissue and age specific modulation of Lin28b and Lin28a expression, could determine whether the expression patterns observed are responsible for modulating the onset of puberty and delineate further the role of this pathway in the HPG axis.", "output": {"entities": {}}, "schema": []}
{"input": "Chinese medicine formula \" Weikang Keli \" induces autophagic cell death on human gastric cancer cell line SGC-7901.", "output": {"entities": {}}, "schema": []}
{"input": "Weikang Keli (constitutes of Root of Codonopsis pilosula, Rhizoma Atractylodis Macrocephalae, Rhizoma Curcumae Aeruginosae, Rhizoma Pinelliae, Actinidia chinensis Planch, and Rhodiola rosea) is a well known Chinese herbal formula for gastric cancer therapy in clinical treatment.", "output": {"entities": {}}, "schema": []}
{"input": "However, the detailed molecular mechanisms involved are still not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we found that Weikang Keli could induce patterns of autophagy in SGC-7901 cells, including intracellular vacuole formation, microtubule-associated protein 1 light chain 3 (LC3) conversion.", "output": {"entities": {}}, "schema": []}
{"input": "Hoechst 33258 staining and Western blot analysis of apoptosis-related proteins showed that WK induced SGC-7901 cell death was not through apoptosis.", "output": {"entities": {"chemical": [{"text": "Hoechst 33258", "start": 0, "end": 13}]}}, "schema": []}
{"input": "In vivo study also revealed that i. g. administration of Weikang Keli once a day for 25 days could significantly reduce tumor volumes by about 50%.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, the current data indicated that Weikang Keli induced gastric cancer cell death by autophagy effects.", "output": {"entities": {}}, "schema": []}
{"input": "Relieving visceral hyperalgesia effect of Kangtai capsule and its potential mechanisms via modulating the 5-HT and NO level in vivo.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 106, "end": 110}, {"text": "NO", "start": 115, "end": 117}]}}, "schema": []}
{"input": "Kangtai capsule (KT) is one type of traditional Chinese medicine preparation derived from the proved recipe, which was frequently applied as an effective clinical treatment of IBS.", "output": {"entities": {}}, "schema": []}
{"input": "However, there still lack the reasonable and all-round analytical approach and the scientific studies on its underlying mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, our study aimed to develop the novel method for evaluating its quality as well as to interpret the potential mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "In our study, high performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of KT.", "output": {"entities": {}}, "schema": []}
{"input": "The neonatal maternal separation (NMS) on Sprague-Dawley pups was employed to evaluate the therapeutic effect of KT by virtue of various parameters including visceral hyperalgesia, serum nitric oxide (NO) level, and tissue 5-hydroxytryptamine (5-HT) level.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 187, "end": 199}, {"text": "NO", "start": 201, "end": 203}, {"text": "5-hydroxytryptamine", "start": 223, "end": 242}, {"text": "5-HT", "start": 244, "end": 248}]}}, "schema": []}
{"input": "Consequently, a chromatographic condition, which was carried at 30 degrees C with a flow rate of 0. 5 ml/min on AQUA 3 mu C18 column with mobile phase of acetonitrile and water-phosphoric acid (100: 0. 1, v/v), was established to give a common fingerprint chromatography under 254 nm with a similarity index of 0. 963 within ten batches of KT samples.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 154, "end": 166}, {"text": "phosphoric acid", "start": 177, "end": 192}]}}, "schema": []}
{"input": "On the NMS model, KT markedly elevated the pain threshold of NMS rats.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, KT at three doses significantly decreased 5-HT content from distal colon of visceral hyperalgesia rats induced by NMS, while the significant decrease of 5-HT content in serum was only observed in the group with KT at high dose.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 55, "end": 59}, {"text": "5-HT", "start": 166, "end": 170}]}}, "schema": []}
{"input": "However, compared with that in NMS rats without KT, there was no apparent difference of 5-HT level from brain issue in the rats with various doses.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 88, "end": 92}]}}, "schema": []}
{"input": "Besides, KT could substantially elevate the concentration of NO in the serum.", "output": {"entities": {"chemical": [{"text": "NO", "start": 61, "end": 63}]}}, "schema": []}
{"input": "The results showed our study developed the simple, rapid, accurate, reproducible qualitative and quantitative analysis by HPLC fingerprint for the quality control for KT.", "output": {"entities": {}}, "schema": []}
{"input": "Data from the pharmacological investigation suggested that the curative effect of KT to the visceral hypersensitivity may be concerned with the level of 5-HT and NO in vivo, promising its potential in irritable bowel syndrome treatment.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 153, "end": 157}, {"text": "NO", "start": 162, "end": 164}]}}, "schema": []}
{"input": "First report of the use of a saxitoxin-protein conjugate to develop a DNA aptamer to a small molecule toxin.", "output": {"entities": {"chemical": [{"text": "saxitoxin", "start": 29, "end": 38}]}}, "schema": []}
{"input": "Saxitoxin (STX) is a low molecular weight neurotoxin mainly produced by certain marine dinoflagellates that, along with its family of similarly related paralytic shellfish toxins, may cause the potentially fatal intoxication known as paralytic shellfish poisoning.", "output": {"entities": {"chemical": [{"text": "Saxitoxin", "start": 0, "end": 9}, {"text": "STX", "start": 11, "end": 14}]}}, "schema": []}
{"input": "Illness and fatality rates are low due to the effective monitoring programs that determine when toxins exceed the established regulatory action level and effectuate shellfish harvesting closures accordingly.", "output": {"entities": {}}, "schema": []}
{"input": "Such monitoring programs rely on the ability to rapidly screen large volumes of samples.", "output": {"entities": {}}, "schema": []}
{"input": "Many of the screening assays currently available employ antibodies or live animals.", "output": {"entities": {}}, "schema": []}
{"input": "This research focused on developing an analytical recognition element that would eliminate the challenges associated with the limited availability of antibodies and the use of animals.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report the discovery of a DNA aptamer that targets STX.", "output": {"entities": {"chemical": [{"text": "STX", "start": 59, "end": 62}]}}, "schema": []}
{"input": "Concentration-dependent and selective binding of the aptamer to STX was determined using a surface plasmon resonance sensor.", "output": {"entities": {"chemical": [{"text": "STX", "start": 64, "end": 67}]}}, "schema": []}
{"input": "Not only does this work represent the first reported aptamer to STX, but also the first aptamer to any marine biotoxin.", "output": {"entities": {"chemical": [{"text": "STX", "start": 64, "end": 67}]}}, "schema": []}
{"input": "A novel strategy of using a toxin-protein conjugate for DNA aptamer selection was successfully implemented to overcome the challenges associated with aptamer selection to small molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Taking advantage of such an approach could lead to increased diversity and accessibility of aptamers to low molecular weight toxins, which could then be incorporated as analytical recognition elements in diagnostic assays for foodborne toxin detection.", "output": {"entities": {}}, "schema": []}
{"input": "The selected STX aptamer sequence is provided here, making it available to any investigator for use in assay development for the detection of STX.", "output": {"entities": {"chemical": [{"text": "STX", "start": 13, "end": 16}, {"text": "STX", "start": 142, "end": 145}]}}, "schema": []}
{"input": "Nanomedicine for the treatment of retinal and optic nerve diseases.", "output": {"entities": {"chemical": [{"text": "retinal", "start": 34, "end": 41}]}}, "schema": []}
{"input": "The earliest impact of nanomedicine in ophthalmology is likely to involve the areas of biopharmaceuticals, implantable materials (e. g. tissue regeneration scaffolds, bioresorbable materials), implantable devices (e. g. glaucoma drainage valves), and diagnostic tools (e. g. intraocular pressure (IOP) monitors).", "output": {"entities": {}}, "schema": []}
{"input": "Nanotechnology will bring about the development of regenerative medicine (i. e. replacement and improvement of cells, tissues, and organs) and artificial vision.", "output": {"entities": {}}, "schema": []}
{"input": "In this chapter, we review ophthalmic applications of nanotechnology in the following areas: drug and trophic factor therapy for glaucoma, retinal degenerative, and retinal vascular disease; gene therapy for retinal degenerative disease; regenerative medicine, including optogenetics and optic nerve regeneration; and diagnostics (minimally invasive IOP monitoring).", "output": {"entities": {"chemical": [{"text": "retinal", "start": 139, "end": 146}]}}, "schema": []}
{"input": "Nanotechnology will play an important role in both early-stage and late-stage intervention in the management of blinding diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of presumptive biomarkers of oxidative stress, immune response and apoptosis in primary open-angle glaucoma.", "output": {"entities": {}}, "schema": []}
{"input": "There is growing interest on the correlation among oxidative stress, inflammation, apoptosis and primary open-angle glaucoma initiation and progression.", "output": {"entities": {}}, "schema": []}
{"input": "Reactive oxygen species are formed in the eyes following a wide variety of stressors, and are largely implicated in glaucoma pathogenesis.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 9, "end": 15}]}}, "schema": []}
{"input": "Immune-inflammatory response mediators have recently become a target of ophthalmologic concern, including glaucoma.", "output": {"entities": {}}, "schema": []}
{"input": "Much attention has been derived to the role of specific pro and anti-apoptotic molecules in glaucoma.", "output": {"entities": {}}, "schema": []}
{"input": "This article reviews the early evidence suggesting that reactive oxygen species, immune inflammatory response mediators, and apoptogenic molecules are engaged in glaucoma disease.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 65, "end": 71}]}}, "schema": []}
{"input": "Moreover, further research concerning the functions, effectors and signaling pathways of the above molecules and their interactions, may lead to specifically develop targeted screening tools based on presumptive biomarkers and surrogate endpoints against primary open-angle glaucoma progression and blindness.", "output": {"entities": {}}, "schema": []}
{"input": "Pushing short DNA fragments to the limit: Phylogenetic relationships of' hydrobioid' gastropods (Caenogastropoda: Rissooidea).", "output": {"entities": {}}, "schema": []}
{"input": "Although phylogenetic studies are increasingly utilizing multi-locus datasets, a review of GenBank data for the Gastropoda indicates a strong bias towards a few short gene fragments (most commonly COI, LSU rRNA, and SSU rRNA).", "output": {"entities": {}}, "schema": []}
{"input": "This is particularly the case for the Rissooidea, one of the largest and most taxonomically difficult gastropod superfamilies.", "output": {"entities": {}}, "schema": []}
{"input": "Here we analyze fragments of these three genes from 90 species to determine whether they can well resolve higher relationships within this superfamily, whether structurally aligned sequence datasets increase phylogenetic signal, and whether the inclusion of highly variable regions introduces noise.", "output": {"entities": {}}, "schema": []}
{"input": "We also used the resulting phylogenetic data in combination with morphological/anatomical evidence to re-evaluate the taxonomic status of' hydrobioid' family-level groups.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that all three of the alignment strategies that were used resulted in phylogenies having similar signal levels.", "output": {"entities": {}}, "schema": []}
{"input": "However, there was a slight advantage to using structural alignment for inferring family-level relationships.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the set of' standard' gastropod genes supported recognition of many previously recognized families and provides new insight into the systematics of several problematic groups.", "output": {"entities": {}}, "schema": []}
{"input": "However, some family-group taxa were unresolved and the relationships among families were also poorly supported, suggesting a need for more extensive sampling and inclusion of additional genes.", "output": {"entities": {}}, "schema": []}
{"input": "Divergence in androgen sensitivity contributes to population differences in sexual dimorphism of electrocommunication behavior.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 14, "end": 22}]}}, "schema": []}
{"input": "Weakly-electric fish (Apteronotidae) produce highly diverse electrocommunication signals.", "output": {"entities": {}}, "schema": []}
{"input": "Electric organ discharges (EODs) vary across species, sexes, and in the magnitude and direction of their sexual dimorphism.", "output": {"entities": {}}, "schema": []}
{"input": "Gonadal steroid hormones can modulate EODs, and differences in androgen sensitivity are hypothesized to underlie variation in the degree of sexual dimorphism across species.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 63, "end": 71}]}}, "schema": []}
{"input": "In this study, we asked whether variation in androgen sensitivity explained variation in sexual dimorphism of EODs within species, at the population level.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 45, "end": 53}]}}, "schema": []}
{"input": "We examined two populations of black ghost knifefish (Apteronotus albifrons), one from the Orinoco and the other from the Amazon River Basin.", "output": {"entities": {}}, "schema": []}
{"input": "EOD frequency (EODf) and chirp rates were measured to characterize diversity in sexual dimorphism across populations.", "output": {"entities": {}}, "schema": []}
{"input": "The magnitude of sexual dimorphism in EODf differed significantly across populations, and was more pronounced in the Orinoco population than in the Amazon population.", "output": {"entities": {}}, "schema": []}
{"input": "Chirp rates were sexually monomorphic in both populations.", "output": {"entities": {}}, "schema": []}
{"input": "11-Ketotestosterone (11-kT) was administered over a two-week period to assess population differences in sensitivity to androgens.", "output": {"entities": {"chemical": [{"text": "11-Ketotestosterone", "start": 0, "end": 19}, {"text": "11-kT", "start": 21, "end": 26}, {"text": "androgens", "start": 119, "end": 128}]}}, "schema": []}
{"input": "11-kT masculinized EODf significantly more in the population with the greater degree of sexual dimorphism.", "output": {"entities": {"chemical": [{"text": "11-kT", "start": 0, "end": 5}]}}, "schema": []}
{"input": "11-kT had no effect on the sexually monomorphic chirping rates.", "output": {"entities": {"chemical": [{"text": "11-kT", "start": 0, "end": 5}]}}, "schema": []}
{"input": "We conclude that population divergence in androgen sensitivity contributes to variation in sexual dimorphism of EODf in A. albifrons.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Effects of phospholipase A2 and metalloprotease fractions of Russell' s viper venom on cytokines and renal hemodynamics in dogs.", "output": {"entities": {}}, "schema": []}
{"input": "Several enzymes in Russell' s viper (Daboia siamensis) venom are involved in the venom effects and renal injury.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of fractional components of Russell' s viper venom, phospholipase A (2) and metalloprotease fractions, were examined in two groups of four experimental dogs each.", "output": {"entities": {}}, "schema": []}
{"input": "Animals received an intravenous injection of 140 mu g/kg of each venom fraction.", "output": {"entities": {}}, "schema": []}
{"input": "The inflammatory effects and renal hemodynamic changes were assessed.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and PGE2 were elevated by both phospholipase A (2) (PLA (2)) and metalloprotease (MP) fractions.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 91, "end": 95}]}}, "schema": []}
{"input": "The plasma level of nitric oxide was increased after PLA (2) fraction injection but not with MP fraction injection.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 20, "end": 32}]}}, "schema": []}
{"input": "Leukocytosis with increase in lymphocytes, monocytes and granulocytes was observed after both PLA (2) and MP injections.", "output": {"entities": {}}, "schema": []}
{"input": "Results from this study suggested that both PLA (2) and MP were inflammatory.", "output": {"entities": {}}, "schema": []}
{"input": "Increased red blood cell count, hematocrit and hemoglobin concentration were observed in animals injected with PLA (2) fraction, but not with MP fraction.", "output": {"entities": {}}, "schema": []}
{"input": "Hemodynamically, PLA (2) fraction induced marked decrease in mean arterial pressure with decreased renal vascular resistance initially followed later by increased renal vascular resistance.", "output": {"entities": {}}, "schema": []}
{"input": "MP fraction caused less decrease of mean arterial pressure but increased renal vascular resistance throughout the experiment.", "output": {"entities": {}}, "schema": []}
{"input": "Both enzymes decreased renal blood flow, glomerular filtration rate and urine flow.", "output": {"entities": {}}, "schema": []}
{"input": "The findings indicate vasodilating effect of PLA (2) fraction and vasoconstricting effect and decreased cardiac function of MP fraction.", "output": {"entities": {}}, "schema": []}
{"input": "Heteromtoxin (HmTx), a novel heterodimeric phospholipase A (2) from Heterometrus laoticus scorpion venom.", "output": {"entities": {}}, "schema": []}
{"input": "Heteromtoxin (HmTx) is a group III phospholipase A (2) produced in Heterometrus laoticus, in Thailand.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, HmTx was purified from venom by separation chromatography, and the PLA (2) activity of the fractions was determined by lecithin agar assay.", "output": {"entities": {}}, "schema": []}
{"input": "The enzyme is an acidic protein with a pI of 5. 6 and an apparent molecular weight of 14018. 4 Da.", "output": {"entities": {}}, "schema": []}
{"input": "The nucleotide sequence of HmTx contains 649 bp, and the mature protein is predicted to have 131 amino acid residues-104 of which make up the large subunit, and 27 of which make up the small subunit.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 4, "end": 14}, {"text": "amino acid", "start": 97, "end": 107}]}}, "schema": []}
{"input": "The subunit structure of HmTx is highly similar to that of the other toxin, Pandinus imperator imperatoxin I (IpTx (i)) and to Mesobuthus tamulus phospholipase A (2) (MtPLA (2)).", "output": {"entities": {}}, "schema": []}
{"input": "The 3D-structure of HmTx consists of three conserved alpha-helices: h1 (Lys24-His34), h2 (Cys59-Asp71), and h3 (Ala80-Phe89).", "output": {"entities": {"chemical": [{"text": "Lys24", "start": 72, "end": 77}, {"text": "His34", "start": 78, "end": 83}, {"text": "Cys59", "start": 90, "end": 95}, {"text": "Asp71", "start": 96, "end": 101}, {"text": "Ala80", "start": 112, "end": 117}, {"text": "Phe89", "start": 118, "end": 123}]}}, "schema": []}
{"input": "The beta-sheet consisted of a single stranded anti-parallel beta-sheet (b1. 1 at Glu43-Lys45 and b1. 2 at Lys48-Asn50) that was highly similar to the conserved sequences (-CGXG-,-CCXXHDXC-and CXCEXXXXXC-) of Apis mellifera (bee) phospholipases.", "output": {"entities": {"chemical": [{"text": "Glu43", "start": 81, "end": 86}, {"text": "Lys45", "start": 87, "end": 92}, {"text": "Lys48", "start": 106, "end": 111}, {"text": "Asn50", "start": 112, "end": 117}]}}, "schema": []}
{"input": "A non-catalytic function of Rev1 in translesion DNA synthesis and mutagenesis is mediated by its stable interaction with Rad5.", "output": {"entities": {}}, "schema": []}
{"input": "DNA damage tolerance consisting of template switching and translesion synthesis is a major cellular mechanism in response to unrepaired DNA lesions during replication.", "output": {"entities": {}}, "schema": []}
{"input": "The Rev1 pathway constitutes the major mechanism of translesion synthesis and base damage-induced mutagenesis in model cell systems.", "output": {"entities": {}}, "schema": []}
{"input": "Rev1 is a dCMP transferase, but additionally plays non-catalytic functions in translesion synthesis.", "output": {"entities": {"chemical": [{"text": "dCMP", "start": 10, "end": 14}]}}, "schema": []}
{"input": "Using the yeast model system, we attempted to gain further insights into the non-catalytic functions of Rev1.", "output": {"entities": {}}, "schema": []}
{"input": "Rev1 stably interacts with Rad5 (a central component of the template switching pathway) via the C-terminal region of Rev1 and the N-terminal region of Rad5.", "output": {"entities": {"chemical": [{"text": "C", "start": 96, "end": 97}, {"text": "N", "start": 130, "end": 131}]}}, "schema": []}
{"input": "Supporting functional significance of this interaction, both the Rev1 pathway and Rad5 are required for translesion synthesis and mutagenesis of 1, N (6)-ethenoadenine.", "output": {"entities": {"chemical": [{"text": "1, N (6)-ethenoadenine", "start": 145, "end": 167}]}}, "schema": []}
{"input": "Furthermore, disrupting the Rev1-Rad5 interaction by mutating Rev1 did not affect its dCMP transferase, but led to inactivation of the Rev1 non-catalytic function in translesion synthesis of UV-induced DNA damage.", "output": {"entities": {"chemical": [{"text": "dCMP", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Deletion analysis revealed that the C-terminal 21-amino acid sequence of Rev1 is uniquely required for its interaction with Rad5 and is essential for its non-catalytic function.", "output": {"entities": {"chemical": [{"text": "C", "start": 36, "end": 37}, {"text": "amino acid", "start": 50, "end": 60}]}}, "schema": []}
{"input": "Deletion analysis additionally implicated a C-terminal region of Rev1 in its negative regulation.", "output": {"entities": {"chemical": [{"text": "C", "start": 44, "end": 45}]}}, "schema": []}
{"input": "These results show that a non-catalytic function of Rev1 in translesion synthesis and mutagenesis is mediated by its interaction with Rad5.", "output": {"entities": {}}, "schema": []}
{"input": "TNF-alpha-induced CXCL8 production by A549 cells: involvement of the non-neuronal cholinergic system.", "output": {"entities": {}}, "schema": []}
{"input": "It was recently suggested that the non-neuronal cholinergic system has a regulatory role in pulmonary inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated this system' s involvement in the control of cytokine production by the A549 human alveolar epithelial cell line.", "output": {"entities": {}}, "schema": []}
{"input": "CXCL8 and acetylcholine (ACh) concentrations were measured using ELISA and LC-MS/MS, respectively.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 10, "end": 23}, {"text": "ACh", "start": 25, "end": 28}]}}, "schema": []}
{"input": "The mRNA expression of muscarinic receptor (MR) subtypes was determined using RT-PCR.", "output": {"entities": {}}, "schema": []}
{"input": "In A549 cells, TNF-alpha increased the release of CXCL8 and ACh and the expression of the subtype 3 MR (M3R).", "output": {"entities": {"chemical": [{"text": "ACh", "start": 60, "end": 63}]}}, "schema": []}
{"input": "Furthermore, TNF-alpha-induced CXCL8 secretion was (i) inhibited by the MR antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine.", "output": {"entities": {"chemical": [{"text": "tiotropium", "start": 86, "end": 96}, {"text": "4-DAMP", "start": 120, "end": 126}, {"text": "pilocarpine", "start": 167, "end": 178}, {"text": "physostigmine", "start": 212, "end": 225}]}}, "schema": []}
{"input": "Taken as a whole, these results suggest that ACh release by A549 cells enhances TNF-alpha-induced CXCL8 secretion through activation of the M3R.", "output": {"entities": {"chemical": [{"text": "ACh", "start": 45, "end": 48}]}}, "schema": []}
{"input": "Western blot analysis revealed that pilocarpine and physostigmine enhanced the TNF-alpha-induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of I kappa B alpha.", "output": {"entities": {"chemical": [{"text": "pilocarpine", "start": 36, "end": 47}, {"text": "physostigmine", "start": 52, "end": 65}]}}, "schema": []}
{"input": "Inhibition of these pathways with specific inhibitors abrogated the pilocarpine-induced CXCL8 release.", "output": {"entities": {"chemical": [{"text": "pilocarpine", "start": 68, "end": 79}]}}, "schema": []}
{"input": "Our results suggest that the TNF-alpha-induced secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latter' s binding to the M3R and the downstream activation of NF-kappa B and the ERK1/2 and p38 MAPK signaling pathways.", "output": {"entities": {"chemical": [{"text": "ACh", "start": 111, "end": 114}]}}, "schema": []}
{"input": "Our findings suggest that MR antagonists may have anti-inflammatory effects by preventing pro-inflammatory events driven by endogenous, non-neuronal ACh.", "output": {"entities": {"chemical": [{"text": "ACh", "start": 149, "end": 152}]}}, "schema": []}
{"input": "Inhibition of vitellogenin gene induction by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin is mediated by aryl hydrocarbon receptor 2 (AHR2) in zebrafish (Danio rerio).", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 45, "end": 83}, {"text": "aryl hydrocarbon", "start": 99, "end": 115}]}}, "schema": []}
{"input": "Vitellogenins are hepatically derived yolk-protein precursors required for oogenesis in all oviparous teleosts.", "output": {"entities": {}}, "schema": []}
{"input": "Altered gene-regulation of vitellogenesis by environmental contaminants can have profound effects on reproductive success, and ultimately population sustainability.", "output": {"entities": {}}, "schema": []}
{"input": "To better understand chemical effects on vitellogenin gene regulation, we tested the hypothesis that activation of the aryl hydrocarbon receptor 2 (AHR2) by dioxin inhibits the estrogen receptor pathway regulation of 3 vitellogenin genes (vtg1-3) in vivo, using zebrafish (Danio rerio) as a model teleost.", "output": {"entities": {"chemical": [{"text": "aryl hydrocarbon", "start": 119, "end": 135}, {"text": "dioxin", "start": 157, "end": 163}, {"text": "estrogen", "start": 177, "end": 185}]}}, "schema": []}
{"input": "Using an embryo-larval bioassay, embryos were either treated with 1000 pptr (parts-per-trillion, pg/mL) 17 alpha-ethynylestradiol (EE2) alone from 6h post fertilization (hpf) to 4 days post fertilization (dpf), or pre-treated with dioxin (4-5 hpf) prior to EE2.", "output": {"entities": {"chemical": [{"text": "17 alpha-ethynylestradiol", "start": 104, "end": 129}, {"text": "EE2", "start": 131, "end": 134}, {"text": "EE2", "start": 257, "end": 260}]}}, "schema": []}
{"input": "Pre-treatment with 400 pptr 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (2, 3, 7, 8-TCDD) or 1, 2, 3, 7, 8-pentachlorodibenzo-p-dioxin inhibited the EE2 induction of vtg1, vtg2 and vtg3 by > 95% (p <= 0. 05).", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 28, "end": 66}, {"text": "2, 3, 7, 8-TCDD", "start": 68, "end": 83}, {"text": "1, 2, 3, 7, 8-pentachlorodibenzo-p-dioxin", "start": 88, "end": 129}, {"text": "EE2", "start": 144, "end": 147}]}}, "schema": []}
{"input": "In comparison, a splice-blocking AHR2 morpholino used to down-regulate ahr2 expression significantly reduced the inhibition of vtg1, vtg2 and vtg3 by 400 pptr 2, 3, 7, 8-TCDD (20. 7-27. 4% rescue).", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-TCDD", "start": 159, "end": 174}]}}, "schema": []}
{"input": "These studies demonstrate that 2, 3, 7, 8-TCDD directly inhibits the vitellogenin pathway in vivo through activation of the AHR2.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-TCDD", "start": 31, "end": 46}]}}, "schema": []}
{"input": "This work provides evidence for AHR2 dependent cross-talk inhibition of vitellogenin genes and offers insight into anti-estrogenic reproductive effects observed in oviparous species exposed to AHR agonist contaminants.", "output": {"entities": {}}, "schema": []}
{"input": "Developing and advancing dry powder inhalation towards enhanced therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Enhanced therapeutics are drug products derived from existing generic drugs that provide additional benefits to the patients and the healthcare system.", "output": {"entities": {}}, "schema": []}
{"input": "Enhanced therapeutics are considered to be an important and relatively low risk source of innovation.", "output": {"entities": {}}, "schema": []}
{"input": "Pulmonary drug delivery is the major delivery route to treat chronic respiratory diseases and has been proven as a potential delivery route for complex drugs that cannot be delivered orally.", "output": {"entities": {}}, "schema": []}
{"input": "Development of dry powder inhalation systems targets the delivery of fine drug particles to the deep lung surface by a combination of drug formulation, primary packaging and a device, whereby each contributes to the overall performance.", "output": {"entities": {}}, "schema": []}
{"input": "Various methodologies for the non-clinical and clinical performance testing of orally inhaled products have been proposed and applied with variable success.", "output": {"entities": {}}, "schema": []}
{"input": "Regulatory pathways have been developed and applied since.", "output": {"entities": {}}, "schema": []}
{"input": "Considerable efforts have been made during the past decade to understand and optimize pulmonary drug delivery including their efficient commercial manufacturing.", "output": {"entities": {}}, "schema": []}
{"input": "Pulmonary drug delivery remains an area of future innovation in the effective treatment of pulmonary diseases as well as the systemic delivery of systemically active complex drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicity in mice of lectin ebulin f present in dwarf Elderberry (Sambucus ebulus L.).", "output": {"entities": {}}, "schema": []}
{"input": "Dwarf elder fruits (Sambucus ebulus) contain the ribosome-inactivating lectin ebulin f structurally related to ricin.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated intraperitoneal toxicity of ebulin f in mice and found that it triggers specific derangement of the intestines.", "output": {"entities": {}}, "schema": []}
{"input": "Ebulin f was much less toxic than ricin to mice when administered intraperitoneally.", "output": {"entities": {}}, "schema": []}
{"input": "The targets were cells of the intestinal crypts, which underwent apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Small intestine crypts were more sensitive than large intestine crypts.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of octylphenol and bisphenol A on the expression of calcium transport genes in the mouse duodenum and kidney during pregnancy.", "output": {"entities": {"chemical": [{"text": "octylphenol", "start": 11, "end": 22}, {"text": "bisphenol A", "start": 27, "end": 38}, {"text": "calcium", "start": 60, "end": 67}]}}, "schema": []}
{"input": "Octylphenol (OP) is the degradative product of alkylphenol ethoxylates that are widely used to produce rubber, pesticides, and paints.", "output": {"entities": {"chemical": [{"text": "Octylphenol", "start": 0, "end": 11}, {"text": "alkylphenol ethoxylates", "start": 47, "end": 70}]}}, "schema": []}
{"input": "Bisphenol A (BPA) is an organic compound with two functional phenol groups, and used for manufacturing polycarbonate plastic and epoxy resins, as well as other applications.", "output": {"entities": {"chemical": [{"text": "Bisphenol A", "start": 0, "end": 11}, {"text": "BPA", "start": 13, "end": 16}, {"text": "phenol", "start": 61, "end": 67}, {"text": "polycarbonate", "start": 103, "end": 116}, {"text": "epoxy", "start": 129, "end": 134}]}}, "schema": []}
{"input": "OP and BPA are known as endocrine disruptors (EDs) with estrogenic activities, and may disturb natural calcium (Ca) metabolism.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 7, "end": 10}, {"text": "calcium", "start": 103, "end": 110}, {"text": "Ca", "start": 112, "end": 114}]}}, "schema": []}
{"input": "In the present study, the effects of OP and BPA on Ca levels in the serum and expression of Ca transport genes in the duodenum, and kidney were investigated in pregnant mice.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 44, "end": 47}, {"text": "Ca", "start": 51, "end": 53}, {"text": "Ca", "start": 92, "end": 94}]}}, "schema": []}
{"input": "Calbindin refers to several Ca-binding proteins originally described as vitamin D-dependent Ca-binding factors in the intestine, and kidney of birds and mammals.", "output": {"entities": {"chemical": [{"text": "Calbindin", "start": 0, "end": 9}, {"text": "vitamin D", "start": 72, "end": 81}, {"text": "Ca", "start": 92, "end": 94}]}}, "schema": []}
{"input": "Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) and transient receptor potential cation channel, subfamily V, member 5 (TRPV5) are Ca entry channels responsible for Ca absorption in the kidney and intestine, respectively.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 158, "end": 160}, {"text": "Ca", "start": 192, "end": 194}]}}, "schema": []}
{"input": "From 6. 5 to 16. 5 day post coitus (dpc), pregnant mice were given oral doses of 17 alpha-ethynylestradiol (EE, 0. 2mg/kg/day), BPA (5 or 50mg/kg/day), or OP (3, 12, or 48 mg/kg/day) dissolved in corn oil.", "output": {"entities": {"chemical": [{"text": "17 alpha-ethynylestradiol", "start": 81, "end": 106}, {"text": "BPA", "start": 128, "end": 131}]}}, "schema": []}
{"input": "Samples of the duodenum, kidney, and blood were obtained from the mice on day 17. 5 of pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Serum Ca levels were decreased in the groups treated with OP and BPA.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 6, "end": 8}, {"text": "BPA", "start": 65, "end": 68}]}}, "schema": []}
{"input": "The expression levels of Ca transport genes, TRPV5 and calbindin-D9k (CaBP-9k), in the kidney were decreased after treatment with OP and BPA.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 25, "end": 27}, {"text": "BPA", "start": 137, "end": 140}]}}, "schema": []}
{"input": "Duodenal expression of TRPV6 was also reduced by BPA and OP administration.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 49, "end": 52}]}}, "schema": []}
{"input": "CaBP-9k expression was differentially regulated by BPA and OP.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 51, "end": 54}]}}, "schema": []}
{"input": "Transcriptional and translational levels of CaBP-9k were decreased by EE and BPA but increased by a high dose of OP.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 77, "end": 80}]}}, "schema": []}
{"input": "Taken together, our findings demonstrate that OP and BPA regulated the expression of genes associated with Ca transport in the pregnant mice, which may result in the decreased serum Ca levels.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 53, "end": 56}, {"text": "Ca", "start": 107, "end": 109}, {"text": "Ca", "start": 182, "end": 184}]}}, "schema": []}
{"input": "Anesthetics interacting with lipid rafts.", "output": {"entities": {}}, "schema": []}
{"input": "The exact mechanism by which anesthetics induce cell membrane-mediated modifications is still an open question.", "output": {"entities": {}}, "schema": []}
{"input": "Although the fluidization effect of the anesthetic molecules on the cellular membrane is widely recognized, it is not known if anesthetics show any preference for specific membrane domains, namely the lipid rafts.", "output": {"entities": {}}, "schema": []}
{"input": "The importance of these membrane micro-domains derives from the fact that they have been associated with cell signaling pathways, as well as with specific drug interactions.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this work is to contribute for the elucidation of this question through the comparison of the anesthetic interactions with membranes of various lipid compositions.", "output": {"entities": {}}, "schema": []}
{"input": "Liposomes prepared with an equimolar mixture of POPC, sphingomyelin and cholesterol, were chosen as models for lipid rafts.", "output": {"entities": {"chemical": [{"text": "POPC", "start": 48, "end": 52}, {"text": "sphingomyelin", "start": 54, "end": 67}, {"text": "cholesterol", "start": 72, "end": 83}]}}, "schema": []}
{"input": "The interactions of these liposomes with two local anesthetics, tetracaine and lidocaine, and one general anesthetic, propofol, were studied.", "output": {"entities": {"chemical": [{"text": "tetracaine", "start": 64, "end": 74}, {"text": "lidocaine", "start": 79, "end": 88}, {"text": "propofol", "start": 118, "end": 126}]}}, "schema": []}
{"input": "The effect of cholesterol was investigated by comparing anesthetic interactions with POPC/SM liposomes and POPC/SM/CHOL liposomes.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 14, "end": 25}, {"text": "POPC", "start": 85, "end": 89}, {"text": "POPC", "start": 107, "end": 111}, {"text": "CHOL", "start": 115, "end": 119}]}}, "schema": []}
{"input": "The following experimental techniques were used: quartz crystal microbalance with dissipation, differential scanning calorimetry and phosphorus nuclear magnetic resonance.", "output": {"entities": {"chemical": [{"text": "quartz", "start": 49, "end": 55}, {"text": "phosphorus", "start": 133, "end": 143}]}}, "schema": []}
{"input": "Although the liposomes investigated by the different techniques are not in the same conditions, it is possible to assemble the information obtained from all experimental techniques employed to reach a general conclusion.", "output": {"entities": {}}, "schema": []}
{"input": "Tetracaine interacts more with raftlike domains, lidocaine induces stronger modifications on POPC/SM liposomes and the results for propofol are not fully conclusive but it seems to be the least prone to lipid interactions.", "output": {"entities": {"chemical": [{"text": "Tetracaine", "start": 0, "end": 10}, {"text": "lidocaine", "start": 49, "end": 58}, {"text": "POPC", "start": 93, "end": 97}, {"text": "propofol", "start": 131, "end": 139}]}}, "schema": []}
{"input": "The results were compared with those obtained with DMPC-containing liposomes, reported in a previous work.", "output": {"entities": {"chemical": [{"text": "DMPC", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Gene transcription and biomarker responses in the clam Ruditapes philippinarum after exposure to ibuprofen.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 97, "end": 106}]}}, "schema": []}
{"input": "Pharmaceuticals are a class of emerging environmental contaminants that continuously enter aquatic environments.", "output": {"entities": {}}, "schema": []}
{"input": "Presently, little information is available about the effects of these substances on non-target organisms, such as bivalves.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the effects of ibuprofen (IBU) on the clam Ruditapes philippinarum.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 31, "end": 40}, {"text": "IBU", "start": 42, "end": 45}]}}, "schema": []}
{"input": "Clams were exposed for 1, 3, 5 and 7 days to 0, 100 and 1000 mu gIBU/L, and established biomarker responses (haemolymph lysozyme, gill acetylcholinesterase and digestive gland superoxide dismutase activities) as well as digestive gland transcriptome were evaluated.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 176, "end": 186}]}}, "schema": []}
{"input": "A two-way ANOVA revealed significant effects of both \" IBU concentration \" and \" exposure duration \" on biomarker responses.", "output": {"entities": {"chemical": [{"text": "IBU", "start": 55, "end": 58}]}}, "schema": []}
{"input": "Overall, the enzyme activities were generally lower in IBU-exposed clams than in controls.", "output": {"entities": {"chemical": [{"text": "IBU", "start": 55, "end": 58}]}}, "schema": []}
{"input": "Although limited knowledge of the mollusc transcriptome makes it difficult to interpret the effects of IBU on clams, the gene transcription analysis using DNA microarrays enabled the identification of the putative molecular mode of action of the IBU.", "output": {"entities": {"chemical": [{"text": "IBU", "start": 103, "end": 106}, {"text": "IBU", "start": 246, "end": 249}]}}, "schema": []}
{"input": "The functional analysis of differentially transcribed genes suggests that IBU can interfere with various signalling pathways in clams, such as arachidonic acid metabolism, apoptosis, peroxisomal proliferator-activated receptors, and nuclear factor-kappa B.", "output": {"entities": {"chemical": [{"text": "IBU", "start": 74, "end": 77}, {"text": "arachidonic acid", "start": 143, "end": 159}]}}, "schema": []}
{"input": "In addition, several genes involved in the metabolism of xenobiotics (e. g., glutathione S-transferase, sulfotransferase, cytochrome P450) were also found to be significantly affected by IBU exposure.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 77, "end": 90}, {"text": "IBU", "start": 187, "end": 190}]}}, "schema": []}
{"input": "In summary, the integrated approach of gene transcription analysis and biomarker responses facilitated the elucidation of the putative mechanisms of action of IBU in non-target species.", "output": {"entities": {"chemical": [{"text": "IBU", "start": 159, "end": 162}]}}, "schema": []}
{"input": "O2-independent formation of the inactive states of NiFe hydrogenase.", "output": {"entities": {"chemical": [{"text": "O2", "start": 0, "end": 2}, {"text": "NiFe", "start": 51, "end": 55}]}}, "schema": []}
{"input": "We studied the mechanism of aerobic inactivation of Desulfovibrio fructosovorans nickel-iron (NiFe) hydrogenase by quantitatively examining the results of electrochemistry, EPR and FTIR experiments.", "output": {"entities": {"chemical": [{"text": "nickel-iron", "start": 81, "end": 92}, {"text": "NiFe", "start": 94, "end": 98}]}}, "schema": []}
{"input": "They suggest that, contrary to the commonly accepted mechanism, the attacking O (2) is not incorporated as an active site ligand but, rather, acts as an electron acceptor.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 78, "end": 83}]}}, "schema": []}
{"input": "Our findings offer new ways toward the understanding of O (2) inactivation and O (2) tolerance in NiFe hydrogenases.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 56, "end": 61}, {"text": "O (2)", "start": 79, "end": 84}, {"text": "NiFe", "start": 98, "end": 102}]}}, "schema": []}
{"input": "Multi-cell type human liver microtissues for hepatotoxicity testing.", "output": {"entities": {}}, "schema": []}
{"input": "Current 2-dimensional hepatic model systems often fail to predict chemically induced hepatotoxicity due to the loss of a hepatocyte-specific phenotype in culture.", "output": {"entities": {}}, "schema": []}
{"input": "For more predictive in vitro models, hepatocytes have to be maintained in a 3-dimensional environment that allows for polarization and cell-cell contacts.", "output": {"entities": {}}, "schema": []}
{"input": "Preferably, the model will reflect an in vivo-like multi-cell type environment necessary for liver-like responses.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report the characterization of a multi-cell type microtissue model, generated from primary human hepatocytes and liver-derived non-parenchymal cells.", "output": {"entities": {}}, "schema": []}
{"input": "Liver microtissues were stable and functional for 5 weeks in culture enabling, for example, long-term toxicity testing of acetaminophen and diclofenac.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 122, "end": 135}, {"text": "diclofenac", "start": 140, "end": 150}]}}, "schema": []}
{"input": "In addition, Kupffer cells were responsive to inflammatory stimuli such as LPS demonstrating the possibility to detect inflammation-mediated toxicity as exemplified by the drug trovafloxacin.", "output": {"entities": {"chemical": [{"text": "trovafloxacin", "start": 177, "end": 190}]}}, "schema": []}
{"input": "Herewith, we present a novel 3D liver model for routine testing in 96-well format capable of reducing the risk of unwanted toxic effects in the clinic.", "output": {"entities": {}}, "schema": []}
{"input": "Thyroid disruption in the lizard Podarcis bocagei exposed to a mixture of herbicides: a field study.", "output": {"entities": {}}, "schema": []}
{"input": "Pesticide exposure has been related with thyroid disrupting effects in different vertebrate species.", "output": {"entities": {}}, "schema": []}
{"input": "However, very little is known about the effects of these compounds in reptiles.", "output": {"entities": {}}, "schema": []}
{"input": "In the Mediterranean area, lacertid lizards are the most abundant vertebrate group in agroecosystems, and have been identified as potential model species for reptile ecotoxicology.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to understand if the herbicides applied in corn fields have thyroid disruptive effects in the lizard Podarcis bocagei.", "output": {"entities": {}}, "schema": []}
{"input": "Adult male lizards were captured in north-western Portugal in corn fields treated with herbicides (exposed sites), and in organic agricultural fields (reference sites).", "output": {"entities": {}}, "schema": []}
{"input": "Thyroid and male gonad morphology and functionality, and testosterone levels were investigated through histological, immunohistochemical and biochemical techniques.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 57, "end": 69}]}}, "schema": []}
{"input": "Lizards from exposed locations displayed thyroid follicular lumens with more reabsorption vacuoles and significantly larger follicular area than those from reference fields.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, testes of lizards from exposed locations had significantly larger seminiferous tubule diameters, significantly higher number of spermatogenic layers and displayed an up-regulation of thyroid hormone receptors when compared with lizards from reference areas.", "output": {"entities": {}}, "schema": []}
{"input": "These findings strongly suggest that the complex mixture of herbicides that lizards are exposed to in agricultural areas have thyroid disrupting effects which ultimately affect the male reproductive system.", "output": {"entities": {}}, "schema": []}
{"input": "Alachlor, which has demonstrated thyroid effects in mammals, may be largely responsible for the observed effects.", "output": {"entities": {"chemical": [{"text": "Alachlor", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Effects of pyrene exposure and temperature on early development of two co-existing Arctic copepods.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 11, "end": 17}]}}, "schema": []}
{"input": "Oil exploration is expected to increase in the near future in Western Greenland.", "output": {"entities": {}}, "schema": []}
{"input": "At present, effects of exposure to oil compounds on early life-stages of the ecologically important Calanus spp. are unknown.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the effects of the oil compound pyrene, on egg hatching and naupliar development of the calanoid copepods Calanus glacialis and C. finmarchicus, two key species in the Disko Bay, Western Greenland.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 48, "end": 54}]}}, "schema": []}
{"input": "At low temperature the nauplii of C. glacialis experienced reduced growth when exposed to pyrene, and survival in both species decreased.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 90, "end": 96}]}}, "schema": []}
{"input": "Naupliar mortality increased with temperature at high pyrene concentration in C. finmarchicus.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 54, "end": 60}]}}, "schema": []}
{"input": "Both Calanus species were affected by pyrene exposure but C. finmarchicus was more sensitive compared to C. glacialis.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 38, "end": 44}]}}, "schema": []}
{"input": "Lowered growth rate and increased mortality of the naupliar stages entail reduced recruitment to copepod populations.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to pyrene from an oil spill may reduce the standing stock of Calanus, which can lead to less energy available to higher trophic levels in the Arctic marine food web.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 12, "end": 18}]}}, "schema": []}
{"input": "A perspective on the contribution of metabolites to drug-drug interaction potential: the need to consider both circulating levels and inhibition potency.", "output": {"entities": {}}, "schema": []}
{"input": "The 2012 drug-drug interaction (DDI) guidance from the European Medicines Agency (EMA) and the draft DDI guidance from the Food and Drug Administration (FDA) have proposed that metabolites present at > 25% of the parent area under the time-concentration curve (AUC) (EMA and FDA) and > 10% of the total drug-related exposure (EMA) should be investigated in vitro for their DDI potential.", "output": {"entities": {}}, "schema": []}
{"input": "This commentary attempts to rationalize the clinically relevant levels of metabolite (s) that contribute to DDI by considering not only the abundance but also inhibition potency, physicochemical properties, and structural alerts of the metabolite.", "output": {"entities": {}}, "schema": []}
{"input": "A decision tree is proposed for levels of metabolites that could trigger in vitro DDI assessment.", "output": {"entities": {}}, "schema": []}
{"input": "When the parent is an inhibitor of cytochrome P450s (P450s), clinical DDI studies will assess the in vivo DDI effect of the combination of parent and metabolite (s).", "output": {"entities": {}}, "schema": []}
{"input": "When the parent is not a P450 inhibitor, it is important to assess the inhibition potential of abundant metabolites in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "The proposal is to apply a default cutoff value of metabolite level which is 100% of the parent AUC.", "output": {"entities": {}}, "schema": []}
{"input": "It is important to note that exceptions can occur, and different metabolite levels may be considered depending on the physiochemical properties of metabolites (e. g., increased lipophilicity) and whether the metabolite contains structural alerts for DDI (e. g., mechanism-based inhibition).", "output": {"entities": {}}, "schema": []}
{"input": "A key objective of this commentary is to stimulate discussions among the scientific community on this important topic, so that appropriate in vitro metabolism studies are conducted on metabolites, to ensure the safety of drugs in development balanced with the desire to avoid creating unnecessary studies that will add little to no value in ensuring patient safety.", "output": {"entities": {}}, "schema": []}
{"input": "Metal-supported aluminosilicate ultrathin films as a versatile tool for studying the surface chemistry of zeolites.", "output": {"entities": {"chemical": [{"text": "aluminosilicate", "start": 16, "end": 31}, {"text": "zeolites", "start": 106, "end": 114}]}}, "schema": []}
{"input": "The application of a variety of \" surface-science \" techniques to elucidate surface structures and mechanisms of chemical reactions at zeolite surfaces has long been considered as almost impossible because of the poor electrical and thermal conductivity of those materials.", "output": {"entities": {"chemical": [{"text": "zeolite", "start": 135, "end": 142}]}}, "schema": []}
{"input": "Here, we show that the growth of a thin aluminosilicate film on a metal single crystal under controlled conditions results in adequate and well-defined model systems for zeolite surfaces.", "output": {"entities": {"chemical": [{"text": "aluminosilicate", "start": 40, "end": 55}, {"text": "zeolite", "start": 170, "end": 177}]}}, "schema": []}
{"input": "In principle, silicate films that contain metals other than Al (e. g. Ti, Fe, etc) may be prepared in a similar way.", "output": {"entities": {"chemical": [{"text": "silicate", "start": 14, "end": 22}, {"text": "Al", "start": 60, "end": 62}, {"text": "Ti", "start": 70, "end": 72}, {"text": "Fe", "start": 74, "end": 76}]}}, "schema": []}
{"input": "We believe that this approach opens up a new playground for experimental and theoretical modeling of zeolites, aimed at a fundamental understanding of structure-reactivity relationships in such materials.", "output": {"entities": {"chemical": [{"text": "zeolites", "start": 101, "end": 109}]}}, "schema": []}
{"input": "In vitro exposure of precision-cut lung slices to 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole lysylamide dihydrochloride (NSC 710305, Phortress) increases inflammatory cytokine content and tissue damage.", "output": {"entities": {"chemical": [{"text": "2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole lysylamide dihydrochloride", "start": 50, "end": 125}, {"text": "NSC 710305", "start": 127, "end": 137}, {"text": "Phortress", "start": 139, "end": 148}]}}, "schema": []}
{"input": "The anticancer drug (2-[4-amino-3-methylphenyl]-5-fluorobenzothiazole lysylamide dihydrochloride) (NSC 710305, Phortress) is a metabolically activated prodrug that causes DNA adduct formation and subsequent toxicity.", "output": {"entities": {"chemical": [{"text": "2-[4-amino-3-methylphenyl]-5-fluorobenzothiazole lysylamide dihydrochloride", "start": 21, "end": 96}, {"text": "NSC 710305", "start": 99, "end": 109}, {"text": "Phortress", "start": 111, "end": 120}]}}, "schema": []}
{"input": "Preclinically, it was found that hepatic, bone marrow, and pulmonary toxicity presented challenges to developing this drug.", "output": {"entities": {}}, "schema": []}
{"input": "An ex vivo precision-cut lung slice (PCLS) model was used to search for concentration dependent effects of NSC 710305 (10, 25, 50, and 100 micro M) on cytokine content, protein content, and immuno/histological endpoints.", "output": {"entities": {"chemical": [{"text": "NSC 710305", "start": 107, "end": 117}]}}, "schema": []}
{"input": "Preparation and culture of PCLS caused an initial spike in proinflammatory cytokine expression and therefore treatment with NSC 710305 was delayed until 48 h after initiating the slice cultures to avoid confounding the response to slicing with any drug response.", "output": {"entities": {"chemical": [{"text": "NSC 710305", "start": 124, "end": 134}]}}, "schema": []}
{"input": "PCLSs were evaluated after 24, 48, and 72 h exposures to NSC 710305.", "output": {"entities": {"chemical": [{"text": "NSC 710305", "start": 57, "end": 67}]}}, "schema": []}
{"input": "Reversibility of toxicity due to the 72-h treatment was evaluated after a 24-h recovery period.", "output": {"entities": {}}, "schema": []}
{"input": "NSC 710305 caused a concentration-dependent cytokine response, and only the toxicity caused by a 72-h exposure to 25 micro M reversed during the 24-h recovery period.", "output": {"entities": {"chemical": [{"text": "NSC 710305", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Immuno/histological examination and quantitation of tissue protein levels indicated that tissue destruction, ED-1 (activated macrophage) staining, and protein levels were associated with the levels of proinflammatory cytokines in the tissue.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the concentration-and time-dependent inflammatory response of PCLS to NSC 710305 preceded relevant tissue damage by a few days.", "output": {"entities": {"chemical": [{"text": "NSC 710305", "start": 85, "end": 95}]}}, "schema": []}
{"input": "The no-observable adverse effect level (NOAEL) for 24, 48, and 72 h exposures was established as 10 micro M NSC 710305.", "output": {"entities": {"chemical": [{"text": "NSC 710305", "start": 108, "end": 118}]}}, "schema": []}
{"input": "Gender difference of childhood overweight and obesity in predicting the risk of incident asthma: a systematic review and meta-analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The aims of our meta-analysis were (i) to quantify the predictability of childhood overweight and obesity on the risk of incident asthma; and (ii) to evaluate the gender difference on this relationship.", "output": {"entities": {}}, "schema": []}
{"input": "The selection criteria included prospective cohort paediatric studies which use age-and sex-specific body mass index (BMI) as a measure of childhood overweight and the primary outcome of incident asthma.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 1, 027 studies were initially identified through online database searches, and finally 6 studies met the inclusion criteria.", "output": {"entities": {}}, "schema": []}
{"input": "The combined result of reported relative risk from the 6 included studies revealed that overweight children conferred increased risks of incident asthma as compared with non-overweight children (relative risk, 1. 19; 95% confidence interval [CI], 1. 03-1. 37).", "output": {"entities": {}}, "schema": []}
{"input": "The relationship was further elevated for obesity vs. non-obesity (relative risk, 2. 02; 95% CI, 1. 16-3. 50).", "output": {"entities": {}}, "schema": []}
{"input": "A dose-responsiveness of elevated BMI on asthma incidence was observed (P for trend, 0. 004).", "output": {"entities": {}}, "schema": []}
{"input": "Obese boys had a significantly larger effect than obese girls (relative risk, boys: 2. 47; 95% CI, 1. 57-3. 87; girls: 1. 25; 95% CI, 0. 51-3. 03), with significant dose-dependent effect.", "output": {"entities": {}}, "schema": []}
{"input": "Proposed mechanisms of gender difference could be through pulmonary mechanics, sleep disordered breathing and leptin.", "output": {"entities": {}}, "schema": []}
{"input": "Further research might be needed to better understand the exact mechanism of gender difference on the obesity-asthma relationship.", "output": {"entities": {}}, "schema": []}
{"input": "Dendrimeric bowties featuring hemispheric-selective decoration of ligands for microRNA-based therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Dendrimers feature a defined number of terminal groups that may bind RNA or be functionalized with bioactive molecules.", "output": {"entities": {}}, "schema": []}
{"input": "These competing uses of terminal groups may create an impasse if the requisite density of ligands depletes the number of terminal groups for binding sufficient RNA, or vice versa.", "output": {"entities": {}}, "schema": []}
{"input": "A novel dendrimeric platform is needed that maintains high ligand density while retaining sufficient microRNA-binding terminal groups.", "output": {"entities": {}}, "schema": []}
{"input": "Here we present a dendrimeric \" bowtie \" consisting of one-half devoted to microRNA binding and the other half to ligand presentation.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate its suitability as a transfection agent by delivering miR-126 to human vascular endothial cells (HUVECs) via polyarginine-and RGD-modified bowties and evaluating the downstream effects on proliferation and tube formation.", "output": {"entities": {"chemical": [{"text": "polyarginine", "start": 124, "end": 136}]}}, "schema": []}
{"input": "Our findings indicate that the bowtie elicits desired responses and may possess superior delivery properties compared to nondecorated dendrimeric materials.", "output": {"entities": {}}, "schema": []}
{"input": "The bowtie system thereby provides a new design model for developing dendrimeric delivery vehicles for RNAi therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "PomZ, a ParA-like protein, regulates Z-ring formation and cell division in Myxococcus xanthus.", "output": {"entities": {}}, "schema": []}
{"input": "Accurate positioning of the division site is essential to generate appropriately sized daughter cells with the correct chromosome number.", "output": {"entities": {}}, "schema": []}
{"input": "In bacteria, division generally depends on assembly of the tubulin homologue FtsZ into the Z-ring at the division site.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that lack of the ParA-like protein PomZ in Myxococcus xanthus resulted in division defects with the formation of chromosome-free minicells and filamentous cells.", "output": {"entities": {}}, "schema": []}
{"input": "Lack of PomZ also caused reduced formation of Z-rings and incorrect positioning of the few Z-rings formed.", "output": {"entities": {}}, "schema": []}
{"input": "PomZ localization is cell cycle regulated, and PomZ accumulates at the division site at midcell after chromosome segregation but prior to FtsZ as well as in the absence of FtsZ.", "output": {"entities": {}}, "schema": []}
{"input": "FtsZ displayed cooperative GTP hydrolysis in vitro but did not form detectable filaments in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "PomZ interacted with FtsZ in M. xanthus cell extracts.", "output": {"entities": {}}, "schema": []}
{"input": "These data show that PomZ is important for Z-ring formation and is a spatial regulator of Z-ring formation and cell division.", "output": {"entities": {}}, "schema": []}
{"input": "The cell cycle-dependent localization of PomZ at midcell provides a mechanism for coupling cell cycle progression and Z-ring formation.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the data suggest that PomZ is part of a system that recruits FtsZ to midcell, thereby, restricting Z-ring formation to this position.", "output": {"entities": {}}, "schema": []}
{"input": "Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1.", "output": {"entities": {"chemical": [{"text": "Mesalamine", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a remitting condition characterized by chronic inflammation of the colon.", "output": {"entities": {"chemical": [{"text": "Mesalamine", "start": 0, "end": 10}, {"text": "5-ASA", "start": 12, "end": 17}]}}, "schema": []}
{"input": "Knowledge about the molecular and cellular targets of 5-ASA is limited and a clear understanding of its activity in intestinal homeostasis and interference with neoplastic progression is lacking.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 54, "end": 59}]}}, "schema": []}
{"input": "We sought to identify molecular pathways interfered by 5-ASA, using CRC cell lines with different genetic background.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 55, "end": 60}]}}, "schema": []}
{"input": "Microarray was performed for gene expression profile of 5-ASA-treated and untreated cells (HCT116 and HT29).", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 56, "end": 61}]}}, "schema": []}
{"input": "Filtering and analysis of data identified three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and beta-catenin/Wnt signaling.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 81, "end": 86}]}}, "schema": []}
{"input": "PAK1 emerged as a consensus target of 5-ASA, orchestrating these pathways.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 38, "end": 43}]}}, "schema": []}
{"input": "We further investigated the effect of 5-ASA on cell adhesion.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 38, "end": 43}]}}, "schema": []}
{"input": "5-ASA increased cell adhesion which was measured by cell adhesion assay and transcellular-resistance measurement.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Moreover, 5-ASA treatment restored membranous expression of adhesion molecules E-cadherin and beta-catenin.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 10, "end": 15}]}}, "schema": []}
{"input": "Role of PAK1 as a mediator of mesalamine activity was validated in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of PAK1 by RNA interference also increased cell adhesion.", "output": {"entities": {}}, "schema": []}
{"input": "PAK1 expression was elevated in APC (min) polyps and 5-ASA treatment reduced its expression.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 53, "end": 58}]}}, "schema": []}
{"input": "Our data demonstrates novel pharmacological mechanism of mesalamine in modulation of cell adhesion and role of PAK1 in APC (min) polyposis.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 57, "end": 67}]}}, "schema": []}
{"input": "We propose that inhibition of PAK1 expression by 5-ASA can impede with neoplastic progression in colorectal carcinogenesis.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 49, "end": 54}]}}, "schema": []}
{"input": "The mechanism of PAK1 inhibition and induction of membranous translocation of adhesion proteins by 5-ASA might be independent of its known anti-inflammatory action.", "output": {"entities": {"chemical": [{"text": "5-ASA", "start": 99, "end": 104}]}}, "schema": []}
{"input": "Emodin-6-O-beta-D-glucoside inhibits HMGB1-induced inflammatory responses in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "Emodin-6-O-beta-D-glucoside", "start": 0, "end": 27}]}}, "schema": []}
{"input": "High mobility group box 1 (HMGB1) protein acts as a potent proinflammatory cytokine and is involved in the pathogenesis of several vascular diseases, such as, systemic vasculitis and sepsis.", "output": {"entities": {}}, "schema": []}
{"input": "Emodin-6-O-beta-D-glucoside (EG) is a new active compound from Reynoutria japonica, and its biologic activities have not been previously investigated.", "output": {"entities": {"chemical": [{"text": "Emodin-6-O-beta-D-glucoside", "start": 0, "end": 27}]}}, "schema": []}
{"input": "In this study, we first investigated the antiinflammatory activities of EG on HMGB1-mediated proinflammatory responses in human umbilical vein endothelial cells (HUVECs) and in a murine cecal ligation and puncture (CLP)-model of sepsis in mice.", "output": {"entities": {}}, "schema": []}
{"input": "EG was found to suppress the release of HMGB1, the production of tumor necrosis factor (TNF)-alpha, and the activation of nuclear factor-kappa B (NF-kappa B) by HMGB1 in HUVECs, and to inhibit HMGB1-mediated hyperpermeability and leukocyte migration in mice.", "output": {"entities": {}}, "schema": []}
{"input": "In the CLP model, HMGB1 was highly released, but this release was prevented by EG.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, EG also increased the survival times of CLP administered mice.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, this study shows EG can protect barrier integrity and inhibit HMGB1-mediated inflammatory responses, which suggests a potential use as a therapy for sepsis or septic shock.", "output": {"entities": {}}, "schema": []}
{"input": "Puerarin mediates hepatoprotection against CCl4-induced hepatic fibrosis rats through attenuation of inflammation response and amelioration of metabolic function.", "output": {"entities": {"chemical": [{"text": "Puerarin", "start": 0, "end": 8}, {"text": "CCl4", "start": 43, "end": 47}]}}, "schema": []}
{"input": "This study was designed to evaluate the potential effects of puerarin (PR), an effective isoflavonoid compound purified from Pueraria lobata, in treating hepatic fibrosis (HF) rats induced by carbon tetrachloride (CCl (4), 2 mL kg (-1) d (-1)).", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 61, "end": 69}, {"text": "isoflavonoid", "start": 89, "end": 101}, {"text": "carbon tetrachloride", "start": 192, "end": 212}, {"text": "CCl (4)", "start": 214, "end": 221}]}}, "schema": []}
{"input": "Compared to model control, PR treatment effectively lowered the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP) in HF rats.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 80, "end": 87}, {"text": "aspartate", "start": 112, "end": 121}]}}, "schema": []}
{"input": "Masson stained analysis showed that the condition of HF rats was mitigated.", "output": {"entities": {}}, "schema": []}
{"input": "Meanwhile, the tumor necrosis factor alpha (TNF-alpha), nuclear factor-kappa B (NF-kappa B) expressions were significantly down-regulated at protein level by PR intervention.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, the activity of superoxide dismutase (SOD) was elevated, while the content of malondialdehyde (MDA) was lessened in liver tissue.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 30, "end": 40}, {"text": "malondialdehyde", "start": 92, "end": 107}, {"text": "MDA", "start": 109, "end": 112}]}}, "schema": []}
{"input": "As revealed by immunohistochemistry assay, PR therapy resulted in reduced production of transforming growth factor-beta l (TGF-beta l).", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, it also was attributed to decreased mRNA level of inducible nitric oxide synthase (iNOS) using RT-PCR analysis.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 70, "end": 82}]}}, "schema": []}
{"input": "These findings demonstrate that puerarin successfully reverses hepatotoxicity in CCl (4)-induced HF rats via the underlying mechanisms of regulating serum enzymes and attenuating TNF-alpha/NF-kappa B pathway for anti-inflammation response, as well as improving metabolic function in liver tissue.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 32, "end": 40}, {"text": "CCl (4)", "start": 81, "end": 88}]}}, "schema": []}
{"input": "Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats.", "output": {"entities": {"chemical": [{"text": "carbon tetrachloride", "start": 69, "end": 89}]}}, "schema": []}
{"input": "This study is an attempt to evaluate the hepatoprotective activity of Gentiana asclepiadea L. against carbon tetrachloride-induced liver injury in rats.", "output": {"entities": {"chemical": [{"text": "carbon tetrachloride", "start": 102, "end": 122}]}}, "schema": []}
{"input": "Methanol extracts of aerial parts (GAA) and roots (GAR) of G. asclepiadea at doses of 100, 200, and 400mg/kg b. w. were orally administered to Wistar rats once daily for 7 days before they were treated with CCl (4).", "output": {"entities": {"chemical": [{"text": "Methanol", "start": 0, "end": 8}, {"text": "CCl (4)", "start": 207, "end": 214}]}}, "schema": []}
{"input": "The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin.", "output": {"entities": {}}, "schema": []}
{"input": "In CCl (4) treated animals, GAA and GAR significantly decreased levels of serum transaminases, alkaline phosphatase and total bilirubin, and increased the level of total protein.", "output": {"entities": {"chemical": [{"text": "CCl (4)", "start": 3, "end": 10}, {"text": "bilirubin", "start": 126, "end": 135}]}}, "schema": []}
{"input": "Treatment with the extracts resulted in a significant increase in the levels of catalase, superoxide dismutase and reduced glutathione, accompanied with a marked reduction in the levels of malondialdehyde, as compared to CCl (4) treated group.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 90, "end": 100}, {"text": "reduced glutathione", "start": 115, "end": 134}, {"text": "malondialdehyde", "start": 189, "end": 204}, {"text": "CCl (4)", "start": 221, "end": 228}]}}, "schema": []}
{"input": "The histopathological studies confirmed protective effects of extracts against CCl (4)-induced liver injuries.", "output": {"entities": {"chemical": [{"text": "CCl (4)", "start": 79, "end": 86}]}}, "schema": []}
{"input": "No genotoxicity was observed in liver cells after GAA treatment, while GAR showed only slight genotoxic effects by comet assay.", "output": {"entities": {}}, "schema": []}
{"input": "Phytochemical analysis revealed the presence of sweroside, swertiamarin and gentiopicrin in high concentrations in both extracts.", "output": {"entities": {"chemical": [{"text": "sweroside", "start": 48, "end": 57}, {"text": "swertiamarin", "start": 59, "end": 71}, {"text": "gentiopicrin", "start": 76, "end": 88}]}}, "schema": []}
{"input": "It could be concluded that the use of G. asclepiadea extracts in the treatment of chemical-induced hepatotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Endocrine disrupting chemicals (EDCs) have the potential to interfere with the hormonal system and may negatively influence human health.", "output": {"entities": {}}, "schema": []}
{"input": "Microarray analysis was used in this study to investigate differential gene expression in human peripheral blood cells (PBMCs) after in vitro exposure to EDCs.", "output": {"entities": {}}, "schema": []}
{"input": "PBMCs, isolated from blood samples of four male and four female healthy individuals, were exposed in vitro for 18h to either a dioxin-like polychlorinated biphenyl (PCB126, 1 mu M), a non-dioxin-like polychlorinated biphenyl (PCB153, 10 mu M), a brominated flame retardant (BDE47, 10 mu M), a perfluorinated alkyl acid (PFOA, 10 mu M) or bisphenol (BPA, 10 mu M).", "output": {"entities": {"chemical": [{"text": "dioxin", "start": 127, "end": 133}, {"text": "polychlorinated biphenyl", "start": 139, "end": 163}, {"text": "PCB126", "start": 165, "end": 171}, {"text": "dioxin", "start": 188, "end": 194}, {"text": "polychlorinated biphenyl", "start": 200, "end": 224}, {"text": "PCB153", "start": 226, "end": 232}, {"text": "BDE47", "start": 274, "end": 279}, {"text": "perfluorinated alkyl acid", "start": 293, "end": 318}, {"text": "PFOA", "start": 320, "end": 324}, {"text": "bisphenol", "start": 338, "end": 347}, {"text": "BPA", "start": 349, "end": 352}]}}, "schema": []}
{"input": "ANOVA analysis revealed a significant change in the expression of 862 genes as a result of EDC exposure.", "output": {"entities": {}}, "schema": []}
{"input": "The gender of the donors did not affect gene expression.", "output": {"entities": {}}, "schema": []}
{"input": "Hierarchical cluster analysis created three groups and clustered: (1) PCB126-exposed samples, (2) PCB153 and BDE47, (3) PFOA and BPA.", "output": {"entities": {"chemical": [{"text": "PCB126", "start": 70, "end": 76}, {"text": "PCB153", "start": 98, "end": 104}, {"text": "BDE47", "start": 109, "end": 114}, {"text": "PFOA", "start": 120, "end": 124}, {"text": "BPA", "start": 129, "end": 132}]}}, "schema": []}
{"input": "The number of differentially expressed genes varied per compound and ranged from 60 to 192 when using fold change and multiplicity corrected p-value as filtering criteria.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to PCB126 induced the AhR signaling pathway.", "output": {"entities": {"chemical": [{"text": "PCB126", "start": 12, "end": 18}]}}, "schema": []}
{"input": "BDE47 and PCB153 are known to disrupt thyroid metabolism and exposure influenced the expression of the nuclear receptors PPAR gamma and ESR2, respectively.", "output": {"entities": {"chemical": [{"text": "BDE47", "start": 0, "end": 5}, {"text": "PCB153", "start": 10, "end": 16}]}}, "schema": []}
{"input": "BPA and PFOA did not induce significant changes in the expression of known nuclear receptors.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 0, "end": 3}, {"text": "PFOA", "start": 8, "end": 12}]}}, "schema": []}
{"input": "Overall, each compound produced a unique gene expression signature affecting pathways and GO processes linked to metabolism and inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-nine genes were significantly altered in expression under all experimental conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Six of these genes (HSD11B2, MMP11, ADIPOQ, CEL, DUSP9 and TUB) could be associated with obesity and metabolic syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, microarray analysis identified that PBMCs altered their gene expression response in vitro when challenged with EDCs.", "output": {"entities": {}}, "schema": []}
{"input": "Our screening approach has identified a number of gene candidates that warrant further study.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism of carvacrol-evoked [Ca2 +] i rises and non-Ca2 +-triggered cell death in OC2 human oral cancer cells.", "output": {"entities": {"chemical": [{"text": "carvacrol", "start": 17, "end": 26}, {"text": "Ca2 +", "start": 35, "end": 40}, {"text": "Ca2 +", "start": 58, "end": 63}]}}, "schema": []}
{"input": "Carvacrol is one of the main substances of essential oil which triggers intracellular Ca (2 +) mobilization and causes cytotoxicity in diverse cell models.", "output": {"entities": {"chemical": [{"text": "Carvacrol", "start": 0, "end": 9}, {"text": "Ca (2 +)", "start": 86, "end": 94}]}}, "schema": []}
{"input": "However, the mechanism of carvacrol-induced Ca (2 +) movement and cytotoxicity is not fully understood.", "output": {"entities": {"chemical": [{"text": "carvacrol", "start": 26, "end": 35}, {"text": "Ca (2 +)", "start": 44, "end": 52}]}}, "schema": []}
{"input": "This study examined the effect of carvacrol on cytosolic free Ca (2 +) concentrations ([Ca (2 +)] (i)), cell viability and apoptosis in OC2 human oral cancer cells.", "output": {"entities": {"chemical": [{"text": "carvacrol", "start": 34, "end": 43}, {"text": "Ca (2 +)", "start": 62, "end": 70}, {"text": "Ca (2 +)", "start": 88, "end": 96}]}}, "schema": []}
{"input": "Carvacrol induced a [Ca (2 +)] (i) rise and the signal was reduced by removal of extracellular Ca (2 +).", "output": {"entities": {"chemical": [{"text": "Carvacrol", "start": 0, "end": 9}, {"text": "Ca (2 +)", "start": 21, "end": 29}, {"text": "Ca (2 +)", "start": 95, "end": 103}]}}, "schema": []}
{"input": "Carvacrol-induced Ca (2 +) entry was not altered by store-operated Ca (2 +) channel inhibitors and protein kinase C (PKC) activator, but was inhibited by a PKC inhibitor.", "output": {"entities": {"chemical": [{"text": "Carvacrol", "start": 0, "end": 9}, {"text": "Ca (2 +)", "start": 18, "end": 26}, {"text": "Ca (2 +)", "start": 67, "end": 75}]}}, "schema": []}
{"input": "In Ca (2 +)-free medium, treatment with the endoplasmic reticulum Ca (2 +) pump inhibitor thapsigargin (TG) or 2, 5-di-tert-butylhydroquinone (BHQ) inhibited carvacrol-induced [Ca (2 +)] (i) rise.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 3, "end": 11}, {"text": "Ca (2 +)", "start": 66, "end": 74}, {"text": "thapsigargin", "start": 90, "end": 102}, {"text": "2, 5-di-tert-butylhydroquinone", "start": 111, "end": 141}, {"text": "BHQ", "start": 143, "end": 146}, {"text": "carvacrol", "start": 158, "end": 167}, {"text": "Ca (2 +)", "start": 177, "end": 185}]}}, "schema": []}
{"input": "Conversely, incubation with carvacrol inhibited TG or BHQ-induced [Ca (2 +)] (i) rise.", "output": {"entities": {"chemical": [{"text": "carvacrol", "start": 28, "end": 37}, {"text": "BHQ", "start": 54, "end": 57}, {"text": "Ca (2 +)", "start": 67, "end": 75}]}}, "schema": []}
{"input": "Inhibition of phospholipase C (PLC) with U73122 abolished carvacrol-induced [Ca (2 +)] (i) rise.", "output": {"entities": {"chemical": [{"text": "U73122", "start": 41, "end": 47}, {"text": "carvacrol", "start": 58, "end": 67}, {"text": "Ca (2 +)", "start": 77, "end": 85}]}}, "schema": []}
{"input": "Carvacrol decreased cell viability, which was not reversed when cytosolic Ca (2 +) was chelated with BAPTA-AM (1, 2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid-acetoxymethyl ester).", "output": {"entities": {"chemical": [{"text": "Carvacrol", "start": 0, "end": 9}, {"text": "Ca (2 +)", "start": 74, "end": 82}, {"text": "BAPTA-AM", "start": 101, "end": 109}, {"text": "1, 2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid-acetoxymethyl ester", "start": 111, "end": 193}]}}, "schema": []}
{"input": "Carvacrol-induced apoptosis and activation of reactive oxygen species (ROS) and caspase-3.", "output": {"entities": {"chemical": [{"text": "Carvacrol", "start": 0, "end": 9}, {"text": "oxygen", "start": 55, "end": 61}]}}, "schema": []}
{"input": "Together, carvacrol induced a [Ca (2 +)] (i) rise by inducing PLC-dependent Ca (2 +) release from the endoplasmic reticulum and Ca (2 +) entry via PKC-sensitive, non store-operated Ca (2 +) channels.", "output": {"entities": {"chemical": [{"text": "carvacrol", "start": 10, "end": 19}, {"text": "Ca (2 +)", "start": 31, "end": 39}, {"text": "Ca (2 +)", "start": 76, "end": 84}, {"text": "Ca (2 +)", "start": 128, "end": 136}, {"text": "Ca (2 +)", "start": 181, "end": 189}]}}, "schema": []}
{"input": "Carvacrol-induced ROS-and caspase-3-associated apoptosis.", "output": {"entities": {"chemical": [{"text": "Carvacrol", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The 2, 2', 4, 4'-tetrabromodiphenyl ether hydroxylated metabolites 5-OH-BDE-47 and 6-OH-BDE-47 stimulate estradiol secretion in the ovary by activating aromatase expression.", "output": {"entities": {"chemical": [{"text": "2, 2', 4, 4'-tetrabromodiphenyl ether", "start": 4, "end": 41}, {"text": "5-OH-BDE-47", "start": 67, "end": 78}, {"text": "6-OH-BDE-47", "start": 83, "end": 94}, {"text": "estradiol", "start": 105, "end": 114}]}}, "schema": []}
{"input": "The aim of the present study was to assess the effect of two hydroxylated BDE-47 metabolites, 5-OH-BDE-47 and 6-OH-BDE-47, on steroidogenesis in the ovary.", "output": {"entities": {"chemical": [{"text": "hydroxylated BDE-47", "start": 61, "end": 80}, {"text": "5-OH-BDE-47", "start": 94, "end": 105}, {"text": "6-OH-BDE-47", "start": 110, "end": 121}]}}, "schema": []}
{"input": "Both metabolites failed to affect the production of androstenedione and testosterone but increased the secretion of estradiol at all concentrations tested.", "output": {"entities": {"chemical": [{"text": "androstenedione", "start": 52, "end": 67}, {"text": "testosterone", "start": 72, "end": 84}, {"text": "estradiol", "start": 116, "end": 125}]}}, "schema": []}
{"input": "The increased secretion of estradiol was due to the stimulation of aromatase gene and protein expression.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Direct assessment of aromatase activity by dibenzylfluorescein assay and indirect assessment of aromatase activity by measurement of the conversion of testosterone to estradiol confirmed that 5-OH-BDE-47 and 6-OH-BDE-47 stimulate aromatase activity.", "output": {"entities": {"chemical": [{"text": "dibenzylfluorescein", "start": 43, "end": 62}, {"text": "testosterone", "start": 151, "end": 163}, {"text": "estradiol", "start": 167, "end": 176}, {"text": "5-OH-BDE-47", "start": 192, "end": 203}, {"text": "6-OH-BDE-47", "start": 208, "end": 219}]}}, "schema": []}
{"input": "The aromatase inhibitor CGS 16949A abolished this stimulatory activity and reduced estradiol levels in the control and treatment groups.", "output": {"entities": {"chemical": [{"text": "CGS 16949A", "start": 24, "end": 34}, {"text": "estradiol", "start": 83, "end": 92}]}}, "schema": []}
{"input": "Cholestatic effect of epigallocatechin gallate in rats is mediated via decreased expression of Mrp2.", "output": {"entities": {"chemical": [{"text": "epigallocatechin gallate", "start": 22, "end": 46}]}}, "schema": []}
{"input": "Epigallocatechin gallate (EGCG) has been shown to be protective in various experimental models of liver injury, although opposite effects have also been reported.", "output": {"entities": {"chemical": [{"text": "Epigallocatechin gallate", "start": 0, "end": 24}, {"text": "EGCG", "start": 26, "end": 30}]}}, "schema": []}
{"input": "Since its effect on biliary physiology has not been thoroughly investigated, the present study evaluated effect of EGCG on bile flow and bile acid homeostasis in rats.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 115, "end": 119}, {"text": "bile acid", "start": 137, "end": 146}]}}, "schema": []}
{"input": "Compared to controls, EGCG treatment decreased bile flow by 23%.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 22, "end": 26}]}}, "schema": []}
{"input": "Hepatic paracellular permeability and biliary bile acid excretion were not altered by EGCG administration, but biliary glutathione excretion was reduced by 70%.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 46, "end": 55}, {"text": "EGCG", "start": 86, "end": 90}, {"text": "glutathione", "start": 119, "end": 130}]}}, "schema": []}
{"input": "Accordingly, the main glutathione transporter on the hepatocyte canalicular membrane, multidrug resistance-associated protein 2 (Mrp2), was significantly decreased at the protein level.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 22, "end": 33}]}}, "schema": []}
{"input": "EGCG administration also doubled plasma bile acid levels compared to controls.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 0, "end": 4}, {"text": "bile acid", "start": 40, "end": 49}]}}, "schema": []}
{"input": "While protein levels of the main hepatic bile acid transporters were unchanged, the rate-limiting enzyme in the bile acid synthesis, Cyp7a1, was significantly increased by EGCG.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 41, "end": 50}, {"text": "bile acid", "start": 112, "end": 121}, {"text": "EGCG", "start": 172, "end": 176}]}}, "schema": []}
{"input": "Enhanced bile acid synthesis in these animals was also confirmed by a 2-fold increase in plasma marker 7 alpha-hydroxy-4-cholesten-3-one.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 9, "end": 18}, {"text": "7 alpha-hydroxy-4-cholesten-3-one", "start": 103, "end": 136}]}}, "schema": []}
{"input": "In contrast, EGCG markedly downregulated major bile acid transporters (Asbt and Ost alpha) and regulatory molecules (Shp and Fgf15) in the ileum.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 13, "end": 17}, {"text": "bile acid", "start": 47, "end": 56}]}}, "schema": []}
{"input": "When EGCG was coadministered with ethinylestradiol, a potent cholestatic agent, it did not show any additional effect on the induced cholestasis.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 5, "end": 9}, {"text": "ethinylestradiol", "start": 34, "end": 50}]}}, "schema": []}
{"input": "This study shows ability of EGCG to raise plasma bile acid concentrations, mainly through Cyp7a1 upregulation, and to decrease bile production through reduction in Mrp2-mediated bile acid-independent bile flow.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 28, "end": 32}, {"text": "bile acid", "start": 49, "end": 58}, {"text": "bile acid", "start": 178, "end": 187}]}}, "schema": []}
{"input": "In conclusion, our data demonstrate that under certain conditions EGCG may induce cholestasis.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 66, "end": 70}]}}, "schema": []}
{"input": "Male mating behaviour in relation to female sexual swellings, socio-sexual behaviour and hormonal changes in wild Barbary macaques.", "output": {"entities": {}}, "schema": []}
{"input": "In many cercopithecine primates females display probabilistic cues of fertility to indicate the periovulatory period to males.", "output": {"entities": {}}, "schema": []}
{"input": "These cues may include female behaviour, acoustic signals, and morphological signs such as the anogenital swelling.", "output": {"entities": {}}, "schema": []}
{"input": "However, the extent to which males can utilise this information varies between species.", "output": {"entities": {}}, "schema": []}
{"input": "We describe male sexual behaviour in relation to changes in anogenital swelling size, timing of ovulation and female socio-sexual behaviour in wild Barbary macaques (Macaca sylvanus).", "output": {"entities": {}}, "schema": []}
{"input": "We further compare male sexual behaviour during conception and post-conception cycles to evaluate if males differentiate between these qualitatively different cycle types.", "output": {"entities": {}}, "schema": []}
{"input": "Our results show that during conception cycles male mating behaviour was concentrated around the fertile phase implying that males inferred information from more than swelling size alone.", "output": {"entities": {}}, "schema": []}
{"input": "Male mating frequency increased in line with female socio-sexual behaviour, namely female presenting and the frequency of copulations with copulation calls.", "output": {"entities": {}}, "schema": []}
{"input": "Most strikingly our results show that males invested equally in mating during fertile and non-fertile, i. e. post-conception, maximum swelling phases.", "output": {"entities": {}}, "schema": []}
{"input": "Whether post-conception swellings were merely a result of changes in hormone concentrations during pregnancy or part of a female reproductive strategy remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "In sum, this study adds to the body of research on the evolution of female sexual signals and how males may infer information from these cues.", "output": {"entities": {}}, "schema": []}
{"input": "Organization of the BcgI restriction-modification protein for the transfer of one methyl group to DNA.", "output": {"entities": {"chemical": [{"text": "methyl", "start": 82, "end": 88}]}}, "schema": []}
{"input": "The Type IIB restriction-modification protein BcgI contains A and B subunits in a 2: 1 ratio: A has the active sites for both endonuclease and methyltransferase functions while B recognizes the DNA.", "output": {"entities": {}}, "schema": []}
{"input": "Like almost all Type IIB systems, BcgI needs two unmethylated sites for nuclease activity; it cuts both sites upstream and downstream of the recognition sequence, hydrolyzing eight phosphodiester bonds in a single synaptic complex.", "output": {"entities": {"chemical": [{"text": "phosphodiester", "start": 181, "end": 195}]}}, "schema": []}
{"input": "This complex may incorporate four A (2) B protomers to give the eight catalytic centres (one per A subunit) needed to cut all eight bonds.", "output": {"entities": {}}, "schema": []}
{"input": "The BcgI recognition sequence contains one adenine in each strand that can be N (6)-methylated.", "output": {"entities": {"chemical": [{"text": "adenine", "start": 43, "end": 50}]}}, "schema": []}
{"input": "Although most DNA methyltransferases operate at both unmethylated and hemi-methylated sites, BcgI methyltransferase is only effective at hemi-methylated sites, where the nuclease component is inactive.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike the nuclease, the methyltransferase acts at solitary sites, functioning catalytically rather than stoichiometrically.", "output": {"entities": {}}, "schema": []}
{"input": "Though it transfers one methyl group at a time, presumably through a single A subunit, BcgI methyltransferase can be activated by adding extra A subunits, either individually or as part of A (2) B protomers, which indicates that it requires an assembly containing at least two A (2) B units.", "output": {"entities": {"chemical": [{"text": "methyl", "start": 24, "end": 30}]}}, "schema": []}
{"input": "The influence of diet on the gut microbiota.", "output": {"entities": {}}, "schema": []}
{"input": "Diet is a major factor driving the composition and metabolism of the colonic microbiota.", "output": {"entities": {}}, "schema": []}
{"input": "The amount, type and balance of the main dietary macronutrients (carbohydrates, proteins and fats) have a great impact on the large intestinal microbiota.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 65, "end": 78}]}}, "schema": []}
{"input": "The human colon contains a dense population of bacterial cells that outnumber host cells 10-fold.", "output": {"entities": {}}, "schema": []}
{"input": "Bacteroidetes, Firmicutes and Actinobacteria are the three major phyla that inhabit the human large intestine and these bacteria possess a fascinating array of enzymes that can degrade complex dietary substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Certain colonic bacteria are able to metabolise a remarkable variety of substrates whilst other species carry out more specialised activities, including primary degradation of plant cell walls.", "output": {"entities": {}}, "schema": []}
{"input": "Microbial metabolism of dietary carbohydrates results mainly in the formation of short chain fatty acids and gases.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 32, "end": 45}, {"text": "fatty acids", "start": 93, "end": 104}]}}, "schema": []}
{"input": "The major bacterial fermentation products are acetate, propionate and butyrate; and the production of these tends to lower the colonic pH.", "output": {"entities": {"chemical": [{"text": "acetate", "start": 46, "end": 53}, {"text": "propionate", "start": 55, "end": 65}, {"text": "butyrate", "start": 70, "end": 78}]}}, "schema": []}
{"input": "These weak acids influence the microbial composition and directly affect host health, with butyrate the preferred energy source for the colonocytes.", "output": {"entities": {"chemical": [{"text": "butyrate", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Certain bacterial species in the colon survive by cross-feeding, using either the breakdown products of complex carbohydrate degradation or fermentation products such as lactic acid for growth.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 112, "end": 124}, {"text": "lactic acid", "start": 170, "end": 181}]}}, "schema": []}
{"input": "Microbial protein metabolism results in additional fermentation products, some of which are potentially harmful to host health.", "output": {"entities": {}}, "schema": []}
{"input": "The current' omic era promises rapid progress towards understanding how diet can be used to modulate the composition and metabolism of the gut microbiota, allowing researchers to provide informed advice, that should improve long-term health status.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-proliferative effect of (19Z)-halichondramide, a novel marine macrolide isolated from the sponge Chondrosia corticata, is associated with G2/M cell cycle arrest and suppression of mTOR signaling in human lung cancer cells.", "output": {"entities": {"chemical": [{"text": "(19Z)-halichondramide", "start": 29, "end": 50}]}}, "schema": []}
{"input": "Five oxazole-containing macrolides isolated from the marine sponge Chondrosia corticata were evaluated for their anti-proliferative activity in a panel of human solid cancer cell lines.", "output": {"entities": {"chemical": [{"text": "oxazole", "start": 5, "end": 12}]}}, "schema": []}
{"input": "(19Z)-Halichondramide ((19Z)-HCA), a novel trisoxazole-containing macrolide, exhibited the highest potency among the macrolides, with IC50 values in the submicro-molar ranges.", "output": {"entities": {"chemical": [{"text": "(19Z)-Halichondramide", "start": 0, "end": 21}, {"text": "(19Z)-HCA", "start": 23, "end": 32}, {"text": "trisoxazole", "start": 43, "end": 54}]}}, "schema": []}
{"input": "Prompted by the high potency of growth inhibition of cancer cells, we investigated the mechanism of action of the anti-proliferative activity of (19Z)-HCA in human A549 lung cancer cells.", "output": {"entities": {"chemical": [{"text": "(19Z)-HCA", "start": 145, "end": 154}]}}, "schema": []}
{"input": "(19Z)-HCA induced cell cycle arrest in the G2/M phase, and this event was highly correlated with the expression of checkpoint proteins, including the up-regulation of p53 and GADD45 alpha and the down-regulation of cyclin B1, cyclin A, CDC2, and CDC25C.", "output": {"entities": {"chemical": [{"text": "(19Z)-HCA", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In addition, the growth inhibition by (19Z)-HCA was associated with the suppression of mTOR and its downstream effector molecules 4EBP1 and p70S6K.", "output": {"entities": {"chemical": [{"text": "(19Z)-HCA", "start": 38, "end": 47}]}}, "schema": []}
{"input": "The modulation of mTOR signaling by (19Z)-HCA was found to be mediated by the regulation of upstream proteins, including the down-regulation of Akt and p38 MAPK and the up-regulation of AMPK.", "output": {"entities": {"chemical": [{"text": "(19Z)-HCA", "start": 36, "end": 45}]}}, "schema": []}
{"input": "These data suggest the potential of (19Z)-HCA to serve as a candidate for cancer chemotherapeutic agents derived from marine organisms by virtue of arresting the cell cycle in the G2/M phase and the modulation of mTOR/AMPK signaling pathways.", "output": {"entities": {"chemical": [{"text": "(19Z)-HCA", "start": 36, "end": 45}]}}, "schema": []}
{"input": "Effect of the disintegrin eristostatin on melanoma-natural killer cell interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Malignant melanoma is difficult to treat due to its resistance to chemotherapeutic regimens.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of new pharmaceuticals with inhibitory potential can be helpful in the development of novel treatments.", "output": {"entities": {}}, "schema": []}
{"input": "The snake venom disintegrin eristostatin, from the viper Eristicophis macmahoni, caused immunodeficient mice to be significantly protected from development of lung colonization when melanoma cells and the disintegrin were co-injected in vivo into the lateral tail vein compared to vehicle controls.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxicity assays suggested that eristostatin makes the melanoma cells a better target for lysis by human natural killer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Direct binding assays using atomic force microscopy showed eristostatin does specifically bind the surface of the six melanoma cell lines tested.", "output": {"entities": {}}, "schema": []}
{"input": "Eristostatin binding was partially inhibited by the addition of soluble RGDS peptide, suggesting an integrin as one likely, but not the sole, binding partner.", "output": {"entities": {}}, "schema": []}
{"input": "Studies done with melanoma cells on a culture dish and natural killer cells attached to a cantilever tip in atomic force microscopy showed four major populations of interactions which exhibited altered frequency and unbinding strength in the presence of eristostatin.", "output": {"entities": {}}, "schema": []}
{"input": "A practical quantification method for Heinz bodies in birds applicable to rapid response field scenarios.", "output": {"entities": {}}, "schema": []}
{"input": "Oil-induced oxidative injury to red blood cells results in Heinz body hemolytic anemia.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we evaluated three Heinz body staining techniques in brown pelican (Pelecanus occidentalis) blood.", "output": {"entities": {}}, "schema": []}
{"input": "Using a range of in vitro acetylphenylhydrazine incubations, we validated a field-adapted technique against laboratory wet-mounts and verified the stability of this technique for one month following preparation.", "output": {"entities": {"chemical": [{"text": "acetylphenylhydrazine", "start": 26, "end": 47}]}}, "schema": []}
{"input": "Employing this technique during petrochemical spill responses allows for delays between sample collection and analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Effects-based marine ecological risk assessment at a polychlorinated biphenyl-contaminated site in Saglek, Labrador, Canada.", "output": {"entities": {"chemical": [{"text": "polychlorinated biphenyl", "start": 53, "end": 77}]}}, "schema": []}
{"input": "Although the presence and distribution of polychlorinated biphenyls (PCBs) in Arctic marine environments has been well documented, the implications for the health of biota are poorly understood.", "output": {"entities": {"chemical": [{"text": "polychlorinated biphenyls", "start": 42, "end": 67}, {"text": "PCBs", "start": 69, "end": 73}]}}, "schema": []}
{"input": "In the present study, multiple lines of evidence, including site-specific effects data, were used to assess PCB-related risks to marine biota at a contaminated military site in Saglek Bay, Labrador, Canada, from 1997 to 1999.", "output": {"entities": {"chemical": [{"text": "PCB", "start": 108, "end": 111}]}}, "schema": []}
{"input": "Risks were evaluated for three components of the ecosystem: benthic invertebrates, a bottom-feeding fish (shorthorn sculpin, Myoxocephalus scorpius), and a diving seabird (black guillemot, Cepphus grylle).", "output": {"entities": {}}, "schema": []}
{"input": "Average sediment PCB concentrations exceeded the Canadian interim sediment quality guideline level by 41-fold.", "output": {"entities": {"chemical": [{"text": "PCB", "start": 17, "end": 20}]}}, "schema": []}
{"input": "However, sediment toxicity testing and a benthic community survey showed no evidence of adverse effects.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, shorthorn sculpin and black guillemot PCB exposures (measured as sum of 55 congeners) were elevated enough to pose risks to survival or reproduction.", "output": {"entities": {"chemical": [{"text": "PCB", "start": 51, "end": 54}]}}, "schema": []}
{"input": "Based on the collective evidence, the authors estimated that risks were posed by sediment PCB concentrations greater than 77 ng/g dry weight for black guillemots and 750 ng/g dry weight for shorthorn sculpins.", "output": {"entities": {"chemical": [{"text": "PCB", "start": 90, "end": 93}]}}, "schema": []}
{"input": "The present study, along with two parallel studies, provided information to support the management decisions concerning potential remedial action on the contaminated sediments.", "output": {"entities": {}}, "schema": []}
{"input": "This ecological risk assessment describes the steps and rationale taken to evaluate the risk posed by an area of PCB-contaminated marine sediments in an otherwise relatively pristine northern coastal environment.", "output": {"entities": {"chemical": [{"text": "PCB", "start": 113, "end": 116}]}}, "schema": []}
{"input": "Metabolically competent human skin models: activation and genotoxicity of benzo [a] pyrene.", "output": {"entities": {"chemical": [{"text": "benzo [a] pyrene", "start": 74, "end": 90}]}}, "schema": []}
{"input": "The polycyclic aromatic hydrocarbon (PAH) benzo [a] pyrene (BP) is metabolized into a complex pattern of BP derivatives, among which the ultimate carcinogen (+)-anti-BP-7, 8-diol-9, 10-epoxide (BPDE) is formed to certain extents.", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbon", "start": 4, "end": 35}, {"text": "PAH", "start": 37, "end": 40}, {"text": "benzo [a] pyrene", "start": 42, "end": 58}, {"text": "(+)-anti-BP-7, 8-diol-9, 10-epoxide", "start": 157, "end": 192}, {"text": "BPDE", "start": 194, "end": 198}]}}, "schema": []}
{"input": "Skin is frequently in contact with PAHs and data on the metabolic capacity of skin tissue toward these compounds are inconclusive.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 35, "end": 39}]}}, "schema": []}
{"input": "We compared BP metabolism in excised human skin, commercially available in vitro 3D skin models and primary 2D skin cell cultures, and analyzed the metabolically catalyzed occurrence of seven different BP follow-up products by means of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).", "output": {"entities": {}}, "schema": []}
{"input": "All models investigated were competent to metabolize BP, and the metabolic profiles generated by ex vivo human skin and skin models were remarkably similar.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the genotoxicity of BP and its derivatives was monitored in these models via comet assays.", "output": {"entities": {}}, "schema": []}
{"input": "In a full-thickness skin, equivalent BP-mediated genotoxic stress was generated via keratinocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Cultured primary keratinocytes revealed a level of genotoxicity comparable with that of direct exposure to 50-100 nM of BPDE.", "output": {"entities": {"chemical": [{"text": "BPDE", "start": 120, "end": 124}]}}, "schema": []}
{"input": "Our data demonstrate that the metabolic capacity of human skin ex vivo, as well as organotypic human 3D skin models toward BP, is sufficient to cause significant genotoxic stress and thus cutaneous bioactivation may potentially contribute to mutations that ultimately lead to skin cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Response to variable light intensity in photoacclimated algae and cyanobacteria exposed to atrazine.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Atrazine is frequently detected in freshwater ecosystems exposed to agricultural waste waters and runoffs worldwide and it can affect non-target organisms (mainly photoautotrophic) and modify community structure.", "output": {"entities": {"chemical": [{"text": "Atrazine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Meanwhile, light environment is known to vary between aquatic ecosystems, but also before and during the exposure to atrazine and these variations may modify the sensitivity to atrazine of photoautotroph organisms.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 117, "end": 125}, {"text": "atrazine", "start": 177, "end": 185}]}}, "schema": []}
{"input": "In this study, 10 species of phytoplankton (chlorophytes, baccilariophytes and cyanophytes) acclimated to low or high light intensities were exposed to atrazine and light of different intensities to compare their combined effect.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 152, "end": 160}]}}, "schema": []}
{"input": "Our data showed that chlorophytes and baccilariophytes were more resistant to atrazine compared to cyanophytes for all light conditions.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 78, "end": 86}]}}, "schema": []}
{"input": "Atrazine was found to inhibit Phi' (M), Psi (0), P (M) and non-photochemical quenching for all species indicating an effect on electron transport, primary production and photoregulation processes.", "output": {"entities": {"chemical": [{"text": "Atrazine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "These data also indicate a higher sensitivity of Psi (0) (average Psi (0)-EC (50) of 91 +/- 11 nM or 19. 6 +/- 0. 9 mu gL (-1)) compared to Phi' (M) (average Phi' (M)-EC (50) of 217 +/- 19 nM or 46. 8 +/- 4. 1 mu gL (-1)) and suggest that photoregulation processes activated in presence of light decrease the effect of atrazine.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 319, "end": 327}]}}, "schema": []}
{"input": "We also showed that increasing light intensity decreased Phi' (M)-EC (50) in both low (except baccilariophytes) and high light acclimated conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Despite this similarity, most species acclimated to high light were found to have higher or similar Phi' (M)-EC (50) compared to low light acclimated cells and thus, were less sensitive to atrazine in low light and high light environments.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 189, "end": 197}]}}, "schema": []}
{"input": "We concluded that an increase in the plastoquinone pool induced by acclimation to high light decreased the sensitivity to atrazine in phytoplankton and we hypothesized that the effect observed was the result of a dilution of atrazine toxicity through increased binding site availability (quinones) combined with increased photoregulation processes capacity.", "output": {"entities": {"chemical": [{"text": "plastoquinone", "start": 37, "end": 50}, {"text": "atrazine", "start": 122, "end": 130}, {"text": "atrazine", "start": 225, "end": 233}, {"text": "quinones", "start": 288, "end": 296}]}}, "schema": []}
{"input": "Short duration of diabetes and disuse of sulfonylurea have any association with insulin cessation of the patients with type 2 diabetes in a clinical setting in Japan (JDDM 30).", "output": {"entities": {"chemical": [{"text": "sulfonylurea", "start": 41, "end": 53}]}}, "schema": []}
{"input": "Insulin therapy is often required to achieve good glycemic control for the patients with type 2 diabetes mellitus (T2DM), while protraction of glycemic control without insulin therapy may be preferable for patients.", "output": {"entities": {}}, "schema": []}
{"input": "To determine the characteristics of and therapeutic regimen in outpatients with T2DM who were able to stop insulin therapy with satisfactory glycemic control in a real clinical practice setting in Japan by a case-control study.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was performed on 928 patients with T2DM who started insulin therapy in 2007.", "output": {"entities": {}}, "schema": []}
{"input": "Data regarding age, sex, body mass index, duration of diabetes, HbA1c, postprandial plasma glucose, plasma fasting C-peptide immunoreactivity and treatment modality were compared between patients who were able to stop insulin therapy and those who continued with insulin.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 91, "end": 98}]}}, "schema": []}
{"input": "Of the 928 patients, 37 had stopped insulin therapy within 1 year.", "output": {"entities": {}}, "schema": []}
{"input": "In the patients who stopped insulin therapy, the duration of diabetes was significantly shorter and the daily insulin dosage at initiation and the prevalence of sulfonylurea pretreatment significantly lower compared with patients who continued on insulin.", "output": {"entities": {"chemical": [{"text": "sulfonylurea", "start": 161, "end": 173}]}}, "schema": []}
{"input": "In conclusion, almost 4% of T2DM patients were able to stop insulin therapy with satisfactory glycemic control in a real clinical practice setting in Japan.", "output": {"entities": {}}, "schema": []}
{"input": "Shorter duration of diabetes and disuse of sulfonylureas prior to insulin may associate with stopping insulin therapy as a near-normoglycemic remission in outpatients with T2DM in Japan.", "output": {"entities": {"chemical": [{"text": "sulfonylureas", "start": 43, "end": 56}]}}, "schema": []}
{"input": "RBFOX2 is an important regulator of mesenchymal tissue-specific splicing in both normal and cancer tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Alternative splicing provides a critical and flexible layer of regulation intervening in many biological processes to regulate the diversity of proteins and impact cell phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "To identify alternative splicing differences that distinguish epithelial from mesenchymal tissues, we have investigated hundreds of cassette exons using a high-throughput reverse transcription-PCR (RT-PCR) platform.", "output": {"entities": {}}, "schema": []}
{"input": "Extensive changes in splicing were noted between epithelial and mesenchymal tissues in both human colon and ovarian tissues, with many changes from mostly one splice variant to predominantly the other.", "output": {"entities": {}}, "schema": []}
{"input": "Remarkably, many of the splicing differences that distinguish normal mesenchymal from normal epithelial tissues matched those that differentiate normal ovarian tissues from ovarian cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, because splicing profiling could classify cancer cell lines according to their epithelial/mesenchymal characteristics, we used these cancer cell lines to identify regulators for these specific splicing signatures.", "output": {"entities": {}}, "schema": []}
{"input": "By knocking down 78 potential splicing factors in five cell lines, we provide an extensive view of the complex regulatory landscape associated with the epithelial and mesenchymal states, thus revealing that RBFOX2 is an important driver of mesenchymal tissue-specific splicing.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis and anticancer activity of N (3), N (11)-bis (2-hydroxyethyl)-14-aryl-14H-dibenzo [a, j] xanthenes-3, 11-dicarboxamide.", "output": {"entities": {"chemical": [{"text": "N (3), N (11)-bis (2-hydroxyethyl)-14-aryl-14H-dibenzo [a, j] xanthenes-3, 11-dicarboxamide", "start": 45, "end": 136}]}}, "schema": []}
{"input": "A series of novel N (3), N (11)-bis (2-hydroxyethyl)-14-aryl-14H-dibenzo [a, j] xanthenes-3, 11-dicarboxamide, three N (3), N (11)-bis (2-hydroxyethyl)-14-aryl-14H-dibenzo [a, j] xanthene-3, 11-dimethanamine derivatives and their intermediates 14-aryl-14H-dibenzo [a, j] xanthenes-3, 11-dicarboxylic acid, were synthesized, and the structures of which were characterized by (1) H-NMR, (13) C-NMR, high resolution (HR)-MS, and IR spectra.", "output": {"entities": {"chemical": [{"text": "N (3), N (11)-bis (2-hydroxyethyl)-14-aryl-14H-dibenzo [a, j] xanthenes-3, 11-dicarboxamide", "start": 18, "end": 109}, {"text": "N (3), N (11)-bis (2-hydroxyethyl)-14-aryl-14H-dibenzo [a, j] xanthene-3, 11-dimethanamine", "start": 117, "end": 207}, {"text": "14-aryl-14H-dibenzo [a, j] xanthenes-3, 11-dicarboxylic acid", "start": 244, "end": 304}, {"text": "(1) H", "start": 374, "end": 379}, {"text": "(13) C", "start": 385, "end": 391}]}}, "schema": []}
{"input": "The antitumor activities of these molecules were evaluated on five cancer cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "The results of in vitro assay against human hepatocellular carcinoma cell lines (SK-HEP-1 and HepG2 and SMMC-7721 cells), acute promyelocytic leukemia NB4 cells and uterine cervix cancer HeLa cells, show several compounds to be endowed with cytotoxicity in micromolar to submicromolar range.", "output": {"entities": {}}, "schema": []}
{"input": "The carboxamide derivatives 6c and 6e exhibitted good inhibition on NB4 cancer cells, and the IC (50) values of which were 0. 82 micro M and 0. 96 micro M, respectively, much lower than 5. 01 micro M of the positive control As (2) O (3).", "output": {"entities": {"chemical": [{"text": "carboxamide", "start": 4, "end": 15}, {"text": "As (2) O (3)", "start": 224, "end": 236}]}}, "schema": []}
{"input": "Flow cytometric analysis results revealed that compounds 6e and 6f may induce tumor cell apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and quantitative structure-activity relationships of selective BCRP inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC transporter superfamily.", "output": {"entities": {}}, "schema": []}
{"input": "This protein has a number of physiological functions, including protection of the human body from xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "The overexpression of BCRP in certain tumor cell lines causes cross-resistance against various drugs used in chemotherapeutic treatment.", "output": {"entities": {}}, "schema": []}
{"input": "In a previous work we showed that a new class of compounds derived from XR9576 (tariquidar) selectively inhibits BCRP.", "output": {"entities": {"chemical": [{"text": "XR9576", "start": 72, "end": 78}, {"text": "tariquidar", "start": 80, "end": 90}]}}, "schema": []}
{"input": "In this work we synthesized more members of this class, with modification on the second and third aromatic rings.", "output": {"entities": {}}, "schema": []}
{"input": "The inhibitory activities against BCRP and P-gp were assayed using a Hoechst 33342 assay for BCRP and a calcein AM assay for P-gp.", "output": {"entities": {"chemical": [{"text": "Hoechst 33342", "start": 69, "end": 82}]}}, "schema": []}
{"input": "Finally, quantitative structure-activity relationships for both aromatic rings were established.", "output": {"entities": {}}, "schema": []}
{"input": "The results obtained show the importance of the electron density on the third aromatic ring, influenced by substituents, pointing to interactions with aromatic residues of the protein binding site.", "output": {"entities": {}}, "schema": []}
{"input": "In the second aromatic ring the activity of compounds is influenced by the steric volume of the substituents.", "output": {"entities": {}}, "schema": []}
{"input": "Reduction of helical content by insertion of a disulfide bond leads to an antimicrobial peptide with decreased hemolytic activity.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 47, "end": 56}]}}, "schema": []}
{"input": "CAPs off to the S-S bond: Application of a strategy involving the introduction of intramolecular disulfide bonds to amphipathic cationic antimicrobial peptides (CAPs) led to decreased alpha-helicity and hydrophobicity.", "output": {"entities": {"chemical": [{"text": "S-S", "start": 16, "end": 19}, {"text": "disulfide", "start": 97, "end": 106}]}}, "schema": []}
{"input": "The mutant peptides were observed to have significantly increased (250-fold) minimum hemolytic concentrations while maintaining MIC values against E. coli, affording more therapeutically selective CAPs.", "output": {"entities": {}}, "schema": []}
{"input": "Hepatic Cyp2d and Cyp26a1 mRNAs and activities are increased during mouse pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "There is considerable evidence that drug disposition is altered during human pregnancy and based on probe drug studies, CYP2D6 activity increases during human pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to determine whether the changes of CYP2D6 activity observed during human pregnancy could be replicated in the mouse, and explore possible mechanisms of increased CYP2D6 activity during pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Cyp2d11, Cyp2d22, Cyp2d26 and Cyp2d40 mRNA was increased (P < 0. 05) on gestational days (GD) 15 and 19 compared with the non-pregnant controls.", "output": {"entities": {}}, "schema": []}
{"input": "There was no change (P > 0. 05) in Cyp2d9 and Cyp2d10 mRNA.", "output": {"entities": {}}, "schema": []}
{"input": "In agreement with the increased Cyp2d mRNA, Cyp2d-mediated dextrorphan formation from dextromethorphan was increased 2. 7-fold (P < 0. 05) on GD19 (56. 8 +/- 39. 4 pmol/min/mg protein) when compared with the non-pregnant controls (20. 8 +/- 11. 2 pmol/min/mg protein).", "output": {"entities": {"chemical": [{"text": "dextrorphan", "start": 59, "end": 70}, {"text": "dextromethorphan", "start": 86, "end": 102}]}}, "schema": []}
{"input": "An increase in Cyp26a1 mRNA (10-fold) and retinoic acid receptor (Rar) beta mRNA (2. 8-fold) was also observed during pregnancy.", "output": {"entities": {"chemical": [{"text": "retinoic acid", "start": 42, "end": 55}]}}, "schema": []}
{"input": "The increase in Cyp26a1 and Rar beta mRNA during pregnancy indicates increased retinoic acid signaling in the liver during pregnancy.", "output": {"entities": {"chemical": [{"text": "retinoic acid", "start": 79, "end": 92}]}}, "schema": []}
{"input": "A putative retinoic acid response element was identified within the Cyp2d40 promoter and the mRNA of Cyp2d40 correlated (P < 0. 05) with Cyp26a1 and Rar beta.", "output": {"entities": {"chemical": [{"text": "retinoic acid", "start": 11, "end": 24}]}}, "schema": []}
{"input": "These results show that Cyp2d mRNA is increased during mouse pregnancy the and mouse may provide a suitable model to investigate the mechanisms underlying the increased clearance of CYP2D6 probes observed during human pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings also suggest that retinoic acid signaling in the liver is increased during pregnancy, which may have broader implications to energy homeostasis in the liver during pregnancy.", "output": {"entities": {"chemical": [{"text": "retinoic acid", "start": 31, "end": 44}]}}, "schema": []}
{"input": "Susceptibility to fatty acid-induced beta-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: a potential link between beta-cell lipotoxicity and islet inflammation.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 18, "end": 28}]}}, "schema": []}
{"input": "beta-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity may be synergistic.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, beta-cell lipotoxicity could be enhanced in models of autoimmune diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "To determine this, we examined the effects of prolonged free fatty acids elevation on beta-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 61, "end": 72}]}}, "schema": []}
{"input": "Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ~ 2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 92, "end": 102}]}}, "schema": []}
{"input": "IH significantly decreased beta-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine.", "output": {"entities": {"chemical": [{"text": "N-acetylcysteine", "start": 268, "end": 284}]}}, "schema": []}
{"input": "Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats.", "output": {"entities": {}}, "schema": []}
{"input": "All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the presence of insulitis was permissive for IH-induced beta-cell dysfunction in the BB rat, which suggests a link between beta-cell lipotoxicity and islet inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Ablation of Egr2-positive cells in male mouse anterior pituitary leads to atypical isolated GH deficiency.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we have investigated the expression and function of the transcription factor early growth response factor 2 (Egr2)/Krox20 in the developing anterior pituitary.", "output": {"entities": {}}, "schema": []}
{"input": "Egr2 is initially expressed in all differentiating hormonal cells types, but its expression is mostly restricted to the somatotroph lineage after birth.", "output": {"entities": {}}, "schema": []}
{"input": "Egr2 knockout results in anterior pituitary hypoplasia.", "output": {"entities": {}}, "schema": []}
{"input": "However, the analysis of a conditional mutant demonstrates that this phenotype does not originate from a lack of Egr2 expression in the pituitary.", "output": {"entities": {}}, "schema": []}
{"input": "Using an Egr2 allele driving a Cre-activable toxin gene, we performed a genetic ablation of Egr2-positive cells in the pituitary.", "output": {"entities": {}}, "schema": []}
{"input": "During the postnatal period, this ablation leads to specific and progressive depletion of the somatotroph population, creating a novel model of early-onset isolated GH deficiency (GHD).", "output": {"entities": {}}, "schema": []}
{"input": "Mutant animals were subjected to a complete metabolic analysis, revealing atypical and expected features.", "output": {"entities": {}}, "schema": []}
{"input": "Consistent with an adult-onset isolated GHD model, mutant animals are hypoglycemic and display increased insulin sensitivity and glucose clearance.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 129, "end": 136}]}}, "schema": []}
{"input": "This latter phenotype is in contrast to the glucose intolerance observed in another early-onset GHD model.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 44, "end": 51}]}}, "schema": []}
{"input": "Surprisingly, increased insulin sensitivity is not accompanied by a modified balance between fat and lean tissues, but by reduced metabolic adaptability between glucose and lipid oxidation conditions.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 161, "end": 168}]}}, "schema": []}
{"input": "This suggests that the relationship between these metabolic features and insulin sensitivity should be reconsidered.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, our mutant may be a valuable genetic model with which to study the effects of long-term GH deficiency, in conditions of normal pancreatic function and unaffected balance between fat and glucose metabolism.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 201, "end": 208}]}}, "schema": []}
{"input": "Assembly of subtype 1 influenza neuraminidase is driven by both the transmembrane and head domains.", "output": {"entities": {}}, "schema": []}
{"input": "Neuraminidase (NA) is one of the two major influenza surface antigens and the main influenza drug target.", "output": {"entities": {}}, "schema": []}
{"input": "Although NA has been well characterized and thought to function as a tetramer, the role of the transmembrane domain (TMD) in promoting proper NA assembly has not been systematically studied.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate that in the absence of the TMD, NA is synthesized and transported in a predominantly inactive state.", "output": {"entities": {}}, "schema": []}
{"input": "Substantial activity was rescued by progressive truncations of the stalk domain, suggesting the TMD contributes to NA maturation by tethering the stalk to the membrane.", "output": {"entities": {}}, "schema": []}
{"input": "To analyze how the TMD supports NA assembly, the TMD was examined by itself.", "output": {"entities": {}}, "schema": []}
{"input": "The NA TMD formed a homotetramer and efficiently trafficked to the plasma membrane, indicating the TMD and enzymatic head domain drive assembly together through matching oligomeric states.", "output": {"entities": {}}, "schema": []}
{"input": "In support of this, an unrelated strong oligomeric TMD rescued almost full NA activity, whereas the weak oligomeric mutant of this TMD restored only half of wild type activity.", "output": {"entities": {}}, "schema": []}
{"input": "These data illustrate that a large soluble domain can force assembly with a poorly compatible TMD; however, optimal assembly requires coordinated oligomerization between the TMD and the soluble domain.", "output": {"entities": {}}, "schema": []}
{"input": "Membrane domains and the \" lipid raft \" concept.", "output": {"entities": {}}, "schema": []}
{"input": "The bulk structure of biological membranes consists of a bilayer of amphipathic lipids.", "output": {"entities": {}}, "schema": []}
{"input": "According to the fluid mosaic model proposed by Singer and Nicholson, the glycerophospholipid bilayer is a two-dimensional fluid construct that allows the lateral movement of membrane components.", "output": {"entities": {"chemical": [{"text": "glycerophospholipid", "start": 74, "end": 93}]}}, "schema": []}
{"input": "Different types of lateral interactions among membrane components can take place, giving rise to multiple levels of lateral order that lead to highly organized structures.", "output": {"entities": {}}, "schema": []}
{"input": "Early observations suggested that some of the lipid components of biological membranes may play active roles in the creation of these levels of order.", "output": {"entities": {}}, "schema": []}
{"input": "In the late 1980s, a diverse series of experimental findings collectively gave rise to the lipid raft hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "Lipid rafts were originally defined as membrane domains, i. e., ordered structures created as a consequence of the lateral segregation of sphingolipids and differing from the surrounding membrane in their molecular composition and properties.", "output": {"entities": {"chemical": [{"text": "sphingolipids", "start": 138, "end": 151}]}}, "schema": []}
{"input": "This definition was subsequently modified to introduce the notion that lipid rafts correspond to membrane areas stabilized by the presence of cholesterol within a liquid-ordered phase.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 142, "end": 153}]}}, "schema": []}
{"input": "During the past two decades, the concept of lipid rafts has become extremely popular among cell biologists, and these structures have been suggested to be involved in a great variety of cellular functions and biological events.", "output": {"entities": {}}, "schema": []}
{"input": "During the same period, however, some groups presented experimental evidence that appeared to contradict the basic tenets that underlie the lipid raft concept.", "output": {"entities": {}}, "schema": []}
{"input": "The concept is currently being re-defined, with greater consistency regarding the true nature and role of lipid rafts.", "output": {"entities": {}}, "schema": []}
{"input": "In this article we will review the concepts, criticisms, and the novel confirmatory findings relating to the lipid raft hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "Regulation of G protein-coupled receptor kinases by phospholipids.", "output": {"entities": {}}, "schema": []}
{"input": "G protein coupled-receptor (GPCR) kinases (GRKs) initiate the deactivation of GPCRs by phosphorylating their cytoplasmic loops and C-terminal tails.", "output": {"entities": {}}, "schema": []}
{"input": "They are regulated not only by allosteric interactions with activated GPCRs, but also by the membrane environment itself.", "output": {"entities": {}}, "schema": []}
{"input": "Herein we describe how the various GRKs are recruited to lipid bilayers and, where evident, how specific anionic phospholipids help regulate their activity.", "output": {"entities": {}}, "schema": []}
{"input": "Using crystal structures representing each of the three vertebrate GRK subfamilies, we map the lipid binding sites in order to better understand how these enzymes are oriented at the cell surface.", "output": {"entities": {}}, "schema": []}
{"input": "This analysis suggests that GRKs bind lipid and active GPCRs in a coordinated manner.", "output": {"entities": {}}, "schema": []}
{"input": "Membrane lipids in the function of serotonin and adrenergic receptors.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 35, "end": 44}]}}, "schema": []}
{"input": "G-protein coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across membranes, and represent major targets in the development of novel drug candidates in all clinical areas.", "output": {"entities": {}}, "schema": []}
{"input": "Since GPCRs are integral membrane proteins, interaction of membrane lipids such as cholesterol and sphingolipids with GPCRs constitutes an emerging area of research in contemporary biology.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 83, "end": 94}, {"text": "sphingolipids", "start": 99, "end": 112}]}}, "schema": []}
{"input": "Cholesterol and sphingolipids represent important lipid components of eukaryotic membranes and play a crucial role in a variety of cellular functions.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 0, "end": 11}, {"text": "sphingolipids", "start": 16, "end": 29}]}}, "schema": []}
{"input": "In this review, we highlight the role of these vital lipids in the function of two representative GPCRs, the serotonin (1A) receptor and the adrenergic receptor.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 109, "end": 118}]}}, "schema": []}
{"input": "We believe that development in deciphering molecular details of the nature of GPCR-lipid interaction would lead to better insight into our overall understanding of GPCR function in health and disease.", "output": {"entities": {}}, "schema": []}
{"input": "GPR55 and its interaction with membrane lipids: comparison with other endocannabinoid-binding receptors.", "output": {"entities": {}}, "schema": []}
{"input": "A number of integral membrane G protein-coupled receptors (GPCRs) share common structural features (including palmytoilated aminoacid residues and consensus sequences specific for interaction with cholesterol) that allow them to interact with lipid rafts, membrane cholesterol-rich microdomains able to regulate GPCR signalling and functions.", "output": {"entities": {"chemical": [{"text": "palmytoilated aminoacid", "start": 110, "end": 133}, {"text": "cholesterol", "start": 197, "end": 208}, {"text": "cholesterol", "start": 265, "end": 276}]}}, "schema": []}
{"input": "Among GPCRs, type-1 and type-2 cannabinoid receptors, the molecular targets of endocannabinoids (eCBs), control many physiological and pathological processes through the activation of several signal transduction pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, the orphan GPR55 receptor has been proved to be activated by many eCBs, thus leading to the hypothesis that it might be the \" type-3 \" cannabinoid receptor.", "output": {"entities": {}}, "schema": []}
{"input": "While the biological activity of eCBs and the influence of membrane lipids on their functions are rather well established, information regarding GPR55 is still scarce and often controversial.", "output": {"entities": {}}, "schema": []}
{"input": "Based on this background, here we shall review current data about GPR55 pharmacology and signalling, highlighting its involvement in several pathophysiological conditions.", "output": {"entities": {}}, "schema": []}
{"input": "We shall also outline the structural features that allow GPR55 to interact with cholesterol and to associate with lipid rafts; how the latter lipid microdomains impact the biological activity of GPR55 is also addressed, as well as their potential for the discovery of new therapeutics useful for the treatment of those human diseases that might be associated with alterations of GPR55 activity.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 80, "end": 91}]}}, "schema": []}
{"input": "2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin", "start": 0, "end": 38}, {"text": "oxygen", "start": 71, "end": 77}]}}, "schema": []}
{"input": "Chloracne is commonly observed in humans exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD); yet, the mechanism of toxicity is not well understood.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 52, "end": 90}, {"text": "TCDD", "start": 92, "end": 96}]}}, "schema": []}
{"input": "Using normal human epidermal keratinocytes, we investigated the mechanism of TCDD-mediated enhancement of epidermal differentiation by integrating functional genomic, metabolomic, and biochemical analyses.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 77, "end": 81}]}}, "schema": []}
{"input": "TCDD increased the expression of 40% of the genes of the epidermal differentiation complex found on chromosome 1q21 and 75% of the genes required for de novo ceramide biosynthesis.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}, {"text": "ceramide", "start": 158, "end": 166}]}}, "schema": []}
{"input": "Lipid analysis demonstrated that eight of the nine classes of ceramides were increased by TCDD, altering the ratio of ceramides to free fatty acids.", "output": {"entities": {"chemical": [{"text": "ceramides", "start": 62, "end": 71}, {"text": "TCDD", "start": 90, "end": 94}, {"text": "ceramides", "start": 118, "end": 127}, {"text": "fatty acids", "start": 136, "end": 147}]}}, "schema": []}
{"input": "TCDD decreased the expression of the glucose transporter, SLC2A1, and most of the glycolytic transcripts, followed by decreases in glycolytic intermediates, including pyruvate.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}, {"text": "glucose", "start": 37, "end": 44}, {"text": "pyruvate", "start": 167, "end": 175}]}}, "schema": []}
{"input": "NADH and Krebs cycle intermediates were decreased, whereas NAD (+) was increased.", "output": {"entities": {"chemical": [{"text": "NADH", "start": 0, "end": 4}, {"text": "NAD (+)", "start": 59, "end": 66}]}}, "schema": []}
{"input": "Mitochondrial glutathione (GSH) reductase activity and the GSH/glutathione disulfide ratio were decreased by TCDD, ultimately leading to mitochondrial dysfunction, characterized by decreased inner mitochondrial membrane potential and ATP production, and increased production of the reactive oxygen species (ROS), hydrogen peroxide.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 14, "end": 25}, {"text": "GSH", "start": 27, "end": 30}, {"text": "GSH", "start": 59, "end": 62}, {"text": "glutathione disulfide", "start": 63, "end": 84}, {"text": "TCDD", "start": 109, "end": 113}, {"text": "ATP", "start": 234, "end": 237}, {"text": "oxygen", "start": 291, "end": 297}, {"text": "hydrogen peroxide", "start": 313, "end": 330}]}}, "schema": []}
{"input": "Aryl hydrocarbon receptor (AHR) antagonists blocked the response of many transcripts to TCDD, and the endpoints of decreased ATP production and differentiation, suggesting regulation by the AHR.", "output": {"entities": {"chemical": [{"text": "Aryl hydrocarbon", "start": 0, "end": 16}, {"text": "TCDD", "start": 88, "end": 92}, {"text": "ATP", "start": 125, "end": 128}]}}, "schema": []}
{"input": "Cotreatment of cells with chemical antioxidants or the enzyme catalase blocked the TCDD-mediated acceleration of keratinocyte cornified envelope formation, an endpoint of terminal differentiation.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 83, "end": 87}]}}, "schema": []}
{"input": "Thus, TCDD-mediated ROS production is a critical step in the mechanism of this chemical to accelerate keratinocyte differentiation.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 6, "end": 10}]}}, "schema": []}
{"input": "Delta 9-tetrahydrocannabinol impairs the inflammatory response to influenza infection: role of antigen-presenting cells and the cannabinoid receptors 1 and 2.", "output": {"entities": {"chemical": [{"text": "Delta 9-tetrahydrocannabinol", "start": 0, "end": 28}]}}, "schema": []}
{"input": "Delta (9)-tetrahydrocannabinol (Delta (9)-THC) has potent immune modulatory properties and can impair pathogen-induced immune defenses, which in part have been attributed to ligation of the cannabinoid receptors 1 (CB (1)) and 2 (CB (2)).", "output": {"entities": {"chemical": [{"text": "Delta (9)-tetrahydrocannabinol", "start": 0, "end": 30}, {"text": "Delta (9)-THC", "start": 32, "end": 45}]}}, "schema": []}
{"input": "Most recently, dendritic cells (DC) were identified for their potential to enhance influenza-induced immunopathology in mice lacking CB (1) and CB (2) (CB (1) (-/-) CB (2) (-/-)).", "output": {"entities": {}}, "schema": []}
{"input": "This study focused on the modulation of the inflammatory immune response to influenza by Delta (9)-THC and the role of CB (1) and/or CB (2) as receptor targets for Delta (9)-THC.", "output": {"entities": {"chemical": [{"text": "Delta (9)-THC", "start": 89, "end": 102}, {"text": "Delta (9)-THC", "start": 164, "end": 177}]}}, "schema": []}
{"input": "C57Bl/6 (wild type) and CB (1) (-/-) CB (2) (-/-) mice were administered Delta (9)-THC (75 mg/kg) surrounding the intranasal instillation of A/PR/8/34 influenza virus.", "output": {"entities": {"chemical": [{"text": "Delta (9)-THC", "start": 73, "end": 86}]}}, "schema": []}
{"input": "Three days post infection (dpi), Delta (9)-THC broadly decreased expression levels of mRNA induced by the innate immune response to influenza, suppressed the percentage of interferon-gamma (IFN-gamma)-producing CD4 (+) and interleukin-17-producing NK1. 1 (+) cells, and reduced the influx of antigen-presenting cells (APC), including inflammatory myeloid cells and monocytes/macrophages, into the lung in a CB (1)-and/or CB (2)-dependent manner.", "output": {"entities": {"chemical": [{"text": "Delta (9)-THC", "start": 33, "end": 46}]}}, "schema": []}
{"input": "Delta (9)-THC had little effect on the expression of CD86, major histocompatibility complex I (MHC I), and MHC II by APC isolated from the lung.", "output": {"entities": {"chemical": [{"text": "Delta (9)-THC", "start": 0, "end": 13}]}}, "schema": []}
{"input": "In vitro studies demonstrated that lipopolysaccharide (LPS)-induced maturation was suppressed by Delta (9)-THC in bone marrow-derived DC (bmDC).", "output": {"entities": {"chemical": [{"text": "Delta (9)-THC", "start": 97, "end": 110}]}}, "schema": []}
{"input": "Furthermore, antigen-specific IFN-gamma production by CD8 (+) T cells after coculture was reduced by Delta (9)-THC treatment of bmDC in a CB (1)-and/or CB (2)-dependent manner.", "output": {"entities": {"chemical": [{"text": "Delta (9)-THC", "start": 101, "end": 114}]}}, "schema": []}
{"input": "Collectively, these studies suggest that Delta (9)-THC potently suppresses myeloid cell immune function, in a manner involving CB (1) and/or CB (2), thereby impairing immune responses to influenza infection.", "output": {"entities": {"chemical": [{"text": "Delta (9)-THC", "start": 41, "end": 54}]}}, "schema": []}
{"input": "Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature.", "output": {"entities": {}}, "schema": []}
{"input": "Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is exacerbated by suppressed parathyroid hormone (PTH) levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and preoperative high bone turnover.", "output": {"entities": {}}, "schema": []}
{"input": "It is a relatively uncommon, but serious adverse effect of parathyroidectomy.", "output": {"entities": {}}, "schema": []}
{"input": "We conducted a literature search of all available studies reporting a' hungry bone syndrome' in patients who had a parathyroidectomy for PHPT, to identify patients at risk and address the pitfalls in their management.", "output": {"entities": {}}, "schema": []}
{"input": "The severe hypocalcaemia is believed to be due to increased influx of calcium into bone, due to the sudden removal of the effect of high circulating levels of PTH on osteoclastic resorption, leading to a decrease in the activation frequency of new remodelling sites and to a decrease in remodelling space, although there is no good documentation for this.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 70, "end": 77}]}}, "schema": []}
{"input": "Various risk factors have been suggested for the development of HBS, including older age, weight/volume of the resected parathyroid glands, radiological evidence of bone disease and vitamin D deficiency.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 182, "end": 191}]}}, "schema": []}
{"input": "The syndrome is reported in 25-90% of patients with radiological evidence of hyperparathyroid bone disease vs only 0-6% of patients without skeletal involvement.", "output": {"entities": {}}, "schema": []}
{"input": "There is insufficient data-based evidence on the best means to treat, minimise or prevent this severe complication of parathyroidectomy.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment is aimed at replenishing the severe calcium deficit by using high doses of calcium supplemented by high doses of active metabolites of vitamin D.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 46, "end": 53}, {"text": "calcium", "start": 85, "end": 92}, {"text": "vitamin D", "start": 145, "end": 154}]}}, "schema": []}
{"input": "Adequate correction of magnesium deficiency and normalisation of bone turnover are required for resolution of the hypocalcaemia which may last for a number of months after successful surgery.", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Preoperative treatment with bisphosphonates has been suggested to reduce post-operative hypocalcaemia, but there are to date no prospective studies addressing this issue.", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 28, "end": 43}]}}, "schema": []}
{"input": "Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is frequently caused by a de novo point mutation at position 1824 in LMNA.", "output": {"entities": {}}, "schema": []}
{"input": "This mutation activates a cryptic splice donor site in exon 11, and leads to an in-frame deletion within the prelamin A mRNA and the production of a dominant-negative lamin A protein, known as progerin.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that primary HGPS skin fibroblasts experience genome-wide correlated alterations in patterns of H3K27me3 deposition, DNA-lamin A/C associations, and, at late passages, genome-wide loss of spatial compartmentalization of active and inactive chromatin domains.", "output": {"entities": {}}, "schema": []}
{"input": "We further demonstrate that the H3K27me3 changes associate with gene expression alterations in HGPS cells.", "output": {"entities": {}}, "schema": []}
{"input": "Our results support a model that the accumulation of progerin in the nuclear lamina leads to altered H3K27me3 marks in heterochromatin, possibly through the down-regulation of EZH2, and disrupts heterochromatin-lamina interactions.", "output": {"entities": {}}, "schema": []}
{"input": "These changes may result in transcriptional misregulation and eventually trigger the global loss of spatial chromatin compartmentalization in late passage HGPS fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Dynorphin-still an extraordinarily potent opioid peptide.", "output": {"entities": {}}, "schema": []}
{"input": "This issue of Molecular Pharmacology is dedicated to Dr. Avram Goldstein, the journal' s founding editor and one of the leaders in the development of modern pharmacology.", "output": {"entities": {}}, "schema": []}
{"input": "This article focuses on his contributions to the discovery of the dynorphins and evidence that members of this family of opioid peptides are endogenous agonists for the kappa opioid receptor.", "output": {"entities": {}}, "schema": []}
{"input": "In his original publication describing the purification and sequencing of dynorphin A, Avram described this peptide as \" extraordinarily potent \" (\" dyn \" from the Greek, dynamis = power and \" orphin \" for endogenous morphine peptide).", "output": {"entities": {}}, "schema": []}
{"input": "The name originally referred to its high affinity and great potency in the bioassay that was used to follow its activity during purification, but the name has come to have a second meaning: studies of its physiologic function in brain continue to provide powerful insights to the molecular mechanisms controlling mood disorders and drug addiction.", "output": {"entities": {}}, "schema": []}
{"input": "During the 30 years since its discovery, we have learned that the dynorphin peptides are released in brain during stress exposure.", "output": {"entities": {}}, "schema": []}
{"input": "After they are released, they activate kappa opioid receptors distributed throughout the brain and spinal cord, where they trigger cellular responses resulting in different stress responses: analgesia, dysphoria-like behaviors, anxiety-like responses, and increased addiction behaviors in experimental animals.", "output": {"entities": {}}, "schema": []}
{"input": "Avram predicted that a detailed molecular analysis of opiate drug actions would someday lead to better treatments for drug addiction, and he would be gratified to know that subsequent studies enabled by his discovery of the dynorphins resulted in insights that hold great promise for new treatments for addiction and depressive disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Development of solid lipid nanoparticles (SLNs) of lopinavir using hot self nano-emulsification (SNE) technique.", "output": {"entities": {"chemical": [{"text": "lopinavir", "start": 51, "end": 60}]}}, "schema": []}
{"input": "Solid lipid nanoparticles (SLNs) of poor orally bioavailable drug lopinavir were prepared using hot self nano-emulsification (SNE) technique.", "output": {"entities": {"chemical": [{"text": "lopinavir", "start": 66, "end": 75}]}}, "schema": []}
{"input": "Hot isotropic mixture of stearic acid, poloxamer and polyethylene glycol was spontaneously self nano-emulsify in hot water and SLNs were formed with subsequent rapid cooling.", "output": {"entities": {"chemical": [{"text": "stearic acid", "start": 25, "end": 37}, {"text": "poloxamer", "start": 39, "end": 48}, {"text": "polyethylene glycol", "start": 53, "end": 72}]}}, "schema": []}
{"input": "Self nano-emulsification ability of stearic acid, poloxamer and polyethylene glycol mixture was assessed by ternary phase diagram study.", "output": {"entities": {"chemical": [{"text": "stearic acid", "start": 36, "end": 48}, {"text": "poloxamer", "start": 50, "end": 59}, {"text": "polyethylene glycol", "start": 64, "end": 83}]}}, "schema": []}
{"input": "Optimized SLNs were having particle size of 180. 6 +/- 2. 32 nm (PDI = 0. 133 +/- 0. 001), 91. 5 +/- 1. 3% entrapment efficiency and zeta potential of-13. 4 +/- 0. 56 mV.", "output": {"entities": {}}, "schema": []}
{"input": "SLNs were evaluated by transmission electron microscopy (TEM) and atomic force microscopy (AFM) for morphological study.", "output": {"entities": {}}, "schema": []}
{"input": "Further, Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) of SLNs were also performed for checking solid state characterization.", "output": {"entities": {}}, "schema": []}
{"input": "Higher oral bioavailability was found for lopinavir loaded SLNs in comparison to bulk lopinavir due to higher lymphatic drug transport (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "lopinavir", "start": 42, "end": 51}, {"text": "lopinavir", "start": 86, "end": 95}]}}, "schema": []}
{"input": "Results indicate that SLNs of higher fatty acids can be successfully prepared by hot SNE technique.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 37, "end": 48}]}}, "schema": []}
{"input": "Retinal drug delivery using eyedrop preparations of poly-L-lysine-modified liposomes.", "output": {"entities": {"chemical": [{"text": "poly-L-lysine", "start": 52, "end": 65}]}}, "schema": []}
{"input": "The purpose of this study was to develop surface-modified liposomes that enhance the efficiency of eye drop drug delivery to the retina.", "output": {"entities": {}}, "schema": []}
{"input": "Various molecular weights and concentrations of the water-soluble cationic polymer poly-L-lysine (PLL) were used to modify the surface of submicronized (100 nm) liposomes.", "output": {"entities": {"chemical": [{"text": "poly-L-lysine", "start": 83, "end": 96}, {"text": "PLL", "start": 98, "end": 101}]}}, "schema": []}
{"input": "Physicochemical properties of surface-modified liposomes were determined in vitro, and the efficiency of drug delivery to the retina was investigated in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Using coumarin-6 as a model drug and fluorescent marker, we show that liposome surface modification by PLL dramatically increased delivery to mouse retina segments after eye drop administration.", "output": {"entities": {"chemical": [{"text": "coumarin-6", "start": 6, "end": 16}, {"text": "PLL", "start": 103, "end": 106}]}}, "schema": []}
{"input": "However, when PLL of high molecular weight (> 30, 000) was used at higher concentrations (> 0. 05%), aggregation of surface-modified liposomes increased particle size and hampered distribution to inner ocular tissues.", "output": {"entities": {"chemical": [{"text": "PLL", "start": 14, "end": 17}]}}, "schema": []}
{"input": "As a result, the efficiency of drug delivery of these aggregated surface-modified liposomes was the same as unmodified liposomes.", "output": {"entities": {}}, "schema": []}
{"input": "The optimal molecular weight and concentration of PLL in drug-delivering liposomes were 15, 000-30, 000 and 0. 005%, respectively.", "output": {"entities": {"chemical": [{"text": "PLL", "start": 50, "end": 53}]}}, "schema": []}
{"input": "Under these conditions, PLL-modified liposomes were not cytotoxic in corneal or conjunctival cells.", "output": {"entities": {"chemical": [{"text": "PLL", "start": 24, "end": 27}]}}, "schema": []}
{"input": "In conclusion, surface-modified liposomes have great potential as effective retinal drug delivery carriers in eye drop formulations.", "output": {"entities": {}}, "schema": []}
{"input": "Amino acid derivatives as transdermal permeation enhancers.", "output": {"entities": {"chemical": [{"text": "Amino acid", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Transdermal permeation enhancers are compounds that temporarily decrease skin barrier properties to promote drug flux.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated enhancers with amino acids (proline, sarcosine, alanine, beta-alanine, and glycine) attached to hydrophobic chain (s) via a biodegradable ester link.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 46, "end": 57}, {"text": "proline", "start": 59, "end": 66}, {"text": "sarcosine", "start": 68, "end": 77}, {"text": "alanine", "start": 79, "end": 86}, {"text": "beta-alanine", "start": 88, "end": 100}, {"text": "glycine", "start": 106, "end": 113}, {"text": "ester", "start": 169, "end": 174}]}}, "schema": []}
{"input": "The double-chain lipid-like substances displayed no enhancing effect, whereas single-chain substances significantly increased skin permeability.", "output": {"entities": {}}, "schema": []}
{"input": "The proline derivative l-Pro2 reached enhancement ratios of up to 40 at 1% concentration, which is higher than that of the well-established and standard enhancers Azone, DDAIP, DDAK, and Transkarbam 12.", "output": {"entities": {"chemical": [{"text": "proline", "start": 4, "end": 11}, {"text": "l-Pro2", "start": 23, "end": 29}, {"text": "Azone", "start": 163, "end": 168}, {"text": "DDAIP", "start": 170, "end": 175}, {"text": "DDAK", "start": 177, "end": 181}, {"text": "Transkarbam 12", "start": 187, "end": 201}]}}, "schema": []}
{"input": "No stereoselectivity was observed.", "output": {"entities": {}}, "schema": []}
{"input": "l-Pro2 acted synergistically with propylene glycol.", "output": {"entities": {"chemical": [{"text": "l-Pro2", "start": 0, "end": 6}, {"text": "propylene glycol", "start": 34, "end": 50}]}}, "schema": []}
{"input": "Infrared studies revealed that l-Pro2 forms a separate liquid ordered phase in the stratum corneum lipids and has no significant effect on proteins.", "output": {"entities": {"chemical": [{"text": "l-Pro2", "start": 31, "end": 37}]}}, "schema": []}
{"input": "l-Pro2 action was at least partially reversible as measured by skin electrical impedance.", "output": {"entities": {"chemical": [{"text": "l-Pro2", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Toxicity in keratinocyte (HaCaT) and fibroblast (3T3) cell lines showed IC (50) values ranging from tens to hundreds of mu M, which is comparable with standard enhancers.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, l-Pro2 was rapidly decomposed in plasma.", "output": {"entities": {"chemical": [{"text": "l-Pro2", "start": 13, "end": 19}]}}, "schema": []}
{"input": "In vivo transdermal absorption studies in rats confirmed the enhancing activity of l-Pro2 and suggested its negligible skin toxicity and minimal effect on transepidermal water loss.", "output": {"entities": {"chemical": [{"text": "l-Pro2", "start": 83, "end": 89}]}}, "schema": []}
{"input": "These properties make l-Pro2 a promising candidate for potential clinical use.", "output": {"entities": {"chemical": [{"text": "l-Pro2", "start": 22, "end": 28}]}}, "schema": []}
{"input": "The onset of antineutrophil cytoplasmic antibody-associated vasculitis immediately after methimazole was switched to propylthiouracil in a woman with Graves' disease who wished to become pregnant.", "output": {"entities": {"chemical": [{"text": "methimazole", "start": 89, "end": 100}, {"text": "propylthiouracil", "start": 117, "end": 133}]}}, "schema": []}
{"input": "Propylthiouracil (PTU) is recommended as a first-line antithyroid drug (ATD) during first trimester organogenesis in pregnancy because recent evidence suggests that methimazole (MMI) may be associated with congenital anomalies.", "output": {"entities": {"chemical": [{"text": "Propylthiouracil", "start": 0, "end": 16}, {"text": "PTU", "start": 18, "end": 21}, {"text": "methimazole", "start": 165, "end": 176}, {"text": "MMI", "start": 178, "end": 181}]}}, "schema": []}
{"input": "However, PTU more commonly causes myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which usually occurs during prolonged treatment, compared with MMI.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 9, "end": 12}, {"text": "MMI", "start": 185, "end": 188}]}}, "schema": []}
{"input": "We report a case of MPO-ANCA-associated vasculitis in a 35-year-old woman with Graves' disease.", "output": {"entities": {}}, "schema": []}
{"input": "Although her thyroid function could be maintained euthyroid by MMI, her ATD was switched to PTU because she wished to become pregnant.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 92, "end": 95}]}}, "schema": []}
{"input": "The patient presented with flu-like symptoms 8 days after starting PTU and developed hemoptysis and dyspnea at 22 days.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 67, "end": 70}]}}, "schema": []}
{"input": "Her MPO-ANCA titer was 21 ELISA units (EUs) before PTU treatment but increased to 259 EUs at 22 days after PTU treatment.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 51, "end": 54}, {"text": "PTU", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Her clinical condition improved with the discontinuation of PTU and with immunosuppressive therapy.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 60, "end": 63}]}}, "schema": []}
{"input": "This case indicated that MPO-ANCA vasculitis occurred within several weeks after the initiation of PTU and that this side effect could be caused by the change from MMI to PTU.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 99, "end": 102}, {"text": "MMI", "start": 164, "end": 167}, {"text": "PTU", "start": 171, "end": 174}]}}, "schema": []}
{"input": "Thus, our clinical observation suggests that patients treated with PTU should be carefully monitored for MPO-ANCA titers and variable manifestations of MPO-ANCA-associated vasculitis regardless of the period of administration.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 67, "end": 70}]}}, "schema": []}
{"input": "RNApathwaysDB--a database of RNA maturation and decay pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Many RNA molecules undergo complex maturation, involving e. g. excision from primary transcripts, removal of introns, post-transcriptional modification and polyadenylation.", "output": {"entities": {}}, "schema": []}
{"input": "The level of mature, functional RNAs in the cell is controlled not only by the synthesis and maturation but also by degradation, which proceeds via many different routes.", "output": {"entities": {}}, "schema": []}
{"input": "The systematization of data about RNA metabolic pathways and enzymes taking part in RNA maturation and degradation is essential for the full understanding of these processes.", "output": {"entities": {}}, "schema": []}
{"input": "RNApathwaysDB, available online at http://iimcb. genesilico. pl/rnapathwaysdb, is an online resource about maturation and decay pathways involving RNA as the substrate.", "output": {"entities": {}}, "schema": []}
{"input": "The current release presents information about reactions and enzymes that take part in the maturation and degradation of tRNA, rRNA and mRNA, and describes pathways in three model organisms: Escherichia coli, Saccharomyces cerevisiae and Homo sapiens.", "output": {"entities": {}}, "schema": []}
{"input": "RNApathwaysDB can be queried with keywords, and sequences of protein enzymes involved in RNA processing can be searched with BLAST.", "output": {"entities": {}}, "schema": []}
{"input": "Options for data presentation include pathway graphs and tables with enzymes and literature data.", "output": {"entities": {}}, "schema": []}
{"input": "Structures of macromolecular complexes involving RNA and proteins that act on it are presented as' potato models' using DrawBioPath-a new javascript tool.", "output": {"entities": {}}, "schema": []}
{"input": "Protein-polyanion interactions for the controlled release of monoclonal antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of the present study was to investigate ionic interactions between alginate and a monoclonal antibody (mAb1) and to utilize those interactions for the sustained release of mAb1.", "output": {"entities": {}}, "schema": []}
{"input": "The existence of ionic interactions between alginate and mAb1 was strongly reflected by their rheological behavior.", "output": {"entities": {}}, "schema": []}
{"input": "A 3-4 times increase in storage modulus (G') was observed by addition of 30 mg/mL mAb1 to a 20 mg/mL alginate solution.", "output": {"entities": {}}, "schema": []}
{"input": "This increase was strongly dependent on pH and ionic strength.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro release studies revealed a marked pH-dependence of release rates and the reversibility of alginate-mAb1 complexation under physiological conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Two alginate-mAb1 sustained release formulations were developed by an internal gelation technique using CaCO (3) and CaHPO (4) as calcium sources for physical cross-linking.", "output": {"entities": {"chemical": [{"text": "CaCO (3)", "start": 104, "end": 112}, {"text": "CaHPO (4)", "start": 117, "end": 126}, {"text": "calcium", "start": 130, "end": 137}]}}, "schema": []}
{"input": "The CaCO (3) formulation provided a stable pH-environment, optimally suited for pH-sensitive proteins.", "output": {"entities": {"chemical": [{"text": "CaCO (3)", "start": 4, "end": 12}]}}, "schema": []}
{"input": "CaHPO (4) led to a lower pH and stronger alginate-mAb1 interactions.", "output": {"entities": {"chemical": [{"text": "CaHPO (4)", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The CaHPO (4) cross-linked alginate released mAb1 over a period of 10-15 days.", "output": {"entities": {"chemical": [{"text": "CaHPO (4)", "start": 4, "end": 13}]}}, "schema": []}
{"input": "The long release period and changes in viscoelastic properties of alginate, when being mixed with mAb1, indicate the incorporation of mAb1 molecules into a mixed network with alginate.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study demonstrate that ionic interactions between polyanions and mAb1 are present and that they can be exploited for sustained release delivery of mAb1.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of antipsychotics on the BDNF in schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "Brain-derived neurotropic factor (BDNF) is involved in the development of the brain, and likely influences the neuroplasticity in schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "BDNF is also believed to interact with other neurotransmitter systems implicated in schizophrenia, such as dopamine, glutamate, serotonin and GABA.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 107, "end": 115}, {"text": "glutamate", "start": 117, "end": 126}, {"text": "serotonin", "start": 128, "end": 137}, {"text": "GABA", "start": 142, "end": 146}]}}, "schema": []}
{"input": "Therefore, BDNF is a candidate gene for schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "In past decades, the blood (serum or plasma) BDNF protein levels and BDNF gene alleles and genotypes to the clinical features of schizophrenia, such as age of onset, clinical subtypes, symptom severity, and drug response, have been evaluated among different populations.", "output": {"entities": {}}, "schema": []}
{"input": "However, the results are still inconsistent.", "output": {"entities": {}}, "schema": []}
{"input": "Further, different drugs have been reported to have different effects on BDNF protein levels.", "output": {"entities": {}}, "schema": []}
{"input": "A cross-sectional survey revealed that serum BDNF levels in chronic schizophrenic patients treated with clozapine exceeded those of patients treated with risperidone or with typical antipsychotics.", "output": {"entities": {"chemical": [{"text": "clozapine", "start": 104, "end": 113}, {"text": "risperidone", "start": 154, "end": 165}]}}, "schema": []}
{"input": "In recent times, BDNF epigenetic studies have also been conducted in clinical studies of schizophrenia to address the question of why patients with the same gene genotype and alleles have different clinical presentations.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the effects of different antipsychotic drugs on gene methylation and protein acetylation have also been reported.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, more data are needed regarding BDNF in the brain and in peripheral blood, including protein levels, single nucleotide polymorphisms, epigenetic regulation, and clinical data in order to understand the role of BDNF in schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "Facilitative effect of serotonin (1A) receptor agonists on cognition in patients with schizophrenia.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Disturbances of cognitive function are considered to largely affect the outcome in patients with schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "There is much attention to the role of psychotropic compounds acting on serotonin (5-HT) receptors in ameliorating cognitive deficits of the disease.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 72, "end": 81}, {"text": "5-HT", "start": 83, "end": 87}]}}, "schema": []}
{"input": "Among the 5-HT receptor subtypes, the 5-HT (1A) receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 10, "end": 14}, {"text": "5-HT", "start": 38, "end": 42}]}}, "schema": []}
{"input": "The neural network underlying the ability of 5-HT (1A) agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and gamma-aminobutyric acid neurons.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 45, "end": 49}, {"text": "dopamine", "start": 128, "end": 136}, {"text": "glutamate", "start": 138, "end": 147}, {"text": "gamma-aminobutyric acid", "start": 153, "end": 176}]}}, "schema": []}
{"input": "Recent advances of electrophysiological measures, such as event-related potentials, have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs or related compounds acting directly or indirectly on 5-HT (1A) receptors.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 237, "end": 241}]}}, "schema": []}
{"input": "These considerations are expected to promote the development of novel therapeutics for the betterment of functional outcome in people suffering from schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "Neurobiological basis of dyskinetic effects induced by antipsychotics: the contribution of animal models.", "output": {"entities": {}}, "schema": []}
{"input": "Tardive dyskinesia (TD) is a movement disorder characterized by abnormal involuntary facial movements induced by chronic therapy with classical antipsychotic medications.", "output": {"entities": {}}, "schema": []}
{"input": "Currently, there is no satisfactory pharmacotherapy for TD, which represents a major limitation to therapy with classical antipsychotics.", "output": {"entities": {}}, "schema": []}
{"input": "In order to develop or optimize therapies for TD, and to develop new APDs with lower indices of motor side effects, the pathology underlying TD must first be understood.", "output": {"entities": {}}, "schema": []}
{"input": "The use of animal models has been used to further this objective.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review different preparations that have been used to model TD and discuss the contribution of neuroimaging studies conducted in these models.", "output": {"entities": {}}, "schema": []}
{"input": "Studies in animal models have lead to several hypotheses of TD pathology, although none has yet emerged as the ultimate underlying cause of this syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "We discuss alterations in functional indices, neuron and synapse morphology and changes in specific neurotransmitter systems that have been described in animal models of TD, and outline how these findings have contributed to our understanding of antipsychotic-induced dyskinesias.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that several non-mutually exclusive theories of TD are supported by animal studies, including increases in oxidative stress leading to structural and functional changes in specific neurotransmitter systems.", "output": {"entities": {}}, "schema": []}
{"input": "Elucidating the mechanisms underlying TD neuropathology partly through the use of animal models will lead to the development of APDs with superior side effect profiles or more effective therapies for TD.", "output": {"entities": {}}, "schema": []}
{"input": "Abnormal striatal dopamine transmission in schizophrenia.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 18, "end": 26}]}}, "schema": []}
{"input": "Despite numerous revisions and reformulations, dopamine (DA) hypothesis of schizophrenia remains a pivotal neurochemical hypothesis of this illness.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 47, "end": 55}]}}, "schema": []}
{"input": "The aim of this review is to expose and discuss findings from positron emission tomography (PET) or single-photon-emission computed tomography (SPECT) studies investigating DA function in the striatum of medicated, drug-naive or drug-free patients with schizophrenia and in individuals at risk compared with healthy volunteers.", "output": {"entities": {}}, "schema": []}
{"input": "DA function was studied at several levels: i) at a presynaptic level where neuroimaging studies investigating DOPA uptake capacity clearly show an increase of DA synthesis in patients with schizophrenia; ii) at a synaptic level where neuroimaging studies investigating dopamine transporter availability (DAT) does not bring any evidence of dysfunction; iii) and finally, neuroimaging studies investigating DA receptor density show a mild increase of D2 receptor density in basic condition and, an hyperreactivity of DA system in dynamic condition.", "output": {"entities": {"chemical": [{"text": "DOPA", "start": 110, "end": 114}, {"text": "dopamine", "start": 269, "end": 277}]}}, "schema": []}
{"input": "These results are discussed regarding laterality, sub-regions of striatum and implications for the at-risk population.", "output": {"entities": {}}, "schema": []}
{"input": "Striatal DA abnormalities are now clearly demonstrated in patients with schizophrenia and at risk population and could constitute an endophenotype of schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "Subtle sub-clinical striatal DA abnormalities in at risk population could be a biomarker of transition from a vulnerability state to the expression of frank psychosis.", "output": {"entities": {}}, "schema": []}
{"input": "Proton magnetic resonance spectroscopy changes after antipsychotic treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Proton magnetic resonance spectroscopy ((1) H MRS) enables the observation of brain function in vivo.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 40, "end": 45}]}}, "schema": []}
{"input": "Several brain metabolites can be measured by the means of (1) H MRS: N-acetylaspartate (NAA), choline containing compounds (Cho), myo-inositol (mI) and glutamate (Glu), glutamine (Gln) and GABA (together as Glx complex or separately).", "output": {"entities": {"chemical": [{"text": "N-acetylaspartate", "start": 69, "end": 86}, {"text": "NAA", "start": 88, "end": 91}, {"text": "choline", "start": 94, "end": 101}, {"text": "myo-inositol", "start": 130, "end": 142}, {"text": "glutamate", "start": 152, "end": 161}, {"text": "Glu", "start": 163, "end": 166}, {"text": "glutamine", "start": 169, "end": 178}, {"text": "Gln", "start": 180, "end": 183}, {"text": "GABA", "start": 189, "end": 193}]}}, "schema": []}
{"input": "(1) H MRS measures have been found to be abnormal in psychotic disorders such as schizophrenia.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Here we specifically review the influence exerted by antipsychotic drugs on brain metabolism, as detected by (1) H MRS.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 109, "end": 114}]}}, "schema": []}
{"input": "We systematically reviewed the available literature and uncovered 27 studies, 16 before-after treatment and 11 cross-sectional.", "output": {"entities": {}}, "schema": []}
{"input": "Most of them addressed the effects of antipsychotics in schizophrenia and mainly focusing on NAA alterations.", "output": {"entities": {"chemical": [{"text": "NAA", "start": 93, "end": 96}]}}, "schema": []}
{"input": "Follow up studies indicated antipsychotic drugs may act by increasing NAA levels in selected brain areas (the frontal lobe and thalamus), especially during the short-time observation.", "output": {"entities": {"chemical": [{"text": "NAA", "start": 70, "end": 73}]}}, "schema": []}
{"input": "This phenomenon seems to vanish after longer observation.", "output": {"entities": {}}, "schema": []}
{"input": "Other studies indicated that glutamate measures are decreasing along with the duration of the disease, suggesting both a neurodegenerative process present in schizophrenic brain as well as an influence of antipsychotics.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 29, "end": 38}]}}, "schema": []}
{"input": "The above results were reviewed according to the most recent theories in the field accounting for the impact of antipsychotics (1) HMRS measures.", "output": {"entities": {"chemical": [{"text": "(1) HMRS", "start": 127, "end": 135}]}}, "schema": []}
{"input": "The next frontier in composite tissue allotransplantation.", "output": {"entities": {}}, "schema": []}
{"input": "Solid organ transplantations became a clinical option in the 1950s.", "output": {"entities": {}}, "schema": []}
{"input": "The hand allograft was the pioneer of composite tissue allotransplantation (CTA), successfully started near the end of the last century despite arguments over the practicality and methods.", "output": {"entities": {}}, "schema": []}
{"input": "Since then, CTA such as hand and face has continued to progress from the theoretical to clinical reality.", "output": {"entities": {}}, "schema": []}
{"input": "The treatment principles, drug combinations, and mechanisms of the immunosuppression medications on which contemporary transplant surgeries have been based continue to develop as researchers and physicians gain more experience in the CTA field.", "output": {"entities": {}}, "schema": []}
{"input": "It could be argued that the ethical issues associated with CTA have prevented evolution of the field rather than surgical or technical skill.", "output": {"entities": {}}, "schema": []}
{"input": "This is particularly true for allo-head and body reconstruction (AHBR).", "output": {"entities": {}}, "schema": []}
{"input": "How can leaders in the field of CTA develop a model that would satisfy ethical concerns?", "output": {"entities": {}}, "schema": []}
{"input": "Bolstered by recent successes in the field, is it time to traverse the next frontier?", "output": {"entities": {}}, "schema": []}
{"input": "Can AHBR ever be a feasible option in the clinical setting?", "output": {"entities": {}}, "schema": []}
{"input": "The reader will be provided with a brief history of CTA from theory to research to clinical practice.", "output": {"entities": {}}, "schema": []}
{"input": "A concise description of AHBR as it pertains to the critical procedure (i. e., surgery design) will also be discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Behavioural and EEG effects of chronic rapamycin treatment in a mouse model of Tuberous Sclerosis Complex.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 39, "end": 48}]}}, "schema": []}
{"input": "Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity.", "output": {"entities": {}}, "schema": []}
{"input": "TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric symptoms, such as epilepsy, intellectual disability, autism, anxiety and depressive behaviour.", "output": {"entities": {}}, "schema": []}
{"input": "Rapamycin is a potent inhibitor of mTOR and its efficacy in treating epilepsy and neurological symptoms remains elusive.", "output": {"entities": {"chemical": [{"text": "Rapamycin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In a mouse model in which Tsc1 has been deleted in embryonic telencephalic neural stem cells, we analyzed anxiety-and depression-like behaviour by elevated-plus maze (EPM), open-field test (OFT), forced-swim test (FST) and tail-suspension test (TST), after chronic administration of rapamycin.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 283, "end": 292}]}}, "schema": []}
{"input": "In addition, spectral analysis of background EEG was performed.", "output": {"entities": {}}, "schema": []}
{"input": "Rapamycin-treated mutant mice displayed a reduction in anxiety-and depression-like phenotype, as shown by the EPM/OFT and FST, respectively.", "output": {"entities": {"chemical": [{"text": "Rapamycin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "These results were inline with EEG power spectra outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "The same effects of rapamycin were observed in wild-type mice.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 20, "end": 29}]}}, "schema": []}
{"input": "Notably, in heterozygous animals we did not observe any EEG and/or behavioural variation after rapamycin treatment.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 95, "end": 104}]}}, "schema": []}
{"input": "Together these results suggest that both TSC1 deletion and chronic rapamycin treatment might have a role in modulating behaviour and brain activity, and point out to the potential usefulness of background EEG analysis in tracking brain dysfunction in parallel with behavioural testing.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 67, "end": 76}]}}, "schema": []}
{"input": "Novel antitussive strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Acute and chronic cough represent one of the most common symptoms of medical importance but effective pharmacotherapy is, to all intents and purposes, absent.", "output": {"entities": {}}, "schema": []}
{"input": "Numerous initiatives targeting the recently discovered tussive pathways are in progress.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review the current antitussive armamentarium and provide an update on the novel strategies and compounds in development.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical risk factors, bone density and fall history in the prediction of incident fracture among men and women.", "output": {"entities": {}}, "schema": []}
{"input": "The FRAX (tr) algorithm uses clinical risk factors (CRF) and bone mineral density (BMD) to predict fracture risk but does not include falls history in the calculation.", "output": {"entities": {}}, "schema": []}
{"input": "Using results from the Hertfordshire Cohort Study, we examined the relative contributions of CRFs, BMD and falls history to fracture prediction.", "output": {"entities": {}}, "schema": []}
{"input": "We studied 2299 participants at a baseline clinic that included completion of a health questionnaire and anthropometric data.", "output": {"entities": {}}, "schema": []}
{"input": "A mean of 5. 5years later (range 2. 9-8. 8years) subjects completed a postal questionnaire detailing fall and fracture history.", "output": {"entities": {}}, "schema": []}
{"input": "In a subset of 368 men and 407 women, bone densitometry was performed using a Hologic QDR 4500 instrument.", "output": {"entities": {}}, "schema": []}
{"input": "There was a significantly increased risk of fracture in men and women with a previous fracture.", "output": {"entities": {}}, "schema": []}
{"input": "A one standard deviation drop in femoral neck BMD was associated with a hazards ratio (HR) of incident fracture (adjusted for CRFs) of 1. 92 (1. 04-3. 54) and 1. 77 (1. 16-2. 71) in men and women respectively.", "output": {"entities": {}}, "schema": []}
{"input": "A history of any fall since the age of 45years resulted in an unadjusted HR of fracture of 7. 31 (3. 78-14. 14) and 8. 56 (4. 85-15. 13) in men and women respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In a ROC curve analysis, the predictive capacity progressively increased as BMD and previous falls were added into an initial model using CRFs alone.", "output": {"entities": {}}, "schema": []}
{"input": "Falls history is a further independent risk factor for fracture.", "output": {"entities": {}}, "schema": []}
{"input": "Falls risk should be taken into consideration when assessing whether or not to commence medication for osteoporosis and should also alert the physician to the opportunity to target falls risk directly.", "output": {"entities": {}}, "schema": []}
{"input": "Season linked responses to fine and quasi-ultrafine Milan PM in cultured cells.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to urbane airborne particulate matter (PM) is related to the onset and exacerbation of cardiovascular and respiratory diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The fine (PM1), and quasi-ultrafine (PM0. 4) Milan particles collected during different seasons have been characterised and the biological effects on human epithelial lung A549, monocytes THP-1 cells and their co-culture, evaluated and compared with the results obtained on the PM10 and PM2. 5 fractions.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical composition and transmission electron microscopy (TEM) analysis of PM0. 4 showed that this fraction was very similar to PM1 for biological responses and dimension.", "output": {"entities": {}}, "schema": []}
{"input": "All the winter fractions increased within 1h the level of reactive oxygen species (ROS), while only summer PM2. 5 had this effect on A549 cells.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 67, "end": 73}]}}, "schema": []}
{"input": "The phosphorylation of H2AX (gamma H2AX), a marker of double strand DNA breaks (DSBs), was increased by all the winter fractions on A549 and THP-1 cells while summer PM samples did not induced this effect.", "output": {"entities": {}}, "schema": []}
{"input": "PM0. 4 and PM1 biological effects are partly similar and related to the season of sampling, with effects on ROS and DNA damage induced only by winter PM fractions.", "output": {"entities": {}}, "schema": []}
{"input": "The winter PM damaging effect on DNA correlates with the presence of organic compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of molecular weight on permeability and microstructure of mixed ethyl-hydroxypropyl-cellulose films.", "output": {"entities": {"chemical": [{"text": "ethyl-hydroxypropyl", "start": 72, "end": 91}]}}, "schema": []}
{"input": "Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations.", "output": {"entities": {"chemical": [{"text": "ethyl", "start": 9, "end": 14}, {"text": "hydroxypropyl", "start": 48, "end": 61}]}}, "schema": []}
{"input": "The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight.", "output": {"entities": {}}, "schema": []}
{"input": "Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that sprayed films were porous throughout the bulk of the films after water immersion.", "output": {"entities": {}}, "schema": []}
{"input": "The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability.", "output": {"entities": {}}, "schema": []}
{"input": "A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species.", "output": {"entities": {}}, "schema": []}
{"input": "The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films.", "output": {"entities": {}}, "schema": []}
{"input": "TGF-beta as a therapeutic target in high grade gliomas-promises and challenges.", "output": {"entities": {}}, "schema": []}
{"input": "Transforming growth factor-beta (TGF-beta) is a cytokine with a key role in tissue homeostasis and cancer.", "output": {"entities": {}}, "schema": []}
{"input": "TGF-beta elicits both tumor suppressive and tumor promoting functions during cancer progression, in a wide range of cancers.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review the tumor promoting function of TGF-beta and its possible promise as a therapeutic target in high grade gliomas, including glioblastoma multiforme (GBM), a disease with very poor prognosis.", "output": {"entities": {}}, "schema": []}
{"input": "TGF-beta signaling is highly active in high grade gliomas and elevated TGF-beta activity has been associated with poor clinical outcome in this deadly disease.", "output": {"entities": {}}, "schema": []}
{"input": "Common features of GBMs include fast cell proliferation, invasion into normal brain parenchyma, hypoxia, high angiogenic-and immunosuppressive activity, characteristics that all have been linked to activation of the TGF-beta pathway.", "output": {"entities": {}}, "schema": []}
{"input": "TGF-beta signaling has also been connected with the cancer stem cell (CSC) phenotype in GBM.", "output": {"entities": {}}, "schema": []}
{"input": "CSCs represent a subset of GBM cells thought to be responsible for tumor initiation, progression and relapse of disease.", "output": {"entities": {}}, "schema": []}
{"input": "Following the description of these different properties of TGF-beta signaling and the underlying mechanisms identified thus far, the promise of TGF-beta targeted therapy in malignant gliomas is discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Several drugs targeting TGF-beta signaling have been developed that showed potent antitumor activity in preclinical models.", "output": {"entities": {}}, "schema": []}
{"input": "A number of agents are currently evaluated in early clinical studies in glioma patients.", "output": {"entities": {}}, "schema": []}
{"input": "Available results of these studies are highlighted and a perspective on the promise of TGF-beta-targeted therapy is given.", "output": {"entities": {}}, "schema": []}
{"input": "Gene expression analysis by ESTs sequencing of the Brazilian frog Phyllomedusa nordestina skin glands.", "output": {"entities": {}}, "schema": []}
{"input": "The subfamily Phyllomedusinae has attracted a great interest of many researchers mainly due to the high diversity of these frog species and plethora of pharmacological activities frequently observed for their skin secretions.", "output": {"entities": {}}, "schema": []}
{"input": "Despite of this fact, mainly for new species, limited information is available regarding the molecular composition of these skin secretions and the cellular components involved in their production.", "output": {"entities": {}}, "schema": []}
{"input": "Phyllomedusa nordestina is a recently described Brazilian frog species also popularly known as' tree-frogs'.", "output": {"entities": {}}, "schema": []}
{"input": "Aiming at contributing to the biological knowledge of this species, we show here the gene expression profile of this frog skin secretion using a global ESTs analysis of a cDNA library.", "output": {"entities": {}}, "schema": []}
{"input": "The marked aspect of this analysis revealed a significant higher transcriptional level of the opioid peptide dermorphins in P. nordestina skin secretion than in Phyllomedusa hypochondrialis, which is its closest related species, belonging both to the same phylogenetic group.", "output": {"entities": {}}, "schema": []}
{"input": "Precursors of bioactive peptides as dermaseptins, phylloseptins, tryptophyllins, and bradykinin-like peptideswere also found in this library.", "output": {"entities": {"chemical": [{"text": "bradykinin", "start": 85, "end": 95}]}}, "schema": []}
{"input": "Transcripts encoding proteins related to ordinary cellular functions and pathways were also described.", "output": {"entities": {}}, "schema": []}
{"input": "Some of them are chiefly involved in the production of the skin secretion.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, the data reported here constitute a contribution to the characterization of the molecular diversity of gene-encoded polypeptides with potential possibility of pharmacological exploitation.", "output": {"entities": {}}, "schema": []}
{"input": "The transcriptional composition of the skin secretion may also help to give the necessary support for the definition of P. nordestina as a new species, which actually relies basically on frog morphological characteristics and geographical distribution.", "output": {"entities": {}}, "schema": []}
{"input": "Aldehyde dehydrogenases: from eye crystallins to metabolic disease and cancer stem cells.", "output": {"entities": {"chemical": [{"text": "Aldehyde", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The aldehyde dehydrogenase (ALDH) superfamily is composed of nicotinamide adenine dinucleotide (phosphate) (NAD (P) (+))-dependent enzymes that catalyze the oxidation of aldehydes to their corresponding carboxylic acids.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 4, "end": 12}, {"text": "nicotinamide adenine dinucleotide (phosphate)", "start": 61, "end": 106}, {"text": "NAD (P) (+)", "start": 108, "end": 119}, {"text": "aldehydes", "start": 170, "end": 179}, {"text": "carboxylic acids", "start": 203, "end": 219}]}}, "schema": []}
{"input": "To date, 24 ALDH gene families have been identified in the eukaryotic genome.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to aldehyde metabolizing capacity, ALDHs have additional catalytic (e. g. esterase and reductase) and non-catalytic activities.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 15, "end": 23}]}}, "schema": []}
{"input": "The latter include functioning as structural elements in the eye (crystallins) and as binding molecules to endobiotics and xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations in human ALDH genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 62, "end": 70}]}}, "schema": []}
{"input": "Most recently ALDH polymorphisms have been associated with gout and osteoporosis.", "output": {"entities": {}}, "schema": []}
{"input": "Aldehyde dehydrogenase enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer.", "output": {"entities": {"chemical": [{"text": "Aldehyde", "start": 0, "end": 8}]}}, "schema": []}
{"input": "This article serves as a comprehensive review of the current state of knowledge regarding the ALDH superfamily and the contribution of ALDHs to various physiological and pathophysiological processes.", "output": {"entities": {}}, "schema": []}
{"input": "Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated protection against maneb-and paraquat-induced hepatotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "N-acetyl cysteine", "start": 40, "end": 57}, {"text": "paraquat", "start": 110, "end": 118}]}}, "schema": []}
{"input": "Oxidative stress is one of the major players in the pathogenesis of maneb (MB) and paraquat (PQ)-induced disorders.", "output": {"entities": {"chemical": [{"text": "paraquat", "start": 83, "end": 91}]}}, "schema": []}
{"input": "N-acetyl cysteine (NAC), a glutathione (GSH) precursor and silymarin (SIL), a naturally occurring antioxidant, encounter oxidative stress-mediated cellular damage.", "output": {"entities": {"chemical": [{"text": "N-acetyl cysteine", "start": 0, "end": 17}, {"text": "NAC", "start": 19, "end": 22}, {"text": "glutathione", "start": 27, "end": 38}, {"text": "GSH", "start": 40, "end": 43}]}}, "schema": []}
{"input": "The present study was aimed to investigate the effects of NAC and SIL against MB and/or PQ-induced hepatotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 58, "end": 61}]}}, "schema": []}
{"input": "The levels of hepatotoxicity markers-alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and total bilirubin, histological changes, oxidative stress indices, phase I and phase II xenobiotic metabolizing enzymes-cytochrome P450 (CYP) and glutathione S-transferase (GST) and pro-inflammatory molecules-inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) were measured in animals treated with MB and/or PQ in the presence or absence of NAC and SIL.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 37, "end": 44}, {"text": "aspartate", "start": 70, "end": 79}, {"text": "bilirubin", "start": 114, "end": 123}, {"text": "glutathione S", "start": 252, "end": 265}, {"text": "nitric oxide", "start": 325, "end": 337}, {"text": "NAC", "start": 511, "end": 514}]}}, "schema": []}
{"input": "MB and/or PQ augmented ALT, AST, total bilirubin, lipid peroxidation and nitrite contents and catalytic activities of superoxide dismutase and glutathione peroxidase however, the GSH content was attenuated.", "output": {"entities": {"chemical": [{"text": "bilirubin", "start": 39, "end": 48}, {"text": "nitrite", "start": 73, "end": 80}, {"text": "superoxide", "start": 118, "end": 128}, {"text": "glutathione", "start": 143, "end": 154}, {"text": "GSH", "start": 179, "end": 182}]}}, "schema": []}
{"input": "NAC and SIL restored the above-mentioned alterations towards basal levels but the restorations were more pronounced in SIL treated groups.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Similarly, MB and/or PQ-mediated histopathological symptoms and changes in the catalytic activities/expressions of CYP1A2, CYP2E1, iNOS, TNF-alpha, and IL-1 beta were alleviated by NAC and SIL.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 181, "end": 184}]}}, "schema": []}
{"input": "Conversely, MB and/or PQ-induced GSTA4-4 expression/activity was further increased by NAC/SIL and glutathione reductase activity was also increased.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 86, "end": 89}, {"text": "glutathione", "start": 98, "end": 109}]}}, "schema": []}
{"input": "The results obtained thus suggest that NAC and SIL protect MB and/or PQ-induced hepatotoxicity by reducing oxidative stress, inflammation and by modulating xenobitic metabolizing machinery and SIL seems to be more effective.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 39, "end": 42}]}}, "schema": []}
{"input": "Renal biomarker changes associated with hyaline droplet nephropathy in rats are time and potentially compound dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Alpha 2u-globulin mediated hyaline droplet nephropathy (HDN) is a male rat specific lesion induced when a compound or metabolite binds to alpha 2u-globulin.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to investigate if the newer and more sensitive renal biomarkers would be altered with HDN as well as be able to distinguish between HDN and oxidative stress-induced kidney injury.", "output": {"entities": {}}, "schema": []}
{"input": "Rats were dosed orally for 7 days to determine (1) if HDN (induced by 2-propanol or D-limonene) altered the newer renal biomarkers and not BUN or creatinine, (2) if renal biomarkers could distinguish between HDN and oxidative stress-induced kidney injury (induced by potassium bromate), (3) sensitivity of HDN-induced renal biomarker changes relative to D-limonene dose, and (4) reversibility of HDN and renal biomarkers, using vehicle or 300 mg/kg/day D-limonene with 7 days of dosing and necropsies scheduled over the period of Days 8-85.", "output": {"entities": {"chemical": [{"text": "2-propanol", "start": 70, "end": 80}, {"text": "D-limonene", "start": 84, "end": 94}, {"text": "creatinine", "start": 146, "end": 156}, {"text": "potassium bromate", "start": 267, "end": 284}, {"text": "D-limonene", "start": 354, "end": 364}, {"text": "D-limonene", "start": 453, "end": 463}]}}, "schema": []}
{"input": "HDN-induced renal biomarker changes in male rats were potentially compound specific: (1) 2-propanol induced mild HDN without increased renal biomarkers, (2) potassium bromate induced moderate HDN with increased clusterin, and (3) D-limonene induced marked HDN with increased alpha GST, mu GST and albumin.", "output": {"entities": {"chemical": [{"text": "2-propanol", "start": 89, "end": 99}, {"text": "potassium bromate", "start": 157, "end": 174}, {"text": "D-limonene", "start": 230, "end": 240}]}}, "schema": []}
{"input": "Administration of potassium bromate did not result in oxidative stress-induced kidney injury, based on histopathology and renal biomarkers creatinine and BUN.", "output": {"entities": {"chemical": [{"text": "potassium bromate", "start": 18, "end": 35}]}}, "schema": []}
{"input": "The compound D-limonene induced a dose dependent increase in HDN severity and renal biomarker changes without altering BUN, creatinine or NAG: (1) minimal induction of HDN and no altered biomarkers at 10 mg/kg/day, (2) mild induction of HDN with increased alpha GST and mu GST at 50 mg/kg/day and (3) marked induction of HDN with increased alpha GST, mu GST and albumin at 300 mg/kg/day.", "output": {"entities": {"chemical": [{"text": "D-limonene", "start": 13, "end": 23}, {"text": "creatinine", "start": 124, "end": 134}]}}, "schema": []}
{"input": "HDN induced by D-limonene was reversible, but with a variable renal biomarker pattern over time: Day 8 there was increased alpha GST, mu GST and albumin; on Day 15 increased clusterin, albumin and Kim-1.", "output": {"entities": {"chemical": [{"text": "D-limonene", "start": 15, "end": 25}]}}, "schema": []}
{"input": "In summary, HDN altered the newer and more sensitive renal biomarkers in a time and possibly compound dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Severe growth deficiency is associated with STAT5b mutations that disrupt protein folding and activity.", "output": {"entities": {}}, "schema": []}
{"input": "The first genetic defect in human signal transducer and activator of transcription (STAT) 5b was identified in an individual with profound short stature and GH insensitivity, immune dysfunction, and severe pulmonary disease, and was caused by an alanine to proline substitution (A630P) within the Src homology-2 (SH2) domain.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 246, "end": 253}, {"text": "proline", "start": 257, "end": 264}]}}, "schema": []}
{"input": "STAT5b (A630P) was found to be an inactive transcription factor based on its aberrant folding, diminished solubility, and propensity for aggregation triggered by its misfolded SH2 domain.", "output": {"entities": {}}, "schema": []}
{"input": "Here we have characterized the second human STAT5b amino acid substitution mutation in an individual with similar pathophysiological features.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 51, "end": 61}]}}, "schema": []}
{"input": "This single nucleotide transition, predicted to change phenyalanine 646 to serine (F646S), also maps to the SH2 domain.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 12, "end": 22}, {"text": "phenyalanine", "start": 55, "end": 67}, {"text": "serine", "start": 75, "end": 81}]}}, "schema": []}
{"input": "Like STAT5b (A630P), STAT5b (F646S) is prone to aggregation, as evidenced by its detection in the insoluble fraction of cell extracts, the presence of dimers and higher-order oligomers in the soluble fraction, and formation of insoluble cytoplasmic inclusion bodies in cells.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike STAT5b (A630P), which showed minimal GH-induced tyrosine phosphorylation and no transcriptional activity, STAT5b (F646S) became tyrosine phosphorylated after GH treatment and could function as a GH-activated transcription factor, although to a substantially lesser extent than STAT5b (WT).", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 55, "end": 63}, {"text": "tyrosine", "start": 135, "end": 143}]}}, "schema": []}
{"input": "Biochemical characterization demonstrated that the isolated SH2 domain containing the F646S substitution closely resembled the wild-type SH2 domain in secondary structure, but exhibited reduced thermodynamic stability and altered tertiary structure that were intermediate between STAT5b (A630P) and STAT5b (WT).", "output": {"entities": {}}, "schema": []}
{"input": "Homology-based structural modeling suggests that the F646S mutation disrupts key hydrophobic interactions and may also distort the phosphopeptide-binding face of the SH2 domain, explaining both the reduced thermodynamic stability and impaired biological activity.", "output": {"entities": {}}, "schema": []}
{"input": "FOXO1 controls thyroid cell proliferation in response to TSH and IGF-I and is involved in thyroid tumorigenesis.", "output": {"entities": {}}, "schema": []}
{"input": "TSH and insulin/IGF-I synergistically induce the proliferation of thyroid cells mainly through the cAMP and phosphatidylinositol 3-kinase (PI3K) pathways.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 99, "end": 103}, {"text": "phosphatidylinositol", "start": 108, "end": 128}]}}, "schema": []}
{"input": "However, the events involved in this cooperative induction remain unknown, and molecules that are potentially controlled by both TSH and IGF-I are interesting candidates as integrators of both stimuli.", "output": {"entities": {}}, "schema": []}
{"input": "The finding that the PI3K pathway is frequently activated in thyroid malignancies has attracted attention to this pathway in the thyroid field.", "output": {"entities": {}}, "schema": []}
{"input": "One of the targets of PI3K is Forkhead box O (FoxO)-1, a widely expressed transcription factor involved in a variety of cellular processes such as differentiation, proliferation, and apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that FoxO1 is highly expressed in differentiated rat thyroid cells and human thyroid tissue compared with human thyroid tumor-derived cells and surgically removed thyroid tumors, in which its expression is reduced.", "output": {"entities": {}}, "schema": []}
{"input": "In differentiated cells, TSH/cAMP treatment decreases FoxO1 mRNA and protein levels through proteasome activation, whereas both TSH and IGF-I control FoxO1 localization by promoting a rapid exclusion from the nucleus in an Akt-dependent manner.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 29, "end": 33}]}}, "schema": []}
{"input": "FoxO1 can control p27 (KIP1) expression in differentiated and tumor cells of the thyroid.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, FoxO1 reexpression in tumor cells promotes a decrease in their proliferation rate, whereas FoxO1 interference in differentiated cells increases their proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "These data point to an important role of FoxO1 in mediating the effects of TSH and IGF-I on thyroid cell proliferation and provide a link between loss of FoxO1 expression and the uncontrolled proliferation of thyroid tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "Gliotransmission and brain glucose sensing: critical role of endozepines.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 27, "end": 34}]}}, "schema": []}
{"input": "Hypothalamic glucose sensing is involved in the control of feeding behavior and peripheral glucose homeostasis, and glial cells are suggested to play an important role in this process.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 13, "end": 20}, {"text": "glucose", "start": 91, "end": 98}]}}, "schema": []}
{"input": "Diazepam-binding inhibitor (DBI) and its processing product the octadecaneuropeptide (ODN), collectively named endozepines, are secreted by astroglia, and ODN is a potent anorexigenic factor.", "output": {"entities": {"chemical": [{"text": "Diazepam", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Therefore, we investigated the involvement of endozepines in brain glucose sensing.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 67, "end": 74}]}}, "schema": []}
{"input": "First, we showed that intracerebroventricular administration of glucose in rats increases DBI expression in hypothalamic glial-like tanycytes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 64, "end": 71}]}}, "schema": []}
{"input": "We then demonstrated that glucose stimulates endozepine secretion from hypothalamic explants.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 26, "end": 33}]}}, "schema": []}
{"input": "Feeding experiments indicate that the anorexigenic effect of central administration of glucose was blunted by coinjection of an ODN antagonist.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 87, "end": 94}]}}, "schema": []}
{"input": "Conversely, the hyperphagic response elicited by central glucoprivation was suppressed by an ODN agonist.", "output": {"entities": {}}, "schema": []}
{"input": "The anorexigenic effects of centrally injected glucose or ODN agonist were suppressed by blockade of the melanocortin-3/4 receptors, suggesting that glucose sensing involves endozepinergic control of the melanocortin pathway.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 47, "end": 54}, {"text": "glucose", "start": 149, "end": 156}]}}, "schema": []}
{"input": "Finally, we found that brain endozepines modulate blood glucose levels, suggesting their involvement in a feedback loop controlling whole-body glucose homeostasis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 56, "end": 63}, {"text": "glucose", "start": 143, "end": 150}]}}, "schema": []}
{"input": "Collectively, these data indicate that endozepines are a critical relay in brain glucose sensing and potentially new targets in treatment of metabolic disorders.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 81, "end": 88}]}}, "schema": []}
{"input": "A kinesin-mediated mechanism that couples centrosomes to nuclei.", "output": {"entities": {}}, "schema": []}
{"input": "The M-type kinesin isoform, Kif9, has recently been implicated in maintaining a physical connection between the centrosome and nucleus in Dictyostelium discoideum.", "output": {"entities": {}}, "schema": []}
{"input": "However, the mechanism by which Kif9 functions to link these two organelles remains obscure.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that the Kif9 protein is localized to the nuclear envelope and is concentrated in the region underlying the centrosome point of attachment.", "output": {"entities": {}}, "schema": []}
{"input": "Nuclear anchorage appears mediated through a specialized transmembrane domain located in the carboxyl terminus.", "output": {"entities": {"chemical": [{"text": "carboxyl", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Kif9 interacts with microtubules in in vitro binding assays and effects an endwise depolymerization of the polymer.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest a model whereby Kif9 is anchored to the nucleus and generates a pulling force that reels the centrosome up against the nucleus.", "output": {"entities": {}}, "schema": []}
{"input": "This is a novel activity for a kinesin motor, one important for progression of cells into mitosis and to ensure centrosome-nuclear parity in a multinuclear environment.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicity of forest fire retardant chemicals to stream-type chinook salmon undergoing parr-smolt transformation.", "output": {"entities": {}}, "schema": []}
{"input": "Long-term fire retardants are used to prevent the spread of wildland fires.", "output": {"entities": {}}, "schema": []}
{"input": "These products are normally applied by aircraft and are intended specifically for terrestrial application, but fire retardants have entered aquatic habitats by misapplication and/or accidental spills and have resulted in fish mortalities.", "output": {"entities": {}}, "schema": []}
{"input": "The authors examined the toxicity of two fire retardant products, PHOS-CHEK 259F and LC-95A, to salmon undergoing parr-smolt transformation.", "output": {"entities": {"chemical": [{"text": "PHOS-CHEK 259F and LC-95A", "start": 66, "end": 91}]}}, "schema": []}
{"input": "Yearling stream-type chinook salmon at the smolt stage were exposed to eight concentrations of each retardant in freshwater and a no-PHOS-CHEK control for 96 h to determine acute toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Concentrations of the products that caused 50% mortality were 140. 5 and 339. 8 mg/L for 259F and LC-95A, respectively, and could occur during accidental drops into aquatic habitats.", "output": {"entities": {"chemical": [{"text": "259F", "start": 89, "end": 93}, {"text": "LC-95A", "start": 98, "end": 104}]}}, "schema": []}
{"input": "Damage to gill tissues seen in histopathological sections was attributed to fire retardant exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Un-ionized ammonia levels, from 259F, were sufficient to cause acute mortality; but additional factors, indicated by increased phagosome prevalence in the gills, might have contributed to mortality during LC-95A exposure.", "output": {"entities": {"chemical": [{"text": "259F", "start": 32, "end": 36}, {"text": "LC-95A", "start": 205, "end": 211}]}}, "schema": []}
{"input": "Seawater and disease challenges were performed to determine sublethal effects of product exposures on fish health.", "output": {"entities": {}}, "schema": []}
{"input": "Although PHOS-CHEK exposure did not adversely affect chinook salmon' s susceptibility to Listonella anguillarum, exposure did significantly reduce seawater survival.", "output": {"entities": {}}, "schema": []}
{"input": "Reduced salmon survival resulting from prior fire retardant exposure during their transition from freshwater rearing environments to seawater may decrease the abundance of salmon populations.", "output": {"entities": {}}, "schema": []}
{"input": "A method for assessing the potential for confounding applied to ionic strength in central Appalachian streams.", "output": {"entities": {}}, "schema": []}
{"input": "Causal relationships derived from field data are potentially confounded by variables that are correlated with both the cause and its effect.", "output": {"entities": {}}, "schema": []}
{"input": "The present study presents a method for assessing the potential for confounding and applies it to the relationship between ionic strength and impairment of benthic invertebrate assemblages in central Appalachian streams.", "output": {"entities": {}}, "schema": []}
{"input": "The method weighs all available evidence for and against confounding by each potential confounder.", "output": {"entities": {}}, "schema": []}
{"input": "It identifies 10 types of evidence for confounding, presents a qualitative scoring system, and provides rules for applying the scores.", "output": {"entities": {}}, "schema": []}
{"input": "Twelve potential confounders were evaluated: habitat, organic enrichment, nutrients, deposited sediments, pH, selenium, temperature, lack of headwaters, catchment area, settling ponds, dissolved oxygen, and metals.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 110, "end": 118}, {"text": "oxygen", "start": 195, "end": 201}]}}, "schema": []}
{"input": "One potential confounder, low pH, was found to be biologically significant and eliminated by removing sites with pH < 6.", "output": {"entities": {}}, "schema": []}
{"input": "Other potential confounders were eliminated based on the weight of evidence.", "output": {"entities": {}}, "schema": []}
{"input": "This method was found to be useful and defensible.", "output": {"entities": {}}, "schema": []}
{"input": "It could be applied to other environmental assessments that use field data to develop causal relationships, including contaminated site remediation or management of natural resources.", "output": {"entities": {}}, "schema": []}
{"input": "Substituent variation drives metal/monolayer/semiconductor junctions from strongly rectifying to ohmic behavior.", "output": {"entities": {}}, "schema": []}
{"input": "An eight-orders of magnitude enhancement in current across Hg/X-styrene-Si junctions is caused by merely altering a substituent, X.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 59, "end": 61}, {"text": "styrene", "start": 64, "end": 71}, {"text": "Si", "start": 72, "end": 74}]}}, "schema": []}
{"input": "Interface states are passivated and, depending on X, the Si Schottky junction encompasses the full range from Ohmic to strongly rectifying.", "output": {"entities": {"chemical": [{"text": "Si", "start": 57, "end": 59}]}}, "schema": []}
{"input": "This powerful electrostatic molecular effect has immediate implications for interface band alignment and sensing.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of silver doping on electron transport in thin films of PbSe nanocrystals.", "output": {"entities": {"chemical": [{"text": "silver", "start": 13, "end": 19}, {"text": "PbSe", "start": 66, "end": 70}]}}, "schema": []}
{"input": "Field-effect transistors are fabricated from thin films of Ag-doped PbSe nanocrystals to analyze the influence of electronically active impurities on electrical transport in this important material for nanocrystal applications.", "output": {"entities": {"chemical": [{"text": "Ag-doped PbSe", "start": 59, "end": 72}]}}, "schema": []}
{"input": "Data is collected as a function of nanocrystal size, dopant concentration, and temperature.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in the Fermi level and transport parameters indicate that Ag is acting as a p-type dopant (acceptor).", "output": {"entities": {"chemical": [{"text": "Ag", "start": 66, "end": 68}]}}, "schema": []}
{"input": "New horizons for diagnostics and therapeutic applications of graphene and graphene oxide.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 61, "end": 69}, {"text": "graphene oxide", "start": 74, "end": 88}]}}, "schema": []}
{"input": "Graphene, a one-atom-thick two-dimensional (2D) layer of sp (2)-bonded carbon, has received worldwide attention owing to its extraordinary physical and chemical properties.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 0, "end": 8}, {"text": "carbon", "start": 71, "end": 77}]}}, "schema": []}
{"input": "Recently, great efforts have been devoted to explore potential applications of graphene and its oxide in life science, especially in disease-related diagnostics, near-Infrared (NIR) phototherapy and imaging.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 79, "end": 87}]}}, "schema": []}
{"input": "Here we will introduce recent advances and new horizons in this area, and focus on the rising progress on NIR photothermal therapy for cancer and Alzheimer' s disease (AD), human telomerase detection, stem cell proliferation and differentiation on graphene substrate, diagnosis of cancer cell and related biomarkers, drug/nucleotide/peptide delivery and cell imaging, which have not been comprehensively reviewed.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 248, "end": 256}, {"text": "nucleotide", "start": 322, "end": 332}]}}, "schema": []}
{"input": "We hope to provide an outlook to the applications of graphene and its oxide, especially on the new horizons in this field, and inspire broader interests across various disciplines.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 53, "end": 61}]}}, "schema": []}
{"input": "SchistoDB: an updated genome resource for the three key schistosomes of humans.", "output": {"entities": {}}, "schema": []}
{"input": "The new release of SchistoDB (http://SchistoDB. net) provides a rich resource of genomic data for key blood flukes (genus Schistosoma) which cause disease in hundreds of millions of people worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "SchistoDB integrates whole-genome sequence and annotation of three species of the genus and provides enhanced bioinformatics analyses and data-mining tools.", "output": {"entities": {}}, "schema": []}
{"input": "A simple, yet comprehensive web interface provided through the Strategies Web Development Kit is available for the mining and visualization of the data.", "output": {"entities": {}}, "schema": []}
{"input": "Genomic scale data can be queried based on BLAST searches, annotation keywords and gene ID searches, gene ontology terms, sequence motifs, protein characteristics and phylogenetic relationships.", "output": {"entities": {}}, "schema": []}
{"input": "Search strategies can be saved within a user' s profile for future retrieval and may also be shared with other researchers using a unique web address.", "output": {"entities": {}}, "schema": []}
{"input": "Combining quantum mechanical ligand conformation analysis and protein modeling to elucidate GPCR-ligand binding modes.", "output": {"entities": {}}, "schema": []}
{"input": "SAR beyond protein-ligand interactions: By combining structure-affinity relationships, protein-ligand modeling studies, and quantum mechanical calculations, we show that ligand conformational energies and basicity play critical roles in ligand binding to the histamine H4 receptor, a GPCR that plays a key role in inflammation.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 259, "end": 268}]}}, "schema": []}
{"input": "Ras-dva is a novel Pit-1-and glucocorticoid-regulated gene in the embryonic anterior pituitary gland.", "output": {"entities": {}}, "schema": []}
{"input": "Glucocorticoids play a role in functional differentiation of pituitary somatotrophs and lactotrophs during embryogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Ras-dva was identified as a gene regulated by anterior neural fold protein-1/homeobox expressed in embryonic stem cells-1, a transcription factor known to be critical in pituitary development, and has an expression profile in the chicken embryonic pituitary gland that is consistent with in vivo regulation by glucocorticoids.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to characterize expression and regulation of ras-dva mRNA in the developing chicken anterior pituitary.", "output": {"entities": {}}, "schema": []}
{"input": "Pituitary ras-dva mRNA levels increased during embryogenesis to a maximum on embryonic day (e) 18 and then decreased and remained low or undetectable after hatch.", "output": {"entities": {}}, "schema": []}
{"input": "Ras-dva expression was highly enriched in the pituitary gland on e18 relative to other tissues examined.", "output": {"entities": {}}, "schema": []}
{"input": "Glucocorticoid treatment of pituitary cells from mid-and late-stage embryos rapidly increased ras-dva mRNA, suggesting it may be a direct transcriptional target of glucocorticoids.", "output": {"entities": {}}, "schema": []}
{"input": "A reporter construct driven by 4 kb of the chicken ras-dva 5'-flanking region, containing six putative pituitary-specific transcription factor-1 (Pit-1) binding sites and two potential glucocorticoid receptor (GR) binding sites, was highly activated in embryonic pituitary cells and up-regulated by corticosterone.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 299, "end": 313}]}}, "schema": []}
{"input": "Mutagenesis of the most proximal Pit-1 site decreased promoter activity in chicken e11 pituitary cells, indicating regulation of ras-dva by Pit-1.", "output": {"entities": {}}, "schema": []}
{"input": "However, mutating putative GR binding sites did not substantially reduce induction of ras-dva promoter activity by corticosterone, suggesting additional DNA elements within the 5'-flanking region are responsible for glucocorticoid regulation.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 115, "end": 129}]}}, "schema": []}
{"input": "We have identified ras-dva as a glucocorticoid-regulated gene that is likely expressed in cells of the Pit-1 lineage within the developing anterior pituitary gland.", "output": {"entities": {}}, "schema": []}
{"input": "The role of the carbohydrate response element-binding protein in male fructose-fed rats.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 16, "end": 28}, {"text": "fructose", "start": 70, "end": 78}]}}, "schema": []}
{"input": "By 2030, nearly half of Americans will have nonalcoholic fatty liver disease.", "output": {"entities": {}}, "schema": []}
{"input": "In part, this epidemic is fueled by the increasing consumption of caloric sweeteners coupled with an innate capacity to convert sugar into fat via hepatic de novo lipogenesis.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 128, "end": 133}]}}, "schema": []}
{"input": "In addition to serving as substrates, monosaccharides also increase the expression of key enzymes involved in de novo lipogenesis via the carbohydrate response element-binding protein (ChREBP).", "output": {"entities": {"chemical": [{"text": "monosaccharides", "start": 38, "end": 53}, {"text": "carbohydrate", "start": 138, "end": 150}]}}, "schema": []}
{"input": "To determine whether ChREBP is a potential therapeutic target, we decreased hepatic expression of ChREBP with a specific antisense oligonucleotide (ASO) in male Sprague-Dawley rats fed either a high-fructose or high-fat diet.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 199, "end": 207}]}}, "schema": []}
{"input": "ChREBP ASO treatment decreased plasma triglyceride concentrations compared with control ASO treatment in both diet groups.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 38, "end": 50}]}}, "schema": []}
{"input": "The reduction was more pronounced in the fructose-fed group and attributed to decreased hepatic expression of ACC2, FAS, SCD1, and MTTP and a decrease in the rate of hepatic triglyceride secretion.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 41, "end": 49}, {"text": "triglyceride", "start": 174, "end": 186}]}}, "schema": []}
{"input": "This was associated with an increase in insulin-stimulated peripheral glucose uptake, as assessed by the hyperinsulinemic-euglycemic clamp.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 70, "end": 77}]}}, "schema": []}
{"input": "In contrast, ChREBP ASO did not alter hepatic lipid content or hepatic insulin sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, fructose-fed rats treated with ChREBP ASO had increased plasma uric acid, alanine transaminase, and aspartate aminotransferase concentrations.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 15, "end": 23}, {"text": "uric acid", "start": 78, "end": 87}, {"text": "alanine", "start": 89, "end": 96}, {"text": "aspartate", "start": 115, "end": 124}]}}, "schema": []}
{"input": "This was associated with decreased expression of fructose aldolase and fructokinase, reminiscent of inherited disorders of fructose metabolism.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 49, "end": 57}, {"text": "fructose", "start": 123, "end": 131}]}}, "schema": []}
{"input": "In summary, these studies suggest that targeting ChREBP may prevent fructose-induced hypertriglyceridemia but without the improvements in hepatic steatosis and hepatic insulin responsiveness.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 68, "end": 76}]}}, "schema": []}
{"input": "Genetic requirements for Moraxella catarrhalis growth under iron-limiting conditions.", "output": {"entities": {"chemical": [{"text": "iron", "start": 60, "end": 64}]}}, "schema": []}
{"input": "Iron sequestration by the human host is a first line defence against respiratory pathogens like Moraxella catarrhalis, which consequently experiences a period of iron starvation during colonization.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "iron", "start": 162, "end": 166}]}}, "schema": []}
{"input": "We determined the genetic requirements for M. catarrhalis BBH18 growth during iron starvation using the high-throughput genome-wide screening technology genomic array footprinting (GAF).", "output": {"entities": {"chemical": [{"text": "iron", "start": 78, "end": 82}]}}, "schema": []}
{"input": "By subjecting a large random transposon mutant library to growth under iron-limiting conditions, mutants of the MCR _ 0996-rhlB-yggW operon, rnd, and MCR _ 0457 were negatively selected.", "output": {"entities": {"chemical": [{"text": "iron", "start": 71, "end": 75}]}}, "schema": []}
{"input": "Growth experiments using directed mutants confirmed the GAF phenotypes with Delta yggW (putative haem-shuttling protein) and Delta MCR _ 0457 (hypothetical protein) most severely attenuated during iron starvation, phenotypes which were restored upon genetic complementation of the deleted genes.", "output": {"entities": {"chemical": [{"text": "iron", "start": 197, "end": 201}]}}, "schema": []}
{"input": "Deletion of yggW resulted in similar attenuated phenotypes in three additional strains.", "output": {"entities": {}}, "schema": []}
{"input": "Transcriptional profiles of Delta yggW and Delta MCR _ 0457 were highly altered with 393 and 192 differentially expressed genes respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In all five mutants, expression of nitrate reductase genes was increased and of nitrite reductase decreased, suggesting an impaired aerobic respiration.", "output": {"entities": {"chemical": [{"text": "nitrate", "start": 35, "end": 42}, {"text": "nitrite", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Alteration of iron metabolism may affect nasopharyngeal colonization as adherence of all mutants to respiratory tract epithelial cells was attenuated.", "output": {"entities": {"chemical": [{"text": "iron", "start": 14, "end": 18}]}}, "schema": []}
{"input": "In conclusion, we elucidated the genetic requirements for M. catarrhalis growth during iron starvation and characterized the roles of the identified genes in bacterial growth and host interaction.", "output": {"entities": {"chemical": [{"text": "iron", "start": 87, "end": 91}]}}, "schema": []}
{"input": "Synaptic plasticity in the hippocampus shows resistance to acute ethanol exposure in transgenic mice with astrocyte-targeted enhanced CCL2 expression.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 65, "end": 72}]}}, "schema": []}
{"input": "It has been shown that ethanol exposure can activate astrocytes and microglia resulting in the production of neuroimmune factors, including the chemokine CCL2.", "output": {"entities": {}}, "schema": []}
{"input": "The role of these neuroimmune factors in the effects of ethanol on the central nervous system has yet to be elucidated.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 56, "end": 63}]}}, "schema": []}
{"input": "To address this question, we investigated the effects of ethanol on synaptic transmission and plasticity in the hippocampus from mice that express elevated levels of CCL2 in the brain and their non-transgenic littermate controls.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 57, "end": 64}]}}, "schema": []}
{"input": "The brains of the transgenic mice simulate one aspect of the alcoholic brain, chronically increased levels of CCL2.", "output": {"entities": {}}, "schema": []}
{"input": "We used extracellular field potential recordings in acutely isolated hippocampal slices to identify neuroadaptive changes produced by elevated levels of CCL2 and how these neuroadaptive changes affect the actions of acute ethanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 222, "end": 229}]}}, "schema": []}
{"input": "Results showed that synaptic transmission and the effects of ethanol on synaptic transmission were similar in the CCL2-transgenic and non-transgenic hippocampus.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 61, "end": 68}]}}, "schema": []}
{"input": "However, long-term potentiation (LTP), a cellular mechanism thought to underlie learning and memory, in the CCL2-transgenic hippocampus was resistant to the ethanol-induced depression of LTP observed in the non-transgenic hippocampus.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 157, "end": 164}]}}, "schema": []}
{"input": "Consistent with these results, ethanol pretreatment significantly impaired cued and contextual fear conditioning in non-transgenic mice, but had no effect in CCL2-transgenic mice.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 31, "end": 38}]}}, "schema": []}
{"input": "These data show that chronically elevated levels of CCL2 in the hippocampus produce neuroadaptive changes that block the depressing effects of ethanol on hippocampal synaptic plasticity and support the hypothesis that CCL2 may provide a neuroprotective effect against the devastating actions of ethanol on hippocampal function.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 143, "end": 150}, {"text": "ethanol", "start": 295, "end": 302}]}}, "schema": []}
{"input": "Supra-normal stimulation of dopamine D1 receptors in the prelimbic cortex blocks behavioral expression of both aversive and rewarding associative memories through a cyclic-AMP-dependent signaling pathway.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 28, "end": 36}, {"text": "cyclic-AMP", "start": 165, "end": 175}]}}, "schema": []}
{"input": "Dopamine (DA) receptor transmission through either D (1) or D (2)-like subtypes is involved critically in the processing of emotional information within the medial prefrontal cortex (mPFC).", "output": {"entities": {"chemical": [{"text": "Dopamine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "However the functional role of specific DA D (1)-like receptor transmission in the expression of emotionally salient associative memories (either aversive or rewarding) is not currently understood.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that specific activation of DA D (1) receptors in the prelimbic (PLC) division of the mPFC causes a transient block in the behavioral expression of both aversive and rewarding associative memories.", "output": {"entities": {}}, "schema": []}
{"input": "We report that intra-PLC microinfusions of a selective D (1) receptor agonist block the spontaneous expression of an associative olfactory fear memory, without altering the stability of the original memory trace.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, using an unbiased place conditioning procedure (CPP), intra-PLC D (1) receptor activation blocks the spontaneous expression of an associative morphine (5 mg/kg; i. p.) reward memory, while leaving morphine-primed memory expression intact.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 155, "end": 163}, {"text": "morphine", "start": 210, "end": 218}]}}, "schema": []}
{"input": "Interestingly, both intra-PLC D (1)-receptor mediated block of either fear-related or reward-related associative memories were dependent upon downstream cyclic-AMP (cAMP) signaling as both effects were rescued by co-administration of a cAMP signaling inhibitor.", "output": {"entities": {"chemical": [{"text": "cyclic-AMP", "start": 153, "end": 163}, {"text": "cAMP", "start": 165, "end": 169}, {"text": "cAMP", "start": 236, "end": 240}]}}, "schema": []}
{"input": "The blockade of both rewarding and aversive associative memories is mediated through a D (1)-specific signaling pathway, as neither forms of spontaneous memory expression were blocked by intra-PLC microinfusions of a D (2)-like receptor agonist.", "output": {"entities": {}}, "schema": []}
{"input": "Our results demonstrate that the spontaneous expression of either rewarding or aversive emotionally salient memories shares a common, D (1)-receptor mediated substrate within the mPFC.", "output": {"entities": {}}, "schema": []}
{"input": "Glucose attenuates impairments in memory and CREB activation produced by an alpha 4 beta 2 but not an alpha 7 nicotinic receptor antagonist.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Glucose improves memory for a variety of tasks when administered to rats and mice near the time of training.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Prior work indicates glucose may enhance memory by increasing the synthesis and release of the neurotransmitter acetylcholine in the brain.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 21, "end": 28}, {"text": "acetylcholine", "start": 112, "end": 125}]}}, "schema": []}
{"input": "To investigate if specific acetylcholine receptor subtypes may mediate some of the memory-enhancing actions of glucose, we examined the effects of subtype-specific nicotinic acetylcholine receptor antagonists on memory in Fischer-344 rats and also examined the ability of glucose to reverse drug-induced impairments.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 27, "end": 40}, {"text": "glucose", "start": 111, "end": 118}, {"text": "acetylcholine", "start": 174, "end": 187}, {"text": "glucose", "start": 272, "end": 279}]}}, "schema": []}
{"input": "Pre-training peripheral injections of methyllycaconitine (MLA) or dihydro-beta-erythroidine (DH beta E), which are specific alpha 7 and alpha 4 beta 2 nicotinic receptor antagonists, respectively, dose-dependently impaired retention latencies in an inhibitory avoidance task when tested 7-days but not 1 h after training.", "output": {"entities": {"chemical": [{"text": "methyllycaconitine", "start": 38, "end": 56}, {"text": "MLA", "start": 58, "end": 61}, {"text": "dihydro-beta-erythroidine", "start": 66, "end": 91}, {"text": "DH beta E", "start": 93, "end": 102}]}}, "schema": []}
{"input": "Immediate post-training glucose injections attenuated the impairments, but were more effective in attenuating the DH beta E-induced impairments.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 24, "end": 31}, {"text": "DH beta E", "start": 114, "end": 123}]}}, "schema": []}
{"input": "Likewise, peripheral or direct intrahippocampal injections of MLA or DH beta E dose-dependently impaired spatial working memory scores on a spontaneous alternation task.", "output": {"entities": {"chemical": [{"text": "MLA", "start": 62, "end": 65}, {"text": "DH beta E", "start": 69, "end": 78}]}}, "schema": []}
{"input": "Concurrent administration of glucose reversed DH beta E-but not MLA-induced impairments.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 29, "end": 36}, {"text": "DH beta E", "start": 46, "end": 55}, {"text": "MLA", "start": 64, "end": 67}]}}, "schema": []}
{"input": "CREB phosphorylation downstream of cholinergic signaling was assessed 30 min after spontaneous alternation testing and intrahippocampal drug infusions.", "output": {"entities": {}}, "schema": []}
{"input": "Both MLA and DH beta E impaired hippocampal CREB phosphorylation; glucose reversed DH beta E-but not MLA-induced deficits.", "output": {"entities": {"chemical": [{"text": "MLA", "start": 5, "end": 8}, {"text": "DH beta E", "start": 13, "end": 22}, {"text": "glucose", "start": 66, "end": 73}, {"text": "DH beta E", "start": 83, "end": 92}, {"text": "MLA", "start": 101, "end": 104}]}}, "schema": []}
{"input": "The effectiveness of glucose in reversing DH beta E-but not MLA-induced impairments in behavioral performance and CREB phosphorylation suggests that activation of alpha 7 receptors may play an important role in memory enhancement by glucose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 21, "end": 28}, {"text": "DH beta E", "start": 42, "end": 51}, {"text": "MLA", "start": 60, "end": 63}, {"text": "glucose", "start": 233, "end": 240}]}}, "schema": []}
{"input": "Enantioselective synthesis of derivatives and structure-activity relationship study in the development of NA255 as a novel host-targeting anti-HCV agent.", "output": {"entities": {"chemical": [{"text": "NA255", "start": 106, "end": 111}]}}, "schema": []}
{"input": "Hepatitis C virus (HCV) infection represents a serious health-care problem.", "output": {"entities": {}}, "schema": []}
{"input": "Previously we reported the identification of NA255 from our natural products library using a HCV sub-genomic replicon cell culture system.", "output": {"entities": {"chemical": [{"text": "NA255", "start": 45, "end": 50}]}}, "schema": []}
{"input": "Herein, we report how the absolute stereochemistry of NA255 was determined and an enantioselective synthetic method for NA255 derivatives was developed.", "output": {"entities": {"chemical": [{"text": "NA255", "start": 54, "end": 59}, {"text": "NA255", "start": 120, "end": 125}]}}, "schema": []}
{"input": "The structure-activity relationship of the NA255 derivatives and rat pharmacokinetic profiles of the representative compounds are disclosed.", "output": {"entities": {"chemical": [{"text": "NA255", "start": 43, "end": 48}]}}, "schema": []}
{"input": "Catalpol inhibits LPS plus IFN-gamma-induced inflammatory response in astrocytes primary cultures.", "output": {"entities": {"chemical": [{"text": "Catalpol", "start": 0, "end": 8}]}}, "schema": []}
{"input": "A large body of evidence suggests that the inflammatory reaction plays an important role in the pathogenesis of neurodegenerative diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Our previous studies described the neuroprotective effects of catalpol in lipopolysaccharide (LPS)-induced inflammatory models, in which catalpol was shown to prevent mesencephalic neuron death and ameliorate cognitive ability animals.", "output": {"entities": {"chemical": [{"text": "catalpol", "start": 62, "end": 70}, {"text": "catalpol", "start": 137, "end": 145}]}}, "schema": []}
{"input": "To further investigate the protective effect and underlying mechanism of catalpol, astrocytes were pretreated with low (0. 1mM) and high dose (0. 5mM) catalpol for 1h prior to LPS plus interferon-gamma stimulation.", "output": {"entities": {"chemical": [{"text": "catalpol", "start": 73, "end": 81}, {"text": "catalpol", "start": 151, "end": 159}]}}, "schema": []}
{"input": "Biochemical analyses showed that NO and ROS production and iNOS activity were significantly reduced by catalpol.", "output": {"entities": {"chemical": [{"text": "NO", "start": 33, "end": 35}, {"text": "catalpol", "start": 103, "end": 111}]}}, "schema": []}
{"input": "Data at transcriptional level also demonstrated that catalpol potently attenuated gene expressions involved in inflammation, such as iNOS, COX-2 and TLR4.", "output": {"entities": {"chemical": [{"text": "catalpol", "start": 53, "end": 61}]}}, "schema": []}
{"input": "In addition, our exploration further revealed that the suppressive action of catalpol on inflammation was mediated via inhibiting nuclear factor-kappa B (NF-kappa B) activation.", "output": {"entities": {"chemical": [{"text": "catalpol", "start": 77, "end": 85}]}}, "schema": []}
{"input": "Collectively, these results suggest that catalpol can exert inhibitory effects on the inflammatory reaction in astrocytes and that inactivation of NF-kappa B could be the major determinant for its anti-inflammatory mechanism.", "output": {"entities": {"chemical": [{"text": "catalpol", "start": 41, "end": 49}]}}, "schema": []}
{"input": "Therefore, catalpol may potentially be a highly effective therapeutic agent in treating neurodegenerative diseases associated with inflammation.", "output": {"entities": {"chemical": [{"text": "catalpol", "start": 11, "end": 19}]}}, "schema": []}
{"input": "Korean red ginseng ameliorates acute 3-nitropropionic acid-induced cochlear damage in mice.", "output": {"entities": {"chemical": [{"text": "3-nitropropionic acid", "start": 37, "end": 58}]}}, "schema": []}
{"input": "3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce an acute cochlear damage.", "output": {"entities": {"chemical": [{"text": "3-Nitropropionic acid", "start": 0, "end": 21}, {"text": "3-NP", "start": 23, "end": 27}]}}, "schema": []}
{"input": "Korean red ginseng (KRG) is known to have protective effects from some types of hearing loss.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to observe the protective effect of KRG in an ototoxic animal model using 3-NP intratympanic injection.", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 91, "end": 95}]}}, "schema": []}
{"input": "BALB/c mice were classified into 5 groups (n = 15) and dose-dependent toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left ear were investigated to determine the appropriate toxicity level of 3-NP.", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 119, "end": 123}, {"text": "3-NP", "start": 219, "end": 223}]}}, "schema": []}
{"input": "For observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500 mM, n = 12) and KRG + 3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP administration, n = 11).", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 76, "end": 80}, {"text": "3-NP", "start": 108, "end": 112}, {"text": "3-NP", "start": 160, "end": 164}]}}, "schema": []}
{"input": "Auditory brain response (ABR) and cochlear morphological evaluations were performed before and after drug administration.", "output": {"entities": {}}, "schema": []}
{"input": "The ABR thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16 and 32 kHz 1 day after 3-NP administration.", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 111, "end": 115}]}}, "schema": []}
{"input": "The ABR threshold in the 500 mM 3-NP + KRG group was significantly lower than that in the 500 mM 3-NP group from post 1 week to 1 month.", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 32, "end": 36}, {"text": "3-NP", "start": 97, "end": 101}]}}, "schema": []}
{"input": "The mean type II fibrocyte counts significantly differed between the control and 3-NP groups and between the 3-NP and 3-NP + KRG groups.", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 81, "end": 85}, {"text": "3-NP", "start": 109, "end": 113}, {"text": "3-NP", "start": 118, "end": 122}]}}, "schema": []}
{"input": "Spiral ganglion cell degeneration in the 3-NP group was more severe than that in the 3-NP + KRG group.", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 41, "end": 45}, {"text": "3-NP", "start": 85, "end": 89}]}}, "schema": []}
{"input": "This animal model exhibited a dose-dependent hearing loss with histological changes.", "output": {"entities": {}}, "schema": []}
{"input": "KRG administration ameliorated the deterioration of hearing by 3-NP.", "output": {"entities": {"chemical": [{"text": "3-NP", "start": 63, "end": 67}]}}, "schema": []}
{"input": "Reproductive and developmental toxicity screening test of 3-cyanopyridine in rats.", "output": {"entities": {"chemical": [{"text": "3-cyanopyridine", "start": 58, "end": 73}]}}, "schema": []}
{"input": "Crl: CD (SD) rats were given 3-cyanopyridine by gavage at 0, 5, 30 or 180 mg/kg/day.", "output": {"entities": {"chemical": [{"text": "3-cyanopyridine", "start": 29, "end": 44}]}}, "schema": []}
{"input": "Males were dosed for 42 days beginning 14 days before mating, and females for 40-53 days beginning 14 days before mating to day 3 of lactation, including throughout the mating and gestation periods.", "output": {"entities": {}}, "schema": []}
{"input": "General toxicity, mainly liver damage, was observed in males at >= 30 mg/kg/day and in females at >= 5 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "Sertoli cell vacuolation was observed at 180 mg/kg/day, and spermatocyte damages were observed at >= 30 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "Effects on estrous cycles, corpora lutea and implantations, and unsuccessfully mated females, despite additional mating, were observed at 180 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "Delayed initiation of delivery, dystocia, and deaths or moribundities of pregnant females were observed at 180 mg/kg/day, and only two pregnant rats delivered live pups at that dose.", "output": {"entities": {}}, "schema": []}
{"input": "The NOAEL for reproductive/developmental toxicity was concluded to be 30 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in Cynomolgus monkeys.", "output": {"entities": {"chemical": [{"text": "rotigotine", "start": 55, "end": 65}]}}, "schema": []}
{"input": "Continuous dopaminergic stimulation (CDS) is an important drug development strategy in the treatment of Parkinson' s disease (PD).", "output": {"entities": {}}, "schema": []}
{"input": "Rotigotine is a non-ergoline D (3)/D (2)/D (1) dopamine receptor agonist for treating PD.", "output": {"entities": {"chemical": [{"text": "Rotigotine", "start": 0, "end": 10}, {"text": "ergoline", "start": 20, "end": 28}, {"text": "dopamine", "start": 47, "end": 55}]}}, "schema": []}
{"input": "As a new treatment option for CDS, rotigotine-loaded microspheres (RoMS), long-acting sustained-release microspheres with poly (lactide-co-glycolide) as drug carrier, are now being evaluated in clinical trial.", "output": {"entities": {"chemical": [{"text": "rotigotine", "start": 35, "end": 45}, {"text": "poly (lactide-co-glycolide)", "start": 122, "end": 149}]}}, "schema": []}
{"input": "In the present study, the subchronic toxicity in Cynomolgus monkeys has been characterized via intramuscular administration with RoMS at 0, 10, 40 and 160 mg/kg, weekly for 3 months with a 1-month recovery period.", "output": {"entities": {}}, "schema": []}
{"input": "The NOAEL was 10 mg/kg/week.", "output": {"entities": {}}, "schema": []}
{"input": "One male at 160 mg/kg died from an extensive pulmonary embolism.", "output": {"entities": {}}, "schema": []}
{"input": "The major toxicological effects were associated with dopamine agonist-related pharmacodynamic properties of rotigotine (e. g., hyperactivity and stereotype, decreased serum prolactin level) and foreign body removal reaction induced by poly (lactide-co-glycolide) and carboxymethycellulose sodium (e. g., increased mononuclear cells and neutrophils, thymus atrophy and vacuolar degeneration of adrenal cortex, foreign body granuloma with foam cells accumulation at injection sites and foam cells accumulation in spleen and multiple lymph sinuses).", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 53, "end": 61}, {"text": "rotigotine", "start": 108, "end": 118}, {"text": "poly (lactide-co-glycolide)", "start": 235, "end": 262}, {"text": "sodium", "start": 289, "end": 295}]}}, "schema": []}
{"input": "At the end of recovery period, above findings recovered to a normal level or to a certain degree except vacuolar degeneration of adrenal gland.", "output": {"entities": {}}, "schema": []}
{"input": "RoMS has exhibited high safety on monkeys.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro combined cytotoxic effects of pesticide cocktails simultaneously found in the French diet.", "output": {"entities": {}}, "schema": []}
{"input": "Although human populations may be constantly exposed to complex pesticide mixtures through their diet, the human health risk of pesticide exposure is currently assessed on the basis of toxicity data on individual compounds.", "output": {"entities": {}}, "schema": []}
{"input": "To investigate the combined toxic effects of pesticide cocktails previously identified in the French diet, we first studied the cytotoxicity induced by seven cocktails composed of two to six pesticides on human hepatic (HepG2) and colon (Caco-2) cell lines using the MTT and neutral red uptake assays.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 267, "end": 270}, {"text": "neutral red", "start": 275, "end": 286}]}}, "schema": []}
{"input": "Secondly, we challenged to assess the combined effects of the two most cytotoxic cocktails by comparing the measured effects of the mixtures with the predictions based on additive effects on two concepts-independent action (IA) and concentration addition (CA).", "output": {"entities": {}}, "schema": []}
{"input": "For the cocktail composed of dichlorodiphenyltrichloroethane (DDT) and dieldrin, the cytotoxicity of the equimolar cocktail proved greater than the additive effect estimated by the two concepts.", "output": {"entities": {"chemical": [{"text": "dichlorodiphenyltrichloroethane", "start": 29, "end": 60}, {"text": "DDT", "start": 62, "end": 65}, {"text": "dieldrin", "start": 71, "end": 79}]}}, "schema": []}
{"input": "Furthermore, apoptosis induction was higher in equimolar cocktail than predicted by summing the effects of DDT and dieldrin.", "output": {"entities": {"chemical": [{"text": "DDT", "start": 107, "end": 110}, {"text": "dieldrin", "start": 115, "end": 123}]}}, "schema": []}
{"input": "Thus, some supra-additive toxicity was found in the DDT-dieldrin cocktail.", "output": {"entities": {"chemical": [{"text": "DDT", "start": 52, "end": 55}, {"text": "dieldrin", "start": 56, "end": 64}]}}, "schema": []}
{"input": "Nevertheless, if IA and CA models could reveal combined effects of pesticide cocktails, an accurate evaluation remains challenging.", "output": {"entities": {}}, "schema": []}
{"input": "EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic response to parathyroid hormone.", "output": {"entities": {}}, "schema": []}
{"input": "Previous reports indicate that ephrinB2 expression by osteoblasts is stimulated by parathyroid hormone (PTH) and its related protein (PTHrP) and that ephrinB2/EphB4 signaling between osteoblasts and osteoclasts stimulates osteoblast differentiation while inhibiting osteoclast differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "To determine the role of the ephrinB2/EphB4 interaction in the skeleton, we used a specific inhibitor, soluble EphB4 (sEphB4), in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "sEphB4 treatment of cultured osteoblasts specifically inhibited EphB4 and ephrinB2 phosphorylation and reduced mRNA levels of late markers of osteoblast/osteocyte differentiation (osteocalcin, dentin matrix protein-1 [DMP-1], sclerostin, matrix-extracellular phosphoglycoprotein [MEPE]), while substantially increasing RANKL.", "output": {"entities": {}}, "schema": []}
{"input": "sEphB4 treatment in vivo in the presence and absence of PTH increased osteoblast formation and mRNA levels of early osteoblast markers (Runx2, alkaline phosphatase, Collagen 1 alpha 1, and PTH receptor [PTHR1]), but despite a substantial increase in osteoblast numbers, there was no significant change in bone formation rate or in late markers of osteoblast/osteocyte differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Rather, in the presence of PTH, sEphB4 treatment significantly increased osteoclast formation, an effect that prevented the anabolic effect of PTH, causing instead a decrease in trabecular number.", "output": {"entities": {}}, "schema": []}
{"input": "This enhancement of osteoclastogenesis by sEphB4 was reproduced in vitro but only in the presence of osteoblasts.", "output": {"entities": {}}, "schema": []}
{"input": "These data indicate that ephrinB2/EphB4 signaling within the osteoblast lineage is required for late stages of osteoblast differentiation and, further, restricts the ability of osteoblasts to support osteoclast formation, at least in part by limiting RANKL production.", "output": {"entities": {}}, "schema": []}
{"input": "This indicates a key role for the ephrinB2/EphB4 interaction within the osteoblast lineage in osteoblast differentiation and support of osteoclastogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Bacteriophages as templates for manufacturing supramolecular structures.", "output": {"entities": {}}, "schema": []}
{"input": "SS phages are genetically enginnered by replacing 2 N-terminal amino acids of the p8 coat protein of the fd phage.", "output": {"entities": {"chemical": [{"text": "N", "start": 52, "end": 53}, {"text": "amino acids", "start": 63, "end": 74}]}}, "schema": []}
{"input": "AGE and zeta potential measurements show that SS phages carry at least 1/4 less net negative surface charge than fd phages.", "output": {"entities": {}}, "schema": []}
{"input": "Morphology and thickness of phages are studied at different counterion concentrations (10 (-3), 10 (-2) and 10 (-1) M) by AFM, SEM and immunofluorescence analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Bundles induced by CoCl2 and CaCl2 are either metallized by chemical reduction or biomineralized for apatite-like material formation.", "output": {"entities": {"chemical": [{"text": "CoCl2", "start": 19, "end": 24}, {"text": "CaCl2", "start": 29, "end": 34}]}}, "schema": []}
{"input": "EDX spectroscopy confirms the presence of Co, P and Ca peaks in mineralized samples.", "output": {"entities": {"chemical": [{"text": "Co", "start": 42, "end": 44}, {"text": "P", "start": 46, "end": 47}, {"text": "Ca", "start": 52, "end": 54}]}}, "schema": []}
{"input": "Such bottom-up manufactured phage scaffolds might be applied in bioengineering studies.", "output": {"entities": {}}, "schema": []}
{"input": "Identification, characterization, and isolation of a common progenitor for osteoclasts, macrophages, and dendritic cells from murine bone marrow and periphery.", "output": {"entities": {}}, "schema": []}
{"input": "Osteoclasts are specialized bone-resorbing cells that derive from monocyte precursors.", "output": {"entities": {}}, "schema": []}
{"input": "We have identified three populations of cells with high osteoclastogenic potential in murine bone marrow, which expressed the phenotype B220 (-) CD3 (-) CD11b (-/low) CD115 (+) and either CD117 (hi), CD117 (intermediate), or CD117 (low).", "output": {"entities": {}}, "schema": []}
{"input": "We have evaluated these populations for their ability to also generate macrophages and dendritic cells.", "output": {"entities": {}}, "schema": []}
{"input": "At a single-cell level, the population expressing higher CD117 levels was able to generate bone-resorbing osteoclasts, phagocytic macrophages, and antigen-presenting dendritic cells in vitro with efficiencies of more than 90%, indicating that there exists a common developmental pathway for these cell types.", "output": {"entities": {}}, "schema": []}
{"input": "Cells with osteoclastogenic potential also exist in blood and peripheral hematopoietic organs.", "output": {"entities": {}}, "schema": []}
{"input": "Their functional meaning and/or their relationship with bone marrow progenitors is not well established.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, we characterized murine peripheral cell populations for their ability to form osteoclasts, macrophages, and dendritic cells in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "The spleen and peripheral blood monocyte progenitors share phenotypic markers with bone marrow progenitors but differ in their expression of CD11b, which was low in bone marrow but high in periphery.", "output": {"entities": {}}, "schema": []}
{"input": "We propose that circulating monocyte progenitors are derived from a common bone marrow osteoclasts/macrophage/dendritic cell progenitor (OcMDC), which we have now characterized at a clonal level.", "output": {"entities": {}}, "schema": []}
{"input": "However, the lineage relationship between the bone marrow and peripheral monocyte progenitors has yet to be defined.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicity evaluation of two typical surfactants to Dunaliella bardawil, an environmentally tolerant alga.", "output": {"entities": {}}, "schema": []}
{"input": "Sodium dodecyl benzene sulfonate (SDBS) and cetyl trimethyl ammonium chloride (CTAC) are two kinds of surfactants widely applied in various industries.", "output": {"entities": {"chemical": [{"text": "Sodium dodecyl benzene sulfonate", "start": 0, "end": 32}, {"text": "SDBS", "start": 34, "end": 38}, {"text": "cetyl trimethyl ammonium chloride", "start": 44, "end": 77}, {"text": "CTAC", "start": 79, "end": 83}]}}, "schema": []}
{"input": "The tremendous direct discharge of these surfactants into natural waters has posed a significant threat to ecosystems.", "output": {"entities": {}}, "schema": []}
{"input": "Dunaliella bardawil was employed in the present research to test the toxic effects of SDBS, CTAC, and their mixture on cell growth, cellular morphology, beta-carotene accumulation, and enzymatic activities of superoxide dismutase (SOD) and catalase (CAT).", "output": {"entities": {"chemical": [{"text": "SDBS", "start": 86, "end": 90}, {"text": "CTAC", "start": 92, "end": 96}, {"text": "beta-carotene", "start": 153, "end": 166}, {"text": "superoxide", "start": 209, "end": 219}]}}, "schema": []}
{"input": "The results showed that SDBS at 200, 550, 900, 1, 350, 1, 800, and 2, 400 mg/L and CTAC at 0. 4, 0. 7, 1. 0, 1. 3, 2. 8, and 3. 5 mg/L inhibited algal growth and beta-carotene accumulation, both of which declined and then increased.", "output": {"entities": {"chemical": [{"text": "SDBS", "start": 24, "end": 28}, {"text": "CTAC", "start": 83, "end": 87}, {"text": "beta-carotene", "start": 162, "end": 175}]}}, "schema": []}
{"input": "In particular, CTAC (median inhibitory concentration at 10 days [IC50] (10 d) = 2. 8 +/- 1. 49 mg/L) was more hazardous than SDBS (IC50 (10 d) = 2, 044 +/- 637. 3 mg/L).", "output": {"entities": {"chemical": [{"text": "CTAC", "start": 15, "end": 19}, {"text": "SDBS", "start": 125, "end": 129}]}}, "schema": []}
{"input": "The additive index (AI) calculated from carotene content data was (-4. 10,-1. 67) < 0, indicating an antagonistic effect between SDBS and CTAC.", "output": {"entities": {"chemical": [{"text": "SDBS", "start": 129, "end": 133}, {"text": "CTAC", "start": 138, "end": 142}]}}, "schema": []}
{"input": "Algae cultivated at level 6 of the binary system showed hormesis due to the mitigated toxicity; SDBS at 2, 400 mg/L, CTAC at 3. 5 mg/L, and combined surfactants at level 6 exerted lethal effects on D. bardawil.", "output": {"entities": {"chemical": [{"text": "SDBS", "start": 96, "end": 100}]}}, "schema": []}
{"input": "Both SOD and CAT activities showed similar associations with varied concentrations of surfactants: SOD was significantly promoted by 550 to 1, 800 mg/L SDBS, 0. 7 to 1. 3 mg/L CTAC, and mixtures at levels 2 to 4; CAT was clearly promoted by 900 mg/L SDBS, 0. 4 to 1. 3 mg/L CTAC, and mixtures at levels 2 to 4.", "output": {"entities": {"chemical": [{"text": "SDBS", "start": 152, "end": 156}, {"text": "CTAC", "start": 176, "end": 180}, {"text": "SDBS", "start": 250, "end": 254}, {"text": "CTAC", "start": 274, "end": 278}]}}, "schema": []}
{"input": "Garcinia xanthones as orally active antitumor agents.", "output": {"entities": {"chemical": [{"text": "xanthones", "start": 9, "end": 18}]}}, "schema": []}
{"input": "Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated.", "output": {"entities": {"chemical": [{"text": "hydroxyxanthone", "start": 88, "end": 103}, {"text": "xanthones", "start": 170, "end": 179}, {"text": "gambogic acid", "start": 189, "end": 202}]}}, "schema": []}
{"input": "A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D 7. 4, aqueous solubility, and permeability at pH 7. 4.", "output": {"entities": {}}, "schema": []}
{"input": "In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.", "output": {"entities": {"chemical": [{"text": "gambogic acid", "start": 113, "end": 126}]}}, "schema": []}
{"input": "Absorption, metabolism and excretion of darexaban (YM150), a new direct factor Xa inhibitor in humans.", "output": {"entities": {"chemical": [{"text": "darexaban", "start": 40, "end": 49}, {"text": "YM150", "start": 51, "end": 56}]}}, "schema": []}
{"input": "1. The absorption, metabolism and excretion of darexaban (YM150), a novel oral direct factor Xa inhibitor, were investigated after a single oral administration of [(14) C] darexaban maleate at a dose of 60 mg in healthy male human subjects.", "output": {"entities": {"chemical": [{"text": "darexaban", "start": 47, "end": 56}, {"text": "YM150", "start": 58, "end": 63}, {"text": "[(14) C] darexaban maleate", "start": 163, "end": 189}]}}, "schema": []}
{"input": "2. [(14) C] Darexaban was rapidly absorbed, with both blood and plasma concentrations peaking at approximately 0. 75 h post-dose.", "output": {"entities": {"chemical": [{"text": "[(14) C] Darexaban", "start": 3, "end": 21}]}}, "schema": []}
{"input": "Plasma concentrations of darexaban glucuronide (M1), the pharmacological activity of which is equipotent to darexaban in vitro, also peaked at approximately 0. 75 h.", "output": {"entities": {"chemical": [{"text": "darexaban glucuronide", "start": 25, "end": 46}, {"text": "darexaban", "start": 108, "end": 117}]}}, "schema": []}
{"input": "3. Similar amounts of dosed radioactivity were excreted via faeces (51. 9%) and urine (46. 4%) by 168 h post-dose, suggesting that at least approximately half of the administered dose is absorbed from the gastrointestinal tract.", "output": {"entities": {}}, "schema": []}
{"input": "4. M1 was the major drug-related component in plasma and urine, accounting for up to 95. 8% of radioactivity in plasma.", "output": {"entities": {}}, "schema": []}
{"input": "The N-oxides of M1, a mixture of two diastereomers designated as M2 and M3, were also present in plasma and urine, accounting for up to 13. 2% of radioactivity in plasma.", "output": {"entities": {"chemical": [{"text": "N-oxides", "start": 4, "end": 12}]}}, "schema": []}
{"input": "In faeces, darexaban was the major drug-related component, and N-demethyl darexaban (M5) was detected as a minor metabolite.", "output": {"entities": {"chemical": [{"text": "darexaban", "start": 11, "end": 20}, {"text": "N-demethyl darexaban", "start": 63, "end": 83}]}}, "schema": []}
{"input": "5. These findings suggested that, following oral administration of darexaban in humans, M1 is quickly formed during first-pass metabolism via UDP-glucuronosyltransferases, exerting its pharmacological activity in blood before being excreted into urine and faeces.", "output": {"entities": {"chemical": [{"text": "darexaban", "start": 67, "end": 76}, {"text": "UDP", "start": 142, "end": 145}]}}, "schema": []}
{"input": "Fabrication of 3-dimensional cellular constructs via microstereolithography using a simple, three-component, poly (ethylene glycol) acrylate-based system.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol) acrylate", "start": 109, "end": 140}]}}, "schema": []}
{"input": "A novel method for the production of inhibitor-and solvent-free resins suitable for three-dimensional (3D) microstereolithography is reported.", "output": {"entities": {}}, "schema": []}
{"input": "Using an exemplar poly (ethylene glycol)-based resin, the control of features in the X, Y, and Z planes is demonstrated such that complex structures can be manufactured.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol)", "start": 18, "end": 40}]}}, "schema": []}
{"input": "Human mesenchymal stem cells cultured on the manufactured scaffolds remained viable during the 7 day assessment period, with proliferation rates comparable to those observed on tissue culture polystyrene.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 192, "end": 203}]}}, "schema": []}
{"input": "These data suggest that this novel, yet simple, method is suitable for the production of 3D scaffolds for tissue engineering and regenerative medicine applications.", "output": {"entities": {}}, "schema": []}
{"input": "8, 8-dialkyldihydroberberines with potent antiprotozoal activity.", "output": {"entities": {"chemical": [{"text": "8, 8-dialkyldihydroberberines", "start": 0, "end": 29}]}}, "schema": []}
{"input": "Semisynthetic 8, 8-dialkyldihydroberberines (8, 8-DDBs) were found to possess mid-to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms.", "output": {"entities": {"chemical": [{"text": "8, 8-dialkyldihydroberberines", "start": 14, "end": 43}, {"text": "8, 8-DDBs", "start": 45, "end": 54}]}}, "schema": []}
{"input": "For example, 8, 8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5. 3 nM against these three parasites, respectively.", "output": {"entities": {"chemical": [{"text": "8, 8-diethyldihydroberberine chloride", "start": 13, "end": 50}]}}, "schema": []}
{"input": "In turn, two 8, 8-dialkylcanadines, obtained by reduction of the corresponding 8, 8-DDBs, were much less potent against these parasites in vitro.", "output": {"entities": {"chemical": [{"text": "8, 8-dialkylcanadines", "start": 13, "end": 34}, {"text": "8, 8-DDBs", "start": 79, "end": 88}]}}, "schema": []}
{"input": "While the natural product berberine is a weak DNA binder, the 8, 8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly (dA. dT) DNA.", "output": {"entities": {"chemical": [{"text": "8, 8-DDBs", "start": 62, "end": 71}, {"text": "poly (dA. dT)", "start": 156, "end": 169}]}}, "schema": []}
{"input": "Selected 8, 8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8, 8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days.", "output": {"entities": {"chemical": [{"text": "8, 8-DDBs", "start": 9, "end": 18}, {"text": "8, 8-dimethyldihydroberberine chloride", "start": 111, "end": 149}]}}, "schema": []}
{"input": "The 8, 8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.", "output": {"entities": {}}, "schema": []}
{"input": "Stiripentol is anticonvulsant by potentiating GABAergic transmission in a model of benzodiazepine-refractory status epilepticus.", "output": {"entities": {"chemical": [{"text": "Stiripentol", "start": 0, "end": 11}, {"text": "benzodiazepine", "start": 83, "end": 97}]}}, "schema": []}
{"input": "Benzodiazepines (BZDs) are first-line therapy for treatment of status epilepticus (SE).", "output": {"entities": {"chemical": [{"text": "Benzodiazepines", "start": 0, "end": 15}, {"text": "BZDs", "start": 17, "end": 21}]}}, "schema": []}
{"input": "However, BZD treatment is negatively affected by seizure duration due to decreases in BZD-sensitive GABA (A) receptors during prolonged SE.", "output": {"entities": {"chemical": [{"text": "BZD", "start": 9, "end": 12}, {"text": "BZD", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Stiripentol (STP) is an anticonvulsant that is used as add-on treatment for Dravet Syndrome.", "output": {"entities": {"chemical": [{"text": "Stiripentol", "start": 0, "end": 11}, {"text": "STP", "start": 13, "end": 16}]}}, "schema": []}
{"input": "Recent studies have shown that STP is a positive allosteric modulator of the GABA (A) receptor.", "output": {"entities": {"chemical": [{"text": "STP", "start": 31, "end": 34}]}}, "schema": []}
{"input": "The subunit selectivity of STP at this receptor suggests that it would be anticonvulsant in both brief as well as prolonged SE.", "output": {"entities": {"chemical": [{"text": "STP", "start": 27, "end": 30}]}}, "schema": []}
{"input": "We tested this possibility by comparing the ability of STP and diazepam (DZP), a commonly used BZD, to terminate behavioral convulsions in a rodent model of pharmacoresistant SE.", "output": {"entities": {"chemical": [{"text": "STP", "start": 55, "end": 58}, {"text": "diazepam", "start": 63, "end": 71}, {"text": "DZP", "start": 73, "end": 76}, {"text": "BZD", "start": 95, "end": 98}]}}, "schema": []}
{"input": "We found that STP was anticonvulsant in this model and remained effective during prolonged SE, unlike DZP which exhibited a 14 fold increase in its ED (50).", "output": {"entities": {"chemical": [{"text": "STP", "start": 14, "end": 17}, {"text": "DZP", "start": 102, "end": 105}]}}, "schema": []}
{"input": "Whole cell recording from hippocampal slices from these animals revealed that STP potentiated GABAergic IPSCs, as well as tonic GABAergic current by acting at a site on the GABA (A) receptor separate from the BDZ binding site.", "output": {"entities": {"chemical": [{"text": "STP", "start": 78, "end": 81}, {"text": "BDZ", "start": 209, "end": 212}]}}, "schema": []}
{"input": "Potentiation of GABAergic currents by STP remained intact during prolonged SE, while potentiation by DZP was lost.", "output": {"entities": {"chemical": [{"text": "STP", "start": 38, "end": 41}, {"text": "DZP", "start": 101, "end": 104}]}}, "schema": []}
{"input": "Both IPSC potentiation and anticonvulsant activity of STP were greater in younger animals than in adults.", "output": {"entities": {"chemical": [{"text": "STP", "start": 54, "end": 57}]}}, "schema": []}
{"input": "These findings suggest that at doses that yield therapeutically relevant concentrations, STP is anticonvulsant by potentiating GABAergic inhibition and that the subunit selectivity profile of STP enables it to remain effective despite GABA (A) receptor subunit changes during prolonged SE.", "output": {"entities": {"chemical": [{"text": "STP", "start": 89, "end": 92}, {"text": "STP", "start": 192, "end": 195}]}}, "schema": []}
{"input": "Regulation of serotonin (5-HT) function by a VGLUT1 dependent glutamate pathway.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 14, "end": 23}, {"text": "5-HT", "start": 25, "end": 29}, {"text": "glutamate", "start": 62, "end": 71}]}}, "schema": []}
{"input": "Unraveling the mechanisms of 5-HT neuron control might provide new insights into depression pathophysiology.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 29, "end": 33}]}}, "schema": []}
{"input": "In addition to the inhibitory 5-HT1A autoreceptors, cortico-raphe glutamatergic descending pathways are suggested to modulate 5-HT activity in the DRN.", "output": {"entities": {"chemical": [{"text": "5-HT1A", "start": 30, "end": 36}]}}, "schema": []}
{"input": "Here we studied how decreased VGLUT1 levels in the brain stem affect glutamate regulation of 5-HT function.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 69, "end": 78}, {"text": "5-HT", "start": 93, "end": 97}]}}, "schema": []}
{"input": "VGLUT1 +/-mice (C57BL/6) and wild type (WT) littermates were used.", "output": {"entities": {}}, "schema": []}
{"input": "VGLUT1 expression in the DRN, 5-HT turnover and immuno histochemical analysis of neuronal activity in different areas was studied.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 30, "end": 34}]}}, "schema": []}
{"input": "Moreover, the functionality of the inhibitory 5-HT1A autoreceptor was assessed using electrophysiological, biochemical and pharmacological approaches.", "output": {"entities": {}}, "schema": []}
{"input": "VGLUT1 immunoreactivity was markedly lower in the DRN of the VGLUT1 +/-mice and specifically, in the surroundings of GABA and 5-HT cell bodies.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 117, "end": 121}, {"text": "5-HT", "start": 126, "end": 130}]}}, "schema": []}
{"input": "These mice showed decreased induced neuronal activity in 5-HT cells bodies and in different forebrain areas, as well as decreased hippocampal cell proliferation and 5-HT turnover.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 57, "end": 61}, {"text": "5-HT", "start": 165, "end": 169}]}}, "schema": []}
{"input": "Further, 5-HT1A autoreceptor desensitization was evidenced by electrophysiological studies, GTP-gamma-S coupling to 5-HT1A autoreceptor and a lower hypothermic response to 5-HT1A activation.", "output": {"entities": {"chemical": [{"text": "GTP-gamma-S", "start": 92, "end": 103}]}}, "schema": []}
{"input": "This study shows first time that VGLUT1 dependent glutamate innervation of the DRN could modulate 5-HT function.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 50, "end": 59}, {"text": "5-HT", "start": 98, "end": 102}]}}, "schema": []}
{"input": "Solid-state NMR studies of micelle-templated mesoporous solids.", "output": {"entities": {}}, "schema": []}
{"input": "In this tutorial review we intend to give an overview of the potential of NMR spectroscopy, and in particular solid-state NMR, in characterising micelle-templated mesoporous materials.", "output": {"entities": {}}, "schema": []}
{"input": "Different topics are covered including the study of formation mechanisms, the characterisation of structures, textures, surfaces and interfaces, functionalisation, dynamic properties and structure-reactivity correlations.", "output": {"entities": {}}, "schema": []}
{"input": "Some selected examples illustrate the variety of information provided by this spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Particular attention is paid to recent technological and/or methodological developments.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role of cytochrome P450s and alcohol dehydrogenase in biotransformation.", "output": {"entities": {"chemical": [{"text": "3-n-butylphthalide", "start": 35, "end": 53}, {"text": "NBP", "start": 55, "end": 58}, {"text": "alcohol", "start": 104, "end": 111}]}}, "schema": []}
{"input": "3-n-Butylphthalide (NBP) is a cardiovascular drug currently used for the treatment of cerebral ischemia.", "output": {"entities": {"chemical": [{"text": "3-n-Butylphthalide", "start": 0, "end": 18}, {"text": "NBP", "start": 20, "end": 23}]}}, "schema": []}
{"input": "The present study aims to investigate the metabolism, pharmacokinetics, and excretion of NBP in humans and identify the enzymes responsible for the formation of major metabolites.", "output": {"entities": {"chemical": [{"text": "NBP", "start": 89, "end": 92}]}}, "schema": []}
{"input": "NBP underwent extensive metabolism after an oral administration of 200 mg NBP and 23 metabolites were identified in human plasma and urine.", "output": {"entities": {"chemical": [{"text": "NBP", "start": 0, "end": 3}, {"text": "NBP", "start": 74, "end": 77}]}}, "schema": []}
{"input": "Principal metabolic pathways included hydroxylation on alkyl side chain, particularly at 3-, omega-1-, and omega-carbons, and further oxidation and conjugation.", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 55, "end": 60}, {"text": "3-, omega-1-, and omega-carbons", "start": 89, "end": 120}]}}, "schema": []}
{"input": "Approximately 81. 6% of the dose was recovered in urine, mainly as NBP-11-oic acid (M5-2) and glucuronide conjugates of M5-2 and mono-hydroxylated products.", "output": {"entities": {"chemical": [{"text": "NBP-11-oic acid", "start": 67, "end": 82}]}}, "schema": []}
{"input": "10-Keto-NBP (M2), 3-hydroxy-NBP (M3-1), 10-hydroxy-NBP (M3-2), and M5-2 were the major circulating metabolites, wherein the areas under the curve values were 1. 6-, 2. 9-, 10. 3-, and 4. 1-fold higher than that of NBP.", "output": {"entities": {"chemical": [{"text": "10-Keto-NBP", "start": 0, "end": 11}, {"text": "3-hydroxy-NBP", "start": 18, "end": 31}, {"text": "10-hydroxy-NBP", "start": 40, "end": 54}, {"text": "NBP", "start": 214, "end": 217}]}}, "schema": []}
{"input": "Reference standards of these four metabolites were obtained through microbial biotransformation by Cunninghamella blakesleana.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro phenotyping studies demonstrated that multiple cytochrome P450 (P450) isoforms, especially CYP3A4, 2E1, and 1A2, were involved in the formation of M3-1, M3-2, and 11-hydroxy-NBP.", "output": {"entities": {"chemical": [{"text": "11-hydroxy-NBP", "start": 172, "end": 186}]}}, "schema": []}
{"input": "Using M3-2 and 11-hydroxy-NBP as substrates, human subcellular fractions experiments revealed that P450, alcohol dehydrogenase, and aldehyde dehydrogenase catalyzed the generation of M2 and M5-2.", "output": {"entities": {"chemical": [{"text": "11-hydroxy-NBP", "start": 15, "end": 29}, {"text": "alcohol", "start": 105, "end": 112}, {"text": "aldehyde", "start": 132, "end": 140}]}}, "schema": []}
{"input": "Formation of M5-2 was much faster than that of M2, and M5-2 can undergo beta-oxidation to yield phthalide-3-acetic acid in rat liver homogenate.", "output": {"entities": {"chemical": [{"text": "phthalide-3-acetic acid", "start": 96, "end": 119}]}}, "schema": []}
{"input": "Overall, our study demonstrated that NBP was well absorbed and extensively metabolized by multiple enzymes to various metabolites prior to urinary excretion.", "output": {"entities": {"chemical": [{"text": "NBP", "start": 37, "end": 40}]}}, "schema": []}
{"input": "Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects.", "output": {"entities": {"chemical": [{"text": "ertugliflozin", "start": 70, "end": 83}, {"text": "PF-04971729", "start": 85, "end": 96}]}}, "schema": []}
{"input": "The disposition of ertugliflozin (PF-04971729), an orally active selective inhibitor of the sodium-dependent glucose cotransporter 2, was studied after a single 25-mg oral dose of [(14) C]-ertugliflozin to healthy human subjects.", "output": {"entities": {"chemical": [{"text": "ertugliflozin", "start": 19, "end": 32}, {"text": "PF-04971729", "start": 34, "end": 45}, {"text": "sodium", "start": 92, "end": 98}, {"text": "glucose", "start": 109, "end": 116}, {"text": "[(14) C]-ertugliflozin", "start": 180, "end": 202}]}}, "schema": []}
{"input": "Mass balance was achieved with approximately 91% of the administered dose recovered in urine and feces.", "output": {"entities": {}}, "schema": []}
{"input": "The total administered radioactivity excreted in feces and urine was 40. 9% and 50. 2%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The absorption of ertugliflozin in humans was rapid with a T (max) at ~ 1. 0 hour.", "output": {"entities": {"chemical": [{"text": "ertugliflozin", "start": 18, "end": 31}]}}, "schema": []}
{"input": "Of the total radioactivity excreted in feces and urine, unchanged ertugliflozin collectively accounted for ~ 35. 3% of the dose, suggestive of moderate metabolic elimination in humans.", "output": {"entities": {"chemical": [{"text": "ertugliflozin", "start": 66, "end": 79}]}}, "schema": []}
{"input": "The principal biotransformation pathway involved glucuronidation of the glycoside hydroxyl groups to yield three regioisomeric metabolites, M4a, M4b, and M4c (~ 39. 3% of the dose in urine), of which M4c was the major regioisomer (~ 31. 7% of the dose).", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 82, "end": 90}]}}, "schema": []}
{"input": "The structure of M4a and M4c were confirmed to be ertugliflozin-4-O-beta-and-3-O-beta-glucuronide, respectively, via comparison of the HPLC retention time and mass spectra with authentic standards.", "output": {"entities": {"chemical": [{"text": "ertugliflozin-4-O-beta-and-3-O-beta-glucuronide", "start": 50, "end": 97}]}}, "schema": []}
{"input": "A minor metabolic fate involved oxidation by cytochrome P450 to yield monohydroxylated metabolites M1 and M3 and des-ethyl ertugliflozin (M2), which accounted for ~ 5. 2% of the dose in excreta.", "output": {"entities": {"chemical": [{"text": "des-ethyl ertugliflozin", "start": 113, "end": 136}]}}, "schema": []}
{"input": "In plasma, unchanged ertugliflozin and the corresponding 4-O-beta-(M4a) and 3-O-beta-(M4c) glucuronides were the principal components, which accounted for 49. 9, 12. 2, and 24. 1% of the circulating radioactivity.", "output": {"entities": {"chemical": [{"text": "ertugliflozin", "start": 21, "end": 34}]}}, "schema": []}
{"input": "Overall, these data suggest that ertugliflozin is well absorbed in humans, and eliminated largely via glucuronidation.", "output": {"entities": {}}, "schema": []}
{"input": "The role of cytochrome P450-dependent metabolism in the regulation of mouse hepatic growth hormone signaling components and target genes by 3-methylcholanthrene.", "output": {"entities": {"chemical": [{"text": "3-methylcholanthrene", "start": 140, "end": 160}]}}, "schema": []}
{"input": "3-Methylcholanthrene (MC) is a readily metabolized aryl hydrocarbon receptor (AHR) agonist.", "output": {"entities": {"chemical": [{"text": "3-Methylcholanthrene", "start": 0, "end": 20}, {"text": "aryl hydrocarbon", "start": 51, "end": 67}]}}, "schema": []}
{"input": "MC disrupts expression of mouse hepatic growth hormone (GH) signaling components and suppresses cytochrome P450 2D9 (Cyp2d9), a male-specific gene controlled by pulsatile GH via signal transducer and activator of transcription 5b (STAT5b).", "output": {"entities": {}}, "schema": []}
{"input": "To determine if these effects of MC depend on hepatic microsomal P450-mediated activity, we examined biologic responses to MC treatment in liver Cpr-null (LCN) mice with hepatocyte-specific conditional deletion of NADPH-cytochrome P450 oxidoreductase (POR).", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 214, "end": 219}]}}, "schema": []}
{"input": "MC caused mild induction of Por and a hepatic inflammatory marker in wild-type mice, whereas MC caused strong induction of AHR target genes, Cyp1a1, Cyp1a2, and Cyp1b1 in wild-type and LCN mice.", "output": {"entities": {}}, "schema": []}
{"input": "Two mouse hepatic STAT5b target genes, Cyp2d9 and major urinary protein 2 (Mup2), were suppressed by MC in wild-type mice, and the CYP2D9 mRNA response was maintained in LCN mice.", "output": {"entities": {}}, "schema": []}
{"input": "In wild-type mice only, MC decreased hepatic GH receptor (GHR) mRNA but increased GHR protein levels.", "output": {"entities": {}}, "schema": []}
{"input": "There was an apparent impairment of STAT5 phosphorylation by MC in wild-type and LCN mice, but large interanimal variation prevented achievement of statistical significance.", "output": {"entities": {}}, "schema": []}
{"input": "In vehicle-treated mice, basal levels of MUP2 mRNA, GHR mRNA, GHR protein, and the activation status of extracellular signal-regulated kinase 2 and Akt were influenced by hepatic Por genetic status.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that the effects of MC on hepatic GH signaling components and target genes are complex, involving aspects that are both dependent and independent of hepatic microsomal P450-mediated activity.", "output": {"entities": {}}, "schema": []}
{"input": "Stroke prevention: from available antiplatelet drugs to novel molecular targets.", "output": {"entities": {}}, "schema": []}
{"input": "Stroke is the third most common cause of death in the industrialized countries and adequate primary and secondary prevention strategies are mandatory.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to lifestyle-changes and correction of cardiovascular risk factors, the mainstay of the atherothrombotic stroke prevention is represented by antiplatelet treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Although aspirin and thienopyridines have proved their efficacy in the prevention of arterial thrombotic events, limited efficacy, increased risk of bleeding, significant inter-individual variability in the response and extended duration of action that cannot be reversed if the need for haemostasis or emergency surgery arises represent major limitations of these drugs.", "output": {"entities": {"chemical": [{"text": "aspirin", "start": 9, "end": 16}, {"text": "thienopyridines", "start": 21, "end": 36}]}}, "schema": []}
{"input": "Moreover, despite recommendations and guidelines about stroke prevention, registries data clearly suggest an underuse of antiplatelet drugs, mainly because of bleeding episodes fear.", "output": {"entities": {}}, "schema": []}
{"input": "At variance with newer anticoagulant drugs, which showed a series of advantages as compared with the traditional warfarin treatment, newer antiplatelet drugs have only partially overcome these limitations.", "output": {"entities": {"chemical": [{"text": "warfarin", "start": 113, "end": 121}]}}, "schema": []}
{"input": "Although ad hoc studies on their efficacy in the stroke prevention are currently lacking, newer antiplatelet agents (mainly ticagrelor and prasugrel) do not provide a significant better protection over and above aspirin and/or clopidogrel in the prevention of atherothrombotic stroke.", "output": {"entities": {"chemical": [{"text": "ticagrelor", "start": 124, "end": 134}, {"text": "prasugrel", "start": 139, "end": 148}, {"text": "aspirin", "start": 212, "end": 219}, {"text": "clopidogrel", "start": 227, "end": 238}]}}, "schema": []}
{"input": "In addition, a significantly increased bleeding risk has been reported in subjects receiving these new thienopyridines.", "output": {"entities": {"chemical": [{"text": "thienopyridines", "start": 103, "end": 118}]}}, "schema": []}
{"input": "According to these data, the identification of further molecular targets is needed, in order to design future antiplatelet drugs.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, after summarizing major literature data about traditional and newer antiplatelet drugs, we will specifically focus on novel potential target candidates for antiplatelet therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Spo0A links de novo fatty acid synthesis to sporulation and biofilm development in Bacillus subtilis.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 20, "end": 30}]}}, "schema": []}
{"input": "During sporulation in Bacillus subtilis, the committed-cell undergoes substantial membrane rearrangements to generate two cells of different sizes and fates: the mother cell and the forespore.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate that the master transcription factor Spo0A reactivates lipid synthesis during development.", "output": {"entities": {}}, "schema": []}
{"input": "Maximal Spo0A-dependent lipid synthesis occurs during the key stages of asymmetric division and forespore engulfment.", "output": {"entities": {}}, "schema": []}
{"input": "Spo0A reactivates the accDA operon that encodes the carboxylase component of the acetyl-CoA carboxylase enzyme, which catalyses the first and rate-limiting step in de novo lipid biosynthesis, malonyl-CoA formation.", "output": {"entities": {"chemical": [{"text": "acetyl-CoA", "start": 81, "end": 91}, {"text": "malonyl-CoA", "start": 192, "end": 203}]}}, "schema": []}
{"input": "The disruption of the Spo0A-binding box in the promoter region of accDA impairs its transcriptional reactivation and blocks lipid synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "The Spo0A-insensitive accDA (0A) cells were proficient in planktonic growth but defective in sporulation (sigma (E) activation) and biofilm development (cell cluster formation and water repellency).", "output": {"entities": {}}, "schema": []}
{"input": "Exogenous fatty acid supplementation to accDA (0A) cells overcomes their inability to synthesize lipids during development and restores sporulation and biofilm proficiencies.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 10, "end": 20}]}}, "schema": []}
{"input": "The transient exclusion of the lipid synthesis regulon from the forespore and the known compartmentalization of Spo0A and ACP in the mother cell suggest that de novo lipid synthesis is confined to the mother cell.", "output": {"entities": {}}, "schema": []}
{"input": "The significance of the Spo0A-controlled de novo lipid synthesis during B. subtilis development is discussed.", "output": {"entities": {}}, "schema": []}
{"input": "The mycobacterial binuclear iron monooxygenases require a specific chaperonin-like protein for functional expression in a heterologous host.", "output": {"entities": {"chemical": [{"text": "iron", "start": 28, "end": 32}]}}, "schema": []}
{"input": "The mimABCD gene clusters in Mycobacterium smegmatis strain mc (2) 155 and Mycobacterium goodii strain 12523 encode binuclear iron monooxygenases that oxidize propane and phenol.", "output": {"entities": {"chemical": [{"text": "iron", "start": 126, "end": 130}, {"text": "propane", "start": 159, "end": 166}, {"text": "phenol", "start": 171, "end": 177}]}}, "schema": []}
{"input": "In this study, we attempted to express each mimABCD gene cluster in a heterologous host.", "output": {"entities": {}}, "schema": []}
{"input": "The actinomycetous strain Rhodococcus opacus B-4, which is phylogenetically close to Mycobacterium, was selected as the host.", "output": {"entities": {}}, "schema": []}
{"input": "Each mimABCD gene cluster was cloned into the Rhodococcus-Escherichia coli shuttle vector, pTip-QC2, and then introduced into R. opacus cells.", "output": {"entities": {}}, "schema": []}
{"input": "Although whole-cell assays were performed with phenol as a substrate, the transformed R. opacus cells did not oxidize this substrate.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 47, "end": 53}]}}, "schema": []}
{"input": "SDS/PAGE analysis revealed that the oxygenase large subunit MimA was expressed in the insoluble fraction of R. opacus cells.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 0, "end": 3}]}}, "schema": []}
{"input": "We found that a gene designated mimG, which lies downstream of mimABCD, exhibits similarity in the amino acid sequence of its product with the products of genes encoding the chaperonin GroEL.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 99, "end": 109}]}}, "schema": []}
{"input": "When the mimG gene was cloned and coexpressed with each mimABCD gene cluster in R. opacus strain B-4, this host successfully acquired oxidation activity towards phenol.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 161, "end": 167}]}}, "schema": []}
{"input": "SDS/PAGE and western blotting analyses demonstrated that MimA was clearly soluble when in the presence of MimG.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 0, "end": 3}]}}, "schema": []}
{"input": "These results indicated that MimG played essential roles in the productive folding of MimA, and that the resulting soluble MimA protein led to the active expression of MimABCD.", "output": {"entities": {}}, "schema": []}
{"input": "Assessment of pre-and postoperative endocrine function in 94 patients with Rathke' s cleft cyst.", "output": {"entities": {}}, "schema": []}
{"input": "We reviewed 94 patients with Rathke' s cleft cyst (RCC) who were surgically treated at Nippon Medical School Hospital between December 1995 and July 2009 to clarify the effect of surgery on their endocrine function.", "output": {"entities": {}}, "schema": []}
{"input": "In our statistical analysis we considered their age and sex, the cyst volume, and preoperative MRI findings.", "output": {"entities": {}}, "schema": []}
{"input": "Using simple linear-and multiple regression analysis we evaluated the association between these factors and their preoperative hormone baseline levels.", "output": {"entities": {}}, "schema": []}
{"input": "To assess pre-and postoperative anterior pituitary function we subjected the results of various hormone loading tests to the Wilcoxon rank sum test.", "output": {"entities": {}}, "schema": []}
{"input": "Surgery improved headache and visual impairment in most patients and elevated PRL levels were significantly normalized after surgery (p = 0. 004).", "output": {"entities": {}}, "schema": []}
{"input": "However, pre-and postoperative anterior pituitary hormone loading tests revealed that the levels of GH, TSH, LH, and FSH were not improved significantly by surgery.", "output": {"entities": {}}, "schema": []}
{"input": "Although the ACTH loading test showed postoperative improvement, the change was not statistically significant.", "output": {"entities": {}}, "schema": []}
{"input": "We suggest that RCC patients with headache or visual impairment are good candidates for surgery.", "output": {"entities": {}}, "schema": []}
{"input": "We also recommend that patients with hyperprolactinemia and those with ACTH deficiency whose MRI findings reveal low-intensity on T1WI and high-intensity on T2WI are likely to benefit from surgery.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, RCC patients with other hormone dysfunctions do not appear to benefit from surgical intervention.", "output": {"entities": {}}, "schema": []}
{"input": "High electrochemical performance based on ultrathin porous CuO nanobelts grown on Cu substrate as integrated electrode.", "output": {"entities": {"chemical": [{"text": "CuO", "start": 59, "end": 62}, {"text": "Cu", "start": 82, "end": 84}]}}, "schema": []}
{"input": "A facile and low-cost approach has been developed to fabricate porous CuO nanobelts directly grown on a Cu substrate.", "output": {"entities": {"chemical": [{"text": "CuO", "start": 70, "end": 73}, {"text": "Cu", "start": 104, "end": 106}]}}, "schema": []}
{"input": "The as-prepared CuO samples can be directly used as integrated electrodes for lithium-ion batteries and pseudo-supercapacitors without the addition of other ancillary materials such as carbon black or a binder to enhance electrode conductivity and cycling stability.", "output": {"entities": {"chemical": [{"text": "CuO", "start": 16, "end": 19}, {"text": "lithium", "start": 78, "end": 85}, {"text": "carbon black", "start": 185, "end": 197}]}}, "schema": []}
{"input": "The unique nanostructural features endow them with excellent electrochemical performance as demonstrated by high capacities of 640 mA h g (-1) after 100 cycles at 0. 2 C rate and an excellent specific capacitance of 340 F g (-1), which corresponds to the energy density of 45 W h kg (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The cyclability of the electrode demonstrates only a 10-15% loss in capacitance over 5000 cycles.", "output": {"entities": {}}, "schema": []}
{"input": "On the origin of the halo stabilization.", "output": {"entities": {}}, "schema": []}
{"input": "Monte Carlo simulations show that charge-regulation alone can cause highly charged zirconium nanoparticles to adsorb to a similarly charged or neutral silica particle and thereby stabilizing the latter.", "output": {"entities": {"chemical": [{"text": "zirconium", "start": 83, "end": 92}, {"text": "silica", "start": 151, "end": 157}]}}, "schema": []}
{"input": "This mechanism, referred to as halo stabilization, is quite general and applicable in a range of systems provided that pH, van der Waals forces, and dissociation constants of the charge-regulating particles are properly chosen.", "output": {"entities": {}}, "schema": []}
{"input": "In our modeling we see an overall attraction at low volume fractions of nanoparticles, while at higher a repulsive barrier is created, stabilizing the microparticles and protecting them from aggregation.", "output": {"entities": {}}, "schema": []}
{"input": "The charge-regulation mechanism also turns the silica surface from positively charged, without nanoparticles, to negatively charged in the presence of nanoparticles.", "output": {"entities": {"chemical": [{"text": "silica", "start": 47, "end": 53}]}}, "schema": []}
{"input": "Comparison of splicing factor 3b inhibitors in human cells.", "output": {"entities": {}}, "schema": []}
{"input": "Name your splice: FR901464 analogues and herboxidiene inhibit constitutive splicing, most likely by inhibiting spliceosomal subunit SF3b.", "output": {"entities": {"chemical": [{"text": "FR901464", "start": 18, "end": 26}, {"text": "herboxidiene", "start": 41, "end": 53}]}}, "schema": []}
{"input": "A parallel comparison of these compounds in a cell-based assay system showed meayamycin B as the most potent splicing inhibitor among these small molecules.", "output": {"entities": {"chemical": [{"text": "meayamycin B", "start": 77, "end": 89}]}}, "schema": []}
{"input": "Contaminant-mobilizing capability of fullerene nanoparticles (nC60): Effect of solvent-exchange process in nC60 formation.", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 37, "end": 46}, {"text": "nC60", "start": 62, "end": 66}, {"text": "nC60", "start": 107, "end": 111}]}}, "schema": []}
{"input": "Fullerene nanoparticles (nC (60)) in aqueous environments can significantly enhance the transport of hydrophobic organic contaminants by serving as a contaminant carrier.", "output": {"entities": {"chemical": [{"text": "Fullerene", "start": 0, "end": 9}, {"text": "nC (60)", "start": 25, "end": 32}]}}, "schema": []}
{"input": "In the present study, the authors examine the effect of the solvent-exchange process on nC (60) aggregate formation and, subsequently, on nC (60)' s contaminant-mobilizing capability.", "output": {"entities": {"chemical": [{"text": "nC (60)", "start": 88, "end": 95}, {"text": "nC (60)", "start": 138, "end": 145}]}}, "schema": []}
{"input": "A series of nC (60) samples were prepared using a modified toluene-water solvent-exchange method through the inclusion of a secondary organic solvent in the phase transfer of molecular C (60) in toluene to nC (60) in water.", "output": {"entities": {"chemical": [{"text": "nC (60)", "start": 12, "end": 19}, {"text": "toluene", "start": 59, "end": 66}, {"text": "C (60)", "start": 185, "end": 191}, {"text": "toluene", "start": 195, "end": 202}, {"text": "nC (60)", "start": 206, "end": 213}]}}, "schema": []}
{"input": "Two groups of solvents--a water-miscible group and a non-water-miscible group-of varied polarity were selected as secondary solvents.", "output": {"entities": {}}, "schema": []}
{"input": "The involvement of a secondary solvent in the phase transfer process had only small effects on the particle size and distribution, zeta potential, and mobility of the nC (60) products but significantly influenced the capability of nC (60) to enhance the transport of 2, 2', 5, 5'-polychlorinated biphenyl (PCB) in a saturated sandy soil column, regardless of whether the secondary solvent was water-miscible or non-water-miscible.", "output": {"entities": {"chemical": [{"text": "nC (60)", "start": 167, "end": 174}, {"text": "nC (60)", "start": 231, "end": 238}, {"text": "2, 2', 5, 5'-polychlorinated biphenyl", "start": 267, "end": 304}, {"text": "PCB", "start": 306, "end": 309}]}}, "schema": []}
{"input": "The two groups of secondary solvents appear to affect the aggregation properties of nC (60) in water via different mechanisms.", "output": {"entities": {"chemical": [{"text": "nC (60)", "start": 84, "end": 91}]}}, "schema": []}
{"input": "In general, nC (60) products made with a secondary water-miscible solvent have stronger capabilities to enhance PCB transport.", "output": {"entities": {"chemical": [{"text": "nC (60)", "start": 12, "end": 19}, {"text": "PCB", "start": 112, "end": 115}]}}, "schema": []}
{"input": "Taken together, the results indicate that according to formation conditions and solvent constituents, nC (60) will vary significantly in its interactions with organic contaminants, specifically as related to adsorption or desorption as well as transport in porous media.", "output": {"entities": {"chemical": [{"text": "nC (60)", "start": 102, "end": 109}]}}, "schema": []}
{"input": "Evaluation of whole effluent toxicity data characteristics and use of Welch' s T-test in the test of significant toxicity analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The U. S.", "output": {"entities": {}}, "schema": []}
{"input": "Environmental Protection Agency (U. S. EPA) and state agencies evaluate the toxicity of effluent and surface water samples based on statistical endpoints derived from multiconcentration tests (e. g., no observed effect concentration, EC25).", "output": {"entities": {}}, "schema": []}
{"input": "The test of significant toxicity (TST) analysis is a two-sample comparison test that uses Welch' s t test to compare organism responses in a sample (effluent or surface water) with responses in a control or site sample.", "output": {"entities": {}}, "schema": []}
{"input": "In general, any form of t test (Welch' s t included) is appropriate only if the data meet assumptions of normality and homogeneous variances.", "output": {"entities": {}}, "schema": []}
{"input": "Otherwise, nonparametric tests are recommended.", "output": {"entities": {}}, "schema": []}
{"input": "TST was designed to use Welch' s t as the statistical test for all whole effluent toxicity (WET) test data.", "output": {"entities": {}}, "schema": []}
{"input": "The authors evaluated the suitability of using Welch' s t test for analyzing two-sample toxicity (WET) data, and within the TST approach, by examining the distribution and variances of data from over 2, 000 WET tests and by conducting multiple simulations of WET test data.", "output": {"entities": {}}, "schema": []}
{"input": "Simulated data were generated having variances and nonnormal distributions similar to observed WET test data for control and the effluent treatment groups.", "output": {"entities": {}}, "schema": []}
{"input": "The authors demonstrate that (1) moderately unequal variances (similar to WET data) have little effect on coverage of the t test or Welch t test (for normally distributed data), and (2) for nonnormally distributed data (similar in distribution to WET data) TST, using Welch' s t test, has close to nominal coverage on the basis of simulations with up to a ninefold difference in variance between the effluent and control groups (~ 95th percentile based on observed WET test data).", "output": {"entities": {}}, "schema": []}
{"input": "Xenobiotic receptor humanized mice and their utility.", "output": {"entities": {}}, "schema": []}
{"input": "The nuclear receptors pregnane X receptor, constitutive androstane receptor, and peroxisome proliferator-activated receptor alpha have important endogenous functions and are also involved in the induction of drug-metabolizing enzymes and transporters in response to exogenous xenobiotics.", "output": {"entities": {"chemical": [{"text": "androstane", "start": 56, "end": 66}]}}, "schema": []}
{"input": "Though not belonging to the same protein family, the Per-Sim-ARNT domain receptor aryl hydrocarbon receptor functionally overlaps with the three nuclear receptors in many aspects and is therefore included in this review.", "output": {"entities": {"chemical": [{"text": "aryl hydrocarbon", "start": 82, "end": 98}]}}, "schema": []}
{"input": "Significant species differences in ligand affinity and biological responses as a result of activation of these receptors have been described.", "output": {"entities": {}}, "schema": []}
{"input": "Several xenobiotic receptor humanized mice have been created to overcome these species differences and to provide in vivo models that are more predictive for human responses.", "output": {"entities": {}}, "schema": []}
{"input": "This review provides an overview of the different xenobiotic receptor humanized mouse models described to date and will summarize how these models can be applied in basic research and improve drug discovery and development.", "output": {"entities": {}}, "schema": []}
{"input": "Some of the key applications in the evaluation of drug induction, drug-drug interactions, nongenotoxic carcinogenicity, other toxicity, or efficacy studies are described.", "output": {"entities": {}}, "schema": []}
{"input": "We also discuss relevant considerations in the interpretation of such data and potential future directions for the use of xenobiotic receptor humanized mice.", "output": {"entities": {}}, "schema": []}
{"input": "The relationship between carotid intima-media thickness and endogenous androgens in young women with polycystic ovary syndrome in Taiwan.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 71, "end": 80}]}}, "schema": []}
{"input": "Polycystic ovary syndrome (PCOS) is a common and complex female endocrinopathy that is associated with multiple vascular risk factors.", "output": {"entities": {}}, "schema": []}
{"input": "Our objective was to investigate the relationship between carotid intima-media thickness (CIMT) and endogenous androgens in young Taiwanese-Chinese women with PCOS.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 111, "end": 120}]}}, "schema": []}
{"input": "We measured CIMT with B-mode ultrasound in 42 young PCOS patients and 43 controls.", "output": {"entities": {}}, "schema": []}
{"input": "Atherosclerosis-associated profiles and endocrinological parameters were also measured.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that although Taiwanese-Chinese PCOS patients tend to possess more risk factors for atherosclerosis than controls, there was no evidence to support that they have a greater CIMT at this age.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, androstenedione appears to be inversely associated with CIMT.", "output": {"entities": {"chemical": [{"text": "androstenedione", "start": 13, "end": 28}]}}, "schema": []}
{"input": "Histopathological effects of waterborne copper nanoparticles and copper sulphate on the organs of rainbow trout (Oncorhynchus mykiss).", "output": {"entities": {"chemical": [{"text": "copper", "start": 40, "end": 46}, {"text": "copper sulphate", "start": 65, "end": 80}]}}, "schema": []}
{"input": "It is unclear whether copper nanoparticles are more toxic than traditional forms of dissolved copper.", "output": {"entities": {"chemical": [{"text": "copper", "start": 22, "end": 28}, {"text": "copper", "start": 94, "end": 100}]}}, "schema": []}
{"input": "This study aimed to describe the pathologies in gill, gut, liver, kidney, brain and muscle of juvenile rainbow trout, Oncorhynchus mykiss, exposed in triplicate to either a control (no added Cu), 20 or 100 mu g l (-1) of either dissolved Cu (as CuSO (4)) or Cu-NPs (mean primary particle size of 87 +/- 27 nm) in a semi-static waterborne exposure regime.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 191, "end": 193}, {"text": "Cu", "start": 238, "end": 240}, {"text": "CuSO (4)", "start": 245, "end": 253}, {"text": "Cu", "start": 258, "end": 260}]}}, "schema": []}
{"input": "Fish were sampled at days 0, 4, and 10 for histology.", "output": {"entities": {}}, "schema": []}
{"input": "All treatments caused organ injuries, and the kinds of pathologies observed with Cu-NPs were broadly of the same type as CuSO (4) including: hyperplasia, aneurisms, and necrosis in the secondary lamellae of the gills; swelling of goblet cells, necrosis in the mucosa layer and vacuole formation in the gut; hepatitis-like injury and cells with pyknotic nuclei in the liver; damage to the epithelium of some renal tubules and increased Bowman' s space in the kidney.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 81, "end": 83}, {"text": "CuSO (4)", "start": 121, "end": 129}]}}, "schema": []}
{"input": "In the brain, some mild changes were observed in the nerve cell bodies in the telencephalon, alteration in the thickness of the mesencephalon layers, and enlargement of blood vessel on the ventral surface of the cerebellum.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in the proportional area of muscle fibres were observed in skeletal muscle.", "output": {"entities": {}}, "schema": []}
{"input": "Overall the data showed that pathology from CuSO (4) and Cu-NPs were of similar types, but there were some material-type effects in the severity or incidence of injuries with Cu-NPs causing more injury in the intestine, liver and brain than the equivalent concentration of CuSO (4) by the end of the experiment, but in the gill and muscle CuSO (4) caused more pathology.", "output": {"entities": {"chemical": [{"text": "CuSO (4)", "start": 44, "end": 52}, {"text": "Cu", "start": 57, "end": 59}, {"text": "Cu", "start": 175, "end": 177}, {"text": "CuSO (4)", "start": 273, "end": 281}, {"text": "CuSO (4)", "start": 339, "end": 347}]}}, "schema": []}
{"input": "Pharmacological and behavioral characterization of the novel CRF (1) antagonist BMS-763534.", "output": {"entities": {"chemical": [{"text": "BMS-763534", "start": 80, "end": 90}]}}, "schema": []}
{"input": "BMS-763534 is a potent (CRF (1) IC (50) = 0. 4 nM) and selective (> 1000-fold selectivity vs. all other sites tested) CRF (1) receptor antagonist (pA2 = 9. 47 vs. CRF (1)-mediated cAMP production in Y79 cells).", "output": {"entities": {"chemical": [{"text": "BMS-763534", "start": 0, "end": 10}, {"text": "cAMP", "start": 180, "end": 184}]}}, "schema": []}
{"input": "BMS-763534 accelerated the dissociation of (125) I-o-CRF from rat frontal cortex membrane CRF (1) receptors consistent with a negative allosteric modulation of CRF binding.", "output": {"entities": {"chemical": [{"text": "BMS-763534", "start": 0, "end": 10}, {"text": "(125) I", "start": 43, "end": 50}]}}, "schema": []}
{"input": "BMS-763534 produced dose-dependent increases in CRF (1) receptor occupancy and anxiolytic efficacy; lowest effective anxiolytic dose = 0. 56 mg/kg, PO, which was associated with 71 +/- 5% CRF (1) receptor occupancy of frontoparietal CRF (1) receptors.", "output": {"entities": {"chemical": [{"text": "BMS-763534", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Sedative/ataxic effects of BMS-763534 were only observed at high dose multiples (54-179 x) relative to the lowest dose required for anxiolytic efficacy.", "output": {"entities": {"chemical": [{"text": "BMS-763534", "start": 27, "end": 37}]}}, "schema": []}
{"input": "At doses of 5-to 18-fold higher than the lowest efficacious dose in the anxiety assay, BMS-763534 shared subjective effects with the benzodiazepine chlordiazepoxide.", "output": {"entities": {"chemical": [{"text": "BMS-763534", "start": 87, "end": 97}, {"text": "chlordiazepoxide", "start": 148, "end": 164}]}}, "schema": []}
{"input": "Interestingly BMS-790318, the O-demethylated metabolite of BMS-763534, showed weak affinity for the TBOB site of the GABA (A) receptor (67% inhibition at 10 mu M) and augmented GABA evoked currents (EC (50) = 1. 6 mu M).", "output": {"entities": {"chemical": [{"text": "BMS-790318", "start": 14, "end": 24}, {"text": "O", "start": 30, "end": 31}, {"text": "BMS-763534", "start": 59, "end": 69}, {"text": "TBOB", "start": 100, "end": 104}, {"text": "GABA", "start": 117, "end": 121}, {"text": "GABA", "start": 177, "end": 181}]}}, "schema": []}
{"input": "Thus, the unanticipated signal in the drug discrimination assay may have resulted from an interaction of the metabolite BMS-790318 with the TBOB site on the GABA (A) channel where it appears to behave as an allosteric potentiator of GABA evoked currents.", "output": {"entities": {"chemical": [{"text": "BMS-790318", "start": 120, "end": 130}, {"text": "TBOB", "start": 140, "end": 144}, {"text": "GABA", "start": 157, "end": 161}, {"text": "GABA", "start": 233, "end": 237}]}}, "schema": []}
{"input": "Chemical characterization, antioxidant and cytotoxic activities of Brazilian red propolis.", "output": {"entities": {}}, "schema": []}
{"input": "Propolis is known for a long time for its health benefits and biological activities.", "output": {"entities": {}}, "schema": []}
{"input": "Here, the red variety from the northeast of Brazil was chemically analyzed and extracts were investigated regarding their antioxidant and antitumor activity.", "output": {"entities": {}}, "schema": []}
{"input": "Hydroalcoholic extracts, obtained from the red propolis, revealed polyphenol content, 2, 2-diphenyl-1-picrylhydrazyl scavenging potential and enzymatic activities for catalase-like and superoxide dismutase-like.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 66, "end": 76}, {"text": "2, 2-diphenyl-1-picrylhydrazyl", "start": 86, "end": 116}, {"text": "superoxide", "start": 185, "end": 195}]}}, "schema": []}
{"input": "Cytotoxic activity was evaluated for human laryngeal epidermoid carcinoma cell (Hep-2), human cervical adenocarcinoma (HeLa) and human normal epithelial embryonic kidney (Hek-293).", "output": {"entities": {}}, "schema": []}
{"input": "Survival analysis for non-tumor cell line showed greater IC50 compared to tumor cell lines, suggesting an increased sensitivity that may correlate with the higher proliferative index of the tumor vs. normal cells.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that the Brazilian red propolis is capable of inhibiting cancer cell growth and constitutes an excellent source of antioxidant and antitumor natural agent.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-inflammatory properties of anthraquinones and their relationship with the regulation of P-glycoprotein function and expression.", "output": {"entities": {"chemical": [{"text": "anthraquinones", "start": 32, "end": 46}]}}, "schema": []}
{"input": "There is a growing interest in natural products that potentially have anti-inflammatory properties and inhibit P-glycoprotein (P-gp) function.", "output": {"entities": {}}, "schema": []}
{"input": "In this report, we assessed the effects of anthraquinone derivatives from rhubarb on LPS-induced RAW 264. 7 macrophages to determine their anti-inflammatory potential.", "output": {"entities": {"chemical": [{"text": "anthraquinone", "start": 43, "end": 56}]}}, "schema": []}
{"input": "The derivatives were also tested in Caco-2 cell lines to evaluate the inhibition of the drug efflux function of P-gp.", "output": {"entities": {}}, "schema": []}
{"input": "The transport abilities were examined and the cellular accumulation of rhodamine-123 (R-123) was also measured.", "output": {"entities": {"chemical": [{"text": "rhodamine-123", "start": 71, "end": 84}, {"text": "R-123", "start": 86, "end": 91}]}}, "schema": []}
{"input": "Electorphoretic mobility shift assay (EMSA) was performed to check the activator protein-1 (AP-1) DNA binding affinity.", "output": {"entities": {}}, "schema": []}
{"input": "Five anthraquinones were tested to determine their inhibitory activities on NO production and the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).", "output": {"entities": {"chemical": [{"text": "anthraquinones", "start": 5, "end": 19}, {"text": "NO", "start": 76, "end": 78}, {"text": "nitric oxide", "start": 139, "end": 151}]}}, "schema": []}
{"input": "Furthermore, the level of prostaglandin E (2) (PGE (2)) was determined in LPS-induced RAW264. 7 macrophages.", "output": {"entities": {"chemical": [{"text": "prostaglandin E (2)", "start": 26, "end": 45}, {"text": "PGE (2)", "start": 47, "end": 54}]}}, "schema": []}
{"input": "Emodin was found to be the most potent inhibitor, and it also reduced paw swelling in the mouse model of carrageenan-induced paw edema.", "output": {"entities": {"chemical": [{"text": "Emodin", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In Caco-2 cells, emodin elevated the accumulation of R-123 and decreased the efflux ratio of R-123, which indicates the inhibition of P-gp function.", "output": {"entities": {"chemical": [{"text": "R-123", "start": 53, "end": 58}, {"text": "R-123", "start": 93, "end": 98}]}}, "schema": []}
{"input": "The inhibition of COX-2 protein by emodin paralleled the decrease in P-gp expression.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, mitogen-activated protein kinase (MAPK) expression was decreased through the prevention of AP-1 DNA binding, which leads to downregulation in the expression of P-gp.", "output": {"entities": {}}, "schema": []}
{"input": "Our data indicate that the decrease of P-gp expression is caused by the decreased expression of COX-2 through the MAPK/AP-1 pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Based on our results, we suggest that anti-inflammatory drugs with COX-2 inhibitory activity might be used to modulate P-gp function and expression.", "output": {"entities": {}}, "schema": []}
{"input": "Structure sensitivity of CO oxidation on Co3O4: a DFT study.", "output": {"entities": {"chemical": [{"text": "CO", "start": 25, "end": 27}, {"text": "Co3O4", "start": 41, "end": 46}]}}, "schema": []}
{"input": "The reaction mechanism of CO oxidation on the Co (3) O (4) (110) and Co (3) O (4) (111) surfaces is investigated by means of spin-polarized density functional theory (DFT) within the GGA + U framework.", "output": {"entities": {"chemical": [{"text": "CO", "start": 26, "end": 28}, {"text": "Co (3) O (4)", "start": 46, "end": 58}, {"text": "Co (3) O (4)", "start": 69, "end": 81}]}}, "schema": []}
{"input": "Adsorption situation and complete reaction cycles for CO oxidation are clarified.", "output": {"entities": {"chemical": [{"text": "CO", "start": 54, "end": 56}]}}, "schema": []}
{"input": "The results indicate that 1) the U value can affect the calculated energetic result significantly, not only the absolute adsorption energy but also the trend in adsorption energy; 2) CO can directly react with surface lattice oxygen atoms (O (2f)/O (3f)) to form CO (2) via the Mars-van Krevelen reaction mechanism on both (110)-B and (111)-B; 3) pre-adsorbed molecular O (2) can enhance CO oxidation through the channel in which it directly reacts with molecular CO to form CO (2) [O (2) (a) + CO (g) --> CO (2) (g) + O (a)] on (110)-A/(111)-A; 4) CO oxidation is a structure-sensitive reaction, and the activation energy of CO oxidation follows the order of Co (3) O (4) (111)-A (0. 78 eV) > Co (3) O (4) (111)-B (0. 68 eV) > Co (3) O (4) (110)-A (0. 51 eV) > Co (3) O (4) (110)-B (0. 41 eV), that is, the (110) surface shows higher reactivity for CO oxidation than the (111) surface; 5) in addition to the O (2f), it was also found that Co (3 +) is more active than Co (2 +), so both O (2f) and Co (3 +) control the catalytic activity of CO oxidation on Co (3) O (4), as opposed to a previous DFT study which concluded that either Co (3 +) or O (2f) is the active site.", "output": {"entities": {"chemical": [{"text": "CO", "start": 183, "end": 185}, {"text": "oxygen", "start": 226, "end": 232}, {"text": "O", "start": 240, "end": 241}, {"text": "O", "start": 247, "end": 248}, {"text": "CO (2)", "start": 263, "end": 269}, {"text": "O (2)", "start": 370, "end": 375}, {"text": "CO", "start": 388, "end": 390}, {"text": "CO", "start": 464, "end": 466}, {"text": "CO (2)", "start": 475, "end": 481}, {"text": "O (2)", "start": 483, "end": 488}, {"text": "CO", "start": 495, "end": 497}, {"text": "CO (2)", "start": 506, "end": 512}, {"text": "O", "start": 519, "end": 520}, {"text": "CO", "start": 549, "end": 551}, {"text": "CO", "start": 626, "end": 628}, {"text": "Co (3) O (4)", "start": 660, "end": 672}, {"text": "Co (3) O (4)", "start": 694, "end": 706}, {"text": "Co (3) O (4)", "start": 728, "end": 740}, {"text": "Co (3) O (4)", "start": 762, "end": 774}, {"text": "CO", "start": 850, "end": 852}, {"text": "O", "start": 909, "end": 910}, {"text": "Co (3 +)", "start": 940, "end": 948}, {"text": "Co (2 +)", "start": 969, "end": 977}, {"text": "O", "start": 987, "end": 988}, {"text": "Co (3 +)", "start": 998, "end": 1006}, {"text": "CO", "start": 1041, "end": 1043}, {"text": "Co (3) O (4)", "start": 1057, "end": 1069}, {"text": "Co (3 +)", "start": 1134, "end": 1142}, {"text": "O", "start": 1146, "end": 1147}]}}, "schema": []}
{"input": "Conformational dynamics of Kir3. 1/Kir3. 2 channel activation via delta-opioid receptors.", "output": {"entities": {}}, "schema": []}
{"input": "This study assessed how conformational information encoded by ligand binding to delta-opioid receptors (DORs) is transmitted to Kir3. 1/Kir3. 2 channels.", "output": {"entities": {}}, "schema": []}
{"input": "Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reciprocal interactions among signaling partners.", "output": {"entities": {}}, "schema": []}
{"input": "These and coimmunoprecipitation studies indicated that DORs, G beta gamma, and Kir3 subunits constitutively interacted with one another.", "output": {"entities": {}}, "schema": []}
{"input": "G alpha oA associated with DORs and G beta gamma, but despite being part of the complex, no evidence of its direct association with the channel was obtained.", "output": {"entities": {}}, "schema": []}
{"input": "DOR activation by different ligands left DOR-Kir3 interactions unmodified but modulated BRET between DOR-G alpha oA, DOR-G beta gamma, G alpha oA-G beta gamma, and G beta gamma-Kir3 interfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Ligand-induced BRET changes assessing G beta gamma-Kir3. 1 subunit interaction 1) followed similar kinetics to those monitoring the G alpha oA-G beta gamma interface, 2) displayed the same order of efficacy as those observed at the DOR-G beta gamma interface, 3) were sensitive to pertussis toxin, and 4) were predictive of whether a ligand could evoke channel currents.", "output": {"entities": {}}, "schema": []}
{"input": "Conformational changes at the G beta gamma/Kir3 interface were lost when Kir3. 1 subunits were replaced by a mutant lacking essential sites for G beta gamma-mediated activation.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, conformational information encoded by agonist binding to the receptor is relayed to the channel via structural rearrangements that involve repositioning of G beta gamma with respect to DORs, G alpha oA, and channel subunits.", "output": {"entities": {}}, "schema": []}
{"input": "Further, the fact that BRET changes at the G beta gamma-Kir3 interface are predictive of a ligand' s ability to induce channel currents points to these conformational biosensors as screening tools for identifying GPCR ligands that induce Kir3 channel activation.", "output": {"entities": {}}, "schema": []}
{"input": "Ginkgo biloba extract attenuates hippocampal neuronal loss and cognitive dysfunction resulting from trimethyltin in mice.", "output": {"entities": {"chemical": [{"text": "trimethyltin", "start": 100, "end": 112}]}}, "schema": []}
{"input": "The present study was an attempt to investigate the neuromodulatory potential of Ginkgo biloba extract (GBE) against hippocamapal structural and functional damages induced by trimethyltin (TMT) a potent neurotoxicant.", "output": {"entities": {"chemical": [{"text": "trimethyltin", "start": 175, "end": 187}, {"text": "TMT", "start": 189, "end": 192}]}}, "schema": []}
{"input": "Male Balb/C mice were administered with Ginkgo biloba extract for 14 days at a dose of 70 mg/kg body weight interperitoneally and on 11-day of treatment animals were exposed to Trimethyltin (2. 5 mg/kg b. w) single intraperitoneal injection.", "output": {"entities": {"chemical": [{"text": "Trimethyltin", "start": 177, "end": 189}]}}, "schema": []}
{"input": "The co-administered of TMT with GBE showed marked improvement in memory and aggressive behavior.", "output": {"entities": {"chemical": [{"text": "TMT", "start": 23, "end": 26}]}}, "schema": []}
{"input": "Which were in turn reflected in the levels of serotonin and acetylcholine esterase.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 46, "end": 55}, {"text": "acetylcholine", "start": 60, "end": 73}]}}, "schema": []}
{"input": "The conjunctive treatment also showed significant decrease in oxidative stress as assessed by MDA levels and the antioxidant enzymes (GSH, GSSH, GPX, total glutathione, Catalase and Superoxide dismutase) which were depressed by TMT treatment was significantly improved by GBE.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 94, "end": 97}, {"text": "GSH", "start": 134, "end": 137}, {"text": "GSSH", "start": 139, "end": 143}, {"text": "glutathione", "start": 156, "end": 167}, {"text": "Superoxide", "start": 182, "end": 192}, {"text": "TMT", "start": 228, "end": 231}]}}, "schema": []}
{"input": "Correspondingly, induction of Bcl-2 mitochondrial apoptotic pathway by trimethyltin was down regulated by Ginkgo biloba treatment.", "output": {"entities": {"chemical": [{"text": "trimethyltin", "start": 71, "end": 83}]}}, "schema": []}
{"input": "The structural analysis of dentate gyrus revealed improvement in degenerating neurons by treatment with GBE.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, it is suggested that prophylactic treatment of Ginkgo biloba extract protects against the trimethyltin induced neurodegenration by multiple mechanism involved in its antioxidant effects and may be useful in developing therapies against neurodegenration.", "output": {"entities": {"chemical": [{"text": "trimethyltin", "start": 101, "end": 113}]}}, "schema": []}
{"input": "Seizure control by ketogenic diet-associated medium chain fatty acids.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 58, "end": 69}]}}, "schema": []}
{"input": "The medium chain triglyceride (MCT) ketogenic diet is used extensively for treating refractory childhood epilepsy.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 17, "end": 29}]}}, "schema": []}
{"input": "This diet increases the plasma levels of medium straight chain fatty acids.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 63, "end": 74}]}}, "schema": []}
{"input": "A role for these and related fatty acids in seizure control has not been established.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 29, "end": 40}]}}, "schema": []}
{"input": "We compared the potency of an established epilepsy treatment, Valproate (VPA), with a range of MCT diet-associated fatty acids (and related branched compounds), using in vitro seizure and in vivo epilepsy models, and assessed side effect potential in vitro for one aspect of teratogenicity, for liver toxicology and in vivo for sedation, and for a neuroprotective effect.", "output": {"entities": {"chemical": [{"text": "Valproate", "start": 62, "end": 71}, {"text": "VPA", "start": 73, "end": 76}, {"text": "fatty acids", "start": 115, "end": 126}]}}, "schema": []}
{"input": "We identify specific medium chain fatty acids (both prescribed in the MCT diet, and related compounds branched on the fourth carbon) that provide significantly enhanced in vitro seizure control compared to VPA.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 34, "end": 45}, {"text": "VPA", "start": 206, "end": 209}]}}, "schema": []}
{"input": "The activity of these compounds on seizure control is independent of histone deacetylase inhibitory activity (associated with the teratogenicity of VPA), and does not correlate with liver cell toxicity.", "output": {"entities": {"chemical": [{"text": "VPA", "start": 148, "end": 151}]}}, "schema": []}
{"input": "In vivo, these compounds were more potent in epilepsy control (perforant pathway stimulation induced status epilepticus), showed less sedation and enhanced neuroprotection compared to VPA.", "output": {"entities": {"chemical": [{"text": "VPA", "start": 184, "end": 187}]}}, "schema": []}
{"input": "Our data therefore implicates medium chain fatty acids in the mechanism of the MCT ketogenic diet, and highlights a related new family of compounds that are more potent than VPA in seizure control with a reduced potential for side effects.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 43, "end": 54}, {"text": "VPA", "start": 174, "end": 177}]}}, "schema": []}
{"input": "This article is part of the Special Issue entitled' New Targets and Approaches to the Treatment of Epilepsy'.", "output": {"entities": {}}, "schema": []}
{"input": "Etazolate, an alpha-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice.", "output": {"entities": {"chemical": [{"text": "Etazolate", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Traumatic brain injury (TBI) evokes an intense neuroinflammatory reaction that is essentially mediated by activated microglia and that has been reported to act as a secondary injury mechanism that further promotes neuronal death.", "output": {"entities": {}}, "schema": []}
{"input": "It involves the excessive production of inflammatory cytokines and the diminution of neuroprotective and neurotrophic factors, such as the soluble form alpha of the amyloid precursor protein (sAPP alpha), generated by the activity of alpha-secretases.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, the aim of this study was to examine the effects of etazolate, an alpha-secretase activator, on acute and belated post-TBI consequences.", "output": {"entities": {"chemical": [{"text": "etazolate", "start": 59, "end": 68}]}}, "schema": []}
{"input": "The mouse model of TBI by mechanical percussion was used and injured mice received either the vehicle or etazolate at the dose of 1, 3 or 10 mg/kg at 2 h post-TBI.", "output": {"entities": {"chemical": [{"text": "etazolate", "start": 105, "end": 114}]}}, "schema": []}
{"input": "Neurological score, cerebral oe dema, IL-1 beta and sAPP alpha levels, microglial activation and lesion size were evaluated from 6 to 24 h post-TBI.", "output": {"entities": {}}, "schema": []}
{"input": "Spontaneous locomotor activity was evaluated from 48 h to 12 weeks post-TBI, memory function at 5 weeks and olfactory bulb lesions at 13 weeks post-TBI.", "output": {"entities": {}}, "schema": []}
{"input": "A single administration of etazolate exerted a dose-dependent anti-inflammatory and anti-oe dematous effect accompanied by lasting memory improvement, reduction of locomotor hyperactivity and olfactory bulb tissue protection, with a therapeutic window of at least 2 h.", "output": {"entities": {"chemical": [{"text": "etazolate", "start": 27, "end": 36}]}}, "schema": []}
{"input": "These effects were associated with the restoration of the levels of the sAPP alpha protein post-TBI.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these results highlight for the first time the therapeutic interest of an alpha-secretase activator in TBI.", "output": {"entities": {}}, "schema": []}
{"input": "Vitamin D receptor signaling mechanisms: integrated actions of a well-defined transcription factor.", "output": {"entities": {"chemical": [{"text": "Vitamin D", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The main physiological actions of the biologically most active metabolite of vitamin D, 1 alpha, 25-dihydroxyvitamin D (3) (1 alpha, 25 (OH) (2) D (3)), are calcium and phosphorus uptake and transport and thereby controlling bone formation.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 77, "end": 86}, {"text": "1 alpha, 25-dihydroxyvitamin D (3)", "start": 88, "end": 122}, {"text": "1 alpha, 25 (OH) (2) D (3)", "start": 124, "end": 150}, {"text": "calcium", "start": 157, "end": 164}, {"text": "phosphorus", "start": 169, "end": 179}]}}, "schema": []}
{"input": "Other emergent areas of 1 alpha, 25 (OH) (2) D (3) action are in the control of immune functions, cellular growth and differentiation.", "output": {"entities": {"chemical": [{"text": "1 alpha, 25 (OH) (2) D (3)", "start": 24, "end": 50}]}}, "schema": []}
{"input": "All genomic actions of 1 alpha, 25 (OH) (2) D (3) are mediated by the transcription factor vitamin D receptor (VDR) that has been the subject of intense study since the 1980' s.", "output": {"entities": {"chemical": [{"text": "1 alpha, 25 (OH) (2) D (3)", "start": 23, "end": 49}, {"text": "vitamin D", "start": 91, "end": 100}]}}, "schema": []}
{"input": "Thus, vitamin D signaling primarily implies the molecular actions of the VDR.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 6, "end": 15}]}}, "schema": []}
{"input": "In this review, we present different perspectives on the VDR that incorporate its role as transcription factor and member of the nuclear receptor superfamily, its dynamic changes in genome-wide locations and DNA binding modes, its interaction with chromatin components and its primary protein-coding and non-protein coding target genes and finally how these aspects are united in regulatory networks.", "output": {"entities": {}}, "schema": []}
{"input": "By comparing the actions of the VDR, a relatively well-understood and characterized protein, with those of other transcription factors, we aim to build a realistic positioning of vitamin D signaling in the context of other intracellular signaling systems.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 179, "end": 188}]}}, "schema": []}
{"input": "Biochemical and biological characterization of two serine proteinases from Colombian Crotalus durissus cumanensis snake venom.", "output": {"entities": {"chemical": [{"text": "serine", "start": 51, "end": 57}]}}, "schema": []}
{"input": "Two clotting serine proteinases, named Cdc SI and Cdc SII, were isolated and characterized for the first time from Colombian Crotalus durissus cumanensis snake venom.", "output": {"entities": {"chemical": [{"text": "serine", "start": 13, "end": 19}]}}, "schema": []}
{"input": "The enzymes were purified using two chromatographic steps: molecular exclusion on Sephacryl S-200 and RP-HPLC on C8 Column.", "output": {"entities": {}}, "schema": []}
{"input": "The molecular masses of the proteins, determined by MALDI-TOF mass spectrometry, were 28, 561. 4 and 28, 799. 2 Da for Cdc SI and Cdc SII, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to evaluate enzymatic, coagulant and toxic properties of the two enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "The serine proteinases hydrolyzed specific chromogenic substrate (BaPNA) and exhibited a Michaelis-Menten behavior.", "output": {"entities": {"chemical": [{"text": "serine", "start": 4, "end": 10}]}}, "schema": []}
{"input": "Cdc SI had V (max) of 0. 038 +/- 0. 003 nmol/min and K (M) of 0. 034 +/- 0. 017 mM, while Cdc SII displayed values of V (max) of 0. 267 +/- 0. 011 nmol/min and K (M) of 0. 145 +/- 0. 023 mM.", "output": {"entities": {}}, "schema": []}
{"input": "N-terminal sequences were VIGGDEXNIN and VIGGDICNINEHNFLVALYE for Cdc SI and Cdc SII, respectively.", "output": {"entities": {"chemical": [{"text": "N", "start": 0, "end": 1}]}}, "schema": []}
{"input": "Molecular masses, N-terminal sequences, inhibition assays, and enzymatic profile suggest that Cdc SI and Cdc SII belong to the family of snake venom thrombin-like enzymes.", "output": {"entities": {"chemical": [{"text": "N", "start": 18, "end": 19}]}}, "schema": []}
{"input": "These serine proteinases differed in their clotting activity on human plasma, showing a minimum coagulant dose of 25 mu g and 0. 571 mu g for Cdc SI and Cdc SII, respectively.", "output": {"entities": {"chemical": [{"text": "serine", "start": 6, "end": 12}]}}, "schema": []}
{"input": "Enzymes also showed coagulant activity on bovine fibrinogen and degraded chain alpha of this protein.", "output": {"entities": {}}, "schema": []}
{"input": "Toxins lack hemorrhagic and myotoxic activities, but are capable to induce defibrin (ogen) ation, moderate edema, and an increase in vascular permeability.", "output": {"entities": {}}, "schema": []}
{"input": "These serine proteinases may contribute indirectly to the local hemorrhage induced by metalloproteinases, by causing blood clotting disturbances, and might also contribute to cardiovascular alterations characteristic of patients envenomed by C.", "output": {"entities": {"chemical": [{"text": "serine", "start": 6, "end": 12}]}}, "schema": []}
{"input": "d. cumanensis in Colombia.", "output": {"entities": {}}, "schema": []}
{"input": "Solubility-pH profiles of some acidic, basic and amphoteric drugs.", "output": {"entities": {}}, "schema": []}
{"input": "The solubility vs. pH profiles of five ionizable drugs of different nature (a monoprotic acid, a monoprotic base, a diprotic base and two amphoteric compounds showing a zwitterionic species each one) have been determined through two different methodologies: the classical shake-flask (S-F) and the potentiometric Cheqsol methods using in both instances the appropriate Henderson-Hasselbalch (H-H) or derived relationships.", "output": {"entities": {}}, "schema": []}
{"input": "The results obtained independently from both approaches are consistent.", "output": {"entities": {}}, "schema": []}
{"input": "A critical revision about the influence of the electrolyte used as buffering agent in the S-F method on the obtained solubility values is also performed.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, some deviations of the experimental points with respect the H-H profiles can be attributed to specific interactions between the buffering electrolyte and the drug due to the hydrotrophic character of citric and lactic acids.", "output": {"entities": {"chemical": [{"text": "citric and lactic acids", "start": 206, "end": 229}]}}, "schema": []}
{"input": "In other cases, the observed deviations are independent of the buffers used since they are caused by the formation of new species such as drug aggregates (cefadroxil) or the precipitation of a salt from a cationic species of the analyzed compound (quetiapine).", "output": {"entities": {"chemical": [{"text": "cefadroxil", "start": 155, "end": 165}, {"text": "quetiapine", "start": 248, "end": 258}]}}, "schema": []}
{"input": "APLF promotes the assembly and activity of non-homologous end joining protein complexes.", "output": {"entities": {}}, "schema": []}
{"input": "Non-homologous end joining (NHEJ) is critical for the maintenance of genetic integrity and DNA double-strand break (DSB) repair.", "output": {"entities": {}}, "schema": []}
{"input": "NHEJ is regulated by a series of interactions between core components of the pathway, including Ku heterodimer, XLF/Cernunnos, and XRCC4/DNA Ligase 4 (Lig4).", "output": {"entities": {}}, "schema": []}
{"input": "However, the mechanisms by which these proteins assemble into functional protein-DNA complexes are not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that the von Willebrand (vWA) domain of Ku80 fulfills a critical role in this process by recruiting Aprataxin-and-PNK-Like Factor (APLF) into Ku-DNA complexes.", "output": {"entities": {}}, "schema": []}
{"input": "APLF, in turn, functions as a scaffold protein and promotes the recruitment and/or retention of XRCC4-Lig4 and XLF, thereby assembling multi-protein Ku complexes capable of efficient DNA ligation in vitro and in cells.", "output": {"entities": {}}, "schema": []}
{"input": "Disruption of the interactions between APLF and either Ku80 or XRCC4-Lig4 disrupts the assembly and activity of Ku complexes, and confers cellular hypersensitivity and reduced rates of chromosomal DSB repair in avian and human cells, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these data identify a role for the vWA domain of Ku80 and a molecular mechanism by which DNA ligase proficient complexes are assembled during NHEJ in mammalian cells, and reveal APLF to be a structural component of this critical DSB repair pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Herb-drug interaction of Fucus vesiculosus extract and amiodarone in rats: a potential risk for reduced bioavailability of amiodarone in clinical practice.", "output": {"entities": {"chemical": [{"text": "amiodarone", "start": 55, "end": 65}, {"text": "amiodarone", "start": 123, "end": 133}]}}, "schema": []}
{"input": "Fucus vesiculosus is a seaweed claimed to be useful for obesity management.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, considering the relationship between obesity and cardiovascular diseases, this work aimed to assess the potential for an herb-drug interaction among a standardized F. vesiculosus extract (GMP certificate) and amiodarone (a narrow therapeutic index drug) in rats.", "output": {"entities": {"chemical": [{"text": "amiodarone", "start": 220, "end": 230}]}}, "schema": []}
{"input": "In a first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of F. vesiculosus (575 mg/kg, p. o.) and amiodarone (50 mg/kg, p. o.); in a second study, rats were pre-treated during 14 days with F. vesiculosus (575 mg/kg/day, p. o.) and received amiodarone (50 mg/kg, p. o.) on the 15th day.", "output": {"entities": {"chemical": [{"text": "amiodarone", "start": 135, "end": 145}, {"text": "amiodarone", "start": 277, "end": 287}]}}, "schema": []}
{"input": "Rats of the control groups received the corresponding volume of vehicle.", "output": {"entities": {}}, "schema": []}
{"input": "After analysis of the pharmacokinetic data it deserves to be highlighted the significant decrease in the peak plasma concentration of amiodarone (55. 4%) as well as the reduction of systemic exposure to the parent drug (~ 30%) following the simultaneous co-administration of F. vesiculosus extract and amiodarone.", "output": {"entities": {"chemical": [{"text": "amiodarone", "start": 134, "end": 144}, {"text": "amiodarone", "start": 302, "end": 312}]}}, "schema": []}
{"input": "This paper reports, for the first time, the herb-drug interaction between F. vesiculosus and amiodarone, which determined a considerable decrease on amiodarone bioavailability in rats.", "output": {"entities": {"chemical": [{"text": "amiodarone", "start": 93, "end": 103}, {"text": "amiodarone", "start": 149, "end": 159}]}}, "schema": []}
{"input": "Therefore, the therapeutic efficacy of amiodarone may be compromised by the concurrent administration of herbal slimming medicines/dietary supplements containing F. vesiculosus.", "output": {"entities": {"chemical": [{"text": "amiodarone", "start": 39, "end": 49}]}}, "schema": []}
{"input": "Garlic-derived diallyl disulfide modulates peroxisome proliferator activated receptor gamma co-activator 1 alpha in neuroblastoma cells.", "output": {"entities": {"chemical": [{"text": "diallyl disulfide", "start": 15, "end": 32}]}}, "schema": []}
{"input": "The peroxisome proliferator activated receptor gamma co-activator 1 alpha (PGC1 alpha) is an inducible transcriptional co-activator with direct function in the induction of mitochondrial biogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "In the present report we show that, in SH-SY5Y neuroblastoma cells, garlic-derived diallyl disulfide (DADS) is able to increase PGC1 alpha expression in a ROS-dependent manner and to induce mitochondrial biogenesis at early stage of treatment that precede cell cycle arrest and apoptosis outcome.", "output": {"entities": {"chemical": [{"text": "diallyl disulfide", "start": 83, "end": 100}]}}, "schema": []}
{"input": "In particular, we demonstrate that DADS elicits: i) the increase of PGC1 alpha within nuclear compartment; ii) the decrease of PGC1 alpha non-active acetylated form; iii) the induction of nuclear-encoded mitochondrial genes such as TFAM and TFBM1.", "output": {"entities": {}}, "schema": []}
{"input": "We also show an accumulation of PGC1 alpha within mitochondria along with an increased association with the regulatory D-Loop region of mtDNA and a concomitant augmented expression of mitochondrial RNA.", "output": {"entities": {}}, "schema": []}
{"input": "Such events are related to a prompt elevation of mitochondrial mass, as assessed by evaluating the content of mtDNA.", "output": {"entities": {}}, "schema": []}
{"input": "We show that the induction of mitochondrial biogenesis is directed to dampen the cytotoxic effect of DADS.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, PGC1 alpha overexpression or down-regulation prevents or exacerbates mtDNA loss and apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Overall the data highlight an anti-apoptotic role of PGC1 alpha-mediated mitochondrial biogenesis in neuroblatoma cells and suggest PGC1 alpha as a potential target for enhancing the effectiveness of therapy in aggressive neuroblastoma with high drug-resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Hyaluronic acid-dependent protection in H9C2 cardiomyocytes: a cell model of heart ischemia-reperfusion injury and treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Hyaluronic acid (HA), a glycosaminoglycan with high molecular weight, has been reported to promote cell proliferation and serves as an important extracellular matrix component.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to in vitro investigate whether HA is able to reduce reactive oxygen species (ROS)-induced heart ischemia-reperfusion injury and activate the cardiomyocyte' s damage surveillance systems.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 88, "end": 94}]}}, "schema": []}
{"input": "Accordingly, rattus cardiomyocyte line, H9C2, was treated with H (2) O (2) as a heart ischemia-reperfusion model followed by incubation with low molecular weight hyaluronan (LMW-HA, 100 kDa) or high molecular weight hyaluronan (HMW-HA, 1000 kDa) and proteomic analysis was performed to investigate the physiologic protection of HA in H (2) O (2)-induced ischemia-reperfusion in cardiomyocyte.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 63, "end": 74}, {"text": "H (2) O (2)", "start": 334, "end": 345}]}}, "schema": []}
{"input": "Our data demonstrated that HA treatment does protect cardiomyocyte in the ROS-induced ischemia-reperfusion model and the molecular weight of HA is a crucial factor.", "output": {"entities": {}}, "schema": []}
{"input": "HMW-HA has been shown to significantly facilitate cell migration and wound healing via cytoskeletal rearrangement.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, 2D-DIGE combined MALDI-TOF/TOF analysis showed that HMW-HA might modulate biosynthetic pathways, cell migration, cell outgrowth and protein folding to stimulate wound healing as well as prevent these ischemia-reperfusion-damaged cardiomyocytes from cell death.", "output": {"entities": {}}, "schema": []}
{"input": "To our knowledge, we report for the first time the cell repair mechanism of HMW-HA against ischemia-reperfusion-damage in cardiomyocytes based on cell biology and proteomic analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of epitopes recognized by monoclonal antibodies: experimental approaches supported by freely accessible bioinformatic tools.", "output": {"entities": {}}, "schema": []}
{"input": "Monoclonal antibodies (mAbs) have been used successfully both in research and for clinical purposes.", "output": {"entities": {}}, "schema": []}
{"input": "The possible use of protective mAbs directed against different microbial pathogens is currently being considered.", "output": {"entities": {}}, "schema": []}
{"input": "The fine definition of the epitope recognized by a protective mAb is an important aspect to be considered for possible development in epitope-based vaccinology.", "output": {"entities": {}}, "schema": []}
{"input": "The most accurate approach to this is the X-ray resolution of mAb/antigen crystal complex.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, this approach is not always feasible.", "output": {"entities": {}}, "schema": []}
{"input": "Under this perspective, several surrogate epitope mapping strategies based on the use of bioinformatics have been developed.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we review the most common, freely accessible, bioinformatic tools used for epitope characterization and provide some basic examples of molecular visualization, editing and computational analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Rat fertility and embryo fetal development: influence of exposure to the Wi-Fi signal.", "output": {"entities": {}}, "schema": []}
{"input": "In recent decades, concern has been growing about decreasing fecundity and fertility in the human population.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to non-ionizing electromagnetic fields (EMF), especially radiofrequency (RF) fields used in wireless communications has been suggested as a potential risk factor.", "output": {"entities": {}}, "schema": []}
{"input": "For the first time, we evaluated the effects of exposure to the 2450MHz Wi-Fi signal (1h/day, 6days/week) on the reproductive system of male and female Wistar rats, pre-exposed to Wi-Fi during sexual maturation.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure lasted 3 weeks (males) or 2 weeks (females), then animals were mated and couples exposed for 3 more weeks.", "output": {"entities": {}}, "schema": []}
{"input": "On the day before delivery, the fetuses were observed for lethality, abnormalities, and clinical signs.", "output": {"entities": {}}, "schema": []}
{"input": "In our experiment, no deleterious effects of Wi-Fi exposure on rat male and female reproductive organs and fertility were observed for 1h per days.", "output": {"entities": {}}, "schema": []}
{"input": "No macroscopic abnormalities in fetuses were noted, even at the critical level of 4W/kg.", "output": {"entities": {}}, "schema": []}
{"input": "Combination chemotherapy using core-shell nanoparticles through the self-assembly of HPMA-based copolymers and degradable polyester.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 85, "end": 89}, {"text": "polyester", "start": 122, "end": 131}]}}, "schema": []}
{"input": "The preparation of core-shell polymeric nanoparticles simultaneously loaded with docetaxel (DTXL) and doxorubicin (DOX) is reported herein.", "output": {"entities": {"chemical": [{"text": "docetaxel", "start": 81, "end": 90}, {"text": "DTXL", "start": 92, "end": 96}, {"text": "doxorubicin", "start": 102, "end": 113}, {"text": "DOX", "start": 115, "end": 118}]}}, "schema": []}
{"input": "The self-assembly of the aliphatic biodegradable copolyester PBS/PBDL (poly (butylene succinate-co-butylene dilinoleate)) and HPMA-based copolymers (N-(2-hydroxypropyl) methacrylamide-based copolymers) hydrophobically modified by the incorporation of cholesterol led to the formation of narrow-size-distributed (PDI < 0. 10) sub-200-nm polymeric nanoparticles suitable for passive tumor-targeting drug delivery based on the size-dependent EPR (enhanced permeability and retention) effect.", "output": {"entities": {"chemical": [{"text": "PBS", "start": 61, "end": 64}, {"text": "PBDL", "start": 65, "end": 69}, {"text": "poly (butylene succinate-co-butylene dilinoleate)", "start": 71, "end": 120}, {"text": "HPMA", "start": 126, "end": 130}, {"text": "N-(2-hydroxypropyl) methacrylamide", "start": 149, "end": 183}, {"text": "cholesterol", "start": 251, "end": 262}]}}, "schema": []}
{"input": "The PHPMA provided to the self-assembled nanoparticle stability against aggregation as evaluated in vitro.", "output": {"entities": {"chemical": [{"text": "PHPMA", "start": 4, "end": 9}]}}, "schema": []}
{"input": "The highly hydrophobic drug docetaxel (DTXL) was physically entrapped within the PBS/PBDL copolyester core and the hydrophilic drug doxorubicin hydrochloride (DOX. HCl) was chemically conjugated to the reactive PHPMA copolymer shell via hydrazone bonding that allowed its pH-sensitive release.", "output": {"entities": {"chemical": [{"text": "docetaxel", "start": 28, "end": 37}, {"text": "DTXL", "start": 39, "end": 43}, {"text": "PBS", "start": 81, "end": 84}, {"text": "PBDL", "start": 85, "end": 89}, {"text": "doxorubicin hydrochloride", "start": 132, "end": 157}, {"text": "DOX. HCl", "start": 159, "end": 167}, {"text": "PHPMA", "start": 211, "end": 216}, {"text": "hydrazone", "start": 237, "end": 246}]}}, "schema": []}
{"input": "This strategy enabled the combination chemotherapy by the simultaneous DOX and DTXL drug delivery.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 71, "end": 74}, {"text": "DTXL", "start": 79, "end": 83}]}}, "schema": []}
{"input": "The structure of the nanoparticles was characterized in detail using static (SLS), dynamic (DLS) and electrophoretic (ELS) light scattering besides transmission electron microscopy (TEM).", "output": {"entities": {}}, "schema": []}
{"input": "The use of nanoparticles simultaneously loaded with DTXL and DOX provided a more efficient suppression of tumor-cell growth in mice bearing EL-4 T cell lymphoma when compared to the effect of nanoparticles loaded with either DTXL or DOX separately.", "output": {"entities": {"chemical": [{"text": "DTXL", "start": 52, "end": 56}, {"text": "DOX", "start": 61, "end": 64}, {"text": "DTXL", "start": 225, "end": 229}, {"text": "DOX", "start": 233, "end": 236}]}}, "schema": []}
{"input": "Additionally, the obtained self-assembled nanoparticles enable further development of targeting strategies based on the use of multiple ligands attached to an HPMA copolymer on the particle surface for simultaneous passive and active targeting and different combination therapies.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 159, "end": 163}]}}, "schema": []}
{"input": "Iron excess disturbs metabolic status and relative gonad mass in rats on high fat, fructose, and salt diets.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "fructose", "start": 83, "end": 91}]}}, "schema": []}
{"input": "The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 108, "end": 116}, {"text": "iron", "start": 144, "end": 148}]}}, "schema": []}
{"input": "Mineral status was also estimated.", "output": {"entities": {}}, "schema": []}
{"input": "Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 98, "end": 106}]}}, "schema": []}
{"input": "The noncontrol diets contained either normal (M) or high level (MFe) of iron.", "output": {"entities": {"chemical": [{"text": "iron", "start": 72, "end": 76}]}}, "schema": []}
{"input": "After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized.", "output": {"entities": {}}, "schema": []}
{"input": "The kidneys and gonads were collected, and blood samples were taken.", "output": {"entities": {}}, "schema": []}
{"input": "Serum levels of insulin, nitric oxide, and iron were measured.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 25, "end": 37}, {"text": "iron", "start": 43, "end": 47}]}}, "schema": []}
{"input": "The iron, zinc, copper, and calcium concentrations of tissues were determined.", "output": {"entities": {"chemical": [{"text": "iron", "start": 4, "end": 8}, {"text": "zinc", "start": 10, "end": 14}, {"text": "copper", "start": 16, "end": 22}, {"text": "calcium", "start": 28, "end": 35}]}}, "schema": []}
{"input": "It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group.", "output": {"entities": {}}, "schema": []}
{"input": "Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads.", "output": {"entities": {"chemical": [{"text": "iron", "start": 62, "end": 66}, {"text": "zinc", "start": 87, "end": 91}, {"text": "copper", "start": 96, "end": 102}, {"text": "calcium", "start": 156, "end": 163}]}}, "schema": []}
{"input": "The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 69, "end": 81}]}}, "schema": []}
{"input": "The high iron level in the modified diet increased the relative mass of the gonads.", "output": {"entities": {"chemical": [{"text": "iron", "start": 9, "end": 13}]}}, "schema": []}
{"input": "The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues.", "output": {"entities": {"chemical": [{"text": "iron", "start": 11, "end": 15}, {"text": "zinc", "start": 48, "end": 52}, {"text": "copper", "start": 54, "end": 60}, {"text": "calcium", "start": 66, "end": 73}]}}, "schema": []}
{"input": "The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 28, "end": 40}, {"text": "iron", "start": 70, "end": 74}, {"text": "fructose", "start": 81, "end": 89}, {"text": "zinc", "start": 133, "end": 137}, {"text": "copper", "start": 139, "end": 145}, {"text": "calcium", "start": 151, "end": 158}]}}, "schema": []}
{"input": "Retraction note to: The effect of lead acetate toxicity on experimental male albino rat.", "output": {"entities": {"chemical": [{"text": "lead acetate", "start": 34, "end": 46}]}}, "schema": []}
{"input": "Retraction to: Biol Trace Elem Res 144 (1-3): 1120-1132, DOI 10. 1007/s12011-011-9149-z.", "output": {"entities": {}}, "schema": []}
{"input": "Article has been retracted due to duplicate publication.", "output": {"entities": {}}, "schema": []}
{"input": "Periphyton responses to nutrient and atrazine mixtures introduced through agricultural runoff.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Agricultural runoff often contains pollutants with antagonistic impacts.", "output": {"entities": {}}, "schema": []}
{"input": "The individual influence of nutrients and atrazine on periphyton has been extensively studied, but their impact when introduced together and with multiple agricultural pollutants is less clear.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 42, "end": 50}]}}, "schema": []}
{"input": "We simulated a field-scale runoff pulse into a riverine wetland that mimicked pollutant composition typical of field runoff of the Mississippi River Alluvial Plain.", "output": {"entities": {}}, "schema": []}
{"input": "Periphyton biomass and functional responses were measured for 2 weeks along a 500 m section.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, laboratory chamber assays were used to identify potential periphyton changes due to nutrients, atrazine, and their interactions.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 109, "end": 117}]}}, "schema": []}
{"input": "Generally, nutrients stimulated, and atrazine reduced chlorophyll a (Chl a) in chambers.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 37, "end": 45}, {"text": "chlorophyll a", "start": 54, "end": 67}, {"text": "Chl a", "start": 69, "end": 74}]}}, "schema": []}
{"input": "In the wetland, nutrient and atrazine relationships with periphyton were weaker, and when found, were often opposite of trends in chambers.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Total nitrogen (TN) was inversely related to Chl a, and total phosphorus was inversely related to respiration (R) rates.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 6, "end": 14}, {"text": "Chl a", "start": 45, "end": 50}, {"text": "phosphorus", "start": 62, "end": 72}]}}, "schema": []}
{"input": "Atrazine (10-20 mu g L (-1) in the wetland) had a positive relationship with ash-free dry mass (AFDM), and weakened the relationship between TN and AFDM.", "output": {"entities": {"chemical": [{"text": "Atrazine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Wetland periphyton biomass was better correlated to total suspended solids than nutrients or atrazine.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Periphyton function was resilient as periphyton gross primary production (GPP)/R ratios were not strongly impacted by runoff.", "output": {"entities": {}}, "schema": []}
{"input": "However, whole-system GPP and R decreased over the 2-week period, suggesting that although periphyton metabolism recovered quickly, whole-system metabolism took longer to recover.", "output": {"entities": {}}, "schema": []}
{"input": "The individual and combined impacts of nutrients and atrazine in complex pollutant mixtures can vary substantially from their influence when introduced separately, and non-linear impacts can occur with distance downstream of the pollutant introduction point.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 53, "end": 61}]}}, "schema": []}
{"input": "Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach.", "output": {"entities": {}}, "schema": []}
{"input": "Developmental neurotoxicity (DNT) and many forms of reproductive toxicity (RT) often manifest themselves in functional deficits that are not necessarily based on cell death, but rather on minor changes relating to cell differentiation or communication.", "output": {"entities": {}}, "schema": []}
{"input": "The fields of DNT/RT would greatly benefit from in vitro tests that allow the identification of toxicant-induced changes of the cellular proteostasis, or of its underlying transcriptome network.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the' human embryonic stem cell (hESC)-derived novel alternative test systems (ESNATS)' European commission research project established RT tests based on defined differentiation protocols of hESC and their progeny.", "output": {"entities": {}}, "schema": []}
{"input": "Valproic acid (VPA) and methylmercury (MeHg) were used as positive control compounds to address the following fundamental questions: (1) Does transcriptome analysis allow discrimination of the two compounds?", "output": {"entities": {"chemical": [{"text": "Valproic acid", "start": 0, "end": 13}, {"text": "VPA", "start": 15, "end": 18}, {"text": "methylmercury", "start": 24, "end": 37}, {"text": "MeHg", "start": 39, "end": 43}]}}, "schema": []}
{"input": "(2) How does analysis of enriched transcription factor binding sites (TFBS) and of individual probe sets (PS) distinguish between test systems?", "output": {"entities": {}}, "schema": []}
{"input": "(3) Can batch effects be controlled?", "output": {"entities": {}}, "schema": []}
{"input": "(4) How many DNA microarrays are needed?", "output": {"entities": {}}, "schema": []}
{"input": "(5) Is the highest non-cytotoxic concentration optimal and relevant for the study of transcriptome changes?", "output": {"entities": {}}, "schema": []}
{"input": "VPA triggered vast transcriptional changes, whereas MeHg altered fewer transcripts.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 52, "end": 56}]}}, "schema": []}
{"input": "To attenuate batch effects, analysis has been focused on the 500 PS with highest variability.", "output": {"entities": {}}, "schema": []}
{"input": "The test systems differed significantly in their responses (< 20% overlap).", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, within one test system, little overlap between the PS changed by the two compounds has been observed.", "output": {"entities": {}}, "schema": []}
{"input": "However, using TFBS enrichment, a relatively large' common response' to VPA and MeHg could be distinguished from' compound-specific' responses.", "output": {"entities": {"chemical": [{"text": "VPA", "start": 72, "end": 75}, {"text": "MeHg", "start": 80, "end": 84}]}}, "schema": []}
{"input": "In conclusion, the ESNATS assay battery allows classification of human DNT/RT toxicants on the basis of their transcriptome profiles.", "output": {"entities": {}}, "schema": []}
{"input": "Therapy of adrenal insufficiency: an update.", "output": {"entities": {}}, "schema": []}
{"input": "Adrenal insufficiency may be caused by the destruction or altered function of the adrenal gland with a primary deficit in cortisol secretion (primary adrenal insufficiency) or by hypothalamic-pituitary pathologies determining a deficit of ACTH (secondary adrenal insufficiency).", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 122, "end": 130}]}}, "schema": []}
{"input": "The clinical picture is determined by the glucocorticoid deficit, which may in some conditions be accompanied by a deficit of mineralcorticoids and adrenal androgens.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 156, "end": 165}]}}, "schema": []}
{"input": "The substitutive treatment is aimed at reducing the signs and symptoms of the disease as well as at preventing the development of an addisonian crisis, a clinical emergency characterized by hypovolemic shock.", "output": {"entities": {}}, "schema": []}
{"input": "The oral substitutive treatment should attempt at mimicking the normal circadian profile of cortisol secretion, by using the lower possible doses able to guarantee an adequate quality of life to patients.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 92, "end": 100}]}}, "schema": []}
{"input": "The currently available hydrocortisone or cortisone acetate preparations do not allow an accurate reproduction of the physiological secretion pattern of cortisol.", "output": {"entities": {"chemical": [{"text": "hydrocortisone", "start": 24, "end": 38}, {"text": "cortisone acetate", "start": 42, "end": 59}, {"text": "cortisol", "start": 153, "end": 161}]}}, "schema": []}
{"input": "A novel dual-release formulation of hydrocortisone, recently approved by EMEA, represents an advancement in the optimization of the clinical management of patients with adrenal insufficiency.", "output": {"entities": {"chemical": [{"text": "hydrocortisone", "start": 36, "end": 50}]}}, "schema": []}
{"input": "Future clinical trials of immunomodulation or immunoprevention will test the possibility to delay (or prevent) the autoimmune destruction of the adrenal gland in autoimmune Addison' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical constituents from the fungus Amauroderma amoiensis and their in vitro acetylcholinesterase inhibitory activities.", "output": {"entities": {}}, "schema": []}
{"input": "One new compound named amauroamoienin (1), together with thirteen known compounds (2-14), was isolated from the EtOAc extract of Amauroderma amoiensis.", "output": {"entities": {"chemical": [{"text": "amauroamoienin", "start": 23, "end": 37}, {"text": "EtOAc", "start": 112, "end": 117}]}}, "schema": []}
{"input": "The structures of these compounds were elucidated by the analysis of 1D and 2D spectroscopic data and the MS technique.", "output": {"entities": {}}, "schema": []}
{"input": "The bioassays of inhibitory activities of these isolates against acetylcholinesterase were evaluated, and compounds 1, 3, and 5 exhibited acetylcholinesterase inhibitory activities.", "output": {"entities": {}}, "schema": []}
{"input": "Three-dimensional hierarchical GeSe2 nanostructures for high performance flexible all-solid-state supercapacitors.", "output": {"entities": {"chemical": [{"text": "GeSe2", "start": 31, "end": 36}]}}, "schema": []}
{"input": "Highly flexible stacked and in-plane all-solid-state supercapacitors are fabricated on 3D hierarchical GeSe2 nanostructures with high performance, and, when configured as a self-powered photodetector nanosystem, can be used to power CdSe nanowire photodetectors.", "output": {"entities": {"chemical": [{"text": "GeSe2", "start": 103, "end": 108}, {"text": "CdSe", "start": 233, "end": 237}]}}, "schema": []}
{"input": "Bottom-up nutrient and top-down fish impacts on insect-mediated mercury flux from aquatic ecosystems.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 64, "end": 71}]}}, "schema": []}
{"input": "Methyl mercury (MeHg) is one of the most hazardous contaminants in the environment, adversely affecting the health of wildlife and humans.", "output": {"entities": {"chemical": [{"text": "Methyl mercury", "start": 0, "end": 14}, {"text": "MeHg", "start": 16, "end": 20}]}}, "schema": []}
{"input": "Recent studies have demonstrated that aquatic insects biotransport MeHg and other contaminants to terrestrial consumers, but the factors that regulate the flux of MeHg out of aquatic ecosystems via emergent insects have not been studied.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 67, "end": 71}, {"text": "MeHg", "start": 163, "end": 167}]}}, "schema": []}
{"input": "The authors used experimental mesocosms to test the hypothesis that insect emergence and the associated flux of MeHg from aquatic to terrestrial ecosystems is affected by both bottom-up nutrient effects and top-down fish consumer effects.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 112, "end": 116}]}}, "schema": []}
{"input": "In the present study, nutrient addition led to an increase in MeHg flux primarily by enhancing the biomass of emerging insects whose tissues were contaminated with MeHg, whereas fish decreased MeHg flux primarily by reducing the biomass of emerging insects.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 62, "end": 66}, {"text": "MeHg", "start": 164, "end": 168}, {"text": "MeHg", "start": 193, "end": 197}]}}, "schema": []}
{"input": "Furthermore, the authors found that these factors are interdependent such that the effects of nutrients are more pronounced when fish are absent, and the effects of fish are more pronounced when nutrient concentrations are high.", "output": {"entities": {}}, "schema": []}
{"input": "The present study is the first to demonstrate that the flux of MeHg from aquatic to terrestrial ecosystems is strongly enhanced by bottom-up nutrient effects and diminished by top-down consumer effects.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 63, "end": 67}]}}, "schema": []}
{"input": "Characterizing the lateral friction of nanoparticles on on-chip integrated black lipid membranes.", "output": {"entities": {}}, "schema": []}
{"input": "The use of nanoparticles (NPs) in biomedical applications creates a need for appropriate model systems to systematically investigate NP-membrane interactions under well-defined conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Black lipid membranes (BLMs) are free-floating membranes with defined composition that are ideally suited for characterizing NP-membrane interactions free of any potential perturbation through a supporting substrate.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, arrays of microfabricated BLMs are integrated into a chip-based platform that is compatible with high-speed optical NP tracking.", "output": {"entities": {}}, "schema": []}
{"input": "This system is used to investigate the lateral diffusion of 40 nm gold spheres tethered to biotinylated lipids through antibody-functionalized ligands (single-stranded DNA or polyethylene glycol).", "output": {"entities": {"chemical": [{"text": "polyethylene glycol", "start": 175, "end": 194}]}}, "schema": []}
{"input": "Although the NPs show an almost free and ergodic diffusion, their lateral motion is subject to substantial drag at the membrane surface, which leads to systematically smaller diffusion coefficients than those obtained for lipids in the membrane through fluorescence recovery after photobleaching.", "output": {"entities": {}}, "schema": []}
{"input": "The lateral mobility of the NPs is influenced by the chemical composition and salt concentration at the NP-membrane interface, but is independent of the ligand density in the membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Together with the observation that nanoprisms, which have a larger relative contact area with the membrane than spherical NPs, show an even slower diffusion, these findings indicate that the lateral mobility of NPs tethered in close vicinity to a membrane is significantly reduced by the friction at the NP-membrane interface.", "output": {"entities": {}}, "schema": []}
{"input": "A new class of room-temperature multiferroic thin films with bismuth-based supercell structure.", "output": {"entities": {"chemical": [{"text": "bismuth", "start": 61, "end": 68}]}}, "schema": []}
{"input": "Intergrowth of two partially miscible phases of BiFeO (3) and BiMnO (3) gives a new class of room-temperature multiferroic phase, Bi (3) Fe (2) Mn (2) O (10 + delta), which has a unique supercell (SC) structure.", "output": {"entities": {"chemical": [{"text": "BiFeO (3)", "start": 48, "end": 57}, {"text": "BiMnO (3)", "start": 62, "end": 71}, {"text": "Bi (3) Fe (2) Mn (2) O (10 + delta)", "start": 130, "end": 165}]}}, "schema": []}
{"input": "The SC heterostructures exhibit simultaneously room-temperature ferrimagnetism and remanent polarization.", "output": {"entities": {}}, "schema": []}
{"input": "These results open up a new avenue for exploring room-temperature single-phase multiferroic thin films by controlling the phase mixing of two perovskite BiRO (3) (R = Cr, Mn, Fe, Co, Ni) materials.", "output": {"entities": {"chemical": [{"text": "perovskite BiRO (3)", "start": 142, "end": 161}, {"text": "Cr", "start": 167, "end": 169}, {"text": "Mn", "start": 171, "end": 173}, {"text": "Fe", "start": 175, "end": 177}, {"text": "Co", "start": 179, "end": 181}, {"text": "Ni", "start": 183, "end": 185}]}}, "schema": []}
{"input": "DDBJ new system and service refactoring.", "output": {"entities": {}}, "schema": []}
{"input": "The DNA data bank of Japan (DDBJ, http://www. ddbj. nig. ac. jp) maintains a primary nucleotide sequence database and provides analytical resources for biological information to researchers.", "output": {"entities": {}}, "schema": []}
{"input": "This database content is exchanged with the US National Center for Biotechnology Information (NCBI) and the European Bioinformatics Institute (EBI) within the framework of the International Nucleotide Sequence Database Collaboration (INSDC).", "output": {"entities": {}}, "schema": []}
{"input": "Resources provided by the DDBJ include traditional nucleotide sequence data released in the form of 27 316 452 entries or 16 876 791 557 base pairs (as of June 2012), and raw reads of new generation sequencers in the sequence read archive (SRA).", "output": {"entities": {}}, "schema": []}
{"input": "A Japanese researcher published his own genome sequence via DDBJ-SRA on 31 July 2012.", "output": {"entities": {}}, "schema": []}
{"input": "To cope with the ongoing genomic data deluge, in March 2012, our computer previous system was totally replaced by a commodity cluster-based system that boasts 122. 5 TFlops of CPU capacity and 5 PB of storage space.", "output": {"entities": {}}, "schema": []}
{"input": "During this upgrade, it was considered crucial to replace and refactor substantial portions of the DDBJ software systems as well.", "output": {"entities": {}}, "schema": []}
{"input": "As a result of the replacement process, which took more than 2 years to perform, we have achieved significant improvements in system performance.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and anti-angiogenic activity of benzothiazole, benzimidazole containing phthalimide derivatives.", "output": {"entities": {"chemical": [{"text": "benzothiazole", "start": 42, "end": 55}, {"text": "benzimidazole", "start": 57, "end": 70}, {"text": "phthalimide", "start": 82, "end": 93}]}}, "schema": []}
{"input": "Benzothiazole and benzimidazole containing phthalimide derivatives (NK037, NK041, NK042, NK0139A and NK0148) have been synthesized and their anti-angiogenic activity was evaluated using ex vivo egg yolk angiogenesis model.", "output": {"entities": {"chemical": [{"text": "Benzothiazole", "start": 0, "end": 13}, {"text": "benzimidazole", "start": 18, "end": 31}, {"text": "phthalimide", "start": 43, "end": 54}, {"text": "NK037", "start": 68, "end": 73}, {"text": "NK041", "start": 75, "end": 80}, {"text": "NK042", "start": 82, "end": 87}, {"text": "NK0139A", "start": 89, "end": 96}, {"text": "NK0148", "start": 101, "end": 107}]}}, "schema": []}
{"input": "A comparative study with pure thalidomide (NKTA) has also been performed to describe the efficacy of these derivatives in blocking angiogenesis.", "output": {"entities": {"chemical": [{"text": "thalidomide", "start": 30, "end": 41}]}}, "schema": []}
{"input": "NK037, NK041 and NK042 were equally potent in blocking egg yolk angiogenesis and the anti-angiogenesis effect was higher than NKTA suggesting the efficacy of these three derivatives in blocking angiogenesis when compare to control.", "output": {"entities": {"chemical": [{"text": "NK037", "start": 0, "end": 5}, {"text": "NK041", "start": 7, "end": 12}, {"text": "NK042", "start": 17, "end": 22}, {"text": "NKTA", "start": 126, "end": 130}]}}, "schema": []}
{"input": "Other two derivatives NK0139A and NK0148 showed effect less than NKTA and stronger than control in ex vivo angiogenesis.", "output": {"entities": {"chemical": [{"text": "NK0139A", "start": 22, "end": 29}, {"text": "NK0148", "start": 34, "end": 40}, {"text": "NKTA", "start": 65, "end": 69}]}}, "schema": []}
{"input": "Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA. TTC) associated with Friedreich' s ataxia.", "output": {"entities": {}}, "schema": []}
{"input": "Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells.", "output": {"entities": {}}, "schema": []}
{"input": "Below, we show that long (230 repeats) tracts of the trinucleotide associated with Friedreich' s ataxia (GAA. TTC) stimulate both large (> 50 bp) deletions and point mutations in a reporter gene located more than 1 kb from the repetitive tract.", "output": {"entities": {}}, "schema": []}
{"input": "Sequence analysis of deletion breakpoints indicates that the deletions reflect non-homologous end joining of double-stranded DNA breaks (DSBs) initiated in the tract.", "output": {"entities": {}}, "schema": []}
{"input": "The tract-induced point mutations appear to reflect a different mechanism involving single-strand annealing of DNA molecules generated by DSBs within the tract, followed by filling-in of single-stranded gaps by the error-prone DNA polymerase zeta.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxicity, antioxidant activity and an effect on CYP3A4 and CYP2D6 of Mutellina purpurea L. extracts.", "output": {"entities": {}}, "schema": []}
{"input": "Mutellina purpurea is an aromatic Apiaceae plant known as Alpine lovage.", "output": {"entities": {}}, "schema": []}
{"input": "Its polar extracts consist of phenolic acids, tannins and flavonoids.", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 30, "end": 44}, {"text": "tannins", "start": 46, "end": 53}, {"text": "flavonoids", "start": 58, "end": 68}]}}, "schema": []}
{"input": "The cytotoxic effect of methanolic and aqueous extracts from M. purpurea was studied on the most frequently used cell lines: HeLa and BHK-21.", "output": {"entities": {}}, "schema": []}
{"input": "Taking into account that the natural products are often used with other medicines there is a risk of reciprocal interaction on the metabolic level.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the influence of M. purpurea extracts was investigated on the activity of CYP2D6 and CYP3A4, which are the most important P450 isoenzymes from the pharmacological and toxicological points of view.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, because M. purpurea contains phenolic compounds, the antioxidative properties of this plant extracts were also studied and compared.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 43, "end": 51}]}}, "schema": []}
{"input": "Control of hypercholesterolemia and atherosclerosis using the cholesterol recognition/interaction amino acid sequence of the translocator protein TSPO.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 98, "end": 108}]}}, "schema": []}
{"input": "The translocator protein (18-kDa) TSPO is an ubiquitous high affinity cholesterol-binding protein reported to be present in the endothelial and smooth muscle cells of the blood vessels; its expression dramatically increased in macrophages found in atherosclerotic plaques.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 70, "end": 81}]}}, "schema": []}
{"input": "A domain in the carboxy-terminus of TSPO was identified and characterized as the cholesterol recognition/interaction amino acid consensus (CRAC).", "output": {"entities": {"chemical": [{"text": "carboxy", "start": 16, "end": 23}, {"text": "cholesterol", "start": 81, "end": 92}, {"text": "amino acid", "start": 117, "end": 127}]}}, "schema": []}
{"input": "The ability of the CRAC domain to bind to cholesterol led us to hypothesize that this peptide could be used as an hypocholesterolemic, with potential anti-atherogenic properties, agent.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 42, "end": 53}]}}, "schema": []}
{"input": "We report herein the therapeutic benefit that resulted for the administration of the VLNYYVWR human CRAC sequence to guinea pigs fed with a high cholesterol diet and ApoE knock-out B6. 129P2-Apoetm1Unc/J mice.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 145, "end": 156}]}}, "schema": []}
{"input": "CRAC treatment (3 and 30mg/kg once daily for 6 weeks) resulted in reduced circulating cholesterol levels in guinea pigs fed with 2% high cholesterol diet and ApoE knock-out B6. 129P2-Apoetm1Unc/J mice.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 86, "end": 97}, {"text": "cholesterol", "start": 137, "end": 148}]}}, "schema": []}
{"input": "In high cholesterol fed guinea pigs, CRAC treatment administered once daily induced an increase in circulating HDL, decreased total, free and LDL cholesterol, and removed atheroma deposits in the aorta in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 8, "end": 19}, {"text": "cholesterol", "start": 146, "end": 157}]}}, "schema": []}
{"input": "The treatment also prevented the high cholesterol diet-induced increase in serum creatine kinase, total and isoforms, markers of neurological, cardiac and muscular damage.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 38, "end": 49}, {"text": "creatine", "start": 81, "end": 89}]}}, "schema": []}
{"input": "No toxicity was observed.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together these results support a role of TSPO in lipid homeostasis and atherosclerosis and indicate that CRAC may constitute a novel and safe treatment of hypercholesterolemia and atherosclerosis.", "output": {"entities": {}}, "schema": []}
{"input": "Disrupted cytoskeletal homeostasis, astrogliosis and apoptotic cell death in the cerebellum of preweaning rats injected with diphenyl ditelluride.", "output": {"entities": {"chemical": [{"text": "diphenyl ditelluride", "start": 125, "end": 145}]}}, "schema": []}
{"input": "In the present report 15 day-old rats were injected with 0. 3 mu mol of diphenyl ditelluride (PhTe) (2)/kg body weight and parameters of neurodegeneration were analyzed in slices from cerebellum 3 and 6 days afterwards.", "output": {"entities": {"chemical": [{"text": "diphenyl ditelluride (PhTe) (2)", "start": 72, "end": 103}]}}, "schema": []}
{"input": "The earlier responses, at day 3 after injection, included hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein-GFAP-and vimentin) and neuron (low-, medium-and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H); increased mitogen-activated protein kinase (MAPK) (Erk and p38MAPK) and cAMP-dependent protein kinase (PKA) activities.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 354, "end": 358}]}}, "schema": []}
{"input": "Also, reactive astrogliosis takes part of the early responses to the insult with (PhTe) (2), evidenced by upregulated GFAP in Western blot, PCR and immunofluorescence analysis.", "output": {"entities": {"chemical": [{"text": "(PhTe) (2)", "start": 81, "end": 91}]}}, "schema": []}
{"input": "Six days after (PhTe) (2) injection we found persistent astrogliosis, increased propidium iodide (PI) positive cells in NeuN positive population evidenced by flow cytometry and reduced immunofluorescence for NeuN, suggesting that the in vivo exposure to (PhTe) (2) progressed to neuronal death.", "output": {"entities": {"chemical": [{"text": "(PhTe) (2)", "start": 15, "end": 25}, {"text": "propidium iodide", "start": 80, "end": 96}, {"text": "(PhTe) (2)", "start": 254, "end": 264}]}}, "schema": []}
{"input": "Moreover, activated caspase 3 suggested apoptotic neuronal death.", "output": {"entities": {}}, "schema": []}
{"input": "Neurodegeneration was related with decreased [(3) H] glutamate uptake and decreased Akt immunoreactivity, however phospho-GSK-3-beta (Ser9) was not altered in (PhTe) (2) injected rat.", "output": {"entities": {"chemical": [{"text": "[(3) H] glutamate", "start": 45, "end": 62}, {"text": "Ser9", "start": 134, "end": 138}, {"text": "(PhTe) (2)", "start": 159, "end": 169}]}}, "schema": []}
{"input": "Therefore, the present results show that the earlier cerebellar responses to (PhTe) (2) include disruption of cytoskeletal homeostasis that could be related with MAPK and PKA activation and reactive astrogliosis.", "output": {"entities": {"chemical": [{"text": "(PhTe) (2)", "start": 77, "end": 87}]}}, "schema": []}
{"input": "Akt inhibition observed at this time could also play a role in the neuronal death evidenced afterwards.", "output": {"entities": {}}, "schema": []}
{"input": "The later events of the neurodegenerative process are characterized by persistent astrogliosis and activation of apoptotic neuronal death through caspase 3 mediated mechanisms, which could be related with glutamate excitotoxicity.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 205, "end": 214}]}}, "schema": []}
{"input": "The progression of these responses are therefore likely to be critical for the outcome of the neurodegeneration provoked by (PhTe) (2) in rat cerebellum.", "output": {"entities": {"chemical": [{"text": "(PhTe) (2)", "start": 124, "end": 134}]}}, "schema": []}
{"input": "The microsomal enzyme 17 beta-hydroxysteroid dehydrogenase 3 faces the cytoplasm and uses NADPH generated by glucose-6-phosphate dehydrogenase.", "output": {"entities": {"chemical": [{"text": "17 beta-hydroxysteroid", "start": 22, "end": 44}, {"text": "NADPH", "start": 90, "end": 95}, {"text": "glucose-6-phosphate", "start": 109, "end": 128}]}}, "schema": []}
{"input": "Recent studies proposed a functional coupling between 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3)-dependent testosterone formation and 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1)-mediated interconversion of glucocorticoids through competition for the luminal pyridine nucleotide pool.", "output": {"entities": {"chemical": [{"text": "17 beta-hydroxysteroid", "start": 54, "end": 76}, {"text": "11 beta-hydroxysteroid", "start": 145, "end": 167}, {"text": "pyridine nucleotide", "start": 279, "end": 298}]}}, "schema": []}
{"input": "To test this hypothesis, we used human embryonic kidney-293 cells transfected with 17 beta-HSD3 and/or 11 beta-HSD1, in the absence or presence of hexose-6-phosphate dehydrogenase that generates reduced nicotinamide adenine dinucleotide phosphate (NADPH) in the endoplasmic reticulum and determined enzyme activities.", "output": {"entities": {"chemical": [{"text": "hexose-6-phosphate", "start": 147, "end": 165}, {"text": "nicotinamide adenine dinucleotide phosphate", "start": 203, "end": 246}, {"text": "NADPH", "start": 248, "end": 253}]}}, "schema": []}
{"input": "As an endogenous cell model, mouse MA-10 Leydig cells were used.", "output": {"entities": {}}, "schema": []}
{"input": "17 beta-HSD3-dependent reduction of Delta 4-androstene-3, 17-dione was affected by neither coexpression with 11 beta-HSD1 nor overexpression or knockdown of hexose-6-phosphate dehydrogenase.", "output": {"entities": {"chemical": [{"text": "Delta 4-androstene-3, 17-dione", "start": 36, "end": 66}, {"text": "hexose-6-phosphate", "start": 157, "end": 175}]}}, "schema": []}
{"input": "In contrast, knockdown of glucose-6-phosphate dehydrogenase decreased 17 beta-HSD3 activity, indicating dependence on cytoplasmic NADPH.", "output": {"entities": {"chemical": [{"text": "glucose-6-phosphate", "start": 26, "end": 45}, {"text": "NADPH", "start": 130, "end": 135}]}}, "schema": []}
{"input": "Upon selective permeabilization of the plasma membrane by digitonin, 17 beta-HSD3 but not 11 beta-HSD1 was detected by antibodies against C-terminal epitope tags, suggesting a cytoplasmic orientation of 17 beta-HSD3.", "output": {"entities": {"chemical": [{"text": "digitonin", "start": 58, "end": 67}, {"text": "C", "start": 138, "end": 139}]}}, "schema": []}
{"input": "The cytoplasmic orientation was confirmed using proteinase K digestion of microsomal preparations and by analysis of glycosylation of wild-type 17 beta-HSD3 and chimera in which the N-terminal anchor sequences between 17 beta-HSD3 and 11 beta-HSD1 were exchanged.", "output": {"entities": {"chemical": [{"text": "N", "start": 182, "end": 183}]}}, "schema": []}
{"input": "In conclusion, the results demonstrate a cytoplasmic orientation of 17 beta-HSD3 and dependence on glucose-6-phosphate dehydrogenase-generated NADPH, explaining the lack of a direct functional coupling with the luminal 11 beta-HSD1-mediated glucocorticoid metabolism.", "output": {"entities": {"chemical": [{"text": "glucose-6-phosphate", "start": 99, "end": 118}, {"text": "NADPH", "start": 143, "end": 148}]}}, "schema": []}
{"input": "A combined nuclear and nucleolar localization motif in activation-induced cytidine deaminase (AID) controls immunoglobulin class switching.", "output": {"entities": {"chemical": [{"text": "cytidine", "start": 74, "end": 82}]}}, "schema": []}
{"input": "Activation-induced cytidine deaminase (AID) is a DNA mutator enzyme essential for adaptive immunity.", "output": {"entities": {"chemical": [{"text": "cytidine", "start": 19, "end": 27}]}}, "schema": []}
{"input": "AID initiates somatic hypermutation and class switch recombination (CSR) by deaminating cytosine to uracil in specific immunoglobulin (Ig) gene regions.", "output": {"entities": {"chemical": [{"text": "cytosine", "start": 88, "end": 96}, {"text": "uracil", "start": 100, "end": 106}]}}, "schema": []}
{"input": "However, other loci, including cancer-related genes, are also targeted.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, tight regulation of AID is crucial to balance immunity versus disease such as cancer.", "output": {"entities": {}}, "schema": []}
{"input": "AID is regulated by several mechanisms including nucleocytoplasmic shuttling.", "output": {"entities": {}}, "schema": []}
{"input": "Here we have studied nuclear import kinetics and subnuclear trafficking of AID in live cells and characterized in detail its nuclear localization signal.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, we find that the nuclear localization signal motif also directs AID to nucleoli where it colocalizes with its interaction partner, catenin-beta-like 1 (CTNNBL1), and physically associates with nucleolin and nucleophosmin.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, we demonstrate that release of AID from nucleoli is dependent on its C-terminal motif.", "output": {"entities": {"chemical": [{"text": "C", "start": 79, "end": 80}]}}, "schema": []}
{"input": "Finally, we find that CSR efficiency correlates strongly with the arithmetic product of AID nuclear import rate and DNA deamination activity.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest that directional nucleolar transit is important for the physiological function of AID and demonstrate that nuclear/nucleolar import and DNA cytosine deamination together define the biological activity of AID.", "output": {"entities": {"chemical": [{"text": "cytosine", "start": 161, "end": 169}]}}, "schema": []}
{"input": "This is the first study on subnuclear trafficking of AID and demonstrates a new level in its complex regulation.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, our results resolve the problem related to dissociation of deamination activity and CSR activity of AID mutants.", "output": {"entities": {}}, "schema": []}
{"input": "One pot synthesis and biological activity evaluation of novel Schiff bases derived from 2-hydrazinyl-1, 3, 4-thiadiazole.", "output": {"entities": {"chemical": [{"text": "Schiff bases", "start": 62, "end": 74}, {"text": "2-hydrazinyl-1, 3, 4-thiadiazole", "start": 88, "end": 120}]}}, "schema": []}
{"input": "Considering the structural features of a group of known potent inhibitors of human platelet aggregation containing hydrazone structural backbone, a series of novel hydrazone derivatives of 2-hydrazinyl-1, 3, 4-thiadiazole were synthesized using a one-pot process and tested for their inhibitory activity against platelet aggregation induced by arachidonic acid and ADP.", "output": {"entities": {"chemical": [{"text": "hydrazone", "start": 115, "end": 124}, {"text": "hydrazone", "start": 164, "end": 173}, {"text": "2-hydrazinyl-1, 3, 4-thiadiazole", "start": 189, "end": 221}, {"text": "arachidonic acid", "start": 344, "end": 360}, {"text": "ADP", "start": 365, "end": 368}]}}, "schema": []}
{"input": "Among the derivatives, compounds 3l, 3o and 3p exhibited the highest antiplatelet aggregation activity.", "output": {"entities": {}}, "schema": []}
{"input": "The derivatives were also screened for their potential antimycobacterial activity and compounds 3g, 3k, 3p and 3q were among the most active compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of ice nucleation by slippery liquid-infused porous surfaces (SLIPS).", "output": {"entities": {}}, "schema": []}
{"input": "Ice repellent coatings have been studied and keenly sought after for many years, where any advances in the durability of such coatings will result in huge energy savings across many fields.", "output": {"entities": {}}, "schema": []}
{"input": "Progress in creating anti-ice and anti-frost surfaces has been particularly rapid since the discovery and development of slippery, liquid infused porous surfaces (SLIPS).", "output": {"entities": {}}, "schema": []}
{"input": "Here we use SLIPS-coated differential scanning calorimeter (DSC) pans to investigate the effects of the surface modification on the nucleation of supercooled water.", "output": {"entities": {}}, "schema": []}
{"input": "This investigation is inherently different from previous studies which looked at the adhesion of ice to SLIPS surfaces, or the formation of ice under high humidity conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Given the stochastic nature of nucleation of ice from supercooled water, multiple runs on the same sample are needed to determine if a given surface coating has a real and statistically significant effect on the nucleation temperature.", "output": {"entities": {}}, "schema": []}
{"input": "We have cycled supercooling to freezing and then thawing of deionized water in hydrophilic (untreated aluminum), hydrophobic, superhydrophobic, and SLIPS-treated DSC pans multiple times to determine the effects of surface treatment on the nucleation and subsequent growth of ice.", "output": {"entities": {"chemical": [{"text": "aluminum", "start": 102, "end": 110}]}}, "schema": []}
{"input": "We find that SLIPS coatings lower the nucleation temperature of supercooled water in contact with statistical significance and show no deterioration or change in the coating performance even after 150 freeze-thaw cycles.", "output": {"entities": {}}, "schema": []}
{"input": "X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 146, "end": 154}]}}, "schema": []}
{"input": "X-chromosomal dystonia parkinsonism syndrome (XDP,' lubag') is associated with sequence changes within the TAF1/DYT3 multiple transcript system.", "output": {"entities": {}}, "schema": []}
{"input": "Although most sequence changes are intronic, one, disease-specific single-nucleotide change 3 (DSC3), is located within an exon (d4).", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 74, "end": 84}]}}, "schema": []}
{"input": "Transcribed exon d4 occurs as part of multiple splice variants.", "output": {"entities": {}}, "schema": []}
{"input": "These variants include exons d3 and d4 spliced to exons of TAF1, and an independent transcript composed of exons d2-d4.", "output": {"entities": {}}, "schema": []}
{"input": "Location of DSC3 in exon d4 and utilization of this exon in multiple splice variants suggest an important role of DSC3 in the XDP pathogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "To test this hypothesis, we transfected neuroblastoma cells with four expression constructs, including exons d2-d4 [d2-d4/wild-type (wt) and d2-d4/DSC3] and d3-d4 (d3-d4/wt and d3-d4/DSC3).", "output": {"entities": {}}, "schema": []}
{"input": "Expression profiling revealed a dramatic effect of DSC3 on overall gene expression.", "output": {"entities": {}}, "schema": []}
{"input": "Three hundred and sixty-two genes differed between cells containing d2-d4/wt and d2-d4/DSC3.", "output": {"entities": {}}, "schema": []}
{"input": "Annotation clustering revealed enrichment of genes related to vesicular transport, dopamine metabolism, synapse function, Ca (2 +) metabolism and oxidative stress.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 83, "end": 91}, {"text": "Ca (2 +)", "start": 122, "end": 130}]}}, "schema": []}
{"input": "Two hundred and eleven genes were differentially expressed in d3-d4/wt versus d3-d4/DSC3.", "output": {"entities": {}}, "schema": []}
{"input": "Annotation clustering highlighted genes in signal transduction and cell-cell interaction.", "output": {"entities": {}}, "schema": []}
{"input": "The data show an important role of physiologically occurring transcript d2-d4 in normal brain function.", "output": {"entities": {}}, "schema": []}
{"input": "Interference with this role by DSC3 is a likely pathological mechanism in XDP.", "output": {"entities": {}}, "schema": []}
{"input": "Disturbance of dopamine function and of Ca (2 +) metabolism can explain abnormal movement; loss of protection against reactive oxygen species may account for the neurodegenerative changes in XDP.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 40, "end": 48}, {"text": "oxygen", "start": 127, "end": 133}]}}, "schema": []}
{"input": "Although d3-d4 also affect genes potentially related to neurodegenerative processes, their physiologic role as splice variants of TAF1 awaits further exploration.", "output": {"entities": {}}, "schema": []}
{"input": "An artificial neural network approach to improving the correlation between protein energetics and the backbone structure.", "output": {"entities": {}}, "schema": []}
{"input": "Computational approaches to modeling protein structures have made significant advances over the past decade.", "output": {"entities": {}}, "schema": []}
{"input": "However, the current limitation in modeling protein structures is to produce protein structures consistently below the limit of 6 A compared to their native structure.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, improvement of protein structures consistently below the 6 A limit using simulation of biophysical forces is of significant interest.", "output": {"entities": {}}, "schema": []}
{"input": "Current protein force fields such as those implemented in CHARMM, AMBER, and NAMD have been deemed complete, yet their use in ab initio approaches to protein structure determination has been unsuccessful.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we introduce a new approach in evaluation of protein structures based on analysis of energy profiles produced by the SCOPE software package.", "output": {"entities": {}}, "schema": []}
{"input": "The latest version of SCOPE produces a hydrogen bond profile that is substantially more informative than a single hydrogen bond energy value.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 39, "end": 47}, {"text": "hydrogen", "start": 114, "end": 122}]}}, "schema": []}
{"input": "We demonstrate how analysis of SCOPE' s energy profile by an artificial neural network shows a significant improvement compared to the traditional force-based approaches to evaluation of structures.", "output": {"entities": {}}, "schema": []}
{"input": "The artificial neural network based analysis of SCOPE' s energy profile showed identification of structures to within the range of 1. 5-3. 0 A of the native structure.", "output": {"entities": {}}, "schema": []}
{"input": "These results have been obtained by testing structures in the same Homology, Topology, Architecture, or Class of the CATH family.", "output": {"entities": {}}, "schema": []}
{"input": "Electronic transition moments of 6-methyl isoxanthopterin--a fluorescent analogue of the nucleic acid base guanine.", "output": {"entities": {"chemical": [{"text": "6-methyl isoxanthopterin", "start": 33, "end": 57}, {"text": "guanine", "start": 107, "end": 114}]}}, "schema": []}
{"input": "Fluorescent nucleic acid base analogues are important spectroscopic tools for understanding local structure and dynamics of DNA and RNA.", "output": {"entities": {}}, "schema": []}
{"input": "We studied the orientations and magnitudes of the electric dipole transition moments (EDTMs) of 6-methyl isoxanthopterin (6-MI), a fluorescent analogue of guanine that has been particularly useful in biological studies.", "output": {"entities": {"chemical": [{"text": "6-methyl isoxanthopterin", "start": 96, "end": 120}, {"text": "6-MI", "start": 122, "end": 126}, {"text": "guanine", "start": 155, "end": 162}]}}, "schema": []}
{"input": "Using a combination of absorption spectroscopy, linear dichroism (LD) and quantum chemical calculations, we identified six electronic transitions that occur within the 25, 000-50, 000 cm (-1) spectral range.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that the two experimentally observed lowest-energy transitions, which occur at 29, 687 cm (-1) (337 nm) and 34, 596 cm (-1) (289 nm), are each polarized within the plane of the 6-MI base.", "output": {"entities": {"chemical": [{"text": "6-MI", "start": 198, "end": 202}]}}, "schema": []}
{"input": "A third in-plane polarized transition is experimentally observed at 47, 547 cm (-1) (210 nm).", "output": {"entities": {}}, "schema": []}
{"input": "The theoretically predicted orientation of the lowest-energy transition moment agrees well with experiment.", "output": {"entities": {}}, "schema": []}
{"input": "Based on these results, we constructed an exciton model to describe the absorption spectra of a 6-MI dinucleotide-substituted double-stranded DNA construct.", "output": {"entities": {"chemical": [{"text": "6-MI", "start": 96, "end": 100}]}}, "schema": []}
{"input": "This model is in good agreement with the experimental data.", "output": {"entities": {}}, "schema": []}
{"input": "The orientations and intensities of the low-energy electronic transitions of 6-MI reported here should be useful for studying local conformations of DNA and RNA in biologically important complexes.", "output": {"entities": {"chemical": [{"text": "6-MI", "start": 77, "end": 81}]}}, "schema": []}
{"input": "Evaluation of romidepsin for clinical activity and radioactive iodine reuptake in radioactive iodine-refractory thyroid carcinoma.", "output": {"entities": {"chemical": [{"text": "romidepsin", "start": 14, "end": 24}, {"text": "radioactive iodine", "start": 51, "end": 69}, {"text": "radioactive iodine", "start": 82, "end": 100}]}}, "schema": []}
{"input": "Background: Historically, systemic therapy for radioactive iodine (RAI)-refractory thyroid cancer has been understudied.", "output": {"entities": {"chemical": [{"text": "radioactive iodine", "start": 47, "end": 65}, {"text": "RAI", "start": 67, "end": 70}]}}, "schema": []}
{"input": "Available drugs have modest efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "Romidepsin is a histone deacetylase inhibitor with potent antitumor effects both in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "Romidepsin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "In thyroid cancer cell lines, romidepsin increases expression of both thyroglobulin and the sodium iodide symporter messenger RNAs, suggesting the possibility of improved iodine concentrating ability of RAI-resistant tumors.", "output": {"entities": {"chemical": [{"text": "sodium iodide", "start": 92, "end": 105}, {"text": "iodine", "start": 171, "end": 177}, {"text": "RAI", "start": 203, "end": 206}]}}, "schema": []}
{"input": "Methods: This was a single-institution Simon 2-stage phase II clinical study.", "output": {"entities": {}}, "schema": []}
{"input": "Eligible patients had progressive, RAI-refractory, recurrent/metastatic, nonmedullary, nonanaplastic thyroid cancer.", "output": {"entities": {"chemical": [{"text": "RAI", "start": 35, "end": 38}]}}, "schema": []}
{"input": "Response Evaluation Criteria in Solid Tumors (RECIST) 1. 0 measurable disease and adequate organ/marrow function were required.", "output": {"entities": {}}, "schema": []}
{"input": "Romidepsin 13 mg/m (2) was administered intravenously on days 1, 8, and 15, in cycles of 28 days.", "output": {"entities": {"chemical": [{"text": "Romidepsin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The primary endpoint was the response rate by RECIST; change in RAI avidity was a secondary endpoint.", "output": {"entities": {"chemical": [{"text": "RAI", "start": 64, "end": 67}]}}, "schema": []}
{"input": "The study closed after the first stage due to the lack of response.", "output": {"entities": {}}, "schema": []}
{"input": "Results: Twenty patients were enrolled: female, 50%; median age, 64 years; histology, 8 papillary/1 follicular/11 H u rthle.", "output": {"entities": {}}, "schema": []}
{"input": "Grade 4-5 adverse events (AEs) possibly related to the drug: grade 5, 1 sudden death; grade 4, 1 pulmonary embolus.", "output": {"entities": {}}, "schema": []}
{"input": "Twelve of 20 subjects had a reported adverse event.", "output": {"entities": {}}, "schema": []}
{"input": "No RECIST major responses have been seen.", "output": {"entities": {}}, "schema": []}
{"input": "Response per protocol: stable disease, 13; disease progression, 7.", "output": {"entities": {}}, "schema": []}
{"input": "Restoration of RAI avidity was documented in two patients.", "output": {"entities": {"chemical": [{"text": "RAI", "start": 15, "end": 18}]}}, "schema": []}
{"input": "Median overall survival and time on study was 33. 2 (1-71 +) and 1. 7 (0. 46-12) months, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: We observed preliminary signs of in vivo reversal of RAI resistance after treatment with romidepsin.", "output": {"entities": {"chemical": [{"text": "RAI", "start": 66, "end": 69}, {"text": "romidepsin", "start": 102, "end": 112}]}}, "schema": []}
{"input": "However, no major responses were observed and accrual was poor after the grade 5 AE.", "output": {"entities": {}}, "schema": []}
{"input": "Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation.", "output": {"entities": {"chemical": [{"text": "prostaglandins", "start": 78, "end": 92}, {"text": "amines", "start": 113, "end": 119}]}}, "schema": []}
{"input": "We have demonstrated that the activation of P2X3 receptor on peripheral afferent neurons is critical to development of inflammatory hyperalgesia in peripheral tissue, although pharmacological administration of prostaglandin E (2) or sympathomimetic amines is enough to sensitize primary afferent neurons by acting directly in neuronal receptors.", "output": {"entities": {"chemical": [{"text": "prostaglandin E (2)", "start": 210, "end": 229}, {"text": "amines", "start": 249, "end": 255}]}}, "schema": []}
{"input": "Therefore, to clarify this ambiguity this study verifies whether P2X3 receptor activation on primary afferent neurons enables the sensitization induced by prostaglandin E (2) or sympathomimetic amine.", "output": {"entities": {"chemical": [{"text": "prostaglandin E (2)", "start": 155, "end": 174}, {"text": "amine", "start": 194, "end": 199}]}}, "schema": []}
{"input": "Initially, this study confirmed that co-administration of A317491 (60 mu g/paw), a selective P2X3 receptor antagonist, or pre-treatment with dexamethasone (1 mg/mL/kg) prevents the mechanical hyperalgesia induced by carrageenan (300 mu g/paw) in the rat' s hind paw.", "output": {"entities": {"chemical": [{"text": "A317491", "start": 58, "end": 65}, {"text": "dexamethasone", "start": 141, "end": 154}]}}, "schema": []}
{"input": "Sub-threshold doses of PGE (2) (4 ng/paw) or dopamine (0. 4 mu g/paw), that do not induce hyperalgesia by themselves, when injected just following alpha beta meATP or carrageenan in rats treated with dexamethasone induced hyperalgesia, which is prevented by A317491 or treatment with periganglionar (DRG-L5) injections of ODN-antisense, against P2X3 receptor.", "output": {"entities": {"chemical": [{"text": "PGE (2)", "start": 23, "end": 30}, {"text": "dopamine", "start": 45, "end": 53}, {"text": "alpha beta meATP", "start": 147, "end": 163}, {"text": "dexamethasone", "start": 200, "end": 213}, {"text": "A317491", "start": 258, "end": 265}]}}, "schema": []}
{"input": "Furthermore, because PKC epsilon translocation induces an increase of neuronal susceptibility to inflammatory mediators, this study demonstrates that alpha beta meATP in peripheral tissue increases the expression of PKC epsilon in cell membranes of DRG-L5, and in contrast, the administration of PKC epsilon translocation inhibitor (1 mu g/paw) in peripheral tissue 45 min before alpha beta meATP, prevented the hyperalgesia induced by sub-threshold dose of PGE (2) (4 ng/paw).", "output": {"entities": {"chemical": [{"text": "alpha beta meATP", "start": 150, "end": 166}, {"text": "alpha beta meATP", "start": 380, "end": 396}, {"text": "PGE (2)", "start": 458, "end": 465}]}}, "schema": []}
{"input": "In conclusion, this study suggests that neuronal P2X3 receptor activation and the consequent PKC epsilon translocation increase the susceptibility of nociceptor to inflammatory mediators allowing the development of inflammatory hyperalgesia.", "output": {"entities": {}}, "schema": []}
{"input": "An ultrasonic-accelerated oxidation method for determining the oxidative stability of biodiesel.", "output": {"entities": {}}, "schema": []}
{"input": "Biodiesel is considered an alternative energy because it is produced from fats and vegetable oils by means of transesterification.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, it consists of fatty acid alkyl esters (FAAS) which have a great influence on biodiesel fuel properties and in the storage lifetime of biodiesel itself.", "output": {"entities": {"chemical": [{"text": "fatty acid alkyl esters", "start": 28, "end": 51}, {"text": "FAAS", "start": 53, "end": 57}]}}, "schema": []}
{"input": "The biodiesel storage stability is directly related to the oxidative stability parameter (Induction Time-IT) which is determined by means of the Rancimat (R) method.", "output": {"entities": {}}, "schema": []}
{"input": "This method uses condutimetric monitoring and induces the degradation of FAAS by heating the sample at a constant temperature.", "output": {"entities": {"chemical": [{"text": "FAAS", "start": 73, "end": 77}]}}, "schema": []}
{"input": "The European Committee for Standardization established a standard (EN 14214) to determine the oxidative stability of biodiesel, which requires it to reach a minimum induction period of 6h as tested by Rancimat (R) method at 110 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "In this research, we aimed at developing a fast and simple alternative method to determine the induction time (IT) based on the FAAS ultrasonic-accelerated oxidation.", "output": {"entities": {"chemical": [{"text": "FAAS", "start": 128, "end": 132}]}}, "schema": []}
{"input": "The sonodegradation of biodiesel samples was induced by means of an ultrasonic homogenizer fitted with an immersible horn at 480Watts of power and 20 duty cycles.", "output": {"entities": {}}, "schema": []}
{"input": "The UV-Vis spectrometry was used to monitor the FAAS sonodegradation by measuring the absorbance at 270nm every 2.", "output": {"entities": {"chemical": [{"text": "FAAS", "start": 48, "end": 52}]}}, "schema": []}
{"input": "Biodiesel samples from different feedstock were studied in this work.", "output": {"entities": {}}, "schema": []}
{"input": "In all cases, IT was established as the inflection point of the absorbance versus time curve.", "output": {"entities": {}}, "schema": []}
{"input": "The induction time values of all biodiesel samples determined using the proposed method was in accordance with those measured through the Rancimat (R) reference method by showing a R (2) = 0. 998.", "output": {"entities": {}}, "schema": []}
{"input": "Quantification of silanol sites for the most common mesoporous ordered silicas and organosilicas: total versus accessible silanols.", "output": {"entities": {"chemical": [{"text": "silanol", "start": 18, "end": 25}, {"text": "silicas", "start": 71, "end": 78}, {"text": "organosilicas", "start": 83, "end": 96}, {"text": "silanols", "start": 122, "end": 130}]}}, "schema": []}
{"input": "IR and NMR spectroscopy were used to determine the silanol content in the most common mesoporous ordered silicas: MCM-41, MCM-48, SBA-15 and SBA-16.", "output": {"entities": {"chemical": [{"text": "silanol", "start": 51, "end": 58}, {"text": "silicas", "start": 105, "end": 112}, {"text": "MCM-41", "start": 114, "end": 120}, {"text": "MCM-48", "start": 122, "end": 128}, {"text": "SBA-15", "start": 130, "end": 136}, {"text": "SBA-16", "start": 141, "end": 147}]}}, "schema": []}
{"input": "In addition, a spray dried MCM-41 and an ethene bridged PMO are investigated.", "output": {"entities": {"chemical": [{"text": "MCM-41", "start": 27, "end": 33}, {"text": "ethene", "start": 41, "end": 47}, {"text": "PMO", "start": 56, "end": 59}]}}, "schema": []}
{"input": "The results are compared with a commercial chromatographic silica (Nucleosil).", "output": {"entities": {"chemical": [{"text": "silica", "start": 59, "end": 65}, {"text": "Nucleosil", "start": 67, "end": 76}]}}, "schema": []}
{"input": "The complete distribution of surface and bulk silanols, and of isolated, geminal and vicinal silanols for all these materials is presented.", "output": {"entities": {"chemical": [{"text": "silanols", "start": 46, "end": 54}, {"text": "geminal and vicinal silanols", "start": 73, "end": 101}]}}, "schema": []}
{"input": "A distinction is made between the total silanol number and the reachable or surface silanol content.", "output": {"entities": {"chemical": [{"text": "silanol", "start": 40, "end": 47}, {"text": "silanol", "start": 84, "end": 91}]}}, "schema": []}
{"input": "The latter is determined by controlled reactions with simple silanes.", "output": {"entities": {"chemical": [{"text": "silanes", "start": 61, "end": 68}]}}, "schema": []}
{"input": "All mesoporous ordered silicas, and especially the thick walled SBA-type materials and the PMO contain a surprisingly high amount of total silanol sites, albeit that up to 90% of these silanols are buried inside the walls and are not reachable for small silanes.", "output": {"entities": {"chemical": [{"text": "silicas", "start": 23, "end": 30}, {"text": "PMO", "start": 91, "end": 94}, {"text": "silanol", "start": 139, "end": 146}, {"text": "silanols", "start": 185, "end": 193}]}}, "schema": []}
{"input": "Effect of structural defects and chemical functionalisation on the intrinsic mechanical properties of graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 102, "end": 110}]}}, "schema": []}
{"input": "Due to its unique mechanical properties, graphene can be applied for reinforcement in nanocomposites.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 41, "end": 49}]}}, "schema": []}
{"input": "We analyse the Young' s modulus of graphene at the semi-empirical PM6 level of theory.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 35, "end": 43}]}}, "schema": []}
{"input": "The internal forces are calculated and the Young' s modulus is predicted for a finite graphene sheet when external strain is applied on the system.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 86, "end": 94}]}}, "schema": []}
{"input": "These results are in a good agreement with theoretical and experimental results from the literature giving values of about 1 TPa for the Young' s modulus.", "output": {"entities": {}}, "schema": []}
{"input": "Stress-strain curves are computed for elongation up to 20%.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the influence of the presence of a single vacancy, as well as for oxygenation of a vacancy, on the mechanical properties of graphene has been analysed.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 137, "end": 145}]}}, "schema": []}
{"input": "Our results indicate that when applying the deformation locally onto the system, higher local stress can be induced, as confirmed by Finite Element Analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Also, the presence of structural defects in the system will stiffen the system upon low strain, but reduces the elastic limit from more than 20% strain for pristine graphene to less than 10% strain when defects are present.", "output": {"entities": {"chemical": [{"text": "pristine graphene", "start": 156, "end": 173}]}}, "schema": []}
{"input": "The role of natriuretic peptides as biomarkers for guiding the management of chronic heart failure.", "output": {"entities": {}}, "schema": []}
{"input": "The current standard treatment of chronic heart failure (HF) is based on clinical judgment, with the goal of achieving the maximally tolerated therapeutic program.", "output": {"entities": {}}, "schema": []}
{"input": "The complexity of this approach may contribute to the well-established treatment gaps that exist in HF management; consequently, the risks for morbidity and mortality in this population remain extremely high.", "output": {"entities": {}}, "schema": []}
{"input": "Alternative means are needed to improve the outcomes of patients with HF.", "output": {"entities": {}}, "schema": []}
{"input": "Natriuretic peptides are biological markers for HF disease--its presence, severity, and prognosis--and show unique interactions with therapeutics known to have benefit in HF.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, interest has recently developed in \" biomarker-guided \" care for HF.", "output": {"entities": {}}, "schema": []}
{"input": "This approach involves applying these assays to identify patients in need of therapy intensification and to provide an objective \" monitor \" of disease status.", "output": {"entities": {}}, "schema": []}
{"input": "This review examines the biology of natriuretic peptides, discusses the rationale for their use in HF, and details the aggregate experience gained thus far in biomarker-guided care.", "output": {"entities": {}}, "schema": []}
{"input": "Lipotoxicity impairs incretin signalling.", "output": {"entities": {}}, "schema": []}
{"input": "The incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide are secreted by enteroendocrine cells and augment glucose-induced insulin secretion in response to food ingestion in a glucose-dependent manner.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 50, "end": 57}, {"text": "glucose", "start": 141, "end": 148}, {"text": "glucose", "start": 210, "end": 217}]}}, "schema": []}
{"input": "This mechanism forms the basis for incretin-based therapies in type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the insulinotropic effect of incretins is diminished in type 2 diabetic patients, due in part to reduced expression of incretin receptors as a consequence of glucotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "In this issue of Diabetologia, Kang et al (DOI: 10. 1007/s00125-012-2776-x) provide evidence that in addition to glucotoxicity, lipotoxicity also affects incretin receptor expression and signalling in insulin-secreting cells and isolated islets.", "output": {"entities": {}}, "schema": []}
{"input": "In animal models of diabetes, the authors show that co-administration of a lipid-lowering drug with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 agonist improved glucose tolerance and beta cell mass.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 181, "end": 188}]}}, "schema": []}
{"input": "These novel findings provide convincing support for the notion that restoring normal circulating lipid levels in type 2 diabetes might help improve the efficacy of incretin-based therapies.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanism of the antiproliferative activity of some naphthalene diimide G-quadruplex ligands.", "output": {"entities": {"chemical": [{"text": "naphthalene diimide", "start": 52, "end": 71}]}}, "schema": []}
{"input": "G-quadruplexes are higher-order nucleic acid structures that can form in G-rich telomeres and promoter regions of oncogenes.", "output": {"entities": {}}, "schema": []}
{"input": "Telomeric quadruplex stabilization by small molecules can lead to telomere uncapping, followed by DNA damage response and senescence, as well as chromosomal fusions leading to deregulation of mitosis, followed by apoptosis and downregulation of oncogene expression.", "output": {"entities": {}}, "schema": []}
{"input": "We report here on investigations into the mechanism of action of tetra-substituted naphthalene diimide ligands on the basis of cell biologic data together with a National Cancer Institute COMPARE study.", "output": {"entities": {"chemical": [{"text": "naphthalene diimide", "start": 83, "end": 102}]}}, "schema": []}
{"input": "We conclude that four principal mechanisms of action are implicated for these compounds: 1) telomere uncapping with subsequent DNA damage response and senescence; 2) inhibition of transcription/translation of oncogenes; 3) genomic instability through telomeric DNA end fusions, resulting in mitotic catastrophe and apoptosis; and 4) induction of chromosomal instability by telomere aggregate formation.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin-degrading enzyme (IDE): a novel heat shock-like protein.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin-degrading enzyme (IDE) is a highly conserved zinc metallopeptidase that is ubiquitously distributed in human tissues, and particularly abundant in the brain, liver, and muscles.", "output": {"entities": {"chemical": [{"text": "zinc", "start": 53, "end": 57}]}}, "schema": []}
{"input": "IDE activity has been historically associated with insulin and beta-amyloid catabolism.", "output": {"entities": {}}, "schema": []}
{"input": "However, over the last decade, several experimental findings have established that IDE is also involved in a wide variety of physiopathological processes, including ubiquitin clearance and Varicella Zoster Virus infection.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we demonstrate that normal and malignant cells exposed to different stresses markedly up-regulate IDE in a heat shock protein (HSP)-like fashion.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, we focused our attention on tumor cells and report that (i) IDE is overexpressed in vivo in tumors of the central nervous system (CNS); (ii) IDE-silencing inhibits neuroblastoma (SHSY5Y) cell proliferation and triggers cell death; (iii) IDE inhibition is accompanied by a decrease of the poly-ubiquitinated protein content and co-immunoprecipitates with proteasome and ubiquitin in SHSY5Y cells.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we propose a novel role for IDE as a heat shock protein with implications in cell growth regulation and cancer progression, thus opening up an intriguing hypothesis of IDE as an anticancer target.", "output": {"entities": {}}, "schema": []}
{"input": "Mangiferin-a bioactive xanthonoid, not only from mango and not just antioxidant.", "output": {"entities": {"chemical": [{"text": "Mangiferin", "start": 0, "end": 10}, {"text": "xanthonoid", "start": 23, "end": 33}]}}, "schema": []}
{"input": "Mangiferin is a plant natural polyphenol of C-glycosylxanthone structure and various pharmacological activities.", "output": {"entities": {"chemical": [{"text": "Mangiferin", "start": 0, "end": 10}, {"text": "polyphenol", "start": 30, "end": 40}, {"text": "C-glycosylxanthone", "start": 44, "end": 62}]}}, "schema": []}
{"input": "It can be found in many plant species, among which the mango tree (Mangifera indica) is one of the primary sources.", "output": {"entities": {}}, "schema": []}
{"input": "Mangiferin is also present in some medicinal herbs, influencing their therapeutic and preventive properties, and in honeybush (Cyclopia sp.), a popular South African herbal tea.", "output": {"entities": {"chemical": [{"text": "Mangiferin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Mangiferin dissolves well in water, so it can be easily extracted into infusions and decoctions.", "output": {"entities": {"chemical": [{"text": "Mangiferin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "In the mangiferin molecule, four aromatic hydroxyl groups determine its strong antiradical and antioxidant properties.", "output": {"entities": {"chemical": [{"text": "mangiferin", "start": 7, "end": 17}, {"text": "aromatic hydroxyl", "start": 33, "end": 50}]}}, "schema": []}
{"input": "Mangiferin is also an efficient iron chelator, therefore preventing the generation of hydroxyl radical in Fenton-type reactions.", "output": {"entities": {"chemical": [{"text": "Mangiferin", "start": 0, "end": 10}, {"text": "iron", "start": 32, "end": 36}, {"text": "hydroxyl", "start": 86, "end": 94}]}}, "schema": []}
{"input": "Numerous published in vitro and in vivo pharmacological studies, demonstrated many other activities of mangiferin: analgesic, antidiabetic, antisclerotic, atimicrobial and antiviral, cardio-, hepato-, and neuroprotective, antiinflammatory, antiallergic, MAO inhibiting and memory improving, as well as radioprotective against X-ray, gamma, and UV radiation.", "output": {"entities": {"chemical": [{"text": "mangiferin", "start": 103, "end": 113}]}}, "schema": []}
{"input": "Several studies indicated also its ability to inhibit cancerogenesis and cancer cells growth by apoptosis induction in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "It is also used in cosmetics, due to antioxidant and UV-protecting properties.", "output": {"entities": {}}, "schema": []}
{"input": "Phenolic compounds as antioxidants: carbonic anhydrase isoenzymes inhibitors.", "output": {"entities": {"chemical": [{"text": "Phenolic", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Antioxidant compounds can scavenge free radicals and increase shelf life by retarding the process of lipid peroxidation, which is one of the major reasons for deterioration of food, medicine and pharmaceutical products during processing and storage.", "output": {"entities": {}}, "schema": []}
{"input": "An antioxidant molecule has been defined as any substance when found in low concentrations compared to that of an oxidizable substrate significantly delays or inhibits the oxidation.", "output": {"entities": {}}, "schema": []}
{"input": "The major antioxidant compounds are especially phenolics and flavonoids, which are responsible for their health benefits.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 47, "end": 56}, {"text": "flavonoids", "start": 61, "end": 71}]}}, "schema": []}
{"input": "Carbonic anhydrase (EC 4. 2. 1. 1., CA) is a pH regulatory/metabolic enzyme in all life kingdoms, being found in organisms all over the phylogenetic tree.", "output": {"entities": {}}, "schema": []}
{"input": "It catalyzes the hydration of carbon dioxide (CO (2)) to bicarbonate (HCO (3)-) and the corresponding dehydration of HCO (3)-in acidic medium with regeneration of CO (2).", "output": {"entities": {"chemical": [{"text": "carbon dioxide", "start": 30, "end": 44}, {"text": "CO (2)", "start": 46, "end": 52}, {"text": "bicarbonate", "start": 57, "end": 68}, {"text": "HCO (3)-", "start": 70, "end": 78}, {"text": "HCO (3)-", "start": 117, "end": 125}, {"text": "CO (2)", "start": 163, "end": 169}]}}, "schema": []}
{"input": "Also, CA isoforms are found in a variety of tissues where they participate in several important biological processes such as acid-base balance, respiration, carbon dioxide and ion transport, bone resorption, ureagenesis, gluconeogenesis, lipogenesis and electrolyte secretion.", "output": {"entities": {"chemical": [{"text": "carbon dioxide", "start": 157, "end": 171}]}}, "schema": []}
{"input": "On the other hand, the phenyl moiety of phenol was found to lay in the hydrophobic part of the CA active site, where CO (2), the physiologic substrate of the CAs, binds in the precatalytic complex, explaining thus the behavior of phenol as a unique CO (2) competitive inhibitor.", "output": {"entities": {"chemical": [{"text": "phenyl", "start": 23, "end": 29}, {"text": "phenol", "start": 40, "end": 46}, {"text": "CO (2)", "start": 117, "end": 123}, {"text": "phenol", "start": 230, "end": 236}, {"text": "CO (2)", "start": 249, "end": 255}]}}, "schema": []}
{"input": "This review consists of two main sections.", "output": {"entities": {}}, "schema": []}
{"input": "The first section is devoted to main phenolic antioxidant compounds in the foodstuffs and beverages.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 37, "end": 45}]}}, "schema": []}
{"input": "The second general section is about some definitions of CA inhibitory effects of the main phenolic compounds used for antioxidant activity.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 90, "end": 98}]}}, "schema": []}
{"input": "The phenolic compounds and acids had marked especially CA I and CA II inhibitory effects and might be used as leads for generating CA isoenzyme inhibitors.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 4, "end": 12}]}}, "schema": []}
{"input": "This class of compounds may lead to isoform-selective inhibitors targeting just one or few of the medicinally relevant CAs.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, there are given some chemical and kinetic basis and technical details related to phenolic antioxidant compounds and carbonic anhydrase isoenzymes.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 94, "end": 102}]}}, "schema": []}
{"input": "Recent studies of antioxidant quinoline derivatives.", "output": {"entities": {"chemical": [{"text": "quinoline", "start": 30, "end": 39}]}}, "schema": []}
{"input": "Quinoline derivatives constitute an important class of compounds for new drug development.", "output": {"entities": {"chemical": [{"text": "Quinoline", "start": 0, "end": 9}]}}, "schema": []}
{"input": "As a large number of experimental and theoretical studies have shown that the quinoline ring system is an important structural unit widely existing in alkaloids, therapeutics and synthetic analogues with exciting biological activities.", "output": {"entities": {"chemical": [{"text": "quinoline", "start": 78, "end": 87}]}}, "schema": []}
{"input": "The present review provides recent antioxidant activities covering in vivo and in vitro studies of natural and synthetic analogues, as well as the proposed mechanisms of action and structure-activity relationships.", "output": {"entities": {}}, "schema": []}
{"input": "Supramolecular hydrogels with reverse thermal gelation properties from (oligo) tyrosine containing block copolymers.", "output": {"entities": {"chemical": [{"text": "(oligo) tyrosine", "start": 71, "end": 87}]}}, "schema": []}
{"input": "Novel block copolymers comprising poly (ethylene glycol) (PEG) and an oligo (tyrosine) block were synthesized in different compositions by N-carboxyanhydride (NCA) polymerization.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol)", "start": 34, "end": 56}, {"text": "PEG", "start": 58, "end": 61}, {"text": "oligo (tyrosine)", "start": 70, "end": 86}, {"text": "N-carboxyanhydride", "start": 139, "end": 157}, {"text": "NCA", "start": 159, "end": 162}]}}, "schema": []}
{"input": "It was shown that PEG2000-Tyr (6) undergoes thermoresponsive hydrogelation at a low concentration range of 0. 25-3. 0 wt% within a temperature range of 25-50 degrees C.", "output": {"entities": {"chemical": [{"text": "PEG2000-Tyr (6)", "start": 18, "end": 33}]}}, "schema": []}
{"input": "Cryogenic transmission electron microscopy (Cryo-TEM) revealed a continuous network of fibers throughout the hydrogel sample, even at concentrations as low as 0. 25 wt%.", "output": {"entities": {}}, "schema": []}
{"input": "Circular dichroism (CD) results suggest that better packing of the beta-sheet tyrosine block at increasing temperature induces the reverse thermogelation.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 78, "end": 86}]}}, "schema": []}
{"input": "A preliminary assessment of the potential of the hydrogel for in vitro application confirmed the hydrogel is not cytotoxic, is biodegradable, and produced a sustained release of a small-molecule drug.", "output": {"entities": {}}, "schema": []}
{"input": "2, 5-Dihydroxy-4-methoxybenzophenone: a novel major in vitro metabolite of benzophenone-3 formed by rat and human liver microsomes.", "output": {"entities": {"chemical": [{"text": "2, 5-Dihydroxy-4-methoxybenzophenone", "start": 0, "end": 36}, {"text": "benzophenone-3", "start": 75, "end": 89}]}}, "schema": []}
{"input": "1. When benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) was incubated with liver microsomes of untreated rats in the presence of NADPH, the 5-hydroxylated metabolite, 2, 5-dihydroxy-4-methoxybenzophenone (5-OH-BP-3), was formed as a major novel metabolite of BP-3.", "output": {"entities": {"chemical": [{"text": "benzophenone-3", "start": 8, "end": 22}, {"text": "2-hydroxy-4-methoxybenzophenone", "start": 24, "end": 55}, {"text": "BP-3", "start": 57, "end": 61}, {"text": "NADPH", "start": 136, "end": 141}, {"text": "2, 5-dihydroxy-4-methoxybenzophenone", "start": 174, "end": 210}, {"text": "5-OH-BP-3", "start": 212, "end": 221}, {"text": "BP-3", "start": 266, "end": 270}]}}, "schema": []}
{"input": "The 4-desmethylated metabolite, 2, 4-dihydroxybenzophenone (2, 4-diOH-BP), previously reported as the major in vivo metabolite of BP-3, was also detected.", "output": {"entities": {"chemical": [{"text": "2, 4-dihydroxybenzophenone", "start": 32, "end": 58}, {"text": "2, 4-diOH-BP", "start": 60, "end": 72}, {"text": "BP-3", "start": 130, "end": 134}]}}, "schema": []}
{"input": "However, the amount of 5-OH-BP-3 formed in vitro was about the same as that of 2, 4-diOH-BP.", "output": {"entities": {"chemical": [{"text": "5-OH-BP-3", "start": 23, "end": 32}, {"text": "2, 4-diOH-BP", "start": 79, "end": 91}]}}, "schema": []}
{"input": "2. The oxidase activity affording 5-OH-BP-3 was inhibited by SKF 525-A and ketoconazole, and partly by quinidine and sulfaphenazole.", "output": {"entities": {"chemical": [{"text": "5-OH-BP-3", "start": 34, "end": 43}, {"text": "SKF 525-A", "start": 61, "end": 70}, {"text": "ketoconazole", "start": 75, "end": 87}, {"text": "quinidine", "start": 103, "end": 112}, {"text": "sulfaphenazole", "start": 117, "end": 131}]}}, "schema": []}
{"input": "The oxidase activity affording 2, 4-diOH-BP was inhibited by SKF 525-A, ketoconazole and alpha-naphthoflavone, and partly by sulfaphenazole.", "output": {"entities": {"chemical": [{"text": "2, 4-diOH-BP", "start": 31, "end": 43}, {"text": "SKF 525-A", "start": 61, "end": 70}, {"text": "ketoconazole", "start": 72, "end": 84}, {"text": "alpha-naphthoflavone", "start": 89, "end": 109}, {"text": "sulfaphenazole", "start": 125, "end": 139}]}}, "schema": []}
{"input": "3. The oxidase activity affording 5-OH-BP-3 was enhanced in liver microsomes of dexamethasone-, phenobarbital-and 3-methylcholanthrene-treated rats.", "output": {"entities": {"chemical": [{"text": "5-OH-BP-3", "start": 34, "end": 43}, {"text": "dexamethasone", "start": 80, "end": 93}, {"text": "phenobarbital", "start": 96, "end": 109}, {"text": "3-methylcholanthrene", "start": 114, "end": 134}]}}, "schema": []}
{"input": "The activity affording 2, 4-diOH-BP was enhanced in liver microsomes of 3-methylcholanthrene-and phenobarbital-treated rats.", "output": {"entities": {"chemical": [{"text": "2, 4-diOH-BP", "start": 23, "end": 35}, {"text": "3-methylcholanthrene", "start": 72, "end": 92}, {"text": "phenobarbital", "start": 97, "end": 110}]}}, "schema": []}
{"input": "4. When examined recombinant rat cytochrome P450 isoforms catalyzing the metabolism of BP-3, 5-hydroxylation was catalyzed by P450 3A2, 1A1, 2B1, 2C6 and 2D1, while 4-desmethylation was catalyzed by P450 2C6 and 1A1.", "output": {"entities": {"chemical": [{"text": "BP-3", "start": 87, "end": 91}]}}, "schema": []}
{"input": "Identifying biases at different spatial and temporal scales of diversification: a case study in the Neotropical parrotlet genus Forpus.", "output": {"entities": {}}, "schema": []}
{"input": "The temporal origins of the extraordinary biodiversity of the Neotropical region are highly debated.", "output": {"entities": {}}, "schema": []}
{"input": "Recent empirical work has found support for alternative models on the tempo of speciation in Neotropical species further fuelling the debate.", "output": {"entities": {}}, "schema": []}
{"input": "However, relationships within many Neotropical lineages are poorly understood, and it is unclear how this uncertainty impacts inferences on the evolution of taxa in the region.", "output": {"entities": {}}, "schema": []}
{"input": "We examined the robustness of diversification patterns in the avian genus Forpus by testing whether the use of different units of biodiversity (i. e. biological species and statistically inferred species) impacted diversification rates and inferences regarding important biogeographic breaks in the genus.", "output": {"entities": {}}, "schema": []}
{"input": "We found that the best-fit model of diversification for the biological species data set was a declining rate of diversification; whereas a model of constant diversification was the best-fit model for statistically inferred species or subspecies.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the relative importance of different landscape features in delimiting genetic structure across the landscape varied across data sets with differing units of biodiversity.", "output": {"entities": {}}, "schema": []}
{"input": "Patterns based on divergence times among biological species indicated old speciation events across major geographic and river barriers.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, data sets more inclusive of the diversity in Forpus illustrate the role of both old divergence across major landscape features and more recent divergences that are possibly attributed to Pleistocene climatic changes.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, these results indicate that conflicting models on the temporal origins of Neotropical birds may be attributable to sampling biases.", "output": {"entities": {}}, "schema": []}
{"input": "Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity.", "output": {"entities": {}}, "schema": []}
{"input": "Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K-cells in response to nutrient ingestion.", "output": {"entities": {}}, "schema": []}
{"input": "GIP potentiates glucose-stimulated insulin secretion and induces energy accumulation into adipose tissue, resulting in obesity.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 16, "end": 23}]}}, "schema": []}
{"input": "Plasma GIP levels are reported to be increased in the obese state.", "output": {"entities": {}}, "schema": []}
{"input": "However, the molecular mechanisms of GIP secretion and high fat diet (HFD)-induced GIP hypersecretion remain unclear, primarily due to difficulties in separating K-cells from other intestinal epithelial cells in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, GIP-GFP knock-in mice that enable us to visualize K-cells by enhanced GFP were established.", "output": {"entities": {}}, "schema": []}
{"input": "Microarray analysis of isolated K-cells from these mice revealed that transcriptional regulatory factor X6 (Rfx6) is expressed exclusively in K-cells.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro experiments using the mouse intestinal cell line STC-1 showed that knockdown of Rfx6 decreased mRNA expression, cellular content, and secretion of GIP.", "output": {"entities": {}}, "schema": []}
{"input": "Rfx6 bound to the region in the gip promoter that regulates gip promoter activity, and overexpression of Rfx6 increased GIP mRNA expression.", "output": {"entities": {}}, "schema": []}
{"input": "HFD induced obesity and GIP hypersecretion in GIP-GFP heterozygous mice in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Immunohistochemical and flow cytometry analysis showed no significant difference in K-cell number between control fat diet-fed (CFD) and HFD-fed mice.", "output": {"entities": {}}, "schema": []}
{"input": "However, GIP content in the upper small intestine and GIP mRNA expression in K-cells were significantly increased in HFD-fed mice compared with those in CFD-fed mice.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, expression levels of Rfx6 mRNA were increased in K-cells of HFD-fed mice.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that Rfx6 increases GIP expression and content in K-cells and is involved in GIP hypersecretion in HFD-induced obesity.", "output": {"entities": {}}, "schema": []}
{"input": "The crystal structure of the protein-disulfide isomerase family member ERp27 provides insights into its substrate binding capabilities.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 37, "end": 46}]}}, "schema": []}
{"input": "About one-third of all cellular proteins pass through the secretory pathway and hence undergo oxidative folding in the endoplasmic reticulum (ER).", "output": {"entities": {}}, "schema": []}
{"input": "Protein-disulfide isomerase (PDI) and related members of the PDI family assist in the folding of substrates by catalyzing the oxidation of two cysteines and isomerization of disulfide bonds as well as by acting as chaperones.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 8, "end": 17}, {"text": "cysteines", "start": 143, "end": 152}, {"text": "disulfide", "start": 174, "end": 183}]}}, "schema": []}
{"input": "In this study, we present the crystal structure of ERp27, a redox-inactive member of the PDI family.", "output": {"entities": {}}, "schema": []}
{"input": "The structure reveals its substrate-binding cleft, which is homologous to PDI, but is able to adapt in size and hydrophobicity.", "output": {"entities": {}}, "schema": []}
{"input": "Isothermal titration calorimetry experiments demonstrate that ERp27 is able to distinguish between folded and unfolded substrates, only interacting with the latter.", "output": {"entities": {}}, "schema": []}
{"input": "ERp27 is up-regulated during ER stress, thus presumably allowing it to bind accumulating misfolded substrates and present them to ERp57 for catalysis.", "output": {"entities": {}}, "schema": []}
{"input": "Silencing alpha 1, 3-fucosyltransferases in human leukocytes reveals a role for FUT9 enzyme during E-selectin-mediated cell adhesion.", "output": {"entities": {}}, "schema": []}
{"input": "Leukocyte adhesion during inflammation is initiated by the binding of sialofucosylated carbohydrates expressed on leukocytes to endothelial E/P-selectin.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 87, "end": 100}]}}, "schema": []}
{"input": "Although the glycosyltransferases (glycoTs) constructing selectin-ligands have largely been identified using knock-out mice, important differences may exist between humans and mice.", "output": {"entities": {}}, "schema": []}
{"input": "To address this, we developed a systematic lentivirus-based shRNA delivery workflow to create human leukocytic HL-60 cell lines that lack up to three glycoTs.", "output": {"entities": {}}, "schema": []}
{"input": "Using this, the contributions of all three myeloid alpha 1, 3-fucosyltransferases (FUT4, FUT7, and FUT9) to selectin-ligand biosynthesis were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "The cell adhesion properties of these modified cells to L-, E-, and P-selectin under hydrodynamic shear were compared with bone marrow-derived neutrophils from Fut4 (-/-) Fut7 (-/-) dual knock-out mice.", "output": {"entities": {}}, "schema": []}
{"input": "Results demonstrate that predominantly FUT7, and to a lesser extent FUT4, forms the selectin-ligand at the N terminus of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) in humans and mice.", "output": {"entities": {"chemical": [{"text": "N", "start": 107, "end": 108}]}}, "schema": []}
{"input": "Here, 85% reduction in leukocyte interaction was observed in human FUT4 (-) 7 (-) dual knockdowns on P/L-selectin substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike Fut4 (-/-) Fut7 (-/-) mouse neutrophils, however, human knockdowns lacking FUT4 and FUT7 only exhibited partial reduction in rolling interaction on E-selectin.", "output": {"entities": {}}, "schema": []}
{"input": "In this case, the third alpha 1, 3-fucosyltransferase FUT9 played an important role because leukocyte adhesion was reduced by 50-60% in FUT9-HL-60, 70-80% in dual knockdown FUT7 (-) 9 (-) cells, and ~ 85% in FUT4 (-) 7 (-) 9 (-) triple knockdowns.", "output": {"entities": {}}, "schema": []}
{"input": "Gene silencing results are in agreement with gain-of-function experiments where all three fucosyltransferases conferred E-selectin-mediated rolling in HEK293T cells.", "output": {"entities": {}}, "schema": []}
{"input": "This study advances new tools to study human glycoT function.", "output": {"entities": {}}, "schema": []}
{"input": "It suggests a species-specific role for FUT9 during the biosynthesis of human E-selectin ligands.", "output": {"entities": {}}, "schema": []}
{"input": "Forkhead box M1 is regulated by heat shock factor 1 and promotes glioma cells survival under heat shock stress.", "output": {"entities": {}}, "schema": []}
{"input": "The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology.", "output": {"entities": {}}, "schema": []}
{"input": "Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1.", "output": {"entities": {}}, "schema": []}
{"input": "Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we demonstrated that FoxM1 was required for the G (2)-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance.", "output": {"entities": {}}, "schema": []}
{"input": "Green asymmetric synthesis: beta-amino alcohol-catalyzed direct asymmetric aldol reactions in aqueous micelles.", "output": {"entities": {"chemical": [{"text": "beta-amino alcohol", "start": 28, "end": 46}, {"text": "aldol", "start": 75, "end": 80}]}}, "schema": []}
{"input": "The ability of chiral beta-amino alcohols to catalyze the direct asymmetric aldol reaction was evaluated for the first time in aqueous micellar media.", "output": {"entities": {"chemical": [{"text": "chiral beta-amino alcohols", "start": 15, "end": 41}, {"text": "aldol", "start": 76, "end": 81}]}}, "schema": []}
{"input": "A family of cheap and easily accessible beta-amino alcohols, obtained in one step from naturally occurring amino acids, was shown to successfully catalyze the asymmetric aldol reaction between a series of ketones and aromatic aldehydes.", "output": {"entities": {"chemical": [{"text": "beta-amino alcohols", "start": 40, "end": 59}, {"text": "amino acids", "start": 107, "end": 118}, {"text": "aldol", "start": 170, "end": 175}, {"text": "ketones", "start": 205, "end": 212}, {"text": "aromatic aldehydes", "start": 217, "end": 235}]}}, "schema": []}
{"input": "These aldol reactions furnished the corresponding beta-hydroxy ketones with up to 93% isolated yield and 89% ee.", "output": {"entities": {"chemical": [{"text": "aldol", "start": 6, "end": 11}, {"text": "beta-hydroxy ketones", "start": 50, "end": 70}]}}, "schema": []}
{"input": "(S)-2-phenylglycinol and Triton X-100 proved to be the best organocatalyst and surfactant, respectively.", "output": {"entities": {"chemical": [{"text": "(S)-2-phenylglycinol", "start": 0, "end": 20}, {"text": "Triton X-100", "start": 25, "end": 37}]}}, "schema": []}
{"input": "Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "The Allen Brain Atlas (http://www. brain-map. org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging].", "output": {"entities": {}}, "schema": []}
{"input": "In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets.", "output": {"entities": {}}, "schema": []}
{"input": "Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously.", "output": {"entities": {}}, "schema": []}
{"input": "All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.", "output": {"entities": {}}, "schema": []}
{"input": "Diet, physical exercise and Orlistat administration increase serum Anti-M u llerian Hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).", "output": {"entities": {"chemical": [{"text": "Orlistat", "start": 28, "end": 36}]}}, "schema": []}
{"input": "The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum Anti-M u llerian Hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls.", "output": {"entities": {"chemical": [{"text": "Orlistat", "start": 82, "end": 90}]}}, "schema": []}
{"input": "Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks.", "output": {"entities": {"chemical": [{"text": "Orlistat", "start": 136, "end": 144}]}}, "schema": []}
{"input": "At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 69, "end": 78}, {"text": "glucose", "start": 117, "end": 124}, {"text": "Androgen", "start": 161, "end": 169}]}}, "schema": []}
{"input": "In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment.", "output": {"entities": {}}, "schema": []}
{"input": "After 12 weeks LH and SHBG were increased, while Testosterone decreased.", "output": {"entities": {"chemical": [{"text": "Testosterone", "start": 49, "end": 61}]}}, "schema": []}
{"input": "After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved.", "output": {"entities": {}}, "schema": []}
{"input": "We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.", "output": {"entities": {"chemical": [{"text": "Orlistat", "start": 58, "end": 66}]}}, "schema": []}
{"input": "Growth and differentiation of prechondrogenic cells on bioactive self-assembled peptide nanofibers.", "output": {"entities": {}}, "schema": []}
{"input": "Restoration of cartilage defect remains a challenge, as the current treatments are ineffective to return tissue to its health.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, developing therapies for treatment of cartilage tissue damage caused by common joint diseases including osteoarthritis, rheumatoid arthritis, and accidents is crucial.", "output": {"entities": {}}, "schema": []}
{"input": "Sulfated glycosaminoglycan molecules are vital constituents of both developing and mature cartilage extracellular matrix.", "output": {"entities": {}}, "schema": []}
{"input": "The interplay between regulator proteins and glycosaminoglycan molecules has an essential role in coordinating differentiation, expansion, and patterning during cartilage development.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we exploited the functional role of an extracellular matrix on chondrogenic differentiation by imitating extracellular matrix both chemically by imparting functional groups of native glycosaminoglycans and structurally through peptide nanofiber network.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, sulfonate, carboxylate, and hydroxyl groups were incorporated on self-assembled peptide nanofibers.", "output": {"entities": {"chemical": [{"text": "sulfonate", "start": 18, "end": 27}, {"text": "carboxylate", "start": 29, "end": 40}, {"text": "hydroxyl", "start": 46, "end": 54}]}}, "schema": []}
{"input": "We observed that when ATDC5 cells were cultured on functional peptide nanofibers, they rapidly aggregated in insulin-free medium and formed cartilage-like nodules and deposited sulfated glycosaminoglycans shown by Safranin-O staining.", "output": {"entities": {"chemical": [{"text": "Safranin-O", "start": 214, "end": 224}]}}, "schema": []}
{"input": "Moreover, collagen II and aggrecan gene expressions revealed by qRT-PCR were significantly enhanced, which indicated the remarkable bioactive role of this nanofiber system on chondrogenic differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, these results show that glycosaminoglycan mimetic peptide nanofiber system provides a promising platform for cartilage regeneration.", "output": {"entities": {}}, "schema": []}
{"input": "Experimentally engineering the edge termination of graphene nanoribbons.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 51, "end": 59}]}}, "schema": []}
{"input": "The edges of graphene nanoribbons (GNRs) have attracted much interest due to their potentially strong influence on GNR electronic and magnetic properties.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Here we report the ability to engineer the microscopic edge termination of high-quality GNRs via hydrogen plasma etching.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 97, "end": 105}]}}, "schema": []}
{"input": "Using a combination of high-resolution scanning tunneling microscopy and first-principles calculations, we have determined the exact atomic structure of plasma-etched GNR edges and established the chemical nature of terminating functional groups for zigzag, armchair, and chiral edge orientations.", "output": {"entities": {}}, "schema": []}
{"input": "We find that the edges of hydrogen-plasma-etched GNRs are generally flat, free of structural reconstructions, and terminated by hydrogen atoms with no rehybridization of the outermost carbon edge atoms.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 26, "end": 34}, {"text": "hydrogen", "start": 128, "end": 136}, {"text": "carbon", "start": 184, "end": 190}]}}, "schema": []}
{"input": "Both zigzag and chiral edges show the presence of edge states.", "output": {"entities": {}}, "schema": []}
{"input": "Arcuate nucleus homeostatic systems are not altered immediately prior to the scheduled consumption of large, binge-type meals of palatable solid or liquid diet in rats and Mice.", "output": {"entities": {}}, "schema": []}
{"input": "Meal feeding is a critical issue in the over-consumption of calories leading to human obesity.", "output": {"entities": {}}, "schema": []}
{"input": "To investigate the mechanisms involved in the regulation of meal feeding in rodents, we studied a scheduled feeding regime that induces substantial food intake over short periods of time.", "output": {"entities": {}}, "schema": []}
{"input": "Male Sprague-Dawley rats and C57BL6 mice were fed one of four palatable diets [45% fat pellet, 60% fat pellet or standard pellet supplemented with Ensure (EN; Abbott Laboratories, Maidenhead, UK) or 12. 5% sucrose (SUC)] either ad lib. or with daily 2-h scheduled access and standard pellet available for 22 h.", "output": {"entities": {}}, "schema": []}
{"input": "Energy balance gene expression in the hypothalamic arcuate nucleus (ARC) and nucleus accumbens (NAcc) reward gene expression were assessed by in situ hybridisation.", "output": {"entities": {}}, "schema": []}
{"input": "Rats fed ad lib. on 45% or 60% fat diet were heavier and fatter than controls, and had reduced neuropeptide Y (NPY) gene expression in the ARC.", "output": {"entities": {}}, "schema": []}
{"input": "Mice fed ad lib. on any of the palatable diets were heavier, fatter and had higher blood leptin than controls, and had reduced NPY and increased cocaine-and-amphetamine-regulated transcript mRNA in the ARC.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 145, "end": 152}, {"text": "amphetamine", "start": 157, "end": 168}]}}, "schema": []}
{"input": "Schedule-fed rats and mice quickly adapted their feeding behaviour to 2-h access on palatable food.", "output": {"entities": {}}, "schema": []}
{"input": "Three schedule-fed groups binged: the percentage of daily calories consumed in 2 h on 45% fat diet, 60% fat diet or EN, respectively, was 55%, 63% and 49% in rats, and 86%, 86% and 45% in mice.", "output": {"entities": {}}, "schema": []}
{"input": "However, changed feeding behaviour was not reflected in an induction of orexigenic neuropeptide or suppression of anorexigenic neuropeptide gene expression in the ARC, in the 2-h period prior to scheduled feeding.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanisms underlying large meal/binge-type eating may be regulated by nonhomeostatic processes involving other genes in the hypothalamus or other brain areas.", "output": {"entities": {}}, "schema": []}
{"input": "However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of the involvement of these genes in driving large meals, at least at the investigated time point.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 34, "end": 42}]}}, "schema": []}
{"input": "A potential practical approach to reduce Ara h 6 allergenicity by gamma irradiation.", "output": {"entities": {}}, "schema": []}
{"input": "Peanut allergen Ara h 6 was isolated and irradiated at 1, 3, 5, or 10 kGy, and a whole peanut protein extract (WPPE) was also treated by irradiation.", "output": {"entities": {}}, "schema": []}
{"input": "Alteration in structure of Ara h 6 was characterised by circular dichroism (CD) spectroscopy, ultraviolet (UV) absorption spectroscopy, fluorescence spectroscopy and SDS-PAGE, and antigenicity was evaluated by immunoblotting and indirect ELISA with anti-Ara h 6 polyclonal antibody.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 166, "end": 169}]}}, "schema": []}
{"input": "Irradiation induced significant changes in the secondary and tertiary structures of Ara h 6, and the antigenicity of both purified Ara h 6 and WPPE were reduced upon increasing the irradiation doses.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, a good correlation between the loss in alpha-helix and IgG binding to Ara h 6 was observed.", "output": {"entities": {}}, "schema": []}
{"input": "This indicated that irradiation might be an efficient approach to reduce or eliminate peanut allergenicity.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of total polyphenols in wines by FIA with highly stable amperometric detection using carbon nanotube-modified electrodes.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 18, "end": 29}, {"text": "carbon", "start": 94, "end": 100}]}}, "schema": []}
{"input": "The use of glassy carbon electrodes (GCEs) modified with multi-walled carbon nanotube (CNT) films for the continuous monitoring of polyphenols in flow systems has been examined.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 18, "end": 24}, {"text": "carbon", "start": 70, "end": 76}, {"text": "polyphenols", "start": 131, "end": 142}]}}, "schema": []}
{"input": "The performance of these modified electrodes was evaluated and compared to bare GCE by cyclic voltammetry experiments and by flow injection analysis (FIA) with amperometric detection monitoring the response of gallic, caffeic, ferulic and p-coumaric acids in 0. 050 M acetate buffer pH 4. 5 containing 100 mM NaCl.", "output": {"entities": {"chemical": [{"text": "gallic, caffeic, ferulic and p-coumaric acids", "start": 210, "end": 255}, {"text": "acetate", "start": 268, "end": 275}, {"text": "NaCl", "start": 309, "end": 313}]}}, "schema": []}
{"input": "The GCE modified with CNT dispersions in polyethyleneimine (PEI) provided lower overpotentials, higher sensitivity and much higher signal stability under a dynamic regime than bare GCEs.", "output": {"entities": {"chemical": [{"text": "polyethyleneimine", "start": 41, "end": 58}, {"text": "PEI", "start": 60, "end": 63}]}}, "schema": []}
{"input": "These properties allowed the estimation of the total polyphenol content in red and white wines with a remarkable long-term stability in the measurements despite the presence of potential fouling substances in the wine matrix.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 53, "end": 63}]}}, "schema": []}
{"input": "In addition, the versatility of the electrochemical methodology allowed the selective estimation of the easily oxidisable polyphenol fraction as well as the total polyphenol content just by tuning the detection potential at + 0. 30 or 0. 70 V, respectively.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 122, "end": 132}, {"text": "polyphenol", "start": 163, "end": 173}]}}, "schema": []}
{"input": "The significance of the electrochemical results was demonstrated through correlation studies with the results obtained with conventional spectrophotometric assays for polyphenols (Folin-Ciocalteu, absorbance at 280 nm index and colour intensity index).", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 167, "end": 178}]}}, "schema": []}
{"input": "Use of an electrodialytic reactor for the simultaneous beta-lactoglobulin enzymatic hydrolysis and fractionation of generated bioactive peptides.", "output": {"entities": {}}, "schema": []}
{"input": "The enzymatic hydrolysis of beta-lactoglobulin and the fractionation of peptides were performed in one step in an electrodialysis cell with ultrafiltration membranes stacked.", "output": {"entities": {}}, "schema": []}
{"input": "After 240 min of treatment, 15 anionic and 4 cationic peptides were detected in the anionic and cationic peptide recovery compartments.", "output": {"entities": {}}, "schema": []}
{"input": "Amongst these 15 anionic peptides, 2 hypocholesterolemic, 3 antihypertensive and 1 antibacterial peptides were recovered and concentrated with migration rates ranging from 5. 5% and 81. 7%.", "output": {"entities": {}}, "schema": []}
{"input": "Amongst the 4 cationic peptides, the peptide sequence ALPMHIR, identified as lactokinin and known to exert an important antihypertensive effect, was recovered with an estimated 66% migration rate.", "output": {"entities": {"chemical": [{"text": "lactokinin", "start": 77, "end": 87}]}}, "schema": []}
{"input": "To our knowledge, it was the first attempt to perform hydrolysis under an electric field and to simultaneously separate anionic and cationic peptides produced.", "output": {"entities": {}}, "schema": []}
{"input": "The heat treatment and the gelation are strong determinants of the kinetics of milk proteins digestion and of the peripheral availability of amino acids.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 141, "end": 152}]}}, "schema": []}
{"input": "This study aimed to determine the kinetics of milk protein digestion and amino acid absorption after ingestion of four dairy matrices by six minipigs: unheated or heated skim milk and corresponding rennet gels.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 73, "end": 83}]}}, "schema": []}
{"input": "Digestive contents and plasma samples were collected over a 7 h-period after meal ingestion.", "output": {"entities": {}}, "schema": []}
{"input": "Gelation of milk slowed down the outflow of the meal from the stomach and the subsequent absorption of amino acids, and decreased their bioavailability in peripheral blood.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 103, "end": 114}]}}, "schema": []}
{"input": "The gelled rennet matrices also led to low levels of milk proteins at the duodenum.", "output": {"entities": {}}, "schema": []}
{"input": "Caseins and beta-lactoglobulin, respectively, were sensitive and resistant to hydrolysis in the stomach with the unheated matrices, but showed similar digestion with the heated matrices, with a heat-induced susceptibility to hydrolysis for beta-lactoglobulin.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest a significant influence of the meal microstructure (resulting from heat treatment) and macrostructure (resulting from gelation process) on the different steps of milk proteins digestion.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of D-fagomine in the human diet from buckwheat-based foodstuffs.", "output": {"entities": {"chemical": [{"text": "D-fagomine", "start": 16, "end": 26}]}}, "schema": []}
{"input": "Buckwheat (Fagopyrum esculentum Moench) groats contain the iminosugar D-fagomine as a minor component that might contribute to the alleged health benefits of this pseudo-cereal.", "output": {"entities": {"chemical": [{"text": "D-fagomine", "start": 70, "end": 80}]}}, "schema": []}
{"input": "This study presents analysis of D-fagomine in buckwheat-based foodstuffs by liquid chromatography coupled to mass spectrometry and an estimation of its presence in the human diet based on a published population-based cross-sectional nutrition survey.", "output": {"entities": {"chemical": [{"text": "D-fagomine", "start": 32, "end": 42}]}}, "schema": []}
{"input": "D-fagomine is present in common buckwheat-based foodstuffs in amounts ranging from 1 to 25 mg/kg or mg/L, it is stable during boiling, baking, frying and fermentation, and it is biosynthesised upon sprouting.", "output": {"entities": {"chemical": [{"text": "D-fagomine", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The estimated total intake of D-fagomine resulting from a diet that includes such foodstuffs would be between 3 and 17 mg per day (mean for both genders; range from P5 to P95).", "output": {"entities": {"chemical": [{"text": "D-fagomine", "start": 30, "end": 40}]}}, "schema": []}
{"input": "A diet rich in buckwheat products would provide a daily amount of D-fagomine that may in part explain the beneficial properties traditionally attributed to buckwheat consumption.", "output": {"entities": {"chemical": [{"text": "D-fagomine", "start": 66, "end": 76}]}}, "schema": []}
{"input": "The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis, Theaceae).", "output": {"entities": {}}, "schema": []}
{"input": "The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis, Theaceae) were investigated with a study of carbon tetrachloride (CCl (4))-induced oxidative stress and hepatic fibrosis in male ICR mice.", "output": {"entities": {"chemical": [{"text": "carbon tetrachloride", "start": 129, "end": 149}, {"text": "CCl (4)", "start": 151, "end": 158}]}}, "schema": []}
{"input": "Oral administration of green tea extract at doses of 125, 625 and 1250 mg/kg for 8 weeks significantly reduced (p < 0. 05) the levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyls in the liver by at least 28% compared with that was induced by CCl (4) (1 mL/kg) in mice.", "output": {"entities": {"chemical": [{"text": "thiobarbituric acid", "start": 137, "end": 156}, {"text": "carbonyls", "start": 197, "end": 206}, {"text": "CCl (4)", "start": 270, "end": 277}]}}, "schema": []}
{"input": "Moreover, green tea extract administration significantly increased (p < 0. 05) the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 107, "end": 118}, {"text": "GSH", "start": 131, "end": 134}, {"text": "glutathione", "start": 143, "end": 154}, {"text": "GSH", "start": 166, "end": 169}]}}, "schema": []}
{"input": "Our study found that oral administration of green tea extract prevented CCl (4)-induced hepatic fibrosis, as evidenced by a decreased hydroxyproline level in the liver and a reduced incidence of hepatic fibrosis by histological observations.", "output": {"entities": {"chemical": [{"text": "CCl (4)", "start": 72, "end": 79}, {"text": "hydroxyproline", "start": 134, "end": 148}]}}, "schema": []}
{"input": "These results indicate that green tea exhibits potent protective effects against CCl (4)-induced oxidative stress and hepatic fibrosis in mice by inhibiting oxidative damage and increasing antioxidant enzyme activities.", "output": {"entities": {"chemical": [{"text": "CCl (4)", "start": 81, "end": 88}]}}, "schema": []}
{"input": "Whey protein hydrolysate enhances the exercise-induced heat shock protein (HSP70) response in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Whey protein has been suggested to be potential protective agent against various forms of stress.", "output": {"entities": {}}, "schema": []}
{"input": "The heat shock protein HSP70 confers greater cellular tolerance against stressors.", "output": {"entities": {}}, "schema": []}
{"input": "The present study evaluated the effects of whey protein intake on HSP70 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Forty-eight male Wistar rats were divided into sedentary and exercised groups, and each group was fed as a protein source casein (CAS), whey protein (WP) or whey protein hydrolysate (WPH) for 3weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Exercise on a treadmill was used as the source of stress in the animals from the exercised group.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed a larger increase in HSP70 expression in the soleus, gastrocnemius and lung of the WPH-fed rats than WP or casein-fed rats.", "output": {"entities": {}}, "schema": []}
{"input": "HSP70 expression in the sedentary rats was very low, independent of the diet or tissue.", "output": {"entities": {}}, "schema": []}
{"input": "Protein carbonyls were lower in the group that consumed WPH.", "output": {"entities": {"chemical": [{"text": "carbonyls", "start": 8, "end": 17}]}}, "schema": []}
{"input": "These data suggest that the consumption of WPH enhances HSP70 expression.", "output": {"entities": {}}, "schema": []}
{"input": "A new QSAR model, for angiotensin I-converting enzyme inhibitory oligopeptides.", "output": {"entities": {"chemical": [{"text": "angiotensin I", "start": 22, "end": 35}]}}, "schema": []}
{"input": "A new quantitative structure activity relationship (QSAR) model is established for oligopeptides that inhibit angiotensin I-converting enzyme (ACE).", "output": {"entities": {"chemical": [{"text": "angiotensin I", "start": 110, "end": 123}]}}, "schema": []}
{"input": "Information concerning the C-terminal pentapeptide is considered to describe the peptide structure in the model.", "output": {"entities": {"chemical": [{"text": "C", "start": 27, "end": 28}]}}, "schema": []}
{"input": "A database is constructed, with 263 ACE inhibitory peptides and 38 physicochemical descriptors, abstracted from the published literature.", "output": {"entities": {}}, "schema": []}
{"input": "The model is generated through a generalised linear model, with a gamma distribution that yields a coefficient of determination of 94. 4%.", "output": {"entities": {}}, "schema": []}
{"input": "The whole C-terminal pentapeptide information is a determinant for modelling the ACE inhibition activity of oligopeptides.", "output": {"entities": {"chemical": [{"text": "C", "start": 10, "end": 11}]}}, "schema": []}
{"input": "Starting from the C-terminus, the C-1 position is the most relevant position in the model; this is followed by position C-4.", "output": {"entities": {"chemical": [{"text": "C", "start": 18, "end": 19}]}}, "schema": []}
{"input": "In C-1, there is a preference for aliphatic and tiny residues.", "output": {"entities": {}}, "schema": []}
{"input": "However, in the C-4 position, the model indicates a clear preference for bulky hydrophobic amino acids and for sulphur-containing amino acids.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 91, "end": 102}, {"text": "sulphur", "start": 111, "end": 118}, {"text": "amino acids", "start": 130, "end": 141}]}}, "schema": []}
{"input": "Due to its good predictive capability, this model could be used as a tool for identifying and prioritizing the potential ACE inhibitory peptides present in a complex matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Total polyphenols, catechin profiles and antioxidant activity of tea products from purple leaf coloured tea cultivars.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 6, "end": 17}, {"text": "catechin", "start": 19, "end": 27}]}}, "schema": []}
{"input": "Black (aerated) and green (unaerated) tea products, processed from 10 green and 18 purple leaf coloured cultivars of Kenyan origin, and two tea products, from the Japanese cultivars, Yabukita and Yutakamidori, were assayed for total polyphenols (TP) content, individual catechin profiles and in vitro antioxidant capacity (AA).", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 233, "end": 244}, {"text": "catechin", "start": 270, "end": 278}]}}, "schema": []}
{"input": "In addition, the phenolic content of the tea products was determined using the Folin-Ciocalteu phenol reagent.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 17, "end": 25}, {"text": "Folin-Ciocalteu phenol", "start": 79, "end": 101}]}}, "schema": []}
{"input": "Catechin fractions were identified using reverse phase high performance liquid chromatography (HPLC) with a binary gradient elution system.", "output": {"entities": {"chemical": [{"text": "Catechin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The AA% of the tea products was determined using a 2, 2'-diphenyl picrylhydrazyl (DPPH) radical assay method.", "output": {"entities": {"chemical": [{"text": "2, 2'-diphenyl picrylhydrazyl", "start": 51, "end": 80}, {"text": "DPPH", "start": 82, "end": 86}]}}, "schema": []}
{"input": "The results showed that TPs, catechin profiles and antioxidant activities were significantly (p <= 0. 05) higher in unaerated than in aerated teas.", "output": {"entities": {"chemical": [{"text": "catechin", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Tea products from the purple leaf coloured tea cultivars had levels of TPs, total catechin (TC) and antioxidant activities similar to those from the green leaf coloured cultivars, except for teas from the Japanese cultivars that were very low in the assayed parameters.", "output": {"entities": {"chemical": [{"text": "catechin", "start": 82, "end": 90}]}}, "schema": []}
{"input": "Caffeine content was significantly (p <= 0. 05) lower in products from the purple leaf coloured cultivars than in those from the green leaf coloured tea cultivars.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Antioxidant activity (%) was higher in tea products from the Kenyan germplasm than in those from the Japanese cultivars.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant potency of tea products was significantly (r = 0. 789 (* *), p <= 0. 01) influenced by the total anthocyanin content of the purple leaf coloured cultivars.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 109, "end": 120}]}}, "schema": []}
{"input": "Cyanidin-3-O-glucoside was the anthocyanin most highly correlated with AA% (r = 0. 843 (* *), p <= 0. 01 in unaerated tea).", "output": {"entities": {"chemical": [{"text": "Cyanidin-3-O-glucoside", "start": 0, "end": 22}, {"text": "anthocyanin", "start": 31, "end": 42}]}}, "schema": []}
{"input": "Total catechins in the unaerated products from the green leaf coloured tea cultivars were also significantly correlated with antioxidant capacity (r = 0. 818 (* *), p <= 0. 01).", "output": {"entities": {"chemical": [{"text": "catechins", "start": 6, "end": 15}]}}, "schema": []}
{"input": "Results from this study suggest that the antioxidant potency of teas is dependent on the predominant flavonoid compound, the type of tea cultivar and the processing method.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 101, "end": 110}]}}, "schema": []}
{"input": "Simple multiresidue extraction method for the determination of fungicides and plant growth regulator in bean sprouts using low temperature partitioning and tandem mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "A simple multiresidue analytical method is developed for the simultaneous determination of carbendazim (CB), thiabendazole (TB), and 6-benzyl aminopurine (6-BA) in bean sprouts.", "output": {"entities": {"chemical": [{"text": "carbendazim", "start": 91, "end": 102}, {"text": "thiabendazole", "start": 109, "end": 122}, {"text": "6-benzyl aminopurine", "start": 133, "end": 153}, {"text": "6-BA", "start": 155, "end": 159}]}}, "schema": []}
{"input": "The samples were extracted with acetonitrile followed by partitioning at-80 degrees C for 5-10 min.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 32, "end": 44}]}}, "schema": []}
{"input": "A YMC C (8) column was used to separate the analytes before being qualitatively and quantitatively determined by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in positive ion mode using multiple reaction monitoring (MRM).", "output": {"entities": {}}, "schema": []}
{"input": "The matrix-matched calibration curves showed good linearity in the range 0. 01-1. 0 mg/kg with correlation coefficients in excess of 0. 998.", "output": {"entities": {}}, "schema": []}
{"input": "The mean recoveries were in the range of 80. 4-96. 3% at 0. 1 and 0. 5 spiked levels, and the relative standard deviations (RSDs) were in the range of 0. 5-7. 6%.", "output": {"entities": {}}, "schema": []}
{"input": "The limits of quantifications (LOQ) were in the range of 0. 005-0. 01 mg/kg.", "output": {"entities": {}}, "schema": []}
{"input": "The method was successfully applied to 90 samples (among which 45 were organic) collected from a commercial bean sprout production house throughout the city.", "output": {"entities": {}}, "schema": []}
{"input": "Except for 6-BA, the rest of the analytes had values lower than their LOQs.", "output": {"entities": {"chemical": [{"text": "6-BA", "start": 11, "end": 15}]}}, "schema": []}
{"input": "In sum, carbendazim, thiabendazole, and 6-BA were extracted in a single step, and no steps for clean-up or concentration of the extracts were needed.", "output": {"entities": {"chemical": [{"text": "carbendazim", "start": 8, "end": 19}, {"text": "thiabendazole", "start": 21, "end": 34}, {"text": "6-BA", "start": 40, "end": 44}]}}, "schema": []}
{"input": "The current method can be used for sensitive and accurate determination and confirmation of residues in bean sprout samples.", "output": {"entities": {}}, "schema": []}
{"input": "Screening of whey protein isolate hydrolysates for their dual functionality: influence of heat pre-treatment and enzyme specificity.", "output": {"entities": {}}, "schema": []}
{"input": "Heat pre-treated and non heat pre-treated whey protein isolate (WPI) were hydrolysed using alpha-chymotrypsin (chymotrypsin), pepsin and trypsin.", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro antioxidant activity, ACE-inhibition activity and surface hydrophobicities of the hydrolysates were measured in order to determine if peptides with dual functionalities were present.", "output": {"entities": {}}, "schema": []}
{"input": "Dual functional peptides have both biological (e. g. antioxidant, ACE-inhibition, opioid activities) and technological (e. g. nanoemulsification abilities) functions in food systems.", "output": {"entities": {}}, "schema": []}
{"input": "Heat pre-treatment marginally enhanced the hydrolysis of WPI by pepsin and trypsin but had no effect on WPI hydrolysis with chymotrypsin.", "output": {"entities": {}}, "schema": []}
{"input": "With the exception of the hydrolysis by trypsin, heat pre-treatment did not affect the peptide profile of the hydrolysates as analysed using size exclusion chromatography, or the antioxidant activity (P > 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Heat pre-treatment significantly affected the ACE-inhibition activities and the surface hydrophobicities of the hydrolysates (P < 0. 05), which was a function of the specificity of the hydrolysing enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Extended hydrolysis (up to 24 h) had no significant effect on the DH and the molecular weight profiles (P > 0. 05) but in some instances caused a reduction in the antioxidant activity of WPI hydrolysates.", "output": {"entities": {}}, "schema": []}
{"input": "The chymotrypsin hydrolysate showed a broad MW size range, and was followed by pepsin and then trypsin.", "output": {"entities": {}}, "schema": []}
{"input": "The bioactivities of the hydrolysates generally decreased in the order; chymotrypsin > trypsin > pepsin.", "output": {"entities": {}}, "schema": []}
{"input": "This study showed that by manipulating protein conformation with pre-hydrolysis heat treatment, combined with careful enzyme selection, peptides with dual functionalities can be produced from WPI for use as functional ingredients in the manufacture of functional foods.", "output": {"entities": {}}, "schema": []}
{"input": "Purification, physicochemical characterisation and anticancer activity of a polysaccharide from Cyclocarya paliurus leaves.", "output": {"entities": {}}, "schema": []}
{"input": "A Cyclocarya paliurus (Batal.) Iljinskaja polysaccharide (CPP) was isolated and purified by hot water extraction, ethanol precipitation, deproteinisation and anion-exchange chromatography.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 114, "end": 121}]}}, "schema": []}
{"input": "Its physicochemical properties were characterised by gel permeation chromatography (GPC), gas chromatography-mass spectrometry (GC-MS), thermal gravimetric analysis (TGA), Fourier transform infrared spectrometry (FTIR), UV-visible spectrophotometry, dynamic light scattering (DLS) and viscometry analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The anticancer effect of CPP in human gastric cancer HeLa cells was also evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.", "output": {"entities": {"chemical": [{"text": "3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide", "start": 86, "end": 148}, {"text": "MTT", "start": 150, "end": 153}]}}, "schema": []}
{"input": "The results showed that the molecular weight of CPP was 900 kDa, and it contained 64. 8% total sugar, 23. 5% uronic acid, 9. 26% protein, and six kinds of monosaccharides, including glucose, rhamnose, arabinose, xylose, mannose and galactose, with molar percentages of 32. 7%, 9. 33%, 30. 6%, 3. 48%, 10. 4%, and 13. 5%, respectively.", "output": {"entities": {"chemical": [{"text": "uronic acid", "start": 109, "end": 120}, {"text": "monosaccharides", "start": 155, "end": 170}, {"text": "glucose", "start": 182, "end": 189}, {"text": "rhamnose", "start": 191, "end": 199}, {"text": "arabinose", "start": 201, "end": 210}, {"text": "xylose", "start": 212, "end": 218}, {"text": "mannose", "start": 220, "end": 227}, {"text": "galactose", "start": 232, "end": 241}]}}, "schema": []}
{"input": "Furthermore, the results showed that CPP exhibited a strong inhibition effect on the growth of human gastric cancer HeLa cells.", "output": {"entities": {}}, "schema": []}
{"input": "Field application of farm-food safety risk assessment (FRAMp) tool for small and medium fresh produce farms.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to develop a farm food safety-risk assessment tool (FRAMp) which serves as a self-assessment and educational tool for fresh produce farms.", "output": {"entities": {}}, "schema": []}
{"input": "FRAMp was developed in Microsoft (R) Excel spreadsheet software using standard mathematical and logical functions and utilised a qualitative risk assessment approach for farmers to evaluate their food safety practices.", "output": {"entities": {}}, "schema": []}
{"input": "The FRAMp tool has since been tested on 12 fresh produce farms throughout UK.", "output": {"entities": {}}, "schema": []}
{"input": "All the farms determined that FRAMp was interesting but 17% found it too long while 25% of the farms felt the tool was too complicated.", "output": {"entities": {}}, "schema": []}
{"input": "The instructions on FRAMp usage were revised and farmers were given the options to skip and select specific steps in the farm risk assessment.", "output": {"entities": {}}, "schema": []}
{"input": "The end users (farmers/farm managers) determined that developing their own action plans and using it as proof of assessment for future third-party audits were most useful to them.", "output": {"entities": {}}, "schema": []}
{"input": "FRAMp tool can be described as an illustrative risk ranking tool to facilitate farms to identify potential risk factors during their crop production.", "output": {"entities": {}}, "schema": []}
{"input": "Long term compulsivity on the 5-choice serial reaction time task after acute Chlorpyrifos exposure.", "output": {"entities": {"chemical": [{"text": "Chlorpyrifos", "start": 77, "end": 89}]}}, "schema": []}
{"input": "Pesticide exposure has been associated with neuropsychological and psychiatric impairments and neurodegenerative disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Pesticide exposure commonly causes a deficit in inhibitory control behaviours.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we investigated whether acute exposure to organophosphate (OP) chlorpyrifos (CPF) is related to long-term lack of inhibitory control; we also examined the possible neurochemical basis of this association.", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 64, "end": 79}, {"text": "chlorpyrifos", "start": 85, "end": 97}, {"text": "CPF", "start": 99, "end": 102}]}}, "schema": []}
{"input": "Lister Hooded rats were exposed to an acute dose of CPF (250 mg/kg).", "output": {"entities": {"chemical": [{"text": "CPF", "start": 52, "end": 55}]}}, "schema": []}
{"input": "Seven months later, we tested inhibitory control with the 5-choice serial reaction time task (5-CSRTT).", "output": {"entities": {}}, "schema": []}
{"input": "We manipulated the baseline conditions of this task and also systemically pre-administered d-amphetamine, quinpirole, dizocilpine (MK-801) or ketanserin.", "output": {"entities": {"chemical": [{"text": "d-amphetamine", "start": 91, "end": 104}, {"text": "quinpirole", "start": 106, "end": 116}, {"text": "dizocilpine", "start": 118, "end": 129}, {"text": "MK-801", "start": 131, "end": 137}, {"text": "ketanserin", "start": 142, "end": 152}]}}, "schema": []}
{"input": "We also analysed the post-mortem baseline levels of monoamines and amino acids in different brain regions.", "output": {"entities": {"chemical": [{"text": "monoamines", "start": 52, "end": 62}, {"text": "amino acids", "start": 67, "end": 78}]}}, "schema": []}
{"input": "On the 5-CSRT task, CPF-exposed rats showed elevated perseverative responses that persisted across manipulation of baseline conditions of the task and under most of the pharmacological challenges tested.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 20, "end": 23}]}}, "schema": []}
{"input": "Only D-amphetamine induced a dose-dependent amelioration of the increased perseverative responses in the CPF group.", "output": {"entities": {"chemical": [{"text": "D-amphetamine", "start": 5, "end": 18}, {"text": "CPF", "start": 105, "end": 108}]}}, "schema": []}
{"input": "The CPF group also exhibited increased levels of dopamine metabolism in the hippocampus and decreased levels of gamma-aminobutyric acid (GABA) and glutamate in the striatum compared to the vehicle group.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 4, "end": 7}, {"text": "dopamine", "start": 49, "end": 57}, {"text": "gamma-aminobutyric acid", "start": 112, "end": 135}, {"text": "GABA", "start": 137, "end": 141}, {"text": "glutamate", "start": 147, "end": 156}]}}, "schema": []}
{"input": "These findings suggest that CPF induced a long-term compulsivity that was apparent in the 5-CSRT task and associated with changes in monoaminergic and amino acid brain systems of inhibitory control function.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 28, "end": 31}, {"text": "amino acid", "start": 151, "end": 161}]}}, "schema": []}
{"input": "Exposure to high doses of OP should be taken into account in studies of environmental causes for neurodegenerative, neuropsychological and neuropsychiatric disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic autoimmune-mediated inflammation: a senescent immune response to injury.", "output": {"entities": {}}, "schema": []}
{"input": "The increasing prevalence of chronic autoimmune-mediated inflammatory diseases (AIMIDs) in ageing western societies is a major challenge for the drug development industry.", "output": {"entities": {}}, "schema": []}
{"input": "The current high medical need for more-effective treatments is at least in part caused by our limited understanding of the mechanisms that drive chronic inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we postulate a role for immunosenescence in the progression of acute to chronic inflammation via a dysregulated response to primary injury at the level of the damaged target organ.", "output": {"entities": {}}, "schema": []}
{"input": "A corollary to this notion is that treatment of acute versus chronic phases of disease might require differential targeting strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and antiplasmodial evaluation of novel (4-aminobutyloxy) quinolines.", "output": {"entities": {"chemical": [{"text": "(4-aminobutyloxy) quinolines", "start": 49, "end": 77}]}}, "schema": []}
{"input": "A variety of 5-, 6-and 8-(4-aminobutyloxy) quinolines as novel oxygen analogues of known 4-and 8-(4-aminobutylamino) quinoline antimalarial drugs was generated from hydroxyquinolines through a three-step approach with a rhodium-catalyzed hydroformylation as the key step.", "output": {"entities": {"chemical": [{"text": "5-, 6-and 8-(4-aminobutyloxy) quinolines", "start": 13, "end": 53}, {"text": "oxygen", "start": 63, "end": 69}, {"text": "4-and 8-(4-aminobutylamino) quinoline", "start": 89, "end": 126}, {"text": "hydroxyquinolines", "start": 165, "end": 182}, {"text": "rhodium", "start": 220, "end": 227}]}}, "schema": []}
{"input": "Antiplasmodial assays of these new quinolines revealed micromolar potency for all representatives against a chloroquine-sensitive strain of Plasmodium falciparum, and three compounds showed submicromolar activity against a chloroquine-resistant strain of P. falciparum with IC (50)-values ranging between 150 and 680 nM.", "output": {"entities": {"chemical": [{"text": "quinolines", "start": 35, "end": 45}, {"text": "chloroquine", "start": 108, "end": 119}, {"text": "chloroquine", "start": 223, "end": 234}]}}, "schema": []}
{"input": "Reproductive experience modifies the effects of estradiol on learning and memory bias in female rats.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 48, "end": 57}]}}, "schema": []}
{"input": "Previous studies have shown that estrogen affects whether a hippocampus-mediated place (allocentric) or a striatum-mediated response (egocentric) memory system is employed by female rats when searching for a food reward in a maze.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 33, "end": 41}]}}, "schema": []}
{"input": "Because it has been suggested that reproductive experience alters some of the responses to E in the brain, two experiments were carried out to investigate whether reproductive experience would also alter the effect of E on place and response learning.", "output": {"entities": {}}, "schema": []}
{"input": "In experiment 1, 152 ovariectomized nulliparous (n = 77; no reproductive experience) and primiparous (n = 74; having had and raised one litter of pups) Wistar rats were trained on an ambiguous t-maze task and tested for memory system bias.", "output": {"entities": {}}, "schema": []}
{"input": "In experiment 2, 35 ovariectomized nulliparous (n = 16) and primiparous (n = 19) Wistar rats were trained on place and response plus-maze tasks.", "output": {"entities": {}}, "schema": []}
{"input": "All rats were exposed to no, chronic low or chronic low with pulsatile high 17 beta-estradiol (E2) replacement.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 76, "end": 93}]}}, "schema": []}
{"input": "Congruent with previous findings, low E2 nulliparous rats showed predominant use of response memory and faster response learning, whereas high E2 nulliparous rats showed a trend towards predominant place memory use.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, the facilitatory effect of low E2 on response task learning and memory seen in nulliparous rats was not observed in low E2 primiparous rats in either experiment.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, E2 levels do dictate the rate at which female rats learn a response task and utilize response memory, but only in those with no reproductive experience.", "output": {"entities": {}}, "schema": []}
{"input": "Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4-1, in the insulin-like growth factor-1 response.", "output": {"entities": {"chemical": [{"text": "phospho", "start": 34, "end": 41}]}}, "schema": []}
{"input": "AKT is a critical effector kinase downstream of the PI3K pathway that regulates a plethora of cellular processes including cell growth, death, differentiation, and migration.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanisms underlying activated phospho-AKT (pAKT) translocation to its action sites remain unclear.", "output": {"entities": {"chemical": [{"text": "phospho", "start": 32, "end": 39}]}}, "schema": []}
{"input": "Here we show that NEDD4-1 is a novel E3 ligase that specifically regulates ubiquitin-dependent trafficking of pAKT in insulin-like growth factor (IGF)-1 signaling.", "output": {"entities": {}}, "schema": []}
{"input": "NEDD4-1 physically interacts with AKT and promotes HECT domain-dependent ubiquitination of exogenous and endogenous AKT.", "output": {"entities": {}}, "schema": []}
{"input": "NEDD4-1 catalyzes K63-type polyubiquitin chain formation on AKT in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma membrane binding is the key step for AKT ubiquitination by NEDD4-1 in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Ubiquitinated pAKT translocates to perinuclear regions, where it is released into the cytoplasm, imported into the nucleus, or coupled with proteasomal degradation.", "output": {"entities": {}}, "schema": []}
{"input": "IGF-1 signaling specifically stimulates NEDD4-1-mediated ubiquitination of pAKT, without altering total AKT ubiquitination.", "output": {"entities": {}}, "schema": []}
{"input": "A cancer-derived plasma membrane-philic mutant AKT (E17K) is more effectively ubiquitinated by NEDD4-1 and more efficiently trafficked into the nucleus compared with wild type AKT.", "output": {"entities": {}}, "schema": []}
{"input": "This study reveals a novel mechanism by which a specific E3 ligase is required for ubiquitin-dependent control of pAKT dynamics in a ligand-specific manner.", "output": {"entities": {}}, "schema": []}
{"input": "AhR-mediated changes in global gene expression in rat liver progenitor cells.", "output": {"entities": {}}, "schema": []}
{"input": "Although the tumor-promoting effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), coplanar polychlorinated biphenyls (PCBs), and related compounds in liver tissue are primarily attributed to the activation of the aryl hydrocarbon receptor (AhR), the underlying molecular mechanisms are still unclear.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 40, "end": 78}, {"text": "TCDD", "start": 80, "end": 84}, {"text": "polychlorinated biphenyls", "start": 96, "end": 121}, {"text": "PCBs", "start": 123, "end": 127}, {"text": "aryl hydrocarbon", "start": 218, "end": 234}]}}, "schema": []}
{"input": "Liver progenitor (oval) cells have been suggested to constitute a potential target for hepatocarcinogenic chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "To better understand AhR-driven pathways, we analyzed the transcriptional program in response to coplanar PCB 126 in contact-inhibited rat liver progenitor WB-F344 cells using high-density microarrays.", "output": {"entities": {"chemical": [{"text": "PCB 126", "start": 106, "end": 113}]}}, "schema": []}
{"input": "After 6-h treatment, we identified 145 significantly deregulated genes considered to be direct AhR-dependent target genes.", "output": {"entities": {}}, "schema": []}
{"input": "The number of differentially regulated genes increased to 658 and 968 genes after 24 and 72 h, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Gene ontology analysis revealed that these genes were primarily involved in drug and lipid metabolism, cell cycle and growth control, cancer developmental processes, cell-cell communication, and adhesion.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, the Wnt and TGF-beta signaling pathways, both being involved in developmental and tumorigenic processes, belonged to the most affected pathways.", "output": {"entities": {}}, "schema": []}
{"input": "AhR-and ARNT-dependent regulation of selected target genes of interest was then confirmed using TCDD as a model AhR agonist, together with pharmacological inhibition of the AhR and by RNA-interference techniques.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 96, "end": 100}]}}, "schema": []}
{"input": "We demonstrated AhR-dependent regulation of emerging and novel AhR target genes, such as Fst, Areg, Hbegf, Ctgf, Btg2, and Foxq1.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, the transcription factor Foxq1, recently suggested to contribute to tumor promotion and/or progression, was found to be regulated at both mRNA and protein levels by AhR/ARNT activation.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistic models describing active renal reabsorption and secretion: a simulation-based study.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of the present study was to evaluate mechanistic pharmacokinetic models describing active renal secretion and reabsorption over a range of Michaelis-Menten parameter estimates and doses.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma concentration and urinary excretion profiles were simulated and renal clearance (CL (r)) was calculated for two pharmacokinetic models describing active renal reabsorption (R1/R2), two models describing active secretion (S1/S2), and a model containing both processes.", "output": {"entities": {}}, "schema": []}
{"input": "A range of doses (1-1, 000 mg/kg) was evaluated, and V (max) and K (m) parameter estimates were varied over a 100-fold range.", "output": {"entities": {}}, "schema": []}
{"input": "Similar CL (r) values were predicted for reabsorption models (R1/R2) with variations in V (max) and K (m).", "output": {"entities": {}}, "schema": []}
{"input": "Tubular secretion models (S1/S2) yielded similar relationships between Michaelis-Menten parameter perturbations and CL (r), but the predicted CL (r) values were threefold higher for model S1.", "output": {"entities": {}}, "schema": []}
{"input": "For both reabsorption and secretion models, the greatest changes in CL (r) were observed with perturbations in V (max), suggesting the need for an accurate estimate of this parameter.", "output": {"entities": {}}, "schema": []}
{"input": "When intrinsic clearance was substituted for Michaelis-Menten parameters, it failed to predict similar CL (r) values even within the linear range.", "output": {"entities": {}}, "schema": []}
{"input": "For models S1 and S2, renal secretion was predominant at low doses, whereas renal clearance was driven by fraction unbound in plasma at high doses.", "output": {"entities": {}}, "schema": []}
{"input": "Simulations demonstrated the importance of Michaelis-Menten parameter estimates (especially V (max)) for determining CL (r).", "output": {"entities": {}}, "schema": []}
{"input": "K (m) estimates can easily be obtained directly from in vitro studies.", "output": {"entities": {}}, "schema": []}
{"input": "However, additional scaling of in vitro V (max) estimates using in vitro/in vivo extrapolation methods are required to incorporate these parameters into pharmacokinetic models.", "output": {"entities": {}}, "schema": []}
{"input": "Diagnostic accuracy of fine needle aspiration biopsy cytology and ultrasonography in patients with thyroid nodules diagnosed as benign or indeterminate before thyroidectomy.", "output": {"entities": {}}, "schema": []}
{"input": "Fine-needle aspiration biopsy cytology (FNABC) and ultrasonography (US) play an important role in differentiating benign thyroid nodules from malignant nodules.", "output": {"entities": {}}, "schema": []}
{"input": "We retrospectively investigated the prevalence of follicular thyroid carcinoma (FTC) in patients with thyroid nodules whose FNABC and US readings were not malignant before thyroidectomy.", "output": {"entities": {}}, "schema": []}
{"input": "Between 2007 and 2008, 3333 patients underwent thyroidectomy at our institution, and the 737 of them who had thyroid nodule that had been diagnosed as hyperplastic nodule or follicular tumor by FNABC and US preoperatively were the subjects in this study.", "output": {"entities": {}}, "schema": []}
{"input": "Postoperative histopathology showed hyperplastic nodule in 416 patients, follicular adenoma in 200 patients, FTC in 99 patients, and other disease in 22 patients.", "output": {"entities": {}}, "schema": []}
{"input": "By FNABC, 34 (6. 7%) of the 505 patients with diagnosis as benign and 65 (28%) of the 232 patients with diagnosis as indeterminate, were diagnosed as having FTC.", "output": {"entities": {}}, "schema": []}
{"input": "The diagnosis was FTC in 56 (9. 6%) of the 582 patients with a preoperative diagnosis of hyperplastic nodule by US and 43 (27. 7%) of the 155 patients with a diagnosis of follicular tumor by US.", "output": {"entities": {}}, "schema": []}
{"input": "The diagnosis of FTC was made in 21 (4. 8%) of 438 patients who were concurrently diagnosed as benign by FNABC and as hyperplastic nodule by US, and in 30 (34. 1%) of 88 patients who were diagnosed as indeterminate by FNABC and follicular tumor by US.", "output": {"entities": {}}, "schema": []}
{"input": "FNABC has been the mainstay for the preoperative evaluation of thyroid nodule.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study showed that US can also be a useful tool for diagnosing FTC.", "output": {"entities": {}}, "schema": []}
{"input": "New pockets in dengue virus 2 surface identified by molecular dynamics simulation.", "output": {"entities": {}}, "schema": []}
{"input": "One of the factors limiting the search of new compounds based on the structure of target proteins involved in diseases is the limited amount of target structural information.", "output": {"entities": {}}, "schema": []}
{"input": "Great advances in the search for lead compounds could be achieved to find new cavities in protein structures that are generated using well established computational chemistry tools.", "output": {"entities": {}}, "schema": []}
{"input": "In the case of dengue, the discovery of pockets in the crystallographic structure of the E protein has contributed to the search for lead compounds aimed at interfering in conformational transitions involved in the pH-dependent fusion process.", "output": {"entities": {}}, "schema": []}
{"input": "This is a complex mechanism triggered by the acid pH of the endosomes that leads to the initial changes in the E protein assembly at the virus surface.", "output": {"entities": {}}, "schema": []}
{"input": "In the present work, an arrangement of three ectodomain portions of the E protein present on the surface of the mature dengue virus was studied through long all-atom molecular dynamics simulations with explicit solvent.", "output": {"entities": {}}, "schema": []}
{"input": "In order to identify new pockets and to evaluate the influence of the acid pH on these pockets, the physiological neutral pH conditions and the acid pH of the endosomes that trigger the fusion process were modeled.", "output": {"entities": {}}, "schema": []}
{"input": "Several pockets presenting pH-dependent characteristics were found in the contact regions between the chains.", "output": {"entities": {}}, "schema": []}
{"input": "Pockets at the protein-protein interfaces induced by a monomer in another monomer were also found.", "output": {"entities": {}}, "schema": []}
{"input": "Some of the pockets are good candidates for the design of lead compounds that could interfere in the rearrangements in E proteins along the fusion process contributing to the development of specific inhibitors of the dengue disease.", "output": {"entities": {}}, "schema": []}
{"input": "Photochemical properties and activity of water-soluble polymer/c (60) nanohybrids for photodynamic therapy.", "output": {"entities": {"chemical": [{"text": "c (60)", "start": 63, "end": 69}]}}, "schema": []}
{"input": "Water-soluble star-like poly (vinyl alcohol)/C (60) and poly {[poly (ethylene glycol) acrylate]-co-(vinyl acetate)}/C (60) nanohybrids are prepared by grafting macroradicals onto C (60) and are assessed as photosensitizers for photodynamic therapy.", "output": {"entities": {"chemical": [{"text": "poly (vinyl alcohol)", "start": 24, "end": 44}, {"text": "C (60)", "start": 45, "end": 51}, {"text": "poly {[poly (ethylene glycol) acrylate]-co-(vinyl acetate)}", "start": 56, "end": 115}, {"text": "C (60)", "start": 116, "end": 122}, {"text": "C (60)", "start": 179, "end": 185}]}}, "schema": []}
{"input": "The photophysical and biological properties of both nanohybrids highlight key characteristics influencing their overall efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "The macromolecular structure (linear/graft) and nature (presence/absence of hydroxyl groups) of the polymeric arms respectively impact the photodynamic activity and the stealthiness of the nanohybrids.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 76, "end": 84}]}}, "schema": []}
{"input": "The advantages of both nanohybrids are encountered in a third one, poly [(N-vinylpyrrolidone)-co-(vinyl acetate)]/C (60), which has linear grafts without hydroxyl groups, and shows a better photodynamic activity.", "output": {"entities": {"chemical": [{"text": "poly [(N-vinylpyrrolidone)-co-(vinyl acetate)]", "start": 67, "end": 113}, {"text": "C (60)", "start": 114, "end": 120}, {"text": "hydroxyl", "start": 154, "end": 162}]}}, "schema": []}
{"input": "Identification of transporters associated with Etoposide sensitivity of stomach cancer cell lines and methotrexate sensitivity of breast cancer cell lines by quantitative targeted absolute proteomics.", "output": {"entities": {"chemical": [{"text": "Etoposide", "start": 47, "end": 56}, {"text": "methotrexate", "start": 102, "end": 114}]}}, "schema": []}
{"input": "Membrane transporter proteins may influence the sensitivity of cancer cells to anticancer drugs that can be recognized as substrates.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to identify proteins that play a key role in the drug sensitivity of stomach and breast cancer cell lines by measuring the absolute protein expression levels of multiple transporters and other membrane proteins and examining their correlation to drug sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "Absolute protein expression levels of 90 membrane proteins were examined by quantitative targeted absolute proteomics using liquid chromatography-linked tandem mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, 11 and 14 membrane proteins, including transporters, were present in quantifiable amounts in membrane fraction of stomach cancer and breast cancer cell lines, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In stomach cancer cell lines, the protein expression level of multidrug resistance-associated protein 1 (MRP1) was inversely correlated with etoposide sensitivity.", "output": {"entities": {"chemical": [{"text": "etoposide", "start": 141, "end": 150}]}}, "schema": []}
{"input": "MK571, an MRP inhibitor, increased both the cell-to-medium ratio of etoposide and the etoposide sensitivity of MRP1-expressing stomach cancer cell lines.", "output": {"entities": {"chemical": [{"text": "MK571", "start": 0, "end": 5}]}}, "schema": []}
{"input": "In breast cancer cell lines, the protein expression level of reduced folate carrier 1 (RFC1) was directly correlated with methotrexate (MTX) sensitivity.", "output": {"entities": {"chemical": [{"text": "methotrexate", "start": 122, "end": 134}, {"text": "MTX", "start": 136, "end": 139}]}}, "schema": []}
{"input": "Initial uptake rate and steady-state cell-to-medium ratio of [(3) H] MTX were correlated with both RFC1 expression level and MTX sensitivity.", "output": {"entities": {"chemical": [{"text": "[(3) H] MTX", "start": 61, "end": 72}, {"text": "MTX", "start": 125, "end": 128}]}}, "schema": []}
{"input": "These results suggest that MRP1 modulates the etoposide sensitivity of stomach cancer cell lines and RFC1 modulates the MTX sensitivity of breast cancer cell lines.", "output": {"entities": {"chemical": [{"text": "etoposide", "start": 46, "end": 55}, {"text": "MTX", "start": 120, "end": 123}]}}, "schema": []}
{"input": "Our results indicate that absolute quantification of multiple membrane proteins could be a useful strategy for identification of candidate proteins involved in drug sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of tolerance and behavioral/physical dependence during chronic CB1 agonist treatment: effects of CB1 agonists, antagonists, and noncannabinoid drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Behavioral studies of chronic CB (1) receptor activation may provide a pharmacological approach to understanding efficacy-related differences among CB (1) ligands as well as mechanistic commonalities between cannabinoid and noncannabinoid drugs.", "output": {"entities": {}}, "schema": []}
{"input": "In the present studies, the effects of CB (1) agonists [(6aR, 10aR)-3-(1-adamantyl)-6, 6, 9-trimethyl-6a, 7, 10, 10a-tetrahydrobenzo [c] chromen-1-ol (AM411), 9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol (AM4054), R-(+)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55, 212. 2), Delta (9)-tetrahydrocannabinol (Delta (9)-THC), (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (methanandamide)], CB (1) antagonists [5-(4-chlorophenyl)-1-(2, 4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (SR141716A), 5-(4-alkylphenyl)-1-(2, 4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (AM4113)], and dopamine (DA)-related [methamphetamine, (+/-)-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrobromide (SKF82958), (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), (6aR)-5, 6, 6a, 7-tetrahydro-6-propyl-4H-dibenzo [de, g] quinoline-10, 11-diol (R-(-)-NPA), haloperidol] and opioid (morphine, naltrexone) drugs on scheduled-controlled responding under a 30-response fixed ratio schedule of stimulus-shock termination in squirrel monkeys were compared before and during chronic treatment with the long-acting CB (1) agonist AM411 (1. 0 mg/kg per day, i. m.).", "output": {"entities": {"chemical": [{"text": "(6aR, 10aR)-3-(1-adamantyl)-6, 6, 9-trimethyl-6a, 7, 10, 10a-tetrahydrobenzo [c] chromen-1-ol", "start": 56, "end": 149}, {"text": "AM411", "start": 151, "end": 156}, {"text": "9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol", "start": 159, "end": 217}, {"text": "AM4054", "start": 219, "end": 225}, {"text": "R-(+)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate", "start": 228, "end": 357}, {"text": "WIN55, 212. 2", "start": 359, "end": 372}, {"text": "Delta (9)-tetrahydrocannabinol", "start": 375, "end": 405}, {"text": "Delta (9)-THC", "start": 407, "end": 420}, {"text": "(R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (methanandamide)", "start": 423, "end": 485}, {"text": "5-(4-chlorophenyl)-1-(2, 4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide", "start": 508, "end": 605}, {"text": "SR141716A", "start": 607, "end": 616}, {"text": "5-(4-alkylphenyl)-1-(2, 4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide", "start": 619, "end": 714}, {"text": "AM4113", "start": 716, "end": 722}, {"text": "dopamine", "start": 730, "end": 738}, {"text": "methamphetamine", "start": 753, "end": 768}, {"text": "(+/-)-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrobromide", "start": 770, "end": 868}, {"text": "SKF82958", "start": 870, "end": 878}, {"text": "(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrochloride", "start": 881, "end": 978}, {"text": "SCH23390", "start": 980, "end": 988}, {"text": "(6aR)-5, 6, 6a, 7-tetrahydro-6-propyl-4H-dibenzo [de, g] quinoline-10, 11-diol", "start": 991, "end": 1069}, {"text": "R-(-)-NPA", "start": 1071, "end": 1080}, {"text": "haloperidol", "start": 1083, "end": 1094}, {"text": "morphine", "start": 1108, "end": 1116}, {"text": "naltrexone", "start": 1118, "end": 1128}, {"text": "AM411", "start": 1348, "end": 1353}]}}, "schema": []}
{"input": "Prechronic treatment with all drugs except naltrexone (1-10 mg/kg) produced dose-related decreases in responses rates.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 43, "end": 53}]}}, "schema": []}
{"input": "Dose-response re-determinations during chronic treatment revealed the following: 1) > 250-fold (AM411, methanandamide) and > 45-fold (AM4054, WIN55, 212. 2, Delta (9)-THC) rightward shifts in the ED (50) values for CB (1) agonists; 2) > 100-fold and > 20-fold leftward shifts in the ED (50) values for SR141716A and AM4113, respectively; and 3) approximately 4. 8-fold and 10-fold rightward shifts in the ED (50) values for methamphetamine and the DA D (2) agonist R-(-)-NPA, respectively.", "output": {"entities": {"chemical": [{"text": "AM411", "start": 96, "end": 101}, {"text": "methanandamide", "start": 103, "end": 117}, {"text": "AM4054", "start": 134, "end": 140}, {"text": "WIN55, 212. 2", "start": 142, "end": 155}, {"text": "Delta (9)-THC", "start": 157, "end": 170}, {"text": "SR141716A", "start": 302, "end": 311}, {"text": "AM4113", "start": 316, "end": 322}, {"text": "methamphetamine", "start": 424, "end": 439}, {"text": "R-(-)-NPA", "start": 465, "end": 474}]}}, "schema": []}
{"input": "Dose-response relationships for other DA-related and opioid drugs were unchanged by chronic CB (1) agonist treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Differences in the magnitude of tolerance among CB (1) agonists during chronic treatment may be indicative of differences in their pharmacological efficacy, whereas the enhanced sensitivity to behaviorally disruptive effects of CB (1) antagonists may provide evidence for CB (1)-related behavioral and/or physical dependence.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, the development of cross-tolerance to methamphetamine and R-(-)-NPA bolsters previous evidence of interplay between CB (1) and DA D (2) signaling mechanisms.", "output": {"entities": {"chemical": [{"text": "methamphetamine", "start": 47, "end": 62}, {"text": "R-(-)-NPA", "start": 67, "end": 76}]}}, "schema": []}
{"input": "SAXS conformational tracking of amylose synthesized by amylosucrases.", "output": {"entities": {}}, "schema": []}
{"input": "Amylose, a linear polymer of alpha (1, 4)-linked glucosyl units and a major constituent of starch granules, can also be enzymatically synthesized in vitro from sucrose by bacterial amylosucrases.", "output": {"entities": {"chemical": [{"text": "sucrose", "start": 160, "end": 167}]}}, "schema": []}
{"input": "Depending on the initial sucrose concentration and the enzyme used, amylose oligomers (or polymers) are formed and self-associate during synthesis into various semicrystalline morphologies.", "output": {"entities": {"chemical": [{"text": "sucrose", "start": 25, "end": 32}]}}, "schema": []}
{"input": "This work describes for the first time a synchrotron SAXS study of the structure in solution of two amylosucrases, namely, NpAS and the thermostable DgAS, under conditions of polymer synthesis and, simultaneously, the amylose conformation.", "output": {"entities": {}}, "schema": []}
{"input": "The structure in solution of both amylosucrases during the reaction was shown to be similar to the known crystallographic structures.", "output": {"entities": {}}, "schema": []}
{"input": "The conformation of amylose produced at an early stage consists of a mixture of wormlike chains and double helical cylindrical structures.", "output": {"entities": {}}, "schema": []}
{"input": "In the case of NpAS, in a second stage, individual double helices pack into clusters before crystallizing and precipitating.", "output": {"entities": {}}, "schema": []}
{"input": "Amylose produced by DgAS never self-associates in such clusters due to the higher temperature used for amylose synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "All the dimensions determined for wormlike chains and cylindrical conformations at different times of NpAS synthesis are in very good agreement with structural features usually observed on gels of amylose extracted from starch.", "output": {"entities": {}}, "schema": []}
{"input": "This provides new insights in understanding the mechanisms of amylose gelation.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple-time-scale motion in molecularly linked nanoparticle arrays.", "output": {"entities": {}}, "schema": []}
{"input": "We explore the transport of electrons between electrodes that encase a two-dimensional array of metallic quantum dots linked by molecular bridges (such as alpha, omega alkaline dithiols).", "output": {"entities": {"chemical": [{"text": "dithiols", "start": 177, "end": 185}]}}, "schema": []}
{"input": "Because the molecules can move at finite temperatures, the entire transport structure comprising the quantum dots and the molecules is in dynamical motion while the charge is being transported.", "output": {"entities": {}}, "schema": []}
{"input": "There are then several physical processes (physical excursions of molecules and quantum dots, electronic migration, ordinary vibrations), all of which influence electronic transport.", "output": {"entities": {}}, "schema": []}
{"input": "Each can occur on a different time scale.", "output": {"entities": {}}, "schema": []}
{"input": "It is therefore not appropriate to use standard approaches to this sort of electron transfer problem.", "output": {"entities": {}}, "schema": []}
{"input": "Instead, we present a treatment in which three different theoretical approaches-kinetic Monte Carlo, classical molecular dynamics, and quantum transport-are all employed.", "output": {"entities": {}}, "schema": []}
{"input": "In certain limits, some of the dynamical effects are unimportant.", "output": {"entities": {}}, "schema": []}
{"input": "But in general, the transport seems to follow a sort of dynamic bond percolation picture, an approach originally introduced as formal models and later applied to polymer electrolytes.", "output": {"entities": {}}, "schema": []}
{"input": "Different rate-determining steps occur in different limits.", "output": {"entities": {}}, "schema": []}
{"input": "This approach offers a powerful scheme for dealing with multiple time scale transport problems, as will exist in many situations with several pathways through molecular arrays or even individual molecules that are dynamically disordered.", "output": {"entities": {}}, "schema": []}
{"input": "Thermally-limited exciton delocalization in superradiant molecular aggregates.", "output": {"entities": {}}, "schema": []}
{"input": "We present two-dimensional Fourier transform optical spectroscopy measurements of two types of molecular J-aggregate thin films and show that temperature-dependent dynamical effects govern exciton delocalization at all temperatures, even in the presence of significant inhomogeneity.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that in the tested molecular aggregates, even when the static structure disorder dominates exciton dephasing dynamics, the extent of exciton delocalization may be limited by dynamical fluctuations, mainly exciton-phonon coupling.", "output": {"entities": {}}, "schema": []}
{"input": "Thus inhomogeneous dephasing may mediate the exciton coherence time whereas dynamical fluctuations mediate the exciton coherence length.", "output": {"entities": {}}, "schema": []}
{"input": "Assessment of immunotoxicity using precision-cut tissue slices.", "output": {"entities": {}}, "schema": []}
{"input": "1. When the immune system encounters incoming infectious agents, this generally leads to immunity.", "output": {"entities": {}}, "schema": []}
{"input": "The evoked immune response is usually robust, but can be severely perturbed by potentially harmful environmental agents such as chemicals, pharmaceuticals and allergens.", "output": {"entities": {}}, "schema": []}
{"input": "2. Immunosuppression, hypersensitivity and autoimmunity may occur due to changed immune activity.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of the immunotoxic potency of agents as part of risk assessment is currently established in vivo with animal models and in vitro with cell lines or primary cells.", "output": {"entities": {}}, "schema": []}
{"input": "3. Although in vivo testing is usually the most relevant situation for many agents, more and more in vitro models are being developed for assessment of immunotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "In this context, hypersensitivity and immunosuppression are considered to be a primary focus for developing in vitro methods.", "output": {"entities": {}}, "schema": []}
{"input": "Three-dimensional organotypic tissue models are also part of current research in immunotoxicology.", "output": {"entities": {}}, "schema": []}
{"input": "4. In recent years, there has been a revival of interest in organotypic tissue models.", "output": {"entities": {}}, "schema": []}
{"input": "In the context of immunotoxicity testing, precision-cut lung slices in particular have been intensively studied.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, this review is very much focused on pulmonary immunotoxicology.", "output": {"entities": {}}, "schema": []}
{"input": "Respiratory hypersensitivity and inflammation are further highlighted aspects of this review.", "output": {"entities": {}}, "schema": []}
{"input": "Immunotoxicity assessment currently is of limited use in other tissue models, which are therefore described only briefly within this review.", "output": {"entities": {}}, "schema": []}
{"input": "Encapsulation of ligninolytic enzymes and its application in clarification of juice.", "output": {"entities": {}}, "schema": []}
{"input": "The thermal stability, physico-chemical properties and effect on juice clarification of hydrogel formulations of ligninolytic enzymes from Phanerochaete chrysosporium were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that enzyme entrapment increase significantly (P < 0. 05) the thermal stability of enzymes at 4 and 75 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "At 75 degrees C, maximum activity decreased to non detectable values of 7. 9% for free laccase, manganese peroxidase (MnP), lignin peroxidase (LiP), respectively; to 94%, 97%, 93% for laccase, MnP and LiP entrapped into Polyacrylamide/pectin, 94%, 98%, 88% for laccase, MnP and LiP encapsulated respectively into polyacrylamide/gelatine and to 87%, 91%, 87% for laccase, MnP and LiP entrapped, respectively into polyacrylamide/carboxymethylcellulose (CMC).", "output": {"entities": {"chemical": [{"text": "manganese", "start": 96, "end": 105}, {"text": "Polyacrylamide", "start": 220, "end": 234}, {"text": "polyacrylamide", "start": 313, "end": 327}, {"text": "polyacrylamide", "start": 412, "end": 426}]}}, "schema": []}
{"input": "When particle size and viscosity of the formulation increased, enzyme stability increased.", "output": {"entities": {}}, "schema": []}
{"input": "The polyphenolic reduction and clarity amelioration in mixed juice of berry and pomegranate was more significant (p > 0. 05) using encapsulated enzymes treatment than free enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "This suggested that enzymatic treatment was efficient for the juice clarification.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of high-pressure treatment on biogenic amines formation in vacuum-packed trout flesh (Oncorhynchus mykiss).", "output": {"entities": {"chemical": [{"text": "amines", "start": 46, "end": 52}]}}, "schema": []}
{"input": "The effects of vacuum packaging followed by high pressure processing on the shelf-life of fillets of rainbow trout (Oncorhynchus mykiss) were examined.", "output": {"entities": {}}, "schema": []}
{"input": "Samples were pressure-treated at 300 and 500 MPa and were stored at 3. 5 and 12 degrees C for up to 28 days (control--0 MPa) and 42 or 70 days (pressure-treated; 12 and 3. 5 degrees C resp.).", "output": {"entities": {}}, "schema": []}
{"input": "The content of eight biogenic amines (putrescine, cadaverine, spermidine, spermine, histamine, tyramine, tryptamine and phenylethylamine) were determined.", "output": {"entities": {"chemical": [{"text": "amines", "start": 30, "end": 36}, {"text": "putrescine", "start": 38, "end": 48}, {"text": "cadaverine", "start": 50, "end": 60}, {"text": "spermidine", "start": 62, "end": 72}, {"text": "spermine", "start": 74, "end": 82}, {"text": "histamine", "start": 84, "end": 93}, {"text": "tyramine", "start": 95, "end": 103}, {"text": "tryptamine", "start": 105, "end": 115}, {"text": "phenylethylamine", "start": 120, "end": 136}]}}, "schema": []}
{"input": "Putrescine, cadaverine and tyramine showed very good correspondence with the level of applied pressure and organoleptic properties.", "output": {"entities": {"chemical": [{"text": "Putrescine", "start": 0, "end": 10}, {"text": "cadaverine", "start": 12, "end": 22}, {"text": "tyramine", "start": 27, "end": 35}]}}, "schema": []}
{"input": "Samples of very good quality contained less than 10 mg/kg of each of these amines.", "output": {"entities": {"chemical": [{"text": "amines", "start": 75, "end": 81}]}}, "schema": []}
{"input": "Polyamines spermidine and spermine did not show statistically significant changes with the level of applied pressure and the time of storage.", "output": {"entities": {"chemical": [{"text": "Polyamines spermidine", "start": 0, "end": 21}, {"text": "spermine", "start": 26, "end": 34}]}}, "schema": []}
{"input": "Tryptamine, phenylethylamine and histamine (with the single exception of a sample stored for 70 days) were not detected in pressure-treated samples kept at 3. 5 degrees C.", "output": {"entities": {"chemical": [{"text": "Tryptamine", "start": 0, "end": 10}, {"text": "phenylethylamine", "start": 12, "end": 28}, {"text": "histamine", "start": 33, "end": 42}]}}, "schema": []}
{"input": "Changes in the bound aroma profiles of' Hayward' and' Hort16A' kiwifruit (Actinidia spp.) during ripening and GC-olfactometry analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Bound volatiles are recognised as a potential source of aroma compounds in fruits.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, the bound volatiles of Actinidia deliciosa' Hayward' and A. chinensis' Hort16A' were studied at three different ripening stages.", "output": {"entities": {}}, "schema": []}
{"input": "The bound volatile content tended to increase as the fruit ripened from under-ripe to ripe, and then decreased in over-ripe fruit.", "output": {"entities": {}}, "schema": []}
{"input": "Glycosides of (Z)-3-hexen-1-ol and hexanol (green-note volatiles) were present in considerable amounts.", "output": {"entities": {"chemical": [{"text": "(Z)-3-hexen-1-ol", "start": 14, "end": 30}, {"text": "hexanol", "start": 35, "end": 42}]}}, "schema": []}
{"input": "beta-Glucosidase activity in' Hayward' and' Hort16A' remained fairly constant throughout ripening.", "output": {"entities": {}}, "schema": []}
{"input": "GC-olfactometry analysis of the hydrolysates of ripe' Hayward' and' Hort16A' revealed the presence of 2-phenylethanol, beta-damascenone, vanillin and 2, 5-dimethyl-4-hydroxy-3 (2H)-furanone (DMHF).", "output": {"entities": {"chemical": [{"text": "2-phenylethanol", "start": 102, "end": 117}, {"text": "beta-damascenone", "start": 119, "end": 135}, {"text": "vanillin", "start": 137, "end": 145}, {"text": "2, 5-dimethyl-4-hydroxy-3 (2H)-furanone", "start": 150, "end": 189}, {"text": "DMHF", "start": 191, "end": 195}]}}, "schema": []}
{"input": "This is the first report of DMHF in' Hayward' kiwifruit.", "output": {"entities": {"chemical": [{"text": "DMHF", "start": 28, "end": 32}]}}, "schema": []}
{"input": "For both' Hayward' and' Hort16A', the odour-active compounds found in the bound volatile extracts were different from those reported as contributors to the aroma of the ripe fruit, suggesting that bound volatiles are probably not significant contributors to the aroma of ripe kiwifruit.", "output": {"entities": {}}, "schema": []}
{"input": "Phase behaviour and in vitro hydrolysis of wheat starch in mixture with whey protein.", "output": {"entities": {}}, "schema": []}
{"input": "Network formation of whey protein isolate (WPI) with increasing concentrations of native wheat starch (WS) has been examined.", "output": {"entities": {}}, "schema": []}
{"input": "Small deformation dynamic oscillation in shear and modulated temperature differential scanning calorimetry enabled analysis of binary mixtures at the macro-and micromolecular level.", "output": {"entities": {}}, "schema": []}
{"input": "Following heat induced gelation, textural hardness was measured by undertaking compression tests.", "output": {"entities": {}}, "schema": []}
{"input": "Environmental scanning electron microscopy provided tangible information on network morphology of polymeric constituents.", "output": {"entities": {}}, "schema": []}
{"input": "Experiments involving in vitro starch digestion also allowed for indirect assessment of phase topology in the binary mixture.", "output": {"entities": {}}, "schema": []}
{"input": "The biochemical component of this work constitutes an attempt to utilise whey protein as a retardant to the enzymatic hydrolysis of starch in a model system with alpha-amylase enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "During heating, rheological profiles of binary mixtures exhibited dramatic increases in G' at temperatures more closely related to those observed for single whey protein rather than pure starch.", "output": {"entities": {}}, "schema": []}
{"input": "Results from this multidisciplinary approach of analysis, utilising rheology, calorimetry and microscopy, argue for the occurrence of phase separation phenomena in the gelled systems.", "output": {"entities": {}}, "schema": []}
{"input": "There is also evidence of whey protein forming the continuous phase with wheat starch being the discontinuous filler, an outcome that is explored in the in vitro study of the enzymatic hydrolysis of starch.", "output": {"entities": {}}, "schema": []}
{"input": "From fish chemical characterisation to the benefit-risk assessment--part A.", "output": {"entities": {}}, "schema": []}
{"input": "Proximate composition, fatty acid profile, cholesterol, alpha-tocoferol content and essential (K, Na, Cl, S, Mg, Ca, Zn, Cu, Fe, Mn, and Se) and contaminant element (Hg/MeHg, Cd, Pb, and As) levels in silver scabbardfish (Lepidopus caudatus), hake (Merluccius merluccius), and ray (Raja spp.) were investigated.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 23, "end": 33}, {"text": "cholesterol", "start": 43, "end": 54}, {"text": "alpha-tocoferol", "start": 56, "end": 71}, {"text": "K", "start": 95, "end": 96}, {"text": "Na", "start": 98, "end": 100}, {"text": "Cl", "start": 102, "end": 104}, {"text": "S", "start": 106, "end": 107}, {"text": "Mg", "start": 109, "end": 111}, {"text": "Ca", "start": 113, "end": 115}, {"text": "Zn", "start": 117, "end": 119}, {"text": "Cu", "start": 121, "end": 123}, {"text": "Fe", "start": 125, "end": 127}, {"text": "Mn", "start": 129, "end": 131}, {"text": "Se", "start": 137, "end": 139}, {"text": "Hg", "start": 166, "end": 168}, {"text": "MeHg", "start": 169, "end": 173}, {"text": "Cd", "start": 175, "end": 177}, {"text": "Pb", "start": 179, "end": 181}, {"text": "As", "start": 187, "end": 189}, {"text": "silver", "start": 201, "end": 207}]}}, "schema": []}
{"input": "Results showed that these species contain high protein, low cholesterol and energy levels, being its consumption recommended.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 60, "end": 71}]}}, "schema": []}
{"input": "Polyunsaturated fatty acids (PUFA) were the dominant group of the fatty acids, being 80% of the n-3 family.", "output": {"entities": {"chemical": [{"text": "Polyunsaturated fatty acids", "start": 0, "end": 27}, {"text": "PUFA", "start": 29, "end": 33}, {"text": "fatty acids", "start": 66, "end": 77}]}}, "schema": []}
{"input": "Attending to the dietary reference intakes (DRIs), these fish species are a good source of Se and the other minerals can give a relevant contribution to the DRIs in a balanced diet.", "output": {"entities": {"chemical": [{"text": "Se", "start": 91, "end": 93}]}}, "schema": []}
{"input": "More than one weekly meal of silver scabbardfish has to be avoided due to the organic mercury concentration.", "output": {"entities": {"chemical": [{"text": "silver", "start": 29, "end": 35}, {"text": "mercury", "start": 86, "end": 93}]}}, "schema": []}
{"input": "More accurate dietary recommendations require a probabilistic assessment, which will be the focus of this study' s Part B.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of paralytic shellfish poisoning toxins by HILIC-MS/MS coupled with dispersive solid phase extraction.", "output": {"entities": {}}, "schema": []}
{"input": "This paper describes the use of QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) for the extraction, cleanup and detection of 10 paralytic shellfish toxins (PSP) in sea food by HILIC-MS/MS with positive ESI.", "output": {"entities": {}}, "schema": []}
{"input": "Matrix matched calibration standards were used to compensate for matrix effects.", "output": {"entities": {}}, "schema": []}
{"input": "The toxins were extracted with acetonitrile/water (90: 10, v/v) containing 0. 1% formic acid and cleaned by HLB and GCB sorbents.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 31, "end": 43}, {"text": "formic acid", "start": 81, "end": 92}, {"text": "GCB", "start": 116, "end": 119}]}}, "schema": []}
{"input": "Qualitative and quantitative detection for the analytes were carried out under the multiple reaction monitoring (MRM) in positive ionization mode after chromatography separation on a TSK-gel Amide-80 (R) column (150 mm x 2. 0 mm x 3 mu m).", "output": {"entities": {"chemical": [{"text": "Amide", "start": 191, "end": 196}]}}, "schema": []}
{"input": "Studies at three fortification levels for the toxins in the range of 8. 1-225. 5 mu g/kg gave mean recoveries from 71. 3% to 104. 6% with relative standard deviation (RSD) <= 15. 8%.", "output": {"entities": {}}, "schema": []}
{"input": "The limit of detection (LOD) was below the recommended regulatory limit of 170 mu gSTX (equ.)/kg and the proposed method fully meets the needs of daily monitoring.", "output": {"entities": {"chemical": [{"text": "gSTX", "start": 82, "end": 86}]}}, "schema": []}
{"input": "Recently introduced foods as new allergenic sources: sensitisation to Goji berries (Lycium barbarum).", "output": {"entities": {}}, "schema": []}
{"input": "Goji berries (GB) have been introduced in Western diet.", "output": {"entities": {}}, "schema": []}
{"input": "Preliminary reports have demonstrated its allergenic capacity.", "output": {"entities": {}}, "schema": []}
{"input": "The objectives of the study were to investigate the frequency of sensitisation and the allergens involved.", "output": {"entities": {}}, "schema": []}
{"input": "566 individuals, with respiratory or cutaneous symptoms were skin-prick tested with GB extract.", "output": {"entities": {}}, "schema": []}
{"input": "Thirty three were positive (5. 8%).", "output": {"entities": {}}, "schema": []}
{"input": "94% were sensitised to other allergens.", "output": {"entities": {}}, "schema": []}
{"input": "Specific IgE to GB, peach, tomato and nut-mix was measured.", "output": {"entities": {}}, "schema": []}
{"input": "Thirteen individuals from 24 available sera (54. 2%) had positive specific IgE.", "output": {"entities": {}}, "schema": []}
{"input": "92. 3% of GB positive patients were positive to peach.", "output": {"entities": {}}, "schema": []}
{"input": "Seven individuals recognised 8 bands and six recognised a 7kDa band.", "output": {"entities": {}}, "schema": []}
{"input": "This band was identified as a LTP by MS/MS.", "output": {"entities": {}}, "schema": []}
{"input": "Cross-reactivity was demonstrated with tomato, tobacco, nutmix, Artemisia pollen and purified Lyc e 3 and Pru p 3.", "output": {"entities": {}}, "schema": []}
{"input": "GB are a new allergenic source with high prevalence of sensitisation.", "output": {"entities": {}}, "schema": []}
{"input": "LTP seems to be the major allergen involved in sensitisation and cross-reactivity.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitors of HIV-1 attachment.", "output": {"entities": {}}, "schema": []}
{"input": "Part 10.", "output": {"entities": {}}, "schema": []}
{"input": "The discovery and structure-activity relationships of 4-azaindole cores.", "output": {"entities": {"chemical": [{"text": "4-azaindole", "start": 54, "end": 65}]}}, "schema": []}
{"input": "A series of 4-azaindole oxoacetic acid piperazine benzamides was synthesized and evaluated in an effort to identify an oral HIV-1 attachment inhibitor with the potential to improve upon the pre-clinical profile of BMS-378806 (7), an initial clinical compound.", "output": {"entities": {"chemical": [{"text": "4-azaindole oxoacetic acid piperazine benzamides", "start": 12, "end": 60}, {"text": "BMS-378806", "start": 214, "end": 224}]}}, "schema": []}
{"input": "Modifications at the 7-position of the 4-azaindole core modulated potency significantly and SAR showed that certain compounds with a 5-membered ring heteroaryl group at that position were the most potent.", "output": {"entities": {"chemical": [{"text": "4-azaindole", "start": 39, "end": 50}]}}, "schema": []}
{"input": "Four of the compounds with the best profiles were evaluated in a rat pharmacokinetic model and all had superior oral bioavailability and lower clearance when compared with 7.", "output": {"entities": {}}, "schema": []}
{"input": "Phosphodiesterase inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Part 5: hybrid PDE3/4 inhibitors as dual bronchorelaxant/anti-inflammatory agents for inhaled administration.", "output": {"entities": {}}, "schema": []}
{"input": "(-)-6-(7-Methoxy-2-(trifluoromethyl) pyrazolo [1, 5-a] pyridin-4-yl)-5-methyl-4, 5-dihydropyridazin-3 (2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti-inflammatory agent.", "output": {"entities": {"chemical": [{"text": "(-)-6-(7-Methoxy-2-(trifluoromethyl) pyrazolo [1, 5-a] pyridin-4-yl)-5-methyl-4, 5-dihydropyridazin-3 (2H)-one", "start": 0, "end": 110}, {"text": "KCA-1490", "start": 112, "end": 120}]}}, "schema": []}
{"input": "N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition.", "output": {"entities": {"chemical": [{"text": "N", "start": 0, "end": 1}, {"text": "pyridazinone", "start": 20, "end": 32}]}}, "schema": []}
{"input": "Addition of a 6-aryl-4, 5-dihydropyridazin-3 (2H)-one extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent PDE3 inhibition.", "output": {"entities": {"chemical": [{"text": "6-aryl-4, 5-dihydropyridazin-3 (2H)-one", "start": 14, "end": 53}, {"text": "N", "start": 71, "end": 72}]}}, "schema": []}
{"input": "Both dihydropyridazinone rings, in the core and extension, can be replaced by achiral 4, 4-dimethylpyrazolone subunits and the core pyrazolopyridine by isosteric bicyclic heteroaromatics.", "output": {"entities": {"chemical": [{"text": "dihydropyridazinone", "start": 5, "end": 24}, {"text": "4, 4-dimethylpyrazolone", "start": 86, "end": 109}, {"text": "pyrazolopyridine", "start": 132, "end": 148}]}}, "schema": []}
{"input": "In combination, these modifications afford potent dual PDE3/4 inhibitors that suppress histamine-induced bronchoconstriction in vivo and exhibit promising anti-inflammatory activity via intratracheal administration.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 87, "end": 96}]}}, "schema": []}
{"input": "Lessons from the dissection of the activation functions (AF-1 and AF-2) of the estrogen receptor alpha in vivo.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 79, "end": 87}]}}, "schema": []}
{"input": "Estrogens influence most of the physiological processes in mammals, including but not limited to reproduction, cognition, behavior, vascular system, metabolism and bone integrity.", "output": {"entities": {"chemical": [{"text": "Estrogens", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Given this widespread role for estrogen in human physiology, it is not surprising that estrogen influence the pathophysiology of numerous diseases, including cancer (of the reproductive tract as breast, endometrial but also colorectal, prostate, ...), as well as neurodegenerative, inflammatory-immune, cardiovascular and metabolic diseases, and osteoporosis.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 31, "end": 39}, {"text": "estrogen", "start": 87, "end": 95}]}}, "schema": []}
{"input": "These actions are mediated by the activation of estrogen receptors (ER) alpha (ER alpha) and beta (ER beta), which regulate target gene transcription (genomic action) through two independent activation functions (AF)-1 and AF-2, but can also elicit rapid membrane initiated steroid signals (MISS).", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 48, "end": 56}, {"text": "steroid", "start": 274, "end": 281}]}}, "schema": []}
{"input": "Targeted ER gene inactivation has shown that although ER beta plays an important role in the central nervous system and in the heart, ER alpha appears to play a prominent role in most of the other tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacological activation or inhibition of ER alpha and/or ER beta provides already the basis for many therapeutic interventions, from hormone replacement at menopause to prevention of the recurrence of breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "However, the use of these estrogens or selective estrogen receptors modulators (SERMs) have also induced undesired effects.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 26, "end": 35}, {"text": "estrogen", "start": 49, "end": 57}]}}, "schema": []}
{"input": "Thus, an important challenge consists now to uncouple the beneficial actions from other deleterious ones.", "output": {"entities": {}}, "schema": []}
{"input": "The in vivo molecular \" dissection \" of ER alpha represents both a molecular and integrated approach that already allowed to delineate in mouse the role of the main \" subfunctions \" of the receptor and that could pave the way to an optimization of the ER modulation.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of quercetin on mRNA expression of steroidogenesis genes in primary cultures of Leydig cells treated with atrazine.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 11, "end": 20}, {"text": "atrazine", "start": 114, "end": 122}]}}, "schema": []}
{"input": "The effect of the phytoestrogen, quercetin (QT) on the reproductive toxicity of atrazine (ATZ) was explored in interstitial Leydig cells (ILCs).", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 33, "end": 42}, {"text": "atrazine", "start": 80, "end": 88}, {"text": "ATZ", "start": 90, "end": 93}]}}, "schema": []}
{"input": "We measured the mRNA expressions of steroidogenesis genes: steroidogenic acute regulatory protein (StAR), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), cytochrome-P450 (CYP) 11A1, insulin-like factor 3 (INSL-3), CYP17A1, inhibin-alpha (INH-alpha), androgen receptor (AR), estrogen receptor-alpha (ER-alpha), and luteinising hormone receptor (LHR) in isolated ILCs by real-time-PCR after cultured cells were treated in vitro with ATZ (232 mu M) and QT (50 mu M).", "output": {"entities": {"chemical": [{"text": "3 beta-hydroxysteroid", "start": 106, "end": 127}, {"text": "androgen", "start": 252, "end": 260}, {"text": "estrogen", "start": 276, "end": 284}, {"text": "ATZ", "start": 433, "end": 436}]}}, "schema": []}
{"input": "The mRNA expression of tested genes increased with ATZ treatment and was normalized by quercetin except AR and ER-alpha expression.", "output": {"entities": {"chemical": [{"text": "ATZ", "start": 51, "end": 54}, {"text": "quercetin", "start": 87, "end": 96}]}}, "schema": []}
{"input": "Treatment of cells with QT alone (15-50 mu M) caused a dose-dependent increase in AR and ER-alpha mRNA expression.", "output": {"entities": {}}, "schema": []}
{"input": "We also found that QT (50 mu M) increased the expressions of AR and ER-alpha in the presence of a sub-threshold level of cyclic-AMP at 1h culture period to the levels seen with maximal stimulation of cyclic-AMP.", "output": {"entities": {"chemical": [{"text": "cyclic-AMP", "start": 121, "end": 131}, {"text": "cyclic-AMP", "start": 200, "end": 210}]}}, "schema": []}
{"input": "Furthermore, the expressions of tested genes were unaffected by cyclic-AMP at 6h when the stimulatory effects of ATZ on tested genes were sustained.", "output": {"entities": {"chemical": [{"text": "cyclic-AMP", "start": 64, "end": 74}, {"text": "ATZ", "start": 113, "end": 116}]}}, "schema": []}
{"input": "These findings suggest that ATZ may stimulate the expression of tested steroidogenesis genes in ILCs via a mechanism independent of cyclic-AMP which was partially antagonize by QT.", "output": {"entities": {"chemical": [{"text": "ATZ", "start": 28, "end": 31}, {"text": "cyclic-AMP", "start": 132, "end": 142}]}}, "schema": []}
{"input": "Effects of pubertal exposure to thiazole-Zn on thyroid function and development in female rats.", "output": {"entities": {"chemical": [{"text": "thiazole", "start": 32, "end": 40}, {"text": "Zn", "start": 41, "end": 43}]}}, "schema": []}
{"input": "Thiazole-Zn is a newly Chinese-created systemic fungicide, and belongs to the sort of thiadiazole compounds, some of which have been found to be thyroid disrupters.", "output": {"entities": {"chemical": [{"text": "Thiazole", "start": 0, "end": 8}, {"text": "Zn", "start": 9, "end": 11}, {"text": "thiadiazole", "start": 86, "end": 97}]}}, "schema": []}
{"input": "To determine the probable adverse effects of thiazole-Zn on thyroid gland and development function, the rodent 20-day Pubertal Female Assay in this study was used.", "output": {"entities": {"chemical": [{"text": "thiazole", "start": 45, "end": 53}, {"text": "Zn", "start": 54, "end": 56}]}}, "schema": []}
{"input": "Postnatal days (PND) 22-old Sprague-Dawley rats were administered with thiazole-Zn daily by oral gavage at doses 0, 40, 100, 200 mg/kg/day for 20 days.", "output": {"entities": {"chemical": [{"text": "thiazole", "start": 71, "end": 79}, {"text": "Zn", "start": 80, "end": 82}]}}, "schema": []}
{"input": "The thyroid endpoints and development endpoints were assessed.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicated that serum TT4 and TSH levels were significantly increased at all concentrations, serum TT3 levels were significantly reduced only at 40 mg/kg thiazole-Zn, but had no difference from controls at the other doses.", "output": {"entities": {"chemical": [{"text": "thiazole", "start": 165, "end": 173}, {"text": "Zn", "start": 174, "end": 176}]}}, "schema": []}
{"input": "Thyroid histology was significantly altered at all doses with a clear dose-dependent hypertrophy and hyperplasia of thyroid cell.", "output": {"entities": {}}, "schema": []}
{"input": "No histological changes were observed in any of the other observed organs.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, this study also found that ovarian weights were significantly decreased, but age and weight at vaginal opening (VO), serum E2 levels were unaffected in all treatment groups.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate that thiazole-Zn is likely a thyroid disrupter, but did not demonstrate that it has estrogenic/anti-estrogenic activity.", "output": {"entities": {"chemical": [{"text": "thiazole", "start": 31, "end": 39}, {"text": "Zn", "start": 40, "end": 42}]}}, "schema": []}
{"input": "A 10-minute point-of-care assay for detection of blood protein adducts resulting from low level exposure to organophosphate nerve agents.", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 108, "end": 123}]}}, "schema": []}
{"input": "The OrganoTox test is a rapid, point-of-care assay capable of detecting clinically relevant organophosphate (OP) poisoning after low-level exposure to sarin, soman, tabun, or VX chemical nerve agents.", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 92, "end": 107}, {"text": "sarin", "start": 151, "end": 156}, {"text": "soman", "start": 158, "end": 163}, {"text": "tabun", "start": 165, "end": 170}]}}, "schema": []}
{"input": "The test utilizes either a finger stick peripheral blood sample or plasma specimen.", "output": {"entities": {}}, "schema": []}
{"input": "While high-level nerve agent exposure can quickly lead to death, low-level exposure produces vague, nondescript signs and symptoms that are not easily clinically differentiated from other conditions.", "output": {"entities": {}}, "schema": []}
{"input": "In initial testing, the OrganoTox test was used to detect the presence of blood protein-nerve agent adducts in exposed blood samples.", "output": {"entities": {}}, "schema": []}
{"input": "In order to mimic the in vivo exposure as closely as possible, nerve agents stored in organic solvents were spiked in minute quantities into whole blood samples.", "output": {"entities": {}}, "schema": []}
{"input": "For performance testing, 40 plasma samples were spiked with sarin, soman, tabun, or VX and 10 normal plasma samples were used as the negative control.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 60, "end": 65}, {"text": "soman", "start": 67, "end": 72}, {"text": "tabun", "start": 74, "end": 79}]}}, "schema": []}
{"input": "The 40 nerve agent-spiked plasma samples included 10 replicates of each agent.", "output": {"entities": {}}, "schema": []}
{"input": "At the clinically relevant low-level exposure of 10ng/ml, the OrganoTox test demonstrated 100% sensitivity for soman, tabun, and VX and 80% sensitivity for sarin.", "output": {"entities": {"chemical": [{"text": "soman", "start": 111, "end": 116}, {"text": "tabun", "start": 118, "end": 123}, {"text": "sarin", "start": 156, "end": 161}]}}, "schema": []}
{"input": "The OrganoTox test demonstrated greater than 97% specificity with 150 blood samples obtained from healthy adults.", "output": {"entities": {}}, "schema": []}
{"input": "No cross-reactivity or interference from pesticide precursor compounds was found.", "output": {"entities": {}}, "schema": []}
{"input": "A rapid test for nerve agent exposure will help identify affected patients earlier in the clinical course and trigger more appropriate medical management in a more timely manner.", "output": {"entities": {}}, "schema": []}
{"input": "Altered expression of genes involved in progesterone biosynthesis, metabolism and action in endometrial cancer.", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 40, "end": 52}]}}, "schema": []}
{"input": "Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "It is associated with prolonged exposure to estrogens that is unopposed by the protective effects of progesterone, which suggests that altered progesterone biosynthesis, metabolism and actions might be implicated in the development of EC.", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 101, "end": 113}, {"text": "progesterone", "start": 143, "end": 155}]}}, "schema": []}
{"input": "Our aim was to evaluate these processes through quantitative real-time PCR expression analysis in up to 47 pairs of EC tissue and adjacent control endometrium.", "output": {"entities": {}}, "schema": []}
{"input": "First, we examined the expression of genes encoding proteins associated with progesterone biosynthesis: steroidogenic acute regulatory protein (STAR); a side chain cleavage enzyme (CYP11A1); and 3 beta-hydroxysteroid dehydrogenase/ketosteroid isomerase (HSD3B).", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 77, "end": 89}, {"text": "3 beta-hydroxysteroid", "start": 195, "end": 216}, {"text": "ketosteroid", "start": 231, "end": 242}]}}, "schema": []}
{"input": "There were 1. 9-and 10. 0-fold decreased expression of STAR and CYP11A1, respectively, in EC versus adjacent control endometrium, with no significant differences in the expression of HSD3B1 and HSD3B2.", "output": {"entities": {}}, "schema": []}
{"input": "Next, we examined expression of genes encoding five progesterone metabolizing enzymes: the 3-keto and 20-ketosteroid reductases (AKR1C1-AKR1C3) and 5 alpha-reductases (SRD5A1 and SRD5A2); and the opposing 20 alpha-hydroxysteroid dehydrogenase (HSD17B2).", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 52, "end": 64}, {"text": "3-keto and 20-ketosteroid", "start": 91, "end": 116}, {"text": "20 alpha-hydroxysteroid", "start": 205, "end": 228}]}}, "schema": []}
{"input": "These genes are expressed in EC and adjacent control endometrium.", "output": {"entities": {}}, "schema": []}
{"input": "No statistically significant differences were seen in mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1.", "output": {"entities": {}}, "schema": []}
{"input": "Expression of HSD17B2 was 3. 0-fold increased, and expression of SRD5A2 was 3. 7-fold decreased, in EC versus adjacent control endometrium.", "output": {"entities": {}}, "schema": []}
{"input": "We also examined mRNA levels of progesterone receptors A and B (PGR), and separately the expression of progesterone receptor B (PR-B).", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 32, "end": 44}, {"text": "progesterone", "start": 103, "end": 115}]}}, "schema": []}
{"input": "Here we saw 1. 8-and 2. 0-fold lower mRNA levels of PGR and PR-B, respectively, in EC versus adjacent control endometrium.", "output": {"entities": {}}, "schema": []}
{"input": "This down-regulation of STAR, CYP11A1 and PGR in endometrial cancer may lead to decreased progesterone biosynthesis and actions although the effects on progesterone levels should be further studied.", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 90, "end": 102}, {"text": "progesterone", "start": 152, "end": 164}]}}, "schema": []}
{"input": "Origin and evolution of medium chain alcohol dehydrogenases.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 37, "end": 44}]}}, "schema": []}
{"input": "Different lines of alcohol dehydrogenases (ADHs) have separate superfamily origins, already recognized but now extended and re-evaluated by re-screening of the latest databank update.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 19, "end": 26}]}}, "schema": []}
{"input": "The short-chain form (SDR) is still the superfamily with most abundant occurrence, most multiple divergence, most prokaryotic emphasis, and most non-complicated architecture.", "output": {"entities": {}}, "schema": []}
{"input": "This pattern is compatible with an early appearance at the time of the emergence of prokaryotic cellular life.", "output": {"entities": {}}, "schema": []}
{"input": "The medium-chain form (MDR) is also old but second in terms of all the parameters above, and therefore compatible with a second emergence.", "output": {"entities": {}}, "schema": []}
{"input": "However, this step appears seemingly earlier than previously considered, and may indicate sub-stages of early emergences at the increased resolution available from the now greater number of data entries.", "output": {"entities": {}}, "schema": []}
{"input": "The Zn-MDR origin constitutes a third stage, possibly compatible with the transition to oxidative conditions on earth.", "output": {"entities": {"chemical": [{"text": "Zn", "start": 4, "end": 6}]}}, "schema": []}
{"input": "Within all these three lines, repeated enzymogeneses gave the present divergence.", "output": {"entities": {}}, "schema": []}
{"input": "MDR-ADH origin (s), at a fourth stage, may also be further resolved in multiple or extended modes, but the classical liver MDR-ADH of the liver type can still be traced to a gene duplication ~ 550 MYA (million years ago), at the early vertebrate radiation, compatible with the post-eon-shift, \" Cambrian explosion \".", "output": {"entities": {}}, "schema": []}
{"input": "Classes and isozymes correspond to subsequent and recent duplicatory events, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "They illustrate a peculiar pattern with functional and emerging evolutionary distinctions between parent and emerging lines, suggesting a parallelism between duplicatory and mutational events, now also visible at separate sub-stages.", "output": {"entities": {}}, "schema": []}
{"input": "Combined, all forms show distinctive patterns at different levels and illustrate correlations with global events.", "output": {"entities": {}}, "schema": []}
{"input": "They further show that simple molecular observations on patterns, multiplicities and occurrence give much information, suggesting common divergence rules not much disturbed by horizontal gene transfers after the initial origins.", "output": {"entities": {}}, "schema": []}
{"input": "pH-responsive lipid core micelles for tumour targeting.", "output": {"entities": {}}, "schema": []}
{"input": "A new acid-sensitive drug-delivery nanocarrier has been developed for tumour targeting.", "output": {"entities": {}}, "schema": []}
{"input": "The self-assembling co-polymer stearoyl-PEG-poly-sulfadimethoxine methacrylate (stearoyl-PEG-polySDM) was prepared to obtain micelles with responsive behaviour in the physiopathologic pH range.", "output": {"entities": {"chemical": [{"text": "stearoyl-PEG-poly-sulfadimethoxine methacrylate", "start": 31, "end": 78}, {"text": "stearoyl-PEG-polySDM", "start": 80, "end": 100}]}}, "schema": []}
{"input": "Stearoyl-PEG-polySDM was synthesised using a multi-step procedure that includes pH-sensitive sulfadimethoxine methacrylate polymerisation by AGET-ATRP at the amino terminal side of stearoyl-PEG-NH2.", "output": {"entities": {"chemical": [{"text": "Stearoyl-PEG-polySDM", "start": 0, "end": 20}, {"text": "sulfadimethoxine methacrylate", "start": 93, "end": 122}, {"text": "amino", "start": 158, "end": 163}, {"text": "stearoyl-PEG-NH2", "start": 181, "end": 197}]}}, "schema": []}
{"input": "Chemical analysis showed that the stearoyl-PEG-polySDM co-polymer contained a mean of seven methacryloyl sulfadimethoxines per molecule.", "output": {"entities": {"chemical": [{"text": "stearoyl-PEG-polySDM", "start": 34, "end": 54}, {"text": "methacryloyl sulfadimethoxines", "start": 92, "end": 122}]}}, "schema": []}
{"input": "Potentiometric and turbidimetric analyses showed that stearoyl-PEG-polySDM has an apparent pKa of 7. 2 and a cloud point at pH 7. 0.", "output": {"entities": {"chemical": [{"text": "stearoyl-PEG-polySDM", "start": 54, "end": 74}]}}, "schema": []}
{"input": "In water at pH 7. 4, the co-polymer assembled spontaneously into 13. 2 +/- 3. 1 nm micelles with a critical micelle concentration (CMC) of 36 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "Cell-culture studies showed that the material was more biocompatible with respect to the control Brij-700 (R).", "output": {"entities": {"chemical": [{"text": "Brij-700", "start": 97, "end": 105}]}}, "schema": []}
{"input": "The paclitaxel loading capacity of the micelles was 3. 25 +/- 0. 25% (w/w,%).", "output": {"entities": {}}, "schema": []}
{"input": "The colloidal formulations were stable at pH 7. 4 for several hours, while at pH 6. 5, they rapidly rearranged and aggregated.", "output": {"entities": {}}, "schema": []}
{"input": "Fluorescence spectroscopic and cytofluorimetric studies showed that the incubation of MCF-7 tumour cells with fluorescein-labelled stearoyl-PEG-polySDM at pH 6. 5 resulted in massive time-dependent cell association, while the incubation at pH 7. 4 showed significantly lower cell interaction.", "output": {"entities": {"chemical": [{"text": "fluorescein", "start": 110, "end": 121}, {"text": "stearoyl-PEG-polySDM", "start": 131, "end": 151}]}}, "schema": []}
{"input": "Confocal microscopy confirmed that at pH 6. 5, the micelles are taken up by cells and that the fluorescein-labelled stearoyl-PEG-polySDM is distributed into the cytosol.", "output": {"entities": {"chemical": [{"text": "fluorescein", "start": 95, "end": 106}, {"text": "stearoyl-PEG-polySDM", "start": 116, "end": 136}]}}, "schema": []}
{"input": "At pH 6. 5, paclitaxel-loaded stearoyl-PEG-polySDM micelles had a higher cytotoxic effect than the micelles incubated at pH 7. 4.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 12, "end": 22}, {"text": "stearoyl-PEG-polySDM", "start": 30, "end": 50}]}}, "schema": []}
{"input": "The former displayed similar cytotoxic activity to free paclitaxel.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 56, "end": 66}]}}, "schema": []}
{"input": "Evidences for the regulation of GnRH and GTH expression by GnIH in the goldfish, Carassius auratus.", "output": {"entities": {"chemical": [{"text": "GnIH", "start": 59, "end": 63}]}}, "schema": []}
{"input": "Gonadotrophin-inhibitory hormone (GnIH) plays an important role in regulating of reproduction in teleosts.", "output": {"entities": {"chemical": [{"text": "Gonadotrophin-inhibitory hormone", "start": 0, "end": 32}, {"text": "GnIH", "start": 34, "end": 38}]}}, "schema": []}
{"input": "To clarify the mode of action of GnIH on the synthesis of gonadotropin releasing hormone (GnRH) and gonadotrophin (GtH), three GnIHR cDNAs were cloned from the goldfish brain.", "output": {"entities": {}}, "schema": []}
{"input": "In situ hybridization results showed that GnIHRs were localized to the hypothalamus and pituitary.", "output": {"entities": {}}, "schema": []}
{"input": "In the hypothalamus, GnIHRs were found in the NPP, NPO and NLT, whereas sGnRH neurons were reported to be located, and potentially regulated by GnIH.", "output": {"entities": {"chemical": [{"text": "GnIHRs", "start": 21, "end": 27}]}}, "schema": []}
{"input": "In the pituitary, only two GnIHRs were observed and they were localized to the PI instead of the adenohypophysis where GtH-expressing cells are localized, suggesting indirect regulation of GtH by GnIH.", "output": {"entities": {"chemical": [{"text": "GnIHRs", "start": 27, "end": 33}]}}, "schema": []}
{"input": "In vivo, intraperitoneal (i. p.) injections of synthetic goldfish GnIH-II peptide and GnIH-III peptide significantly decreased sGnRH and FSH beta mRNA levels.", "output": {"entities": {"chemical": [{"text": "GnIH", "start": 66, "end": 70}, {"text": "GnIH", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Only GnIH-II decreased LH beta mRNA levels significantly.", "output": {"entities": {"chemical": [{"text": "GnIH", "start": 5, "end": 9}]}}, "schema": []}
{"input": "In vitro, both GnIH-II and GnIH-III showed no effect on GtH synthesis, but an inhibition of GnRH-stimulated LH beta and FSH beta synthesis was observed when GnIH-III was applied to primary pituitary cells in culture.", "output": {"entities": {"chemical": [{"text": "GnIH", "start": 15, "end": 19}, {"text": "GnIH", "start": 27, "end": 31}, {"text": "GnIH", "start": 157, "end": 161}]}}, "schema": []}
{"input": "Thus, GnIH could contribute to the regulation of gonadotropin in the brain and pituitary in teleosts.", "output": {"entities": {"chemical": [{"text": "GnIH", "start": 6, "end": 10}]}}, "schema": []}
{"input": "Aggression-and sex-induced neural activity across vasotocin populations in the brown anole.", "output": {"entities": {"chemical": [{"text": "vasotocin", "start": 50, "end": 59}]}}, "schema": []}
{"input": "Activity within the social behavior neural network is modulated by the neuropeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP).", "output": {"entities": {"chemical": [{"text": "arginine vasotocin", "start": 84, "end": 102}, {"text": "AVT", "start": 104, "end": 107}, {"text": "arginine vasopressin", "start": 137, "end": 157}, {"text": "AVP", "start": 159, "end": 162}]}}, "schema": []}
{"input": "However, central AVT/AVP release causes different behavioral effects across species and social environments.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 17, "end": 20}, {"text": "AVP", "start": 21, "end": 24}]}}, "schema": []}
{"input": "These differences may be due to the activation of different neuronal AVT/AVP populations or to similar activity patterns causing different behavioral outputs.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 69, "end": 72}, {"text": "AVP", "start": 73, "end": 76}]}}, "schema": []}
{"input": "We examined neural activity (assessed as Fos induction) within AVT neurons in male brown anole lizards (Anolis sagrei) participating in aggressive or sexual encounters.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 63, "end": 66}]}}, "schema": []}
{"input": "Lizards possess simple amniote nervous systems, and their examination provides a comparative framework to complement avian and mammalian studies.", "output": {"entities": {}}, "schema": []}
{"input": "In accordance with findings in other species, AVT neurons in the anole paraventricular nucleus (PVN) were activated during aggressive encounters; but unlike in other species, a positive correlation was found between aggression levels and activation.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 46, "end": 49}]}}, "schema": []}
{"input": "Activation of AVT neurons within the supraoptic nucleus (SON) occurred nonspecifically with participation in either aggressive or sexual encounters.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 14, "end": 17}]}}, "schema": []}
{"input": "Activation of AVT neurons in the preoptic area (POA) and bed nucleus of the stria terminalis (BNST) was associated with engagement in sexual behaviors.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 14, "end": 17}]}}, "schema": []}
{"input": "The above findings are congruent with neural activation patterns observed in other species, even when the behavioral outputs (i. e., aggression level) differed.", "output": {"entities": {}}, "schema": []}
{"input": "However, aggressive encounters also increased activation of AVT neurons in the BNST, which is incongruous with findings in other species.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 60, "end": 63}]}}, "schema": []}
{"input": "Thus, some species differences involve the encoding of social stimuli as different neural activation patterns within the AVT/AVP network, whereas other behavioral differences arise downstream of this system.", "output": {"entities": {"chemical": [{"text": "AVT", "start": 121, "end": 124}, {"text": "AVP", "start": 125, "end": 128}]}}, "schema": []}
{"input": "Fenamiphos is recalcitrant to the hydrolysis by alloforms PON1 Q192R of human serum.", "output": {"entities": {"chemical": [{"text": "Fenamiphos", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Fenamiphos (ethyl 4-methylthio-m-tolyl isopropylphosphoramidate) is a racemic organophosphorus nematicide widely used in agriculture around the world.", "output": {"entities": {"chemical": [{"text": "Fenamiphos", "start": 0, "end": 10}, {"text": "ethyl 4-methylthio-m-tolyl isopropylphosphoramidate", "start": 12, "end": 63}, {"text": "organophosphorus", "start": 78, "end": 94}]}}, "schema": []}
{"input": "The paraoxonase 1 from human serum (PON1) is a phosphotriesterase (PTE) that hydrolyses several xenobiotics including drugs and organophosphorus compounds (OPs).", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 128, "end": 144}]}}, "schema": []}
{"input": "In this work, the separation of the enantiomers of fenamiphos by HPLC using the column CHIRALCEL OJ and a mobile phase of hexane/ethanol (99/1) is presented.", "output": {"entities": {"chemical": [{"text": "fenamiphos", "start": 51, "end": 61}, {"text": "hexane", "start": 122, "end": 128}, {"text": "ethanol", "start": 129, "end": 136}]}}, "schema": []}
{"input": "A liquid-liquid extraction method was implemented for the characterization of commercial nematicide hydrolysis by PON1 Q192R alloforms of human serum from children and adults.", "output": {"entities": {}}, "schema": []}
{"input": "The results show a recovery of 94% for each isomer from the biological matrix.", "output": {"entities": {}}, "schema": []}
{"input": "The method resulted linear response in a range concentration between 50 and 800 mu M with a detection and quantification limit between 0. 6 and 2 mu M for the (+)-fenamiphos, and between 0. 7 and 2. 3 mu M for the (-)-fenamiphos.", "output": {"entities": {"chemical": [{"text": "(+)-fenamiphos", "start": 159, "end": 173}, {"text": "(-)-fenamiphos", "start": 214, "end": 228}]}}, "schema": []}
{"input": "The levels of the Ca (2 +)-dependent hydrolysis (residual concentration [mu M]) quantified during 30min of reaction were only just 4-14% for both fenamiphos enantiomers with the three alloforms of PON1 Q192R of the two groups of serum studied.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 18, "end": 26}, {"text": "fenamiphos", "start": 146, "end": 156}]}}, "schema": []}
{"input": "These results demonstrate that human serum PON1 is could be involved in the detoxification of a limited number of organophosphorus insecticides.", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 114, "end": 130}]}}, "schema": []}
{"input": "Reduced plasma oxytocin levels in female patients with borderline personality disorder.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 15, "end": 23}]}}, "schema": []}
{"input": "The neuropeptide oxytocin is involved in social cognition and interaction across species and plays a crucial role in the regulation of affiliative behaviors.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 17, "end": 25}]}}, "schema": []}
{"input": "Oxytocin levels in cerebrospinal fluid (CSF), but also in plasma or urine, have been shown to be negatively associated with childhood traumata, aggressive behavior, and suicide attempts.", "output": {"entities": {"chemical": [{"text": "Oxytocin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Recently, an altered activity of the oxytocin system has been discussed to play a prominent role in borderline personality disorder (BPD), which is thought to be closely related to traumatic experiences in childhood and is characterized by (para) suicidal behaviors as well as aggressive outbursts.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 37, "end": 45}]}}, "schema": []}
{"input": "In the present study, we compared plasma oxytocin levels of women with and without BPD in the follicular phase and assessed the relationship between oxytocin concentrations and childhood traumata.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 41, "end": 49}, {"text": "oxytocin", "start": 149, "end": 157}]}}, "schema": []}
{"input": "Women diagnosed with BPD had significantly reduced oxytocin concentrations, even after controlling for estrogen, progesterone, and contraceptive intake.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 51, "end": 59}, {"text": "estrogen", "start": 103, "end": 111}, {"text": "progesterone", "start": 113, "end": 125}]}}, "schema": []}
{"input": "In addition, plasma oxytocin correlated negatively with experiences of childhood traumata, in particular with emotional neglect and abuse.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 20, "end": 28}]}}, "schema": []}
{"input": "The results of mediation analyses do not support a model of oxytocin being a prominent mediator in the link between childhood trauma and BPD.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 60, "end": 68}]}}, "schema": []}
{"input": "Thus, the findings indicate dysregulations in the oxytocin system of patients diagnosed with BPD with more longitudinal research being necessary to disentangle the relationship between childhood adversities, oxytocin system, and psychopathology.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 50, "end": 58}, {"text": "oxytocin", "start": 208, "end": 216}]}}, "schema": []}
{"input": "Antimutagenic evaluation of vitamins B1, B6 and B12 in vitro and in vivo, with the Ames test.", "output": {"entities": {"chemical": [{"text": "vitamins B1, B6 and B12", "start": 28, "end": 51}]}}, "schema": []}
{"input": "The aim of this work is to evaluate vitamins B antimutagenic effect against alkylatings methyl-N-nitro-N-nitrosoguanidine (MNNG), ethyl-N-nitro-N'-nitrosoguanidine (ENNG), frameshift mutagens 2-aminoanthracene (2AA) and 2-acetyl-amino-fluorene (2AF) and ROS-generating antibiotics norfloxacin (NOR) and nalidixic acid (NLX), using the in vitro Ames test.", "output": {"entities": {"chemical": [{"text": "vitamins B", "start": 36, "end": 46}, {"text": "methyl-N-nitro-N-nitrosoguanidine", "start": 88, "end": 121}, {"text": "MNNG", "start": 123, "end": 127}, {"text": "ethyl-N-nitro-N'-nitrosoguanidine", "start": 130, "end": 163}, {"text": "ENNG", "start": 165, "end": 169}, {"text": "2-aminoanthracene", "start": 192, "end": 209}, {"text": "2AA", "start": 211, "end": 214}, {"text": "2-acetyl-amino-fluorene", "start": 220, "end": 243}, {"text": "2AF", "start": 245, "end": 248}, {"text": "norfloxacin", "start": 281, "end": 292}, {"text": "NOR", "start": 294, "end": 297}, {"text": "nalidixic acid", "start": 303, "end": 317}, {"text": "NLX", "start": 319, "end": 322}]}}, "schema": []}
{"input": "In vivo antimutagenesis studies were performed against urinary mutagens induced by NOR (70 mg/kg) or NLX (100 mg/kg) in CD1 mice.", "output": {"entities": {"chemical": [{"text": "NOR", "start": 83, "end": 86}, {"text": "NLX", "start": 101, "end": 104}]}}, "schema": []}
{"input": "Vitamin B1 was antimutagenic against alkylatings MNNG (P < 0. 05) or ENNG (P < 0. 001).", "output": {"entities": {"chemical": [{"text": "Vitamin B1", "start": 0, "end": 10}, {"text": "MNNG", "start": 49, "end": 53}, {"text": "ENNG", "start": 69, "end": 73}]}}, "schema": []}
{"input": "In fact as per the results observed during the current study, none of the vitamins reduced mutagenesis caused by frameshift mutagens.", "output": {"entities": {}}, "schema": []}
{"input": "All of them reduced mutagenesis of NOR or NLX (P < 0. 001).", "output": {"entities": {"chemical": [{"text": "NOR", "start": 35, "end": 38}, {"text": "NLX", "start": 42, "end": 45}]}}, "schema": []}
{"input": "In vivo studies showed that vitamins B1 and B6 (10 or 100 mg/kg) reduced urinary mutagens from NOR (P < 0. 001) or NLX (P < 0. 02) either free or beta-glucoronidase-conjugates.", "output": {"entities": {"chemical": [{"text": "vitamins B1 and B6", "start": 28, "end": 46}, {"text": "NOR", "start": 95, "end": 98}, {"text": "NLX", "start": 115, "end": 118}]}}, "schema": []}
{"input": "None of the studied samples were toxic for the employed antimutagenic system.", "output": {"entities": {}}, "schema": []}
{"input": "Vitamin B12 (4 mg/kg) reduced urinary mutagens of NOR or NLX (P < 0. 02).", "output": {"entities": {"chemical": [{"text": "Vitamin B12", "start": 0, "end": 11}, {"text": "NOR", "start": 50, "end": 53}, {"text": "NLX", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Vitamins B inhibited DNA mutations induced by ROS generated by NLX or NOR, both in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "Vitamins B", "start": 0, "end": 10}, {"text": "NLX", "start": 63, "end": 66}, {"text": "NOR", "start": 70, "end": 73}]}}, "schema": []}
{"input": "Vitamin B1is antimutagenic against mutations induced by the alkylating MNNG or ENNG.", "output": {"entities": {"chemical": [{"text": "Vitamin B1is", "start": 0, "end": 12}, {"text": "MNNG", "start": 71, "end": 75}, {"text": "ENNG", "start": 79, "end": 83}]}}, "schema": []}
{"input": "Based on the observations, employment of vitamins B in vivo can be a promising alternative to reduce genotoxic risk exposure to ROS.", "output": {"entities": {"chemical": [{"text": "vitamins B", "start": 41, "end": 51}]}}, "schema": []}
{"input": "Effect of body-weight loading onto the articular cartilage on the occurrence of quinolone-induced chondrotoxicity in juvenile rats.", "output": {"entities": {"chemical": [{"text": "quinolone", "start": 80, "end": 89}]}}, "schema": []}
{"input": "The effect of body-weight loading onto the articular cartilage on the occurrence of chondrotoxicity was investigated in male juvenile Sprague-Dawley rats given ofloxacin (OFLX) orally once at 900 mg/kg.", "output": {"entities": {"chemical": [{"text": "ofloxacin", "start": 160, "end": 169}, {"text": "OFLX", "start": 171, "end": 175}]}}, "schema": []}
{"input": "Just after dosing of OFLX, hindlimb unloading was performed for 0, 2, 4, or 8 h by a tail-suspension method.", "output": {"entities": {"chemical": [{"text": "OFLX", "start": 21, "end": 25}]}}, "schema": []}
{"input": "Animals were sacrificed at 8h post-dose, and then the distal femoral articular cartilage was subjected to a histological examination and an investigation for gene expression of tumor necrosis factor receptor superfamily, member 12a (Tnfrsf12a); prostaglandin-endoperoxide synthase 2 (Ptgs2); plasminogen activator, urokinase receptor (Plaur); and matrix metalloproteinase 3 (Mmp3) by qRT-PCR analysis.", "output": {"entities": {"chemical": [{"text": "prostaglandin", "start": 245, "end": 258}]}}, "schema": []}
{"input": "As a result, cartilage lesions and up-regulations of these 4 genes that were seen in rats without the tail suspension were not observed in rats with the 8-h tail suspension, and a tendency to decrease in the incidence of the cartilage lesions and the gene expression was noted in a tail-suspension time dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Our results clearly indicate that body-weight loading onto the cartilage is necessary to induce cartilage lesions and gene expression of Tnfrsf12a, Ptgs2, Plaur, and Mmp3 in juvenile rats treated with OFLX.", "output": {"entities": {"chemical": [{"text": "OFLX", "start": 201, "end": 205}]}}, "schema": []}
{"input": "Acute and sub-chronic (28days) oral toxicity evaluation of hydroethanolic extract of Bridelia ferruginea Benth root bark in male rodent animals.", "output": {"entities": {}}, "schema": []}
{"input": "The present investigation was carried out to evaluate the safety of hydro-ethanol extract of Bridelia ferruginea Benth (Euphorbiaceae) root bark.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 74, "end": 81}]}}, "schema": []}
{"input": "For acute toxicity study, a single dose of 2000 and 5000 mg/kg of the B. ferruginea root bark extract was given orally to healthy male Wistar rats and Balb/c mice.", "output": {"entities": {}}, "schema": []}
{"input": "The animals were observed for mortality and clinical signs for 3 h and then daily for 14 days.", "output": {"entities": {}}, "schema": []}
{"input": "In the sub-chronic toxicity study, the extract was administered orally at doses of 250, 500 and 1000 mg/kg/day for 28 days to male Wistar rats.", "output": {"entities": {}}, "schema": []}
{"input": "Animals were sacrificed to examine their organs, and urine and blood serum were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "In the acute toxicity study, B. ferruginea root bark extract caused neither significant visible signs of toxicity, nor mortality in Wistar rats and Balb/c mice.", "output": {"entities": {}}, "schema": []}
{"input": "In sub-chronic toxicity study, administration of the B. ferruginea root bark extract at 250, 500, and 1000 mg/kg for 28 consecutive days to Wistar rats did not produce mortality.", "output": {"entities": {}}, "schema": []}
{"input": "No significant differences were found in relative organ weights, biochemical studied parameters in treated groups compared to control group.", "output": {"entities": {}}, "schema": []}
{"input": "No obvious histological changes were observed in organs of B. ferruginea extract treated animals compared to controls.", "output": {"entities": {}}, "schema": []}
{"input": "High levels of ephrinB2 over-expression increases the osteogenic differentiation of human mesenchymal stem cells and promotes enhanced cell mediated mineralisation in a polyethyleneimine-ephrinB2 gene-activated matrix.", "output": {"entities": {"chemical": [{"text": "polyethyleneimine", "start": 169, "end": 186}]}}, "schema": []}
{"input": "Gene therapy can be combined with tissue engineering constructs to produce gene-activated matrices (GAMs) with enhanced capacity for repair.", "output": {"entities": {}}, "schema": []}
{"input": "Polyethyleneimine (PEI), a non-viral vector, has previously been optimised for high efficiency gene transfer in rat mesenchymal stem cells (rMSCs).", "output": {"entities": {"chemical": [{"text": "Polyethyleneimine", "start": 0, "end": 17}, {"text": "PEI", "start": 19, "end": 22}]}}, "schema": []}
{"input": "The use of PEI to transfect human MSCs (hMSCs) with ephrinB2 is assessed here.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 11, "end": 14}]}}, "schema": []}
{"input": "Recently a role for the ephrinB2 ligand and EphB4 receptor duo has been proposed in bone remodelling.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, over-expression of the ephrinB2 ligand resulted in increased osteogenic differentiation in hMSCs.", "output": {"entities": {}}, "schema": []}
{"input": "As ephrinB2 is a cell surface anchored ligand which only interacts with cells expressing the cognate EphB4 receptor through direct contact, we have shown that direct cell-cell contact between two neighbouring cells is responsible for enhanced osteogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "In an effort to begin to elucidate the molecular mechanisms at play downstream of ephrinB2 over-expression, RT-PCR was performed on the GAMs which revealed no significant changes in runx2 or BMP2 expression but an upregulation of osterix (Osx) and Dlx5 expression prompting the belief that the mode of osteogenesis is independent of the BMP2 pathway.", "output": {"entities": {}}, "schema": []}
{"input": "This select interaction, coupled with the transient gene expression profile of PEI, makes the PEI-ephrinB2 GAM an ideal candidate matrix for a bone targeted GAM.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 79, "end": 82}, {"text": "PEI", "start": 94, "end": 97}]}}, "schema": []}
{"input": "Cardioprotective effect of salvianolic acid B against arsenic trioxide-induced injury in cardiac H9c2 cells via the PI3K/Akt signal pathway.", "output": {"entities": {"chemical": [{"text": "salvianolic acid B", "start": 27, "end": 45}, {"text": "arsenic trioxide", "start": 54, "end": 70}]}}, "schema": []}
{"input": "The clinical use of arsenic trioxide (ATO), a potent anti-neoplastic agent, is often limited because of its severe cardiotoxicity.", "output": {"entities": {"chemical": [{"text": "arsenic trioxide", "start": 20, "end": 36}, {"text": "ATO", "start": 38, "end": 41}]}}, "schema": []}
{"input": "Salviae miltiorrhiza is widely used for the treatment of cardiovascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "One of the most abundant ingredients of S. miltiorrhiza is salvianolic acid B (Sal B).", "output": {"entities": {"chemical": [{"text": "salvianolic acid B", "start": 59, "end": 77}, {"text": "Sal B", "start": 79, "end": 84}]}}, "schema": []}
{"input": "The present study was designed to evaluate whether Sal B protects against ATO-induced cardiac cell injury in vitro.", "output": {"entities": {"chemical": [{"text": "Sal B", "start": 51, "end": 56}, {"text": "ATO", "start": 74, "end": 77}]}}, "schema": []}
{"input": "With MTT cell viability assay, LDH release, ROS generation, caspase-3 activity assay and Hoechst 33342/PI staining, we found that Sal B pretreatment provided significantly protection against ATO-induced cell death.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 5, "end": 8}, {"text": "Hoechst 33342", "start": 89, "end": 102}, {"text": "Sal B", "start": 130, "end": 135}, {"text": "ATO", "start": 191, "end": 194}]}}, "schema": []}
{"input": "The effect was correlated with the activation of the PI3K/Akt signal pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, blocking Akt activation with the PI3K inhibitor LY294002 effectively suppressed the protective effect of Sal B against ATO-induced cell apoptosis.", "output": {"entities": {"chemical": [{"text": "LY294002", "start": 60, "end": 68}, {"text": "Sal B", "start": 117, "end": 122}, {"text": "ATO", "start": 131, "end": 134}]}}, "schema": []}
{"input": "In addition, the PI3K inhibitor partially blocked the effects of Sal B on the upregulation of Bcl-2 and Bcl-xl protein expression, and downregulation of Bax protein expression.", "output": {"entities": {"chemical": [{"text": "Sal B", "start": 65, "end": 70}]}}, "schema": []}
{"input": "Collectively, the results showed that Sal B decreased the apoptosis and necrosis of H9c2 cardiomyocytes caused by ATO treatment, and PI3K played a crucial role in enhancing cell survival during this process.", "output": {"entities": {"chemical": [{"text": "Sal B", "start": 38, "end": 43}, {"text": "ATO", "start": 114, "end": 117}]}}, "schema": []}
{"input": "These observations indicate that Sal B has the potential to exert cardioprotective effects against ATO toxicity.", "output": {"entities": {"chemical": [{"text": "Sal B", "start": 33, "end": 38}, {"text": "ATO", "start": 99, "end": 102}]}}, "schema": []}
{"input": "Differences in lead tolerance between Kandelia obovata and Acanthus ilicifolius seedlings under varying treatment times.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of short-term (1 day) and long-term (49 days) of lead (Pb) stress on growth and physiological responses in the leaves and roots of two mangrove plants, Kandelia obovata and Acanthus ilicifolius, were compared.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 67, "end": 69}]}}, "schema": []}
{"input": "The growth of both species was affected by Pb at Day 49, whereas the root to shoot ratio of K. obovata remained unchanged.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 43, "end": 45}]}}, "schema": []}
{"input": "Compared with A. ilicifolius, less Pb accumulated in leaves of K. obovata, which indicates that this species is a typical Pb-excluder.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 35, "end": 37}, {"text": "Pb", "start": 122, "end": 124}]}}, "schema": []}
{"input": "Significant linear relationships were observed between the Pb concentrations in the roots and leaves and the Pb treatment concentrations in the sediments in A. ilicifolius but not in K. obovata.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 59, "end": 61}, {"text": "Pb", "start": 109, "end": 111}]}}, "schema": []}
{"input": "The proline concentration increased in both mangrove species at Day 49, especially in A. ilicifolius, but no changes were observed at Day 1.", "output": {"entities": {}}, "schema": []}
{"input": "The tolerant species K. obovata tended to acclimate to metal stress by restricting the translocation of toxic metals and by increasing and/or maintaining high superoxide dismutase (SOD) activity, minimizing lipid peroxidation, and exhibiting prolonged unaltered growth (49 days) under Pb treatment.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 159, "end": 169}, {"text": "Pb", "start": 285, "end": 287}]}}, "schema": []}
{"input": "The non-tolerant species, A. ilicifolius, did not acclimate to metal stress, its leaves were seriously damaged with significant increased MDA content, and its SOD activity was decreased.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 138, "end": 141}]}}, "schema": []}
{"input": "An increase of endogenous jasmonic acid concentration was observed only in K. obovata, both at Day 1 and at Day 49, which suggests that this hormone plays an important role in metal tolerance under short-term and long-term metal treatment.", "output": {"entities": {"chemical": [{"text": "jasmonic acid", "start": 26, "end": 39}]}}, "schema": []}
{"input": "Tightly bound trions in monolayer MoS2.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 34, "end": 38}]}}, "schema": []}
{"input": "Two-dimensional (2D) atomic crystals, such as graphene and transition-metal dichalcogenides, have emerged as a new class of materials with remarkable physical properties.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 46, "end": 54}, {"text": "transition-metal dichalcogenides", "start": 59, "end": 91}]}}, "schema": []}
{"input": "In contrast to graphene, monolayer MoS (2) is a non-centrosymmetric material with a direct energy gap.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 15, "end": 23}, {"text": "MoS (2)", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Strong photoluminescence, a current on/off ratio exceeding 10 (8) in field-effect transistors, and efficient valley and spin control by optical helicity have recently been demonstrated in this material.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report the spectroscopic identification in a monolayer MoS (2) field-effect transistor of tightly bound negative trions, a quasiparticle composed of two electrons and a hole.", "output": {"entities": {"chemical": [{"text": "MoS (2)", "start": 63, "end": 70}]}}, "schema": []}
{"input": "These quasiparticles, which can be optically created with valley and spin polarized holes, have no analogue in conventional semiconductors.", "output": {"entities": {}}, "schema": []}
{"input": "They also possess a large binding energy (~ 20 meV), rendering them significant even at room temperature.", "output": {"entities": {}}, "schema": []}
{"input": "Our results open up possibilities both for fundamental studies of many-body interactions and for optoelectronic and valleytronic applications in 2D atomic crystals.", "output": {"entities": {}}, "schema": []}
{"input": "A rechargeable room-temperature sodium superoxide (NaO2) battery.", "output": {"entities": {"chemical": [{"text": "sodium superoxide", "start": 32, "end": 49}, {"text": "NaO2", "start": 51, "end": 55}]}}, "schema": []}
{"input": "In the search for room-temperature batteries with high energy densities, rechargeable metal-air (more precisely metal-oxygen) batteries are considered as particularly attractive owing to the simplicity of the underlying cell reaction at first glance.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 118, "end": 124}]}}, "schema": []}
{"input": "Atmospheric oxygen is used to form oxides during discharging, which-ideally-decompose reversibly during charging.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 12, "end": 18}, {"text": "oxides", "start": 35, "end": 41}]}}, "schema": []}
{"input": "Much work has been focused on aprotic Li-O (2) cells (mostly with carbonate-based electrolytes and Li (2) O (2) as a potential discharge product), where large overpotentials are observed and a complex cell chemistry is found.", "output": {"entities": {"chemical": [{"text": "Li-O (2)", "start": 38, "end": 46}, {"text": "carbonate", "start": 66, "end": 75}, {"text": "Li (2) O (2)", "start": 99, "end": 111}]}}, "schema": []}
{"input": "In fact, recent studies evidence that Li-O (2) cells suffer from irreversible electrolyte decomposition during cycling.", "output": {"entities": {"chemical": [{"text": "Li-O (2)", "start": 38, "end": 46}]}}, "schema": []}
{"input": "Here we report on a Na-O (2) cell reversibly discharging/charging at very low overpotentials (< 200 mV) and current densities as high as 0. 2 mA cm (-2) using a pure carbon cathode without an added catalyst.", "output": {"entities": {"chemical": [{"text": "Na-O (2)", "start": 20, "end": 28}, {"text": "carbon", "start": 166, "end": 172}]}}, "schema": []}
{"input": "Crystalline sodium superoxide (NaO (2)) forms in a one-electron transfer step as a solid discharge product.", "output": {"entities": {"chemical": [{"text": "sodium superoxide", "start": 12, "end": 29}, {"text": "NaO (2)", "start": 31, "end": 38}]}}, "schema": []}
{"input": "This work demonstrates that substitution of lithium by sodium may offer an unexpected route towards rechargeable metal-air batteries.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 44, "end": 51}, {"text": "sodium", "start": 55, "end": 61}]}}, "schema": []}
{"input": "High-resolution solid-state 13C NMR spectroscopy of the paramagnetic metal-organic frameworks, STAM-1 and HKUST-1.", "output": {"entities": {"chemical": [{"text": "13C", "start": 28, "end": 31}]}}, "schema": []}
{"input": "Solid-state (13) C magic-angle spinning (MAS) NMR spectroscopy is used to investigate the structure of the Cu (II)-based metal-organic frameworks (MOFs), HKUST-1 and STAM-1, and the structural changes occurring within these MOFs upon activation (dehydration).", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 12, "end": 18}, {"text": "Cu (II)", "start": 107, "end": 114}]}}, "schema": []}
{"input": "NMR spectroscopy is an attractive technique for the investigation of these materials, owing to its high sensitivity to local structure, without any requirement for longer-range order.", "output": {"entities": {}}, "schema": []}
{"input": "However, interactions between nuclei and unpaired electrons in paramagnetic systems (e. g., Cu (II)-based MOFs) pose a considerable challenge, not only for spectral acquisition, but also in the assignment and interpretation of the spectral resonances.", "output": {"entities": {"chemical": [{"text": "Cu (II)", "start": 92, "end": 99}]}}, "schema": []}
{"input": "Here, we exploit the rapid T (1) relaxation of these materials to obtain (13) C NMR spectra using a spin-echo pulse sequence at natural abundance levels, and employ frequency-stepped acquisition to ensure uniform excitation of resonances over a wide frequency range.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 73, "end": 79}]}}, "schema": []}
{"input": "We then utilise selective (13) C isotopic labelling of the organic linker molecules to enable an unambiguous assignment of NMR spectra of both MOFs for the first time.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 26, "end": 32}]}}, "schema": []}
{"input": "We show that the monomethylated linker can be recovered from STAM-1 intact, demonstrating not only the interesting use of this MOF as a protecting group, but also the ability (for both STAM-1 and HKUST-1) to recover isotopically-enriched linkers, thereby reducing significantly the overall cost of the approach.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases.", "output": {"entities": {"chemical": [{"text": "nitrile", "start": 51, "end": 58}]}}, "schema": []}
{"input": "Coronaviral infection is associated with up to 5% of respiratory tract diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The 3C-like protease (3CL (pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection.", "output": {"entities": {}}, "schema": []}
{"input": "We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL (pro) of severe-acute-respiratory-syndrome-coronavirus.", "output": {"entities": {"chemical": [{"text": "nitrile", "start": 33, "end": 40}, {"text": "N", "start": 88, "end": 89}]}}, "schema": []}
{"input": "The IC (50) values of the inhibitors were in the range of 4. 6-49 mu M, demonstrating that the nitrile warhead can effectively inactivate the 3CL (pro) autocleavage process.", "output": {"entities": {"chemical": [{"text": "nitrile", "start": 95, "end": 102}]}}, "schema": []}
{"input": "The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ~ 10x more potent than the other inhibitors tested.", "output": {"entities": {"chemical": [{"text": "Cbz", "start": 20, "end": 23}, {"text": "CN", "start": 29, "end": 31}, {"text": "N", "start": 40, "end": 41}, {"text": "carbobenzyloxy", "start": 51, "end": 65}]}}, "schema": []}
{"input": "Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL (pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets.", "output": {"entities": {"chemical": [{"text": "nitrile", "start": 69, "end": 76}, {"text": "Cys145", "start": 150, "end": 156}]}}, "schema": []}
{"input": "We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL (pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC (50) values ranging from 1. 3 to 3. 7 mu M, but no detectable inhibition against caspase-3.", "output": {"entities": {"chemical": [{"text": "Cbz", "start": 58, "end": 61}, {"text": "CN", "start": 67, "end": 69}]}}, "schema": []}
{"input": "In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL (pro), and they inhibit 3CL (pro) from a broad range of coronaviruses.", "output": {"entities": {"chemical": [{"text": "nitrile", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and antibacterial and antifungal evaluation of some chalcone based sulfones and bisulfones.", "output": {"entities": {"chemical": [{"text": "chalcone", "start": 62, "end": 70}, {"text": "sulfones", "start": 77, "end": 85}, {"text": "bisulfones", "start": 90, "end": 100}]}}, "schema": []}
{"input": "Two series of chalcone based sulfone and bisulfone derivatives were synthesized using chalcone, thiophenol and sodium metal at room temperature, followed by oxidation of chalcone sulfides with m-CPBA at 0 degrees C in a novel method.", "output": {"entities": {"chemical": [{"text": "chalcone", "start": 14, "end": 22}, {"text": "sulfone", "start": 29, "end": 36}, {"text": "bisulfone", "start": 41, "end": 50}, {"text": "chalcone", "start": 86, "end": 94}, {"text": "thiophenol", "start": 96, "end": 106}, {"text": "sodium", "start": 111, "end": 117}, {"text": "chalcone sulfides", "start": 170, "end": 187}, {"text": "m-CPBA", "start": 193, "end": 199}]}}, "schema": []}
{"input": "Both sulfones and bisulfones were evaluated for their antimicrobial activities against Aspergillus niger and Candida albicans (yeast), Bacillus subtilis and Staphylococcus aureus (Gram (+) bacteria) and Pseudomonas aeruginosa and Salmonella typhimurium (Gram (-) bacteria) strains.", "output": {"entities": {"chemical": [{"text": "sulfones", "start": 5, "end": 13}, {"text": "bisulfones", "start": 18, "end": 28}]}}, "schema": []}
{"input": "Among them, compounds 2c, 3c, 6c, 7c, 8c and 9c have shown high antifungal activity against C. albicans compare to reference drugs viz.", "output": {"entities": {}}, "schema": []}
{"input": "Amphotericin-B and Nystatin.", "output": {"entities": {"chemical": [{"text": "Amphotericin-B", "start": 0, "end": 14}, {"text": "Nystatin", "start": 19, "end": 27}]}}, "schema": []}
{"input": "Compound 1c has shown slightly better antibacterial activity against B. subtilis and compounds 5c, 6c and 7c have shown excellent antibacterial activity against S. typhimurium in compare to reference drugs Ampicillin and Kanamycin.", "output": {"entities": {"chemical": [{"text": "Ampicillin", "start": 206, "end": 216}, {"text": "Kanamycin", "start": 221, "end": 230}]}}, "schema": []}
{"input": "Identification of novel chromenone derivatives as interleukin-5 inhibitors.", "output": {"entities": {"chemical": [{"text": "chromenone", "start": 24, "end": 34}]}}, "schema": []}
{"input": "A series of (E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones (4) and (E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones (5) were synthesized and evaluated for their IL-5 inhibitory activity.", "output": {"entities": {"chemical": [{"text": "(E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones", "start": 12, "end": 72}, {"text": "(E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones", "start": 81, "end": 145}]}}, "schema": []}
{"input": "Propenone analogs 4 possess some of the structurally important characteristics of isoflavone 2 and chalcone 3 previously known as potent IL-5 inhibitor.", "output": {"entities": {"chemical": [{"text": "Propenone", "start": 0, "end": 9}, {"text": "isoflavone", "start": 82, "end": 92}, {"text": "chalcone", "start": 99, "end": 107}]}}, "schema": []}
{"input": "However, the inhibitory activity of 4 was weak and therefore this structural hybridization appears to be ineffective for the design of IL-5 inhibitor.", "output": {"entities": {}}, "schema": []}
{"input": "Meanwhile the potent activity profile of compounds 5 was discovered.", "output": {"entities": {}}, "schema": []}
{"input": "This enhanced activity of 5 compared to 4 could be due to the effective location of hydroxyl group of allylic alcohol moiety of 5 in the 3D structure.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 84, "end": 92}, {"text": "allylic alcohol", "start": 102, "end": 117}]}}, "schema": []}
{"input": "The electron withdrawing substituents at position 4 of phenyl ring of 5 enhances the activity possibly due to an increase in the strength of hydrogen bonding property of hydroxyl group of allylic alcohol moiety.", "output": {"entities": {"chemical": [{"text": "phenyl", "start": 55, "end": 61}, {"text": "hydrogen", "start": 141, "end": 149}, {"text": "hydroxyl", "start": 170, "end": 178}, {"text": "allylic alcohol", "start": 188, "end": 203}]}}, "schema": []}
{"input": "Synthesis, antibacterial activity and docking of 14-membered 9-O-(3-arylalkyl) oxime 11, 12-cyclic carbonate ketolides.", "output": {"entities": {"chemical": [{"text": "14-membered 9-O-(3-arylalkyl) oxime 11, 12-cyclic carbonate ketolides", "start": 49, "end": 118}]}}, "schema": []}
{"input": "A series of 9-O-(3-aryl-2-propargyl) oxime ketolides 8 was synthesized and evaluated for in vitro antibacterial activity.", "output": {"entities": {"chemical": [{"text": "9-O-(3-aryl-2-propargyl) oxime ketolides", "start": 12, "end": 52}]}}, "schema": []}
{"input": "Among 8, 8b-8d, and 8h-8l displayed dramatically improved potency against inducibly MLS (B)-resistant and efflux-resistant pathogens as compared to clarithromycin and azithromycin.", "output": {"entities": {"chemical": [{"text": "clarithromycin", "start": 148, "end": 162}, {"text": "azithromycin", "start": 167, "end": 179}]}}, "schema": []}
{"input": "Especially, 8i (Ar = 4-isoquinolyl) possessed an MIC of 0. 064 mu g/mL against constitutively MLS (B)-resistant Streptococcus pneumoniae, and MICs of 0. 032-0. 064 mu g/mL against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus hominis.", "output": {"entities": {"chemical": [{"text": "4-isoquinolyl", "start": 21, "end": 34}, {"text": "methicillin", "start": 180, "end": 191}, {"text": "methicillin", "start": 228, "end": 239}]}}, "schema": []}
{"input": "The analog 10 with a propyl linker was less effective than both the corresponding 8 and 9 containing propynyl and propenyl linkers.", "output": {"entities": {"chemical": [{"text": "propyl", "start": 21, "end": 27}, {"text": "propynyl", "start": 101, "end": 109}, {"text": "propenyl", "start": 114, "end": 122}]}}, "schema": []}
{"input": "A docking study was performed to gain insight into the binding mode of series 8 and 9 and to rationalize the disparity found in the SAR of 8 and 9.", "output": {"entities": {}}, "schema": []}
{"input": "Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates.", "output": {"entities": {"chemical": [{"text": "furoxanyl N-acylhydrazone", "start": 7, "end": 32}]}}, "schema": []}
{"input": "Neglected diseases represent a major health problem.", "output": {"entities": {}}, "schema": []}
{"input": "It is estimated that one third of the world population is infected with tuberculosis and additionally Leishmaniosis and Chagas disease affect approximately 30 million people.", "output": {"entities": {}}, "schema": []}
{"input": "N-Acylhydrazone moiety is a repeated functional group present in several prototypes and drug candidates for these neglected diseases.", "output": {"entities": {"chemical": [{"text": "N-Acylhydrazone", "start": 0, "end": 15}]}}, "schema": []}
{"input": "On the other hand, furoxan system has been studied as pharmacophore for Leishmaniosis and Chagas diseases.", "output": {"entities": {"chemical": [{"text": "furoxan", "start": 19, "end": 26}]}}, "schema": []}
{"input": "Here we report on the design and preparation of forty hybrid furoxanyl N-acylhydrazones and on their activity on Mycobacterium tuberculosis, H37Rv and MDR strains, Trypanosoma cruzi, and Leishmania amazonensis.", "output": {"entities": {"chemical": [{"text": "furoxanyl N-acylhydrazones", "start": 61, "end": 87}]}}, "schema": []}
{"input": "Among them, four derivatives displayed excellent to good selectivity indexes against the three different microorganisms.", "output": {"entities": {}}, "schema": []}
{"input": "Hybrid compound N'-(4-phenyl-3-furoxanylmethylidene) isoniazide 9 showed the best antibacterial profile with MIC value 4. 5 lesser than the value for the reference isoniazid against MDR strain.", "output": {"entities": {"chemical": [{"text": "N'-(4-phenyl-3-furoxanylmethylidene) isoniazide", "start": 16, "end": 63}, {"text": "isoniazid", "start": 164, "end": 173}]}}, "schema": []}
{"input": "Furoxanyl N-acylhydrazone (E)-2-methyl-N'-(4-phenyl-3-furoxanylmethylidene)-4H-imidazo [1, 2-a] pyridine-3-carbohydrazide 15 was ten-fold more potent against T. cruzi Amastigotes than the standard drug nifurtimox.", "output": {"entities": {"chemical": [{"text": "Furoxanyl N-acylhydrazone (E)-2-methyl-N'-(4-phenyl-3-furoxanylmethylidene)-4H-imidazo [1, 2-a] pyridine-3-carbohydrazide", "start": 0, "end": 121}]}}, "schema": []}
{"input": "On the other hand, derivatives (E)-N'-(5-benzofuroxanylmethylidene) benzo [d] [1, 3] dioxole-5-carbohydrazide 25 and (E)-N'-(4-hydroxy-3-methoxyphenylmethylidene)-3-methylfuroxan-4-carbohydrazide 37 emerged as leads for the development of new leishmanicidal agents.", "output": {"entities": {"chemical": [{"text": "(E)-N'-(5-benzofuroxanylmethylidene) benzo [d] [1, 3] dioxole-5-carbohydrazide", "start": 31, "end": 109}, {"text": "(E)-N'-(4-hydroxy-3-methoxyphenylmethylidene)-3-methylfuroxan-4-carbohydrazide", "start": 117, "end": 195}]}}, "schema": []}
{"input": "The adequate stability, in simulated biological system and plasma, and the lack of mutagenicity of these derivatives allow us to propose them as candidates for further pre-clinical studies.", "output": {"entities": {}}, "schema": []}
{"input": "The protein amide (1) H (N) chemical shift temperature coefficient reflects thermal expansion of the N-H... O = C hydrogen bond.", "output": {"entities": {"chemical": [{"text": "(1) H (N)", "start": 18, "end": 27}, {"text": "N-H", "start": 101, "end": 104}, {"text": "O = C hydrogen", "start": 108, "end": 122}]}}, "schema": []}
{"input": "The protein amide (1) H (N) chemical shift temperature coefficient can be determined with high accuracy by recording spectra at different temperatures, but the physical mechanism responsible for this temperature dependence is not well understood.", "output": {"entities": {"chemical": [{"text": "(1) H (N)", "start": 18, "end": 27}]}}, "schema": []}
{"input": "In this work, we find that this coefficient strongly correlates with the temperature coefficient of the through-hydrogen-bond coupling, (3h) J (NC'), based on NMR measurements of protein GB3.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 112, "end": 120}]}}, "schema": []}
{"input": "Parallel tempering molecular dynamics simulation suggests that the hydrogen bond distance variation at different temperatures/replicas is largely responsible for the (1) H (N) chemical shift temperature dependence, from which an empirical equation is proposed to predict the hydrogen bond thermal expansion coefficient, revealing responses of individual hydrogen bonds to temperature changes.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 67, "end": 75}, {"text": "(1) H (N)", "start": 166, "end": 175}, {"text": "hydrogen", "start": 275, "end": 283}, {"text": "hydrogen", "start": 354, "end": 362}]}}, "schema": []}
{"input": "Different expansion patterns have been observed for various networks formed by beta strands.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, characterization and pharmacodynamics of vitamin-B (12)-conjugated glucagon-like peptide-1.", "output": {"entities": {"chemical": [{"text": "vitamin-B (12)", "start": 52, "end": 66}]}}, "schema": []}
{"input": "Clearing the way: Glucagon-like peptide-1 (GLP-1) receptor agonists are proving a potent weapon in the treatment of type II diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "A new vitamin B (12)-GLP-1 conjugate is investigated and shown to have insulinotropic properties similar to the unmodified peptide.", "output": {"entities": {"chemical": [{"text": "vitamin B (12)", "start": 6, "end": 20}]}}, "schema": []}
{"input": "These results are critical to the exploitation of the vitamin B (12) oral uptake pathway for peptide delivery.", "output": {"entities": {"chemical": [{"text": "vitamin B (12)", "start": 54, "end": 68}]}}, "schema": []}
{"input": "TCDD inhibits heart regeneration in adult zebrafish.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Normal adult zebrafish can completely regenerate lost myocardium following partial amputation of the ventricle apex.", "output": {"entities": {}}, "schema": []}
{"input": "We report that 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) significantly impairs this regeneration.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 15, "end": 53}, {"text": "TCDD", "start": 55, "end": 59}]}}, "schema": []}
{"input": "Adult male zebrafish were injected with vehicle (control) or TCDD (70ng/g, ip) 1 day prior to partial amputation of the ventricle apex.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 61, "end": 65}]}}, "schema": []}
{"input": "Gross observation and histological analysis of the amputated heart at 21 days postamputation revealed that TCDD-exposed fish had not progressed beyond the initial clot formation stage, whereas the vehicle control fish showed substantial recovery and almost complete resolution of the formed clot.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 107, "end": 111}]}}, "schema": []}
{"input": "In contrast, hearts that were not surgically wounded showed no signs of TCDD toxicity.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 72, "end": 76}]}}, "schema": []}
{"input": "Striking features in the TCDD-exposed hearts were the absence of the normal sheath of new tissue enveloping the wound and the absence of intense cell proliferation at the site of the wound.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 25, "end": 29}]}}, "schema": []}
{"input": "In addition, the patterns of collagen deposition at the wound site were different between the TCDD and vehicle groups.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 94, "end": 98}]}}, "schema": []}
{"input": "Because the receptor for TCDD is the aryl hydrocarbon receptor ligand-activated transcriptional regulator, we examined the effects of TCDD exposure on gene expression in the ventricle using DNA microarrays.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 25, "end": 29}, {"text": "aryl hydrocarbon", "start": 37, "end": 53}, {"text": "TCDD", "start": 134, "end": 138}]}}, "schema": []}
{"input": "Samples were collected just prior to amputation and at 6h and 7 days postamputation.", "output": {"entities": {}}, "schema": []}
{"input": "TCDD-pretreated hearts had dysregulated expression of genes involved in heart function, tissue regeneration, cell growth, and extracellular matrix.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Because embryonic, but not adult, hearts are major targets for TCDD-induced cardiotoxicity, we speculate that the need for embryonic-like cells in regeneration is connected with the effects of TCDD in inhibiting the response to wounding.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 63, "end": 67}, {"text": "TCDD", "start": 193, "end": 197}]}}, "schema": []}
{"input": "iReckon: simultaneous isoform discovery and abundance estimation from RNA-seq data.", "output": {"entities": {}}, "schema": []}
{"input": "High-throughput RNA sequencing (RNA-seq) promises to revolutionize our understanding of genes and their role in human disease by characterizing the RNA content of tissues and cells.", "output": {"entities": {}}, "schema": []}
{"input": "The realization of this promise, however, is conditional on the development of effective computational methods for the identification and quantification of transcripts from incomplete and noisy data.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we introduce iReckon, a method for simultaneous determination of the isoforms and estimation of their abundances.", "output": {"entities": {}}, "schema": []}
{"input": "Our probabilistic approach incorporates multiple biological and technical phenomena, including novel isoforms, intron retention, unspliced pre-mRNA, PCR amplification biases, and multimapped reads.", "output": {"entities": {}}, "schema": []}
{"input": "iReckon utilizes regularized expectation-maximization to accurately estimate the abundances of known and novel isoforms.", "output": {"entities": {}}, "schema": []}
{"input": "Our results on simulated and real data demonstrate a superior ability to discover novel isoforms with a significantly reduced number of false-positive predictions, and our abundance accuracy prediction outmatches that of other state-of-the-art tools.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we have applied iReckon to two cancer transcriptome data sets, a triple-negative breast cancer patient sample and the MCF7 breast cancer cell line, and show that iReckon is able to reconstruct the complex splicing changes that were not previously identified.", "output": {"entities": {}}, "schema": []}
{"input": "QT-PCR validations of the isoforms detected in the MCF7 cell line confirmed all of iReckon' s predictions and also showed strong agreement (r (2) = 0. 94) with the predicted abundances.", "output": {"entities": {}}, "schema": []}
{"input": "The calmodulin regulator protein, PEP-19, sensitizes ATP-induced Ca2 + release.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 53, "end": 56}, {"text": "Ca2 +", "start": 65, "end": 70}]}}, "schema": []}
{"input": "PEP-19 is a small, intrinsically disordered protein that binds to the C-domain of calmodulin (CaM) via an IQ motif and tunes its Ca (2 +) binding properties via an acidic sequence.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 129, "end": 137}]}}, "schema": []}
{"input": "We show here that the acidic sequence of PEP-19 has intrinsic Ca (2 +) binding activity, which may modulate Ca (2 +) binding to CaM by stabilizing an initial Ca (2 +)-CaM complex or by electrostatically steering Ca (2 +) to and from CaM.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 62, "end": 70}, {"text": "Ca (2 +)", "start": 108, "end": 116}, {"text": "Ca (2 +)", "start": 158, "end": 166}, {"text": "Ca (2 +)", "start": 212, "end": 220}]}}, "schema": []}
{"input": "Because PEP-19 is expressed in cells that exhibit highly active Ca (2 +) dynamics, we tested the hypothesis that it influences ligand-dependent Ca (2 +) release.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 64, "end": 72}, {"text": "Ca (2 +)", "start": 144, "end": 152}]}}, "schema": []}
{"input": "We show that PEP-19 increases the sensitivity of HeLa cells to ATP-induced Ca (2 +) release to greatly increase the percentage of cells responding to sub-saturating doses of ATP and increases the frequency of Ca (2 +) oscillations.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 63, "end": 66}, {"text": "Ca (2 +)", "start": 75, "end": 83}, {"text": "ATP", "start": 174, "end": 177}, {"text": "Ca (2 +)", "start": 209, "end": 217}]}}, "schema": []}
{"input": "Mutations in the acidic sequence of PEP-19 that inhibit or prevent it from modulating Ca (2 +) binding to CaM greatly inhibit its effect on ATP-induced Ca (2 +) release.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 86, "end": 94}, {"text": "ATP", "start": 140, "end": 143}, {"text": "Ca (2 +)", "start": 152, "end": 160}]}}, "schema": []}
{"input": "Thus, this cellular effect of PEP-19 does not depend simply on binding to CaM via the IQ motif but requires its acidic metal binding domain.", "output": {"entities": {}}, "schema": []}
{"input": "Tuning the activities of Ca (2 +) mobilization pathways places PEP-19 at the top of CaM signaling cascades, with great potential to exert broad effects on downstream CaM targets, thus expanding the biological significance of this small regulator of CaM signaling.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 25, "end": 33}]}}, "schema": []}
{"input": "Effects of single or repeated silymarin administration on pharmacokinetics of risperidone and its major metabolite, 9-hydroxyrisperidone in rats.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 78, "end": 89}, {"text": "9-hydroxyrisperidone", "start": 116, "end": 136}]}}, "schema": []}
{"input": "1. The interactions between herbal dietary supplements and therapeutic drugs have emerged as an important issue and P-glycoprotein (P-gp) has been reported as one of the significant factors of these interactions.", "output": {"entities": {}}, "schema": []}
{"input": "2. The objective of this article is to examine the effects of single and repeated administrations of silymarin on pharmacokinetics of a P-gp substrate, risperidone, and its major metabolite, 9-hydroxyrisperidone, in rats.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 152, "end": 163}, {"text": "9-hydroxyrisperidone", "start": 191, "end": 211}]}}, "schema": []}
{"input": "3. To determine the plasma levels of risperidone and 9-hydroxyrisperidone in rats, a HPLC method was developed using a liquid-liquid acid back extraction.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 37, "end": 48}, {"text": "9-hydroxyrisperidone", "start": 53, "end": 73}]}}, "schema": []}
{"input": "When risperidone (6 mg/kg) was co-administered with silymarin (40 mg/kg) to rats orally, the C (max) of 9-hydroxyrisperidone was significantly increased to1. 3-fold (p < 0. 05), while the other pharmacokinetic parameters did not show any significant differences.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 5, "end": 16}, {"text": "9-hydroxyrisperidone", "start": 104, "end": 124}]}}, "schema": []}
{"input": "Expanding the experiment where rats were repeatedly administered with silymarin for 5 days prior to giving risperidone, the C (max) of risperidone and 9-hydroxyrisperidone were significantly increased to 2. 4-fold (p < 0. 001) and 1. 7-fold (p < 0. 001), respectively, and the AUC (0-t), as well to 1. 7-fold (p < 0. 05) and 2. 1-fold (p < 0. 01), respectively.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 107, "end": 118}, {"text": "risperidone", "start": 135, "end": 146}, {"text": "9-hydroxyrisperidone", "start": 151, "end": 171}]}}, "schema": []}
{"input": "4. The repeated exposures of silymarin, compared to single administration of silymarin, increased oral bioavailability and affected the pharmacokinetics of risperidone and 9-hydroxyrisperidone, by inhibiting P-gp.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 156, "end": 167}, {"text": "9-hydroxyrisperidone", "start": 172, "end": 192}]}}, "schema": []}
{"input": "Acute pulmonary effects of sidestream secondhand smoke at simulated car concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "1. Exposure to secondhand smoke (SHS) can occur in many places; however, regulations banning smoking may reduce the sources of exposure to SHS to personal areas such as the family car, a source of brief but potently intense exposure.", "output": {"entities": {}}, "schema": []}
{"input": "2. Fifteen non-smoking volunteers were exposed to sidestream SHS concentrations of 5000 micro g/m (3), within a simulated car setting.", "output": {"entities": {}}, "schema": []}
{"input": "The Fraction of Exhaled Nitric Oxide (FeNO) was calculated, dynamic flow volumes were assessed through spirometry; while airway impedance (Z), resistance (R), and reactance (X) was assessed through impulse oscillometry before and after exposure.", "output": {"entities": {"chemical": [{"text": "Nitric Oxide", "start": 24, "end": 36}]}}, "schema": []}
{"input": "3. Exposure to sidestream SHS within this experimental condition did not affect dynamic flow volumes, however FENO decreased from 15. 34 ppb to 11. 15 ppb, (p < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "Increases in airway resistance at R5Hz by 0. 114 kPa/(L/s) (p = 0. 002), at R10Hz by 0. 093 [kPa/(L/s)] (p = 0. 006) and at R20Hz by 0. 093 [kPa/(L/s)] (p = 0. 008) were noted.", "output": {"entities": {}}, "schema": []}
{"input": "Correspondingly overall peripheral and central airway resistance was also found to increase by 40% (by 0. 083 kPa/(L/s), p = 0. 038) and 25% (by 0. 045 kPa/(L/s), p = 0. 047) respectively.", "output": {"entities": {}}, "schema": []}
{"input": "4. Brief but elevated exposure to sidestream SHS can alter airway resistance, and impedance indicating a potential additional mechanistic pathway between exposure to SHS and the development of respiratory disease.", "output": {"entities": {}}, "schema": []}
{"input": "Further research is needed to verify these pilot results.", "output": {"entities": {}}, "schema": []}
{"input": "A new perfluoropolyether-based hydrophobic and chemically resistant photoresist structured by two-photon polymerization.", "output": {"entities": {"chemical": [{"text": "perfluoropolyether", "start": 6, "end": 24}]}}, "schema": []}
{"input": "Two-photon polymerization technology has been used to fabricate submicrometer three-dimensional (3D) structures using a new polyfunctional perfluoropolyether-based resist, which is a polymer intrinsically hydrophobic and chemically resistant.", "output": {"entities": {"chemical": [{"text": "perfluoropolyether", "start": 139, "end": 157}]}}, "schema": []}
{"input": "The fluorinated resist was designed and synthesized in this work and successfully employed to fabricate woodpile structures in various experimental conditions.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first demonstration of the capability to fabricate hydrophobic and chemically resistant 3D structures with submicrometer resolution and arbitrary geometry.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of the lipid environment, cholesterol and bile acids on the function of the purified and reconstituted human ABCG2 protein.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 34, "end": 45}, {"text": "bile acids", "start": 50, "end": 60}]}}, "schema": []}
{"input": "The human ABCG2 multidrug transporter actively extrudes a wide range of hydrophobic drugs and xenobiotics recognized by the transporter in the membrane phase.", "output": {"entities": {}}, "schema": []}
{"input": "In order to examine the molecular nature of the transporter and its effects on the lipid environment, we have established an efficient protocol for the purification and reconstitution of the functional protein.", "output": {"entities": {}}, "schema": []}
{"input": "We found that the drug-stimulated ATPase and the transport activity of ABCG2 are fully preserved by applying excess lipids and mild detergents during solubilization, whereas a detergent-induced dissociation of the ABCG2 dimer causes an irreversible inactivation.", "output": {"entities": {}}, "schema": []}
{"input": "By using the purified and reconstituted protein we demonstrate that cholesterol is an essential activator, whereas bile acids are important modulators of ABCG2 activity.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 68, "end": 79}, {"text": "bile acids", "start": 115, "end": 125}]}}, "schema": []}
{"input": "Both wild-type ABCG2 and its R482G mutant variant require cholesterol for full activity, although they exhibit different cholesterol sensitivities.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 58, "end": 69}, {"text": "cholesterol", "start": 121, "end": 132}]}}, "schema": []}
{"input": "Bile acids strongly decrease the basal ABCG2-ATPase activity both in the wild-type ABCG2 and in the mutant variant.", "output": {"entities": {"chemical": [{"text": "Bile acids", "start": 0, "end": 10}]}}, "schema": []}
{"input": "These data reinforce the results for the modulatory effects of cholesterol and bile acids of ABCG2 investigated in a complex cell membrane environment.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 63, "end": 74}, {"text": "bile acids", "start": 79, "end": 89}]}}, "schema": []}
{"input": "Moreover, these experiments open the possibility to perform functional and structural studies with a purified, reconstituted and highly active ABCG2 multidrug transporter.", "output": {"entities": {}}, "schema": []}
{"input": "Spontaneous periodic diameter oscillations in InP nanowires: the role of interface instabilities.", "output": {"entities": {"chemical": [{"text": "InP", "start": 46, "end": 49}]}}, "schema": []}
{"input": "We have observed that thin InP nanowires generated by vapor-liquid-solid growth display spontaneous periodic diameter oscillations when large group III supersaturations are used.", "output": {"entities": {"chemical": [{"text": "InP", "start": 27, "end": 30}]}}, "schema": []}
{"input": "Diameter variations are associated with a large number of stacking faults and crystallographic phase changes (wurtzite/zinc-blende); also the axial distance between oscillations depends on the indium precursor flow used during the run.", "output": {"entities": {"chemical": [{"text": "wurtzite", "start": 110, "end": 118}, {"text": "zinc-blende", "start": 119, "end": 130}, {"text": "indium", "start": 193, "end": 199}]}}, "schema": []}
{"input": "We attribute the morphology changes to a substantial deformation of the triple phase line (vapor-liquid-solid) at the catalyst nanoparticle edge originated from multistep nucleation during growth.", "output": {"entities": {}}, "schema": []}
{"input": "The deformation alters the mechanical force balance acting on the nanoparticle during growth in such a way that the particle displaces from the nanowire top and wets the nanowire sidewall.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, as catalytic growth occurs at the sidewall, the associated increase in diameter will eventually push the NP back to its original wire-top position until the onset of a new instability at the triple phase line.", "output": {"entities": {}}, "schema": []}
{"input": "Flexible fiber nanogenerator with 209 V output voltage directly powers a light-emitting diode.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of a vertically aligned ultralong Pb (Zr (0. 52) Ti (0. 48)) O (3) (PZT) nanowire array fabricated using electrospinning nanofibers, we developed a new type of integrated nanogenerator (NG) with ultrahigh output voltage of 209 V and current density of 23. 5 mu A/cm (2), which are 3. 6 times and 2. 9 times of the previous record values, respectively.", "output": {"entities": {"chemical": [{"text": "Pb (Zr (0. 52) Ti (0. 48)) O (3)", "start": 47, "end": 79}, {"text": "PZT", "start": 81, "end": 84}]}}, "schema": []}
{"input": "The output electricity can be directly used to stimulate the frog' s sciatic nerve and to induce a contraction of a frog' s gastrocnemius.", "output": {"entities": {}}, "schema": []}
{"input": "The NG can instantaneously power a commercial light-emitting diode (LED) without the energy storage process.", "output": {"entities": {}}, "schema": []}
{"input": "Interactions of sarin with polyelectrolyte membranes: a molecular dynamics simulation study.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 16, "end": 21}]}}, "schema": []}
{"input": "Nanostructured polyelectrolyte membranes (PEMs), which are widely used as permselective diffusion barriers in fuel cell technologies and electrochemical processing, are considered as protective membranes suitable for blocking warfare toxins, including water-soluble nerve agents such as sarin.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 287, "end": 292}]}}, "schema": []}
{"input": "In this article, we examine the mechanisms of sorption and diffusion of sarin in hydrated PEMs by means of atomistic molecular dynamics simulations.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 72, "end": 77}]}}, "schema": []}
{"input": "Three PEMs are considered: Nafion, sulfonated polystyrene (sPS) that forms the hydrophilic subphase of segregated sPS-polyolefin block copolymers, and random sPS-polyethylene copolymer.", "output": {"entities": {"chemical": [{"text": "Nafion", "start": 27, "end": 33}, {"text": "sulfonated polystyrene", "start": 35, "end": 57}, {"text": "sPS", "start": 59, "end": 62}, {"text": "sPS", "start": 114, "end": 117}, {"text": "polyolefin", "start": 118, "end": 128}, {"text": "sPS", "start": 158, "end": 161}, {"text": "polyethylene", "start": 162, "end": 174}]}}, "schema": []}
{"input": "We found that sarin concentrates at the interface between the hydrophilic and hydrophobic subphases of hydrated Nafion acting as a surfactant.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 14, "end": 19}, {"text": "hydrated Nafion", "start": 103, "end": 118}]}}, "schema": []}
{"input": "In hydrated sPS, where the scale of water-polymer segregation is much smaller (1-2 nm), sarin also interacts favorably with hydrophobic and hydrophilic components.", "output": {"entities": {"chemical": [{"text": "hydrated sPS", "start": 3, "end": 15}, {"text": "sarin", "start": 88, "end": 93}]}}, "schema": []}
{"input": "Water diffusion slows as the sarin content increases despite the overall increase in solvent content, which suggests that sarin and water have somewhat different pathways through the segregated membrane.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 29, "end": 34}, {"text": "sarin", "start": 122, "end": 127}]}}, "schema": []}
{"input": "Upon replacement of counterions of monovalent potassium with those of divalent calcium, sarin diffusion slows but remains substantial in all ionomers considered, especially at high sarin concentrations.", "output": {"entities": {"chemical": [{"text": "potassium", "start": 46, "end": 55}, {"text": "calcium", "start": 79, "end": 86}, {"text": "sarin", "start": 88, "end": 93}, {"text": "sarin", "start": 181, "end": 186}]}}, "schema": []}
{"input": "The behavior of sarin is similar to that of its common simulant, dimethyl methylphosphonate.", "output": {"entities": {"chemical": [{"text": "sarin", "start": 16, "end": 21}, {"text": "dimethyl methylphosphonate", "start": 65, "end": 91}]}}, "schema": []}
{"input": "Invasion genetics of the introduced black rat (Rattus rattus) in Senegal, West Africa.", "output": {"entities": {}}, "schema": []}
{"input": "An understanding of the evolutionary history and dynamics of invasive species is required for the construction of predictive models of future spread and the design of biological management measures.", "output": {"entities": {}}, "schema": []}
{"input": "The black rat (Rattus rattus) is a major vertebrate invader with a worldwide distribution.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the severe ecological, economic and health impacts of this species, its evolutionary history has been little studied.", "output": {"entities": {}}, "schema": []}
{"input": "We carried out extensive specimen sampling in Senegal, West Africa, and used microsatellite markers to describe the pattern and processes of invasion in this large continental area.", "output": {"entities": {}}, "schema": []}
{"input": "The genetic data obtained were combined with historical knowledge concerning the presence of this species in Senegal.", "output": {"entities": {}}, "schema": []}
{"input": "Data were analysed by a combination of Bayesian clustering and approximate Bayesian computation methods.", "output": {"entities": {}}, "schema": []}
{"input": "The invasion pathways closely paralleled the history of human trade routes in Senegal.", "output": {"entities": {}}, "schema": []}
{"input": "In several places, we detected the occurrence of multiple introductions from genetically different sources.", "output": {"entities": {}}, "schema": []}
{"input": "Long-distance migration between towns and villages was also observed.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest that genetic bottlenecks and admixture have played a major role in shaping the genetics of invasive black rats.", "output": {"entities": {}}, "schema": []}
{"input": "These two processes may generate genetic novelty and favour rapid evolution along the invasion pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Multifunctional Fe3O4 @Ag/SiO2/Au core-shell microspheres as a novel SERS-activity label via long-range plasmon coupling.", "output": {"entities": {"chemical": [{"text": "Fe3O4", "start": 16, "end": 21}, {"text": "Ag", "start": 23, "end": 25}, {"text": "SiO2", "start": 26, "end": 30}, {"text": "Au", "start": 31, "end": 33}]}}, "schema": []}
{"input": "Noble metallic nanostructures exhibit a phenomenon known as surface-enhanced Raman scattering (SERS) in which the Raman scattering cross sections are dramatically enhanced for the molecules adsorbed thereon.", "output": {"entities": {}}, "schema": []}
{"input": "Due to their wide accessible potential range in aqueous solutions and the high biocompatibility, Au supports are preferred for spectro-electrochemical investigations.", "output": {"entities": {"chemical": [{"text": "Au", "start": 97, "end": 99}]}}, "schema": []}
{"input": "However, the optical range in SERS spectroscopy is restricted to excitation lines above 600 nm, which is shorter than the Ag supports.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 122, "end": 124}]}}, "schema": []}
{"input": "In addition, these SERS-activity materials are not easy to separate and reused.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, the present article reports the novel multifunctional Fe (3) O (4) @Ag/SiO (2)/Au core-shell microspheres that display long-range plasmon transfer of Ag to Au leading to enhanced Raman scattering.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 62, "end": 74}, {"text": "Ag", "start": 76, "end": 78}, {"text": "SiO (2)", "start": 79, "end": 86}, {"text": "Au", "start": 87, "end": 89}, {"text": "Ag", "start": 158, "end": 160}, {"text": "Au", "start": 164, "end": 166}]}}, "schema": []}
{"input": "The well-designed microspheres have high magnetization and uniform sphere size.", "output": {"entities": {}}, "schema": []}
{"input": "As a result, Fe (3) O (4) @Ag/SiO (2)/Au microspheres have the best enhancement effect in the Raman active research by using Rhodamine-b (RdB) as a probe molecule.", "output": {"entities": {"chemical": [{"text": "Fe (3) O (4)", "start": 13, "end": 25}, {"text": "Ag", "start": 27, "end": 29}, {"text": "SiO (2)", "start": 30, "end": 37}, {"text": "Au", "start": 38, "end": 40}, {"text": "Rhodamine-b", "start": 125, "end": 136}, {"text": "RdB", "start": 138, "end": 141}]}}, "schema": []}
{"input": "The enhancement factor is estimated to be 2. 2 x 10 (4) for RdB from the long-range plasmon transfer of Ag to Au, corresponding to an attenuation of the enhancement by a factor of only 0. 672 x 10 (4) compared to RdB adsorbed directly on the Fe (3) O (4) @Ag microspheres.", "output": {"entities": {"chemical": [{"text": "RdB", "start": 60, "end": 63}, {"text": "Ag", "start": 104, "end": 106}, {"text": "Au", "start": 110, "end": 112}, {"text": "RdB", "start": 213, "end": 216}, {"text": "Fe (3) O (4)", "start": 242, "end": 254}, {"text": "Ag", "start": 256, "end": 258}]}}, "schema": []}
{"input": "RdB can be detected down to 10 (-9) M even without the resonance SERS effect.", "output": {"entities": {"chemical": [{"text": "RdB", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The unique nanostructure makes the microspheres novel stable and a high-enhancement effect for Raman detection.", "output": {"entities": {}}, "schema": []}
{"input": "Belatacept utilization recommendations: an expert position.", "output": {"entities": {}}, "schema": []}
{"input": "INTRODUCTION: There is a continuing need for an immunosuppressive therapy that offers a high benefit-risk profile for renal transplant recipients, supporting long-term patient and graft survival while minimizing cumulative nephrotoxicity and other side effects.", "output": {"entities": {}}, "schema": []}
{"input": "Belatacept, the first biological agent developed for primary maintenance immunosuppression, was recently approved for use in Europe.", "output": {"entities": {}}, "schema": []}
{"input": "Belatacept combined with corticosteroids and a mycophenolic acid is indicated for prophylaxis of graft rejection in adults receiving renal transplant.", "output": {"entities": {"chemical": [{"text": "corticosteroids", "start": 25, "end": 40}, {"text": "mycophenolic acid", "start": 47, "end": 64}]}}, "schema": []}
{"input": "Its use is contraindicated in Epstein-Barr virus seronegative or serostatus unknown patients due to increased risk of developing posttransplant lymphoproliferative disorder.", "output": {"entities": {}}, "schema": []}
{"input": "AREAS COVERED: This review provides practical recommendations for the use of belatacept, based on safety and efficacy data from Phase II and Phase III clinical trials in de novo kidney transplant recipients.", "output": {"entities": {}}, "schema": []}
{"input": "EXPERT OPINION: Treatment with belatacept is associated with improved long-term graft function, making belatacept an important option for prevention of kidney allograft rejection.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, efficacy and safety data over several years of therapy suggest that belatacept is particularly suitable for long-term immunosuppression, and the selective targeting offered by belatacept may help avoid some of the non-specific chronic safety risks associated with calcineurin inhibitors and steroids.", "output": {"entities": {}}, "schema": []}
{"input": "Future studies will clarify the optimal regimen for belatacept usage.", "output": {"entities": {}}, "schema": []}
{"input": "Highly solvatochromic fluorescent naphthalimides: design, synthesis, photophysical properties and fluorescence switch-on sensing of ct-DNA.", "output": {"entities": {"chemical": [{"text": "naphthalimides", "start": 34, "end": 48}]}}, "schema": []}
{"input": "We report the design, synthesis and photophysical properties of highly solvatochromic donor/acceptor substituted naphthalimide based fluorophores.", "output": {"entities": {"chemical": [{"text": "naphthalimide", "start": 113, "end": 126}]}}, "schema": []}
{"input": "The synthesized naphthalimides containing propargyl ends showed highly solvatochromic intramolecular charge transfer (ICT) feature as was revealed from the UV-visible, fluorescence photophysical properties of these fluorophores and DFT/TDDFT calculation.", "output": {"entities": {"chemical": [{"text": "naphthalimides", "start": 16, "end": 30}, {"text": "propargyl", "start": 42, "end": 51}]}}, "schema": []}
{"input": "Fluorescence life times for the imide fluorophores were also measured in different solvents.", "output": {"entities": {"chemical": [{"text": "imide", "start": 32, "end": 37}]}}, "schema": []}
{"input": "The solid state photophysical property of donor substituted naphthalimide 1 showed promising for future application in material sciences.", "output": {"entities": {"chemical": [{"text": "naphthalimide", "start": 60, "end": 73}]}}, "schema": []}
{"input": "Furthermore, both the donor/acceptor substituted naphthalimide fluorophores 1-2 were exploited in sensing calf-thymus DNA via switch-on fluorescence response.", "output": {"entities": {"chemical": [{"text": "naphthalimide", "start": 49, "end": 62}]}}, "schema": []}
{"input": "The propargyl linker containing naphthalimides can further be exploited for the synthesis of labeled biomolecular building blocks.", "output": {"entities": {"chemical": [{"text": "propargyl", "start": 4, "end": 13}, {"text": "naphthalimides", "start": 32, "end": 46}]}}, "schema": []}
{"input": "Design, synthesis and bioevalution of novel benzamides derivatives as HDAC inhibitors.", "output": {"entities": {"chemical": [{"text": "benzamides", "start": 44, "end": 54}]}}, "schema": []}
{"input": "A series of novel benzamides derivatives was designed and synthesized as HDAC inhibitors.", "output": {"entities": {"chemical": [{"text": "benzamides", "start": 18, "end": 28}]}}, "schema": []}
{"input": "Exploration of the structure-activity relationships resulted in compounds that are potent in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the best compound 1a exhibited an acceptable pharmacokinetic profile with bioavailability in rat of 81% and could be considered as a candidate compound for further development.", "output": {"entities": {}}, "schema": []}
{"input": "A systematic study of the degradation of dimethyl phthalate using a high-frequency ultrasonic process.", "output": {"entities": {"chemical": [{"text": "dimethyl phthalate", "start": 41, "end": 59}]}}, "schema": []}
{"input": "A comprehensive study of the sonochemical degradation of dimethyl phthalate (DMP) was carried out using high-frequency ultrasonic processes.", "output": {"entities": {"chemical": [{"text": "dimethyl phthalate", "start": 57, "end": 75}, {"text": "DMP", "start": 77, "end": 80}]}}, "schema": []}
{"input": "The effects of various operating parameters were investigated, including ultrasonic frequency, power density, initial DMP concentration, solution pH and the presence of hydrogen peroxide.", "output": {"entities": {"chemical": [{"text": "DMP", "start": 118, "end": 121}, {"text": "hydrogen peroxide", "start": 169, "end": 186}]}}, "schema": []}
{"input": "In general, a frequency of 400kHz was the optimum for achieving the highest DMP degradation rate.", "output": {"entities": {"chemical": [{"text": "DMP", "start": 76, "end": 79}]}}, "schema": []}
{"input": "The degradation rate was directly proportional to the power density and inversely related to the initial DMP concentration.", "output": {"entities": {"chemical": [{"text": "DMP", "start": 105, "end": 108}]}}, "schema": []}
{"input": "It was interesting to find that faster removal rate was observed under weakly acidic condition, while hydrolysis effect dominated in extreme-basic condition.", "output": {"entities": {}}, "schema": []}
{"input": "The addition of hydrogen peroxide can increase the radical generation to some extent.", "output": {"entities": {"chemical": [{"text": "hydrogen peroxide", "start": 16, "end": 33}]}}, "schema": []}
{"input": "Furthermore, both hydroxylation of the aromatic ring and oxidation of the aliphatic chain appear to be the major mechanism of DMP degradation by sonolysis based on LC/ESI-MS analysis.", "output": {"entities": {"chemical": [{"text": "DMP", "start": 126, "end": 129}]}}, "schema": []}
{"input": "Among the principle reaction intermediates identified, tri-and tetra-hydroxylated derivatives of DMP, as well as hydroxylated monomethyl phthalates and hydroxylated phthalic acid were reported for the first time in this study.", "output": {"entities": {"chemical": [{"text": "DMP", "start": 97, "end": 100}, {"text": "hydroxylated monomethyl phthalates", "start": 113, "end": 147}, {"text": "hydroxylated phthalic acid", "start": 152, "end": 178}]}}, "schema": []}
{"input": "Reaction pathways for DMP sonolysis are proposed based on the detected intermediates.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of hydroxyl radical formation in aqueous solutions at different ultrasound frequencies and powers using the salicylic acid dosimeter.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 14, "end": 22}, {"text": "salicylic acid", "start": 119, "end": 133}]}}, "schema": []}
{"input": "Ultrasonic frequencies of 20kHz, 382kHz, 584kHz, 862kHz (and 998kHz) have been compared with regard to energy output and hydroxyl radical formation utilising the salicylic acid dosimeter.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 121, "end": 129}, {"text": "salicylic acid", "start": 162, "end": 176}]}}, "schema": []}
{"input": "The 862kHz frequency inputs 6 times the number of Watts into water, as measured by calorimetry, with the other frequencies having roughly the same value under very similar conditions.", "output": {"entities": {}}, "schema": []}
{"input": "A plausible explanation involving acoustic fountain formation is proposed although enhanced coupling between this frequency and water cannot be discounted.", "output": {"entities": {}}, "schema": []}
{"input": "Using the salicylic acid dosimeter and inputting virtually the same Wattages it is established that 862kHz is around 10% more efficient at generating hydroxyl radicals than the 382kHz but both of these are far more effective than the other frequencies.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 10, "end": 24}, {"text": "hydroxyl", "start": 150, "end": 158}]}}, "schema": []}
{"input": "Also, it is found that as temperature increases to 42 degrees C then the total dihydroxybenzoic acid (Total DHBA) produced is virtually identical for 382kHz and 862kHz, though 582kHz is substantially lower, when the power levels are set at approximately 9W for all systems.", "output": {"entities": {"chemical": [{"text": "dihydroxybenzoic acid", "start": 79, "end": 100}, {"text": "DHBA", "start": 108, "end": 112}]}}, "schema": []}
{"input": "An equivalent power level of 9W could not be obtained for the 998kHz transducer so a direct comparison could not be made in this instance.", "output": {"entities": {}}, "schema": []}
{"input": "These results have implications for the optimum frequencies chosen for both Advanced Oxidation Processes (AOPs) and organic synthesis augmented by ultrasound.", "output": {"entities": {}}, "schema": []}
{"input": "Ion-exchange and iontophoresis-controlled delivery of apomorphine.", "output": {"entities": {"chemical": [{"text": "apomorphine", "start": 54, "end": 65}]}}, "schema": []}
{"input": "The objective of this study was to test a drug delivery system that combines iontophoresis and cation-exchange fibers as drug matrices for the controlled transdermal delivery of antiparkinsonian drug apomorphine.", "output": {"entities": {"chemical": [{"text": "apomorphine", "start": 200, "end": 211}]}}, "schema": []}
{"input": "Positively charged apomorphine was bound to the ion-exchange groups of the cation-exchange fibers until it was released by mobile counter-ions in the external solution.", "output": {"entities": {"chemical": [{"text": "apomorphine", "start": 19, "end": 30}]}}, "schema": []}
{"input": "The release of the drug was controlled by modifying either the fiber type or the ionic composition of the external solution.", "output": {"entities": {}}, "schema": []}
{"input": "Due to high affinity of apomorphine toward the ion-exchanger, a clear reduction in the in vitro transdermal fluxes from the fibers was observed compared to the respective fluxes from apomorphine solutions.", "output": {"entities": {"chemical": [{"text": "apomorphine", "start": 24, "end": 35}, {"text": "apomorphine", "start": 183, "end": 194}]}}, "schema": []}
{"input": "Changes in the ionic composition of the donor formulations affected both the release and iontophoretic flux of the drug.", "output": {"entities": {}}, "schema": []}
{"input": "Upon the application of higher co-ion concentrations or co-ions of higher valence in the donor formulation, the release from the fibers was enhanced, but the iontophoretic steady-state flux was decreased.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, the present study has demonstrated a promising approach using ion-exchange fibers for controlling the release and iontophoretic transdermal delivery of apomorphine.", "output": {"entities": {"chemical": [{"text": "apomorphine", "start": 161, "end": 172}]}}, "schema": []}
{"input": "Combining QSAR classification models for predictive modeling of human monoamine oxidase inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Due to their role in the metabolism of monoamine neurotransmitters, MAO-A and MAO-B present a significant pharmacological interest.", "output": {"entities": {}}, "schema": []}
{"input": "For instance the inhibitors of human MAO-B are considered useful tools for the treatment of Parkinson Disease.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the rational design and synthesis of new MAOs inhibitors is considered of great importance for the development of new and more effective treatments of Parkinson Disease.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, Quantitative Structure Activity Relationships (QSAR) has been developed to predict the human MAO inhibitory activity and selectivity.", "output": {"entities": {}}, "schema": []}
{"input": "The first step was the selection of a suitable dataset of heterocyclic compounds that include chromones, coumarins, chalcones, thiazolylhydrazones, etc.", "output": {"entities": {"chemical": [{"text": "chromones", "start": 94, "end": 103}, {"text": "coumarins", "start": 105, "end": 114}, {"text": "chalcones", "start": 116, "end": 125}, {"text": "thiazolylhydrazones", "start": 127, "end": 146}]}}, "schema": []}
{"input": "These compounds were previously synthesized in one of our laboratories, or elsewhere, and their activities measured by the same assays and for the same laboratory staff.", "output": {"entities": {}}, "schema": []}
{"input": "Applying linear discriminant analysis to data derived from a variety of molecular representations and feature selection algorithms, reliable QSAR models were built which could be used to predict for test compounds the inhibitory activity and selectivity toward human MAO.", "output": {"entities": {}}, "schema": []}
{"input": "This work also showed how several QSAR models can be combined to make better predictions.", "output": {"entities": {}}, "schema": []}
{"input": "The final models exhibit significant statistics, interpretability, as well as displaying predictive power on an external validation set made up of chromone derivatives with unknown activity (that are being reported here for first time) synthesized by our group, and coumarins recently reported in the literature.", "output": {"entities": {"chemical": [{"text": "coumarins", "start": 266, "end": 275}]}}, "schema": []}
{"input": "Triterpene saponins from Clethra barbinervis and their hyaluronidase inhibitory activities.", "output": {"entities": {"chemical": [{"text": "Triterpene saponins", "start": 0, "end": 19}]}}, "schema": []}
{"input": "An extract of Clethra barbinervis with an inhibitory effect on hyaluronidase activity was fractionated guided by the results of an assay.", "output": {"entities": {}}, "schema": []}
{"input": "From the active fractions, seven new triterpene saponins (1-4, 6-8) and a new lignan glycoside (14) were isolated together with 14 known compounds (5, 9-13, 15-22).", "output": {"entities": {"chemical": [{"text": "triterpene saponins", "start": 37, "end": 56}, {"text": "lignan glycoside", "start": 78, "end": 94}]}}, "schema": []}
{"input": "Some of the saponins (2, 3, 9) were revealed as hyaluronidase inhibitors similar to epicatechin (17).", "output": {"entities": {"chemical": [{"text": "saponins", "start": 12, "end": 20}, {"text": "epicatechin", "start": 84, "end": 95}]}}, "schema": []}
{"input": "Simple colorimetric bacterial detection and high-throughput drug screening based on a graphene-enzyme complex.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 86, "end": 94}]}}, "schema": []}
{"input": "A simple, colorimetric, sensitive, cost-effective and high-throughput system based on a positively charged graphene oxide-enzyme complex was developed for bacterial detection and drug screening.", "output": {"entities": {"chemical": [{"text": "graphene oxide", "start": 107, "end": 121}]}}, "schema": []}
{"input": "From in situ to in vivo: an in situ click-chemistry-derived carbonic anhydrase II imaging agent for positron emission tomography.", "output": {"entities": {}}, "schema": []}
{"input": "CA II makes a good PET: Discovering positron emission tomography (PET) probes with high target affinities is challenging.", "output": {"entities": {}}, "schema": []}
{"input": "PET probe discovery using in situ click chemistry uses (19) F-bearing fragments as (18) F surrogates.", "output": {"entities": {"chemical": [{"text": "(19) F", "start": 55, "end": 61}, {"text": "(18) F", "start": 83, "end": 89}]}}, "schema": []}
{"input": "This ensures that the lead hits and PET probes have equivalent chemical or biological characteristics, making PET probe discovery predictable and reliable.", "output": {"entities": {}}, "schema": []}
{"input": "Enantiospecific total synthesis of (-)-bengamide E.", "output": {"entities": {"chemical": [{"text": "(-)-bengamide E", "start": 35, "end": 50}]}}, "schema": []}
{"input": "Total synthesis of the polyhydroxy caprolactam amide natural product, bengamide E, is accomplished starting from tartaric acid.", "output": {"entities": {"chemical": [{"text": "polyhydroxy caprolactam amide", "start": 23, "end": 52}, {"text": "bengamide E", "start": 70, "end": 81}, {"text": "tartaric acid", "start": 113, "end": 126}]}}, "schema": []}
{"input": "Key reactions in the synthesis include desymmetrization of the bis (dimethylamide) unit of tartaric acid, Zn (BH (4)) (2)-mediated anti-selective reduction, and a Horner-Wadsworth-Emmons olefination.", "output": {"entities": {"chemical": [{"text": "bis (dimethylamide)", "start": 63, "end": 82}, {"text": "tartaric acid", "start": 91, "end": 104}, {"text": "Zn (BH (4)) (2)", "start": 106, "end": 121}]}}, "schema": []}
{"input": "Protein-DNA arrays as tools for detection of protein-protein interactions by mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of multiple protein-protein interactions using microarray technology remains challenging, and site-specific immobilization of functional proteins is a key step in these approaches.", "output": {"entities": {}}, "schema": []}
{"input": "Here we establish the efficient synthesis of protein-DNA conjugates for several members of a small family of GTPases.", "output": {"entities": {}}, "schema": []}
{"input": "The family of Rab/Ypt GTPases is intimately involved in vesicular trafficking in yeast and serves as a model for the much larger group of analogous human proteins, the Rab protein family, with more than 60 members.", "output": {"entities": {}}, "schema": []}
{"input": "The Ypt-DNA hybrid molecules described here are used for DNA-directed immobilization on glass-and silica-based microarrays.", "output": {"entities": {"chemical": [{"text": "silica", "start": 98, "end": 104}]}}, "schema": []}
{"input": "Methods for the detection of protein-DNA conjugates, as well as approaches for nucleotide exchange and distinguishing between GDP-and GTP-bound Ypts on microarrays, are reported.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 79, "end": 89}, {"text": "GDP", "start": 126, "end": 129}, {"text": "GTP", "start": 134, "end": 137}]}}, "schema": []}
{"input": "The high specificity of different Rab/Ypt-effector interactions, which also depends on the bound nucleotide, is shown by fluorescence readout of microarrays.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 97, "end": 107}]}}, "schema": []}
{"input": "Furthermore, initial experiments demonstrate that direct readout by mass spectrometry can be achieved with commercially available instruments.", "output": {"entities": {}}, "schema": []}
{"input": "These developments will significantly contribute to the elucidation of complex transport networks in eukaryotic cells.", "output": {"entities": {}}, "schema": []}
{"input": "Functional requirement for a highly conserved charged residue at position 75 in the gap junction protein connexin 32.", "output": {"entities": {}}, "schema": []}
{"input": "Charcot Marie Tooth disease (CMT) is a group of inherited disorders characterized clinically by exclusively or predominantly peripheral nerve dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "CMT1X, the most common form of X-linked CMT is caused by mutations in connexin 32 (Cx32).", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we used dual whole cell patch clamp recording to examine the functional effects of mutations at the Arg (75) position.", "output": {"entities": {"chemical": [{"text": "Arg", "start": 114, "end": 117}]}}, "schema": []}
{"input": "This residue is highly conserved among members of the connexin family, and disease-causing mutations have been identified at this (or the corresponding) position in Cx26, Cx43, and Cx46.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, a better understanding of the effects of mutations of this position in Cx32 may have relevance to pathogenesis of a number of different human diseases.", "output": {"entities": {}}, "schema": []}
{"input": "All three mutants associated with CMT1X (R75P, R75Q, and R75W) showed very low levels of coupling similar to those of the cells transfected with vector alone.", "output": {"entities": {}}, "schema": []}
{"input": "Heterotypic pairing with Cx32 WT showed that the absence of coupling for these mutants in the homotypic configuration could be explained by shifts in their hemichannel G (j)-V (j) relations.", "output": {"entities": {}}, "schema": []}
{"input": "Examination of the expression levels and gating characteristics of seven additional mutants (R75A, R75D, R75E, R75H, R75K, R75L, and R75V) at this position suggest that the positive charge at position 75 in Cx32 is required for normal channel function but not for gap junction assembly.", "output": {"entities": {}}, "schema": []}
{"input": "Our studies also suggest that disease treatment strategies for CMT1X, which correct trafficking abnormalities in Cx32, may be ineffective for the group of mutations also conferring changes in gating properties of Cx32 channels.", "output": {"entities": {}}, "schema": []}
{"input": "Simulations of the two-dimensional electronic spectroscopy of the photosystem II reaction center.", "output": {"entities": {}}, "schema": []}
{"input": "We report simulations of the two-dimensional electronic spectroscopy of the Q (y) band of the D1-D2-Cyt b559 photosystem II reaction center at 77 K.", "output": {"entities": {}}, "schema": []}
{"input": "We base the simulations on an existing Hamiltonian that was derived by simultaneous fitting to a wide range of linear spectroscopic measurements and described within modified Redfield theory.", "output": {"entities": {}}, "schema": []}
{"input": "The model obtains reasonable agreement with most aspects of the two-dimensional spectra, including the overall peak shapes and excited state absorption features.", "output": {"entities": {}}, "schema": []}
{"input": "It does not reproduce the rapid equilibration from high energy to low energy excitonic states evident by a strong cross-peak below the diagonal.", "output": {"entities": {}}, "schema": []}
{"input": "We explore modifications to the model to incorporate new structural data and improve agreement with the two-dimensional spectra.", "output": {"entities": {}}, "schema": []}
{"input": "We find that strengthening the system-bath coupling and lowering the degree of disorder significantly improves agreement with the cross-peak feature, while lessening agreement with the relative diagonal/antidiagonal width of the 2D spectra.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that two-dimensional electronic spectroscopy provides a sensitive test of excitonic models of the photosystem II reaction center and discuss avenues for further refinement of such models.", "output": {"entities": {}}, "schema": []}
{"input": "Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study.", "output": {"entities": {}}, "schema": []}
{"input": "Small-molecule modulation of protein-protein interactions (PPIs) is one of the most exciting but also difficult fields in chemical biology and drug development.", "output": {"entities": {}}, "schema": []}
{"input": "As one of the most important \" hub \" proteins with at least 200-300 interaction partners, the 14-3-3 proteins are an especially fruitful case for PPI intervention.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we summarize recent success stories in small-molecule modulation, both inhibition and stabilization, of 14-3-3 PPIs.", "output": {"entities": {}}, "schema": []}
{"input": "The chemical breath of modulators includes natural products such as fusicoccin A and derivatives but also compounds identified via high-throughput and in silico screening, which has yielded a toolbox of useful inhibitors and stabilizers for this interesting class of adapter proteins.", "output": {"entities": {"chemical": [{"text": "fusicoccin A", "start": 68, "end": 80}]}}, "schema": []}
{"input": "Protein-protein interactions (PPIs) are involved in almost all biological processes, with any given protein typically engaged in complexes with other proteins for the majority of its lifetime.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, proteins function not simply as single, isolated entities but display their roles by interacting with other cellular components.", "output": {"entities": {}}, "schema": []}
{"input": "These different interaction patterns are presumably as important as the intrinsic biochemical activity status of the protein itself.", "output": {"entities": {}}, "schema": []}
{"input": "The biological role of a protein is therefore decisively dependent on the underlying PPI network that furthermore can show great spatial and temporal variations.", "output": {"entities": {}}, "schema": []}
{"input": "A thorough appreciation and understanding of this concept and its regulation mechanisms could help to develop new therapeutic agents and concepts.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembly process of soft ferritin-PNIPAAm conjugate bionanoparticles at polar-apolar interfaces.", "output": {"entities": {"chemical": [{"text": "PNIPAAm", "start": 39, "end": 46}]}}, "schema": []}
{"input": "We describe an in-depth investigation on the dynamics and assembly behavior at polar-apolar interfaces of ferritin-PNIPAAm conjugates (poly-N-isopropylacrylamide).", "output": {"entities": {"chemical": [{"text": "PNIPAAm", "start": 115, "end": 122}, {"text": "poly-N-isopropylacrylamide", "start": 135, "end": 161}]}}, "schema": []}
{"input": "The stabilization of oil-water interfaces by the modified ferritin was investigated by dynamic surface tension measurements and compared to the individual components of the bionanoparticle conjugate, namely, unmodified ferritin and pure PNIMAAm of similar molecular weight.", "output": {"entities": {"chemical": [{"text": "PNIMAAm", "start": 237, "end": 244}]}}, "schema": []}
{"input": "It was found that the modified ferritin, even at a low particle concentration, rapidly reduces the interfacial tension.", "output": {"entities": {}}, "schema": []}
{"input": "The difference in interfacial stabilization was also shown by cryo-scanning electron microscopy and scanning force microscopy, which displayed very different morphologies at the polar-apolar interface for the unmodified ferritin, pure PNIPAAm, and the ferritin-PNIPAAm conjugate, respectively.", "output": {"entities": {"chemical": [{"text": "PNIPAAm", "start": 235, "end": 242}, {"text": "PNIPAAm", "start": 261, "end": 268}]}}, "schema": []}
{"input": "The self-assembly of the ferritin-PNIPAAm was further analyzed by cryo-transmission electron microscopy and fluorescence microscopy, for which a fluorescently labeled polymer was used.", "output": {"entities": {"chemical": [{"text": "PNIPAAm", "start": 34, "end": 41}]}}, "schema": []}
{"input": "Both techniques revealed details on the assembly of the protein-polymer conjugate at the oil-water interface.", "output": {"entities": {}}, "schema": []}
{"input": "Simultaneous control of composition and register of an AAB-type collagen heterotrimer.", "output": {"entities": {}}, "schema": []}
{"input": "Control over composition and register of the peptide chains in AAB-type collagen mimetic heterotrimers is critical in developing systems that show fidelity to native collagen.", "output": {"entities": {}}, "schema": []}
{"input": "However, their design is challenging due to the eight competing states possible for a mixture of nonidentical peptides A and B.", "output": {"entities": {}}, "schema": []}
{"input": "Interpeptide salt-bridges have been used previously as keystone interactions to bias the population of competing states to favor a target heterotrimer.", "output": {"entities": {}}, "schema": []}
{"input": "The designed heterotrimers were electroneutral and relied on pairing of acidic and basic residues but could not differentiate between all of the competing states and reported systems populated either multiple heterotrimer compositions or registers.", "output": {"entities": {}}, "schema": []}
{"input": "Here our design methodology includes both positive and negative elements.", "output": {"entities": {}}, "schema": []}
{"input": "First, an excess of acidic or basic residues, which always remain unpaired, introduces a negative design component to destabilize the competing triple helical compositions and registers.", "output": {"entities": {}}, "schema": []}
{"input": "Second, charge pairs introduce a positive design component and stabilize the target assembly.", "output": {"entities": {}}, "schema": []}
{"input": "These antagonistic factors are optimized in the target heterotrimer that forms the maximum number of charge pairs and minimizes unpaired charged residues.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, we find that not just the number of paired and unpaired residues are important, but also the type.", "output": {"entities": {}}, "schema": []}
{"input": "By a systematic study of different types of charge pairs and unpaired residues, we are able to populate a single composition-single register AAB heterotrimer.", "output": {"entities": {}}, "schema": []}
{"input": "The insights gained here may be useful in designing composition and register specific heterotrimeric ligands with domains that recognize collagen-binding proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Photoreversible micellar solution as a smart drag-reducing fluid for use in district heating/cooling systems.", "output": {"entities": {}}, "schema": []}
{"input": "A photoresponsive micellar solution is developed as a promising working fluid for district heating/cooling systems (DHCs).", "output": {"entities": {}}, "schema": []}
{"input": "It can be reversibly switched between a drag reduction (DR) mode and an efficient heat transfer (EHT) mode by light irradiation.", "output": {"entities": {}}, "schema": []}
{"input": "The DR mode is advantageous during fluid transport, and the EHT mode is favored when the fluid passes through heat exchangers.", "output": {"entities": {}}, "schema": []}
{"input": "This smart fluid is an aqueous solution of cationic surfactant oleyl bis (2-hydroxyethyl) methyl ammonium chloride (OHAC, 3. 4 mM) and the sodium salt of 4-phenylazo benzoic acid (ACA, 2 mM).", "output": {"entities": {"chemical": [{"text": "oleyl bis (2-hydroxyethyl) methyl ammonium chloride", "start": 63, "end": 114}, {"text": "OHAC", "start": 116, "end": 120}, {"text": "sodium", "start": 139, "end": 145}, {"text": "4-phenylazo benzoic acid", "start": 154, "end": 178}, {"text": "ACA", "start": 180, "end": 183}]}}, "schema": []}
{"input": "Initially, ACA is in a trans configuration and the OHAC/ACA solution is viscoelastic and exhibits DR (of up to 80% relative to pure water).", "output": {"entities": {"chemical": [{"text": "ACA", "start": 11, "end": 14}, {"text": "OHAC", "start": 51, "end": 55}, {"text": "ACA", "start": 56, "end": 59}]}}, "schema": []}
{"input": "At the same time, this solution is not effective for heat transfer.", "output": {"entities": {}}, "schema": []}
{"input": "Upon UV irradiation, trans-ACA is converted to cis-ACA, and in turn, the solution is converted to its EHT mode (i. e., it loses its viscoelasticity and DR) but it now has a heat-transfer capability comparable to that of water.", "output": {"entities": {"chemical": [{"text": "trans-ACA", "start": 21, "end": 30}, {"text": "cis-ACA", "start": 47, "end": 54}]}}, "schema": []}
{"input": "Subsequent irradiation with visible light reverts the fluid to its viscoelastic DR mode.", "output": {"entities": {}}, "schema": []}
{"input": "The above property changes are connected to photoinduced changes in the nanostructure of the fluid.", "output": {"entities": {}}, "schema": []}
{"input": "In the DR mode, the OHAC/trans-ACA molecules assemble into long threadlike micelles that impart viscoelasticity and DR capability to the fluid.", "output": {"entities": {"chemical": [{"text": "OHAC", "start": 20, "end": 24}, {"text": "trans-ACA", "start": 25, "end": 34}]}}, "schema": []}
{"input": "Conversely, in the EHT mode the mixture of OHAC and cis-ACA forms much shorter cylindrical micelles that contribute to negligible viscoelasticity and effective heat transfer.", "output": {"entities": {"chemical": [{"text": "OHAC", "start": 43, "end": 47}, {"text": "cis-ACA", "start": 52, "end": 59}]}}, "schema": []}
{"input": "These nanostructural changes are confirmed by cryo-transmission electron microscopy (cryo-TEM), and the photoisomerization of trans-ACA and cis-ACA is verified by (1) H NMR.", "output": {"entities": {"chemical": [{"text": "trans-ACA", "start": 126, "end": 135}, {"text": "cis-ACA", "start": 140, "end": 147}, {"text": "(1) H", "start": 163, "end": 168}]}}, "schema": []}
{"input": "Kinase CK2 inhibition: an update.", "output": {"entities": {}}, "schema": []}
{"input": "Protein kinase CK2 (Casein Kinase 2) is an essential, ubiquitous and highly pleiotropic protein kinase, implicated in several human diseases.", "output": {"entities": {}}, "schema": []}
{"input": "In the last decade, several inhibitors of CK2, have been discovered and characterized to be ATP-competitive compounds.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 92, "end": 95}]}}, "schema": []}
{"input": "However, only one of them, CX-4945, has recently completed Phase I clinical trial as potential anticancer drug.", "output": {"entities": {"chemical": [{"text": "CX-4945", "start": 27, "end": 34}]}}, "schema": []}
{"input": "In this review, we report all chemical classes of CK2 inhibitors available in literature, focusing our attention on conventional ATP-competitive and on non ATP-competitive inhibitors, which could represent a new frontier in CK2 inhibition and, consequently, a promising field of study in discovering new drug candidates.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 129, "end": 132}, {"text": "ATP", "start": 156, "end": 159}]}}, "schema": []}
{"input": "Bioprocessing of plant in vitro systems for the mass production of pharmaceutically important metabolites: paclitaxel and its derivatives.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 107, "end": 117}]}}, "schema": []}
{"input": "Taxol (paclitaxel) and its derivatives are microtubule-stabilizing drugs widely used in the treatment of several types of cancer, including mammary, prostate, ovarian and non-small-cell lung carcinoma, as well as AIDS-associated Kaposi' s sarcoma and other types of tumor.", "output": {"entities": {"chemical": [{"text": "Taxol", "start": 0, "end": 5}, {"text": "paclitaxel", "start": 7, "end": 17}]}}, "schema": []}
{"input": "Taxanes stabilize microtubules by enhancing their polymerization and inhibiting depolymerization.", "output": {"entities": {"chemical": [{"text": "Taxanes", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Microtubule dynamics are crucial to mitotic spindle formation and function; therefore, cells exposed to taxanes are unable to undergo chromosomal separation during mitosis, become arrested in the G2/M phases of the cell cycle, and are subsequently targeted for apoptosis.", "output": {"entities": {"chemical": [{"text": "taxanes", "start": 104, "end": 111}]}}, "schema": []}
{"input": "Plant cell cultures are used for industrial-scale biotechnological production of important bioactive plant secondary metabolites, including the anticancer agent paclitaxel.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 161, "end": 171}]}}, "schema": []}
{"input": "In the last two decades, there have been numerous empirical approaches to improve the biotechnological production of taxanes, leading to the conclusion that treatment of Taxus sp. cells with methyl jasmonate or other elicitors is the most effective strategy.", "output": {"entities": {"chemical": [{"text": "taxanes", "start": 117, "end": 124}, {"text": "methyl jasmonate", "start": 191, "end": 207}]}}, "schema": []}
{"input": "However, little insight has been gained into how the elicitors increase taxane biosynthesis or how this process is regulated.", "output": {"entities": {"chemical": [{"text": "taxane", "start": 72, "end": 78}]}}, "schema": []}
{"input": "In recent years, with the help of \" omics \" tools, a rational approach has provided new information about taxane metabolism and its control.", "output": {"entities": {"chemical": [{"text": "taxane", "start": 106, "end": 112}]}}, "schema": []}
{"input": "Once pathway bottlenecks have been identified, it will be possible to engineer Taxus sp. cell lines with overexpression of genes that control the flux-limiting steps, thus boosting taxane productivity.", "output": {"entities": {"chemical": [{"text": "taxane", "start": 181, "end": 187}]}}, "schema": []}
{"input": "This review describes the chemical and biological characterization of paclitaxel and its derivatives and discusses future prospects for their biotechnological production.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 70, "end": 80}]}}, "schema": []}
{"input": "The pentacyclic triterpenoids in herbal medicines and their pharmacological activities in diabetes and diabetic complications.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenoids", "start": 4, "end": 29}]}}, "schema": []}
{"input": "Pentacyclic triterpenoids including the oleanane, ursane and lupane groups are widely distributed in many medicinal plants, such as Glycyrrhiza species, Gymnema species, Centella asiatica, Camellia sinensis, Crataegus species and Olea europaea, which are commonly used in traditional medicine for the treatment of diabetes and diabetic complications.", "output": {"entities": {"chemical": [{"text": "Pentacyclic triterpenoids", "start": 0, "end": 25}, {"text": "oleanane", "start": 40, "end": 48}, {"text": "ursane", "start": 50, "end": 56}, {"text": "lupane", "start": 61, "end": 67}]}}, "schema": []}
{"input": "A large number of bioactive pentacyclic triterpenoids, such as oleanolic acid, glycyrrhizin, glycyrrhetinic acid, ursolic acid, betulin, betulinic acid and lupeol have shown multiple biological activities with apparent effects on glucose absorption, glucose uptake, insulin secretion, diabetic vascular dysfunction, retinopathy and nephropathy.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenoids", "start": 28, "end": 53}, {"text": "oleanolic acid", "start": 63, "end": 77}, {"text": "glycyrrhizin", "start": 79, "end": 91}, {"text": "glycyrrhetinic acid", "start": 93, "end": 112}, {"text": "ursolic acid", "start": 114, "end": 126}, {"text": "betulin", "start": 128, "end": 135}, {"text": "betulinic acid", "start": 137, "end": 151}, {"text": "lupeol", "start": 156, "end": 162}, {"text": "glucose", "start": 230, "end": 237}, {"text": "glucose", "start": 250, "end": 257}]}}, "schema": []}
{"input": "The versatility of the pentacyclic triterpenes provides a promising approach for diabetes management.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenes", "start": 23, "end": 46}]}}, "schema": []}
{"input": "Marine natural products with anti-HIV activities in the last decade.", "output": {"entities": {}}, "schema": []}
{"input": "Marine organisms have been proven to be excellent sources of biologically active compounds against HIV.", "output": {"entities": {}}, "schema": []}
{"input": "This review gives an overview of 132 natural products from marine sources obtained during the last decade (2002-2011), which exhibit anti-HIV activity toward different biological targets.", "output": {"entities": {}}, "schema": []}
{"input": "Sponges contribute more than half of all anti-HIV natural products from marine organisms, mainly as alkaloids and cyclic depsipeptides.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, some macromolecules are considered as potential anti-HIV agents, including lectins from algae and marine invertebrates, as well as sulfated polysaccharides from algae.", "output": {"entities": {}}, "schema": []}
{"input": "In the reviewed marine natural products, many active ingredients act as HIV entry inhibitors, one class of new anti-HIV agents, and may be regarded as potential candidates for the development of novel anti-HIV agents.", "output": {"entities": {}}, "schema": []}
{"input": "The other features of development in the marine original anti-HIV natural products in this ten years are also discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Differential action of phytochemicals on platelet apoptosis: a biological overview.", "output": {"entities": {}}, "schema": []}
{"input": "Platelets are anuclear blood cells originating from bone megakaryocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Despite being anuclear, their number is maintained by apoptosis, a process of programmed cell death.", "output": {"entities": {}}, "schema": []}
{"input": "The rate of apoptotic death of platelets is accelerated by oxidative and shear stress, ex vivo storage (blood banking conditions) and certain pathophysiological disorders.", "output": {"entities": {}}, "schema": []}
{"input": "These factors initiate apoptotic events through the mitochondria-mediated intrinsic pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Besides, apoptotic platelets also release phosphatidylserine-positive membrane fractions called microparticles, which cause fibrin deposition and thrombus formation, and are involved in the promulgation of a host of disease conditions including cardiovascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "In this context, several phytochemicals have been reported to be cardioprotective and work by inhibiting platelet aggregation or by dissolving the fibrin clots.", "output": {"entities": {}}, "schema": []}
{"input": "Besides, ample reports focus on the positive effects of phytochemicals on normal physiology of platelets, but do not focus on their adverse effects on platelets.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, platelets are reported to be extremely sensitive to therapeutic components in the blood.", "output": {"entities": {}}, "schema": []}
{"input": "For example, resveratrol and thymoquinone are hitherto known compounds to possess proapoptotic effects on platelets.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 13, "end": 24}, {"text": "thymoquinone", "start": 29, "end": 41}]}}, "schema": []}
{"input": "In contrast, cinnamtannin B1 and crocin exhibit antiapoptotic effects.", "output": {"entities": {"chemical": [{"text": "cinnamtannin B1", "start": 13, "end": 28}, {"text": "crocin", "start": 33, "end": 39}]}}, "schema": []}
{"input": "Thus, the current review aims to elucidate the underlying mechanisms through which the phytochemicals mediate their effects on platelet apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the need for scrutiny of therapeutic compounds for their effects on platelet functions before including them in treatment regimen is also being emphasized.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutically important proteins from in vitro plant tissue culture systems.", "output": {"entities": {}}, "schema": []}
{"input": "Plant cells cultured in liquid medium in bioreactors are now being used commercially to produce biopharmaceutical proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The emergence of in vitro plant cell culture as a production vehicle reflects the importance of key biosafety and biocontainment concerns affecting the competitiveness of alternative systems such as mammalian cell culture and agriculture.", "output": {"entities": {}}, "schema": []}
{"input": "Food plant species are particularly attractive as hosts for in vitro protein production: the risk of transgene escape and food chain contamination is eliminated using containment facilities, while regulatory approval for oral delivery of drugs may be easier than if non-edible species were used.", "output": {"entities": {}}, "schema": []}
{"input": "As in whole plants, proteolysis in cultured plant cells can lead to significant degradation of foreign proteins after synthesis; however, substantial progress has been made to counter the destructive effects of proteases in plant systems.", "output": {"entities": {}}, "schema": []}
{"input": "Although protein secretion into the culture medium is advantageous for product recovery and purification, measures are often required to minimise extracellular protease activity and product losses due to irreversible surface adsorption.", "output": {"entities": {}}, "schema": []}
{"input": "Disposable plastic bioreactors, which are being used increasingly in mammalian cell bioprocessing, are also being adopted for plant cell culture to allow rapid scale-up and generation of saleable product.", "output": {"entities": {}}, "schema": []}
{"input": "This review examines a range of technical and regulatory issues affecting the choice of industrial production platform for foreign proteins, and assesses progress in the development of in vitro plant systems for biopharmaceutical production.", "output": {"entities": {}}, "schema": []}
{"input": "Multi-aspect candidates for repositioning: data fusion methods using heterogeneous information sources.", "output": {"entities": {}}, "schema": []}
{"input": "Drug repositioning, an innovative therapeutic application of an old drug, has received much attention as a particularly costeffective strategy in drug R & D Recent work has indicated that repositioning can be promoted by utilizing a wide range of information sources, including medicinal chemical, target, mechanism, main and side-effect-related information, and also bibliometric and taxonomical fingerprints, signatures and knowledge bases.", "output": {"entities": {}}, "schema": []}
{"input": "This article describes the adaptation of a conceptually novel, more efficient approach for the identification of new possible therapeutic applications of approved drugs and drug candidates, based on a kernel-based data fusion method.", "output": {"entities": {}}, "schema": []}
{"input": "This strategy includes (1) the potentially multiple representation of information sources, (2) the automated weighting and statistically optimal combination of information sources, and (3) the automated weighting of parts of the query compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The performance was systematically evaluated by using Anatomical Therapeutic Chemical Classification System classes in a cross-validation framework.", "output": {"entities": {}}, "schema": []}
{"input": "The results confirmed that kernel-based data fusion can integrate heterogeneous information sources significantly better than standard rank-based fusion can, and this method provides a unique solution for repositioning; it can also be utilized for de novo drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "The advantages of kernel-based data fusion are illustrated with examples and open problems that are particularly relevant for pharmaceutical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and HIV-1 inhibitory activities of dicaffeoyl and digalloyl esters of quinic acid derivatives.", "output": {"entities": {"chemical": [{"text": "dicaffeoyl and digalloyl esters", "start": 45, "end": 76}, {"text": "quinic acid", "start": 80, "end": 91}]}}, "schema": []}
{"input": "Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared.", "output": {"entities": {"chemical": [{"text": "dicaffeoylquinic acids", "start": 61, "end": 83}, {"text": "DCQAs", "start": 85, "end": 90}]}}, "schema": []}
{"input": "Their IC (50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC (50) against HIV-1 were measured in cells (ex vivo).", "output": {"entities": {}}, "schema": []}
{"input": "Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36.", "output": {"entities": {"chemical": [{"text": "cyclohexylidene", "start": 37, "end": 52}]}}, "schema": []}
{"input": "Removal of these groups, however, correlated with potent inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.", "output": {"entities": {"chemical": [{"text": "digalloyls", "start": 30, "end": 40}]}}, "schema": []}
{"input": "Histone methyltransferase inhibitors: novel epigenetic agents for cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Epigenetics is defined as heritable changes in gene activity and expression that occur without alteration in DNA sequence.", "output": {"entities": {}}, "schema": []}
{"input": "The gene transcription is strictly correlated to chromatin structure, which could undergo covalent modifications of histones involving acetylation, methylation, phosphorylation and ubiquitination.", "output": {"entities": {}}, "schema": []}
{"input": "Alterations in histones are implicated in many diseases, including cancer, by leading to tumor suppressor silencing or pro-apoptotic proteins downregulation.", "output": {"entities": {}}, "schema": []}
{"input": "Although post-translational addition of methyl groups to the histone lysine has been discovered three decades ago, the importance of this epigenetic modification has emerged only in the last few years.", "output": {"entities": {"chemical": [{"text": "methyl", "start": 40, "end": 46}, {"text": "lysine", "start": 69, "end": 75}]}}, "schema": []}
{"input": "Thenceforward histone methyltransferase inhibitors have been developed as potential therapeutic cancer agents.", "output": {"entities": {}}, "schema": []}
{"input": "It should not be long before some selective inhibitors make their way into clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "This review is mainly focused on the evolution in the development of new epigenetic modifier molecules modulating histone marks.", "output": {"entities": {}}, "schema": []}
{"input": "Probing of field-induced structures and tunable rheological properties of surfactant capped magnetically polarizable nanofluids.", "output": {"entities": {}}, "schema": []}
{"input": "Oil-based nanofluid containing surfactant-capped magnetite nanoparticles are synthesized by a simple coprecipitation approach, and their magnetorheological properties are studied for different magnetic field strengths and volume fractions.", "output": {"entities": {}}, "schema": []}
{"input": "We observe a distinct \" plateau-like region \" in the shear thinning viscosity curve, under an external magnetic field, possibly due to a peculiar alignment of the chains with respect to the field direction where the structure is stable against fragmentation.", "output": {"entities": {}}, "schema": []}
{"input": "The observed plateau regime is reminiscent to that of kinetically arrested gel networks.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, such a plateau regime has been observed only above certain critical magnetic field when the dipolar interaction strength is much greater than the thermal energy where the aggregation becomes a nonequilibrium transport-limited process.", "output": {"entities": {}}, "schema": []}
{"input": "The good collapse of specific viscosity data against Mason number for different magnetic field strengths onto a single curve suggests the dominance of hydrodynamic and magnetic forces on thermal force above a certain magnetic field strength.", "output": {"entities": {}}, "schema": []}
{"input": "The observed increase in both static and dynamic yield stresses under the magnetic field confirms the formation of columnar structures that hinder the flow behavior.", "output": {"entities": {}}, "schema": []}
{"input": "The hysteresis observed in the magnetic sweep experiments shows the inability of the chains to relax within the measurement time.", "output": {"entities": {}}, "schema": []}
{"input": "The dynamic measurements confirm that the field-induced structures impart elastic behavior to the dispersion, which is found to increase with magnetic field and saturates at higher field strengths.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of dopamine D2/D3 receptor ligands on food-cocaine choice in socially housed male cynomolgus monkeys.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 11, "end": 19}, {"text": "cocaine", "start": 51, "end": 58}]}}, "schema": []}
{"input": "Dopamine D2/D3 receptor partial agonists have been suggested as medications for cocaine dependence.", "output": {"entities": {"chemical": [{"text": "Dopamine", "start": 0, "end": 8}, {"text": "cocaine", "start": 80, "end": 87}]}}, "schema": []}
{"input": "The present experiments examined the effect of acute and repeated administration of drugs with varying intrinsic efficacy at D2/D3 receptors on the relative reinforcing strength of cocaine.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 181, "end": 188}]}}, "schema": []}
{"input": "Use of socially housed cynomolgus monkeys permitted the assessment of whether social status, known to alter D2/D3 receptor availability, influenced the behavioral effects of D2/D3 receptor compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The high-efficacy agonist R (-)-norpropylapomorphine [(-)-NPA], low-efficacy agonist aripiprazole (ARI), and antagonist eticlopride (ETIC) were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine self-administration dose-effect curve was determined daily.", "output": {"entities": {"chemical": [{"text": "R (-)-norpropylapomorphine", "start": 26, "end": 52}, {"text": "(-)-NPA", "start": 54, "end": 61}, {"text": "aripiprazole", "start": 85, "end": 97}, {"text": "ARI", "start": 99, "end": 102}, {"text": "eticlopride", "start": 120, "end": 131}, {"text": "ETIC", "start": 133, "end": 137}, {"text": "cocaine", "start": 195, "end": 202}, {"text": "cocaine", "start": 216, "end": 223}, {"text": "cocaine", "start": 252, "end": 259}]}}, "schema": []}
{"input": "The effects of 5-day treatment with ARI and (-)-NPA were characterized under conditions in which monkeys did (ARI) or did not [ARI and (-)-NPA] self-administer cocaine during treatment.", "output": {"entities": {"chemical": [{"text": "(-)-NPA", "start": 44, "end": 51}, {"text": "ARI", "start": 110, "end": 113}, {"text": "ARI", "start": 127, "end": 130}, {"text": "(-)-NPA", "start": 135, "end": 142}, {"text": "cocaine", "start": 160, "end": 167}]}}, "schema": []}
{"input": "When administered acutely, ARI and ETIC increased the choice of low cocaine doses, and only (-)-NPA decreased the choice of higher cocaine doses and cocaine intake; effects were similar across social ranks.", "output": {"entities": {"chemical": [{"text": "ARI", "start": 27, "end": 30}, {"text": "ETIC", "start": 35, "end": 39}, {"text": "cocaine", "start": 68, "end": 75}, {"text": "(-)-NPA", "start": 92, "end": 99}, {"text": "cocaine", "start": 131, "end": 138}, {"text": "cocaine", "start": 149, "end": 156}]}}, "schema": []}
{"input": "When administered repeatedly while self administration occurred only on days 1 and 5 of treatment, ARI, but not (-)-NPA, decreased cocaine choice in dominant monkeys, whereas (-)-NPA, but not ARI, did so in subordinates.", "output": {"entities": {"chemical": [{"text": "ARI", "start": 99, "end": 102}, {"text": "(-)-NPA", "start": 112, "end": 119}, {"text": "cocaine", "start": 131, "end": 138}, {"text": "(-)-NPA", "start": 175, "end": 182}, {"text": "ARI", "start": 192, "end": 195}]}}, "schema": []}
{"input": "When dominant monkeys self-administered cocaine on all five days of ARI treatment, however, these effects were not observed.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 40, "end": 47}, {"text": "ARI", "start": 68, "end": 71}]}}, "schema": []}
{"input": "The results indicate that the behavioral effects of D2/D3 receptor agonists can differ according to intrinsic efficacy and subject characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, these results suggest that exposure to cocaine during treatment can counteract treatment-induced reductions in the reinforcing effects of cocaine.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 49, "end": 56}, {"text": "cocaine", "start": 148, "end": 155}]}}, "schema": []}
{"input": "Protective effect of 70% ethanolic extract of Lindera obtusiloba Blume on tert-butyl hydroperoxide-induced oxidative hepatotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "tert-butyl hydroperoxide", "start": 74, "end": 98}]}}, "schema": []}
{"input": "Lindera obtusiloba Blume, a native plant of East Asia, has traditionally been used as a folk medicine for liver disease.", "output": {"entities": {}}, "schema": []}
{"input": "We studied the in vitro antioxidant and in vivo hepatoprotective activities of a 70% ethanolic extract of L. obtusiloba (LOE) containing 62. 9% quercitrin and 22. 0% afzelin.", "output": {"entities": {"chemical": [{"text": "quercitrin", "start": 144, "end": 154}, {"text": "afzelin", "start": 166, "end": 173}]}}, "schema": []}
{"input": "LOE prevented tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "tert-butyl hydroperoxide", "start": 14, "end": 38}, {"text": "t-BHP", "start": 40, "end": 45}]}}, "schema": []}
{"input": "Along with its high antioxidant potency in vitro, our animal study confirmed that pretreatment with LOE (500 or 2000 mg/kg) for 7 days prior to a single dose of t-BHP (i. p.: 0. 5 mmol/kg) significantly lowered the serum levels of alanine and aspartate aminotransferases.", "output": {"entities": {"chemical": [{"text": "t-BHP", "start": 161, "end": 166}, {"text": "alanine", "start": 231, "end": 238}, {"text": "aspartate", "start": 243, "end": 252}]}}, "schema": []}
{"input": "In addition, glutathione levels were increased in the liver, and lipid peroxidation levels were decreased in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 13, "end": 24}]}}, "schema": []}
{"input": "The histopathological examinations of rat livers showed that LOE significantly reduced the incidence of liver lesions induced by t-BHP.", "output": {"entities": {"chemical": [{"text": "t-BHP", "start": 129, "end": 134}]}}, "schema": []}
{"input": "Therefore, we concluded that LOE has merit as a potent candidate to protect the liver against oxidative damage.", "output": {"entities": {}}, "schema": []}
{"input": "Steroid receptor coactivator-1 mediates estrogenic actions to prevent body weight gain in female mice.", "output": {"entities": {"chemical": [{"text": "Steroid", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Estrogen receptor-alpha (ER alpha) expressed by hypothalamic proopiomelanocortin and steroidogenic factor-1 neurons largely mediates the antiobesity effects of estrogens in females.", "output": {"entities": {"chemical": [{"text": "Estrogen", "start": 0, "end": 8}, {"text": "estrogens", "start": 160, "end": 169}]}}, "schema": []}
{"input": "However, the critical molecular events that are coupled to ER alpha and mediate estrogenic effects on energy balance remain unknown.", "output": {"entities": {}}, "schema": []}
{"input": "In the current study, we demonstrated that steroid receptor coactivator-1 (SRC1), a nuclear receptor coactivator, is abundantly expressed by both proopiomelanocortin and steroidogenic factor-1 neurons.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 43, "end": 50}]}}, "schema": []}
{"input": "We further showed that central administration of an ER alpha agonist, propyl pyrazole triol, acutely increases physical interaction between SRC1 and ER alpha in the hypothalamus.", "output": {"entities": {"chemical": [{"text": "propyl pyrazole triol", "start": 70, "end": 91}]}}, "schema": []}
{"input": "Finally, we demonstrated that the effects of estrogens on energy homeostasis are significantly blunted in female mice lacking SRC1 globally.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 45, "end": 54}]}}, "schema": []}
{"input": "Collectively our results indicate that SRC1 is functionally required to mediate the antiobesity effects of estrogen-ER alpha signals.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 107, "end": 115}]}}, "schema": []}
{"input": "ADP-ribosylation of guanosine by SCO5461 protein secreted from Streptomyces coelicolor.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 0, "end": 3}, {"text": "guanosine", "start": 20, "end": 29}]}}, "schema": []}
{"input": "The Streptomyces coelicolor A3 (2) genome encodes a possible secretion protein, SCO5461, that shares a 30% homology with the activity domains of two toxic ADP-ribosyltransferases, pierisins and mosquitocidal toxin.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 155, "end": 158}]}}, "schema": []}
{"input": "We found ADP-ribosylating activity for the SCO5461 protein product through its co-incubation with guanosine and NAD (+), which resulted in the formation of N (2)-(ADP-ribos-1-yl)-guanosine ((ar2) Guo), with a K (m) value of 110 mu M.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 9, "end": 12}, {"text": "guanosine", "start": 98, "end": 107}, {"text": "NAD (+)", "start": 112, "end": 119}, {"text": "N (2)-(ADP-ribos-1-yl)-guanosine", "start": 156, "end": 188}, {"text": "(ar2) Guo", "start": 190, "end": 199}]}}, "schema": []}
{"input": "SCO5461 was further found to ADP-ribosylate deoxyguanosine, GMP, dGMP, GTP, dGTP, and cyclic GMP with k (cat) values of 150-370 s (-1).", "output": {"entities": {"chemical": [{"text": "ADP", "start": 29, "end": 32}, {"text": "deoxyguanosine", "start": 44, "end": 58}, {"text": "GMP", "start": 60, "end": 63}, {"text": "dGMP", "start": 65, "end": 69}, {"text": "GTP", "start": 71, "end": 74}, {"text": "dGTP", "start": 76, "end": 80}, {"text": "cyclic GMP", "start": 86, "end": 96}]}}, "schema": []}
{"input": "Oligo (dG), oligo (G), and yeast tRNA were also ADP-ribosylated by this protein, although with much lower k (cat) values of 0. 2 s (-1) or less.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 48, "end": 51}]}}, "schema": []}
{"input": "SCO5461 showed maximum ADP-ribosylation activity towards guanosine at 30 degrees C, and maintained 20% of these maximum activity levels even at 0 degrees C.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 23, "end": 26}]}}, "schema": []}
{"input": "This is the first report of the ADP-ribosylation of guanosine and guanine mononucleotides among the family members of various ADP-ribosylating enzymes.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 32, "end": 35}, {"text": "guanosine", "start": 52, "end": 61}, {"text": "guanine mononucleotides", "start": 66, "end": 89}, {"text": "ADP", "start": 126, "end": 129}]}}, "schema": []}
{"input": "We additionally observed secretion of the putative gene product, SCO5461, in liquid cultures of S. coelicolor.", "output": {"entities": {}}, "schema": []}
{"input": "We thus designated the SCO5461 protein product as S. coelicolor ADP-ribosylating protein, ScARP.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 64, "end": 67}]}}, "schema": []}
{"input": "Our current results could offer new insights into not only the ADP-ribosylation of small molecules but also signal transduction events via enzymatic nucleoside modification by toxin-related enzymes.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 63, "end": 66}, {"text": "nucleoside", "start": 149, "end": 159}]}}, "schema": []}
{"input": "New avenues for anticoagulation in atrial fibrillation.", "output": {"entities": {}}, "schema": []}
{"input": "Vitamin K antagonists (VKAs) were, until recently, the only option for chronic anticoagulation in patients with atrial fibrillation.", "output": {"entities": {"chemical": [{"text": "Vitamin K", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Three new oral anticoagulants have been tested for this indication in recent randomized trials: dabigatran, rivaroxaban, and apixaban.", "output": {"entities": {"chemical": [{"text": "dabigatran", "start": 96, "end": 106}, {"text": "rivaroxaban", "start": 108, "end": 119}, {"text": "apixaban", "start": 125, "end": 133}]}}, "schema": []}
{"input": "They offer the promise of consistent effect without the need for monitoring drug levels.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, efficacy and safety appear to be noninferior, and in some instances superior, to warfarin.", "output": {"entities": {"chemical": [{"text": "warfarin", "start": 90, "end": 98}]}}, "schema": []}
{"input": "However, the new drugs have their downsides, and switching from warfarin is not recommended for all patients.", "output": {"entities": {"chemical": [{"text": "warfarin", "start": 64, "end": 72}]}}, "schema": []}
{"input": "This review focuses on the available evidence and attempts to provide guidance to clinicians in the field.", "output": {"entities": {}}, "schema": []}
{"input": "Computation as the mechanistic bridge between precision medicine and systems therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Over the past 50 years, like molecular cell biology, medicine and pharmacology have been driven by a reductionist approach.", "output": {"entities": {}}, "schema": []}
{"input": "The focus on individual genes and cellular components as disease loci and drug targets has been a necessary step in understanding the basic mechanisms underlying tissue/organ physiology and drug action.", "output": {"entities": {}}, "schema": []}
{"input": "Recent progress in genomics and proteomics, as well as advances in other technologies that enable large-scale data gathering and computational approaches, is providing new knowledge of both normal and disease states.", "output": {"entities": {}}, "schema": []}
{"input": "Systems-biology approaches enable integration of knowledge from different types of data for precision medicine and systems therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we describe recent studies that contribute to these emerging fields and discuss how together these fields can lead to a mechanism-based therapy for individual patients.", "output": {"entities": {}}, "schema": []}
{"input": "Theoretical study of the reaction of CH2XO (X = F, Cl, Br) radicals with the NO radical.", "output": {"entities": {"chemical": [{"text": "CH2XO", "start": 37, "end": 42}, {"text": "F", "start": 48, "end": 49}, {"text": "Cl", "start": 51, "end": 53}, {"text": "Br", "start": 55, "end": 57}, {"text": "NO", "start": 77, "end": 79}]}}, "schema": []}
{"input": "In this paper, we focus on the multiple-channel reactions of CH (2) XO (X = F, Cl, Br) radicals with the NO radical by means of direct dynamic methods.", "output": {"entities": {"chemical": [{"text": "CH (2) XO", "start": 61, "end": 70}, {"text": "F", "start": 76, "end": 77}, {"text": "Cl", "start": 79, "end": 81}, {"text": "Br", "start": 83, "end": 85}, {"text": "NO", "start": 105, "end": 107}]}}, "schema": []}
{"input": "All structures of the stationary points were obtained at the MP2/6-311 + G (d, p) level and vibrational frequency analysis was also performed at this level of theory.", "output": {"entities": {}}, "schema": []}
{"input": "The minimum energy path (MEP) was obtained via the intrinsic reaction coordinate (IRC) theory at the MP2/6-311 + G (d, p) level, and higher-level energetic information was refined by the MC-QCISD method.", "output": {"entities": {}}, "schema": []}
{"input": "The rate constants for the three hydrogen abstraction reaction channels over the temperature range 200-1, 500 K were calculated by the improved canonical variational transition state theory (ICVT) with a correction for small-curvature tunneling (SCT).", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 33, "end": 41}]}}, "schema": []}
{"input": "The rate constants calculated in this manner were in good agreement with the available experimental data, and the three-parameter rate-temperature formulae for the temperature range 200-1, 500 K were k (1a) (T) = 0. 32 x 10 (-18) T (1. 83) exp (1748. 54/T), k (2a) (T) = 0. 22 x 10 (-19) T (2. 19) exp (1770. 19/T), k (3a) (T) = 0. 88 x 10 (-20) T (2. 20) exp (1513. 82/T) (in units of cm (3) molecule (-1) s (-1)).", "output": {"entities": {}}, "schema": []}
{"input": "The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits.", "output": {"entities": {}}, "schema": []}
{"input": "Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition.", "output": {"entities": {}}, "schema": []}
{"input": "Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin.", "output": {"entities": {}}, "schema": []}
{"input": "We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes.", "output": {"entities": {"chemical": [{"text": "Val", "start": 46, "end": 49}]}}, "schema": []}
{"input": "We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that prestin subunits are individually functional within a given multimer.", "output": {"entities": {}}, "schema": []}
{"input": "Adsorption of phenanthrene, 2-naphthol, and 1-naphthylamine to colloidal oxidized multiwalled carbon nanotubes: effects of humic acid and surfactant modification.", "output": {"entities": {"chemical": [{"text": "phenanthrene", "start": 14, "end": 26}, {"text": "2-naphthol", "start": 28, "end": 38}, {"text": "1-naphthylamine", "start": 44, "end": 59}, {"text": "carbon", "start": 94, "end": 100}]}}, "schema": []}
{"input": "Carbon nanotubes (CNTs) can exist in the form of colloidal suspension in aquatic environments, particularly in the presence of natural organic matter or surfactants, and may significantly affect the fate and transport of organic contaminants.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In the present study, the authors examined the adsorption of phenanthrene, 2-naphthol, and 1-naphthylamine to three colloidal CNTs, including a stable suspension of oxidized multiwalled carbon nanotubes (O-MWNT), a humic acid (HA)-modified colloidal O-MWNT, and a sodium dodecyl sulfate (SDS)-modified colloidal O-MWNT.", "output": {"entities": {"chemical": [{"text": "phenanthrene", "start": 61, "end": 73}, {"text": "2-naphthol", "start": 75, "end": 85}, {"text": "1-naphthylamine", "start": 91, "end": 106}, {"text": "carbon", "start": 186, "end": 192}, {"text": "sodium dodecyl sulfate", "start": 264, "end": 286}, {"text": "SDS", "start": 288, "end": 291}]}}, "schema": []}
{"input": "All three colloidal O-MWNTs exhibit strong adsorption affinities to the three test compounds (with K (OC) values orders of magnitude greater than those of natural organic matter), likely resulting from strong nonhydrophobic interactions such as pi-pi electron donor-acceptor interactions and Lewis acid-base interactions.", "output": {"entities": {"chemical": [{"text": "Lewis acid", "start": 292, "end": 302}]}}, "schema": []}
{"input": "When thoroughly mixed, HA (at ~ 310 mg HA/g CNT) and SDS (at ~ 750 mg SDS/g CNT) significantly affected the aggregation properties of O-MWNT, causing individually dispersed tubes to form a loosely entangled network.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 53, "end": 56}, {"text": "SDS", "start": 70, "end": 73}]}}, "schema": []}
{"input": "The effects of HA or SDS modification on adsorption are twofold.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 21, "end": 24}]}}, "schema": []}
{"input": "Adsorption of HA/SDS significantly reduces surface areas of O-MWNT; however, the entangled network allows adsorbate molecules to interact simultaneously with multiple tubes.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 17, "end": 20}]}}, "schema": []}
{"input": "An important implication is that humic substances and surfactant-like materials not only facilitate the formation of colloidal carbon nanoparticles but also affect how these colloidal carbon nanoparticles adsorb organic contaminants.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 127, "end": 133}, {"text": "carbon", "start": 184, "end": 190}]}}, "schema": []}
{"input": "Immunological and reproductive health assessment in herring gulls and black-crowned night herons in the Hudson-Raritan Estuary.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies have shown inexplicable declines in breeding waterbirds within western New York/New Jersey Harbor between 1996 and 2002 and elevated polychlorinated dibenzo-p-dioxins and polychlorinated biphenyls (PCBs) in double-crested cormorant (Phalacrocorax auritus) eggs.", "output": {"entities": {"chemical": [{"text": "polychlorinated dibenzo-p-dioxins", "start": 150, "end": 183}, {"text": "polychlorinated biphenyls", "start": 188, "end": 213}, {"text": "PCBs", "start": 215, "end": 219}]}}, "schema": []}
{"input": "The present study assessed associations between immune function, prefledgling survival, and selected organochlorine compounds and metals in herring gulls (Larus argentatus) and black-crowned night herons (Nycticorax nycticorax) in lower New York Harbor during 2003.", "output": {"entities": {"chemical": [{"text": "organochlorine", "start": 101, "end": 115}]}}, "schema": []}
{"input": "In pipping gull embryos, lymphoid cells were counted in the thymus and bursa of Fabricius (sites of T and B lymphocyte maturation, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "The phytohemagglutinin (PHA) skin response assessed T cell function in gull and heron chicks.", "output": {"entities": {}}, "schema": []}
{"input": "Lymphocyte proliferation was measured in vitro in adult and prefledgling gulls.", "output": {"entities": {}}, "schema": []}
{"input": "Reference data came from the Great Lakes and Bay of Fundy.", "output": {"entities": {}}, "schema": []}
{"input": "Survival of prefledgling gulls was poor, with only 0. 68 and 0. 5 chicks per nest surviving to three and four weeks after hatch, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Developing lymphoid cells were reduced 51% in the thymus and 42% in the bursa of gull embryos from New York Harbor.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro lymphocyte assays demonstrated reduced spontaneous proliferation, reduced T cell mitogen-induced proliferation, and increased B cell mitogen-induced proliferation in gull chicks from New York Harbor.", "output": {"entities": {}}, "schema": []}
{"input": "The PHA skin response was suppressed 70 to 80% in gull and heron chicks.", "output": {"entities": {}}, "schema": []}
{"input": "Strong negative correlations (r =-0. 95 to-0. 98) between the PHA response and dioxins and PCBs in gull livers was strong evidence suggesting that these chemicals contribute significantly to immunosuppression in New York Harbor waterbirds.", "output": {"entities": {"chemical": [{"text": "dioxins", "start": 79, "end": 86}, {"text": "PCBs", "start": 91, "end": 95}]}}, "schema": []}
{"input": "Reduced graphene oxide nanoribbon networks: a novel approach towards scalable fabrication of transparent conductive films.", "output": {"entities": {"chemical": [{"text": "Reduced graphene oxide", "start": 0, "end": 22}]}}, "schema": []}
{"input": "An innovative approach is developed for the high-throughput, large-area, and low-cost fabrication of reduced graphene oxide (RGO) nanoribbon networks by using electrospun polymer-based nanowires as the etching mask.", "output": {"entities": {"chemical": [{"text": "reduced graphene oxide", "start": 101, "end": 123}, {"text": "RGO", "start": 125, "end": 128}]}}, "schema": []}
{"input": "Combined with their tunable, controllable structures and transmittance/conductivity properties, the as-fabricated RGO nanoribbon networks exhibit potential as transparent conductive film electrodes, for example, in electrochromic devices.", "output": {"entities": {"chemical": [{"text": "RGO", "start": 114, "end": 117}]}}, "schema": []}
{"input": "Estradiol exerts antiapoptotic effects in skeletal myoblasts via mitochondrial PTP and MnSOD.", "output": {"entities": {"chemical": [{"text": "Estradiol", "start": 0, "end": 9}]}}, "schema": []}
{"input": "17 beta-Estradiol (E (2)) protects several non-reproductive tissues from apoptosis, including skeletal muscle.", "output": {"entities": {"chemical": [{"text": "17 beta-Estradiol", "start": 0, "end": 17}]}}, "schema": []}
{"input": "We have shown that E (2) at physiological concentrations prevented apoptosis induced by H (2) O (2) in C2C12 skeletal myoblasts.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 88, "end": 99}]}}, "schema": []}
{"input": "As we also demonstrated the presence of estrogen receptors in mitochondria, the present work was focused on the effects of E (2) on this organelle.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 40, "end": 48}]}}, "schema": []}
{"input": "Specifically, we evaluated the actions of E (2) on the mitochondrial permeability transition pore (MPTP) by the calcein-acetoxymethylester/cobalt method using fluorescence microscopy and flow cytometry.", "output": {"entities": {"chemical": [{"text": "calcein", "start": 112, "end": 119}, {"text": "acetoxymethylester", "start": 120, "end": 138}, {"text": "cobalt", "start": 139, "end": 145}]}}, "schema": []}
{"input": "Pretreatment with E (2) prevented MPTP opening induced by H (2) O (2), which preceded loss of mitochondrial membrane potential.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 58, "end": 69}]}}, "schema": []}
{"input": "In addition, it was observed that H (2) O (2) induced translocation of Bax to mitochondria; however, in the presence of the steroid this effect was abrogated suggesting that members of the Bcl-2 family may be regulated by E (2) to exert an antiapoptotic effect.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 34, "end": 45}, {"text": "steroid", "start": 124, "end": 131}]}}, "schema": []}
{"input": "Moreover, E (2) increased mitochondrial manganese superoxide dismutase protein expression and activity, as part of a mechanism activated by E (2) that improved mitochondrial performance.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 50, "end": 60}]}}, "schema": []}
{"input": "Our results suggest a role of E (2) in the regulation of apoptosis with a clear action at the mitochondrial level in C2C12 skeletal myoblast cells.", "output": {"entities": {}}, "schema": []}
{"input": "Tracking the mechanism of fibril assembly by simulated two-dimensional ultraviolet spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Alzheimer' s disease (AD) is a neurodegenerative disorder characterized by the accumulation of plaque deposits in the human brain.", "output": {"entities": {}}, "schema": []}
{"input": "The main component of these plaques consists of highly ordered structures called amyloid fibrils, formed by the amyloid beta-peptide (A beta).", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism connecting A beta and AD is yet undetermined.", "output": {"entities": {}}, "schema": []}
{"input": "In a previous study, a coarse-grained united-residue model and molecular dynamics simulations were used to model the growth mechanism of A beta amyloid fibrils.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of these simulations, a dock/lock mechanism was proposed, in which A beta fibrils grow by adding monomers at either end of an amyloid fibril template.", "output": {"entities": {}}, "schema": []}
{"input": "To examine the structures in the early time-scale formation and growth of amyloid fibrils, simulated two-dimensional ultraviolet spectroscopy is used.", "output": {"entities": {}}, "schema": []}
{"input": "These early structures are monitored in the far ultraviolet regime (lambda = 190-250 nm) in which the computed signals originate from the backbone n pi * and pi pi * transitions.", "output": {"entities": {}}, "schema": []}
{"input": "These signals show distinct cross-peak patterns that can be used, in combination with molecular dynamics, to monitor local dynamics and conformational changes in the secondary structure of A beta-peptides.", "output": {"entities": {}}, "schema": []}
{"input": "The protein geometry-correlated chiral xxxy signal and the non-chiral combined signal xyxy-xyyx were found to be sensitive to, and in agreement with, a dock/lock pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Preparation of functionalized alkynyl magnetic microspheres for the selective enrichment of cell glycoproteins based on click chemistry.", "output": {"entities": {"chemical": [{"text": "alkynyl", "start": 30, "end": 37}]}}, "schema": []}
{"input": "Functionalized alkynyl polyvinyl alcohol magnetic microspheres (PVA MMs) were developed for the specific enrichment of sialic acid-rich glycoproteins by click chemistry.", "output": {"entities": {"chemical": [{"text": "alkynyl polyvinyl alcohol", "start": 15, "end": 40}, {"text": "PVA", "start": 64, "end": 67}, {"text": "sialic acid", "start": 119, "end": 130}]}}, "schema": []}
{"input": "The capture capability for proteins was evaluated through a novel dual-labeled bovine serum albumin (BSA) that utilizes fluorescence resonance energy transfer (FRET).", "output": {"entities": {}}, "schema": []}
{"input": "The PVA MM parameters, including the size and coverage of functionalized groups, were optimized by response surface methodology.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 4, "end": 7}]}}, "schema": []}
{"input": "The optimal parameters obtained were 1. 25-6. 31 mu m in size and 48. 53-73. 05% in coverage.", "output": {"entities": {}}, "schema": []}
{"input": "Then, the optimal PVA MMs were synthesized, and the morphology and surface chemical properties were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR).", "output": {"entities": {"chemical": [{"text": "PVA", "start": 18, "end": 21}]}}, "schema": []}
{"input": "To capture glycoproteins from the cell surface, a bioorthogonal chemical method was applied to metabolically label them with an azide group.", "output": {"entities": {"chemical": [{"text": "azide", "start": 128, "end": 133}]}}, "schema": []}
{"input": "The functionalized alkynyl PVA MMs showed a high specificity and strong binding capability for glycoproteins through a [3 + 2] cycloaddition reaction.", "output": {"entities": {"chemical": [{"text": "alkynyl PVA", "start": 19, "end": 30}]}}, "schema": []}
{"input": "The results indicated that the functionalized alkynyl PVA MMs could be applied to the enrichment of cell glycoproteins, and the merits of the MMs suggested an attractive and potential way to facilitate glycoprotein research.", "output": {"entities": {"chemical": [{"text": "alkynyl PVA", "start": 46, "end": 57}]}}, "schema": []}
{"input": "Functional imaging of legumain in cancer using a new quenched activity-based probe.", "output": {"entities": {}}, "schema": []}
{"input": "Legumain is a lysosomal cysteine protease whose biological function remains poorly defined.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Legumain activity is up-regulated in most human cancers and inflammatory diseases most likely as the result of high expression in populations of activated macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "Within the tumor microenvironment, legumain activity is thought to promote tumorigenesis.", "output": {"entities": {}}, "schema": []}
{"input": "To obtain a greater understanding of the role of legumain activity during cancer progression and inflammation, we developed an activity-based probe that becomes fluorescent only upon binding active legumain.", "output": {"entities": {}}, "schema": []}
{"input": "This probe is highly selective for legumain, even in the context of whole cells and tissues, and is also a more effective label of legumain than previously reported probes.", "output": {"entities": {}}, "schema": []}
{"input": "Here we present the synthesis and application of our probe to the analysis of legumain activity in primary macrophages and in two mouse models of cancer.", "output": {"entities": {}}, "schema": []}
{"input": "We find that legumain activity is highly correlated with macrophage activation and furthermore that it is an ideal marker for primary tumor inflammation and early stage metastatic lesions.", "output": {"entities": {}}, "schema": []}
{"input": "Optical pumping of a single electron spin bound to a fluorine donor in a ZnSe nanostructure.", "output": {"entities": {"chemical": [{"text": "fluorine", "start": 53, "end": 61}, {"text": "ZnSe", "start": 73, "end": 77}]}}, "schema": []}
{"input": "Here we demonstrate optical pumping of a single electron within a semiconductor nanostructure comprised of a single fluorine donor located within a ZnSe/ZnMgSe quantum well.", "output": {"entities": {"chemical": [{"text": "fluorine", "start": 116, "end": 124}, {"text": "ZnSe", "start": 148, "end": 152}, {"text": "ZnMgSe", "start": 153, "end": 159}]}}, "schema": []}
{"input": "Experiments were performed to detect optical pumping behavior by observing single photons emitted from the nanostructure when the electron changes spin state.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate initialization and read-out of the electron spin qubit and open the door for coherent optical manipulation of a spin by taking advantage of an unconventional nanostructure.", "output": {"entities": {}}, "schema": []}
{"input": "Improved analysis for determining diffusion coefficients from short, single-molecule trajectories with photoblinking.", "output": {"entities": {}}, "schema": []}
{"input": "Two maximum likelihood estimation (MLE) methods were developed for optimizing the analysis of single-molecule trajectories that include phenomena such as experimental noise, photoblinking, photobleaching, and translation or rotation out of the collection plane.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, short, single-molecule trajectories with photoblinking were studied, and our method was compared to existing analytical techniques applied to simulated data.", "output": {"entities": {}}, "schema": []}
{"input": "The optimal method for various experimental cases was established, and the optimized MLE method was applied to a real experimental system: single-molecule diffusion of fluorescent molecular machines known as nanocars.", "output": {"entities": {}}, "schema": []}
{"input": "Aqueous extracts of Roselle (Hibiscus sabdariffa Linn.) varieties inhibit alpha-amylase and alpha-glucosidase activities in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "This study sought to investigate the inhibitory effect of aqueous extracts of two varieties (red and white) of Hibiscus sabdariffa (Roselle) calyces on carbohydrate hydrolyzing enzymes (alpha-amylase and alpha-glucosidase), with the aim of providing the possible mechanism for their antidiabetes properties.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 152, "end": 164}]}}, "schema": []}
{"input": "Aqueous extracts were prepared (1: 100 w/v) and the supernatant used for the analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The extracts caused inhibition of alpha-amylase and alpha-glucosidase activities in vitro. The IC (50) revealed that the red variety (25. 2 mu g/mL) exhibited higher alpha-glucosidase inhibitory activity than the white variety (47. 4 mu g/mL), while the white variety (90. 5 mu g/mL) exhibited higher alpha-amylase inhibitory activity than the red variety (187. 9 mu g/mL).", "output": {"entities": {}}, "schema": []}
{"input": "However, the alpha-glucosidase inhibitory activities of both calyces were higher than that of their alpha-amylase.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the red variety possessed higher antioxidant capacity as exemplified by the (*) OH scavenging abilities, Fe (2 +) chelating ability, and inhibition of Fe (2 +)-induced pancreatic lipid peroxidation in vitro.", "output": {"entities": {"chemical": [{"text": "(*) OH", "start": 89, "end": 95}, {"text": "Fe (2 +)", "start": 118, "end": 126}, {"text": "Fe (2 +)", "start": 164, "end": 172}]}}, "schema": []}
{"input": "The enzyme inhibitory activities and antioxidant properties of the roselle extracts agreed with their phenolic content.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 102, "end": 110}]}}, "schema": []}
{"input": "Hence, inhibition of alpha-amylase and alpha-glucosidase, coupled with strong antioxidant properties could be the possible underlying mechanism for the antidiabetes properties of H. sabdariffa calyces; however, the red variety appeared to be more potent.", "output": {"entities": {}}, "schema": []}
{"input": "Extruder scale-up assessment in the process of extrusion-spheronization: comparison of radial and axial systems by a design of experiments approach.", "output": {"entities": {}}, "schema": []}
{"input": "Scaling-up the extrusion-spheronization process involves the separate scale-up of each of the five process steps: dry mixing, granulation, extrusion, spheronization, and drying.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the study was to compare two screw extrusion systems regarding their suitability for scaling-up.", "output": {"entities": {}}, "schema": []}
{"input": "Two drug substances of high-and low-solubility in water were retained at different concentrations as formulation variables.", "output": {"entities": {}}, "schema": []}
{"input": "Different spheronization times were tested.", "output": {"entities": {}}, "schema": []}
{"input": "The productivity of the process was followed up using the extrusion rate and yield.", "output": {"entities": {}}, "schema": []}
{"input": "Pellets were characterized by their size and shape, and by their structural and mechanical properties.", "output": {"entities": {}}, "schema": []}
{"input": "A response surface design of experiments was built to evaluate the influence of the different variables and their interactions on each response, and to select the type of extrusion which provides the best results in terms of product quality, the one which shows less influence on the product after scale-up (\" scalability \") and when the formula used changes (\" robustness \"), and the one which allows the possibility to adjust pellet properties with spheronization variables (\" flexibility \").", "output": {"entities": {}}, "schema": []}
{"input": "Axial system showed the best characteristics in terms of product quality at lab and industrial scales, the best robustness at industrial scale, and the best scalability, by comparison with radial system.", "output": {"entities": {}}, "schema": []}
{"input": "Axial system thus appeared as the easiest scaled-up system.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to lab scale, the conclusions observed at industrial scale were the same in terms of product quality, but different for robustness and flexibility, which confirmed the importance to test the systems at industrial scale before acquiring the equipment.", "output": {"entities": {}}, "schema": []}
{"input": "Ameliorative effect of aspalathin from rooibos (Aspalathus linearis) on acute oxidative stress in Caenorhabditis elegans.", "output": {"entities": {"chemical": [{"text": "aspalathin", "start": 23, "end": 33}]}}, "schema": []}
{"input": "Rooibos leaves and fine stems (Aspalathus linearis; Fabaceae) are increasingly enjoyed as herbal tea, largely in fermented (oxidised) red-brown form, but also in unfermented (unoxidised) green form.", "output": {"entities": {}}, "schema": []}
{"input": "Rooibos is rich in antioxidant polyphenols, with the dihydrochalcone, aspalathin, as a major active ingredient.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 31, "end": 42}, {"text": "dihydrochalcone", "start": 53, "end": 68}, {"text": "aspalathin", "start": 70, "end": 80}]}}, "schema": []}
{"input": "We used Caenorhabditis elegans as model organism to investigate the effect of rooibos extracts against oxidative stress in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "In a high glucose environment, C. elegans treated with rooibos extract exhibited an extended lifespan.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 10, "end": 17}]}}, "schema": []}
{"input": "Furthermore, green rooibos was a more potent antioxidant than red rooibos, probably due to its substantially higher aspalathin content.", "output": {"entities": {"chemical": [{"text": "aspalathin", "start": 116, "end": 126}]}}, "schema": []}
{"input": "In addition, rooibos decreased acute oxidative damage caused by the superoxide anion radical generator, juglone, with aspalathin playing a major role in improving the survival rate of C. elegans.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 68, "end": 78}, {"text": "juglone", "start": 104, "end": 111}, {"text": "aspalathin", "start": 118, "end": 128}]}}, "schema": []}
{"input": "Quantitative real-time PCR results demonstrated that aspalathin targets stress and ageing related genes, reducing the endogenous intracellular level of ROS.", "output": {"entities": {"chemical": [{"text": "aspalathin", "start": 53, "end": 63}]}}, "schema": []}
{"input": "These findings suggest that rooibos increases stress resistance and promotes longevity under stress, probably mediated via a regulation of the DAF-16/FOXO insulin-like signalling pathway, supporting some of the health claims put forward for rooibos tea.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin.", "output": {"entities": {"chemical": [{"text": "monocarbonyl", "start": 64, "end": 76}, {"text": "curcumin", "start": 90, "end": 98}]}}, "schema": []}
{"input": "A series of novel monocarbonyl analogues of curcumin have been designed, synthesized and tested for their activity against Molt4, HeLa, PC3, DU145 and KB cancer cell lines.", "output": {"entities": {"chemical": [{"text": "monocarbonyl", "start": 18, "end": 30}, {"text": "curcumin", "start": 44, "end": 52}]}}, "schema": []}
{"input": "Six of the analogues showed potent cytotoxicity towards these cell lines with IC (50) values below 1 mu M, which is better than doxorubicin, a US FDA approved drug.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 128, "end": 139}]}}, "schema": []}
{"input": "Several analogues were also found to be active against both CQ-resistant (W2 clone) and CQ-sensitive (D6) strains of Plasmodium falciparum in an in-vitro antimalarial screening.", "output": {"entities": {}}, "schema": []}
{"input": "This level of activity warrants further investigation of the compounds for development as anticancer and antimalarial agents.", "output": {"entities": {}}, "schema": []}
{"input": "Combining structure and function to evaluate glaucomatous progression: implications for the design of clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "The selection of a suitable method for assessment of glaucomatous progression and estimation of rates of change is an essential component of the design of clinical trials investigating neuroprotective therapies for the disease.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the limitations of currently available tests, approaches combining structural and functional tests are essential in order to provide reliable detection of endpoints.", "output": {"entities": {}}, "schema": []}
{"input": "This could also potentially enable shorter clinical trials with relatively smaller sample size requirements.", "output": {"entities": {}}, "schema": []}
{"input": "A recent approach for estimating rates of retinal ganglion cell loss using a combination of structural and functional tests has been shown to perform better than isolated parameters from conventional tests for diagnosing, staging and detecting glaucoma progression and may prove useful as an outcome measure in clinical trials of the disease.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitory effects of metachromins L-Q and its related analogs against receptor tyrosine kinases EGFR and HER2.", "output": {"entities": {"chemical": [{"text": "metachromins L-Q", "start": 22, "end": 38}, {"text": "tyrosine", "start": 80, "end": 88}]}}, "schema": []}
{"input": "Metachromins are a series of sesquiterpenoid quinones isolated from Okinawan marine sponges.", "output": {"entities": {"chemical": [{"text": "Metachromins", "start": 0, "end": 12}, {"text": "sesquiterpenoid quinones", "start": 29, "end": 53}]}}, "schema": []}
{"input": "Inhibitory effects of metachromins L-Q (1-6), sesquiterpenoid quinones with an amino acid residue, and their related analogs (7-18) prepared from metachromins A (19) and C (20) against receptor tyrosine kinases EGFR and HER2 were investigated.", "output": {"entities": {"chemical": [{"text": "metachromins L-Q", "start": 22, "end": 38}, {"text": "sesquiterpenoid quinones", "start": 46, "end": 70}, {"text": "amino acid", "start": 79, "end": 89}, {"text": "metachromins", "start": 146, "end": 158}, {"text": "tyrosine", "start": 194, "end": 202}]}}, "schema": []}
{"input": "Two analogs 11 and 12 showed relatively stronger inhibitory activity against EGFR, while metachromins L-Q (1-6) and seven analogs (8, 10, 11, and 15-18) showed inhibitory activities against HER2.", "output": {"entities": {"chemical": [{"text": "metachromins L-Q", "start": 89, "end": 105}]}}, "schema": []}
{"input": "Anti-diabetic activities of Gegen Qinlian Decoction in high-fat diet combined with streptozotocin-induced diabetic rats and in 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 83, "end": 97}]}}, "schema": []}
{"input": "Gegen Qinlian Decoction (GGQLD) is one of the well-known traditional Chinese medicines.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, it was reported that GGQLD had good clinical effects on type 2 diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "However, few studies have confirmed in detail the anti-diabetic activities of GGQLD in vivo and in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we investigated the anti-diabetic effects of GGQLD in high-fat diet combined with streptozotocin-induced diabetic rats and in 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 104, "end": 118}]}}, "schema": []}
{"input": "The present results suggested GGQLD (4. 95, 11. 55 and 18. 15 g/kg) decreased significantly fasting blood glucose, glycosylated serum protein, and glycosylated hemoglobin of diabetic rats (p < 0. 05), and GGQLD (4. 95 and 18. 15 g/kg) decreased significantly fasting serum insulin levels of diabetic rats (p < 0. 05); in 3T3-L1 adipocytes, Gegen Qinlian Decoction-containing serum (GGQLD-CS) (4%, 8% and 16%) enhanced glucose consumption, triglyceride (TG) content, adiponectin protein concentration and the mRNA expression of adiponectin.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 106, "end": 113}, {"text": "glucose", "start": 418, "end": 425}, {"text": "triglyceride", "start": 439, "end": 451}]}}, "schema": []}
{"input": "Adiponectin contributes to the regulation of lipid and glucose metabolism, and can play a critical role in the development of diabetes mellitus; the mechanisms of action of GGQLD might be related to augmentation of adiponectin protein concentration and up-regulation of the mRNA expression of adiponectin.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 55, "end": 62}]}}, "schema": []}
{"input": "However, the multi-target mechanisms of action of GGQLD need to be clarified further.", "output": {"entities": {}}, "schema": []}
{"input": "The present study further validated the beneficial effects of GGQLD as an anti-diabetic agent.", "output": {"entities": {}}, "schema": []}
{"input": "These findings provide a new insight into the anti-diabetic application for GGQLD in clinic and display the potential of GGQLD as a new drug candidate for the treatment of diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma.", "output": {"entities": {}}, "schema": []}
{"input": "Osteosarcoma is characterized by a high malignant and metastatic potential.", "output": {"entities": {}}, "schema": []}
{"input": "Angiogenesis is essential for the caner metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers.", "output": {"entities": {}}, "schema": []}
{"input": "However, the relationship between IL-6 and vascular endothelial growth factor (VEGF) expression in human osteosarcoma is mostly unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Here we found that the IL-6 and VEGF expression was correlated with tumor stage and significantly higher than that in normal bone.", "output": {"entities": {}}, "schema": []}
{"input": "Incubation of osteosarcoma cells with IL-6 increased VEGF mRNA and protein expression.", "output": {"entities": {}}, "schema": []}
{"input": "Pretreatment of cells with IL-6R antibody reduced IL-6-mediated VEGF production.", "output": {"entities": {}}, "schema": []}
{"input": "The apoptosis signal-regulating kinase 1 (ASK1)/p38/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced VEGF expression was abolished by the specific inhibitor and siRNA of ASK1, p38, and AP-1 cascades.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, knockdown IL-6 reduced VEGF expression and abolished osteosarcoma conditional medium-mediated angiogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these results indicate that IL-6 occurs through ASK1 and p38, which in turn activates AP-1, resulting in the activations of VEGF expression and contributing the angiogenesis of human osteosarcoma cells.", "output": {"entities": {}}, "schema": []}
{"input": "4-tert-Octylphenol stimulates the expression of cathepsins in human breast cancer cells and xenografted breast tumors of a mouse model via an estrogen receptor-mediated signaling pathway.", "output": {"entities": {"chemical": [{"text": "4-tert-Octylphenol", "start": 0, "end": 18}, {"text": "estrogen", "start": 142, "end": 150}]}}, "schema": []}
{"input": "Endocrine disrupting chemicals (EDCs) are defined as environmental compounds that modulate steroid hormone receptor-dependent responses an abnormal manner, resulting in adverse health problems for humans such as cancer growth and metastasis.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 91, "end": 98}]}}, "schema": []}
{"input": "Cathepsins are proteases that have been implicated in cancer progression.", "output": {"entities": {}}, "schema": []}
{"input": "However, there have been few studies about the association between cathepsins and estrogenic chemicals during the cancer progression.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we examined the effect (s) of 4-tert-octylphenol (OP), a potent EDC, on the expression of cathepsins B and D in human MCF-7 breast cancer cells and a xenograft mouse model.", "output": {"entities": {"chemical": [{"text": "4-tert-octylphenol", "start": 45, "end": 63}]}}, "schema": []}
{"input": "Treatment with OP significantly induced the proliferation MCF-7 cells in an MTT assay.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 76, "end": 79}]}}, "schema": []}
{"input": "In addition, the expression of cathepsins B and D was markedly enhanced in MCF-7 cells at both the transcriptional and the translational levels following treatment with E2 or OP up to 48h.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrated the ability of OP to disrupt normal transcriptional regulation of cathepsins B and D in human breast cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "However, the effects of OP on cell growth or overexpression of cathepsins by inhibiting ER-mediated signaling were abolished by an ER antagonist and siRNA specific for ER alpha.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, our findings suggest that OP at 10 (-6) M, like E2, may accelerate breast cancer cell proliferation and the expression of cathepsins through an ER-mediated signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the breast cancer cells exposed with OP to a xenograft mouse model were more aggressive according to our histological analysis and showed markedly increased expression of cathepsin B.", "output": {"entities": {}}, "schema": []}
{"input": "These effects of mouse model resulted in an increased potential for metastasis in breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, we determined that OP can adversely affect human health by promoting cancer proliferation and metastasis through the amplification of cathepsins B and D via the ER-mediated signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of lead exposure on brain iron homeostasis and the expression of DMT1/FP1 in the brain in developing and aged rats.", "output": {"entities": {}}, "schema": []}
{"input": "The relation between lead (Pb) and iron (Fe) becomes increasingly concerned because they are both divalent metals that are absorbed by the same intestinal mechanism, and Pb exposure and Fe deficiency in the developmental brain, as well as Fe overload in the aged brain, can cause cognitive deficits.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 27, "end": 29}, {"text": "iron", "start": 35, "end": 39}, {"text": "Fe", "start": 41, "end": 43}, {"text": "Pb", "start": 170, "end": 172}, {"text": "Fe", "start": 186, "end": 188}, {"text": "Fe", "start": 239, "end": 241}]}}, "schema": []}
{"input": "However, the interaction between Pb exposure and Fe status in the brain has not been established.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 33, "end": 35}, {"text": "Fe", "start": 49, "end": 51}]}}, "schema": []}
{"input": "Therefore, in the current study, we examined the effects of maternal ingestion of Pb in drinking water during gestation and lactation on the Fe status and the expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) in the brain of offspring.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 82, "end": 84}, {"text": "Fe", "start": 141, "end": 143}]}}, "schema": []}
{"input": "The offspring were followed through old age, with measurements taken at postnatal week 3 (PNW3), 41 (PNW41) and 70 (PNW70).", "output": {"entities": {}}, "schema": []}
{"input": "Pb exposure increases the Fe content in the old-aged rats' brain, which might be not subjected to DMT1 mediating, but may be associated with the decrease expression of FP1.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 0, "end": 2}, {"text": "Fe", "start": 26, "end": 28}]}}, "schema": []}
{"input": "Furthermore, the effect of Pb on FP1 expression is regulated at transcriptional and posttranscriptional levels.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 27, "end": 29}]}}, "schema": []}
{"input": "The perturbation in Fe homeostasis may contribute to the neurotoxicology consequences induced by Pb exposure, and FP1 may play a role in Pb-induced Fe cumulation in the brain.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 20, "end": 22}, {"text": "Pb", "start": 97, "end": 99}, {"text": "Pb", "start": 137, "end": 139}, {"text": "Fe", "start": 148, "end": 150}]}}, "schema": []}
{"input": "Antiviral activity of (+)-sattabacin against varicella zoster.", "output": {"entities": {"chemical": [{"text": "(+)-sattabacin", "start": 22, "end": 36}]}}, "schema": []}
{"input": "The first report of the antiviral activity of (+)-sattabacin against varicella-zoster virus (VZV) is described.", "output": {"entities": {"chemical": [{"text": "(+)-sattabacin", "start": 46, "end": 60}]}}, "schema": []}
{"input": "Our results show that (+)-sattabacin potently inhibits the growth of VZV at concentrations in the range of other drugs commonly prescribed for VZV infection.", "output": {"entities": {"chemical": [{"text": "(+)-sattabacin", "start": 22, "end": 36}]}}, "schema": []}
{"input": "Experiments detailing the synthesis of (+)-sattabacin, quantification of cytotoxicity and gene expression data in human fibroblast cells are also presented.", "output": {"entities": {"chemical": [{"text": "(+)-sattabacin", "start": 39, "end": 53}]}}, "schema": []}
{"input": "Gene expression data was obtained through microarray analysis from human fibroblast cells exposed to sattabacin in order to identify a possible mechanism by which (+)-sattabacin inhibits VZV replication.", "output": {"entities": {"chemical": [{"text": "sattabacin", "start": 101, "end": 111}, {"text": "(+)-sattabacin", "start": 163, "end": 177}]}}, "schema": []}
{"input": "N-POMC1-28 increases cyclin D expression and inhibits P27 (kip1) in the adrenal cortex.", "output": {"entities": {}}, "schema": []}
{"input": "The Adrenocorticotropic hormone (ACTH) and Pro-opimelanocortin (POMC) 1-28N-terminal peptide (N-POMC1-28) have been shown to act as an adrenal mitogen in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "A possible role for cyclin E in the zona glomerulosa (ZG) proliferation, following ACTH and/or N-POMC1-28 administration, has been previously demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated the effect of ACTH and N-POMC1-28 on the expression of adrenal cortex proteins related to cell cycle control such as cyclins D and P27 (kip1).", "output": {"entities": {}}, "schema": []}
{"input": "The administration of N-POMC upregulated cyclin D1 and D2 expression in the outer zone of the adrenal cortex; cyclin D3 expression was upregulated in the cortex inner zone even after administration of ACTH.", "output": {"entities": {}}, "schema": []}
{"input": "Both ACTH and N-POMC peptides induced a decrease in the P27 (kip1) expression in the ZG.", "output": {"entities": {}}, "schema": []}
{"input": "These novel findings suggest that the POMC-derivate peptides, ACTH and N-POMC, promote proliferation in the adrenal cortex by upregulating the D2 and D3 cyclins and downregulating the P27 (kip1) expression.", "output": {"entities": {}}, "schema": []}
{"input": "3-Hydroxykynurenine: an intriguing molecule exerting dual actions in the Central Nervous System.", "output": {"entities": {"chemical": [{"text": "3-Hydroxykynurenine", "start": 0, "end": 19}]}}, "schema": []}
{"input": "Kynurenine pathway is gaining attention due to the many metabolic processes in which it has been involved.", "output": {"entities": {"chemical": [{"text": "Kynurenine", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The tryptophan conversion into several other metabolites through this pathway provides neuronal and redox modulators useful for maintenance of major functions in the brain.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 4, "end": 14}]}}, "schema": []}
{"input": "However, when physiopathological conditions prevail-i. e. oxidative stress, excitotoxicity, and inflammation-preferential formation and accumulation of toxic metabolites could trigger factors for degeneration in neurological disorders.", "output": {"entities": {}}, "schema": []}
{"input": "3-Hydroxykynurenine has been largely described as one of these toxic metabolites capable of inducing oxidative damage and cell death; consequently, this metabolite has been hypothesized to play a pivotal role in different neurological and psychiatric disorders.", "output": {"entities": {"chemical": [{"text": "3-Hydroxykynurenine", "start": 0, "end": 19}]}}, "schema": []}
{"input": "Supporting evidence has shown altered 3-hydroxykynurenine levels in samples of patients from several disorders.", "output": {"entities": {"chemical": [{"text": "3-hydroxykynurenine", "start": 38, "end": 57}]}}, "schema": []}
{"input": "In contrast, some experimental studies have provided evidence of antioxidant and scavenging properties inherent to this molecule.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we explored most of literature favoring one or the other concept, in order to provide an accurate vision on the real participation of this tryptophan metabolite in both experimental paradigms and human brain pathologies.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 155, "end": 165}]}}, "schema": []}
{"input": "Through this collected evidence, we provide an integrative hypothesis on how 3-hydroxykynurenine is exerting its dual actions in the Central Nervous System and what will be the course of investigations in this field for the next years.", "output": {"entities": {"chemical": [{"text": "3-hydroxykynurenine", "start": 77, "end": 96}]}}, "schema": []}
{"input": "3-(1H-indol-3-yl)-2-[3-(4-nitrophenyl) ureido] propanamide enantiomers with human formyl-peptide receptor agonist activity: molecular modeling of chiral recognition by FPR2.", "output": {"entities": {"chemical": [{"text": "3-(1H-indol-3-yl)-2-[3-(4-nitrophenyl) ureido] propanamide", "start": 0, "end": 58}, {"text": "formyl", "start": 82, "end": 88}]}}, "schema": []}
{"input": "N-formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) that play critical roles in inflammatory reactions, and FPR-specific interactions can possibly be used to facilitate the resolution of pathological inflammatory reactions.", "output": {"entities": {"chemical": [{"text": "N-formyl", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Recent studies indicated that FPRs have stereo-selective preference for chiral ligands.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we investigated the structure-activity relationship of 24 chiral ureidopropanamides, including previously reported compounds PD168368/PD176252 and their close analogs, and used molecular modeling to define chiral recognition by FPR2.", "output": {"entities": {"chemical": [{"text": "ureidopropanamides", "start": 71, "end": 89}, {"text": "PD168368", "start": 131, "end": 139}, {"text": "PD176252", "start": 140, "end": 148}]}}, "schema": []}
{"input": "Unlike previously reported 6-methyl-2, 4-disubstituted pyridazin-3 (2H)-ones, whose R-forms preferentially activated FPR1/FPR2, we found that four S-enantiomers in the seven ureidopropanamide pairs tested preferentially activated intracellular Ca (2 +) flux in FPR2-transfected cells, while the R-counterpart was more active in two enantiomer pairs.", "output": {"entities": {"chemical": [{"text": "6-methyl-2, 4-disubstituted pyridazin-3 (2H)-ones", "start": 27, "end": 76}, {"text": "ureidopropanamide", "start": 174, "end": 191}, {"text": "Ca (2 +)", "start": 244, "end": 252}]}}, "schema": []}
{"input": "Thus, active enantiomers of FPR2 agonists can be in either R-or S-configurations, depending on the molecular scaffold and specific substituents at the chiral center.", "output": {"entities": {}}, "schema": []}
{"input": "Using molecular modeling approaches, including field point methodology, homology modeling, and docking studies, we propose a model that can explain stereoselective activity of chiral FPR2 agonists.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, our docking studies of FPR2 chiral agonists correlated well with the FPR2 pharmacophore model derived previously.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that the ability of FPR2 to discriminate between the enantiomers is the consequence of the arrangement of the three asymmetric hydrophobic subpockets at the main orthosteric FPR2 binding site with specific orientation of charged regions in the subpockets.", "output": {"entities": {}}, "schema": []}
{"input": "Biological impact of phthalates.", "output": {"entities": {"chemical": [{"text": "phthalates", "start": 21, "end": 31}]}}, "schema": []}
{"input": "Esters of phthalic acid are chemical agents used to improve the plasticity of industrial polymers.", "output": {"entities": {"chemical": [{"text": "Esters", "start": 0, "end": 6}, {"text": "phthalic acid", "start": 10, "end": 23}]}}, "schema": []}
{"input": "Their ubiquitous use in multiple commercial products results in extensive exposure to humans and the environment.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigated cytotoxicity, endocrine disruption, effects mediated via AhR, lipid peroxidation and effects on expression of enzymes of xenobiotic metabolism caused by di-(2-ethy hexyl) phthalate (DEHP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and benzyl butyl phthalate (BBP) in developing fish embryos.", "output": {"entities": {"chemical": [{"text": "di-(2-ethy hexyl) phthalate", "start": 177, "end": 204}, {"text": "DEHP", "start": 206, "end": 210}, {"text": "diethyl phthalate", "start": 213, "end": 230}, {"text": "DEP", "start": 232, "end": 235}, {"text": "dibutyl phthalate", "start": 238, "end": 255}, {"text": "DBP", "start": 257, "end": 260}, {"text": "benzyl butyl phthalate", "start": 266, "end": 288}, {"text": "BBP", "start": 290, "end": 293}]}}, "schema": []}
{"input": "Oxidative stress was identified as the critical mechanism of toxicity (CMTA) in the case of DEHP and DEP, while the efficient removal of DBP and BBP by phase 1 enzymes resulted in lesser toxicity.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 92, "end": 96}, {"text": "DEP", "start": 101, "end": 104}, {"text": "DBP", "start": 137, "end": 140}, {"text": "BBP", "start": 145, "end": 148}]}}, "schema": []}
{"input": "DEHP and DEP did not mimic estradiol (E (2)) in transactivation studies, but at concentrations of 10mg/L synthesis of sex steroid hormones was affected.", "output": {"entities": {"chemical": [{"text": "DEHP", "start": 0, "end": 4}, {"text": "DEP", "start": 9, "end": 12}, {"text": "estradiol", "start": 27, "end": 36}, {"text": "steroid", "start": 122, "end": 129}]}}, "schema": []}
{"input": "Exposure to 10mg BBP/L resulted in weak transactivation of the estrogen receptor (ER).", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 63, "end": 71}]}}, "schema": []}
{"input": "All phthalates exhibited weak potency as agonists of the aryl hydrocarbon receptor (AhR).", "output": {"entities": {"chemical": [{"text": "phthalates", "start": 4, "end": 14}, {"text": "aryl hydrocarbon", "start": 57, "end": 73}]}}, "schema": []}
{"input": "The order of potency of the 4 phthalates studied was; DEHP > DEP > BBP > DBP.", "output": {"entities": {"chemical": [{"text": "phthalates", "start": 30, "end": 40}, {"text": "DEHP", "start": 54, "end": 58}, {"text": "DEP", "start": 61, "end": 64}, {"text": "BBP", "start": 67, "end": 70}, {"text": "DBP", "start": 73, "end": 76}]}}, "schema": []}
{"input": "The study highlights the need for simultaneous assessment of: (1) multiple cellular targets affected by phthalates and (2) phthalate mixtures to account for additive effects when multiple phthalates modulate the same pathway.", "output": {"entities": {"chemical": [{"text": "phthalates", "start": 104, "end": 114}, {"text": "phthalate", "start": 123, "end": 132}, {"text": "phthalates", "start": 188, "end": 198}]}}, "schema": []}
{"input": "Such cumulative assessment of multiple biological parameters is more realistic, and offers the possibility of more accurately identifying the CMTA.", "output": {"entities": {}}, "schema": []}
{"input": "Doxorubicin decreases paraquat accumulation and toxicity in Caco-2 cells.", "output": {"entities": {"chemical": [{"text": "Doxorubicin", "start": 0, "end": 11}, {"text": "paraquat", "start": 22, "end": 30}]}}, "schema": []}
{"input": "P-glycoprotein (P-gp) is an efflux pump belonging to the ATP-binding cassette transporter superfamily expressed in several organs.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Considering its potential protective effects, the induction of de novo synthesis of P-gp could be used therapeutically in the treatment of intoxications by its substrates.", "output": {"entities": {}}, "schema": []}
{"input": "The herbicide paraquat (PQ) is a P-gp substrate responsible for thousands of fatal intoxications worldwide that still lacks an effective antidote.", "output": {"entities": {"chemical": [{"text": "paraquat", "start": 14, "end": 22}]}}, "schema": []}
{"input": "The aim of the present work was to evaluate the effectiveness of such an antidote by testing whether doxorubicin (DOX), a known P-gp inducer, could efficiently protect Caco-2 cells against PQ cytotoxicity, 6 h after the incubation with the herbicide, reflecting a real-life intoxication scenario.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 101, "end": 112}, {"text": "DOX", "start": 114, "end": 117}]}}, "schema": []}
{"input": "Cytotoxicity was evaluated by the MTT assay and PQ intracellular concentrations were measured by gas chromatography-ion trap-mass spectrometry (GC-IT-MS).", "output": {"entities": {"chemical": [{"text": "MTT", "start": 34, "end": 37}]}}, "schema": []}
{"input": "Also, the DOX modulatory effect on choline uptake transport system was assessed by measuring the uptake of [(3) H]-choline.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 10, "end": 13}, {"text": "choline", "start": 35, "end": 42}, {"text": "[(3) H]-choline", "start": 107, "end": 122}]}}, "schema": []}
{"input": "The results show that DOX exerts protective effects against PQ cytotoxicity, preventing the intracellular accumulation of the herbicide.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 22, "end": 25}]}}, "schema": []}
{"input": "These protective effects were not completely prevented by the incubation with the UIC2 antibody, a specific P-gp inhibitor, suggesting the involvement of alternative protection mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "In fact, DOX also efficiently inhibited the choline transport system that influences PQ cellular uptake.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 9, "end": 12}, {"text": "choline", "start": 44, "end": 51}]}}, "schema": []}
{"input": "In conclusion, in this cellular model, DOX effectively protects against PQ toxicity by inducing P-gp and through the interaction with the choline transporter, suggesting that compounds presenting this double feature of promoting the efflux and limiting the uptake of PQ could be used as effective antidotes to treat intoxications.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 39, "end": 42}, {"text": "choline", "start": 138, "end": 145}]}}, "schema": []}
{"input": "Capreomycin supergenerics for pulmonary tuberculosis treatment: preparation, in vitro, and in vivo characterization.", "output": {"entities": {"chemical": [{"text": "Capreomycin", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The pulmonary route is one of the main strategies investigated to improve tuberculosis therapy.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to develop a simple and scalable method to produce capreomycin inhalable powders to use as supergeneric.", "output": {"entities": {"chemical": [{"text": "capreomycin", "start": 77, "end": 88}]}}, "schema": []}
{"input": "In vitro antimycobacterial activity and in vivo acute toxicity were assessed using agar proportion susceptibility test on Mycobacterium tuberculosis and chicken chorioallantoic membrane assay, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Capreomycin and three different hydrophobic counterions, namely oleate, linoleate, and linolenate, were combined in solution to obtain hydrophobic ion-pairs that were successively spray-dried.", "output": {"entities": {"chemical": [{"text": "Capreomycin", "start": 0, "end": 11}, {"text": "oleate", "start": 64, "end": 70}, {"text": "linoleate", "start": 72, "end": 81}, {"text": "linolenate", "start": 87, "end": 97}]}}, "schema": []}
{"input": "Ion-pairing efficiency was influenced by the spray-dryer employed to produce the powder.", "output": {"entities": {}}, "schema": []}
{"input": "In the case of capreomycin oleate, both instruments, mini and nano spray-dryer, were suitable to maintain a high ion-paired content, while for capreomycin linoleate and linolenate, mini spray-dryer was the most appropriate instrument.", "output": {"entities": {"chemical": [{"text": "capreomycin oleate", "start": 15, "end": 33}, {"text": "capreomycin linoleate and linolenate", "start": 143, "end": 179}]}}, "schema": []}
{"input": "The three formulations showed morphology and particle sizes potentially suitable for inhalation.", "output": {"entities": {}}, "schema": []}
{"input": "Capreomycin oleate and linoleate showed the same efficacy of capreomycin sulfate against M. tuberculosis, while capreomycin linolenate showed a reduced efficacy, even though strain growth was inhibited at 10 (-4) mycobacterial inoculum.", "output": {"entities": {"chemical": [{"text": "Capreomycin oleate and linoleate", "start": 0, "end": 32}, {"text": "capreomycin sulfate", "start": 61, "end": 80}, {"text": "capreomycin linolenate", "start": 112, "end": 134}]}}, "schema": []}
{"input": "In vivo acute toxicity studies evidenced the lowest toxic potential for capreomycin oleate when compared to the single components or the other two salts.", "output": {"entities": {"chemical": [{"text": "capreomycin oleate", "start": 72, "end": 90}]}}, "schema": []}
{"input": "Overall, capreomycin oleate seems to possess the most promising characteristics to be used as supergenerics in pulmonary tuberculosis treatment.", "output": {"entities": {"chemical": [{"text": "capreomycin oleate", "start": 9, "end": 27}]}}, "schema": []}
{"input": "Evernia prunastri and Pseudoevernia furfuraceae lichens and their major metabolites as antioxidant, antimicrobial and anticancer agents.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study is to investigate chemical composition of acetone extracts of the lichens Evernia prunastri and Pseudoevernia furfuraceae and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts and some their major metabolites.", "output": {"entities": {"chemical": [{"text": "acetone", "start": 64, "end": 71}]}}, "schema": []}
{"input": "HPLC-UV method was used for identification of secondary metabolites.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activity was evaluated by free radical scavenging, superoxide anion radical scavenging, reducing power and determination of total phenolic compounds.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 63, "end": 73}, {"text": "phenolic", "start": 142, "end": 150}]}}, "schema": []}
{"input": "As a result of the study physodic acid had largest antioxidant activities.", "output": {"entities": {}}, "schema": []}
{"input": "Total content of phenol in extracts was determined as pyrocatechol equivalent.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 17, "end": 23}, {"text": "pyrocatechol", "start": 54, "end": 66}]}}, "schema": []}
{"input": "The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method.", "output": {"entities": {}}, "schema": []}
{"input": "The most active was also physodic acid.", "output": {"entities": {"chemical": [{"text": "physodic acid", "start": 25, "end": 38}]}}, "schema": []}
{"input": "Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using MTT method.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 112, "end": 115}]}}, "schema": []}
{"input": "Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells.", "output": {"entities": {"chemical": [{"text": "bile salts", "start": 58, "end": 68}]}}, "schema": []}
{"input": "This study was designed to investigate the cytotoxicity of bile salt-lecithin mixed micelles on the Caco-2 cell model.", "output": {"entities": {"chemical": [{"text": "bile salt", "start": 59, "end": 68}]}}, "schema": []}
{"input": "Cell viability and proliferation after mixed micelles treatments were evaluated with the MTT assay, and the integrity of Caco-2 cell monolayer was determined by quantitating the transepithelial electrical resistance and the flux of tracer, FITC-dextran 4400.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 89, "end": 92}, {"text": "FITC", "start": 240, "end": 244}]}}, "schema": []}
{"input": "The apoptosis induced by mixed micelles treatments was investigated with the annexin V/PI protocol.", "output": {"entities": {}}, "schema": []}
{"input": "The particle size of mixed micelles was all smaller than 100 nm.", "output": {"entities": {}}, "schema": []}
{"input": "The mixed micelles with lower than 0. 2mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation.", "output": {"entities": {"chemical": [{"text": "sodium deoxycholate", "start": 42, "end": 61}, {"text": "SDC", "start": 63, "end": 66}]}}, "schema": []}
{"input": "When the level of SDC was higher than 0. 4mM and the lecithin/SDC ratio was lower than 2: 1, the mixed micelles caused significant changes in cell viability and proliferation.", "output": {"entities": {"chemical": [{"text": "SDC", "start": 18, "end": 21}, {"text": "SDC", "start": 62, "end": 65}]}}, "schema": []}
{"input": "Furthermore, the mixed micelles affected tight junctions in a composition-dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, the tight junctions were transiently opened rather than damaged by the mixed micelles with SDC of between 0. 2 and 0. 6mM.", "output": {"entities": {"chemical": [{"text": "SDC", "start": 105, "end": 108}]}}, "schema": []}
{"input": "The mixed micelles with more lecithin also induced less apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate that relatively higher concentrations of mixed micelles are toxic to Caco-2 cells, while phospholipids can attenuate the toxicity of the bile salts.", "output": {"entities": {"chemical": [{"text": "bile salts", "start": 163, "end": 173}]}}, "schema": []}
{"input": "A simple molecular modeling method for the characterization of polymeric drug carriers.", "output": {"entities": {}}, "schema": []}
{"input": "A simple molecular modeling method for the characterization of polymeric drug carriers is presented.", "output": {"entities": {}}, "schema": []}
{"input": "Six biodegradable polymers have been investigated as drug carriers using molecular simulations: l-polylactide, d-polylactide, chitosan, polyglycolic acid, polyethylene glycol and cellulose.", "output": {"entities": {"chemical": [{"text": "l-polylactide", "start": 96, "end": 109}, {"text": "d-polylactide", "start": 111, "end": 124}, {"text": "polyglycolic acid", "start": 136, "end": 153}, {"text": "polyethylene glycol", "start": 155, "end": 174}]}}, "schema": []}
{"input": "Cyclosporine A has been chosen as a model drug substance.", "output": {"entities": {"chemical": [{"text": "Cyclosporine A", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Classical molecular dynamics and docking calculations were employed to model and predict polymer-drug interactions.", "output": {"entities": {}}, "schema": []}
{"input": "These interactions have been analyzed by non-bond interaction energy and interaction parameter calculated using Flory-Huggins theory.", "output": {"entities": {}}, "schema": []}
{"input": "Flexibility of polymer chains has been characterized by the change of gyration radius along the molecular dynamics trajectory.", "output": {"entities": {}}, "schema": []}
{"input": "The relationship between mixing energy, chain length and chain flexibility has been revealed for each polymer/drug system.", "output": {"entities": {}}, "schema": []}
{"input": "Improvement in pelvic pain with botulinum toxin type A-Single vs. repeat injections.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this prospective study was to report the outcomes of pain and vaginal pressures of successive botulinum toxin type A injections for women with objective pelvic floor muscle overactivity and a two-year history of pelvic pain.", "output": {"entities": {}}, "schema": []}
{"input": "Between 2005 and 2008, 37 women underwent injection of 100 IU of botulinum toxin type A into the puborectalis and pubococcygeous muscles with dysmenorrhoea, dyspareunia, dyschesia, and non-menstrual pelvic pain assessed using a visual analogue scale (VAS), and vaginal pressure measured by vaginal manometry, at 0, 4, 12 and 26 weeks from each injection.", "output": {"entities": {}}, "schema": []}
{"input": "26 women (70%) had one injection of botulinum toxin type A and 11 (30%) had 2 or more injections.", "output": {"entities": {}}, "schema": []}
{"input": "The second injection was performed at the earliest at 26 weeks after the first, with subsequent injections having a median time to re-injection of 33. 4 weeks (range 9. 4-122. 7 weeks).", "output": {"entities": {}}, "schema": []}
{"input": "Single and repeated injections both demonstrated a statistically significant reduction in dyspareunia by VAS scores from 54 to 30 in the single injection group and from 51 to 23 in the multiple injection group (p =. 001), non-menstrual pelvic pain VAS from 37 to 25 (p =. 04), as well as vaginal pressures; 40 versus 34 cm H (2) O (p =. 02).", "output": {"entities": {"chemical": [{"text": "H (2) O", "start": 323, "end": 330}]}}, "schema": []}
{"input": "No statistically significant difference in dysmenorrhoea or dyschesia was observed for either group from their baseline scores.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple injections of botulinum toxin type A in women with pelvic floor muscle overactivity provide significant relief from dyspareunia and non-menstrual pelvic pain.", "output": {"entities": {}}, "schema": []}
{"input": "The upper limit between re-injection is not yet determined, nor is the maximum number of treatments.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical outcomes for single and subsequent injection of botulinum toxin type A for recurrent pelvic pain are equivalent.", "output": {"entities": {}}, "schema": []}
{"input": "Women who have had benefit from a single injection of botulinum toxin type A can be reassured that if symptoms reoccur, repeated injections can be expected to be equally efficacious.", "output": {"entities": {}}, "schema": []}
{"input": "A polyacetylene-rich extract from Gymnaster koraiensis strongly inhibits colitis-associated colon cancer in mice.", "output": {"entities": {"chemical": [{"text": "polyacetylene", "start": 2, "end": 15}]}}, "schema": []}
{"input": "Gymnaster koraiensis (GK) is a Korean herb used in folk medicine and recently found to positively impact liver health.", "output": {"entities": {}}, "schema": []}
{"input": "Because GK contains polyacetylenes and because other polyacetylenes have been found to exhibit anti-inflammatory and anti-cancer activities, we hypothesized that the polyacetylene gymnasterkoreayne B (GKB), known to increase hepatic detoxification enzymes, may also exert anti-inflammatory and anti-cancer activities.", "output": {"entities": {"chemical": [{"text": "polyacetylenes", "start": 20, "end": 34}, {"text": "polyacetylenes", "start": 53, "end": 67}, {"text": "polyacetylene gymnasterkoreayne B", "start": 166, "end": 199}, {"text": "GKB", "start": 201, "end": 204}]}}, "schema": []}
{"input": "We fed male C57BL/6 mice purified AIN93G diets containing no additions, GKB or the GKB-rich fraction of an ethanol extract (GE) from GK to determine if these diets would slow or prevent either inflammation or inflammation-enhanced colon cancer, using the dextran sulfate sodium/azoxymethane mouse model.", "output": {"entities": {"chemical": [{"text": "GKB", "start": 72, "end": 75}, {"text": "GKB", "start": 83, "end": 86}, {"text": "ethanol", "start": 107, "end": 114}, {"text": "sodium", "start": 271, "end": 277}, {"text": "azoxymethane", "start": 278, "end": 290}]}}, "schema": []}
{"input": "The GKB (500 mu mol/kg diet daily) showed some anti-inflammatory activity, but GE, containing an equal dose of GKB, protected strongly against both inflammation and colon cancer, decreasing adenocarcinomas by 90%.", "output": {"entities": {"chemical": [{"text": "GKB", "start": 4, "end": 7}, {"text": "GKB", "start": 111, "end": 114}]}}, "schema": []}
{"input": "These data support further research into GK as a promising potential anti-cancer agent.", "output": {"entities": {}}, "schema": []}
{"input": "The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1, NAG-1, is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily that plays a complex but poorly understood role in several human diseases including cancer.", "output": {"entities": {}}, "schema": []}
{"input": "NAG-1 expression is substantially increased during cancer development and progression especially in gastrointestinal, prostate, pancreatic, colorectal, breast, melanoma, and glioblastoma brain tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Aberrant increases in the serum levels of secreted NAG-1 correlate with poor prognosis and patient survival rates in some cancers.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the expression of NAG-1 is up-regulated by several tumor suppressor pathways including p53, GSK-3 beta, and EGR-1.", "output": {"entities": {}}, "schema": []}
{"input": "NAG-1 expression is also induced by many drugs and dietary compounds which are documented to prevent the development and progression of cancer in mouse models.", "output": {"entities": {}}, "schema": []}
{"input": "Studies with transgenic mice expressing human NAG-1 demonstrated that the expression of NAG-1 inhibits the development of intestinal tumors and prostate tumors in animal models.", "output": {"entities": {}}, "schema": []}
{"input": "Laboratory and clinical evidence suggest that NAG-1, like other TGF-beta family members, may have different or pleiotropic functions in the early and late stages of carcinogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Upon understanding the molecular mechanism and function of NAG-1 during carcinogenesis, NAG-1 may serve as a potential biomarker for the diagnosis and prognosis of cancer and a therapeutic target for the inhibition and treatment of cancer development and progression.", "output": {"entities": {}}, "schema": []}
{"input": "The estrogenic effects of benzylparaben at low doses based on uterotrophic assay in immature SD rats.", "output": {"entities": {"chemical": [{"text": "benzylparaben", "start": 26, "end": 39}]}}, "schema": []}
{"input": "Benzylparaben (BzP), a type of parabens being used as a preservative agent in cosmetics, food, and pharmaceutical products, may be ingested by humans.", "output": {"entities": {"chemical": [{"text": "Benzylparaben", "start": 0, "end": 13}, {"text": "BzP", "start": 15, "end": 18}]}}, "schema": []}
{"input": "In this study, we performed an immature uterotrophic assay using Sprague Dawley (SD) rats by intragastric administration to determine the estrogenic effects of BzP and found significant increases in uterine weight with doses of 0. 16 mg/kg body weight and higher (P < 0. 05).", "output": {"entities": {"chemical": [{"text": "BzP", "start": 160, "end": 163}]}}, "schema": []}
{"input": "The in vivo estrogenicity of BzP was supported by in vitro results from the human estrogen receptor alpha (hER alpha)-coactivator recruiting assay and in silico molecular docking analysis performed in this study.", "output": {"entities": {"chemical": [{"text": "BzP", "start": 29, "end": 32}, {"text": "estrogen", "start": 82, "end": 90}]}}, "schema": []}
{"input": "The in vitro estrogenic activity of BzP can be observed at concentrations of 1. 0 x 10 (-8) M and higher.", "output": {"entities": {"chemical": [{"text": "BzP", "start": 36, "end": 39}]}}, "schema": []}
{"input": "Molecular docking analysis showed that BzP fits well into the agonist pocket of hER alpha.", "output": {"entities": {"chemical": [{"text": "BzP", "start": 39, "end": 42}]}}, "schema": []}
{"input": "The lowest observed effect dose (LOED) (0. 16 mg/kg/day) of BzP is much lower than the documented LOEDs of other parabens.", "output": {"entities": {"chemical": [{"text": "BzP", "start": 60, "end": 63}, {"text": "parabens", "start": 113, "end": 121}]}}, "schema": []}
{"input": "Actual risk may exist for people who consume a diet high in BzP or use BzP-laden cosmetics.", "output": {"entities": {"chemical": [{"text": "BzP", "start": 60, "end": 63}, {"text": "BzP", "start": 71, "end": 74}]}}, "schema": []}
{"input": "In addition, we tested the sensitivity of Wistar rats to 17 beta-estradiol by immature uterotrophic assay, and no obvious uterotrophic response was observed in the rats given doses up to 100 mu g/kg body weight.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 57, "end": 74}]}}, "schema": []}
{"input": "MAPK signaling pathways regulate mitochondrial-mediated apoptosis induced by isoorientin in human hepatoblastoma cancer cells.", "output": {"entities": {"chemical": [{"text": "isoorientin", "start": 77, "end": 88}]}}, "schema": []}
{"input": "Isoorientin (ISO) (CAS RN: 4261-42-1) is a flavonoid compound that can be extracted from several plant species, such as Phyllostachys pubescens, Patrinia, and Drosophyllum lusitanicum.", "output": {"entities": {"chemical": [{"text": "Isoorientin", "start": 0, "end": 11}, {"text": "ISO", "start": 13, "end": 16}, {"text": "4261-42-1", "start": 27, "end": 36}, {"text": "flavonoid", "start": 43, "end": 52}]}}, "schema": []}
{"input": "ISO is able to induce apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cells, however, the effects of ISO on MAPK signaling pathways remain unknown.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 0, "end": 3}, {"text": "ISO", "start": 151, "end": 154}]}}, "schema": []}
{"input": "The present study investigated the effects of ISO on this pathway, and the roles of MAPK kinases on mitochondrial-mediated apoptosis in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 46, "end": 49}]}}, "schema": []}
{"input": "The results showed that ISO induced cell death in a dose-and time-dependent manner, and induction apoptosis is main cause for ISO-induced cytotoxicity in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 24, "end": 27}, {"text": "ISO", "start": 126, "end": 129}]}}, "schema": []}
{"input": "ISO significantly inhibited the levels of ERK1/2 kinase and increased the expression of JNK and p38 kinases.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Furthermore, U0126 (an ERK1/2 inhibitor) significantly enhanced the ISO-induced the Bax/Bcl-2 ratio, the release of cytochrome c to the cytosol fraction, and the levels of cleaved caspase-3.", "output": {"entities": {"chemical": [{"text": "U0126", "start": 13, "end": 18}, {"text": "ISO", "start": 68, "end": 71}]}}, "schema": []}
{"input": "While SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor) markedly prevented the expression of these proteins induced by ISO.", "output": {"entities": {"chemical": [{"text": "SP600125", "start": 6, "end": 14}, {"text": "SB203580", "start": 37, "end": 45}, {"text": "ISO", "start": 127, "end": 130}]}}, "schema": []}
{"input": "Furthermore, the ROS inhibitor (NAC) notably promoted the inhibited effect of ISO on the ERK1/2 kinase.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 32, "end": 35}, {"text": "ISO", "start": 78, "end": 81}]}}, "schema": []}
{"input": "NAC also suppressed the p-JNK and p-p38, but failed to reverse the effects of ISO.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 0, "end": 3}, {"text": "ISO", "start": 78, "end": 81}]}}, "schema": []}
{"input": "These results demonstrated for the first time that ISO induces apoptosis in HepG2 cells through inactivating ERK1/2 kinase and activating JNK and p38 kinases, and ROS stimulated by ISO is able to activate the MAPK singaling pathway as the upstream signaling molecules.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 51, "end": 54}, {"text": "ISO", "start": 181, "end": 184}]}}, "schema": []}
{"input": "Initiating event of the mitochondrial-mediated apoptosis induced by ISO is MAPK signals.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 68, "end": 71}]}}, "schema": []}
{"input": "Hepatic metabolism of sulfur amino acids in db/db mice.", "output": {"entities": {"chemical": [{"text": "sulfur amino acids", "start": 22, "end": 40}]}}, "schema": []}
{"input": "To determine the effect of type-2 diabetes and obesity on the hepatic metabolism of sulfur amino acids, hepatic sulfur amino acid metabolism was determined in db/db mice.", "output": {"entities": {"chemical": [{"text": "sulfur amino acids", "start": 84, "end": 102}, {"text": "sulfur amino acid", "start": 112, "end": 129}]}}, "schema": []}
{"input": "Hepatic methionine was markedly decreased in db/db mice, although the hepatic activity of betaine homocysteine methyltransferase was increased.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 8, "end": 18}, {"text": "homocysteine", "start": 98, "end": 110}]}}, "schema": []}
{"input": "The decrease in hepatic methionine was reflected by decreased sulfur-containing methionine metabolites, including S-adenosylmethionine, homocysteine, cysteine, and hypotaurine in liver and plasma.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 24, "end": 34}, {"text": "sulfur", "start": 62, "end": 68}, {"text": "methionine", "start": 80, "end": 90}, {"text": "S-adenosylmethionine", "start": 114, "end": 134}, {"text": "homocysteine", "start": 136, "end": 148}, {"text": "cysteine", "start": 150, "end": 158}, {"text": "hypotaurine", "start": 164, "end": 175}]}}, "schema": []}
{"input": "In contrast, S-adenosylhomocysteine, putrescine, and spermidine were increased in db/db mice.", "output": {"entities": {"chemical": [{"text": "S-adenosylhomocysteine", "start": 13, "end": 35}, {"text": "putrescine", "start": 37, "end": 47}, {"text": "spermidine", "start": 53, "end": 63}]}}, "schema": []}
{"input": "The hepatic level and activity of methionine adenosyltransferase I/III, an S-adenosylmethionine synthesizing enzyme, were significantly increased.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 34, "end": 44}, {"text": "S-adenosylmethionine", "start": 75, "end": 95}]}}, "schema": []}
{"input": "These results suggest that increased polyamine synthesis, in conjunction with decreased hepatic methionine levels, is partly responsible for the reduction in hepatic S-adenosylmethionine.", "output": {"entities": {"chemical": [{"text": "polyamine", "start": 37, "end": 46}, {"text": "methionine", "start": 96, "end": 106}, {"text": "S-adenosylmethionine", "start": 166, "end": 186}]}}, "schema": []}
{"input": "Decreased homocysteine in liver and plasma may be attributable to the decrease in hepatic methionine and upregulation of hepatic betaine homocysteine methyltransferase.", "output": {"entities": {"chemical": [{"text": "homocysteine", "start": 10, "end": 22}, {"text": "methionine", "start": 90, "end": 100}, {"text": "homocysteine", "start": 137, "end": 149}]}}, "schema": []}
{"input": "Glutathione in liver and plasma did not change despite decreased gamma-glutamylcysteine ligase activity.", "output": {"entities": {"chemical": [{"text": "Glutathione", "start": 0, "end": 11}, {"text": "gamma-glutamylcysteine", "start": 65, "end": 87}]}}, "schema": []}
{"input": "The decreased hepatic hypotaurine may be attributable to the downregulation of cysteine dioxygenase.", "output": {"entities": {"chemical": [{"text": "hypotaurine", "start": 22, "end": 33}, {"text": "cysteine", "start": 79, "end": 87}]}}, "schema": []}
{"input": "The major finding of this study is that db/db mice exhibited decreases in hepatic methionine and its sulfurcontaining metabolites.", "output": {"entities": {}}, "schema": []}
{"input": "Antithrombotic and profibrinolytic activities of isorhamnetin-3-O-galactoside and hyperoside.", "output": {"entities": {"chemical": [{"text": "isorhamnetin-3-O-galactoside", "start": 49, "end": 77}, {"text": "hyperoside", "start": 82, "end": 92}]}}, "schema": []}
{"input": "The potential anticoagulant activities of two single compounds, isorhamnetin-3-O-galactoside (IMG) and hyperoside, from Oenanthe javanica, were tested.", "output": {"entities": {"chemical": [{"text": "isorhamnetin-3-O-galactoside", "start": 64, "end": 92}, {"text": "IMG", "start": 94, "end": 97}, {"text": "hyperoside", "start": 103, "end": 113}]}}, "schema": []}
{"input": "The anticoagulant activities were investigated by measuring activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the ability to inhibit production of thrombin and activated factor X (FXa) was investigated in human umbilical vein endothelial cells (HUVECs).", "output": {"entities": {}}, "schema": []}
{"input": "And, the effects of the compounds on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-(TNF)-alpha activated HUVECs.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment with IMG and hyperoside resulted in significantly prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and IMG or hyperoside inhibited production of thrombin and FXa in HUVECs.", "output": {"entities": {"chemical": [{"text": "IMG", "start": 15, "end": 18}, {"text": "hyperoside", "start": 23, "end": 33}, {"text": "IMG", "start": 140, "end": 143}, {"text": "hyperoside", "start": 147, "end": 157}]}}, "schema": []}
{"input": "In accordance with these anticoagulant activities, both agents elicited anticoagulant effects in mouse.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, treatment with IMG and hyperoside resulted in inhibition of TNF-alpha-induced production of PAI-1, and treatment with IMG resulted in significant reduction of the PAI-1 to t-PA ratio.", "output": {"entities": {"chemical": [{"text": "IMG", "start": 28, "end": 31}, {"text": "hyperoside", "start": 36, "end": 46}, {"text": "IMG", "start": 131, "end": 134}]}}, "schema": []}
{"input": "The anticoagulant and profibrinolytic effects of IMG were greater than those of hyperoside, indicating positive regulation of its anticoagulant function by the methoxy group of IMG.", "output": {"entities": {"chemical": [{"text": "IMG", "start": 49, "end": 52}, {"text": "hyperoside", "start": 80, "end": 90}, {"text": "methoxy", "start": 160, "end": 167}, {"text": "IMG", "start": 177, "end": 180}]}}, "schema": []}
{"input": "IMG and hyperoside possess antithrombotic activities and offer bases for development of a novel anticoagulant.", "output": {"entities": {"chemical": [{"text": "IMG", "start": 0, "end": 3}, {"text": "hyperoside", "start": 8, "end": 18}]}}, "schema": []}
{"input": "Sirtuins as emerging anti-parasitic targets.", "output": {"entities": {}}, "schema": []}
{"input": "Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of NAD (+)-dependent protein N (epsilon)-acetyl-lysine (AcK) deacetylases.", "output": {"entities": {"chemical": [{"text": "NAD (+)", "start": 74, "end": 81}, {"text": "N (epsilon)-acetyl-lysine", "start": 100, "end": 125}, {"text": "AcK", "start": 127, "end": 130}]}}, "schema": []}
{"input": "Sirtuins are also evolutionarily conserved proteins that are present in all kingdoms of life ranging from bacteria to humans.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, it was recently found that the sirtuins found in various human parasites (especially the Plasmodium, Trypanosoma, and Leishmania species) were pro-survival for the parasites under various conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, these parasitic sirtuins have emerged as novel anti-parasitic therapeutic targets.", "output": {"entities": {}}, "schema": []}
{"input": "This article reviews the currently available structural, biochemical, pharmacological, and medicinal chemistry studies on these enzymes, and discusses the perspectives of selectively targeting the parasitic sirtuins as a novel therapeutic strategy for the human parasitic diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Hepatic glucose metabolism in late pregnancy: normal versus high-fat and-fructose diet.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 8, "end": 15}, {"text": "fructose", "start": 73, "end": 81}]}}, "schema": []}
{"input": "Net hepatic glucose uptake (NHGU) is an important contributor to postprandial glycemic control.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 12, "end": 19}]}}, "schema": []}
{"input": "We hypothesized that NHGU is reduced during normal pregnancy and in a pregnant diet-induced model of impaired glucose intolerance/gestational diabetes mellitus (IGT/GDM).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 110, "end": 117}]}}, "schema": []}
{"input": "Dogs (n = 7 per group) that were nonpregnant (N), normal pregnant (P), or pregnant with IGT/GDM (pregnant dogs fed a high-fat and-fructose diet [P-HFF]) underwent a hyperinsulinemic-hyperglycemic clamp with intraportal glucose infusion.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 130, "end": 138}, {"text": "glucose", "start": 219, "end": 226}]}}, "schema": []}
{"input": "Clamp period insulin, glucagon, and glucose concentrations and hepatic glucose loads did not differ among groups.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 36, "end": 43}, {"text": "glucose", "start": 71, "end": 78}]}}, "schema": []}
{"input": "The N dogs reached near-maximal NHGU rates within 30 min; mean +/- SEM NHGU was 105 +/- 9 micro mol. 100 g liver-(1). min-(1).", "output": {"entities": {}}, "schema": []}
{"input": "The P and P-HFF dogs reached maximal NHGU in 90-120 min; their NHGU was blunted (68 +/- 9 and 16 +/- 17 micro mol. 100 g liver-(1). min-(1), respectively).", "output": {"entities": {}}, "schema": []}
{"input": "Hepatic glycogen synthesis was reduced 20% in P versus N and 40% in P-HFF versus P dogs.", "output": {"entities": {}}, "schema": []}
{"input": "This was associated with a reduction (> 70%) in glycogen synthase activity in P-HFF versus P and increased glycogen phosphorylase (GP) activity in both P (1. 7-fold greater than N) and P-HFF (1. 8-fold greater than P) dogs.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, NHGU under conditions mimicking the postprandial state is delayed and suppressed in normal pregnancy, with concomitant reduction in glycogen storage.", "output": {"entities": {}}, "schema": []}
{"input": "NHGU is further blunted in IGT/GDM.", "output": {"entities": {}}, "schema": []}
{"input": "This likely contributes to postprandial hyperglycemia during pregnancy, with potential adverse outcomes for the fetus and mother.", "output": {"entities": {}}, "schema": []}
{"input": "Hot charge-transfer excitons set the time limit for charge separation at donor/acceptor interfaces in organic photovoltaics.", "output": {"entities": {}}, "schema": []}
{"input": "Photocurrent generation in organic photovoltaics (OPVs) relies on the dissociation of excitons into free electrons and holes at donor/acceptor heterointerfaces.", "output": {"entities": {}}, "schema": []}
{"input": "The low dielectric constant of organic semiconductors leads to strong Coulomb interactions between electron-hole pairs that should in principle oppose the generation of free charges.", "output": {"entities": {}}, "schema": []}
{"input": "The exact mechanism by which electrons and holes overcome this Coulomb trapping is still unsolved, but increasing evidence points to the critical role of hot charge-transfer (CT) excitons in assisting this process.", "output": {"entities": {}}, "schema": []}
{"input": "Here we provide a real-time view of hot CT exciton formation and relaxation using femtosecond nonlinear optical spectroscopies and non-adiabatic mixed quantum mechanics/molecular mechanics simulations in the phthalocyanine-fullerene model OPV system.", "output": {"entities": {"chemical": [{"text": "phthalocyanine", "start": 208, "end": 222}, {"text": "fullerene", "start": 223, "end": 232}]}}, "schema": []}
{"input": "For initial excitation on phthalocyanine, hot CT excitons are formed in 10 (-13) s, followed by relaxation to lower energies and shorter electron-hole distances on a 10 (-12) s timescale.", "output": {"entities": {"chemical": [{"text": "phthalocyanine", "start": 26, "end": 40}]}}, "schema": []}
{"input": "This hot CT exciton cooling process and collapse of charge separation sets the fundamental time limit for competitive charge separation channels that lead to efficient photocurrent generation.", "output": {"entities": {}}, "schema": []}
{"input": "Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetic cardiomyopathy is associated with suppression of cardiac autophagy, and activation of AMP-activated protein kinase (AMPK) restores cardiac autophagy and prevents cardiomyopathy in diabetic mice, albeit by an unknown mechanism.", "output": {"entities": {"chemical": [{"text": "AMP", "start": 95, "end": 98}]}}, "schema": []}
{"input": "We hypothesized that AMPK-induced autophagy ameliorates diabetic cardiomyopathy by inhibiting cardiomyocyte apoptosis and examined the effects of AMPK on the interaction between Beclin1 and Bcl-2, a switch between autophagy and apoptosis, in diabetic mice and high glucose-treated H9c2 cardiac myoblast cells.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 265, "end": 272}]}}, "schema": []}
{"input": "Exposure of H9c2 cells to high glucose reduced AMPK activity, inhibited Jun NH2-terminal kinase 1 (JNK1)-B-cell lymphoma 2 (Bcl-2) signaling, and promoted Beclin1 binding to Bcl-2.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 31, "end": 38}, {"text": "NH2", "start": 76, "end": 79}]}}, "schema": []}
{"input": "Conversely, activation of AMPK by metformin stimulated JNK1-Bcl-2 signaling and disrupted the Beclin1-Bcl-2 complex.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of AMPK, which normalized cardiac autophagy, attenuated high glucose-induced apoptosis in cultured H9c2 cells.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 72, "end": 79}]}}, "schema": []}
{"input": "This effect was attenuated by inhibition of autophagy.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, chronic administration of metformin in diabetic mice restored cardiac autophagy by activating JNK1-Bcl-2 pathways and dissociating Beclin1 and Bcl-2.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 35, "end": 44}]}}, "schema": []}
{"input": "The induction of autophagy protected against cardiac apoptosis and improved cardiac structure and function in diabetic mice.", "output": {"entities": {}}, "schema": []}
{"input": "We concluded that dissociation of Bcl-2 from Beclin1 may be an important mechanism for preventing diabetic cardiomyopathy via AMPK activation that restores autophagy and protects against cardiac apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Induction of hepatic CYP3A enzymes by pregnancy-related hormones: studies in human hepatocytes and hepatic cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "CYP3A activity is induced by approximately 2-fold during the third trimester of human pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Placental growth hormone (PGH), estrogens (primarily 17 beta-estradiol), cortisol, and progesterone have the potential to modulate CYP3A activity.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 32, "end": 41}, {"text": "17 beta-estradiol", "start": 53, "end": 70}, {"text": "cortisol", "start": 73, "end": 81}, {"text": "progesterone", "start": 87, "end": 99}]}}, "schema": []}
{"input": "Therefore, we determined whether the elevated plasma concentrations of these hormones during pregnancy induce hepatic CYP3A expression.", "output": {"entities": {}}, "schema": []}
{"input": "We incubated sandwich-cultured human hepatocytes (SCHH) from premenopausal female donors (n = 2) with the physiologic (unbound, 1 x total) and the 10 x total third trimester hormone plasma concentrations (individually and in combination) and determined their effect on CYP3A activity and the transcripts of CYP3A4, CYP3A5, and the respective hormone receptors (growth hormone receptor, glucocorticoid receptor, and estrogen receptor alpha).", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 415, "end": 423}]}}, "schema": []}
{"input": "Of all the hormones, cortisol was the most potent inducer of CYP3A activity and CYP3A4, CYP3A5 mRNA expression.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 21, "end": 29}]}}, "schema": []}
{"input": "The combination of PGH/growth hormone and cortisol induced CYP3A activity and expression significantly more than did cortisol alone.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 42, "end": 50}, {"text": "cortisol", "start": 117, "end": 125}]}}, "schema": []}
{"input": "When incubated with the unbound or total plasma concentration of all the hormones, CYP3A activity in SCHH was induced to an extent comparable to that observed in vivo during the third trimester.", "output": {"entities": {}}, "schema": []}
{"input": "These hormones had only a modest effect on the mRNA expression of the hormone receptors.", "output": {"entities": {}}, "schema": []}
{"input": "The pattern of induction observed in SCHH was reproduced in HepaRG cells but not in HuH7/HepG2 cells.", "output": {"entities": {}}, "schema": []}
{"input": "SCHH or HepaRG cells could be used to determine the mechanistic basis of CYP3A induction during pregnancy and to predict the magnitude of induction likely to be observed during the first and second trimesters, when phenotyping studies to measure in vivo CYP3A activity are logistically difficult to perform.", "output": {"entities": {}}, "schema": []}
{"input": "Aqueous phase synthesis of copper nanoparticles: a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems.", "output": {"entities": {"chemical": [{"text": "copper", "start": 27, "end": 33}]}}, "schema": []}
{"input": "We demonstrate aqueous phase biosynthesis of phase-pure metallic copper nanoparticles (CuNPs) using a silver resistant bacterium Morganella morganii.", "output": {"entities": {"chemical": [{"text": "copper", "start": 65, "end": 71}, {"text": "silver", "start": 102, "end": 108}]}}, "schema": []}
{"input": "This is particularly important considering that there has been no report that demonstrates biosynthesis and stabilization of pure copper nanoparticles in the aqueous phase.", "output": {"entities": {}}, "schema": []}
{"input": "Electrochemical analysis of bacterial cells exposed to Cu (2 +) ions provides new insights into the mechanistic aspect of Cu (2 +) ion reduction within the bacterial cell and indicates a strong link between the silver and copper resistance machinery of bacteria in the context of metal ion reduction.", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 55, "end": 63}, {"text": "Cu (2 +)", "start": 122, "end": 130}, {"text": "silver", "start": 211, "end": 217}, {"text": "copper", "start": 222, "end": 228}]}}, "schema": []}
{"input": "The outcomes of this study take us a step closer towards designing rational strategies for biosynthesis of different metal nanoparticles using microorganisms.", "output": {"entities": {}}, "schema": []}
{"input": "Membrane protein native state discrimination by implicit membrane models.", "output": {"entities": {}}, "schema": []}
{"input": "Four implicit membrane models [IMM1, generalized Born (GB)-surface area-implicit membrane (GBSAIM), GB with a simple switching (GBSW), and heterogeneous dielectric GB (HDGB)] were tested for their ability to discriminate the native conformation of five membrane proteins from 450 decoys generated by the Rosetta-Membrane program.", "output": {"entities": {}}, "schema": []}
{"input": "The energy ranking of the native state and Z-scores were used to assess the performance of the models.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of membrane thickness was examined and was found to be substantial.", "output": {"entities": {}}, "schema": []}
{"input": "Quite satisfactory discrimination was achieved with the all-atom IMM1 and GBSW models at 25. 4 A thickness and with the HDGB model at 28. 5 A thickness.", "output": {"entities": {}}, "schema": []}
{"input": "The energy components by themselves were not discriminative.", "output": {"entities": {}}, "schema": []}
{"input": "Both van der Waals and electrostatic interactions contributed to native state discrimination, to a different extent in each model.", "output": {"entities": {}}, "schema": []}
{"input": "Computational efficiency of the models decreased in the order: extended-atom IMM1 > all-atom IMM1 > GBSAIM > GBSW > HDGB.", "output": {"entities": {}}, "schema": []}
{"input": "These results encourage the further development and use of implicit membrane models for membrane protein structure prediction.", "output": {"entities": {}}, "schema": []}
{"input": "2-Phenoxy-nicotinamides are potent agonists at the bile acid receptor GPBAR1 (TGR5).", "output": {"entities": {"chemical": [{"text": "2-Phenoxy-nicotinamides", "start": 0, "end": 23}, {"text": "bile acid", "start": 51, "end": 60}]}}, "schema": []}
{"input": "Potency with potential: 2-Phenoxy-nicotinamides were identified as potent agonists at the GPBAR1 receptor, a target in the treatment of obesity, type 2 diabetes and metabolic syndrome.", "output": {"entities": {"chemical": [{"text": "2-Phenoxy-nicotinamides", "start": 24, "end": 47}]}}, "schema": []}
{"input": "Extensive structure-activity relationship studies supported by homology modeling and docking resulted in the identification of optimized GPBAR1 agonists, potent against both human and mouse receptors, endowed with favorable physicochemical properties and good metabolic stability.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of ganglioside GM3 synthase gene knockout on the glycoprotein N-glycan profile of mouse embryonic fibroblast.", "output": {"entities": {"chemical": [{"text": "ganglioside", "start": 10, "end": 21}]}}, "schema": []}
{"input": "The structural and clinical significance of cellular glycoproteins and glycosphingolipids (GSLs) are often separately discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Considering the biosynthetic pathway of glycoconjugates, glycans of cell-surface glycoproteins and GSLs might partially share functions in maintaining cellular homeostatis.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study is to establish a general and comprehensive glycomics protocol for cellular GSLs and N-glycans of glycoproteins.", "output": {"entities": {}}, "schema": []}
{"input": "To test the feasibility of a glycoblotting-based protocol, whole glycans released both from GSLs and glycoproteins were profiled concurrently by using GM3 synthase-deficient mouse embryonic fibroblast GM3 (-/-).", "output": {"entities": {}}, "schema": []}
{"input": "GM3 (-/-) cells did not synthesize GM3 or any downstream product of GM3 synthase.", "output": {"entities": {}}, "schema": []}
{"input": "Instead, expression levels of o-series gangliosides involving GM1-b and GD1-alpha increased dramatically, whereas a-/b-series gangliosides were predominantly detected in wild-type (WT) cells.", "output": {"entities": {"chemical": [{"text": "gangliosides", "start": 39, "end": 51}]}}, "schema": []}
{"input": "We also discovered that glycoprotein N-glycan profiles of GM3 (-/-) cells are significantly altered as compared to WT cells, although GM3 synthase is responsible only for GSLs synthesis and is not associated with glycoprotein N-glycan biosynthesis.", "output": {"entities": {}}, "schema": []}
{"input": "The present approach allows for high-throughput profiling of cellular glycomes enriched by different classes of glycoconjugates, and our results demonstrated that gene knockout of the enzymes responsible for GSL biosynthesis significantly influences the N-glycans of glycoproteins.", "output": {"entities": {}}, "schema": []}
{"input": "Organotins: A review of their reproductive toxicity, biochemistry, and environmental fate.", "output": {"entities": {"chemical": [{"text": "Organotins", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The review purposes are to (1) evaluate the experimental evidence for adverse effects on reproduction and metabolism and (2) identify the current knowledge of analytical procedures, biochemistry and environmental aspects relating to organotins.", "output": {"entities": {"chemical": [{"text": "organotins", "start": 233, "end": 243}]}}, "schema": []}
{"input": "Organotins are pollutants that are used as biocides in antifouling paints.", "output": {"entities": {"chemical": [{"text": "Organotins", "start": 0, "end": 10}]}}, "schema": []}
{"input": "They produce endocrine-disrupting effects in mollusks, such as imposex.", "output": {"entities": {}}, "schema": []}
{"input": "In rodents, organotin exposure induces developmental and reproductive toxicity as well as alteration of metabolic homeostasis through its action as an obesogen.", "output": {"entities": {"chemical": [{"text": "organotin", "start": 12, "end": 21}]}}, "schema": []}
{"input": "The adverse effects that appear in rodents have raised concerns about organotins' potential health risk to humans in relation to organotin exposure.", "output": {"entities": {"chemical": [{"text": "organotins", "start": 70, "end": 80}, {"text": "organotin", "start": 129, "end": 138}]}}, "schema": []}
{"input": "At present, triorganotin, such as tributyltin, have been demonstrated to produce imposex, and mammalian reproductive and metabolic toxicity.", "output": {"entities": {"chemical": [{"text": "triorganotin", "start": 12, "end": 24}, {"text": "tributyltin", "start": 34, "end": 45}]}}, "schema": []}
{"input": "For most mammals, triorganotin exposure predominantly occurs through the ingestion, and this compound can cross the placenta.", "output": {"entities": {"chemical": [{"text": "triorganotin", "start": 18, "end": 30}]}}, "schema": []}
{"input": "With these risks in mind, it is important to improve our knowledge of organotins' effects on environmental health.", "output": {"entities": {"chemical": [{"text": "organotins", "start": 70, "end": 80}]}}, "schema": []}
{"input": "Multiple microRNAs may regulate the DNA repair enzyme uracil-DNA glycosylase.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 54, "end": 60}]}}, "schema": []}
{"input": "Human nuclear uracil-DNA glycosylase UNG2 is essential for post-replicative repair of uracil in DNA, and UNG2 protein and mRNA levels rapidly decline in G2/M phase.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 14, "end": 20}, {"text": "uracil", "start": 86, "end": 92}]}}, "schema": []}
{"input": "Previous work has demonstrated regulation of UNG2 at the transcriptional level, as well as by protein phosphorylation and ubiquitylation.", "output": {"entities": {}}, "schema": []}
{"input": "UNG2 mRNA, encoded by the UNG gene, contains a long 3' untranslated region (3' UTR) of previously unknown function.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate that several conserved regions in the 3' UTR are potential seed sites for microRNAs (miRNAs), such as miR-16, miR-34c, and miR-199a.", "output": {"entities": {}}, "schema": []}
{"input": "Our results show that these miRNAs down-regulate UNG activity, UNG mRNA, and UNG protein levels.", "output": {"entities": {}}, "schema": []}
{"input": "Down-regulation was dependent on the 3' UTR, indicating that the miRNAs directly target the conserved seed sites in the 3' UTR.", "output": {"entities": {}}, "schema": []}
{"input": "These results add miRNAs as a new modality to UNG' s increasing list of complex regulatory mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative characterization of non-contact microdispensing technologies for the sub-microliter range.", "output": {"entities": {}}, "schema": []}
{"input": "This work describes how to effectively compare non-contact dispensing technologies for automated liquid handling under high-throughput screening (HTS) conditions in the range of 0. 05-10 mu l.", "output": {"entities": {}}, "schema": []}
{"input": "Exemplarily, we characterize five established technologies and categorize them into valve-based and positive displacement-based technologies.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore we introduce dispensing accuracy and precision in an' intra-run',' inter-run' and' tip-to-tip' context as universally applicable performance parameters.", "output": {"entities": {}}, "schema": []}
{"input": "A NIST traceable spectrophotometric measurement method is utilized for experimental characterization.", "output": {"entities": {}}, "schema": []}
{"input": "It yields an Intra-Run CV (Inter-Run CV) between 0. 4% to 7. 7% (0. 5 to 10. 9%) and a Tip-to-Tip CV between 1. 4% and 9. 9% for target volumes < 1 mu l.", "output": {"entities": {}}, "schema": []}
{"input": "An absolute accuracy of better than 5. 0% is generally difficult to achieve in the sub-microliter range.", "output": {"entities": {}}, "schema": []}
{"input": "Targeting VEGF signalling via the neuropilin co-receptor.", "output": {"entities": {}}, "schema": []}
{"input": "The blockade of tumour vascularisation and angiogenesis continues to be a focus for drug development in oncology and other pathologies.", "output": {"entities": {}}, "schema": []}
{"input": "Historically, targeting vascular endothelial growth factor (VEGF) activity and its association with VEGF receptors (VEGFRs) has represented the most promising line of attack.", "output": {"entities": {}}, "schema": []}
{"input": "More recently, the recognition that VEGFR co-receptors, neuropilin-1 and-2 (NRP1 and NRP2), are also engaged by specific VEGF isoforms in tandem with the VEGFRs has expanded the landscape for the development of modulators of VEGF-dependent signalling.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review the recent structural characterisation of VEGF interactions with NRP subdomains and the impact this has had on drug development activity in this area.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative modification of neurofilament-L and neuronal cell death induced by the catechol neurotoxin, tetrahydropapaveroline.", "output": {"entities": {"chemical": [{"text": "catechol", "start": 81, "end": 89}, {"text": "tetrahydropapaveroline", "start": 102, "end": 124}]}}, "schema": []}
{"input": "Tetrahydropapaveroline (THP), which is an endogenous neurotoxin, has been suspected to be associated with dopaminergic neurotoxicity of l-DOPA.", "output": {"entities": {"chemical": [{"text": "Tetrahydropapaveroline", "start": 0, "end": 22}, {"text": "THP", "start": 24, "end": 27}, {"text": "l-DOPA", "start": 136, "end": 142}]}}, "schema": []}
{"input": "In this study, we examined oxidative modification of neurofilament-L (NF-L) and neuronal cell death induced by THP.", "output": {"entities": {"chemical": [{"text": "THP", "start": 111, "end": 114}]}}, "schema": []}
{"input": "When disassembled NF-L was incubated with THP, protein aggregation was increased in a time-and THP dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "THP", "start": 42, "end": 45}, {"text": "THP", "start": 95, "end": 98}]}}, "schema": []}
{"input": "The formation of carbonyl compounds and dityrosine were observed in the THP-mediated NF-L aggregates.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 17, "end": 25}, {"text": "dityrosine", "start": 40, "end": 50}, {"text": "THP", "start": 72, "end": 75}]}}, "schema": []}
{"input": "Radical scavengers reduced THP-mediated NF-L modification.", "output": {"entities": {"chemical": [{"text": "THP", "start": 27, "end": 30}]}}, "schema": []}
{"input": "These results suggest that the modification of NF-L by THP may be due to oxidative damage resulting from the generation of reactive oxygen species (ROS).", "output": {"entities": {"chemical": [{"text": "THP", "start": 55, "end": 58}, {"text": "oxygen", "start": 132, "end": 138}]}}, "schema": []}
{"input": "When THP exposed NF-L was subjected to amino acid analysis, glutamate, proline and lysine residues were found to be particularly sensitive.", "output": {"entities": {"chemical": [{"text": "THP", "start": 5, "end": 8}, {"text": "amino acid", "start": 39, "end": 49}, {"text": "glutamate", "start": 60, "end": 69}, {"text": "proline", "start": 71, "end": 78}, {"text": "lysine", "start": 83, "end": 89}]}}, "schema": []}
{"input": "We also investigated the effects of copper ions on THP-mediated NF-L modification.", "output": {"entities": {"chemical": [{"text": "copper", "start": 36, "end": 42}, {"text": "THP", "start": 51, "end": 54}]}}, "schema": []}
{"input": "At a low concentration of THP, copper ions enhanced the modification of NF-L.", "output": {"entities": {"chemical": [{"text": "THP", "start": 26, "end": 29}, {"text": "copper", "start": 31, "end": 37}]}}, "schema": []}
{"input": "Treatment of C6 astrocyte cells with THP led to a concentration-dependent reduction in cell viability.", "output": {"entities": {"chemical": [{"text": "THP", "start": 37, "end": 40}]}}, "schema": []}
{"input": "When these cells were treated with 100 mu M THP, the levels of ROS increased 3. 5-fold compared with control cells.", "output": {"entities": {"chemical": [{"text": "THP", "start": 44, "end": 47}]}}, "schema": []}
{"input": "Furthermore, treatment of cells with THP increased NF-L aggregate formation, suggesting the involvement of NF-L modification in THP-induced cell damage.", "output": {"entities": {"chemical": [{"text": "THP", "start": 37, "end": 40}, {"text": "THP", "start": 128, "end": 131}]}}, "schema": []}
{"input": "Synthesis and antibacterial evaluation of novel 11, 4''-disubstituted azithromycin analogs with greatly improved activity against erythromycin-resistant bacteria.", "output": {"entities": {"chemical": [{"text": "11, 4''-disubstituted azithromycin", "start": 48, "end": 82}, {"text": "erythromycin", "start": 130, "end": 142}]}}, "schema": []}
{"input": "A series of novel 11, 4''-disubstituted azithromycin analogs were synthesized and evaluated for their antibacterial activity.", "output": {"entities": {"chemical": [{"text": "11, 4''-disubstituted azithromycin", "start": 18, "end": 52}]}}, "schema": []}
{"input": "All the 11, 4''-disubstituted analogs exhibited excellent activity (0. 03-0. 12 mu g/ml) against erythromycin-susceptible Streptococcus pneumoniae, and significantly improved activity against three phenotypes of erythromycin-resistant S. pneumoniae compared with erythromycin A, clarithromycin or azithromycin.", "output": {"entities": {"chemical": [{"text": "erythromycin", "start": 97, "end": 109}, {"text": "erythromycin", "start": 212, "end": 224}, {"text": "erythromycin A", "start": 263, "end": 277}, {"text": "clarithromycin", "start": 279, "end": 293}, {"text": "azithromycin", "start": 297, "end": 309}]}}, "schema": []}
{"input": "Among them, compounds 26-28 showed the most potent activity (0. 25, 0. 03 and 2 mu g/ml) against S. pneumoniae expressing the erm gene, the mef gene and the erm and mef genes, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, compound 28 was the most effective (0. 03 and 0. 12 mu g/ml) against erythromycin-susceptible S. pneumoniae and Staphylococcus aureus as well.", "output": {"entities": {"chemical": [{"text": "erythromycin", "start": 82, "end": 94}]}}, "schema": []}
{"input": "It is noteworthy that the most active compounds described above possess the same terminal 3, 5-dinitrophenyl groups on their C-4'' bisamide side chains.", "output": {"entities": {"chemical": [{"text": "3, 5-dinitrophenyl", "start": 90, "end": 108}, {"text": "bisamide", "start": 131, "end": 139}]}}, "schema": []}
{"input": "Neutral and charged phosphine/scorpionate copper (I) complexes: effects of ligand assembly on their antiproliferative activity.", "output": {"entities": {"chemical": [{"text": "phosphine/scorpionate copper (I) complexes", "start": 20, "end": 62}]}}, "schema": []}
{"input": "Ligand-exchange reactions of copper (I) precursors ([Cu (CH (3) CN) (4)] BF (4), CuCl) with a panel of bis (azolyl) borates or poly (pyrazolyl) methanes and a tertiary monodentate phosphine (PTA = 1, 3, 5-triaza-7-phosphaadamantane, PCN = tris (cyanoethyl) phosphine) produced two series of heteroleptic, either' 2 + 1 + 1'-or' 3 + 1'-type complexes, which have been characterized by elemental analysis, FT-IR, ESI-MS and multinuclear (31) P and (1) H NMR.", "output": {"entities": {"chemical": [{"text": "copper (I)", "start": 29, "end": 39}, {"text": "[Cu (CH (3) CN) (4)] BF (4)", "start": 52, "end": 79}, {"text": "CuCl", "start": 81, "end": 85}, {"text": "bis (azolyl) borates", "start": 103, "end": 123}, {"text": "poly (pyrazolyl) methanes", "start": 127, "end": 152}, {"text": "tertiary monodentate phosphine", "start": 159, "end": 189}, {"text": "PTA", "start": 191, "end": 194}, {"text": "1, 3, 5-triaza-7-phosphaadamantane", "start": 197, "end": 231}, {"text": "PCN", "start": 233, "end": 236}, {"text": "tris (cyanoethyl) phosphine", "start": 239, "end": 266}, {"text": "(31) P", "start": 435, "end": 441}, {"text": "(1) H", "start": 446, "end": 451}]}}, "schema": []}
{"input": "' 2 + 1 + 1'-type complexes include a N, N-bidentate chelate and two monodentate phosphines (1-8) and' 3 + 1'-type complexes comprise a N, N, O-or N, N, N-tridentate chelate and one monodentate phosphine (9-12).", "output": {"entities": {"chemical": [{"text": "N", "start": 38, "end": 39}, {"text": "N", "start": 41, "end": 42}, {"text": "phosphines", "start": 81, "end": 91}, {"text": "N", "start": 136, "end": 137}, {"text": "N", "start": 139, "end": 140}, {"text": "O", "start": 142, "end": 143}, {"text": "N", "start": 147, "end": 148}, {"text": "N", "start": 150, "end": 151}, {"text": "N", "start": 153, "end": 154}, {"text": "phosphine", "start": 194, "end": 203}]}}, "schema": []}
{"input": "All these complexes adopt a four-coordinate, tetrahedral geometry.", "output": {"entities": {}}, "schema": []}
{"input": "' 3 + 1' complexes show better red-ox stability and a greater tendency to retain the native' 3 + 1' mixed-ligand structure.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely,' 2 + 1 + 1' complexes exhibit increased propensity to dissociation as shown by ESI-MS measurements and X-ray structure determination at low temperature (150 K) of the polymeric complex {[H (2) B (tz (NO2)) (2)] Cu [PCN]} (n) 6b.", "output": {"entities": {"chemical": [{"text": "{[H (2) B (tz (NO2)) (2)] Cu [PCN]} (n)", "start": 197, "end": 236}]}}, "schema": []}
{"input": "In this complex, either the bis (triazolyl) borate and the PCN ligands act as bidentate, with PCN being also the mu (2)-bridiging linker between adjacent monomers.", "output": {"entities": {"chemical": [{"text": "bis (triazolyl) borate", "start": 28, "end": 50}, {"text": "PCN", "start": 59, "end": 62}, {"text": "PCN", "start": 94, "end": 97}]}}, "schema": []}
{"input": "Compound 6b is the first reported example of a polymeric PCN compound with a tetra-coordinate metal centre.", "output": {"entities": {"chemical": [{"text": "PCN", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Cytotoxic activity of all compounds has been evaluated by MTT test against a panel of several human tumor cell lines including examples of breast (MCF-7), colon (HCT-15 and LoVo), lung (A549), cervix (A431) and ovarian (2008 and its cisplatin resistant variant, C13 *) carcinoma, melanoma (A375) and promyelocytic leukemia (HL60).", "output": {"entities": {"chemical": [{"text": "MTT", "start": 58, "end": 61}, {"text": "cisplatin", "start": 233, "end": 242}]}}, "schema": []}
{"input": "Copper complexes generally show in vitro antitumour activity comparable to that of cisplatin.", "output": {"entities": {"chemical": [{"text": "Copper", "start": 0, "end": 6}, {"text": "cisplatin", "start": 83, "end": 92}]}}, "schema": []}
{"input": "In particular, neutral' 3 + 1'-type complexes 9 and 10, show IC (50) values appreciably lower than those exhibited by the reference metallodrug.", "output": {"entities": {}}, "schema": []}
{"input": "Utilizing Eisenia andrei to assess the ecotoxicity of platinum mine tailings disposal facilities.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 54, "end": 62}]}}, "schema": []}
{"input": "South Africa is an important platinum mining country which results in environmental impacts due to the construction of tailing disposal facilities (TDFs).", "output": {"entities": {"chemical": [{"text": "platinum", "start": 29, "end": 37}]}}, "schema": []}
{"input": "It is unclear what the effects of ageing are on the ecotoxicity of TDFs and whether it increases or decreases over time.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to determine the ecotoxicity of differently aged TDFs by investigating earthworm (Eisenia andrei) responses viz. growth, reproduction, neutral red retention times (NRRT) and tissue metal concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "Further, to evaluate the status of these in terms of a geoaccumulation index (I (geo)), pollution index and integrated pollution index.", "output": {"entities": {}}, "schema": []}
{"input": "Results indicated that earthworms showed reduced reproductive success (hatchlings per cocoon) and decreased NRRT in all the sites.", "output": {"entities": {}}, "schema": []}
{"input": "Juveniles per cocoon between all of the different treatment groups were; control (2. 83 +/- 0. 54) > site 2 (20 years old; 1. 83 +/- 0. 27) > sites 1 and 3 (40 years old; 1. 06 +/- 0. 15 and 6 years old; 0. 88 +/- 0. 39).", "output": {"entities": {}}, "schema": []}
{"input": "This might be ascribed to the elevated levels of Cr (+/- 200 to 1, 166 mu g g (-1)) and Ni (+/- 100 to 316 mu g g (-1)) in all of the sites.", "output": {"entities": {"chemical": [{"text": "Cr", "start": 49, "end": 51}, {"text": "Ni", "start": 88, "end": 90}]}}, "schema": []}
{"input": "Earthworms did not bioaccumulate metals with bioconcentration factors for all the different treatments < 0. 01.", "output": {"entities": {}}, "schema": []}
{"input": "Studies like these could be useful when establishing a ranking of TDFs in the future to provide legislative institutions with an indication of the environmental liabilities of platinum mines.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 176, "end": 184}]}}, "schema": []}
{"input": "Oxidative folding of peptides with cystine-knot architectures: kinetic studies and optimization of folding conditions.", "output": {"entities": {"chemical": [{"text": "cystine", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Bioactive peptides often contain several disulfide bonds that provide the main contribution to conformational rigidity and structural, thermal, or biological stability.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 41, "end": 50}]}}, "schema": []}
{"input": "Among them, cystine-knot peptides-commonly named \" knottins \"-make up a subclass with several thousand natural members.", "output": {"entities": {"chemical": [{"text": "cystine", "start": 12, "end": 19}]}}, "schema": []}
{"input": "Hence, they are considered promising frameworks for peptide-based pharmaceuticals.", "output": {"entities": {}}, "schema": []}
{"input": "Although cystine-knot peptides are available through chemical and recombinant synthetic routes, oxidative folding to afford the bioactive isomers still remains a crucial step.", "output": {"entities": {"chemical": [{"text": "cystine", "start": 9, "end": 16}]}}, "schema": []}
{"input": "We therefore investigated the oxidative folding of ten protease-inhibiting peptides from two knottin families, as well as that of an HIV entry inhibitor and of aprotinin, under two conventional sets of folding conditions and by a newly developed procedure.", "output": {"entities": {}}, "schema": []}
{"input": "Kinetic studies identified folding conditions that resulted in correctly folded miniproteins with high rates of conversion even for highly hydrophobic and aggregation-prone peptides in concentrated solutions.", "output": {"entities": {}}, "schema": []}
{"input": "Identification and characterization of a potent activator of p53-independent cellular senescence via a small-molecule screen for modifiers of the integrated stress response.", "output": {"entities": {}}, "schema": []}
{"input": "The Integrated Stress Response (ISR) is a signaling program that enables cellular adaptation to stressful conditions like hypoxia and nutrient deprivation in the tumor microenvironment.", "output": {"entities": {}}, "schema": []}
{"input": "An important effector of the ISR is activating transcription factor 4 (ATF4), a transcription factor that regulates genes involved in redox homeostasis and amino acid metabolism and transport.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 156, "end": 166}]}}, "schema": []}
{"input": "Because both inhibition and overactivation of the ISR can induce tumor cell death, modulators of ATF4 expression could prove to be clinically useful.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, chemical libraries were screened for modulators of ATF4 expression.", "output": {"entities": {}}, "schema": []}
{"input": "We identified one compound, E235 (N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo [d] imidazo [2, 1-b] thiazole-7-carboxamide), that activated the ISR and dose-dependently increased levels of ATF4 in transformed cells.", "output": {"entities": {"chemical": [{"text": "E235 (N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo [d] imidazo [2, 1-b] thiazole-7-carboxamide)", "start": 28, "end": 132}]}}, "schema": []}
{"input": "A dose-dependent decrease in viability was observed in several mouse and human tumor cell lines, and knockdown of ATF4 significantly increased the antiproliferative effects of E235.", "output": {"entities": {"chemical": [{"text": "E235", "start": 176, "end": 180}]}}, "schema": []}
{"input": "Interestingly, low mu M doses of E235 induced senescence in many cell types, including HT1080 human fibrosarcoma and B16F10 mouse melanoma cells.", "output": {"entities": {"chemical": [{"text": "E235", "start": 33, "end": 37}]}}, "schema": []}
{"input": "E235-mediated induction of senescence was not dependent on p21 or p53; however, p21 conferred protection against the growth inhibitory effects of E235.", "output": {"entities": {"chemical": [{"text": "E235", "start": 0, "end": 4}, {"text": "E235", "start": 146, "end": 150}]}}, "schema": []}
{"input": "Treatment with E235 resulted in an increase in cells arrested at the G2/M phase with a concurrent decrease in S-phase cells.", "output": {"entities": {"chemical": [{"text": "E235", "start": 15, "end": 19}]}}, "schema": []}
{"input": "E235 also activated DNA damage response signaling, resulting in increased levels of Ser15-phosphorylated p53, gamma-H2AX, and phosphorylated checkpoint kinase 2 (Chk2), although E235 does not appear to cause physical DNA damage.", "output": {"entities": {"chemical": [{"text": "E235", "start": 0, "end": 4}, {"text": "Ser15", "start": 84, "end": 89}, {"text": "E235", "start": 178, "end": 182}]}}, "schema": []}
{"input": "Induction of gamma-H2AX was abrogated in ATF4 knockdown cells.", "output": {"entities": {}}, "schema": []}
{"input": "Together, these results suggest that modulation of the ISR pathway with the small molecule E235 could be a promising antitumor strategy.", "output": {"entities": {"chemical": [{"text": "E235", "start": 91, "end": 95}]}}, "schema": []}
{"input": "PHF6 regulates cell cycle progression by suppressing ribosomal RNA synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Mutation of PHF6, which results in the X-linked mental retardation disorder B o rjeson-Forssman-Lehmann syndrome, is also present in about 38% of adult T-cell acute lymphoblastic leukemias and 3% of adult acute myeloid leukemias.", "output": {"entities": {}}, "schema": []}
{"input": "However, it remains to be determined exactly how PHF6 acts in vivo and what functions of PHF6 may be associated with its putative tumor suppressor function.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate that PHF6 is a nucleolus, ribosomal RNA promoter-associated protein.", "output": {"entities": {}}, "schema": []}
{"input": "PHF6 directly interacts with upstream binding factor (UBF) through its PHD1 domain and suppresses ribosomal RNA (rRNA) transcription by affecting the protein level of UBF.", "output": {"entities": {}}, "schema": []}
{"input": "Knockdown of PHF6 impairs cell proliferation and arrests cells at G (2)/M phase, which is accompanied by an increased level of phosphorylated H2AX, indicating that PHF6 deficiency leads to the accumulation of DNA damage in the cell.", "output": {"entities": {}}, "schema": []}
{"input": "We found that increased DNA damage occurs at the ribosomal DNA (rDNA) locus in PHF6-deficient cells.", "output": {"entities": {}}, "schema": []}
{"input": "This effect could be reversed by knocking down UBF or overexpressing RNASE1, which removes RNA-DNA hybrids, suggesting that there is a functional link between rRNA synthesis and genomic stability at the rDNA locus.", "output": {"entities": {}}, "schema": []}
{"input": "Together, these results reveal that the key function of PHF6 is involved in regulating rRNA synthesis, which may contribute to its roles in cell cycle control, genomic maintenance, and tumor suppression.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding how noncatalytic carbohydrate binding modules can display specificity for xyloglucan.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 31, "end": 43}]}}, "schema": []}
{"input": "Plant biomass is central to the carbon cycle and to environmentally sustainable industries exemplified by the biofuel sector.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 32, "end": 38}]}}, "schema": []}
{"input": "Plant cell wall degrading enzymes generally contain noncatalytic carbohydrate binding modules (CBMs) that fulfil a targeting function, which enhances catalysis.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 65, "end": 77}]}}, "schema": []}
{"input": "CBMs that bind beta-glucan chains often display broad specificity recognizing beta 1, 4-glucans (cellulose), beta 1, 3-beta 1, 4-mixed linked glucans and xyloglucan, a beta 1, 4-glucan decorated with alpha 1, 6-xylose residues, by targeting structures common to the three polysaccharides.", "output": {"entities": {"chemical": [{"text": "alpha 1, 6-xylose", "start": 200, "end": 217}]}}, "schema": []}
{"input": "Thus, CBMs that recognize xyloglucan target the beta 1, 4-glucan backbone and only accommodate the xylose decorations.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that two closely related CBMs, CBM65A and CBM65B, derived from EcCel5A, a Eubacterium cellulosolvens endoglucanase, bind to a range of beta-glucans but, uniquely, display significant preference for xyloglucan.", "output": {"entities": {}}, "schema": []}
{"input": "The structures of the two CBMs reveal a beta-sandwich fold.", "output": {"entities": {}}, "schema": []}
{"input": "The ligand binding site comprises the beta-sheet that forms the concave surface of the proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Binding to the backbone chains of beta-glucans is mediated primarily by five aromatic residues that also make hydrophobic interactions with the xylose side chains of xyloglucan, conferring the distinctive specificity of the CBMs for the decorated polysaccharide.", "output": {"entities": {"chemical": [{"text": "xylose", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Significantly, and in contrast to other CBMs that recognize beta-glucans, CBM65A utilizes different polar residues to bind cellulose and mixed linked glucans.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, Gln (106) is central to cellulose recognition, but is not required for binding to mixed linked glucans.", "output": {"entities": {"chemical": [{"text": "Gln", "start": 6, "end": 9}]}}, "schema": []}
{"input": "This report reveals the mechanism by which beta-glucan-specific CBMs can distinguish between linear and mixed linked glucans, and show how these CBMs can exploit an extensive hydrophobic platform to target the side chains of decorated beta-glucans.", "output": {"entities": {}}, "schema": []}
{"input": "EBEC 2012--an energetic time in Freiburg.", "output": {"entities": {}}, "schema": []}
{"input": "The seventeenth European Bioenergetics Conference (EBEC) took place in September 2012 at the Albert-Ludwigs-University in Freiburg, Germany, and was hosted by Thorsten Friedrich.", "output": {"entities": {}}, "schema": []}
{"input": "The conference is a biannual event that brings together researchers from across the globe to discuss progress in this diverse and challenging field.", "output": {"entities": {}}, "schema": []}
{"input": "The bovine ATP-binding cassette transporter ABCG2 Tyr581Ser single-nucleotide polymorphism increases milk secretion of the fluoroquinolone danofloxacin.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 11, "end": 14}, {"text": "danofloxacin", "start": 139, "end": 151}]}}, "schema": []}
{"input": "The bovine adenosine triphosphate-binding cassette transporter G2 (ABCG2/breast cancer resistance protein) polymorphism Tyr581Ser (Y581S) has recently been shown to increase in vitro transepithelial transport of antibiotics.", "output": {"entities": {"chemical": [{"text": "adenosine triphosphate", "start": 11, "end": 33}]}}, "schema": []}
{"input": "Since this transporter has been extensively related to the active secretion of drugs into milk, the potential in vivo effect of this polymorphism on secretion of xenobiotics in livestock could have striking consequences for milk production, the dairy industry, and public health.", "output": {"entities": {}}, "schema": []}
{"input": "Our purpose was to study the in vivo effect of this polymorphism on the secretion of danofloxacin, a widely used veterinary antibiotic, into milk.", "output": {"entities": {"chemical": [{"text": "danofloxacin", "start": 85, "end": 97}]}}, "schema": []}
{"input": "Danofloxacin (1. 25 mg/kg) was administered to six Y/Y 581 homozygous and six Y/S 581 heterozygous lactating cows, and plasma and milk samples were collected and analyzed by high-performance liquid chromatography.", "output": {"entities": {"chemical": [{"text": "Danofloxacin", "start": 0, "end": 12}]}}, "schema": []}
{"input": "No differences were found in the pharmacokinetic parameters of danofloxacin in plasma between the two groups of animals.", "output": {"entities": {"chemical": [{"text": "danofloxacin", "start": 63, "end": 75}]}}, "schema": []}
{"input": "In contrast, Y/S heterozygous cows showed a 2-fold increase in danofloxacin levels in milk.", "output": {"entities": {"chemical": [{"text": "danofloxacin", "start": 63, "end": 75}]}}, "schema": []}
{"input": "In addition, the pharmacokinetic elimination parameters, mean residence time and elimination half-life, were significantly lower in the milk of the animals carrying the Y/S polymorphism.", "output": {"entities": {}}, "schema": []}
{"input": "These in vivo results are in agreement with our previously published in vitro data, which showed a greater capacity of the S581 variant in accumulation assays, and demonstrate, for the first time, an important effect of the Y581S single-nucleotide polymorphism on antibiotic secretion into cow milk.", "output": {"entities": {}}, "schema": []}
{"input": "These findings could be extended to other ABCG2 substrates, and may be relevant for the treatment of mastitis and for the design of accurate and novel strategies to handle milk residues.", "output": {"entities": {}}, "schema": []}
{"input": "Sequences associated with centromere competency in the human genome.", "output": {"entities": {}}, "schema": []}
{"input": "Centromeres, the sites of spindle attachment during mitosis and meiosis, are located in specific positions in the human genome, normally coincident with diverse subsets of alpha satellite DNA.", "output": {"entities": {}}, "schema": []}
{"input": "While there is strong evidence supporting the association of some subfamilies of alpha satellite with centromere function, the basis for establishing whether a given alpha satellite sequence is or is not designated a functional centromere is unknown, and attempts to understand the role of particular sequence features in establishing centromere identity have been limited by the near identity and repetitive nature of satellite sequences.", "output": {"entities": {}}, "schema": []}
{"input": "Utilizing a broadly applicable experimental approach to test sequence competency for centromere specification, we have carried out a genomic and epigenetic functional analysis of endogenous human centromere sequences available in the current human genome assembly.", "output": {"entities": {}}, "schema": []}
{"input": "The data support a model in which functionally competent sequences confer an opportunity for centromere specification, integrating genomic and epigenetic signals and promoting the concept of context-dependent centromere inheritance.", "output": {"entities": {}}, "schema": []}
{"input": "Equilibrium gold nanoclusters quenched with biodegradable polymers.", "output": {"entities": {}}, "schema": []}
{"input": "Although sub-100 nm nanoclusters of metal nanoparticles are of interest in many fields including biomedical imaging, sensors, and catalysis, it has been challenging to control their morphologies and chemical properties.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, a new concept is presented to assemble equilibrium Au nanoclusters of controlled size by tuning the colloidal interactions with a polymeric stabilizer, PLA (1k)-b-PEG (10k)-b-PLA (1k).", "output": {"entities": {"chemical": [{"text": "Au", "start": 59, "end": 61}, {"text": "PLA", "start": 160, "end": 163}, {"text": "PEG", "start": 171, "end": 174}, {"text": "PLA", "start": 183, "end": 186}]}}, "schema": []}
{"input": "The nanoclusters form upon mixing a dispersion of ~ 5 nm Au nanospheres with a polymer solution followed by partial solvent evaporation.", "output": {"entities": {"chemical": [{"text": "Au", "start": 57, "end": 59}]}}, "schema": []}
{"input": "A weakly adsorbed polymer quenches the equilibrium nanocluster size and provides steric stabilization.", "output": {"entities": {}}, "schema": []}
{"input": "Nanocluster size is tuned from ~ 20 to ~ 40 nm by experimentally varying the final Au nanoparticle concentration and the polymer/Au ratio, along with the charge on the initial Au nanoparticle surface.", "output": {"entities": {"chemical": [{"text": "Au", "start": 83, "end": 85}, {"text": "Au", "start": 129, "end": 131}, {"text": "Au", "start": 176, "end": 178}]}}, "schema": []}
{"input": "Upon biodegradation of the quencher, the nanoclusters reversibly and fully dissociate to individual ~ 5 nm primary particles.", "output": {"entities": {}}, "schema": []}
{"input": "Equilibrium cluster size is predicted semiquantitatively with a free energy model that balances short-ranged depletion and van der Waals attractions with longer-ranged electrostatic repulsion, as a function of the Au and polymer concentrations.", "output": {"entities": {"chemical": [{"text": "Au", "start": 214, "end": 216}]}}, "schema": []}
{"input": "The close spacings of the Au nanoparticles in the clusters produce strong NIR extinction over a broad range of wavelengths from 650 to 900 nm, which is of practical interest in biomedical imaging.", "output": {"entities": {"chemical": [{"text": "Au", "start": 26, "end": 28}]}}, "schema": []}
{"input": "Porphyrin metabolisms in human skin commensal Propionibacterium acnes bacteria: potential application to monitor human radiation risk.", "output": {"entities": {"chemical": [{"text": "Porphyrin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Propionibacterium acnes (P. acnes), a Gram-positive anaerobic bacterium, is a commensal organism in human skin.", "output": {"entities": {}}, "schema": []}
{"input": "Like human cells, the bacteria produce porphyrins, which exhibit fluorescence properties and make bacteria visible with a Wood' s lamp.", "output": {"entities": {"chemical": [{"text": "porphyrins", "start": 39, "end": 49}]}}, "schema": []}
{"input": "In this review, we compare the porphyrin biosynthesis in humans and P. acnes.", "output": {"entities": {"chemical": [{"text": "porphyrin", "start": 31, "end": 40}]}}, "schema": []}
{"input": "Also, since P. acnes living on the surface of skin receive the same radiation exposure as humans, we envision that the changes in porphyrin profiles (the absorption spectra and/or metabolism) of P. acnes by radiation may mirror the response of human cells to radiation.", "output": {"entities": {"chemical": [{"text": "porphyrin", "start": 130, "end": 139}]}}, "schema": []}
{"input": "The porphyrin profiles of P. acnes may be a more accurate reflection of radiation risk to the patient than other biodosimeters/biomarkers such as gene up-/down-regulation, which may be non-specific due to patient related factors such as autoimmune diseases.", "output": {"entities": {"chemical": [{"text": "porphyrin", "start": 4, "end": 13}]}}, "schema": []}
{"input": "Lastly, we discuss the challenges and possible solutions for using the P. acnes response to predict the radiation risk.", "output": {"entities": {}}, "schema": []}
{"input": "Collective proton dynamics at highly charged interfaces studied by ab initio metadynamics.", "output": {"entities": {}}, "schema": []}
{"input": "Surface proton conduction is of utmost importance in biology, materials science, and electrochemistry; yet experimental findings of ultrafast proton transport at densely packed arrays of anionic surface groups have remained controversial and unexplained.", "output": {"entities": {}}, "schema": []}
{"input": "We present an ab initio molecular dynamics study of proton dynamics at sulfonic-acid terminated surface groups.", "output": {"entities": {"chemical": [{"text": "sulfonic-acid", "start": 71, "end": 84}]}}, "schema": []}
{"input": "Results furnish a highly efficient collective mechanism of hydronium ion translocations at a critical surface group separation of ~ 6. 5 A.", "output": {"entities": {"chemical": [{"text": "hydronium", "start": 59, "end": 68}]}}, "schema": []}
{"input": "Orientational fluctuations of SG trigger hydrogen bond breaking that sets off the hydronium ion motion.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 41, "end": 49}, {"text": "hydronium", "start": 82, "end": 91}]}}, "schema": []}
{"input": "The activation free energy of this process is 0. 3 eV (+/- 0. 1 eV).", "output": {"entities": {}}, "schema": []}
{"input": "The soliton-like nature of this mechanism is owed to the trigonal symmetry of sulfonate anions and exceptionally strong interfacial hydrogen bonding.", "output": {"entities": {"chemical": [{"text": "sulfonate", "start": 78, "end": 87}, {"text": "hydrogen", "start": 132, "end": 140}]}}, "schema": []}
{"input": "These insights should stimulate surface conductance studies at SG monolayers with sulfonic acid groups, and they bolster efforts in designing proton conducting polymers conducive to fuel cell operation above ~ 100 degrees C.", "output": {"entities": {"chemical": [{"text": "sulfonic acid", "start": 82, "end": 95}]}}, "schema": []}
{"input": "Synthesis of polystyrene/polysilsesquioxane core/shell composite particles via emulsion polymerization in the existence of poly (gamma-methacryloxypropyl trimethoxysilane) sol.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 13, "end": 24}, {"text": "polysilsesquioxane", "start": 25, "end": 43}, {"text": "poly (gamma-methacryloxypropyl trimethoxysilane)", "start": 123, "end": 171}]}}, "schema": []}
{"input": "Here, we synthesized the polystyrene/polysilsesquioxane (PS/PSQ) core/shell latex particles via emulsion polymerization, which behave as an amusing morphology.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 25, "end": 36}, {"text": "polysilsesquioxane", "start": 37, "end": 55}, {"text": "PSQ", "start": 60, "end": 63}]}}, "schema": []}
{"input": "First, the nanosized PSQ particles were prepared by the hydrolysis-condensation reaction of gamma-methacryloxypropyl trimethoxysilane (MPTS) in ethanol medium.", "output": {"entities": {"chemical": [{"text": "PSQ", "start": 21, "end": 24}, {"text": "gamma-methacryloxypropyl trimethoxysilane", "start": 92, "end": 133}, {"text": "MPTS", "start": 135, "end": 139}, {"text": "ethanol", "start": 144, "end": 151}]}}, "schema": []}
{"input": "Subsequently, the as-obtained methacryloxypropylene functionalized PSQ (PMPTS) sol was directly added into the emulsion system of styrene (St) monomer, and PS/PSQ composite particles with core/shell structure were obtained through emulsion polymerization.", "output": {"entities": {"chemical": [{"text": "methacryloxypropylene", "start": 30, "end": 51}, {"text": "PSQ", "start": 67, "end": 70}, {"text": "PMPTS", "start": 72, "end": 77}, {"text": "styrene", "start": 130, "end": 137}, {"text": "PSQ", "start": 159, "end": 162}]}}, "schema": []}
{"input": "We found that the structure of the composite particles can be affected by the synthesis parameters such as reaction time, content of PMPTS added in the reaction, amount of coemulsifier, and the pH value of emulsion system, which were systemically explored by transmission electron microscopy (TEM), scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and thermogravimetric analysis (TGA) in this work.", "output": {"entities": {"chemical": [{"text": "PMPTS", "start": 133, "end": 138}]}}, "schema": []}
{"input": "These results indicate that the PMPTS particles in the size of about 5 nm could first absorb onto the surface of PS latex particles so as to assemble in a strawberry-like morphology.", "output": {"entities": {"chemical": [{"text": "PMPTS", "start": 32, "end": 37}]}}, "schema": []}
{"input": "The further coalescence among the PMPTS particles would result in a continuous PMPTS shell around the PS core.", "output": {"entities": {"chemical": [{"text": "PMPTS", "start": 34, "end": 39}, {"text": "PMPTS", "start": 79, "end": 84}]}}, "schema": []}
{"input": "Moreover, the hollow PSQ capsules were prepared after extraction of the PS core by organic solvent, further confirming the core/shell structure of the as-synthesized PS/PMPTS particles.", "output": {"entities": {"chemical": [{"text": "PSQ", "start": 21, "end": 24}, {"text": "PMPTS", "start": 169, "end": 174}]}}, "schema": []}
{"input": "Meanwhile, we also explored the application of the PS/PSQ core/shell particles as a new kind of Pickering emulsifier in the emulsion polymerization of St, and composite particles with complex patchy morphologies have been obtained finally under different ratios of styrene monomer to PS/PMPTS colloidal emulsifier.", "output": {"entities": {"chemical": [{"text": "PSQ", "start": 54, "end": 57}, {"text": "PMPTS", "start": 287, "end": 292}]}}, "schema": []}
{"input": "Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors.", "output": {"entities": {"chemical": [{"text": "4-phenyl-2-phenylaminopyridine", "start": 13, "end": 43}]}}, "schema": []}
{"input": "A series of compounds based on a 4-phenyl-2-phenylaminopyridine scaffold that are potent and selective inhibitors of Traf2-and Nck-interacting kinase (TNIK) activity are described.", "output": {"entities": {"chemical": [{"text": "4-phenyl-2-phenylaminopyridine", "start": 33, "end": 63}]}}, "schema": []}
{"input": "These compounds were used as tools to test the importance of TNIK kinase activity in signaling and proliferation in Wnt-activated colorectal cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that pharmacological inhibition of TNIK kinase activity has minimal effects on either Wnt/TCF4/beta-catenin-driven transcription or viability.", "output": {"entities": {}}, "schema": []}
{"input": "The findings suggest that the kinase activity of TNIK may be less important to Wnt signaling than other aspects of TNIK function, such as its putative role in stabilizing the TCF4/beta-catenin transcriptional complex.", "output": {"entities": {}}, "schema": []}
{"input": "Korean red ginseng (Panax ginseng) prevents obesity by inhibiting angiogenesis in high fat diet-induced obese C57BL/6J mice.", "output": {"entities": {}}, "schema": []}
{"input": "Adipose tissue growth and development are thought to be associated with angiogenesis and extracellular matrix remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Because ginseng has been shown to inhibit angiogenesis and matrix metalloproteinase (MMP) activity, we hypothesized that adipose tissue growth and obesity can be regulated by Korean ginseng (Panax ginseng C. A. Meyer).", "output": {"entities": {}}, "schema": []}
{"input": "Wild-type C57BL/6J mice were fed for 8 weeks with a low fat diet, a high fat diet (HFD), or HFD supplemented with 0. 5% or 5% Korean red ginseng extract.", "output": {"entities": {}}, "schema": []}
{"input": "We measured body weight, adipose tissue mass, food intake, MMP activity, and the expression of genes involved in angiogenesis and MMPs.", "output": {"entities": {}}, "schema": []}
{"input": "Administering ginseng to HFD-induced obese mice produced reductions in body weight and adipose tissue mass compared with untreated counterparts.", "output": {"entities": {}}, "schema": []}
{"input": "Ginseng treatment decreased blood vessel density and MMP activity in adipose tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Ginseng also reduced mRNA levels of angiogenic factors (e. g., VEGF-A and FGF-2) and MMPs (e. g., MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (e. g., TSP-1, TIMP-1, and TIMP-2) in adipose tissues.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate that ginseng effectively reduces adipose tissue mass and prevents obesity in diet-induced obese mice and that this process may be mediated in part through the anti-angiogenic actions of ginseng.", "output": {"entities": {}}, "schema": []}
{"input": "Citalopram at the recommended human doses after long-term treatment is genotoxic for male germ cell.", "output": {"entities": {"chemical": [{"text": "Citalopram", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The present study was aimed to examine if multiple oral administration of citalopram, an antidepressant drug, has any genotoxic potential on germ cells of male mice.", "output": {"entities": {"chemical": [{"text": "citalopram", "start": 74, "end": 84}]}}, "schema": []}
{"input": "Mice were treated with citalopram for 4 or 8 weeks at the doses of 6, 12 and 24 mg/kg/day and were sacrificed 24 h after the last dose.", "output": {"entities": {"chemical": [{"text": "citalopram", "start": 23, "end": 33}]}}, "schema": []}
{"input": "Multiple exposures to 12 and 24 mg/kg/day citalopram significantly increased sperm DNA strand breaks (14. 0 and 16. 0, respectively, compared to the concurrent control of 6. 8 at week 4 and 15. 2 and 20. 7, respectively, compared to the concurrent control of 7. 2 at week 8) and aberrant primary spermatocytes (6. 6% and 7. 6%, respectively, compared to the control of 2. 8% at week 4 and 7. 4% and 8. 4%, respectively, compared to the control of 3. 2% at week 8) as well as oxidative DNA damage (2. 7 and 3. 1, respectively, compared to the control of 1. 6 at week 4 and 3. 3 and 3. 9, respectively, compared to the control of 1. 7 at week 8).", "output": {"entities": {"chemical": [{"text": "citalopram", "start": 42, "end": 52}]}}, "schema": []}
{"input": "Overall, this study provides that citalopram at the recommended human doses after long-term treatment is genotoxic for mouse germ cells.", "output": {"entities": {"chemical": [{"text": "citalopram", "start": 34, "end": 44}]}}, "schema": []}
{"input": "Thus, male patients receiving citalopram may stand at higher risk for abnormal reproductive outcomes, particularly in the reproductive ages.", "output": {"entities": {"chemical": [{"text": "citalopram", "start": 30, "end": 40}]}}, "schema": []}
{"input": "Aberrant transcription of the LHCGR gene caused by a mutation in exon 6A leads to Leydig cell hypoplasia type II.", "output": {"entities": {}}, "schema": []}
{"input": "The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for normal male sex differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, the additional primate-specific exon 6A of the LHCGR was discovered and it was shown to act as regulatory element at the transcriptional level.", "output": {"entities": {}}, "schema": []}
{"input": "Compound heterozygous mutations in exon 6A (c. 580 A > G) and exon 11 (c. 1244T > C) were identified in the LHCGR of a male 46, XY patient with genital malformation.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis revealed that mutation c. 580A > G in exon 6A affects the splicing pattern resulting in an increase of transcripts containing the internal variants of exon 6A prone to nonsense-mediated decay.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, mutation c. 1244T > C results in an amino acid substitution (Ile415Thr), which abolishes signal transduction due to structural changes.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 49, "end": 59}]}}, "schema": []}
{"input": "When inherited in a compound heterozygous fashion these mutations result in Leydig cell hypoplasia (LCH) type II.", "output": {"entities": {}}, "schema": []}
{"input": "Thus this study provides proof that mutations causing aberrant transcription can impair receptor function and thereby be causative of LCH.", "output": {"entities": {}}, "schema": []}
{"input": "New amide alkaloids from Piper longum.", "output": {"entities": {"chemical": [{"text": "amide alkaloids", "start": 4, "end": 19}]}}, "schema": []}
{"input": "Bioassay-guided phytochemical investigation on Piper longum resulted in the isolation of two new compounds.", "output": {"entities": {}}, "schema": []}
{"input": "By analyses of the MS, IR, UV, 1D and 2D NMR data, the two new compounds were identified as 3 beta, 4 alpha-dihydroxy-1-(3-phenylpropanoyl)-piperidine-2-one (1) and (2E, 4E, 14Z)-6-hydroxyl-N-isobutyleicosa-2, 4, 14-trienamide (2).", "output": {"entities": {"chemical": [{"text": "3 beta, 4 alpha-dihydroxy-1-(3-phenylpropanoyl)-piperidine-2-one", "start": 92, "end": 156}, {"text": "(2E, 4E, 14Z)-6-hydroxyl-N-isobutyleicosa-2, 4, 14-trienamide", "start": 165, "end": 226}]}}, "schema": []}
{"input": "In vitro anti-HBV bioassay demonstrated compound 1 possessed remarkable activity suppressing the secretion of HBeAg in Hep G2. 2. 15 cell line, with an IC (50) value of 0. 21mM and SI value of 16. 4.", "output": {"entities": {}}, "schema": []}
{"input": "pi-Extended isomeric and expanded porphyrins.", "output": {"entities": {"chemical": [{"text": "porphyrins", "start": 34, "end": 44}]}}, "schema": []}
{"input": "The phenomenon of pi-extension has been widely applied to, and exploited within, the field porphyrin chemistry.", "output": {"entities": {"chemical": [{"text": "porphyrin", "start": 91, "end": 100}]}}, "schema": []}
{"input": "The development of reliable synthetic routes to various useful starting materials has facilitated the underlying preparative work.", "output": {"entities": {}}, "schema": []}
{"input": "The chemical resemblance between porphyrins and expanded and isomeric porphyrins, as well as the increasing accessibility of the requisite starting materials is giving birth to the hybrid field of pi-extended expanded and isomeric porphyrins.", "output": {"entities": {"chemical": [{"text": "porphyrins", "start": 33, "end": 43}, {"text": "porphyrins", "start": 70, "end": 80}, {"text": "porphyrins", "start": 231, "end": 241}]}}, "schema": []}
{"input": "This tutorial review is intended to provide an overview of up-to-date published synthetic efforts and to summarize the effect of annulation on the properties of expanded and isomeric porphyrins.", "output": {"entities": {"chemical": [{"text": "porphyrins", "start": 183, "end": 193}]}}, "schema": []}
{"input": "Human mesenchymal stem-cell behaviour on direct laser micropatterned electrospun scaffolds with hierarchical structures.", "output": {"entities": {}}, "schema": []}
{"input": "Direct laser machining and electrospinning are utilized to obtain a bi-layered hybrid scaffold with hierarchical topographical features to mimic extracellular matrix-like microenvironment of cells.", "output": {"entities": {}}, "schema": []}
{"input": "Adult bone marrow derived human mesenchymal stem cells (hMSCs) are cultured in vitro in these hybrid scaffolds, and cell orientation, proliferation, viability, and differentiation are evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "The results show that this novel hybrid scaffold not only supports cell growth like traditional scaffolds, but also elicits positive responses from the cells, like lineage commitment and alignment, which are essential features of future scaffolds.", "output": {"entities": {}}, "schema": []}
{"input": "Polariton dynamics under strong light-molecule coupling.", "output": {"entities": {}}, "schema": []}
{"input": "We present a comprehensive experimental study of the photophysical properties of a molecule-cavity system under strong coupling conditions, using steady-state and femtosecond time-resolved emission and absorption techniques to selectively excite the lower and upper polaritons as well as the reservoir of uncoupled molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Our results demonstrate the complex decay routes in such hybrid systems and that, contrary to expectations, the lower polariton is intrinsically long-lived.", "output": {"entities": {}}, "schema": []}
{"input": "Event based analysis of chlorothalonil concentrations following application to managed turf.", "output": {"entities": {"chemical": [{"text": "chlorothalonil", "start": 24, "end": 38}]}}, "schema": []}
{"input": "Chlorothalonil concentrations exceeding acute toxicity levels for certain organisms have been measured in surface water discharge events from managed turf watersheds.", "output": {"entities": {"chemical": [{"text": "Chlorothalonil", "start": 0, "end": 14}]}}, "schema": []}
{"input": "The duration of exceedence and the timing of these events related to precipitation/runoff and time since application, however, have not been explored.", "output": {"entities": {}}, "schema": []}
{"input": "Chlorothalonil concentrations were measured from discharge waters draining a managed turf watershed in Duluth, Minnesota, USA, between 2003 and 2009.", "output": {"entities": {"chemical": [{"text": "Chlorothalonil", "start": 0, "end": 14}]}}, "schema": []}
{"input": "The median chlorothalonil concentration was 0. 58 micro g/L.", "output": {"entities": {"chemical": [{"text": "chlorothalonil", "start": 11, "end": 25}]}}, "schema": []}
{"input": "Approximately 2% of all measured concentrations exceeded the 7. 6 micro g/L median lethal concentration (LC50) acute toxicity level for rainbow trout.", "output": {"entities": {}}, "schema": []}
{"input": "One-twentieth the LC50 concentration, equivalent to the level of concern (0. 38 micro g/L) for endangered species, was exceeded 31% of the time during the present study.", "output": {"entities": {}}, "schema": []}
{"input": "The concentrations that exceeded the LC50 threshold were associated with eight rainfall/runoff events.", "output": {"entities": {}}, "schema": []}
{"input": "Low dose exposures are a more important biological concern than acute occurrences.", "output": {"entities": {}}, "schema": []}
{"input": "Exceedence concentrations associated with acute effects were significantly (p < 0. 05) correlated to time since application and were measured only in the fall following extensive application.", "output": {"entities": {}}, "schema": []}
{"input": "A conflict exists between the transportability of chlorothalonil as suggested by its chemical properties and the data collected in the present study.", "output": {"entities": {"chemical": [{"text": "chlorothalonil", "start": 50, "end": 64}]}}, "schema": []}
{"input": "With respect to course-wide golf course application, avoiding application until after the major autumn rainfall period but before the first snow coverage is recommended to reduce occurrence of chlorothalonil concentrations that exceed toxic levels associated with acute and chronic levels of concern.", "output": {"entities": {"chemical": [{"text": "chlorothalonil", "start": 193, "end": 207}]}}, "schema": []}
{"input": "Genotype imputation via matrix completion.", "output": {"entities": {}}, "schema": []}
{"input": "Most current genotype imputation methods are model-based and computationally intensive, taking days to impute one chromosome pair on 1000 people.", "output": {"entities": {}}, "schema": []}
{"input": "We describe an efficient genotype imputation method based on matrix completion.", "output": {"entities": {}}, "schema": []}
{"input": "Our matrix completion method is implemented in MATLAB and tested on real data from HapMap 3, simulated pedigree data, and simulated low-coverage sequencing data derived from the 1000 Genomes Project.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with leading imputation programs, the matrix completion algorithm embodied in our program MENDEL-IMPUTE achieves comparable imputation accuracy while reducing run times significantly.", "output": {"entities": {}}, "schema": []}
{"input": "Implementation in a lower-level language such as Fortran or C is apt to further improve computational efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Design and synthesis of diazatricyclodecane agonists of the G-protein-coupled receptor 119.", "output": {"entities": {"chemical": [{"text": "diazatricyclodecane", "start": 24, "end": 43}]}}, "schema": []}
{"input": "A series of GPR119 agonists based on a 2, 6-diazatricyclo [3. 3. 1. 1 ~ 3, 7 ~] decane ring system is described.", "output": {"entities": {"chemical": [{"text": "2, 6-diazatricyclo [3. 3. 1. 1 ~ 3, 7 ~] decane", "start": 39, "end": 86}]}}, "schema": []}
{"input": "Also provided is a detailed account of the development of a multigram scale synthesis of the diazatricyclic ring system, which was achieved using a Hofmann-L o ffler-Freytag reaction as the key step.", "output": {"entities": {"chemical": [{"text": "diazatricyclic", "start": 93, "end": 107}]}}, "schema": []}
{"input": "The basis for the use of this complex framework lies in an attempt to constrain one end of the molecule in the \" agonist conformation \" as was previously described for 3-oxa-7-aza-bicyclo [3. 3. 1] nonanes.", "output": {"entities": {"chemical": [{"text": "3-oxa-7-aza-bicyclo [3. 3. 1] nonanes", "start": 168, "end": 205}]}}, "schema": []}
{"input": "Optimization of carbamate analogues of the diazatricylic compounds led to the identification of 32i as a potent agonist of the GPR119 receptor with low unbound human liver microsomal clearance.", "output": {"entities": {"chemical": [{"text": "carbamate", "start": 16, "end": 25}, {"text": "diazatricylic", "start": 43, "end": 56}]}}, "schema": []}
{"input": "The use of an agonist response weighted ligand lipophilic efficiency (LLE) termed AgLLE is discussed along with the issues of applying efficiency measures to agonist programs.", "output": {"entities": {}}, "schema": []}
{"input": "Ultimately, solubility limited absorption and poor exposure reduced further interest in these molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Functionalization of monodisperse iron oxide NPs and their properties as magnetically recoverable catalysts.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 34, "end": 44}]}}, "schema": []}
{"input": "Here we report the functionalization of monodisperse iron oxide nanoparticles (NPs) with commercially available functional acids containing multiple double bonds such as linolenic (LLA) and linoleic (LEA) acids or pyridine moieties such as 6-methylpyridine-2-carboxylic acid, isonicotinic acid, 3-hydroxypicolinic acid, and 6-(1-piperidinyl) pyridine-3-carboxlic acid (PPCA).", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 53, "end": 63}, {"text": "linolenic (LLA) and linoleic (LEA) acids", "start": 170, "end": 210}, {"text": "pyridine", "start": 214, "end": 222}, {"text": "6-methylpyridine-2-carboxylic acid", "start": 240, "end": 274}, {"text": "isonicotinic acid", "start": 276, "end": 293}, {"text": "3-hydroxypicolinic acid", "start": 295, "end": 318}, {"text": "6-(1-piperidinyl) pyridine-3-carboxlic acid", "start": 324, "end": 367}, {"text": "PPCA", "start": 369, "end": 373}]}}, "schema": []}
{"input": "Both double bonds and pyridine groups can be reacted with noble metal compounds to form catalytically active species in the exterior of magnetic NPs, thus making them promising magnetically recoverable catalysts.", "output": {"entities": {}}, "schema": []}
{"input": "We determined that both LLA and LEA stabilize magnetic iron oxide NPs, allowing the formation of pi-complexes with bis (acetonitrile) dichloropalladium (II) in the NP shells.", "output": {"entities": {"chemical": [{"text": "LLA", "start": 24, "end": 27}, {"text": "LEA", "start": 32, "end": 35}, {"text": "iron oxide", "start": 55, "end": 65}, {"text": "bis (acetonitrile) dichloropalladium (II)", "start": 115, "end": 156}]}}, "schema": []}
{"input": "In both cases, this leads to the formation of NP aggregates because of interparticle complexation.", "output": {"entities": {}}, "schema": []}
{"input": "In the case of pyridine-containing ligands, only PPCA with two N-containing rings is able to provide NP stabilization and functionalization whereas other pyridine-containing acids did now allow sufficient steric stabilization.", "output": {"entities": {"chemical": [{"text": "pyridine", "start": 15, "end": 23}, {"text": "PPCA", "start": 49, "end": 53}, {"text": "N", "start": 63, "end": 64}, {"text": "pyridine", "start": 154, "end": 162}]}}, "schema": []}
{"input": "The interaction of PPCA-based particles with Pd acetate also leads to aggregation because of interparticle interactions, but the aggregates that are formed are much smaller.", "output": {"entities": {"chemical": [{"text": "PPCA", "start": 19, "end": 23}, {"text": "Pd acetate", "start": 45, "end": 55}]}}, "schema": []}
{"input": "Nevertheless, the catalytic properties in the selective hydrogenation of dimethylethynylcarbinol (DMEC) to dimethylvinylcarbinol were the best for the catalyst based on LLA, demonstrating that the NP aggregates in all cases are penetrable for DMEC.", "output": {"entities": {"chemical": [{"text": "dimethylethynylcarbinol", "start": 73, "end": 96}, {"text": "DMEC", "start": 98, "end": 102}, {"text": "dimethylvinylcarbinol", "start": 107, "end": 128}, {"text": "LLA", "start": 169, "end": 172}, {"text": "DMEC", "start": 243, "end": 247}]}}, "schema": []}
{"input": "Easy magnetic separation of this catalyst from the reaction solution makes it promising as a magnetically recoverable catalyst.", "output": {"entities": {}}, "schema": []}
{"input": "70-kDa heat shock cognate protein hsc70 mediates calmodulin-dependent nuclear import of the sex-determining factor SRY.", "output": {"entities": {}}, "schema": []}
{"input": "We recently showed that the developmentally important family of SOX (SRY (sex determining region on the Y chromosome)-related high mobility group (HMG) box) proteins require the calcium-binding protein calmodulin (CaM) for optimal nuclear accumulation, with clinical mutations in SRY that specifically impair nuclear accumulation via this pathway resulting in XY sex reversal.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 178, "end": 185}]}}, "schema": []}
{"input": "However, the mechanism by which CaM facilitates nuclear accumulation is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show, for the first time, that the 70-kDa heat shock cognate protein hsc70 plays a key role in CaM-dependent nuclear import of SRY.", "output": {"entities": {}}, "schema": []}
{"input": "Using a reconstituted nuclear import assay, we show that antibodies to hsc70 significantly reduce nuclear accumulation of wild type SRY and mutant derivatives thereof that retain CaM-dependent nuclear import, with an increased rate of nuclear accumulation upon addition of both CaM and hsc70, in contrast to an SRY mutant derivative with impaired CaM binding.", "output": {"entities": {}}, "schema": []}
{"input": "siRNA knockdown of hsc70 in intact cells showed similar results, indicating clear dependence upon hsc70 for CaM-dependent nuclear import.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis using the technique of fluorescence recovery after photobleaching indicated that hsc70 is required for the maximal rate of SRY nuclear import in living cells but has no impact upon SRY nuclear retention/nuclear dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we demonstrate direct binding of hsc70 to the SRY. CaM complex, with immunoprecipitation experiments from cell extracts showing association of hsc70 with wild type SRY, but not with a mutant derivative with impaired CaM binding, dependent on Ca (2 +).", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 251, "end": 259}]}}, "schema": []}
{"input": "Our novel findings strongly implicate hsc70 in CaM-dependent nuclear import of SRY.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of multilayer structure on cyclic performance of Si/Fe anode electrode in lithium-ion secondary batteries.", "output": {"entities": {"chemical": [{"text": "Si", "start": 56, "end": 58}, {"text": "Fe", "start": 59, "end": 61}, {"text": "lithium", "start": 81, "end": 88}]}}, "schema": []}
{"input": "A buffer-strengthened Si/Fe multilayer film, consisting of amorphous silicon layers and polycrystalline Fe layers, is investigated as the anode for Li-ion batteries.", "output": {"entities": {"chemical": [{"text": "Si", "start": 22, "end": 24}, {"text": "Fe", "start": 25, "end": 27}, {"text": "silicon", "start": 69, "end": 76}, {"text": "Fe", "start": 104, "end": 106}, {"text": "Li", "start": 148, "end": 150}]}}, "schema": []}
{"input": "This film can achieve a stable cycle-life performance with a high capacity.", "output": {"entities": {}}, "schema": []}
{"input": "Decreasing the thickness of the Fe layer can lead to a higher capacity, which is related to the fast transport of the Li ion, but the cyclic performance deteriorates with repeated cycling.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 32, "end": 34}, {"text": "Li", "start": 118, "end": 120}]}}, "schema": []}
{"input": "In contrast, increasing the thickness of the Fe buffer layers and the number of deposit stacks improves the cycle life with high reversibility.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 45, "end": 47}]}}, "schema": []}
{"input": "Because of the strain in the Si layers suppressed by the primary multilayer structure, the long-term strength is preserved and the substantial fracture toughness is enhanced by the increasing numbers of effective grain boundaries and interfacial layers.", "output": {"entities": {"chemical": [{"text": "Si", "start": 29, "end": 31}]}}, "schema": []}
{"input": "In addition, we demonstrate that the Ti underlayer promotes the electrochemical properties in the Si/Fe multilayer for various Fe layer thicknesses because of the enhanced adhesion of the interfacial electrode and current collector.", "output": {"entities": {"chemical": [{"text": "Ti", "start": 37, "end": 39}, {"text": "Si", "start": 98, "end": 100}, {"text": "Fe", "start": 101, "end": 103}, {"text": "Fe", "start": 127, "end": 129}]}}, "schema": []}
{"input": "The mechanically optimized Si/Fe multilayer films can have superior cycle-life performances and higher capacities.", "output": {"entities": {"chemical": [{"text": "Si", "start": 27, "end": 29}, {"text": "Fe", "start": 30, "end": 32}]}}, "schema": []}
{"input": "Notably, the 16-bilayer deposited electrode exhibits an excellent capacity retention of ~ 95% with ~ 204 mAh g (-1) over 300 cycles at a 1 C rate.", "output": {"entities": {}}, "schema": []}
{"input": "Control of CYP11B2/CYP11B1 expression ratio and consequences for the zonation of the adrenal cortex.", "output": {"entities": {}}, "schema": []}
{"input": "Access of corticotropin to glucocorticoid synthesis in adrenocortical cells is provided by the expression of the ACTH receptor (MC2R).", "output": {"entities": {}}, "schema": []}
{"input": "Activation of the MC2R increases stimulatory G-protein, adenylyl cyclase, and protein kinase A (PKA) activities.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, PKA phosphorylates transcription factors that have a stimulating effect on glucocorticoid synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Sensitivity of adrenocortical cells to renin/angiotensin-2 is conferred by the expression of the inhibitory G-protein-linked angiotensin-2 type 1 receptor (AT1R) that additionally associates to the phospholipase C-activating G-protein q.", "output": {"entities": {}}, "schema": []}
{"input": "The AT1R is connected to the adrenal potassium sensory system and regulates calcium influx as well as phospholipase C-beta (PLC-beta) and thus calmodulin kinase-dependent transcription of steroidogenic enzymes.", "output": {"entities": {"chemical": [{"text": "potassium", "start": 37, "end": 46}, {"text": "calcium", "start": 76, "end": 83}]}}, "schema": []}
{"input": "While AT1R signaling suppresses the influence of corticotropin on the generation of cyclic adenosine monophosphate, the expression of the AT1R and its associated enzyme activities are under the control of glucocorticoids.", "output": {"entities": {"chemical": [{"text": "cyclic adenosine monophosphate", "start": 84, "end": 114}]}}, "schema": []}
{"input": "Thus, dominance of one of the two signaling pathways is dependent on two factors: the extracellular concentration of their ligands and the products of their signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "These findings are in favor of the hypothesis that the centripetal blood flow through the adrenal gland builds up a glucocorticoid gradient creating a morphogenetic field along which adrenal cortical cells adopt different functional states, leading to the typical zonation of the adrenal cortex.", "output": {"entities": {}}, "schema": []}
{"input": "Sulfonylureas have antifungal activity and are potent inhibitors of Candida albicans acetohydroxyacid synthase.", "output": {"entities": {"chemical": [{"text": "Sulfonylureas", "start": 0, "end": 13}]}}, "schema": []}
{"input": "The sulfonylurea herbicides exert their activity by inhibiting plant acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway.", "output": {"entities": {"chemical": [{"text": "sulfonylurea", "start": 4, "end": 16}, {"text": "amino acid", "start": 142, "end": 152}]}}, "schema": []}
{"input": "It has previously been shown that if the gene for AHAS is deleted in Candida albicans, attenuation of virulence is achieved, suggesting AHAS as an antifungal drug target.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we have cloned, expressed, and purified C. albicans AHAS and shown that several sulfonylureas are inhibitors of this enzyme and possess antifungal activity.", "output": {"entities": {"chemical": [{"text": "sulfonylureas", "start": 88, "end": 101}]}}, "schema": []}
{"input": "The most potent of these compounds is ethyl 2-(N-((4-iodo-6-methoxypyrimidin-2-yl) carbamoyl) sulfamoyl) benzoate (10c), which has a K (i) value of 3. 8 nM for C. albicans AHAS and an MIC 9 0 of 0. 7 mu g/mL for this fungus in cell-based assays.", "output": {"entities": {"chemical": [{"text": "ethyl 2-(N-((4-iodo-6-methoxypyrimidin-2-yl) carbamoyl) sulfamoyl) benzoate", "start": 38, "end": 113}]}}, "schema": []}
{"input": "For the sulfonylureas tested there was a strong correlation between inhibitory activity toward C. albicans AHAS and fungicidal activity, supporting the hypothesis that AHAS is the target for their inhibitory activity within the cell.", "output": {"entities": {"chemical": [{"text": "sulfonylureas", "start": 8, "end": 21}]}}, "schema": []}
{"input": "Calcium-dependent ligand binding and G-protein signaling of family B GPCR parathyroid hormone 1 receptor purified in nanodiscs.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 0, "end": 7}]}}, "schema": []}
{"input": "GPCRs mediate intracellular signaling upon external stimuli, making them ideal drug targets.", "output": {"entities": {}}, "schema": []}
{"input": "However, little is known about their activation mechanisms due to the difficulty in purification.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we introduce a method to purify GPCRs in nanodiscs, which incorporates GPCRs into lipid bilayers immediately after membrane solubilization, followed by single-step purification.", "output": {"entities": {}}, "schema": []}
{"input": "Using this approach, we purified a family B GPCR, parathyroid hormone 1 receptor (PTH1R), which regulates calcium and phosphate homeostasis and is a drug target for osteoporosis.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 106, "end": 113}, {"text": "phosphate", "start": 118, "end": 127}]}}, "schema": []}
{"input": "We demonstrated that the purified PTH1R in nanodiscs can bind to PTH (1-34) and activate G protein.", "output": {"entities": {}}, "schema": []}
{"input": "We also observed that Ca (2 +) is a weak agonist of PTH1R, and Ca (2 +) in millimolar concentration can switch PTH (1-34) from an inverse agonist to an agonist.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 22, "end": 30}, {"text": "Ca (2 +)", "start": 63, "end": 71}]}}, "schema": []}
{"input": "Hence, our results show that nanodiscs are a viable vehicle for GPCR purification, enabling studies of GPCRs under precise experimental conditions without interference from other cellular or membrane components.", "output": {"entities": {}}, "schema": []}
{"input": "Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation.", "output": {"entities": {"chemical": [{"text": "Isoliquiritigenin", "start": 0, "end": 17}, {"text": "UDP", "start": 68, "end": 71}, {"text": "4-methylumbelliferone", "start": 120, "end": 141}, {"text": "4-MU", "start": 143, "end": 147}]}}, "schema": []}
{"input": "Isoliquiritigenin, a herbal ingredient with chalcone structure, has been speculated to be able to inhibit one of the most drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferase (UGT).", "output": {"entities": {"chemical": [{"text": "Isoliquiritigenin", "start": 0, "end": 17}, {"text": "chalcone", "start": 44, "end": 52}, {"text": "UDP", "start": 155, "end": 158}]}}, "schema": []}
{"input": "Therefore, the aim of the present study was to investigate the inhibition of isoliquiritigenin towards important UGT isoforms in the liver and intestine, including UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10.", "output": {"entities": {"chemical": [{"text": "isoliquiritigenin", "start": 77, "end": 94}]}}, "schema": []}
{"input": "The recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as probe reactions.", "output": {"entities": {"chemical": [{"text": "4-methylumbelliferone", "start": 30, "end": 51}, {"text": "4-MU", "start": 53, "end": 57}]}}, "schema": []}
{"input": "The results showed that 100 mu M of isoliquiritigenin inhibited the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 by 95. 2%, 76. 1%, 78. 9%, 87. 2%, 67. 2%, 94. 8%, and 91. 7%, respectively.", "output": {"entities": {"chemical": [{"text": "isoliquiritigenin", "start": 36, "end": 53}]}}, "schema": []}
{"input": "The data fitting using Dixon plot and Lineweaver-Burk plot showed that the inhibition of UGT1A1, UGT1A9 and UGT1A10 by isoliquiritigenin was all best fit to the competitive inhibition, and the second plot using the slopes from the Lineweaver-Burk plot versus isoliquiritigenin concentrations was used to calculate the inhibition kinetic parameter (K (i)) to be 0. 7 mu M, 0. 3 mu M, and 18. 3 mu M for UGT1A1, UGT1A9, and UGT1A10, respectively.", "output": {"entities": {"chemical": [{"text": "isoliquiritigenin", "start": 119, "end": 136}, {"text": "isoliquiritigenin", "start": 259, "end": 276}]}}, "schema": []}
{"input": "All these results indicated the risk of clinical application of isoliquiritigenin on the drug-drug interaction and other possible diseases induced by the inhibition of isoliquiritigenin towards these UGT isoforms.", "output": {"entities": {"chemical": [{"text": "isoliquiritigenin", "start": 64, "end": 81}, {"text": "isoliquiritigenin", "start": 168, "end": 185}]}}, "schema": []}
{"input": "Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.", "output": {"entities": {"chemical": [{"text": "piperidine", "start": 49, "end": 59}, {"text": "urea", "start": 72, "end": 76}, {"text": "epoxide", "start": 85, "end": 92}]}}, "schema": []}
{"input": "A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed.", "output": {"entities": {"chemical": [{"text": "amide", "start": 19, "end": 24}, {"text": "urea", "start": 29, "end": 33}, {"text": "epoxide", "start": 56, "end": 63}]}}, "schema": []}
{"input": "The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs.", "output": {"entities": {"chemical": [{"text": "epoxide", "start": 26, "end": 33}, {"text": "epoxyeicosatrienoic acids", "start": 72, "end": 97}, {"text": "EETs", "start": 99, "end": 103}]}}, "schema": []}
{"input": "Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.", "output": {"entities": {}}, "schema": []}
{"input": "Catalytic properties of a bacterial acylating acetaldehyde dehydrogenase: evidence for several active oligomeric states and coenzyme A activation upon binding.", "output": {"entities": {"chemical": [{"text": "acetaldehyde", "start": 46, "end": 58}]}}, "schema": []}
{"input": "Until the last decade, two unrelated aldehyde dehydrogenase (ALDH) superfamilies, i. e. the phosphorylating and non-phosphorylating superfamilies, were known to catalyze the oxidation of aldehydes to activated or non-activated acids.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 37, "end": 45}, {"text": "aldehydes", "start": 187, "end": 196}]}}, "schema": []}
{"input": "However, a third one was discovered by the crystal structure of a bifunctional enzyme 4-hydroxy-2-ketovalerate aldolase/acylating acetaldehyde dehydrogenase (DmpFG) from Pseudomonas sp. strain CF600 (Manjasetty et al., Proc. Natl. Acad. Sci. USA 100 (2003) 6992-6997).", "output": {"entities": {"chemical": [{"text": "4-hydroxy-2-ketovalerate", "start": 86, "end": 110}, {"text": "acetaldehyde", "start": 130, "end": 142}]}}, "schema": []}
{"input": "Indeed, DmpF exhibits a non-phosphorylating CoA-dependent ALDH activity, but is structurally related to the phosphorylating superfamily.", "output": {"entities": {"chemical": [{"text": "CoA", "start": 44, "end": 47}]}}, "schema": []}
{"input": "In this study, we undertook the characterization of the catalytic and structural properties of MhpEF from Escherichia coli, an ortholog of DmpFG in which MhpF converts acetaldehyde, produced by the cleavage of 4-hydroxy-2-ketovalerate by MhpE, into acetyl-CoA.", "output": {"entities": {"chemical": [{"text": "acetaldehyde", "start": 168, "end": 180}, {"text": "4-hydroxy-2-ketovalerate", "start": 210, "end": 234}, {"text": "acetyl-CoA", "start": 249, "end": 259}]}}, "schema": []}
{"input": "The kinetic data obtained under steady-state and pre-steady-state conditions show that the aldehyde dehydrogenase, MhpF, is active as a monomer, a unique feature relative to the phosphorylating and non-phosphorylating ALDH superfamilies.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Our results also reveal that the catalytic properties of MhpF are not dependent on its oligomeric state, supporting the hypothesis of a structurally and catalytically independent entity.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the transthioesterification is shown to be rate-limiting and, when compared with a chemical model, its catalytic efficiency is increased 10 (4)-fold.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, CoA binding to MhpF increases its reactivity and optimizes its positioning relative to the thioacylenzyme intermediate, thus enabling the formation of an efficient deacylation complex.", "output": {"entities": {"chemical": [{"text": "CoA", "start": 11, "end": 14}]}}, "schema": []}
{"input": "Age dependent differences in the regulation of hippocampal steroid hormones and receptor genes: relations to motivation and cognition in male rats.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 59, "end": 66}]}}, "schema": []}
{"input": "Estrogen and estrogenic functions are age-dependently involved in the modulation of learning, memory and mood in female humans and animals.", "output": {"entities": {"chemical": [{"text": "Estrogen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "However, the investigation of estrogenic effects in males has been largely neglected.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we investigated the hippocampal gene expression of estrogen receptors alpha and beta (ER alpha, beta) in 8-week-old, 12-week-old and 24-week-old male rats.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 62, "end": 70}]}}, "schema": []}
{"input": "To control for possible interactions between the expression of the estrogen receptor genes and other learning-related steroid receptors, androgen receptors (AR), corticosterone-binding glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) were also measured.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 67, "end": 75}, {"text": "steroid", "start": 118, "end": 125}, {"text": "androgen", "start": 137, "end": 145}, {"text": "corticosterone", "start": 162, "end": 176}]}}, "schema": []}
{"input": "Furthermore, the concentrations of the ligands 17 beta-estradiol, testosterone and corticosterone were measured.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 47, "end": 64}, {"text": "testosterone", "start": 66, "end": 78}, {"text": "corticosterone", "start": 83, "end": 97}]}}, "schema": []}
{"input": "The spatial training was conducted in a hole-board.", "output": {"entities": {}}, "schema": []}
{"input": "The 8-week-old rats exhibited higher levels of general activity and exploration during the training and performed best with respect to spatial learning and memory, whereas no difference was found between the 12-week-old and 24-week-old rats.", "output": {"entities": {}}, "schema": []}
{"input": "The trained 8-week-old rats exhibited increased gene expression of ER alpha compared with the untrained rats in this age group as well as the trained 12-week-old and 24-week-old rats.", "output": {"entities": {}}, "schema": []}
{"input": "The concentrations of estradiol and testosterone, however, were generally higher in the 24-week-old rats than in the 8-week-old and 12-week-old rats.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 22, "end": 31}, {"text": "testosterone", "start": 36, "end": 48}]}}, "schema": []}
{"input": "The ER alpha mRNA concentrations correlated positively with behavior that indicate general learning motivation.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest a specific role of ER alpha in the age-related differences in motivation and subsequent success in the task.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, estrogen and estrogenic functions may play a more prominent role in young male behavior and development than has been previously assumed.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 6, "end": 14}]}}, "schema": []}
{"input": "Single cell gene expression profiling of cortical osteoblast lineage cells.", "output": {"entities": {}}, "schema": []}
{"input": "In tissues with complex architectures such as bone, it is often difficult to purify and characterize specific cell types via molecular profiling.", "output": {"entities": {}}, "schema": []}
{"input": "Single cell gene expression profiling is an emerging technology useful for characterizing transcriptional profiles of individual cells isolated from heterogeneous populations.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we describe a novel procedure for the isolation and characterization of gene expression profiles of single osteoblast lineage cells derived from cortical bone.", "output": {"entities": {}}, "schema": []}
{"input": "Mixed populations of different cell types were isolated from adult long bones of C57BL/6J mice by enzymatic digestion, and subsequently subjected to FACS to purify and characterize osteoblast lineage cells via a selection strategy using antibodies against CD31, CD45, and alkaline phosphatase (AP), specific for mature osteoblasts.", "output": {"entities": {}}, "schema": []}
{"input": "The purified individual osteoblast lineage cells were then profiled at the single cell level via nanofluidic PCR.", "output": {"entities": {}}, "schema": []}
{"input": "This method permits robust gene expression profiling on single osteoblast lineage cells derived from mature bone, potentially from anatomically distinct sites.", "output": {"entities": {}}, "schema": []}
{"input": "In conjunction with this technique, we have also shown that it is possible to carry out single cell profiling on cells purified from fixed and frozen bone samples without compromising the gene expression signal.", "output": {"entities": {}}, "schema": []}
{"input": "The latter finding means the technique can be extended to biopsies of bone from diseased individuals.", "output": {"entities": {}}, "schema": []}
{"input": "Our approach for single cell expression profiling provides a new dimension to the transcriptional profile of the primary osteoblast lineage population in vivo, and has the capacity to greatly expand our understanding of how these cells may function in vivo under normal and diseased states.", "output": {"entities": {}}, "schema": []}
{"input": "Directional scrolling of SiGe/Si/Cr nanoribbon on Si (111) surfaces controlled by two-fold rotational symmetry underetching.", "output": {"entities": {"chemical": [{"text": "SiGe", "start": 25, "end": 29}, {"text": "Si", "start": 30, "end": 32}, {"text": "Cr", "start": 33, "end": 35}, {"text": "Si", "start": 50, "end": 52}]}}, "schema": []}
{"input": "The controllable fabrication of self-scrolling SiGe/Si/Cr helical nanoribbons on Si (111) substrates is investigated.", "output": {"entities": {"chemical": [{"text": "SiGe", "start": 47, "end": 51}, {"text": "Si", "start": 52, "end": 54}, {"text": "Cr", "start": 55, "end": 57}, {"text": "Si", "start": 81, "end": 83}]}}, "schema": []}
{"input": "The initial lateral etching profile of the Si (111) substrates shows a 2-fold rotational symmetry using 4% ammonia solution, which provides guidance for initial scrolling of one-end-fixed nanoribbons to form helical structures.", "output": {"entities": {"chemical": [{"text": "Si", "start": 43, "end": 45}, {"text": "ammonia", "start": 107, "end": 114}]}}, "schema": []}
{"input": "The chirality of the SiGe/Si/Cr helices with isotropic Young' s moduli is governed by the anisotropic underetching in the initial stage, which can be precisely judged, as the orientation of the ribbon is predesigned.", "output": {"entities": {"chemical": [{"text": "SiGe", "start": 21, "end": 25}, {"text": "Si", "start": 26, "end": 28}, {"text": "Cr", "start": 29, "end": 31}]}}, "schema": []}
{"input": "Furthermore, the helicity angle and radius of the formed helices are investigated by the lateral etching behavior and Cosserat curve theory of the Si (111) substrates, respectively, which are consistent with the experimental data.", "output": {"entities": {"chemical": [{"text": "Si", "start": 147, "end": 149}]}}, "schema": []}
{"input": "The present work provides the scrolling rule of nanoribbons with an isotropic Young' s modulus and anisotropic underetching in the formation of micro-/nanohelices.", "output": {"entities": {}}, "schema": []}
{"input": "Modulation of multidrug resistance in cancer cells by chelidonine and Chelidonium majus alkaloids.", "output": {"entities": {"chemical": [{"text": "chelidonine", "start": 54, "end": 65}]}}, "schema": []}
{"input": "Cancer cells often develop multidrug resistance (MDR) which is a multidimensional problem involving several mechanisms and targets.", "output": {"entities": {}}, "schema": []}
{"input": "This study demonstrates that chelidonine and an alkaloid extract from Chelidonium majus, which contains protoberberine and benzo [c] phenanthridine alkaloids, has the ability to overcome MDR of different cancer cell lines through interaction with ABC-transporters, CYP3A4 and GST, by induction of apoptosis, and cytotoxic effects.", "output": {"entities": {"chemical": [{"text": "chelidonine", "start": 29, "end": 40}, {"text": "protoberberine and benzo [c] phenanthridine alkaloids", "start": 104, "end": 157}]}}, "schema": []}
{"input": "Chelidonine and the alkaloid extract inhibited P-gp/MDR1 activity in a concentration-dependent manner in Caco-2 and CEM/ADR5000 and reversed their doxorubicin resistance.", "output": {"entities": {"chemical": [{"text": "Chelidonine", "start": 0, "end": 11}, {"text": "doxorubicin", "start": 147, "end": 158}]}}, "schema": []}
{"input": "In addition, chelidonine and the alkaloid extract inhibited the activity of the drug modifying enzymes CYP3A4 and GST in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "chelidonine", "start": 13, "end": 24}]}}, "schema": []}
{"input": "The alkaloids induced apoptosis in MDR cells which was accompanied by an activation of caspase-3,-8,-6/9, and phosphatidyl serine (PS) exposure.", "output": {"entities": {"chemical": [{"text": "phosphatidyl serine", "start": 110, "end": 129}]}}, "schema": []}
{"input": "cDNA arrays were applied to identify differentially expressed genes after treatment with chelidonine and the alkaloid extract.", "output": {"entities": {"chemical": [{"text": "chelidonine", "start": 89, "end": 100}]}}, "schema": []}
{"input": "The expression analysis identified a common set of regulated genes related to apoptosis, cell cycle, and drug metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment of Caco-2 cells with 50 mu g/ml alkaloid extract and 50 mu M chelidonine for up to 48 h resulted in a significant decrease in mRNA levels of P-gp/MDR1, MRP1, BCRP, CYP3A4, GST, and hPXR and in a significant increase in caspase-3 and caspase-8 mRNA.", "output": {"entities": {"chemical": [{"text": "chelidonine", "start": 71, "end": 82}]}}, "schema": []}
{"input": "Thus, chelidonine is a promising model compound for overcoming MDR and for enhancing cytotoxicity of chemotherapeutics, especially against leukaemia cells.", "output": {"entities": {"chemical": [{"text": "chelidonine", "start": 6, "end": 17}]}}, "schema": []}
{"input": "Its efficacy needs to be confirmed in animal models.", "output": {"entities": {}}, "schema": []}
{"input": "Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Design and functionalization strategies for multifunctional nanocarriers (e. g., nanoparticles, micelles, polymersomes) based on biodegradable/biocompatible polymers intended to be employed for active targeting and drug delivery are reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "This review will focus on the nature of the polymers involved in the preparation of targeted nanocarriers, the synthesis methods to achieve the desired macromolecular architecture, the selected coupling strategy, the choice of the homing molecules (vitamins, hormones, peptides, proteins, etc.), as well as the various strategies to display them at the surface of nanocarriers.", "output": {"entities": {}}, "schema": []}
{"input": "The resulting morphologies and the main colloidal features will be given as well as an overview of the biological activities, with a special focus on the main in vivo achievements.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of arsenic resistant bacteria from arsenic rich groundwater of West Bengal, India.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 20, "end": 27}, {"text": "arsenic", "start": 52, "end": 59}]}}, "schema": []}
{"input": "Sixty-four arsenic (As) resistant bacteria isolated from an arsenic rich groundwater sample of West Bengal were characterized to investigate their potential role in subsurface arsenic mobilization.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 11, "end": 18}, {"text": "As", "start": 20, "end": 22}, {"text": "arsenic", "start": 60, "end": 67}, {"text": "arsenic", "start": 176, "end": 183}]}}, "schema": []}
{"input": "Among the isolated strains predominance of genera Agrobacterium/Rhizobium, Ochrobactrum and Achromobacter which could grow chemolitrophically and utilize arsenic as electron donor were detected.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 154, "end": 161}]}}, "schema": []}
{"input": "Higher tolerance to As (3 +) [maximum tolerable concentration (MTC): >= 10 mM], As (5 +) (MTC: >= 100 mM) and other heavy metals like Cu (2 +), Cr (2 +), Ni (2 +) etc.", "output": {"entities": {"chemical": [{"text": "As (3 +)", "start": 20, "end": 28}, {"text": "As", "start": 80, "end": 82}, {"text": "Cu (2 +)", "start": 134, "end": 142}, {"text": "Cr (2 +)", "start": 144, "end": 152}, {"text": "Ni (2 +)", "start": 154, "end": 162}]}}, "schema": []}
{"input": "(MTC: >= 10 mM), presence of arsenate reductase and siderophore was frequently observed among the isolates.", "output": {"entities": {"chemical": [{"text": "arsenate", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Ability to produce arsenite oxidase and phosphatase enzyme was detected in 50 and 34% of the isolates, respectively.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 19, "end": 27}]}}, "schema": []}
{"input": "Although no direct correlation among taxonomic identity of bacterial strains and their metabolic abilities as mentioned above was apparent, several isolates affiliated to genera Ochrobactrum, Achromobacter and unclassified Rhizobiaceae members were found to be highly resistant to As (3 +) and As (5 +) and positive for all the test properties.", "output": {"entities": {"chemical": [{"text": "As (3 +)", "start": 281, "end": 289}, {"text": "As (5 +)", "start": 294, "end": 302}]}}, "schema": []}
{"input": "Arsenate reductase activity was found to be conferred by arsC gene, which in many strains was coupled with arsenite efflux gene arsB as well.", "output": {"entities": {"chemical": [{"text": "Arsenate", "start": 0, "end": 8}, {"text": "arsenite", "start": 107, "end": 115}]}}, "schema": []}
{"input": "Phylogenetic incongruence between the 16S rRNA and ars genes lineages indicated possible incidence of horizontal gene transfer for ars genes.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the results we propose that under the prevailing low nutrient condition inhabitant bacteria capable of using inorganic electron donors play a synergistic role wherein siderophores and phosphatase activities facilitate the release of sediment bound As (5 +), which is subsequently reduced by arsenate reductase resulting into the mobilization of As (3 +) in groundwater.", "output": {"entities": {"chemical": [{"text": "As (5 +)", "start": 257, "end": 265}, {"text": "arsenate", "start": 300, "end": 308}, {"text": "As (3 +)", "start": 354, "end": 362}]}}, "schema": []}
{"input": "Phase 1 and phase 2 drug metabolism and bile acid production of HepaRG cells in a bioartificial liver in absence of dimethyl sulfoxide.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 40, "end": 49}, {"text": "dimethyl sulfoxide", "start": 116, "end": 134}]}}, "schema": []}
{"input": "The human liver cell line HepaRG has been recognized as a promising source for in vitro testing of metabolism and toxicity of compounds.", "output": {"entities": {}}, "schema": []}
{"input": "However, currently the hepatic differentiation of these cells relies on exposure to dimethylsulfoxide (DMSO), which, as a side effect, has a cytotoxic effect and represses an all-round hepatic functionality.", "output": {"entities": {"chemical": [{"text": "dimethylsulfoxide", "start": 84, "end": 101}, {"text": "DMSO", "start": 103, "end": 107}]}}, "schema": []}
{"input": "The AMC-bioartificial liver (AMC-BAL) is a three-dimensional bioreactor that has previously been shown to upregulate various liver functions of cultured cells.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore cultured HepaRG cells in the AMC-BAL without DMSO and characterized the drug metabolism.", "output": {"entities": {"chemical": [{"text": "DMSO", "start": 58, "end": 62}]}}, "schema": []}
{"input": "Within 14 days of culture, the HepaRG-AMC-BALs contained highly polarized viable liver-like tissue with heterogeneous expression of CYP3A4.", "output": {"entities": {}}, "schema": []}
{"input": "We found a substantial metabolism of the tested substrates, ranging from 26% (UDP-glucuronosyltransferase 1A1), 47% (CYP3A4), to 240% (CYP2C9) of primary human hepatocytes.", "output": {"entities": {"chemical": [{"text": "UDP", "start": 78, "end": 81}]}}, "schema": []}
{"input": "The CYP3A4 activity could be induced 2-fold by rifampicin, whereas CYP2C9 activity remained equally high.", "output": {"entities": {"chemical": [{"text": "rifampicin", "start": 47, "end": 57}]}}, "schema": []}
{"input": "The HepaRG-AMC-BAL secreted bile acids at 43% the rate of primary human hepatocytes and demonstrated hydroxylation, conjugation, and transport of bile salts.", "output": {"entities": {"chemical": [{"text": "bile acids", "start": 28, "end": 38}, {"text": "bile salts", "start": 146, "end": 156}]}}, "schema": []}
{"input": "Concluding, culturing HepaRG cells in the AMC-BAL yields substantial phase 1 and phase 2 drug metabolism, while maintaining high viability, rendering DMSO addition superfluous for the promotion of drug metabolism.", "output": {"entities": {"chemical": [{"text": "DMSO", "start": 150, "end": 154}]}}, "schema": []}
{"input": "Therefore, AMC-BAL culturing makes the HepaRG cells more suitable for testing metabolism and toxicity of drugs.", "output": {"entities": {}}, "schema": []}
{"input": "FRET-capture: a sensitive method for the detection of dynamic protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Caught in the act: The FRET-Capture approach exploits a bound solvatochromic fluorophore, 4-N, N-dimethylamino-1, 8-naphthalimide, as a FRET donor in both inter-and intramolecular energy transfer.", "output": {"entities": {"chemical": [{"text": "4-N, N-dimethylamino-1, 8-naphthalimide", "start": 90, "end": 129}]}}, "schema": []}
{"input": "A unique feature of this method is the additional level of signal selectivity as the FRET signal is only turned on when the donor is specifically bound to the protein of interest, eliminating high background and false positive signals.", "output": {"entities": {}}, "schema": []}
{"input": "3, 14-Bis (p-nitrophenyl)-17, 17-dipentyltetrabenzo [a, c, g, i]-fluorene: a new fluorophore displaying both remarkable solvatochromism and crystalline-induced emission.", "output": {"entities": {"chemical": [{"text": "3, 14-Bis (p-nitrophenyl)-17, 17-dipentyltetrabenzo [a, c, g, i]-fluorene", "start": 0, "end": 73}]}}, "schema": []}
{"input": "A series of 17, 17-dialkyl-3, 14-diaryltetrabenzofluorenes were efficiently prepared by using Suzuki-Miyaura cross-coupling reactions of the corresponding 3, 14-dibromo derivatives.", "output": {"entities": {"chemical": [{"text": "17, 17-dialkyl-3, 14-diaryltetrabenzofluorenes", "start": 12, "end": 58}, {"text": "3, 14-dibromo", "start": 155, "end": 168}]}}, "schema": []}
{"input": "Studies of the unique fluorescence properties of these compounds showed that they display intense blue to yellow fluorescence with high quantum yields in the solution state and blue to orange fluorescence with moderate quantum yields in the solid state.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the fluorescence wavelength of the bis (p-nitrophenyl) derivative is remarkably solvent-dependent in a manner that correlates with the solvent polarity parameter E (T) (30).", "output": {"entities": {"chemical": [{"text": "bis (p-nitrophenyl)", "start": 48, "end": 67}]}}, "schema": []}
{"input": "The results of density function theory calculations suggest that the intramolecular charge-transfer character of the HOMO-LUMO transition is responsible for the large solvent effect.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, addition of water to a tetrahydrofuran (THF) solution of this compound leads to quenching of the yellow fluorescence owing to an increase in the solvent polarity.", "output": {"entities": {"chemical": [{"text": "tetrahydrofuran", "start": 33, "end": 48}, {"text": "THF", "start": 50, "end": 53}]}}, "schema": []}
{"input": "However, when the amount of water fraction exceeds 70%, a new fluorescence band appears at the same orange-red emission wavelength as that of the solid-state fluorescence.", "output": {"entities": {}}, "schema": []}
{"input": "This observation suggests the occurrence of a crystallization-induced emission (CIE) phenomenon in highly aqueous THF.", "output": {"entities": {"chemical": [{"text": "THF", "start": 114, "end": 117}]}}, "schema": []}
{"input": "Loading metal nanostructures on cotton fabrics as recyclable catalysts.", "output": {"entities": {}}, "schema": []}
{"input": "Noble metal nanostructures of varying compositions and shapes are loaded on cotton fabrics.", "output": {"entities": {}}, "schema": []}
{"input": "The fabric-supported metal nanostructures can function as effective catalysts for different liquid-phase catalytic reactions.", "output": {"entities": {}}, "schema": []}
{"input": "They exhibit superior recyclability, with the catalytic activities remaining nearly unchanged even after ten cycles of catalytic reactions for all of the three tested reactions.", "output": {"entities": {}}, "schema": []}
{"input": "Controlled Synthesis of Double-Wall a-FePO4 Nanotubes and their LIB Cathode Properties.", "output": {"entities": {"chemical": [{"text": "FePO4", "start": 38, "end": 43}]}}, "schema": []}
{"input": "Double-wall amorphous FePO4 nanotubes are prepared by an oil-phase chemical route.", "output": {"entities": {"chemical": [{"text": "FePO4", "start": 22, "end": 27}]}}, "schema": []}
{"input": "The inward diffusion of vacancies and outward diffusion of ions through passivation layers result in double-wall nanotubes with thin walls.", "output": {"entities": {}}, "schema": []}
{"input": "Such a process can be extended to prepare hollow polydedral nanocrystals and hollow ellipsoids.", "output": {"entities": {}}, "schema": []}
{"input": "The double-wall FePO4 nanotubes show interesting cathode performance in Li ion batteries.", "output": {"entities": {"chemical": [{"text": "FePO4", "start": 16, "end": 21}, {"text": "Li", "start": 72, "end": 74}]}}, "schema": []}
{"input": "High-throughput screening of substrate chemistry for embryonic stem cell attachment, expansion, and maintaining pluripotency.", "output": {"entities": {}}, "schema": []}
{"input": "Appropriate surface attachment is essential for growing embryonic stem (ES) cells in an undifferentiated state.", "output": {"entities": {}}, "schema": []}
{"input": "It is challenging to identify the optimal surface chemistry of the substrata for ES cell attachment and maintenance.", "output": {"entities": {}}, "schema": []}
{"input": "Using a rapid, high-throughput polymerization and screening platform with a comprehensive library of 66 monomer-grafted membrane surfaces, the optimal substrate, N-[3-(dimethylamino) propyl] methacrylamide (DMAPMA) has been identified to support strong attachment, high expansion capacity, and long-term self-renewal of ES cells (up to 7 passages).", "output": {"entities": {"chemical": [{"text": "N-[3-(dimethylamino) propyl] methacrylamide", "start": 162, "end": 205}, {"text": "DMAPMA", "start": 207, "end": 213}]}}, "schema": []}
{"input": "This monomer-based, chemically defined, scalable, sustainable, relatively inexpensive, covalently grafted, and controllable polymeric substrate provides a new opportunity to manipulate surface chemistry for pluripotent stem culture.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the dark and light-enhanced bactericidal action of cationic conjugated polyelectrolytes and oligomers.", "output": {"entities": {}}, "schema": []}
{"input": "A multiscale investigation was carried out to study the dark and light-enhanced bactericidal mechanisms of poly (phenylene ethynylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and oligo-phenylene ethynylenes (OPEs).", "output": {"entities": {"chemical": [{"text": "poly (phenylene ethynylene)", "start": 107, "end": 134}, {"text": "PPE", "start": 136, "end": 139}, {"text": "oligo-phenylene ethynylenes", "start": 195, "end": 222}, {"text": "OPEs", "start": 224, "end": 228}]}}, "schema": []}
{"input": "On the morphological scale, Gram-negative E. coli cells exposed to CPE and OPE compounds in the dark show damage to the cell envelope, plasma membrane, and in some cases the cytoplasm, while with UV-irradiation, E. coli sustained catastrophic damages to both the cell envelope and cytoplasm.", "output": {"entities": {"chemical": [{"text": "OPE", "start": 75, "end": 78}]}}, "schema": []}
{"input": "In contrast, the Gram-positive S. epi bacteria appeared intact when exposed to CPE and OPE compounds in the dark but showed damages to the cell envelope with UV-irradiation.", "output": {"entities": {"chemical": [{"text": "OPE", "start": 87, "end": 90}]}}, "schema": []}
{"input": "To better understand the molecular basis of CPE-and OPE-induced morphological changes and damages to bacteria, we investigated the effect of these compounds on model bacterial plasma membrane and bacterial proteins and plasmid DNA.", "output": {"entities": {"chemical": [{"text": "OPE", "start": 52, "end": 55}]}}, "schema": []}
{"input": "Measurements of dark membrane perturbation activity of the CPEs and OPEs using model lipid membranes support a carpet or detergent-like mechanism by which the antimicrobial compounds induce membrane collapse and phase transitions.", "output": {"entities": {"chemical": [{"text": "OPEs", "start": 68, "end": 72}]}}, "schema": []}
{"input": "Under UV-irradiation, E. coli bacteria exposed to CPEs and OPEs showed covalent modifications and damages to both cellular protein and plasmid DNA, likely through oxidative pathways mediated by singlet oxygen and subsequent reactive oxygen species sensitized by the CPE and OPE compounds.", "output": {"entities": {"chemical": [{"text": "OPEs", "start": 59, "end": 63}, {"text": "oxygen", "start": 202, "end": 208}, {"text": "oxygen", "start": 233, "end": 239}, {"text": "OPE", "start": 274, "end": 277}]}}, "schema": []}
{"input": "Our finding thus show that the antimicrobial polymers and oligomers exert toxicity toward Gram-negative bacteria by disrupting the morphology and structures of cell envelope and cytoplasm, including cellular components such as proteins and DNA, while exert toxicity toward Gram-positive bacteria by binding to and disrupting just the cell wall.", "output": {"entities": {}}, "schema": []}
{"input": "Unconventional growth mechanism for monolithic integration of III-V on silicon.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 71, "end": 78}]}}, "schema": []}
{"input": "The heterogeneous integration of III-V optoelectronic devices with Si electronic circuits is highly desirable because it will enable many otherwise unattainable capabilities.", "output": {"entities": {"chemical": [{"text": "Si", "start": 67, "end": 69}]}}, "schema": []}
{"input": "However, direct growth of III-V thin film on silicon substrates has been very challenging because of large mismatches in lattice constants and thermal coefficients.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 45, "end": 52}]}}, "schema": []}
{"input": "Furthermore, the high epitaxial growth temperature is detrimental to transistor performance.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present a detailed studies on a novel growth mode which yields a catalyst-free (Al, In) GaAs nanopillar laser on a silicon substrate by metal-organic chemical vapor deposition at the low temperature of 400 degrees C.", "output": {"entities": {"chemical": [{"text": "Al", "start": 89, "end": 91}, {"text": "In", "start": 93, "end": 95}, {"text": "GaAs", "start": 97, "end": 101}, {"text": "silicon", "start": 124, "end": 131}]}}, "schema": []}
{"input": "We study the growth and misfit stress relaxation mechanism by cutting through the center of the InGaAs/GaAs nanopillars using focused ion beam and inspecting with high-resolution transmission electron microscopy.", "output": {"entities": {"chemical": [{"text": "InGaAs", "start": 96, "end": 102}, {"text": "GaAs", "start": 103, "end": 107}]}}, "schema": []}
{"input": "The bulk material of the nanopillar is in pure wurtzite crystal phase, despite the 6% lattice mismatch with the substrate, with all stacking disorders well confined in the bottom-most transition region and terminated horizontally.", "output": {"entities": {"chemical": [{"text": "wurtzite", "start": 47, "end": 55}]}}, "schema": []}
{"input": "Furthermore, InGaAs was found to be in direct contact with silicon, in agreement with the observed crystal orientation alignment and good electrical conduction across the interface.", "output": {"entities": {"chemical": [{"text": "InGaAs", "start": 13, "end": 19}, {"text": "silicon", "start": 59, "end": 66}]}}, "schema": []}
{"input": "This is in sharp contrast to many III-V nanowires on silicon which are observed to stem from thin SiN (x), SiO (2), or SiO (2)/Si openings.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 53, "end": 60}, {"text": "SiN (x)", "start": 98, "end": 105}, {"text": "SiO (2)", "start": 107, "end": 114}, {"text": "SiO (2)", "start": 119, "end": 126}, {"text": "Si", "start": 127, "end": 129}]}}, "schema": []}
{"input": "In addition, GaAs was found to grow perfectly as a shell layer on In (0. 2) Ga (0. 8) As with an extraordinary thickness, which is 15 times greater than the theoretical thin-film critical thickness for a 1. 5% lattice mismatch.", "output": {"entities": {"chemical": [{"text": "GaAs", "start": 13, "end": 17}, {"text": "In (0. 2) Ga (0. 8) As", "start": 66, "end": 88}]}}, "schema": []}
{"input": "This is attributed to the core-shell radial geometry allowing the outer layers to expand and release the strain due to lattice mismatch.", "output": {"entities": {}}, "schema": []}
{"input": "The findings in this study redefine the rules for lattice-mismatched growth on heterogeneous substrates and device structure design.", "output": {"entities": {}}, "schema": []}
{"input": "A comparative study of the rotational dynamics of PF6 (-) anions in the crystals and liquid states of 1-butyl-3-methylimidazolium hexafluorophosphate: results from 31P NMR spectroscopy.", "output": {"entities": {"chemical": [{"text": "PF6 (-)", "start": 50, "end": 57}, {"text": "1-butyl-3-methylimidazolium hexafluorophosphate", "start": 102, "end": 149}, {"text": "31P", "start": 164, "end": 167}]}}, "schema": []}
{"input": "The rotational dynamics of the hexafluorophosphate anion (PF (6) (-)) in the crystalline and liquid states of the archetypal room temperature ionic liquid (RTIL) 1-butyl-3-methylimidazolium hexafluorophosphate ([C (4) mim] PF (6)) are investigated using (31) P NMR spectroscopy line shape analyses and spin-lattice relaxation time measurements.", "output": {"entities": {"chemical": [{"text": "hexafluorophosphate", "start": 31, "end": 50}, {"text": "PF (6) (-)", "start": 58, "end": 68}, {"text": "1-butyl-3-methylimidazolium hexafluorophosphate", "start": 162, "end": 209}, {"text": "[C (4) mim] PF (6)", "start": 211, "end": 229}, {"text": "(31) P", "start": 254, "end": 260}]}}, "schema": []}
{"input": "The PF (6) (-) anion performs isotropic rotation in all three polymorphic crystals phases alpha, beta, and gamma as well as in the liquid state with a characteristic time scale that ranges from a few ps to a few hundred ps over a temperature range of 180-280 K.", "output": {"entities": {"chemical": [{"text": "PF (6) (-)", "start": 4, "end": 14}]}}, "schema": []}
{"input": "The rotational correlation time tau (c) for PF (6) (-) rotation follows the sequence gamma-phase < alpha-phase =~ liquid < beta-phase.", "output": {"entities": {"chemical": [{"text": "PF (6) (-)", "start": 44, "end": 54}]}}, "schema": []}
{"input": "On the other hand, in the liquid state, all local motions in the cation as well as its global rotational reorientation are characterized by time scales that are slower compared to that for the PF (6) (-) anion rotation.", "output": {"entities": {"chemical": [{"text": "PF (6) (-)", "start": 193, "end": 203}]}}, "schema": []}
{"input": "The time scale tau (c) and the activation energy of PF (6) (-) rotation in this RTIL are found to be comparable with those observed in ordinary alkali and ammonium salts despite the large counterion size and low melting point of the former.", "output": {"entities": {"chemical": [{"text": "PF (6) (-)", "start": 52, "end": 62}, {"text": "ammonium salts", "start": 155, "end": 169}]}}, "schema": []}
{"input": "The high sphericity of the PF (6) (-) ion is hypothesized to play an important role in the decoupling of its rotational dynamics that appear to be practically independent of the averaged cation-anion interaction.", "output": {"entities": {"chemical": [{"text": "PF (6) (-)", "start": 27, "end": 37}]}}, "schema": []}
{"input": "Multiphoton imaging reveals a new leukocyte recruitment paradigm in the glomerulus.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast with many capillary beds, the glomerulus readily supports leukocyte recruitment.", "output": {"entities": {}}, "schema": []}
{"input": "However, little is known regarding the actions of leukocytes following their recruitment to glomeruli.", "output": {"entities": {}}, "schema": []}
{"input": "We used multiphoton confocal microscopy to examine leukocyte behavior in the glomerular microvasculature.", "output": {"entities": {}}, "schema": []}
{"input": "In normal glomeruli, neutrophils and monocytes were retained in capillaries for several minutes, remaining static or migrating intravascularly.", "output": {"entities": {}}, "schema": []}
{"input": "Induction of glomerular inflammation resulted in an increase in the duration of retention of static and migratory leukocytes.", "output": {"entities": {}}, "schema": []}
{"input": "In response to immune complex deposition, both static and migratory neutrophils generated oxidants in inflamed glomeruli via a Mac-1-dependent mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "Our results describe a new paradigm for glomerular inflammation, suggesting that the major effect of acute inflammation is to increase the duration of leukocyte retention in the glomerulus.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, these findings describe a previously unknown form of multicellular intravascular patrolling that involves both monocytes and neutrophils, which may underlie the susceptibility of the glomerulus to inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Complementary detection of embryotoxic properties of substances in the neural and cardiac embryonic stem cell tests.", "output": {"entities": {}}, "schema": []}
{"input": "In developmental toxicity testing, in vitro screening assays are highly needed to increase efficiency and to reduce animal use.", "output": {"entities": {}}, "schema": []}
{"input": "A promising in vitro assay is the cardiac embryonic stem cell test (ESTc), in which the effect of developmental toxicants on cardiomyocyte differentiation is assessed.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, we developed a neural differentiation variant of the stem cell test (neural embryonic stem cell test [ESTn]).", "output": {"entities": {}}, "schema": []}
{"input": "In both of these models, we have previously performed a series of transcriptomic studies to characterize gene expression changes (1) across time during normal differentiation and (2) in response to a series of developmental toxicants in the ESTn and ESTc.", "output": {"entities": {}}, "schema": []}
{"input": "Here, using the cumulative of these studies, we compared gene expression profiles of ESTn and ESTc over time as well as model-specific changes induced by seven compounds, comprising six known in vivo developmental toxicants and one negative control.", "output": {"entities": {}}, "schema": []}
{"input": "Time-related gene expression profiles showed similarities between the two EST systems.", "output": {"entities": {}}, "schema": []}
{"input": "However, specific genes could be identified changing over time differently in each model related to the two different lineages of differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, compound-induced gene expression changes were generally model specific, especially for methylmercury and flusilazole, which were predicted better in ESTn and ESTc, respectively.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 102, "end": 115}, {"text": "flusilazole", "start": 120, "end": 131}]}}, "schema": []}
{"input": "Valproic acid-induced gene expression changes were most comparable out of the six developmental toxicants between the ESTn and ESTc.", "output": {"entities": {"chemical": [{"text": "Valproic acid", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Direct transcriptomic comparisons between the ESTn and ESTc indicate that combined transcriptomic analyses support and complement each other.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, a combined approach incorporating ESTc and ESTn may improve developmental toxicant detection over individual assays.", "output": {"entities": {}}, "schema": []}
{"input": "General methodology of using oil-in-water and water-in-oil emulsions for coiling nanofilaments.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrophobic carbon nanotubes (CNTs) and hydrophilic nanofilaments such as oxidized CNTs, Pd nanowires (NWs), and MnO (2) NWs are transformed from wires to rings by a general methodology.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 12, "end": 18}, {"text": "Pd", "start": 89, "end": 91}, {"text": "MnO (2)", "start": 113, "end": 120}]}}, "schema": []}
{"input": "We show that both oil-in-water and water-in-oil emulsions, so long as their droplet size is sufficiently small, can exert significant force to the entrapped nanostructures, causing their deformation.", "output": {"entities": {}}, "schema": []}
{"input": "This effect can be easily achieved by simply mixing a few solutions in correct ratios.", "output": {"entities": {}}, "schema": []}
{"input": "Even preformed oil droplets can take in CNTs from the aqueous solution converting them into rings, indicating the important role of thermodynamics: The question here is not if the droplets can exert sufficient force to bend the nanofilaments, because their random vibration may be already doing it.", "output": {"entities": {}}, "schema": []}
{"input": "As long as the difference in solvation energy is large enough for a nanofilament, it would \" want \" to move away from the bulk solution and fit inside tiny droplets, even at the cost of induced strain energy.", "output": {"entities": {}}, "schema": []}
{"input": "That said, the specific interactions between a droplet and a filament are also of importance.", "output": {"entities": {}}, "schema": []}
{"input": "For example, when an oil droplet rapidly shrinks in size, it can compress the entrapped CNTs in multiple stages into structures with higher curvatures (thus higher strain) than that of a circular ring, which has minimal induced strain inside a spherical droplet.", "output": {"entities": {}}, "schema": []}
{"input": "Preparation of raspberry-like polymer particles by a heterocoagulation technique utilizing hydrogen bonding interactions between steric stabilizers.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Large polystyrene particles stabilized by poly (acrylic acid) (PAA) (L-PS (PAA)) (as the core) and small polystyrene particles stabilized by poly (vinyl pyrrolidone) (PVP) (S-PS (PVP)) (as the corona) were successfully used to prepare raspberry-like particles by a heterocoagulation technique utilizing the hydrogen bonding interaction between PAA and PVP.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 6, "end": 17}, {"text": "poly (acrylic acid)", "start": 42, "end": 61}, {"text": "PAA", "start": 63, "end": 66}, {"text": "PS (PAA)", "start": 71, "end": 79}, {"text": "polystyrene", "start": 105, "end": 116}, {"text": "poly (vinyl pyrrolidone)", "start": 141, "end": 165}, {"text": "PVP", "start": 167, "end": 170}, {"text": "PS (PVP)", "start": 175, "end": 183}, {"text": "hydrogen", "start": 307, "end": 315}, {"text": "PAA", "start": 344, "end": 347}, {"text": "PVP", "start": 352, "end": 355}]}}, "schema": []}
{"input": "The coverage of L-PS (PAA) by S-PS (PVP) could be controlled by adding PVP homopolymer to the L-PS (PAA) dispersion and by changing the molecular weight of the stabilizers.", "output": {"entities": {"chemical": [{"text": "PS (PAA)", "start": 18, "end": 26}, {"text": "PS (PVP)", "start": 32, "end": 40}, {"text": "PVP", "start": 71, "end": 74}, {"text": "PS (PAA)", "start": 96, "end": 104}]}}, "schema": []}
{"input": "Moreover, the heterocoagulation of large poly (methyl methacrylate) particles stabilized by PAA (L-PMMA (PAA)) and S-PS (PVP) particles was also accomplished, resulting in the formation of L-PMMA (PAA)-core/S-PS (PVP)-corona raspberry-like composite particles.", "output": {"entities": {"chemical": [{"text": "poly (methyl methacrylate)", "start": 41, "end": 67}, {"text": "PAA", "start": 92, "end": 95}, {"text": "PMMA (PAA)", "start": 99, "end": 109}, {"text": "PS (PVP)", "start": 117, "end": 125}, {"text": "PMMA (PAA)", "start": 191, "end": 201}, {"text": "PS (PVP)", "start": 209, "end": 217}]}}, "schema": []}
{"input": "These results suggested that the raspberry-like particles composed of various polymer particles could be formed by the heterocoagulation technique utilizing the hydrogen bonding interaction.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 161, "end": 169}]}}, "schema": []}
{"input": "Generation of B-doped graphene nanoplatelets using a solution process and their supercapacitor applications.", "output": {"entities": {"chemical": [{"text": "B-doped graphene", "start": 14, "end": 30}]}}, "schema": []}
{"input": "Chemically modified graphene (CMG) nanoplatelets have shown great promise in various applications due to their electrical properties and high surface area.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 20, "end": 28}]}}, "schema": []}
{"input": "Chemical doping is one of the most effective methods to tune the electronic properties of graphene materials.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 90, "end": 98}]}}, "schema": []}
{"input": "In this work, novel B-doped nanoplatelets (borane-reduced graphene oxide, B-rG-O) were produced on a large scale via the reduction of graphene oxide by a borane-tetrahydrofuran adduct under reflux, and their use for supercapacitor electrodes was studied.", "output": {"entities": {"chemical": [{"text": "B", "start": 20, "end": 21}, {"text": "borane", "start": 43, "end": 49}, {"text": "graphene oxide", "start": 58, "end": 72}, {"text": "B", "start": 74, "end": 75}, {"text": "O", "start": 79, "end": 80}, {"text": "graphene oxide", "start": 134, "end": 148}, {"text": "borane", "start": 154, "end": 160}, {"text": "tetrahydrofuran", "start": 161, "end": 176}]}}, "schema": []}
{"input": "This is the first report on the production of B-doped graphene nanoplatelets from a solution process and on the use of B-doped graphene materials in supercapacitors.", "output": {"entities": {"chemical": [{"text": "B-doped graphene", "start": 46, "end": 62}, {"text": "B-doped graphene", "start": 119, "end": 135}]}}, "schema": []}
{"input": "The B-rG-O had a high specific surface area of 466 m (2)/g and showed excellent supercapacitor performance including a high specific capacitance of 200 F/g in aqueous electrolyte as well as superior surface area-normalized capacitance to typical carbon-based supercapacitor materials and good stability after 4500 cycles.", "output": {"entities": {"chemical": [{"text": "B", "start": 4, "end": 5}, {"text": "O", "start": 9, "end": 10}, {"text": "carbon", "start": 246, "end": 252}]}}, "schema": []}
{"input": "Two-and three-electrode cell measurements showed that energy storage in the B-rG-O supercapacitors was contributed by ion adsorption on the surface of the nanoplatelets in addition to electrochemical redox reactions.", "output": {"entities": {"chemical": [{"text": "B", "start": 76, "end": 77}, {"text": "O", "start": 81, "end": 82}]}}, "schema": []}
{"input": "Unique aggregation behavior of a carboxylate gemini surfactant with a long rigid spacer in aqueous solution.", "output": {"entities": {"chemical": [{"text": "carboxylate", "start": 33, "end": 44}]}}, "schema": []}
{"input": "A new gemini surfactant with a long and rigid spacer, O, O'-bis (sodium 2-dodecylcarboxylate)-p-dibenzenediol (referred to as C (12) phi (2) C (12)), has been synthesized.", "output": {"entities": {"chemical": [{"text": "O, O'-bis (sodium 2-dodecylcarboxylate)-p-dibenzenediol", "start": 54, "end": 109}, {"text": "C (12) phi (2) C (12)", "start": 126, "end": 147}]}}, "schema": []}
{"input": "Its aggregation in aqueous solution has been studied using static and dynamic light scattering measurements.", "output": {"entities": {}}, "schema": []}
{"input": "The homologue O, O'-bis (sodium 2-dodecylcarboxylate)-p-benzenediol (C (12) phi C (12)) whose spacer only contains a single phenyl group was also examined for comparison.", "output": {"entities": {"chemical": [{"text": "O, O'-bis (sodium 2-dodecylcarboxylate)-p-benzenediol", "start": 14, "end": 67}, {"text": "C (12) phi C (12)", "start": 69, "end": 86}, {"text": "phenyl", "start": 124, "end": 130}]}}, "schema": []}
{"input": "Dynamic light scattering (DLS) revealed the unexpected existence of large aggregates in the solution of C (12) phi (2) C (12).", "output": {"entities": {"chemical": [{"text": "C (12) phi (2) C (12)", "start": 104, "end": 125}]}}, "schema": []}
{"input": "However, C (12) phi C (12) showed rather normal aggregation behavior.", "output": {"entities": {"chemical": [{"text": "C (12) phi C (12)", "start": 9, "end": 26}]}}, "schema": []}
{"input": "Both the results of intrinsic viscosity and light scattering demonstrated a loose structure for the large aggregates of C (12) phi (2) C (12).", "output": {"entities": {"chemical": [{"text": "C (12) phi (2) C (12)", "start": 120, "end": 141}]}}, "schema": []}
{"input": "This behavior was attributed to an extending configuration of C (12) phi (2) C (12) with the two alkyl tails stretching toward the solution due to the rigidity of the long spacer.", "output": {"entities": {"chemical": [{"text": "C (12) phi (2) C (12)", "start": 62, "end": 83}, {"text": "alkyl", "start": 97, "end": 102}]}}, "schema": []}
{"input": "The large network-like aggregate formation was an inevitable outcome of spontaneously reducing the energy of the system.", "output": {"entities": {}}, "schema": []}
{"input": "Freeze-fracture transmission electron microscopy (FF-TEM) images and (1) H NMR measurements supported this speculation.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 69, "end": 74}]}}, "schema": []}
{"input": "Due to the columnar-like molecular geometry, the large network-like aggregates were directly transformed into rodlike micelles with increasing surfactant concentration.", "output": {"entities": {}}, "schema": []}
{"input": "Depending on further micellar growth, the wormlike micelles were finally formed as confirmed by rheological measurements.", "output": {"entities": {}}, "schema": []}
{"input": "Contrasting toxicokinetic evaluations and interspecies pharmacokinetic scaling approaches for small molecules and biologics: applicability to biosimilar development.", "output": {"entities": {}}, "schema": []}
{"input": "1. A 2-fold threshold typically used for prediction accuracy of interspecies scaling of clearance (CL) may be too liberal when using pharmacokinetic similarity in animals to advance biosimilar candidate selection for clinical testing.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this review is to identify interspecies scaling methods for use in de-risking biosimilar development prior to clinical testing.", "output": {"entities": {}}, "schema": []}
{"input": "2. Scaling approaches for predicting macromolecule CL were identified through literature review.", "output": {"entities": {}}, "schema": []}
{"input": "Reports that evaluated predicted and observed human CLs for >= 5 individual compounds were considered.", "output": {"entities": {}}, "schema": []}
{"input": "Absolute average fold-error (AAFE) was calculated for each method along with the proportion of compounds with individual fold-error values within a tighter threshold of 0. 7-1. 3.", "output": {"entities": {}}, "schema": []}
{"input": "3. Traditional simple allometry with a minimum of three species and the rule of exponents performed inconsistently with some groups of compounds resulting in a greater than 2-fold error (i. e. AAFE > 2).", "output": {"entities": {}}, "schema": []}
{"input": "For monoclonal antibodies (mAbs), simplified allometric approaches employing a single species (monkey) with a fixed exponent of 0. 85 consistently resulted in lower AAFEs and a higher proportion of compounds within the tighter range of 0. 7-1. 3.", "output": {"entities": {}}, "schema": []}
{"input": "4. For macromolecules, and particularly mAbs, employing single-species monkey \" simplified \" allometric approaches with a fixed exponent of 0. 85 may be more appropriate than traditional allometric approaches.", "output": {"entities": {}}, "schema": []}
{"input": "Peptide/protein separation with cationic polymer brush nanosponges for MALDI-MS analysis.", "output": {"entities": {}}, "schema": []}
{"input": "A cationic polymer nanobrush was synthesized, attached to a MALDI target, and used for the fractionation of peptides and proteins based on their pI, prior to analysis by MALDI-MS.", "output": {"entities": {}}, "schema": []}
{"input": "The cationic polymer nanobrush was synthesized on a gold substrate by AIBN photoinitiated polymerization, using a 70: 30 ratio of 2-aminoethyl methacrylate hydrochloride (AEMA): N-isopropylacrylamide (NIPAAM).", "output": {"entities": {"chemical": [{"text": "AIBN", "start": 70, "end": 74}, {"text": "2-aminoethyl methacrylate hydrochloride", "start": 130, "end": 169}, {"text": "AEMA", "start": 171, "end": 175}, {"text": "N-isopropylacrylamide", "start": 178, "end": 199}, {"text": "NIPAAM", "start": 201, "end": 207}]}}, "schema": []}
{"input": "This brush showed selectivity for adsorption of acidic peptides and proteins and allowed fractionation of simple two-component mixtures to be completed in less than 10 min.", "output": {"entities": {}}, "schema": []}
{"input": "The brush-adsorbed biomolecules were recovered by treating the nanobrush with ammonium hydroxide, which effectively collapsed the brush, thereby releasing the trapped compounds for MALDI MS analysis.", "output": {"entities": {"chemical": [{"text": "ammonium hydroxide", "start": 78, "end": 96}]}}, "schema": []}
{"input": "These results demonstrate that nanobrush can serve as a convenient platform for rapid fractionation of biomolecules prior to analysis by MALDI-MS.", "output": {"entities": {}}, "schema": []}
{"input": "Direct measurement of Dirac point energy at the graphene/oxide interface.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 48, "end": 56}, {"text": "oxide", "start": 57, "end": 62}]}}, "schema": []}
{"input": "We report the direct measurement of the Dirac point, the Fermi level, and the work function of graphene by performing internal photoemission measurements on a graphene/SiO (2)/Si structure with a unique optical-cavity enhanced test structure.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 95, "end": 103}, {"text": "graphene", "start": 159, "end": 167}, {"text": "SiO (2)", "start": 168, "end": 175}, {"text": "Si", "start": 176, "end": 178}]}}, "schema": []}
{"input": "A complete electronic band alignment at the graphene/SiO (2)/Si interfaces is accurately established.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 44, "end": 52}, {"text": "SiO (2)", "start": 53, "end": 60}, {"text": "Si", "start": 61, "end": 63}]}}, "schema": []}
{"input": "The observation of enhanced photoemission from a one-atom thick graphene layer was possible by taking advantage of the constructive optical interference in the SiO (2) cavity.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 64, "end": 72}, {"text": "SiO (2)", "start": 160, "end": 167}]}}, "schema": []}
{"input": "The photoemission yield was found to follow the well-known linear density-of-states dispersion in the vicinity of the Dirac point.", "output": {"entities": {}}, "schema": []}
{"input": "At the flat band condition, the Fermi level was extracted and found to reside 3. 3 eV +/- 0. 05 eV below the bottom of the SiO (2) conduction band.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 123, "end": 130}]}}, "schema": []}
{"input": "When combined with the shift of the Fermi level from the Dirac point, we are able to ascertain the position of the Dirac point at 3. 6 eV +/- 0. 05 eV with respect to the bottom of the SiO (2) conduction band edge, yielding a work function of 4. 5 eV +/- 0. 05 eV which is in an excellent agreement with theory.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 185, "end": 192}]}}, "schema": []}
{"input": "The accurate determination of the work function of graphene is of significant importance to the engineering of graphene-based devices, and the measurement technique we have advanced in this Letter will have significant impact on numerous applications for emerging graphene-like 2-dimensional material systems.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 51, "end": 59}, {"text": "graphene", "start": 111, "end": 119}, {"text": "graphene", "start": 264, "end": 272}]}}, "schema": []}
{"input": "Sheehan' s syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Sheehan' s syndrome (SS) is characterized by various degrees of hypopituitarism, and develops as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage.", "output": {"entities": {}}, "schema": []}
{"input": "Increased pituitary volume, small sella size, disseminated intravascular coagulation and autoimmunity are the proposed factors in the pathogenesis of SS.", "output": {"entities": {}}, "schema": []}
{"input": "Hormonal insufficiencies, ranging from single pituitary hormone insufficiency to total hypopituitarism, are observed in patients.", "output": {"entities": {}}, "schema": []}
{"input": "The fi rst most important issue in the diagnosis is being aware of the syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Lack of lactation and failure of menstrual resumption after delivery that complicated with severe hemorrhage are the most important clues in diagnosing SS.", "output": {"entities": {}}, "schema": []}
{"input": "The most frequent endocrine disorders are the deficiencies of growth hormone and prolactin.", "output": {"entities": {}}, "schema": []}
{"input": "In patients with typical obstetric history, prolactin response to TRH seems to be the most sensitive screening test in diagnosing SS.", "output": {"entities": {}}, "schema": []}
{"input": "Other than typical pituitary deficiency, symptoms such as anemia, pancytopenia, osteoporosis, impairment in cognitive functions and impairment in the quality of life are also present in these patients.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment of SS is based on the appropriate replacement of deficient hormones.", "output": {"entities": {}}, "schema": []}
{"input": "Growth hormone replacement has been found to have positive effects; however, risk to benefit ratio, side effects and cost of the treatment should be taken into account.", "output": {"entities": {}}, "schema": []}
{"input": "A dimeric form of N-methoxycarbonyl-2-amino-1, 8-naphthyridine bound to the A-A mismatch in the CAG/CAG base triad in dsRNA.", "output": {"entities": {"chemical": [{"text": "N-methoxycarbonyl-2-amino-1, 8-naphthyridine", "start": 18, "end": 62}]}}, "schema": []}
{"input": "A dimeric form of N-methoxycarbonyl-2-amino-1, 8-naphthyridine (MCND) connected at the C2 position with a three-atom linker was examined for the binding to mismatches in double stranded RNA.", "output": {"entities": {"chemical": [{"text": "N-methoxycarbonyl-2-amino-1, 8-naphthyridine", "start": 18, "end": 62}, {"text": "MCND", "start": 64, "end": 68}]}}, "schema": []}
{"input": "Despite the fully complementary hydrogen bonding groups to guanine, MCND did not bind to guanine-guanine mismatch but did to adenine-adenine mismatch.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 32, "end": 40}, {"text": "guanine", "start": 59, "end": 66}, {"text": "MCND", "start": 68, "end": 72}, {"text": "guanine", "start": 89, "end": 96}, {"text": "guanine", "start": 97, "end": 104}, {"text": "adenine", "start": 125, "end": 132}, {"text": "adenine", "start": 133, "end": 140}]}}, "schema": []}
{"input": "The base pairs flanking the mismatch had weak effect on the binding, with showing the strongest binding to the A-A mismatch in the CAG/CAG sequence.", "output": {"entities": {}}, "schema": []}
{"input": "The A-A mismatch in the GAC/GAC sequence was a poor substrate for the MCND binding.", "output": {"entities": {"chemical": [{"text": "MCND", "start": 70, "end": 74}]}}, "schema": []}
{"input": "A monomeric derivative of MCND and another derivative lacking a methylcarbamate group showed negligilble binding to the A-A mismatch and the sequence selectivity.", "output": {"entities": {"chemical": [{"text": "MCND", "start": 26, "end": 30}, {"text": "methylcarbamate", "start": 64, "end": 79}]}}, "schema": []}
{"input": "These results are important clues for the better molecular design of RNA binding small molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Naphthyridinone (NTD) integrase inhibitors: N1 protio and methyl combination substituent effects with C3 amide groups.", "output": {"entities": {"chemical": [{"text": "Naphthyridinone", "start": 0, "end": 15}, {"text": "NTD", "start": 17, "end": 20}, {"text": "methyl", "start": 58, "end": 64}, {"text": "amide", "start": 105, "end": 110}]}}, "schema": []}
{"input": "Substituent effects of a series of N1 protio and methyl naphthyridinone HIV-1 integrase strand-transfer inhibitors has been explored.", "output": {"entities": {"chemical": [{"text": "methyl naphthyridinone", "start": 49, "end": 71}]}}, "schema": []}
{"input": "The effects of combinations of the N1 substituent and C3 amide groups was extensively studied to compare enzyme inhibition, antiviral activity and protein binding effects on potency.", "output": {"entities": {"chemical": [{"text": "amide", "start": 57, "end": 62}]}}, "schema": []}
{"input": "The impact of substitution on ligand efficiency was considered and several compounds were advanced into in vivo pharmacokinetic studies ultimately leading to the clinical candidate GSK364735.", "output": {"entities": {"chemical": [{"text": "GSK364735", "start": 181, "end": 190}]}}, "schema": []}
{"input": "Overexpression of Escherichia coli nucleotide excision repair genes after cisplatin-induced damage.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 35, "end": 45}, {"text": "cisplatin", "start": 74, "end": 83}]}}, "schema": []}
{"input": "Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication.", "output": {"entities": {"chemical": [{"text": "Cisplatin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "It is a commonly used chemotherapeutic agent binding mono-or bifunctionally to guanines in DNA.", "output": {"entities": {"chemical": [{"text": "guanines", "start": 79, "end": 87}]}}, "schema": []}
{"input": "Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 49, "end": 59}, {"text": "cisplatin", "start": 129, "end": 138}]}}, "schema": []}
{"input": "The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1. 5 h after ultraviolet radiation (UV).", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 161, "end": 170}]}}, "schema": []}
{"input": "Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 38, "end": 47}]}}, "schema": []}
{"input": "Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 10, "end": 19}]}}, "schema": []}
{"input": "Cockayne syndrome b maintains neural precursor function.", "output": {"entities": {}}, "schema": []}
{"input": "Neurodevelopmental defects are observed in the hereditary disorder Cockayne syndrome (CS).", "output": {"entities": {}}, "schema": []}
{"input": "The gene most frequently mutated in CS, Cockayne Syndrome B (CSB), is required for the repair of bulky DNA adducts in transcribed genes during transcription-coupled nucleotide excision repair.", "output": {"entities": {}}, "schema": []}
{"input": "CSB also plays a role in chromatin remodeling and mitochondrial function.", "output": {"entities": {}}, "schema": []}
{"input": "The role of CSB in neural development is poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report that the abundance of neural progenitors is normal in Csb (-/-) mice and the frequency of apoptotic cells in the neurogenic niche of the adult subependymal zone is similar in Csb (-/-) and wild type mice.", "output": {"entities": {}}, "schema": []}
{"input": "Both embryonic and adult Csb (-/-) neural precursors exhibited defective self-renewal in the neurosphere assay.", "output": {"entities": {}}, "schema": []}
{"input": "In Csb (-/-) neural precursors, self-renewal progressively decreased in serially passaged neurospheres.", "output": {"entities": {}}, "schema": []}
{"input": "The data also indicate that Csb and the nucleotide excision repair protein Xpa preserve embryonic neural stem cell self-renewal after UV DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Although Csb (-/-) neural precursors do not exhibit altered neuronal lineage commitment after low-dose UV (1J/m (2)) in vitro, neurons differentiated in vitro from Csb (-/-) neural precursors that had been irradiated with 1J/m (2) UV exhibited defective neurite outgrowth.", "output": {"entities": {}}, "schema": []}
{"input": "These findings identify a function for Csb in neural precursors.", "output": {"entities": {}}, "schema": []}
{"input": "Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes.", "output": {"entities": {}}, "schema": []}
{"input": "Meiotic chromosomes are organized into arrays of loops that are anchored to the chromosome axis structure.", "output": {"entities": {}}, "schema": []}
{"input": "Programmed DNA double-strand breaks (DSBs) that initiate meiotic recombination, catalyzed by Spo11 and accessory DSB proteins, form in loop sequences in promoters, whereas the DSB proteins are located on chromosome axes.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanisms bridging these two chromosomal regions for DSB formation have remained elusive.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that Spp1, a conserved member of the histone H3K4 methyltransferase Set1 complex, is required for normal levels of DSB formation and is associated with chromosome axes during meiosis, where it physically interacts with the Mer2 DSB protein.", "output": {"entities": {}}, "schema": []}
{"input": "The PHD finger module of Spp1, which reads H3K4 methylation close to promoters, promotes DSB formation by tethering these regions to chromosome axes and activating cleavage by the DSB proteins.", "output": {"entities": {}}, "schema": []}
{"input": "This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination.", "output": {"entities": {}}, "schema": []}
{"input": "Spontaneous renal tumors in two rats from a thirteen week rodent feeding study with grain from molecular stacked trait lepidopteran and coleopteran resistant (DP-O O 4114-3) maize.", "output": {"entities": {}}, "schema": []}
{"input": "A thirteen week feeding study was conducted by feeding young adult male and female Sprague Dawley [Crl: CD (R) (SD)] rats diets containing grain from genetically modified (GM) DP-O O 4114-3 maize that was either untreated (4114) or treated in the field with glufosinate ammonium (4114GLU).", "output": {"entities": {"chemical": [{"text": "glufosinate ammonium", "start": 258, "end": 278}]}}, "schema": []}
{"input": "Control rats were fed diets containing the same concentration of near isogenic, non-GM maize grain (091) or one of three types of commercially available non-GM maize grain.", "output": {"entities": {}}, "schema": []}
{"input": "At the end of the in-life phase, renal tubule tumors were reported in two male rats consuming diets containing 4114 maize grain.", "output": {"entities": {}}, "schema": []}
{"input": "An expert panel of pathologists was convened as a Pathology Working Group (PWG) to review coded kidney histology sections from control (091) and treated (4114 and 4114GLU) male rats.", "output": {"entities": {}}, "schema": []}
{"input": "The objectives were for the panel to characterize the histopathologic findings and to interpret their relationship to consumption of the indicated diet.", "output": {"entities": {}}, "schema": []}
{"input": "The PWG concluded unanimously that the kidney tumors were characteristic of amphophilic-vacuolar (AV) tumors and AV atypical tubular hyperplasia which represent a distinctive phenotype that has been reported to occur sporadically in young Sprague Dawley Rats.", "output": {"entities": {}}, "schema": []}
{"input": "The PWG determined that the neoplasms and atypical tubular hyperplasias were multicentric and bilateral which typifies tumors of familial origin.", "output": {"entities": {}}, "schema": []}
{"input": "Degenerative/regenerative or cytotoxic changes consistent with nephrotoxicity leading to tumor induction were not observed in these rats and thus supports the conclusion that tumors were unrelated to consumption of the test diet.", "output": {"entities": {}}, "schema": []}
{"input": "It was the unanimous opinion of the PWG that the proliferative renal tubule cell lesions were spontaneous and not related to consumption of diets containing 4114 maize grain.", "output": {"entities": {}}, "schema": []}
{"input": "Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes.", "output": {"entities": {"chemical": [{"text": "Gd", "start": 10, "end": 12}, {"text": "phosphatidyldiglycerol", "start": 74, "end": 96}]}}, "schema": []}
{"input": "Thermosensitive liposomes (TSL) with encapsulated magnetic resonance imaging (MRI) longitudinal relaxation time (T (1)) contrast agents (CAs) have been proposed for MRI assisted interventional thermotherapy in solid tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Here the feasibility of 6 clinically approved CAs (Gd-DTPA, Gd-BOPTA, Gd-DOTA, Gd-BT-DO3A, Gd-DTPA-BMA, and Gd-HP-DO3A) for formulation into TSL was investigated.", "output": {"entities": {"chemical": [{"text": "Gd-DTPA", "start": 51, "end": 58}, {"text": "Gd-BOPTA", "start": 60, "end": 68}, {"text": "Gd-DOTA", "start": 70, "end": 77}, {"text": "Gd-BT-DO3A", "start": 79, "end": 89}, {"text": "Gd-DTPA-BMA", "start": 91, "end": 102}, {"text": "Gd-HP-DO3A", "start": 108, "end": 118}]}}, "schema": []}
{"input": "CAs were passively encapsulated with 323 mOs kg (-1) into 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine/1, 2-distearoyl-sn-glycero-3-phosphocholine/1, 2-dipalmitoyl-sn-glycero-3-phosphodiglycerol 50/20/30 (mol/mol) TSL (DPPG (2)-TSL) to obtain stable formulations.", "output": {"entities": {"chemical": [{"text": "1, 2-dipalmitoyl-sn-glycero-3-phosphocholine", "start": 58, "end": 102}, {"text": "1, 2-distearoyl-sn-glycero-3-phosphocholine", "start": 103, "end": 146}, {"text": "1, 2-dipalmitoyl-sn-glycero-3-phosphodiglycerol", "start": 147, "end": 194}, {"text": "DPPG (2)", "start": 219, "end": 227}]}}, "schema": []}
{"input": "T (1) relaxivity (r (1)) and diffusive permeability to water (P (d)) across the membrane were determined.", "output": {"entities": {}}, "schema": []}
{"input": "Shelf life at 4 degrees C was investigated by determining lysolipid content up to 10 weeks after preparation.", "output": {"entities": {}}, "schema": []}
{"input": "All preparations were monodispersed with comparable small vesicle sizes (~ 135 nm).", "output": {"entities": {}}, "schema": []}
{"input": "Neither zeta potential nor phase transition temperature (T (m)) was affected by the CA.", "output": {"entities": {}}, "schema": []}
{"input": "The formulations showed an increase in r (1) in the temperature range between 38 and 44 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "This correlated with the phase transition.", "output": {"entities": {}}, "schema": []}
{"input": "Change in r (1) (Delta r (1) = r (1) (45. 3 degrees C)-r (1) (37. 6 degrees C)) and r (1) (T < T (m)) depended on the encapsulated CA concentration.", "output": {"entities": {}}, "schema": []}
{"input": "P (d) at T <= 37. 6 degrees C was lower for DPPG (2)-TSL encapsulating non-ionic Gd-BT-DO3A, Gd-DTPA-BMA, and Gd-HP-DO3A.", "output": {"entities": {}}, "schema": []}
{"input": "All CAs except Gd-DTPA-BMA induced phospholipid hydrolysis, which resulted in unwanted CA leakage.", "output": {"entities": {}}, "schema": []}
{"input": "The serum proteins HSA and IgG both contributed to the increase of MRI signal at 30 degrees C by increasing P (d).", "output": {"entities": {}}, "schema": []}
{"input": "A high concentration of encapsulated CA is a prerequisite to achieve a sufficiently high Delta r (1) during heat triggered CA release combined with a low r (1) at 37 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, the optimal CA is characterized by a non-ionic structure and a low contribution to osmolality.", "output": {"entities": {}}, "schema": []}
{"input": "Wogonin inhibits H2O2-induced vascular permeability through suppressing the phosphorylation of caveolin-1.", "output": {"entities": {"chemical": [{"text": "Wogonin", "start": 0, "end": 7}, {"text": "H2O2", "start": 17, "end": 21}]}}, "schema": []}
{"input": "Wogonin, a naturally occurring monoflavonoid extracted from the root of Scutellaria baicalensis Georgi, has been reported for its anti-oxidant activity.", "output": {"entities": {"chemical": [{"text": "Wogonin", "start": 0, "end": 7}, {"text": "monoflavonoid", "start": 31, "end": 44}]}}, "schema": []}
{"input": "However, it is still unclear whether wogonin can inhibit oxidant-induced vascular permeability.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 37, "end": 44}]}}, "schema": []}
{"input": "In this study, we evaluated the effects of wogonin on H2O2-induced vascular permeability in human umbilical vein endothelial cells (HUVECs).", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 43, "end": 50}, {"text": "H2O2", "start": 54, "end": 58}]}}, "schema": []}
{"input": "We found that wogonin can suppress the H2O2-stimulated actin remodeling and albumin uptake of HUVECs, as well as transendothelial cell migration of the human breast carcinoma cell MDA-MB-231.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 14, "end": 21}, {"text": "H2O2", "start": 39, "end": 43}]}}, "schema": []}
{"input": "The mechanism revealed that wogonin inhibited H2O2-induced phosphorylation of caveolin-1 (cav-1) associating with the suppression of stabilization of VE-cadherin and beta-catenin.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 28, "end": 35}, {"text": "H2O2", "start": 46, "end": 50}]}}, "schema": []}
{"input": "Moreover, wogonin repressed anisomycin-induced phosphorylation of p38, cav-1 and vascular permeability.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 10, "end": 17}, {"text": "anisomycin", "start": 28, "end": 38}]}}, "schema": []}
{"input": "These results suggested that wogonin could inhibit H2O2-induced vascular permeability by downregulating the phosphorylation of cav-1, and that it might have a therapeutic potential for the diseases associated with the development of both oxidant and vascular permeability.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 29, "end": 36}, {"text": "H2O2", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Inhibitory effect of Crotalus durissus terrificus venom on chronic edema induced by injection of bacillus Calmette-Gu e rin into the footpad of mice.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we evaluated the effect of the Crotalus durissus terrificus (Cdt) venom on the chronic paw edema induced by the injection of bacillus Calmette-Gu e rin (BCG) into the footpad of mice.", "output": {"entities": {}}, "schema": []}
{"input": "The BCG injection evoked chronic edema, which was significantly diminished in animals treated subcutaneously (s. c.) with Cdt venom 1 h before or after the BCG injection.", "output": {"entities": {}}, "schema": []}
{"input": "This inhibition persisted throughout the evaluation period (15 days).", "output": {"entities": {}}, "schema": []}
{"input": "In mice injected with Cdt venom 6 or 11 days after injection of BCG, we observed a significant reduction in edema only in the period after the venom injection.", "output": {"entities": {}}, "schema": []}
{"input": "While studying possible mechanisms involved in this inhibition, we observed that pre-treatment with dexamethasone, zileuton or Boc2 (a selective antagonist of formyl peptide receptors), but not with indomethacin, canceled out the inhibitory effect of Cdt venom on the edema induced by BCG.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 100, "end": 113}, {"text": "zileuton", "start": 115, "end": 123}, {"text": "Boc2", "start": 127, "end": 131}, {"text": "formyl", "start": 159, "end": 165}, {"text": "indomethacin", "start": 199, "end": 211}]}}, "schema": []}
{"input": "These results strongly suggest that this rattlesnake venom can stimulate the generation of mediators from the lipoxygenase pathway, which can down-regulate this chronic inflammatory edema.", "output": {"entities": {}}, "schema": []}
{"input": "Using fractionated venom, the results indicated that crotoxin was the only component of Cdt venom responsible for this inhibitory effect.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicated that crotoxin, the main toxin of the C. durissus terrificus venom, has a significant inhibitory effect on BCG-induced chronic edema, possibly by generating anti-inflammatory mediators from the lipoxygenase pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of genotoxicity in leukocytes and testis following intra-vasal contraception with RISUG and its reversal by DMSO and NaHCO3 in Wistar albino rats.", "output": {"entities": {"chemical": [{"text": "DMSO", "start": 119, "end": 123}, {"text": "NaHCO3", "start": 128, "end": 134}]}}, "schema": []}
{"input": "Evaluation of genotoxicity of RISUG ((R))-a vas based contraceptive, was carried out in the present study.", "output": {"entities": {}}, "schema": []}
{"input": "Animals were allotted into groups of sham operated control, vas occlusion with RISUG (5-7 mu l) for 360 days and reversal by DMSO (250-500 mu l) and 5% NaHCO3 (500 mu l).", "output": {"entities": {"chemical": [{"text": "DMSO", "start": 125, "end": 129}, {"text": "NaHCO3", "start": 152, "end": 158}]}}, "schema": []}
{"input": "Blood samples and testis were collected at 360 days of vas occlusion and 90 days of vas occlusion reversal for comet analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrogen peroxide induced samples were used as positive control.", "output": {"entities": {"chemical": [{"text": "Hydrogen peroxide", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Olive moment, tail length and percentage DNA in tail were recorded with minimum variation in all groups for both leukocytes and testis.", "output": {"entities": {}}, "schema": []}
{"input": "When compared with positive control the variation was highly significant for both 20 mu M and 50 mu M H2O2 (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 102, "end": 106}]}}, "schema": []}
{"input": "It is concluded that vas occlusion with RISUG at the contraceptive dose regimen is not associated with genotoxicity in leukocytes or the testis of pre-and post-reversal rats.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus.", "output": {"entities": {"chemical": [{"text": "methyl cytosine", "start": 85, "end": 100}]}}, "schema": []}
{"input": "Developmental exposure to lead (Pb) has adverse effects on cognitive functioning and behavior that can persist into adulthood.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 32, "end": 34}]}}, "schema": []}
{"input": "Exposures that occur during fetal or early life periods may produce changes in brain related to physiological re-programming from an epigenetic influence such as altered DNA methylation status.", "output": {"entities": {}}, "schema": []}
{"input": "Since DNA methylation is regulated by DNA methyltransferases and methyl cytosine-binding proteins, this study assessed the extent to which developmental Pb exposure might affect expression of these proteins in the hippocampus.", "output": {"entities": {"chemical": [{"text": "methyl cytosine", "start": 65, "end": 80}, {"text": "Pb", "start": 153, "end": 155}]}}, "schema": []}
{"input": "Long Evans dams were fed chow with or without added Pb acetate (0, 150, 375, 750 ppm) prior to breeding and remained on the same diet through weaning (perinatal exposure group).", "output": {"entities": {"chemical": [{"text": "Pb acetate", "start": 52, "end": 62}]}}, "schema": []}
{"input": "Other animals were exposed to the same doses of Pb but exposure started on postnatal day 1 and continued through weaning (early postnatal exposure group).", "output": {"entities": {"chemical": [{"text": "Pb", "start": 48, "end": 50}]}}, "schema": []}
{"input": "All animals were euthanized on day 55 and hippocampi were removed.", "output": {"entities": {}}, "schema": []}
{"input": "Western blot analyses showed significant effects of Pb exposure on DNMT1, DNMT3a, and MeCP2 expression, with effects often seen at the lowest level of exposure and modified by sex and developmental window of Pb exposure.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 52, "end": 54}, {"text": "Pb", "start": 208, "end": 210}]}}, "schema": []}
{"input": "These data suggest potential epigenetic effects of developmental Pb exposure on DNA methylation mediated at least in part through dysregulation of methyltransferases.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 65, "end": 67}]}}, "schema": []}
{"input": "New formulation approaches to improve solubility and drug release from fixed dose combinations: Case examples pioglitazone/glimepiride and ezetimibe/simvastatin.", "output": {"entities": {"chemical": [{"text": "pioglitazone", "start": 110, "end": 122}, {"text": "glimepiride", "start": 123, "end": 134}, {"text": "ezetimibe", "start": 139, "end": 148}, {"text": "simvastatin", "start": 149, "end": 160}]}}, "schema": []}
{"input": "Low aqueous solubility is often a limiting aspect to the bioavailability of poorly soluble, but highly permeable drugs (class II compounds according to the Biopharmaceutics Classification System-BCS) administered in single drug products or as fixed dose combinations.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present series of experiments was to improve the solubility and dissolution of two fixed dose combination formulations (FDC), each consisting of two BCS class II drugs.", "output": {"entities": {}}, "schema": []}
{"input": "The first FDC contained a weak acid (glimepiride) and a weak base (pioglitazone), while the second FDC contained two compounds (simvastatin and ezetimibe) that are essentially non-ionised over the physiological pH range.", "output": {"entities": {"chemical": [{"text": "glimepiride", "start": 37, "end": 48}, {"text": "pioglitazone", "start": 67, "end": 79}, {"text": "simvastatin", "start": 128, "end": 139}, {"text": "ezetimibe", "start": 144, "end": 153}]}}, "schema": []}
{"input": "The formulation approaches used were as follows: (a) an inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), (b) a solid dispersion with Soluplus (R), a new highly water soluble polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and (c) a ternary inclusion complex with both HP-beta-CD and Soluplus (R).", "output": {"entities": {"chemical": [{"text": "hydroxypropyl-beta-cyclodextrin", "start": 79, "end": 110}, {"text": "HP-beta-CD", "start": 112, "end": 122}, {"text": "Soluplus", "start": 153, "end": 161}, {"text": "polyvinyl caprolactam", "start": 194, "end": 215}, {"text": "polyvinyl acetate", "start": 216, "end": 233}, {"text": "polyethylene glycol", "start": 234, "end": 253}, {"text": "HP-beta-CD", "start": 316, "end": 326}, {"text": "Soluplus", "start": 331, "end": 339}]}}, "schema": []}
{"input": "Solid state analysis was performed for the pure drugs, and all formulations using powder X-ray diffraction (PXRD).", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro performance of the different formulation approaches, as gauged by solubility and dissolution experiments, was compared with that of the marketed products containing the respective fixed dose combinations, Tandemact (R) 30mg/4mg tablets and Inegy (R) 10mg/40mg tablets.", "output": {"entities": {"chemical": [{"text": "Tandemact", "start": 218, "end": 227}, {"text": "Inegy", "start": 253, "end": 258}]}}, "schema": []}
{"input": "The FDCs of the pure drugs and the marketed products showed very poor (and especially for pioglitazone, strongly pH-dependent) dissolution.", "output": {"entities": {"chemical": [{"text": "pioglitazone", "start": 90, "end": 102}]}}, "schema": []}
{"input": "By contrast, all binary and ternary inclusion complexes showed enhanced release for both drugs in the FDC.", "output": {"entities": {}}, "schema": []}
{"input": "The ternary inclusion complex generated synergistic improvement in solubility and dissolution results for both FDCs.", "output": {"entities": {}}, "schema": []}
{"input": "For example, in pH conditions of the fasted small intestine after a test duration of 240min, we observed 100% dissolution of both drugs from the ternary pioglitazone/glimepiride (30mg/4mg) complex formulation, whereas from the marketed formulation less than 5% pioglitazone, and only 25% glimepiride dissolved.", "output": {"entities": {"chemical": [{"text": "pioglitazone", "start": 153, "end": 165}, {"text": "glimepiride", "start": 166, "end": 177}, {"text": "pioglitazone", "start": 261, "end": 273}, {"text": "glimepiride", "start": 288, "end": 299}]}}, "schema": []}
{"input": "Using the same conditions, 60% ezetimibe and 85% simvastatin dissolved from the ternary ezetimibe/simvastatin (10mg/40mg) complex formulation, whereas with less than 5% ezetimibe and 10% simvastatin dissolved after 240min, the marketed FDC formulation showed poor dissolution.", "output": {"entities": {"chemical": [{"text": "ezetimibe", "start": 31, "end": 40}, {"text": "simvastatin", "start": 49, "end": 60}, {"text": "ezetimibe", "start": 88, "end": 97}, {"text": "simvastatin", "start": 98, "end": 109}, {"text": "ezetimibe", "start": 169, "end": 178}, {"text": "simvastatin", "start": 187, "end": 198}]}}, "schema": []}
{"input": "Based on the results of the present study, the bioavailability of both drugs in the fixed dose combination is likely to be increased after oral administration of the new formulations, especially when the fixed dose combination is formulated as a ternary complex consisting of HP-beta-CD and Soluplus (R).", "output": {"entities": {"chemical": [{"text": "HP-beta-CD", "start": 276, "end": 286}, {"text": "Soluplus", "start": 291, "end": 299}]}}, "schema": []}
{"input": "Preparation of highly porous gastroretentive metformin tablets using a sublimation method.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 45, "end": 54}]}}, "schema": []}
{"input": "The present investigation is aimed to formulate floating gastroretentive tablets containing metformin using a sublimation material.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 92, "end": 101}]}}, "schema": []}
{"input": "In this study, the release of the drug from a matrix tablet was highly dependent on the polymer concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "In all formulations, initial rapid drug release was observed, possibly due to the properties of the drug and polymer.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of the amount of PEO on swelling and eroding of the tablets was determined.", "output": {"entities": {"chemical": [{"text": "PEO", "start": 28, "end": 31}]}}, "schema": []}
{"input": "The water-uptake and erosion behavior of the gastroretentive (GR) tablets were highly dependent on the amount of PEO.", "output": {"entities": {"chemical": [{"text": "PEO", "start": 113, "end": 116}]}}, "schema": []}
{"input": "The water-uptake increased with increasing PEO concentration in the tablet matrix.", "output": {"entities": {"chemical": [{"text": "PEO", "start": 43, "end": 46}]}}, "schema": []}
{"input": "The weight loss from tablets decreased with increasing amounts of PEO.", "output": {"entities": {"chemical": [{"text": "PEO", "start": 66, "end": 69}]}}, "schema": []}
{"input": "Camphor was used as the sublimation material to prepare GR tablets that are low-density and easily floatable.", "output": {"entities": {"chemical": [{"text": "Camphor", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Camphor was changed to pores in the tablet during the sublimation process.", "output": {"entities": {"chemical": [{"text": "Camphor", "start": 0, "end": 7}]}}, "schema": []}
{"input": "SEM revealed that the GR tablets have a highly porous morphology.", "output": {"entities": {}}, "schema": []}
{"input": "Floating properties of tablets and tablet density were affected by the sublimation of camphor.", "output": {"entities": {"chemical": [{"text": "camphor", "start": 86, "end": 93}]}}, "schema": []}
{"input": "Prepared floating gastroretentive tablets floated for over 24 h and had no floating lag time.", "output": {"entities": {}}, "schema": []}
{"input": "However, as the amount of camphor in the tablet matrix increased, the crushing strength of the tablet decreased after sublimation.", "output": {"entities": {"chemical": [{"text": "camphor", "start": 26, "end": 33}]}}, "schema": []}
{"input": "Release profiles of the drug from the GR tablets were not affected by tablet density or porosity.", "output": {"entities": {}}, "schema": []}
{"input": "In pharmacokinetic studies, the mean plasma concentration of the GR tablets after oral administration was greater than the concentration of glucophase XR.", "output": {"entities": {}}, "schema": []}
{"input": "Also, the mean AUC (0-infinity) values for the GR tablets were significantly greater than the plasma concentrations of glucophase XR.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative genomics, molecular evolution and computational modeling of ALDH1B1 and ALDH2.", "output": {"entities": {}}, "schema": []}
{"input": "Vertebrate ALDH2 genes encode mitochondrial enzymes capable of metabolizing acetaldehyde and other biological aldehydes in the body.", "output": {"entities": {"chemical": [{"text": "acetaldehyde", "start": 76, "end": 88}, {"text": "aldehydes", "start": 110, "end": 119}]}}, "schema": []}
{"input": "Mammalian ALDH1B1, another mitochondrial enzyme sharing 72% identity with ALDH2, is also capable of metabolizing acetaldehyde but has a tissue distribution and pattern of activity distinct from that of ALDH2.", "output": {"entities": {"chemical": [{"text": "acetaldehyde", "start": 113, "end": 125}]}}, "schema": []}
{"input": "Bioinformatic analyses of several vertebrate genomes were undertaken using known ALDH2 and ALDH1B1 amino acid sequences.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 99, "end": 109}]}}, "schema": []}
{"input": "Phylogenetic analysis of many representative vertebrate species (including fish, amphibians, birds and mammals) indicated the presence of ALDH1B1 in many mammalian species and in frogs (Xenopus tropicalis); no evidence was found for ALDH1B1 in the genomes of birds, reptiles or fish.", "output": {"entities": {}}, "schema": []}
{"input": "Predicted vertebrate ALDH2 and ALDH1B1 subunit sequences and structures were highly conserved, including residues previously shown to be involved in catalysis and coenzyme binding for human ALDH2.", "output": {"entities": {}}, "schema": []}
{"input": "Studies of ALDH1B1 sequences supported the hypothesis that the ALDH1B1 gene originated in early vertebrates from a retrotransposition of the vertebrate ALDH2 gene.", "output": {"entities": {}}, "schema": []}
{"input": "Given the high degree of similarity between ALDH2 and ALDH1B1, it is surprising that individuals with an inactivating mutation in ALDH2 (ALDH2 * 2) do not exhibit a compensatory increase in ALDH1B1 activity.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that the similarity between the two ALDHs would allow for dominant negative heterotetramerization between the inactive ALDH2 mutants and ALDH1B1.", "output": {"entities": {}}, "schema": []}
{"input": "Computational-based molecular modeling studies examining predicted protein-protein interactions indicated that heterotetramerization between ALDH2 and ALDH1B1 subunits was highly probable and may partially explain a lack of compensation by ALDH1B1 in ALDH2 (*) 2 individuals.", "output": {"entities": {}}, "schema": []}
{"input": "MolShaCS: a free and open source tool for ligand similarity identification based on Gaussian descriptors.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular similarity evaluation is an important step in most drug development strategies, since molecular similarity is usually related to functional similarity.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we developed a method based on the Gaussian description of molecular shape and charge distribution for molecular similarity identification.", "output": {"entities": {}}, "schema": []}
{"input": "The method was evaluated using the Directory of Useful Decoys (DUD) and a retrospective test.", "output": {"entities": {}}, "schema": []}
{"input": "Enrichment factors computed for DUD targets showed that the proposed method performs very well in recognizing molecules with similar physicochemical properties and dissimilar topologies, reaching an average AUC of 0. 63 and enrichment factor of 10 at 0. 5% of decoys.", "output": {"entities": {}}, "schema": []}
{"input": "A retrospective test also showed that nine mineralocorticoid ligands were ranked among the top ten molecules in a search of a database of approved drugs for molecules similar to aldosterone.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 178, "end": 189}]}}, "schema": []}
{"input": "Altogether, these data show that the Gaussian-based description of molecular shape and charge distribution implemented in the program MolShaCS is an efficient method for molecular similarity identification.", "output": {"entities": {}}, "schema": []}
{"input": "The program is publicly available at the address http://www. ifsc. usp. br/biotechmol.", "output": {"entities": {}}, "schema": []}
{"input": "Colloids in Flatland: a perspective on 2D phase-separated systems, characterisation methods, and lineactant design.", "output": {"entities": {}}, "schema": []}
{"input": "In 1861 Thomas Graham gave birth to a new field of science, today known as colloid science.", "output": {"entities": {}}, "schema": []}
{"input": "Nowadays, the notion \" colloid \" is often used referring to systems consisting of two immiscible phases, one of which is finely dispersed into the other.", "output": {"entities": {}}, "schema": []}
{"input": "Research on colloids deals mostly with sols (solids dispersed in a liquid), emulsions (liquids dispersed in liquid), and foams (gas dispersed in a liquid).", "output": {"entities": {}}, "schema": []}
{"input": "Because the dispersed particles are small, there is a lot of interface per unit mass.", "output": {"entities": {}}, "schema": []}
{"input": "Not surprisingly, therefore, the properties of the interface have often a decisive effect on the behaviour of colloids.", "output": {"entities": {}}, "schema": []}
{"input": "Water-air interfaces have a special relevance in this field: many water-insoluble molecules can be spread on water and, given the right spreading conditions and enough available surface area, their spreading proceeds until a monolayer (a one-molecule thick layer) eventually remains.", "output": {"entities": {}}, "schema": []}
{"input": "Several 2D phases have been identified for such monolayers, like \" gas \", \" liquid expanded \", \" liquid condensed \", and \" solid \".", "output": {"entities": {}}, "schema": []}
{"input": "The central question of this review is whether these 2D phases can also exist as colloidal systems, and what stabilizes the dispersed state in such systems.", "output": {"entities": {}}, "schema": []}
{"input": "We shall present several systems capable of yielding 2D phase separation, from those based on either natural or fluorinated amphiphiles, to polymer-based ones.", "output": {"entities": {}}, "schema": []}
{"input": "We shall seek for analogies in 3D and we shall try to clarify if the lines between these 2D objects play a similar role as the interfaces between 3D colloidal systems.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, we shall consider the special role of molecules that tend to accumulate at the phase boundaries, that is, at the contact lines, which will therefore be denoted \" line-actants \" (molecules that adsorb at a 1D interface, separating two 2D colloidal entities), by analogy to the term \" surfactant \" (which indicates a molecule that adsorbs at a 2D interface separating two 3D colloidal entities).", "output": {"entities": {}}, "schema": []}
{"input": "Observation of direct vibrational excitation in gas-surface collisions of CO with Au (111): a new model system for surface dynamics.", "output": {"entities": {"chemical": [{"text": "CO", "start": 74, "end": 76}, {"text": "Au", "start": 82, "end": 84}]}}, "schema": []}
{"input": "We report vibrational excitation of CO from its ground (v = 0) to first excited (v = 1) vibrational state in collision with Au (111) at an incidence energy of translation of E (I) = 0. 45 eV.", "output": {"entities": {"chemical": [{"text": "CO", "start": 36, "end": 38}, {"text": "Au", "start": 124, "end": 126}]}}, "schema": []}
{"input": "Unlike past work, we can exclude an excitation mechanism involving temporary adsorption on the surface followed by thermalization and desorption.", "output": {"entities": {}}, "schema": []}
{"input": "The angular distributions of the scattered CO molecules are narrow, consistent with direct scattering occurring on a sub-ps time scale.", "output": {"entities": {"chemical": [{"text": "CO", "start": 43, "end": 45}]}}, "schema": []}
{"input": "The absolute excitation probabilities are about 3% of those expected from thermal accommodation.", "output": {"entities": {}}, "schema": []}
{"input": "The surface temperature dependence of excitation, which was measured between 373 and 973 K, is Arrhenius-like with an activation energy equal to the energy required for vibrational excitation.", "output": {"entities": {}}, "schema": []}
{"input": "Our measurements are consistent with a vibrational excitation mechanism involving coupling of thermally excited electron-hole pairs of the solid to CO vibration.", "output": {"entities": {"chemical": [{"text": "CO", "start": 148, "end": 150}]}}, "schema": []}
{"input": "Selective focused-ion-beam sculpting of TiO2 nanotubes and mechanism understanding.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 40, "end": 44}]}}, "schema": []}
{"input": "Anodic TiO (2) nanotubes with different structures, doping agents, and decorations have been studied in order to improve energy conversion and storage efficiencies such as in dye sensitized solar cells, solar fuels, and electrochemical supercapacitors.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 7, "end": 14}]}}, "schema": []}
{"input": "However, the top surface modification of TiO (2) nanotubes has never been addressed.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 41, "end": 48}]}}, "schema": []}
{"input": "In this study, anodic TiO (2) nanotubes have been selectively closed by high energy focused ion beams and re-opened by low energy focused ion beams.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 22, "end": 29}]}}, "schema": []}
{"input": "Under a 30 kV Ga (+) beam, TiO (2) nanotubes are closed with a 65 nm shield layer covering the top entrance when the ion dose is larger than 1. 2 x 10 (17) ions per cm (2); under a 5 kV Ga (+) beam, the shield layer is removed and the closed tubes are re-opened.", "output": {"entities": {"chemical": [{"text": "Ga (+)", "start": 14, "end": 20}, {"text": "TiO (2)", "start": 27, "end": 34}, {"text": "Ga (+)", "start": 186, "end": 192}]}}, "schema": []}
{"input": "An ion-induced viscous flow model has been proposed to explain the influence of Ga (+) ion beam flux, substrate temperature, initial tube diameter, ion beam dwell time, and the incidence angle of the ion beam.", "output": {"entities": {"chemical": [{"text": "Ga (+)", "start": 80, "end": 86}]}}, "schema": []}
{"input": "Gene transcription reflects poor health status of resident European eel chronically exposed to environmental pollutants.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the effects of chronic exposure to pollutants on the genome and transcriptome of diadromous fish populations is crucial for their resilience under combined anthropogenic and environmental selective pressures.", "output": {"entities": {}}, "schema": []}
{"input": "The catadromous European eel (Anguilla anguilla L.) has suffered a dramatic decline in recruitment for three decades, necessitating a thorough assessment of the transcriptional effects of environmental pollutants on resident and migrating eels in natural systems.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the relationship between muscular bioaccumulation levels of metals (Hg, Cd, Pb, Cu, Zn, Ni, Cr, As and Se), PCBs and organochlorine pesticides (DDTs), the health status (condition factor and lipid reserves) and the associated transcriptional response in liver and gill tissues for genes involved in metal detoxification (metallothionein, MT) and oxidative metabolism (cytochrome P4501A, CYP1A) of xenobiotic compounds.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 84, "end": 86}, {"text": "Cd", "start": 88, "end": 90}, {"text": "Pb", "start": 92, "end": 94}, {"text": "Cu", "start": 96, "end": 98}, {"text": "Zn", "start": 100, "end": 102}, {"text": "Ni", "start": 104, "end": 106}, {"text": "Cr", "start": 108, "end": 110}, {"text": "As", "start": 112, "end": 114}, {"text": "Se", "start": 119, "end": 121}, {"text": "PCBs", "start": 124, "end": 128}, {"text": "DDTs", "start": 160, "end": 164}]}}, "schema": []}
{"input": "In total 84 resident eels originating from three Belgian river basins (Scheldt, Meuse and Yzer) were analyzed along with five unpolluted aquaculture samples as control group.", "output": {"entities": {}}, "schema": []}
{"input": "There was a large spatial variation in individual contaminant intensity and profile, while tissue pollution levels were strongly and negatively associated with condition indices, suggesting an important impact of pollution on the health of sub-adult resident eels.", "output": {"entities": {}}, "schema": []}
{"input": "Gene transcription patterns revealed a complex response mechanism to a cocktail of pollutants, with a high variation at low pollution levels, but strongly down-regulated hepatic and gill gene transcription in highly polluted eels.", "output": {"entities": {}}, "schema": []}
{"input": "Resident eels clearly experience a high pollution burden and seem to show a dysfunctional gene transcription regulation of detoxification genes at higher pollutant levels, correlated with low energy reserves and condition.", "output": {"entities": {}}, "schema": []}
{"input": "To fully understand the evolutionary implications of pollutants on eel reproductive fitness, analyses of mature migrating eels and the characterization of their transcriptome-wide gene transcription response would be appropriate to unveil the complex responses associated with multiple interacting stressors and the long-term consequences at the entire species level.", "output": {"entities": {}}, "schema": []}
{"input": "In the meanwhile, jointly monitoring environmental and tissue pollution levels at a European scale should be initiated, while preserving high quality habitats to increase the recovery chance of European eel in the future.", "output": {"entities": {}}, "schema": []}
{"input": "A comparative VCD study of methyl mandelate in methanol, dimethyl sulfoxide, and chloroform: explicit and implicit solvation models.", "output": {"entities": {"chemical": [{"text": "methyl mandelate", "start": 27, "end": 43}, {"text": "methanol", "start": 47, "end": 55}, {"text": "dimethyl sulfoxide", "start": 57, "end": 75}, {"text": "chloroform", "start": 81, "end": 91}]}}, "schema": []}
{"input": "Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of methyl mandelate, a prototype chiral molecule, in a series of organic solvents, namely methanol (MeOH-d (4)), dimethyl sulfoxide (DMSO-d (6)), and chloroform (CDCl (3)), have been measured in the finger print region from 1800 to 1150 cm (-1).", "output": {"entities": {"chemical": [{"text": "methyl mandelate", "start": 80, "end": 96}, {"text": "methanol", "start": 167, "end": 175}, {"text": "MeOH-d (4)", "start": 177, "end": 187}, {"text": "dimethyl sulfoxide", "start": 190, "end": 208}, {"text": "DMSO-d (6)", "start": 210, "end": 220}, {"text": "chloroform", "start": 227, "end": 237}, {"text": "CDCl (3)", "start": 239, "end": 247}]}}, "schema": []}
{"input": "Implicit solvation models in the form of polarizable continuum model and explicit solvation models have been employed independently and simultaneously.", "output": {"entities": {}}, "schema": []}
{"input": "The goal is to evaluate their efficiencies in dealing with solvent effects in each solution and to establish a general strategy to adequately account for effects of solvents.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular dynamics (MD) simulation and radial distribution function analysis have been performed to aid the construction of the explicit solvation models.", "output": {"entities": {}}, "schema": []}
{"input": "Initial geometry searches have been carried out at the B3LYP/6-31G (d) level for the methyl mandelate monomer and its explicit 1: 1 and 1: 2 solute-solvent hydrogen-bonded complexes.", "output": {"entities": {"chemical": [{"text": "methyl mandelate", "start": 85, "end": 101}, {"text": "hydrogen", "start": 156, "end": 164}]}}, "schema": []}
{"input": "B3LYP/cc-pVTZ has been used for all the final geometry optimizations, the vibrational frequency, VA and VCD intensity, and optical rotation dispersion (ORD) calculations.", "output": {"entities": {}}, "schema": []}
{"input": "The results show that inclusion of solvent explicitly and implicitly at the same time has significant impacts on the appearance of the VA and VCD spectra, and is crucial for reliable spectral assignments when solvents are capable of hydrogen-bonding interactions with solutes.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 233, "end": 241}]}}, "schema": []}
{"input": "When no strong solvent-solute hydrogen-bonding interactions in the case of chloroform are expected, the gas phase monomer model is adequate for spectral interpretation, while inclusion of implicit solvation improves the frequency agreement with experiment.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 30, "end": 38}, {"text": "chloroform", "start": 75, "end": 85}]}}, "schema": []}
{"input": "ORD spectra of methyl mandelate in the aforementioned solvents at different concentrations under 5 excitation wavelengths have also been measured.", "output": {"entities": {"chemical": [{"text": "methyl mandelate", "start": 15, "end": 31}]}}, "schema": []}
{"input": "The comparison between the calculated and the experimental ORD spectra supports the conclusions drawn from the VA and VCD investigations.", "output": {"entities": {}}, "schema": []}
{"input": "Association of Shiga toxin glycosphingolipid receptors with membrane microdomains of toxin-sensitive lymphoid and myeloid cells.", "output": {"entities": {"chemical": [{"text": "glycosphingolipid", "start": 27, "end": 44}]}}, "schema": []}
{"input": "Glycosphingolipids (GSLs) of the globo-series constitute specific receptors for Shiga toxins (Stxs) released by certain types of pathogenic Escherichia coli strains.", "output": {"entities": {"chemical": [{"text": "Glycosphingolipids", "start": 0, "end": 18}]}}, "schema": []}
{"input": "Stx-loaded leukocytes may act as transporter cells in the blood and transfer the toxin to endothelial target cells.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we performed a thorough investigation on the expression of globo-series GSLs in serum-free cultivated Raji and Jurkat cells, representing B-and T-lymphocyte descendants, respectively, as well as THP-1 and HL-60 cells of the monocyte and granulocyte lineage, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of Stx-receptors in GSL preparations of Raji and THP-1 cells and the absence in Jurkat and HL-60 cells revealed high compliance of solid-phase immunodetection assays with the expression profiles of receptor-related glycosyltransferases, performed by qRT-PCR analysis, and Stx2-caused cellular damage.", "output": {"entities": {}}, "schema": []}
{"input": "Canonical microdomain association of Stx GSL receptors, sphingomyelin, and cholesterol in membranes of Raji and THP-1 cells was assessed by comparative analysis of detergent-resistant membrane (DRM) and nonDRM fractions obtained by density gradient centrifugation and showed high correlation based on nonparametric statistical analysis.", "output": {"entities": {"chemical": [{"text": "sphingomyelin", "start": 56, "end": 69}, {"text": "cholesterol", "start": 75, "end": 86}]}}, "schema": []}
{"input": "Our comprehensive study on the expression of Stx-receptors and their subcellular distribution provides the basis for exploring the functional role of lipid raft-associated Stx-receptors in cells of leukocyte origin.", "output": {"entities": {}}, "schema": []}
{"input": "Extremely flexible nanoscale ultrathin body silicon integrated circuits on plastic.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 44, "end": 51}]}}, "schema": []}
{"input": "In recent years, flexible devices based on nanoscale materials and structures have begun to emerge, exploiting semiconductor nanowires, graphene, and carbon nanotubes.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 136, "end": 144}, {"text": "carbon", "start": 150, "end": 156}]}}, "schema": []}
{"input": "This is primarily to circumvent the existing shortcomings of the conventional flexible electronics based on organic and amorphous semiconductors.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this new class of flexible nanoelectronics is to attain high-performance devices with increased packing density.", "output": {"entities": {}}, "schema": []}
{"input": "However, highly integrated flexible circuits with nanoscale transistors have not yet been demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show nanoscale flexible circuits on 60 A thick silicon, including functional ring oscillators and memory cells.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 56, "end": 63}]}}, "schema": []}
{"input": "The 100-stage ring oscillators exhibit the stage delay of ~ 16 ps at a power supply voltage of 0. 9 V, the best reported for any flexible circuits to date.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanical flexibility is achieved by employing the controlled spalling technology, enabling the large-area transfer of the ultrathin body silicon devices to a plastic substrate at room temperature.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 143, "end": 150}]}}, "schema": []}
{"input": "These results provide a simple and cost-effective pathway to enable ultralight flexible nanoelectronics with unprecedented level of system complexity based on mainstream silicon technology.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 170, "end": 177}]}}, "schema": []}
{"input": "Enhancement of the water solubility of flavone glycosides by disruption of molecular planarity of the aglycone moiety.", "output": {"entities": {"chemical": [{"text": "flavone glycosides", "start": 39, "end": 57}]}}, "schema": []}
{"input": "Enhancement of the water solubility by disruption of molecular planarity has recently been reviewed as a feasible approach in small-molecule drug discovery programs.", "output": {"entities": {}}, "schema": []}
{"input": "We applied this strategy to some natural flavone glycosides, especially diosmin, a highly insoluble citroflavonoid prescribed as an oral phlebotropic drug.", "output": {"entities": {"chemical": [{"text": "flavone glycosides", "start": 41, "end": 59}, {"text": "diosmin", "start": 72, "end": 79}, {"text": "citroflavonoid", "start": 100, "end": 114}]}}, "schema": []}
{"input": "Disruption of planarity at the aglycone moiety by 3-bromination or chlorination afforded 3-bromo-and 3-chlorodiosmin, displaying a dramatic solubility increase compared with the parent compound.", "output": {"entities": {"chemical": [{"text": "3-bromo-and 3-chlorodiosmin", "start": 89, "end": 116}]}}, "schema": []}
{"input": "Interplay between structure and relaxations in perfluorosulfonic acid proton conducting membranes.", "output": {"entities": {"chemical": [{"text": "perfluorosulfonic acid", "start": 47, "end": 69}]}}, "schema": []}
{"input": "This study focuses on changes in the structure of ionomer membranes, provided by the 3M Fuel Cells Component Group, as a function of the equivalent weight (EW) and the relationship between the structure and the properties of the membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Wide-angle X-ray diffraction results showed evidence of both non-crystalline and crystalline ordered hydrophobic regions in all the EW membranes except the 700 EW membrane.", "output": {"entities": {}}, "schema": []}
{"input": "The spectral changes evident in the vibrational spectra of the 3M membranes can be associated with two major phenomena: (1) dissociation of the proton from the sulfonic acid groups even in the presence of small amounts of water; and (2) changes in the conformation or the degree of crystallinity of the poly (tetrafluoroethylene) hydrophobic domains both as a function of EW and membrane water content.", "output": {"entities": {"chemical": [{"text": "sulfonic acid", "start": 160, "end": 173}, {"text": "poly (tetrafluoroethylene)", "start": 303, "end": 329}]}}, "schema": []}
{"input": "All the membranes, regardless of EW, are thermally stable up to 360 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "The wet membranes have conductivities between 7 and 20 mS/cm at 125 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "In this condition, the conductivity values follow VTF behavior, which suggests that the proton migration occurs via proton exchange processes between delocalization bodies (DBs) that are facilitated by the dynamics of the host polymer.", "output": {"entities": {}}, "schema": []}
{"input": "The conductivity along the interface between the hydrophobic and hydrophilic domains makes a larger contribution in the smaller EW membranes likely due to the existence of a greater number of interfaces in the membrane.", "output": {"entities": {}}, "schema": []}
{"input": "The larger crystalline domains present in the higher EW membranes provide percolation pathways for charge migration between DBs, which reduces the probability of charge transfer along the interface.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, at higher EWs although there is charge migration along the interface within the hydrophobic-hydrophilic domains, the exchange of protons between different DBs is likely the rate-limiting step of the overall conduction process.", "output": {"entities": {}}, "schema": []}
{"input": "Phase behavior and molecular dynamics simulation studies of new aqueous two-phase separation systems induced by HEPES buffer.", "output": {"entities": {}}, "schema": []}
{"input": "Here, for the first time, we show that with addition of a biological buffer, 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid (HEPES), into aqueous solutions of tetrahydrofuran (THF), 1, 3-dioxolane, 1, 4-dioxane, 1-propanol, 2-propanol, tert-butanol, acetonitrile, or acetone, the organic solvent can be excluded from water to form a new liquid phase.", "output": {"entities": {"chemical": [{"text": "4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid", "start": 77, "end": 128}, {"text": "HEPES", "start": 130, "end": 135}, {"text": "tetrahydrofuran", "start": 164, "end": 179}, {"text": "THF", "start": 181, "end": 184}, {"text": "1, 3-dioxolane, 1, 4-dioxane, 1-propanol", "start": 187, "end": 227}, {"text": "2-propanol", "start": 229, "end": 239}, {"text": "tert-butanol", "start": 241, "end": 253}, {"text": "acetonitrile", "start": 255, "end": 267}, {"text": "acetone", "start": 272, "end": 279}]}}, "schema": []}
{"input": "The phase diagrams have been determined at ambient temperature.", "output": {"entities": {}}, "schema": []}
{"input": "In order to understand why and how a zwitterion solute (HEPES) induced phase separation of the investigated systems, molecular dynamics (MD) simulation studies are performed for HEPES + water + THF system.", "output": {"entities": {"chemical": [{"text": "HEPES", "start": 56, "end": 61}, {"text": "HEPES", "start": 178, "end": 183}, {"text": "THF", "start": 194, "end": 197}]}}, "schema": []}
{"input": "The MD simulations were conducted for the aqueous mixtures with 12 different compositions.", "output": {"entities": {}}, "schema": []}
{"input": "The reliability of the simulation results of HEPES in pure water and beyond the phase separation mixtures was justified by comparing the densities obtained from MD with the experimental values.", "output": {"entities": {"chemical": [{"text": "HEPES", "start": 45, "end": 50}]}}, "schema": []}
{"input": "The simulation results of HEPES in pure THF and in a composition inside the phase separation region were justified qualitatively.", "output": {"entities": {"chemical": [{"text": "HEPES", "start": 26, "end": 31}, {"text": "THF", "start": 40, "end": 43}]}}, "schema": []}
{"input": "Interestingly, all HEPES molecules entirely aggregated in pure THF.", "output": {"entities": {"chemical": [{"text": "HEPES", "start": 19, "end": 24}, {"text": "THF", "start": 63, "end": 66}]}}, "schema": []}
{"input": "This reveals that HEPES is insoluble in pure THF, which is consistent with the experimental results.", "output": {"entities": {"chemical": [{"text": "HEPES", "start": 18, "end": 23}, {"text": "THF", "start": 45, "end": 48}]}}, "schema": []}
{"input": "Even more interestingly, the MD simulation for the mixture with composition inside the phase separation region showed the formation of two phases.", "output": {"entities": {}}, "schema": []}
{"input": "The THF molecules are squeezed out from the water network into a new liquid phase.", "output": {"entities": {"chemical": [{"text": "THF", "start": 4, "end": 7}]}}, "schema": []}
{"input": "The hydrogen bonds (HBs), HB lifetime, HB Gibbs energy (Delta G), radial distribution functions (RDFs), coordination numbers (CNs), electrostatic interactions, and the van der Waals interactions between the different species have been analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "Further, MD simulations for the other phase separation systems by choosing a composition inside the two liquids region for each system were also simulated.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings will therefore pave the way for designing new benign separation auxiliary agents.", "output": {"entities": {}}, "schema": []}
{"input": "Recent developments in the study of opioid receptors.", "output": {"entities": {}}, "schema": []}
{"input": "It is now about 40 years since Avram Goldstein proposed the use of the stereoselectivity of opioid receptors to identify these receptors in neural membranes.", "output": {"entities": {}}, "schema": []}
{"input": "In 2012, the crystal structures of the four members of the opioid receptor family were reported, providing a structural basis for understanding of critical features affecting the actions of opiate drugs.", "output": {"entities": {}}, "schema": []}
{"input": "This minireview summarizes these recent developments in our understanding of opiate receptors.", "output": {"entities": {}}, "schema": []}
{"input": "Receptor function is also influenced by amino acid substitutions in the protein sequence.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 40, "end": 50}]}}, "schema": []}
{"input": "Among opioid receptor genes, one polymorphism is much more frequent in human populations than the many others that have been found, but the functional significance of this single nucleotide polymorphism (SNP) has been unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies have shed new light on how this SNP might influence opioid receptor function.", "output": {"entities": {}}, "schema": []}
{"input": "In this minireview, the functional significance of the most prevalent genetic polymorphism among the opioid receptor genes is also considered.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanisms limiting distribution of the threonine-protein kinase B-RaF (V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases.", "output": {"entities": {"chemical": [{"text": "threonine", "start": 40, "end": 49}, {"text": "dabrafenib", "start": 89, "end": 99}]}}, "schema": []}
{"input": "Brain metastases are a common cause of death in stage IV metastatic melanoma.", "output": {"entities": {}}, "schema": []}
{"input": "Dabrafenib is a BRAF (gene encoding serine/threonine-protein kinase B-Raf) inhibitor that has been developed to selectively target the valine 600 to glutamic acid substitution (BRAF (V600E)), which is commonly found in metastatic melanoma.", "output": {"entities": {"chemical": [{"text": "serine", "start": 36, "end": 42}, {"text": "threonine", "start": 43, "end": 52}, {"text": "valine", "start": 135, "end": 141}, {"text": "glutamic acid", "start": 149, "end": 162}]}}, "schema": []}
{"input": "Clinical trials with dabrafenib have shown encouraging results; however, the central nervous system distribution of dabrafenib remains unknown.", "output": {"entities": {"chemical": [{"text": "dabrafenib", "start": 21, "end": 31}, {"text": "dabrafenib", "start": 116, "end": 126}]}}, "schema": []}
{"input": "Thus, the objective of the current study was to evaluate the brain distribution of dabrafenib in mice, and to see whether active efflux by P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) restricts its delivery across the blood-brain barrier (BBB).", "output": {"entities": {"chemical": [{"text": "dabrafenib", "start": 83, "end": 93}]}}, "schema": []}
{"input": "In vitro accumulation studies conducted in Madin-Darby canine kidney II cells indicate that dabrafenib is an avid substrate for both P-gp and BCRP.", "output": {"entities": {"chemical": [{"text": "dabrafenib", "start": 92, "end": 102}]}}, "schema": []}
{"input": "Directional flux studies revealed greater transport in the basolateral to apical direction with corrected efflux ratios greater than 2 for both P-gp and Bcrp1 transfected cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo, the ratio of area under the concentration-time curve (AUC) (brain) to AUC (plasma) (K (p)) of dabrafenib after an i. v. dose (2. 5 mg/kg) was 0. 023, which increased by 18-fold in Mdr1 a/b (-/-) Bcrp1 (-/-) mice to 0. 42.", "output": {"entities": {"chemical": [{"text": "dabrafenib", "start": 103, "end": 113}]}}, "schema": []}
{"input": "Dabrafenib plasma exposure was ~ 2-fold greater in Mdr1 a/b (-/-) Bcrp1 (-/-) mice as compared with wild-type with an oral dose (25 mg/kg); however, the brain distribution was increased by ~ 10-fold with a resulting K (p) of 0. 25.", "output": {"entities": {"chemical": [{"text": "Dabrafenib", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Further, compared with vemurafenib, another BRAF (V600E) inhibitor, dabrafenib showed greater brain penetration with a similar dose.", "output": {"entities": {"chemical": [{"text": "vemurafenib", "start": 23, "end": 34}, {"text": "dabrafenib", "start": 68, "end": 78}]}}, "schema": []}
{"input": "In conclusion, the dabrafenib brain distribution is limited in an intact BBB model, and the data presented herein may have clinical implications in the prevention and treatment of melanoma brain metastases.", "output": {"entities": {"chemical": [{"text": "dabrafenib", "start": 19, "end": 29}]}}, "schema": []}
{"input": "Pharmacological inhibition of mitochondrial carbonic anhydrases protects mouse cerebral pericytes from high glucose-induced oxidative stress and apoptosis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 108, "end": 115}]}}, "schema": []}
{"input": "Diabetes-associated complications in the microvasculature of the brain are caused by oxidative stress, generated by overproduction of reactive oxygen species from hyperglycemia-induced accelerated oxidative metabolism of glucose.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 143, "end": 149}, {"text": "glucose", "start": 221, "end": 228}]}}, "schema": []}
{"input": "Pericytes, essential for the viability of the microvasculature, are especially susceptible to oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial carbonic anhydrases, regulators of the oxidative metabolism of glucose, determine the rate of reactive oxygen species production and inhibition of mitochondrial carbonic anhydrases rescues glucose-induced pericyte loss in the diabetic mouse brain.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 77, "end": 84}, {"text": "oxygen", "start": 117, "end": 123}, {"text": "glucose", "start": 203, "end": 210}]}}, "schema": []}
{"input": "We hypothesized that high glucose induces intracellular oxidative stress and pericyte apoptosis and that inhibition of mitochondrial carbonic anhydrases protects pericytes from oxidative stress-induced apoptosis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 26, "end": 33}]}}, "schema": []}
{"input": "To validate our hypothesis, conditionally immortalized cerebral pericyte (IPC) cultures were established from Immortomice to investigate the effect of high glucose on oxidative stress and pericyte apoptosis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 156, "end": 163}]}}, "schema": []}
{"input": "The IPCs expressed pericyte markers and induced high transendothelial electrical resistance and low permeability in brain endothelial cell monolayers comparable with pericytes in primary cultures.", "output": {"entities": {}}, "schema": []}
{"input": "The IPCs also secreted cytokines constitutively and in response to lipopolysaccharide similar to pericytes.", "output": {"entities": {}}, "schema": []}
{"input": "High glucose caused oxidative stress and apoptosis of these cells, with both oxidative stress and apoptosis significantly reduced after mitochondrial carbonic anhydrase inhibition.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 5, "end": 12}]}}, "schema": []}
{"input": "These results provide the first evidence that pharmacological inhibition of mitochondrial carbonic anhydrases attenuates pericyte apoptosis caused by high glucose-induced oxidative stress.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 155, "end": 162}]}}, "schema": []}
{"input": "Carbonic anhydrase inhibitors have a long history of safe clinical use and can be immediately evaluated for this new indication in translational research.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, mitochondrial carbonic anhydrases may provide a new therapeutic target for oxidative stress-related illnesses of the brain.", "output": {"entities": {}}, "schema": []}
{"input": "An engineered human follistatin variant: insights into the pharmacokinetic and pharmocodynamic relationships of a novel molecule with broad therapeutic potential.", "output": {"entities": {}}, "schema": []}
{"input": "Human follistatin is a regulatory glycoprotein with widespread biologic functions, including antiinflammatory activities, wound-healing properties, and muscle-stimulating effects.", "output": {"entities": {}}, "schema": []}
{"input": "The role of follistatin in a wide range of biologic activities shows promise for potential clinical application, which has prompted considerable interest in the investigation of the protein as a potential disease-modifying agent.", "output": {"entities": {}}, "schema": []}
{"input": "In spite of this potential, the development of follistatin as a broad use biotherapeutic has been severely hindered by a poor understanding and characterization of its pharmacokinetic/pharmacodynamic (PK/PD) relationships.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, to better define these relationships, we performed in-depth analyses of the PK/PD relationships of native follistatin-315 (FST315).", "output": {"entities": {}}, "schema": []}
{"input": "Our data indicate that the intrinsic PK/PD properties of native FST315 are poorly suited for acting as a parentally administered biotherapeutic with broad systemic effects.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we leveraged protein engineering to modify the PK characteristics of the native molecule by fusing FST315 to a murine IgG (1) Fc and removing the intrinsic heparan sulfate-binding activity of follistatin.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 170, "end": 177}]}}, "schema": []}
{"input": "The engineered variant molecule had ~ 100-and ~ 1600-fold improvements in terminal half-life and exposure, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to the native FST315, the variant showed a robust, dose-dependent pharmacological effect when administered subcutaneously on a weekly basis in mouse models of muscle atrophy and degeneration.", "output": {"entities": {}}, "schema": []}
{"input": "These studies highlight the underappreciated and critical relationship between optimizing multiple physical and chemical properties of follistatin on its overall PK/PD profile.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, our findings provide the first documented strategy toward the development of a follistatin therapeutic with potential use in patients affected with skeletal muscle diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Rapid and specific purification of Argonaute-small RNA complexes from crude cell lysates.", "output": {"entities": {}}, "schema": []}
{"input": "Small interfering RNAs (siRNAs) direct Argonaute proteins, the core components of the RNA-induced silencing complex (RISC), to cleave complementary target RNAs.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we describe a method to purify active RISC containing a single, unique small RNA guide sequence.", "output": {"entities": {}}, "schema": []}
{"input": "We begin by capturing RISC using a complementary 2'-O-methyl oligonucleotide tethered to beads.", "output": {"entities": {"chemical": [{"text": "2'-O-methyl", "start": 49, "end": 60}]}}, "schema": []}
{"input": "Unlike other methods that capture RISC but do not allow its recovery, our strategy purifies active, soluble RISC in good yield.", "output": {"entities": {}}, "schema": []}
{"input": "The method takes advantage of the finding that RISC partially paired to a target through its siRNA guide dissociates more than 300 times faster than a fully paired siRNA in RISC.", "output": {"entities": {}}, "schema": []}
{"input": "We use this strategy to purify fly Ago1-and Ago2-RISC, as well as mouse AGO2-RISC.", "output": {"entities": {}}, "schema": []}
{"input": "The method can discriminate among RISCs programmed with different guide strands, making it possible to deplete and recover specific RISC populations.", "output": {"entities": {}}, "schema": []}
{"input": "Endogenous microRNA: Argonaute complexes can also be purified from cell lysates.", "output": {"entities": {}}, "schema": []}
{"input": "Our method scales readily and takes less than a day to complete.", "output": {"entities": {}}, "schema": []}
{"input": "Associations between diabetes, leanness, and the risk of death in the Japanese general population: the jichi medical school cohort study.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE To examine the BMI-stratified associations between diabetes and the risks of all-cause death, cardiovascular disease (CVD) death, and cancer death.", "output": {"entities": {}}, "schema": []}
{"input": "RESEARCH DESIGN AND METHODS Using a prospective study with 12 rural Japanese general populations (n = 3, 641, mean age, 53. 7 years; 33. 5% men), we examined the associations between diabetes and the risk of all-cause death, CVD death, and cancer death.", "output": {"entities": {}}, "schema": []}
{"input": "We also examined the effects of BMI and age on such associations.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS During an average duration of 10. 2 years (37, 278 person-years), 240 deaths occurred (54 deaths from CVD, 101 from cancer, and 85 from other causes).", "output": {"entities": {}}, "schema": []}
{"input": "Cox regression analysis showed leanness (defined as the lowest quartile of entire BMI; mean, 19. 5 kg/m (2)), but not obesity (BMI >= 25 kg/m (2)), and diabetes were independently associated with an increased risk of all-cause death (hazard ratio [HR] 1. 70 and 1. 65, respectively; both P < 0. 01.).", "output": {"entities": {}}, "schema": []}
{"input": "Stratification with cause-specific deaths showed that leanness and obesity were associated with CVD death (HR 3. 77 and 2. 94, respectively), whereas diabetes was associated with cancer death (HR 1. 87; all P < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "The increased risk of all-cause death in diabetes was substantially higher in lean subjects aged < 65 years (HR 3. 4) or those aged >= 65 years (HR 4. 2), whereas the risk in obese diabetes patients was significant only in subjects aged < 65 years (HR 2. 32; all P < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS Among the Japanese general population, diabetes confers an increased risk of all-cause death.", "output": {"entities": {}}, "schema": []}
{"input": "Particular attention must be paid to the pronounced high mortality in diabetes accompanied with leanness, regardless of age.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of percutaneous absorption of esculetin: effect of chemical enhancers.", "output": {"entities": {"chemical": [{"text": "esculetin", "start": 41, "end": 50}]}}, "schema": []}
{"input": "Percutaneous transdermal absorption of esculetin (6, 7-dihydroxycoumarin), an oxidative damage inhibitor, was evaluated by means of in vitro permeation studies in which vertical Franz-type diffusion cells and pig ear skin were employed.", "output": {"entities": {"chemical": [{"text": "esculetin", "start": 39, "end": 48}, {"text": "6, 7-dihydroxycoumarin", "start": 50, "end": 72}]}}, "schema": []}
{"input": "To determine the absorption of esculetin, we validated a simple, accurate, precise, and rapid HPLC-UV method.", "output": {"entities": {"chemical": [{"text": "esculetin", "start": 31, "end": 40}]}}, "schema": []}
{"input": "Additionally, the effects of several percutaneous enhancers were studied.", "output": {"entities": {}}, "schema": []}
{"input": "Pretreatment of porcine skin was performed with ethanol (control vehicle), decenoic acid, oleic acid, R-(+)-limonene, and laurocapram (Azone (R)) (5% in ethanol, w/w, respectively).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 48, "end": 55}, {"text": "decenoic acid", "start": 75, "end": 88}, {"text": "oleic acid", "start": 90, "end": 100}, {"text": "R-(+)-limonene", "start": 102, "end": 116}, {"text": "laurocapram", "start": 122, "end": 133}, {"text": "Azone", "start": 135, "end": 140}, {"text": "ethanol", "start": 153, "end": 160}]}}, "schema": []}
{"input": "Pretreatment of skin with oleic acid or laurocapram led to statistically significant differences in the transdermal flux of esculetin with respect to controls.", "output": {"entities": {"chemical": [{"text": "oleic acid", "start": 26, "end": 36}, {"text": "laurocapram", "start": 40, "end": 51}, {"text": "esculetin", "start": 124, "end": 133}]}}, "schema": []}
{"input": "Of the two enhancers, laurocapram showed the greatest capacity to enhance the flux of esculetin across pig skin.", "output": {"entities": {"chemical": [{"text": "laurocapram", "start": 22, "end": 33}, {"text": "esculetin", "start": 86, "end": 95}]}}, "schema": []}
{"input": "Design and exploration of novel boronic acid inhibitors reveals important interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) beta-lactamase.", "output": {"entities": {"chemical": [{"text": "boronic acid", "start": 32, "end": 44}, {"text": "clavulanic acid", "start": 94, "end": 109}, {"text": "sulfhydryl", "start": 120, "end": 130}]}}, "schema": []}
{"input": "Inhibitor resistant (IR) class A beta-lactamases pose a significant threat to many current antibiotic combinations.", "output": {"entities": {}}, "schema": []}
{"input": "The K234R substitution in the SHV beta-lactamase, from Klebsiella pneumoniae, results in resistance to ampicillin/clavulanate.", "output": {"entities": {"chemical": [{"text": "ampicillin", "start": 103, "end": 113}, {"text": "clavulanate", "start": 114, "end": 125}]}}, "schema": []}
{"input": "After site-saturation mutagenesis of Lys-234 in SHV, microbiological and biochemical characterization of the resulting beta-lactamases revealed that only-Arg conferred resistance to ampicillin/clavulanate.", "output": {"entities": {"chemical": [{"text": "Lys", "start": 37, "end": 40}, {"text": "Arg", "start": 154, "end": 157}, {"text": "ampicillin", "start": 182, "end": 192}, {"text": "clavulanate", "start": 193, "end": 204}]}}, "schema": []}
{"input": "X-ray crystallography revealed two conformations of Arg-234 and Ser-130 in SHV K234R.", "output": {"entities": {"chemical": [{"text": "Arg", "start": 52, "end": 55}, {"text": "Ser", "start": 64, "end": 67}]}}, "schema": []}
{"input": "The movement of Ser-130 is the principal cause of the observed clavulanate resistance.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 16, "end": 19}, {"text": "clavulanate", "start": 63, "end": 74}]}}, "schema": []}
{"input": "A panel of boronic acid inhibitors was designed and tested against SHV-1 and SHV K234R.", "output": {"entities": {"chemical": [{"text": "boronic acid", "start": 11, "end": 23}]}}, "schema": []}
{"input": "A chiral ampicillin analogue was discovered to have a 2. 4 +/- 0. 2 nM K (i) for SHV K234R; the chiral ampicillin analogue formed a more complex hydrogen-bonding network in SHV K234R vs SHV-1.", "output": {"entities": {"chemical": [{"text": "ampicillin", "start": 9, "end": 19}, {"text": "ampicillin", "start": 103, "end": 113}, {"text": "hydrogen", "start": 145, "end": 153}]}}, "schema": []}
{"input": "Consideration of the spatial position of Ser-130 and Lys-234 and this hydrogen-bonding network will be important in the design of novel antibiotics targeting IR beta-lactamases.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 41, "end": 44}, {"text": "Lys", "start": 53, "end": 56}, {"text": "hydrogen", "start": 70, "end": 78}]}}, "schema": []}
{"input": "Architecturing hierarchical function layers on self-assembled viral templates as 3D nano-array electrodes for integrated Li-ion microbatteries.", "output": {"entities": {"chemical": [{"text": "Li", "start": 121, "end": 123}]}}, "schema": []}
{"input": "This work enables an elegant bottom-up solution to engineer 3D microbattery arrays as integral power sources for microelectronics.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, multilayers of functional materials were hierarchically architectured over tobacco mosaic virus (TMV) templates that were genetically modified to self-assemble in a vertical manner on current-collectors, so that optimum power and energy densities accompanied with excellent cycle-life could be achieved on a minimum footprint.", "output": {"entities": {}}, "schema": []}
{"input": "The resultant microbattery based on self-aligned LiFePO (4) nanoforests of shell-core-shell structure, with precise arrangement of various auxiliary material layers including a central nanometric metal core as direct electronic pathway to current collector, delivers excellent energy density and stable cycling stability only rivaled by the best Li-ion batteries of conventional configurations, while providing rate performance per foot-print and on-site manufacturability unavailable from the latter.", "output": {"entities": {"chemical": [{"text": "LiFePO (4)", "start": 49, "end": 59}, {"text": "Li", "start": 346, "end": 348}]}}, "schema": []}
{"input": "This approach could open a new avenue for microelectromechanical systems (MEMS) applications, which would significantly benefit from the concept that electrochemically active components be directly engineered and fabricated as an integral part of the integrated circuit (IC).", "output": {"entities": {}}, "schema": []}
{"input": "Selective separation of similarly sized proteins with tunable nanoporous block copolymer membranes.", "output": {"entities": {}}, "schema": []}
{"input": "An integral asymmetric membrane was fabricated in a fast and one-step process by combining the self-assembly of an amphiphilic block copolymer (PS-b-P4VP) with nonsolvent-induced phase separation.", "output": {"entities": {"chemical": [{"text": "PS-b-P4VP", "start": 144, "end": 153}]}}, "schema": []}
{"input": "The structure was found to be composed of a thin layer of densely packed highly ordered cylindrical channels with uniform pore sizes perpendicular to the surface on top of a nonordered sponge-like layer.", "output": {"entities": {}}, "schema": []}
{"input": "The as-assembled membrane obtained a water flux of more than 3200 L m (-2) h (-1) bar (-1), which was at least an order of magnitude higher than the water fluxes of commercially available membranes with comparable pore sizes, making this membrane particularly well suited to size-selective and charge-based separation of biomolecules.", "output": {"entities": {}}, "schema": []}
{"input": "To test the performance of the membrane, we conducted diffusion experiments at the physiological pH of 7. 4 using bovine serum albumin (BSA) and globulin-gamma, two proteins with different diameters but too close in size (2-fold difference in molecular mass) to be efficiently separated via conventional dialysis membrane processes.", "output": {"entities": {}}, "schema": []}
{"input": "The diffusion rate differed by a factor of 87, the highest value reported to date.", "output": {"entities": {}}, "schema": []}
{"input": "We also analyzed charge-based diffusive transport and separation of two proteins of similar molecular weight (BSA and bovine hemoglobin (BHb)) through the membrane as a function of external pH.", "output": {"entities": {}}, "schema": []}
{"input": "The membrane achieved a selectivity of about 10 at pH 4. 7, the isoelectric point (pI) of BSA.", "output": {"entities": {}}, "schema": []}
{"input": "We then positively charged the membrane to improve the separation selectivity.", "output": {"entities": {}}, "schema": []}
{"input": "With the modified membrane BSA was completely blocked when the pH was 7. 0, the pI of BHb, while BHb was completely blocked at pH 4. 7.", "output": {"entities": {}}, "schema": []}
{"input": "Our results demonstrate the potential of our asymmetric membrane to efficiently separate biological substances/pharmaceuticals in bioscience, biotechnology, and biomedicine applications.", "output": {"entities": {}}, "schema": []}
{"input": "Low-noise nano superconducting quantum interference device operating in Tesla magnetic fields.", "output": {"entities": {}}, "schema": []}
{"input": "Superconductivity in the cuprate YBa (2) Cu (3) O (7) (YBCO) persists up to huge magnetic fields (B) up to several tens of Teslas, and sensitive direct current (dc) superconducting quantum interference devices (SQUIDs) can be realized in epitaxially grown YBCO films by using grain boundary Josephson junctions (GBJs).", "output": {"entities": {"chemical": [{"text": "YBa (2) Cu (3) O (7)", "start": 33, "end": 53}, {"text": "YBCO", "start": 55, "end": 59}, {"text": "YBCO", "start": 256, "end": 260}]}}, "schema": []}
{"input": "Here we present the realization of high-quality YBCO nanoSQUIDs, patterned by focused ion beam milling.", "output": {"entities": {"chemical": [{"text": "YBCO", "start": 48, "end": 52}]}}, "schema": []}
{"input": "We demonstrate low-noise performance of such a SQUID up to B = 1 T applied parallel to the plane of the SQUID loop at the temperature T = 4. 2 K.", "output": {"entities": {}}, "schema": []}
{"input": "The GBJs are shunted by a thin Au layer to provide nonhysteretic current voltage characteristics, and the SQUID incorporates a 90 nm wide constriction which is used for on-chip modulation of the magnetic flux through the SQUID loop.", "output": {"entities": {"chemical": [{"text": "Au", "start": 31, "end": 33}]}}, "schema": []}
{"input": "The white flux noise of the device increases only slightly from 1. 3 mu Phi (0)/(Hz) (1/2) at B = 0 to 2. 3 mu Phi (0)/(Hz)) (1/2) at 1 T.", "output": {"entities": {}}, "schema": []}
{"input": "Assuming that a point-like magnetic particle with magnetization in the plane of the SQUID loop is placed directly on top of the constriction and taking into account the geometry of the SQUID, we calculate a spin sensitivity S (mu) (1/2) = 62 mu (B)/(Hz)) (1/2) at B = 0 and 110 mu (B)/(Hz)) (1/2) at 1 T.", "output": {"entities": {}}, "schema": []}
{"input": "The demonstration of low noise of such a SQUID in Tesla fields is a decisive step toward utilizing the full potential of ultrasensitive nanoSQUIDs for direct measurements of magnetic hysteresis curves of magnetic nanoparticles and molecular magnets.", "output": {"entities": {}}, "schema": []}
{"input": "Role of pharmacogenetics in busulfan/cyclophosphamide conditioning therapy prior to hematopoietic stem cell transplantation.", "output": {"entities": {"chemical": [{"text": "busulfan", "start": 28, "end": 36}, {"text": "cyclophosphamide", "start": 37, "end": 53}]}}, "schema": []}
{"input": "Hematopoietic stem cell transplantation (HSCT) is a curative treatment for several malignant and nonmalignant disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Busulfan (Bu) and cyclophosphamide (Cy) are the most commonly used alkylators in high-dose pretransplant conditioning for HSCT; a treatment that is correlated with drug-related toxicity and relapse.", "output": {"entities": {"chemical": [{"text": "Busulfan", "start": 0, "end": 8}, {"text": "cyclophosphamide", "start": 18, "end": 34}]}}, "schema": []}
{"input": "Pharmacogenetic investigations have shown that CYP450, as well as aldehyde dehydrogenase, are clearly involved with Cy metabolism and are associated with altered treatment response, Cy metabolism and the unique stem-cell sparing capacity.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Moreover, glutathione-S-transferase isoenzymes have been associated with cellular outward transport of various alkylating agents, including Cy metabolites, melphalan, Bu and chlorambucil.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 10, "end": 21}, {"text": "S", "start": 22, "end": 23}, {"text": "melphalan", "start": 156, "end": 165}, {"text": "chlorambucil", "start": 174, "end": 186}]}}, "schema": []}
{"input": "A shift from genetic-based studies to whole-genome-based investigations of Cy-and Bu-associated markers may contribute to personalizing the conditioning therapy and enhancing the clinical outcome of HSCT.", "output": {"entities": {}}, "schema": []}
{"input": "Mass accommodation of water: bridging the gap between molecular dynamics simulations and kinetic condensation models.", "output": {"entities": {}}, "schema": []}
{"input": "The condensational growth of submicrometer aerosol particles to climate relevant sizes is sensitive to their ability to accommodate vapor molecules, which is described by the mass accommodation coefficient.", "output": {"entities": {}}, "schema": []}
{"input": "However, the underlying processes are not yet fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "We have simulated the mass accommodation and evaporation processes of water using molecular dynamics, and the results are compared to the condensation equations derived from the kinetic gas theory to shed light on the compatibility of the two.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular dynamics simulations were performed for a planar TIP4P-Ew water surface at four temperatures in the range 268-300 K as well as two droplets, with radii of 1. 92 and 4. 14 nm at T = 273. 15 K.", "output": {"entities": {}}, "schema": []}
{"input": "The evaporation flux from molecular dynamics was found to be in good qualitative agreement with that predicted by the simple kinetic condensation equations.", "output": {"entities": {}}, "schema": []}
{"input": "Water droplet growth was also modeled with the kinetic multilayer model KM-GAP of Shiraiwa et al.", "output": {"entities": {}}, "schema": []}
{"input": "[Atmos. Chem. Phys. 2012, 12, 2777].", "output": {"entities": {}}, "schema": []}
{"input": "It was found that, due to the fast transport across the interface, the growth of a pure water droplet is controlled by gas phase diffusion.", "output": {"entities": {}}, "schema": []}
{"input": "These facts indicate that the simple kinetic treatment is sufficient in describing pure water condensation and evaporation.", "output": {"entities": {}}, "schema": []}
{"input": "The droplet size was found to have minimal effect on the value of the mass accommodation coefficient.", "output": {"entities": {}}, "schema": []}
{"input": "The mass accommodation coefficient was found to be unity (within 0. 004) for all studied surfaces, which is in agreement with previous simulation work.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, the simulated evaporation fluxes imply that the evaporation coefficient is also unity.", "output": {"entities": {}}, "schema": []}
{"input": "Comparing the evaporation rates of the mass accommodation and evaporation simulations indicated that the high collision flux, corresponding to high supersaturation, present in typical molecular dynamics mass accommodation simulations can under certain conditions lead to an increase in the evaporation rate.", "output": {"entities": {}}, "schema": []}
{"input": "Consequently, in such situations the mass accommodation coefficient can be overestimated, but in the present cases the corrected values were still close to unity with the lowest value at =~ 0. 99.", "output": {"entities": {}}, "schema": []}
{"input": "Accounting for receptor flexibility and enhanced sampling methods in computer-aided drug design.", "output": {"entities": {}}, "schema": []}
{"input": "Protein flexibility plays a major role in biomolecular recognition.", "output": {"entities": {}}, "schema": []}
{"input": "In many cases, it is not obvious how molecular structure will change upon association with other molecules.", "output": {"entities": {}}, "schema": []}
{"input": "In proteins, these changes can be major, with large deviations in overall backbone structure, or they can be more subtle as in a side-chain rotation.", "output": {"entities": {}}, "schema": []}
{"input": "Either way the algorithms that predict the favorability of biomolecular association require relatively accurate predictions of the bound structure to give an accurate assessment of the energy involved in association.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review a number of techniques that have been proposed to accommodate receptor flexibility in the simulation of small molecules binding to protein receptors.", "output": {"entities": {}}, "schema": []}
{"input": "We investigate modifications to standard rigid receptor docking algorithms and also explore enhanced sampling techniques, and the combination of free energy calculations and enhanced sampling techniques.", "output": {"entities": {}}, "schema": []}
{"input": "The understanding and allowance for receptor flexibility are helping to make computer simulations of ligand protein binding more accurate.", "output": {"entities": {}}, "schema": []}
{"input": "These developments may help improve the efficiency of drug discovery and development.", "output": {"entities": {}}, "schema": []}
{"input": "Efficiency will be essential as we begin to see personalized medicine tailored to individual patients, which means specific drugs are needed for each patient' s genetic makeup.", "output": {"entities": {}}, "schema": []}
{"input": "Vasorelaxing effects and inhibition of nitric oxide in macrophages by new iron-containing carbon monoxide-releasing molecules (CO-RMs).", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 39, "end": 51}, {"text": "iron", "start": 74, "end": 78}, {"text": "carbon monoxide", "start": 90, "end": 105}]}}, "schema": []}
{"input": "Carbon monoxide-releasing molecules (CO-RMs) are a class of organometallo carbonyl complexes capable of delivering controlled quantities of CO gas to cells and tissues thus exerting a broad spectrum of pharmacological effects.", "output": {"entities": {"chemical": [{"text": "Carbon monoxide", "start": 0, "end": 15}, {"text": "CO", "start": 37, "end": 39}, {"text": "organometallo carbonyl", "start": 60, "end": 82}, {"text": "CO", "start": 140, "end": 142}]}}, "schema": []}
{"input": "Here we report on the chemical synthesis, CO releasing properties, cytotoxicity profile and pharmacological activities of four novel structurally related iron-allyl carbonyls.", "output": {"entities": {"chemical": [{"text": "CO", "start": 42, "end": 44}, {"text": "iron-allyl carbonyls", "start": 154, "end": 174}]}}, "schema": []}
{"input": "The major difference among the new CO-RMs tested was that three compounds (CORM-307, CORM-308 and CORM-314) were soluble in dimethylsulfoxide (DMSO), whereas a fourth one (CORM-319) was rendered water-soluble by reacting the iron-carbonyl with hydrogen tetrafluoroborate.", "output": {"entities": {"chemical": [{"text": "CO", "start": 35, "end": 37}, {"text": "CORM-307", "start": 75, "end": 83}, {"text": "CORM-308", "start": 85, "end": 93}, {"text": "CORM-314", "start": 98, "end": 106}, {"text": "dimethylsulfoxide", "start": 124, "end": 141}, {"text": "DMSO", "start": 143, "end": 147}, {"text": "CORM-319", "start": 172, "end": 180}, {"text": "iron-carbonyl", "start": 225, "end": 238}, {"text": "hydrogen tetrafluoroborate", "start": 244, "end": 270}]}}, "schema": []}
{"input": "We found that despite the fact all compounds liberated CO, CO-RMs soluble in DMSO caused a more pronounced toxic effect both in vascular and inflammatory cells as well as in isolated vessels.", "output": {"entities": {"chemical": [{"text": "CO", "start": 55, "end": 57}, {"text": "CO", "start": 59, "end": 61}, {"text": "DMSO", "start": 77, "end": 81}]}}, "schema": []}
{"input": "More specifically, iron carbonyls soluble in DMSO released CO with a fast kinetic and displayed a marked cytotoxic effect in smooth muscle cells and RAW 247. 6 macrophages despite exerting a rapid and pronounced vasorelaxation ex vivo.", "output": {"entities": {"chemical": [{"text": "iron carbonyls", "start": 19, "end": 33}, {"text": "DMSO", "start": 45, "end": 49}, {"text": "CO", "start": 59, "end": 61}]}}, "schema": []}
{"input": "In contrast, CORM-319 that is soluble in water and liberated CO with a slower rate, preserved smooth muscle cell viability, relaxed aortic tissue and exerted a significant anti-inflammatory effect in macrophages challenged with endotoxin.", "output": {"entities": {"chemical": [{"text": "CORM-319", "start": 13, "end": 21}, {"text": "CO", "start": 61, "end": 63}]}}, "schema": []}
{"input": "These data suggest that iron carbonyls can be used as scaffolds for the design and synthesis of pharmacologically active CO-RMs and indicate that increasing water solubility and controlling the rate of CO release are important parameters for limiting their potential toxic effects.", "output": {"entities": {"chemical": [{"text": "iron carbonyls", "start": 24, "end": 38}, {"text": "CO", "start": 121, "end": 123}, {"text": "CO", "start": 202, "end": 204}]}}, "schema": []}
{"input": "Estradiol negative and positive feedback in a prenatal androgen-induced mouse model of polycystic ovarian syndrome.", "output": {"entities": {"chemical": [{"text": "Estradiol", "start": 0, "end": 9}, {"text": "androgen", "start": 55, "end": 63}]}}, "schema": []}
{"input": "Gonadal steroid hormone feedback is impaired in polycystic ovarian syndrome (PCOS), a common endocrine disorder characterized by hyperandrogenism and an associated increase in LH pulse frequency.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 8, "end": 15}]}}, "schema": []}
{"input": "Using a prenatal androgen (PNA)-treated mouse model of PCOS, we aimed to investigate negative and positive feedback effects of estrogens on the hypothalamic-pituitary axis regulation of LH.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 17, "end": 25}, {"text": "estrogens", "start": 127, "end": 136}]}}, "schema": []}
{"input": "PNA-treated mice exhibited severely disrupted estrous cycles, hyperandrogenism, significantly reduced fertility, and altered ovarian morphology.", "output": {"entities": {}}, "schema": []}
{"input": "To assess the negative feedback effects of estrogens, LH was measured before and after ovariectomy and after estradiol (E2) administration.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 43, "end": 52}, {"text": "estradiol", "start": 109, "end": 118}]}}, "schema": []}
{"input": "Compared with controls, PNA-treated mice exhibited a blunted postcastration rise in LH (P <. 001) and an absence of LH suppression after E2 administration.", "output": {"entities": {}}, "schema": []}
{"input": "To assess E2-positive feedback, control and PNA-treated GnRH-green fluorescent protein transgenic mice were subjected to a standard ovariectomy with E2-replacement regimen, and both plasma and perfusion-fixed brains were collected at the time of the expected GnRH/LH surge.", "output": {"entities": {}}, "schema": []}
{"input": "Immunocytochemistry and confocal imaging of cFos and green fluorescent protein were used to assess GnRH neuron activation and spine density.", "output": {"entities": {}}, "schema": []}
{"input": "In the surged group, both control and PNA-treated mice had significantly increased LH and cFos activation in GnRH neurons (P <. 05) compared with nonsurged animals.", "output": {"entities": {}}, "schema": []}
{"input": "Spine density was quantified in cFos-positive and-negative GnRH neurons to examine whether there was an increase in spine density in cFos-expressing GnRH neurons of surged mice as expected.", "output": {"entities": {}}, "schema": []}
{"input": "A significant increase in spine density in cFos-expressing GnRH neurons was evident in control animals; however, no significant increase was observed in the PNA-treated mice because spine density was elevated across all GnRH neurons.", "output": {"entities": {}}, "schema": []}
{"input": "These data support that PNA treatment results in a PCOS-like phenotype that includes impaired E2-negative feedback.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, although E2-positive feedback capability is retained in PNA mice, elevated GnRH neuron spine density may reflect altered synaptic regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitory effects of a bazedoxifene/conjugated equine estrogen combination on human breast cancer cells in vitro.", "output": {"entities": {"chemical": [{"text": "bazedoxifene", "start": 24, "end": 36}, {"text": "estrogen", "start": 55, "end": 63}]}}, "schema": []}
{"input": "Breast cancer incidence is increased in women receiving menopausal hormone therapy with estrogen plus progestin but not with estrogen alone.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 88, "end": 96}, {"text": "estrogen", "start": 125, "end": 133}]}}, "schema": []}
{"input": "The use of a tissue-selective estrogen complex (TSEC) has been proposed as a novel menopausal hormone therapy strategy to eliminate the requirement for a progestogen.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 30, "end": 38}, {"text": "progestogen", "start": 154, "end": 165}]}}, "schema": []}
{"input": "Combination of bazedoxifene (BZA) with conjugated estrogens (CEs), the first TSEC, has shown beneficial effects.", "output": {"entities": {"chemical": [{"text": "bazedoxifene", "start": 15, "end": 27}, {"text": "BZA", "start": 29, "end": 32}, {"text": "estrogens", "start": 50, "end": 59}]}}, "schema": []}
{"input": "Whether it would exert antiestrogenic effects on breast cancer is not clear.", "output": {"entities": {}}, "schema": []}
{"input": "To address this issue, we compared estradiol (E (2)) and CE alone on proliferation and apoptosis in MCF-7 breast cancer cells.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 35, "end": 44}]}}, "schema": []}
{"input": "CE stimulated growth of MCF-7 cells at a peak concentration 10-fold higher than required for E (2).", "output": {"entities": {}}, "schema": []}
{"input": "Both CE and E (2) alone increased DNA synthesis and reduced apoptosis with activation of MAPK, Akt, and p70S6K and up-regulation of antiapoptotic factors survivin, Bcl-2, and X-linked inhibitor of apoptosis protein, These effects could be completely blocked by BZA.", "output": {"entities": {"chemical": [{"text": "BZA", "start": 261, "end": 264}]}}, "schema": []}
{"input": "Gene expression studies demonstrated that CE and E (2) were equally potent on expression of cMyc, pS2, and WNT1 inducible signaling pathway protein 2, whereas the stimulatory effects of CE on progesterone receptor and amphiregulin expression were weaker than E (2).", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 192, "end": 204}]}}, "schema": []}
{"input": "BZA effectively blocked each of these effects and showed no estrogen agonistic effects when used alone.", "output": {"entities": {"chemical": [{"text": "BZA", "start": 0, "end": 3}, {"text": "estrogen", "start": 60, "end": 68}]}}, "schema": []}
{"input": "Our results indicate that the stimulatory effects of E (2) or CE on breast cancer cells could be completely abrogated by BZA.", "output": {"entities": {"chemical": [{"text": "BZA", "start": 121, "end": 124}]}}, "schema": []}
{"input": "These studies imply that the CE/BZA, TSEC, exerts antiestrogenic effects on breast cancer cells and might block the growth of occult breast neoplasms in postmenopausal women, resulting in an overall reduction in tumor incidence.", "output": {"entities": {"chemical": [{"text": "BZA", "start": 32, "end": 35}]}}, "schema": []}
{"input": "Synthesis and characterization of self-bridged silver vanadium oxide/CNTs composite and its enhanced lithium storage performance.", "output": {"entities": {"chemical": [{"text": "silver vanadium oxide", "start": 47, "end": 68}, {"text": "lithium", "start": 101, "end": 108}]}}, "schema": []}
{"input": "The improvement of the electrochemical properties of electrode materials with large capacity and good capacity retention is becoming an important task in the field of lithium ion batteries (LIBs).", "output": {"entities": {"chemical": [{"text": "lithium", "start": 167, "end": 174}]}}, "schema": []}
{"input": "We designed a function-oriented hybrid material consisting of silver vanadium oxide (beta-AgVO (3)) nanowires modified with uniform Ag nanoparticles and multi-walled carbon nanotubes (CNTs) as a high-performance cathode material for LIBs.", "output": {"entities": {"chemical": [{"text": "silver vanadium oxide", "start": 62, "end": 83}, {"text": "AgVO (3)", "start": 90, "end": 98}, {"text": "Ag", "start": 132, "end": 134}, {"text": "carbon", "start": 166, "end": 172}]}}, "schema": []}
{"input": "The Ag nanoparticles which precipitated automatically in the synthetic process act as a bridge between the beta-AgVO (3) nanowires and CNTs, creating a self-bridged network structure.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 4, "end": 6}, {"text": "AgVO (3)", "start": 112, "end": 120}]}}, "schema": []}
{"input": "The Ag particles at the junction of the nanowires and CNTs facilitate electron transport from the CNTs to the nanowires, and thereby improve the electrical conductivity of the beta-AgVO (3) nanowires and the composite.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 4, "end": 6}, {"text": "AgVO (3)", "start": 181, "end": 189}]}}, "schema": []}
{"input": "Moreover, the self-bridged network is hierarchically porous with a high surface area.", "output": {"entities": {}}, "schema": []}
{"input": "When used as a cathode material, this composite electrode reveals high discharge capacities, excellent rate capability, and good cycling stability.", "output": {"entities": {}}, "schema": []}
{"input": "The improved performance of the composite arises from its unique nanosized beta-AgVO (3) nanowires with short diffusion pathway for lithium ions, efficient electron collection and transfer in the presence of Ag nanoparticles, together with excellent electrical conductivity of CNTs.", "output": {"entities": {"chemical": [{"text": "AgVO (3)", "start": 80, "end": 88}, {"text": "lithium", "start": 132, "end": 139}, {"text": "Ag", "start": 208, "end": 210}]}}, "schema": []}
{"input": "Noncanonical WNT-5A signaling regulates TGF-beta-induced extracellular matrix production by airway smooth muscle cells.", "output": {"entities": {}}, "schema": []}
{"input": "Transforming growth factor beta (TGF-beta), a key mediator of fibrotic responses, is increased in asthma and drives airway remodeling by inducing expression of extracellular matrix (ECM) proteins.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the molecular mechanisms underlying TGF-beta-induced ECM expression by airway smooth muscle cells and demonstrate a novel link between TGF-beta and Wingless/integrase 1 (WNT) signaling in ECM deposition.", "output": {"entities": {}}, "schema": []}
{"input": "Airway smooth muscle expresses abundant WNT ligands, with the noncanonical WNT-5A being the most profoundly expressed.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, WNT-5A shows ~ 2-fold higher abundance in airway smooth muscle cells isolated from individuals with asthma than individuals without asthma.", "output": {"entities": {}}, "schema": []}
{"input": "WNT-5A is markedly induced in response to TGF-beta (4-16-fold; EC50 0. 3 ng/ml) and is required for collagen and fibronectin expression by airway smooth muscle.", "output": {"entities": {}}, "schema": []}
{"input": "WNT-5A engages noncanonical WNT signaling pathways, as inhibition of Ca (2 +) and c-Jun N-terminal kinase (JNK) signaling attenuated this TGF-beta response, whereas the canonical WNT antagonist Dickkopf 1 (DKK-1) did not.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 69, "end": 77}, {"text": "N", "start": 88, "end": 89}]}}, "schema": []}
{"input": "Accordingly, WNT-5A induced JNK phosphorylation and nuclear translocation of nuclear factor of activated T cells c1 (NFATc1).", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, silencing of the WNT-5A receptors Frizzled 8 (FZD8) and RYK attenuated TGF-beta-induced ECM expression.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these findings demonstrate that noncanonical WNT-5A signaling is activated by and necessary for TGF-beta-induced ECM production by airway smooth muscle cells, which could have significance in asthma pathogenesis.-Kumawat, K., Menzen, M.", "output": {"entities": {}}, "schema": []}
{"input": "H.., Bos, I.", "output": {"entities": {}}, "schema": []}
{"input": "S.", "output": {"entities": {}}, "schema": []}
{"input": "T., Baarsma, H.", "output": {"entities": {}}, "schema": []}
{"input": "A., Borger, P., Roth, M., Tamm, M., Halayko, A.", "output": {"entities": {}}, "schema": []}
{"input": "J., Simoons, M., Prins, A., Postma, D.", "output": {"entities": {}}, "schema": []}
{"input": "S., Schmidt, M., and Gosens, R.", "output": {"entities": {}}, "schema": []}
{"input": "Noncanonical WNT-5A signaling regulates TGF-beta-induced extracellular matrix production by airway smooth muscle cells.", "output": {"entities": {}}, "schema": []}
{"input": "The photophysics of 7-(N, N'-diethylamino) coumarin-3-carboxylic acid in water/AOT/isooctane reverse micelles: an excitation wavelength dependent study.", "output": {"entities": {"chemical": [{"text": "7-(N, N'-diethylamino) coumarin-3-carboxylic acid", "start": 20, "end": 69}, {"text": "AOT", "start": 79, "end": 82}, {"text": "isooctane", "start": 83, "end": 92}]}}, "schema": []}
{"input": "In this manuscript we have studied the photophysics of 7-(N, N'-diethylamino) coumarin-3-carboxylic acid (7-DCCA) in water/AOT/isooctane reverse micelles.", "output": {"entities": {"chemical": [{"text": "7-(N, N'-diethylamino) coumarin-3-carboxylic acid", "start": 55, "end": 104}, {"text": "7-DCCA", "start": 106, "end": 112}, {"text": "AOT", "start": 123, "end": 126}, {"text": "isooctane", "start": 127, "end": 136}]}}, "schema": []}
{"input": "For this purpose we have used steady state absorption and fluorescence emission spectroscopy and time resolved fluorescence spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "We have studied the spectral behaviour of 7-DCCA inside the water/AOT/isooctane reverse micelles with variation of excitation wavelength.", "output": {"entities": {"chemical": [{"text": "7-DCCA", "start": 42, "end": 48}, {"text": "AOT", "start": 66, "end": 69}, {"text": "isooctane", "start": 70, "end": 79}]}}, "schema": []}
{"input": "We have studied the dynamics of solvent and rotational relaxation by using two different excitation wavelengths (lambda (exi) = 375 nm and lambda (exi) = 405 nm).", "output": {"entities": {}}, "schema": []}
{"input": "We have observed the excitation wavelength dependent dynamics of 7-DCCA in the reverse micelles.", "output": {"entities": {"chemical": [{"text": "7-DCCA", "start": 65, "end": 71}]}}, "schema": []}
{"input": "The fluorescence quantum yield, decay time, solvent relaxation time and rotational relaxation time of 7-DCCA in reverse micelles vary with the excitation wavelength.", "output": {"entities": {"chemical": [{"text": "7-DCCA", "start": 102, "end": 108}]}}, "schema": []}
{"input": "A two step and wobbling-in-cone model was used to interpret the rotational relaxation dynamics of 7-DCCA in reverse micelles.", "output": {"entities": {"chemical": [{"text": "7-DCCA", "start": 98, "end": 104}]}}, "schema": []}
{"input": "Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 77, "end": 84}]}}, "schema": []}
{"input": "A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 107, "end": 114}]}}, "schema": []}
{"input": "In this platform, integration of ligand-receptor recognition, nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of disease-associated N-linked glycoproteins.", "output": {"entities": {"chemical": [{"text": "N", "start": 39, "end": 40}]}}, "schema": []}
{"input": "N-linked glycoproteins play important roles in biological processes, including cell-to-cell recognition, growth, differentiation, and programmed cell death.", "output": {"entities": {"chemical": [{"text": "N", "start": 0, "end": 1}]}}, "schema": []}
{"input": "Specific N-linked glycoprotein changes are associated with disease progression and identification of these N-linked glycoproteins has potential for use in disease diagnosis, prognosis, and prediction of treatments.", "output": {"entities": {"chemical": [{"text": "N", "start": 9, "end": 10}, {"text": "N", "start": 107, "end": 108}]}}, "schema": []}
{"input": "In this review, we summarize common strategies for N-linked glycoprotein characterization and applications of these strategies to identification of glycoprotein changes associated with disease states.", "output": {"entities": {"chemical": [{"text": "N", "start": 51, "end": 52}]}}, "schema": []}
{"input": "We also review the N-linked glycoproteins altered in diseases such as breast cancer, lung cancer, and prostate cancer.", "output": {"entities": {"chemical": [{"text": "N", "start": 19, "end": 20}]}}, "schema": []}
{"input": "Although assays for these glycoproteins have potential clinical utility, research is needed to translate these glycoproteins to clinical biomarkers.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of guanidinylation on the properties of poly (2-aminoethylmethacrylate)-based antibacterial materials.", "output": {"entities": {"chemical": [{"text": "poly (2-aminoethylmethacrylate)", "start": 47, "end": 78}]}}, "schema": []}
{"input": "The effect of converting ammonium into guanidine moieties, compared to other factors such as molecular weight or hydrophobicity, on the antibacterial activity is investigated for homo-and copolymers of 2-aminoethylmethacrylate in solution or coatings.", "output": {"entities": {"chemical": [{"text": "ammonium", "start": 25, "end": 33}, {"text": "guanidine", "start": 39, "end": 48}, {"text": "2-aminoethylmethacrylate", "start": 202, "end": 226}]}}, "schema": []}
{"input": "Polymers are obtained by free radical polymerization, polymer-analogous guanidinylation is conducted with cyanamide; non-leaching immobilization is achieved by LBL assembly of homopolymers or crosslinking of functional sidegroups in copolymers.", "output": {"entities": {"chemical": [{"text": "cyanamide", "start": 106, "end": 115}]}}, "schema": []}
{"input": "Antibacterial activity to Escherichia coli or Bacillus subtilis is determined by different standard methods.", "output": {"entities": {}}, "schema": []}
{"input": "Guanidinylation improves antibacterial activity and speed as well as cytotoxicity of hydrophilic homo-and copolymers in solution or coatings.", "output": {"entities": {}}, "schema": []}
{"input": "A metabonomics investigation of multiple sclerosis by nuclear magnetic resonance.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple sclerosis (MS) is a nervous system disease that affects the fatty myelin sheaths around the axons of the brain and spinal cord, leading to demyelination and a broad range of signs and symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "MS can be difficult to diagnose because its signs and symptoms may be similar to other medical problems.", "output": {"entities": {}}, "schema": []}
{"input": "To find out which metabolites in serum are effective for the diagnosis of MS, we utilized metabolic profiling using proton nuclear magnetic resonance spectroscopy ((1) H-NMR).", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 164, "end": 169}]}}, "schema": []}
{"input": "Random forest (RF) was used to classify the MS patients and healthy subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Atomic absorption spectroscopy was used to measure the serum levels of selenium.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 71, "end": 79}]}}, "schema": []}
{"input": "The results showed that the levels of selenium were lower in the MS group, when compared with the control group.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 38, "end": 46}]}}, "schema": []}
{"input": "RF was used to identify the metabolites that caused selenium changes in people with MS by building a correlation model between these metabolites and serum levels of selenium.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 52, "end": 60}, {"text": "selenium", "start": 165, "end": 173}]}}, "schema": []}
{"input": "For the external test set, the obtained classification model showed a 93% correct classification of MS and healthy subjects.", "output": {"entities": {}}, "schema": []}
{"input": "The regression model of levels of selenium and metabolites showed the correlation (R (2)) value of 0. 88 for the external test set.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 34, "end": 42}]}}, "schema": []}
{"input": "The results indicate the suitability of NMR as a screen for identifying MS patients and healthy subjects.", "output": {"entities": {}}, "schema": []}
{"input": "A novel model with good prediction outcomes was constructed between serum levels of selenium and NMR data.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 84, "end": 92}]}}, "schema": []}
{"input": "Nanoscale thermomechanics of wear-resilient polymeric bilayer systems.", "output": {"entities": {}}, "schema": []}
{"input": "We explore the effect of an ultrathin elastic coating to optimize the mechanical stability of an underlying polymer film for nanoscale applications.", "output": {"entities": {}}, "schema": []}
{"input": "The coating consists of a several nanometer thin plasma-polymerized norbornene layer.", "output": {"entities": {"chemical": [{"text": "norbornene", "start": 68, "end": 78}]}}, "schema": []}
{"input": "Scanning probes are used to characterize the system in terms of shear-force-induced wear and thermally assisted indentation.", "output": {"entities": {}}, "schema": []}
{"input": "The layer transforms a weakly performing polystyrene film into a highly wear-resistive system, ideal for high-density and low-power data storage applications.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 41, "end": 52}]}}, "schema": []}
{"input": "The result can be understood from the indentation characteristics with a hot and sharp indenter tip.", "output": {"entities": {}}, "schema": []}
{"input": "The latter gives rise to a deformation mode in the fully plastic regime, enabling a simple interpretation of the results.", "output": {"entities": {}}, "schema": []}
{"input": "The softening transition and the yield stress of the system on a microsecond time scale and a nanometer size scale were obtained.", "output": {"entities": {}}, "schema": []}
{"input": "We show that the plastic deformation is governed by yielding in the polystyrene sublayer, which renders the overall system soft for plastic deformation.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 68, "end": 79}]}}, "schema": []}
{"input": "The ultrathin protection layer contributes as an elastic skin, which shields part of the temperature and pressure and enables the high wear resistance against lateral forces.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the method of probing polymers at microsecond and nanometer size scales opens up new opportunities for studying polymer physics in a largely unexplored regime.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, we find softening temperatures of more than 100 degrees C above the polystyrene glass transition, which implies that for the short interaction time scales the glassy state of the polymer is preserved up to this temperature.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 74, "end": 85}]}}, "schema": []}
{"input": "Aspartic protease inhibitors: effective drugs against the human fungal pathogen Candida albicans.", "output": {"entities": {}}, "schema": []}
{"input": "Candida albicans can invade humans and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients.", "output": {"entities": {}}, "schema": []}
{"input": "In this context, both the host immune status and the ability of C. albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance; in this last case, culminating in the establishment of successful infection known as candidiasis.", "output": {"entities": {}}, "schema": []}
{"input": "C. albicans possesses a potent armamentarium consisting of several virulence molecules that help the fungal cells to escape from the host immune responses.", "output": {"entities": {}}, "schema": []}
{"input": "There is no doubt that the secretion of aspartic proteases, designated as Saps, is one of the major virulence attributes produced by C. albicans cells, since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions.", "output": {"entities": {}}, "schema": []}
{"input": "For these reasons, Saps clearly hold promise as new potential drug targets.", "output": {"entities": {}}, "schema": []}
{"input": "Corroborating this hypothesis, the introduction of anti-human immunodeficiency virus drugs of the aspartic protease inhibitor-type (HIV PIs) have emerged as new agents for the inhibition of Saps.", "output": {"entities": {}}, "schema": []}
{"input": "The introduction of HIV PIs has revolutionized the treatment of HIV disease, reducing the opportunistic infections, especially candidiasis.", "output": {"entities": {}}, "schema": []}
{"input": "The attenuation of candidal infections in HIV-infected individuals might not solely has not only resulted from improved immunological status, but also as a result of direct inhibition of C. albicans Saps as well as the blockage of several biological processes controlled by these proteolytic enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "The present article will discuss the updates on the functional implications of HIV PIs on the development of candidiasis.", "output": {"entities": {}}, "schema": []}
{"input": "Optical activity of achiral ligand SCH3 adsorbed on achiral Ag55 clusters: relationship between adsorption site and circular dichroism.", "output": {"entities": {"chemical": [{"text": "SCH3", "start": 35, "end": 39}, {"text": "Ag55", "start": 60, "end": 64}]}}, "schema": []}
{"input": "The electronic circular dichroism (CD) spectra of a methyl-thiol adsorbed at different sites on an icosahedral silver nanoparticle is studied by using time-perturbed density functional theory.", "output": {"entities": {"chemical": [{"text": "methyl-thiol", "start": 52, "end": 64}, {"text": "silver", "start": 111, "end": 117}]}}, "schema": []}
{"input": "Despite that separately molecule and nanoparticle are achiral and consequently optically inactive, the Ag (55)-SCH (3) compound emerges with a new symmetry, which may be chiral or not depending on the adsorption site and orientation of the molecule.", "output": {"entities": {"chemical": [{"text": "Ag (55)-SCH (3)", "start": 103, "end": 118}]}}, "schema": []}
{"input": "It is found that chirality is favored when the thiol is adsorbed between two atoms of different coordination number.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 47, "end": 52}]}}, "schema": []}
{"input": "Chiral compounds have characteristic CD spectra in the UV-visible region, where Ag (55) shows optical absorption but SCH (3) does not; revealing that highly degenerated molecular-like electronic states of Ag (55) are modified by the presence of the molecule inducing optical activity.", "output": {"entities": {"chemical": [{"text": "Ag (55)", "start": 80, "end": 87}, {"text": "SCH (3)", "start": 117, "end": 124}, {"text": "Ag (55)", "start": 205, "end": 212}]}}, "schema": []}
{"input": "It is concluded that CD line-shapes and magnitude strongly depend on the site where the adsorption takes place, while its intensity is modulated by the molecule orientation.", "output": {"entities": {}}, "schema": []}
{"input": "Surfactant-Assisted Assembly of Fullerene (C (60)) Nanorods and Nanotubes Formed at a Liquid-Liquid Interface.", "output": {"entities": {"chemical": [{"text": "Fullerene", "start": 32, "end": 41}, {"text": "C (60)", "start": 43, "end": 49}]}}, "schema": []}
{"input": "Herein we report the surfactant-triggered assembly of fullerene (C (60)) into 3D flowerlike microcrystals at the liquid-liquid interface.", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 54, "end": 63}, {"text": "C (60)", "start": 65, "end": 71}]}}, "schema": []}
{"input": "C (60) crystals were grown using a liquid-liquid interfacial precipitation (LLIP) method by layering surfactant solution in butanol with a saturated solution of C (60) in benzene.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 0, "end": 6}, {"text": "butanol", "start": 124, "end": 131}, {"text": "C (60)", "start": 161, "end": 167}, {"text": "benzene", "start": 171, "end": 178}]}}, "schema": []}
{"input": "In the LLIP method, it is suggested that the crystal formation mechanism is driven by supersaturation related to the low C (60) solubility in alcohol.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 121, "end": 127}]}}, "schema": []}
{"input": "We found that the dimensions of the synthesized C (60) flowers depend on the concentration and surfactant type.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 48, "end": 54}]}}, "schema": []}
{"input": "In the absence of surfactant (i. e., in the butanol/benzene system), 1D C (60) nanowhiskers (nanorods) and C (60) nanotubes (diameter 400 nm-2 mu m and length 5-20 mu m) are obtained.", "output": {"entities": {"chemical": [{"text": "butanol", "start": 44, "end": 51}, {"text": "benzene", "start": 52, "end": 59}, {"text": "C (60)", "start": 72, "end": 78}, {"text": "C (60)", "start": 107, "end": 113}]}}, "schema": []}
{"input": "However, when surfactants are incorporated into the system flowerlike microcrystals consisting of C (60) nanotubes are observed.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 98, "end": 104}]}}, "schema": []}
{"input": "For instance, crystals grown at the interface of a 0. 01% diglycerol monolaurate (C (12) G (2)) nonionic surfactant in butanol with benzene lead to the formation of flower-shaped microcrystals of average sizes in the range of 10-35 mu m.", "output": {"entities": {"chemical": [{"text": "diglycerol monolaurate", "start": 58, "end": 80}, {"text": "C (12) G (2)", "start": 82, "end": 94}, {"text": "butanol", "start": 119, "end": 126}, {"text": "benzene", "start": 132, "end": 139}]}}, "schema": []}
{"input": "To the best of our knowledge, this is the first example of the surfactant-assisted assembly of C (60) crystals.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 95, "end": 101}]}}, "schema": []}
{"input": "X-ray diffraction (XRD) and transmission electron microscopy (TEM) measurements have shown that fullerene flowers have a hexagonal structure with cell dimensions of a = 2. 539 nm and c = 1. 021 nm, which differ from that of pristine C (60).", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 96, "end": 105}, {"text": "C (60)", "start": 233, "end": 239}]}}, "schema": []}
{"input": "Mixtures of flower-shaped C (60) crystals and free-standing C (60) nanotubes are found in the 0. 1% C (12) G (2)/butanol system.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 26, "end": 32}, {"text": "C (60)", "start": 60, "end": 66}, {"text": "C (12) G (2)", "start": 100, "end": 112}, {"text": "butanol", "start": 113, "end": 120}]}}, "schema": []}
{"input": "However, clusters or giant aggregates of nanowhiskers lacking any specific shape are observed in the 1% C (12) G (2)/butanol system although these crystals exhibit hexagonal close-packed structures.", "output": {"entities": {"chemical": [{"text": "C (12) G (2)", "start": 104, "end": 116}]}}, "schema": []}
{"input": "Flower-shaped C (60) microcrystals are also observed with anionic surfactants cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC).", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 14, "end": 20}, {"text": "cetyltrimethylammonium bromide", "start": 78, "end": 108}, {"text": "CTAB", "start": 110, "end": 114}, {"text": "cetyltrimethylammonium chloride", "start": 120, "end": 151}, {"text": "CTAC", "start": 153, "end": 157}]}}, "schema": []}
{"input": "C (60) flowers obtained from 0. 01% CTAB and 0. 01% CTAC also exhibit hexagonal structures with cell dimensions of a = 2. 329 nm and c = 1. 273 nm, a = 2. 459 nm and c = 0. 938 nm, respectively.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 0, "end": 6}, {"text": "CTAB", "start": 36, "end": 40}, {"text": "CTAC", "start": 52, "end": 56}]}}, "schema": []}
{"input": "Our C (60) flowers exhibit intense photoluminescence (PL) and a blue-shifted PL intensity maximum compared to the same parameters for pristine C (60), demonstrating the potential to control the optoelectronic properties of fullerene-based nanostructures.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 4, "end": 10}, {"text": "C (60)", "start": 143, "end": 149}, {"text": "fullerene", "start": 223, "end": 232}]}}, "schema": []}
{"input": "Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clinical study design.", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 35, "end": 45}]}}, "schema": []}
{"input": "1. This work investigated the drug interaction potential of GSK1292263, a novel GPR119 agonist, with the HMG-coA reductase inhibitors simvastatin and rosuvastatin.", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 60, "end": 70}, {"text": "simvastatin", "start": 134, "end": 145}, {"text": "rosuvastatin", "start": 150, "end": 162}]}}, "schema": []}
{"input": "2. In vitro experiments assessed the inhibition of transporters and CYP enzymes by GSK1292263, and a clinical drug interaction study investigated the effect of GSK1292263 (300 mg BID) on the pharmacokinetic profile of simvastatin (40 mg single dose) and rosuvastatin (10 mg single dose).", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 83, "end": 93}, {"text": "GSK1292263", "start": 160, "end": 170}, {"text": "simvastatin", "start": 218, "end": 229}, {"text": "rosuvastatin", "start": 254, "end": 266}]}}, "schema": []}
{"input": "3. In vitro, GSK1292263 demonstrated little/weak inhibition (IC50 values > 30 mu M) towards CYPs (CYP1A2, 2C9, 2C19, 2D6, 3A4), Pgp, OATP1B3, or OCT2.", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 13, "end": 23}]}}, "schema": []}
{"input": "However, GSK1292263 inhibited BCRP and OATP1B1, which are transporters involved in statin disposition.", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 9, "end": 19}]}}, "schema": []}
{"input": "4. In the clinical study, small increases in the AUC (0-inf) of simvastatin [mean ratio (90% CI) of 1. 34 (1. 22, 1. 48)] and rosuvastatin [mean ratio (90% CI) of 1. 39 (1. 30, 1. 49)] were observed when co-administered with GSK1292263, which is consistent with an inhibitory effect on intestinal BCRP and CYP3A4.", "output": {"entities": {"chemical": [{"text": "simvastatin", "start": 64, "end": 75}, {"text": "rosuvastatin", "start": 126, "end": 138}, {"text": "GSK1292263", "start": 225, "end": 235}]}}, "schema": []}
{"input": "In contrast, GSK1292263 did not inhibit OATP1B1 based on the lack of changes in simvastatin acid exposure [mean AUC (0-inf) ratio (90% CI) of 1. 05 (0. 91, 1. 21)].", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 13, "end": 23}, {"text": "simvastatin", "start": 80, "end": 91}]}}, "schema": []}
{"input": "5. GSK1292263 has a weak drug interaction with simvastatin and rosuvastain.", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 3, "end": 13}, {"text": "simvastatin", "start": 47, "end": 58}, {"text": "rosuvastain", "start": 63, "end": 74}]}}, "schema": []}
{"input": "This study provides a mechanistic understanding of the in vivo inhibition of transporters and enzymes by GSK1292263.", "output": {"entities": {"chemical": [{"text": "GSK1292263", "start": 105, "end": 115}]}}, "schema": []}
{"input": "Iridium-catalyzed enantioselective allylic vinylation.", "output": {"entities": {"chemical": [{"text": "Iridium", "start": 0, "end": 7}]}}, "schema": []}
{"input": "The first example of Ir-catalyzed asymmetric substitution reaction with vinyl trifluoroborates is described.", "output": {"entities": {"chemical": [{"text": "Ir", "start": 21, "end": 23}, {"text": "vinyl trifluoroborates", "start": 72, "end": 94}]}}, "schema": []}
{"input": "The direct reaction between branched, racemic allylic alcohols and potassium alkenyltrifluoroborates proceeded with high site selectivity and excellent enantioselectivity (up to 99%) mediated by an Ir-(P, olefin) complex.", "output": {"entities": {"chemical": [{"text": "allylic alcohols", "start": 46, "end": 62}, {"text": "potassium alkenyltrifluoroborates", "start": 67, "end": 100}, {"text": "Ir-(P, olefin)", "start": 198, "end": 212}]}}, "schema": []}
{"input": "This method allows rapid access to various 1, 4-dienes or trienes including the biologically active natural products (-)-nyasol and (-)-hinokiresinol.", "output": {"entities": {"chemical": [{"text": "1, 4-dienes", "start": 43, "end": 54}, {"text": "trienes", "start": 58, "end": 65}, {"text": "(-)-nyasol", "start": 117, "end": 127}, {"text": "(-)-hinokiresinol", "start": 132, "end": 149}]}}, "schema": []}
{"input": "Can we delay the accelerated lung aging in COPD?", "output": {"entities": {}}, "schema": []}
{"input": "Anti-aging molecules and interventions.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging.", "output": {"entities": {}}, "schema": []}
{"input": "The prevalence of COPD is age-dependent suggesting an intimate relationship between the pathogenesis of COPD and aging.", "output": {"entities": {}}, "schema": []}
{"input": "Lung function decline, the hallmark feature of COPD evolution, is more prominent with increasing age and this decline is greater in smoking individuals.", "output": {"entities": {}}, "schema": []}
{"input": "One of the major goals of COPD pharmacotherapy is the development of drugs that would be able to result in a decrease of the decline in lung function over years.", "output": {"entities": {}}, "schema": []}
{"input": "However, till nowadays smoking cessation is the only known intervention which is able to decelerate lung function decline.", "output": {"entities": {}}, "schema": []}
{"input": "Several mechanisms of aging, including oxidative stress, inflammation and telomere shortening have been shown to be implicated in COPD.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, numerous anti-aging molecules, including sirtuins and Nrf-2 are reduced, and pathways such as mTOR and genes such as Klotho have also been shown to be abnormal in the lungs of COPD patients.", "output": {"entities": {}}, "schema": []}
{"input": "The above mechanisms have been associated with the accelerated lung aging in COPD patients.", "output": {"entities": {}}, "schema": []}
{"input": "Numerous therapeutic interventions have been studied in an attempt to reverse accelerated lung aging, and some of them have already been tested in clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present review is to summarize the mechanisms associated with the accelerated lung aging in COPD and to provide information about the possible therapeutic implications targeting those mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Managing comorbidity in COPD: a difficult task.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic obstructive pulmonary disease is a public health problem that results in high morbidity, disability and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Comorbidities are highly prevalent in COPD patients because of aging, common risk factors and pathways, rising mortality, and disability.", "output": {"entities": {}}, "schema": []}
{"input": "In this review article we present the most prevalent co-morbidities in COPD patients, we face the issue of multimorbidity and discuss the practical management approach relevant to chest physicians and general practitioners.", "output": {"entities": {}}, "schema": []}
{"input": "Issues on comorbidities management according to general guidelines as well as their implications for COPD are raised.", "output": {"entities": {}}, "schema": []}
{"input": "The aim is to give clinicians an easy update with specific recommendations for each comorbidity.", "output": {"entities": {}}, "schema": []}
{"input": "The implications of several medications used for comorbidities in COPD in terms of benefits, concerns, medication preference, medication avoidance and contraindications are also discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Stem cell therapy in chronic obstructive pulmonary disease.", "output": {"entities": {}}, "schema": []}
{"input": "Seeking the prometheus effect.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic obstructive pulmonary disease is characterized by dramatic alterations in lung architecture associated to an exaggerated inflammatory process, alveolar epithelial cell apoptosis, endothelial dysfunction and extracellular matrix destruction due to a protease and anti-protease imbalance.", "output": {"entities": {}}, "schema": []}
{"input": "In addition a significant inflammatory spillover into systemic circulation has been suggested to be responsible for a wide range of fatal comorbidities.", "output": {"entities": {}}, "schema": []}
{"input": "In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will fulfill the unmet need of modulating both local and systemic inflammation and at the same time accelerate alveolar epithelial and endothelial turnover intervening into disease natural course and not only relieving patient' s symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "Regenerative medicine based on stem cells properties represents one promising option with several fruitful therapeutic applications in patients with COPD.", "output": {"entities": {}}, "schema": []}
{"input": "Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administrated stem cells within the COPD lung as well as the mechanisms regulating activation of resident progenitor cells.", "output": {"entities": {}}, "schema": []}
{"input": "The above evidence coupled with the rather disappointing results emerging from the first stem cell clinical trials in COPD patients underline the need for careful study design by setting realistic goals to assess efficacy such as biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn.", "output": {"entities": {}}, "schema": []}
{"input": "Novel modalities and agents in bronchoscopic lung volume reduction.", "output": {"entities": {}}, "schema": []}
{"input": "The NETT study has shown the effectiveness of lung volume reduction surgery (LVRS) in improving functional parameters and exercise tolerance in selected patients with severe pulmonary emphysema of upper lobe predominance.", "output": {"entities": {}}, "schema": []}
{"input": "A number of bronchoscopic techniques have since been developed under the term \" bronchoscopic lung volume reduction \" (BLVR), aiming to lower the complications and the cost while facilitating the procedure of lung volume approach in patients with emphysema.", "output": {"entities": {}}, "schema": []}
{"input": "These include airway bypass by creation of airway/parenchyma communications, one-way endobronchial valves occluding the airways of the targeted lobes, endobronchial coils which mechanically contract the parenchyma, hot vapour ablation thermally destroying the targeted sites and sealant which fill the alveoli with polymer material.", "output": {"entities": {}}, "schema": []}
{"input": "These methods are generally simple and safe, with a favourable complications profile, requiring less infrastructure and interventional experience than the open surgical approach.", "output": {"entities": {}}, "schema": []}
{"input": "Bronchial valves have produced promising results in a very narrow phenotype of emphysema patients and have the major advantage of being reversible in their action.", "output": {"entities": {}}, "schema": []}
{"input": "Parenchymal interventions at the cost of producing permanent effects and a transient inflammatory syndrome, may be effective in larger group of patients regardless of the fissure integrity and the presence of collateral ventilation.", "output": {"entities": {}}, "schema": []}
{"input": "New, more extensive multicentre studies are underway which aim at better selection and stratification of patients in order to further evaluate the safety and effectiveness of these techniques, before wider use of this revolutionary approach for severe lung emphysema can be advocated.", "output": {"entities": {}}, "schema": []}
{"input": "Steroid toxicity and detoxification in ascomycetous fungi.", "output": {"entities": {"chemical": [{"text": "Steroid", "start": 0, "end": 7}]}}, "schema": []}
{"input": "In the last couple of decades fungal infections have become a significant clinical problem.", "output": {"entities": {}}, "schema": []}
{"input": "A major interest into fungal steroid action has been provoked since research has proven that steroid hormones are toxic to fungi and affect the host/fungus relationship.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 29, "end": 36}, {"text": "steroid", "start": 93, "end": 100}]}}, "schema": []}
{"input": "Steroid hormones were found to differ in their antifungal activity in ascomycetous fungi Hortaea werneckii, Saccharomyces cerevisiae and Aspergillus oryzae.", "output": {"entities": {"chemical": [{"text": "Steroid", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Dehydroepiandrosterone was shown to be the strongest inhibitor of growth in all three varieties of fungi followed by androstenedione and testosterone.", "output": {"entities": {"chemical": [{"text": "androstenedione", "start": 117, "end": 132}, {"text": "testosterone", "start": 137, "end": 149}]}}, "schema": []}
{"input": "For their protection, fungi use several mechanisms to lower the toxic effects of steroids.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 81, "end": 89}]}}, "schema": []}
{"input": "The efficiency of biotransformation in detoxification depended on the microorganism and steroid substrate used.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 88, "end": 95}]}}, "schema": []}
{"input": "Biotransformation was a relatively slow process as it also depended on the growth phase of the fungus.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to biotransformation, steroid extrusion out of the cells contributed to the lowering of the active intracellular steroid concentration.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 34, "end": 41}, {"text": "steroid", "start": 125, "end": 132}]}}, "schema": []}
{"input": "Plasma membrane Pdr5 transporter was found to be the most effective, followed by Snq2 transporter and vacuolar transporters Ybt1 and Ycf1.", "output": {"entities": {}}, "schema": []}
{"input": "Proteins Aus1 and Dan1 were not found to be involved in steroid import.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 56, "end": 63}]}}, "schema": []}
{"input": "The research of possible targets of steroid hormone action in fungi suggests that steroid hormones inhibit ergosterol biosynthesis in S. cerevisiae and H. werneckii.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 36, "end": 43}, {"text": "steroid", "start": 82, "end": 89}, {"text": "ergosterol", "start": 107, "end": 117}]}}, "schema": []}
{"input": "Results of this inhibition caused changes in the sterol content of the cellular membrane.", "output": {"entities": {"chemical": [{"text": "sterol", "start": 49, "end": 55}]}}, "schema": []}
{"input": "The presence of steroid hormones most probably causes the degradation of the Tat2 permease and impairment of tryptophan import.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 16, "end": 23}, {"text": "tryptophan", "start": 109, "end": 119}]}}, "schema": []}
{"input": "ADX71743, a potent and selective negative allosteric modulator of metabotropic glutamate receptor 7: in vitro and in vivo characterization.", "output": {"entities": {"chemical": [{"text": "ADX71743", "start": 0, "end": 8}, {"text": "glutamate", "start": 79, "end": 88}]}}, "schema": []}
{"input": "Metabotropic glutamate receptor 7 (mGlu (7)) has been suggested to be a promising novel target for treatment of a range of disorders, including anxiety, post-traumatic stress disorder, depression, drug abuse, and schizophrenia.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 13, "end": 22}]}}, "schema": []}
{"input": "Here we characterized a potent and selective mGlu (7) negative allosteric modulator (NAM) (+)-6-(2, 4-dimethylphenyl)-2-ethyl-6, 7-dihydrobenzo [d] oxazol-4 (5H)-one (ADX71743).", "output": {"entities": {"chemical": [{"text": "(+)-6-(2, 4-dimethylphenyl)-2-ethyl-6, 7-dihydrobenzo [d] oxazol-4 (5H)-one", "start": 90, "end": 165}, {"text": "ADX71743", "start": 167, "end": 175}]}}, "schema": []}
{"input": "In vitro, Schild plot analysis and reversibility tests at the target confirmed the NAM properties of the compound and attenuation of L-(+)-2-amino-4-phosphonobutyric acid-induced synaptic depression confirmed activity at the native receptor.", "output": {"entities": {"chemical": [{"text": "L-(+)-2-amino-4-phosphonobutyric acid", "start": 133, "end": 170}]}}, "schema": []}
{"input": "The pharmacokinetic analysis of ADX71743 in mice and rats revealed that it is bioavailable after s. c. administration and is brain penetrant (cerebrospinal fluid concentration/total plasma concentration ratio at C (max) = 5. 3%).", "output": {"entities": {"chemical": [{"text": "ADX71743", "start": 32, "end": 40}]}}, "schema": []}
{"input": "In vivo, ADX71743 (50, 100, 150 mg/kg, s. c.) caused no impairment of locomotor activity in rats and mice or activity on rotarod in mice.", "output": {"entities": {"chemical": [{"text": "ADX71743", "start": 9, "end": 17}]}}, "schema": []}
{"input": "ADX71743 had an anxiolytic-like profile in the marble burying and elevated plus maze tests, dose-dependently reducing the number of buried marbles and increasing open arm exploration, respectively.", "output": {"entities": {"chemical": [{"text": "ADX71743", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Whereas ADX71743 caused a small reduction in amphetamine-induced hyperactivity in mice, it was inactive in the mouse 2, 5-dimethoxy-4-iodoamphetamine-induced head twitch and the rat conditioned avoidance response tests.", "output": {"entities": {"chemical": [{"text": "ADX71743", "start": 8, "end": 16}, {"text": "amphetamine", "start": 45, "end": 56}, {"text": "2, 5-dimethoxy-4-iodoamphetamine", "start": 117, "end": 149}]}}, "schema": []}
{"input": "In addition, the compound was inactive in the mouse forced swim test.", "output": {"entities": {}}, "schema": []}
{"input": "These data suggest that ADX71743 is a suitable compound to help unravel the physiologic role of mGlu (7) and to better understand its implication in central nervous system diseases.", "output": {"entities": {"chemical": [{"text": "ADX71743", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Our in vivo tests using ADX71743, reported here, suggest that pharmacological inhibition of mGlu (7) is a valid approach for developing novel pharmacotherapies to treat anxiety disorders, but may not be suitable for treatment of depression or psychosis.", "output": {"entities": {"chemical": [{"text": "ADX71743", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Synthesis of substituted 6-amino-4-(2, 4-dimethoxyphenyl)-[1, 2] dithiolo [4, 3-b] pyrrol-5-ones and their raising leukocyte count activities.", "output": {"entities": {"chemical": [{"text": "6-amino-4-(2, 4-dimethoxyphenyl)-[1, 2] dithiolo [4, 3-b] pyrrol-5-ones", "start": 25, "end": 96}]}}, "schema": []}
{"input": "The design and synthesis of a series of substituted 6-amino-4-(2, 4-dimethoxyphenyl)-[1, 2] dithiolo [4, 3-b] pyrrol-5-ones are described.", "output": {"entities": {"chemical": [{"text": "6-amino-4-(2, 4-dimethoxyphenyl)-[1, 2] dithiolo [4, 3-b] pyrrol-5-ones", "start": 52, "end": 123}]}}, "schema": []}
{"input": "All the synthesized compounds were evaluated for raising leukocyte count activities in normal mice.", "output": {"entities": {}}, "schema": []}
{"input": "Four compounds (8a, b, d, h) exhibited raising leukocyte count activities close or higher than positive control recombinant human granulocyte colony stimulating factor (rhG-CSF), and some (8e-g, k, p, r) had a moderate effect.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, the most potent compound 8a was evaluated for its antileukopenia activity in cyclophosphamide (CTX) treated mice.", "output": {"entities": {"chemical": [{"text": "cyclophosphamide", "start": 89, "end": 105}]}}, "schema": []}
{"input": "Interestingly, 8a exhibited significant antileukopenia activity as compared to rhG-CSF.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest that this kind of compounds might be utilized for the development of new candidate for treatment of leukocytopenia.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of steroidogenic enzyme expression in aldosterone-producing adenoma: a comparison with various human adrenal tumors.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 55, "end": 66}]}}, "schema": []}
{"input": "We analyzed the expression profiles of several steroidogenic enzymes in normal adrenals, aldosterone-producing adenomas (APA), cortisol-producing adenomas combined with Cushing' s syndrome (CPA) or with subclinical Cushing' s syndrome (SCPA), and nonfunctioning adrenal adenomas (NFA) to clarify the nature and characteristics of steroidogenesis in APA.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 89, "end": 100}, {"text": "cortisol", "start": 127, "end": 135}]}}, "schema": []}
{"input": "Clinical data were collected for all subjects.", "output": {"entities": {}}, "schema": []}
{"input": "In resected adrenal glands (normal adrenals, APA, CPA, SCPA, and NFA), the mRNA expression levels of the CYP17, HSD3B2, CYP11B1, and CYP11B2 genes were studied using real-time quantitative PCR and immunohistochemistry.", "output": {"entities": {}}, "schema": []}
{"input": "The CYP11B2 mRNA level in APA was significantly higher than that in other groups.", "output": {"entities": {}}, "schema": []}
{"input": "The CYP17/HSD3B2 ratio for mRNA in APA was significantly lower than those in the other groups.", "output": {"entities": {}}, "schema": []}
{"input": "Low ratio of CYP17/HSD3B2 with high expression of CYP11B2 seems to explain steroidogenic characteristics of APA.", "output": {"entities": {}}, "schema": []}
{"input": "A theoretical analysis of the effect of the hydrogenation of graphene to graphane on its mechanical properties.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 61, "end": 69}, {"text": "graphane", "start": 73, "end": 81}]}}, "schema": []}
{"input": "We investigated the effect of the hydrogenation of graphene to graphane on its mechanical properties using first-principles calculations based on density-functional theory.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 51, "end": 59}, {"text": "graphane", "start": 63, "end": 71}]}}, "schema": []}
{"input": "The hydrogenation reduces the ultimate strengths in all three tested deformation modes--armchair, zigzag, and biaxial--and the in-plane stiffness by 1/3.", "output": {"entities": {}}, "schema": []}
{"input": "The Poisson ratio was reduced from 0. 178 to 0. 078, a 56% decrease.", "output": {"entities": {}}, "schema": []}
{"input": "However, the ultimate strain in zigzag deformation was increased by 8. 7%.", "output": {"entities": {}}, "schema": []}
{"input": "The shear mode elastic constants are more sensitive than longitudinal ones to hydrogenation.", "output": {"entities": {}}, "schema": []}
{"input": "The fourth and fifth order longitudinal mode elastic constants are inert to the hydrogenation, in contrast to a large decrease of those in second and third order.", "output": {"entities": {}}, "schema": []}
{"input": "The hydrogenation does not change the monotonic decrement of the Poisson ratio with increasing pressure, but the rate is tripled.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that graphene-graphane systems could be used for hydrogen storage with high speed of charge-discharge of hydrogen.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 26, "end": 34}, {"text": "graphane", "start": 35, "end": 43}, {"text": "hydrogen", "start": 70, "end": 78}, {"text": "hydrogen", "start": 126, "end": 134}]}}, "schema": []}
{"input": "(4, 4')-Bipyridine in vacuo and in solvents: a quantum chemical study of a prototypical floppy molecule from a molecular transport perspective.", "output": {"entities": {"chemical": [{"text": "(4, 4')-Bipyridine", "start": 0, "end": 18}]}}, "schema": []}
{"input": "We report results of quantum chemical calculations for the neutral and anionic species of (4, 4')-bipyridine (44BPY), a prototypical molecule with a floppy degree of freedom, placed in vacuo and in solvents.", "output": {"entities": {"chemical": [{"text": "(4, 4')-bipyridine", "start": 90, "end": 108}, {"text": "44BPY", "start": 110, "end": 115}]}}, "schema": []}
{"input": "In addition to equilibrium geometries and vibrational frequencies and spectra, we present adiabatic energy curves for the vibrational modes with significant intramolecular reorganization upon charge transfer.", "output": {"entities": {}}, "schema": []}
{"input": "Special attention is paid to the floppy strongly anharmonic degree of freedom of 44BPY, which is related to the most salient structural feature, namely the twist angle theta between the two pyridine rings.", "output": {"entities": {"chemical": [{"text": "44BPY", "start": 81, "end": 86}, {"text": "pyridine", "start": 190, "end": 198}]}}, "schema": []}
{"input": "The relevance of the present results for molecular transport will be emphasized.", "output": {"entities": {}}, "schema": []}
{"input": "We show that the solvent acts as a selective gate electrode and propose a scissor operator to account for solvent effects on molecular transport.", "output": {"entities": {}}, "schema": []}
{"input": "Our result on the conductance G vs. cos (2) theta is consistent with a significant transmission in perpendicular conformation indicated by previous microscopic analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Detailed mechanism for the orthogonal polarization switching of gold nanorod plasmons.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we describe an electro-optic material capable of orthogonally switching the polarization of the localized surface plasmon resonance scattering of single gold nanorods, independent of their orientation.", "output": {"entities": {}}, "schema": []}
{"input": "Liquid crystal samples are prepared in a sandwich configuration with electrodes arranged so that an applied voltage induces alignment-switching of the liquid crystal molecules covering individual gold nanorods.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the birefringence of the nematic liquid crystal, the reorientation in the nematic director alignment causes a change in the output polarization of the scattered light.", "output": {"entities": {}}, "schema": []}
{"input": "We propose the underlying mechanism to be based on a homogeneous nematic to twisted nematic phase transition and provide support for it via Jones calculus by modelling the effect of ideally aligned homogeneous nematic and twisted nematic phases on polarized light transmitted through the sample.", "output": {"entities": {}}, "schema": []}
{"input": "In the model, we include the effects of sample thickness and surface plasmon resonance wavelength, expressed in terms of the phase retardation, chi, on the observed output polarization.", "output": {"entities": {}}, "schema": []}
{"input": "We find four distinctively different trends for the output polarization as a function of the incident polarization as chi is varied.", "output": {"entities": {}}, "schema": []}
{"input": "Two of these cases provide reproducible orthogonal polarization switching of the surface plasmon resonance while maintaining a high degree of polarization.", "output": {"entities": {}}, "schema": []}
{"input": "These results are verified experimentally with liquid crystal cells of different thicknesses.", "output": {"entities": {}}, "schema": []}
{"input": "The deviation of the experimental samples from ideal behaviour can be explained by the inherent variations in the surface plasmon resonance maximum and local cell thickness.", "output": {"entities": {}}, "schema": []}
{"input": "5-cholesten-3 beta, 25-diol 3-sulfate decreases lipid accumulation in diet-induced nonalcoholic fatty liver disease mouse model.", "output": {"entities": {"chemical": [{"text": "5-cholesten-3 beta, 25-diol 3-sulfate", "start": 0, "end": 37}]}}, "schema": []}
{"input": "Sterol regulatory element-binding protein-1c (SREBP-1c) increases lipogenesis at the transcriptional level, and its expression is upregulated by liver X receptor alpha (LXR alpha).", "output": {"entities": {}}, "schema": []}
{"input": "The LXR alpha/SREBP-1c signaling may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).", "output": {"entities": {}}, "schema": []}
{"input": "We previously reported that a cholesterol metabolite, 5-cholesten-3 beta, 25-diol 3-sulfate (25HC3S), inhibits the LXR alpha signaling and reduces lipogenesis by decreasing SREBP-1c expression in primary hepatocytes.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 30, "end": 41}, {"text": "5-cholesten-3 beta, 25-diol 3-sulfate", "start": 54, "end": 91}, {"text": "25HC3S", "start": 93, "end": 99}]}}, "schema": []}
{"input": "The present study aims to investigate the effects of 25HC3S on lipid homeostasis in diet-induced NAFLD mouse models.", "output": {"entities": {"chemical": [{"text": "25HC3S", "start": 53, "end": 59}]}}, "schema": []}
{"input": "NAFLD was induced by feeding a high-fat diet (HFD) in C57BL/6J mice.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of 25HC3S on lipid homeostasis, inflammatory responses, and insulin sensitivity were evaluated after acute treatments or long-term treatments.", "output": {"entities": {"chemical": [{"text": "25HC3S", "start": 15, "end": 21}]}}, "schema": []}
{"input": "Acute treatments with 25HC3S decreased serum lipid levels, and long-term treatments decreased hepatic lipid accumulation in the NAFLD mice.", "output": {"entities": {"chemical": [{"text": "25HC3S", "start": 22, "end": 28}]}}, "schema": []}
{"input": "Gene expression analysis showed that 25HC3S significantly suppressed the SREBP-1c signaling pathway that was associated with the suppression of the key enzymes involved in lipogenesis: fatty acid synthase, acetyl-CoA carboxylase 1, and glycerol-3-phosphate acyltransferase.", "output": {"entities": {"chemical": [{"text": "25HC3S", "start": 37, "end": 43}, {"text": "fatty acid", "start": 185, "end": 195}, {"text": "acetyl-CoA", "start": 206, "end": 216}, {"text": "glycerol-3-phosphate", "start": 236, "end": 256}]}}, "schema": []}
{"input": "In addition, 25HC3S significantly reduced HFD-induced hepatic inflammation as evidenced by decreasing tumor necrosis factor and interleukin 1 alpha/beta mRNA levels.", "output": {"entities": {"chemical": [{"text": "25HC3S", "start": 13, "end": 19}]}}, "schema": []}
{"input": "A glucose tolerance test and insulin tolerance test showed that 25HC3S administration improved HFD-induced insulin resistance.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 2, "end": 9}, {"text": "25HC3S", "start": 64, "end": 70}]}}, "schema": []}
{"input": "The present results indicate that 25HC3S as a potent endogenous regulator decreases lipogenesis, and oxysterol sulfation can be a key protective regulatory pathway against lipid accumulation and lipid-induced inflammation in vivo.", "output": {"entities": {"chemical": [{"text": "25HC3S", "start": 34, "end": 40}]}}, "schema": []}
{"input": "From the bottom up: dimensional control and characterization in molecular monolayers.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembled monolayers are a unique class of nanostructured materials, with properties determined by their molecular lattice structures, as well as the interfaces with their substrates and environments.", "output": {"entities": {}}, "schema": []}
{"input": "As with other nanostructured materials, defects and dimensionality play important roles in the physical, chemical, and biological properties of the monolayers.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we discuss monolayer structures ranging from surfaces (two-dimensional) down to single molecules (zero-dimensional), with a focus on applications of each type of structure, and on techniques that enable characterization of monolayer physical properties down to the single-molecule scale.", "output": {"entities": {}}, "schema": []}
{"input": "Oxygen tracer diffusion along interfaces of strained Y2O3/YSZ multilayers.", "output": {"entities": {"chemical": [{"text": "Oxygen", "start": 0, "end": 6}, {"text": "Y2O3", "start": 53, "end": 57}, {"text": "YSZ", "start": 58, "end": 61}]}}, "schema": []}
{"input": "Heterophase boundaries can offer fast transport paths in solid electrolyte materials.", "output": {"entities": {}}, "schema": []}
{"input": "In recent studies an enhancement of the ionic conductivity was indeed observed in micro-/nanoscaled Y (2) O (3)-stabilised ZrO (2) (YSZ) composites and hetero multilayers of thin films.", "output": {"entities": {"chemical": [{"text": "Y (2) O (3)", "start": 100, "end": 111}, {"text": "ZrO (2)", "start": 123, "end": 130}, {"text": "YSZ", "start": 132, "end": 135}]}}, "schema": []}
{"input": "As space charge regions can be neglected due to high charger carrier concentrations, we assume that strain and microstructural changes at the heterophase boundaries are responsible for the observed conductivity effects.", "output": {"entities": {}}, "schema": []}
{"input": "In order to obtain independent information on the role of heterophase boundaries for fast transport in strained solid electrolytes, systematic measurements of the (18) O-tracer diffusion coefficient in nanoscaled YSZ/Y (2) O (3) multilayers were performed.", "output": {"entities": {"chemical": [{"text": "(18) O", "start": 163, "end": 169}, {"text": "YSZ", "start": 213, "end": 216}, {"text": "Y (2) O (3)", "start": 217, "end": 228}]}}, "schema": []}
{"input": "Multilayer samples were prepared by Pulsed Laser Deposition (PLD) on (0001) Al (2) O (3) substrates and characterised by X-Ray Diffraction (XRD), Scanning Electron Microscopy (HRSEM) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS).", "output": {"entities": {"chemical": [{"text": "Al (2) O (3)", "start": 76, "end": 88}]}}, "schema": []}
{"input": "To separate interface and bulk transport from the total oxygen diffusivity of the multilayer system, the (average) thickness of the YSZ-layers in the multilayers was varied from 45 nm to 12 nm.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 56, "end": 62}, {"text": "YSZ", "start": 132, "end": 135}]}}, "schema": []}
{"input": "Upon decreasing the thickness of the YSZ layers, respectively increasing the density of parallel interfaces, the total diffusion coefficient of the multilayer system is increased by a factor of 2 compared to bulk YSZ.", "output": {"entities": {"chemical": [{"text": "YSZ", "start": 37, "end": 40}, {"text": "YSZ", "start": 213, "end": 216}]}}, "schema": []}
{"input": "The experimental results agree well with formerly published data for ionic conductivity measurements.", "output": {"entities": {}}, "schema": []}
{"input": "They also support a negligible contribution of partial electronic conductivity in the multilayer.", "output": {"entities": {}}, "schema": []}
{"input": "Oral exposure to industrial effluent with exceptionally high levels of drugs does not indicate acute toxic effects in rats.", "output": {"entities": {}}, "schema": []}
{"input": "The Patancheru area near Hyderabad in India is recognized as a key link in the global supply chain for many bulk drugs.", "output": {"entities": {}}, "schema": []}
{"input": "A central treatment plant receives wastewater from approximately 90 different manufacturers, and the resulting complex effluent has contaminated surface, ground, and drinking water in the region.", "output": {"entities": {}}, "schema": []}
{"input": "Ecotoxicological testing of the effluent has shown adverse effects for several organisms, including aquatic vertebrates, at high dilutions.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, a recent study of microbial communities in river sediment indicated that the contamination of antibiotic substances might contribute to the emergence and spread of antibiotic resistance genes.", "output": {"entities": {}}, "schema": []}
{"input": "In an attempt to start investigating how exposure to effluent-contaminated water may directly affect humans and other terrestrial vertebrates, rats were tube-fed effluent.", "output": {"entities": {}}, "schema": []}
{"input": "Several pharmaceuticals present in the effluent could be detected in rat blood serum at low concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "However, results from exploratory microarray and quantitative polymerase chain reaction assays indicated no marked effects on hepatic gene transcription after 5 d of exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical analysis of blood serum constituents, used as biomarkers for human disease did not reveal any significant changes, nor was there an effect on weight gain.", "output": {"entities": {}}, "schema": []}
{"input": "The authors could not find evidence for any acute toxicity in the rat; however, the authors cannot rule out that was there an effect on weight gain higher doses of effluent or a longer exposure time may still be associated with risks for terrestrial vertebrates.", "output": {"entities": {}}, "schema": []}
{"input": "Iron L-edge X-ray absorption spectroscopy of oxy-picket fence porphyrin: experimental insight into Fe-O2 bonding.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "porphyrin", "start": 62, "end": 71}, {"text": "Fe", "start": 99, "end": 101}, {"text": "O2", "start": 102, "end": 104}]}}, "schema": []}
{"input": "The electronic structure of the Fe-O (2) center in oxy-hemoglobin and oxy-myoglobin is a long-standing issue in the field of bioinorganic chemistry.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 32, "end": 34}, {"text": "O (2)", "start": 35, "end": 40}]}}, "schema": []}
{"input": "Spectroscopic studies have been complicated by the highly delocalized nature of the porphyrin, and calculations require interpretation of multideterminant wave functions for a highly covalent metal site.", "output": {"entities": {"chemical": [{"text": "porphyrin", "start": 84, "end": 93}]}}, "schema": []}
{"input": "Here, iron L-edge X-ray absorption spectroscopy, interpreted using a valence bond configuration interaction multiplet model, is applied to directly probe the electronic structure of the iron in the biomimetic Fe-O (2) heme complex [Fe (pfp) (1-MeIm) O (2)] (pfp (\" picket fence porphyrin \") = meso-tetra (alpha, alpha, alpha, alpha-o-pivalamidophenyl) porphyrin or TpivPP).", "output": {"entities": {"chemical": [{"text": "iron", "start": 6, "end": 10}, {"text": "iron", "start": 186, "end": 190}, {"text": "Fe", "start": 209, "end": 211}, {"text": "O (2) heme", "start": 212, "end": 222}, {"text": "[Fe (pfp) (1-MeIm) O (2)]", "start": 231, "end": 256}, {"text": "pfp", "start": 258, "end": 261}, {"text": "picket fence porphyrin", "start": 265, "end": 287}, {"text": "meso-tetra (alpha, alpha, alpha, alpha-o-pivalamidophenyl) porphyrin", "start": 293, "end": 361}, {"text": "TpivPP", "start": 365, "end": 371}]}}, "schema": []}
{"input": "This method allows separate estimates of sigma-donor, pi-donor, and pi-acceptor interactions through ligand-to-metal charge transfer and metal-to-ligand charge transfer mixing pathways.", "output": {"entities": {}}, "schema": []}
{"input": "The L-edge spectrum of [Fe (pfp) (1-MeIm) O (2)] is further compared to those of [Fe (II) (pfp) (1-MeIm) (2)], [Fe (II) (pfp)], and [Fe (III) (tpp) (ImH) (2)] Cl (tpp = meso-tetraphenylporphyrin) which have Fe (II) S = 0, Fe (II) S = 1, and Fe (III) S = 1/2 ground states, respectively.", "output": {"entities": {"chemical": [{"text": "[Fe (pfp) (1-MeIm) O (2)]", "start": 23, "end": 48}, {"text": "[Fe (II) (pfp) (1-MeIm) (2)]", "start": 81, "end": 109}, {"text": "[Fe (II) (pfp)]", "start": 111, "end": 126}, {"text": "[Fe (III) (tpp) (ImH) (2)] Cl", "start": 132, "end": 161}, {"text": "tpp", "start": 163, "end": 166}, {"text": "meso-tetraphenylporphyrin", "start": 169, "end": 194}, {"text": "Fe (II)", "start": 207, "end": 214}, {"text": "Fe (II)", "start": 222, "end": 229}, {"text": "Fe (III)", "start": 241, "end": 249}]}}, "schema": []}
{"input": "These serve as references for the three possible contributions to the ground state of oxy-pfp.", "output": {"entities": {"chemical": [{"text": "oxy-pfp", "start": 86, "end": 93}]}}, "schema": []}
{"input": "The Fe-O (2) pfp site is experimentally determined to have both significant sigma-donation and a strong pi-interaction of the O (2) with the iron, with the latter having implications with respect to the spin polarization of the ground state.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 4, "end": 6}, {"text": "O (2) pfp", "start": 7, "end": 16}, {"text": "O (2)", "start": 126, "end": 131}, {"text": "iron", "start": 141, "end": 145}]}}, "schema": []}
{"input": "Probing the Bonding and Electronic Structure of Single Atom Dopants in Graphene with Electron Energy Loss Spectroscopy.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 71, "end": 79}]}}, "schema": []}
{"input": "A combination of scanning transmission electron microscopy, electron energy loss spectroscopy, and ab initio calculations reveal striking electronic structure differences between two distinct single substitutional Si defect geometries in graphene.", "output": {"entities": {"chemical": [{"text": "Si", "start": 214, "end": 216}, {"text": "graphene", "start": 238, "end": 246}]}}, "schema": []}
{"input": "Optimised acquisition conditions allow for exceptional signal-to-noise levels in the spectroscopic data.", "output": {"entities": {}}, "schema": []}
{"input": "The near-edge fine structure can be compared with great accuracy to simulations and reveal either an sp (3)-like configuration for a trivalent Si or a more complicated hybridized structure for a tetravalent Si impurity.", "output": {"entities": {"chemical": [{"text": "Si", "start": 143, "end": 145}, {"text": "Si", "start": 207, "end": 209}]}}, "schema": []}
{"input": "Controlling the pulsed-laser-induced size reduction of Au and Ag nanoparticles via changes in the external pressure, laser intensity, and excitation wavelength.", "output": {"entities": {"chemical": [{"text": "Au", "start": 55, "end": 57}, {"text": "Ag", "start": 62, "end": 64}]}}, "schema": []}
{"input": "The laser-induced size reduction of aqueous noble metal nanoparticles has been the subject of intensive research, because of the mechanistic interest in the light-nanoparticle interactions and its potential application to size control.", "output": {"entities": {}}, "schema": []}
{"input": "The photothermal evaporation hypothesis has gained solid support.", "output": {"entities": {}}, "schema": []}
{"input": "However, the polydispersity of the final products is considered as an inherent drawback of the method.", "output": {"entities": {}}, "schema": []}
{"input": "It is likely that the polydispersity arises from the uncontrolled heat dissipation caused by vapor bubble formation in the ambient atmosphere.", "output": {"entities": {}}, "schema": []}
{"input": "To overcome this problem, we applied high pressures of 30-100 MPa.", "output": {"entities": {}}, "schema": []}
{"input": "The particle size was regulated by adjusting three parameters: the pressure, laser intensity, and excitation wavelength.", "output": {"entities": {}}, "schema": []}
{"input": "For example, starting from a colloidal solution of 100 nm diameter gold nanoparticles, highly monodisperse (+/- 3-5%) spheres with various diameters ranging from 90 to 30 nm were fabricated by tuning the laser intensity at 100 MPa, using an excitation wavelength of 532 nm.", "output": {"entities": {}}, "schema": []}
{"input": "Further size reduction of the diameter to 20 nm was achieved by reducing the pressure and switching the excitation wavelength to 355 nm.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that the application of high pressures led to the heat loss-controlled size-reduction of the gold nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "More complicated results were obtained for 100 nm silver nanoparticles, possibly because of the different size-dependent light-absorbing nature of these particles.", "output": {"entities": {"chemical": [{"text": "silver", "start": 50, "end": 56}]}}, "schema": []}
{"input": "Based on our extensive experimental studies, a detailed picture was developed for the nanosecond laser-induced fabrication of gold and silver nanoparticles, leading to unprecedented size control.", "output": {"entities": {"chemical": [{"text": "silver", "start": 135, "end": 141}]}}, "schema": []}
{"input": "Multimode multidrop serial coalescence effects during condensation on hierarchical superhydrophobic surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "The prospect of enhancing the condensation rate by decreasing the maximum drop departure diameter significantly below the capillary length through spontaneous drop motion has generated significant interest in condensation on superhydrophobic surfaces (SHS).", "output": {"entities": {}}, "schema": []}
{"input": "The mobile coalescence leading to spontaneous drop motion was initially reported to occur only on hierarchical SHS, consisting of both nanoscale and microscale topological features.", "output": {"entities": {}}, "schema": []}
{"input": "However, subsequent studies have shown that mobile coalescence also occurs on solely nanostructured SHS.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, recent focus has been on understanding the condensation process on nanostructured surfaces rather than on hierarchical SHS.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we investigate the impact of microscale topography of hierarchical SHS on the droplet coalescence dynamics and wetting states during the condensation process.", "output": {"entities": {}}, "schema": []}
{"input": "We show that isolated mobile and immobile coalescence between two drops, almost exclusively focused on in previous studies, are rare.", "output": {"entities": {}}, "schema": []}
{"input": "We identify several new droplet shedding modes, which are aided by tangential propulsion of mobile drops.", "output": {"entities": {}}, "schema": []}
{"input": "These droplet shedding modes comprise of multiple droplets merging during serial coalescence events, which culminate in formation of a drop that either departs or remains anchored to the surface.", "output": {"entities": {}}, "schema": []}
{"input": "We directly relate postmerging drop adhesion to formation of drops in nanoscale as well as microscale Wenzel and Cassie-Baxter wetting states.", "output": {"entities": {}}, "schema": []}
{"input": "We identify the optimal microscale feature spacing of the hierarchical SHS, which promotes departure of the highest number of microdroplets.", "output": {"entities": {}}, "schema": []}
{"input": "This optimal surface architecture consists of microscale features spaced close enough to enable transition of larger droplets into micro-Cassie state yet, at the same time, provides sufficient spacing in-between the features for occurrence of mobile coalescence.", "output": {"entities": {}}, "schema": []}
{"input": "Novel strategy for preparation of graphene-Pd, Pt composite, and its enhanced electrocatalytic activity for alcohol oxidation.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 34, "end": 42}, {"text": "Pd", "start": 43, "end": 45}, {"text": "Pt", "start": 47, "end": 49}, {"text": "alcohol", "start": 108, "end": 115}]}}, "schema": []}
{"input": "As advanced electrodes for direct alcohol fuel cells, graphene-Pd and graphene-Pt composites with a trace of SnO (2) have been successfully synthesized by a modified electroless plating technique.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 34, "end": 41}, {"text": "graphene", "start": 54, "end": 62}, {"text": "Pd", "start": 63, "end": 65}, {"text": "graphene", "start": 70, "end": 78}, {"text": "Pt", "start": 79, "end": 81}, {"text": "SnO (2)", "start": 109, "end": 116}]}}, "schema": []}
{"input": "The surface of graphene oxide is first sensitized by Sn (2 +) ions, and subsequently, Pd or Pt nanoparticles are deposited on the surface of graphene oxide.", "output": {"entities": {"chemical": [{"text": "graphene oxide", "start": 15, "end": 29}, {"text": "Sn (2 +)", "start": 53, "end": 61}, {"text": "Pd", "start": 86, "end": 88}, {"text": "Pt", "start": 92, "end": 94}, {"text": "graphene oxide", "start": 141, "end": 155}]}}, "schema": []}
{"input": "Finally, graphene oxide was reduced to graphene by further adding NaBH (4).", "output": {"entities": {"chemical": [{"text": "graphene oxide", "start": 9, "end": 23}, {"text": "graphene", "start": 39, "end": 47}, {"text": "NaBH (4)", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Compared to other carbon-(e. g., Vulcan XC-72R) supported Pd and Pt, the resultant graphene-Pd and Pt composites exhibit better electrocatalytic activity and long-term stability toward alcohol electrooxidation.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 18, "end": 24}, {"text": "Vulcan XC-72R", "start": 33, "end": 46}, {"text": "Pd", "start": 58, "end": 60}, {"text": "Pt", "start": 65, "end": 67}, {"text": "graphene", "start": 83, "end": 91}, {"text": "Pd", "start": 92, "end": 94}, {"text": "Pt", "start": 99, "end": 101}, {"text": "alcohol", "start": 185, "end": 192}]}}, "schema": []}
{"input": "Additionally, a trace amount of SnO (2) formed around active catalysts may also be beneficial to the enhancement of electrochemical activity.", "output": {"entities": {"chemical": [{"text": "SnO (2)", "start": 32, "end": 39}]}}, "schema": []}
{"input": "Simple strategy to functionalize polymeric substrates via surface-initiated ATRP for biomedical applications.", "output": {"entities": {}}, "schema": []}
{"input": "The functionalization of polymer surfaces via surface-initiated atom transfer radical polymerization (ATRP) is of crucial importance to prepare various functional materials.", "output": {"entities": {}}, "schema": []}
{"input": "It is generally complicated to conduct ATRP on different organic material surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, a facile photoinduced one-step method was first developed for the covalent immobilization of ATRP initiators on the C-H group-containing substrates such as biaxially oriented polypropylene (BOPP).", "output": {"entities": {"chemical": [{"text": "C-H", "start": 130, "end": 133}, {"text": "polypropylene", "start": 189, "end": 202}]}}, "schema": []}
{"input": "The C-H bonds of precise location of inert polymer surfaces were readily transferred to bromoalkyl initiator, followed by ATRP of 2-(dimethylamino) ethyl methacrylate (DMAEMA) and glycidyl methacrylate (GMA), respectively, to produce the resultant patterned BOPP-g-P (DMAEMA) and BOPP-g-P (GMA) films.", "output": {"entities": {"chemical": [{"text": "C-H", "start": 4, "end": 7}, {"text": "bromoalkyl", "start": 88, "end": 98}, {"text": "2-(dimethylamino) ethyl methacrylate", "start": 130, "end": 166}, {"text": "DMAEMA", "start": 168, "end": 174}, {"text": "glycidyl methacrylate", "start": 180, "end": 201}, {"text": "GMA", "start": 203, "end": 206}, {"text": "P (DMAEMA)", "start": 265, "end": 275}, {"text": "P (GMA)", "start": 287, "end": 294}]}}, "schema": []}
{"input": "The epoxy groups of the P (GMA) microdomains can be aminated for covalently coupling IgG, while the P (DMAEMA) microdomains were used for immobilizing IgG via electronic interactions.", "output": {"entities": {"chemical": [{"text": "epoxy", "start": 4, "end": 9}, {"text": "P (GMA)", "start": 24, "end": 31}, {"text": "P (DMAEMA)", "start": 100, "end": 110}]}}, "schema": []}
{"input": "The resultant IgG-coupled microdomains could interact with the corresponding target proteins, anti-IgG.", "output": {"entities": {}}, "schema": []}
{"input": "Selective inhibitors and tailored activity probes for lipoprotein-associated phospholipase A (2).", "output": {"entities": {}}, "schema": []}
{"input": "Lipoprotein-associated phospholipase A (2) (Lp-PLA (2) or PLA (2) G7) binds to low-density lipoprotein (LDL) particles, where it is thought to hydrolyze oxidatively truncated phospholipids.", "output": {"entities": {}}, "schema": []}
{"input": "Lp-PLA (2) has also been implicated as a pro-tumorigenic enzyme in human prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Several inhibitors of Lp-PLA (2) have been described, including darapladib, which is currently in phase 3 clinical development for the treatment of atherosclerosis.", "output": {"entities": {"chemical": [{"text": "darapladib", "start": 64, "end": 74}]}}, "schema": []}
{"input": "The selectivity that darapladib and other Lp-PLA (2) inhibitors display across the larger serine hydrolase family has not, however, been reported.", "output": {"entities": {"chemical": [{"text": "darapladib", "start": 21, "end": 31}, {"text": "serine", "start": 90, "end": 96}]}}, "schema": []}
{"input": "Here, we describe the use of both general and tailored activity-based probes for profiling Lp-PLA (2) and inhibitors of this enzyme in native biological systems.", "output": {"entities": {}}, "schema": []}
{"input": "We show that both darapladib and a novel class of structurally distinct carbamate inhibitors inactivate Lp-PLA (2) in mouse tissues and human cell lines with high selectivity.", "output": {"entities": {"chemical": [{"text": "darapladib", "start": 18, "end": 28}, {"text": "carbamate", "start": 72, "end": 81}]}}, "schema": []}
{"input": "Our findings thus identify both inhibitors and chemoproteomic probes that are suitable for investigating Lp-PLA (2) function in biological systems.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of benzofuran central cores for the inhibition of leukotriene A (4) hydrolase.", "output": {"entities": {"chemical": [{"text": "benzofuran", "start": 18, "end": 28}, {"text": "leukotriene A (4)", "start": 65, "end": 82}]}}, "schema": []}
{"input": "Leukotrienes (LT' s) are known to play a physiological role in inflammatory immune response.", "output": {"entities": {"chemical": [{"text": "Leukotrienes", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Leukotriene A (4) hydrolase (LTA (4) H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA (4) to LTB (4).", "output": {"entities": {"chemical": [{"text": "Leukotriene A (4)", "start": 0, "end": 17}, {"text": "LTA (4)", "start": 29, "end": 36}, {"text": "LTB (4)", "start": 128, "end": 135}]}}, "schema": []}
{"input": "LTB (4) is a known pro-inflammatory mediator.", "output": {"entities": {"chemical": [{"text": "LTB (4)", "start": 0, "end": 7}]}}, "schema": []}
{"input": "This paper describes the identification and synthesis of substituted benzofurans as LTH (4) H inhibitors.", "output": {"entities": {"chemical": [{"text": "benzofurans", "start": 69, "end": 80}]}}, "schema": []}
{"input": "The benzofuran series demonstrated reduced mouse and human whole blood LTB (4) levels in vitro and led to the identification one analog for advanced profiling.", "output": {"entities": {"chemical": [{"text": "benzofuran", "start": 4, "end": 14}, {"text": "LTB (4)", "start": 71, "end": 78}]}}, "schema": []}
{"input": "Benzofuran 28 showed dose responsive target engagement and provides a useful tool to explore a LTA (4) H inhibitor for the treatment of inflammatory diseases, such as asthma and inflammatory bowel disease (IBD).", "output": {"entities": {"chemical": [{"text": "Benzofuran", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Cell-cycle and DNA damage regulation of the DNA mismatch repair protein Msh2 occurs at the transcriptional and post-transcriptional level.", "output": {"entities": {}}, "schema": []}
{"input": "DNA mismatch repair during replication is a conserved process essential for maintaining genomic stability.", "output": {"entities": {}}, "schema": []}
{"input": "Mismatch repair is also implicated in cell-cycle arrest and apoptosis after DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Because yeast and human mismatch repair systems are well conserved, we have employed the budding yeast Saccharomyces cerevisiae to understand the regulation and function of the mismatch repair gene MSH2.", "output": {"entities": {}}, "schema": []}
{"input": "Using a luciferase-based transcriptional reporter, we defined a 218-bp region upstream of MSH2 that contains cell-cycle and DNA damage responsive elements.", "output": {"entities": {}}, "schema": []}
{"input": "The 5' end of the MSH2 transcript was mapped by primer extension and was found to encode a small upstream open reading frame (uORF).", "output": {"entities": {}}, "schema": []}
{"input": "Mutagenesis of the uORF start codon or of the uORF stop codon, which creates a continuous reading frame with MSH2, increased Msh2 steady-state protein levels ~ 2-fold.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we found that the cell-cycle transcription factors Swi6, Swi4, and Mbp1-along with SCB/MCB cell-cycle binding sites upstream of MSH2-are all required for full basal expression of MSH2.", "output": {"entities": {}}, "schema": []}
{"input": "Mutagenesis of the cell-cycle boxes resulted in a minor reduction in basal Msh2 levels and a 3-fold defect in mismatch repair.", "output": {"entities": {}}, "schema": []}
{"input": "Disruption of the cell-cycle boxes also affected growth in a DNA polymerase-defective strain background where mismatch repair is essential, particularly in the presence of the DNA damaging agent methyl methane sulfonate (MMS).", "output": {"entities": {"chemical": [{"text": "methyl methane sulfonate", "start": 195, "end": 219}, {"text": "MMS", "start": 221, "end": 224}]}}, "schema": []}
{"input": "Promoter replacements conferring constitutive expression of MSH2 revealed that the transcriptional induction in response to MMS is required to maintain induced levels of Msh2.", "output": {"entities": {"chemical": [{"text": "MMS", "start": 124, "end": 127}]}}, "schema": []}
{"input": "Turnover experiments confirmed an elevated rate of degradation in the presence of MMS.", "output": {"entities": {"chemical": [{"text": "MMS", "start": 82, "end": 85}]}}, "schema": []}
{"input": "Taken together, the data show that the DNA damage regulation of Msh2 occurs at the transcriptional and post-transcriptional levels.", "output": {"entities": {}}, "schema": []}
{"input": "The transcriptional and translational control elements identified are conserved in mammalian cells, underscoring the use of yeast as a model system to examine the regulation of MSH2.", "output": {"entities": {}}, "schema": []}
{"input": "3, 4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptors.", "output": {"entities": {"chemical": [{"text": "3, 4-Methylenedioxy-methamphetamine", "start": 0, "end": 35}, {"text": "nicotine", "start": 156, "end": 164}]}}, "schema": []}
{"input": "Nicotine (NIC), the main psychostimulant compound of smoked tobacco, exerts its effects through activation of central nicotinic acetylcholine receptors (nAChR), which become up-regulated after chronic administration.", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}, {"text": "NIC", "start": 10, "end": 13}, {"text": "acetylcholine", "start": 128, "end": 141}]}}, "schema": []}
{"input": "Recent work has demonstrated that the recreational drug 3, 4-methylenedioxy-methamphetamine (MDMA) has affinity for nAChR and also induces up-regulation of nAChR in PC 12 cells.", "output": {"entities": {"chemical": [{"text": "3, 4-methylenedioxy-methamphetamine", "start": 56, "end": 91}, {"text": "MDMA", "start": 93, "end": 97}]}}, "schema": []}
{"input": "Tobacco and MDMA are often consumed together.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 12, "end": 16}]}}, "schema": []}
{"input": "In the present work we studied the in vivo effect of a classic chronic dosing schedule of MDMA in rats, alone or combined with a chronic schedule of NIC, on the density of nAChR and on serotonin reuptake transporters.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 90, "end": 94}, {"text": "NIC", "start": 149, "end": 152}, {"text": "serotonin", "start": 185, "end": 194}]}}, "schema": []}
{"input": "MDMA induced significant decreases in [(3) H] paroxetine binding in the cortex and hippocampus measured 24h after the last dose and these decreases were not modified by the association with NIC.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 0, "end": 4}, {"text": "[(3) H] paroxetine", "start": 38, "end": 56}, {"text": "NIC", "start": 190, "end": 193}]}}, "schema": []}
{"input": "In the prefrontal cortex, NIC and MDMA each induced significant increases in [(3) H] epibatidine binding (29. 5 and 34. 6%, respectively) with respect to saline-treated rats, and these increases were significantly potentiated (up to 72. 1%) when the two drugs were associated.", "output": {"entities": {"chemical": [{"text": "NIC", "start": 26, "end": 29}, {"text": "MDMA", "start": 34, "end": 38}, {"text": "[(3) H] epibatidine", "start": 77, "end": 96}]}}, "schema": []}
{"input": "Also in this area, [(3) H] methyllycaconitine binding was increased a 42. 1% with NIC + MDMA but not when they were given alone.", "output": {"entities": {"chemical": [{"text": "[(3) H] methyllycaconitine", "start": 19, "end": 45}, {"text": "NIC", "start": 82, "end": 85}, {"text": "MDMA", "start": 88, "end": 92}]}}, "schema": []}
{"input": "In the hippocampus, MDMA potentiated the alpha 7 regulatory effects of NIC (raising a 25. 5% increase to 52. 5%) but alone was devoid of effect.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 20, "end": 24}, {"text": "NIC", "start": 71, "end": 74}]}}, "schema": []}
{"input": "MDMA had no effect on heteromeric nAChR in striatum and a coronal section of the midbrain containing superior colliculi, geniculate nuclei, substantia nigra and ventral tegmental area.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Specific immunoprecipitation of solubilised receptors suggests that the up-regulated heteromeric nAChRs contain alpha 4 and beta 2 subunits.", "output": {"entities": {}}, "schema": []}
{"input": "Western blots with specific alpha 4 and alpha 7 antibodies showed no significant differences between the groups, indicating that, as reported for nicotine, up-regulation caused by MDMA is due to post-translational events rather than increased receptor synthesis.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 146, "end": 154}, {"text": "MDMA", "start": 180, "end": 184}]}}, "schema": []}
{"input": "Cloning, expression and analysis of the olfactory glutathione S-transferases in coho salmon.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 50, "end": 63}]}}, "schema": []}
{"input": "The glutathione S-transferases (GSTs) provide cellular protection by detoxifying xenobiotics, maintaining redox status, and modulating secondary messengers, all of which are critical to maintaining olfaction in salmonids.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 4, "end": 17}]}}, "schema": []}
{"input": "Here, we characterized the major coho salmon olfactory GSTs (OlfGSTs), namely omega, pi, and rho subclasses.", "output": {"entities": {}}, "schema": []}
{"input": "OlfGST omega contained an open reading frame of 720bp and encoded a protein of 239 amino acids.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 83, "end": 94}]}}, "schema": []}
{"input": "OlfGST pi and OlfGST rho contained open reading frames of 627 and 681nt, respectively, and encoded proteins of 208 and 226 amino acids.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 123, "end": 134}]}}, "schema": []}
{"input": "Whole-protein mass spectrometry yielded molecular weights of 29, 950, 23, 354, and 26, 655Da, respectively, for the GST omega, pi, and rho subunits.", "output": {"entities": {}}, "schema": []}
{"input": "Homology modeling using four protein-structure prediction algorithms suggest that the active sites in all three OlfGST isoforms resembled counterparts in other species.", "output": {"entities": {}}, "schema": []}
{"input": "The olfactory GSTs conjugated prototypical GST substrates, but only OlfGST rho catalyzed the demethylation of the pesticide methyl parathion.", "output": {"entities": {"chemical": [{"text": "methyl parathion", "start": 124, "end": 140}]}}, "schema": []}
{"input": "OlfGST pi and rho exhibited thiol oxidoreductase activity toward 2-hydroxyethyl disulfide (2-HEDS) and conjugated 4-hydroxynonenal (HNE), a toxic aldehyde with neurodegenerative properties.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 28, "end": 33}, {"text": "2-hydroxyethyl disulfide", "start": 65, "end": 89}, {"text": "2-HEDS", "start": 91, "end": 97}, {"text": "4-hydroxynonenal", "start": 114, "end": 130}, {"text": "HNE", "start": 132, "end": 135}, {"text": "aldehyde", "start": 146, "end": 154}]}}, "schema": []}
{"input": "The kinetic parameters for OlfGST pi conjugation of HNE were K (M) = 0. 16 +/- 0. 06mM and V (max) = 0. 5 +/- 0. 1 mu molmin-(1) mg-(1), whereas OlfGST rho was more efficient at catalyzing HNE conjugation (K (M) = 0. 022 +/- 0. 008 mM and V (max) = 0. 47 +/- 0. 05 mu molmin-(1) mg-(1)).", "output": {"entities": {"chemical": [{"text": "HNE", "start": 52, "end": 55}, {"text": "HNE", "start": 189, "end": 192}]}}, "schema": []}
{"input": "Our findings indicate that the peripheral olfactory system of coho expresses GST isoforms that detoxify certain electrophiles and pesticides and that help maintain redox status and signal transduction.", "output": {"entities": {}}, "schema": []}
{"input": "Salsolinol induced apoptotic changes in neural stem cells: amelioration by neurotrophin support.", "output": {"entities": {"chemical": [{"text": "Salsolinol", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Salsolinol (SAL), a catechol isoquinoline has invited considerable attention due to its structural similarity with dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).", "output": {"entities": {"chemical": [{"text": "Salsolinol", "start": 0, "end": 10}, {"text": "SAL", "start": 12, "end": 15}, {"text": "catechol isoquinoline", "start": 20, "end": 41}, {"text": "1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine", "start": 139, "end": 186}, {"text": "MPTP", "start": 188, "end": 192}]}}, "schema": []}
{"input": "Its high endogenous presence in Parkinsonian brain implicated its possible association with the disease process.", "output": {"entities": {}}, "schema": []}
{"input": "SAL is also present in alcohol beverages and certain food materials and can get access to brain especially in conditions of immature or impaired BBB.", "output": {"entities": {"chemical": [{"text": "SAL", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Besides this, the effect of SAL on neural stem cells (NSCs) which are potential candidates for adult neurogenesis and transplantation mediated rejuvenating attempts for Parkinson' s disease (PD) brain has not been known so far.", "output": {"entities": {"chemical": [{"text": "SAL", "start": 28, "end": 31}]}}, "schema": []}
{"input": "NSCs in both the cases have to overcome suppressive cues of diseased brain for their survival and function.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we explored the toxicity of SAL toward NSCs focusing on apoptosis and status of PI3K survival signaling.", "output": {"entities": {"chemical": [{"text": "SAL", "start": 42, "end": 45}]}}, "schema": []}
{"input": "NSCs cultured from embryonic day 11 rat fetal brain including those differentiated to TH (+ ve) colonies, when challenged with SAL (1-100 mu M), elicited a concentration and time dependent cell death/loss of mitochondrial viability.", "output": {"entities": {"chemical": [{"text": "SAL", "start": 127, "end": 130}]}}, "schema": []}
{"input": "10 mu M SAL on which significant mitochondrial impairment initiated was further used to study mechanism of toxicity.", "output": {"entities": {"chemical": [{"text": "SAL", "start": 8, "end": 11}]}}, "schema": []}
{"input": "Morphological impairment, enhanced TUNEL positivity, cleaved caspase-3 and decreased Bcl-2: Bax suggested apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Sal toxicity coincided with reduced pAkt level and its downstream effectors: pCREB, pGSK-3 beta, Bcl-2 and neurotrophins GDNF, BDNF suggesting repressed PI3K/Akt signaling.", "output": {"entities": {"chemical": [{"text": "Sal", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Multiple neurotrophic factor support in the form of Olfactory Ensheathing Cell' s Conditioned Media (OEC CM) potentially protected NSCs against SAL through activating PI3K/Akt pathway.", "output": {"entities": {"chemical": [{"text": "SAL", "start": 144, "end": 147}]}}, "schema": []}
{"input": "This was confirmed on adding LY294002 the PI3K inhibitor which abolished the protection.", "output": {"entities": {"chemical": [{"text": "LY294002", "start": 29, "end": 37}]}}, "schema": []}
{"input": "We inferred that SAL exerts substantial toxicity toward NSCs.", "output": {"entities": {"chemical": [{"text": "SAL", "start": 17, "end": 20}]}}, "schema": []}
{"input": "These findings will lead to better understanding of endogenous threats that might affect the fate of transplanted NSCs and their probable antidotes.", "output": {"entities": {}}, "schema": []}
{"input": "Assessment of an automated in vitro basal cytotoxicity test system based on metabolically-competent cells.", "output": {"entities": {}}, "schema": []}
{"input": "When in vitro test systems are evaluated for assessment of the toxicity of chemical compounds, particular efforts are made to mimic the in vivo reality as close as possible.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular models with appropriate metabolic competence, i. e. with the potency to biotransform chemical compounds, are considered crucial since some metabolites have a different toxicity than their parent compounds.", "output": {"entities": {}}, "schema": []}
{"input": "In this study a cell based in vitro test system is proposed to investigate the basal cytotoxicity of several reference chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Both metabolic competent HepaRG cells and cells with no or low hepatic enzyme activity (undifferentiated HepaRG and proliferating HepG2) were used.", "output": {"entities": {}}, "schema": []}
{"input": "The classic Neutral Red Uptake (NRU) assay proved to be robust and reliable to be applied as viability assay.", "output": {"entities": {"chemical": [{"text": "Neutral Red", "start": 12, "end": 23}]}}, "schema": []}
{"input": "The test was performed on a robotic platform, which enabled fully automated and simultaneous screening of the compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The outcome of these tests grouped the tested compounds in three categories following their detoxification effect (benzo (a) pyrene, valproic acid), their bio-activation effect (aflatoxin B1) and their specific effect on inhibition of cell proliferation (cycloheximide, sodium lauryl sulphate, atropine sulphate monohydrate, acetylsalicylic acid).", "output": {"entities": {"chemical": [{"text": "benzo (a) pyrene", "start": 115, "end": 131}, {"text": "valproic acid", "start": 133, "end": 146}, {"text": "aflatoxin B1", "start": 178, "end": 190}, {"text": "cycloheximide", "start": 255, "end": 268}, {"text": "sodium lauryl sulphate", "start": 270, "end": 292}, {"text": "atropine sulphate monohydrate", "start": 294, "end": 323}, {"text": "acetylsalicylic acid", "start": 325, "end": 345}]}}, "schema": []}
{"input": "Data management in large-scale collaborative toxicity studies: How to file experimental data for automated statistical analysis.", "output": {"entities": {}}, "schema": []}
{"input": "High-throughput screening approaches are carried out for the toxicity assessment of a large number of chemical compounds.", "output": {"entities": {}}, "schema": []}
{"input": "In such large-scale in vitro toxicity studies several hundred or thousand concentration-response experiments are conducted.", "output": {"entities": {}}, "schema": []}
{"input": "The automated evaluation of concentration-response data using statistical analysis scripts saves time and yields more consistent results in comparison to data analysis performed by the use of menu-driven statistical software.", "output": {"entities": {}}, "schema": []}
{"input": "Automated statistical analysis requires that concentration-response data are available in a standardised data format across all compounds.", "output": {"entities": {}}, "schema": []}
{"input": "To obtain consistent data formats, a standardised data management workflow must be established, including guidelines for data storage, data handling and data extraction.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper two procedures for data management within large-scale toxicological projects are proposed.", "output": {"entities": {}}, "schema": []}
{"input": "Both procedures are based on Microsoft Excel files as the researcher' s primary data format and use a computer programme to automate the handling of data files.", "output": {"entities": {}}, "schema": []}
{"input": "The first procedure assumes that data collection has not yet started whereas the second procedure can be used when data files already exist.", "output": {"entities": {}}, "schema": []}
{"input": "Successful implementation of the two approaches into the European project ACuteTox is illustrated.", "output": {"entities": {}}, "schema": []}
{"input": "Thirteen week rodent feeding study with grain from molecular stacked trait lepidopteran and coleopteran protected (DP-O O 4114-3) maize.", "output": {"entities": {}}, "schema": []}
{"input": "The results from a subchronic feeding study conducted in Sprague-Dawley rats fed with diets containing grain from 4114 (OECD unique identifier: DP-O O 4114-3) maize that was untreated (4114) or sprayed in field with glufosinate ammonium (4114GLU) in a design similar to previous studies are reported.", "output": {"entities": {"chemical": [{"text": "glufosinate ammonium", "start": 216, "end": 236}]}}, "schema": []}
{"input": "The test material, 4114 maize, is a hybrid maize produced by transformation with a DNA construct encoding 4 different transgenic proteins for resistance to lepidopteran pests, coleopteran pests, and tolerance to the herbicidal active ingredient glufosinate ammonium.", "output": {"entities": {"chemical": [{"text": "glufosinate ammonium", "start": 245, "end": 265}]}}, "schema": []}
{"input": "There were a total of 144 rats divided into 12 groups of 12 rats/sex/group.", "output": {"entities": {}}, "schema": []}
{"input": "All experimental diets were formulated by Purina Mills, LLC (St. Louis, MO) in accordance with the standards of Purina Mills Labdiet (R) Certified Rodent LabDiet (R) 5002.", "output": {"entities": {}}, "schema": []}
{"input": "The incorporation rate of maize grain in all diets was 32% (wt/wt).", "output": {"entities": {}}, "schema": []}
{"input": "No biologically significant, treatment related differences in body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis, or organ weight) were observed in rats consuming the diets containing 4114 maize grain compared with rats fed conventional maize diets.", "output": {"entities": {}}, "schema": []}
{"input": "A number of histologic observations were noted in this study but were background lesions and representative of what would be expected for rats of this age and strain.", "output": {"entities": {}}, "schema": []}
{"input": "An independent panel of experts determined certain observations to be spontaneous and not related to the test diet.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, these results support the conclusion that 4114 maize grain is as safe and nutritious as conventional maize grain.", "output": {"entities": {}}, "schema": []}
{"input": "Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 10, "end": 20}]}}, "schema": []}
{"input": "Breast cancer constitutes a major health problem for women worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "However, its incidence varies between populations and geographical locations.", "output": {"entities": {}}, "schema": []}
{"input": "These variations could be diet-related, since there are several carcinogenic compounds in the modern diet, while natural products contain various anti-cancer elements.", "output": {"entities": {}}, "schema": []}
{"input": "Several lines of evidence indicate that, in addition to their clear preventive effect, these compounds could also be used as therapeutic agents.", "output": {"entities": {}}, "schema": []}
{"input": "In the present report we have shown that oleuropein, a pharmacologically safe natural product of olive leaf, has potent anti-breast cancer properties.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 41, "end": 51}]}}, "schema": []}
{"input": "Indeed, oleuropein exhibits specific cytotoxicity against breast cancer cells, with higher effect on the basal-like MDA-MB-231 cells than on the luminal MCF-7 cells.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 8, "end": 18}]}}, "schema": []}
{"input": "This effect is mediated through the induction of apoptosis via the mitochondrial pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, oleuropein inhibits cell proliferation by delaying the cell cycle at S phase and up-regulated the cyclin-dependent inhibitor p21.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 10, "end": 20}]}}, "schema": []}
{"input": "Furthermore, oleuropein inhibited the anti-apoptosis and pro-proliferation protein NF-kappa B and its main oncogenic target cyclin D1.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 13, "end": 23}]}}, "schema": []}
{"input": "This inhibition could explain the great effect of oleuropein on cell proliferation and cell death of breast cancer cells.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 50, "end": 60}]}}, "schema": []}
{"input": "Therefore, oleuropein warrants further investigations to prove its utility in preventing/treating breast cancer, especially the less-responsive basal-like type.", "output": {"entities": {"chemical": [{"text": "oleuropein", "start": 11, "end": 21}]}}, "schema": []}
{"input": "Monotropein isolated from the roots of Morinda officinalis ameliorates proinflammatory mediators in RAW 264. 7 macrophages and dextran sulfate sodium (DSS)-induced colitis via NF-kappa B inactivation.", "output": {"entities": {"chemical": [{"text": "Monotropein", "start": 0, "end": 11}, {"text": "sodium", "start": 143, "end": 149}]}}, "schema": []}
{"input": "We previously demonstrated that monotropein isolated from the roots of Morinda officinalis (Rubiaceae) has anti-inflammatory effects in vivo.", "output": {"entities": {"chemical": [{"text": "monotropein", "start": 32, "end": 43}]}}, "schema": []}
{"input": "In the present study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of monotropein in lipopolysaccharide (LPS)-induced RAW 264. 7 macrophages and dextran sulfate sodium (DSS)-induced colitis mouse model.", "output": {"entities": {"chemical": [{"text": "monotropein", "start": 107, "end": 118}, {"text": "sodium", "start": 198, "end": 204}]}}, "schema": []}
{"input": "Monotropein was found to inhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) mRNA in LPS-induced RAW 264. 7 macrophages.", "output": {"entities": {"chemical": [{"text": "Monotropein", "start": 0, "end": 11}, {"text": "nitric oxide", "start": 62, "end": 74}]}}, "schema": []}
{"input": "Treatment with monotropein decreased the DNA binding activity of nuclear factor-kappa B (NF-kappa B).", "output": {"entities": {"chemical": [{"text": "monotropein", "start": 15, "end": 26}]}}, "schema": []}
{"input": "Consistent with these findings, monotropein also suppressed phosphorylation and degradation of inhibitory kappa B-alpha (I kappa B-alpha), and consequently the translocations of NF-kappa B.", "output": {"entities": {"chemical": [{"text": "monotropein", "start": 32, "end": 43}]}}, "schema": []}
{"input": "In the DSS-induced colitis model, monotropein reduced disease activity index (DAI), myeloperoxidase (MPO) activity, and inflammation-related protein expressions by suppressing NF-kappa B activation in colon mucosa.", "output": {"entities": {"chemical": [{"text": "monotropein", "start": 34, "end": 45}]}}, "schema": []}
{"input": "Taken together, these findings suggest that the anti-inflammatory effects of monotropein are mainly related to the inhibition of the expressions of inflammatory mediators via NF-kappa B inactivation, and support its possible therapeutic role in colitis.", "output": {"entities": {"chemical": [{"text": "monotropein", "start": 77, "end": 88}]}}, "schema": []}
{"input": "Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "gentamicin", "start": 113, "end": 123}]}}, "schema": []}
{"input": "Drug nephrotoxicity is a serious health and economic problem worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Rats can be acutely sensitized to acute kidney injury (AKI) by subnephrotoxic treatments with potentially nephrotoxic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Acquired sensitization to AKI poses a silent risk impossible to diagnose pre-emptively with the technology available at the clinical level.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we hypothesized whether a chronic, subnephrotoxic insult to the kidneys might result in chronically acquired sensitization to AKI, and whether chronic sensitization might be detected through specific urinary markers.", "output": {"entities": {}}, "schema": []}
{"input": "To this end, rats were treated with a subtoxic dosage of the experimental nephrotoxin uranyl nitrate (UN) in the drinking water for 21 weeks, or plain water (as control), and then with low-dose gentamicin for 7 days.", "output": {"entities": {"chemical": [{"text": "nitrate", "start": 93, "end": 100}, {"text": "gentamicin", "start": 194, "end": 204}]}}, "schema": []}
{"input": "Renal function and renal tissue damage were evaluated through the experiment.", "output": {"entities": {}}, "schema": []}
{"input": "The mild renal damage caused by gentamicin was markedly magnified in rats having received UN chronically, which was evident both at the functional and histological level.", "output": {"entities": {"chemical": [{"text": "gentamicin", "start": 32, "end": 42}]}}, "schema": []}
{"input": "Four proteins, namely albumin, hemopexin, transferrin and vitamin D binding protein were increased in the urine in temporal association with the appearance of chronic predisposition.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 58, "end": 67}]}}, "schema": []}
{"input": "Although further studies are necessary, our results suggest that these proteins might be potentially used as markers of hidden, chronic predisposition to gentamicin nephrotoxicity, in order to appropriately and pre-emptively stratify and handle individuals according to their specific risk in the long term, and to conveniently optimize their life conditions or additional clinical procedures or treatments that might trigger the disease.", "output": {"entities": {"chemical": [{"text": "gentamicin", "start": 154, "end": 164}]}}, "schema": []}
{"input": "This might reduce AKI incidence and severity and the associated costs.", "output": {"entities": {}}, "schema": []}
{"input": "Chemokine expression is upregulated in chondrocytes in diabetic fracture healing.", "output": {"entities": {}}, "schema": []}
{"input": "Chemokines are thought to play an important role in several aspects of bone metabolism including the recruitment of leukocytes and the formation of osteoclasts.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the impact of diabetes on chemokine expression in normal and diabetic fracture healing.", "output": {"entities": {}}, "schema": []}
{"input": "Fracture of the femur was performed in streptozotocin-induced diabetic and matched normoglycemic control mice.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 39, "end": 53}]}}, "schema": []}
{"input": "Microarray analysis was carried out and chemokine mRNA levels in vivo were assessed.", "output": {"entities": {}}, "schema": []}
{"input": "CCL4 were examined in fracture calluses by immunohistochemistry and the role of TNF in diabetes-enhanced expression was investigated by treatment of animals with the TNF-specific inhibitor, pegsunercept.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro studies were conducted with ATDC5 chondrocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetes significantly upregulated mRNA levels of several chemokines in vivo including CCL4, CCL8, CCL6, CCL11, CCL20, CCL24, CXCL2, CXCL5 and chemokine receptors CCR5 and CXCR4.", "output": {"entities": {}}, "schema": []}
{"input": "Chondrocytes were identified as a significant source of CCL4 and its expression in diabetic fractures was dependent on TNF (P < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "TNF-alpha significantly increased mRNA levels of several chemokines in vitro which were knocked down with FOXO1 siRNA (P < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "CCL4 expression at the mRNA and proteins levels was induced by FOXO1 over-expression and reduced by FOXO1 knockdown.", "output": {"entities": {}}, "schema": []}
{"input": "The current studies point to the importance of TNF-alpha as a mechanism for diabetes enhanced chemokine expression by chondrocytes, which may contribute to the accelerated loss of cartilage observed in diabetic fracture healing.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, in vitro results point to FOXO1 as a potentially important transcription factor in mediating this effect.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, crystal structure and antidiabetic activity of substituted (E)-3-(Benzo [d] thiazol-2-ylamino) phenylprop-2-en-1-one.", "output": {"entities": {"chemical": [{"text": "(E)-3-(Benzo [d] thiazol-2-ylamino) phenylprop-2-en-1-one", "start": 70, "end": 127}]}}, "schema": []}
{"input": "A novel series of substituted (E)-3-(Benzo [d] thiazol-2-ylamino) phenylprop-2-en-1-onewere synthesized starting from 2-aminobenzothiazole and 1-aryl-3, 3-bis-(methylsulfanyl)-2-propen-1-onesin the presence of a catalytic amount of sodium hydride in THF.", "output": {"entities": {"chemical": [{"text": "(E)-3-(Benzo [d] thiazol-2-ylamino) phenylprop-2-en-1-onewere", "start": 30, "end": 91}, {"text": "2-aminobenzothiazole", "start": 118, "end": 138}, {"text": "1-aryl-3, 3-bis-(methylsulfanyl)-2-propen-1-onesin", "start": 143, "end": 193}, {"text": "sodium hydride", "start": 232, "end": 246}, {"text": "THF", "start": 250, "end": 253}]}}, "schema": []}
{"input": "The synthesised compounds' structures were confirmed by IR, Mass spectrometry, (1) H NMR, (13) C NMR and HRMS spectral data.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 79, "end": 84}, {"text": "(13) C", "start": 90, "end": 96}]}}, "schema": []}
{"input": "These compounds were evaluated for their antidiabetic activity, and most of the derivatives of (E)-3-(Benzo [d] thiazol-2-ylamino) phenylprop-2-en-1-one displayed significant antidiabetic activity.", "output": {"entities": {"chemical": [{"text": "(E)-3-(Benzo [d] thiazol-2-ylamino) phenylprop-2-en-1-one", "start": 95, "end": 152}]}}, "schema": []}
{"input": "Water soluble polymer films for intravascular drug delivery of antithrombotic biomolecules.", "output": {"entities": {}}, "schema": []}
{"input": "Over the past 10years, the number of percutaneous coronary intervention (PCI) procedures performed in the United States has increased by 33%; however, restenosis, which inhibits complete functional recovery of the vessel wall, remains a complication of this procedure.", "output": {"entities": {}}, "schema": []}
{"input": "To traverse the complications associated with PCI, the investigation of therapeutic delivery has become an integral topic in modern research.", "output": {"entities": {}}, "schema": []}
{"input": "One such therapeutic, a mimic of the proteoglycan decorin, termed DS-SILY, can mask exposed collagen and thereby effectively decrease platelet activation, has recently been developed by our lab.", "output": {"entities": {}}, "schema": []}
{"input": "Drawing inspiration from coating technologies developed by the pharmaceutical industry, a fast-dissolving polymer film has been developed to deliver active therapeutic agents from a balloon catheter during PCI.", "output": {"entities": {}}, "schema": []}
{"input": "This research investigates the release of DS-SILY from fast-dissolving polymer films composed of poly (vinyl alcohol) (PVA) and poly (ethylene glycol) (PEG).", "output": {"entities": {"chemical": [{"text": "poly (vinyl alcohol)", "start": 97, "end": 117}, {"text": "PVA", "start": 119, "end": 122}, {"text": "poly (ethylene glycol)", "start": 128, "end": 150}, {"text": "PEG", "start": 152, "end": 155}]}}, "schema": []}
{"input": "Thin, uniform polymer films were produced via spin coating technique.", "output": {"entities": {}}, "schema": []}
{"input": "The dissolution speed of the polymer films was found to be dependent on the concentration of polymer solution, where at least 65% of the films were shown to dissolve into nanometer sized polymer fragments within 2min.", "output": {"entities": {}}, "schema": []}
{"input": "DS-SILY, up to 6. 26 mu g/cm (2), was loaded into the films and functional release of the mimic was demonstrated by its successful binding to collagen upon release.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, DS-SILY released from films resulted in increased platelet inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that use of fast-dissolving polymer films allow for the successful release of biomolecules and further investigation of their use for localized drug delivery during PCI procedures is warranted.", "output": {"entities": {}}, "schema": []}
{"input": "Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems.", "output": {"entities": {}}, "schema": []}
{"input": "TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days.", "output": {"entities": {}}, "schema": []}
{"input": "The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres.", "output": {"entities": {}}, "schema": []}
{"input": "Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model.", "output": {"entities": {}}, "schema": []}
{"input": "This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and evaluation of a backbone biodegradable multiblock HPMA copolymer nanocarrier for the systemic delivery of paclitaxel.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 64, "end": 68}, {"text": "paclitaxel", "start": 120, "end": 130}]}}, "schema": []}
{"input": "The performance and safety of current antineoplastic agents, particularly water-insoluble drugs, are still far from satisfactory.", "output": {"entities": {}}, "schema": []}
{"input": "For example, the currently widely used Cremophor EL (R)-based paclitaxel (PTX) formulation exhibits pharmacokinetic concerns and severe side effects.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 62, "end": 72}, {"text": "PTX", "start": 74, "end": 77}]}}, "schema": []}
{"input": "Thus, the concept of a biodegradable polymeric drug-delivery system, which can significantly improve therapeutic efficacy and reduce side effects is advocated.", "output": {"entities": {}}, "schema": []}
{"input": "The present work aims to develop a new-generation of long-circulating, biodegradable carriers for effective delivery of PTX.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 120, "end": 123}]}}, "schema": []}
{"input": "First, a multiblock backbone biodegradable N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-PTX conjugate (mP-PTX) with molecular weight (Mw) of 335 kDa was synthesized by RAFT (reversible addition-fragmentation chain transfer) copolymerization, followed by chain extension.", "output": {"entities": {"chemical": [{"text": "N-(2-hydroxypropyl) methacrylamide", "start": 43, "end": 77}, {"text": "HPMA", "start": 79, "end": 83}, {"text": "PTX", "start": 95, "end": 98}, {"text": "PTX", "start": 113, "end": 116}]}}, "schema": []}
{"input": "In vitro studies on human ovarian carcinoma A2780 cells were carried out to investigate the cytotoxicity of free PTX, HPMA copolymer-PTX conjugate with Mw of 48 kDa (P-PTX), and mP-PTX.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 113, "end": 116}, {"text": "HPMA", "start": 118, "end": 122}, {"text": "PTX", "start": 133, "end": 136}, {"text": "PTX", "start": 168, "end": 171}, {"text": "PTX", "start": 181, "end": 184}]}}, "schema": []}
{"input": "The experiments demonstrated that mP-PTX has a similar cytotoxic effect against A2780 cells as free PTX and P-PTX.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 37, "end": 40}, {"text": "PTX", "start": 100, "end": 103}, {"text": "PTX", "start": 110, "end": 113}]}}, "schema": []}
{"input": "To further compare the behavior of this new biodegradable conjugate (mP-PTX) with free PTX and P-PTX in vivo evaluation was performed using female nu/nu mice bearing orthotopic A2780 ovarian tumors.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 72, "end": 75}, {"text": "PTX", "start": 87, "end": 90}, {"text": "PTX", "start": 97, "end": 100}]}}, "schema": []}
{"input": "Pharmacokinetics study showed that high Mw mP-PTX was cleared more slowly from the blood than commercial PTX formulation and low Mw P-PTX.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 46, "end": 49}, {"text": "PTX", "start": 105, "end": 108}, {"text": "PTX", "start": 134, "end": 137}]}}, "schema": []}
{"input": "SPECT/CT imaging and biodistribution studies demonstrated biodegradability as well as elimination of mP-PTX from the body.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 104, "end": 107}]}}, "schema": []}
{"input": "The tumors in the mP-PTX treated group grew more slowly than those treated with saline, free PTX, and P-PTX (single dose at 20 mg PTX/kg equivalent).", "output": {"entities": {"chemical": [{"text": "PTX", "start": 21, "end": 24}, {"text": "PTX", "start": 93, "end": 96}, {"text": "PTX", "start": 104, "end": 107}, {"text": "PTX", "start": 130, "end": 133}]}}, "schema": []}
{"input": "Moreover, mice treated with mP-PTX had no obvious ascites and body-weight loss.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 31, "end": 34}]}}, "schema": []}
{"input": "Histological analysis indicated that mP-PTX had no toxicity in liver and spleen, but induced massive cell death in the tumor.", "output": {"entities": {"chemical": [{"text": "PTX", "start": 40, "end": 43}]}}, "schema": []}
{"input": "In summary, this biodegradable drug delivery system has a great potential to improve performance and safety of current antineoplastic agents.", "output": {"entities": {}}, "schema": []}
{"input": "C (22)-steroidal lactone glycosides from stems and leaves of Paris polyphylla var. yunnanensis.", "output": {"entities": {"chemical": [{"text": "C (22)-steroidal lactone glycosides", "start": 0, "end": 35}]}}, "schema": []}
{"input": "Further phytochemical investigation on the stems and leaves of Paris polyphylla var. yunnanensis has led to the isolation of three C (22)-steroidal lactone glycosides.", "output": {"entities": {"chemical": [{"text": "C (22)-steroidal lactone glycosides", "start": 131, "end": 166}]}}, "schema": []}
{"input": "Two of these are new compounds, designated as chonglouoside SL-7 (1) and chonglouoside SL-8 (2).", "output": {"entities": {"chemical": [{"text": "chonglouoside SL-7", "start": 46, "end": 64}, {"text": "chonglouoside SL-8", "start": 73, "end": 91}]}}, "schema": []}
{"input": "Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as comparison with the reported spectroscopic data.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first report of C (22)-steroidal lactone glycosides isolated from the Paris genus.", "output": {"entities": {"chemical": [{"text": "C (22)-steroidal lactone glycosides", "start": 28, "end": 63}]}}, "schema": []}
{"input": "Compounds 1 and 3 showed moderate antimicrobic activity against Propionibacterium acnes with MIC values of 31. 3 and 3. 9 mu g/mL, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Caffeine-induced inhibition of the activity of glutamate transporter type 3 expressed in Xenopus oocytes.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 0, "end": 8}, {"text": "glutamate", "start": 47, "end": 56}]}}, "schema": []}
{"input": "Caffeine has been known to trigger seizures, however, the precise mechanism about the proconvulsive effect of caffeine remains unclear.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 0, "end": 8}, {"text": "caffeine", "start": 110, "end": 118}]}}, "schema": []}
{"input": "Glutamate transporters play an important role to maintain the homeostasis of glutamate concentration in the brain tissue.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 0, "end": 9}, {"text": "glutamate", "start": 77, "end": 86}]}}, "schema": []}
{"input": "Especially, dysfunction of excitatory amino acid transporter type 3 (EAAT3) can lead to seizures.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 38, "end": 48}]}}, "schema": []}
{"input": "We investigated the effects of caffeine on the activity of EAAT3 and the involvement of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K).", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 31, "end": 39}]}}, "schema": []}
{"input": "Rat EAAT3 was expressed in Xenopus oocytes by injecting EAAT3 mRNA.", "output": {"entities": {}}, "schema": []}
{"input": "l-Glutamate (30 mu M)-induced inward currents were recorded via the two-electrode voltage clamp method.", "output": {"entities": {"chemical": [{"text": "l-Glutamate", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Caffeine decreased EAAT3 activity in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Caffeine (30 mu M for 3min) significantly reduced V (max), but did not alter K (m) value of EAAT3 for glutamate.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 0, "end": 8}, {"text": "glutamate", "start": 102, "end": 111}]}}, "schema": []}
{"input": "When preincubated oocytes with phorbol-12-myristate-13-acetate (PMA, a PKC activator) were exposed to caffeine, PMA-induced increase in EAAT3 activity was abolished.", "output": {"entities": {"chemical": [{"text": "phorbol-12-myristate-13-acetate", "start": 31, "end": 62}, {"text": "PMA", "start": 64, "end": 67}, {"text": "caffeine", "start": 102, "end": 110}, {"text": "PMA", "start": 112, "end": 115}]}}, "schema": []}
{"input": "Two PKC inhibitors (chelerythrine and staurosporine) significantly reduced basal EAAT3 activity.", "output": {"entities": {"chemical": [{"text": "chelerythrine", "start": 20, "end": 33}, {"text": "staurosporine", "start": 38, "end": 51}]}}, "schema": []}
{"input": "Whereas, there were no significant differences among the PKC inhibitors, caffeine, and PKC inhibitors + caffeine groups.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 73, "end": 81}, {"text": "caffeine", "start": 104, "end": 112}]}}, "schema": []}
{"input": "In similarly fashion, wortmannin (a PI3K inhibitor) significantly decreased EAAT3 activity, however no statistical differences were observed among the wortmannin, caffeine, and wortmannin + caffeine groups.", "output": {"entities": {"chemical": [{"text": "wortmannin", "start": 22, "end": 32}, {"text": "wortmannin", "start": 151, "end": 161}, {"text": "caffeine", "start": 163, "end": 171}, {"text": "wortmannin", "start": 177, "end": 187}, {"text": "caffeine", "start": 190, "end": 198}]}}, "schema": []}
{"input": "Our results demonstrate that caffeine attenuates EAAT3 activity and this reducing effect of caffeine seems to be mediated by PKC and PI3K.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 29, "end": 37}, {"text": "caffeine", "start": 92, "end": 100}]}}, "schema": []}
{"input": "The electroreduction of benzoic acid: voltammetric observation of adsorbed hydrogen at a platinum microelectrode in room temperature ionic liquids.", "output": {"entities": {"chemical": [{"text": "benzoic acid", "start": 24, "end": 36}, {"text": "hydrogen", "start": 75, "end": 83}, {"text": "platinum", "start": 89, "end": 97}]}}, "schema": []}
{"input": "The electrochemical reduction of benzoic acid in the presence and absence of hydrogen (H (2)) has been investigated using a 10 mu m diameter platinum microelectrode in four different room temperature ionic liquids (RTILs), namely [C (4) mim] [NTf (2)], [C (4) mpyrr] [NTf (2)], [C (4) mim] [OTf] and [C (4) mim] [BF (4)], versus Ag/Ag (+).", "output": {"entities": {"chemical": [{"text": "benzoic acid", "start": 33, "end": 45}, {"text": "hydrogen", "start": 77, "end": 85}, {"text": "H (2)", "start": 87, "end": 92}, {"text": "platinum", "start": 141, "end": 149}, {"text": "[C (4) mim] [NTf (2)]", "start": 230, "end": 251}, {"text": "[C (4) mpyrr] [NTf (2)]", "start": 253, "end": 276}, {"text": "[C (4) mim] [OTf]", "start": 278, "end": 295}, {"text": "[C (4) mim] [BF (4)]", "start": 300, "end": 320}, {"text": "Ag", "start": 329, "end": 331}, {"text": "Ag (+)", "start": 332, "end": 338}]}}, "schema": []}
{"input": "In all cases, reductive voltammetry is observed, and is suggested to occur via a CE mechanism in which dissociation of benzoic acid is followed by electron transfer to H (+) ultimately forming adsorbed hydrogen.", "output": {"entities": {"chemical": [{"text": "benzoic acid", "start": 119, "end": 131}, {"text": "H (+)", "start": 168, "end": 173}, {"text": "hydrogen", "start": 202, "end": 210}]}}, "schema": []}
{"input": "Furthermore, the adsorbed H atoms, formed from the reduction of benzoic acid, could be used to achieve the rapid hydrogenolysis of the organic compound (bis (benzyloxycarbonyl)-l-lysine) on the timescale of the voltammetric technique under moderate conditions (25 degrees C).", "output": {"entities": {"chemical": [{"text": "H", "start": 26, "end": 27}, {"text": "benzoic acid", "start": 64, "end": 76}, {"text": "bis (benzyloxycarbonyl)-l-lysine", "start": 153, "end": 185}]}}, "schema": []}
{"input": "Rational design of the survivin/CDK4 complex by combining protein-protein docking and molecular dynamics simulations.", "output": {"entities": {}}, "schema": []}
{"input": "Survivin, the smallest inhibitor of apoptosis protein (IAP), is a valid target for cancer research.", "output": {"entities": {}}, "schema": []}
{"input": "It mediates both the apoptosis pathway and the cell cycle and has been proposed to form a complex with the cyclin-dependent kinase protein CDK4.", "output": {"entities": {}}, "schema": []}
{"input": "The resulting complex transports CDK4 from the cytosol to the nucleus, where CDK4 participates in cell division.", "output": {"entities": {}}, "schema": []}
{"input": "Survivin has been recognized as a node protein that interacts with several partners; disruption of the formed complexes can lead to new anticancer compounds.", "output": {"entities": {}}, "schema": []}
{"input": "We propose a rational model of the survivin/CDK4 complex that fulfills the experimental evidence and that can be used for structure-based design of inhibitors modifying its interface recognition.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, the suggested complex involves the alpha helical domain of survivin and resembles the mode of binding of survivin in the survivin/borealin X-ray structure.", "output": {"entities": {}}, "schema": []}
{"input": "The proposed model has been obtained by combining protein-protein docking, fractal-based shape complementarity, electrostatics studies and extensive molecular dynamics simulations.", "output": {"entities": {}}, "schema": []}
{"input": "Probing the structural, electronic and magnetic properties of multicenter Fe 2 S 2 0/-, Fe 3 S 4 0/-and Fe 4 S 4 0/-clusters.", "output": {"entities": {"chemical": [{"text": "Fe 2 S 2", "start": 74, "end": 82}, {"text": "Fe 3 S 4", "start": 88, "end": 96}, {"text": "Fe 4 S 4", "start": 104, "end": 112}]}}, "schema": []}
{"input": "The structural, electronic and magnetic properties of neutral and anion Fe2S2, Fe3S4 and Fe4S4 have been investigated with the aid of previous photoelectron spectroscopy and density functional theory calculations.", "output": {"entities": {"chemical": [{"text": "Fe2S2", "start": 72, "end": 77}, {"text": "Fe3S4", "start": 79, "end": 84}, {"text": "Fe4S4", "start": 89, "end": 94}]}}, "schema": []}
{"input": "Theoretical electron detachment energies (both vertical and adiabatic) of anion clusters for the lowest energy structure were computed and compared with the experimental results to verify the ground states.", "output": {"entities": {}}, "schema": []}
{"input": "The optimized structures show that the ground state structures of Fe2S2 (0/-), Fe3S4 (0/-) and Fe4S4 (0/-) favor high spin state and are similar to their structures in proteins.", "output": {"entities": {"chemical": [{"text": "Fe2S2", "start": 66, "end": 71}, {"text": "Fe3S4", "start": 79, "end": 84}, {"text": "Fe4S4", "start": 95, "end": 100}]}}, "schema": []}
{"input": "The electron delocalization pattern for all the clusters and the nature of bonding between Fe and S atoms were studied by analyzing molecular orbitals.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 91, "end": 93}, {"text": "S", "start": 98, "end": 99}]}}, "schema": []}
{"input": "Natural population analysis demonstrates that Fe atoms act as an electron donor in all clusters, and the electron density difference map clearly shows the direction of the electron flow over the whole complex.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 46, "end": 48}]}}, "schema": []}
{"input": "Furthermore, the investigated magnetism shows that the Fe atoms carried most of the magnetic moments, which is due mainly to the 3d state, while only very small magnetic moments are found on S atoms.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 55, "end": 57}, {"text": "S", "start": 191, "end": 192}]}}, "schema": []}
{"input": "Methylation-controlled J-protein MCJ acts in the import of proteins into human mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "Loss of expression of the methylation-controlled J gene, MCJ (DNAJC15), is observed in cases of several tumors and plays a crucial role in the chemoresistance of ovarian cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Aside from the pathophysiological effects, almost nothing is known about the cellular function of MCJ.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we provide the first evidence that MCJ acts in the biogenesis of mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "Our results demonstrate that MCJ is located in mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "It is anchored in the mitochondrial inner membrane with the C-terminal J domain facing the matrix space.", "output": {"entities": {"chemical": [{"text": "C", "start": 60, "end": 61}]}}, "schema": []}
{"input": "We show that MCJ forms a stable subcomplex with a component of the mitochondrial import motor, MAGMAS, a protein overexpressed in cells treated with granulocyte-macrophage colony-stimulating factor and in prostate carcinomas.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, MCJ and MAGMAS interact with the core components of the TIM23 pre-protein translocase.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that the recombinant soluble MCJ domain stimulates the ATPase activity of the human mtHsp70 chaperone, mortalin, the central component of the import motor of the TIM23 translocase.", "output": {"entities": {}}, "schema": []}
{"input": "This stimulation is counteracted by MAGMAS.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, pre-protein import into mitochondria is impaired in the absence of MCJ.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, MCJ is able to take over the function of Tim14, the essential J co-chaperone of the mitochondrial protein import motor in yeast.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, our results show that MCJ functions as J co-chaperone of the human TIM23 pre-protein translocase, suggesting a link between mitochondrial pre-protein import and tumorigenesis.", "output": {"entities": {}}, "schema": []}
{"input": "The yeast eukaryotic translation initiation factor 2B translation initiation complex interacts with the fatty acid synthesis enzyme YBR159W and endoplasmic reticulum membranes.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 104, "end": 114}]}}, "schema": []}
{"input": "Using affinity purifications coupled with mass spectrometry and yeast two-hybrid assays, we show the Saccharomyces cerevisiae translation initiation factor complex eukaryotic translation initiation factor 2B (eIF2B) and the very-long-chain fatty acid (VLCFA) synthesis keto-reductase enzyme YBR159W physically interact.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 240, "end": 250}]}}, "schema": []}
{"input": "The data show that the interaction is specifically between YBR159W and eIF2B and not between other members of the translation initiation or VLCFA pathways.", "output": {"entities": {}}, "schema": []}
{"input": "A ybr159w Delta null strain has a slow-growth phenotype and a reduced translation rate but a normal GCN4 response to amino acid starvation.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 117, "end": 127}]}}, "schema": []}
{"input": "Although YBR159W localizes to the endoplasmic reticulum membrane, subcellular fractionation experiments show that a fraction of eIF2B cofractionates with lipid membranes in a YBR159W-independent manner.", "output": {"entities": {}}, "schema": []}
{"input": "We show that a ybr159w Delta yeast strain and other strains with null mutations in the VLCFA pathway cause eIF2B to appear as numerous foci throughout the cytoplasm.", "output": {"entities": {}}, "schema": []}
{"input": "The response of soil organism communities to the application of the insecticide lindane in terrestrial model ecosystems.", "output": {"entities": {"chemical": [{"text": "lindane", "start": 80, "end": 87}]}}, "schema": []}
{"input": "The EU plant protection regulation 1107/2009/EC defines the requirements for active ingredients to be approved, specifically including the assessment of effects on biodiversity and ecosystems.", "output": {"entities": {}}, "schema": []}
{"input": "According to that, semi-field methods are expected to be more important in the near future.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, a higher-tier experiment suitable to assess the risk for soil organisms was conducted to further develop the TME (terrestrial model ecosystems) methodology in a dose-response design with the persistent insecticidal model compound lindane (gamma-HCH).", "output": {"entities": {"chemical": [{"text": "lindane", "start": 241, "end": 248}, {"text": "gamma-HCH", "start": 250, "end": 259}]}}, "schema": []}
{"input": "The effects of lindane on soil communities such as collembolans, oribatid mites, nematodes, soil fungi and plant biomass were determined in 42 TME.", "output": {"entities": {"chemical": [{"text": "lindane", "start": 15, "end": 22}]}}, "schema": []}
{"input": "Intact TME-soil cores (diameter 300 mm, height 400 mm) from undisturbed grassland were stored outdoor under natural climatic conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Lindane was applied in five concentrations between 0. 032 mg active ingredients (ai)/kg dry soil and 3. 2 mg ai/kg dry weight soil, six-fold replicated each.", "output": {"entities": {"chemical": [{"text": "Lindane", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Twelve TME served as untreated controls.", "output": {"entities": {}}, "schema": []}
{"input": "Abundance and community structures of oribatids, collembolans, enchytraeids, nematodes and fungi were recorded.", "output": {"entities": {}}, "schema": []}
{"input": "Oribatid mites' community responded 3 months after treatment, although they were not significantly affected by the overall treatment regimen.", "output": {"entities": {}}, "schema": []}
{"input": "Collembolans in total and species-specific abundance as well as the community endpoints (principal response curves, diversity measures) were adversely affected by moderate dosages of lindane.", "output": {"entities": {}}, "schema": []}
{"input": "Effects were transient between 3 and 5 months after treatment with a recovery within 1 year.", "output": {"entities": {}}, "schema": []}
{"input": "No significant effects could be detected for enchytraeids, nematodes and fungi.", "output": {"entities": {}}, "schema": []}
{"input": "The study design and the obtained results allow for calculations of no observed effect concentrations below the highest treatment level for populations and for soil communities as defined entities, as well as effective concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "The paper discusses the limits of effect detection in the light of achievable coefficients of variation and by means of minimum detectable differences.", "output": {"entities": {}}, "schema": []}
{"input": "Outdoor TME are useful to analyze and assess functional and structural endpoints in soil organisms' communities and their possible recovery after pesticide treatment within 1 year.", "output": {"entities": {}}, "schema": []}
{"input": "Significance of peptide transporter 1 in the intestinal permeability of valacyclovir in wild-type and PepT1 knockout mice.", "output": {"entities": {"chemical": [{"text": "valacyclovir", "start": 72, "end": 84}]}}, "schema": []}
{"input": "The purpose of this study was to quantitatively determine the contribution of PepT1 [peptide transporter 1 (SLC15A1)] to the intestinal permeability of valacyclovir, an ester prodrug of the antiviral drug acyclovir.", "output": {"entities": {"chemical": [{"text": "valacyclovir", "start": 152, "end": 164}, {"text": "acyclovir", "start": 205, "end": 214}]}}, "schema": []}
{"input": "In situ single-pass intestinal perfusions were employed (pH 6. 5 x 90 minutes) to assess the effective permeability (P (eff)) of 100 mu M [(3) H] valacyclovir in wild-type and PepT1 knockout mice.", "output": {"entities": {"chemical": [{"text": "[(3) H] valacyclovir", "start": 138, "end": 158}]}}, "schema": []}
{"input": "Acyclovir pharmacokinetics was also evaluated after oral administration of 25 nmol/g valacyclovir.", "output": {"entities": {"chemical": [{"text": "Acyclovir", "start": 0, "end": 9}, {"text": "valacyclovir", "start": 85, "end": 97}]}}, "schema": []}
{"input": "In wild-type mice, jejunal uptake of valacyclovir was best described by both saturable (K (m) = 10. 2 mM) and nonsaturable components where the saturable pathway accounted for 82% of total transport.", "output": {"entities": {"chemical": [{"text": "valacyclovir", "start": 37, "end": 49}]}}, "schema": []}
{"input": "Valacyclovir P (eff) was 2. 4 x 10 (-4) cm/s in duodenum, 1. 7 x 10 (-4) cm/s in jejunum, 2. 1 x 10 (-4) cm/s in ileum, and 0. 27 x 10 (-4) cm/s in colon.", "output": {"entities": {"chemical": [{"text": "Valacyclovir", "start": 0, "end": 12}]}}, "schema": []}
{"input": "In Pept1 knockout mice, P (eff) values were about 10% of that in wild-type animals for these small intestinal segments.", "output": {"entities": {}}, "schema": []}
{"input": "Valacyclovir P (eff) was similar in the colon of both genotypes.", "output": {"entities": {"chemical": [{"text": "Valacyclovir", "start": 0, "end": 12}]}}, "schema": []}
{"input": "There were no differences in valacyclovir P (eff) between any of the intestinal segments of PepT1 knockout mice.", "output": {"entities": {"chemical": [{"text": "valacyclovir", "start": 29, "end": 41}]}}, "schema": []}
{"input": "Valacyclovir P (eff) was significantly reduced by the dipeptide glycylsarcosine and the aminocephalosporin cefadroxil, but not by the amino acids l-valine or l-histidine, the organic acid p-aminohippurate, or the organic base tetraethylammonium (all at 25 mM).", "output": {"entities": {"chemical": [{"text": "Valacyclovir", "start": 0, "end": 12}, {"text": "glycylsarcosine", "start": 64, "end": 79}, {"text": "aminocephalosporin cefadroxil", "start": 88, "end": 117}, {"text": "amino acids l-valine", "start": 134, "end": 154}, {"text": "l-histidine", "start": 158, "end": 169}, {"text": "p-aminohippurate", "start": 188, "end": 204}, {"text": "tetraethylammonium", "start": 226, "end": 244}]}}, "schema": []}
{"input": "PepT1 ablation resulted in 3-to 5-fold reductions in the in vivo rate and extent of valacyclovir absorption.", "output": {"entities": {"chemical": [{"text": "valacyclovir", "start": 84, "end": 96}]}}, "schema": []}
{"input": "Our findings conclusively demonstrate, using in situ and in vivo validations in genetically modified mice, that PepT1 has a major influence in improving the oral absorption of valacyclovir.", "output": {"entities": {"chemical": [{"text": "valacyclovir", "start": 176, "end": 188}]}}, "schema": []}
{"input": "Mammalian frataxin controls sulfur production and iron entry during de novo Fe4S4 cluster assembly.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 28, "end": 34}, {"text": "iron", "start": 50, "end": 54}, {"text": "Fe4S4", "start": 76, "end": 81}]}}, "schema": []}
{"input": "Iron-sulfur (Fe-S) cluster-containing proteins are essential components of cells.", "output": {"entities": {"chemical": [{"text": "Iron-sulfur", "start": 0, "end": 11}, {"text": "Fe-S", "start": 13, "end": 17}]}}, "schema": []}
{"input": "In eukaryotes, Fe-S clusters are synthesized by the mitochondrial iron-sulfur cluster (ISC) machinery and the cytosolic iron-sulfur assembly (CIA) system.", "output": {"entities": {"chemical": [{"text": "Fe-S", "start": 15, "end": 19}, {"text": "iron-sulfur", "start": 66, "end": 77}, {"text": "iron-sulfur", "start": 120, "end": 131}]}}, "schema": []}
{"input": "In the mammalian ISC machinery, preassembly of the Fe-S cluster on the scaffold protein (ISCU) involves a cysteine desulfurase complex (NFS1/ISD11) and frataxin (FXN), the protein deficient in Friedreich' s ataxia.", "output": {"entities": {"chemical": [{"text": "Fe-S", "start": 51, "end": 55}, {"text": "cysteine", "start": 106, "end": 114}]}}, "schema": []}
{"input": "Here, by comparing the biochemical and spectroscopic properties of quaternary (ISCU/NFS1/ISD11/FXN) and ternary (ISCU/NFS1/ISD11) complexes, we show that FXN stabilizes the quaternary complex and controls iron entry to the complex through activation of cysteine desulfurization.", "output": {"entities": {"chemical": [{"text": "iron", "start": 205, "end": 209}, {"text": "cysteine", "start": 253, "end": 261}]}}, "schema": []}
{"input": "Furthermore, we show for the first time that in the presence of iron and L-cysteine, an [Fe (4) S (4)] cluster is formed within the quaternary complex that can be transferred to mammalian aconitase (mACO2) to generate an active enzyme.", "output": {"entities": {"chemical": [{"text": "iron", "start": 64, "end": 68}, {"text": "L-cysteine", "start": 73, "end": 83}, {"text": "Fe (4) S (4)", "start": 89, "end": 101}]}}, "schema": []}
{"input": "In the absence of FXN, although the ternary complex can assemble an Fe-S cluster, the cluster is inefficiently transferred to ACO2.", "output": {"entities": {"chemical": [{"text": "Fe-S", "start": 68, "end": 72}]}}, "schema": []}
{"input": "Taken together, these data help to unravel further the Fe-S cluster assembly process and the molecular basis of Friedreich' s ataxia.", "output": {"entities": {"chemical": [{"text": "Fe-S", "start": 55, "end": 59}]}}, "schema": []}
{"input": "Dynamic behavior of water droplet impact on microtextured surfaces: the effect of geometrical parameters on anisotropic wetting and the maximum spreading diameter.", "output": {"entities": {}}, "schema": []}
{"input": "Textured silicon surfaces decorated by square arrays of pillars with adjustable pitch were fabricated.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 9, "end": 16}]}}, "schema": []}
{"input": "The wetting behavior, especially for direction-dependent water contact angles on textured silicon surfaces after silanization, was investigated by incorporating the contact line fraction into a modified Wenzel model.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 90, "end": 97}]}}, "schema": []}
{"input": "Also, the effect of geometrical parameters on the anisotropic wetting behavior of water was examined with respect to water droplet impact on the textured surface.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the maximum spreading factor was studied theoretically in terms of energy conservation, allowing for surface topography and viscous friction of the liquid flowing among the arrays of the posts.", "output": {"entities": {}}, "schema": []}
{"input": "Theoretical models were found to be in good agreement with experimental data.", "output": {"entities": {}}, "schema": []}
{"input": "Mineral and sensory profile of seasoned cracked olives packed in diverse salt mixtures.", "output": {"entities": {}}, "schema": []}
{"input": "This work studies the effect of packing cracked seasoned olives with NaCl, KCl, and CaCl (2) mixture brines on their mineral nutrients and sensory attributes, using RSM methodology.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 69, "end": 73}, {"text": "KCl", "start": 75, "end": 78}, {"text": "CaCl (2)", "start": 84, "end": 92}]}}, "schema": []}
{"input": "The Na, K, Ca, and residual natural Mn contents in flesh as well as saltiness, bitterness and fibrousness were significantly related to the initial concentrations of salts in the packing solution.", "output": {"entities": {"chemical": [{"text": "Na", "start": 4, "end": 6}, {"text": "K", "start": 8, "end": 9}, {"text": "Ca", "start": 11, "end": 13}, {"text": "Mn", "start": 36, "end": 38}]}}, "schema": []}
{"input": "This new process led to table olives with a significantly lower sodium content (about 31%) than the traditional product but fortified in K and Ca.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 64, "end": 70}, {"text": "K", "start": 137, "end": 138}, {"text": "Ca", "start": 143, "end": 145}]}}, "schema": []}
{"input": "High levels of Na and Ca in the flesh led to high scores of acidity and saltiness (the first descriptor) and bitterness (the second) while the K content was unrelated to any sensory descriptor.", "output": {"entities": {"chemical": [{"text": "Na", "start": 15, "end": 17}, {"text": "Ca", "start": 22, "end": 24}, {"text": "K", "start": 143, "end": 144}]}}, "schema": []}
{"input": "The new presentations using moderate proportions of alternative salts will therefore have improved nutritional value and healthier characteristics but only a slightly modified sensory profile.", "output": {"entities": {}}, "schema": []}
{"input": "Direct potentiometric determination of starch using a platinum redox sensor.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 54, "end": 62}]}}, "schema": []}
{"input": "Here, we describe the development of a platinum redox sensor for the direct potentiometric quantification of starch in solution.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 39, "end": 47}]}}, "schema": []}
{"input": "The sensor measures the decrease in free triiodide ion after it complexes with starch to form a starch-triiodide complex.", "output": {"entities": {"chemical": [{"text": "triiodide", "start": 41, "end": 50}, {"text": "triiodide", "start": 103, "end": 112}]}}, "schema": []}
{"input": "This decrease was, therefore, correlated with starch concentration, and the composition and stability of the potassium triiodide solution were optimised.", "output": {"entities": {"chemical": [{"text": "potassium triiodide", "start": 109, "end": 128}]}}, "schema": []}
{"input": "The starch-triiodide complex was characterized potentiometrically at variable starch and triiodide concentrations.", "output": {"entities": {"chemical": [{"text": "triiodide", "start": 11, "end": 20}, {"text": "triiodide", "start": 89, "end": 98}]}}, "schema": []}
{"input": "We also propose a response mechanism for the platinum redox sensor towards starch and an appropriate theoretical model.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 45, "end": 53}]}}, "schema": []}
{"input": "The optimised method exhibited satisfactory accuracy and precision and was in good agreement with a standard spectrophotometric method.", "output": {"entities": {}}, "schema": []}
{"input": "The sensor was tested over a range of 0. 4-9 mg starch, with recoveries ranging from 97. 8% to 103. 4% and a detection limit of 0. 01 mg starch.", "output": {"entities": {}}, "schema": []}
{"input": "Rapid detection and quantification of milk adulteration using infrared microspectroscopy and chemometrics analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The application of attenuated total reflectance mid-infrared microspectroscopy (MIR-microspectroscopy) was evaluated as a rapid method for detection and quantification of milk adulteration.", "output": {"entities": {}}, "schema": []}
{"input": "Milk samples were purchased from local grocery stores (Columbus, OH, USA) and spiked at different concentrations of whey, hydrogen peroxide, synthetic urine, urea and synthetic milk.", "output": {"entities": {"chemical": [{"text": "hydrogen peroxide", "start": 122, "end": 139}, {"text": "urea", "start": 158, "end": 162}]}}, "schema": []}
{"input": "Samples were place on a 192-well microarray slide, air-dried and spectra were collected by using MIR-microspectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Pattern recognition analysis by Soft Independent Modeling of Class Analogy (SIMCA) showed tight and well-separated clusters allowing discrimination of control samples from adulterated milk.", "output": {"entities": {}}, "schema": []}
{"input": "Partial Least Squares Regression (PLSR) showed standard error of prediction (SEP) ~ 2. 33, 0. 06, 0. 41, 0. 30 and 0. 014 g/L for estimation of levels of adulteration with whey, synthetic milk, synthetic urine, urea and hydrogen peroxide, respectively.", "output": {"entities": {"chemical": [{"text": "urea", "start": 211, "end": 215}, {"text": "hydrogen peroxide", "start": 220, "end": 237}]}}, "schema": []}
{"input": "Results showed that MIR-microspectroscopy can provide an alternative methodology to the dairy industry for screening potential fraudulent practice for economic adulteration of cow' s milk.", "output": {"entities": {}}, "schema": []}
{"input": "Cashew apple (Anacardium occidentale L.) extract from by-product of juice processing: a focus on carotenoids.", "output": {"entities": {}}, "schema": []}
{"input": "Cashew apple fibrous residue is a by-product of the cashew juice industry.", "output": {"entities": {}}, "schema": []}
{"input": "After pressing using a helical type continuous press followed by crossflow microfiltration, an aqueous extract was obtained from these cashew apple fibres.", "output": {"entities": {}}, "schema": []}
{"input": "It was characterised by an intense yellow colour due to carotenoid pigments.", "output": {"entities": {}}, "schema": []}
{"input": "Carotenoids were identified and quantified in the cashew apple before extraction, in its aqueous extract and in the concentrate obtained by microfiltration.", "output": {"entities": {}}, "schema": []}
{"input": "Cashew apple aqueous extract and its concentrate presented a carotenoid profile with 11 carotenoids, most of them were tentatively identified by HPLC-DAD-MS and are xanthophylls present under an esterified form.", "output": {"entities": {}}, "schema": []}
{"input": "Auroxanthin and beta-cryptoxanthin represented around 50% of total carotenoids.", "output": {"entities": {"chemical": [{"text": "beta-cryptoxanthin", "start": 16, "end": 34}]}}, "schema": []}
{"input": "Concentration of the extract by microfiltration led to epoxy-furanoxy rearrangement of violaxanthin and antheraxanthin.", "output": {"entities": {"chemical": [{"text": "epoxy", "start": 55, "end": 60}, {"text": "furanoxy", "start": 61, "end": 69}, {"text": "violaxanthin", "start": 87, "end": 99}, {"text": "antheraxanthin", "start": 104, "end": 118}]}}, "schema": []}
{"input": "The process allowed an increase of 10 times total carotenoid content compared with initial cashew apple.", "output": {"entities": {}}, "schema": []}
{"input": "Total carotenoid content of the final concentrated extract reached 54 mg/kg.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition effects and induction of apoptosis of flavonoids on the prostate cancer cell line PC-3 in vitro.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 49, "end": 59}]}}, "schema": []}
{"input": "Myricetin and myricitrin are naturally occurring flavonoids have been suggested to play a role in inhibition of proliferation and transformation of carcinogenic cell.", "output": {"entities": {"chemical": [{"text": "Myricetin", "start": 0, "end": 9}, {"text": "myricitrin", "start": 14, "end": 24}, {"text": "flavonoids", "start": 49, "end": 59}]}}, "schema": []}
{"input": "However, the underlying molecular mechanisms of their activity have not yet to be revealed.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to clarify the molecular mechanisms of apoptosis cell on the prostate cancer induced by myricetin, myricitrin, quercetin and quercitrin.", "output": {"entities": {"chemical": [{"text": "myricetin", "start": 121, "end": 130}, {"text": "myricitrin", "start": 132, "end": 142}, {"text": "quercetin", "start": 144, "end": 153}, {"text": "quercitrin", "start": 158, "end": 168}]}}, "schema": []}
{"input": "The MTT assay confirmed that myricetin had the strongest inhibitory effect on human prostate cancer cell line PC-3, myricitrin was second, and quercitrin was the weakest.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 4, "end": 7}, {"text": "myricetin", "start": 29, "end": 38}, {"text": "myricitrin", "start": 116, "end": 126}, {"text": "quercitrin", "start": 143, "end": 153}]}}, "schema": []}
{"input": "A noticeable synergistic effect was observed with the inhibition of cell proliferation when myricetin was used in combination with myricitrin.", "output": {"entities": {"chemical": [{"text": "myricetin", "start": 92, "end": 101}, {"text": "myricitrin", "start": 131, "end": 141}]}}, "schema": []}
{"input": "In the concentration range of 37. 5-300 mu mol/L, the inhibitory effects of these flavonoids were enhanced with increasing dose and treatment time.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 82, "end": 92}]}}, "schema": []}
{"input": "The acridine orange analysis and annexin V-FITC/PI double-staining results confirmed that myricetin and myricitrin were effective in inducing PC-3 cell apoptosis.", "output": {"entities": {"chemical": [{"text": "acridine orange", "start": 4, "end": 19}, {"text": "FITC", "start": 43, "end": 47}, {"text": "myricetin", "start": 90, "end": 99}, {"text": "myricitrin", "start": 104, "end": 114}]}}, "schema": []}
{"input": "The results showed that myricetin was more effective than myricitrin in inducing cell apoptosis.", "output": {"entities": {"chemical": [{"text": "myricetin", "start": 24, "end": 33}, {"text": "myricitrin", "start": 58, "end": 68}]}}, "schema": []}
{"input": "The apoptosis rate increased with increasing flavonoid concentration in a dose dependent manner.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 45, "end": 54}]}}, "schema": []}
{"input": "A synergistic effect was observed on the apoptosis rate when myricetin was used in combination with myricitrin.", "output": {"entities": {"chemical": [{"text": "myricetin", "start": 61, "end": 70}, {"text": "myricitrin", "start": 100, "end": 110}]}}, "schema": []}
{"input": "Assessment of DFG-S19 method for the determination of common endocrine disruptor pesticides in wine samples with an estimation of the uncertainty of the analytical results.", "output": {"entities": {}}, "schema": []}
{"input": "A gas chromatographic method for the determination of endocrine disruptor pesticides (Chlorpyrifos, Penconazole, Procymidone, Iprodione, Bromopropylate and Lambda-Cyhalothrin) in wine samples is described.", "output": {"entities": {"chemical": [{"text": "Chlorpyrifos", "start": 86, "end": 98}, {"text": "Penconazole", "start": 100, "end": 111}, {"text": "Procymidone", "start": 113, "end": 124}, {"text": "Iprodione", "start": 126, "end": 135}, {"text": "Bromopropylate", "start": 137, "end": 151}, {"text": "Lambda-Cyhalothrin", "start": 156, "end": 174}]}}, "schema": []}
{"input": "A general DFG-S19 method for residual pesticide determination in all kind of food stuff was investigated to simplify and adopt for wine samples in this work.", "output": {"entities": {}}, "schema": []}
{"input": "Alternative sample preparation routes were elucidated and compared according to their recovery values.", "output": {"entities": {}}, "schema": []}
{"input": "Four different separation techniques were tested and the method employing florosil column after a LLE procedure was applied for wine samples with satisfactory recovery ratios (72-97%).", "output": {"entities": {"chemical": [{"text": "florosil", "start": 74, "end": 82}]}}, "schema": []}
{"input": "The pesticides were extracted from the sample by cyclohexane-ethyl acetate mixture (1: 1 v/v) and cleaned up by florosil column.", "output": {"entities": {"chemical": [{"text": "cyclohexane", "start": 49, "end": 60}, {"text": "ethyl acetate", "start": 61, "end": 74}, {"text": "florosil", "start": 112, "end": 120}]}}, "schema": []}
{"input": "The regression coefficients were at least 0. 99 and relative standard deviations were no higher than 16%.", "output": {"entities": {}}, "schema": []}
{"input": "Detection limits were in the range of 0. 6-2. 9 ng/mL and the relative expanded measurement uncertainties were calculated in the 7-22% range.", "output": {"entities": {}}, "schema": []}
{"input": "Quality of bread supplemented with mushroom mycelia.", "output": {"entities": {}}, "schema": []}
{"input": "Mushroom mycelia of Antrodia camphorata, Agaricus blazei, Hericium erinaceus and Phellinus linteus were used to substitute 5% of wheat flour to make bread.", "output": {"entities": {}}, "schema": []}
{"input": "Bread quality, including specific volume, colour property, equivalent umami concentration (EUC), texture profile analysis, sensory evaluation and functional components, was analysed.", "output": {"entities": {}}, "schema": []}
{"input": "Mycelium-supplemented bread was smaller in loaf volume and coloured, and had lower lightness and white index values.", "output": {"entities": {}}, "schema": []}
{"input": "White bread contained the lowest amounts of free umami amino acids and umami 5'-nucleotides and showed the lowest EUC value.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 55, "end": 66}, {"text": "nucleotides", "start": 80, "end": 91}]}}, "schema": []}
{"input": "Incorporating 5% mushroom mycelia into the bread formula did not adversely affect the texture profile of the bread.", "output": {"entities": {}}, "schema": []}
{"input": "However, incorporating 5% mushroom mycelia into the bread formula did lower bread' s acceptability.", "output": {"entities": {}}, "schema": []}
{"input": "After baking, mycelium-supplemented bread still contained substantial amounts of gamma-aminobutyric acid and ergothioneine (0. 23-0. 86 and 0. 79-2. 10 mg/g dry matter, respectively).", "output": {"entities": {"chemical": [{"text": "gamma-aminobutyric acid", "start": 81, "end": 104}, {"text": "ergothioneine", "start": 109, "end": 122}]}}, "schema": []}
{"input": "Overall, mushroom mycelium could be incorporated into bread to provide its beneficial health effects.", "output": {"entities": {}}, "schema": []}
{"input": "Natural occurrence of deoxynivalenol in wheat from Paran a State, Brazil and estimated daily intake by wheat products.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 22, "end": 36}]}}, "schema": []}
{"input": "The occurrence of deoxynivalenol (DON) was evaluated in 113 wheat samples from the northern and central/southwestern regions of Paran a State, Brazil during the 2008 and 2009 growing seasons, and this rate of occurrence was used to estimate the DON dietary exposure.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 18, "end": 32}, {"text": "DON", "start": 34, "end": 37}, {"text": "DON", "start": 245, "end": 248}]}}, "schema": []}
{"input": "The DON determination was carried out by an indirect competitive enzyme-linked immunosorbent assay.", "output": {"entities": {"chemical": [{"text": "DON", "start": 4, "end": 7}]}}, "schema": []}
{"input": "DON was detected in 66. 4% samples at levels ranging from 206. 3 to 4732. 3 mu g/kg (mean 1894. 9 mu g/kg).", "output": {"entities": {"chemical": [{"text": "DON", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The estimated daily intake (EDI) of DON through bread and pasta was evaluated in the inhabitants of Londrina City in northern Paran a State, Brazil.", "output": {"entities": {"chemical": [{"text": "DON", "start": 36, "end": 39}]}}, "schema": []}
{"input": "The average intake of these inhabitants was 0. 79 mu g/kg body weight (b. w.) for bread and 0. 35 mu g/kg b. w. for pasta.", "output": {"entities": {}}, "schema": []}
{"input": "The total EDI was 1. 13 mu g/kg, which is above the Provisional Tolerable Daily Maximum Intake (PTDMI) of 1 mu g/kg b. w.", "output": {"entities": {}}, "schema": []}
{"input": "To our knowledge, this is the first report on natural DON occurrence in wheat and DON dietary exposure estimation from Paran a, Brazil.", "output": {"entities": {"chemical": [{"text": "DON", "start": 54, "end": 57}, {"text": "DON", "start": 82, "end": 85}]}}, "schema": []}
{"input": "Hepatoprotective effect of 2, 3-dehydrosilybin on carbon tetrachloride-induced liver injury in rats.", "output": {"entities": {"chemical": [{"text": "2, 3-dehydrosilybin", "start": 27, "end": 46}, {"text": "carbon tetrachloride", "start": 50, "end": 70}]}}, "schema": []}
{"input": "The aim of this study was to investigate the protective effect of 2, 3-dehydrosilybin (DHS) against carbon tetrachloride (CCl (4))-induced liver injury in rats.", "output": {"entities": {"chemical": [{"text": "2, 3-dehydrosilybin", "start": 66, "end": 85}, {"text": "DHS", "start": 87, "end": 90}, {"text": "carbon tetrachloride", "start": 100, "end": 120}, {"text": "CCl (4)", "start": 122, "end": 129}]}}, "schema": []}
{"input": "Administration of DHS significantly attenuated the levels of serum aspartate aminotransferase, alanine aminotransferase, and liver lipid peroxidation in CCl (4)-treated rats.", "output": {"entities": {"chemical": [{"text": "DHS", "start": 18, "end": 21}, {"text": "aspartate", "start": 67, "end": 76}, {"text": "alanine", "start": 95, "end": 102}, {"text": "CCl (4)", "start": 153, "end": 160}]}}, "schema": []}
{"input": "Moreover, we showed that DHS prevented DNA damage and decreased the protein levels of gamma-H2AX, which is a specific DNA damage marker, in CCl (4)-treated rat livers.", "output": {"entities": {"chemical": [{"text": "DHS", "start": 25, "end": 28}, {"text": "CCl (4)", "start": 140, "end": 147}]}}, "schema": []}
{"input": "DHS also markedly increased the activity of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in CCl (4)-treated rat livers.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 73, "end": 83}, {"text": "glutathione", "start": 105, "end": 116}, {"text": "CCl (4)", "start": 158, "end": 165}]}}, "schema": []}
{"input": "Furthermore, we found that DHS significantly inhibited the production of serum nitric oxide as well as the levels of serum IL-6, IFN-gamma, and TNF-alpha in CCl (4)-treated rats.", "output": {"entities": {"chemical": [{"text": "DHS", "start": 27, "end": 30}, {"text": "nitric oxide", "start": 79, "end": 91}, {"text": "CCl (4)", "start": 157, "end": 164}]}}, "schema": []}
{"input": "Additionally, DHS significantly suppressed iNOS expression on the protein levels in CCl (4)-treated rat livers.", "output": {"entities": {"chemical": [{"text": "DHS", "start": 14, "end": 17}, {"text": "CCl (4)", "start": 84, "end": 91}]}}, "schema": []}
{"input": "Collectively, the present study suggests that DHS protects the liver from CCl (4)-induced hepatic damage via antioxidant and anti-inflammatory mechanisms.", "output": {"entities": {"chemical": [{"text": "DHS", "start": 46, "end": 49}, {"text": "CCl (4)", "start": 74, "end": 81}]}}, "schema": []}
{"input": "Development of a rapid and simple voltammetric method to determine total antioxidative capacity of edible oils.", "output": {"entities": {}}, "schema": []}
{"input": "In this work we report on a new, rapid and simple voltammetric method to determine the total antioxidant capacity (TAC) of the edible oils.", "output": {"entities": {}}, "schema": []}
{"input": "The method explores the ABTS radical (2, 2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid)) assay as a redox probe and it relays on measuring catalytic voltammetric currents.", "output": {"entities": {"chemical": [{"text": "ABTS", "start": 24, "end": 28}, {"text": "2, 2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid)", "start": 38, "end": 94}]}}, "schema": []}
{"input": "The electrocatalysis comprises redox regeneration of the electrochemically created ABTS (+) radical either by Trolox (6-hydroxy-2, 5, 7, 8-tetramethychroman-2-carboxylic acid) or by antioxidants present in studied oils.", "output": {"entities": {"chemical": [{"text": "ABTS (+)", "start": 83, "end": 91}, {"text": "Trolox", "start": 110, "end": 116}, {"text": "6-hydroxy-2, 5, 7, 8-tetramethychroman-2-carboxylic acid", "start": 118, "end": 174}]}}, "schema": []}
{"input": "The detection limit of the method is determined to be 0. 5 mg/L of Trolox equivalent, being a slightly lower than the corresponding UV-VIS spectrophotometric method.", "output": {"entities": {"chemical": [{"text": "Trolox", "start": 67, "end": 73}]}}, "schema": []}
{"input": "Applying the proposed voltammetric method the total antioxidant capacity of three types of commercially available cold-pressed edible oils are determined, and the results are found to be in a very good agreement with those obtained by UV-VIS spectrophotometry.", "output": {"entities": {}}, "schema": []}
{"input": "The reported voltammetric method is cheap, rapid and simple, and it can be used as a sustainable alternative to the UV-VIS methods for the determination of total antioxidant capacitance of oils and other liquid lipophilic nutrients.", "output": {"entities": {}}, "schema": []}
{"input": "Potent antioxidant capacity of studied oils was also confirmed by electron paramagnetic resonance spectroscopy of superoxide anion produced by macrophages.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 114, "end": 124}]}}, "schema": []}
{"input": "Effect of the genistein metabolite on leptin secretion in murine adipocytes in vitro.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 14, "end": 23}]}}, "schema": []}
{"input": "Soy isoflavonoids have many useful properties.", "output": {"entities": {"chemical": [{"text": "isoflavonoids", "start": 4, "end": 17}]}}, "schema": []}
{"input": "However, they are metabolized in vivo, including in humans.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of the metabolism of soy isoflavonoids on their properties is not fully understood.", "output": {"entities": {"chemical": [{"text": "isoflavonoids", "start": 36, "end": 49}]}}, "schema": []}
{"input": "We have isolated the bacterial strain SY8519, which has been shown to metabolize daidzein to O-desmethylangolensin and to produce 2-(4-hydroxyphenyl) propionic acid from genistein.", "output": {"entities": {"chemical": [{"text": "daidzein", "start": 81, "end": 89}, {"text": "O-desmethylangolensin", "start": 93, "end": 114}, {"text": "2-(4-hydroxyphenyl) propionic acid", "start": 130, "end": 164}, {"text": "genistein", "start": 170, "end": 179}]}}, "schema": []}
{"input": "According to chiral HPLC analysis, the 2-(4-hydroxyphenyl) propionic acid obtained from the bacterium was optically active.", "output": {"entities": {"chemical": [{"text": "2-(4-hydroxyphenyl) propionic acid", "start": 39, "end": 73}]}}, "schema": []}
{"input": "To determine the absolute stereochemistry of the microbial product, we prepared (S)-2-(4-hydroxyphenyl) propionic acid from (S)-2-phenylpropionic and concluded that the microbial product had an R-configuration by chiral HPLC analysis.", "output": {"entities": {"chemical": [{"text": "(S)-2-(4-hydroxyphenyl) propionic acid", "start": 80, "end": 118}, {"text": "(S)-2-phenylpropionic", "start": 124, "end": 145}]}}, "schema": []}
{"input": "We also applied the metabolite to mouse adipocytes and found that 2-HPPA was less effective at reducing leptin secretion than the parent compound genistein.", "output": {"entities": {"chemical": [{"text": "2-HPPA", "start": 66, "end": 72}, {"text": "genistein", "start": 146, "end": 155}]}}, "schema": []}
{"input": "Our results suggested that' O-desmethylangolensin-production' attenuates the effect of soy isoflavonoids by reducing not only the activity of daidzein but also that of genistein.", "output": {"entities": {"chemical": [{"text": "O-desmethylangolensin", "start": 28, "end": 49}, {"text": "isoflavonoids", "start": 91, "end": 104}, {"text": "daidzein", "start": 142, "end": 150}, {"text": "genistein", "start": 168, "end": 177}]}}, "schema": []}
{"input": "Simultaneous detection of flavonoids and phenolic acids in Herba Lysimachiae and Herba Desmodii Styracifolii using liquid chromatography tandem mass spectrometry.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 26, "end": 36}, {"text": "phenolic acids", "start": 41, "end": 55}]}}, "schema": []}
{"input": "A sensitive liquid chromatography and tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous analysis of 15 flavonoids and 3 phenolic acids in Herba Lysimachiae and Herba Desmodii Styracifolii.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 145, "end": 155}, {"text": "phenolic acids", "start": 162, "end": 176}]}}, "schema": []}
{"input": "Separation was performed using a Diamonsil C (18) column, which was eluted with methanol (A) and 0. 1 /1000 acetic acid (B).", "output": {"entities": {"chemical": [{"text": "methanol", "start": 80, "end": 88}, {"text": "acetic acid", "start": 108, "end": 119}]}}, "schema": []}
{"input": "The gradient condition was as follows: 0-34 min, 20-34% A; 34-38 min, 34-95% A; maintained 95% A for the next 4 min.", "output": {"entities": {}}, "schema": []}
{"input": "Analytes were detected using a hybrid quadrupole linear ion trap mass spectrometer that was equipped with an electrospray ionisation source in the negative ion and multiple-reaction monitoring modes.", "output": {"entities": {}}, "schema": []}
{"input": "A full validation of the method was performed, including the linearity, precision, and accuracy, as well as limits of detection and quantification.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicated that the developed method was simple, sensitive and reliable.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the method was successfully applied to differentiate 16 batches of Herba Lysimachiae and 21 batches of Herba Desmodii Styracifolii.", "output": {"entities": {}}, "schema": []}
{"input": "Differentiation of Sparidae species by DNA sequence analysis, PCR-SSCP and IEF of sarcoplasmic proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The increasing global trade of fishery and aquaculture products makes it necessary to develop methods for species identification in case of fish fillets or other highly processed seafood with external morphological characteristics (e. g. gills, fins) of the original fish being removed.", "output": {"entities": {}}, "schema": []}
{"input": "Species identification methods based on DNA-or protein-analysis, like DNA sequencing of PCR products, PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism), and isoelectric focusing (IEF) of water-soluble proteins of fish fillet were applied successfully to distinguish between various sparid species including Sparus aurata, Spondyliosoma cantharus, Boops boops, Acanthopagrus bifasciatus, Argyrops spinifer, Pagellus bogaraveo and Lithognathus mormyrus of the family Sparidae available on European markets.", "output": {"entities": {}}, "schema": []}
{"input": "Indication of the presence of parvalbumins in light muscle of all of the studied species is presented by the location of heat-stable proteins in the anodic range of the IEF gels.", "output": {"entities": {}}, "schema": []}
{"input": "Exploration of Vanilla pompona from the Peruvian Amazon as a potential source of vanilla essence: quantification of phenolics by HPLC-DAD.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 116, "end": 125}]}}, "schema": []}
{"input": "This study provides the first chemical investigation of wild-harvested fruits of Vanilla pompona ssp. grandiflora (Lindl.) Soto-Arenas developed in their natural habitat in the Peruvian Amazon.", "output": {"entities": {}}, "schema": []}
{"input": "Flowers were hand-pollinated and the resulting fruits were analysed at different developmental stages using an HPLC-DAD method validated for the quantification of glucovanillin and seven other compounds.", "output": {"entities": {"chemical": [{"text": "glucovanillin", "start": 163, "end": 176}]}}, "schema": []}
{"input": "The method showed satisfactory linearity (r (2) > 0. 9969), precision (coefficient of variation < 2%), recoveries (70-100%), limit of detection (0. 008-0. 212 mu g/ml), and limit of quantification (0. 027-0. 707 mu g/ml).", "output": {"entities": {}}, "schema": []}
{"input": "The evaluation of crude and enzyme-hydrolyzed Soxhlet-extracted samples confirmed the leading role of glucosides in fruit development.", "output": {"entities": {}}, "schema": []}
{"input": "LC-ESI-MS studies corroborated the identities of four glucosides and seven aglycones, among them vanillin (5. 7/100 g), 4-hydroxybenzyl alcohol (3. 6/100 g), and anisyl alcohol (7. 1/100 g) were found in high concentrations.", "output": {"entities": {"chemical": [{"text": "vanillin", "start": 97, "end": 105}, {"text": "4-hydroxybenzyl alcohol", "start": 120, "end": 143}, {"text": "anisyl alcohol", "start": 162, "end": 176}]}}, "schema": []}
{"input": "The attractive flavor/aroma profile exhibited by wild V. pompona fruits supports studies focused on the development of this species as a specialty crop.", "output": {"entities": {}}, "schema": []}
{"input": "Nutritive value of masau (Ziziphus mauritiana) fruits from Zambezi Valley in Zimbabwe.", "output": {"entities": {}}, "schema": []}
{"input": "Ziziphus mauritiana (masau) fruits are consumed by many people in Zimbabwe.", "output": {"entities": {}}, "schema": []}
{"input": "The fruits contribute significantly to people' s diet when they are in season.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to determine the nutritional content of the fruits and, hence, quantify their contribution to the diet.", "output": {"entities": {}}, "schema": []}
{"input": "Samples of masau were collected in two seasons (August 2006 and August 2007).", "output": {"entities": {}}, "schema": []}
{"input": "Both macronutrients and micronutrients were determined using standard AOAC methods of analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Dry matter content ranged from 21. 1 +/- 0. 2 to 24. 1 +/- 0. 3 g 100 g (-1) of edible portion of the sweet and sour fruits, and 84. 8 +/- 0. 2 to 87. 2 +/- 0. 2 g 100 g (-1) for the dried fruit.", "output": {"entities": {}}, "schema": []}
{"input": "Crude protein per 100g edible portion of dry weight ranged between 7. 9 +/- 0. 0 and 8. 7 +/- 0. 0 g, crude fat from 0. 8 +/- 0. 0 to 1. 5 +/- 0. 0 g, crude fibre from 4. 9 +/- 0. 0 to 7. 3 +/- 0. 0 g, ash between 3. 0 +/- 0. 0 and 4. 3 +/- 0. 0 g and carbohydrate between 79. 5 +/- 0. 0 and 83. 2 +/- 0. 0 g.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 252, "end": 264}]}}, "schema": []}
{"input": "The fruits were rich in vitamin C (15. 0 +/- 0. 0-43. 8 +/- 0. 02 mg 100 g (-1)) and the energy values ranged between 1516. 0 +/- 1. 73 and 1575. 0 +/- 2. 3 kJ 100 g (-1).", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 24, "end": 33}]}}, "schema": []}
{"input": "Furthermore, the fruits contained (mg 100 g (-1) of dry weight) potassium from 1865. 0 +/- 1. 3 to 2441. 0 +/- 1. 1, calcium from 160. 0 +/- 0. 3 to 254. 0 +/- 0. 1, sodium between 185. 0 +/- 0. 1 and 223. 0 +/- 0. 2, magnesium between 83. 0 +/- 0. 0 and 150. 0 +/- 0. 13 and phosphorous from 87. 0 +/- 0. 1 to 148. 0 +/- 0. 5.", "output": {"entities": {"chemical": [{"text": "potassium", "start": 64, "end": 73}, {"text": "calcium", "start": 117, "end": 124}, {"text": "sodium", "start": 166, "end": 172}, {"text": "magnesium", "start": 218, "end": 227}, {"text": "phosphorous", "start": 276, "end": 287}]}}, "schema": []}
{"input": "Manganese and copper contents ranged between 0. 7 +/- 0. 03 and 1. 6 +/- 0. 03, while iron and zinc ranged between 2. 1 +/- 0. 43 and 4. 3 +/- 0. 1, and 0. 6 +/- 0. 0-0. 9 +/- 0. 0 mg 100 g (-1) of dry weight, respectively.", "output": {"entities": {"chemical": [{"text": "Manganese", "start": 0, "end": 9}, {"text": "copper", "start": 14, "end": 20}, {"text": "iron", "start": 86, "end": 90}, {"text": "zinc", "start": 95, "end": 99}]}}, "schema": []}
{"input": "The masau fruit is therefore a good potential source of carbohydrates, proteins and micronutrients, such as calcium, potassium, sodium, phosphorous, copper, iron, Vitamin C and zinc.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 56, "end": 69}, {"text": "calcium", "start": 108, "end": 115}, {"text": "potassium", "start": 117, "end": 126}, {"text": "sodium", "start": 128, "end": 134}, {"text": "phosphorous", "start": 136, "end": 147}, {"text": "copper", "start": 149, "end": 155}, {"text": "iron", "start": 157, "end": 161}, {"text": "Vitamin C", "start": 163, "end": 172}, {"text": "zinc", "start": 177, "end": 181}]}}, "schema": []}
{"input": "Development of sample preparation method for isoliquiritigenin, liquiritin, and glycyrrhizic acid analysis in licorice by ionic liquids-ultrasound based extraction and high-performance liquid chromatography detection.", "output": {"entities": {"chemical": [{"text": "isoliquiritigenin", "start": 45, "end": 62}, {"text": "liquiritin", "start": 64, "end": 74}, {"text": "glycyrrhizic acid", "start": 80, "end": 97}]}}, "schema": []}
{"input": "An ionic liquid-based ultrasonic-assisted extraction (ILUAE) method had been used for the effective extraction of isoliquiritigenin (IQ), liquiritin (LQ) and glycyrrhizic acid (GA) from licorice.", "output": {"entities": {"chemical": [{"text": "isoliquiritigenin", "start": 114, "end": 131}, {"text": "liquiritin", "start": 138, "end": 148}, {"text": "glycyrrhizic acid", "start": 158, "end": 175}]}}, "schema": []}
{"input": "The ionic liquids with different cations and anions were investigated in this work and 0. 5 M 1-butyl-3-methylimidazolium bromide solution was selected as solvent.", "output": {"entities": {"chemical": [{"text": "1-butyl-3-methylimidazolium bromide", "start": 94, "end": 129}]}}, "schema": []}
{"input": "In addition, the technical parameters including soaking time, solid-liquid ratio, ultrasonic power and time were optimized.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with the conventional solvent extraction, the proposed approach exhibited higher efficiency, which indicated the ILUAE was an efficient, rapid and simple sample preparation technique.", "output": {"entities": {}}, "schema": []}
{"input": "There was no degradation of the target analytes had been observed at the optimum conditions which was evidenced by the stability studies performed with standard of IQ, LQ and GA.", "output": {"entities": {}}, "schema": []}
{"input": "The proposed method also showed high reproducibility and was environmental friendly.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative formation of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in creatinine/phenylalanine and creatinine/phenylalanine/4-oxo-2-nonenal reaction mixtures.", "output": {"entities": {"chemical": [{"text": "2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine", "start": 25, "end": 75}, {"text": "PhIP", "start": 77, "end": 81}, {"text": "creatinine", "start": 86, "end": 96}, {"text": "phenylalanine", "start": 97, "end": 110}, {"text": "creatinine", "start": 115, "end": 125}, {"text": "phenylalanine", "start": 126, "end": 139}, {"text": "4-oxo-2-nonenal", "start": 140, "end": 155}]}}, "schema": []}
{"input": "The comparative formation of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in both creatinine/phenylalanine (CRN/Phe) and creatinine/phenylalanine/4-oxo-2-nonenal (CRN/Phe/ON) systems was studied to analyse the ability of lipid-derived reactive carbonyls to promote PhIP formation.", "output": {"entities": {"chemical": [{"text": "2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine", "start": 61, "end": 111}, {"text": "PhIP", "start": 113, "end": 117}, {"text": "creatinine", "start": 127, "end": 137}, {"text": "phenylalanine", "start": 138, "end": 151}, {"text": "CRN", "start": 153, "end": 156}, {"text": "Phe", "start": 157, "end": 160}, {"text": "creatinine", "start": 166, "end": 176}, {"text": "phenylalanine", "start": 177, "end": 190}, {"text": "4-oxo-2-nonenal", "start": 191, "end": 206}, {"text": "CRN", "start": 208, "end": 211}, {"text": "Phe", "start": 212, "end": 215}, {"text": "carbonyls", "start": 289, "end": 298}, {"text": "PhIP", "start": 310, "end": 314}]}}, "schema": []}
{"input": "Although PhIP was produced to some extent in the CRN/Phe system, the presence of the oxidized lipid increased considerably the amount of PhIP produced.", "output": {"entities": {"chemical": [{"text": "PhIP", "start": 9, "end": 13}, {"text": "CRN", "start": 49, "end": 52}, {"text": "Phe", "start": 53, "end": 56}, {"text": "PhIP", "start": 137, "end": 141}]}}, "schema": []}
{"input": "This increase seemed to be a consequence of the decrease in the E (a) of the reaction when the lipid was present, which diminished from 112. 9 to 80. 9 kJ/mol.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, the addition of the lipid did not seem to produce PhIP by an alternative mechanism because PhIP was formed analogously in both CRN/Phe and CRN/Phe/ON systems as a function of pH, creatinine concentration, phenylalanine concentration, time, temperature, oxygen concentration in the reaction atmosphere, and the addition of different amounts of ammonia.", "output": {"entities": {"chemical": [{"text": "PhIP", "start": 69, "end": 73}, {"text": "PhIP", "start": 110, "end": 114}, {"text": "CRN", "start": 146, "end": 149}, {"text": "Phe", "start": 150, "end": 153}, {"text": "CRN", "start": 158, "end": 161}, {"text": "Phe", "start": 162, "end": 165}, {"text": "creatinine", "start": 198, "end": 208}, {"text": "phenylalanine", "start": 224, "end": 237}, {"text": "oxygen", "start": 272, "end": 278}, {"text": "ammonia", "start": 362, "end": 369}]}}, "schema": []}
{"input": "All these results suggest that the ability of lipid oxidation products to produce PhIP is related to their capacity to induce the Strecker degradation of phenylalanine to phenylacetaldehyde.", "output": {"entities": {"chemical": [{"text": "PhIP", "start": 82, "end": 86}, {"text": "phenylalanine", "start": 154, "end": 167}, {"text": "phenylacetaldehyde", "start": 171, "end": 189}]}}, "schema": []}
{"input": "Therefore, any other reactive carbonyl compound that can produce the Strecker degradation of phenylalanine should also be considered as a potential inducer of PhIP formation under appropriate conditions.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 30, "end": 38}, {"text": "phenylalanine", "start": 93, "end": 106}, {"text": "PhIP", "start": 159, "end": 163}]}}, "schema": []}
{"input": "Rapid detecting total acid content and classifying different types of vinegar based on near infrared spectroscopy and least-squares support vector machine.", "output": {"entities": {}}, "schema": []}
{"input": "More than 3. 2 million litres of vinegar is consumed every day in China.", "output": {"entities": {}}, "schema": []}
{"input": "There are many types of vinegar in China.", "output": {"entities": {}}, "schema": []}
{"input": "How to control the quality of vinegar is problem.", "output": {"entities": {}}, "schema": []}
{"input": "Near infrared spectroscopy (NIR) transmission technique was applied to achieve this purpose.", "output": {"entities": {}}, "schema": []}
{"input": "Ninety-five vinegar samples from 14 origins covering 11 provinces in China were collected.", "output": {"entities": {}}, "schema": []}
{"input": "They were classified into mature vinegar, aromatic vinegar, rice vinegar, fruit vinegar, and white vinegar.", "output": {"entities": {}}, "schema": []}
{"input": "Fruit vinegar and white vinegar were separated from the other traditional categories in the two-dimension principal component space of NIR after principle component analysis (PCA).", "output": {"entities": {}}, "schema": []}
{"input": "Least-squares support vector machine (LS-SVM) as the pattern recognition was firstly applied to identify mature vinegar, aromatic vinegar, rice vinegar in this study.", "output": {"entities": {}}, "schema": []}
{"input": "The top two principal components (PCs) were extracted as the input of LS-SVM classifiers by principal component analysis (PCA).", "output": {"entities": {}}, "schema": []}
{"input": "The best experimental results were obtained using the radial basis function (RBF) LS-SVM classifier with sigma = 0. 8.", "output": {"entities": {}}, "schema": []}
{"input": "The accuracies of identification were more than 85% for three traditional vinegar categories.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with the back propagation artificial neural network (BP-ANN) approach, LS-SVM algorithm showed its excellent generalisation for identification results.", "output": {"entities": {}}, "schema": []}
{"input": "As total acid content (TAC) is highly connecting with the quality of vinegar, NIR was used to prediction the TAC of samples.", "output": {"entities": {}}, "schema": []}
{"input": "LS-SVM was applied to building the TAC prediction model based on spectral transmission rate.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with partial least-square (PLS) model, LS-SVM model gave better precision and accuracy in predicting TAC.", "output": {"entities": {}}, "schema": []}
{"input": "The determination coefficient for prediction (R (p)) of the LS-SVM model was 0. 919 and root mean square error for prediction (RMSEP) was 0. 3226.", "output": {"entities": {}}, "schema": []}
{"input": "This work demonstrated that near infrared spectroscopy technique coupled with LS-SVM could be used as a quality control method for vinegar.", "output": {"entities": {}}, "schema": []}
{"input": "Microwave distillation followed by headspace single drop microextraction coupled to gas chromatography-mass spectrometry (GC-MS) for fast analysis of volatile components of Echinophora platyloba DC.", "output": {"entities": {}}, "schema": []}
{"input": "To avoid the traditional and time consuming hydrodistillation, the analyses of volatile components in aerial parts of Echinophora platyloba DC was carried out by a simple microwave distillation followed by headspace single drop microextraction (MD-HS-SDME) coupled to gas chromatography-mass spectrometry (GC-MS).", "output": {"entities": {}}, "schema": []}
{"input": "The headspace volatile compounds were collected after irradiation using a single drop of n-heptadecan.", "output": {"entities": {"chemical": [{"text": "n-heptadecan", "start": 89, "end": 101}]}}, "schema": []}
{"input": "The extraction conditions were optimised using the relative peak areas as index.", "output": {"entities": {}}, "schema": []}
{"input": "The chemical composition of the MD-HS-SDME extracts was confirmed according to their retention indexes and mass spectra.", "output": {"entities": {}}, "schema": []}
{"input": "Fifty-three components were extracted and identified by using the MD-HS-SDME method.", "output": {"entities": {}}, "schema": []}
{"input": "E-beta-ocimene (53. 81%), R-D-decalactone (12. 75%), alpha-pinene (6. 43%), n-heptanol (6. 27%), beta-phellanderne (2. 70%) and linalool (1. 89%) were the major constituents.", "output": {"entities": {"chemical": [{"text": "E-beta-ocimene", "start": 0, "end": 14}, {"text": "alpha-pinene", "start": 53, "end": 65}, {"text": "n-heptanol", "start": 76, "end": 86}, {"text": "beta-phellanderne", "start": 97, "end": 114}, {"text": "linalool", "start": 128, "end": 136}]}}, "schema": []}
{"input": "Compositional analysis of leaf cuticular membranes isolated from tea plants (Camellia sinensis L.).", "output": {"entities": {}}, "schema": []}
{"input": "Chemical constituents of cuticular membranes (CMs) isolated from three tea cultivars (Camellia sinensis (L.) O. Kuntze cvs. Yabukita, Samidori and Gokou) were compared.", "output": {"entities": {}}, "schema": []}
{"input": "All CMs from the adaxial side of the leaves showed higher accumulation of wax, cutin and polysaccharide, while those from the abaxial side were abundant in cutan, showing the adaptation of the adaxial side to abiotic stresses, such as wind and rain, in contrast to the abaxial side, which provides defence against pathogens.", "output": {"entities": {}}, "schema": []}
{"input": "Yabukita, a major tea cultivar in Japan, developed thick CMs while Samidori and Gokou, shade-cultivated tea cultivars, had lighter CMs, reflecting their thin and soft leaves.", "output": {"entities": {}}, "schema": []}
{"input": "CMs rapidly accumulated 9, 10-epoxy-18-hydroxyoctadecanoic acid at a very early stage of leaf development.", "output": {"entities": {"chemical": [{"text": "9, 10-epoxy-18-hydroxyoctadecanoic acid", "start": 24, "end": 63}]}}, "schema": []}
{"input": "Additionally, shade treatment did not influence cutin biosynthesis in CMs, reflecting high adaptation of tea leaves under low light levels.", "output": {"entities": {}}, "schema": []}
{"input": "UPLC and HPLC of caffeoyl esters in wild and cultivated Arctium lappa L.", "output": {"entities": {"chemical": [{"text": "caffeoyl esters", "start": 17, "end": 32}]}}, "schema": []}
{"input": "Analytical methods including ultra-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC) with photodiode array (PDA) detector were developed for the analysis of caffeoylquinic acid derivatives in seeds, leaves and roots of Arctium lappa L.", "output": {"entities": {"chemical": [{"text": "caffeoylquinic acid", "start": 198, "end": 217}]}}, "schema": []}
{"input": "Separation was performed on C (18) column utilising 5% (v/v) acetic acid in water and acetonitrile at 330 nm.", "output": {"entities": {"chemical": [{"text": "acetic acid", "start": 61, "end": 72}, {"text": "acetonitrile", "start": 86, "end": 98}]}}, "schema": []}
{"input": "Both methodologies were validated in terms of linearity, precision, and recovery.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that the major advantages of UPLC, over HPLC were the fast analysis, narrow peaks, high sensitivity, and reduction of solvent consumption.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently the methods were applied for the identification and quantification of chlorogenic acid (5-CQA) and 1, 5-dicaffeoylquinic acid (1, 5-DCQA) as main compounds in samples.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 83, "end": 99}, {"text": "5-CQA", "start": 101, "end": 106}, {"text": "1, 5-dicaffeoylquinic acid", "start": 112, "end": 138}, {"text": "1, 5-DCQA", "start": 140, "end": 149}]}}, "schema": []}
{"input": "The total phenolic content of samples ranged from 3. 93 to 14. 13 g of 5-CQA equivalent/100g dry weight (DW).", "output": {"entities": {"chemical": [{"text": "5-CQA", "start": 71, "end": 76}]}}, "schema": []}
{"input": "There was a significant variability from 89 to 571 mg/100g for 5-CQA and 48 to 486 mg/100g for 1, 5-DCQA in dry material.", "output": {"entities": {"chemical": [{"text": "5-CQA", "start": 63, "end": 68}, {"text": "1, 5-DCQA", "start": 95, "end": 104}]}}, "schema": []}
{"input": "Structural property of soybean lunasin and development of a method to quantify lunasin in plasma using an optimized immunoassay protocol.", "output": {"entities": {}}, "schema": []}
{"input": "Lunasin is a 43-amino acid naturally occurring chemopreventive peptide with demonstrated anti-cancer and anti-inflammatory properties.", "output": {"entities": {}}, "schema": []}
{"input": "The objectives of this study were to determine the effect of temperature on the secondary structure of lunasin, to develop a method of isolating lunasin from human plasma using an ion-exchange microspin column and to quantify the amount of lunasin using an optimized enzyme-linked immunosorbent assay.", "output": {"entities": {}}, "schema": []}
{"input": "Lunasin was purified using a combination of ion-exchange chromatography, ultrafiltration and gel filtration chromatography.", "output": {"entities": {}}, "schema": []}
{"input": "Circular dichroism showed that increased in temperature from 25 to 100 degrees C resulted in changes on the secondary structure of lunasin and its capability to interact with rabbit polyclonal antibody.", "output": {"entities": {}}, "schema": []}
{"input": "Enzyme linked immunosorbent assay showed that lunasin rabbit polyclonal antibody has a titer of 250 and a specific activity of 0. 05 mL/mu g.", "output": {"entities": {}}, "schema": []}
{"input": "A linear response was detected between 16 to 48 ng lunasin per mL (y = 0. 03x-0. 38, R (2) = 0. 96).", "output": {"entities": {}}, "schema": []}
{"input": "The use of diethylaminoethyl microspin column to isolate spiked lunasin in human plasma showed that most lunasin (37. 8-46. 5%) bound to the column eluted with Tris-HCl buffer, pH 7. 5 with a yield up to 76. 6%.", "output": {"entities": {"chemical": [{"text": "diethylaminoethyl", "start": 11, "end": 28}, {"text": "Tris-HCl", "start": 160, "end": 168}]}}, "schema": []}
{"input": "In conclusion, lunasin can be isolated from human plasma by a simple DEAE microspin column technique and can be quantified using a validated and optimized immunoassay procedure.", "output": {"entities": {}}, "schema": []}
{"input": "This method can be used directly to quantify lunasin from plasma in different human and animal studies aiming to determine its bioavailability.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of extraction procedures on phenolic content and antioxidant activity of Cretan barberry herb.", "output": {"entities": {}}, "schema": []}
{"input": "The main goal of present study was the development, optimization and application of different extraction protocols, especially those employing green technologies, in order to obtain from Berberis cretica extracts with high antioxidant capacity.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, the applied methods: maceration, ASE and SFE coupled with ASE were incorporated.", "output": {"entities": {}}, "schema": []}
{"input": "The antioxidant assessment was carried out using DPPH and total phenolic content (Folin-Ciocalteu) assays.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 49, "end": 53}]}}, "schema": []}
{"input": "Major constituents were elucidated using HPLC-DAD and UHPLC-HRMS/MS (hybrid IT-Orbital trap spectrometer) equipped with an ESI probe.", "output": {"entities": {}}, "schema": []}
{"input": "The chromatographic and spectral data revealed the presence of several simple phenolic acids, derivatives of both caffeic and benzoic acids, and flavonoids in the produced extracts.", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 78, "end": 92}, {"text": "caffeic and benzoic acids", "start": 114, "end": 139}, {"text": "flavonoids", "start": 145, "end": 155}]}}, "schema": []}
{"input": "It was clearly evidenced that the extraction method and solvents used affected both the activity and the chemical content of the results, significantly.", "output": {"entities": {}}, "schema": []}
{"input": "The most beneficial conditions were calculated for methanol and water: ethanol (50: 50) extracts derived from the combination of SFE and ASE methodologies.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 51, "end": 59}, {"text": "ethanol", "start": 71, "end": 78}]}}, "schema": []}
{"input": "Obtained results classify Cretan barberry as a strong antioxidant agent.", "output": {"entities": {}}, "schema": []}
{"input": "Purification, antioxidant activity and protein-precipitating capacity of punicalin from pomegranate husk.", "output": {"entities": {"chemical": [{"text": "punicalin", "start": 73, "end": 82}]}}, "schema": []}
{"input": "Punicalin is a kind of ellagitannin, existing in pomegranate husk, and has shown remarkable biological activities.", "output": {"entities": {"chemical": [{"text": "Punicalin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "A rapid and large-scale separation method of punicalin from pomegranate husk was established, using medium pressure liquid chromatography (MPLC).", "output": {"entities": {"chemical": [{"text": "punicalin", "start": 45, "end": 54}]}}, "schema": []}
{"input": "The optimal mobile phase consisted of 5% methanol and 0. 1% (v/v) TFA in water, and the optimal loading amount and flow rate were 1. 0 g and 80 ml/min, respectively.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 41, "end": 49}, {"text": "TFA", "start": 66, "end": 69}]}}, "schema": []}
{"input": "Under this condition, 339 mg of 95. 9% punicalin could be obtained in 40 min.", "output": {"entities": {"chemical": [{"text": "punicalin", "start": 39, "end": 48}]}}, "schema": []}
{"input": "59. 7 mg of 78. 0% gallic acid could be separated simultaneously.", "output": {"entities": {"chemical": [{"text": "gallic acid", "start": 19, "end": 30}]}}, "schema": []}
{"input": "This method was practical for industrial utilisation of pomegranate husk.", "output": {"entities": {}}, "schema": []}
{"input": "Afterwards, the antioxidant and protein-precipitating capacities of the purified punicalin, together with punicalagin, were evaluated.", "output": {"entities": {"chemical": [{"text": "punicalin", "start": 81, "end": 90}, {"text": "punicalagin", "start": 106, "end": 117}]}}, "schema": []}
{"input": "Results showed that punicalin had strong antioxidant activity, and it exhibited a low affinity for protein.", "output": {"entities": {"chemical": [{"text": "punicalin", "start": 20, "end": 29}]}}, "schema": []}
{"input": "This suggested that the antioxidant of punicalin would not be greatly masked by tannin-protein precipitation in application, and hence confirmed punicalin to be a promising antioxidant.", "output": {"entities": {"chemical": [{"text": "punicalin", "start": 39, "end": 48}, {"text": "tannin", "start": 80, "end": 86}, {"text": "punicalin", "start": 145, "end": 154}]}}, "schema": []}
{"input": "Binding of vitamin A with milk alpha-and beta-caseins.", "output": {"entities": {"chemical": [{"text": "vitamin A", "start": 11, "end": 20}]}}, "schema": []}
{"input": "The binding sites of retinol and retinoic acid with milk alpha-and beta-caseins were determined, using constant protein concentration and various retinoid contents.", "output": {"entities": {"chemical": [{"text": "retinol", "start": 21, "end": 28}, {"text": "retinoic acid", "start": 33, "end": 46}]}}, "schema": []}
{"input": "FTIR, UV-visible and fluorescence spectroscopic methods as well as molecular modelling were used to analyse retinol and retinoic acid binding sites, the binding constant and the effect of retinoid complexation on the stability and conformation of caseins.", "output": {"entities": {"chemical": [{"text": "retinol", "start": 108, "end": 115}, {"text": "retinoic acid", "start": 120, "end": 133}, {"text": "retinoid", "start": 188, "end": 196}]}}, "schema": []}
{"input": "Structural analysis showed that retinoids bind caseins via both hydrophilic and hydrophobic contacts with overall binding constants of K (retinol-) (alpha) (-caseins) = 1. 21 (+/- 0. 4) x 10 (5) M (-1) and K (retinol-) (beta) (-caseins) = 1. 11 (+/- 0. 5) x 10 (5) M (-1) and K (retinoic acid-) (alpha) (-caseins) = 6. 2 (+/- 0. 6) x 10 (4) M (-1) and K (retinoic acid-) (beta) (-caseins) = 6. 3 (+/- 0. 6) x 10 (4) M (-1).", "output": {"entities": {"chemical": [{"text": "retinoids", "start": 32, "end": 41}, {"text": "retinol", "start": 138, "end": 145}, {"text": "retinol", "start": 209, "end": 216}, {"text": "retinoic acid", "start": 279, "end": 292}, {"text": "retinoic acid", "start": 355, "end": 368}]}}, "schema": []}
{"input": "The number of bound retinol molecules per protein (n) was 1. 5 (+/- 0. 1) for alpha-casein and 1. 0 (+/- 0. 1) for beta-casein, while 1 molecule of retinoic acid was bound in the alpha-and beta-casein complexes.", "output": {"entities": {"chemical": [{"text": "retinol", "start": 20, "end": 27}, {"text": "retinoic acid", "start": 148, "end": 161}]}}, "schema": []}
{"input": "Molecular modelling showed different binding sites for retinol and retinoic acid on alpha-and beta-caseins with more stable complexes formed with alpha-casein.", "output": {"entities": {"chemical": [{"text": "retinol", "start": 55, "end": 62}, {"text": "retinoic acid", "start": 67, "end": 80}]}}, "schema": []}
{"input": "Retinoid-casein complexation induced minor alterations of protein conformation.", "output": {"entities": {"chemical": [{"text": "Retinoid", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Caseins might act as carriers for transportation of retinoids to target molecules.", "output": {"entities": {"chemical": [{"text": "retinoids", "start": 52, "end": 61}]}}, "schema": []}
{"input": "Effect of genotype, environment, and their interaction on phytochemical compositions and antioxidant properties of soft winter wheat flour.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of genotype (G), growing environment (E), and their interaction (G x E) on the antioxidant properties and chemical compositions were investigated using the flour samples of 10 wheat varieties grown in four different locations in Maryland.", "output": {"entities": {}}, "schema": []}
{"input": "Lutein content of wheat flour ranged from 0. 10 to 0. 69 mu g/g, and alpha-tocopherol ranged from 0. 12 to 0. 83 mu g/g.", "output": {"entities": {"chemical": [{"text": "Lutein", "start": 0, "end": 6}, {"text": "alpha-tocopherol", "start": 69, "end": 85}]}}, "schema": []}
{"input": "Total carotenoids were primarily affected by E (45. 7%), while G x E interaction had a larger effect on the level of total tocopherols (71. 6%).", "output": {"entities": {"chemical": [{"text": "tocopherols", "start": 123, "end": 134}]}}, "schema": []}
{"input": "E had the largest effect on antioxidant activity against oxygen, hydroxyl, and ABTS (. +) radicals.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 57, "end": 63}, {"text": "hydroxyl", "start": 65, "end": 73}, {"text": "ABTS (. +)", "start": 79, "end": 89}]}}, "schema": []}
{"input": "G had the least influence on the measured phytochemicals and antioxidant activity assays.", "output": {"entities": {}}, "schema": []}
{"input": "Total carotenoids had a significant correlation with average low air temperature (r = 0. 359, p < 0. 01) as well as precipitation level (r = 0. 214, p < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "ABTS (. +) radical scavenging capacity had a positive correlation with average air temperature (r = 0. 705, p < 0. 01), while hydroxyl radical scavenging capacity had a negative correlation with temperature (r =-0. 269. p < 0. 01).", "output": {"entities": {"chemical": [{"text": "ABTS (. +)", "start": 0, "end": 10}, {"text": "hydroxyl", "start": 126, "end": 134}]}}, "schema": []}
{"input": "These results show that environment, genotype, and their interaction could influence the levels of lipophilic antioxidants and antioxidant activities of wheat flour.", "output": {"entities": {}}, "schema": []}
{"input": "Arsenic speciation analysis in mono-varietal wines by on-line ionic liquid-based dispersive liquid-liquid microextraction.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "A highly efficient separation and pre-concentration method for arsenic species determination, based on ionic liquid (IL) dispersive microextraction technique implemented in a flow analysis system, is proposed.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Highly selective separation of arsenite species [As (III)] was achieved by chelation with sodium diethyldithiocarbamate (DDTC) followed by dispersion with 40 mg of 1-octyl-3-methylimidazolium hexafluorophosphate ([C (8) mim] [PF (6)]) IL.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 31, "end": 39}, {"text": "As (III)", "start": 49, "end": 57}, {"text": "sodium diethyldithiocarbamate", "start": 90, "end": 119}, {"text": "DDTC", "start": 121, "end": 125}, {"text": "1-octyl-3-methylimidazolium hexafluorophosphate", "start": 164, "end": 211}, {"text": "[C (8) mim] [PF (6)]", "start": 213, "end": 233}]}}, "schema": []}
{"input": "Analyte extraction, retention and separation of IL phase were achieved with a packed microcolumn and As (III) was determined in eluent solution by electrothermal atomic absorption spectrometry (ETAAS).", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 101, "end": 109}]}}, "schema": []}
{"input": "Concentration of As (V) was deduced by the difference between total inorganic arsenic and As (III).", "output": {"entities": {"chemical": [{"text": "As (V)", "start": 17, "end": 23}, {"text": "arsenic", "start": 78, "end": 85}, {"text": "As (III)", "start": 90, "end": 98}]}}, "schema": []}
{"input": "Thus, determination of total arsenic was performed by previous degradation of organo-arsenic species, followed by a reduction.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 29, "end": 36}, {"text": "organo-arsenic", "start": 78, "end": 92}]}}, "schema": []}
{"input": "Under optimal conditions, As (III) extraction efficiency was 100% and a sensitivity enhancement factor of 46 was obtained with only 4. 0 ml of sample The method was successfully applied for arsenic speciation studies in mono-varietal wines.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 26, "end": 34}, {"text": "arsenic", "start": 190, "end": 197}]}}, "schema": []}
{"input": "Stabilization of anthocyanin and skullcap flavone complexes--investigations with computer simulation and experimental methods.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 17, "end": 28}, {"text": "flavone", "start": 42, "end": 49}]}}, "schema": []}
{"input": "We examined the stabilization of anthocyanins with flavones from the practical and theoretical perspective.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 33, "end": 45}, {"text": "flavones", "start": 51, "end": 59}]}}, "schema": []}
{"input": "The influence of addition of skullcap flavones, heating to 50 degrees C, and 12 day storage time (in the presence and absence of light) on the stability of anthocyanins in honeysuckle concentrates was investigated experimentally.", "output": {"entities": {"chemical": [{"text": "flavones", "start": 38, "end": 46}, {"text": "anthocyanins", "start": 156, "end": 168}]}}, "schema": []}
{"input": "Theoretical study was conducted with molecular dynamics methods in a model system, preceded by simulated annealing and thermalization.", "output": {"entities": {}}, "schema": []}
{"input": "By the methods of the computer simulation of the copigmentation process we determined the sites responsible for the stabilization of a cyanidin quinoidal base-baicalin complex.", "output": {"entities": {"chemical": [{"text": "cyanidin quinoidal base", "start": 135, "end": 158}, {"text": "baicalin", "start": 159, "end": 167}]}}, "schema": []}
{"input": "We revealed both direct and water-mediated hydrogen bondings that keep the lamellar stacking structure of these molecules in the bounded form in water medium.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 43, "end": 51}]}}, "schema": []}
{"input": "The stacking occurs also due to hydrophobic interactions of the rings of both molecules.", "output": {"entities": {}}, "schema": []}
{"input": "The experimental part of the study confirmed the effectiveness of anthocyanins stabilization in a concentrate of honeysuckle with the use of skullcap flavones.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 66, "end": 78}, {"text": "flavones", "start": 150, "end": 158}]}}, "schema": []}
{"input": "Burdock fructooligosaccharide induces fungal resistance in postharvest Kyoho grapes by activating the salicylic acid-dependent pathway and inhibiting browning.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 102, "end": 116}]}}, "schema": []}
{"input": "Burdock fructooligosaccharide (BFO) is a natural elicitor from Arcitum lappa.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of BFO in controlling postharvest disease in grape, apple, banana, kiwi, citrus, strawberry, and pear were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The disease index, decay percentage, and area under the disease progress curve indicated that BFO has general control effects on postharvest disease of fruits.", "output": {"entities": {}}, "schema": []}
{"input": "Kyoho grapes were studied to elucidate the mechanism of BFO in boosting the resistance of grapes to Botrytis cinerea infection.", "output": {"entities": {}}, "schema": []}
{"input": "BFO treatment induced upregulation of the npr1, pr1, pal, and sts genes, and inhibited the total phenol content decrease, which activated chitinase and beta-1, 3-glucanase.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 97, "end": 103}]}}, "schema": []}
{"input": "These results indicated that the salicylic acid-dependent signalling pathway was induced.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 33, "end": 47}]}}, "schema": []}
{"input": "The delayed colour change and peroxidase and polyphenoloxidase activity suggested that BFO delayed grape browning.", "output": {"entities": {}}, "schema": []}
{"input": "The reduced respiration rate, weight loss, and titratable acidity prolonged the shelf life of postharvest grapes.", "output": {"entities": {}}, "schema": []}
{"input": "BFO is a promising elicitor in postharvest disease control.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.).", "output": {"entities": {}}, "schema": []}
{"input": "Legumes are the bas e s diet in several countries.", "output": {"entities": {}}, "schema": []}
{"input": "They hold a high nutritional value, but other properties related to human health are nowadays being studied.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c. v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS.", "output": {"entities": {"chemical": [{"text": "Phenolic", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The antioxidant activity was evaluated by ORAC.", "output": {"entities": {}}, "schema": []}
{"input": "Astrocytes cultures (U-373) have been used to test their neuroprotective effect.", "output": {"entities": {}}, "schema": []}
{"input": "Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method.", "output": {"entities": {"chemical": [{"text": "sulphorhodamine B", "start": 155, "end": 172}]}}, "schema": []}
{"input": "Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 44, "end": 52}]}}, "schema": []}
{"input": "Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 51, "end": 57}, {"text": "phenolic", "start": 251, "end": 259}, {"text": "anthocyanins", "start": 278, "end": 290}]}}, "schema": []}
{"input": "This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Glucose, fructose and sucrose increase the solubility of protein-tannin complexes and at high concentration, glucose and sucrose interfere with bisulphite bleaching of wine pigments.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}, {"text": "fructose", "start": 9, "end": 17}, {"text": "sucrose", "start": 22, "end": 29}, {"text": "tannin", "start": 65, "end": 71}, {"text": "glucose", "start": 109, "end": 116}, {"text": "sucrose", "start": 121, "end": 128}, {"text": "bisulphite", "start": 144, "end": 154}]}}, "schema": []}
{"input": "Wines were modified with increasing sugar concentrations and decreasing tannin concentrations and analysed by a combination of protein precipitation and bisulphite bleaching.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 36, "end": 41}, {"text": "tannin", "start": 72, "end": 78}, {"text": "bisulphite", "start": 153, "end": 163}]}}, "schema": []}
{"input": "Increasing sugar concentration decreased the precipitation of tannin and protein-precipitable polymeric pigments (PPP).", "output": {"entities": {"chemical": [{"text": "sugar", "start": 11, "end": 16}, {"text": "tannin", "start": 62, "end": 68}]}}, "schema": []}
{"input": "The use of a hydrogen bond disruptor (urea) to reduce protein-tannin and protein-pigment complex formation showed that the effect of sugar concentration occurred by increasing the solubility of the tannin-protein complex, not by interfering with protein-tannin complex formation.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 13, "end": 21}, {"text": "urea", "start": 38, "end": 42}, {"text": "tannin", "start": 62, "end": 68}, {"text": "sugar", "start": 133, "end": 138}, {"text": "tannin", "start": 198, "end": 204}, {"text": "tannin", "start": 254, "end": 260}]}}, "schema": []}
{"input": "By increasing the solubility of pigment-protein complexes, non-protein-precipitable polymeric pigments (nPPP) appeared to increase.", "output": {"entities": {}}, "schema": []}
{"input": "There was also an increase in total polymeric pigments at each tannin concentration with increasing glucose and sucrose concentration, indicating that sugar concentration might also affect bisulphite bleaching of wine pigments.", "output": {"entities": {"chemical": [{"text": "tannin", "start": 63, "end": 69}, {"text": "glucose", "start": 100, "end": 107}, {"text": "sucrose", "start": 112, "end": 119}, {"text": "sugar", "start": 151, "end": 156}, {"text": "bisulphite", "start": 189, "end": 199}]}}, "schema": []}
{"input": "While a significant effect of sugar concentration on tannin-protein complex solubility was observed, these effects were greatest at sugar concentrations far in excess of normal wine making conditions.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 30, "end": 35}, {"text": "tannin", "start": 53, "end": 59}, {"text": "sugar", "start": 132, "end": 137}]}}, "schema": []}
{"input": "Under normal wine making conditions, sugar concentration will have a negligible effect on protein-precipitable tannin, PPP and nPPP concentrations.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 37, "end": 42}, {"text": "tannin", "start": 111, "end": 117}]}}, "schema": []}
{"input": "Structure and antioxidant activity of beta-lactoglobulin-glycoconjugates obtained by high-intensity-ultrasound-induced Maillard reaction in aqueous model systems under neutral conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Sonication is a new processing technology in the dairy industry.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to test glycation of beta-lactoglobulin (BLG) in Maillard reaction (MR) induced by high-intensity ultrasound in aqueous solution under neutral conditions at 10-15 degrees C, which is not favourable for the MR.", "output": {"entities": {}}, "schema": []}
{"input": "BLG was sonicated in the presence of glucose, galactose, lactose, fructose, ribose and arabinose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 37, "end": 44}, {"text": "galactose", "start": 46, "end": 55}, {"text": "lactose", "start": 57, "end": 64}, {"text": "fructose", "start": 66, "end": 74}, {"text": "ribose", "start": 76, "end": 82}, {"text": "arabinose", "start": 87, "end": 96}]}}, "schema": []}
{"input": "Formation of Maillard reaction products (MRPs) was monitored by mass spectrometry, spectrophotometry and fluorimetry.", "output": {"entities": {}}, "schema": []}
{"input": "Ultrasound treatment resulted in formation of MRPs with all tested carbohydrates.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 67, "end": 80}]}}, "schema": []}
{"input": "Ribose induced the highest degree of modification resulting in 76% of BLG modified and an average of three anhydroribose units attached.", "output": {"entities": {"chemical": [{"text": "Ribose", "start": 0, "end": 6}, {"text": "anhydroribose", "start": 107, "end": 120}]}}, "schema": []}
{"input": "Circular dichroism spectra analyses indicated only minor alterations in secondary and tertiary structures.", "output": {"entities": {}}, "schema": []}
{"input": "MRP obtained by ultrasound exhibited 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity and possessed increased iron-chelating activity and reducing power.", "output": {"entities": {"chemical": [{"text": "1, 1-diphenyl-2-picrylhydrazyl", "start": 37, "end": 67}, {"text": "DPPH", "start": 69, "end": 73}, {"text": "iron", "start": 119, "end": 123}]}}, "schema": []}
{"input": "High-intensity ultrasound efficiently promotes BLG-glycoconjugates formation by MR in aqueous solutions under non-denaturing conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of processing on the volatile profile of strawberry spreads made with isomaltulose.", "output": {"entities": {"chemical": [{"text": "isomaltulose", "start": 80, "end": 92}]}}, "schema": []}
{"input": "A new strawberry spread formulated with fructose and isomaltulose (replacing sucrose partially or totally) and a high percentage of fruit was developed in line with the new trend of healthier products.", "output": {"entities": {"chemical": [{"text": "fructose", "start": 40, "end": 48}, {"text": "isomaltulose", "start": 53, "end": 65}, {"text": "sucrose", "start": 77, "end": 84}]}}, "schema": []}
{"input": "This work studies the influence of some process variables (percentage of sugar, pectin and citric acid, and time of thermal treatment) on the volatile profile of these spreads with different formulations.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 73, "end": 78}, {"text": "citric acid", "start": 91, "end": 102}]}}, "schema": []}
{"input": "The ripeness of the raw strawberries influences the concentrations of some of the compounds in the spreads, such as isobutyl acetate, butyl butyrate, 3-hexen-1-yl acetate or propan-2-ol.", "output": {"entities": {"chemical": [{"text": "isobutyl acetate", "start": 116, "end": 132}, {"text": "butyl butyrate", "start": 134, "end": 148}, {"text": "3-hexen-1-yl acetate", "start": 150, "end": 170}, {"text": "propan-2-ol", "start": 174, "end": 185}]}}, "schema": []}
{"input": "The process conditions have an important effect on the volatile profiles.", "output": {"entities": {}}, "schema": []}
{"input": "Most of the esters and alcohols decreased whereas 13 new compounds appear, mostly furans (furfural, 2-acetylfurane, 5-methyl furfural, mesifurane) and aldehydes (octanal, nonanal, decanal and benzaldeyhde).", "output": {"entities": {"chemical": [{"text": "esters", "start": 12, "end": 18}, {"text": "alcohols", "start": 23, "end": 31}, {"text": "furans", "start": 82, "end": 88}, {"text": "furfural", "start": 90, "end": 98}, {"text": "2-acetylfurane", "start": 100, "end": 114}, {"text": "5-methyl furfural", "start": 116, "end": 133}, {"text": "mesifurane", "start": 135, "end": 145}, {"text": "aldehydes", "start": 151, "end": 160}, {"text": "octanal", "start": 162, "end": 169}, {"text": "nonanal", "start": 171, "end": 178}, {"text": "decanal", "start": 180, "end": 187}, {"text": "benzaldeyhde", "start": 192, "end": 204}]}}, "schema": []}
{"input": "In general, the spreads formulated with sucrose-isomaltulose that contained higher levels of pectin and citric acid gave better results in the preservation of the original aromatic compounds in raw strawberries.", "output": {"entities": {"chemical": [{"text": "sucrose", "start": 40, "end": 47}, {"text": "isomaltulose", "start": 48, "end": 60}, {"text": "citric acid", "start": 104, "end": 115}]}}, "schema": []}
{"input": "Optimization of ABTS radical cation assay specifically for determination of antioxidant capacity of intracellular extracts of microalgae and cyanobacteria.", "output": {"entities": {"chemical": [{"text": "ABTS radical cation", "start": 16, "end": 35}]}}, "schema": []}
{"input": "A renewed interest in antioxidants has arisen in recent years; microalgae and cyanobacteria are potential sources thereof for use as food/feed ingredients.", "output": {"entities": {}}, "schema": []}
{"input": "However, improved methods for comprehensive screening of antioxidant capacity specifically in intracellular extracts of marine microorganisms are required-encompassing lipophilic and hydrophilic compounds simultaneously.", "output": {"entities": {}}, "schema": []}
{"input": "The original ABTS method was thus improved, and in particular the procedures of cell disruption and storage were optimized.", "output": {"entities": {"chemical": [{"text": "ABTS", "start": 13, "end": 17}]}}, "schema": []}
{"input": "The best solvent found was ethanol/water (1: 1, v/v).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 27, "end": 34}]}}, "schema": []}
{"input": "The reaction to form ABTS (+) in said solvent was essentially complete by eight hours, and this radical cation was stable for at least 6 days; at room temperature, the ABTS (+) solution remained within an allowable analytical range for up to 13 h.", "output": {"entities": {"chemical": [{"text": "ABTS (+)", "start": 21, "end": 29}, {"text": "ABTS (+)", "start": 168, "end": 176}]}}, "schema": []}
{"input": "Ultra Turrax was the best cell disruption method, and refrigeration was the best preservation method.", "output": {"entities": {}}, "schema": []}
{"input": "This improved methodology was validated with four representative strains that respond poorly to cell disruption.", "output": {"entities": {}}, "schema": []}
{"input": "Biogenic amines formation in Streptococcus thermophilus isolated from home-made natural yogurt.", "output": {"entities": {"chemical": [{"text": "amines", "start": 9, "end": 15}]}}, "schema": []}
{"input": "Twelve different biogenic amines formation in 58 isolates of Streptococcus thermophilus from home-made natural yogurt were investigated in histidine (HDB) and lysine decarboxylase broth (LDB).", "output": {"entities": {"chemical": [{"text": "amines", "start": 26, "end": 32}, {"text": "histidine", "start": 139, "end": 148}, {"text": "lysine", "start": 159, "end": 165}]}}, "schema": []}
{"input": "All S. thermophilus isolates had an ability to produce twelve different biogenic amines in HDB and LDB.", "output": {"entities": {"chemical": [{"text": "amines", "start": 81, "end": 87}]}}, "schema": []}
{"input": "Most of the S. thermophilus isolates formed low amounts of histamine (1-50 mg/L) from histidine.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 59, "end": 68}, {"text": "histidine", "start": 86, "end": 95}]}}, "schema": []}
{"input": "Apart from one isolate, S. thermophilus produced tyramine at low (47 isolates) and medium (10 isolates) levels.", "output": {"entities": {"chemical": [{"text": "tyramine", "start": 49, "end": 57}]}}, "schema": []}
{"input": "The amount of each specific biogenic amine produced by S. thermophilus was generally lower than 100 mg L (-1).", "output": {"entities": {"chemical": [{"text": "amine", "start": 37, "end": 42}]}}, "schema": []}
{"input": "Also, the presence of hdcA gene was investigated using PCR technique and relation between gene and histamine production was conducted in S. thermophilus isolates.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 99, "end": 108}]}}, "schema": []}
{"input": "This study showed that most of the S. thermophilus isolates have the ability to form biogenic amines, especially histamine, and tyramine, which is an important consideration when selecting strains as starter cultures.", "output": {"entities": {"chemical": [{"text": "amines", "start": 94, "end": 100}, {"text": "histamine", "start": 113, "end": 122}, {"text": "tyramine", "start": 128, "end": 136}]}}, "schema": []}
{"input": "Shelf-life of infrared dry-roasted almonds.", "output": {"entities": {}}, "schema": []}
{"input": "Infrared heating was recently used to develop a more efficient roasting technology than traditional hot air roasting.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, in this study, we evaluated the shelf-life of almonds roasted with three different approaches, namely infrared (IR), sequential infrared and hot air (SIRHA) and regular hot air (HA).", "output": {"entities": {}}, "schema": []}
{"input": "Nine medium roasted almond samples produced by the aforementioned heating methods were processed at three different temperatures (130, 140 and 150 degrees C), packed in paper bags and then stored at 37 degrees C for three, six or eight months.", "output": {"entities": {}}, "schema": []}
{"input": "Shelf-life of the roasted almonds was determined by measuring the changes in colour, peroxide value, moisture content, water activity, volatile components and sensory quality.", "output": {"entities": {"chemical": [{"text": "peroxide", "start": 85, "end": 93}]}}, "schema": []}
{"input": "No significant difference was observed in moisture content and water activity among the almond samples processed with different roasting methods and stored under the same conditions.", "output": {"entities": {}}, "schema": []}
{"input": "GC/MS analysis showed that aldehydes, alcohols, and pyrazines were the main volatile components of almonds.", "output": {"entities": {"chemical": [{"text": "aldehydes", "start": 27, "end": 36}, {"text": "alcohols", "start": 38, "end": 46}, {"text": "pyrazines", "start": 52, "end": 61}]}}, "schema": []}
{"input": "Aliphatic aldehydes such as hexanal, (E)-2-octenal, and nonanal were produced as off-odours during storage.", "output": {"entities": {"chemical": [{"text": "Aliphatic aldehydes", "start": 0, "end": 19}, {"text": "hexanal", "start": 28, "end": 35}, {"text": "(E)-2-octenal", "start": 37, "end": 50}, {"text": "nonanal", "start": 56, "end": 63}]}}, "schema": []}
{"input": "Although the overall quality of roasted almonds produced with SIRHA and HA heating was similar during the first three months of storage, their peroxide value and concentration of aliphatic aldehydes differed significantly for different roasting methods and increased significantly in all roasted samples during storage.", "output": {"entities": {"chemical": [{"text": "peroxide", "start": 143, "end": 151}, {"text": "aliphatic aldehydes", "start": 179, "end": 198}]}}, "schema": []}
{"input": "We postulate that hexanal and nonanal might be better indicators of the shelf life of roasted almonds than the current standard, peroxide value.", "output": {"entities": {"chemical": [{"text": "hexanal", "start": 18, "end": 25}, {"text": "nonanal", "start": 30, "end": 37}, {"text": "peroxide", "start": 129, "end": 137}]}}, "schema": []}
{"input": "Synthesis of new triazole acetamides with inotropic effects.", "output": {"entities": {"chemical": [{"text": "triazole acetamides", "start": 17, "end": 36}]}}, "schema": []}
{"input": "A series of new triazole acetamides 5a-w were synthesized and evaluated for their positive inotropic activity of left atrium stroke volume on isolated rabbit-heart preparations.", "output": {"entities": {"chemical": [{"text": "triazole acetamides", "start": 16, "end": 35}]}}, "schema": []}
{"input": "The majority of the derivatives presented favorable in vitro activity compared with the reference drug, milrinone.", "output": {"entities": {"chemical": [{"text": "milrinone", "start": 104, "end": 113}]}}, "schema": []}
{"input": "Among them triazole acetamide 5a was identified as the most potent with 20. 29 +/- 0. 18% increased stroke volume (milrinone: 2. 46 +/- 0. 07%) at a concentration of 3 x 10 (-5) M.", "output": {"entities": {"chemical": [{"text": "triazole acetamide", "start": 11, "end": 29}, {"text": "milrinone", "start": 115, "end": 124}]}}, "schema": []}
{"input": "The chronotropic effects of the compounds having inotropic effects were also evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Novel limonene and citral based 2, 5-disubstituted-1, 3, 4-oxadiazoles: a natural product coupled approach to semicarbazones for antiepileptic activity.", "output": {"entities": {"chemical": [{"text": "limonene", "start": 6, "end": 14}, {"text": "citral", "start": 19, "end": 25}, {"text": "2, 5-disubstituted-1, 3, 4-oxadiazoles", "start": 32, "end": 70}, {"text": "semicarbazones", "start": 110, "end": 124}]}}, "schema": []}
{"input": "Two novel series of N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(2-methyl-5-(prop-1-en-2-yl) cyclohex-2-enylidene) semicarbazide and N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(3, 7-dimethylocta-3, 6-dienylidene)-semicarbazide were synthesized to meet structural prerequisite indispensable for anticonvulsant activity.", "output": {"entities": {"chemical": [{"text": "N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(2-methyl-5-(prop-1-en-2-yl) cyclohex-2-enylidene) semicarbazide", "start": 20, "end": 150}, {"text": "N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(3, 7-dimethylocta-3, 6-dienylidene)-semicarbazide", "start": 155, "end": 271}]}}, "schema": []}
{"input": "The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models.", "output": {"entities": {"chemical": [{"text": "pentylenetrtrazole", "start": 120, "end": 138}, {"text": "strychnine", "start": 164, "end": 174}]}}, "schema": []}
{"input": "The rotorod test was conducted to evaluate neurotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Some of the selected active compounds were subjected to GABA assay to confirm their mode of action.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 56, "end": 60}]}}, "schema": []}
{"input": "The outcome of the present investigations proved that the four binding sites pharmacophore model is vital for anticonvulsant activity.", "output": {"entities": {}}, "schema": []}
{"input": "The efforts were also made to establish structure-activity relationships among test compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Lead optimization of isocytosine-derived xanthine oxidase inhibitors.", "output": {"entities": {"chemical": [{"text": "isocytosine", "start": 21, "end": 32}, {"text": "xanthine", "start": 41, "end": 49}]}}, "schema": []}
{"input": "We report our attempts at improving the oral efficacy of low-nanomolar inhibitors of xanthine oxidase from isocytosine series through chemical modifications.", "output": {"entities": {"chemical": [{"text": "xanthine", "start": 85, "end": 93}, {"text": "isocytosine", "start": 107, "end": 118}]}}, "schema": []}
{"input": "Our lead compound had earlier shown good in vivo efficacy when administered intraperitoneally but not orally.", "output": {"entities": {}}, "schema": []}
{"input": "Several modifications are reported here which achieved more than twofold improvement in exposure.", "output": {"entities": {}}, "schema": []}
{"input": "A compound with significant improvement in oral efficacy was also obtained.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery and preliminary structure-activity relationship analysis of 1, 14-sperminediphenylacetamides as potent and selective antimalarial lead compounds.", "output": {"entities": {"chemical": [{"text": "1, 14-sperminediphenylacetamides", "start": 70, "end": 102}]}}, "schema": []}
{"input": "Screening of synthesized and isolated marine natural products for in vitro activity against four parasitic protozoa has identified the ascidian metabolite 1, 14-sperminedihomovanillamide (orthidine F, 1) as being a non-toxic, moderate growth inhibitor of Plasmodium falciparum (IC (50) 0. 89 mu M).", "output": {"entities": {"chemical": [{"text": "1, 14-sperminedihomovanillamide", "start": 155, "end": 186}, {"text": "orthidine F", "start": 188, "end": 199}]}}, "schema": []}
{"input": "Preliminary structure-activity relationship investigation identified essentiality of the spermine polyamine core and the requirement for 1, 14-disubstitution for potent activity.", "output": {"entities": {"chemical": [{"text": "spermine polyamine", "start": 89, "end": 107}]}}, "schema": []}
{"input": "One analogue, 1, 14-spermine-di-(2-hydroxyphenylacetamide) (3), exhibited two orders of magnitude increased anti-P.", "output": {"entities": {"chemical": [{"text": "1, 14-spermine-di-(2-hydroxyphenylacetamide)", "start": 14, "end": 58}]}}, "schema": []}
{"input": "f activity (IC (50) 8. 6 nM) with no detectable in vitro toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The ease of synthesis of phenylacetamido-polyamines, coupled with potent nM levels of activity towards dual drug resistant strains of P. falciparum makes this compound class of interest in the development of new antimalarial therapeutics.", "output": {"entities": {"chemical": [{"text": "phenylacetamido-polyamines", "start": 25, "end": 51}]}}, "schema": []}
{"input": "Lead optimization of a dihydropyrrolopyrimidine inhibitor against phosphoinositide 3-kinase (PI3K) to improve the phenol glucuronic acid conjugation.", "output": {"entities": {"chemical": [{"text": "dihydropyrrolopyrimidine", "start": 23, "end": 47}, {"text": "phenol glucuronic acid", "start": 114, "end": 136}]}}, "schema": []}
{"input": "Our lead compound for a phosphoinositide 3-kinase (PI3K) inhibitor (1) was metabolically unstable because of rapid glucuronidation of the phenol moiety.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 138, "end": 144}]}}, "schema": []}
{"input": "Based on structure-activity relationship (SAR) information and a FlexSIS docking simulation score, aminopyrimidine was identified as a bioisostere of phenol.", "output": {"entities": {"chemical": [{"text": "aminopyrimidine", "start": 99, "end": 114}, {"text": "phenol", "start": 150, "end": 156}]}}, "schema": []}
{"input": "An X-ray structure study revealed a hydrogen bonding pattern of aminopyrimidine derivatives.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 36, "end": 44}, {"text": "aminopyrimidine", "start": 64, "end": 79}]}}, "schema": []}
{"input": "Finally, aminopyrimidine derivatives 33 showed strong tumor growth inhibition against a KPL-4 breast cancer xenograft model in vivo.", "output": {"entities": {"chemical": [{"text": "aminopyrimidine", "start": 9, "end": 24}]}}, "schema": []}
{"input": "Heterobivalent dual-target probe for targeting GRP and Y1 receptors on tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "Receptor targeting ligands for imaging and/or therapy of cancer are limited by heterogeneity of receptor expression by tumor cells, both inter-patient and intra-patient.", "output": {"entities": {}}, "schema": []}
{"input": "It is often more important for imaging agents to identify local and distant spread of disease than it is to identify a specific receptor presence.", "output": {"entities": {}}, "schema": []}
{"input": "Two natural hormone peptide receptors, GRPR and Y1, are specifically interesting because expression of GRPR, Y1 or both is up-regulated in most breast cancers.", "output": {"entities": {}}, "schema": []}
{"input": "We describe here the design and development of a new heterobivalent peptide ligand, truncated bombesin (t-BBN)/BVD15-DO3A, for dual-targeting of GRPR and Y1, and validation of its dual binding capability.", "output": {"entities": {"chemical": [{"text": "bombesin", "start": 94, "end": 102}]}}, "schema": []}
{"input": "Such a probe should be useful in imaging cells, tissues and tumors that are GRPR and/or Y1 positive and should target radioisotopes, for example, (68) Ga and/or (177) Lu, to more tumors cells than single GRPR or Y1 targeted probes.", "output": {"entities": {}}, "schema": []}
{"input": "A GRP targeting ligand, J-G-Abz4-QWAVGHLM-NH (2) (J-G-Abz4-t-BBN), and an Y1 targeting ligand, INP-K [epsilon-J-(alpha-DO3A-epsilon-DGa)-K]-YRLRY-NH (2) ([epsilon-J-(alpha-DO3A-epsilon-DGa)-K]-BVD-15), were synthesized and coupled to produce the heterobivalent ligand, t-BBN/BVD15-DO3A.", "output": {"entities": {}}, "schema": []}
{"input": "Competitive displacement binding assays using t-BBN/BVD15-DO3A against (125) I-Tyr (4)-BBN yielded an IC (50) value of 18 +/- 0. 7 nM for GRPR in T-47D cells, a human breast cancer cell line.", "output": {"entities": {"chemical": [{"text": "(125) I", "start": 71, "end": 78}, {"text": "Tyr", "start": 79, "end": 82}]}}, "schema": []}
{"input": "A similar assay using t-BBN/BVD15-DO3A against porcine (125) I-NPY showed IC (50) values of 80 +/- 11 nM for Y1 receptor in MCF7 cells, another human breast cancer cell line.", "output": {"entities": {"chemical": [{"text": "(125) I", "start": 55, "end": 62}]}}, "schema": []}
{"input": "In conclusion, it is possible to construct a single DO3A chelate containing probe that can target both GRPR and Y1 on human tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole.", "output": {"entities": {"chemical": [{"text": "benzimidazole", "start": 87, "end": 100}]}}, "schema": []}
{"input": "A chemically diverse library of about 400, 000 small molecules was screened for antiviral activity against lentiviral pseudotypes with the Lassa virus envelope glycoprotein (LASV GP) gene incorporated.", "output": {"entities": {}}, "schema": []}
{"input": "High-throughput screening resulted in discovery of a hit compound (ST-37) possessing a benzimidazole core which led to a potent compound series.", "output": {"entities": {"chemical": [{"text": "ST-37", "start": 67, "end": 72}, {"text": "benzimidazole", "start": 87, "end": 100}]}}, "schema": []}
{"input": "Herein, we report SAR studies which involved structural modifications to the phenyl rings and methylamino linker portion attached to the benzimidazole core.", "output": {"entities": {"chemical": [{"text": "phenyl", "start": 77, "end": 83}, {"text": "methylamino", "start": 94, "end": 105}, {"text": "benzimidazole", "start": 137, "end": 150}]}}, "schema": []}
{"input": "Many analogs in this study possessed single digit nanomolar potency against LASV pseudotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds in this benzimidazole series also exhibited nanomolar antiviral activity against pseudotypes generated from other arenavirus envelopes indicating the potential for development of a broad-spectrum inhibitor.", "output": {"entities": {"chemical": [{"text": "benzimidazole", "start": 18, "end": 31}]}}, "schema": []}
{"input": "Ultimately, lead compound ST-193 was identified and later found to be efficacious in a lethal LASV guinea pig model showing superior protection compared to ribavirin treatment.", "output": {"entities": {"chemical": [{"text": "ST-193", "start": 26, "end": 32}]}}, "schema": []}
{"input": "Calpains participate in nerve terminal degeneration induced by spider and snake presynaptic neurotoxins.", "output": {"entities": {}}, "schema": []}
{"input": "alpha-latrotoxin and snake presynaptic phospholipases A2 neurotoxins target the presynaptic membrane of axon terminals of the neuromuscular junction causing paralysis.", "output": {"entities": {}}, "schema": []}
{"input": "These neurotoxins display different biochemical activities, but similarly alter the presynaptic membrane permeability causing Ca (2 +) overload within the nerve terminals, which in turn induces nerve degeneration.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 126, "end": 134}]}}, "schema": []}
{"input": "Using different methods, here we show that the calcium-activated proteases calpains are involved in the cytoskeletal rearrangements that we have previously documented in neurons exposed to alpha-latrotoxin or to snake presynaptic phospholipases A2 neurotoxins.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 47, "end": 54}]}}, "schema": []}
{"input": "These results indicate that calpains, activated by the massive calcium influx from the extracellular medium, target fundamental components of neuronal cytoskeleton such as spectrin and neurofilaments, whose cleavage is functional to the ensuing nerve terminal fragmentation.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Spontaneous and experimental poisoning by Marsdenia megalantha Goyder & Morillo in ruminants and a pig.", "output": {"entities": {}}, "schema": []}
{"input": "Marsdenia megalantha is a rupicolous shrub with succulent roots from the semiarid region of Brazil that is known to cause fatal poisoning in livestock.", "output": {"entities": {}}, "schema": []}
{"input": "We reported spontaneous cases of poisoning by M. megalantha roots in bovine, caprine, ovine, and equine species.", "output": {"entities": {}}, "schema": []}
{"input": "The clinical and pathological findings of experimental administration of M. megalantha to sheep, goats, a calf and a pig are reported.", "output": {"entities": {}}, "schema": []}
{"input": "Three goats, two sheep and a calf were dosed once orally with freshly chopped roots at dose of 25 g wet plant/kg bw; another sheep and a pig were dosed with 10 g wet plant/kg bw.", "output": {"entities": {}}, "schema": []}
{"input": "Poisoning occurred in all of the animals except the three goats.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical signs of poisoning included tachycardia, opisthotonus, ruminal bloat, dyspnea, nystagmus, mydriasis, ataxia, and recumbence with paddling movements.", "output": {"entities": {}}, "schema": []}
{"input": "Pathological evaluation showed segmental laminar neuronal necrosis and spongiosis in the telencephalic cortex and degeneration of Purkinje cells.", "output": {"entities": {}}, "schema": []}
{"input": "The picrate paper procedure detected no cyanide in the plant roots, but the reaction used for nitrate detection gave a strongly positive response.", "output": {"entities": {"chemical": [{"text": "cyanide", "start": 40, "end": 47}, {"text": "nitrate", "start": 94, "end": 101}]}}, "schema": []}
{"input": "In conclusion, M. megalantha is a poisonous plant that produces acute poisoning characterized mainly by nervous disturbances.", "output": {"entities": {}}, "schema": []}
{"input": "Livestock producers should offer alternative food during the dry and early rainy seasons to avoid the poisoning by this plant.", "output": {"entities": {}}, "schema": []}
{"input": "Small and colorful stones make beautiful mosaics: fragment-based chemogenomics.", "output": {"entities": {}}, "schema": []}
{"input": "Smaller stones with a wide variety of colors make a higher resolution mosaic.", "output": {"entities": {}}, "schema": []}
{"input": "In much the same way, smaller chemical entities that are structurally diverse are better able to interrogate protein binding sites.", "output": {"entities": {}}, "schema": []}
{"input": "This feature article describes the construction of a diverse fragment library and an analysis of the screening of six representative protein targets belonging to three diverse target classes (G protein-coupled receptors ADRB2, H1R, H3R, and H4R, the ligand-gated ion channel 5-HT3R, and the kinase PKA) using chemogenomics approaches.", "output": {"entities": {}}, "schema": []}
{"input": "The integration of experimentally determined bioaffinity profiles across related and unrelated protein targets and chemogenomics analysis of fragment binding and protein structure allow the identification of: (i) unexpected similarities and differences in ligand binding properties, and (ii) subtle ligand affinity and selectivity cliffs.", "output": {"entities": {}}, "schema": []}
{"input": "With a wealth of fragment screening data being generated in industry and academia, such approaches will contribute to a more detailed structural understanding of ligand-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Retinol deprivation partially rescues the skeletal mineralization defects of Phex-deficient Hyp mice.", "output": {"entities": {"chemical": [{"text": "Retinol", "start": 0, "end": 7}]}}, "schema": []}
{"input": "X-linked hypophosphatemic rickets (XLH) is a genetic disorder caused by mutational inactivation of the PHEX gene, encoding a transmembrane endopeptidase expressed in osteoblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Since several experiments involving Phex-deficient Hyp mice have demonstrated that an increased expression of Fgf23 in osteoblasts is causative for the renal phosphate loss characteristic of XLH, we performed genome-wide expression analysis to compare differentiated osteoblasts from wildtype and Hyp mice.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 158, "end": 167}]}}, "schema": []}
{"input": "Here we did not only observe the expected increase of Fgf23 expression in the latter ones, but also a differential expression of genes that are either induced by or involved in retinoic acid signaling, which led us to analyze whether dietary retinol deprivation would influence the phenotype of Hyp mice.", "output": {"entities": {"chemical": [{"text": "retinoic acid", "start": 177, "end": 190}, {"text": "retinol", "start": 242, "end": 249}]}}, "schema": []}
{"input": "Unexpectedly, feeding a retinol-free diet resulted in a partial rescue of the growth plate and bone mineralization defects in 6 weeks old Hyp mice.", "output": {"entities": {}}, "schema": []}
{"input": "When we fed the same diet for 24 weeks the amount of non-mineralized bone matrix (osteoid) was reduced by more than 70%, although phosphate homeostasis was unaffected.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 130, "end": 139}]}}, "schema": []}
{"input": "In contrast, a dietary normalization of serum phosphate levels in Hyp mice reduced the osteoid amount by less than 30%, thereby demonstrating a previously unknown impact of retinol on the cell-autonomous mineralization defect of Phex-deficient osteoblasts.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 46, "end": 55}]}}, "schema": []}
{"input": "Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 11, "end": 20}]}}, "schema": []}
{"input": "Baicalein is a bioactive flavonoid that is widely used in ancient China.", "output": {"entities": {"chemical": [{"text": "Baicalein", "start": 0, "end": 9}, {"text": "flavonoid", "start": 25, "end": 34}]}}, "schema": []}
{"input": "However, its effects on the most common primary malignant bone tumor, osteosarcoma, remain unknown.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we investigated the effects of baicalein in osteosarcoma cells.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 53, "end": 62}]}}, "schema": []}
{"input": "Our results indicate baicalein might be an efficacious anti-osteosarcoma drug.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 21, "end": 30}]}}, "schema": []}
{"input": "We found that baicalein could inhibit cell proliferation in a time-and dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 14, "end": 23}]}}, "schema": []}
{"input": "Additionally, we demonstrated that baicalein promotes osteosarcoma cell apoptosis, and our mechanistic studies suggest that this is mediated by caspase activation, especially caspase-3.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 35, "end": 44}]}}, "schema": []}
{"input": "We also showed that the down-regulation of Bcl-2 and concurrent increase in Bax and Bim levels contribute to the apoptosis induced by baicalein.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 134, "end": 143}]}}, "schema": []}
{"input": "In addition, we observed that baicalein induces G1 cell cycle arrest by decreasing cyclin D1 and cyclin-dependent kinase 4 (CDK4).", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 30, "end": 39}]}}, "schema": []}
{"input": "Furthermore, our data verifies that baicalein can reduce osteosarcoma cell adhesion, migration and invasion in vitro, which indicates its potential to inhibit osteosarcoma metastasis.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 36, "end": 45}]}}, "schema": []}
{"input": "The decrease in expression of matrix metalloproteinases (MMP)-2 and MMP-9 may contribute to the effects of baicalein.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 107, "end": 116}]}}, "schema": []}
{"input": "Taken together, our results provide evidence that baicalein plays important roles in anti-osteosarcoma therapy, and thus may serve as a novel and efficient candidate agent for osteosarcoma treatment.", "output": {"entities": {"chemical": [{"text": "baicalein", "start": 50, "end": 59}]}}, "schema": []}
{"input": "Tri-and diorganotin (IV) complexes of biologically important orotic acid: synthesis, spectroscopic studies, in vitro anti-cancer, DNA fragmentation, enzyme assays and in vivo anti-inflammatory activities.", "output": {"entities": {"chemical": [{"text": "Tri-and diorganotin (IV)", "start": 0, "end": 24}, {"text": "orotic acid", "start": 61, "end": 72}]}}, "schema": []}
{"input": "Tri-and diorganotin (IV) orotates of general formula, R (n) Sn (H (2) Or) (m) [n = 3/2, m = 1/2, R = Me, n-Bu, n-Oct and Ph; H (2) Or (-) = monoanion of orotic acid (H (3) Or)] (n-Bu (2) Sn (HOr) as an exception) have been synthesized.", "output": {"entities": {"chemical": [{"text": "Tri-and diorganotin (IV) orotates", "start": 0, "end": 33}, {"text": "R (n) Sn (H (2) Or) (m)", "start": 54, "end": 77}, {"text": "Me", "start": 101, "end": 103}, {"text": "n-Bu", "start": 105, "end": 109}, {"text": "n-Oct", "start": 111, "end": 116}, {"text": "Ph", "start": 121, "end": 123}, {"text": "H (2) Or (-)", "start": 125, "end": 137}, {"text": "orotic acid", "start": 153, "end": 164}, {"text": "H (3) Or", "start": 166, "end": 174}, {"text": "n-Bu (2) Sn (HOr)", "start": 178, "end": 195}]}}, "schema": []}
{"input": "On the basis of various spectroscopic studies it is revealed that R (3) Sn (H (2) Or) and R (2) Sn (H (2) Or) (2) exhibit distorted trigonal-bipyramidal and distorted octahedral geometry, respectively, and n-Bu (2) Sn (HOr) shows both five and six coordination geometry around tin.", "output": {"entities": {"chemical": [{"text": "R (3) Sn (H (2) Or)", "start": 66, "end": 85}, {"text": "R (2) Sn (H (2) Or) (2)", "start": 90, "end": 113}, {"text": "n-Bu (2) Sn (HOr)", "start": 206, "end": 223}]}}, "schema": []}
{"input": "In vitro anti-cancer screening against MCF-7 (mammary), HEK-293 (kidney), PC-3 (prostate), HCT-15 (colon) and HepG-2 (liver) cancer cell lines suggest that the n-Oct (2) Sn (H (2) Or) (2) is the most active complex among all of the studied complexes.", "output": {"entities": {"chemical": [{"text": "n-Oct (2) Sn (H (2) Or) (2)", "start": 160, "end": 187}]}}, "schema": []}
{"input": "DNA fragmentation and antioxidant enzyme assays suggest that cytotoxic effect of the complexes is selectively mediated through the induction of apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "They also exhibit low toxicity and good anti-inflammatory activity (in vivo).", "output": {"entities": {}}, "schema": []}
{"input": "Determination of bioactive, free isothiocyanates from a glucosinolate-containing phytotherapeutic agent: a pilot study with in vitro models and human intervention.", "output": {"entities": {"chemical": [{"text": "isothiocyanates", "start": 33, "end": 48}, {"text": "glucosinolate", "start": 56, "end": 69}]}}, "schema": []}
{"input": "Isothiocyanates (ITCs) derived from plants of the order Brassicales are known for their antibacterial, anti-inflammatory or anticarcinogenic potential.", "output": {"entities": {"chemical": [{"text": "Isothiocyanates", "start": 0, "end": 15}, {"text": "ITCs", "start": 17, "end": 21}]}}, "schema": []}
{"input": "Although only the free ITCs exert bioactivity, quantification in vivo is almost exclusively performed on total ITC/metabolite content.", "output": {"entities": {"chemical": [{"text": "ITCs", "start": 23, "end": 27}, {"text": "ITC", "start": 111, "end": 114}]}}, "schema": []}
{"input": "We therefore investigated in a pilot study the amount of free ITC at different steps critical for therapeutic efficacy.", "output": {"entities": {"chemical": [{"text": "ITC", "start": 62, "end": 65}]}}, "schema": []}
{"input": "A sensitive and specific GC-MS/MS method for the simultaneous quantification of individual free ITC after solid-phase extraction (SPE) was developed.", "output": {"entities": {"chemical": [{"text": "ITC", "start": 96, "end": 99}]}}, "schema": []}
{"input": "We show here that release of biologically active ITC from plants occurs at not only alkaline but also acidic pH.", "output": {"entities": {"chemical": [{"text": "ITC", "start": 49, "end": 52}]}}, "schema": []}
{"input": "Furthermore, in human urine conversion of the ultimate, inactive mercapturic acid conjugate back into its corresponding bioactive form is increased at alkaline as compared to neutral pH.", "output": {"entities": {"chemical": [{"text": "mercapturic acid", "start": 65, "end": 81}]}}, "schema": []}
{"input": "This was also observed in the urine of human volunteers, where-in correlation with the pH value-a mean of 0. 16 to 1. 03 mu mol ITC was detected after oral application of a phytotherapeutic agent containing 30. 4 mu mol of the initial pro-drugs.", "output": {"entities": {"chemical": [{"text": "ITC", "start": 128, "end": 131}]}}, "schema": []}
{"input": "The amounts of free ITC being necessary for bioactivity in vitro were found to be indeed achieved in vivo.", "output": {"entities": {"chemical": [{"text": "ITC", "start": 20, "end": 23}]}}, "schema": []}
{"input": "These data might be helpful to better understand the beneficial effects of ITC observed in vivo.", "output": {"entities": {"chemical": [{"text": "ITC", "start": 75, "end": 78}]}}, "schema": []}
{"input": "Fucoidan prevents multiple myeloma cell escape from chemotherapy-induced drug cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Minimal residual disease (MRD) occurrence with some chemotherapy drugs that promote tumor cell escape is also a key factor in blood malignancy relapse.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that cytarabine promotes multiple myeloma (MM) cell escape and that the number of cells in the lower chamber increased with increasing clinical disease stage in in vitro model which was constructed by a Boyden chamber, matrigel glue and serum from MM patients in different disease stages.", "output": {"entities": {"chemical": [{"text": "cytarabine", "start": 17, "end": 27}]}}, "schema": []}
{"input": "The mechanism of cytarabine that promotes MM cell escape is closely associated with the up-regulation of CXCR4.", "output": {"entities": {"chemical": [{"text": "cytarabine", "start": 17, "end": 27}]}}, "schema": []}
{"input": "SDF-1 alpha can up-regulate the expression of MMP9 and RHoC proteins in MM cells with up-regulated CXCR4, and further promote the cell escape.", "output": {"entities": {}}, "schema": []}
{"input": "Fucoidan, a sulfated polysaccharide in the cell wall matrix of brown algae, has attracted much attention for its multiple biological activities, and we further explored the effects and possible underlying mechanisms of fucoidan on MM cell escape from cytarabine cytotoxicity.", "output": {"entities": {"chemical": [{"text": "cytarabine", "start": 251, "end": 261}]}}, "schema": []}
{"input": "The results show that fucoidan may decrease MM cell escape from cytarabine cytotoxicity, and that fucoidan can down-regulate CXCR4, MMP9 and RHoC expression.", "output": {"entities": {"chemical": [{"text": "cytarabine", "start": 64, "end": 74}]}}, "schema": []}
{"input": "This research provides new direction for investigating MRD occurrence and prevention.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica.", "output": {"entities": {"chemical": [{"text": "phytosterol", "start": 53, "end": 64}]}}, "schema": []}
{"input": "Fourteen sterols (1-14), including two new sterols, trihydroxysitosterol (2) and 5 alpha, 6 beta, 7 alpha-7 alpha-acetoxysitosterol (3), were isolated from the branches and leaves of Phyllanthus emblica L.", "output": {"entities": {"chemical": [{"text": "sterols", "start": 9, "end": 16}, {"text": "sterols", "start": 43, "end": 50}, {"text": "trihydroxysitosterol", "start": 52, "end": 72}, {"text": "5 alpha, 6 beta, 7 alpha-7 alpha-acetoxysitosterol", "start": 81, "end": 131}]}}, "schema": []}
{"input": "The isolated compounds and a structurally related sterol 15 from Aphanamixis grandifolia were screened for cytotoxicity in two tumor cell lines (HL-60 and SMMC-7721) and a non-tumor cell line (HL-7702) using RSB assay.", "output": {"entities": {"chemical": [{"text": "sterol", "start": 50, "end": 56}]}}, "schema": []}
{"input": "Within the series of phytosterol derivatives tested, compound 15 was the most active, displaying potent cytotoxicity against HL-60 with IC (50) of 5. 10 mu mol/L, and most of the active compounds showed selective cytotoxicity against tumor and non-tumor cell lines, especially compound 10 with a safety index of 4. 42.", "output": {"entities": {"chemical": [{"text": "phytosterol", "start": 21, "end": 32}]}}, "schema": []}
{"input": "Talin1 has unique expression versus talin 2 in the heart and modifies the hypertrophic response to pressure overload.", "output": {"entities": {}}, "schema": []}
{"input": "Integrins are adhesive, signaling, and mechanotransduction proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Talin (Tln) activates integrins and links it to the actin cytoskeleton.", "output": {"entities": {}}, "schema": []}
{"input": "Vertebrates contain two talin genes, tln1 and tln2.", "output": {"entities": {}}, "schema": []}
{"input": "How Tln1 and Tln2 function in cardiac myocytes (CMs) is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Tln1 and Tln2 expression were evaluated in the normal embryonic and adult mouse heart as well as in control and failing human adult myocardium.", "output": {"entities": {}}, "schema": []}
{"input": "Tln1 function was then tested in the basal and mechanically stressed myocardium after cardiomyocyte-specific excision of the Tln1 gene.", "output": {"entities": {}}, "schema": []}
{"input": "During embryogenesis, both Tln forms are highly expressed in CMs, but in the mature heart Tln2 becomes the main Tln isoform, localizing to the costameres.", "output": {"entities": {}}, "schema": []}
{"input": "Tln1 expression is minimal in the adult CM.", "output": {"entities": {}}, "schema": []}
{"input": "With pharmacological and mechanical stress causing hypertrophy, Tln1 is up-regulated in CMs and is specifically detected at costameres, suggesting its importance in the compensatory response to CM stress.", "output": {"entities": {}}, "schema": []}
{"input": "In human failing heart, CM Tln1 also increases compared with control samples from normal functioning myocardium.", "output": {"entities": {}}, "schema": []}
{"input": "To directly test Tln1 function in CMs, we generated CM-specific Tln1 knock-out mice (Tln1cKO).", "output": {"entities": {}}, "schema": []}
{"input": "Tln1cKO mice showed normal basal cardiac structure and function but when subjected to pressure overload showed blunted hypertrophy, less fibrosis, and improved cardiac function versus controls.", "output": {"entities": {}}, "schema": []}
{"input": "Acute responses of ERK1/2, p38, Akt, and glycogen synthase kinase 3 after mechanical stress were strongly blunted in Tln1cKO mice.", "output": {"entities": {}}, "schema": []}
{"input": "Given these results, we conclude that Tln1 and Tln2 have distinct functions in the myocardium.", "output": {"entities": {}}, "schema": []}
{"input": "Our data show that reduction of CM Tln1 expression can lead to improved cardiac remodeling following pressure overload.", "output": {"entities": {}}, "schema": []}
{"input": "A novel non-radioactive primase-pyrophosphatase activity assay and its application to the discovery of inhibitors of Mycobacterium tuberculosis primase DnaG.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterial DNA primase DnaG synthesizes RNA primers required for chromosomal DNA replication.", "output": {"entities": {}}, "schema": []}
{"input": "Biochemical assays measuring primase activity have been limited to monitoring formation of radioactively labelled primers because of the intrinsically low catalytic efficiency of DnaG.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, DnaG is prone to aggregation and proteolytic degradation.", "output": {"entities": {}}, "schema": []}
{"input": "These factors have impeded discovery of DnaG inhibitors by high-throughput screening (HTS).", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we expressed and purified the previously uncharacterized primase DnaG from Mycobacterium tuberculosis (Mtb DnaG).", "output": {"entities": {}}, "schema": []}
{"input": "By coupling the activity of Mtb DnaG to that of another essential enzyme, inorganic pyrophosphatase from M. tuberculosis (Mtb PPiase), we developed the first non-radioactive primase-pyrophosphatase assay.", "output": {"entities": {}}, "schema": []}
{"input": "An extensive optimization of the assay enabled its efficient use in HTS (Z' = 0. 7 in the 384-well format).", "output": {"entities": {}}, "schema": []}
{"input": "HTS of 2560 small molecules to search for inhibitory compounds yielded several hits, including suramin, doxorubicin and ellagic acid.", "output": {"entities": {"chemical": [{"text": "suramin", "start": 95, "end": 102}, {"text": "doxorubicin", "start": 104, "end": 115}, {"text": "ellagic acid", "start": 120, "end": 132}]}}, "schema": []}
{"input": "We demonstrate that these three compounds inhibit Mtb DnaG.", "output": {"entities": {}}, "schema": []}
{"input": "Both suramin and doxorubicin are potent (low-micro M) DNA-and nucleotide triphosphate-competitive priming inhibitors that interact with more than one site on Mtb DnaG.", "output": {"entities": {"chemical": [{"text": "suramin", "start": 5, "end": 12}, {"text": "doxorubicin", "start": 17, "end": 28}, {"text": "nucleotide triphosphate", "start": 62, "end": 85}]}}, "schema": []}
{"input": "This novel assay should be applicable to other primases and inefficient DNA/RNA polymerases, facilitating their characterization and inhibitor discovery.", "output": {"entities": {}}, "schema": []}
{"input": "Electrical method to quantify nanoparticle interaction with lipid bilayers.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding as well as rapidly screening the interaction of nanoparticles with cell membranes is of central importance for biological applications such as drug and gene delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, we have shown that \" striped \" mixed-monolayer-coated gold nanoparticles spontaneously penetrate a variety of cell membranes through a passive pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report an electrical approach to screen and readily quantify the interaction between nanoparticles and bilayer lipid membranes.", "output": {"entities": {}}, "schema": []}
{"input": "Membrane adsorption is monitored through the capacitive increase of suspended planar lipid membranes upon fusion with nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "We adopt a Langmuir isotherm model to characterize the adsorption of nanoparticles by bilayer lipid membranes and extract the partition coefficient, K, and the standard free energy gain by this spontaneous process, for a variety of sizes of cell-membrane-penetrating nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "We believe that the method presented here will be a useful qualitative and quantitative tool to determine nanoparticle interaction with lipid bilayers and consequently with cell membranes.", "output": {"entities": {}}, "schema": []}
{"input": "Development of hypoxia-inducible factor (HIF)-1 alpha inhibitors: effect of ortho-carborane substituents on HIF transcriptional activity under hypoxia.", "output": {"entities": {"chemical": [{"text": "ortho-carborane", "start": 76, "end": 91}]}}, "schema": []}
{"input": "A series of substituted ortho-carboranylphenoxyacetanilides were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter assay in HeLa cells expressing the HRE-dependent firefly luciferase reporter construct (HRE-Luc) and constitutively expressing CMV-driven Renilla luciferase reporter, and their ability to inhibit cell growth (GI (50)) using the MTT assay.", "output": {"entities": {"chemical": [{"text": "ortho-carboranylphenoxyacetanilides", "start": 24, "end": 59}, {"text": "MTT", "start": 423, "end": 426}]}}, "schema": []}
{"input": "Among the compounds synthesized, 1g and 1l showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity (IC (50): 1. 9 +/- 0. 4 and 1. 4 +/- 0. 2 mu M, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "Both compounds suppressed HIF-1 alpha accumulation in a concentration-dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited human Hsp60 chaperone activity (IC (50): 6. 80 +/- 0. 25 mu M) and this inhibition activity was higher than that of ETB (IC (50): 10. 9 +/- 0. 63 mu M).", "output": {"entities": {"chemical": [{"text": "malate", "start": 18, "end": 24}, {"text": "ETB", "start": 213, "end": 216}]}}, "schema": []}
{"input": "NMDA and AMPA receptor mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rat: ameliorating effects of curcumin.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 0, "end": 4}, {"text": "AMPA", "start": 9, "end": 13}, {"text": "streptozotocin", "start": 69, "end": 83}, {"text": "curcumin", "start": 130, "end": 138}]}}, "schema": []}
{"input": "Functional activity of neurotransmitter receptor and their sensitivity to regulation are altered in DM.", "output": {"entities": {}}, "schema": []}
{"input": "We evaluated the neuroprotective effect of curcumin in glutamate mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rats.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 43, "end": 51}, {"text": "glutamate", "start": 55, "end": 64}, {"text": "streptozotocin", "start": 111, "end": 125}]}}, "schema": []}
{"input": "Gene expression studies in diabetic rats showed a down regulation of glutamate decarboxylase mRNA leading to accumulation of glutamate.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 69, "end": 78}, {"text": "glutamate", "start": 125, "end": 134}]}}, "schema": []}
{"input": "Radioreceptor binding assays showed a significant increase in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate receptors density which was confirmed by immunohistochemical studies.", "output": {"entities": {"chemical": [{"text": "alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate", "start": 62, "end": 115}, {"text": "N-methyl-D-aspartate", "start": 120, "end": 140}]}}, "schema": []}
{"input": "Decreased glutathione peroxidases gene expression indicates enhanced oxidative stress in diabetic rats.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 10, "end": 21}]}}, "schema": []}
{"input": "This leads to decreased expression of glutamate aspartate transporter, which in turn reduces glutamate transport.", "output": {"entities": {"chemical": [{"text": "glutamate aspartate", "start": 38, "end": 57}, {"text": "glutamate", "start": 93, "end": 102}]}}, "schema": []}
{"input": "All these events lead to excitotoxic neuronal death in the cerebral cortex, which was confirmed by the increased expression of caspase 3, caspase 8 and BCL2-associated X protein.", "output": {"entities": {}}, "schema": []}
{"input": "Curcumin and insulin treatment reversed these altered parameters to near control.", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "We establish, a novel therapeutic role of curcumin by reducing the glutamate mediated excitotoxicity in cerebral cortex of diabetes through modulating the altered neurochemical parameters.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 42, "end": 50}, {"text": "glutamate", "start": 67, "end": 76}]}}, "schema": []}
{"input": "First-time-in-human study with GSK249320, a myelin-associated glycoprotein inhibitor, in healthy volunteers.", "output": {"entities": {}}, "schema": []}
{"input": "GSK249320, a monoclonal antibody directed against myelin-associated glycoprotein (MAG), is being developed for the enhancement of recovery of function poststroke.", "output": {"entities": {}}, "schema": []}
{"input": "Potential safety concerns of adverse effects on myelin led to the inclusion of pharmacodynamic measures of peripheral and central neuronal function in this first-time-in-human (FTIH) study.", "output": {"entities": {}}, "schema": []}
{"input": "The study also evaluated general safety, pharmacokinetics, and immunogenicity of GSK249320.", "output": {"entities": {}}, "schema": []}
{"input": "Single intravenous infusions of GSK249320 (0. 04, 0. 4, 1. 2, 3. 5, 10, and 25 mg/kg) or placebo were administered to 47 healthy subjects aged 18-60 years.", "output": {"entities": {}}, "schema": []}
{"input": "GSK249320 was well tolerated at all doses.", "output": {"entities": {}}, "schema": []}
{"input": "No clinically significant abnormalities were observed in neurological examinations, nerve conduction tests (NCTs), quantitative sensory tests (QSTs), clinical laboratory tests, or electrocardiograms.", "output": {"entities": {}}, "schema": []}
{"input": "There were no severe or serious adverse events.", "output": {"entities": {}}, "schema": []}
{"input": "GSK249320 had a half-life (HL) of 21 days and a volume of distribution at steady state of 45. 8 ml/kg, with AUC showing dose linearity.", "output": {"entities": {}}, "schema": []}
{"input": "GSK249320 did not induce antidrug antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant properties of Neu2000 on mitochondrial free radicals and oxidative damage.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 26, "end": 33}]}}, "schema": []}
{"input": "Neu2000 [2-hydroxy-5-(2, 3, 5, 6-tetrafluoro-4 trifluoromethylbenzylamino) benzoic acid] is a dual-acting neuroprotective agent that functions both as a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist and a free radical scavenger.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 0, "end": 7}, {"text": "2-hydroxy-5-(2, 3, 5, 6-tetrafluoro-4 trifluoromethylbenzylamino) benzoic acid", "start": 9, "end": 87}, {"text": "N-methyl-d-aspartate", "start": 168, "end": 188}]}}, "schema": []}
{"input": "In the present study, we investigated the scavenging activity of Neu2000 on various classes of reactive oxygen species and reactive nitrogen species (ROS/RNS) as well as its efficacy for reducing free radicals and oxidative stress/damage induced in spinal cord mitochondrial preparations.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 65, "end": 72}, {"text": "oxygen", "start": 104, "end": 110}, {"text": "nitrogen", "start": 132, "end": 140}]}}, "schema": []}
{"input": "Neu2000 exerted scavenging activity against superoxide, nitric oxide, and hydroxyl radicals, and efficiently scavenged peroxynitrite.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 0, "end": 7}, {"text": "superoxide", "start": 44, "end": 54}, {"text": "nitric oxide", "start": 56, "end": 68}, {"text": "hydroxyl", "start": 74, "end": 82}, {"text": "peroxynitrite", "start": 119, "end": 132}]}}, "schema": []}
{"input": "In the mitochondrial studies, Neu2000 markedly inhibited ROS/RNS and hydrogen peroxide levels following antimycin treatment.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 30, "end": 37}, {"text": "hydrogen peroxide", "start": 69, "end": 86}, {"text": "antimycin", "start": 104, "end": 113}]}}, "schema": []}
{"input": "In addition, Neu2000 effectively scavenged hydroxyl radicals generated by iron (III)-ascorbate, reduced protein carbonyl formation mediated by hydroxyl radicals and peroxynitrite, and prevented glutathione oxidation caused by tert-butyl hydroperoxide in isolated mitochondria.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 13, "end": 20}, {"text": "hydroxyl", "start": 43, "end": 51}, {"text": "iron (III)-ascorbate", "start": 74, "end": 94}, {"text": "carbonyl", "start": 112, "end": 120}, {"text": "hydroxyl", "start": 143, "end": 151}, {"text": "peroxynitrite", "start": 165, "end": 178}, {"text": "glutathione", "start": 194, "end": 205}, {"text": "tert-butyl hydroperoxide", "start": 226, "end": 250}]}}, "schema": []}
{"input": "Interestingly, incubation of isolated mitochondria with Neu2000 followed by centrifugation and removal of the supernatant also resulted in a concentration-dependent decrease in lipid peroxidation.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 56, "end": 63}]}}, "schema": []}
{"input": "This observation suggests that Neu2000 enters mitochondria to target free radicals or indirectly affects mitochondrial function in a manner that promotes antioxidant activity.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 31, "end": 38}]}}, "schema": []}
{"input": "The results of the present study demonstrate that Neu2000 possesses potent in vitro antioxidant activity due, most likely, to its active phenoxy group.", "output": {"entities": {"chemical": [{"text": "Neu2000", "start": 50, "end": 57}, {"text": "phenoxy", "start": 137, "end": 144}]}}, "schema": []}
{"input": "GBSA: a comprehensive software for analysing whole genome bisulfite sequencing data.", "output": {"entities": {"chemical": [{"text": "bisulfite", "start": 58, "end": 67}]}}, "schema": []}
{"input": "High-throughput sequencing is increasingly being used in combination with bisulfite (BS) assays to study DNA methylation at nucleotide resolution.", "output": {"entities": {"chemical": [{"text": "bisulfite", "start": 74, "end": 83}, {"text": "nucleotide", "start": 124, "end": 134}]}}, "schema": []}
{"input": "Although several programmes provide genome-wide alignment of BS-treated reads, the resulting information is not readily interpretable and often requires further bioinformatic steps for meaningful analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Current post-alignment BS-sequencing programmes are generally focused on the gene-specific level, a restrictive feature when analysis in the non-coding regions, such as enhancers and intergenic microRNAs, is required.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present Genome Bisulfite Sequencing Analyser (GBSA-http://ctrad-csi. nus. edu. sg/gbsa), a free open-source software capable of analysing whole-genome bisulfite sequencing data with either a gene-centric or gene-independent focus.", "output": {"entities": {"chemical": [{"text": "Bisulfite", "start": 24, "end": 33}, {"text": "bisulfite", "start": 160, "end": 169}]}}, "schema": []}
{"input": "Through analysis of the largest published data sets to date, we demonstrate GBSA' s features in providing sequencing quality assessment, methylation scoring, functional data management and visualization of genomic methylation at nucleotide resolution.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, we show that GBSA' s output can be easily integrated with other high-throughput sequencing data, such as RNA-Seq or ChIP-seq, to elucidate the role of methylated intergenic regions in gene regulation.", "output": {"entities": {}}, "schema": []}
{"input": "In essence, GBSA allows an investigator to explore not only known loci but also all the genomic regions, for which methylation studies could lead to the discovery of new regulatory mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial Permeability Transition Pore Inhibitors Prevent Ethanol-Induced Neuronal Death in Mice.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 62, "end": 69}]}}, "schema": []}
{"input": "Ethanol induces brain injury by a mechanism that remains partly unknown.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Mitochondria play a key role in cell death processes, notably through the opening of the permeability transition pore (PTP).", "output": {"entities": {}}, "schema": []}
{"input": "Here, we tested the effect of ethanol and PTP inhibitors on mitochondrial physiology and cell viability both in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 30, "end": 37}]}}, "schema": []}
{"input": "Direct addition of ethanol up to 100 mM on isolated mouse brain mitochondria slightly decreased oxygen consumption but did not affect PTP regulation.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 19, "end": 26}, {"text": "oxygen", "start": 96, "end": 102}]}}, "schema": []}
{"input": "In comparison, when isolated from ethanol-treated (two doses of 2 g/kg, 2 h apart) 7-day-old mouse pups, brain mitochondria displayed a transient decrease in oxygen consumption but no change in PTP regulation or H (2) O (2) production.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 34, "end": 41}, {"text": "oxygen", "start": 158, "end": 164}, {"text": "H (2) O (2)", "start": 212, "end": 223}]}}, "schema": []}
{"input": "Conversely, exposure of primary cultured astrocytes and neurons to 20 mM ethanol for 3 days led to a transient PTP opening in astrocytes without affecting cell viability and to a permanent PTP opening in 10 to 20% neurons with the same percentage of cell death.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 73, "end": 80}]}}, "schema": []}
{"input": "Ethanol-treated mouse pups displayed a widespread caspase-3 activation in neurons but not in astrocytes and dramatic behavioral alterations.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Interestingly, two different PTP inhibitors (namely, cyclosporin A and nortriptyline) prevented both ethanol-induced neuronal death in vivo and ethanol-induced behavioral modifications.", "output": {"entities": {"chemical": [{"text": "cyclosporin A", "start": 53, "end": 66}, {"text": "nortriptyline", "start": 71, "end": 84}, {"text": "ethanol", "start": 101, "end": 108}, {"text": "ethanol", "start": 144, "end": 151}]}}, "schema": []}
{"input": "We conclude that PTP opening is involved in ethanol-induced neurotoxicity in the mouse.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 44, "end": 51}]}}, "schema": []}
{"input": "A simplified confinement method for calculating absolute free energies and free energy and entropy differences.", "output": {"entities": {}}, "schema": []}
{"input": "A simple and robust formulation of the path-independent confinement method for the calculation of free energies is presented.", "output": {"entities": {}}, "schema": []}
{"input": "The simplified confinement method (SCM) does not require matrix diagonalization or switching off the molecular force field, and has a simple convergence criterion.", "output": {"entities": {}}, "schema": []}
{"input": "The method can be readily implemented in molecular dynamics programs with minimal or no code modifications.", "output": {"entities": {}}, "schema": []}
{"input": "Because the confinement method is a special case of thermodynamic integration, it is trivially parallel over the integration variable.", "output": {"entities": {}}, "schema": []}
{"input": "The accuracy of the method is demonstrated using a model diatomic molecule, for which exact results can be computed analytically.", "output": {"entities": {}}, "schema": []}
{"input": "The method is then applied to the alanine dipeptide in vacuum, and to the alpha-helix <--> beta-sheet transition in a 16-residue peptide modeled in implicit solvent.", "output": {"entities": {}}, "schema": []}
{"input": "The SCM requires less effort for the calculation of free energy differences than previous formulations because it does not require computing normal modes.", "output": {"entities": {}}, "schema": []}
{"input": "The SCM has a diminished advantage for determining absolute free energy values, because it requires decreasing the MD integration step to obtain accurate results.", "output": {"entities": {}}, "schema": []}
{"input": "An approximate confinement procedure is introduced, which can be used to estimate directly the configurational entropy difference between two macrostates, without the need for additional computation of the difference in the free energy or enthalpy.", "output": {"entities": {}}, "schema": []}
{"input": "The approximation has convergence properties similar to those of the standard confinement method for the calculation of free energies.", "output": {"entities": {}}, "schema": []}
{"input": "The use of the approximation requires about 5 times less wall-clock simulation time than that needed to compute enthalpy differences to similar precision from an MD trajectory.", "output": {"entities": {}}, "schema": []}
{"input": "For the biomolecular systems considered in this study, the errors in the entropy approximation are under 10%.", "output": {"entities": {}}, "schema": []}
{"input": "Practical applications of the methods to proteins are currently limited to implicit solvent simulations.", "output": {"entities": {}}, "schema": []}
{"input": "The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses psychomotor abnormalities and recognition memory deficits in mice lacking the pituitary adenylate cyclase-activating polypeptide.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 27, "end": 36}, {"text": "MGS0028", "start": 58, "end": 65}]}}, "schema": []}
{"input": "Previous studies suggest that metabotropic glutamate 2/3 receptors are involved in psychiatric disorders.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 43, "end": 52}]}}, "schema": []}
{"input": "In this study, we examined the effects of the selective metabotropic glutamate 2/3 (mGlu2/3) receptor agonist MGS0028 on behavioral abnormalities in mice lacking the pituitary adenylate cyclase-activating polypeptide (PACAP), an experimental model of psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 69, "end": 78}, {"text": "MGS0028", "start": 110, "end": 117}]}}, "schema": []}
{"input": "We found that PACAP-deficient mice showed impairments in the novel object recognition test and these impairments were improved by MGS0028 (0. 1 mg/kg).", "output": {"entities": {"chemical": [{"text": "MGS0028", "start": 130, "end": 137}]}}, "schema": []}
{"input": "Similarly, MGS0028 improved hyperactivity and jumping behaviors, but did not reverse increased immobility times in the forced swim test in PACAP-deficient mice.", "output": {"entities": {"chemical": [{"text": "MGS0028", "start": 11, "end": 18}]}}, "schema": []}
{"input": "These results suggest that MGS0028 may be a potential, novel treatment for psychiatric disorders.", "output": {"entities": {"chemical": [{"text": "MGS0028", "start": 27, "end": 34}]}}, "schema": []}
{"input": "Challenges of bringing next generation sequencing technologies to clinical molecular diagnostic laboratories.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular diagnosis of complex dual genome mitochondrial disorders is a challenge.", "output": {"entities": {}}, "schema": []}
{"input": "It requires the identification of deleterious mutations in one of the ~ 1, 500 nuclear genes and the mitochondrial genome.", "output": {"entities": {}}, "schema": []}
{"input": "If the molecular defect is in the mitochondrial genome, quantification of degree of mutation load (heteroplasmy) in affected tissues is important.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the extreme clinical and genetic heterogeneity, conventional sequence analysis of the candidate genes one-by-one is impractical, if not impossible.", "output": {"entities": {}}, "schema": []}
{"input": "The newly developed massively parallel next generation sequencing (NGS) technique, that allows simultaneous sequence analysis of multiple target genes, when appropriately validated with deep coverage and proper quality controls, can be used as an effective comprehensive diagnostic approach in CLIA certified clinical laboratories.", "output": {"entities": {}}, "schema": []}
{"input": "Differential Effects of Crambescins and Crambescidin 816 in Voltage-Gated Sodium, Potassium and Calcium Channels in Neurons.", "output": {"entities": {"chemical": [{"text": "Crambescidin 816", "start": 40, "end": 56}, {"text": "Sodium", "start": 74, "end": 80}, {"text": "Potassium", "start": 82, "end": 91}, {"text": "Calcium", "start": 96, "end": 103}]}}, "schema": []}
{"input": "Crambescins and crambescidins are two families of guanidine alkaloids from the marine sponge Crambe crambe.", "output": {"entities": {"chemical": [{"text": "Crambescins", "start": 0, "end": 11}, {"text": "crambescidins", "start": 16, "end": 29}, {"text": "guanidine alkaloids", "start": 50, "end": 69}]}}, "schema": []}
{"input": "Although very little information about their biological effect has been reported, it is known that crambescidin 816 (Cramb816) blocks calcium channels in a neuroblastoma X glioma cell line.", "output": {"entities": {"chemical": [{"text": "crambescidin 816", "start": 99, "end": 115}, {"text": "Cramb816", "start": 117, "end": 125}, {"text": "calcium", "start": 134, "end": 141}]}}, "schema": []}
{"input": "Taking this into account, and the fact that ion channels are frequent targets for natural toxins, we examined the effect of Cramb816 and three compounds from the crambescin family, norcrambescin A2 (NcrambA2), crambescin A2 (CrambA2), and crambescin C1 (CrambC1), in the main voltage-dependent ion channels in neurons: sodium, potassium, and calcium channels.", "output": {"entities": {"chemical": [{"text": "Cramb816", "start": 124, "end": 132}, {"text": "crambescin", "start": 162, "end": 172}, {"text": "norcrambescin A2", "start": 181, "end": 197}, {"text": "NcrambA2", "start": 199, "end": 207}, {"text": "crambescin A2", "start": 210, "end": 223}, {"text": "CrambA2", "start": 225, "end": 232}, {"text": "crambescin C1", "start": 239, "end": 252}, {"text": "CrambC1", "start": 254, "end": 261}, {"text": "sodium", "start": 319, "end": 325}, {"text": "potassium", "start": 327, "end": 336}, {"text": "calcium", "start": 342, "end": 349}]}}, "schema": []}
{"input": "Electrophysiological recordings of voltage gated sodium, potassium, and calcium currents, in the presence of these guanidine alkaloids, were performed in cortical neurons from embryonic mice.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 49, "end": 55}, {"text": "potassium", "start": 57, "end": 66}, {"text": "calcium", "start": 72, "end": 79}, {"text": "guanidine alkaloids", "start": 115, "end": 134}]}}, "schema": []}
{"input": "Different effects were discovered: crambescins inhibited K (+) currents with the following potency: NcrambA2 > CrambC1 > CrambA2, while Cramb816 lacked an effect.", "output": {"entities": {"chemical": [{"text": "crambescins", "start": 35, "end": 46}, {"text": "K (+)", "start": 57, "end": 62}, {"text": "NcrambA2", "start": 100, "end": 108}, {"text": "CrambC1", "start": 111, "end": 118}, {"text": "CrambA2", "start": 121, "end": 128}, {"text": "Cramb816", "start": 136, "end": 144}]}}, "schema": []}
{"input": "Only CrambC1 and Cramb816 partially blocked Na (+) total current.", "output": {"entities": {"chemical": [{"text": "CrambC1", "start": 5, "end": 12}, {"text": "Cramb816", "start": 17, "end": 25}, {"text": "Na (+)", "start": 44, "end": 50}]}}, "schema": []}
{"input": "However, Cramb816 partially blocked Ca (2 +), while NcrambA2 did not.", "output": {"entities": {"chemical": [{"text": "Cramb816", "start": 9, "end": 17}, {"text": "Ca (2 +)", "start": 36, "end": 44}, {"text": "NcrambA2", "start": 52, "end": 60}]}}, "schema": []}
{"input": "Since the blocking effect of Cramb816 on calcium currents has not been previously reported in detail, we further pharmacologically isolated the two main fractions of HVA Ca (2 +) channels in neurons and investigated the Cramb816 effect on them.", "output": {"entities": {"chemical": [{"text": "Cramb816", "start": 29, "end": 37}, {"text": "calcium", "start": 41, "end": 48}, {"text": "Ca (2 +)", "start": 170, "end": 178}, {"text": "Cramb816", "start": 220, "end": 228}]}}, "schema": []}
{"input": "Here, we revealed that Cav1 or L-type calcium channels are the main target for Cramb816.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 38, "end": 45}, {"text": "Cramb816", "start": 79, "end": 87}]}}, "schema": []}
{"input": "These two families of guanidine alkaloids clearly showed a structure-activity relationship with the crambescins acting on voltage-gated potassium channels, while Cramb816 blocks the voltage-gated calcium channel Cav1 with higher potency than nifedipine.", "output": {"entities": {"chemical": [{"text": "guanidine alkaloids", "start": 22, "end": 41}, {"text": "crambescins", "start": 100, "end": 111}, {"text": "potassium", "start": 136, "end": 145}, {"text": "Cramb816", "start": 162, "end": 170}, {"text": "calcium", "start": 196, "end": 203}, {"text": "nifedipine", "start": 242, "end": 252}]}}, "schema": []}
{"input": "The novel evidence that Cramb816 partially blocked Ca (V) and Na (V) channels in neurons suggests that this compound might be involved in decreasing the neurotransmitter release and synaptic transmission in the central nervous system.", "output": {"entities": {"chemical": [{"text": "Cramb816", "start": 24, "end": 32}, {"text": "Ca", "start": 51, "end": 53}, {"text": "Na", "start": 62, "end": 64}]}}, "schema": []}
{"input": "The findings presented here provide the first detailed approach on the different effects of crambescin and crambescidin compounds in voltage-gated sodium, potassium, and calcium channels in neurons and thus provide a basis for future studies.", "output": {"entities": {"chemical": [{"text": "crambescin", "start": 92, "end": 102}, {"text": "crambescidin", "start": 107, "end": 119}, {"text": "sodium", "start": 147, "end": 153}, {"text": "potassium", "start": 155, "end": 164}, {"text": "calcium", "start": 170, "end": 177}]}}, "schema": []}
{"input": "Protein synthesis inhibition and oxidative stress induced by cylindrospermopsin elicit apoptosis in primary rat hepatocytes.", "output": {"entities": {"chemical": [{"text": "cylindrospermopsin", "start": 61, "end": 79}]}}, "schema": []}
{"input": "The increasing presence of cyanotoxin producers in several regions of the world is hazardous for humans and animals.", "output": {"entities": {}}, "schema": []}
{"input": "Cylindrospermopsin (CYN) is nowadays recognized as a widely distributed freshwater cyanobacterial toxin.", "output": {"entities": {"chemical": [{"text": "Cylindrospermopsin", "start": 0, "end": 18}, {"text": "CYN", "start": 20, "end": 23}]}}, "schema": []}
{"input": "This toxin has been shown to induce protein synthesis inhibition as well as inhibition of glutathione synthesis.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 90, "end": 101}]}}, "schema": []}
{"input": "Given that the liver seems to be the main target of cylindrospermopsin, in this work we used cultures of primary rat hepatocytes to study the type of cell death induced by CYN nanomolar concentrations.", "output": {"entities": {"chemical": [{"text": "cylindrospermopsin", "start": 52, "end": 70}, {"text": "CYN", "start": 172, "end": 175}]}}, "schema": []}
{"input": "The involvement of reactive oxygen species in toxin induced cell death, the relationship between protein synthesis inhibition and toxicity, and the cell endogenous antioxidant response regulation were studied.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 28, "end": 34}]}}, "schema": []}
{"input": "We show that cylindrospermopsin induces apoptosis in primary rat hepatocytes.", "output": {"entities": {"chemical": [{"text": "cylindrospermopsin", "start": 13, "end": 31}]}}, "schema": []}
{"input": "At the concentrations used in this work, protein synthesis inhibition and oxidative stress were involved in the cytotoxic effect elicited by the toxin.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, activation of the cell antioxidant response was observed at the transcriptional and translational levels.", "output": {"entities": {}}, "schema": []}
{"input": "Noncovalent tailoring of the binding pocket of self-assembled cages by remote bulky ancillary groups.", "output": {"entities": {}}, "schema": []}
{"input": "The binding properties of a self-assembled coordination cage were subtly tuned by ancillary groups on the metal corners of the cage.", "output": {"entities": {}}, "schema": []}
{"input": "Since the bulky mesityl groups of the ligand hang over the cage cavity, the effective cavity volume is reduced.", "output": {"entities": {"chemical": [{"text": "mesityl", "start": 16, "end": 23}]}}, "schema": []}
{"input": "Due to the tighter guest packing inside the shrunken cavity, smaller guests were efficiently bound and guest motion was restricted even at high temperatures.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and insight into the structure-activity relationships of chalcones as antimalarial agents.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 67, "end": 76}]}}, "schema": []}
{"input": "Licochalcone A (I), isolated from the roots of Chinese licorice, is the most promising antimalarial compound reported so far.", "output": {"entities": {"chemical": [{"text": "Licochalcone A", "start": 0, "end": 14}]}}, "schema": []}
{"input": "In continuation of our drug discovery program, we isolated two similar chalcones, medicagenin (II) and munchiwarin (III), from Crotalaria medicagenia, which exhibited antimalarial activity against Plasmodium falciparum.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 71, "end": 80}, {"text": "medicagenin", "start": 82, "end": 93}, {"text": "munchiwarin", "start": 103, "end": 114}]}}, "schema": []}
{"input": "A library of 88 chalcones were synthesized and evaluated for their in vitro antimalarial activity.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 16, "end": 25}]}}, "schema": []}
{"input": "Among these, 67, 68, 74, 77, and 78 exhibited good in vitro antimalarial activity against P. falciparum strains 3D7 and K1 with low cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "These chalcones also showed reduction in parasitemia and increased survival time of Swiss mice infected with Plasmodium yoelii (strain N-67).", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 6, "end": 15}]}}, "schema": []}
{"input": "Pharmacokinetic studies indicated that low oral bioavailability due to poor ADME properties.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular docking studies revealed the binding orientation of these inhibitors in active sites of falcipain-2 (FP-2) enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 67, 68, and 78 showed modest inhibitory activity against the major hemoglobin degrading cysteine protease FP-2.", "output": {"entities": {}}, "schema": []}
{"input": "Exploring key orientations at protein-protein interfaces with small molecule probes.", "output": {"entities": {}}, "schema": []}
{"input": "Small molecule probes that selectively perturb protein-protein interactions (PPIs) are pivotal to biomedical science, but their discovery is challenging.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that conformational resemblance of semirigid scaffolds expressing amino acid side-chains to PPI-interface regions could guide this process.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 82, "end": 92}]}}, "schema": []}
{"input": "Consequently, a data mining algorithm was developed to sample huge numbers of PPIs to find ones that match preferred conformers of a selected semirigid scaffold.", "output": {"entities": {}}, "schema": []}
{"input": "Conformations of one such chemotype (1aaa; all methyl side-chains) matched several biomedically significant PPIs, including the dimerization interface of HIV-1 protease.", "output": {"entities": {"chemical": [{"text": "methyl", "start": 47, "end": 53}]}}, "schema": []}
{"input": "On the basis of these observations, four molecules 1 with side-chains corresponding to the matching HIV-1 dimerization interface regions were prepared; all four inhibited HIV-1 protease via perturbation of dimerization.", "output": {"entities": {}}, "schema": []}
{"input": "These data indicate this approach may inspire design of small molecule interface probes to perturb PPIs.", "output": {"entities": {}}, "schema": []}
{"input": "Coming full circle: contributions of central and peripheral oxytocin actions to energy balance.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 60, "end": 68}]}}, "schema": []}
{"input": "The neuropeptide oxytocin has emerged as an important anorexigen in the regulation of energy balance.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 17, "end": 25}, {"text": "anorexigen", "start": 54, "end": 64}]}}, "schema": []}
{"input": "Its effects on food intake have largely been attributed to limiting meal size through interactions in key regulatory brain regions such as the hypothalamus and hindbrain.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacologic and pair-feeding studies indicate that its ability to reduce body mass extends beyond that of food intake, affecting multiple factors that determine energy balance such as energy expenditure, lipolysis, and glucose regulation.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 221, "end": 228}]}}, "schema": []}
{"input": "Systemic administration of oxytocin recapitulates many of its effects when administered centrally, raising the questions of whether and to what extent circulating oxytocin contributes to energy regulation.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 27, "end": 35}, {"text": "oxytocin", "start": 163, "end": 171}]}}, "schema": []}
{"input": "Its therapeutic potential to treat metabolic conditions remains to be determined, but data from diet-induced and genetically obese rodent models as well as application of oxytocin in humans in other areas of research have revealed promising results thus far.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 171, "end": 179}]}}, "schema": []}
{"input": "Safrole-2', 3'-oxide induces atherosclerotic plaque vulnerability in apolipoprotein E-knockout mice.", "output": {"entities": {"chemical": [{"text": "Safrole-2', 3'-oxide", "start": 0, "end": 20}]}}, "schema": []}
{"input": "Safrole-2', 3'-oxide (SFO) is the major electrophilic metabolite of safrole (4-allyl-1, 2-methylenedioxybenzene), a natural plant constituent found in essential oils of numerous edible herbs and spices and in food containing these herbs, such as pesto sauce, cola beverages and bologna sausages.", "output": {"entities": {"chemical": [{"text": "Safrole-2', 3'-oxide", "start": 0, "end": 20}, {"text": "SFO", "start": 22, "end": 25}, {"text": "safrole", "start": 68, "end": 75}, {"text": "4-allyl-1, 2-methylenedioxybenzene", "start": 77, "end": 111}]}}, "schema": []}
{"input": "The effects of SFO in mammalian systems, especially the cardiovascular system, are little known.", "output": {"entities": {"chemical": [{"text": "SFO", "start": 15, "end": 18}]}}, "schema": []}
{"input": "Disruption of vulnerable atherosclerotic plaques in atherosclerosis, a chronic inflammatory disease, is the main cause of cardiovascular events.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated SFO-induced atherosclerotic plaque vulnerability (possibility of rupture) in apolipoprotein E-knockout (apoE (-/-)) mice.", "output": {"entities": {"chemical": [{"text": "SFO", "start": 31, "end": 34}]}}, "schema": []}
{"input": "Lipid area in vessel wall reached 59. 8% in high dose SFO (SFO-HD) treated group, which is only 31. 2% in control group.", "output": {"entities": {"chemical": [{"text": "SFO", "start": 54, "end": 57}, {"text": "SFO", "start": 59, "end": 62}]}}, "schema": []}
{"input": "SFO treatment changed the lesion composition to an unstable phenotype, increased the number of apoptotic cells in plaque and the endothelium in plaques was damaged after SFO treatment.", "output": {"entities": {"chemical": [{"text": "SFO", "start": 0, "end": 3}, {"text": "SFO", "start": 170, "end": 173}]}}, "schema": []}
{"input": "Furthermore, compared with control groups, the plaque endothelium level of p75 (NTR) was 3-fold increased and the liver level of p75 (NTR) was 17. 4-fold increased by SFO-HD.", "output": {"entities": {"chemical": [{"text": "SFO", "start": 167, "end": 170}]}}, "schema": []}
{"input": "Meanwhile, the serum level of KC (a functional homolog of IL-8 and the main proinflammatory alpha chemokine in mice) in apoE (-/-) mice was up to 357pg/ml in SFO-HD treated group.", "output": {"entities": {"chemical": [{"text": "SFO", "start": 158, "end": 161}]}}, "schema": []}
{"input": "Thus, SFO contributes to the instability of atherosclerotic plaque in apoE (-/-) mice through activating p75 (NTR) and IL-8 and cell apoptosis in plaque.", "output": {"entities": {"chemical": [{"text": "SFO", "start": 6, "end": 9}]}}, "schema": []}
{"input": "The interactions of apamin and tetraethylammonium are differentially affected by single mutations in the pore mouth of small conductance calcium-activated potassium (SK) channels.", "output": {"entities": {"chemical": [{"text": "tetraethylammonium", "start": 31, "end": 49}, {"text": "calcium", "start": 137, "end": 144}, {"text": "potassium", "start": 155, "end": 164}]}}, "schema": []}
{"input": "Valine residues in the pore region of SK2 (V366) and SK3 (V520) were replaced by either an alanine or a phenylalanine to evaluate the impact on the interactions with the allosteric blocker apamin.", "output": {"entities": {"chemical": [{"text": "Valine", "start": 0, "end": 6}, {"text": "alanine", "start": 91, "end": 98}, {"text": "phenylalanine", "start": 104, "end": 117}]}}, "schema": []}
{"input": "Unlike TEA which showed high sensitivity to phenylalanine mutated channels, the binding affinity of apamin to the phenylalanine mutants was strongly reduced.", "output": {"entities": {"chemical": [{"text": "TEA", "start": 7, "end": 10}, {"text": "phenylalanine", "start": 44, "end": 57}, {"text": "phenylalanine", "start": 114, "end": 127}]}}, "schema": []}
{"input": "In addition, currents from phenylalanine mutants were largely resistant to block by apamin.", "output": {"entities": {"chemical": [{"text": "phenylalanine", "start": 27, "end": 40}]}}, "schema": []}
{"input": "On the other hand, when the valine residue was replaced by an alanine residue, an increase of the binding affinity and the amount of block by apamin was observed for alanine mutated SK2 channels, but not for mutated SK3 channels.", "output": {"entities": {"chemical": [{"text": "valine", "start": 28, "end": 34}, {"text": "alanine", "start": 62, "end": 69}, {"text": "alanine", "start": 166, "end": 173}]}}, "schema": []}
{"input": "Interestingly, the VA mutation reduced the sensitivity to TEA.", "output": {"entities": {"chemical": [{"text": "TEA", "start": 58, "end": 61}]}}, "schema": []}
{"input": "In silico data confirmed these experimental results.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, such mutations in the pore region of SK channels show that the three-dimensional structure of the SK tetramers can be disorganized in the outer pore region leading to reduced interaction of apamin with its target.", "output": {"entities": {}}, "schema": []}
{"input": "Curcumin reverses glomerular hemodynamic alterations and oxidant stress in 5/6 nephrectomized rats.", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The administration of curcumin before and throughout the study attenuates oxidant stress and glomerular hemodynamic alterations induced by 5/6 nephrectomy (5/6NX).", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 22, "end": 30}]}}, "schema": []}
{"input": "The purpose of this work was to study if curcumin is able to reverse established glomerular hemodynamic alterations (e. g. hyperfiltration and glomerular hypertension) and oxidant stress in rats with 5/6NX.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 41, "end": 49}]}}, "schema": []}
{"input": "Curcumin (120 mg/kg) was given to rats with established renal injury (30 days after surgery) and continued for 30 days (days 31-60 of the study).", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "All rats were studied on day 60 after surgery.", "output": {"entities": {}}, "schema": []}
{"input": "Curcumin was able (a) to reverse 5/6NX-induced glomerular hypertension and hyperfiltration, (b) to induce cell proliferation and nuclear translocation of Nrf2 and (c) to reverse 5/6NX-induced oxidant stress and decrease in antioxidant enzymes.", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "These beneficial effects of curcumin were associated with the ability of this antioxidant to reverse renal structural alterations, proteinuria, hypertension, interstitial fibrosis, fibrotic glomeruli, tubular atrophy and mesangial expansion.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 28, "end": 36}]}}, "schema": []}
{"input": "It has been shown for the first time that curcumin is able to reverse established oxidants stress glomerular hypertension and hyperfiltration in rats with 5/6NX.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 42, "end": 50}]}}, "schema": []}
{"input": "These novel findings may play a key role in the attenuation of proteinuria and progression of renal damage in rats with 5/6NX.", "output": {"entities": {}}, "schema": []}
{"input": "These data suggest that curcumin may be useful to reverse established hemodynamic alterations and renal injury in patients with chronic renal failure.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 24, "end": 32}]}}, "schema": []}
{"input": "In vitro and in vivo anti-inflammatory effects of 4-methoxy-5-hydroxycanthin-6-one, a natural alkaloid from Picrasma quassioides.", "output": {"entities": {"chemical": [{"text": "4-methoxy-5-hydroxycanthin-6-one", "start": 50, "end": 82}]}}, "schema": []}
{"input": "In the present study, we evaluated the anti-inflammatory effect of 4-methoxy-5-hydroxycanthin-6-one (CAN), a natural alkaloid isolated from Picrasma quassioides.", "output": {"entities": {"chemical": [{"text": "4-methoxy-5-hydroxycanthin-6-one", "start": 67, "end": 99}, {"text": "CAN", "start": 101, "end": 104}]}}, "schema": []}
{"input": "CAN significantly inhibited the production of NO and the release of TNF-alpha induced by LPS in macrophage RAW 264. 7.", "output": {"entities": {"chemical": [{"text": "CAN", "start": 0, "end": 3}, {"text": "NO", "start": 46, "end": 48}]}}, "schema": []}
{"input": "Western blot showed that CAN can downregulate the expression of iNOS protein.", "output": {"entities": {"chemical": [{"text": "CAN", "start": 25, "end": 28}]}}, "schema": []}
{"input": "After oral administration, CAN (3, 9, and 27 mg/kg) reduced the development of carrageenan-induced paw edema and complete Freund' s adjuvant (CFA)-induced chronic arthritis in rats.", "output": {"entities": {"chemical": [{"text": "CAN", "start": 27, "end": 30}]}}, "schema": []}
{"input": "The observed results indicated that pre-treatment with CAN might be an effective therapeutic intervention against inflammatory diseases including chronic arthritis.", "output": {"entities": {"chemical": [{"text": "CAN", "start": 55, "end": 58}]}}, "schema": []}
{"input": "Ovarian function is restored after grafting of cryopreserved immature ovary in ewes.", "output": {"entities": {}}, "schema": []}
{"input": "As a result of advances in medical treatment, almost 80% of children who are diagnosed with cancer survive long-term.", "output": {"entities": {}}, "schema": []}
{"input": "The adverse consequences of cancer treatments include impaired puberty and fertility.", "output": {"entities": {}}, "schema": []}
{"input": "In prepubertal girls, the only therapeutic option is the cryopreservation of an ovary.", "output": {"entities": {}}, "schema": []}
{"input": "To date, a dozen births have been reported after reimplantation of cryopreserved mature ovaries.", "output": {"entities": {}}, "schema": []}
{"input": "To analyze ovarian function after immature grafts, we performed ovarian grafting in a ewe model.", "output": {"entities": {}}, "schema": []}
{"input": "Fresh or cryopreserved ovaries from immature ewes were autografted in prepubertal or adult ewes.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclic hormonal activity was recovered 3 mo after grafting.", "output": {"entities": {}}, "schema": []}
{"input": "Histological analysis demonstrated the presence of all follicle populations and corpora lutea not affected by cryopreservation.", "output": {"entities": {}}, "schema": []}
{"input": "After 3 reproductive seasons, births had been observed in all groups, and the follicle-stimulating hormone status was under the limit, which indicated an exhausted ovary.", "output": {"entities": {}}, "schema": []}
{"input": "As an indicator of potential imprinting default, the methylation status of the Igf2r gene was analyzed and did not show significant alteration compared with that of nonmanipulated animals.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these results demonstrate that immature ovarian grafting is able to restore spontaneous puberty and fertility and could guide the reimplantation of immature cortex in women.-Sauvat, F., Bouilly, J., Capito, C., Lef e vre, A., Blach e re, T., Borenstein, N., Sarnacki, S., Dandolo, L., Binart, N.", "output": {"entities": {}}, "schema": []}
{"input": "Ovarian function is restored after grafting of cryopreserved immature ovary in ewes.", "output": {"entities": {}}, "schema": []}
{"input": "Bioavailability of stabilised ferrous gluconate with glycine in fresh cheese matrix: a novel iron compound for food fortification.", "output": {"entities": {"chemical": [{"text": "ferrous gluconate", "start": 30, "end": 47}, {"text": "glycine", "start": 53, "end": 60}, {"text": "iron", "start": 93, "end": 97}]}}, "schema": []}
{"input": "Iron fortification of foods continues to be one of the preferred ways of improving the iron status of the population.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "iron", "start": 87, "end": 91}]}}, "schema": []}
{"input": "Dairy product is a common product in the diet; therefore, it is a plausible vehicle for iron fortification.", "output": {"entities": {"chemical": [{"text": "iron", "start": 88, "end": 92}]}}, "schema": []}
{"input": "This study aims to investigate the bioavailability of ferrous gluconate stabilised with glycine (FGSG) in a fresh cheese fortified with zinc.", "output": {"entities": {"chemical": [{"text": "ferrous gluconate", "start": 54, "end": 71}, {"text": "glycine", "start": 88, "end": 95}, {"text": "zinc", "start": 136, "end": 140}]}}, "schema": []}
{"input": "The iron bioavailability of fresh cheese fortified with either FGSG and with or without zinc and FGSG in aqueous solution and a water solution of ferrous ascorbate (reference dose) was studied using double radio iron ((55) Fe and (59) Fe) erythrocyte incorporation in 15 male subjects.", "output": {"entities": {"chemical": [{"text": "iron", "start": 4, "end": 8}, {"text": "zinc", "start": 88, "end": 92}, {"text": "ferrous ascorbate", "start": 146, "end": 163}, {"text": "radio iron", "start": 206, "end": 216}, {"text": "(55) Fe", "start": 218, "end": 225}, {"text": "(59) Fe", "start": 230, "end": 237}]}}, "schema": []}
{"input": "All subjects presented with normal values for iron status parameters.", "output": {"entities": {"chemical": [{"text": "iron", "start": 46, "end": 50}]}}, "schema": []}
{"input": "The geometric mean of iron bioavailability for the water solution of FGSG was 38. 2%, adjusted to 40% from reference doses (N. S.).", "output": {"entities": {"chemical": [{"text": "iron", "start": 22, "end": 26}]}}, "schema": []}
{"input": "Iron bioavailability in fresh cheese fortified with Ca and Zn was 15. 4% and was 23. 1% without Zn, adjusted to 40% from reference doses (N. S.).", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "Ca", "start": 52, "end": 54}, {"text": "Zn", "start": 59, "end": 61}, {"text": "Zn", "start": 96, "end": 98}]}}, "schema": []}
{"input": "The results of the present study show that the novel iron compound ferrous gluconate stabilised with glycine in a fresh cheese matrix is a good source of iron and can be used in iron fortification programmes.", "output": {"entities": {"chemical": [{"text": "iron", "start": 53, "end": 57}, {"text": "ferrous gluconate", "start": 67, "end": 84}, {"text": "glycine", "start": 101, "end": 108}, {"text": "iron", "start": 154, "end": 158}, {"text": "iron", "start": 178, "end": 182}]}}, "schema": []}
{"input": "Source apportionment of trace element pollution in surface sediments using positive matrix factorization combined support vector machines: application to the Jinjiang River, China.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, a method of positive matrix factorization (PMF) combined support vector machines (SVMs) was adopted to identify possible sources and apportion contributions for trace element pollution in surface sediments from the Jinjiang River, Southeastern China.", "output": {"entities": {}}, "schema": []}
{"input": "Utilizing diagnostics tools, four significant factors were extracted from sediment samplers, which were collected in December 2010 at 15 different sites.", "output": {"entities": {}}, "schema": []}
{"input": "By treating source identification as a pattern recognition problem, the factor loadings derived from PMF were classified by SVM classifiers which have been trained and validated with fingerprints of eight potential source categories.", "output": {"entities": {}}, "schema": []}
{"input": "Using SVM, industrial wastewater from lead ore mining and metal handcraft manufacture, atmospheric deposition, and natural background were identified as main sources of trace element pollution in surface sediments from the Jinjiang River, which were affirmed by visually comparing compound patterns and the differences between the predicted and actual fractional compositions.", "output": {"entities": {}}, "schema": []}
{"input": "Apportionment results showed that source of lead ore mining made the largest contribution (33. 62%), followed by atmospheric deposition (30. 99%), metal handcraft manufacture (30. 09%), and natural background (5. 29%).", "output": {"entities": {}}, "schema": []}
{"input": "Interaction of cisplatin with adenine and guanine: a combined IRMPD, MS/MS, and theoretical study.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 15, "end": 24}, {"text": "adenine", "start": 30, "end": 37}, {"text": "guanine", "start": 42, "end": 49}]}}, "schema": []}
{"input": "Infrared multiple photon dissociation (IRMPD) spectroscopy of cis-[Pt (NH (3)) (2) (G) Cl] (+) and cis-[Pt (NH (3)) (2) (A) Cl] (+) ions (where A is adenine and G is guanine) has been performed in two spectral regions, 950-1900 and 2900-3700 cm (-1).", "output": {"entities": {"chemical": [{"text": "cis-[Pt (NH (3)) (2) (G) Cl] (+)", "start": 62, "end": 94}, {"text": "cis-[Pt (NH (3)) (2) (A) Cl] (+)", "start": 99, "end": 131}, {"text": "adenine", "start": 149, "end": 156}, {"text": "guanine", "start": 166, "end": 173}]}}, "schema": []}
{"input": "Quantum chemical calculations at the B3LYP/LACV3P/6-311G * * level yield the optimized geometries and IR spectra for the conceivable isomers of cis-[Pt (NH (3)) (2) (G) Cl] (+) and cis-[Pt (NH (3)) (2) (A) Cl] (+), whereby the cisplatin residue is attached to the N7, N3, or carbonyl oxygen atom, (O6), of guanine and to the N7, N3, or N1 position of adenine, respectively.", "output": {"entities": {"chemical": [{"text": "cis-[Pt (NH (3)) (2) (G) Cl] (+)", "start": 144, "end": 176}, {"text": "cis-[Pt (NH (3)) (2) (A) Cl] (+)", "start": 181, "end": 213}, {"text": "cisplatin", "start": 227, "end": 236}, {"text": "carbonyl oxygen", "start": 275, "end": 290}, {"text": "O6", "start": 298, "end": 300}, {"text": "guanine", "start": 306, "end": 313}, {"text": "adenine", "start": 351, "end": 358}]}}, "schema": []}
{"input": "In addition to the conventional binding sites of native adenine, complexes with N7-H tautomers have also been considered.", "output": {"entities": {"chemical": [{"text": "adenine", "start": 56, "end": 63}]}}, "schema": []}
{"input": "In agreement with computational results, the IR characterization of cis-[Pt (NH (3)) (2) (G) Cl] (+) points to a covalent structure where Pt is bound to the N7 atom of guanine.", "output": {"entities": {"chemical": [{"text": "cis-[Pt (NH (3)) (2) (G) Cl] (+)", "start": 68, "end": 100}, {"text": "Pt", "start": 138, "end": 140}, {"text": "guanine", "start": 168, "end": 175}]}}, "schema": []}
{"input": "The characterized conformer has a hydrogen-bonding interaction between a hydrogen atom of one NH (3) ligand and the carbonyl group of guanine.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 34, "end": 42}, {"text": "hydrogen", "start": 73, "end": 81}, {"text": "NH (3)", "start": 94, "end": 100}, {"text": "carbonyl", "start": 116, "end": 124}, {"text": "guanine", "start": 134, "end": 141}]}}, "schema": []}
{"input": "The experimental C = O stretching feature of cis-[Pt (NH (3)) (2) (G) Cl] (+) at 1718 cm (-1), remarkably red-shifted with respect to an unperturbed C = O stretching mode, is indicative of a lengthened CO bond in guanine, a signature that this group is involved in hydrogen bonding.", "output": {"entities": {"chemical": [{"text": "C = O", "start": 17, "end": 22}, {"text": "cis-[Pt (NH (3)) (2) (G) Cl] (+)", "start": 45, "end": 77}, {"text": "C = O", "start": 149, "end": 154}, {"text": "CO", "start": 202, "end": 204}, {"text": "guanine", "start": 213, "end": 220}, {"text": "hydrogen", "start": 265, "end": 273}]}}, "schema": []}
{"input": "The IRMPD spectra of cis-[Pt (NH (3)) (2) (A) Cl] (+) are consistent with the presence of two major isomers, PtAN3 and PtAN1, where Pt is bound to the N3 and N1 positions of native adenine, respectively.", "output": {"entities": {"chemical": [{"text": "cis-[Pt (NH (3)) (2) (A) Cl] (+)", "start": 21, "end": 53}, {"text": "PtAN3", "start": 109, "end": 114}, {"text": "PtAN1", "start": 119, "end": 124}, {"text": "Pt", "start": 132, "end": 134}, {"text": "adenine", "start": 181, "end": 188}]}}, "schema": []}
{"input": "Non-productive DNA damage binding by DNA glycosylase-like protein Mag2 from Schizosaccharomyces pombe.", "output": {"entities": {}}, "schema": []}
{"input": "Schizosaccharomyces pombe contains two paralogous proteins, Mag1 and Mag2, related to the helix-hairpin-helix (HhH) superfamily of alkylpurine DNA glycosylases from yeast and bacteria.", "output": {"entities": {"chemical": [{"text": "alkylpurine", "start": 131, "end": 142}]}}, "schema": []}
{"input": "Phylogenetic analysis of related proteins from four Schizosaccharomyces and other fungal species shows that the Mag1/Mag2 duplication is unique to the genus Schizosaccharomyces and most likely occurred in its ancestor.", "output": {"entities": {}}, "schema": []}
{"input": "Mag1 excises N3-and N7-alkylguanines and 1, N (6)-ethenoadenine from DNA, whereas Mag2 has been reported to have no detectible alkylpurine base excision activity despite high sequence and active site similarity to Mag1.", "output": {"entities": {"chemical": [{"text": "N3-and N7-alkylguanines", "start": 13, "end": 36}, {"text": "1, N (6)-ethenoadenine", "start": 41, "end": 63}, {"text": "alkylpurine", "start": 127, "end": 138}]}}, "schema": []}
{"input": "To understand this discrepancy we determined the crystal structure of Mag2 bound to abasic DNA and compared it to our previously determined Mag1-DNA structure.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to Mag1, Mag2 does not flip the abasic moiety into the active site or stabilize the DNA strand 5' to the lesion, suggesting that it is incapable of forming a catalytically competent protein-DNA complex.", "output": {"entities": {}}, "schema": []}
{"input": "Subtle differences in Mag1 and Mag2 interactions with the DNA duplex illustrate how Mag2 can stall at damage sites without fully engaging the lesion.", "output": {"entities": {}}, "schema": []}
{"input": "We tested our structural predictions by mutational analysis of base excision and found a single amino acid responsible at least in part for Mag2' s lack of activity.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 96, "end": 106}]}}, "schema": []}
{"input": "Substitution of Mag2 Asp56, which caps the helix at the base of the DNA intercalation loop, with the corresponding serine residue in Mag1 endows Mag2 with epsilon A excision activity comparable to Mag1.", "output": {"entities": {"chemical": [{"text": "serine", "start": 115, "end": 121}]}}, "schema": []}
{"input": "This work provides novel insight into the chemical and physical determinants by which the HhH glycosylases engage DNA in a catalytically productive manner.", "output": {"entities": {}}, "schema": []}
{"input": "Nanodomain coupling at an excitatory cortical synapse.", "output": {"entities": {}}, "schema": []}
{"input": "The coupling distance between presynaptic Ca (2 +) influx and the sensor for vesicular transmitter release determines speed and reliability of synaptic transmission.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Nanodomain coupling (< 100 nm) favors fidelity and is employed by synapses specialized for escape reflexes and by inhibitory synapses involved in synchronizing fast network oscillations.", "output": {"entities": {}}, "schema": []}
{"input": "Cortical glutamatergic synapses seem to forgo the benefits of tight coupling, yet quantitative detail is lacking.", "output": {"entities": {}}, "schema": []}
{"input": "The reduced transmission fidelity of loose coupling, however, raises the question whether it is indeed a general characteristic of cortical synapses.", "output": {"entities": {}}, "schema": []}
{"input": "Here we analyzed excitatory parallel fiber to Purkinje cell synapses, major processing sites for sensory information and well suited for analysis because they typically harbor only a single active zone.", "output": {"entities": {}}, "schema": []}
{"input": "We quantified the coupling distance by combining multiprobability fluctuation analyses, presynaptic Ca (2 +) imaging, and reaction-diffusion simulations in wild-type and calretinin-deficient mice.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 100, "end": 108}]}}, "schema": []}
{"input": "We found a coupling distance of < 30 nm at these synapses, much shorter than at any other glutamatergic cortical synapse investigated to date.", "output": {"entities": {}}, "schema": []}
{"input": "Our results suggest that nanodomain coupling is a general characteristic of conventional cortical synapses involved in high-frequency transmission, allowing for dense gray matter packing and cost-effective neurotransmission.", "output": {"entities": {}}, "schema": []}
{"input": "eRNAs are required for p53-dependent enhancer activity and gene transcription.", "output": {"entities": {}}, "schema": []}
{"input": "Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression.", "output": {"entities": {}}, "schema": []}
{"input": "Using genome-wide chromatin-binding profiles, we describe binding of p53 also to regions located distantly from any known p53 target gene.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that these p53-bound enhancer regions (p53BERs) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, p53BERs produce, in a p53-dependent manner, enhancer RNAs (eRNAs) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, eRNA production from p53BERs is required for efficient p53 transcription enhancement.", "output": {"entities": {}}, "schema": []}
{"input": "Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacokinetics of various important drugs are known to be significantly influenced by the human ABC transporter P-glycoprotein (P-gp), which may lead to clinically relevant drug-drug interactions.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to therapeutic drugs, emerging drugs of abuse (DOA) are sold and consumed without any safety pharmacology testing.", "output": {"entities": {}}, "schema": []}
{"input": "Only some studies on their metabolism were published, but none about their affinity to the transporter systems.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, 47 DOAs from various classes were tested for their P-gp affinity using human P-gp (hP-gp) to predict possible drug-drug interactions.", "output": {"entities": {}}, "schema": []}
{"input": "DOAs were initially screened for general hP-gp affinity and further characterized by modeling classic Michaelis-Menten kinetics and assessing their K (m) and V (max) values.", "output": {"entities": {}}, "schema": []}
{"input": "Among the tested drugs, 12 showed a stimulation of ATPase activity.", "output": {"entities": {}}, "schema": []}
{"input": "The most intensive stimulating DOAs were further investigated and compared with the known P-gp model substrates sertraline and verapamil.", "output": {"entities": {"chemical": [{"text": "sertraline", "start": 112, "end": 122}, {"text": "verapamil", "start": 127, "end": 136}]}}, "schema": []}
{"input": "ATPase stimulation kinetics could be modeled for the entactogen 3, 4-methylenedioxy-alpha-ethylphenethylamine (3, 4-BDB), the hallucinogen 2, 5-dimethoxy-4-iodoamphetamine (DOI), the abused alkaloid glaucine, the opioid-like drugs N-iso-propyl-1, 2-diphenylethylamine (NPDPA), and N-(1-phenylcyclohexyl)-3-ethoxypropanamine (PCEPA), with K (m) and V (max) values within the same range as for verapamil or sertraline.", "output": {"entities": {"chemical": [{"text": "3, 4-methylenedioxy-alpha-ethylphenethylamine", "start": 64, "end": 109}, {"text": "3, 4-BDB", "start": 111, "end": 119}, {"text": "2, 5-dimethoxy-4-iodoamphetamine", "start": 139, "end": 171}, {"text": "DOI", "start": 173, "end": 176}, {"text": "glaucine", "start": 199, "end": 207}, {"text": "N-iso-propyl-1, 2-diphenylethylamine", "start": 231, "end": 267}, {"text": "NPDPA", "start": 269, "end": 274}, {"text": "N-(1-phenylcyclohexyl)-3-ethoxypropanamine", "start": 281, "end": 323}, {"text": "PCEPA", "start": 325, "end": 330}, {"text": "verapamil", "start": 392, "end": 401}, {"text": "sertraline", "start": 405, "end": 415}]}}, "schema": []}
{"input": "As a consequence interactions with other drugs being P-gp substrates might be considered to be very likely and further studies should be encouraged.", "output": {"entities": {}}, "schema": []}
{"input": "6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-kappa B factors.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 0, "end": 6}]}}, "schema": []}
{"input": "6-Hydroxydopamine (6-OHDA) is a neurotoxin that generates an experimental model of Parkinson' s disease in rodents and is commonly employed to induce a lesion in dopaminergic pathways.", "output": {"entities": {"chemical": [{"text": "6-Hydroxydopamine", "start": 0, "end": 17}, {"text": "6-OHDA", "start": 19, "end": 25}]}}, "schema": []}
{"input": "The characterization of those molecular mechanisms linked to 6-OHDA-induced early toxicity is needed to better understand the cellular events further leading to neurodegeneration.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 61, "end": 67}]}}, "schema": []}
{"input": "The present work explored how 6-OHDA triggers early downstream signaling pathways that activate neurotoxicity in the rat striatum.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 30, "end": 36}]}}, "schema": []}
{"input": "Mitochondrial function, caspases-dependent apoptosis, kinases signaling (Akt, ERK 1/2, SAP/JNK and p38) and crosstalk between nuclear factor kappa B (NF-kappa B) and nuclear factor-erythroid-2-related factor 2 (Nrf2) were evaluated at early times post-lesion.", "output": {"entities": {}}, "schema": []}
{"input": "We found that 6-OHDA initiates cell damage via mitochondrial complex I inhibition, cytochrome c and apoptosis-inducing factor (AIF) release, as well as activation of caspases 9 and 3 to induce apoptosis, kinase signaling modulation and NF-kappa B-mediated inflammatory responses, accompanied by inhibition of antioxidant systems regulated by the Nrf2 pathway.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 14, "end": 20}]}}, "schema": []}
{"input": "Our results suggest that kinases SAP/JNK and p38 up-regulation may play a role in the early stages of 6-OHDA toxicity to trigger intrinsic pathways for apoptosis and enhanced NF-kappa B activation.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 102, "end": 108}]}}, "schema": []}
{"input": "In turn, these cellular events inhibit the activation of cytoprotective mechanisms, thereby leading to a condition of general damage.", "output": {"entities": {}}, "schema": []}
{"input": "The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterial transcription is initiated after RNA polymerase (RNAP) binds to promoter DNA, melts ~ 14 bp around the transcription start site and forms a single-stranded \" transcription bubble \" within a catalytically active RNAP-DNA open complex (RP (o)).", "output": {"entities": {}}, "schema": []}
{"input": "There is significant flexibility in the transcription start site, which causes variable spacing between the promoter elements and the start site; this in turn causes differences in the length and sequence at the 5' end of RNA transcripts and can be important for gene regulation.", "output": {"entities": {}}, "schema": []}
{"input": "The start-site variability also implies the presence of some flexibility in the positioning of the DNA relative to the RNAP active site in RP (o).", "output": {"entities": {}}, "schema": []}
{"input": "The flexibility may occur in the positioning of the transcription bubble prior to RNA synthesis and may reflect bubble expansion (\" scrunching \") or bubble contraction (\" unscrunching \").", "output": {"entities": {}}, "schema": []}
{"input": "Here, we assess the presence of dynamic flexibility in RP (o) with single-molecule FRET (F o rster resonance energy transfer).", "output": {"entities": {}}, "schema": []}
{"input": "We obtain experimental evidence for dynamic flexibility in RP (o) using different FRET rulers and labeling positions.", "output": {"entities": {}}, "schema": []}
{"input": "An analysis of FRET distributions of RP (o) using burst variance analysis reveals conformational fluctuations in RP (o) in the millisecond timescale.", "output": {"entities": {}}, "schema": []}
{"input": "Further experiments using subsets of nucleotides and DNA mutations allowed us to reprogram the transcription start sites, in a way that can be described by repositioning of the single-stranded transcription bubble relative to the RNAP active site within RP (o).", "output": {"entities": {}}, "schema": []}
{"input": "Our study marks the first experimental observation of conformational dynamics in the transcription bubble of RP (o) and indicates that DNA dynamics within the bubble affect the search for transcription start sites.", "output": {"entities": {}}, "schema": []}
{"input": "The use of Reamer Irrigator Aspirator (RIA) autograft harvest in the treatment of critical-sized iliac wing defects in sheep: investigation of dexamethasone and beta-tricalcium phosphate augmentation.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 143, "end": 156}, {"text": "beta-tricalcium phosphate", "start": 161, "end": 186}]}}, "schema": []}
{"input": "Bone grafts are commonly used for the treatment of segmental bone defects and fracture non-unions.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, osseous particles obtained during intermedullary canal reaming (using a Reamer-Irrigator-Aspirator (RIA) device) have been evaluated as graft material during in vitro and clinical studies.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to evaluate and quantify new bone formation after implantation of bone graft material obtained after reaming of the tibia in a bilateral critical-sized iliac wing defect in sheep and to investigate the effect of the augmentation of this graft.", "output": {"entities": {}}, "schema": []}
{"input": "A reamer bone graft alone, or after short term incubation in a dexamethasone enriched solution, and a reamer graft collected using beta-tricalcium phosphate (beta-TCP) granules in the filter of the RIA collection device were compared to autologous iliac wing graft.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 63, "end": 76}, {"text": "beta-tricalcium phosphate", "start": 131, "end": 156}, {"text": "beta-TCP", "start": 158, "end": 166}]}}, "schema": []}
{"input": "In addition, reamer graft was combined with the cellular fraction collected from the irrigation fluid with and without short-term incubation in a dexamethasone enriched solution.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 146, "end": 159}]}}, "schema": []}
{"input": "It was hypothesized that the amount of physical bone in the reamer bone graft groups would be higher than the amount in the autologous iliac wing graft group and that augmentation of a reamer bone graft would increase bone formation.", "output": {"entities": {}}, "schema": []}
{"input": "Three months after implantation, the amount of new bone formation (as percentage of the total defect volume) in the defects was evaluated ex-vivo by means of micro-CT and histomorphometry.", "output": {"entities": {}}, "schema": []}
{"input": "The mean amount of bone in the autologous iliac wing graft group was 17. 7% and 16. 8% for micro-CT and histomorphometry, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The mean amount of bone in all reamer graft groups ranged between 20. 4-29. 2% (micro-CT) and 17. 0-25. 4% (histomorphometry).", "output": {"entities": {}}, "schema": []}
{"input": "Reamer graft collected using beta-TCP granules (29. 2 +/- 1. 7%) in the filter produced a significantly higher amount of bone in comparison to an autologous iliac wing graft evaluated by micro-CT.", "output": {"entities": {"chemical": [{"text": "beta-TCP", "start": 29, "end": 37}]}}, "schema": []}
{"input": "RIA bone grafts added a small increase in bone volume to the 3month graft volume in this preclinical sheep model.", "output": {"entities": {}}, "schema": []}
{"input": "The current model does not support the use of short-term high concentration dexamethasone for augmentation of a graft volume.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 76, "end": 89}]}}, "schema": []}
{"input": "If avoidance of an iliac wing graft is desirable, or a reaming procedure is required, then a RIA graft or RIA graft plus beta-TCP granules are as good as the current gold standard for this model.", "output": {"entities": {"chemical": [{"text": "beta-TCP", "start": 121, "end": 129}]}}, "schema": []}
{"input": "Pharmacokinetics explain in vivo/in vitro discrepancies of carcinogen-induced gene expression alterations in rat liver and cultivated hepatocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Cultivated hepatocytes represent a well-established in vitro system.", "output": {"entities": {}}, "schema": []}
{"input": "However, the applicability of hepatocytes in toxicogenomics is still controversially discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, an in vivo/in vitro discrepancy has been described, whereby the non-genotoxic rat liver carcinogen methapyrilene alters the expression of the metabolizing genes SULT1A1 and ABAT, as well as the DNA damage response gene GADD34 in vitro, but not in vivo.", "output": {"entities": {"chemical": [{"text": "methapyrilene", "start": 109, "end": 122}]}}, "schema": []}
{"input": "If the collagen sandwich cultures of hepatocytes really produce false-positive data, this would compromise its application in toxicogenomics.", "output": {"entities": {}}, "schema": []}
{"input": "To revisit the putative in vivo/in vitro discrepancy, we first analyzed and modeled methapyrilene concentrations in the portal vein of rats.", "output": {"entities": {"chemical": [{"text": "methapyrilene", "start": 84, "end": 97}]}}, "schema": []}
{"input": "The relatively short half-life of 2. 8 h implies a rapid decrease in orally administered methapyrilene in vivo below concentrations that can cause gene expression alterations.", "output": {"entities": {"chemical": [{"text": "methapyrilene", "start": 89, "end": 102}]}}, "schema": []}
{"input": "This corresponded to the time-dependent alteration levels of GADD34, ABAT and SULT1A1 RNA in the liver: RNA levels are altered 1, 6 and 12 h after methapyrilene administration, but return to control levels after 24 and 72 h.", "output": {"entities": {"chemical": [{"text": "methapyrilene", "start": 147, "end": 160}]}}, "schema": []}
{"input": "In contrast, methapyrilene concentrations in the culture medium supernatant of primary rat hepatocyte cultures decreased slowly.", "output": {"entities": {"chemical": [{"text": "methapyrilene", "start": 13, "end": 26}]}}, "schema": []}
{"input": "This explains why GADD34, ABAT and SULT1A1 were still deregulated after 24 h exposure in vitro, but not in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "It should also be considered that the earliest analyzed time point in the previous in vivo studies was 24 h after methapyrilene administration.", "output": {"entities": {"chemical": [{"text": "methapyrilene", "start": 114, "end": 127}]}}, "schema": []}
{"input": "In conclusion, previously observed in vitro/in vivo discrepancy can be explained by different pharmacokinetics present in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "When the in vivo half-life is short, levels of some initially altered genes may have returned to control levels already 24 h after administration.", "output": {"entities": {}}, "schema": []}
{"input": "New targets for the antitumor activity of gambogic acid in hematologic malignancies.", "output": {"entities": {"chemical": [{"text": "gambogic acid", "start": 42, "end": 55}]}}, "schema": []}
{"input": "Gambogic acid (GA) is the main active ingredient of gamboge, a brownish to orange dry resin secreted from Garcinia hanburyi, a plant that is widely distributed in nature.", "output": {"entities": {"chemical": [{"text": "Gambogic acid", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Recent in vitro and in vivo studies have demonstrated that GA exerts potent antitumor effects against solid tumors of various derivations, and its antitumor mechanisms have been thoroughly investigated.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, normal cells remain relatively resistant to GA, indicating a therapeutic window.", "output": {"entities": {}}, "schema": []}
{"input": "GA is currently in clinical trials in China.", "output": {"entities": {}}, "schema": []}
{"input": "Over the last decade, our laboratory demonstrates that GA exhibits potent anticancer activities against hematological malignancies.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on the new mechanisms through which GA inhibits proliferation and induces apoptosis in malignant hematological cells.", "output": {"entities": {}}, "schema": []}
{"input": "These include the regulation of expression and intracellular positioning of nucleoporin and nucleophosmin; downregulation of steroid receptor coactivator-3 (SRC-3) and its downstream proteins; upregulation of death inducer-obliterator (DIO-1); downregulation of HERG potassium channel; as well as induction of reactive oxygen species (ROS) accumulation.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 125, "end": 132}, {"text": "potassium", "start": 267, "end": 276}, {"text": "oxygen", "start": 319, "end": 325}]}}, "schema": []}
{"input": "Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells.", "output": {"entities": {"chemical": [{"text": "spirolactone", "start": 13, "end": 25}, {"text": "diterpenoid", "start": 31, "end": 42}, {"text": "kaurene", "start": 60, "end": 67}, {"text": "oridonin", "start": 73, "end": 81}]}}, "schema": []}
{"input": "A series of novel spirolactone-type diterpenoid derivatives of oridonin (12a-j) were designed and synthesized.", "output": {"entities": {"chemical": [{"text": "spirolactone", "start": 18, "end": 30}, {"text": "diterpenoid", "start": 36, "end": 47}, {"text": "oridonin", "start": 63, "end": 71}]}}, "schema": []}
{"input": "All the target compounds showed improved anti-proliferative activity against a panel of human cancer cell lines and the most effective compound 12j was more potent than positive control Taxol in K562 and Bel-7402 cells with IC (50) values of 0. 39 mu M and 1. 39 mu M, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The cellular mechanisms showed that compound 12j induced apoptosis at low micromolar concentrations in human hepatoma Bel-7402 cells.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate that the spirolactone-type diterpenoid derivatives of oridonin have optimized growth inhibitory activity against cancer cells and interesting apoptosis-inducing ability.", "output": {"entities": {"chemical": [{"text": "spirolactone", "start": 35, "end": 47}, {"text": "diterpenoid", "start": 53, "end": 64}, {"text": "oridonin", "start": 80, "end": 88}]}}, "schema": []}
{"input": "Effects of water restriction on reproductive physiology and affiliative behavior in an opportunistically-breeding and monogamous songbird, the zebra finch.", "output": {"entities": {}}, "schema": []}
{"input": "Wild zebra finches form long-term monogamous pair-bonds that are actively maintained year-round, even when not in breeding condition.", "output": {"entities": {}}, "schema": []}
{"input": "These desert finches are opportunistic breeders, and breeding is highly influenced by unpredictable rainfall.", "output": {"entities": {}}, "schema": []}
{"input": "Their high levels of affiliation and complex breeding patterns make zebra finches an excellent model in which to study the endocrine regulation of affiliation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we compared zebra finch pairs that were provided with water ad libitum (control) or water restricted.", "output": {"entities": {}}, "schema": []}
{"input": "We examined (1) reproductive physiology, (2) pair-maintenance behaviors in several contexts, and (3) circulating and brain steroid levels.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 123, "end": 130}]}}, "schema": []}
{"input": "In females, water restriction profoundly reduced largest ovarian follicle size, ovary size, oviduct size, and egg laying.", "output": {"entities": {}}, "schema": []}
{"input": "In males, water restriction had no effect on testes size but decreased systemic testosterone levels.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 80, "end": 92}]}}, "schema": []}
{"input": "However, in the hypothalamus, local testosterone and estradiol levels were unaffected by water restriction in both sexes.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 36, "end": 48}, {"text": "estradiol", "start": 53, "end": 62}]}}, "schema": []}
{"input": "Systemic and local levels of the androgen precursor dehydroepiandrosterone (DHEA) were also unaffected by water restriction.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 33, "end": 41}, {"text": "dehydroepiandrosterone", "start": 52, "end": 74}, {"text": "DHEA", "start": 76, "end": 80}]}}, "schema": []}
{"input": "Lastly, in three different behavioral paradigms, we examined a variety of pair-maintenance behaviors, and none were reduced by water restriction.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these correlational data are consistent with the hypothesis that local production of sex steroids in the brain promotes the expression of pair-maintenance behaviors in non-breeding zebra finches.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 105, "end": 113}]}}, "schema": []}
{"input": "Trichothecene toxicity in eukaryotes: cellular and molecular mechanisms in plants and animals.", "output": {"entities": {"chemical": [{"text": "Trichothecene", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Trichothecenes are sesquiterpenoid mycotoxins commonly found as contaminants in cereal grains and are a major health and food safety concern due to their toxicity to humans and farm animals.", "output": {"entities": {"chemical": [{"text": "Trichothecenes", "start": 0, "end": 14}, {"text": "sesquiterpenoid mycotoxins", "start": 19, "end": 45}]}}, "schema": []}
{"input": "Trichothecenes are predominantly produced by the phytopathogenic Fusarium fungus, and in plants they act as a virulence factor aiding the spread of the fungus during disease development.", "output": {"entities": {"chemical": [{"text": "Trichothecenes", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Known for their inhibitory effect on eukaryotic protein synthesis, trichothecenes also induce oxidative stress, DNA damage and cell cycle arrest and affect cell membrane integrity and function in eukaryotic cells.", "output": {"entities": {"chemical": [{"text": "trichothecenes", "start": 67, "end": 81}]}}, "schema": []}
{"input": "In animals, trichothecenes can be either immunostimulatory or immunosuppressive and induce apoptosis via mitochondria-mediated or-independent pathway.", "output": {"entities": {"chemical": [{"text": "trichothecenes", "start": 12, "end": 26}]}}, "schema": []}
{"input": "In plants, trichothecenes induce programmed cell death via production of reactive oxygen species.", "output": {"entities": {"chemical": [{"text": "trichothecenes", "start": 11, "end": 25}]}}, "schema": []}
{"input": "Recent advances in molecular techniques have led to the elucidation of signal transduction pathways that manifest trichothecene toxicity in eukaryotes.", "output": {"entities": {"chemical": [{"text": "trichothecene", "start": 114, "end": 127}]}}, "schema": []}
{"input": "In animals, trichothecenes induce mitogen-activated protein kinase (MAPK) signalling cascades via ribotoxic stress response and/or endoplasmic reticulum stress response.", "output": {"entities": {"chemical": [{"text": "trichothecenes", "start": 12, "end": 26}]}}, "schema": []}
{"input": "The upstream signalling events that lead to the activation trichothecene-induced ribotoxic stress response are discussed.", "output": {"entities": {"chemical": [{"text": "trichothecene", "start": 59, "end": 72}]}}, "schema": []}
{"input": "In plants, trichothecenes exhibit elicitor-like activity leading to the inductions MAPKs and genes involved in oxidative stress, cell death and plant defence response.", "output": {"entities": {"chemical": [{"text": "trichothecenes", "start": 11, "end": 25}]}}, "schema": []}
{"input": "Trichothecenes might also modulate hormone-mediated defence signalling and abiotic stress signalling in plants.", "output": {"entities": {"chemical": [{"text": "Trichothecenes", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Cationic nanoparticles disrupt cellular signaling in a cholesterol dependent manner.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 55, "end": 66}]}}, "schema": []}
{"input": "In this study, we investigate the interaction of charged polystyrene particles with respiratory epithelial cells.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 57, "end": 68}]}}, "schema": []}
{"input": "Experiments were designed to reveal the effect of cellular interaction with particles of varying size and charge and how such interactions could alter cytokine induced cellular processes.", "output": {"entities": {}}, "schema": []}
{"input": "A549 cells, containing a stably transfected Interleukin-8 (IL-8) Luciferase promoter construct, were cultured in the presence of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and polystyrene particles for 4. 5h.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 202, "end": 213}]}}, "schema": []}
{"input": "Several endpoints were measured: IL-8 gene expression, IL-6 protein, IL-8 protein, and NF-k B translocation.", "output": {"entities": {}}, "schema": []}
{"input": "At 4. 5h, cellular viability was maintained for the particle exposed cells.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, we found that only the cationic nanoparticles have the ability to disrupt the TNF-alpha stimulated cellular signaling by reducing the IL-8 promoter activity, IL-6 and IL-8 protein.", "output": {"entities": {}}, "schema": []}
{"input": "Cationic nanoparticles reduce these processes through interfering with NF-kappa B translocation.", "output": {"entities": {}}, "schema": []}
{"input": "However, the activity of the cationic nanoparticles on the IL-8 promoter and NF-kappa B translocation is lost when cholesterol is depleted from A549 cells before particle exposure, which suggests that cationic nanoparticles rely on membrane cholesterol integrity to disrupt cellular signaling.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 115, "end": 126}, {"text": "cholesterol", "start": 241, "end": 252}]}}, "schema": []}
{"input": "Fecal microbiota composition differs between children with beta-cell autoimmunity and those without.", "output": {"entities": {}}, "schema": []}
{"input": "The role of the intestinal microbiota as a regulator of autoimmune diabetes in animal models is well-established, but data on human type 1 diabetes are tentative and based on studies including only a few study subjects.", "output": {"entities": {}}, "schema": []}
{"input": "To exclude secondary effects of diabetes and HLA risk genotype on gut microbiota, we compared the intestinal microbiota composition in children with at least two diabetes-associated autoantibodies (n = 18) with autoantibody-negative children matched for age, sex, early feeding history, and HLA risk genotype using pyrosequencing.", "output": {"entities": {}}, "schema": []}
{"input": "Principal component analysis indicated that a low abundance of lactate-producing and butyrate-producing species was associated with beta-cell autoimmunity.", "output": {"entities": {"chemical": [{"text": "lactate", "start": 63, "end": 70}, {"text": "butyrate", "start": 85, "end": 93}]}}, "schema": []}
{"input": "In addition, a dearth of the two most dominant Bifidobacterium species, Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and an increased abundance of the Bacteroides genus were observed in the children with beta-cell autoimmunity.", "output": {"entities": {}}, "schema": []}
{"input": "We did not find increased fecal calprotectin or IgA as marker of inflammation in children with beta-cell autoimmunity.", "output": {"entities": {}}, "schema": []}
{"input": "Functional studies related to the observed alterations in the gut microbiome are warranted because the low abundance of bifidobacteria and butyrate-producing species could adversely affect the intestinal epithelial barrier function and inflammation, whereas the apparent importance of the Bacteroides genus in development of type 1 diabetes is insufficiently understood.", "output": {"entities": {"chemical": [{"text": "butyrate", "start": 139, "end": 147}]}}, "schema": []}
{"input": "EphA5-EphrinA5 interactions within the ventromedial hypothalamus influence counterregulatory hormone release and local glutamine/glutamate balance during hypoglycemia.", "output": {"entities": {"chemical": [{"text": "glutamine", "start": 119, "end": 128}, {"text": "glutamate", "start": 129, "end": 138}]}}, "schema": []}
{"input": "Activation of beta-cell EphA5 receptors by its ligand ephrinA5 from adjacent beta-cells has been reported to decrease insulin secretion during hypoglycemia.", "output": {"entities": {}}, "schema": []}
{"input": "Given the similarities between islet and ventromedial hypothalamus (VMH) glucose sensing, we tested the hypothesis that the EphA5/ephrinA5 system might function within the VMH during hypoglycemia to stimulate counterregulatory hormone release as well.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 73, "end": 80}]}}, "schema": []}
{"input": "Counterregulatory responses and glutamine/glutamate concentrations in the VMH were assessed during a hyperinsulinemic-hypoglycemic glucose clamp study in chronically catheterized awake male Sprague-Dawley rats that received an acute VMH microinjection of ephrinA5-Fc, chronic VMH knockdown, or overexpression of ephrinA5 using an adenoassociated viral construct.", "output": {"entities": {"chemical": [{"text": "glutamine", "start": 32, "end": 41}, {"text": "glutamate", "start": 42, "end": 51}, {"text": "glucose", "start": 131, "end": 138}]}}, "schema": []}
{"input": "Local stimulation of VMH EphA5 receptors by ephrinA5-Fc or ephrinA5 overexpression increased, whereas knockdown of VMH ephrinA5 reduced counterregulatory responses during hypoglycemia.", "output": {"entities": {}}, "schema": []}
{"input": "Overexpression of VMH ephrinA5 transiently increased local glutamate concentrations, whereas ephrinA5 knockdown produced profound suppression of VMH interstitial fluid glutamine concentrations in the basal state and during hypoglycemia.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 59, "end": 68}, {"text": "glutamine", "start": 168, "end": 177}]}}, "schema": []}
{"input": "Changes in ephrinA5/EphA5 interactions within the VMH, a key brain glucose-sensing region, act in concert with islets to restore glucose homeostasis during acute hypoglycemia, and its effect on counterregulation may be mediated by changes in glutamate/glutamine cycling.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 67, "end": 74}, {"text": "glucose", "start": 129, "end": 136}, {"text": "glutamate", "start": 242, "end": 251}, {"text": "glutamine", "start": 252, "end": 261}]}}, "schema": []}
{"input": "Electrical Stimuli Release ATP to Increase GLUT4 Translocation and Glucose Uptake via PI3K gamma-Akt-AS160 in Skeletal Muscle Cells.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 27, "end": 30}, {"text": "Glucose", "start": 67, "end": 74}]}}, "schema": []}
{"input": "Skeletal muscle glucose uptake in response to exercise is preserved in insulin-resistant conditions, but the signals involved are debated.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 16, "end": 23}]}}, "schema": []}
{"input": "ATP is released from skeletal muscle by contractile activity and can autocrinely signal through purinergic receptors, and we hypothesized it may influence glucose uptake.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 0, "end": 3}, {"text": "glucose", "start": 155, "end": 162}]}}, "schema": []}
{"input": "Electrical stimulation, ATP, and insulin each increased fluorescent 2-NBD-Glucose (2-NBDG) uptake in primary myotubes, but only electrical stimulation and ATP-dependent 2-NBDG uptake were inhibited by adenosine-phosphate phosphatase and by purinergic receptor blockade (suramin).", "output": {"entities": {"chemical": [{"text": "ATP", "start": 24, "end": 27}, {"text": "2-NBD-Glucose", "start": 68, "end": 81}, {"text": "2-NBDG", "start": 83, "end": 89}, {"text": "ATP", "start": 155, "end": 158}, {"text": "2-NBDG", "start": 169, "end": 175}, {"text": "adenosine-phosphate", "start": 201, "end": 220}, {"text": "suramin", "start": 270, "end": 277}]}}, "schema": []}
{"input": "Electrical stimulation transiently elevated extracellular ATP and caused Akt phosphorylation that was additive to insulin and inhibited by suramin.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 58, "end": 61}, {"text": "suramin", "start": 139, "end": 146}]}}, "schema": []}
{"input": "Exogenous ATP transiently activated Akt and, inhibiting phosphatidylinositol 3-kinase (PI3K) or Akt as well as dominant-negative Akt mutant, reduced ATP-dependent 2-NBDG uptake and Akt phosphorylation.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 10, "end": 13}, {"text": "ATP", "start": 149, "end": 152}, {"text": "2-NBDG", "start": 163, "end": 169}]}}, "schema": []}
{"input": "ATP-dependent 2-NBDG uptake was also inhibited by the G protein beta gamma subunit-interacting peptide beta ark-ct and by the phosphatidylinositol 3-kinase-gamma (PI3K gamma) inhibitor AS605240.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 0, "end": 3}, {"text": "2-NBDG", "start": 14, "end": 20}, {"text": "AS605240", "start": 185, "end": 193}]}}, "schema": []}
{"input": "ATP caused translocation of GLUT4myc-eGFP to the cell surface, mechanistically mediated by increased exocytosis involving AS160/Rab8A reduced by dominant-negative Akt or PI3K gamma kinase-dead mutants, and potentiated by myristoylated PI3K gamma.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 0, "end": 3}]}}, "schema": []}
{"input": "ATP stimulated 2-NBDG uptake in normal and insulin-resistant adult muscle fibers, resembling the reported effect of exercise.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 0, "end": 3}, {"text": "2-NBDG", "start": 15, "end": 21}]}}, "schema": []}
{"input": "Hence, the ATP-induced pathway may be tapped to bypass insulin resistance.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 11, "end": 14}]}}, "schema": []}
{"input": "Permanent Neonatal Diabetes in INSC94Y Transgenic Pigs.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations in the insulin (INS) gene may cause permanent neonatal diabetes mellitus (PNDM).", "output": {"entities": {}}, "schema": []}
{"input": "Ins2 mutant mouse models provided important insights into the disease mechanisms of PNDM but have limitations for translational research.", "output": {"entities": {}}, "schema": []}
{"input": "To establish a large animal model of PNDM, we generated INS (C94Y) transgenic pigs.", "output": {"entities": {}}, "schema": []}
{"input": "A line expressing high levels of INS (C94Y) mRNA (70-86% of wild-type INS transcripts) exhibited elevated blood glucose soon after birth but unaltered beta-cell mass at the age of 8 days.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 112, "end": 119}]}}, "schema": []}
{"input": "At 4. 5 months, INS (C94Y) transgenic pigs exhibited 41% reduced body weight, 72% decreased beta-cell mass (-53% relative to body weight), and 60% lower fasting insulin levels compared with littermate controls.", "output": {"entities": {}}, "schema": []}
{"input": "beta-cells of INS (C94Y) transgenic pigs showed a marked reduction of insulin secretory granules and severe dilation of the endoplasmic reticulum.", "output": {"entities": {}}, "schema": []}
{"input": "Cataract development was already visible in 8-day-old INS (C94Y) transgenic pigs and became more severe with increasing age.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetes-associated pathological alterations of kidney and nervous tissue were not detected during the observation period of 1 year.", "output": {"entities": {}}, "schema": []}
{"input": "The stable diabetic phenotype and its rescue by insulin treatment make the INS (C94Y) transgenic pig an attractive model for insulin supplementation and islet transplantation trials, and for studying developmental consequences of maternal diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Nogo-a downregulation improves insulin secretion in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Type 2 diabetes (T2D) is characterized by beta-cell dysfunction and the subsequent depletion of insulin production, usually in a context of increased peripheral insulin resistance.", "output": {"entities": {}}, "schema": []}
{"input": "T2D patients are routinely treated with oral antidiabetic agents such as sulfonylureas or dipeptidyl peptidase-4 antagonists, which promote glucose-and incretin-dependent insulin secretion, respectively.", "output": {"entities": {"chemical": [{"text": "sulfonylureas", "start": 73, "end": 86}, {"text": "glucose", "start": 140, "end": 147}]}}, "schema": []}
{"input": "Interestingly, insulin secretion may also be induced by neural stimulation.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report the expression of Nogo-A in beta-cells.", "output": {"entities": {}}, "schema": []}
{"input": "Nogo-A is a membrane protein that inhibits neurite outgrowth and cell migration in the central nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that Nogo-A-deficient mice display improved insulin secretion and glucose clearance.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 78, "end": 85}]}}, "schema": []}
{"input": "This was associated with a stronger parasympathetic input and higher sensitivity of beta-cells to the cholinergic analog carbachol.", "output": {"entities": {"chemical": [{"text": "carbachol", "start": 121, "end": 130}]}}, "schema": []}
{"input": "Insulin secretion was also improved in diabetic db/db mice treated with neutralizing antibody against Nogo-A.", "output": {"entities": {}}, "schema": []}
{"input": "Together, these findings suggest that promoting the vagal stimulation of insulin secretion through the selective inhibition of Nogo-A could be a novel therapeutic approach in T2D.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro cytotoxicity and genotoxicity studies of titanium dioxide (TiO2) nanoparticles in Chinese hamster lung fibroblast cells.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 50, "end": 66}, {"text": "TiO2", "start": 68, "end": 72}]}}, "schema": []}
{"input": "There are increasing safety concerns about the development and abundant use of nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "The unique physical and chemical characteristics of titanium dioxide (TiO2) nanoparticles result in different chemical and biological activities compared to their larger micron-sized counterparts, and can subsequently play an important role in influencing toxicity.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 52, "end": 68}, {"text": "TiO2", "start": 70, "end": 74}]}}, "schema": []}
{"input": "Therefore, our objective was to investigate the cytotoxicity and genotoxicity of commercially available TiO2 nanoparticles with respect to their selected physicochemical properties, as well as the role of surface coating of these nanoparticles.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 104, "end": 108}]}}, "schema": []}
{"input": "While all types of tested TiO2 samples decrease cell viability in a mass-based concentration-and size-dependent manner, the polyacrylate-coated nano-TiO2 product was only cytotoxic at higher concentrations.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 26, "end": 30}, {"text": "polyacrylate", "start": 124, "end": 136}, {"text": "TiO2", "start": 149, "end": 153}]}}, "schema": []}
{"input": "A similar pattern of response was observed for induction of apoptosis/necrosis, and no DNA damage was detected in the polyacrylate-coated nano-TiO2 model.", "output": {"entities": {"chemical": [{"text": "polyacrylate", "start": 118, "end": 130}, {"text": "TiO2", "start": 143, "end": 147}]}}, "schema": []}
{"input": "Given the increasing production of TiO2 nanoparticles, toxicological studies should take into account the physiochemical properties of these nanoparticles that may help researchers to develop new nanoparticles with minimum toxicity.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 35, "end": 39}]}}, "schema": []}
{"input": "A novel stimuli-synchronized alloy-treated matrix for space-defined gastrointestinal delivery of mesalamine in the Large White pig model.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 97, "end": 107}]}}, "schema": []}
{"input": "The study focussed on designing a Stimuli-Synchronized Matrix (SSM) for space-defined colonic delivery of the anti-inflammatory drug mesalamine.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 133, "end": 143}]}}, "schema": []}
{"input": "The configured matrix provided time-independent delivery and stimuli targeting.", "output": {"entities": {}}, "schema": []}
{"input": "Formulations were optimized according to a Box-Behnken experimental design that constituted mesalamine-loaded BaSO4-crosslinked chitosan dispersed within a pectin, carboxymethylcellulose and xanthan gum complex.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 92, "end": 102}, {"text": "BaSO4", "start": 110, "end": 115}]}}, "schema": []}
{"input": "The complex was compressed into matrices and subsequently alloy-treated with pectin and ethylcellulose.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro drug release was determined in the presence and absence of colonic enzymes and the mean dissolution time was used for formulation optimization.", "output": {"entities": {}}, "schema": []}
{"input": "To mechanistically elucidate the synchronous catalytic action of the enzymes pectinase and glucosidase on the matrix, computer-aided 3D modelling of active fractions of the enzyme-substrate complexes was generated to predict the orientation of residues affecting the substrate domain.", "output": {"entities": {}}, "schema": []}
{"input": "Drug release profiles revealed distinct colonic enzyme responsiveness with fractions of 0. 402 and 0. 152 of mesalamine released in the presence and absence of enzymes, respectively after 24h.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 109, "end": 119}]}}, "schema": []}
{"input": "The commercial comparator product showed irreproducible release profiles over the same period (SD = 0. 550) compared to the SSM formulation (SD = 0. 037).", "output": {"entities": {}}, "schema": []}
{"input": "FTIR spectra of alloy-treated matrices showed no peaks from 1589 to 1512cm (-1) after colonic enzyme exposure.", "output": {"entities": {}}, "schema": []}
{"input": "With increasing enzyme exposure there were also no peaks between 1646 and 1132cm (-1).", "output": {"entities": {}}, "schema": []}
{"input": "This indicated polymeric enzyme cleavage for controlled and space-defined release of mesalamine.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 85, "end": 95}]}}, "schema": []}
{"input": "Plasma concentration profiles in the Large White pig model produced a Cmax of 3. 77 +/- 1. 375 mu g/mL compared to 10. 604 +/- 2. 846 mu g/mL for the comparator formulation.", "output": {"entities": {}}, "schema": []}
{"input": "The SSM formulation proved superior over the comparator product by providing superiorly controlled enzyme-responsive colonic drug delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Discriminative stimulus effects of the GABAB receptor-positive modulator rac-BHFF: comparison with GABAB receptor agonists and drugs of abuse.", "output": {"entities": {"chemical": [{"text": "rac-BHFF", "start": 73, "end": 81}]}}, "schema": []}
{"input": "GABA (B) receptor-positive modulators are thought to have advantages as potential medications for anxiety, depression, and drug addiction.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "They may have fewer side effects than GABA (B) receptor agonists, because selective enhancement of activated receptors could have effects different from nonselective activation of all receptors.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 38, "end": 42}]}}, "schema": []}
{"input": "To examine this, pigeons were trained to discriminate the GABA (B) receptor-positive modulator (R, S)-5, 7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF) from its vehicle.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 58, "end": 62}, {"text": "(R, S)-5, 7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one", "start": 95, "end": 168}, {"text": "rac-BHFF", "start": 170, "end": 178}]}}, "schema": []}
{"input": "The discriminative stimulus effects of rac-BHFF were not mimicked by the GABA (B) receptor agonists baclofen and gamma-hydroxybutyrate (GHB), not by diazepam, and not by alcohol, cocaine, and nicotine, whose self-administration has been reported to be attenuated by GABA (B) receptor-positive modulators.", "output": {"entities": {"chemical": [{"text": "rac-BHFF", "start": 39, "end": 47}, {"text": "GABA", "start": 73, "end": 77}, {"text": "baclofen", "start": 100, "end": 108}, {"text": "gamma-hydroxybutyrate", "start": 113, "end": 134}, {"text": "GHB", "start": 136, "end": 139}, {"text": "diazepam", "start": 149, "end": 157}, {"text": "alcohol", "start": 170, "end": 177}, {"text": "cocaine", "start": 179, "end": 186}, {"text": "nicotine", "start": 192, "end": 200}, {"text": "GABA", "start": 266, "end": 270}]}}, "schema": []}
{"input": "The discriminative stimulus effects of rac-BHFF were not antagonized by the GABA (B) receptor antagonist 3-aminopropyl (diethoxymethyl) phosphinic acid (CGP35348) but were attenuated by the less efficacious GABA (B) receptor-positive modulator 2, 6-di-tert-butyl-4-(3-hydroxy-2, 2-dimethylpropyl) phenol (CGP7930), suggesting the possibility that rac-BHFF produces its discriminative stimulus effects by directly activating GABA (B2) subunits of GABA (B) receptors.", "output": {"entities": {"chemical": [{"text": "rac-BHFF", "start": 39, "end": 47}, {"text": "GABA", "start": 76, "end": 80}, {"text": "3-aminopropyl (diethoxymethyl) phosphinic acid", "start": 105, "end": 151}, {"text": "CGP35348", "start": 153, "end": 161}, {"text": "GABA", "start": 207, "end": 211}, {"text": "2, 6-di-tert-butyl-4-(3-hydroxy-2, 2-dimethylpropyl) phenol", "start": 244, "end": 303}, {"text": "CGP7930", "start": 305, "end": 312}, {"text": "rac-BHFF", "start": 347, "end": 355}, {"text": "GABA", "start": 424, "end": 428}, {"text": "GABA", "start": 446, "end": 450}]}}, "schema": []}
{"input": "At a dose 10-fold lower than the training dose, rac-BHFF enhanced the discriminative stimulus effects of baclofen, but not of GHB.", "output": {"entities": {"chemical": [{"text": "rac-BHFF", "start": 48, "end": 56}, {"text": "baclofen", "start": 105, "end": 113}, {"text": "GHB", "start": 126, "end": 129}]}}, "schema": []}
{"input": "This study provides evidence that the effects of GABA (B) receptor-positive modulators are not identical to those of GABA (B) receptor agonists.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 49, "end": 53}, {"text": "GABA", "start": 117, "end": 121}]}}, "schema": []}
{"input": "In addition, the results suggest that positive modulation of GABA (B) receptors does not produce discriminative stimulus effects similar to those of benzodiazepines, alcohol, cocaine, and nicotine.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 61, "end": 65}, {"text": "benzodiazepines", "start": 149, "end": 164}, {"text": "alcohol", "start": 166, "end": 173}, {"text": "cocaine", "start": 175, "end": 182}, {"text": "nicotine", "start": 188, "end": 196}]}}, "schema": []}
{"input": "Finally, the finding that rac-BHFF enhanced effects of baclofen but not of GHB is consistent with converging evidence that the populations of GABA (B) receptors mediating the effects of baclofen and GHB are not identical.", "output": {"entities": {"chemical": [{"text": "rac-BHFF", "start": 26, "end": 34}, {"text": "baclofen", "start": 55, "end": 63}, {"text": "GHB", "start": 75, "end": 78}, {"text": "GABA", "start": 142, "end": 146}, {"text": "baclofen", "start": 186, "end": 194}, {"text": "GHB", "start": 199, "end": 202}]}}, "schema": []}
{"input": "Biocompatibility and levofloxacin delivery of mesoporous materials.", "output": {"entities": {"chemical": [{"text": "levofloxacin", "start": 21, "end": 33}]}}, "schema": []}
{"input": "A comparative study of mesoporous matrices designed for both drug-loading methods, impregnation (IP) and surfactant-assisted drug loading (also denoted as one-pot, OP), has been carried out evaluating their physicochemical characteristics, cell response, drug delivery profiles, and antibacterial activity.", "output": {"entities": {}}, "schema": []}
{"input": "Surfactant-free (calcined) and surfactant-templated (non-calcined) mesoporous silica have been used as IP and OP starting matrices, respectively.", "output": {"entities": {"chemical": [{"text": "silica", "start": 78, "end": 84}]}}, "schema": []}
{"input": "Both non-calcined and calcined matrices do not exert any cytotoxic effect on osteoblasts.", "output": {"entities": {}}, "schema": []}
{"input": "However, non-calcined matrices induce on fibroblasts a significant proliferation delay with morphological alterations and dose-dependent increases in fibroblast size, internal complexity, and intracellular calcium content but without cell lysis and apoptosis.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 206, "end": 213}]}}, "schema": []}
{"input": "Residual ethanol and the surface silanol groups in these non-calcined matrices are involved in the observed fibroblast changes.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 9, "end": 16}, {"text": "silanol", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Finally, both IP and OP matrices have been loaded with levofloxacin to compare them as drug delivery systems.", "output": {"entities": {"chemical": [{"text": "levofloxacin", "start": 55, "end": 67}]}}, "schema": []}
{"input": "Both IP and OP matrices exhibit similar in vitro levofloxacin release profiles, showing an initial fast delivery followed by a sustained release during long time periods.", "output": {"entities": {"chemical": [{"text": "levofloxacin", "start": 49, "end": 61}]}}, "schema": []}
{"input": "These profiles and the antimicrobial activity results suggest the use of these IP and OP matrices as local drug delivery systems in the osteomyelitis and other bone infection treatments.", "output": {"entities": {}}, "schema": []}
{"input": "The COP9 signalosome interacts with and regulates interferon regulatory factor 5 protein stability.", "output": {"entities": {}}, "schema": []}
{"input": "The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization.", "output": {"entities": {}}, "schema": []}
{"input": "Tight regulation of IRF5 is thus warranted for an efficient response toward extracellular stressors and for limiting autoimmune and inflammatory responses.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability.", "output": {"entities": {}}, "schema": []}
{"input": "The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations.", "output": {"entities": {}}, "schema": []}
{"input": "The CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single internal deletion from amino acids 455 to 466 (Delta 455-466) was found to significantly reduce IRF5 protein stability.", "output": {"entities": {"chemical": [{"text": "carboxyl", "start": 41, "end": 49}, {"text": "amino", "start": 54, "end": 59}, {"text": "amino acids", "start": 109, "end": 120}]}}, "schema": []}
{"input": "CSN subunit 3 (CSN3) was identified as a direct interacting partner of IRF5, and knockdown of this subunit with small interfering RNAs resulted in enhanced degradation.", "output": {"entities": {}}, "schema": []}
{"input": "Degradation was further augmented by knockdown of CSN1 and CSN3 together.", "output": {"entities": {}}, "schema": []}
{"input": "The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor MG132 prevented IRF5 degradation, supporting the idea that its stability is regulated by the ubiquitin-proteasome system.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, activation of IRF5 by the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction.", "output": {"entities": {}}, "schema": []}
{"input": "This study defines CSN to be a new interacting partner of IRF5 that controls its stability.", "output": {"entities": {}}, "schema": []}
{"input": "Osteoblast lineage-specific effects of notch activation in the skeleton.", "output": {"entities": {}}, "schema": []}
{"input": "Transgenic overexpression of the Notch1 intracellular domain inhibits osteoblast differentiation and causes osteopenia, and inactivation of Notch1 and Notch2 increases bone volume transiently and induces osteoblastic differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "However, the biology of Notch is cell-context-dependent, and consequences of Notch activation in cells of the osteoblastic lineage at various stages of differentiation and in osteocytes have not been defined.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, Rosa (Notch) mice, where a loxP-flanked STOP cassette placed between the Rosa26 promoter and the NICD coding sequence, were crossed with transgenics expressing the Cre recombinase under the control of the Osterix (Osx), Osteocalcin (Oc), Collagen 1a1 (Col2. 3), or Dentin matrix protein1 (Dmp1) promoters.", "output": {"entities": {}}, "schema": []}
{"input": "At 1 month, Osx-Cre; Rosa (Notch) and Oc-Cre; Rosa (Notch) mice exhibited osteopenia due to impaired bone formation.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, Col2. 3-Cre; Rosa (Notch) and Dmp1-Cre; Rosa (Notch) exhibited increased femoral trabecular bone volume due to a decrease in osteoclast number and eroded surface.", "output": {"entities": {}}, "schema": []}
{"input": "In the four lines studied, cortical bone was either not present, was porous, or had the appearance of trabecular bone.", "output": {"entities": {}}, "schema": []}
{"input": "Oc-Cre; Rosa (Notch) and Col2. 3-Cre; Rosa (Notch) mice exhibited early lethality so that their adult phenotype was not established.", "output": {"entities": {}}, "schema": []}
{"input": "At 3 months, Osx-Cre; Rosa (Notch) and Dmp1-Cre; Rosa (Notch) mice displayed increased bone volume, and increased osteoblasts although calcein-demeclocycline labels were diffuse and fragmented, indicating abnormal bone formation.", "output": {"entities": {"chemical": [{"text": "calcein", "start": 135, "end": 142}]}}, "schema": []}
{"input": "In conclusion, Notch effects in the skeleton are cell-context-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "When expressed in immature osteoblasts, Notch arrests their differentiation, causing osteopenia, and when expressed in osteocytes, it causes an initial suppression of bone resorption and increased bone volume, a phenotype that evolves as the mice mature.", "output": {"entities": {}}, "schema": []}
{"input": "RNA dimerization plays a role in ribosomal frameshifting of the SARS coronavirus.", "output": {"entities": {}}, "schema": []}
{"input": "Messenger RNA encoded signals that are involved in programmed-1 ribosomal frameshifting (-1 PRF) are typically two-stemmed hairpin (H)-type pseudoknots (pks).", "output": {"entities": {}}, "schema": []}
{"input": "We previously described an unusual three-stemmed pseudoknot from the severe acute respiratory syndrome (SARS) coronavirus (CoV) that stimulated-1 PRF.", "output": {"entities": {}}, "schema": []}
{"input": "The conserved existence of a third stem-loop suggested an important hitherto unknown function.", "output": {"entities": {}}, "schema": []}
{"input": "Here we present new information describing structure and function of the third stem of the SARS pseudoknot.", "output": {"entities": {}}, "schema": []}
{"input": "We uncovered RNA dimerization through a palindromic sequence embedded in the SARS-CoV Stem 3.", "output": {"entities": {}}, "schema": []}
{"input": "Further in vitro analysis revealed that SARS-CoV RNA dimers assemble through' kissing' loop-loop interactions.", "output": {"entities": {}}, "schema": []}
{"input": "We also show that loop-loop kissing complex formation becomes more efficient at physiological temperature and in the presence of magnesium.", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 129, "end": 138}]}}, "schema": []}
{"input": "When the palindromic sequence was mutated, in vitro RNA dimerization was abolished, and frameshifting was reduced from 15 to 5. 7%.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the inability to dimerize caused by the silent codon change in Stem 3 of SARS-CoV changed the viral growth kinetics and affected the levels of genomic and subgenomic RNA in infected cells.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that the homodimeric RNA complex formed by the SARS pseudoknot occurs in the cellular environment and that loop-loop kissing interactions involving Stem 3 modulate-1 PRF and play a role in subgenomic and full-length RNA synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Survey of recent literature related to the biologically active 4 (3H)-quinazolinones containing fused heterocycles.", "output": {"entities": {"chemical": [{"text": "4 (3H)-quinazolinones", "start": 63, "end": 84}]}}, "schema": []}
{"input": "The present review focuses on the synthesis and biological evaluation of polycyclic 4 (3H)-quinazolinones containing fused aromatic or heteroaromatic rings.", "output": {"entities": {"chemical": [{"text": "polycyclic 4 (3H)-quinazolinones", "start": 73, "end": 105}]}}, "schema": []}
{"input": "The first part of the review is related to compounds with ring fused to the pyrimidine part of the quinazoline core.", "output": {"entities": {"chemical": [{"text": "pyrimidine", "start": 76, "end": 86}, {"text": "quinazoline", "start": 99, "end": 110}]}}, "schema": []}
{"input": "Most of the quinazolinone alkaloids belong to this class of molecules.", "output": {"entities": {"chemical": [{"text": "quinazolinone alkaloids", "start": 12, "end": 35}]}}, "schema": []}
{"input": "The second part presents molecules bearing extra ring (s) fused to the benzo moiety of the quinazolinone skeleton.", "output": {"entities": {"chemical": [{"text": "benzo", "start": 71, "end": 76}, {"text": "quinazolinone", "start": 91, "end": 104}]}}, "schema": []}
{"input": "Their structural diversity opens new fields in the search of active molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Deregulation of HOX B13 expression in urinary bladder cancer progression.", "output": {"entities": {}}, "schema": []}
{"input": "Urinary bladder cancer is a common malignancy in industrialized countries.", "output": {"entities": {}}, "schema": []}
{"input": "More than 90% of bladder cancer originates in the transitional cells.", "output": {"entities": {}}, "schema": []}
{"input": "Bladder transitional cancer prognosis is, according to the most recent definition related to the level of tumor infiltration, characterized by two main phenotypes, Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC).", "output": {"entities": {}}, "schema": []}
{"input": "The genetic profile and the clinical course of the two subtypes are completely different, however among NMIBC the prognosis is not completely predictable, since 20% of the cases experience a relapse, even in the form of MIBC.", "output": {"entities": {}}, "schema": []}
{"input": "It has recently been reported that the chromosomal region 12q13-15, containing crucial cancer genes such as MDM2, CDK4, GLI and an entire cluster of HOX genes, is amplified in bladder cancer.", "output": {"entities": {}}, "schema": []}
{"input": "HOX genes codify for transcriptionl factor, involved in embryonal development and cancer progression, with main nuclear expression.", "output": {"entities": {}}, "schema": []}
{"input": "Particularly it was also described the strong involvement of HOX B13 in several tumors of urogenital system.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we have been investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX B13 expression in bladder cancer evolution and progression, evaluating its ability to discriminate between NMIBC and MBCI phenotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Cytoplasmic HOX B13 delocalization significantly relates with muscle invasion (p 0. 004).", "output": {"entities": {}}, "schema": []}
{"input": "In addition in the series of NMIBC nuclear HOX B13 expression loss is significantly associated to shorter disease free survival (p-value = 0. 038) defining a potential prognostic role.", "output": {"entities": {}}, "schema": []}
{"input": "Overexpression of HOX B13 in more aggressive phenotype is also demonstrate at gene level by quantitative RT-PCR.", "output": {"entities": {}}, "schema": []}
{"input": "The de-regulation and delocalization of HOX B13 in urinary bladder cancer supports again the important role of HOX genes in tumor evolution and represents a starting point to establish an integrated analysis, in which HOX genes represent important prognostic and predictive markers for bladder cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Display of amino groups on substrate surfaces by simple dip-coating of methacrylate-based polymers and its application to DNA immobilization.", "output": {"entities": {"chemical": [{"text": "amino", "start": 11, "end": 16}, {"text": "methacrylate", "start": 71, "end": 83}]}}, "schema": []}
{"input": "The implementation of a reactive functional group onto a material surface is of great importance.", "output": {"entities": {}}, "schema": []}
{"input": "Reactive functional groups (e. g., an amino group and a hydroxyl group) are usually hydrophilic, which makes it difficult to display them on a dry polymer surface.", "output": {"entities": {"chemical": [{"text": "amino", "start": 38, "end": 43}, {"text": "hydroxyl", "start": 56, "end": 64}]}}, "schema": []}
{"input": "We here propose a novel method for displaying amino groups on the surfaces of polymeric substrates through dip-coating of a methacrylate-based copolymer.", "output": {"entities": {"chemical": [{"text": "amino", "start": 46, "end": 51}, {"text": "methacrylate", "start": 124, "end": 136}]}}, "schema": []}
{"input": "We synthesized copolymers composed of methyl methacrylate and 2-aminoethyl methacrylate with different protecting groups or ion-complexes on their amino groups, then dip-coated the copolymers onto a poly (methyl methacrylate) (PMMA) substrate.", "output": {"entities": {"chemical": [{"text": "methyl methacrylate", "start": 38, "end": 57}, {"text": "2-aminoethyl methacrylate", "start": 62, "end": 87}, {"text": "amino", "start": 147, "end": 152}, {"text": "poly (methyl methacrylate)", "start": 199, "end": 225}, {"text": "PMMA", "start": 227, "end": 231}]}}, "schema": []}
{"input": "Evaluation using a cleavable fluorescent compound, which was synthesized in the present study to quantify a small amount (pmol/cm (2)) of amino groups on a solid surface, revealed that the protection of amino groups affected their surface segregation in the copolymer coating.", "output": {"entities": {"chemical": [{"text": "amino", "start": 138, "end": 143}, {"text": "amino", "start": 203, "end": 208}]}}, "schema": []}
{"input": "p-Toluenesulfonate ion-complex and tert-butoxycarbonyl (Boc) protection of amino groups were found to effectively display amino groups on the surface (more than 70 pmol/cm (2)).", "output": {"entities": {"chemical": [{"text": "p-Toluenesulfonate", "start": 0, "end": 18}, {"text": "tert-butoxycarbonyl", "start": 35, "end": 54}, {"text": "Boc", "start": 56, "end": 59}, {"text": "amino", "start": 75, "end": 80}, {"text": "amino", "start": 122, "end": 127}]}}, "schema": []}
{"input": "The density of amino groups displayed on a surface can be easily controlled by mixing the copolymer and PMMA before dip-coating.", "output": {"entities": {"chemical": [{"text": "amino", "start": 15, "end": 20}, {"text": "PMMA", "start": 104, "end": 108}]}}, "schema": []}
{"input": "Dip-coating of the copolymer with Boc protection on various polymeric substrates also successfully displayed amino groups on their surfaces.", "output": {"entities": {"chemical": [{"text": "Boc", "start": 34, "end": 37}, {"text": "amino", "start": 109, "end": 114}]}}, "schema": []}
{"input": "Finally, we demonstrated that the amino groups displayed can be utilized for the immobilization of a DNA oligonucleotide on a substrate surface.", "output": {"entities": {"chemical": [{"text": "amino", "start": 34, "end": 39}]}}, "schema": []}
{"input": "Kinetics of the reaction of crystal violet with hydroxide ion in the critical solution of 2-butoxyethanol + water.", "output": {"entities": {"chemical": [{"text": "crystal violet", "start": 28, "end": 42}, {"text": "hydroxide", "start": 48, "end": 57}, {"text": "2-butoxyethanol", "start": 90, "end": 105}]}}, "schema": []}
{"input": "The kinetics of alkaline fading of crystal violet (CV) has been studied by UV spectrophotometry and microcalorimetry in the critical binary solution of 2-butoxyethanol + water at the initial reaction stage and various temperatures.", "output": {"entities": {"chemical": [{"text": "crystal violet", "start": 35, "end": 49}, {"text": "2-butoxyethanol", "start": 152, "end": 167}]}}, "schema": []}
{"input": "It was found that the first-order rate constants obtained from these two methods are well accorded with each other, and the temperature dependence of the rate constant obeyed the Arrhenius equation in a temperature region far from the critical point.", "output": {"entities": {}}, "schema": []}
{"input": "The critical slowing down was detected by both methods near the critical point.", "output": {"entities": {}}, "schema": []}
{"input": "A simple empirical crossover model was proposed and used to analyze the experimental data to obtain the critical exponents, which were 0. 158 +/- 0. 013 and 0. 133 +/- 0. 012 from UV spectrophotometry and microcalorimetry, respectively, and the former was in good agreement with the theoretical prediction of 0. 151.", "output": {"entities": {}}, "schema": []}
{"input": "The slight lower value derived from microcalorimetry was attributed to the stirring in the microcalorimeter, which weakened the critical reduction of the diffusion coefficient.", "output": {"entities": {}}, "schema": []}
{"input": "Spatial variation of available electronic excitations within individual quantum dots.", "output": {"entities": {}}, "schema": []}
{"input": "Quantum dots (QDs) allow for manipulation of the position and energy levels of electrons at sub-10 nm length scales through control of material chemistry, size, and shape.", "output": {"entities": {}}, "schema": []}
{"input": "It is known from optical studies that the bandgap of semiconductor QDs increases as their size decreases due to the narrowing of the quantum confinement potential.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism of quantum confinement also indicates that the localized properties within individual QDs should depend on their shape in addition to their size, but direct observations of this effect have proven challenging due to the limited spatial resolution of measurement techniques at this scale and the ability to remove contributions from the surroundings.", "output": {"entities": {}}, "schema": []}
{"input": "Here we present experimental evidence of spatial variations in the lowest available electron transition energy within a series of single electrically isolated QDs due to a dome-shaped geometry, measured using electron energy-loss spectroscopy in a (scanning) transmission electron microscope [(S) TEM-EELS].", "output": {"entities": {}}, "schema": []}
{"input": "We observe a consistent increase in the energy onset of electronic excitations from the lateral center of the dot toward the edges, which we attribute purely to shape.", "output": {"entities": {}}, "schema": []}
{"input": "This trend is in qualitative agreement with a simple quantum simulation of the local density of states in a dome-shaped QD.", "output": {"entities": {}}, "schema": []}
{"input": "PGRMC2, a yet uncharacterized protein with potential as tumor suppressor, migration inhibitor, and regulator of cytochrome P450 enzyme activity.", "output": {"entities": {}}, "schema": []}
{"input": "PGRMC2 (progesterone receptor membrane component 2) is highly homologous if compared with PGRMC1, a cytochrome-related protein, which is induced in several cancers and linked to cell growth in these cancers.", "output": {"entities": {}}, "schema": []}
{"input": "Further it seems to be involved in progesterone signalling and cytochrome P450 binding.", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 35, "end": 47}]}}, "schema": []}
{"input": "For PGRMC2 only sparse information is available.", "output": {"entities": {}}, "schema": []}
{"input": "Recent data show that PGRMC1 and 2 share several similar characteristics, but there are also important differences in expression and function of the both proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Several findings point to the fact that PGRMC2 might play a role in cancer as well.", "output": {"entities": {}}, "schema": []}
{"input": "The protein influences the migration rate of ovarian cancer cells and a loss of PGRMC2 might result in higher metastasis rates.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to PGRMC1 it seems more likely to act as a tumor suppressor than a promoter.", "output": {"entities": {}}, "schema": []}
{"input": "Altered PGRMC2 expression was further detected in the context of term and preterm labour, though the implications of this finding are currently unknown and need further examination.", "output": {"entities": {}}, "schema": []}
{"input": "PGRMC2 further might play a role in gynaecologic diseases like preterm labour and endometriosis.", "output": {"entities": {}}, "schema": []}
{"input": "PGRMC2 shares the cellular localisation and the ability to bind cytochrome enzymes with PGRMC1.", "output": {"entities": {}}, "schema": []}
{"input": "Further the protein was shown to influence the activity of CYP3A4.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, though not much is known about PGRMC2 so far, it deserves further examination as data point to a role of PGRMC2 as tumor suppressor, migration inhibitor and regulator of cytochrome P450 proteins.", "output": {"entities": {}}, "schema": []}
{"input": "PXR-mediated P-glycoprotein induction by small molecule tyrosine kinase inhibitors.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 56, "end": 64}]}}, "schema": []}
{"input": "The rapid development of drug resistance as a result of exposure to small molecule tyrosine kinase inhibitors (TKIs) is an important drawback to the successful use of these agents in the clinic.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 83, "end": 91}]}}, "schema": []}
{"input": "Although one of the most established mechanisms by which cells acquire drug resistance to anticancer drugs is the up regulation of drug efflux transporters such as P-glycoprotein (PGP), it is currently still unknown whether TKIs have the propensity to induce PGP.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of TKIs on the protein expression and activity of PGP was assessed after treatment of LS180 cells with clinically relevant concentrations of the TKIs.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the involvement of the nuclear pregnane X receptor (PXR), a known regulator of PGP expression, was determined.", "output": {"entities": {"chemical": [{"text": "pregnane", "start": 44, "end": 52}]}}, "schema": []}
{"input": "At least five out of the nine tested TKIs (erlotinib, gefitinib, nilotinib, sorafenib, vandetanib) were able to induce the expression of PGP within 48 h in LS180 cells.", "output": {"entities": {"chemical": [{"text": "erlotinib", "start": 43, "end": 52}, {"text": "gefitinib", "start": 54, "end": 63}, {"text": "nilotinib", "start": 65, "end": 74}, {"text": "sorafenib", "start": 76, "end": 85}, {"text": "vandetanib", "start": 87, "end": 97}]}}, "schema": []}
{"input": "Accordingly, these TKIs were also shown to affect the accumulation of a P-glycoprotein specific probe substrate.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we showed that the pregnane X receptor (PXR), which is an important regulator of PGP induction, is involved in the upregulation of PGP protein expression following exposure to these TKIs.", "output": {"entities": {"chemical": [{"text": "pregnane", "start": 32, "end": 40}]}}, "schema": []}
{"input": "Our data show that PXR-mediated upregulation of PGP expression by TKIs might be a possible mechanism underlying acquired drug resistance in cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections.", "output": {"entities": {"chemical": [{"text": "acyl-homoserine-lactone", "start": 43, "end": 66}]}}, "schema": []}
{"input": "In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections.", "output": {"entities": {}}, "schema": []}
{"input": "It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells.", "output": {"entities": {}}, "schema": []}
{"input": "PvdQ is an acyl-homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS.", "output": {"entities": {"chemical": [{"text": "acyl-homoserine lactone", "start": 11, "end": 34}, {"text": "AHL", "start": 36, "end": 39}]}}, "schema": []}
{"input": "The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model.", "output": {"entities": {}}, "schema": []}
{"input": "For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 101, "end": 109}, {"text": "trehalose", "start": 111, "end": 120}]}}, "schema": []}
{"input": "The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20 degrees C and 55 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 98, "end": 106}, {"text": "trehalose", "start": 108, "end": 117}]}}, "schema": []}
{"input": "However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55 degrees C for at least 4 weeks.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 9, "end": 17}, {"text": "trehalose", "start": 99, "end": 108}]}}, "schema": []}
{"input": "The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 35, "end": 43}, {"text": "trehalose", "start": 148, "end": 157}]}}, "schema": []}
{"input": "The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of ~ 1. 8 mu m implying that they are suitable for pulmonary delivery.", "output": {"entities": {"chemical": [{"text": "trehalose", "start": 4, "end": 13}]}}, "schema": []}
{"input": "This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation.", "output": {"entities": {"chemical": [{"text": "AHL", "start": 36, "end": 39}]}}, "schema": []}
{"input": "(R)-beta-lysine-modified elongation factor P functions in translation elongation.", "output": {"entities": {"chemical": [{"text": "(R)-beta-lysine", "start": 0, "end": 15}]}}, "schema": []}
{"input": "Post-translational modification of bacterial elongation factor P (EF-P) with (R)-beta-lysine at a conserved lysine residue activates the protein in vivo and increases puromycin reactivity of the ribosome in vitro.", "output": {"entities": {"chemical": [{"text": "(R)-beta-lysine", "start": 77, "end": 92}]}}, "schema": []}
{"input": "The additional hydroxylation of EF-P at the same lysine residue by the YfcM protein has also recently been described.", "output": {"entities": {"chemical": [{"text": "lysine", "start": 49, "end": 55}]}}, "schema": []}
{"input": "The roles of modified and unmodified EF-P during different steps in translation, and how this correlates to its physiological role in the cell, have recently been linked to the synthesis of polyproline stretches in proteins.", "output": {"entities": {"chemical": [{"text": "polyproline", "start": 190, "end": 201}]}}, "schema": []}
{"input": "Polysome analysis indicated that EF-P functions in translation elongation, rather than initiation as proposed previously.", "output": {"entities": {}}, "schema": []}
{"input": "This was further supported by the inability of EF-P to enhance the rate of formation of fMet-Lys or fMet-Phe, indicating that the role of EF-P is not to specifically stimulate formation of the first peptide bond.", "output": {"entities": {"chemical": [{"text": "fMet-Lys", "start": 88, "end": 96}, {"text": "fMet-Phe", "start": 100, "end": 108}]}}, "schema": []}
{"input": "Investigation of hydroxyl-(beta)-lysyl-EF-P showed 30% increased puromycin reactivity but no differences in dipeptide synthesis rates when compared with the beta-lysylated form.", "output": {"entities": {"chemical": [{"text": "hydroxyl-(beta)-lysyl", "start": 17, "end": 38}, {"text": "puromycin", "start": 65, "end": 74}]}}, "schema": []}
{"input": "Unlike disruption of the other genes required for EF-P modification, deletion of yfcM had no phenotypic consequences in Salmonella.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our findings indicate that EF-P functions in translation elongation, a role critically dependent on post-translational beta-lysylation but not hydroxylation.", "output": {"entities": {}}, "schema": []}
{"input": "Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid and o-cresol and blood toluene).", "output": {"entities": {"chemical": [{"text": "toluene", "start": 14, "end": 21}, {"text": "mercapturic acids", "start": 40, "end": 57}, {"text": "hippuric acid", "start": 97, "end": 110}, {"text": "o-cresol", "start": 115, "end": 123}, {"text": "toluene", "start": 134, "end": 141}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "Toluene (TOL) is a neurotoxic, ototoxic and reprotoxic solvent which is metabolized via the glutathione pathway, producing benzylmercapturic, o-, m-and p-toluylmercapturic acids (MAs).", "output": {"entities": {"chemical": [{"text": "Toluene", "start": 0, "end": 7}, {"text": "TOL", "start": 9, "end": 12}, {"text": "glutathione", "start": 92, "end": 103}, {"text": "benzylmercapturic, o-, m-and p-toluylmercapturic acids", "start": 123, "end": 177}, {"text": "MAs", "start": 179, "end": 182}]}}, "schema": []}
{"input": "These metabolites could be useful as biomarkers of TOL exposure.", "output": {"entities": {"chemical": [{"text": "TOL", "start": 51, "end": 54}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "The aims of this study were (1) to provide data on MAs excretion in rat urine following TOL exposure by inhalation, (2) to compare them to data from traditional TOL biomarkers, i. e. TOL in blood (Tol-B), and urinary hippuric acid (HA) and o-cresol (oCre) and (3) to establish a relationship between these different indicators and the airborne TOL concentration (Tol-A).", "output": {"entities": {"chemical": [{"text": "MAs", "start": 51, "end": 54}, {"text": "TOL", "start": 88, "end": 91}, {"text": "TOL", "start": 161, "end": 164}, {"text": "TOL", "start": 183, "end": 186}, {"text": "Tol", "start": 197, "end": 200}, {"text": "hippuric acid", "start": 217, "end": 230}, {"text": "o-cresol", "start": 240, "end": 248}, {"text": "oCre", "start": 250, "end": 254}, {"text": "TOL", "start": 344, "end": 347}, {"text": "Tol", "start": 363, "end": 366}]}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "Sprague-Dawley rats were exposed to a range of TOL concentrations.", "output": {"entities": {"chemical": [{"text": "TOL", "start": 47, "end": 50}]}}, "schema": []}
{"input": "Blood and urine were collected and analyzed to determine biomarker levels.", "output": {"entities": {}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "Levels of the four MAs correlate strongly with Tol-A (comparable to the correlation with Tol-B).", "output": {"entities": {"chemical": [{"text": "MAs", "start": 19, "end": 22}, {"text": "Tol", "start": 47, "end": 50}, {"text": "Tol", "start": 89, "end": 92}]}}, "schema": []}
{"input": "5.", "output": {"entities": {}}, "schema": []}
{"input": "MAs are thus clearly superior to oCre and HA as potential markers of exposure to TOL.", "output": {"entities": {"chemical": [{"text": "MAs", "start": 0, "end": 3}, {"text": "oCre", "start": 33, "end": 37}, {"text": "TOL", "start": 81, "end": 84}]}}, "schema": []}
{"input": "Evolving therapeutic targets in ischemic stroke: a concise review.", "output": {"entities": {}}, "schema": []}
{"input": "Ischemic stroke is the leading cause of mortality and morbidity worldwide for which the assemblage of therapeutic interventions has remained outstandingly limited.", "output": {"entities": {}}, "schema": []}
{"input": "Several new insights into the causes of neuronal death during ischemic event have led to the identification of some important novel targets for intervention.", "output": {"entities": {}}, "schema": []}
{"input": "This article highlights some of the promising protein targets, which are in the validation process and have the potential to get translated into viable neurotherapeutics against ischemic stroke.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment of estrogen receptor-positive breast cancer.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive.", "output": {"entities": {"chemical": [{"text": "Estrogen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER + tumors, who may receive ET alone or in combination with cytotoxic therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs).", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 74, "end": 82}]}}, "schema": []}
{"input": "In patients with ER + tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone.", "output": {"entities": {"chemical": [{"text": "gonadotropin-releasing hormone", "start": 66, "end": 96}]}}, "schema": []}
{"input": "Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues.", "output": {"entities": {"chemical": [{"text": "Tamoxifen", "start": 0, "end": 9}]}}, "schema": []}
{"input": "For these reasons, other SERMs have been developed.", "output": {"entities": {}}, "schema": []}
{"input": "Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus.", "output": {"entities": {"chemical": [{"text": "Fulvestrant", "start": 0, "end": 11}, {"text": "tamoxifen", "start": 149, "end": 158}, {"text": "estrogen", "start": 166, "end": 174}]}}, "schema": []}
{"input": "The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs.", "output": {"entities": {}}, "schema": []}
{"input": "In postmenopausal patients with ER + BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy.", "output": {"entities": {"chemical": [{"text": "tamoxifen", "start": 126, "end": 135}]}}, "schema": []}
{"input": "Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.", "output": {"entities": {}}, "schema": []}
{"input": "Targeted approaches to triple-negative breast cancer: current practice and future directions.", "output": {"entities": {}}, "schema": []}
{"input": "Triple-negative breast cancer (TNBC), that is breast cancer which stains negatively at immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2), comprises a particularly aggressive subtype of breast cancer, with high rate of early local and distant relapse.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 112, "end": 120}, {"text": "progesterone", "start": 136, "end": 148}]}}, "schema": []}
{"input": "TNBC have demonstrated sensitivity to cytotoxic treatment regimens, but in the absence of HER2, ER and PR there is no benefit from hormonal therapy or trastuzumab.", "output": {"entities": {}}, "schema": []}
{"input": "The lack of known specific molecular targets has promoted abundant research in order to find possible \" vulnerabilities \" in TNBC and the evaluation of novel biomarkers overcoming the traditional approach based on hormonal receptors and HER2-targeted therapy is one of the priorities in breast cancer research.", "output": {"entities": {}}, "schema": []}
{"input": "Drugs under investigation can be broadly subdivided into four groups: (1) Agents that create DNA damage (i. e. cisplatin, cyclophosphamide); (2) Agents that inhibit poly (ADP-ribose) polymerase (PARP); (3) Tyrosin-kinase inhibitors and monoclonal antibodies; (4) Agents that inhibit downstream signals.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 111, "end": 120}, {"text": "cyclophosphamide", "start": 122, "end": 138}, {"text": "poly (ADP-ribose)", "start": 165, "end": 182}, {"text": "Tyrosin", "start": 206, "end": 213}]}}, "schema": []}
{"input": "Several preclinical and early phase clinical trials for the treatment or management of patients with triple-negative breast tumors are underway.", "output": {"entities": {}}, "schema": []}
{"input": "Nonetheless, so far the major issue to deal with when trying to provide evidence for TNBC is the small numbers of the sample in the clinical studies and the retrospective nature of most of them.", "output": {"entities": {}}, "schema": []}
{"input": "Future large studies could help in defining optimal treatment strategies for TNBC, both in the advanced setting as well as in the (neo) adjuvant setting.", "output": {"entities": {}}, "schema": []}
{"input": "Entry inhibitors directed towards glycoprotein gp120: an overview on a promising target for HIV-1 therapy.", "output": {"entities": {}}, "schema": []}
{"input": "In spite of the unquestionable positive impact of HAART in the treatment of HIV infection, the discovery and development of novel agents directed towards other targets of the replicative cycle of the virus that differ from those targeted by the clinically approved drugs, emerges nowadays as an imperative need.", "output": {"entities": {}}, "schema": []}
{"input": "The blockade of HIV entry is a highly promising strategy against the pathogen and glycoprotein gp120 is a central actor in this process.", "output": {"entities": {}}, "schema": []}
{"input": "This review discusses the current status in the research of anti-HIV agents targeting specifically the envelope protein gp120.", "output": {"entities": {}}, "schema": []}
{"input": "The diverse approaches devoted to the achievement of therapeutic agents against gp120 currently under study are organized and analyzed critically according to their specific mechanism of inhibition and structural features.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of novel androgen receptor antagonists using structure-and ligand-based methods.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer (PCa).", "output": {"entities": {"chemical": [{"text": "Androgen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The AR hormone-binding site (HBS) is intensively studied and represents the target area for current antiandrogens including Bicalutamide and structurally related Enzalutamide.", "output": {"entities": {"chemical": [{"text": "Bicalutamide", "start": 124, "end": 136}, {"text": "Enzalutamide", "start": 162, "end": 174}]}}, "schema": []}
{"input": "As resistance to antiandrogens invariably emerges in advanced prostate cancer, there exists a high medical need for the identification and development of novel AR antagonists of different chemotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Given the wealth of structural information on the AR in complex with a variety of ligands, we have applied an integrated structure-and ligand-based virtual screening methodology to identify novel AR antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "Virtual hits generated by a consensus voting approach were experimentally evaluated and resulted in the discovery of a number of structurally diverse submicromolar antagonists of the AR.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, one identified compound demonstrated anti-AR potency in vitro that is comparable to the clinically used Bicalutamide.", "output": {"entities": {}}, "schema": []}
{"input": "These results set a ground for the development of novel classes of PCa drugs that are structurally different from current AR antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "Structure-based design, synthesis and evaluation of novel anthra [1, 2-d] imidazole-6, 11-dione derivatives as telomerase inhibitors and potential for cancer polypharmacology.", "output": {"entities": {"chemical": [{"text": "anthra [1, 2-d] imidazole-6, 11-dione", "start": 58, "end": 95}]}}, "schema": []}
{"input": "A series of anthra [1, 2-d] imidazole-6, 11-dione derivatives were synthesized and evaluated for telomerase inhibition, hTERT expression and suppression of cancer cell growth in vitro.", "output": {"entities": {"chemical": [{"text": "anthra [1, 2-d] imidazole-6, 11-dione", "start": 12, "end": 49}]}}, "schema": []}
{"input": "All of the compounds tested, except for compounds 4, 7, 16, 24, 27 and 28 were selected by the NCI screening system.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, compounds 16, 39, and 40 repressed hTERT expression without greatly affecting cell growth, suggesting for the selectivity toward hTERT expression.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase and polypharmacological targeting strategy.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological activity against Trypanosoma cruzi of substituted 1, 4-naphthoquinones.", "output": {"entities": {"chemical": [{"text": "1, 4-naphthoquinones", "start": 75, "end": 95}]}}, "schema": []}
{"input": "The discovery and development of essential drugs for Chagas disease is a major concern worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "New substituted 1, 4-naphthoquinones were synthesized and tested against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease.", "output": {"entities": {"chemical": [{"text": "1, 4-naphthoquinones", "start": 16, "end": 36}]}}, "schema": []}
{"input": "These products exhibited substantial activity against T. cruzi, especially 2-((8E, 11Z)-heptadeca-8, 11-dienyl)-3-hydroxynaphthalene-1, 4-dione (9) with IC (50) of 7. 8 mu M.", "output": {"entities": {"chemical": [{"text": "2-((8E, 11Z)-heptadeca-8, 11-dienyl)-3-hydroxynaphthalene-1, 4-dione", "start": 75, "end": 143}]}}, "schema": []}
{"input": "Synthesis and Biological Evaluation of [1, 2, 4] Triazolo [3, 4-a] phthalazine and Tetrazolo [5, 1-a] phthalazine Derivatives Bearing Substituted Benzylpiperazine Moieties as Positive Inotropic Agents.", "output": {"entities": {"chemical": [{"text": "[1, 2, 4] Triazolo [3, 4-a] phthalazine", "start": 39, "end": 78}, {"text": "Tetrazolo [5, 1-a] phthalazine", "start": 83, "end": 113}, {"text": "Benzylpiperazine", "start": 146, "end": 162}]}}, "schema": []}
{"input": "Two series of [1, 2, 4] triazolo [3, 4-a] phthalazine and tetrazolo [5, 1-a] phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations.", "output": {"entities": {"chemical": [{"text": "[1, 2, 4] triazolo [3, 4-a] phthalazine", "start": 14, "end": 53}, {"text": "tetrazolo [5, 1-a] phthalazine", "start": 58, "end": 88}, {"text": "benzylpiperazine", "start": 121, "end": 137}]}}, "schema": []}
{"input": "The majority of the derivatives exhibited better in vitro activity than the existing drug, milrinone, and 6-((4-(4-methoxyphenyl) piperazin-1-yl) methyl) tetrazolo [5, 1-a] phthalazine.", "output": {"entities": {"chemical": [{"text": "milrinone", "start": 91, "end": 100}, {"text": "6-((4-(4-methoxyphenyl) piperazin-1-yl) methyl) tetrazolo [5, 1-a] phthalazine", "start": 106, "end": 184}]}}, "schema": []}
{"input": "8 m in particular was identified as the most potent with an increased stroke volume of 12. 02 +/- 0. 20% (milrinone: 2. 46 +/- 0. 07%) at a concentration of 3 x 10 (-5) m.", "output": {"entities": {"chemical": [{"text": "milrinone", "start": 106, "end": 115}]}}, "schema": []}
{"input": "The chronotropic effects of the compounds that exhibited good potency were also evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Combined effects of the herbicide terbuthylazine and temperature on different flagellates from the Northern Adriatic Sea.", "output": {"entities": {"chemical": [{"text": "terbuthylazine", "start": 34, "end": 48}]}}, "schema": []}
{"input": "The triazinic herbicide terbuthylazine (TBA) is becoming an emergent contaminant in Italian rivers and in coastal and groundwater.", "output": {"entities": {"chemical": [{"text": "terbuthylazine", "start": 24, "end": 38}, {"text": "TBA", "start": 40, "end": 43}]}}, "schema": []}
{"input": "A preliminary analysis of the sensitivity of marine flagellates to TBA was performed by monitoring the photosynthetic efficiency of nine species (belonging to the Dinophyceae or Raphidophyceae class) isolated from the Adriatic Sea.", "output": {"entities": {"chemical": [{"text": "TBA", "start": 67, "end": 70}]}}, "schema": []}
{"input": "Different sensitivity levels for each flagellate were observed and the most sensitive microalgae, based on PSII inhibition, were: Gonyaulax spinifera > Fibrocapsa japonica > Lingulodinium polyedrum while the most resistant were two species belonging to the Prorocentrum genus.", "output": {"entities": {}}, "schema": []}
{"input": "Then the response of two microalgae to drivers, such as temperature and terbuthylazine, applied in combination was also investigated.", "output": {"entities": {"chemical": [{"text": "terbuthylazine", "start": 72, "end": 86}]}}, "schema": []}
{"input": "Two potentially toxic flagellates, Prorocentrum minimum and G. spinifera, were exposed, under different temperature conditions (15, 20 and 25 degrees C), to TBA concentrations that did not completely affect PSII.", "output": {"entities": {"chemical": [{"text": "TBA", "start": 157, "end": 160}]}}, "schema": []}
{"input": "For both flagellates, effects of TBA on algal growth, measured through cell density and carbon analysis, as well as on the photosynthetic activity are reported.", "output": {"entities": {"chemical": [{"text": "TBA", "start": 33, "end": 36}, {"text": "carbon", "start": 88, "end": 94}]}}, "schema": []}
{"input": "All parameters analyzed showed a negative effect of TBA from the exponential phase.", "output": {"entities": {"chemical": [{"text": "TBA", "start": 52, "end": 55}]}}, "schema": []}
{"input": "TBA effect on algal growth was significantly enhanced at the optimal temperature conditions (20 and 25 degrees C), while no difference between control and herbicide treatments were detected for G. spinifera grown at 15 degrees C, which represented a stress condition for this species.", "output": {"entities": {"chemical": [{"text": "TBA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The maximum inhibition of photosynthetic efficiency was found at 20 degrees C for both organisms.", "output": {"entities": {}}, "schema": []}
{"input": "Both flagellates increased cell carbon and nitrogen content in herbicide treatments compared to the control, except G. spinifera grown at 15 degrees C.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 32, "end": 38}, {"text": "nitrogen", "start": 43, "end": 51}]}}, "schema": []}
{"input": "Chlorophyll-a production was increased only in G. spinifera exposed to 5 mu g L (-1) of TBA and the effect was enhanced with the increase of temperature.", "output": {"entities": {"chemical": [{"text": "Chlorophyll-a", "start": 0, "end": 13}, {"text": "TBA", "start": 88, "end": 91}]}}, "schema": []}
{"input": "Herbicide-induced variations in cellular components determined changes in cellular carbon: nitrogen (C: N) and chlorophyll: carbon (Chl: C) ratios.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 83, "end": 89}, {"text": "nitrogen", "start": 91, "end": 99}, {"text": "C", "start": 101, "end": 102}, {"text": "N", "start": 104, "end": 105}, {"text": "chlorophyll", "start": 111, "end": 122}, {"text": "carbon", "start": 124, "end": 130}, {"text": "Chl", "start": 132, "end": 135}, {"text": "C", "start": 137, "end": 138}]}}, "schema": []}
{"input": "The C: N ratio decreased in both species, while only G. spinifera showed an increase in the Chl: C ratio at all temperature conditions.", "output": {"entities": {"chemical": [{"text": "C", "start": 4, "end": 5}, {"text": "N", "start": 7, "end": 8}, {"text": "Chl", "start": 92, "end": 95}, {"text": "C", "start": 97, "end": 98}]}}, "schema": []}
{"input": "In response to TBA exposure G. spinifera increased extracellular polysaccharides release at 20 and 25 degrees C, while no difference was reported for P. minimum.", "output": {"entities": {"chemical": [{"text": "TBA", "start": 15, "end": 18}]}}, "schema": []}
{"input": "Changes in nutrient uptake rates were also observed for P. minimum.", "output": {"entities": {}}, "schema": []}
{"input": "Nitrate and phosphate uptake significantly increased in the presence of TBA and this response was enhanced at 25 degrees C, while nitrate uptake increased in G. spinifera only when grown at 25 degrees C.", "output": {"entities": {"chemical": [{"text": "Nitrate", "start": 0, "end": 7}, {"text": "phosphate", "start": 12, "end": 21}, {"text": "TBA", "start": 72, "end": 75}, {"text": "nitrate", "start": 130, "end": 137}]}}, "schema": []}
{"input": "As for growth rates, the observed changes in intracellular component contents increased at optimal temperature conditions.", "output": {"entities": {}}, "schema": []}
{"input": "In this work it is shown that temperature conditions can have an important role on the effect of terbuthylazine on algal growth and on the physiological responses of different species.", "output": {"entities": {"chemical": [{"text": "terbuthylazine", "start": 97, "end": 111}]}}, "schema": []}
{"input": "Furthermore, the algal resistance and recovery can be dependent on nutrient availability.", "output": {"entities": {}}, "schema": []}
{"input": "Mode of action of human pharmaceuticals in fish: the effects of the 5-alpha-reductase inhibitor, dutasteride, on reproduction as a case study.", "output": {"entities": {"chemical": [{"text": "dutasteride", "start": 97, "end": 108}]}}, "schema": []}
{"input": "In recent years, a growing number of human pharmaceuticals have been detected in the aquatic environment, generally at low concentrations (sub-ng/L-low mu g/L).", "output": {"entities": {}}, "schema": []}
{"input": "In most cases, these compounds are characterised by highly specific modes of action, and the evolutionary conservation of drug targets in wildlife species suggests the possibility that pharmaceuticals present in the environment may cause toxicological effects by acting through the same targets as they do in humans.", "output": {"entities": {}}, "schema": []}
{"input": "Our research addressed the question of whether or not dutasteride, a pharmaceutical used to treat benign prostatic hyperplasia, may cause adverse effects in a teleost fish, the fathead minnow (Pimephales promelas), by inhibiting the activity of both isoforms of 5 alpha-reductase (5 alpha R), the enzyme that converts testosterone into dihydrotestosterone (DHT).", "output": {"entities": {"chemical": [{"text": "dutasteride", "start": 54, "end": 65}, {"text": "testosterone", "start": 318, "end": 330}, {"text": "dihydrotestosterone", "start": 336, "end": 355}, {"text": "DHT", "start": 357, "end": 360}]}}, "schema": []}
{"input": "Mammalian pharmacological and toxicological information were used to guide the experimental design and the selection of relevant endpoints, according to the so-called \" read-across approach \", suggesting that dutasteride may affect male fertility and steroid hormone dynamics.", "output": {"entities": {"chemical": [{"text": "dutasteride", "start": 209, "end": 220}, {"text": "steroid hormone", "start": 251, "end": 266}]}}, "schema": []}
{"input": "Therefore, a 21-day reproduction study was conducted to determine the effects of dutasteride (10, 32 and 100 mu g/L) on fish reproduction.", "output": {"entities": {"chemical": [{"text": "dutasteride", "start": 81, "end": 92}]}}, "schema": []}
{"input": "Exposure to dutasteride significantly reduced fecundity of fish and affected several aspects of reproductive endocrine functions in both males and females.", "output": {"entities": {"chemical": [{"text": "dutasteride", "start": 12, "end": 23}]}}, "schema": []}
{"input": "However, none of the observed adverse effects occurred at concentrations of exposure lower than 32 mu g/L; this, together with the low volume of drug prescribed every year (10. 34 kg in the UK in 2011), and the extremely low predicted environmental concentration (0. 03 ng/L), suggest that, at present, the potential presence of dutasteride in the environment does not represent a threat to wild fish populations.", "output": {"entities": {"chemical": [{"text": "dutasteride", "start": 329, "end": 340}]}}, "schema": []}
{"input": "Evaluation of zebra mussels (Dreissena polymorpha) as biomonitors of mercury contamination in aquatic ecosystems.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 69, "end": 76}]}}, "schema": []}
{"input": "Zebra mussels have invaded many lakes in the United States and could be a useful tool for monitoring responses of aquatic biota to changes in mercury loading.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 142, "end": 149}]}}, "schema": []}
{"input": "The goal of the present study was to evaluate zebra mussels for use as a biomonitor of mercury contamination by comparing zebra mussel mercury concentrations between a lake with only indirect atmospheric mercury contamination (Otisco Lake, NY, USA) and a lake that was directly contaminated by mercury discharges (Onondaga Lake, NY, USA).", "output": {"entities": {"chemical": [{"text": "mercury", "start": 87, "end": 94}, {"text": "mercury", "start": 135, "end": 142}, {"text": "mercury", "start": 204, "end": 211}, {"text": "mercury", "start": 294, "end": 301}]}}, "schema": []}
{"input": "Zebra mussels were sampled in both the spring and fall of 2004 and 2005.", "output": {"entities": {}}, "schema": []}
{"input": "Total mercury (THg) concentrations in zebra mussels were approximately seven times greater in Onondaga Lake than in Otisco Lake, and water column mercury concentrations differed by an order of magnitude between the two lakes.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 6, "end": 13}, {"text": "mercury", "start": 146, "end": 153}]}}, "schema": []}
{"input": "Seasonal differences resulted in significantly higher zebra mussel THg concentrations during the fall for both lakes.", "output": {"entities": {}}, "schema": []}
{"input": "There was also significant variation among different sampling sites in Onondaga Lake.", "output": {"entities": {}}, "schema": []}
{"input": "Mussel methylmercury concentrations averaged 53% of THg concentrations but were highly variable.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 7, "end": 20}]}}, "schema": []}
{"input": "Strong relationships between water column THg and zebra mussel THg suggest that zebra mussels are a good indicator of aquatic mercury concentrations and could be used as an effective biomonitor of mercury contamination in aquatic ecosystems.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 126, "end": 133}, {"text": "mercury", "start": 197, "end": 204}]}}, "schema": []}
{"input": "Estrogenic effects along the river Saale.", "output": {"entities": {}}, "schema": []}
{"input": "Sediments along the river Saale, one of the main tributaries of the river Elbe, were characterized with the yeast estrogen screen to elucidate possible sources of endocrine-disrupting compounds that might contribute to the downstream contamination of the river Elbe.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 114, "end": 122}]}}, "schema": []}
{"input": "At two sampling sites, elevated levels of estrogenic activity up to 55, 000 ng ethinylestradiol equivalents per kilogram sediment dry weight were detected in the respective sediment extracts.", "output": {"entities": {"chemical": [{"text": "ethinylestradiol", "start": 79, "end": 95}]}}, "schema": []}
{"input": "Aliquots of the sediment extracts were analyzed for 4-nonylphenols and natural steroidal estrogens as possible candidates with an estrogenic potential.", "output": {"entities": {"chemical": [{"text": "4-nonylphenols", "start": 52, "end": 66}, {"text": "steroidal estrogens", "start": 79, "end": 98}]}}, "schema": []}
{"input": "The maximal concentrations of 4-iso-nonylphenol and estrone were 115 mg/kg dry weight and 20 micro g/kg dry weight at the sampling site Luppe, which showed in accordance the highest biological activity.", "output": {"entities": {"chemical": [{"text": "4-iso-nonylphenol", "start": 30, "end": 47}, {"text": "estrone", "start": 52, "end": 59}]}}, "schema": []}
{"input": "Under consideration of compound concentration and compound specific estrogenic activity the 4-iso-nonylphenols contributed most to the observed estrogenic effect.", "output": {"entities": {"chemical": [{"text": "4-iso-nonylphenols", "start": 92, "end": 110}]}}, "schema": []}
{"input": "A strong correlation between the measured estrogenic activity and the concentration of the sediment-associated 4-iso-nonylphenol underlines the relevance of this compound class as a xenoestrogen in the catchment area of the river Saale.", "output": {"entities": {"chemical": [{"text": "4-iso-nonylphenol", "start": 111, "end": 128}]}}, "schema": []}
{"input": "Persistence of the tricyclic antidepressant drugs amitriptyline and nortriptyline in agriculture soils.", "output": {"entities": {"chemical": [{"text": "amitriptyline", "start": 50, "end": 63}, {"text": "nortriptyline", "start": 68, "end": 81}]}}, "schema": []}
{"input": "Amitriptyline and nortriptyline are widely used tricyclic antidepressant drugs.", "output": {"entities": {"chemical": [{"text": "Amitriptyline", "start": 0, "end": 13}, {"text": "nortriptyline", "start": 18, "end": 31}]}}, "schema": []}
{"input": "They have been detected in wastewater, surface runoff, and effluents from sewage treatment plants.", "output": {"entities": {}}, "schema": []}
{"input": "As such, they could potentially reach agriculture land through the application of municipal biosolids or reclaimed water.", "output": {"entities": {}}, "schema": []}
{"input": "In the absence of data on their fate in the environment, the persistence and dissipation pathways of radiolabeled amitriptyline were determined in three agriculture soils varying widely in texture and chemical properties (loam soil, clay loam soil, and sandy loam soil).", "output": {"entities": {"chemical": [{"text": "amitriptyline", "start": 114, "end": 127}]}}, "schema": []}
{"input": "Tritiated amitriptyline was added to laboratory microcosms containing soils, and the metabolism of the extractable (3) H was monitored during incubation at 30 degrees C.", "output": {"entities": {"chemical": [{"text": "Tritiated amitriptyline", "start": 0, "end": 23}, {"text": "(3) H", "start": 115, "end": 120}]}}, "schema": []}
{"input": "The total solvent extractable radioactivity decreased in all three soils with times to dissipate 50% of material (DT50) ranging from 34. 1 +/- 3. 2 (loam soil) to 85. 3 +/- 3. 2 d (sandy soil).", "output": {"entities": {}}, "schema": []}
{"input": "Nortriptyline (N-desmethyl amitriptyline) and amitriptyline-N-oxide were identified as major transformation products in all three soils by high performance liquid chromatography with photodiode array detector and time-of-flight mass spectrometry (HPLC-TOF-MS/UV).", "output": {"entities": {"chemical": [{"text": "Nortriptyline", "start": 0, "end": 13}, {"text": "N-desmethyl amitriptyline", "start": 15, "end": 40}, {"text": "amitriptyline-N-oxide", "start": 46, "end": 67}]}}, "schema": []}
{"input": "The addition of liquid municipal biosolids to the loam soil had no effect on the dissipation of amitriptyline.", "output": {"entities": {"chemical": [{"text": "amitriptyline", "start": 96, "end": 109}]}}, "schema": []}
{"input": "The persistence of nortriptyline was evaluated in the loam soil.", "output": {"entities": {"chemical": [{"text": "nortriptyline", "start": 19, "end": 32}]}}, "schema": []}
{"input": "The DT50 of nortriptyline was 40. 5 +/- 3. 2 d estimated with HPLC-TOF-MS/UV.", "output": {"entities": {"chemical": [{"text": "nortriptyline", "start": 12, "end": 25}]}}, "schema": []}
{"input": "Approximately 10% of added nortriptyline was converted to hydroxylated products after 50 d of incubation.", "output": {"entities": {"chemical": [{"text": "nortriptyline", "start": 27, "end": 40}]}}, "schema": []}
{"input": "In summary, amitriptyline persisted in agricultural soils with major dissipation mechanisms, including forming nonextractable residues and producing various transformation products including the psychoactive drug nortriptyline.", "output": {"entities": {"chemical": [{"text": "amitriptyline", "start": 12, "end": 25}, {"text": "nortriptyline", "start": 213, "end": 226}]}}, "schema": []}
{"input": "Mercury in the seafood and human exposure in coastal area of Guangdong province, South China.", "output": {"entities": {"chemical": [{"text": "Mercury", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Consumption of fish and aquatic products is considered to be the main pathway of human exposure to methylmercury (MeHg).", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 99, "end": 112}, {"text": "MeHg", "start": 114, "end": 118}]}}, "schema": []}
{"input": "To assess human health risk through seafood consumption in a coastal area of Guangdong Province, South China, a total of 518 seafood samples (including fish, shrimp, crabs, and mollusks) were collected from 11 coastal cities for total mercury (THg) analysis.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 235, "end": 242}]}}, "schema": []}
{"input": "The THg concentrations varied significantly among different seafood groups and ranged from 0. 11 to 317 ng/g (with a mean of 37. 2 ng/g).", "output": {"entities": {}}, "schema": []}
{"input": "The THg concentrations were relatively low compared with fish from Europe and North America, and no samples exceeded the national limit recommended by the Standardization Administration of China (0. 5 ng/g wet wt).", "output": {"entities": {}}, "schema": []}
{"input": "The ecological functional groups and cultured styles have significant effects on THg concentrations in the fish tissue.", "output": {"entities": {}}, "schema": []}
{"input": "The median of probable daily intakes (PDIs) of MeHg via seafood consumption ranged from 42. 6 to 71. 4 ng/g for different age groups, with fish contributing the major portion (84%).", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 47, "end": 51}]}}, "schema": []}
{"input": "The results indicated potential health risks associated with seafood consumption for the general population in the coastal area of Guangdong Province, South China.", "output": {"entities": {}}, "schema": []}
{"input": "A carbon nanotube synapse with dynamic logic and learning.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 2, "end": 8}]}}, "schema": []}
{"input": "A carbon nanotube (CNT) synapse emulates a biological synapse with its dynamic logic, learning, and memory functions induced by the interactions between CNTs and hydrogen ions in an electrochemical cell.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 2, "end": 8}, {"text": "hydrogen", "start": 162, "end": 170}]}}, "schema": []}
{"input": "A circuit of CNT synapses operates with extremely low-energy consumption and could potentially emulate the functions of the neuronal network.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrosoluble benzo [e] pyridoindolones as potent inhibitors of aurora kinases.", "output": {"entities": {"chemical": [{"text": "benzo [e] pyridoindolones", "start": 13, "end": 38}]}}, "schema": []}
{"input": "Aurora kinases play an essential role in mitotic progression and are potentially druggable targets in cancer therapy.", "output": {"entities": {}}, "schema": []}
{"input": "We identified benzo [e] pyridoindoles (BePI) as powerful aurora kinase inhibitors.", "output": {"entities": {"chemical": [{"text": "benzo [e] pyridoindoles", "start": 14, "end": 37}, {"text": "BePI", "start": 39, "end": 43}]}}, "schema": []}
{"input": "Their efficiency was demonstrated both in enzymatic inhibition studies and in cell culture assays.", "output": {"entities": {}}, "schema": []}
{"input": "New BePI molecules were synthesized, and a structure-activity relationship study was conducted with the aim of improving the activity and solubility of the lead compound.", "output": {"entities": {"chemical": [{"text": "BePI", "start": 4, "end": 8}]}}, "schema": []}
{"input": "Tetracyclic BePI derivatives are characterized by a particular curved shape, and the presence of an oxo group on the pyridine ring was found to be required for aurora kinase B inhibition.", "output": {"entities": {"chemical": [{"text": "Tetracyclic BePI", "start": 0, "end": 16}, {"text": "oxo", "start": 100, "end": 103}, {"text": "pyridine", "start": 117, "end": 125}]}}, "schema": []}
{"input": "New hydrosoluble benzo [e] pyridoindolones were subsequently designed, and their efficacy was tested by a combination of cell-cycle analysis and time-lapse experiments in live cells.", "output": {"entities": {"chemical": [{"text": "benzo [e] pyridoindolones", "start": 17, "end": 42}]}}, "schema": []}
{"input": "The most active BePI derivative, 13 b, inhibited the cell cycle, drove cells to polyploidy, and eventually induced apoptosis.", "output": {"entities": {"chemical": [{"text": "BePI", "start": 16, "end": 20}]}}, "schema": []}
{"input": "It exhibited high antiproliferative activity in HeLa cells with an IC (50) value of 63 nM.", "output": {"entities": {}}, "schema": []}
{"input": "Relative to compounds tested in clinical trials, this antiproliferative potency places 13 b among the top 10 aurora kinase inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Our results justify further in vivo evaluation in preclinical animal models of cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Practical synthesis of (20S)-10-(3-aminopropyloxy)-7-ethylcamptothecin, a water-soluble analogue of camptothecin.", "output": {"entities": {"chemical": [{"text": "(20S)-10-(3-aminopropyloxy)-7-ethylcamptothecin", "start": 23, "end": 70}, {"text": "camptothecin", "start": 100, "end": 112}]}}, "schema": []}
{"input": "A robust, practical synthesis of (20S)-10-(3-aminopropyloxy)-7-ethylcamptothecin (T-2513, 5), which is a water-soluble analogue of camptothecin, has been developed.", "output": {"entities": {"chemical": [{"text": "(20S)-10-(3-aminopropyloxy)-7-ethylcamptothecin", "start": 33, "end": 80}, {"text": "T-2513", "start": 82, "end": 88}, {"text": "camptothecin", "start": 131, "end": 143}]}}, "schema": []}
{"input": "The key step in this synthesis is a highly diastereoselective ethylation at the C20 position by using N-arylsulfonyl-(R)-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid ester as a chiral auxiliary, which affords the key intermediate ethyl-(S)-2-acyloxy-2-(6-cyano-5-oxo-1, 2, 3, 5-tetrahydroindolizin-7-yl) butanoate (8k) in 93% yield and 87% de.", "output": {"entities": {"chemical": [{"text": "N-arylsulfonyl-(R)-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid ester", "start": 102, "end": 178}, {"text": "ethyl-(S)-2-acyloxy-2-(6-cyano-5-oxo-1, 2, 3, 5-tetrahydroindolizin-7-yl) butanoate", "start": 237, "end": 320}]}}, "schema": []}
{"input": "Optically pure compound 8k was obtained by a single recrystallization from acetone and its further elaboration through Friedlander condensation afforded compound 5.", "output": {"entities": {"chemical": [{"text": "acetone", "start": 75, "end": 82}]}}, "schema": []}
{"input": "This synthesis does not require any chromatographic purification steps and can provide compound 5 on a multi-gram scale in 6. 3% overall yield (16 steps).", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembled BolA-like amphiphilic peptides as viral-mimetic gene vectors for cancer cell targeted gene delivery.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, two types of BolA-like amphiphilic peptides with dual ligands comprising a tumor-targeting moiety of RGD sequence and a cell-penetrating moiety of R8 sequence are designed and synthesized as gene vectors.", "output": {"entities": {}}, "schema": []}
{"input": "The BolA-structural peptide carriers can self-assemble into spherical nanoparticles with a hydrophilic core and shell, which are similar to the viral capsid and can bind plasmid DNA in an aqueous medium to form viral-mimetic complexes.", "output": {"entities": {}}, "schema": []}
{"input": "It is found that the BolA-like dual ligands system exhibits significantly enhanced gene expression in both HeLa and 293T cell lines, as compared with poly (ethylenimine) PEI.", "output": {"entities": {"chemical": [{"text": "poly (ethylenimine) PEI", "start": 150, "end": 173}]}}, "schema": []}
{"input": "These BolA-like amphiphilic peptides are promising in clinical trials of gene therapy.", "output": {"entities": {}}, "schema": []}
{"input": "New cyclomyrsinol diterpenes from Euphorbia aellenii with their immunomodulatory effects.", "output": {"entities": {"chemical": [{"text": "cyclomyrsinol diterpenes", "start": 4, "end": 28}]}}, "schema": []}
{"input": "Chloroform-acetone extract of the aerial parts of Euphorbia aellenii Rech.", "output": {"entities": {"chemical": [{"text": "Chloroform", "start": 0, "end": 10}, {"text": "acetone", "start": 11, "end": 18}]}}, "schema": []}
{"input": "f.", "output": {"entities": {}}, "schema": []}
{"input": "(Euphorbiaceae) was investigated for its diterpenoidal constituents.", "output": {"entities": {"chemical": [{"text": "diterpenoidal", "start": 41, "end": 54}]}}, "schema": []}
{"input": "This led to the isolation of two new and one known cyclomyrsinol-type diterpenes 1-3.", "output": {"entities": {"chemical": [{"text": "cyclomyrsinol", "start": 51, "end": 64}, {"text": "diterpenes", "start": 70, "end": 80}]}}, "schema": []}
{"input": "The structures were elucidated on the basis of 1D and 2D (1) H and (13) C NMR techniques, and in vitro immunomodulatory activity was evaluated by standard proliferation of human peripheral blood lymphocytes.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 57, "end": 62}, {"text": "(13) C", "start": 67, "end": 73}]}}, "schema": []}
{"input": "Results showed that all the three compounds were found to inhibit lymphocyte proliferation significantly (p < 0. 05) at 50 mu g/ml concentration.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, compound 2 showed more activity against phytohemagglutinin-activated T-cell proliferation with an IC (50) of 40. 4 +/- 9. 35 mu g/ml.", "output": {"entities": {}}, "schema": []}
{"input": "Fusion of bolaamphiphile micelles: a method to prepare stable supported biomimetic membranes.", "output": {"entities": {}}, "schema": []}
{"input": "Supported biomimetic membranes (SBMs) on solid substrates have been commonly prepared from vesicle-forming double-tail lipids, such as zwitterionic phospholipids, using the method of vesicle fusion.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report on the preparation of SBMs on silica surfaces via a similar process of \" micelle fusion \" from a cationic single-tail bolaamphiphile GLH-20 that forms spherical and elongated thread-like micelles in solution.", "output": {"entities": {"chemical": [{"text": "silica", "start": 45, "end": 51}]}}, "schema": []}
{"input": "We demonstrate that, in contrast to zwitterionic phospholipids, GLH-20 self-assembles into a stable contiguous SBM at both low and high ionic strengths.", "output": {"entities": {}}, "schema": []}
{"input": "The cationic charge of GLH-20 promotes the formation of a stable SBM through enhanced double-layer interactions with the negatively charged silica surface.", "output": {"entities": {"chemical": [{"text": "silica", "start": 140, "end": 146}]}}, "schema": []}
{"input": "It is also shown that spinach aquaporin PM-28 was successfully incorporated within bolaamphiphile SBM in a manner similar to SBMs prepared by vesicle/proteoliposome fusion; thereby the inherent curvature of the micelle surface does not inhibit protein reconstitution.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest that SBMs based on charged bolaamphiphiles might be an attractive platform for applications such as water purification and biosensors, where the stability and low defect rate of SBMs in diverse conditions are crucial for achieving desired performance.", "output": {"entities": {}}, "schema": []}
{"input": "Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion.", "output": {"entities": {}}, "schema": []}
{"input": "Mediator release from mast cells is a critical step in allergic and inflammatory disease.", "output": {"entities": {}}, "schema": []}
{"input": "However, the processes regulating the latter stages of granule release are yet to be fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "Rab27 small GTPases regulate release of secretory lysosomes in a variety of cells, including mast cell granules.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, using murine bone marrow-derived mast cells (BMMC) from Rab27-deficient mutant mice, we found that, in contrast to Rab27b, Rab27a primarily plays an inhibitory role in regulating degranulation.", "output": {"entities": {}}, "schema": []}
{"input": "Immunofluorescence analysis revealed that resting Rab27a-deficient (ashen) BMMCs display abnormal cortical F-actin distribution.", "output": {"entities": {}}, "schema": []}
{"input": "Actin disassembly prior to IgE cross-linking increased wild-type BMMC secretion to ashen levels, suggesting that changes in the integrity of cortical F-actin underlie the ashen phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of the secretory impairment of Rab27b knockout and Rab27a/b double knockout BMMCs highlighted a secondary positive role for Rab27a in enhancing degranulation.", "output": {"entities": {}}, "schema": []}
{"input": "Rab27 is known to interact with actin via its effectors melanophilin (Mlph) and myosin Va (MyoVa) in other cell types.", "output": {"entities": {}}, "schema": []}
{"input": "To better understand the differing roles of Rab27 proteins, we analysed the secretory phenotype of BMMCs derived from mice lacking Rab27 effector proteins.", "output": {"entities": {}}, "schema": []}
{"input": "These experiments revealed that the phenotype of BMMCs deficient in Mlph (leaden) and BMMCs deficient in MyoVa (dilute) resembles the hyper-secretion of ashen BMMCs, while Munc13-4-deficient (jinx) BMMCs phenocopy the Rab27b knockout and double Rab27a/b knockout secretory impairment.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that Rab27a and Rab27b regulate distinct steps in the BMMC degranulation pathway, with Rab27a/Mlph/MyoVa regulating cortical actin stability upstream of Rab27a/b/Munc13-4-dependent granule exocytosis.", "output": {"entities": {}}, "schema": []}
{"input": "A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro.", "output": {"entities": {"chemical": [{"text": "5-nitro-2-furancarboxylamides", "start": 11, "end": 40}]}}, "schema": []}
{"input": "Recently, the World Health Organization approved the nifurtimox-eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases.", "output": {"entities": {"chemical": [{"text": "nifurtimox", "start": 53, "end": 63}, {"text": "eflornithine", "start": 64, "end": 76}]}}, "schema": []}
{"input": "In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, ~ 1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells.", "output": {"entities": {"chemical": [{"text": "5-nitro-2-furancarboxylamides", "start": 53, "end": 82}, {"text": "nifurtimox", "start": 152, "end": 162}]}}, "schema": []}
{"input": "More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa.", "output": {"entities": {"chemical": [{"text": "nifurtimox", "start": 83, "end": 93}]}}, "schema": []}
{"input": "This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites.", "output": {"entities": {"chemical": [{"text": "5-nitro-2-furancarboxylamides", "start": 80, "end": 109}, {"text": "nifurtimox", "start": 199, "end": 209}]}}, "schema": []}
{"input": "The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.", "output": {"entities": {}}, "schema": []}
{"input": "Thyroid hormone replacement therapy attenuates the decline of renal function in chronic kidney disease patients with subclinical hypothyroidism.", "output": {"entities": {"chemical": [{"text": "Thyroid hormone", "start": 0, "end": 15}]}}, "schema": []}
{"input": "Background: Subclinical hypothyroidism (SH) is not a rare condition in females, the elderly, or patients with chronic kidney disease (CKD).", "output": {"entities": {}}, "schema": []}
{"input": "Even though previous studies have demonstrated that thyroid hormone replacement therapy (THRT) improved cardiac function and dyslipidemia in patients with subclinical hypothyroidism, it remains unclear as to whether THRT can improve renal function in CKD patients with SH.", "output": {"entities": {"chemical": [{"text": "thyroid hormone", "start": 52, "end": 67}]}}, "schema": []}
{"input": "This study investigated the impact of THRT on changes in estimated glomerular filtration rates (eGFR) in this patient population.", "output": {"entities": {}}, "schema": []}
{"input": "Methods: A total of 113 CKD patients with SH who were treated with L-thyroxine and had eGFR available for at least 24 months before and after THRT were enrolled between January 2005 and December 2011.", "output": {"entities": {"chemical": [{"text": "L-thyroxine", "start": 67, "end": 78}]}}, "schema": []}
{"input": "A linear mixed model was used to compare patients' clinical and biochemical parameters at various time points.", "output": {"entities": {}}, "schema": []}
{"input": "The slope of the decline in eGFR over time, both before and after THRT, was also calculated and compared using a linear mixed model.", "output": {"entities": {}}, "schema": []}
{"input": "Results: The mean age of the study participants was 63. 2 +/- 12. 7 years, and 36 patients (31. 9%) were male.", "output": {"entities": {}}, "schema": []}
{"input": "The mean follow-up duration before and after THRT was 28. 6 +/- 4. 5 and 30. 6 +/- 6. 4 months, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "At 24-months of THRT, TSH levels were significantly reduced [8. 86 (0. 49) vs. 1. 41 (0. 73) <F06D> IU/mL, P < 0. 001], but there were no significant changes in T3 and fT4 concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "Serum albumin, calcium, phosphate, cholesterol, and triglyceride levels were also comparable after THRT.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 15, "end": 22}, {"text": "phosphate", "start": 24, "end": 33}, {"text": "cholesterol", "start": 35, "end": 46}, {"text": "triglyceride", "start": 52, "end": 64}]}}, "schema": []}
{"input": "The rates of decline in eGFR were significantly attenuated by THRT [-4. 31 (0. 51) vs.-1. 08 (0. 36) mL/min/year/1. 73 m2, P < 0. 001] even after adjustment for age, gender, diabetes, mean arterial pressure, serum albumin, cholesterol, and triglyceride concentrations (P < 0. 001).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 223, "end": 234}, {"text": "triglyceride", "start": 240, "end": 252}]}}, "schema": []}
{"input": "Conclusion: THRT attenuated the rate of decline in renal function in CKD patients with SH, suggesting that THRT may delay reaching end-stage renal disease in these patients.", "output": {"entities": {}}, "schema": []}
{"input": "Two [4Fe-4S] clusters containing radical SAM enzyme SkfB catalyze thioether bond formation during the maturation of the sporulation killing factor.", "output": {"entities": {"chemical": [{"text": "4Fe-4S", "start": 5, "end": 11}, {"text": "thioether", "start": 66, "end": 75}]}}, "schema": []}
{"input": "The sporulation killing factor (SKF) is a 26-residue ribosomally assembled and posttranslationally modified sactipeptide.", "output": {"entities": {}}, "schema": []}
{"input": "It is produced by Bacillus subtilis 168 and plays a key role in its sporulation.", "output": {"entities": {}}, "schema": []}
{"input": "Like all sactipeptides, SKF contains a thioether bond, which links the cysteine residue Cys4 with the alpha-carbon of the methionine residue Met12.", "output": {"entities": {"chemical": [{"text": "thioether", "start": 39, "end": 48}, {"text": "cysteine", "start": 71, "end": 79}, {"text": "Cys4", "start": 88, "end": 92}, {"text": "alpha-carbon", "start": 102, "end": 114}, {"text": "methionine", "start": 122, "end": 132}, {"text": "Met12", "start": 141, "end": 146}]}}, "schema": []}
{"input": "In this study we demonstrate that this bond is generated by the two [4Fe-4S] clusters containing radical SAM enzyme SkfB, which is encoded in the skf operon.", "output": {"entities": {"chemical": [{"text": "4Fe-4S", "start": 69, "end": 75}, {"text": "SAM", "start": 105, "end": 108}]}}, "schema": []}
{"input": "By mutational analysis of both cluster-binding sites, we were able to postulate a mechanism for thioether generation which is in agreement with that of AlbA.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we were able to show that thioether bond formation is specific toward hydrophobic amino acids at the acceptor site.", "output": {"entities": {"chemical": [{"text": "thioether", "start": 39, "end": 48}, {"text": "amino acids", "start": 95, "end": 106}]}}, "schema": []}
{"input": "Additionally we demonstrate that generation of the thioether linkage is leader-peptide-dependent, suggesting that this reaction is the first step in SKF maturation.", "output": {"entities": {"chemical": [{"text": "thioether", "start": 51, "end": 60}]}}, "schema": []}
{"input": "Structure-based investigation of rat aldehyde oxidase inhibition by flavonoids.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 37, "end": 45}, {"text": "flavonoids", "start": 68, "end": 78}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "Flavonoids are a group of polyphenolic plant metabolites most commonly known for their antioxidant activities.", "output": {"entities": {"chemical": [{"text": "Flavonoids", "start": 0, "end": 10}, {"text": "polyphenolic", "start": 26, "end": 38}]}}, "schema": []}
{"input": "They also show inhibitory activities on molybdo-flavoenzymes family of enzymes which are involved in biotransformation of some exogenous and endogenous chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Most notably, aldehyde oxidase (AO), a member of this family, is responsible for metabolism of some therapeutic agents.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 14, "end": 22}]}}, "schema": []}
{"input": "On the other hand, there are some therapeutics which inhibit AO.", "output": {"entities": {}}, "schema": []}
{"input": "As flavonoids are ubiquitous in human diet and have potential to interact with AO, it is important to investigate their effects at the molecular details.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 3, "end": 13}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "The inhibitory effects of 15 flavonoids on the activity of rat liver AO were assessed.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 29, "end": 39}]}}, "schema": []}
{"input": "Quantitative structure-activity relationship studies were performed using genetic algorithm coupled partial least square and stepwise multiple linear regression methods to elucidate the important structural properties responsible for the observed inhibitory effects.", "output": {"entities": {}}, "schema": []}
{"input": "To further understand the mode of interaction between these flavonoids and AO, a homology model of the enzyme was built and flavonoids were docked into its active site.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 60, "end": 70}, {"text": "flavonoids", "start": 124, "end": 134}]}}, "schema": []}
{"input": "The most important amino acids involved in the interactions were identified.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 19, "end": 30}]}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "Quercetin, myricetin and genistein were the most potent inhibitors establishing favorable interactions with the enzyme.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "myricetin", "start": 11, "end": 20}, {"text": "genistein", "start": 25, "end": 34}]}}, "schema": []}
{"input": "However, the glycosylated flavonoids showed relatively weaker inhibition which may be attributed to their hindered binding into the active site of AO by bulky sugar groups.", "output": {"entities": {"chemical": [{"text": "glycosylated flavonoids", "start": 13, "end": 36}, {"text": "sugar", "start": 159, "end": 164}]}}, "schema": []}
{"input": "Aaptamine derivatives from the Indonesian sponge Aaptos suberitoides.", "output": {"entities": {"chemical": [{"text": "Aaptamine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Four new aaptamine derivatives (1-4) along with aaptamine (5) and three related compounds (6-8) were isolated from the ethanol extract of the sponge Aaptos suberitoides collected in Indonesia.", "output": {"entities": {"chemical": [{"text": "aaptamine", "start": 9, "end": 18}, {"text": "aaptamine", "start": 48, "end": 57}, {"text": "ethanol", "start": 119, "end": 126}]}}, "schema": []}
{"input": "The structures of the new compounds were unambiguously determined by one-and two-dimensional NMR and by HRESIMS measurements.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 3, 5, and 6 showed cytotoxic activity against the murine lymphoma L5178Y cell line, with IC (50) values ranging from 0. 9 to 8. 3 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "Why is quercetin a better antioxidant than taxifolin?", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 7, "end": 16}, {"text": "taxifolin", "start": 43, "end": 52}]}}, "schema": []}
{"input": "Theoretical study of mechanisms involving activated forms.", "output": {"entities": {}}, "schema": []}
{"input": "The stronger antioxidant capacity of the flavonoid quercetin (Q) compared with taxifolin (dihydroquercetin, T) has been the subject of previous experimental and theoretical studies.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 51, "end": 60}, {"text": "taxifolin", "start": 79, "end": 88}, {"text": "dihydroquercetin", "start": 90, "end": 106}]}}, "schema": []}
{"input": "Theoretical work has focused on the analysis of hydrogen bond dissociation energies (BDE) of the OH phenolic groups, but consider mechanisms that only involve the transfer of one hydrogen atom.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 48, "end": 56}, {"text": "OH phenolic", "start": 97, "end": 108}, {"text": "hydrogen", "start": 179, "end": 187}]}}, "schema": []}
{"input": "In the present work we consider other mechanisms involving a second hydrogen transfer in reactions with free radicals.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 68, "end": 76}]}}, "schema": []}
{"input": "The relative stability of the radicals formed after the first hydrogen transfer reaction is considered in discussing the antioxidant activity of Q and T.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 62, "end": 70}]}}, "schema": []}
{"input": "In terms of global and local theoretical reactivity descriptors, we propose that the radical arising from Q should be more persistent in the environment and with the capability to react with a second radical by hydrogen transfer, proton transfer and electron transfer mechanisms.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 211, "end": 219}]}}, "schema": []}
{"input": "These mechanisms could be responsible of the stronger antioxidant capacity of Q.", "output": {"entities": {}}, "schema": []}
{"input": "Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza (\" Danshen \").", "output": {"entities": {}}, "schema": []}
{"input": "The roots of Salvia miltiorrhiza (\" Danshen \") are used in traditional Chinese medicine for the treatment of numerous ailments including cardiovascular disease, hypertension, and ischemic stroke.", "output": {"entities": {}}, "schema": []}
{"input": "Extracts of S. miltiorrhiza roots in the formulation \" Compound Danshen Dripping Pill \" are undergoing clinical trials in the United States.", "output": {"entities": {}}, "schema": []}
{"input": "To date, the active components of this material have not been conclusively identified.", "output": {"entities": {}}, "schema": []}
{"input": "We have determined that S. miltiorrhiza roots contain potent human carboxylesterase (CE) inhibitors, due to the presence of tanshinones.", "output": {"entities": {}}, "schema": []}
{"input": "K (i) values in the nM range were determined for inhibition of both the liver and intestinal CEs.", "output": {"entities": {}}, "schema": []}
{"input": "As CEs hydrolyze clinically used drugs, the ability of tanshinones and S. miltiorrhiza root extracts to modulate the metabolism of the anticancer prodrug irinotecan (CPT-11) was assessed.", "output": {"entities": {"chemical": [{"text": "irinotecan", "start": 154, "end": 164}, {"text": "CPT-11", "start": 166, "end": 172}]}}, "schema": []}
{"input": "Our results indicate that marked inhibition of human CEs occurs following incubation with both pure compounds and crude material and that drug hydrolysis is significantly reduced.", "output": {"entities": {}}, "schema": []}
{"input": "Consequently, a reduction in the cytotoxicity of irinotecan is observed following dosing with either purified tanshinones or S. miltiorrhiza root extracts.", "output": {"entities": {}}, "schema": []}
{"input": "It is concluded that remedies containing tanshinones should be avoided when individuals are taking esterified agents and that patients should be warned of the potential drug-drug interaction that may occur with this material.", "output": {"entities": {}}, "schema": []}
{"input": "Multifunctional mesoporous nanocomposites with magnetic, optical, and sensing features: synthesis, characterization, and their oxygen-sensing performance.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 127, "end": 133}]}}, "schema": []}
{"input": "In this paper, the fabrication, characterization, and application in oxygen sensing are reported for a novel multifunctional nanomaterial of [Ru (bpy) (2) phen-MMS] (bpy, 2, 2'-bipyridyl; phen, phenathrolin) which was simply prepared by covalently grafting the ruthenium (II) polypyridyl compounds into the channels of magnetic mesoporous silica nanocomposites (MMS).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 69, "end": 75}, {"text": "Ru (bpy) (2) phen", "start": 142, "end": 159}, {"text": "bpy", "start": 166, "end": 169}, {"text": "2, 2'-bipyridyl", "start": 171, "end": 186}, {"text": "phen", "start": 188, "end": 192}, {"text": "phenathrolin", "start": 194, "end": 206}, {"text": "ruthenium (II) polypyridyl", "start": 261, "end": 287}, {"text": "silica", "start": 339, "end": 345}]}}, "schema": []}
{"input": "Scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, N (2) adsorption-desorption, a superconducting quantum interference device, UV-vis spectroscopy, and photoluminescence spectra were used to characterize the samples.", "output": {"entities": {}}, "schema": []}
{"input": "The well-designed multifunctional nanocomposites show superparamagnetic behavior and ordered mesoporous characteristics and exhibit a strong red-orange metal-to-ligand charge transfer emission.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the obtained nanocomposites give high performance in oxygen sensing with high sensitivity (I (0)/I (100) = 5. 2), good Stern-Volmer characteristics (R (2) = 0. 9995), and short response/recovery times (t v = 6 s and t ^ = 12 s).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 66, "end": 72}]}}, "schema": []}
{"input": "The magnetic, mesoporous, luminescent, and oxygen-sensing properties of this multifunctional nanostructure make it hold great promise as a novel multifunctional oxygen-sensing system for chemical/biosensor.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 43, "end": 49}, {"text": "oxygen", "start": 161, "end": 167}]}}, "schema": []}
{"input": "Lipofection and nucleofection of substrate plasmid can generate widely different readings of DNA end-joining efficiency in different cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo plasmid end-joining assays are valuable tools for dissecting important qualitative and quantitative aspects of non-homologous end-joining (NHEJ)--a key mechanism for the repair of DNA double-strand breaks (DSBs) in higher eukaryotes.", "output": {"entities": {}}, "schema": []}
{"input": "They enable the use of defined DNA ends as substrates for end-joining and the analysis by sequencing of the resulting junctions to identify the repair pathways engaged.", "output": {"entities": {}}, "schema": []}
{"input": "Yet, plasmid assays have generated divergent results of end-joining capacity in the same DSB repair mutants when used under different conditions, which implies contributions from undefined and therefore uncontrolled parameters.", "output": {"entities": {}}, "schema": []}
{"input": "To help standardize these assays, we searched for parameters underpinning these variations and identified transfection method as an important determinant.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we compare a lipid-based transfection method, lipofection, with an electroporation method, nucleofection, and find large, unanticipated and cell line-dependent differences in percent end-joining without recognizable trends.", "output": {"entities": {}}, "schema": []}
{"input": "For example, in rodent cells, transfection using lipofection gives nearly WT end-joining in DNA-PKcs mutants and only mildly inhibited end-joining in Lig4 and Ku mutants.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, transfection using nucleofection shows marked end-joining inhibition in all NHEJ mutants tested as compared to the WT.", "output": {"entities": {}}, "schema": []}
{"input": "In human HCT116 cells, end-joining after nucleofection is strongly suppressed even in the WT and the differences to the mutants are small.", "output": {"entities": {}}, "schema": []}
{"input": "After lipofection, in contrast, end-joining is high in WT cells and markedly suppressed in the mutants.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that better understanding and control of the physicochemical/biological and analytical parameters underpinning these differences will be required to generate with plasmid assays results with quantitative power comparable to that of well-established methods of DSB analysis such as pulsed-field gel electrophoresis or gamma-H2AX foci scoring.", "output": {"entities": {}}, "schema": []}
{"input": "Until then, caution is needed in the interpretation of the results obtained-particularly with reference to pathway efficiency and residual damage-and confirmation of critical results with alternative transfection approaches is advisable.", "output": {"entities": {}}, "schema": []}
{"input": "Development of an in vitro skin sensitization test based on ROS production in THP-1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, it has been reported that reactive oxygen species (ROS) produced by contact allergens can affect dendritic cell migration and contact hypersensitivity.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 45, "end": 51}]}}, "schema": []}
{"input": "The aim of the present study was to develop a new in vitro assay that could predict the skin sensitizing potential of chemicals by measuring ROS production in THP-1 (human monocytic leukemia cell line) cells.", "output": {"entities": {}}, "schema": []}
{"input": "THP-1 cells were pre-loaded with a ROS sensitive fluorescent dye, 5-(and 6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA), for 15min, then incubated with test chemicals for 30min.", "output": {"entities": {"chemical": [{"text": "5-(and 6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate", "start": 66, "end": 133}, {"text": "acetyl ester", "start": 135, "end": 147}, {"text": "CM-H2DCFDA", "start": 149, "end": 159}]}}, "schema": []}
{"input": "The fluorescence intensity was measured by flow cytometry.", "output": {"entities": {}}, "schema": []}
{"input": "For the skin sensitizers, 25 out of 30 induced over a 2-fold ROS production at more than 90% of cell viability.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, increases were only seen in 4 out of 20 non-sensitizers.", "output": {"entities": {}}, "schema": []}
{"input": "The overall accuracy for the local lymph node assay (LLNA) was 82% for 50 chemicals tested.", "output": {"entities": {}}, "schema": []}
{"input": "A correlation was found between the estimated concentration showing 2-fold ROS production in the ROS assay and the EC3 values (estimated concentration required to induce positive response) of the LLNA.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicated that the THP-1 cell-based ROS assay was a rapid and highly sensitive detection system able to predict skin sensitizing potentials and potency of chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Role for membrane remodeling in cell death: implication for health and disease.", "output": {"entities": {}}, "schema": []}
{"input": "Recently it has become clear that exposure to xenobiotics may result in various forms of cell death; not only passive cell deaths like necrosis, or programmed cell deaths such as apoptosis, but also regulated necrosis, autophagy, senescence, or mitotic catastrophe.", "output": {"entities": {}}, "schema": []}
{"input": "Complex cell signaling networks influence the processing of cell death.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, recent research has revealed early complex molecular interactions between organelles prior to the final triggering of cell death.", "output": {"entities": {}}, "schema": []}
{"input": "The plasma membrane may play an important role in the early cell death signaling events.", "output": {"entities": {}}, "schema": []}
{"input": "Regarding this latter aspect, drugs and environmental pollutants have been reported to affect plasma membrane characteristics which may further affect cell fate.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in membrane fluidity or in composition and function of specialized membrane microdomains (plasma membrane remodeling) have been proven to be involved in the regulation of many important physiological signaling pathways, including cell death.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, it has been suggested that a crosstalk between chemical-induced cellular membrane effects and other organelles may be of vital importance to explain the final outcome of chemical exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review the effects of plasma membrane remodeling on cell survival and cell death; we describe how the cell signaling pathways activated by changes in plasma membrane characteristics may influence cell fate.", "output": {"entities": {}}, "schema": []}
{"input": "Since plasma membrane function plays an important role in the regulation of a number of cellular responses, it has been implicated in the development or progress of several diseases.", "output": {"entities": {}}, "schema": []}
{"input": "A better knowledge of the effects of various chemicals on plasma membrane remodeling may be important for understanding the pathogenesis of major diseases, and may assist in developing new therapeutic strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of T-type calcium channels disrupts Akt signaling and promotes apoptosis in glioblastoma cells.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 21, "end": 28}]}}, "schema": []}
{"input": "Glioblastoma multiforme (GBM) are brain tumors that are exceptionally resistant to both radio-and chemotherapy regimens and novel approaches to treatment are needed.", "output": {"entities": {}}, "schema": []}
{"input": "T-type calcium channels are one type of low voltage-gated channel (LVCC) involved in embryonic cell proliferation and differentiation; however they are often over-expressed in tumors, including GBM.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 7, "end": 14}]}}, "schema": []}
{"input": "In this study, we found that inhibition of T-type Ca (2 +) channels in GBM cells significantly reduced their survival and resistance to therapy.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 50, "end": 58}]}}, "schema": []}
{"input": "Moreover, either T-type selective antagonists, such as mibefradil, or siRNA-mediated knockdown of the T-type channel alpha subunits not only reduced cell viability and clonogenic potential, but also induced apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "In response to channel blockade or ablation, we observed reduced phosphorylation of Akt and Rictor, suggesting inhibition of the mTORC2/Akt pathway.", "output": {"entities": {}}, "schema": []}
{"input": "This was followed by reduction in phosphorylation of anti-apoptotic Bad and caspases activation.", "output": {"entities": {}}, "schema": []}
{"input": "The apoptotic response was specific for T-type Ca (2 +) channels, as inhibition of L-type Ca (2 +) channels did not induce similar effects.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 47, "end": 55}, {"text": "Ca (2 +)", "start": 90, "end": 98}]}}, "schema": []}
{"input": "Our results implicate T-type Ca (2 +) channels as distinct entities for survival signaling in GBM cells and suggest that they are a novel molecular target for tumor therapy.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Differential anti-ischemic efficacy and therapeutic time window of trans-and cis-hinokiresinols: Stereo-specific antioxidant and anti-inflammatory activities.", "output": {"entities": {"chemical": [{"text": "trans-and cis-hinokiresinols", "start": 67, "end": 95}]}}, "schema": []}
{"input": "During cerebral ischemia, neurons are injured by various mechanisms including excitotoxicity, oxidative stress, and inflammatory responses.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, pharmacological manipulation of multiple cytotoxic pathways has been pursued for the treatment of ischemic injury.", "output": {"entities": {}}, "schema": []}
{"input": "Cis-hinokiresinol, a naturally occurring phenylpropanoid, was previously reported to possess anti-oxidant, anti-inflammatory and estrogen-like activities.", "output": {"entities": {"chemical": [{"text": "Cis-hinokiresinol", "start": 0, "end": 17}, {"text": "phenylpropanoid", "start": 41, "end": 56}, {"text": "estrogen", "start": 129, "end": 137}]}}, "schema": []}
{"input": "In the present study, we investigated anti-ischemic effects of trans-and cis-hinokiresinols using in vitro as well as in vivo experimental models.", "output": {"entities": {"chemical": [{"text": "trans-and cis-hinokiresinols", "start": 63, "end": 91}]}}, "schema": []}
{"input": "The ORAC and DPPH assays showed that two isomers had similar free radical scavenging activities.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 13, "end": 17}]}}, "schema": []}
{"input": "However, only trans-hinokiresinol significantly decreased neuronal injury in cultured cortical neurons exposed to oxygen-glucose deprivation (75 min) followed by re-oxygenation (9 h).", "output": {"entities": {"chemical": [{"text": "trans-hinokiresinol", "start": 14, "end": 33}, {"text": "oxygen", "start": 114, "end": 120}, {"text": "glucose", "start": 121, "end": 128}]}}, "schema": []}
{"input": "The differential neuroprotective effect could be due to the stereo-specific augmentation of Cu/Zn-SOD activity by trans-hinokiresinol, when compared with cis-hinokiresinol.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 92, "end": 94}, {"text": "Zn", "start": 95, "end": 97}, {"text": "trans-hinokiresinol", "start": 114, "end": 133}, {"text": "cis-hinokiresinol", "start": 154, "end": 171}]}}, "schema": []}
{"input": "Similarly, in rats subjected to transient middle cerebral artery occlusion (1. 5 h) followed by 24-h reperfusion, pre-ischemic treatment with trans-hinokiresinol, but not with cis-isomer, reduced cerebral infarct volume.", "output": {"entities": {"chemical": [{"text": "trans-hinokiresinol", "start": 142, "end": 161}]}}, "schema": []}
{"input": "Interestingly, however, post-ischemic treatment with both hinokiresinols (2 and 7 h after onset of ischemia) significantly reduced cerebral infarct.", "output": {"entities": {"chemical": [{"text": "hinokiresinols", "start": 58, "end": 72}]}}, "schema": []}
{"input": "When administered after onset of ischemia, trans-hinokiresinol, but not its cis-isomer reduced nitrotyrosine immunoreactivity in ischemic regions.", "output": {"entities": {"chemical": [{"text": "trans-hinokiresinol", "start": 43, "end": 62}, {"text": "nitrotyrosine", "start": 95, "end": 108}]}}, "schema": []}
{"input": "In contrast, both hinokiresinols suppressed neutrophil infiltration and IL-1 beta release to a similar extent.", "output": {"entities": {"chemical": [{"text": "hinokiresinols", "start": 18, "end": 32}]}}, "schema": []}
{"input": "The observed differential anti-oxidant, but comparable anti-inflammatory, activities may explain the stereo-specific anti-ischemic activities and different therapeutic time windows of the hinokiresinols examined.", "output": {"entities": {"chemical": [{"text": "hinokiresinols", "start": 188, "end": 202}]}}, "schema": []}
{"input": "More detailed delineation of the anti-ischemic mechanism (s) of hinokiresinols may provide a better strategy for development of efficacious regimens for cerebral ischemic stroke.", "output": {"entities": {"chemical": [{"text": "hinokiresinols", "start": 64, "end": 78}]}}, "schema": []}
{"input": "Sunset yellow FCF, a permitted food dye, alters functional responses of splenocytes at non-cytotoxic dose.", "output": {"entities": {"chemical": [{"text": "Sunset yellow FCF", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Sunset yellow FCF (SY), a permitted food color, is extensively used in various food preparations and quite often exceeds the permissible levels (100-200 mg/kg).", "output": {"entities": {"chemical": [{"text": "Sunset yellow FCF", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Several toxicity studies on SY are reported, however immunomodulatory properties have not been explored yet.", "output": {"entities": {}}, "schema": []}
{"input": "To investigate the immunotoxic properties of SY, splenocytes were isolated, cultured and subjected to mitogen stimulated proliferation assay (lipopolysaccharide, LPS or concanavalin A, Con A), mixed lymphocyte reaction (MLR) assay, immunophenotypic analysis of cell surface receptor expression and assay for cytokines release in the culture supernatants were performed in the presence of SY.", "output": {"entities": {}}, "schema": []}
{"input": "Since SY did not exhibit any cytotoxicity up to 250 mu g/ml, this dose was used for further studies.", "output": {"entities": {}}, "schema": []}
{"input": "It was observed that SY (250 mu g/ml) significantly (p < 0. 05) suppressed the mitogen induced proliferation of splenocytes and MLR response.", "output": {"entities": {}}, "schema": []}
{"input": "Further, immunophenotypic analysis revealed that SY alters the relative expression of CD3e/CD4/CD8 in T cells and CD19 in B-cells.", "output": {"entities": {}}, "schema": []}
{"input": "Consistent with the suppression of T-cell and B-cell responses and altered surface receptor expression, SY also lowered the expression of IL2, IL4, IL6, IL-17, IFN-gamma and TNF-alpha cytokines.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that non-cytotoxic dose of SY may have immunomodulatory effects.", "output": {"entities": {}}, "schema": []}
{"input": "Trypsin and chymotrypsin inhibitor peptides from the venom of Chinese Daboia russellii siamensis.", "output": {"entities": {}}, "schema": []}
{"input": "Two trypsin inhibitors and one chymotrypsin inhibitor from Chinese Daboia russellii siamensis venom, denoted as CBPTI-1, CBPTI-2 and CBPTI-3 were purified, characterized and cloned from lyophilized venom-derived cDNA libraries.", "output": {"entities": {}}, "schema": []}
{"input": "The N-terminus of CBPTI-1 was modified and not amenable to Edman degradation sequencing, however an internal partial sequence was found to be SGRCRGHLRRIYYNPDSNKCE.", "output": {"entities": {"chemical": [{"text": "N", "start": 4, "end": 5}]}}, "schema": []}
{"input": "The N-termini of CBPTI-2 and CBPTI-3 were unmodified and their partial sequences were established as HDRPTFCNLAPESGRCRAH and HDRPKFCYLPADPGECMAYIRSFYYDS respectively.", "output": {"entities": {"chemical": [{"text": "N", "start": 4, "end": 5}]}}, "schema": []}
{"input": "From cloning studies CBPTI-1 was found to consist of 66 amino acid residues, while CBPTI-2 and CBPTI-3 precursors consist of 60 amino acid residues, including 6 cysteine residues.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 56, "end": 66}, {"text": "amino acid", "start": 128, "end": 138}, {"text": "cysteine", "start": 161, "end": 169}]}}, "schema": []}
{"input": "Another cDNA sequence (CBPTI-4) was also obtained.", "output": {"entities": {}}, "schema": []}
{"input": "Alignment of cDNA sequences showed that CBPTI-3 exhibited similar sequence homology to CBPTI-4 cDNA except for an 8 nucleotide deletion in the open-reading frame.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 116, "end": 126}]}}, "schema": []}
{"input": "CBPTI-1 and CBPTI-2 were demonstrated to be potent trypsin inhibitors, but were also shown to be effectively potent in chymotrypsin inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "The K (i) values of CBPTI-1 and CBPTI-2 for trypsin inhibition were 4. 07 x 10 (-7) M and 6. 66 x 10 (-7) M, respectively, and they were non-competitive in their activity.", "output": {"entities": {}}, "schema": []}
{"input": "CBPTI-3 showed chymotrypsin inhibition activity with a K (i) value of 2. 55 x 10 (-9) M, but did not show trypsin inhibitor activity.", "output": {"entities": {}}, "schema": []}
{"input": "Marked toxicity of Albizia bernieri extracts on embryo-larval development in the medaka fish (Oryzias latipes).", "output": {"entities": {}}, "schema": []}
{"input": "Previous phytochemical studies have shown that the plants of the Albizia genus (Fabaceae) contain bioactive saponins, lignans, spermine alkaloids, flavonoids, glycosides phenols and pyridoxine derivatives.", "output": {"entities": {"chemical": [{"text": "saponins", "start": 108, "end": 116}, {"text": "lignans", "start": 118, "end": 125}, {"text": "spermine alkaloids", "start": 127, "end": 145}, {"text": "flavonoids", "start": 147, "end": 157}, {"text": "glycosides phenols", "start": 159, "end": 177}, {"text": "pyridoxine", "start": 182, "end": 192}]}}, "schema": []}
{"input": "Their extracts sometimes display medical properties, but can have also toxic effects.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of our study was to determine the in vivo toxicity of Albizia bernieri seeds in the experimental model of the medaka fish embryo, which is recommended for use in toxicity studies.", "output": {"entities": {}}, "schema": []}
{"input": "Our results show clearly that incubating the embryos or larvae of the medaka fish in a medium containing A. bernieri extracts caused a dose-dependent reduction in embryo or larvae survival.", "output": {"entities": {}}, "schema": []}
{"input": "Embryos exposed to an extract of A. bernieri displayed cerebral lesions, such as cell lysis and the emergence of lysosomes in the glial tissue.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that when comparing with data obtained with different plant extracts tested on medaka development in our laboratory, A. bernieri displays an unusually high toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Focussing on the cerebral target as well as the fish behaviour could bring more specific informations.", "output": {"entities": {}}, "schema": []}
{"input": "Remarkable stabilization of antiparallel DNA triplexes by strong stacking effects of consecutively modified nucleobases containing thiocarbonyl groups.", "output": {"entities": {"chemical": [{"text": "thiocarbonyl", "start": 131, "end": 143}]}}, "schema": []}
{"input": "The consecutive arrangement of 2'-deoxy-6-thioguanosines (s (6) Gs) and 4-thiothymidines (s (4) Ts) in antiparallel triplex-forming oligonucleotides (TFOs) considerably stabilized the resulting antiparallel triplexes with high base recognition ability by the strong stacking effects of thiocarbonyl groups.", "output": {"entities": {"chemical": [{"text": "2'-deoxy-6-thioguanosines", "start": 31, "end": 56}, {"text": "s (6) Gs", "start": 58, "end": 66}, {"text": "4-thiothymidines", "start": 72, "end": 88}, {"text": "s (4) Ts", "start": 90, "end": 98}, {"text": "thiocarbonyl", "start": 286, "end": 298}]}}, "schema": []}
{"input": "This result was remarkable because chemical modifications of the sugar moieties and nucleobases of antiparallel TFOs generally destabilize triplex structures.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 65, "end": 70}]}}, "schema": []}
{"input": "Moreover, in comparison with unmodified TFOs, it was found that TFOs containing s (6) Gs and s (4) Ts could selectively bind to the complementary DNA duplex but not to mismatched DNA duplexes or single-stranded RNA.", "output": {"entities": {"chemical": [{"text": "s (6) Gs", "start": 80, "end": 88}, {"text": "s (4) Ts", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Influence of DNA repair on nonlinear dose-responses for mutation.", "output": {"entities": {}}, "schema": []}
{"input": "Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response.", "output": {"entities": {}}, "schema": []}
{"input": "Emerging evidence suggests that the model alkylating agents methyl-and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL).", "output": {"entities": {"chemical": [{"text": "methyl", "start": 60, "end": 66}, {"text": "ethylmethanesulfonate", "start": 71, "end": 92}, {"text": "methylnitrosourea", "start": 97, "end": 114}, {"text": "MNU", "start": 116, "end": 119}, {"text": "ethylnitrosourea", "start": 125, "end": 141}]}}, "schema": []}
{"input": "Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs.", "output": {"entities": {}}, "schema": []}
{"input": "MNU is one of the most mutagenic simple alkylators.", "output": {"entities": {"chemical": [{"text": "MNU", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents.", "output": {"entities": {"chemical": [{"text": "MNU", "start": 81, "end": 84}]}}, "schema": []}
{"input": "Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0. 0075 micro g/ml (72. 8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476).", "output": {"entities": {"chemical": [{"text": "MNU", "start": 16, "end": 19}, {"text": "hypoxanthine", "start": 179, "end": 191}, {"text": "guanine", "start": 193, "end": 200}]}}, "schema": []}
{"input": "Mechanistic studies reveal that the NOGEL is dependent upon repair of O (6)-methylguanine (O (6) MeG) by the suicide enzyme O (6) MeG-DNA methyltransferase (MGMT).", "output": {"entities": {"chemical": [{"text": "O (6)-methylguanine", "start": 70, "end": 89}, {"text": "O (6) MeG", "start": 91, "end": 100}, {"text": "O (6) MeG", "start": 124, "end": 133}]}}, "schema": []}
{"input": "Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis.", "output": {"entities": {"chemical": [{"text": "MNU", "start": 41, "end": 44}]}}, "schema": []}
{"input": "An animal model of marginal iodine deficiency during development: the thyroid axis and neurodevelopmental outcome.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 28, "end": 34}]}}, "schema": []}
{"input": "Thyroid hormones (THs) are essential for brain development, and iodine is required for TH synthesis.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 64, "end": 70}]}}, "schema": []}
{"input": "Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low-level TH disruption.", "output": {"entities": {}}, "schema": []}
{"input": "This study examined the dose-response characteristics of marginal iodine deficiency (ID) on parameters of thyroid function and neurodevelopment.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 66, "end": 72}]}}, "schema": []}
{"input": "Diets deficient in iodine were prepared by adding 975, 200, 125, 25, or 0 micro g/kg potassium iodate to the base casein diet to produce five nominal iodine levels ranging from ample (Diet 1: 1000 mu g iodine/kg chow, D1) to deficient (Diet 5: 25 micro g iodine/kg chow, D5).", "output": {"entities": {"chemical": [{"text": "iodine", "start": 19, "end": 25}, {"text": "potassium iodate", "start": 85, "end": 101}, {"text": "iodine", "start": 150, "end": 156}, {"text": "iodine", "start": 202, "end": 208}, {"text": "iodine", "start": 255, "end": 261}]}}, "schema": []}
{"input": "Female Long Evans rats were maintained on these diets beginning 7 weeks prior to breeding until the end of lactation.", "output": {"entities": {}}, "schema": []}
{"input": "Dams were sacrificed on gestational days 16 and 20, or when pups were weaned on postnatal day (PN) 21.", "output": {"entities": {}}, "schema": []}
{"input": "Fetal tissue was harvested from the dams, and pups were sacrificed on PN14 and PN21.", "output": {"entities": {}}, "schema": []}
{"input": "Blood, thyroid gland, and brain were collected for analysis of iodine, TH, and TH precursors and metabolites.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 63, "end": 69}]}}, "schema": []}
{"input": "Serum and thyroid gland iodine and TH were reduced in animals receiving two diets that were most deficient in iodine.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 24, "end": 30}, {"text": "iodine", "start": 110, "end": 116}]}}, "schema": []}
{"input": "T4 was reduced in the fetal brain but was not altered in the neonatal brain.", "output": {"entities": {}}, "schema": []}
{"input": "Neurobehavior, assessed by acoustic startle, water maze learning, and fear conditioning, was unchanged in adult offspring, but excitatory synaptic transmission was impaired in the dentate gyrus in animals receiving two diets that were most deficient in iodine.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 253, "end": 259}]}}, "schema": []}
{"input": "A 15% reduction in cortical T4 in the fetal brain was sufficient to induce permanent reductions in synaptic function in adults.", "output": {"entities": {}}, "schema": []}
{"input": "These findings have implications for regulation of TH-disrupting chemicals and suggest that standard behavioral assays do not readily detect neurotoxicity induced by modest developmental TH disruption.", "output": {"entities": {}}, "schema": []}
{"input": "Sunitinib, a tyrosine kinase inhibitor, induces cytochrome P450 1A1 gene in human breast cancer MCF7 cells through ligand-independent aryl hydrocarbon receptor activation.", "output": {"entities": {"chemical": [{"text": "Sunitinib", "start": 0, "end": 9}, {"text": "tyrosine", "start": 13, "end": 21}, {"text": "aryl hydrocarbon", "start": 134, "end": 150}]}}, "schema": []}
{"input": "Sunitinib (SUN) is a new multi-targeted oral tyrosine kinase inhibitor that has both anti-angiogenic and anti-tumor activities.", "output": {"entities": {"chemical": [{"text": "Sunitinib", "start": 0, "end": 9}, {"text": "SUN", "start": 11, "end": 14}, {"text": "tyrosine", "start": 45, "end": 53}]}}, "schema": []}
{"input": "However, information reported in the literature on the effects of SUN on the constitutive expression of cytochrome P450 1A1 (CYP1A1) gene in cells from mammalian species remains unclear.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 66, "end": 69}]}}, "schema": []}
{"input": "Therefore, the main objectives of the current work were to investigate the potentiality of SUN to induce CYP1A1 gene expression in human breast cancer MCF7 cells and to explore the molecular mechanisms involved.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 91, "end": 94}]}}, "schema": []}
{"input": "Our results showed that SUN induced the CYP1A1 mRNA, protein, and activity levels in a concentration-dependent manner in MCF7 cells.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 24, "end": 27}]}}, "schema": []}
{"input": "The increase in CYP1A1 mRNA by SUN was completely blocked by the transcriptional inhibitor, actinomycin D; implying that SUN increased de novo RNA synthesis.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 31, "end": 34}, {"text": "actinomycin D", "start": 92, "end": 105}, {"text": "SUN", "start": 121, "end": 124}]}}, "schema": []}
{"input": "Furthermore, the ability of SUN to increase luciferase reporter gene expression suggests an aryl hydrocarbon receptor (AhR)-dependent transcriptional control and excludes the possibility of any posttranscriptional mechanisms.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 28, "end": 31}, {"text": "aryl hydrocarbon", "start": 92, "end": 108}]}}, "schema": []}
{"input": "In addition, blocking of AhR activation by resveratrol, a well-known AhR antagonist, prevented the SUN-induced CYP1A1 gene expression, further confirms the involvement of AhR.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 99, "end": 102}]}}, "schema": []}
{"input": "Interestingly, this was associated with the inability of SUN to directly bind to and induce transformation of cytosolic AhR to its DNA-binding form in vitro, suggesting that the effect of SUN does not involve direct binding to AhR.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 57, "end": 60}, {"text": "SUN", "start": 188, "end": 191}]}}, "schema": []}
{"input": "The current manuscript provides the first evidence for the ability of SUN to induce CYP1A1 gene expression in MCF7 cells through AhR ligand-independent mechanisms.", "output": {"entities": {"chemical": [{"text": "SUN", "start": 70, "end": 73}]}}, "schema": []}
{"input": "Drug repositioning by structure-based virtual screening.", "output": {"entities": {}}, "schema": []}
{"input": "Approved drugs have favourable or validated pharmacokinetic properties and toxicological profiles, and the repositioning of existing drugs for new indications can potentially avoid expensive costs associated with early-stage testing of the hit compounds.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years, technological advances in virtual screening methodologies have allowed medicinal chemists to rapidly screen drug libraries for therapeutic activity against new biomolecular targets in a cost-effective manner.", "output": {"entities": {}}, "schema": []}
{"input": "This review article outlines the basic principles and recent advances in structure-based virtual screening and highlights the powerful synergy of in silico techniques in drug repositioning as demonstrated in several recent reports.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetic profile of artemisinin derivatives and companion drugs used in artemisinin-based combination therapies for the treatment of Plasmodium falciparum malaria in children.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 27, "end": 38}, {"text": "artemisinin", "start": 79, "end": 90}]}}, "schema": []}
{"input": "Malaria is one of the most common parasitic infections worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Plasmodium falciparum is the most prevalent strain in Africa and also the most fatal.", "output": {"entities": {}}, "schema": []}
{"input": "The disease especially affects children, with those under age 5 years accounting for approximately 86% of malaria deaths in 2010.", "output": {"entities": {}}, "schema": []}
{"input": "The objectives of this review are to summarize and evaluate published literature reporting the pharmacokinetic parameters of artemisinin-based combinations used to treat P. falciparum in paediatric populations and to identify and discuss controversies regarding pharmacokinetics of these agents in children.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 125, "end": 136}]}}, "schema": []}
{"input": "A search of MEDLINE (1948-September 2012), EMBASE (1980-September 2012), International Pharmaceutical Abstracts (1970-September 2012), Google and Google Scholar was conducted for articles describing pharmacokinetics of antimalarials in children.", "output": {"entities": {}}, "schema": []}
{"input": "Our search produced 30 articles, of which 23 were included in the review: artemisinin compounds, 12 articles; lumefantrine, four articles; amodiaquine, five articles; sulfadoxine, six articles; pyrimethamine, one article; mefloquine, three articles; and piperaquine, two articles.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 74, "end": 85}, {"text": "lumefantrine", "start": 110, "end": 122}, {"text": "amodiaquine", "start": 139, "end": 150}, {"text": "sulfadoxine", "start": 167, "end": 178}, {"text": "pyrimethamine", "start": 194, "end": 207}, {"text": "mefloquine", "start": 222, "end": 232}, {"text": "piperaquine", "start": 254, "end": 265}]}}, "schema": []}
{"input": "Studies were summarized based on comparison groups and major findings.", "output": {"entities": {}}, "schema": []}
{"input": "Many controversies were identified, including pharmacokinetic equivalence of novel dosage forms, altered pharmacokinetic parameters in children versus adults, effect of drug interactions, and association of pharmacokinetic changes with clinical outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "A large variation in pharmacokinetic parameters of many antimalarial agents was shown, which may be a consequence of the wide range of ages and/or bodyweights of each paediatric cohort.", "output": {"entities": {}}, "schema": []}
{"input": "These studies may mask important associations with age and bodyweight and produce mean data that do not adequately represent the paediatric population as a whole.", "output": {"entities": {}}, "schema": []}
{"input": "In order to properly assess the clinical implications of such pharmacokinetic changes and recommend safe and effective dosage regimens, there is an urgent need for dose-optimization studies for all recommended first-and second-line agents, along with the different drug formulations, used in paediatric populations with P. falciparum.", "output": {"entities": {}}, "schema": []}
{"input": "Regiospecificity and stereospecificity of human UDP-glucuronosyltransferases in the glucuronidation of estriol, 16-epiestriol, 17-epiestriol, and 13-epiestradiol.", "output": {"entities": {"chemical": [{"text": "UDP", "start": 48, "end": 51}, {"text": "estriol", "start": 103, "end": 110}, {"text": "16-epiestriol", "start": 112, "end": 125}, {"text": "17-epiestriol", "start": 127, "end": 140}, {"text": "13-epiestradiol", "start": 146, "end": 161}]}}, "schema": []}
{"input": "The glucuronidation of estriol, 16-epiestriol, and 17-epiestriol by the human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A, and 2B was examined.", "output": {"entities": {"chemical": [{"text": "estriol", "start": 23, "end": 30}, {"text": "16-epiestriol", "start": 32, "end": 45}, {"text": "17-epiestriol", "start": 51, "end": 64}, {"text": "UDP", "start": 78, "end": 81}]}}, "schema": []}
{"input": "UGT1A10 is highly active in the conjugation of the 3-OH in all these estriols, whereas UGT2B7 is the most active UGT toward one of the ring D hydroxyls, the 16-OH in estriol and 16-epiestriol, but the 17-OH in 17-epiestriol.", "output": {"entities": {"chemical": [{"text": "3-OH", "start": 51, "end": 55}, {"text": "estriols", "start": 69, "end": 77}, {"text": "16-OH", "start": 157, "end": 162}, {"text": "estriol", "start": 166, "end": 173}, {"text": "16-epiestriol", "start": 178, "end": 191}, {"text": "17-OH", "start": 201, "end": 206}, {"text": "17-epiestriol", "start": 210, "end": 223}]}}, "schema": []}
{"input": "Kinetic analyses indicated that the 17-OH configuration plays a major role in the affinity of UGT2B7 for estrogens.", "output": {"entities": {"chemical": [{"text": "17-OH", "start": 36, "end": 41}, {"text": "estrogens", "start": 105, "end": 114}]}}, "schema": []}
{"input": "The glucuronidation of the different estriols by the human liver and intestine microsomes reflects the activity of UGT1A10 and UGT2B7 in combination with the tissues' difference in UGT1A10 expression.", "output": {"entities": {"chemical": [{"text": "estriols", "start": 37, "end": 45}]}}, "schema": []}
{"input": "The UGT1A10 mutant 1A10-F93G exhibited much higher V (max) values than UGT1A10 in estriol and 17-epiestriol glucuronidation, but a significantly lower value in 16-epiestriol glucuronidation.", "output": {"entities": {"chemical": [{"text": "estriol", "start": 82, "end": 89}, {"text": "17-epiestriol", "start": 94, "end": 107}, {"text": "16-epiestriol", "start": 160, "end": 173}]}}, "schema": []}
{"input": "To this study on estriol glucuronidation we have added experiments with 13-epiestradiol, a synthetic estradiol in which the spatial arrangement of the methyl on C18 and the hydroxyl on C17 is significantly different than in other estrogens.", "output": {"entities": {"chemical": [{"text": "estriol", "start": 17, "end": 24}, {"text": "13-epiestradiol", "start": 72, "end": 87}, {"text": "estradiol", "start": 101, "end": 110}, {"text": "methyl", "start": 151, "end": 157}, {"text": "hydroxyl", "start": 173, "end": 181}, {"text": "estrogens", "start": 230, "end": 239}]}}, "schema": []}
{"input": "In comparison with estradiol glucuronidation, the C13 configuration change decreases the turnover of UGTs that conjugate the 3-OH, but increases it in UGTs that primarily conjugate the 17-OH.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 19, "end": 28}, {"text": "3-OH", "start": 125, "end": 129}, {"text": "17-OH", "start": 185, "end": 190}]}}, "schema": []}
{"input": "Unexpectedly, UGT2B17 exhibited similar conjugation rates of both the 17-OH and 3-OH of 13-espiestradiol.", "output": {"entities": {"chemical": [{"text": "17-OH", "start": 70, "end": 75}, {"text": "3-OH", "start": 80, "end": 84}, {"text": "13-espiestradiol", "start": 88, "end": 104}]}}, "schema": []}
{"input": "The combined results reveal the strong preference of UGT1A10 for the 3-OH of physiologic estrogens and the equivalently strong preference of UGT2B7 and UGT2B17 for the hydroxyls on ring D of such steroid hormones.", "output": {"entities": {"chemical": [{"text": "3-OH", "start": 69, "end": 73}, {"text": "estrogens", "start": 89, "end": 98}, {"text": "hydroxyls", "start": 168, "end": 177}, {"text": "steroid hormones", "start": 196, "end": 212}]}}, "schema": []}
{"input": "Induced expression of cytochrome P450 1A and NAD (P) H: quinone oxidoreductase determined at mRNA, protein, and enzyme activity levels in rats exposed to the carcinogenic azo dye 1-phenylazo-2-naphthol (Sudan I).", "output": {"entities": {"chemical": [{"text": "NAD (P) H", "start": 45, "end": 54}, {"text": "quinone", "start": 56, "end": 63}, {"text": "azo", "start": 171, "end": 174}, {"text": "1-phenylazo-2-naphthol", "start": 179, "end": 201}, {"text": "Sudan I", "start": 203, "end": 210}]}}, "schema": []}
{"input": "Sudan I (1-phenylazo-2-hydroxynaphthol) is a suspected human carcinogen causing tumors in the livers and urinary bladders of rats, mice, and rabbits.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 0, "end": 7}, {"text": "1-phenylazo-2-hydroxynaphthol", "start": 9, "end": 38}]}}, "schema": []}
{"input": "Here, we investigated for the first time the influence of Sudan I exposure on the expression of several biotransformation enzymes in the livers, kidneys, and lungs of rats concomitantly at the mRNA and protein levels and assayed their enzymatic activities.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 58, "end": 65}]}}, "schema": []}
{"input": "We also studied its effect on the formation of Sudan I-derived DNA adducts in vitro.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 47, "end": 54}]}}, "schema": []}
{"input": "Sudan I increased the total amounts of cytochrome P450 (P450) in all organs tested.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Western blots using antibodies raised against various P450s, NADPH: P450 reductase, and NAD (P) H: quinone oxidoreductase 1 (NQO1) showed that the expression of P450 1A1 and NQO1 was induced in the liver, kidney, and lung of rats treated with Sudan I.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 61, "end": 66}, {"text": "NAD (P) H", "start": 88, "end": 97}, {"text": "quinone", "start": 99, "end": 106}, {"text": "Sudan I", "start": 243, "end": 250}]}}, "schema": []}
{"input": "The higher protein levels correlated with increased enzyme activities of P450 1A1/2 and NQO1.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, 9. 9-, 5. 9-, and 2. 8-fold increases in the formation of Sudan I oxidative metabolites catalyzed by microsomes isolated from the liver, kidney, and lung, respectively, of rats treated with Sudan I were found.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 71, "end": 78}, {"text": "Sudan I", "start": 203, "end": 210}]}}, "schema": []}
{"input": "The relative amounts of P450 1A and NQO1 mRNA, measured by real-time polymerase chain reaction (RT-PCR) analysis, demonstrated that Sudan I induced the expression of P450 1A1 and NQO1 mRNA in the liver, kidney, and lung, and of P450 1A2 mRNA in kidney and lung.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 132, "end": 139}]}}, "schema": []}
{"input": "Finally, microsomes isolated from livers, kidneys, and lungs of Sudan I exposed rats more effectively catalyzed the formation of Sudan I-DNA adducts than microsomes from organs of control rats.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 64, "end": 71}, {"text": "Sudan I", "start": 129, "end": 136}]}}, "schema": []}
{"input": "This was attributable to the higher P450 1A1 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Because P450 1A1 is playing a major role in the bioactivation of Sudan I in rat and human systems, its induction by Sudan I may have a profound effect on cancer risk by this azo dye.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 65, "end": 72}, {"text": "Sudan I", "start": 116, "end": 123}, {"text": "azo", "start": 174, "end": 177}]}}, "schema": []}
{"input": "In addition, the induction of P450 1A1/2 and NQO1 enzymes can influence individual human susceptibility to other environmental carcinogens and have an effect on cancer risk.", "output": {"entities": {}}, "schema": []}
{"input": "A beta interacts with both the iron center and the porphyrin ring of heme: mechanism of heme' s action on A beta aggregation and disaggregation.", "output": {"entities": {"chemical": [{"text": "iron", "start": 31, "end": 35}, {"text": "porphyrin", "start": 51, "end": 60}, {"text": "heme", "start": 69, "end": 73}, {"text": "heme", "start": 88, "end": 92}]}}, "schema": []}
{"input": "Amyloid beta peptide (A beta) aggregation is a pathological hallmark of Alzheimer' s disease (AD).", "output": {"entities": {}}, "schema": []}
{"input": "Modulation of the self-assembly processes, therefore, is thought to be an attractive strategy for the prevention and treatment of AD.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, heme has been found to inhibit A beta aggregation and even dismantle A beta aggregates.", "output": {"entities": {"chemical": [{"text": "heme", "start": 15, "end": 19}]}}, "schema": []}
{"input": "However, the mechanism remains unresolved.", "output": {"entities": {}}, "schema": []}
{"input": "Recent research has shown that heme binds preferentially to the His (13) residue of A beta with the iron center, while the hydrophobic domain of A beta is also able to bind to heme.", "output": {"entities": {"chemical": [{"text": "heme", "start": 31, "end": 35}, {"text": "His", "start": 64, "end": 67}, {"text": "iron", "start": 100, "end": 104}, {"text": "heme", "start": 176, "end": 180}]}}, "schema": []}
{"input": "Herein, absorption spectrometric, Thioflavin T fluorescence, and circular dichroism spectroscopic and transmission electron microscopic measurements revealed that the iron center is not required for the inhibition of A beta aggregation but do influence the binding affinity of heme toward A beta and the dismantlement rate and degree of the A beta aggregates.", "output": {"entities": {"chemical": [{"text": "Thioflavin T", "start": 34, "end": 46}, {"text": "iron", "start": 167, "end": 171}, {"text": "heme", "start": 277, "end": 281}]}}, "schema": []}
{"input": "By studying the interaction of different truncated or mutated A beta peptides with heme or protoporphyrin, we further found that the porphyrin ring of heme is implicated to interact preferentially with the Phe (19) residue, facilitating the binding of heme to A beta and disturbing the interstrand aromatic interaction between the Phe residues, which is crucial for A beta fibrillation.", "output": {"entities": {"chemical": [{"text": "heme", "start": 83, "end": 87}, {"text": "protoporphyrin", "start": 91, "end": 105}, {"text": "porphyrin", "start": 133, "end": 142}, {"text": "heme", "start": 151, "end": 155}, {"text": "Phe", "start": 206, "end": 209}, {"text": "heme", "start": 252, "end": 256}, {"text": "Phe", "start": 331, "end": 334}]}}, "schema": []}
{"input": "These findings open new avenues in the understanding of the interaction between the heme and A beta and the pathways for modulation of A beta aggregation and disaggregation, which would be helpful in designing therapeutic strategies against AD.", "output": {"entities": {"chemical": [{"text": "heme", "start": 84, "end": 88}]}}, "schema": []}
{"input": "Antimutagenic effect of aqueous extract from Agaricus brasiliensis on culture of human lymphocytes.", "output": {"entities": {}}, "schema": []}
{"input": "The mushroom Agaricus brasiliensis (sun mushroom), native from the southeast of Brazil, is well known by its medicinal properties that include effects on diabetes, cholesterol levels, and osteoporosis.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 164, "end": 175}]}}, "schema": []}
{"input": "The antimutagenic effects of A. brasiliensis has been investigated recently and revealed some controversial results depending on the temperature by which the A. brasiliensis tea is obtained.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we evaluated the effect of the A. brasiliensis extract prepared in two different temperatures, 4 degrees C and 25 degrees C, on the doxorubicin-induced DNA strand breaks and chromosomal aberrations (CAs) in human lymphocytes.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 154, "end": 165}]}}, "schema": []}
{"input": "The results demonstrated that A. brasiliensis was able to reduce the DXR-induced DNA damage in both temperatures; however, the CA test was more sensitive to demonstrate a better reduction when the cells were treated with an extract obtained at 25 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "A. brasiliensis extract obtained in different temperatures exhibited antigenotoxic and anticlastogenic effects in human lymphocytes.", "output": {"entities": {}}, "schema": []}
{"input": "A new strategy for intracellular delivery of enzyme using mesoporous silica nanoparticles: superoxide dismutase.", "output": {"entities": {"chemical": [{"text": "silica", "start": 69, "end": 75}, {"text": "superoxide", "start": 91, "end": 101}]}}, "schema": []}
{"input": "We developed mesoporous silica nanoparticle (MSN) as a multifunctional vehicle for enzyme delivery.", "output": {"entities": {"chemical": [{"text": "silica", "start": 24, "end": 30}]}}, "schema": []}
{"input": "Enhanced transmembrane delivery of a superoxide dismutase (SOD) enzyme embedded in MSN was demonstrated.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 37, "end": 47}]}}, "schema": []}
{"input": "Conjugation of the cell-penetrating peptide derived from the human immunodeficiency virus 1 (HIV) transactivator protein (TAT) to mesoporous silica nanoparticle is shown to be an effective way to enhance transmembrane delivery of nanoparticles for intracellular and molecular therapy.", "output": {"entities": {"chemical": [{"text": "silica", "start": 141, "end": 147}]}}, "schema": []}
{"input": "Cu, Zn-superoxide dismutase (SOD) is a key antioxidant enzyme that detoxifies intracellular reactive oxygen species, ROS, thereby protecting cells from oxidative damage.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 0, "end": 2}, {"text": "Zn", "start": 4, "end": 6}, {"text": "superoxide", "start": 7, "end": 17}, {"text": "oxygen", "start": 101, "end": 107}]}}, "schema": []}
{"input": "In this study, we fused a human Cu, Zn-SOD gene with TAT in a bacterial expression vector to produce a genetic in-frame His-tagged TAT-SOD fusion protein.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 32, "end": 34}, {"text": "Zn", "start": 36, "end": 38}]}}, "schema": []}
{"input": "The His-tagged TAT-SOD fusion protein was expressed in E. coli using IPTG induction and purified using FMSN-Ni-NTA.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 108, "end": 110}]}}, "schema": []}
{"input": "The purified TAT-SOD was conjugated to FITC-MSN forming FMSN-TAT-SOD.", "output": {"entities": {}}, "schema": []}
{"input": "The effectiveness of FMSN-TAT-SOD as an agent against ROS was investigated, which included the level of ROS and apoptosis after free radicals induction and functional recovery after ROS damage.", "output": {"entities": {}}, "schema": []}
{"input": "Confocal microscopy on live unfixed cells and flow cytometry analysis showed characteristic nonendosomal distribution of FMSN-TAT-SOD.", "output": {"entities": {}}, "schema": []}
{"input": "Results suggested that FMSN-TAT-SOD may provide a strategy for the therapeutic delivery of antioxidant enzymes that protect cells from ROS damage.", "output": {"entities": {}}, "schema": []}
{"input": "Neuron-type specific cannabinoid-mediated G protein signalling in mouse hippocampus.", "output": {"entities": {}}, "schema": []}
{"input": "Type 1 cannabinoid receptor (CB1) is expressed in different neuronal populations in the mammalian brain.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, CB1 on GABAergic or glutamatergic neurons exerts different functions and display different pharmacological properties in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "This suggests the existence of neuron-type specific signalling pathways activated by different subpopulations of CB1.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we analysed CB1 expression, binding and signalling in the hippocampus of conditional mutant mice, bearing CB1 deletion in GABAergic (GABA-CB1-KO mice) or cortical glutamatergic neurons (Glu-CB1-KO mice).", "output": {"entities": {"chemical": [{"text": "Glu", "start": 201, "end": 204}]}}, "schema": []}
{"input": "Compared to their wild-type littermates, Glu-CB1-KO displayed a small decrease of CB1 mRNA amount, immunoreactivity and [(3) H] CP55, 940 binding.", "output": {"entities": {"chemical": [{"text": "Glu", "start": 41, "end": 44}, {"text": "[(3) H] CP55, 940", "start": 120, "end": 137}]}}, "schema": []}
{"input": "Conversely, GABA-CB1-KO mice showed a drastic reduction of these parameters, confirming that CB1 is present at much higher density on hippocampal GABAergic interneurons than glutamatergic neurons.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 12, "end": 16}]}}, "schema": []}
{"input": "Surprisingly, however, saturation analysis of HU210-stimulated [(35) S] GTP gamma S binding demonstrated that' glutamatergic' CB1 is more efficiently coupled to G protein signalling than' GABAergic' CB1.", "output": {"entities": {"chemical": [{"text": "HU210", "start": 46, "end": 51}, {"text": "[(35) S] GTP gamma S", "start": 63, "end": 83}]}}, "schema": []}
{"input": "Thus, the minority of CB1 on glutamatergic neurons is paradoxically several fold more strongly coupled to G protein signalling than' GABAergic' CB1.", "output": {"entities": {}}, "schema": []}
{"input": "This selective signalling mechanism raises the possibility of designing novel cannabinoid ligands that differentially activate only a subset of physiological effects of CB1 stimulation, thereby optimizing therapeutic action.", "output": {"entities": {}}, "schema": []}
{"input": "Class III phosphatidylinositol 3-kinase and its catalytic product PtdIns3P in regulation of endocytic membrane traffic.", "output": {"entities": {"chemical": [{"text": "phosphatidylinositol", "start": 10, "end": 30}, {"text": "PtdIns3P", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Endocytosis and subsequent membrane traffic through endosomes are cellular processes that are integral to eukaryotic evolution, and numerous human diseases are associated with their dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Consequently, it is important to untangle the molecular machineries that regulate membrane dynamics and protein flow in the endocytic pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Central in this context is class III phosphatidylinositol 3-kinase, an evolutionarily conserved enzyme complex that phosphorylates phosphatidylinositol into phosphatidylinositol 3-phosphate.", "output": {"entities": {"chemical": [{"text": "phosphatidylinositol", "start": 37, "end": 57}, {"text": "phosphatidylinositol", "start": 131, "end": 151}, {"text": "phosphatidylinositol 3-phosphate", "start": 157, "end": 189}]}}, "schema": []}
{"input": "Phosphatidylinositol 3-phosphate recruits specific effector proteins, most of which contain FYVE or PX domains, to promote endocytosis, endosome fusion, endosome motility and endosome maturation, as well as cargo sorting to lysosomes, the biosynthetic pathway or the plasma membrane.", "output": {"entities": {"chemical": [{"text": "Phosphatidylinositol 3-phosphate", "start": 0, "end": 32}]}}, "schema": []}
{"input": "Here we review the functions of key phosphatidylinositol 3-phosphate effectors in regulation of endocytic membrane dynamics and protein sorting.", "output": {"entities": {"chemical": [{"text": "phosphatidylinositol 3-phosphate", "start": 36, "end": 68}]}}, "schema": []}
{"input": "Design, synthesis, characterization and biological evaluation of novel pyrazole integrated benzophenones.", "output": {"entities": {"chemical": [{"text": "pyrazole", "start": 71, "end": 79}, {"text": "benzophenones", "start": 91, "end": 104}]}}, "schema": []}
{"input": "A series of novel pyrazole integrated benzophenones (9a-j) have been designed, synthesized from 1-methyl-5-(2, 4, 6-trimethoxy-phenyl)-1H-pyrazole 6.", "output": {"entities": {"chemical": [{"text": "pyrazole", "start": 18, "end": 26}, {"text": "benzophenones", "start": 38, "end": 51}, {"text": "1-methyl-5-(2, 4, 6-trimethoxy-phenyl)-1H-pyrazole", "start": 96, "end": 146}]}}, "schema": []}
{"input": "The structures of the regioisomers 6 and 7 were determined by 2D (1) H-(1) H COSY, (1) H-(13) C HSQC and (1) H-(13) C HMBC experiments.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 65, "end": 70}, {"text": "(1) H", "start": 71, "end": 76}, {"text": "(1) H", "start": 83, "end": 88}, {"text": "(13) C", "start": 89, "end": 95}, {"text": "(1) H", "start": 105, "end": 110}, {"text": "(13) C", "start": 111, "end": 117}]}}, "schema": []}
{"input": "The newly synthesized compounds (9a-j) were evaluated for in vivo anti-inflammatory activity by carrageenan paw edema in rats and in vitro COX-1/COX-2 inhibition and antioxidant potential.", "output": {"entities": {}}, "schema": []}
{"input": "Among the synthesized compounds, compounds 9b, 9d and 9f, were found to be active anti-inflammatory agents in addition to having potent antioxidant activity.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of HIV-1 replication by a tricyclic coumarin GUT-70 in acutely and chronically infected cells.", "output": {"entities": {"chemical": [{"text": "tricyclic coumarin GUT-70", "start": 37, "end": 62}]}}, "schema": []}
{"input": "The anti-HIV-1 activity of GUT-70, a natural product derived from the stem bark of Chlophyllum brasiliense, was evaluated.", "output": {"entities": {"chemical": [{"text": "GUT-70", "start": 27, "end": 33}]}}, "schema": []}
{"input": "GUT-70 inhibited HIV-1 replication in both acutely and chronically infected cells through suppression of NF-kappa B.", "output": {"entities": {"chemical": [{"text": "GUT-70", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Our results strengthen the idea that NF-kappa B pathway is one of the potential targets to control HIV-1 replication and that GUT-70 could serve as a lead compound to develop novel therapeutic agents against HIV-1 infection.", "output": {"entities": {"chemical": [{"text": "GUT-70", "start": 126, "end": 132}]}}, "schema": []}
{"input": "Risk factors for atherosclerosis in patients with chronic kidney disease: recognition and management.", "output": {"entities": {}}, "schema": []}
{"input": "Heart disease is the most common cause of death in patients with chronic kidney disease (CKD), particularly in those receiving dialysis.", "output": {"entities": {}}, "schema": []}
{"input": "Atherosclerosic cardiovascular (CV) disease (CVD) accounts for a large number of these deaths.", "output": {"entities": {}}, "schema": []}
{"input": "Atherosclerosis is accelerated in patients with CKD due predominantly to the high prevalence of traditional CVD risk factors in the CKD population.", "output": {"entities": {}}, "schema": []}
{"input": "CKD aggravates pre-existent traditional risk factors such as hypertension and dyslipidemia due to secondary renal parenchymal hypertension and secondary dyslipidemia.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, a variety of non-traditional risk factors that occur commonly in CKD patients contribute to CV risk.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies suggest that CKD itself may be an independent risk factor for CVD, particularly coronary heart disease (CHD).", "output": {"entities": {}}, "schema": []}
{"input": "Many therapies aimed at CV risk factor modification that have been successful in reducing CV risk in the general population are less effective or ineffective in favorably modifying CV risk in CKD.", "output": {"entities": {}}, "schema": []}
{"input": "Biophysical characterization of the drug-membrane interactions: The case of propranolol and acebutolol.", "output": {"entities": {"chemical": [{"text": "propranolol", "start": 76, "end": 87}, {"text": "acebutolol", "start": 92, "end": 102}]}}, "schema": []}
{"input": "The interaction of propranolol and acebutolol with biological membranes was assessed in the present work by using a range of biophysical techniques and liposomes, as membrane mimetic models.", "output": {"entities": {"chemical": [{"text": "propranolol", "start": 19, "end": 30}, {"text": "acebutolol", "start": 35, "end": 45}]}}, "schema": []}
{"input": "Liposomes were made of zwitterionic phosphatidylcholines and experiments were performed at physiologic pH and at various membrane physical states (gel, ripple and fluid phases).", "output": {"entities": {"chemical": [{"text": "phosphatidylcholines", "start": 36, "end": 56}]}}, "schema": []}
{"input": "Fluorescence techniques were used to study the partition coefficient of beta-blockers, the influence of drugs on membrane fluidity and the drugs-membrane binding.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, small and wide angle X-ray scattering techniques were used to evaluate the beta-blockers effect on long range bilayer order and hydrocarbon chain packing.", "output": {"entities": {"chemical": [{"text": "hydrocarbon", "start": 138, "end": 149}]}}, "schema": []}
{"input": "The gathered results highlighted the importance of electrostatic interactions between propranolol and acebutolol with membranes.", "output": {"entities": {"chemical": [{"text": "propranolol", "start": 86, "end": 97}, {"text": "acebutolol", "start": 102, "end": 112}]}}, "schema": []}
{"input": "Furthermore, both beta-blockers exhibited a membrane-fluidizing effect and the capacity to disturb the membrane organization.", "output": {"entities": {}}, "schema": []}
{"input": "In general, propranolol unveiled a more pronounced effect on membrane fluidity and structure than acebutolol.", "output": {"entities": {"chemical": [{"text": "propranolol", "start": 12, "end": 23}, {"text": "acebutolol", "start": 98, "end": 108}]}}, "schema": []}
{"input": "In the current study, the obtained results were also correlated with the cardioprotective properties of the beta-blockers studied.", "output": {"entities": {}}, "schema": []}
{"input": "Cholinesterase and carboxylesterase inhibition in Planorbarius corneus exposed to binary mixtures of azinphos-methyl and chlorpyrifos.", "output": {"entities": {"chemical": [{"text": "azinphos-methyl", "start": 101, "end": 116}, {"text": "chlorpyrifos", "start": 121, "end": 133}]}}, "schema": []}
{"input": "Though pesticide mixtures are commonly encountered in fresh water systems, the knowledge of their effects on non-target aquatic species is scarce.", "output": {"entities": {}}, "schema": []}
{"input": "The present investigation was undertaken to explore the in vivo inhibition of the freshwater gastropod snail Planorbarius corneus cholinesterase (ChE) and carboxylesterases (CES) activities by the organophosphorus pesticides azinphos-methyl (AZM) and chlorpyrifos (CPF).", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 197, "end": 213}, {"text": "azinphos-methyl", "start": 225, "end": 240}, {"text": "AZM", "start": 242, "end": 245}, {"text": "chlorpyrifos", "start": 251, "end": 263}, {"text": "CPF", "start": 265, "end": 268}]}}, "schema": []}
{"input": "To this end, snails were exposed for 48 h to different concentrations of AZM and CPF in single-chemical and binary-mixture studies, and ChE and CES activities were measured in the whole soft body tissues and hemolymph.", "output": {"entities": {"chemical": [{"text": "AZM", "start": 73, "end": 76}, {"text": "CPF", "start": 81, "end": 84}]}}, "schema": []}
{"input": "ChE activity was measured with acetylthiocholine as substrate and CES activity was measured with four substrates: p-nitrophenyl acetate, p-nitrophenyl butyrate, 1-and 2-naphthyl acetate.", "output": {"entities": {"chemical": [{"text": "acetylthiocholine", "start": 31, "end": 48}, {"text": "p-nitrophenyl acetate", "start": 114, "end": 135}, {"text": "p-nitrophenyl butyrate", "start": 137, "end": 159}, {"text": "1-and 2-naphthyl acetate", "start": 161, "end": 185}]}}, "schema": []}
{"input": "Single-chemical experiments showed that CPF was a more potent inhibitor of ChE activity than AZM (350 and 27 times for the whole soft tissue and hemolymph, respectively).", "output": {"entities": {"chemical": [{"text": "CPF", "start": 40, "end": 43}, {"text": "AZM", "start": 93, "end": 96}]}}, "schema": []}
{"input": "CES were 15 times more sensitive than ChE when the activities were measured in the whole soft tissue of the animals exposed to AZM.", "output": {"entities": {"chemical": [{"text": "AZM", "start": 127, "end": 130}]}}, "schema": []}
{"input": "Based on a default assumption of concentration addition, P. corneus snails were exposed to mixtures of AZM + CPF designed to yield predicted soft tissue ChE inhibitions of 31% (mixture 1), 50% (mixture 2) and 61% (mixture 3).", "output": {"entities": {"chemical": [{"text": "AZM", "start": 103, "end": 106}, {"text": "CPF", "start": 109, "end": 112}]}}, "schema": []}
{"input": "Results showed that ChE inhibition produced by mixture 1 followed a model of concentration addition.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the other mixtures showed synergism, both in whole soft tissue and hemolymph.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, results obtained when the snails were exposed sequentially to the pesticides showed that the sequence AZM/CPF produced at 48 h a higher ChE inhibition than the sequence CPF/CPF.", "output": {"entities": {"chemical": [{"text": "AZM", "start": 115, "end": 118}, {"text": "CPF", "start": 119, "end": 122}, {"text": "CPF", "start": 182, "end": 185}, {"text": "CPF", "start": 186, "end": 189}]}}, "schema": []}
{"input": "A range of metabolic pathways and responses associated with bioactivation or detoxification may play important roles in organophosphorus interactions.", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 120, "end": 136}]}}, "schema": []}
{"input": "In particular, the data presented in the present study indicate that CES enzymes would be important factors in determining the effects of the mixtures of OPs on P. corneus ChE activity.", "output": {"entities": {"chemical": [{"text": "OPs", "start": 154, "end": 157}]}}, "schema": []}
{"input": "Sub-lethal coral stress: detecting molecular responses of coral populations to environmental conditions over space and time.", "output": {"entities": {}}, "schema": []}
{"input": "In order for sessile organisms to survive environmental fluctuations and exposures to pollutants, molecular mechanisms (i. e. stress responses) are elicited.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, detrimental effects of natural and anthropogenic stressors on coral health could not be ascertained until significant physiological responses resulted in visible signs of stress (e. g. tissue necrosis, bleaching).", "output": {"entities": {}}, "schema": []}
{"input": "In this study, a focused anthozoan holobiont microarray was used to detect early and sub-lethal effects of spatial and temporal environmental changes on gene expression patterns in the scleractinian coral, Montastraea cavernosa, on south Florida reefs.", "output": {"entities": {}}, "schema": []}
{"input": "Although all colonies appeared healthy (i. e. no visible tissue necrosis or bleaching), corals were differentially physiologically compensating for exposure to stressors that varied over time.", "output": {"entities": {}}, "schema": []}
{"input": "Corals near the Port of Miami inlet experienced significant changes in expression of stress responsive and symbiont (zooxanthella)-specific genes after periods of heavy precipitation.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, coral populations did not demonstrate stress responses during periods of increased water temperature (up to 29 degrees C).", "output": {"entities": {}}, "schema": []}
{"input": "Specific acute and long-term localized responses to other stressors were also evident.", "output": {"entities": {}}, "schema": []}
{"input": "A correlation between stress response genes and symbiont-specific genes was also observed, possibly indicating early processes involved in the maintenance or disruption of the coral-zooxanthella symbiosis.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first study to reveal spatially-and temporally-related variation in gene expression in response to different stressors of in situ coral populations, and demonstrates that microarray technology can be used to detect specific sub-lethal physiological responses to specific environmental conditions that are not visually detectable.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro study of intestinal transport of fluoride using the Caco-2 cell line.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Water and food are the main sources of fluoride exposure and therefore it is necessary to study intestinal absorption in order to make a correct evaluation of the risk/benefit associated with exposure to fluoride.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 39, "end": 47}, {"text": "fluoride", "start": 204, "end": 212}]}}, "schema": []}
{"input": "The present study characterizes intestinal transport of fluoride, using the Caco-2 cell line as a model of the intestinal epithelium, and evaluates the coefficients of apparent permeability and intracellular accumulation in various conditions (pH, temperature, opening of cell junctions, presence of anions).", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 56, "end": 64}]}}, "schema": []}
{"input": "The results indicate that fluoride is an element with moderate absorption (< 70%) in both directions (absorptive and secretory).", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 26, "end": 34}]}}, "schema": []}
{"input": "Both in absorption (apical-basolateral) and in secretion (basolateral-apical) there is transport by the paracellular pathway, which may be considered predominant.", "output": {"entities": {}}, "schema": []}
{"input": "Absorption and secretion of fluoride increase at acid pH levels, possibly because of its non-ionized state at these pHs and/or because of participation of a F (-)/H (+) cotransporter or a F (-)/OH (-) antiporter.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 28, "end": 36}, {"text": "F (-)", "start": 157, "end": 162}, {"text": "H (+)", "start": 163, "end": 168}, {"text": "F (-)", "start": 188, "end": 193}, {"text": "OH (-)", "start": 194, "end": 200}]}}, "schema": []}
{"input": "The results also suggest transcellular participation of mechanisms involved in transport of Cl (-) and of an active transport in the secretory direction.", "output": {"entities": {"chemical": [{"text": "Cl (-)", "start": 92, "end": 98}]}}, "schema": []}
{"input": "The present study extend the knowledge on the cellular transport of fluoride and provide the basis for future studies aimed at identifying potential transporters involved in human fluoride absorption.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 68, "end": 76}, {"text": "fluoride", "start": 180, "end": 188}]}}, "schema": []}
{"input": "Bombesin receptor subtype-3 (BRS-3), a novel candidate as therapeutic molecular target in obesity and diabetes.", "output": {"entities": {"chemical": [{"text": "Bombesin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "BRS-3 KO-mice developed obesity and unbalanced glucose metabolism, suggesting an important role of BRS-3 receptor in glucose homeostasis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 47, "end": 54}, {"text": "glucose", "start": 117, "end": 124}]}}, "schema": []}
{"input": "We explored BRS-3 expression in skeletal muscle from normal, obese or type-2 diabetic (T2D) patients, and the effect of [D-Phe (6), beta-Ala (11), Phe (13), Nle (14)] bombesin (6-14)-BRS-3-agonist-peptide (BRS-3-AP)-on glucose-related effects, before or after BRS-3 gene silencing.", "output": {"entities": {"chemical": [{"text": "D-Phe", "start": 121, "end": 126}, {"text": "beta-Ala", "start": 132, "end": 140}, {"text": "Phe", "start": 147, "end": 150}, {"text": "Nle", "start": 157, "end": 160}, {"text": "bombesin", "start": 167, "end": 175}, {"text": "glucose", "start": 219, "end": 226}]}}, "schema": []}
{"input": "In muscle tissue and primary cultured myocytes from altered metabolic states, BRS-3 gene/protein expressions were down-regulated.", "output": {"entities": {}}, "schema": []}
{"input": "In normal, obese and T2D cells: A) BRS-3-AP as insulin enhanced BRS-3 and GLUT-4 mRNA/protein levels; improving glucotransporter translocation to plasma membrane, and B) BRS-3-AP caused a concentration-related-stimulation of glucose transport, being obese and T2D myocytes more sensitive to the ligand than normal.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 225, "end": 232}]}}, "schema": []}
{"input": "Wortmannin and PD98059, but not rapamycin, abolished the stimulatory action of BRS-3-AP on glucose transport.", "output": {"entities": {"chemical": [{"text": "Wortmannin", "start": 0, "end": 10}, {"text": "PD98059", "start": 15, "end": 22}, {"text": "rapamycin", "start": 32, "end": 41}, {"text": "glucose", "start": 91, "end": 98}]}}, "schema": []}
{"input": "BRS-3 plays an important role in glucose metabolism, and could be use as a molecular target, and/or its ligand, as a therapeutic agent for obesity and diabetes treatments.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Aryl hydrocarbon receptor activation attenuates Per1 gene induction and influences circadian clock resetting.", "output": {"entities": {"chemical": [{"text": "Aryl hydrocarbon", "start": 0, "end": 16}]}}, "schema": []}
{"input": "Light-stimulated adjustment of the circadian clock is an important adaptive physiological response that allows maintenance of behavioral synchrony with solar time.", "output": {"entities": {}}, "schema": []}
{"input": "Our previous studies indicate that the aryl hydrocarbon receptor (AhR) agonist 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin attenuates light-induced phase resetting in early night.", "output": {"entities": {"chemical": [{"text": "aryl hydrocarbon", "start": 39, "end": 55}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 79, "end": 117}]}}, "schema": []}
{"input": "However, the mechanism of inhibition remains unclear.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we showed that another potent AhR agonist-beta-naphthoflavone (BNF)-significantly decreased light-induced phase shifts in wild-type (WT) mice, whereas AhR knockout mice had an enhanced response to light that was unaffected by BNF.", "output": {"entities": {"chemical": [{"text": "beta-naphthoflavone", "start": 57, "end": 76}, {"text": "BNF", "start": 78, "end": 81}, {"text": "BNF", "start": 241, "end": 244}]}}, "schema": []}
{"input": "Mechanistically, BNF blocked light induction of the Per1 transcript in suprachiasmatic nucleus and liver in WT mice, and BNF blocked forskolin (FSK)-induced Per1 transcripts in Hepa-1c1c7 (c7) cells.", "output": {"entities": {"chemical": [{"text": "BNF", "start": 17, "end": 20}, {"text": "BNF", "start": 121, "end": 124}, {"text": "forskolin", "start": 133, "end": 142}, {"text": "FSK", "start": 144, "end": 147}]}}, "schema": []}
{"input": "An E-box decoy did not affect BNF inhibition of FSK-induced Per1 transcripts in c7 cells.", "output": {"entities": {"chemical": [{"text": "BNF", "start": 30, "end": 33}, {"text": "FSK", "start": 48, "end": 51}]}}, "schema": []}
{"input": "cAMP-response element (CRE)-dependent induction of Per1 promoter activity in response to FSK in combination with phorbol 12-tetradecanoate 13-acetate was suppressed in cells that expressed high levels of AhR (c7) compared with cells lacking functional AhR activity (c12).", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 0, "end": 4}, {"text": "FSK", "start": 89, "end": 92}, {"text": "phorbol 12-tetradecanoate 13-acetate", "start": 113, "end": 149}]}}, "schema": []}
{"input": "In addition, the inhibitory effect of BNF on FSK-induced Per1 was dependent on phosphorylation of JNK.", "output": {"entities": {"chemical": [{"text": "BNF", "start": 38, "end": 41}, {"text": "FSK", "start": 45, "end": 48}]}}, "schema": []}
{"input": "Together, these results suggest that AhR activation inhibits light-induced phase resetting through the activation of JNK, negative regulation of CREs in the Per1 promoter, and suppression of Per1.", "output": {"entities": {}}, "schema": []}
{"input": "Preparation, preliminary screening of new types of steroid conjugates and their activities on steroid receptors.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 51, "end": 58}, {"text": "steroid", "start": 94, "end": 101}]}}, "schema": []}
{"input": "There were synthesized new types of ribbon type steroidal dimers derived from three types of steroidal skeletons (cholic acid, etienic acid, estrone) using Cu (I) catalyzed 1, 3-dipolar cycloaddition reaction.", "output": {"entities": {"chemical": [{"text": "cholic acid", "start": 114, "end": 125}, {"text": "etienic acid", "start": 127, "end": 139}, {"text": "estrone", "start": 141, "end": 148}, {"text": "Cu (I)", "start": 156, "end": 162}]}}, "schema": []}
{"input": "Steroid parts of the molecular \" ribbons \" are linked by heterocyclic moiety, namely by 2, 6-bis ((1H-1, 2, 3-triazol-1-yl)-methyl) pyridine.", "output": {"entities": {"chemical": [{"text": "Steroid", "start": 0, "end": 7}, {"text": "2, 6-bis ((1H-1, 2, 3-triazol-1-yl)-methyl) pyridine", "start": 88, "end": 140}]}}, "schema": []}
{"input": "Compounds synthesized possess different cytotoxic and hormone receptor modulating activities.", "output": {"entities": {}}, "schema": []}
{"input": "Altered matrix mineralization in a case of a sclerosing osteosarcoma.", "output": {"entities": {}}, "schema": []}
{"input": "Little is known about the tumor matrix mineralization of highly sclerotic osteosarcoma.", "output": {"entities": {}}, "schema": []}
{"input": "We used quantitative backscattered electron imaging (qBEI) to determine the Bone mineralization density distribution (BMDD) of a highly sclerosing osteosarcoma of the proximal tibia as well as adjacent normal bone of a 10-year-old girl following chemotherapy according to the EURAMOS-1 protocol.", "output": {"entities": {}}, "schema": []}
{"input": "Data were compared to recently published normative reference data for young individuals.", "output": {"entities": {}}, "schema": []}
{"input": "Backscattered electron imaging of the tumor region revealed a dense accumulation of mineralized tumor bone matrix (up to 90% of the medullar space).", "output": {"entities": {}}, "schema": []}
{"input": "The BMDD was shifted tremendously towards higher matrix mineralization (CaMean + 18. 5%, CaPeak + 22. 5%, CaHigh + 100 fold) compared to normal bone.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally the BMDD became much wider, indicating a higher heterogeneity in mineralization (CaWidth + 40%).", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to lamellar bone, which mineralizes via a mineralization front, the mineralization of the tumor matrix starts by randomly distributed spots of mineral clusters fusing together to a highly mineralized non-lamellar bone matrix.", "output": {"entities": {}}, "schema": []}
{"input": "We also found an altered BMDD of the patient' s normal bone when compared with the reference BMDD of young individuals.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion this high radiodensity region of the sclerosing sarcoma is not only due to the high amount of tumor matrix but also to its high mineralization density.", "output": {"entities": {}}, "schema": []}
{"input": "Chemotherapy may lead to altered matrix mineralization of normal bone due to suppression of bone turnover.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism of matrix mineralization in a sclerosing osteosarcoma warrants further studies.", "output": {"entities": {}}, "schema": []}
{"input": "Pregabalin abuse and dependence in Germany: results from a database query.", "output": {"entities": {"chemical": [{"text": "Pregabalin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "PURPOSE: Pregabalin (PRG) is approved for the treatment of neuropathic pain, partial seizures and generalised anxiety disorder in many countries and currently under study for other indications.", "output": {"entities": {"chemical": [{"text": "Pregabalin", "start": 9, "end": 19}, {"text": "PRG", "start": 21, "end": 24}]}}, "schema": []}
{"input": "Supported by case reports and the results of a limited number of studies there is an ongoing debate on the potential of PRG to cause addictive behaviours.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 120, "end": 123}]}}, "schema": []}
{"input": "However, currently available evidence on this issue is sparse, and any definitive assessment of PRG' s potential for abuse and dependence is not yet in sight.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 96, "end": 99}]}}, "schema": []}
{"input": "The aim of our study was to identify the number of cases of PRG abuse or dependence reported to the database of a German medical regulatory body and to obtain insights into further usage-specific parameters.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 60, "end": 63}]}}, "schema": []}
{"input": "METHODS: We conducted a query of the entire database of the German Federal Institute for Drugs and Medical Devices (BfArM) regarding reports of PRG abuse or dependence and analysed these cases on the basis of several parameters.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 144, "end": 147}]}}, "schema": []}
{"input": "RESULTS: A total of 55 reports of PRG abuse or dependence were identified (mean age 36 years, 64% of reports involved males).", "output": {"entities": {"chemical": [{"text": "PRG", "start": 34, "end": 37}]}}, "schema": []}
{"input": "The first reports were submitted to BfArM in 2008, and the reporting frequency has increased up to the present.", "output": {"entities": {}}, "schema": []}
{"input": "Mean daily PRG dosage was 1424 mg.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 11, "end": 14}]}}, "schema": []}
{"input": "Current or previous polytoxicomania was present in 40 and 42% of cases, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Psychiatric diagnoses other than substance-related disorders were reported in 13 (24%) cases.", "output": {"entities": {}}, "schema": []}
{"input": "In about one-third of the patients withdrawal syndromes subsequent to discontinuation of PRG were reported.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 89, "end": 92}]}}, "schema": []}
{"input": "CONCLUSIONS: Cases of PRG abuse or dependence have been reported to the BfArM since 2008, with a marked increase of such reports in subsequent years.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 22, "end": 25}]}}, "schema": []}
{"input": "Male sex and a history of polytoxicomania may be possible risk factors for the development of addictive behaviours related to PRG.", "output": {"entities": {"chemical": [{"text": "PRG", "start": 126, "end": 129}]}}, "schema": []}
{"input": "Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 82, "end": 89}]}}, "schema": []}
{"input": "The aim of this study is to investigate glucose metabolism longitudinally during pregnancy to explore mechanisms underlying gestational diabetes mellitus (GDM).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 40, "end": 47}]}}, "schema": []}
{"input": "We reviewed a total of 62 pregnant Japanese women who underwent a 75g oral glucose tolerance test (OGTT) twice during pregnancy (median: early, 13; late, 28 weeks' gestation) because of positive GDM screening.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 75, "end": 82}]}}, "schema": []}
{"input": "All showed normal OGTT results in early pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Based on late OGTT, 15 had GDM (late-onset GDM) and 47 normal glucose tolerance (NGT).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 62, "end": 69}]}}, "schema": []}
{"input": "In early pregnancy, there were no significant differences in insulin sensitivity (insulin sensitivity index derived from OGTT [ISOGTT] and homeostasis model assessment for insulin resistance [HOMA-IR]) and insulin secretion (a ratio of the total area-under-the-insulin-curve to the total area-under-the-glucose-curve [AUCins/glu] and insulinogenic index [IGI]) between the NGT and late-onset GDM groups.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 303, "end": 310}]}}, "schema": []}
{"input": "In each group, insulin sensitivity significantly decreased from early to late pregnancy, most in the late-onset GDM group (each p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "The insulin secretion showed no significant changes with advancing pregnancy in both of the groups, although late-onset GDM showed significantly lower IGI compared with NGT in late OGTT (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "When assessed beta cell function by OGTT-derived disposition index (i. e. Insulin Secretion-Sensitivity Index-2 and IGI/fasting insulin), the indices significantly decreased from early to late pregnancy in the both groups (each p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Women with late-onset GDM showed significantly lower indices compared with NGT (each p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "The failure of beta cell to compensate for decreased insulin sensitivity could contribute to the development of the late-onset GDM.", "output": {"entities": {}}, "schema": []}
{"input": "Expanding the genetic code in Xenopus laevis oocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Heterologous expression of ligand-gated ion channels (LGICs) in Xenopus laevis oocytes combined with site-directed mutagenesis has been demonstrated to be a powerful approach to study structure-function relationships.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, introducing unnatural amino acids (UAAs) has enabled modifications that are not found in natural proteins.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 37, "end": 48}]}}, "schema": []}
{"input": "However, the current strategy relies on the technically demanding in vitro synthesis of aminoacylated suppressor tRNA.", "output": {"entities": {}}, "schema": []}
{"input": "We report here a general method that circumvents this limitation by utilizing orthogonal aminoacyl-tRNA synthetase (aaRS)/suppressor tRNA (CUA) pairs to genetically encode UAAs in Xenopus oocytes.", "output": {"entities": {}}, "schema": []}
{"input": "We show that UAAs inserted in the N-terminal domain of N-methyl-D-aspartate receptors (NMDARs) serve as photo-crosslinkers that lock the receptor in a discrete conformational state in response to UV photo treatment.", "output": {"entities": {"chemical": [{"text": "N", "start": 34, "end": 35}, {"text": "N-methyl-D-aspartate", "start": 55, "end": 75}]}}, "schema": []}
{"input": "Our method should be generally applicable to studies of other LGICs in Xenopus oocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Plasmon-Mediated Synthesis of Silver Cubes with Unusual Twinning Structures Using Short Wavelength Excitation.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 30, "end": 36}]}}, "schema": []}
{"input": "The plasmon-mediated synthesis of silver nanoparticles is a versatile synthetic method which leverages the localized surface plasmon resonance (LSPR) of nanoscale silver to generate particles with non-spherical shapes and control over dimensions.", "output": {"entities": {"chemical": [{"text": "silver", "start": 34, "end": 40}, {"text": "silver", "start": 163, "end": 169}]}}, "schema": []}
{"input": "Herein, a method is reported for controlling the twinning structure of silver nanoparticles, and consequently their shape, via the plasmon-mediated synthesis, solely by varying the excitation wavelength between 400, 450, and 500 nm, which modulates the rate of Ag (+) reduction.", "output": {"entities": {"chemical": [{"text": "silver", "start": 71, "end": 77}, {"text": "Ag (+)", "start": 261, "end": 267}]}}, "schema": []}
{"input": "Shorter, higher energy excitation wavelengths lead to faster rates of reaction, which in turn yield structures containing a greater number of twin boundaries.", "output": {"entities": {}}, "schema": []}
{"input": "With this method, silver cubes can be synthesized using 450 nm excitation, which represents the first time this shape has been realized by a plasmon-mediated synthetic approach.", "output": {"entities": {"chemical": [{"text": "silver", "start": 18, "end": 24}]}}, "schema": []}
{"input": "In addition, these cubes contain an unusual twinning structure composed of two intersecting twin boundaries or multiple parallel twin boundaries.", "output": {"entities": {}}, "schema": []}
{"input": "With respect to their twinning structure, these cubes fall between planar-twinned and multiply twinned nanoparticles, which are synthesized using 500 and 400 nm excitation, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Effects on gene expression in rat liver after administration of RXR agonists: UAB30, 4-methyl-UAB30, and Targretin (Bexarotene).", "output": {"entities": {"chemical": [{"text": "UAB30", "start": 78, "end": 83}, {"text": "4-methyl-UAB30", "start": 85, "end": 99}, {"text": "Targretin", "start": 105, "end": 114}, {"text": "Bexarotene", "start": 116, "end": 126}]}}, "schema": []}
{"input": "Examination of three retinoid X receptor (RXR) agonists [Targretin (TRG), UAB30, and 4-methyl-UAB30 (4-Me-UAB30)] showed that all inhibited mammary cancer in rodents and two (TRG and 4-Me-UAB30) strikingly increased serum triglyceride levels.", "output": {"entities": {"chemical": [{"text": "retinoid", "start": 21, "end": 29}, {"text": "Targretin", "start": 57, "end": 66}, {"text": "TRG", "start": 68, "end": 71}, {"text": "UAB30", "start": 74, "end": 79}, {"text": "4-methyl-UAB30", "start": 85, "end": 99}, {"text": "4-Me-UAB30", "start": 101, "end": 111}, {"text": "TRG", "start": 175, "end": 178}, {"text": "4-Me-UAB30", "start": 183, "end": 193}, {"text": "triglyceride", "start": 222, "end": 234}]}}, "schema": []}
{"input": "Agents were administered in diets to female Sprague-Dawley rats.", "output": {"entities": {}}, "schema": []}
{"input": "Liver RNA was isolated and microarrayed on the Affymetrix GeneChip Rat Exon 1. 0 ST array.", "output": {"entities": {}}, "schema": []}
{"input": "Statistical tests identified genes that exhibited differential expression and fell into groups, or modules, with differential expression among agonists.", "output": {"entities": {}}, "schema": []}
{"input": "Genes in specific modules were changed by one, two, or all three agonists.", "output": {"entities": {}}, "schema": []}
{"input": "An interactome analysis assessed the effects on genes that heterodimerize with known nuclear receptors.", "output": {"entities": {}}, "schema": []}
{"input": "For proliferator-activated receptor alpha/RXR-activated genes, the strongest response was TRG > 4-Me-UAB30 > UAB30.", "output": {"entities": {"chemical": [{"text": "TRG", "start": 90, "end": 93}, {"text": "4-Me-UAB30", "start": 96, "end": 106}, {"text": "UAB30", "start": 109, "end": 114}]}}, "schema": []}
{"input": "Many liver X receptor/RXR-related genes (e. g., Scd-1 and Srebf1, which are associated with increased triglycerides) were highly expressed in TRG and 4-Me-UAB30-but not UAB30-treated livers.", "output": {"entities": {"chemical": [{"text": "triglycerides", "start": 102, "end": 115}, {"text": "TRG", "start": 142, "end": 145}, {"text": "4-Me-UAB30", "start": 150, "end": 160}, {"text": "UAB30", "start": 169, "end": 174}]}}, "schema": []}
{"input": "Minimal expression changes were associated with retinoic acid receptor or vitamin D receptor heterodimers by any of the agonists.", "output": {"entities": {"chemical": [{"text": "retinoic acid", "start": 48, "end": 61}, {"text": "vitamin D", "start": 74, "end": 83}]}}, "schema": []}
{"input": "UAB30 unexpectedly and uniquely activated genes associated with the aryl hydrocarbon hydroxylase (Ah) receptor (Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1).", "output": {"entities": {"chemical": [{"text": "UAB30", "start": 0, "end": 5}, {"text": "aryl hydrocarbon", "start": 68, "end": 84}]}}, "schema": []}
{"input": "Based on the Ah receptor activation, UAB30 was tested for its ability to prevent dimethylbenzanthracene (DMBA)-induced mammary cancers, presumably by inhibiting DMBA activation, and was highly effective.", "output": {"entities": {"chemical": [{"text": "UAB30", "start": 37, "end": 42}, {"text": "dimethylbenzanthracene", "start": 81, "end": 103}, {"text": "DMBA", "start": 105, "end": 109}, {"text": "DMBA", "start": 161, "end": 165}]}}, "schema": []}
{"input": "Gene expression changes were determined by reverse transcriptase-polymerase chain reaction in rat livers treated with Targretin for 2. 3, 7, and 21 days.", "output": {"entities": {"chemical": [{"text": "Targretin", "start": 118, "end": 127}]}}, "schema": []}
{"input": "These showed similar gene expression changes at all three time points, arguing some steady-state effect.", "output": {"entities": {}}, "schema": []}
{"input": "Different patterns of gene expression among the agonists provided insight into molecular differences and allowed one to predict certain physiologic consequences of agonist treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Assessing the quality of absolute hydration free energies among CHARMM-compatible ligand parameterization schemes.", "output": {"entities": {}}, "schema": []}
{"input": "Multipurpose atom-typer for CHARMM (MATCH), an atom-typing toolset for molecular mechanics force fields, was recently developed in our laboratory.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we assess the ability of MATCH-generated parameters and partial atomic charges to reproduce experimental absolute hydration free energies for a series of 457 small neutral molecules in GBMV2, Generalized Born with a smooth SWitching (GBSW), and fast analytical continuum treatment of solvation (FACTS) implicit solvent models.", "output": {"entities": {}}, "schema": []}
{"input": "The quality of hydration free energies associated with small molecule parameters obtained from ParamChem, SwissParam, and Antechamber are compared.", "output": {"entities": {}}, "schema": []}
{"input": "Given optimized surface tension coefficients for scaling the surface area term in the nonpolar contribution, these automated parameterization schemes with GBMV2 and GBSW demonstrate reasonable agreement with experimental hydration free energies (average unsigned errors of 0. 9-1. 5 kcal/mol and R (2) of 0. 63-0. 87).", "output": {"entities": {}}, "schema": []}
{"input": "GBMV2 and GBSW consistently provide slightly more accurate estimates than FACTS, whereas Antechamber parameters yield marginally more accurate estimates than the current generation of MATCH, ParamChem, and SwissParam parameterization strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Modeling with MATCH libraries that are derived from different CHARMM topology and parameter files highlights the importance of having sufficient coverage of chemical space within the underlying databases of these automated schemes and the benefit of targeting specific functional groups for parameterization efforts to maximize both the breadth and the depth of the parameterized space.", "output": {"entities": {}}, "schema": []}
{"input": "Deletion of STK40 protein in mice causes respiratory failure and death at birth.", "output": {"entities": {}}, "schema": []}
{"input": "STK40 is a putative serine/threonine kinase and was shown to induce extraembryonic endoderm differentiation from mouse embryonic stem cells.", "output": {"entities": {"chemical": [{"text": "serine", "start": 20, "end": 26}, {"text": "threonine", "start": 27, "end": 36}]}}, "schema": []}
{"input": "However, little is known about its physiological function in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we generate Stk40 knock-out mice and demonstrate that loss of the Stk40 gene causes neonatal lethality at birth.", "output": {"entities": {}}, "schema": []}
{"input": "Further examination reveals that the respiratory distress and atelectasis occur in the homozygous mutants.", "output": {"entities": {}}, "schema": []}
{"input": "The maturation of lung and alveolar epithelium is delayed in the mutant, as indicated by narrowed air spaces, thickened interstitial septa, and increased glycogen content in the lungs of Stk40 (-/-) mice.", "output": {"entities": {}}, "schema": []}
{"input": "The reduction in levels of T1-alpha, SP-B, and SP-C indicates delayed maturation of both type I and type II respiratory epithelial cells in Stk40 (-/-) lungs.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, Stk40 is found to be most highly expressed in lungs of both fetal and adult mice among all organs tested.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistically, a genome-wide RNA microarray analysis reveals significantly altered expression of multiple genes known to participate in lung development.", "output": {"entities": {}}, "schema": []}
{"input": "The expression of some genes involved in lipid metabolism, immune response, and glycogen metabolism is also disrupted in the lung of Stk40 (-/-) mice.", "output": {"entities": {}}, "schema": []}
{"input": "Protein affinity purification identifies RCN2, an activator of ERK/MAPK signaling, as an STK40-associated protein.", "output": {"entities": {}}, "schema": []}
{"input": "Consistently, Stk40 deficiency attenuates the ERK/MAPK activation, and inhibition of ERK/MAPK activities reduces surfactant protein gene expression in lung epithelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, this study uncovers an important role of STK40 for lung maturation and neonatal survival.", "output": {"entities": {}}, "schema": []}
{"input": "STK40 may associate with RCN2 to activate ERK/MAPK signaling and control the expression of multiple key regulators of lung development.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary exposure of mink (Mustela vison) to fish from the upper Hudson River, New York, USA: effects on organ mass and pathology.", "output": {"entities": {}}, "schema": []}
{"input": "The authors evaluated effects of feeding ranch mink (Mustela vison) diets containing polychlorinated biphenyl (PCB)-contaminated fish from the upper Hudson River (New York, USA) on adult and offspring organ mass and pathology.", "output": {"entities": {"chemical": [{"text": "polychlorinated biphenyl", "start": 85, "end": 109}, {"text": "PCB", "start": 111, "end": 114}]}}, "schema": []}
{"input": "Diets contained 2. 5 to 20% Hudson River fish, providing 0. 72 to 6. 1 micro g Sigma PCBs/g feed (4. 8-38 pg toxic equivalents [TEQWHO 2005]/g feed).", "output": {"entities": {"chemical": [{"text": "PCBs", "start": 85, "end": 89}]}}, "schema": []}
{"input": "Absolute thyroid and adrenal gland masses were increased in adult females and 31-week-old juveniles, respectively, and absolute liver and heart masses were decreased in six-week-old kits exposed to dietary PCBs.", "output": {"entities": {"chemical": [{"text": "PCBs", "start": 206, "end": 210}]}}, "schema": []}
{"input": "Dietary concentrations of 0. 72 micro g Sigma PCBs/g feed (4. 8 pg TEQWHO 2005/g feed) and greater induced mandibular and maxillary squamous epithelial proliferation in adult animals.", "output": {"entities": {"chemical": [{"text": "PCBs", "start": 46, "end": 50}]}}, "schema": []}
{"input": "The dietary concentration of Sigma PCBs predicted to result in 20% incidence of the jaw lesion (EC20) was 2. 3 micro g Sigma PCBs/g feed (15 pg TEQWHO 2005/g feed), and the hepatic concentration was 2. 8 micro g Sigma PCBs/g liver (89 pg TEQWHO 2005/g liver).", "output": {"entities": {"chemical": [{"text": "PCBs", "start": 35, "end": 39}, {"text": "PCBs", "start": 125, "end": 129}, {"text": "PCBs", "start": 218, "end": 222}]}}, "schema": []}
{"input": "The EC20 values were greater than the dietary and hepatic concentrations predicted to result in a 20% increase in kit mortality (LC20) at six weeks of age (0. 34 micro g Sigma PCBs/g feed or 2. 6 pg TEQWHO 2005/g feed and 0. 80 micro g Sigma PCBs/g liver or 13 pg TEQWHO 2005/g liver).", "output": {"entities": {"chemical": [{"text": "PCBs", "start": 176, "end": 180}, {"text": "PCBs", "start": 242, "end": 246}]}}, "schema": []}
{"input": "However, the EC20 values reflect exposure of adults to PCBs for approximately six months, and the LC20 values reflect exposure of offspring from conception onward.", "output": {"entities": {"chemical": [{"text": "PCBs", "start": 55, "end": 59}]}}, "schema": []}
{"input": "Antigenotoxic potencies of a lichen species, Evernia prunastri.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, the genotoxic and antigenotoxic effects of methanol extract of Evernia prunastri (Huds.) Willd.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 60, "end": 68}]}}, "schema": []}
{"input": "(MEP) were studied using WP2, Ames (TA1535 and TA1537) and sister chromatid exchange (SCE) test systems.", "output": {"entities": {}}, "schema": []}
{"input": "The results obtained from bacterial test systems demonstrated that MEP has strong antimutagenic potencies on TA1537 and WP2 strains.", "output": {"entities": {}}, "schema": []}
{"input": "The highest inhibition rates for MEP on TA1537 and WP2 strains were 37. 70% and 69. 70%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "According to the SCE test system, MEP reduced the genotoxic effects of aflatoxin.", "output": {"entities": {"chemical": [{"text": "aflatoxin", "start": 71, "end": 80}]}}, "schema": []}
{"input": "In order to clarify the mechanism underlying the antigenotoxic effects of MEP, the antioxidants were determined.", "output": {"entities": {}}, "schema": []}
{"input": "Cotreatments of 5, 10 and 20 micro g/mL concentrations of MEP with aflatoxin B (1) decreased the frequencies of SCE and the malondialdehyde level and increased amount of superoxide dismutase, glutathione and glutathione peroxidase which were decreased by aflatoxin.", "output": {"entities": {"chemical": [{"text": "aflatoxin B (1)", "start": 67, "end": 82}, {"text": "malondialdehyde", "start": 124, "end": 139}, {"text": "superoxide", "start": 170, "end": 180}, {"text": "glutathione", "start": 192, "end": 203}, {"text": "glutathione", "start": 208, "end": 219}, {"text": "aflatoxin", "start": 255, "end": 264}]}}, "schema": []}
{"input": "The data obtained from this work have clearly shown that MEP has significant antigenotoxic effects which are thought to be partly due to the antioxidant activities and antioxidant inducing capability of MEP.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first report indicating the antigenotoxic activities of MEP against several mutagen agents such as N-methyl-N'-nitro-N-nitrosoguanidine, acridin and aflatoxin.", "output": {"entities": {"chemical": [{"text": "N-methyl-N'-nitro-N-nitrosoguanidine", "start": 111, "end": 147}, {"text": "acridin", "start": 149, "end": 156}, {"text": "aflatoxin", "start": 161, "end": 170}]}}, "schema": []}
{"input": "Effects of trona on the redox status of cellular system of male rats.", "output": {"entities": {"chemical": [{"text": "trona", "start": 11, "end": 16}]}}, "schema": []}
{"input": "The effects of trona (Kaun), a food additive, on the redox status of the liver and kidney of male Wistar rats were investigated.", "output": {"entities": {"chemical": [{"text": "trona", "start": 15, "end": 20}, {"text": "Kaun", "start": 22, "end": 26}]}}, "schema": []}
{"input": "A total of 60 male rats (145 +/- 2. 52 g) were grouped into four: A, B, C and D, where group A (the control) received 1 mL of distilled water orally while those in groups B, C and D (test groups) received orally, same volume of trona preparation corresponding to 100, 200 and 400 mg/kg body weight, respectively, for 28 days.", "output": {"entities": {"chemical": [{"text": "trona", "start": 228, "end": 233}]}}, "schema": []}
{"input": "Administration of trona significantly reduced (p < 0. 05) alkaline phosphatase activity in the liver and kidney with corresponding increases in the serum enzyme.", "output": {"entities": {"chemical": [{"text": "trona", "start": 18, "end": 23}]}}, "schema": []}
{"input": "Acid phosphatase activity increased significantly (p < 0. 05) in the liver and kidney with no significant change (p > 0. 05) in the activity of the serum enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and the levels of reduced glutathione, vitamins C and E in the liver and kidney of the animals decreased significantly (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 18, "end": 28}, {"text": "glutathione", "start": 50, "end": 61}, {"text": "glutathione", "start": 74, "end": 85}, {"text": "reduced glutathione", "start": 114, "end": 133}, {"text": "vitamins C and E", "start": 135, "end": 151}]}}, "schema": []}
{"input": "In contrast, malondialdehyde and lipid hydroperoxide of trona-treated animals increased significantly (p < 0. 05) in liver and kidney.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 13, "end": 28}, {"text": "hydroperoxide", "start": 39, "end": 52}, {"text": "trona", "start": 56, "end": 61}]}}, "schema": []}
{"input": "Overall, data from this study revealed that trona exhibited its toxic effect by suppressing or depleting the antioxidant systems and increasing the risk of attack by oxidants generated either from its metabolites or from other in vivo means on the rat cellular system.", "output": {"entities": {"chemical": [{"text": "trona", "start": 44, "end": 49}]}}, "schema": []}
{"input": "In vitro assessment of drug-drug interaction potential of boceprevir associated with drug metabolizing enzymes and transporters.", "output": {"entities": {"chemical": [{"text": "boceprevir", "start": 58, "end": 68}]}}, "schema": []}
{"input": "The inhibitory effect of boceprevir (BOC), an inhibitor of hepatitis C virus nonstructural protein 3 protease was evaluated in vitro against a panel of drug-metabolizing enzymes and transporters.", "output": {"entities": {"chemical": [{"text": "boceprevir", "start": 25, "end": 35}, {"text": "BOC", "start": 37, "end": 40}]}}, "schema": []}
{"input": "BOC, a known substrate for cytochrome P450 (P450) CYP3A and aldo-ketoreductases, was a reversible time-dependent inhibitor (k (inact) = 0. 12 minute (-1), K (I) = 6. 1 micro M) of CYP3A4/5 but not an inhibitor of other major P450s, nor of UDP-glucuronosyltransferases 1A1 and 2B7.", "output": {"entities": {"chemical": [{"text": "BOC", "start": 0, "end": 3}, {"text": "UDP", "start": 239, "end": 242}]}}, "schema": []}
{"input": "BOC showed weak to no inhibition of breast cancer resistance protein (BCRP), P-glycoprotein (Pgp), or multidrug resistance protein 2.", "output": {"entities": {"chemical": [{"text": "BOC", "start": 0, "end": 3}]}}, "schema": []}
{"input": "It was a moderate inhibitor of organic anion transporting polypeptide (OATP) 1B1 and 1B3, with an IC (50) of 18 and 4. 9 micro M, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In human hepatocytes, BOC inhibited CYP3A-mediated metabolism of midazolam, OATP1B-mediated hepatic uptake of pitavastatin, and both the uptake and metabolism of atorvastatin.", "output": {"entities": {"chemical": [{"text": "BOC", "start": 22, "end": 25}, {"text": "pitavastatin", "start": 110, "end": 122}, {"text": "atorvastatin", "start": 162, "end": 174}]}}, "schema": []}
{"input": "The inhibitory potency of BOC was lower than known inhibitors of CYP3A (ketoconazole), OATP1B (rifampin), or both (telaprevir).", "output": {"entities": {"chemical": [{"text": "BOC", "start": 26, "end": 29}, {"text": "ketoconazole", "start": 72, "end": 84}, {"text": "rifampin", "start": 95, "end": 103}, {"text": "telaprevir", "start": 115, "end": 125}]}}, "schema": []}
{"input": "BOC was a substrate for Pgp and BCRP but not for OATP1B1, OATP1B3, OATP2B1, organic cation transporter, or sodium/taurocholate cotransporting peptide.", "output": {"entities": {"chemical": [{"text": "BOC", "start": 0, "end": 3}, {"text": "sodium", "start": 107, "end": 113}, {"text": "taurocholate", "start": 114, "end": 126}]}}, "schema": []}
{"input": "Overall, our data suggest that BOC has the potential to cause pharmacokinetic interactions via inhibition of CYP3A and CYP3A/OATP1B interplay, with the interaction magnitude lower than those observed with known potent inhibitors.", "output": {"entities": {"chemical": [{"text": "BOC", "start": 31, "end": 34}]}}, "schema": []}
{"input": "Conversely, pharmacokinetic interactions of BOC, either as a perpetrator or victim, via other major P450s and transporters tested are less likely to be of clinical significance.", "output": {"entities": {"chemical": [{"text": "BOC", "start": 44, "end": 47}]}}, "schema": []}
{"input": "The results from clinical drug-drug interaction studies conducted thus far are generally supportive of these conclusions.", "output": {"entities": {}}, "schema": []}
{"input": "Identification and characterization of new DNA G-quadruplex binders selected by a combination of ligand and structure-based virtual screening approaches.", "output": {"entities": {}}, "schema": []}
{"input": "Nowadays, it has been demonstrated that DNA G-quadruplex arrangements are involved in cellular aging and cancer, thus boosting the discovery of selective binders for these DNA secondary structures.", "output": {"entities": {}}, "schema": []}
{"input": "By taking advantage of available structural and biological information on these structures, we performed a high throughput in silico screening of commercially available molecules databases by merging ligand-and structure-based approaches by means of docking experiments.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds selected by the virtual screening procedure were then tested for their ability to interact with the human telomeric G-quadruplex folding by circular dichroism, fluorescence spectroscopy, and photodynamic techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, our screening succeeded in retrieving a new promising scaffold for G-quadruplex binders characterized by a psoralen moiety.", "output": {"entities": {}}, "schema": []}
{"input": "Mathematical modeling of oral absorption and bioavailability of a fluoroquinolone after its precipitation in the gastrointestinal tract.", "output": {"entities": {"chemical": [{"text": "fluoroquinolone", "start": 66, "end": 81}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "The objective was to characterize the in vivo absorption and bioavailability (BA) of a low solubility, high permeability fluoroquinolone (CNV97101) that precipitates in the gastrointestinal (GI) tract by mathematical modeling approach.", "output": {"entities": {"chemical": [{"text": "fluoroquinolone", "start": 121, "end": 136}, {"text": "CNV97101", "start": 138, "end": 146}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "In situ rat intestinal perfusion studies were performed to characterize the absorption mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "The oral fraction absorbed in vivo was lower than the predicted based on the in situ intestinal permeability.", "output": {"entities": {}}, "schema": []}
{"input": "Two additional routes of administration, intraduodenal (ID) and intraperitoneal (IP) were investigated to explore if precipitation in stomach and subsequent partial re-dissolution were the causes of the lower in vivo BA.", "output": {"entities": {}}, "schema": []}
{"input": "Ex vivo precipitation studies with the stomach content of fasted rats were also carried out.", "output": {"entities": {}}, "schema": []}
{"input": "Fitting procedures were performed with NONMEM VII 1. 2.", "output": {"entities": {}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "The in situ experiments confirmed simultaneous passive and carrier-mediated absorption processes.", "output": {"entities": {}}, "schema": []}
{"input": "The ex vivo experiments confirmed precipitation in stomach lowering in vivo the oral fraction absorbed compared with the IP and ID administrations.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the almost complete availability of CNV97101 following IP administration, a first hepatic pass could be excluded.", "output": {"entities": {"chemical": [{"text": "CNV97101", "start": 43, "end": 51}]}}, "schema": []}
{"input": "The ex vivo assay results and the pharmacokinetic modeling of in vivo data supported the hypothesis of precipitation in the stomach and partial re-dissolution.", "output": {"entities": {}}, "schema": []}
{"input": "Nevertheless, other factors such as residence time in the GI may reduce the fraction absorbed even for low oral doses for which re-dissolution was almost complete in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Arundinols A-C and arundinones A and B from the plant endophytic fungus Microsphaeropsis arundinis.", "output": {"entities": {"chemical": [{"text": "Arundinols A-C", "start": 0, "end": 14}, {"text": "arundinones A and B", "start": 19, "end": 38}]}}, "schema": []}
{"input": "Three new ent-eudesmane sesquiterpenoids, arundinols A-C (1-3), one isochroman-1-one, arundinone A (4), and a polyoxygenated benzofuran-3 (2H)-one dimer, arundinone B (5), were isolated from the extract of a plant endophytic fungus, Microsphaeropsis arundinis.", "output": {"entities": {"chemical": [{"text": "ent-eudesmane sesquiterpenoids", "start": 10, "end": 40}, {"text": "arundinols A-C", "start": 42, "end": 56}, {"text": "isochroman-1-one", "start": 68, "end": 84}, {"text": "arundinone A", "start": 86, "end": 98}, {"text": "polyoxygenated benzofuran-3 (2H)-one", "start": 110, "end": 146}, {"text": "arundinone B", "start": 154, "end": 166}]}}, "schema": []}
{"input": "Their structures were elucidated primarily by NMR experiments, and 1 was confirmed by X-ray crystallography.", "output": {"entities": {}}, "schema": []}
{"input": "The absolute configuration of 1 was assigned by X-ray crystallography using Cu K alpha radiation, whereas those of the C-11 tertiary alcohols in 2 and 3 were deduced via the circular dichroism data of the in situ formed [Rh (2) (OCOCF (3)) (4)] complexes.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 76, "end": 78}, {"text": "tertiary alcohols", "start": 124, "end": 141}, {"text": "[Rh (2) (OCOCF (3)) (4)]", "start": 220, "end": 244}]}}, "schema": []}
{"input": "Arundinone B (5) represents the first dimeric benzofuran-3 (2H)-one, showing cytotoxicity against T24 and A549 cells.", "output": {"entities": {"chemical": [{"text": "Arundinone B", "start": 0, "end": 12}, {"text": "benzofuran-3 (2H)-one", "start": 46, "end": 67}]}}, "schema": []}
{"input": "The co-isolated known compound 6 showed a modest inhibitory effect against Staphylococcus aureus.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitors of the Yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 35, "end": 43}]}}, "schema": []}
{"input": "The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 22, "end": 30}]}}, "schema": []}
{"input": "Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches.", "output": {"entities": {}}, "schema": []}
{"input": "The identified inhibitors represent a diversity of chemotypes and novel pTyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that the applications of high throughput and virtual screening, when guided by structural binding mode analysis, is an effective approach for identifying potent and selective inhibitors of YopH and other protein phosphatases for rational drug design.", "output": {"entities": {}}, "schema": []}
{"input": "S-nitrosoglutathione covalently modifies cysteine residues of human carbonyl reductase 1 and affects its activity.", "output": {"entities": {"chemical": [{"text": "S-nitrosoglutathione", "start": 0, "end": 20}, {"text": "cysteine", "start": 41, "end": 49}, {"text": "carbonyl", "start": 68, "end": 76}]}}, "schema": []}
{"input": "Carbonyl reductase 1 (CBR1 or SDR21C1) is a ubiquitously-expressed, cytosolic, monomeric, and NADPH-dependent enzyme.", "output": {"entities": {"chemical": [{"text": "Carbonyl", "start": 0, "end": 8}, {"text": "NADPH", "start": 94, "end": 99}]}}, "schema": []}
{"input": "CBR1 participates in apoptosis, carcinogenesis and drug resistance, and has a protective role in oxidative stress, cancer and neurodegeneration.", "output": {"entities": {}}, "schema": []}
{"input": "S-Nitrosoglutathione (GSNO) represents the newest addition to its diverse substrate spectrum, which includes a wide range of xenobiotics and endogenous substances.", "output": {"entities": {"chemical": [{"text": "S-Nitrosoglutathione", "start": 0, "end": 20}, {"text": "GSNO", "start": 22, "end": 26}]}}, "schema": []}
{"input": "GSNO has also been shown to covalently modify and inhibit CBR1.", "output": {"entities": {"chemical": [{"text": "GSNO", "start": 0, "end": 4}]}}, "schema": []}
{"input": "The aim of the present study was to quantify and characterize the resulting modifications.", "output": {"entities": {}}, "schema": []}
{"input": "Of five candidate cysteines for modification by 2 mM GSNO (positions 26, 122, 150, 226, 227), the last four were analyzed using MALDI-TOF/TOF mass spectrometry and then quantified using the Selected Reaction Monitoring Approach on hyphenated HPLC with a triple quadrupole mass spectrometer.", "output": {"entities": {"chemical": [{"text": "GSNO", "start": 53, "end": 57}]}}, "schema": []}
{"input": "The analysis confirmed GSNO concentration-dependent S-glutathionylation of cysteines at positions 122, 150, 226, 227 which was 2-700 times higher compared to wild-type CBR1 (WT-CBR1).", "output": {"entities": {"chemical": [{"text": "GSNO", "start": 23, "end": 27}, {"text": "S-glutathionylation", "start": 52, "end": 71}, {"text": "cysteines", "start": 75, "end": 84}]}}, "schema": []}
{"input": "Moreover, a disulfide bond between neighboring Cys-226 and Cys-227 was detected.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 12, "end": 21}, {"text": "Cys", "start": 47, "end": 50}, {"text": "Cys", "start": 59, "end": 62}]}}, "schema": []}
{"input": "We suggest a role of these two cysteines as a redox-sensitive cysteine pair.", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 31, "end": 40}]}}, "schema": []}
{"input": "The catalytic properties of wild-type and enzyme modified with 2 mM GSNO were also investigated by steady state kinetic experiments with various substrates.", "output": {"entities": {"chemical": [{"text": "GSNO", "start": 68, "end": 72}]}}, "schema": []}
{"input": "GSNO treatment of CBR1 resulted in a 2-5-fold decrease in kcat with menadione, 4-benzoylpyridine, 2, 3-hexanedione, daunorubicin and 1, 4-naphthoquinone.", "output": {"entities": {"chemical": [{"text": "GSNO", "start": 0, "end": 4}, {"text": "menadione", "start": 68, "end": 77}, {"text": "4-benzoylpyridine", "start": 79, "end": 96}, {"text": "2, 3-hexanedione", "start": 98, "end": 114}, {"text": "daunorubicin", "start": 116, "end": 128}, {"text": "1, 4-naphthoquinone", "start": 133, "end": 152}]}}, "schema": []}
{"input": "In contrast, the same treatment increased kcat for substrates containing a 1, 2-diketo group in a ring structure (1, 2-naphthoquinone, 9, 10-phenanthrenequinone, isatin).", "output": {"entities": {"chemical": [{"text": "1, 2-diketo", "start": 75, "end": 86}, {"text": "1, 2-naphthoquinone", "start": 114, "end": 133}, {"text": "9, 10-phenanthrenequinone", "start": 135, "end": 160}, {"text": "isatin", "start": 162, "end": 168}]}}, "schema": []}
{"input": "Except for 9, 10-phenanthrenequinone, all changes in kcat were at least in part compensated for by a similar change in Km, overall yielding no drastic changes in catalytic efficiency.", "output": {"entities": {"chemical": [{"text": "9, 10-phenanthrenequinone", "start": 11, "end": 36}]}}, "schema": []}
{"input": "The findings indicate that GSNO-induced covalent modification of cysteine residues affects the kinetic mechanism of CBR1 both in terms of substrate binding and turnover rate, probably by covalent modification of Cys-226 and/or Cys-227.", "output": {"entities": {"chemical": [{"text": "GSNO", "start": 27, "end": 31}, {"text": "cysteine", "start": 65, "end": 73}, {"text": "Cys", "start": 212, "end": 215}, {"text": "Cys", "start": 227, "end": 230}]}}, "schema": []}
{"input": "Daily sperm production: application in studies of prenatal exposure to nanoparticles in mice.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the influence of maternal airway exposure to nanoparticulate titanium dioxide (TiO2, UV-Titan) and carbon black (CB, Printex90), on male reproductive function in the two following generations.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 77, "end": 93}, {"text": "TiO2", "start": 95, "end": 99}, {"text": "carbon black", "start": 115, "end": 127}, {"text": "Printex90", "start": 133, "end": 142}]}}, "schema": []}
{"input": "Time-mated C57BL/6J mice were exposed by inhalation to UV-Titan, or by intratracheal instillation with Printex90.", "output": {"entities": {"chemical": [{"text": "Printex90", "start": 103, "end": 112}]}}, "schema": []}
{"input": "Body and testicle weight, sperm content per g testicular parenchyma and daily sperm production (DSP) were assessed.", "output": {"entities": {}}, "schema": []}
{"input": "The protocol for assessment of DSP was optimized for application in mice (C57BL/6J) and the influence of different parameters was studied.", "output": {"entities": {}}, "schema": []}
{"input": "Maternal particulate exposure did not affect DSP statistically significantly in the F1 generation, although TiO2 tended to reduce sperm counts.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 108, "end": 112}]}}, "schema": []}
{"input": "Overall, time-to-first F2 litter increased with decreasing sperm production.", "output": {"entities": {}}, "schema": []}
{"input": "There was no effect on sperm production in the F2 generation originating after TiO2 exposure.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 79, "end": 83}]}}, "schema": []}
{"input": "F2 offspring, whose fathers were prenatally exposed to Printex90, showed lowered sperm production.", "output": {"entities": {"chemical": [{"text": "Printex90", "start": 55, "end": 64}]}}, "schema": []}
{"input": "Furthermore, we report statistically significant differences in sperm production between mouse strains.", "output": {"entities": {}}, "schema": []}
{"input": "SKF83959 is a potent allosteric modulator of sigma-1 receptor.", "output": {"entities": {"chemical": [{"text": "SKF83959", "start": 0, "end": 8}]}}, "schema": []}
{"input": "SKF83959 (3-methyl-6-chloro-7, 8-hydroxy-1-[3-methylphenyl]-2, 3, 4, 5-tetrahydro-1H-3-benzazepine), an atypical dopamine receptor-1 (D (1) receptor) agonist, has shown many D (1) receptor-independent effects, such as neuroprotection, blockade of Na (+) channel, and promotion of spontaneous glutamate release, which resemble the effects of the sigma-1 receptor activation.", "output": {"entities": {"chemical": [{"text": "SKF83959", "start": 0, "end": 8}, {"text": "3-methyl-6-chloro-7, 8-hydroxy-1-[3-methylphenyl]-2, 3, 4, 5-tetrahydro-1H-3-benzazepine", "start": 10, "end": 98}, {"text": "dopamine", "start": 113, "end": 121}, {"text": "Na (+)", "start": 247, "end": 253}, {"text": "glutamate", "start": 292, "end": 301}]}}, "schema": []}
{"input": "In the present work, we explored the potential modulation of SKF83959 on the sigma-1 receptor.", "output": {"entities": {"chemical": [{"text": "SKF83959", "start": 61, "end": 69}]}}, "schema": []}
{"input": "The results indicated that SKF83959 dramatically promoted the binding of (3) H (+)-pentazocine (a selective sigma-1 receptor agonist) to the sigma-1 receptor in brain and liver tissues but produced no effect on (3) H-progesterone binding (a sigma-1 receptor antagonist).", "output": {"entities": {"chemical": [{"text": "SKF83959", "start": 27, "end": 35}, {"text": "(3) H (+)-pentazocine", "start": 73, "end": 94}, {"text": "(3) H-progesterone", "start": 211, "end": 229}]}}, "schema": []}
{"input": "The saturation assay and the dissociation kinetics assay confirmed the allosteric effect.", "output": {"entities": {}}, "schema": []}
{"input": "We further demonstrated that the SKF83959 analogs, such as SCH22390 [(R)-(1)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrochloride] and SKF38393 [(+/-)-1-phenyl-2, 3, 4, 5-tetrahydro-(1H)-3-benzazepine-7, 8-diol hydrobromide], also showed the similar allosteric effect on the sigma-1 receptor in the liver tissue but not in the brain tissue.", "output": {"entities": {"chemical": [{"text": "SKF83959", "start": 33, "end": 41}, {"text": "SCH22390", "start": 59, "end": 67}, {"text": "(R)-(1)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrochloride", "start": 69, "end": 166}, {"text": "SKF38393", "start": 172, "end": 180}, {"text": "(+/-)-1-phenyl-2, 3, 4, 5-tetrahydro-(1H)-3-benzazepine-7, 8-diol hydrobromide", "start": 182, "end": 260}]}}, "schema": []}
{"input": "Moreover, all three tested chemicals elicited no significant effect on (3) H-1, 3-di (2-tolyl)-guanidine ((3) H-DTG) binding to the sigma-2 receptor.", "output": {"entities": {"chemical": [{"text": "(3) H-1, 3-di (2-tolyl)-guanidine", "start": 71, "end": 104}, {"text": "(3) H-DTG", "start": 106, "end": 115}]}}, "schema": []}
{"input": "The present data uncovered a new role of SKF83959 and its analogs on the sigma-1 receptor, which, in turn, may reveal the underlying mechanism for the D (1) receptor-independent effect of the drug.", "output": {"entities": {"chemical": [{"text": "SKF83959", "start": 41, "end": 49}]}}, "schema": []}
{"input": "Direct transcriptional regulation of human hepatic cytochrome P450 3A4 (CYP3A4) by peroxisome proliferator-activated receptor alpha (PPAR alpha).", "output": {"entities": {}}, "schema": []}
{"input": "The nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha is known primarily as a regulator of fatty acid metabolism, energy balance, and inflammation, but evidence suggests a wider role in regulating the biotransformation of drugs and other lipophilic chemicals.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 114, "end": 124}]}}, "schema": []}
{"input": "We investigated whether PPAR alpha directly regulates the transcription of cytochrome P450 3A4, the major human drug-metabolizing enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Using chromatin immunoprecipitation in human primary hepatocytes as well as electrophoretic mobility shift and luciferase reporter-gene assays, we identified three functional PPAR alpha-binding regions (PBR-I,-II, and-III) within ~ 12 kb of the CYP3A4 upstream sequence.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, a humanized CYP3A4/3A7 mouse model showed in vivo induction of CYP3A4 mRNA and protein by [4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio] acetic acid (WY14, 643) in liver but not in intestine, whereas hepatic occupancy of PBRs by PPAR alpha was ligand independent.", "output": {"entities": {"chemical": [{"text": "4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio] acetic acid", "start": 104, "end": 161}, {"text": "WY14, 643", "start": 163, "end": 172}]}}, "schema": []}
{"input": "Using lentiviral gene knock-down and treatment with WY14, 643 in primary human hepatocytes, PPAR alpha was further shown to affect the expression of a distinct set of CYPs, including 1A1, 1A2, 2B6, 2C8, 3A4, and 7A1, but not 2C9, 2C19, 2D6, or 2E1.", "output": {"entities": {"chemical": [{"text": "WY14, 643", "start": 52, "end": 61}]}}, "schema": []}
{"input": "Interestingly, the common phospholipid 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16: 0/18: 1-PC), previously proposed to reflect nutritional status and shown to be a specific endogenous ligand of PPAR alpha, induced CYP3A4 (up to 4-fold) and other biotransformation genes in hepatocytes with similar selectivity and potency as WY14, 643.", "output": {"entities": {"chemical": [{"text": "1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine", "start": 39, "end": 88}, {"text": "WY14, 643", "start": 336, "end": 345}]}}, "schema": []}
{"input": "These data establish PPAR alpha as a direct transcriptional regulator of hepatic CYP3A4.", "output": {"entities": {}}, "schema": []}
{"input": "This finding warrants investigation of both known and newly developed PPAR alpha-targeted drugs for their drug-drug interaction potential.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, our data suggest that nutritional status can influence drug biotransformation capacity via endogenous phospholipid signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Polymeric triamcinolone acetonide nanoparticles as a new alternative in the treatment of uveitis: In vitro and in vivo studies.", "output": {"entities": {"chemical": [{"text": "Polymeric triamcinolone acetonide", "start": 0, "end": 33}]}}, "schema": []}
{"input": "The purpose of this work was to improve the efficacy of triamcinolone acetonide (TA) in the treatment of endotoxin-induced uveitis (EIU) using a polymeric nanoparticulate drug delivery system.", "output": {"entities": {"chemical": [{"text": "triamcinolone acetonide", "start": 56, "end": 79}]}}, "schema": []}
{"input": "Poly (d, l-lactide-co-glycolide) (PLGA) nanoparticles were prepared using a modified emulsification/solvent diffusion method.", "output": {"entities": {"chemical": [{"text": "Poly (d, l-lactide-co-glycolide)", "start": 0, "end": 32}, {"text": "PLGA", "start": 34, "end": 38}]}}, "schema": []}
{"input": "Processing factors affecting loading and size were also studied.", "output": {"entities": {}}, "schema": []}
{"input": "After physicochemical studies including in vitro release, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy, in vivo studies were conducted using nanoparticles sized 195nm with 3. 16% drug loading.", "output": {"entities": {}}, "schema": []}
{"input": "Inflammatory factors such as flare, cell, and fibrin were studied in rabbit' s eye over 96h period, using laser flare meter and slit lamp examination.", "output": {"entities": {}}, "schema": []}
{"input": "Inflammatory mediators such as NO, PGE2, cell, and protein were measured quantitatively 36h after intravitreal injection of endotoxin in aqueous humor, and the therapeutic effects were compared in different groups.", "output": {"entities": {"chemical": [{"text": "NO", "start": 31, "end": 33}, {"text": "PGE2", "start": 35, "end": 39}]}}, "schema": []}
{"input": "Results indicated statistically significant differences between the effect of nanoparticles in the treatment of EIU compared to microparticles of TA and prednisolone acetate (PA).", "output": {"entities": {"chemical": [{"text": "prednisolone acetate", "start": 153, "end": 173}]}}, "schema": []}
{"input": "There were no significant differences between the effects of TA injection and TA nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, sustain release biodegradable TA nanoparticles are potential new topical treatment options which can provide better patient compliance.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of A and B-site cations on surface exchange coefficient for ABO3 perovskite materials.", "output": {"entities": {"chemical": [{"text": "perovskite", "start": 72, "end": 82}]}}, "schema": []}
{"input": "A novel approach, called isothermal isotope exchange (IIE), was applied to varying A-and B-site lanthanum manganites, ferrites, and cobaltites in the perovskite crystal structure in order to extract accurate surface exchange coefficients (k *).", "output": {"entities": {"chemical": [{"text": "lanthanum manganites", "start": 96, "end": 116}, {"text": "ferrites", "start": 118, "end": 126}, {"text": "cobaltites", "start": 132, "end": 142}, {"text": "perovskite", "start": 150, "end": 160}]}}, "schema": []}
{"input": "Pure electronic conductors revealed temperature dependent isotope exchange, while for mixed ionic and electronic conductors (MIEC) the extent of exchange was independent of temperature.", "output": {"entities": {}}, "schema": []}
{"input": "MIEC materials have higher k * values than pure electronic conductors in the temperature range from 500-850 degrees C, demonstrating the importance of both electronic species and oxygen vacancies being present for surface exchange.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 179, "end": 185}]}}, "schema": []}
{"input": "Strontium doped perovskites exhibited opposite temperature dependencies to parent materials.", "output": {"entities": {"chemical": [{"text": "Strontium doped perovskites", "start": 0, "end": 27}]}}, "schema": []}
{"input": "Some perovskites exhibited an apparent negative activation energy for k *, the behavior of which is explained by a precursor-mediated mechanism for dissociative adsorption.", "output": {"entities": {"chemical": [{"text": "perovskites", "start": 5, "end": 16}]}}, "schema": []}
{"input": "The results have significant implications for the improvement of the oxygen reduction reaction for fuel cells, metal-air batteries, and numerous other energy technologies.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 69, "end": 75}]}}, "schema": []}
{"input": "Dissection of pilus tip assembly by the FimD usher monomer.", "output": {"entities": {}}, "schema": []}
{"input": "Type 1 pili are representative of a class of bacterial surface structures assembled by the conserved chaperone/usher pathway and used by uropathogenic Escherichia coli to attach to bladder cells during infection.", "output": {"entities": {}}, "schema": []}
{"input": "The outer membrane assembly platform-the usher-is critical for the formation of pili, catalysing the polymerisation of pilus subunits and enabling the secretion of the nascent pilus.", "output": {"entities": {}}, "schema": []}
{"input": "Despite extensive structural characterisation of the usher, a number of questions about its mechanism remain, notably its oligomerisation state, and how it orchestrates the ordered assembly of pilus subunits.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate here that the FimD usher is able to catalyse in vitro pilus assembly effectively in its monomeric form.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, by establishing the kinetics of usher-catalysed reactions between various pilus subunits, we establish a complete kinetic model of tip fibrillum assembly, able to account for the order of subunits in native type 1 pili.", "output": {"entities": {}}, "schema": []}
{"input": "A new scheme for significant enhancement of the second order nonlinear optical response from molecules to ordered aggregates.", "output": {"entities": {}}, "schema": []}
{"input": "How to achieve maximum nonlinear optical (NLO) properties from the molecular to the macro block is very crucial to the development of nonlinear optical materials, which is the impetus of the present work.", "output": {"entities": {}}, "schema": []}
{"input": "Buckybowls present large first hyperpolarizability ascribed to noncentrosymmetric charge distribution due to the curved shape of the system.", "output": {"entities": {}}, "schema": []}
{"input": "The role of their packing pattern in maximizing the NLO response of buckybowl aggregates is investigated.", "output": {"entities": {}}, "schema": []}
{"input": "In (corannulene) (10) and (sumanene) (10) aggregates, the first order hyperpolarizabilities (beta (0)) per molecule are enhanced 5. 59 and 6. 21 times with respect to a single entity respectively.", "output": {"entities": {"chemical": [{"text": "corannulene", "start": 4, "end": 15}, {"text": "sumanene", "start": 27, "end": 35}]}}, "schema": []}
{"input": "For a larger buckybowl, C (36) H (12), the beta (0) value per molecule of its pentamer reaches 191. 4 x 10 (-30) esu which is much higher than conventional dipolar or octupolar NLO chromophores ones.", "output": {"entities": {"chemical": [{"text": "C (36) H (12)", "start": 24, "end": 37}]}}, "schema": []}
{"input": "The cohesive coupling among electric dipoles in packing of buckybowls is responsible for significant enhancement of the nonlinear optical response of the aggregates, which could pave the way for designing large 2nd order NLO materials with a good balance of nonlinearity, transparency, and stability.", "output": {"entities": {}}, "schema": []}
{"input": "Endocrine disrupting effects of ochratoxin A at the level of nuclear receptor activation and steroidogenesis.", "output": {"entities": {"chemical": [{"text": "ochratoxin A", "start": 32, "end": 44}]}}, "schema": []}
{"input": "Ochratoxin A (OTA) is a mycotoxin and extrolite of fungi which has been reported in a range of foods.", "output": {"entities": {"chemical": [{"text": "Ochratoxin A", "start": 0, "end": 12}, {"text": "OTA", "start": 14, "end": 17}]}}, "schema": []}
{"input": "This study uses mammalian reporter gene assays (RGAs) with natural steroid receptors and the H295R steroidogenesis assay to assess the endocrine disrupting activity of OTA.", "output": {"entities": {"chemical": [{"text": "OTA", "start": 168, "end": 171}]}}, "schema": []}
{"input": "At the receptor level, OTA (within a concentration range of 0. 25-2500 ng/ml) did not induce an agonistic response in an oestrogen, androgen, progestagen or glucocorticoid RGA.", "output": {"entities": {"chemical": [{"text": "OTA", "start": 23, "end": 26}, {"text": "oestrogen", "start": 121, "end": 130}, {"text": "androgen", "start": 132, "end": 140}, {"text": "progestagen", "start": 142, "end": 153}]}}, "schema": []}
{"input": "An antagonistic effect was observed in all of the RGAs at the highest concentration tested (2500 ng/ml).", "output": {"entities": {}}, "schema": []}
{"input": "However, while there was no significant cytotoxic effect observed in the MTT (thiazolyl blue tetrazolium bromide) cell viability assay at this concentration, there was a corresponding change in cell morphology which may be related to the resulting antagonistic effect.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 73, "end": 76}, {"text": "thiazolyl blue tetrazolium bromide", "start": 78, "end": 112}]}}, "schema": []}
{"input": "At the hormone production level, H295R cells were used as a steroidogenesis model and exposed to OTA (within a concentration range of 0. 1-1000 ng/ml).", "output": {"entities": {}}, "schema": []}
{"input": "Treatment of the cells with 1000 ng/ml OTA increased the production of estradiol (117 +/- 14 ng/ml) over 3 times that of the solvent control (36 +/- 9 pg/ml).", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 71, "end": 80}]}}, "schema": []}
{"input": "Western blotting confirmed an increase in aromatase protein.", "output": {"entities": {}}, "schema": []}
{"input": "Overall the results indicate that OTA does not appear to interact with steroid receptors but has the potential to cause endocrine disruption by interfering with steroidogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first study identifying the effect OTA may have on production of the steroid hormone estradiol.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 81, "end": 88}, {"text": "estradiol", "start": 97, "end": 106}]}}, "schema": []}
{"input": "Comparison of tolerance to morphine-induced respiratory and analgesic effects in mice.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 27, "end": 35}]}}, "schema": []}
{"input": "Morphine is responsible for severe poisonings in chronically treated patients.", "output": {"entities": {"chemical": [{"text": "Morphine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "We hypothesize that toxicity could be related to the development of weaker tolerance for morphine-induced deleterious respiratory effects in comparison to analgesic effects.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Our objectives were to compare tolerance to both effects in mice and investigate possible mechanisms for such possible differences.", "output": {"entities": {}}, "schema": []}
{"input": "Tolerance to morphine-induced analgesia and respiratory effects was assessed using hot plate response latencies and plethysmography, respectively.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Mechanisms of tolerance were investigated using binding studies to mu-opioid receptors (MOR) and adenylate cyclase (AC) activity measurement in homogenates of cell membranes from the periaqueductal gray region (PAG) and brainstem.", "output": {"entities": {}}, "schema": []}
{"input": "Morphine (2. 5 mg/kg) was responsible for analgesia with significant increase in inspiratory time.", "output": {"entities": {"chemical": [{"text": "Morphine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Acute tolerance to analgesia (p < 0. 01) and effects on respiratory frequency (p < 0. 05) was observed in mice pre-treated with 100 mg/kg morphine in comparison to saline.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 138, "end": 146}]}}, "schema": []}
{"input": "Following repetitive administration (2. 5 mg/kg/day during 10 days), we observed a 13-fold increase in the effective dose-50% (ED 5 0) of morphine-induced analgesia in comparison to a 2-or 4-fold increase in the ED 5 0 of its related increase in inspiratory time determined in air and 4% CO 2, respectively.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 138, "end": 146}, {"text": "CO 2", "start": 288, "end": 292}]}}, "schema": []}
{"input": "No significant alteration in MOR expression was observed in either PAG or brainstem following repeated morphine administration.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 103, "end": 111}]}}, "schema": []}
{"input": "However, in PAG, in contrast to brainstem, superactivation of AC was observed in morphine-treated mice in comparison to controls (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "morphine", "start": 81, "end": 89}]}}, "schema": []}
{"input": "In conclusion, tolerance to morphine-induced respiratory effects is much more limited than tolerance to its analgesic effects in repeatedly morphine-treated mice.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 28, "end": 36}, {"text": "morphine", "start": 140, "end": 148}]}}, "schema": []}
{"input": "The difference in morphine-induced AC activation between the brainstem and the PAG contributes to the observed difference in tolerance between both morphine effects.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 18, "end": 26}, {"text": "morphine", "start": 148, "end": 156}]}}, "schema": []}
{"input": "Membrane-initiated estradiol signaling in immortalized hypothalamic N-38 neurons.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 19, "end": 28}]}}, "schema": []}
{"input": "Regulation of sexual reproduction by estradiol involves the activation of estrogen receptors (ERs) in the hypothalamus.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 37, "end": 46}, {"text": "estrogen", "start": 74, "end": 82}]}}, "schema": []}
{"input": "Of the two classical ERs involved in reproduction, ER alpha appears to be the critical isoform.", "output": {"entities": {}}, "schema": []}
{"input": "The role of ER alpha in reproduction has been found to involve a nuclear ER alpha that induces a genomic mechanism of action.", "output": {"entities": {}}, "schema": []}
{"input": "More recently, a plasma membrane ER alpha has been shown to trigger signaling pathways involved in reproduction.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanisms underlying membrane-initiated estradiol signaling are emerging, including evidence that activation of plasma membrane ER alpha involves receptor trafficking.", "output": {"entities": {}}, "schema": []}
{"input": "The present study examined the insertion of ER alpha into the plasma membrane of N-38 neurons, an immortalized murine hypothalamic cell line.", "output": {"entities": {}}, "schema": []}
{"input": "We identified, using western blotting and PCR that N-38 neurons express full-length 66kDa ER alpha and a 52kDa ER alpha spliced variant missing the fourth exon-ER alpha Delta 4.", "output": {"entities": {}}, "schema": []}
{"input": "Using surface biotinylation, we observed that treatment of N-38 neurons with estradiol or with a membrane impermeant estradiol elevated plasma membrane ER alpha protein levels, indicating that membrane signaling increased receptor insertion into the cell membrane.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 77, "end": 86}, {"text": "estradiol", "start": 117, "end": 126}]}}, "schema": []}
{"input": "Insertion of ER alpha was blocked by the ER antagonist ICI 182, 780 or with the protein kinase C (PKC) pathway inhibitor bisindolylmaleimide (BIS).", "output": {"entities": {"chemical": [{"text": "ICI 182, 780", "start": 55, "end": 67}, {"text": "bisindolylmaleimide", "start": 121, "end": 140}, {"text": "BIS", "start": 142, "end": 145}]}}, "schema": []}
{"input": "Downstream membrane-initiated signaling was confirmed by estradiol activation of PKC-theta (PKC theta) and the release of intracellular calcium.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 57, "end": 66}]}}, "schema": []}
{"input": "These results indicate that membrane ER alpha levels in N-38 neurons are dynamically autoregulated by estradiol.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 102, "end": 111}]}}, "schema": []}
{"input": "The effect of remelting on the physical properties of borotellurite glass doped with manganese.", "output": {"entities": {"chemical": [{"text": "borotellurite", "start": 54, "end": 67}, {"text": "manganese", "start": 85, "end": 94}]}}, "schema": []}
{"input": "A systematic set of borotellurite glasses doped with manganese (1-x) [(B (2) O (3)) (0. 3) (TeO (2)) (0. 7)]-xMnO, with x = 0. 1, 0. 2, 0. 3 and 0. 4 mol%, were successfully synthesized by using a conventional melt and quench-casting technique.", "output": {"entities": {"chemical": [{"text": "borotellurite", "start": 20, "end": 33}, {"text": "manganese (1-x) [(B (2) O (3)) (0. 3) (TeO (2)) (0. 7)]-xMnO", "start": 53, "end": 113}]}}, "schema": []}
{"input": "In this study, the remelting effect of the glass samples on their microstructure was investigated through density measurement and FT-IR spectra and evaluated by XRD techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Initial experimental results from XRD evaluation show that there are two distinct phases of glassy and crystallite microstructure due to the existence of peaks in the sample.", "output": {"entities": {}}, "schema": []}
{"input": "The different physical behaviors of the studied glasses were closely related to the concentration of manganese in each phase.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 101, "end": 110}]}}, "schema": []}
{"input": "FTIR spectra revealed that the addition of manganese oxide contributes the transformation of TeO (4) trigonal bipyramids with bridging oxygen (BO) to TeO (3) trigonal pyramids with non-bridging oxygen (NBO).", "output": {"entities": {"chemical": [{"text": "manganese oxide", "start": 43, "end": 58}, {"text": "TeO (4)", "start": 93, "end": 100}, {"text": "oxygen", "start": 135, "end": 141}, {"text": "TeO (3)", "start": 150, "end": 157}, {"text": "oxygen", "start": 194, "end": 200}]}}, "schema": []}
{"input": "Signalling Pathways that Inhibit the Capacity of Precursor Cells for Myelin Repair.", "output": {"entities": {}}, "schema": []}
{"input": "In demyelinating disorders such as Multiple Sclerosis (MS), targets of injury are myelin and oligodendrocytes, leading to severe neurological dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Regenerative therapies aimed at promoting oligodendrocyte maturation and remyelination are promising strategies for treatment in demyelinating disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Endogenous precursor cells or exogenous transplanted cells are potential sources for remyelinating oligodendrocytes in the central nervous system (CNS).", "output": {"entities": {}}, "schema": []}
{"input": "Several signalling pathways have been implicated in regulating the capacity of these cell populations for myelin repair.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review neural precursor cells and oligodendrocyte progenitor cells as potential sources for remyelinating oligodendrocytes and evidence for the functional role of key signalling pathways in inhibiting regeneration from these precursor cell populations.", "output": {"entities": {}}, "schema": []}
{"input": "Liver transplantation and cell therapies for inborn errors of metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "Liver transplantation is now very successful with > 85% long term survival into adult life.", "output": {"entities": {}}, "schema": []}
{"input": "When considering the impact of liver transplantation for metabolic disease two independent factors need to be considered; whether or not the defect causes liver disease and whether or not it is confined to the liver.", "output": {"entities": {}}, "schema": []}
{"input": "When considering transplantation many factors need to be considered including the local success of transplantation, the impact of the metabolic disease on the patient and family and the potential for future therapeutic developments.", "output": {"entities": {}}, "schema": []}
{"input": "Where transplantation is undertaken for a liver based defect there is a lifelong complete correction of the defect.", "output": {"entities": {}}, "schema": []}
{"input": "Where there is a residual extrahepatic defect this will have an impact on the outcome of liver transplantation and the severity of this defect must be considered as part of the transplant assessment process.", "output": {"entities": {}}, "schema": []}
{"input": "Access to a multi-disciplinary team with expertise in metabolic disease, liver disease and other relevant organ based specialists is crucial.", "output": {"entities": {}}, "schema": []}
{"input": "Most children will receive transplantation from cadaveric donor but living related transplantation from a heterozygote parent is usually safe and effective.", "output": {"entities": {}}, "schema": []}
{"input": "Auxiliary liver transplantation has a small but useful role where partial correction of the defect is helpful and there is a future prospect of gene therapy.", "output": {"entities": {}}, "schema": []}
{"input": "The first-generation of hepatocyte transplants have shown proof of principle but to date have had a rather modest and temporary metabolic effect.", "output": {"entities": {}}, "schema": []}
{"input": "Stem cells may have the potential to produce a more sustained and significant metabolic correction, but must be shown to be effective in controlled trials.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of Wine Polyphenol Resveratrol on the Contractions Elicited Electrically or by Norepinephrine in the Rat Portal Vein.", "output": {"entities": {"chemical": [{"text": "Polyphenol Resveratrol", "start": 15, "end": 37}, {"text": "Norepinephrine", "start": 86, "end": 100}]}}, "schema": []}
{"input": "We investigated the effects of resveratrol on rat portal vein (RPV) contractility without endothelium.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 31, "end": 42}]}}, "schema": []}
{"input": "Contractions were produced by electrical field stimulation of perivascular nerves (EFS), norepinephrine (NE), adenosine 5'-triphosphate (ATP), high K (+) solution and by calcium chloride (CaCl (2)) in Ca (2 +)-free and high K (+), Ca (2 +)-free solution.", "output": {"entities": {"chemical": [{"text": "norepinephrine", "start": 89, "end": 103}, {"text": "adenosine 5'-triphosphate", "start": 110, "end": 135}, {"text": "ATP", "start": 137, "end": 140}, {"text": "K (+)", "start": 148, "end": 153}, {"text": "calcium chloride", "start": 170, "end": 186}, {"text": "CaCl (2)", "start": 188, "end": 196}, {"text": "Ca (2 +)", "start": 201, "end": 209}, {"text": "K (+)", "start": 224, "end": 229}, {"text": "Ca (2 +)", "start": 231, "end": 239}]}}, "schema": []}
{"input": "The EFS-evoked contractions were more sensitive to resveratrol and to NS1619-selective openers of big calcium-sensitive (BK (Ca)) channels, than NE-evoked contractions.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 51, "end": 62}, {"text": "NS1619", "start": 70, "end": 76}, {"text": "calcium", "start": 102, "end": 109}, {"text": "Ca", "start": 125, "end": 127}]}}, "schema": []}
{"input": "Effects of resveratrol on the ATP-evoked contractions were weak.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 11, "end": 22}, {"text": "ATP", "start": 30, "end": 33}]}}, "schema": []}
{"input": "Blockers of BK (Ca) channels partly inhibited the effect of resveratrol only in EFS-contracted preparations.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 16, "end": 18}, {"text": "resveratrol", "start": 60, "end": 71}]}}, "schema": []}
{"input": "Western blotting showed that RPV expressed K (Ca) 1. 1 protein.", "output": {"entities": {"chemical": [{"text": "K", "start": 43, "end": 44}, {"text": "Ca", "start": 46, "end": 48}]}}, "schema": []}
{"input": "Inhibitors of ATP-and voltage-sensitive K (+) channels did not modify the effects of resveratrol.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 14, "end": 17}, {"text": "K (+)", "start": 40, "end": 45}, {"text": "resveratrol", "start": 85, "end": 96}]}}, "schema": []}
{"input": "None of the antagonists of K (+) channels affected the resveratrol inhibition of NE-evoked contractions and effect of high concentrations of resveratrol on the EFS-evoked contractions.", "output": {"entities": {"chemical": [{"text": "K (+)", "start": 27, "end": 32}, {"text": "resveratrol", "start": 55, "end": 66}, {"text": "resveratrol", "start": 141, "end": 152}]}}, "schema": []}
{"input": "Resveratrol more potently inhibited CaCl (2) than potassium chloride contractions of RPV.", "output": {"entities": {"chemical": [{"text": "Resveratrol", "start": 0, "end": 11}, {"text": "CaCl (2)", "start": 36, "end": 44}, {"text": "potassium chloride", "start": 50, "end": 68}]}}, "schema": []}
{"input": "Thus, BK (Ca) channels partly mediate the inhibitory effect of resveratrol on the neurogenic contractions of RPV.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 10, "end": 12}, {"text": "resveratrol", "start": 63, "end": 74}]}}, "schema": []}
{"input": "The smooth muscle Ca (2 +) channels and/or Ca (2 +) mobilizing through cells might be involved in the effects of resveratrol on the contractility of RPV.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 18, "end": 26}, {"text": "Ca (2 +)", "start": 43, "end": 51}, {"text": "resveratrol", "start": 113, "end": 124}]}}, "schema": []}
{"input": "Our results are important for better understanding the impact of resveratrol on the portal circulation.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 65, "end": 76}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "The antinociceptive effect of milnacipran in the monosodium iodoacetate model of osteoarthritis pain and its relation to changes in descending inhibition.", "output": {"entities": {"chemical": [{"text": "milnacipran", "start": 30, "end": 41}, {"text": "monosodium iodoacetate", "start": 49, "end": 71}]}}, "schema": []}
{"input": "Osteoarthritis (OA) is a chronic joint disorder whose principal symptom is chronic pain.", "output": {"entities": {}}, "schema": []}
{"input": "Current analgesics are inadequate and the mechanisms contributing to this pain are poorly understood but likely to include both local joint changes and central consequences.", "output": {"entities": {}}, "schema": []}
{"input": "These studies used monoamine receptor agents combined with behavioral studies and single-unit dorsal horn recordings to examine whether descending noradrenergic and serotonergic inhibitions are altered in the monosodium iodoacetate model of OA pain, and whether increasing these inhibitions with the serotonin/noradrenaline reuptake inhibitor milnacipran can attenuate the attendant hypersensitivity.", "output": {"entities": {"chemical": [{"text": "monoamine", "start": 19, "end": 28}, {"text": "monosodium iodoacetate", "start": 209, "end": 231}, {"text": "serotonin", "start": 300, "end": 309}, {"text": "noradrenaline", "start": 310, "end": 323}, {"text": "milnacipran", "start": 343, "end": 354}]}}, "schema": []}
{"input": "Early and late in the course of this model, milnacipran (s. c.) reduced behavioral hypersensitivity, and inhibited evoked responses from sensitized dorsal horn neurons.", "output": {"entities": {"chemical": [{"text": "milnacipran", "start": 44, "end": 55}]}}, "schema": []}
{"input": "In na i ve animals and the early, but not late, phase of the model, spinal administration of the alpha (2)-adrenoceptor antagonist atipamezole fully reversed this neuronal inhibition, whereas atipamezole administered alone revealed that endogenous noradrenergic inhibition was reduced in the late phase.", "output": {"entities": {"chemical": [{"text": "atipamezole", "start": 131, "end": 142}, {"text": "atipamezole", "start": 192, "end": 203}]}}, "schema": []}
{"input": "Blocking spinal 5-hydroxytryptamine-7 receptors with (2R)-1-[(3-hydroxyphenyl) sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine hydrochloride suggested that the effects of milnacipran in the late phase were partly mediated by these receptors, and that descending serotonergic inhibition was increased in this phase.", "output": {"entities": {"chemical": [{"text": "5-hydroxytryptamine", "start": 16, "end": 35}, {"text": "(2R)-1-[(3-hydroxyphenyl) sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine hydrochloride", "start": 53, "end": 151}, {"text": "milnacipran", "start": 182, "end": 193}]}}, "schema": []}
{"input": "An opioidergic mechanism behind the effects of milnacipran was indicated by a partial reversal of these effects with naloxone.", "output": {"entities": {"chemical": [{"text": "milnacipran", "start": 47, "end": 58}, {"text": "naloxone", "start": 117, "end": 125}]}}, "schema": []}
{"input": "These studies demonstrate antinociceptive effects for milnacipran in a model of OA pain, whose effects come via descending serotonergic and noradrenergic, as well as opioidergic, pathways.", "output": {"entities": {"chemical": [{"text": "milnacipran", "start": 54, "end": 65}]}}, "schema": []}
{"input": "Variations in the activity of these pathways over the course of this model may contribute to the presence of behavioral hypersensitivity and determine through which endogenous systems milnacipran exerts its effects.", "output": {"entities": {"chemical": [{"text": "milnacipran", "start": 184, "end": 195}]}}, "schema": []}
{"input": "Sources of mercury in a contaminated stream-implications for the timescale of recovery.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 11, "end": 18}]}}, "schema": []}
{"input": "Mercury contamination in East Fork Poplar Creek in Tennessee arises from dissolved mercury exiting a headwater industrial complex and residual mercury in the streambed and soil throughout the watershed downstream.", "output": {"entities": {"chemical": [{"text": "Mercury", "start": 0, "end": 7}, {"text": "mercury", "start": 83, "end": 90}, {"text": "mercury", "start": 143, "end": 150}]}}, "schema": []}
{"input": "The headwater inputs generate chronic base flow concentrations of total mercury of about 1, 000 ng/L, but most of the annual export of mercury from the system appears to originate farther downstream.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 72, "end": 79}, {"text": "mercury", "start": 135, "end": 142}]}}, "schema": []}
{"input": "Effective targeting of remedial efforts requires determining how long downstream sources might continue to contaminate the system following elimination of the headwater mercury inputs.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 169, "end": 176}]}}, "schema": []}
{"input": "The authors calculations suggest that (1) contaminated soils and sediments account for > 80% of the annual mercury export from the entire watershed, with most export occurring during wet weather events; (2) bank erosion and resuspension of streambed particulates are the major mercury sources maintaining high annual mercury export rates; and (3) the inventory of particle-associated mercury in the streambed was not large enough to sustain the estimated export rates for more than a few years.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 107, "end": 114}, {"text": "mercury", "start": 277, "end": 284}, {"text": "mercury", "start": 317, "end": 324}, {"text": "mercury", "start": 384, "end": 391}]}}, "schema": []}
{"input": "The authors findings imply that to prevent waterborne mercury contamination in this system from continuing for decades, remedial actions will have to control the headwater mercury source that sustains day-to-day base flow mercury concentrations and the riparian stream-bank sources that generate most of the mercury export from the system.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 54, "end": 61}, {"text": "mercury", "start": 172, "end": 179}, {"text": "mercury", "start": 222, "end": 229}, {"text": "mercury", "start": 308, "end": 315}]}}, "schema": []}
{"input": "Effect of major cations (Ca (2 +), Mg (2 +), Na (+), K (+)) and anions (SO 42-, Cl (-), NO 3-) on Ni accumulation and toxicity in aquatic plant (Lemna minor L.): implications For Ni risk assessment.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 25, "end": 33}, {"text": "Mg (2 +)", "start": 35, "end": 43}, {"text": "Na (+)", "start": 45, "end": 51}, {"text": "K (+)", "start": 53, "end": 58}, {"text": "SO 42-", "start": 72, "end": 78}, {"text": "Cl (-)", "start": 80, "end": 86}, {"text": "NO 3-", "start": 88, "end": 93}, {"text": "Ni", "start": 98, "end": 100}, {"text": "Ni", "start": 179, "end": 181}]}}, "schema": []}
{"input": "The effect of major cation activity (Ca (2 +), Mg (2 +), Na (+), K (+)) on Ni toxicity, with dose expressed as exposure (total dissolved Ni concentration NiTot) or free Ni ion activity (in solution Ni (2 +)), or as tissue residue (Ni concentration in plant tissue NiTiss) to the aquatic plant Lemna minor L. was examined.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 37, "end": 45}, {"text": "Mg (2 +)", "start": 47, "end": 55}, {"text": "Na (+)", "start": 57, "end": 63}, {"text": "K (+)", "start": 65, "end": 70}, {"text": "Ni", "start": 75, "end": 77}, {"text": "Ni", "start": 137, "end": 139}, {"text": "NiTot", "start": 154, "end": 159}, {"text": "Ni (2 +)", "start": 198, "end": 206}, {"text": "Ni", "start": 231, "end": 233}]}}, "schema": []}
{"input": "In addition, Ni accumulation kinetics was explored to provide mechanistic insight into current approaches of toxicity modeling, such as the tissue residue approach and the biotic ligand model (BLM), and the implications for plant Ni risk assessment.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 13, "end": 15}, {"text": "Ni", "start": 230, "end": 232}]}}, "schema": []}
{"input": "Major cations did not inhibit Ni accumulation via competitive inhibition as expected by the BLM framework.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 30, "end": 32}]}}, "schema": []}
{"input": "For example, Ca (2 +) and Mg (2 +) (sulfate as counter-anion) had an anticompetitive effect on Ni accumulation, suggesting that Ca or Mg forms a ternary complex with Ni-biotic ligand.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 13, "end": 21}, {"text": "Mg (2 +)", "start": 26, "end": 34}, {"text": "sulfate", "start": 36, "end": 43}, {"text": "Ni", "start": 95, "end": 97}, {"text": "Ca", "start": 128, "end": 130}, {"text": "Mg", "start": 134, "end": 136}, {"text": "Ni", "start": 166, "end": 168}]}}, "schema": []}
{"input": "The counter-anion of the added Ca (sulfate, chloride, or nitrate) affected plant response (percentage of root growth inhibition) to Ni.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 31, "end": 33}, {"text": "sulfate", "start": 35, "end": 42}, {"text": "chloride", "start": 44, "end": 52}, {"text": "nitrate", "start": 57, "end": 64}, {"text": "Ni", "start": 132, "end": 134}]}}, "schema": []}
{"input": "Generally, sulfate and chloride influenced plant response while nitrate did not, even when compared within the same range of Ca (2 +), which suggests that the anion dominated the observed plant response.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 11, "end": 18}, {"text": "chloride", "start": 23, "end": 31}, {"text": "nitrate", "start": 64, "end": 71}, {"text": "Ca (2 +)", "start": 125, "end": 133}]}}, "schema": []}
{"input": "Overall, although an effect of major cations on Ni toxicity to L. minor L. was observed at a physiological level, Ni (2 +) or NiTot alone modeled plant response, generally within a span of twofold, over a wide range of water chemistry.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 48, "end": 50}, {"text": "Ni (2 +)", "start": 114, "end": 122}]}}, "schema": []}
{"input": "Thus, consideration of major cation competition for improving Ni toxicity predictions in risk assessment for aquatic plants may not be necessary.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 62, "end": 64}]}}, "schema": []}
{"input": "The CMT4B disease-causing phosphatases Mtmr2 and Mtmr13 localize to the Schwann cell cytoplasm and endomembrane compartments, where they depend upon each other to achieve wild-type levels of protein expression.", "output": {"entities": {}}, "schema": []}
{"input": "The demyelinating peripheral neuropathy Charcot-Marie-Tooth type 4B (CMT4B) is characterized by axonal degeneration and myelin outfoldings.", "output": {"entities": {}}, "schema": []}
{"input": "CMT4B results from mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13 (CMT4B2), phosphoinositide (PI) 3-phosphatases that dephosphorylate phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns (3, 5) P2, lipids which regulate endo-lysosomal membrane traffic.", "output": {"entities": {"chemical": [{"text": "phosphatidylinositol 3-phosphate", "start": 164, "end": 196}, {"text": "PtdIns3P", "start": 198, "end": 206}, {"text": "PtdIns (3, 5) P2", "start": 212, "end": 228}]}}, "schema": []}
{"input": "The catalytically active MTMR2 and catalytically inactive MTMR13 physically associate, although the significance of this association is not well understood.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that Mtmr13 loss leads to axonal degeneration in sciatic nerves of older mice.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, CMT4B2-like myelin outfoldings are present in Mtmr13 (-/-) nerves at postnatal day 3.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, Mtmr13 (-/-) mice show both the initial dysmyelination and later degenerative pathology of CMT4B2.", "output": {"entities": {}}, "schema": []}
{"input": "Given the key role of PI 3-kinase-Akt signaling in myelination, we investigated the state of the pathway in nerves of CMT4B models.", "output": {"entities": {}}, "schema": []}
{"input": "We found that Akt activation is unaltered in Mtmr13 (-/-) and Mtmr2 (-/-) mice.", "output": {"entities": {}}, "schema": []}
{"input": "Mtmr2 and Mtmr13 are found within the Schwann cell cytoplasm, where the proteins are partially localized to punctate compartments, suggesting that Mtmr2-Mtmr13 may dephosphorylate their substrates on specific intracellular compartments.", "output": {"entities": {}}, "schema": []}
{"input": "Mtmr2-Mtmr13 substrates play essential roles in endo-lysosomal membrane traffic.", "output": {"entities": {}}, "schema": []}
{"input": "However, endosomes and lysosomes of Mtmr13 (-/-) and Mtmr2 (-/-) Schwann cells are morphologically indistinguishable from those of controls, indicating that loss of these proteins does not cause wholesale dysregulation of the endo-lysosomal system.", "output": {"entities": {}}, "schema": []}
{"input": "Notably, Mtmr2 and Mtmr13 depend upon each other to achieve wild-type levels of protein expression.", "output": {"entities": {}}, "schema": []}
{"input": "Mtmr2 stabilizes Mtmr13 on membranes, indicating that the Mtmr13 pseudophosphatase is regulated by its catalytically active binding partner.", "output": {"entities": {}}, "schema": []}
{"input": "Polar constituents composition of endemic Sideritis italica (MILL.) GREUTER et BURTER from Central Italy.", "output": {"entities": {}}, "schema": []}
{"input": "Endemic Sideritis italica (MILL.) GREUTER et BURTER (Lamiaceae) occurs mainly in Southern Italy and Sicily and has previously only been studied for the essential oil composition.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, we complete the phytochemical study of a sample of S. italica, previously analysed for its volatile constituents, occurring in the Appennino Umbro-Marchigiano (Central Italy), which is the northern border of the areal distribution of the species.", "output": {"entities": {}}, "schema": []}
{"input": "The analysis of medium polarity constituents led to the isolation of several glycosides, such as flavonoids, i. e. scutellarein derivatives; phenylethanoids, i. e. verbascoside; and iridoids, i. e. melittoside and 5-allosyloxy-aucubin, besides the diterpene siderol.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 97, "end": 107}, {"text": "scutellarein", "start": 115, "end": 127}, {"text": "phenylethanoids", "start": 141, "end": 156}, {"text": "verbascoside", "start": 164, "end": 176}, {"text": "iridoids", "start": 182, "end": 190}, {"text": "melittoside", "start": 198, "end": 209}, {"text": "5-allosyloxy-aucubin", "start": 214, "end": 234}, {"text": "siderol", "start": 258, "end": 265}]}}, "schema": []}
{"input": "The data reported have chemotaxonomic relevance, since they are in contrast with the hypothesis that in Lamiaceae the species producing iridoids do not usually have relevant essential oil production and vice versa.", "output": {"entities": {"chemical": [{"text": "iridoids", "start": 136, "end": 144}]}}, "schema": []}
{"input": "Effects of garlic fractions consumption on male reproductive functions.", "output": {"entities": {}}, "schema": []}
{"input": "Many researchers have focused on the preventive and curative effects of garlic (Allium sativum), particularly on cardiovascular diseases and cancer.", "output": {"entities": {}}, "schema": []}
{"input": "However, its impacts on the male reproductive system have not been clearly defined.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, the effect of chronic consumption of two garlic fractions was tested: one soluble in water (aqueous solution obtained by grinding and centrifugation) and the other one precipitated by ethanol (alcoholic precipitate obtained by precipitation of the aqueous solution), on different variables of male rats' reproductive functions.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 199, "end": 206}]}}, "schema": []}
{"input": "These two fractions were targeted to try to identify the nature of the active garlic compounds responsible for the different modifications observed on testicular parameters.", "output": {"entities": {}}, "schema": []}
{"input": "The observation of seminiferous tubules of rats treated with garlic fractions showed an increased number of tubules deprived of spermatozoa.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, garlic fractions induced apoptosis of testicular germ cells (TdT-mediated dUTP-X nick-end labeling [TUNEL] approach) and a decrease of serum testosterone levels and seminiferous tubule DNA concentrations.", "output": {"entities": {"chemical": [{"text": "dUTP", "start": 87, "end": 91}, {"text": "testosterone", "start": 154, "end": 166}]}}, "schema": []}
{"input": "In summary, our histological and molecular results suggest that one or several substances, soluble in water and precipitated by alcohol, impaired spermatogenesis.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 128, "end": 135}]}}, "schema": []}
{"input": "Essential oils of Thymus leucospermus Hartvig, a Greek endemic rich in phenolic monoterpenes.", "output": {"entities": {"chemical": [{"text": "phenolic monoterpenes", "start": 71, "end": 92}]}}, "schema": []}
{"input": "Thymus leucospermus Hartvig is a Greek endemic species of Section Teucrioides Jalas.", "output": {"entities": {}}, "schema": []}
{"input": "The essential oils obtained from five populations growing wild in the National Park of Northern Pindhos (NW Greece) were studied.", "output": {"entities": {}}, "schema": []}
{"input": "The oil content ranged between 1. 1 and 2. 0 mL per 100 g of dry plant weight.", "output": {"entities": {}}, "schema": []}
{"input": "The oils were particularly rich in phenolic monoterpenes: they had a high thymol (64. 7-92. 0%) or carvacrol (93. 4%) content, whereas in one of the oils considerable amount of both compounds was found (thymol 61. 6% and carvacrol 26. 4%).", "output": {"entities": {"chemical": [{"text": "phenolic monoterpenes", "start": 35, "end": 56}, {"text": "thymol", "start": 74, "end": 80}, {"text": "carvacrol", "start": 99, "end": 108}, {"text": "thymol", "start": 203, "end": 209}, {"text": "carvacrol", "start": 221, "end": 230}]}}, "schema": []}
{"input": "Our results show that T. leucospermus is a high-quality thyme species, with respect to both oil content and composition.", "output": {"entities": {}}, "schema": []}
{"input": "Systematic literature review of the effects of food and drink advertising on food and drink-related behaviour, attitudes and beliefs in adult populations.", "output": {"entities": {}}, "schema": []}
{"input": "A large body of research confirms that food advertising affects the food preferences and behaviour of children.", "output": {"entities": {}}, "schema": []}
{"input": "The impact of food advertising on adults is less clear.", "output": {"entities": {}}, "schema": []}
{"input": "We conducted a systematic review exploring the effects of advertising of food and non-alcoholic drinks (referred to as' food' throughout) on food-related behaviour, attitudes and beliefs in adult populations.", "output": {"entities": {}}, "schema": []}
{"input": "We searched seven electronic databases, grey literature sources, and references and citations of included material for experimental studies written in English investigating the effects of commercial food advertising on the food-related behaviours, attitudes and beliefs of adults aged 16 years and over.", "output": {"entities": {}}, "schema": []}
{"input": "Nine studies, rated moderate to poor quality, were included in the review; all were from developed countries and explored the impact of televised food advertising.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, the results did not show conclusively whether or not food advertising affects food-related behaviour, attitudes or beliefs in adults, but suggest that the impact varies inconsistently within subgroups, including gender, weight and existing food psychology.", "output": {"entities": {}}, "schema": []}
{"input": "The identification of a small number of relevant studies, none of which were high quality, and with substantial heterogeneity, highlights the need for further research.", "output": {"entities": {}}, "schema": []}
{"input": "Future studies investigating longer term outcomes, diverse advertising formats, and in countries with different levels of economic development will be of particular value.", "output": {"entities": {}}, "schema": []}
{"input": "Tunable morphology and mesophase formation by naphthalene-containing poly (aryl ether) dendron-based low-molecular-weight fluorescent gels.", "output": {"entities": {"chemical": [{"text": "naphthalene", "start": 46, "end": 57}, {"text": "poly (aryl ether)", "start": 69, "end": 86}]}}, "schema": []}
{"input": "Novel poly (aryl ether) dendron-based low-molecular-weight organogelaters (LMWG) containing naphthalene units at the core have been synthesized, and the self-assembly of the system has been examined in a variety of solvents and solvent mixtures.", "output": {"entities": {"chemical": [{"text": "poly (aryl ether)", "start": 6, "end": 23}, {"text": "naphthalene", "start": 92, "end": 103}]}}, "schema": []}
{"input": "The compounds readily form gels with attractive critical gel concentration values associated with gelation-induced enhanced emission (GIEE).", "output": {"entities": {}}, "schema": []}
{"input": "In addition to the remarkable properties of the previously reported anthracene and pyrene analogues (Rajamalli, P.; Prasad, E. Org. Lett. 2011, 13, 3714 and Rajamalli, P.; Prasad, E. Soft Matter2012, 8, 8896), the self-assembled systems exhibit distinctly different structure-property relationships.", "output": {"entities": {"chemical": [{"text": "anthracene", "start": 68, "end": 78}, {"text": "pyrene", "start": 83, "end": 89}]}}, "schema": []}
{"input": "Unlike the reported ones, the present system forms sheetlike morphology in nonpolar solvent mixtures, giant vesicles in polar solvent mixtures, and lamellar or hexagonal columnar phases in single solvents.", "output": {"entities": {}}, "schema": []}
{"input": "The unique properties of the self-assembled systems, which were analyzed through electron microscopic (SEM, TEM, AFM) and spectroscopic techniques (POM, fluorescence), are attributed to the replacement of anthracene/pyrene units by naphthalene units.", "output": {"entities": {"chemical": [{"text": "anthracene", "start": 205, "end": 215}, {"text": "pyrene", "start": 216, "end": 222}, {"text": "naphthalene", "start": 232, "end": 243}]}}, "schema": []}
{"input": "The present work unravels the subtle role of minute structural change in altering the properties of LMWGs based on poly (aryl ether) dendrons.", "output": {"entities": {"chemical": [{"text": "poly (aryl ether)", "start": 115, "end": 132}]}}, "schema": []}
{"input": "Mechanism of solid state amorphization of glucose upon milling.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 42, "end": 49}]}}, "schema": []}
{"input": "Crystalline alpha-glucose is known to amorphize upon milling at-15 degrees C while it remains structurally invariant upon milling at room temperature.", "output": {"entities": {"chemical": [{"text": "alpha-glucose", "start": 12, "end": 25}]}}, "schema": []}
{"input": "We have taken advantage of this behavior to compare the microstructural evolutions of the material in both conditions in order to identify the essential microstructural features which drive the amorphization process upon milling.", "output": {"entities": {}}, "schema": []}
{"input": "The investigations have been performed by differential scanning calorimetry and by powder X-ray diffraction.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that two different amorphization mechanisms occur upon milling: an amorphization at the surface of crystallites due to the mechanical shocks and a spontaneous amorphization of the crystallites as they reach a critical size, which is close to 200 A in the particular case of alpha-glucose.", "output": {"entities": {"chemical": [{"text": "alpha-glucose", "start": 295, "end": 308}]}}, "schema": []}
{"input": "Luminol as in situ light source in meso-tetraphenylporphyrin-mediated photodynamic therapy.", "output": {"entities": {"chemical": [{"text": "Luminol", "start": 0, "end": 7}, {"text": "meso-tetraphenylporphyrin", "start": 35, "end": 60}]}}, "schema": []}
{"input": "The light sources used in current photodynamic therapy are mainly lasers or light emitting diodes, which are not suitable to treat large-volume tumors and those located in the inner body.", "output": {"entities": {}}, "schema": []}
{"input": "To overcome the limitation, we propose an in situ light source to activate the photosensitizer and kill the cancer cells directly.", "output": {"entities": {}}, "schema": []}
{"input": "In the present work, we use luminol as light source and meso-tetraphenylporphyrin as the photosensitizer.", "output": {"entities": {"chemical": [{"text": "luminol", "start": 28, "end": 35}, {"text": "meso-tetraphenylporphyrin", "start": 56, "end": 81}]}}, "schema": []}
{"input": "According to the results, cells incubated with meso-tetraphenylporphyrin, subsequently triggered by luminol, decreased significantly in assays including cell viability and cytotoxicity, while the other groups showed only minor differences.", "output": {"entities": {"chemical": [{"text": "meso-tetraphenylporphyrin", "start": 47, "end": 72}, {"text": "luminol", "start": 100, "end": 107}]}}, "schema": []}
{"input": "The flow cytometric and fluorescent microscopy analysis showed similar results as well.", "output": {"entities": {}}, "schema": []}
{"input": "In the analysis of cell death pathway, cell shrinkage was noticed after photodynamic therapy treatment, which might refer to apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Briefly, we suggest that luminol is a promising light source in meso-tetraphenylporphyrin-mediated photodynamic therapy for its greater penetration depth and well matched emission wavelength.", "output": {"entities": {"chemical": [{"text": "luminol", "start": 25, "end": 32}, {"text": "meso-tetraphenylporphyrin", "start": 64, "end": 89}]}}, "schema": []}
{"input": "Usefulness of ancillary methods for diagnosis, prognosis and targeted therapy in thyroid pathology.", "output": {"entities": {}}, "schema": []}
{"input": "The development of molecular analyses for thyroid pathologies is on going.", "output": {"entities": {}}, "schema": []}
{"input": "These analyses provide new diagnostic tools with the aim of accurately distinguishing malignant and benign thyroid tumors.", "output": {"entities": {}}, "schema": []}
{"input": "They are particularly useful as most of them can be done preoperatively on thyroid fine-needle aspiration biopsy samples.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, molecular biomarkers may play a promising role since they are able to predict the prognosis of patients with thyroid tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, identification of molecular markers as well as a better understanding of thyroid carcinogenesis will help develop innovative targeted therapies, particularly in patients with metastatic iodo-resistant thyroid carcinoma.", "output": {"entities": {"chemical": [{"text": "iodo", "start": 196, "end": 200}]}}, "schema": []}
{"input": "To date, four types of somatic genetic alterations are known to hold potential interest for the diagnosis and/or prognosis of follicular cell-derived thyroid carcinomas: BRAF and RAS mutations, and RET/PTC and PAX8/PPAR gamma rearrangements.", "output": {"entities": {}}, "schema": []}
{"input": "Other recent molecular biomarkers have been investigated in thyroid oncology, in particular different microRNA signatures.", "output": {"entities": {}}, "schema": []}
{"input": "This review describes the different aspects of ancillary methods, including those bassed on molecular biology, that are of current interest for the diagnosis, prognosis and treatment of follicular cell-derived thyroid carcinomas.", "output": {"entities": {}}, "schema": []}
{"input": "Silver nanoparticles in cancer: therapeutic efficacy and toxicity.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In recent years, there has been escalating interest in the biomedical applications of nanoparticles (NPs).", "output": {"entities": {}}, "schema": []}
{"input": "In particular, silver nanoparticles (AgNPs) are increasingly being investigated as tools for novel cancer therapeutics, capitalizing on their unique properties to enhance potential therapeutic efficacy.", "output": {"entities": {"chemical": [{"text": "silver", "start": 15, "end": 21}]}}, "schema": []}
{"input": "However, questions as to are we able to contain or control the toxicity effects of AgNPs, and how much do we know about the toxicological profile of AgNPs which are commonly used in emerging nanotechnology-based applications, still remain.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, serious considerations have to be given to the hazards and risks of toxicity associated with the use of AgNPs.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on the current applications of AgNPs, their known effects and toxicity, as well as the potential of harnessing them for use in cancer therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease.", "output": {"entities": {"chemical": [{"text": "tris-tetrahydrofuran", "start": 9, "end": 29}, {"text": "GRL-0519", "start": 61, "end": 69}]}}, "schema": []}
{"input": "GRL-0519 (1) is a potent antiviral inhibitor of HIV-1 protease (PR) possessing tris-tetrahydrofuran (tris-THF) at P2.", "output": {"entities": {"chemical": [{"text": "GRL-0519", "start": 0, "end": 8}, {"text": "tris-tetrahydrofuran", "start": 79, "end": 99}, {"text": "tris-THF", "start": 101, "end": 109}]}}, "schema": []}
{"input": "The high resolution X-ray crystal structures of inhibitor 1 in complexes with single substitution mutants PR (R8Q), PR (D30N), PR (I50V), PR (I54M), and PR (V82A) were analyzed in relation to kinetic data.", "output": {"entities": {}}, "schema": []}
{"input": "The smaller valine side chain in PR (I50V) eliminated hydrophobic interactions with inhibitor and the other subunit consistent with 60-fold worse inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Asn30 in PR (D30N) showed altered interactions with neighboring residues and 18-fold worse inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations V82A and I54M showed compensating structural changes consistent with 6-7-fold lower inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Gln8 in PR (R8Q) replaced the ionic interactions of wild type Arg8 with hydrogen bond interactions without changing the inhibition significantly.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 72, "end": 80}]}}, "schema": []}
{"input": "The carbonyl oxygen of Gly48 showed two alternative conformations in all structures likely due to the snug fit of the large tris-THF group in the S2 subsite in agreement with high antiviral efficacy of 1 on resistant virus.", "output": {"entities": {"chemical": [{"text": "carbonyl oxygen", "start": 4, "end": 19}, {"text": "tris-THF", "start": 124, "end": 132}]}}, "schema": []}
{"input": "A design of experiments to optimize a new manufacturing process for high activity protein-containing submicron particles.", "output": {"entities": {}}, "schema": []}
{"input": "A novel method for the manufacture of protein/peptide-containing submicron particles was developed in an attempt to provide particles with increased activity while using high energy input technologies.", "output": {"entities": {}}, "schema": []}
{"input": "The method consists of antisolvent co-precipitation from an aqueous solution containing both an amino acid core material (e. g. D, L-valine), and either bovine serum albumin (BSA) or lysozyme (Lys) as model proteins.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 96, "end": 106}, {"text": "D, L-valine", "start": 128, "end": 139}]}}, "schema": []}
{"input": "The aqueous solution was added to the organic phase by means of a nebulizer to increase the total surface area of interaction for the precipitation process.", "output": {"entities": {}}, "schema": []}
{"input": "Sonication proved to be an effective method to produce small particle sizes while maintaining high activity of Lys.", "output": {"entities": {}}, "schema": []}
{"input": "The use of a polysorbate or sorbitan ester derivatives as stabilizers proved to be necessary to yield submicron particles.", "output": {"entities": {"chemical": [{"text": "polysorbate", "start": 13, "end": 24}, {"text": "sorbitan ester", "start": 28, "end": 42}]}}, "schema": []}
{"input": "Particles with very high yields (approximately 100%) and very high activity after manufacture (approximately 100%) could be obtained.", "output": {"entities": {}}, "schema": []}
{"input": "A particle size of 439. 0 nm, with a yield of 48. 8% and with final remaining activity of98. 7% was obtained.", "output": {"entities": {}}, "schema": []}
{"input": "By studying various factors using a design of experiments strategy (DoE) we were able to establish the critical controlling factors for this new method of manufacture.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, characterization and targeting potential of zidovudine loaded sialic acid conjugated-mannosylated poly (propyleneimine) dendrimers.", "output": {"entities": {"chemical": [{"text": "zidovudine", "start": 55, "end": 65}, {"text": "sialic acid", "start": 73, "end": 84}, {"text": "mannosylated poly (propyleneimine)", "start": 96, "end": 130}]}}, "schema": []}
{"input": "The present investigation was aimed at exploring dual targeting of anti-HIV drug, zidovudine (ZDV) via sialic acid conjugated-mannosylated poly (propyleneimine) (PPI) dendritic nano-constructs.", "output": {"entities": {"chemical": [{"text": "zidovudine", "start": 82, "end": 92}, {"text": "ZDV", "start": 94, "end": 97}, {"text": "sialic acid", "start": 103, "end": 114}, {"text": "mannosylated poly (propyleneimine)", "start": 126, "end": 160}, {"text": "PPI", "start": 162, "end": 165}]}}, "schema": []}
{"input": "Fourth generation PPI dendrimers, sialic acid conjugated PPI dendrimers (SPPI), mannose conjugated PPI dendrimers (MPPI) and dual ligand system i. e. sialic acid conjugated-mannosylated PPI dendrimers (SMPPI) were synthesized and characterized by FT-IR and (1) H NMR spectroscopies and were further confirmed by size exclusion chromatography and differential scanning calorimetry.", "output": {"entities": {"chemical": [{"text": "PPI", "start": 18, "end": 21}, {"text": "sialic acid", "start": 34, "end": 45}, {"text": "PPI", "start": 57, "end": 60}, {"text": "mannose", "start": 80, "end": 87}, {"text": "PPI", "start": 99, "end": 102}, {"text": "sialic acid", "start": 150, "end": 161}, {"text": "mannosylated PPI", "start": 173, "end": 189}, {"text": "(1) H", "start": 257, "end": 262}]}}, "schema": []}
{"input": "Various parameters like drug loading, pH dependent in vitro release, hemolytic toxicity, macrophage uptake and cytotoxicity concerning PPI, SPPI, MPPI and SMPPI dendrimers were evaluated.", "output": {"entities": {"chemical": [{"text": "PPI", "start": 135, "end": 138}]}}, "schema": []}
{"input": "ZDV loaded SMPPI, SPPI and MPPI have shown reduced hemolytic toxicity, cytotoxicity and in vitro drug release at pH 7. 4.", "output": {"entities": {"chemical": [{"text": "ZDV", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Extremely significant (P < 0. 001) increase in cellular uptake of ZDV by macrophage cells was observed in case of SMPPI as compared to PPI and free drug.", "output": {"entities": {"chemical": [{"text": "ZDV", "start": 66, "end": 69}]}}, "schema": []}
{"input": "The in vivo blood level and tissue distribution studies in albino rats also demonstrated potential of dual targeted system towards sialoadhesin and carbohydrate receptors.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 148, "end": 160}]}}, "schema": []}
{"input": "The drug concentration in lymph nodes was increased to about 28 times in case of SMPPI (1335 +/- 17. 6 ng/g) as compared to free drug (48 +/- 5. 8 ng/g) at 6th hr.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggested that such dual ligand dendritic system (SMPPI) hold potential to enhance biocompatibility and site specific delivery of antiretroviral drug, ZDV.", "output": {"entities": {"chemical": [{"text": "ZDV", "start": 163, "end": 166}]}}, "schema": []}
{"input": "Lamivudine permeability study: a comparison between PAMPA, ex vivo and in situ Single-Pass Intestinal Perfusion (SPIP) in rat jejunum.", "output": {"entities": {"chemical": [{"text": "Lamivudine", "start": 0, "end": 10}]}}, "schema": []}
{"input": "In order to reach the bloodstream and thus the target receptor, an orally-administered drug must first cross the intestinal barrier, which can occur via a paracellular, passive transcellular, or carrier-mediated uptake and/or efflux process (active or concentration gradient-driven).", "output": {"entities": {}}, "schema": []}
{"input": "Our work aimed to explore the transport mechanism of the antiretroviral lamivudine (deoxycytidine nucleoside analogue), using a three-part strategy: in vitro, an ex vivo and an in situ method, represented by PAMPA, rat jejunum patches and rat Single Pass Intestinal Perfusion (SPIP), respectively.", "output": {"entities": {"chemical": [{"text": "lamivudine", "start": 72, "end": 82}, {"text": "deoxycytidine nucleoside", "start": 84, "end": 108}]}}, "schema": []}
{"input": "The determined permeability coefficients were compared with those from a published Caco-2 and MDCK study.", "output": {"entities": {}}, "schema": []}
{"input": "Computational prediction of human jejunal permeability was explored, using various non-human permeability coefficients as descriptors.", "output": {"entities": {}}, "schema": []}
{"input": "The ex vivo technique was performed in Franz-type diffusion cells, mounted with male Wistar rat jejunum segment patches.", "output": {"entities": {}}, "schema": []}
{"input": "PAMPA was performed with an acceptor solution simulating the binding of serum proteins, an artificial membrane impregnated with egg lecithin/cholesterol and a gradient of pH between donor and acceptor solutions.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 141, "end": 152}]}}, "schema": []}
{"input": "The SPIP was conducted by proximal jejunum cannulation and drug perfusion in a constant flow rate of 0. 2 mL/min.", "output": {"entities": {}}, "schema": []}
{"input": "The outcomes of our studies showed the following predicted pattern for lamivudine effective jejunal permeability: P (eff) (exvivoA > B) > P (eff) (SPIP) > P (eff) (exvivo B > A) > P (eff) (Caco-2) =~ P (eff) (MDCK) =~ P (eff) (PAMPA), strongly suggesting that this compound has carrier-mediated uptake as its dominant transport mechanism.", "output": {"entities": {"chemical": [{"text": "lamivudine", "start": 71, "end": 81}]}}, "schema": []}
{"input": "Notwithstanding, Caco-2 cells may indicate an under-expression of uptake transporters and possibly an over-expression efflux transporters, compared to that found in the rat jejunum.", "output": {"entities": {}}, "schema": []}
{"input": "Biodegradable core-shell nanoassemblies for the delivery of docetaxel and Zn (II)-phthalocyanine inspired by combination therapy for cancer.", "output": {"entities": {"chemical": [{"text": "docetaxel", "start": 60, "end": 69}, {"text": "Zn (II)", "start": 74, "end": 81}, {"text": "phthalocyanine", "start": 82, "end": 96}]}}, "schema": []}
{"input": "Combination therapies for cancer aim to exploit either additive or synergistic effects arising from the action of two species with the final goal to maximize the therapeutic efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we develop multifunctional nanoparticles (NPs) for co-delivery of the conventional anticancer drug docetaxel (DTX) and the second generation photosensitizer zinc-phthalocyanine (ZnPc) as potential dual carrier system for the combination of chemotherapy and photodynamic therapy (PDT).", "output": {"entities": {"chemical": [{"text": "docetaxel", "start": 113, "end": 122}, {"text": "DTX", "start": 124, "end": 127}, {"text": "zinc", "start": 171, "end": 175}, {"text": "phthalocyanine", "start": 176, "end": 190}, {"text": "ZnPc", "start": 192, "end": 196}]}}, "schema": []}
{"input": "Biodegradable and amphiphilic block copolymers based on poly (epsilon-caprolactone) (PCL = B) and poly (ethylene oxide) (PEO = A), with AB and ABA architectures, were assembled in \" core-shell \" NPs and loaded with both DTX and ZnPc employing the melting/sonication method.", "output": {"entities": {"chemical": [{"text": "poly (epsilon-caprolactone)", "start": 56, "end": 83}, {"text": "PCL", "start": 85, "end": 88}, {"text": "poly (ethylene oxide)", "start": 98, "end": 119}, {"text": "PEO", "start": 121, "end": 124}, {"text": "DTX", "start": 220, "end": 223}, {"text": "ZnPc", "start": 228, "end": 232}]}}, "schema": []}
{"input": "Hydrodynamic diameters within the range 60-100nm and low polydispersity indexes were obtained.", "output": {"entities": {}}, "schema": []}
{"input": "Zeta potential was negative for all the formulations and unaffected by drug encapsulation.", "output": {"entities": {}}, "schema": []}
{"input": "Concerning drug loading ability of NPs, the entrapment efficiency was related to initial ZnPc/DTX ratio.", "output": {"entities": {"chemical": [{"text": "ZnPc", "start": 89, "end": 93}, {"text": "DTX", "start": 94, "end": 97}]}}, "schema": []}
{"input": "Steady-stationary and time-resolved emission fluorescence measurements pointed out the embedding of monomeric ZnPc in the NPs, excluding the presence of ZnPc self-supramolecular oligomers.", "output": {"entities": {"chemical": [{"text": "ZnPc", "start": 110, "end": 114}, {"text": "ZnPc", "start": 153, "end": 157}]}}, "schema": []}
{"input": "The release of DTX was biphasic whereas ZnPc remained mainly associated with NPs.", "output": {"entities": {"chemical": [{"text": "DTX", "start": 15, "end": 18}, {"text": "ZnPc", "start": 40, "end": 44}]}}, "schema": []}
{"input": "Singlet oxygen generation was observed when ZnPc-loaded NPs were irradiated at 610nm within a 45min time range, despite that ZnPc was not released in the medium.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 8, "end": 14}, {"text": "ZnPc", "start": 44, "end": 48}, {"text": "ZnPc", "start": 125, "end": 129}]}}, "schema": []}
{"input": "Stability of NPs in the presence of serum proteins and plasma was excellent and no toxicity toward red blood cells was found.", "output": {"entities": {}}, "schema": []}
{"input": "NPs cytotoxicity was evaluated in HeLa cells irradiated for 30min with a halogen lamp.", "output": {"entities": {}}, "schema": []}
{"input": "After 72h, viability of cells treated with ZnPc/DTX-loaded NPs strongly decreased as compared to NPs loaded only with DTX, thus showing a combined effect of both DTX and ZnPc.", "output": {"entities": {"chemical": [{"text": "ZnPc", "start": 43, "end": 47}, {"text": "DTX", "start": 48, "end": 51}, {"text": "DTX", "start": 118, "end": 121}, {"text": "DTX", "start": 162, "end": 165}, {"text": "ZnPc", "start": 170, "end": 174}]}}, "schema": []}
{"input": "Superior antitumor activity of ZnPc/DTX-loaded NPs as compared to DTX-loaded NPs was confirmed in an animal model of orthotopic amelanotic melanoma, thus pointing to the application of PEO-PCL NPs in the combined chemo-photodynamic therapy of cancer.", "output": {"entities": {"chemical": [{"text": "ZnPc", "start": 31, "end": 35}, {"text": "DTX", "start": 36, "end": 39}, {"text": "DTX", "start": 66, "end": 69}, {"text": "PEO", "start": 185, "end": 188}, {"text": "PCL", "start": 189, "end": 192}]}}, "schema": []}
{"input": "Polyethylenimine combined with liposomes and with decreased numbers of primary amine residues strongly enhanced therapeutic antiviral efficiency against herpes simplex virus type 2 in a mouse model.", "output": {"entities": {"chemical": [{"text": "Polyethylenimine", "start": 0, "end": 16}, {"text": "primary amine", "start": 71, "end": 84}]}}, "schema": []}
{"input": "The development of antiviral agents that have novel mechanisms of action is urgently required in the topical therapy of herpes simplex virus type 2 (HSV-2) infections.", "output": {"entities": {}}, "schema": []}
{"input": "We reported previously that topical application of branched 3610-Da polyethylenimine (PEI) exhibited preventative antiviral activity.", "output": {"entities": {"chemical": [{"text": "polyethylenimine", "start": 68, "end": 84}, {"text": "PEI", "start": 86, "end": 89}]}}, "schema": []}
{"input": "In this study, to develop therapeutic anti-HSV-2 agents, the most potent PEI combined with ~ 200 nm-sized liposomes with or without oleic acid (liposomes/PEI) was selected in vitro and further evaluated using in vivo studies.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 73, "end": 76}, {"text": "oleic acid", "start": 132, "end": 142}, {"text": "PEI", "start": 154, "end": 157}]}}, "schema": []}
{"input": "The mechanism of action in vivo was elucidated using PEIs with decreased numbers of primary amine residues, resulting from ethylene carbonate treatment, and polyallylamine, a linear polyamine consisting of primary amines.", "output": {"entities": {"chemical": [{"text": "PEIs", "start": 53, "end": 57}, {"text": "primary amine", "start": 84, "end": 97}, {"text": "ethylene carbonate", "start": 123, "end": 141}, {"text": "polyallylamine", "start": 157, "end": 171}, {"text": "polyamine", "start": 182, "end": 191}, {"text": "primary amines", "start": 206, "end": 220}]}}, "schema": []}
{"input": "Cytotoxicity and antiviral activity in vitro, and the appearance of acute herpetic disease and virus yields in mice intravaginally administered with liposomes/PEI were evaluated in cell culture assays and a mouse genital herpes model, respectively.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 159, "end": 162}]}}, "schema": []}
{"input": "In addition, the cellular association of liposome/PEI was examined by flow cytometry and confocal microscopy.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 50, "end": 53}]}}, "schema": []}
{"input": "PEI showed higher antiviral activity postinfection than preinfection in vivo.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Liposome/PEI and PEI with decreased numbers of primary amine residues at a dose of 0. 2 mg PEI/mouse exhibited more potent therapeutic antiviral activity than acyclovir and PEI alone without acute lesion appearance or toxicity pre-or postinfection, but polyallylamine was moderately effective only preinfection.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 9, "end": 12}, {"text": "PEI", "start": 17, "end": 20}, {"text": "primary amine", "start": 47, "end": 60}, {"text": "PEI", "start": 91, "end": 94}, {"text": "acyclovir", "start": 159, "end": 168}, {"text": "PEI", "start": 173, "end": 176}, {"text": "polyallylamine", "start": 253, "end": 267}]}}, "schema": []}
{"input": "Liposome concentrations were important for the effectiveness of liposome/PEI.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 73, "end": 76}]}}, "schema": []}
{"input": "This finding suggests that PEI combined with liposomes and with slightly decreased numbers of primary amines may be an effective vaginally administrated antiviral drug, and secondary and tertiary amine residues of PEI may contribute to the inhibitory efficiency against viral infection.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 27, "end": 30}, {"text": "primary amines", "start": 94, "end": 108}, {"text": "secondary and tertiary amine", "start": 173, "end": 201}, {"text": "PEI", "start": 214, "end": 217}]}}, "schema": []}
{"input": "In situ forming nimodipine depot system based on microparticles for the treatment of posthemorrhagic cerebral vasospasm.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 16, "end": 26}]}}, "schema": []}
{"input": "The present study was conducted to examine the feasibility of nimodipine-loaded PLGA microparticles suspended in Tisseel (TM) fibrin sealant as an in situ forming depot system.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 62, "end": 72}, {"text": "PLGA", "start": 80, "end": 84}]}}, "schema": []}
{"input": "This device locally placed can be used for the treatment of vasospasm after a subarachnoid hemorrhage.", "output": {"entities": {}}, "schema": []}
{"input": "Microparticles were prepared via spray-drying by using the vibration mesh spray technology of Nano Spray Dryer B-90.", "output": {"entities": {}}, "schema": []}
{"input": "Spherically shaped microparticles with different loadings and high encapsulation efficiencies of 93. 3-97. 8% were obtained.", "output": {"entities": {}}, "schema": []}
{"input": "Depending on nimodipine loading (10-40%), the particle diameter ranged from 1. 9 +/- 1. 2 mu m to 2. 4 +/- 1. 3 mu m.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 13, "end": 23}]}}, "schema": []}
{"input": "Thermal analyses using DSC revealed that nimodipine is dissolved in the PLGA matrix.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 41, "end": 51}]}}, "schema": []}
{"input": "Also, fluorescent dye loaded microparticles were encapsulated in Tisseel (TM) to examine the homogeneity of particles.", "output": {"entities": {}}, "schema": []}
{"input": "3D-pictures of the in situ forming devices displayed uniform particle homogeneity in the sealant matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Drug release was examined by fluorescence spectrophotometry which demonstrated a drug release proportional to the square root of time.", "output": {"entities": {}}, "schema": []}
{"input": "A prolonged drug release of 19. 5h was demonstrated under in vitro conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, the nimodipine in situ forming device could be a promising candidate for the local treatment of vasospasm after a subarachnoid hemorrhage.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 13, "end": 23}]}}, "schema": []}
{"input": "Induction of HO-1 through p38 MAPK/Nrf2 signaling pathway by ethanol extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264. 7 cells and CLP-induced septic mice.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 61, "end": 68}]}}, "schema": []}
{"input": "High mobility group box 1 (HMGB1) plays a crucial mediator in the pathogenesis of many inflammatory diseases.", "output": {"entities": {}}, "schema": []}
{"input": "We recently proposed that heme oxygenase-1 (HO-1) negatively regulates HMGB1 in inflammatory conditions.", "output": {"entities": {"chemical": [{"text": "heme", "start": 26, "end": 30}]}}, "schema": []}
{"input": "We investigated whether ethanol extract of Inula helenium L.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 24, "end": 31}]}}, "schema": []}
{"input": "(EIH) activates p38 MAPK/Nrf2/HO-1 pathways in RAW264. 7 cells and reduces inflammation in CLP-induced septic mice.", "output": {"entities": {}}, "schema": []}
{"input": "EIH induced expression of HO-1 protein in a time-and concentration-dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "EIH significantly diminished HO-1 expression in siNrf2 RNA-transfected cells.", "output": {"entities": {}}, "schema": []}
{"input": "As expected, the inhibited expression of iNOS/NO, COX-2/PGE2, HMGB1 release by EIH in LPS-activated RAW264. 7 cells was significantly reversed by siHO-1RNA transfection.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, EIH not only inhibited NF-kappa B luciferase activity, phosphorylation of I kappa B alpha in LPS-activated cells but also significantly suppressed expression of adhesion molecules (ICAM-1 and VCAM-1) in TNF-alpha activated human umbilical vein endothelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "The induction of HO-1 by EIH was inhibited by SB203580 but not by SP600125, PD98059, nor LY294002.", "output": {"entities": {"chemical": [{"text": "SB203580", "start": 46, "end": 54}, {"text": "SP600125", "start": 66, "end": 74}, {"text": "PD98059", "start": 76, "end": 83}, {"text": "LY294002", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Most importantly, administration of EIH significantly reduced not only increase in blood HMGB1, ALT, AST, BUN, creatinine levels but also decrease macrophage infiltrate in the liver of septic mice, which were reversed by ZnPPIX, a HO-1 inhibitor.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 111, "end": 121}]}}, "schema": []}
{"input": "We concluded that EIH has anti-inflammatory effect via the induction of p38 MAPK-dependent HO-1 signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of insulin-like growth factor acid-labile subunit as a potential biomarker of effect for deoxynivalenol-induced proinflammatory cytokine expression.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 100, "end": 114}]}}, "schema": []}
{"input": "Consumption of the trichothecene deoxynivalenol (DON) suppresses growth in experimental animals-an adverse effect that was used to establish the tolerable daily intake for this toxin.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 33, "end": 47}, {"text": "DON", "start": 49, "end": 52}]}}, "schema": []}
{"input": "DON ingestion has been recently found to suppress plasma insulin-like growth factor acid-labile subunit (IGFALS), a protein essential for growth.", "output": {"entities": {"chemical": [{"text": "DON", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Studies were conducted to explore the feasibility of using plasma IGFALS as a biomarker of effect for DON.", "output": {"entities": {"chemical": [{"text": "DON", "start": 102, "end": 105}]}}, "schema": []}
{"input": "In the first study, weanling mice were fed 0, 1, 2. 5, 5 and 10 ppm DON and weight and plasma IGFALS determined at intervals over 9 wk.", "output": {"entities": {"chemical": [{"text": "DON", "start": 68, "end": 71}]}}, "schema": []}
{"input": "Reduced body weight gains were detectable beginning at wk 5 in the 10 ppm dose and wk 7 at the 5 ppm dose.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma IGFALS was significantly depressed at wk 5 in the 5 and 10 ppm groups at wk 9 in the 10 ppm group.", "output": {"entities": {}}, "schema": []}
{"input": "Depressed IGFALS significantly correlated with reduced body weight at wk 5 and 9.", "output": {"entities": {}}, "schema": []}
{"input": "Benchmark dose modeling revealed the BMDL and BMD for plasma IGFALS reduction were 1. 1 and 3. 0 ppm DON and for weight reduction were 2. 1 and 4. 5 ppm DON.", "output": {"entities": {"chemical": [{"text": "DON", "start": 101, "end": 104}, {"text": "DON", "start": 153, "end": 156}]}}, "schema": []}
{"input": "In the second study, it was demonstrated that mice fed 15 ppm DON diet had significantly less plasma IGFALS than mice fed identical amounts of control diet.", "output": {"entities": {"chemical": [{"text": "DON", "start": 62, "end": 65}]}}, "schema": []}
{"input": "Thus DON' s influence on IGFALS likely reflects the combined effects of reduced food intake as well as its physiological action involving suppressors of cytokine signaling.", "output": {"entities": {"chemical": [{"text": "DON", "start": 5, "end": 8}]}}, "schema": []}
{"input": "Taken together, these findings suggest that plasma IGFALS might be a useful biomarker for DON' s adverse effects on growth.", "output": {"entities": {"chemical": [{"text": "DON", "start": 90, "end": 93}]}}, "schema": []}
{"input": "Locally administered prostaglandin E2 prevents aeroallergen-induced airway sensitization in mice through immunomodulatory mechanisms.", "output": {"entities": {"chemical": [{"text": "prostaglandin E2", "start": 21, "end": 37}]}}, "schema": []}
{"input": "Prostaglandin E2 attenuates airway pathology in asthmatic patients and exerts a protective effect in antigen-sensitized mice when administered systemically.", "output": {"entities": {"chemical": [{"text": "Prostaglandin E2", "start": 0, "end": 16}]}}, "schema": []}
{"input": "We aimed to establish the consequences of intranasal PGE2 administration on airway reactivity to aeroallergens in mice and reveal the underlying immunoinflammatory mechanisms.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 53, "end": 57}]}}, "schema": []}
{"input": "PGE2 was administered either daily during a 10-day exposure to house dust mite (HDM) extracts or for limited intervals.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Airway hyperreactivity was measured by whole-body and invasive plethysmography.", "output": {"entities": {}}, "schema": []}
{"input": "The phenotypes of lung immune cells and cytokine production were analysed by flow cytometry and ELISA, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Airway hyperreactivity was sustainably reduced only when PGE2 administration was restricted to the initial 5 days of exposure to HDM.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 57, "end": 61}]}}, "schema": []}
{"input": "Lung inflammation, IL-4 production, and airway mast cell activity were also prevented under this early short-term treatment with PGE2.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 129, "end": 133}]}}, "schema": []}
{"input": "Interestingly, a Th2 response was already committed on day 5 of exposure to HDM.", "output": {"entities": {}}, "schema": []}
{"input": "This was paralleled by GM-CSF and osteopontin upregulation and a decreased number of plasmacytoid dendritic and T regulatory cells, as well as a trend towards reduced IL-10 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Local PGE2 administration prevented the increase of airway IL-13 and osteopontin and kept lung plasmacytoid dendritic cell counts close to baseline.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 6, "end": 10}]}}, "schema": []}
{"input": "GM-CSF and Tregs were unaffected by the treatment.", "output": {"entities": {}}, "schema": []}
{"input": "These findings suggest that the protection provided by PGE2 is a result of the modulation of early lung immunomodulatory mechanisms, and possibly a shift in the balance of dendritic cells towards a tolerogenic profile.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 55, "end": 59}]}}, "schema": []}
{"input": "Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency.", "output": {"entities": {"chemical": [{"text": "benzyloxazoles", "start": 16, "end": 30}, {"text": "nucleoside", "start": 38, "end": 48}]}}, "schema": []}
{"input": "Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 14, "end": 24}]}}, "schema": []}
{"input": "Optimization of the 4-R substituent in 1 led to ethyl and isopropyl analogs 1e and 1f with 1-7 nM potency towards both the wild-type virus and a Tyr181C variant.", "output": {"entities": {"chemical": [{"text": "ethyl", "start": 48, "end": 53}, {"text": "isopropyl", "start": 58, "end": 67}]}}, "schema": []}
{"input": "Methadone N-demethylation by the common CYP2B6 allelic variant CYP2B6. 6.", "output": {"entities": {"chemical": [{"text": "Methadone N", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP), catalyzed predominantly by CYP2B6.", "output": {"entities": {"chemical": [{"text": "Methadone", "start": 0, "end": 9}, {"text": "N", "start": 52, "end": 53}, {"text": "2-ethyl-1, 5-dimethyl-3, 3-diphenylpyrrolidine", "start": 71, "end": 117}, {"text": "EDDP", "start": 119, "end": 123}]}}, "schema": []}
{"input": "Retrospective studies suggest that the common allele variant CYP2B6 * 6 may influence methadone plasma concentrations.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 86, "end": 95}]}}, "schema": []}
{"input": "The catalytic activity of CYP2B6. 6, encoded by CYP2B6 * 6, is highly substrate-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "This investigation compared methadone N-demethylation by CYP2B6. 6 with that by wild-type CYP2B6. 1.", "output": {"entities": {"chemical": [{"text": "methadone N", "start": 28, "end": 39}]}}, "schema": []}
{"input": "Methadone enantiomer and racemate N-demethylation by recombinant-expressed CYP2B6. 6 and CYP2B6. 1 was determined.", "output": {"entities": {"chemical": [{"text": "Methadone", "start": 0, "end": 9}, {"text": "N", "start": 34, "end": 35}]}}, "schema": []}
{"input": "At substrate concentrations (0. 25-2 micro M) approximating plasma concentrations occurring clinically, rates of methadone enantiomer N-demethylation by CYP2B6. 6, incubated individually or as the racemate, were one-third to one-fourth those by CYP2B6. 1.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 113, "end": 122}, {"text": "N", "start": 134, "end": 135}]}}, "schema": []}
{"input": "For methadone individual enantiomers and metabolism by CYP2B6. 6 compared with CYP2B6. 1, Vmax was diminished, Ks was greater and the in vitro intrinsic clearance was diminished 5-to 6-fold.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 4, "end": 13}]}}, "schema": []}
{"input": "The intrinsic clearance for R-and S-EDDP formation from racemic methadone was diminished approximately 6-fold and 3-fold for R-and S-methadone, respectively.", "output": {"entities": {"chemical": [{"text": "R-and S-EDDP", "start": 28, "end": 40}, {"text": "racemic methadone", "start": 56, "end": 73}, {"text": "R-and S-methadone", "start": 125, "end": 142}]}}, "schema": []}
{"input": "Both CYP2B6. 6 and CYP2B6. 1 showed similar stereoselectivity (S > R-methadone).", "output": {"entities": {"chemical": [{"text": "S > R-methadone", "start": 63, "end": 78}]}}, "schema": []}
{"input": "Human liver microsomes with diminished CYP2B6 content due to a CYP2B6 * 6 allele had lower rates of methadone N-demethylation.", "output": {"entities": {"chemical": [{"text": "methadone N", "start": 100, "end": 111}]}}, "schema": []}
{"input": "Results show that methadone N-demethylation catalyzed by CYP2B6. 6, the CYP2B6 variant encoded by the CYP2B6 * 6 polymorphism, is catalytically deficient compared with wild-type CYP2B6. 1.", "output": {"entities": {"chemical": [{"text": "methadone N", "start": 18, "end": 29}]}}, "schema": []}
{"input": "Diminished methadone N-demethylation by CYP2B6. 6 may provide a mechanistic explanation for clinical observations of altered methadone disposition in individuals carrying the CYP2B6 * 6 polymorphism.", "output": {"entities": {"chemical": [{"text": "methadone N", "start": 11, "end": 22}, {"text": "methadone", "start": 125, "end": 134}]}}, "schema": []}
{"input": "3D structures and ligand specificities of nuclear xenobiotic receptors CAR, PXR and VDR.", "output": {"entities": {}}, "schema": []}
{"input": "The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters.", "output": {"entities": {"chemical": [{"text": "androstane", "start": 35, "end": 45}, {"text": "pregnane", "start": 62, "end": 70}, {"text": "vitamin D", "start": 92, "end": 101}]}}, "schema": []}
{"input": "3D structures for the ligand-binding domain (LBD) of these receptors are abundantly available, providing valuable insights into the ligand-binding specificity as well as the activation mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "The ligand-binding site of PXR is large and flexible, whereas those of CAR and VDR are compact and rigid, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In general, the ligand profiles of the receptors are in agreement with the LBD structures.", "output": {"entities": {}}, "schema": []}
{"input": "The crystal structures have greatly helped us to understand the promiscuity and/or specificity of CAR, PXR and VDR.", "output": {"entities": {}}, "schema": []}
{"input": "A 5-year retrospective evaluation of snakebite cases in Hatay, Turkey.", "output": {"entities": {}}, "schema": []}
{"input": "Snakebites are relatively rare medical emergency cases that might lead to serious consequences.", "output": {"entities": {}}, "schema": []}
{"input": "This study aims to evaluate snakebite cases in terms of medical follow-up, antivenom therapy and antivenom reactions.", "output": {"entities": {}}, "schema": []}
{"input": "Medical records of patients admitted to emergency department between January 1, 2006 and December 31, 2010 were retrospectively investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Snakebite-related cases of a total of 125 patients were included in the scope of the study.", "output": {"entities": {}}, "schema": []}
{"input": "Of the total 125 cases, 54. 4% were male and 45. 6% were female.", "output": {"entities": {}}, "schema": []}
{"input": "Most of cases (n: 65, 52%) were aged over 30 years, while the mean age was 34. 87 +/- 19. 29 years.", "output": {"entities": {}}, "schema": []}
{"input": "Snakebite-related applications to the emergency department were mostly seen in June with 27 cases.", "output": {"entities": {}}, "schema": []}
{"input": "Upon admitting, all patients were recorded to be conscious and showing good general conditions; however, they suffered from pain and edema at the site of bite.", "output": {"entities": {}}, "schema": []}
{"input": "Of all, 25 patients only suffered from bite injury and ecchymosis due to snakebite.", "output": {"entities": {}}, "schema": []}
{"input": "The site of bite was upper extremities in 66 patients (52. 8%), whereas it was lower extremities in 58 (46. 4%).", "output": {"entities": {}}, "schema": []}
{"input": "Of all, antivenom was unnecessary in 25 (20%) patients, while four antivenoms were administered to each of the 23 (18. 4%) patients.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, six (4. 8%) patients needed nine antivenom administrations for each.", "output": {"entities": {}}, "schema": []}
{"input": "Anaphylaxis (n: 2, 1. 6%), compartment syndrome (n: 2, 1. 6%) and serum sickness (n: 1, 0. 8%) encountered in remaining cases.", "output": {"entities": {}}, "schema": []}
{"input": "Of all, 86 (68. 8%) patients were hospitalized in the emergency department, while 25 (20. 0%) patients were followed up by observation in emergency service.", "output": {"entities": {}}, "schema": []}
{"input": "Only one patient was treated and followed up in intensive care unit.", "output": {"entities": {}}, "schema": []}
{"input": "Implementation of antivenom therapy is considered unnecessary for the treatment of all snakebite cases.", "output": {"entities": {}}, "schema": []}
{"input": "Antivenom reactions and number of related cases might be reduced by continuous close monitoring, appropriate prophylaxis and controlled slow infusion administration of medications.", "output": {"entities": {}}, "schema": []}
{"input": "Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats.", "output": {"entities": {"chemical": [{"text": "pyrethroids", "start": 61, "end": 72}, {"text": "piperonyl butoxide", "start": 74, "end": 92}, {"text": "tetramethrin", "start": 98, "end": 110}]}}, "schema": []}
{"input": "In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes.", "output": {"entities": {}}, "schema": []}
{"input": "Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days.", "output": {"entities": {"chemical": [{"text": "cypermethrin", "start": 100, "end": 112}, {"text": "piperonyl butoxide", "start": 115, "end": 133}, {"text": "PBO", "start": 135, "end": 138}, {"text": "alphacypermethrin", "start": 150, "end": 167}, {"text": "PBO", "start": 170, "end": 173}, {"text": "deltamethrin", "start": 184, "end": 196}, {"text": "PBO", "start": 199, "end": 202}, {"text": "cypermethrin", "start": 213, "end": 225}, {"text": "PBO", "start": 228, "end": 231}, {"text": "tetramethrin", "start": 234, "end": 246}, {"text": "alphacypermethrin", "start": 257, "end": 274}, {"text": "PBO", "start": 277, "end": 280}, {"text": "tetramethrin", "start": 283, "end": 295}, {"text": "deltamethrin", "start": 310, "end": 322}, {"text": "PBO", "start": 325, "end": 328}]}}, "schema": []}
{"input": "During the study period, mortality and serious clinical findings were not observed in any animal.", "output": {"entities": {}}, "schema": []}
{"input": "However, feed consumptions decreased in groups 1 and 3 (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "cypermethrin", "start": 73, "end": 85}, {"text": "alphacypermethrin", "start": 90, "end": 107}]}}, "schema": []}
{"input": "Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups.", "output": {"entities": {}}, "schema": []}
{"input": "Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "cypermethrin", "start": 71, "end": 83}, {"text": "alphacypermethrin", "start": 88, "end": 105}]}}, "schema": []}
{"input": "The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver.", "output": {"entities": {}}, "schema": []}
{"input": "It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.", "output": {"entities": {"chemical": [{"text": "pyrethroid", "start": 78, "end": 88}]}}, "schema": []}
{"input": "A Serum-Tolerant Hydroxyl-Modified Polyethylenimine as Versatile Carriers of pDNA/siRNA.", "output": {"entities": {"chemical": [{"text": "Hydroxyl", "start": 17, "end": 25}, {"text": "Polyethylenimine", "start": 35, "end": 51}]}}, "schema": []}
{"input": "The polyethylenimine (PEI) derivatives (PTn) are prepared by treating PEI25k with Tris (hydroxymethyl) acrylamidomethane via the Michael addition.", "output": {"entities": {"chemical": [{"text": "polyethylenimine", "start": 4, "end": 20}, {"text": "PEI", "start": 22, "end": 25}, {"text": "Tris (hydroxymethyl) acrylamidomethane", "start": 82, "end": 120}]}}, "schema": []}
{"input": "These PTns can effectively condense nucleic acids into nanosized particles with positive surface charges.", "output": {"entities": {}}, "schema": []}
{"input": "The PTns show lower cytotoxicity and better serum-resistant capacity than PEI25k.", "output": {"entities": {}}, "schema": []}
{"input": "Specially, the transfection efficiency of PT26/DNA is 29-fold higher than that of PEI25k in HeLa cells in serum-containing medium.", "output": {"entities": {}}, "schema": []}
{"input": "The PTn/siRNA complexes show superior knockdown effect in CT26 cells in serum-containing medium.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, flow cytometry analysis shows that the PTns can efficiently mediate the entry of nucleic acids into the cell.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, PTns are potentially applicable as non-viral carriers of nucleic acids and warrant further development for use in gene therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Sociocultural behavior, sex-biased admixture, and effective population sizes in Central African Pygmies and non-Pygmies.", "output": {"entities": {}}, "schema": []}
{"input": "Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography.", "output": {"entities": {}}, "schema": []}
{"input": "In Central Africa, diverging patterns of sex-specific genetic variation have been observed between mobile hunter-gatherer Pygmies and sedentary agricultural non-Pygmies.", "output": {"entities": {}}, "schema": []}
{"input": "However, their sex-specific demography remains largely unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers.", "output": {"entities": {}}, "schema": []}
{"input": "We found much larger effective population sizes and migration rates among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups.", "output": {"entities": {}}, "schema": []}
{"input": "We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations.", "output": {"entities": {}}, "schema": []}
{"input": "In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, Pygmy populations showed variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages.", "output": {"entities": {}}, "schema": []}
{"input": "Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context.", "output": {"entities": {}}, "schema": []}
{"input": "We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history.", "output": {"entities": {}}, "schema": []}
{"input": "Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated With Increased Insulin Resistance and Higher Risk of Developing Gestational Diabetes Mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVETo evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, beta-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. RESEARCH DESIGN AND METHODSWe performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters.", "output": {"entities": {}}, "schema": []}
{"input": "Diagnosis of GDM was made at 2nd trimester, based on a 75-g oral glucose tolerance test (International Association of Diabetes and Pregnancy Study Group criteria).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 65, "end": 72}]}}, "schema": []}
{"input": "Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), beta-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC (insulin/glucose)), and beta-cell compensation (insulin secretion sensitivity index-2).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 210, "end": 217}]}}, "schema": []}
{"input": "Adiponectin was measured by radioimmunoassay. RESULTSAmong the 445 participants included in this study, 38 women developed GDM.", "output": {"entities": {}}, "schema": []}
{"input": "Women who developed GDM had lower 1st-trimester adiponectin levels (9. 67 +/- 3. 84 vs. 11. 92 +/- 4. 59 micro g/mL in women with normal glucose tolerance).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 137, "end": 144}]}}, "schema": []}
{"input": "Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1. 12 per 1 micro g/mL decrease of adiponectin levels; P = 0. 02, adjusted for BMI and HbA (1c) at 1st trimester).", "output": {"entities": {}}, "schema": []}
{"input": "Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r =-0. 22, P < 0. 0001) and Matsuda index (r = 0. 28, P < 0. 0001, and r = 0. 29, P < 0. 0001).", "output": {"entities": {}}, "schema": []}
{"input": "After adjustment for confounding factors, we found no significant association with HOMA-B and AUC (insulin/glucose). CONCLUSIONSPregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 107, "end": 114}]}}, "schema": []}
{"input": "Nanoparticle adhesion to the cell membrane and its effect on nanoparticle uptake efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "The interactions between nanosized particles and living systems are commonly mediated by what adsorbs to the nanoparticle in the biological environment, its biomolecular corona, rather than the pristine surface.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we characterize the adhesion toward the cell membrane of nanoparticles of different material and size and study how this is modulated by the presence or absence of a corona on the nanoparticle surface.", "output": {"entities": {}}, "schema": []}
{"input": "The results are corroborated with adsorption to simple model supported lipid bilayers using a quartz crystal microbalance.", "output": {"entities": {"chemical": [{"text": "quartz", "start": 94, "end": 100}]}}, "schema": []}
{"input": "We conclude that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticle uptake is described as a two-step process, where the nanoparticles initially adhere to the cell membrane and subsequently are internalized by the cells via energy-dependent pathways.", "output": {"entities": {}}, "schema": []}
{"input": "The lowered adhesion in the presence of proteins thereby causes a concomitant decrease in nanoparticle uptake efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of a biomolecular corona may confer specific interactions between the nanoparticle-corona complex and the cell surface including triggering of regulated cell uptake.", "output": {"entities": {}}, "schema": []}
{"input": "An important effect of the corona is, however, a reduction in the purely unspecific interactions between the bare material and the cell membrane, which in itself disregarding specific interactions, causes a decrease in cellular uptake.", "output": {"entities": {}}, "schema": []}
{"input": "We suggest that future nanoparticle-cell studies include, together with characterization of size, charge, and dispersion stability, an evaluation of the adhesion properties of the material to relevant membranes.", "output": {"entities": {}}, "schema": []}
{"input": "Aminoalkyl derivatives of guanidine diaromatic minor groove binders with antiprotozoal activity.", "output": {"entities": {"chemical": [{"text": "Aminoalkyl", "start": 0, "end": 10}, {"text": "guanidine", "start": 26, "end": 35}]}}, "schema": []}
{"input": "Considering the strong DNA minor groove binding observed for our previous series of diaromatic symmetric and asymmetric guanidinium and 2-aminoimidazolinium derivatives, we report now the synthesis of new aminoalkyl derivatives of diaromatic guanidines with potential as DNA minor groove binders and antiprotozoal activity.", "output": {"entities": {"chemical": [{"text": "guanidinium", "start": 120, "end": 131}, {"text": "2-aminoimidazolinium", "start": 136, "end": 156}, {"text": "aminoalkyl", "start": 205, "end": 215}]}}, "schema": []}
{"input": "The preparation of these aminoalkyl derivatives (12a-e, 13a-e, 14a-c, e, 15a-e, 16a-e) is presented as well as their affinity for DNA which was evaluated by means of DNA thermal denaturation experiments.", "output": {"entities": {"chemical": [{"text": "aminoalkyl", "start": 25, "end": 35}]}}, "schema": []}
{"input": "Finally, the antiprotozoal activity of most of these aminoalkyl minor groove binders was evaluated in vitro against Trypanosoma brucei rhodesiense (8 compounds) and Plasmodium falciparum (18 compounds).", "output": {"entities": {"chemical": [{"text": "aminoalkyl", "start": 53, "end": 63}]}}, "schema": []}
{"input": "The O-linked derivatives 13c and 14c showed 100 nM activities against P. falciparum, whereas for T.", "output": {"entities": {"chemical": [{"text": "O", "start": 4, "end": 5}]}}, "schema": []}
{"input": "b. rhodesiense all compounds tested showed micromolar activity.", "output": {"entities": {}}, "schema": []}
{"input": "Some of the derivatives prepared seem to exert the antimalarial activity by binding to the DNA minor groove whereas other sets of compounds could exert this antimalarial activity by inhibiting the parasite dihydrofolate reductase, for example.", "output": {"entities": {"chemical": [{"text": "dihydrofolate", "start": 206, "end": 219}]}}, "schema": []}
{"input": "Phenyl linker-induced dense PEG conformation improves the efficacy of C-terminally monoPEGylated staphylokinase.", "output": {"entities": {"chemical": [{"text": "Phenyl", "start": 0, "end": 6}, {"text": "PEG", "start": 28, "end": 31}, {"text": "C", "start": 70, "end": 71}]}}, "schema": []}
{"input": "PEGylation can improve the protein efficacy by prolonging serum half-life and reducing proteolytic sensitivity and immunogenicity.", "output": {"entities": {}}, "schema": []}
{"input": "However, PEGylation may decrease the bioactivity of a protein by interfering with binding of its substrate or receptors.", "output": {"entities": {}}, "schema": []}
{"input": "Here, staphylokinase (SAK), a thrombolysis agent for therapy of myocardial infarction, was mono-PEGylated at the C-terminus of SAK far from its bioactive domain.", "output": {"entities": {"chemical": [{"text": "C", "start": 113, "end": 114}]}}, "schema": []}
{"input": "Phenyl, propyl, and amyl moieties were used as linkers between SAK and polyethylene glycol (PEG), respectively.", "output": {"entities": {"chemical": [{"text": "Phenyl", "start": 0, "end": 6}, {"text": "propyl", "start": 8, "end": 14}, {"text": "amyl", "start": 20, "end": 24}, {"text": "polyethylene glycol", "start": 71, "end": 90}, {"text": "PEG", "start": 92, "end": 95}]}}, "schema": []}
{"input": "Flexible propyl and amyl linkers lead to loose conformation.", "output": {"entities": {"chemical": [{"text": "propyl", "start": 9, "end": 15}, {"text": "amyl", "start": 20, "end": 24}]}}, "schema": []}
{"input": "In contrast, rigid and hydrophobic phenyl linker induces dense PEG conformation that can extensively shield most domains adjacent to C-terminus (e. g., the antigen epitopes and proteolytic sites) of SAK and inefficiently shield its bioactive domain.", "output": {"entities": {"chemical": [{"text": "phenyl", "start": 35, "end": 41}, {"text": "PEG", "start": 63, "end": 66}, {"text": "C", "start": 133, "end": 134}]}}, "schema": []}
{"input": "As compared with loose PEG conformation, dense PEG conformation is more efficient to maintain the bioactivity, increase the plasma half-life, and decrease the proteolytic sensitivity and immunogenicity of the PEGylated SAK.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 23, "end": 26}, {"text": "PEG", "start": 47, "end": 50}]}}, "schema": []}
{"input": "Optical probing of the electronic interaction between graphene and hexagonal boron nitride.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 54, "end": 62}, {"text": "boron nitride", "start": 77, "end": 90}]}}, "schema": []}
{"input": "Even weak van der Waals (vdW) adhesion between two-dimensional solids may perturb their various materials properties owing to their low dimensionality.", "output": {"entities": {}}, "schema": []}
{"input": "Although the electronic structure of graphene has been predicted to be modified by the vdW interaction with other materials, its optical characterization has not been successful.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 37, "end": 45}]}}, "schema": []}
{"input": "In this report, we demonstrate that Raman spectroscopy can be utilized to detect a few percent decrease in the Fermi velocity (v (F)) of graphene caused by the vdW interaction with underlying hexagonal boron nitride (hBN).", "output": {"entities": {"chemical": [{"text": "graphene", "start": 137, "end": 145}, {"text": "boron nitride", "start": 202, "end": 215}]}}, "schema": []}
{"input": "Our study also establishes Raman spectroscopic analysis which enables separation of the effects by the vdW interaction from those by mechanical strain or extra charge carriers.", "output": {"entities": {}}, "schema": []}
{"input": "The analysis reveals that spectral features of graphene on hBN are mainly affected by change in v (F) and mechanical strain but not by charge doping, unlike graphene supported on SiO 2 substrates.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 47, "end": 55}, {"text": "graphene", "start": 157, "end": 165}, {"text": "SiO 2", "start": 179, "end": 184}]}}, "schema": []}
{"input": "Graphene on hBN was also found to be less susceptible to thermally induced hole doping.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Bioactive flavaglines and other constituents isolated from Aglaia perviridis.", "output": {"entities": {"chemical": [{"text": "flavaglines", "start": 10, "end": 21}]}}, "schema": []}
{"input": "Eight new compounds, including two cyclopenta [b] benzopyran derivatives (1, 2), two cyclopenta [b] benzofuran derivatives (3, 4), three cycloartane triterpenoids (5-7), and an apocarotenoid (8), together with 16 known compounds, were isolated from the chloroform-soluble partitions of separate methanol extracts of a combination of the fruits, leaves, and twigs and of the roots of Aglaia perviridis collected in Vietnam.", "output": {"entities": {"chemical": [{"text": "cyclopenta [b] benzopyran", "start": 35, "end": 60}, {"text": "cyclopenta [b] benzofuran", "start": 85, "end": 110}, {"text": "cycloartane triterpenoids", "start": 137, "end": 162}, {"text": "chloroform", "start": 253, "end": 263}, {"text": "methanol", "start": 295, "end": 303}]}}, "schema": []}
{"input": "Isolation work was monitored using human colon cancer cells (HT-29) and facilitated with an LC/MS dereplication procedure.", "output": {"entities": {}}, "schema": []}
{"input": "The structures of the new compounds (1-8) were determined on the basis of spectroscopic data interpretation.", "output": {"entities": {}}, "schema": []}
{"input": "The Mosher ester method was employed to determine the absolute configurations of 5-7, and the absolute configuration of the 9, 10-diol unit of compound 8 was established by a dimolybdenum tetraacetate [Mo2 (AcO) 4] induced circular dichroism procedure.", "output": {"entities": {"chemical": [{"text": "diol", "start": 130, "end": 134}, {"text": "dimolybdenum tetraacetate", "start": 175, "end": 200}, {"text": "Mo2 (AcO) 4", "start": 202, "end": 213}]}}, "schema": []}
{"input": "Seven known rocaglate derivatives (9-15) exhibited significant cytotoxicity against the HT-29 cell line, with rocaglaol (9) being the most potent (ED50 0. 0007 mu M).", "output": {"entities": {"chemical": [{"text": "rocaglate", "start": 12, "end": 21}, {"text": "rocaglaol", "start": 110, "end": 119}]}}, "schema": []}
{"input": "The new compounds 2-4 were also active against this cell line, with ED50 values ranging from 0. 46 to 4. 7 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "The cytotoxic compounds were evaluated against a normal colon cell line, CCD-112CoN.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant NF-kappa B (p65) inhibitory activity in an ELISA assay.", "output": {"entities": {"chemical": [{"text": "perviridicin B", "start": 30, "end": 44}, {"text": "rocaglate", "start": 62, "end": 71}, {"text": "sesquiterpene", "start": 109, "end": 122}, {"text": "2-oxaisodauc-5-en-12-al", "start": 124, "end": 147}]}}, "schema": []}
{"input": "Increasing the order parameter of quasi-hexagonal micellar nanostructures by ultrasound annealing.", "output": {"entities": {}}, "schema": []}
{"input": "Nanopatterning with block copolymers finds many applications ranging from optics to bioscience.", "output": {"entities": {}}, "schema": []}
{"input": "Many of these uses demand highly ordered patterns that are difficult to obtain because of environmental influences during fabrication.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that ultrasonication improves the hexagonal order of artificially disturbed micellar nanopatterns.", "output": {"entities": {}}, "schema": []}
{"input": "A powerful aluminum catalyst for the synthesis of highly functional organic carbonates.", "output": {"entities": {"chemical": [{"text": "aluminum", "start": 11, "end": 19}, {"text": "organic carbonates", "start": 68, "end": 86}]}}, "schema": []}
{"input": "An aluminum complex based on an amino triphenolate ligand scaffold shows unprecedented high activity (initial TOFs up to 36, 000 h (-1)), broad substrate scope, and functional group tolerance in the formation of highly functional organic carbonates prepared from epoxides and CO (2).", "output": {"entities": {"chemical": [{"text": "aluminum", "start": 3, "end": 11}, {"text": "amino triphenolate", "start": 32, "end": 50}, {"text": "organic carbonates", "start": 230, "end": 248}, {"text": "epoxides", "start": 263, "end": 271}, {"text": "CO (2)", "start": 276, "end": 282}]}}, "schema": []}
{"input": "The developed catalytic protocol is further characterized by low catalyst loadings and relative mild reaction conditions using a cheap, abundant, and nontoxic metal.", "output": {"entities": {}}, "schema": []}
{"input": "A chemical approach to searching for bioactive ingredients in cigarette smoke.", "output": {"entities": {}}, "schema": []}
{"input": "Cigarette smoke, a collection of many toxic chemicals, contributes to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease and cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Much work has been done on the chemical analysis of ingredients in cigarette smoke, but there are few reports on the active ingredients that can modify biomolecules.", "output": {"entities": {}}, "schema": []}
{"input": "We used a sensitive liquid chromatography-mass spectrometry (LC/MS) and LC/MS/MS method to show that L-tyrosine (Tyr), an amino acid with a highly reactive hydroxyl group, readily reacts with cigarette smoke extract (CSE) at body temperature (37 degrees C) to form various Tyr derivatives.", "output": {"entities": {"chemical": [{"text": "L-tyrosine", "start": 101, "end": 111}, {"text": "Tyr", "start": 113, "end": 116}, {"text": "amino acid", "start": 122, "end": 132}, {"text": "hydroxyl", "start": 156, "end": 164}, {"text": "Tyr", "start": 273, "end": 276}]}}, "schema": []}
{"input": "Among these derivatives were N-(3-oxobutyl)-Tyr and two acetylated compounds, N-acetyl-Tyr and O-acetyl-Tyr, which were synthesized by reaction of Tyr with methyl vinyl ketone and acetic anhydride, respectively, at 37 degrees C.", "output": {"entities": {"chemical": [{"text": "N-(3-oxobutyl)-Tyr", "start": 29, "end": 47}, {"text": "N-acetyl-Tyr", "start": 78, "end": 90}, {"text": "O-acetyl-Tyr", "start": 95, "end": 107}, {"text": "Tyr", "start": 147, "end": 150}, {"text": "methyl vinyl ketone", "start": 156, "end": 175}, {"text": "acetic anhydride", "start": 180, "end": 196}]}}, "schema": []}
{"input": "The presence of methyl vinyl ketone and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS).", "output": {"entities": {"chemical": [{"text": "methyl vinyl ketone", "start": 16, "end": 35}, {"text": "acetic anhydride", "start": 40, "end": 56}]}}, "schema": []}
{"input": "These results indicate that Tyr can easily react with active ingredients in CSE.", "output": {"entities": {"chemical": [{"text": "Tyr", "start": 28, "end": 31}]}}, "schema": []}
{"input": "The present analytical methods should aid the search for active ingredients in cigarette smoke.", "output": {"entities": {}}, "schema": []}
{"input": "Schisphenlignans A-E: five new dibenzocyclooctadiene lignans from Schisandra sphenanthera.", "output": {"entities": {"chemical": [{"text": "Schisphenlignans A-E", "start": 0, "end": 20}, {"text": "dibenzocyclooctadiene lignans", "start": 31, "end": 60}]}}, "schema": []}
{"input": "Five new dibenzocyclooctadiene lignans, schisphenlignans A-E (1-5), together with eight known ones, were isolated from the stems of Schisandra sphenanthera.", "output": {"entities": {"chemical": [{"text": "dibenzocyclooctadiene lignans", "start": 9, "end": 38}, {"text": "schisphenlignans A-E", "start": 40, "end": 60}]}}, "schema": []}
{"input": "The structures of 1-5 were elucidated based on the analysis of their NMR, MS and circular dichroism (CD) spectra.", "output": {"entities": {}}, "schema": []}
{"input": "Some isolates were tested for their acute activities on insulin sensitivity in 3T3-L1 differentiated adipocytes, but none of them showed significant bioactivity with 10 micro M administration of the tested compounds.", "output": {"entities": {}}, "schema": []}
{"input": "EPR spin Hamiltonian parameters of encapsulated spin-labels: impact of the hydrogen bonding topology.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 75, "end": 83}]}}, "schema": []}
{"input": "Encapsulation of spin-labels into \" host \" compounds, like cucurbit [n] urils or cyclodextrins, in solutions has profound effects on the EPR spin Hamiltonian parameters of the spin-labels.", "output": {"entities": {}}, "schema": []}
{"input": "In this work we study the microscopic origin of the EPR spin Hamiltonian parameters of spin-labels enclosed in hydrophobic cavities.", "output": {"entities": {}}, "schema": []}
{"input": "We focus on the dependence of the EPR properties of encapsulated spin-labels on the hydrogen bonding topologies that occur upon encapsulation, and quantize various contributions to these parameters according to specific hydrogen bonding patterns.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 84, "end": 92}, {"text": "hydrogen", "start": 220, "end": 228}]}}, "schema": []}
{"input": "The obtained results provide refined insight into the role of the hydrogen bonding induced encapsulation shifts of EPR spin Hamiltonian parameters in solvated \" spin-label @host compound \" complexes.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Lactobacillus johnsonii inhibits indoleamine 2, 3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.", "output": {"entities": {"chemical": [{"text": "indoleamine", "start": 33, "end": 44}, {"text": "tryptophan", "start": 73, "end": 83}]}}, "schema": []}
{"input": "In our previous work, we found that feeding Lactobacillus johnsonii to BioBreeding diabetes-prone (BBDP) rats decreased the incidence of diabetes development.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to investigate host pathways affected by L. johnsonii, with specific focus on the rate-limiting enzyme of tryptophan catabolism, indoleamine 2, 3-dioxygenase (IDO).", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 132, "end": 142}, {"text": "indoleamine", "start": 155, "end": 166}]}}, "schema": []}
{"input": "Suspensions of L. johnsonii or an equal volume of vehicle were orally administered to BBDP rats.", "output": {"entities": {}}, "schema": []}
{"input": "Tissue IDO was investigated using quantitative RT-PCR and Western blot, whereas tryptophan, kynurenine, and 5-hydroxytryptamine (5-HT) concentrations were quantified by HPLC and ELISA.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 80, "end": 90}, {"text": "kynurenine", "start": 92, "end": 102}, {"text": "5-hydroxytryptamine", "start": 108, "end": 127}, {"text": "5-HT", "start": 129, "end": 133}]}}, "schema": []}
{"input": "IDO activity was also investigated using L. johnsonii culture cell-free supernatant (CFS) with affinity-purified IDO and HT-29 intestinal epithelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "L. johnsonii feeding resulted in a 17% reduction in serum kynurenine compared with that in vehicle-fed controls, correlating with a 1. 4-fold elevation in 5-HT levels.", "output": {"entities": {"chemical": [{"text": "kynurenine", "start": 58, "end": 68}, {"text": "5-HT", "start": 155, "end": 159}]}}, "schema": []}
{"input": "H2O2 produced by L. johnsonii abolished IDO activity in vitro, and L. johnsonii feeding resulted in a 3. 9-fold increase in ileum lumen H2O2.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 0, "end": 4}, {"text": "H2O2", "start": 136, "end": 140}]}}, "schema": []}
{"input": "L. johnsonii CFS significantly reduced IDO activity in HT-29 intestinal epithelial cells (47% reduction) compared with that in vehicle-treated controls, an effect abolished by catalase treatment.", "output": {"entities": {}}, "schema": []}
{"input": "These data support the role of H2O2 in commensal bacteria-host interactions and highlight the influence of commensal bacteria-derived H2O2 on host physiology.-Valladares, R., Bojilova, L., Potts, A.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 31, "end": 35}, {"text": "H2O2", "start": 134, "end": 138}]}}, "schema": []}
{"input": "H., Cameron, E., Gardner, C., Lorca, G., Gonzalez, C.", "output": {"entities": {}}, "schema": []}
{"input": "F.", "output": {"entities": {}}, "schema": []}
{"input": "Lactobacillus johnsonii inhibits indoleamine 2, 3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.", "output": {"entities": {"chemical": [{"text": "indoleamine", "start": 33, "end": 44}, {"text": "tryptophan", "start": 73, "end": 83}]}}, "schema": []}
{"input": "Roughening of Pt nanoparticles induced by surface-oxide formation.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 14, "end": 16}, {"text": "oxide", "start": 50, "end": 55}]}}, "schema": []}
{"input": "Using density functional theory (DFT) and thermodynamic considerations we studied the equilibrium shape of Pt nanoparticles (NPs) under electrochemical conditions.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 107, "end": 109}]}}, "schema": []}
{"input": "We found that at very high oxygen coverage, obtained at high electrode potentials, the experimentally-observed tetrahexahedral (THH) NPs consist of high-index (520) faces.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 27, "end": 33}]}}, "schema": []}
{"input": "Since high-index surfaces often show higher (electro-) chemical activity in comparison to their close-packed counterparts, the THH NPs can be promising candidates for various (electro-) catalytic applications.", "output": {"entities": {}}, "schema": []}
{"input": "Sample solution constraints on motor-driven diagnostic nanodevices.", "output": {"entities": {}}, "schema": []}
{"input": "The last decade has seen appreciable advancements in efforts towards increased portability of lab-on-a-chip devices by substituting microfluidics with molecular motor-based transportation.", "output": {"entities": {}}, "schema": []}
{"input": "As of now, first proof-of-principle devices have analyzed protein mixtures of low complexity, such as target protein molecules in buffer solutions optimized for molecular motor performance.", "output": {"entities": {}}, "schema": []}
{"input": "However, in a diagnostic work-up, lab-on-a-chip devices need to be compatible with complex biological samples.", "output": {"entities": {}}, "schema": []}
{"input": "While it has been shown that such samples do not interfere with crucial steps in molecular diagnostics (for example antibody-antigen recognition), their effect on molecular motors is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "This critical and long overlooked issue is addressed here.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, we studied the effects of blood, cell lysates and solutions containing genomic DNA extracts on actomyosin and kinesin-microtubule-based transport, the two biomolecular motor systems that are most promising for lab-on-a-chip applications.", "output": {"entities": {}}, "schema": []}
{"input": "We found that motor function is well preserved at defined dilutions of most of the investigated biological samples and demonstrated a molecular motor-driven label-free blood type test.", "output": {"entities": {}}, "schema": []}
{"input": "Our results support the feasibility of molecular-motor driven nanodevices for diagnostic point-of-care applications and also demonstrate important constraints imposed by sample composition and device design that apply both to kinesin-microtubule and actomyosin driven applications.", "output": {"entities": {}}, "schema": []}
{"input": "Enhancing catalytic selectivity of supported metal nanoparticles with capping ligands.", "output": {"entities": {}}, "schema": []}
{"input": "Enhancing catalytic selectivity of supported metal nanoparticles with capping ligands is demonstrated using an Au/SiO (2) catalyst in liquid phase aerobic oxidation of benzyl alcohol.", "output": {"entities": {"chemical": [{"text": "Au", "start": 111, "end": 113}, {"text": "SiO (2)", "start": 114, "end": 121}, {"text": "benzyl alcohol", "start": 168, "end": 182}]}}, "schema": []}
{"input": "Chemisorption of an appropriate amount of polyvinylpyrrolidone on the Au/SiO (2) catalyst greatly enhances the benzaldehyde selectivity from 43% to ~ 100% and its yield from 4. 9% to 7. 2%.", "output": {"entities": {"chemical": [{"text": "polyvinylpyrrolidone", "start": 42, "end": 62}, {"text": "Au", "start": 70, "end": 72}, {"text": "SiO (2)", "start": 73, "end": 80}, {"text": "benzaldehyde", "start": 111, "end": 123}]}}, "schema": []}
{"input": "Voltage tuning of ferromagnetic resonance with bistable magnetization switching in energy-efficient magnetoelectric composites.", "output": {"entities": {}}, "schema": []}
{"input": "Dual E-and H-field control of microwave performance with enhanced ferromagnetic resonance (FMR) tunability has been demonstrated in microwave composites FeGaB/PZN-PT (011).", "output": {"entities": {"chemical": [{"text": "FeGaB", "start": 153, "end": 158}, {"text": "PZN-PT", "start": 159, "end": 165}]}}, "schema": []}
{"input": "A voltage-impulse-induced non-volatile magnetization switching was also realized in this work, resulting from the hysteretic type of phase transition in PZN-PT (011) at high electric fields.", "output": {"entities": {"chemical": [{"text": "PZN-PT", "start": 153, "end": 159}]}}, "schema": []}
{"input": "The results provide a framework for developing lightweight, energy efficient, voltage-tunable RF/microwave devices.", "output": {"entities": {}}, "schema": []}
{"input": "Halogen bonding: an interim discussion.", "output": {"entities": {"chemical": [{"text": "Halogen", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Halogen bonding is a noncovalent interaction that is receiving rapidly increasing attention because of its significance in biological systems and its importance in the design of new materials in a variety of areas, for example, electronics, nonlinear optical activity, and pharmaceuticals.", "output": {"entities": {"chemical": [{"text": "Halogen", "start": 0, "end": 7}]}}, "schema": []}
{"input": "The interactions can be understood in terms of electrostatics/polarization and dispersion; they involve a region of positive electrostatic potential on a covalently bonded halogen and a negative site, such as the lone pair of a Lewis base.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 172, "end": 179}]}}, "schema": []}
{"input": "The positive potential, labeled a sigma hole, is on the extension of the covalent bond to the halogen, which accounts for the characteristic near-linearity of halogen bonding.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 94, "end": 101}, {"text": "halogen", "start": 159, "end": 166}]}}, "schema": []}
{"input": "In many instances, the lateral sides of the halogen have negative electrostatic potentials, allowing it to also interact favorably with positive sites.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 44, "end": 51}]}}, "schema": []}
{"input": "In this discussion, after looking at some of the experimental observations of halogen bonding, we address the origins of sigma holes, the factors that govern the magnitudes of their electrostatic potentials, and the properties of the resulting complexes with negative sites.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 78, "end": 85}]}}, "schema": []}
{"input": "The relationship of halogen and hydrogen bonding is examined.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 20, "end": 27}, {"text": "hydrogen", "start": 32, "end": 40}]}}, "schema": []}
{"input": "We also point out that sigma-hole interactions are not limited to halogens, but can also involve covalently bonded atoms of Groups IV-VI.", "output": {"entities": {"chemical": [{"text": "halogens", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Examples of applications in biological/medicinal chemistry and in crystal engineering are mentioned, taking note that halogen bonding can be \" tuned \" to fit various requirements, that is, strength of interaction, steric factors, and so forth.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 118, "end": 125}]}}, "schema": []}
{"input": "STEPS: a grid search methodology for optimized peptide identification filtering of MS/MS database search results.", "output": {"entities": {}}, "schema": []}
{"input": "For bottom-up proteomics, there are wide variety of database-searching algorithms in use for matching peptide sequences to tandem MS spectra.", "output": {"entities": {}}, "schema": []}
{"input": "Likewise, there are numerous strategies being employed to produce a confident list of peptide identifications from the different search algorithm outputs.", "output": {"entities": {}}, "schema": []}
{"input": "Here we introduce a grid-search approach for determining optimal database filtering criteria in shotgun proteomics data analyses that is easily adaptable to any search.", "output": {"entities": {}}, "schema": []}
{"input": "Systematic Trial and Error Parameter Selection--referred to as STEPS--utilizes user-defined parameter ranges to test a wide array of parameter combinations to arrive at an optimal \" parameter set \" for data filtering, thus maximizing confident identifications.", "output": {"entities": {}}, "schema": []}
{"input": "The benefits of this approach in terms of numbers of true-positive identifications are demonstrated using datasets derived from immunoaffinity-depleted blood serum and a bacterial cell lysate, two common proteomics sample types.", "output": {"entities": {}}, "schema": []}
{"input": "Proteomic methods reveal cyclophilin a function as a host restriction factor against rotavirus infection.", "output": {"entities": {}}, "schema": []}
{"input": "Rotavirus (RV) infection is the main cause of acute dehydrating diarrhea in infants and young children below 5 years old worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "RV infection causes a global shutoff of host proteins as many other viruses do.", "output": {"entities": {}}, "schema": []}
{"input": "However, previous studies revealed that RV could selectively upregulated the expression of some host proteins that then played important roles in RV infection.", "output": {"entities": {}}, "schema": []}
{"input": "To globally explor such host proteins that were upregulated in early human rotavirus (HRV) infection, proteomic methods were used and a total of ten upregulated host proteins were unambiguously identified.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclophilin A (CYPA), a peptidyl-prolyl cis-trans isomerase, was among these upregulated host proteins.", "output": {"entities": {"chemical": [{"text": "prolyl", "start": 33, "end": 39}]}}, "schema": []}
{"input": "Following infection, CYPA was recruited to the viroplasm and interacted with HRV structural protein VP2; CYPA reduced host susceptibility to HRV infection and inhibited replication of HRV by repressing the expression of viral proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we found that the increased expression of CYPA in enterocytes of small intestine correlated to the period when BALB/c mice became resistant to RV diarrhea.", "output": {"entities": {}}, "schema": []}
{"input": "Together, we identified CYPA as a novel host restriction factor that confered protection against RV infection and might contribute to host susceptibility to RV diarrhea.", "output": {"entities": {}}, "schema": []}
{"input": "A fluorescent \" allosteric scorpionand \" complex visualizes a biological recognition event.", "output": {"entities": {}}, "schema": []}
{"input": "We describe a new class of fluorescent reporter and its employment to visualize the biotin/avidin binding interaction.", "output": {"entities": {"chemical": [{"text": "biotin", "start": 84, "end": 90}]}}, "schema": []}
{"input": "Derivatives of the azamacrocycle cyclam that contain a pendant naphthalimide dye are inherently fluorescent when zinc (II) is coordinated.", "output": {"entities": {"chemical": [{"text": "cyclam", "start": 33, "end": 39}, {"text": "naphthalimide", "start": 63, "end": 76}, {"text": "zinc (II)", "start": 113, "end": 122}]}}, "schema": []}
{"input": "Introducing a second pendant group--biotin--affords an unsymmetrical bis-triazole-scorpionand ligand that interacts specifically with avidin.", "output": {"entities": {"chemical": [{"text": "biotin", "start": 36, "end": 42}, {"text": "bis-triazole", "start": 69, "end": 81}]}}, "schema": []}
{"input": "This ligand has been assembled by using a one-pot \" double-click \" strategy and complexed with copper (II) and zinc (II).", "output": {"entities": {"chemical": [{"text": "copper (II)", "start": 95, "end": 106}, {"text": "zinc (II)", "start": 111, "end": 120}]}}, "schema": []}
{"input": "The zinc (II) complex is fluorescent, and its fluorescence output changes in the presence of avidin.", "output": {"entities": {"chemical": [{"text": "zinc (II)", "start": 4, "end": 13}]}}, "schema": []}
{"input": "Upon avidin binding, the fluorescence output is diminished by interaction with the protein, at [complex]/[avidin] ratios of up to 4: 1.", "output": {"entities": {}}, "schema": []}
{"input": "The observed change might arise from a specific quenching effect in the biotin binding pocket or from a binding-induced change in the coordination geometry of the complex.", "output": {"entities": {"chemical": [{"text": "biotin", "start": 72, "end": 78}]}}, "schema": []}
{"input": "Promiscuous catalysis of asymmetric Michael-type additions of linear aldehydes to beta-nitrostyrene by the proline-based enzyme 4-oxalocrotonate tautomerase.", "output": {"entities": {"chemical": [{"text": "aldehydes", "start": 69, "end": 78}, {"text": "beta-nitrostyrene", "start": 82, "end": 99}, {"text": "proline", "start": 107, "end": 114}, {"text": "4-oxalocrotonate", "start": 128, "end": 144}]}}, "schema": []}
{"input": "Exploiting catalytic promiscuity: The proline-based enzyme 4-oxalocrotonate tautomerase (4-OT) promiscuously catalyzes asymmetric Michael-type additions of linear aldehydes--ranging from acetaldehyde to octanal--to trans-beta-nitrostyrene in aqueous solvent.", "output": {"entities": {"chemical": [{"text": "proline", "start": 38, "end": 45}, {"text": "4-oxalocrotonate", "start": 59, "end": 75}, {"text": "4-OT", "start": 89, "end": 93}, {"text": "aldehydes", "start": 163, "end": 172}, {"text": "acetaldehyde", "start": 187, "end": 199}, {"text": "octanal", "start": 203, "end": 210}, {"text": "trans-beta-nitrostyrene", "start": 215, "end": 238}]}}, "schema": []}
{"input": "The presence of 1. 4 mol% of 4-OT effected formation of the anticipated gamma-nitroaldehydes in fair to good yields with dr values of up to 93: 7 and ee values of up to 81%.", "output": {"entities": {"chemical": [{"text": "4-OT", "start": 29, "end": 33}, {"text": "gamma-nitroaldehydes", "start": 72, "end": 92}]}}, "schema": []}
{"input": "Successful application of an ionic liquid carrying the fluoride counter-ion in biomacromolecular chemistry: microwave-assisted acylation of cellulose in the presence of 1-allyl-3-methylimidazolium fluoride/DMSO mixtures.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 55, "end": 63}, {"text": "1-allyl-3-methylimidazolium fluoride", "start": 169, "end": 205}, {"text": "DMSO", "start": 206, "end": 210}]}}, "schema": []}
{"input": "The use of ionic liquids with fluoride anion (IL-F) is challenging because of side reactions.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 30, "end": 38}]}}, "schema": []}
{"input": "Neat 1-allyl-3-methylimidazolium fluoride (AlMeImF) is used as a solvent in microwave-assisted acylation of cellulose.", "output": {"entities": {"chemical": [{"text": "1-allyl-3-methylimidazolium fluoride", "start": 5, "end": 41}, {"text": "AlMeImF", "start": 43, "end": 50}]}}, "schema": []}
{"input": "The results are disappointing due to side reactions in the IL proper, and F (-)-mediated hydrolysis of the produced ester.", "output": {"entities": {"chemical": [{"text": "F (-)", "start": 74, "end": 79}, {"text": "ester", "start": 116, "end": 121}]}}, "schema": []}
{"input": "A dramatic improvement is observed, when AlMeImF/DMSO mixture is employed.", "output": {"entities": {"chemical": [{"text": "AlMeImF", "start": 41, "end": 48}, {"text": "DMSO", "start": 49, "end": 53}]}}, "schema": []}
{"input": "The results are comparable to those obtained when pure 1-allyl-3-methylimidazolium chloride is employed.", "output": {"entities": {"chemical": [{"text": "1-allyl-3-methylimidazolium chloride", "start": 55, "end": 91}]}}, "schema": []}
{"input": "FTIR spectroscopy shows that dissolving a carboxylic acid anhydride in IL-F leads to the formation of acyl fluoride.", "output": {"entities": {"chemical": [{"text": "carboxylic acid anhydride", "start": 42, "end": 67}, {"text": "acyl fluoride", "start": 102, "end": 115}]}}, "schema": []}
{"input": "Thus ILs are far from being \" spectator \" solvents.", "output": {"entities": {}}, "schema": []}
{"input": "The new approach (use of IL-F/DMSO) is attractive because of its efficiency, low cost, and applicability to the derivatization of any polymer.", "output": {"entities": {"chemical": [{"text": "DMSO", "start": 30, "end": 34}]}}, "schema": []}
{"input": "Semisynthesis and myocardial activity of thaliporphine N-homologues.", "output": {"entities": {"chemical": [{"text": "thaliporphine N", "start": 41, "end": 56}]}}, "schema": []}
{"input": "The N-homologues and optical isomers of thaliporphine (5a), a potent antiarrhythmic agent, were prepared starting from laurolitsine (1), an abundant aporphine present in Phoebe formosana.", "output": {"entities": {"chemical": [{"text": "N", "start": 4, "end": 5}, {"text": "thaliporphine", "start": 40, "end": 53}, {"text": "laurolitsine", "start": 119, "end": 131}, {"text": "aporphine", "start": 149, "end": 158}]}}, "schema": []}
{"input": "Treating N-propylnorglaucine with 90% H2SO4 yielded one additional product, an 11-sulfonyl-1, 11-anhydroaporphine.", "output": {"entities": {"chemical": [{"text": "N-propylnorglaucine", "start": 9, "end": 28}, {"text": "H2SO4", "start": 38, "end": 43}, {"text": "11-sulfonyl-1, 11-anhydroaporphine", "start": 79, "end": 113}]}}, "schema": []}
{"input": "Reaction of N-formylnorglaucine (3a) with 90% H2SO4, however, yielded the 9-sulfonyl-seco product as a major product.", "output": {"entities": {"chemical": [{"text": "N-formylnorglaucine", "start": 12, "end": 31}, {"text": "H2SO4", "start": 46, "end": 51}, {"text": "9-sulfonyl-seco", "start": 74, "end": 89}]}}, "schema": []}
{"input": "Treatment of 3a with 98% H2SO4 yielded pancordine (10), which, upon catalytic hydrogenation, yielded (+/-)-wilsonirine.", "output": {"entities": {"chemical": [{"text": "H2SO4", "start": 25, "end": 30}, {"text": "(+/-)-wilsonirine", "start": 101, "end": 118}]}}, "schema": []}
{"input": "(1) H NMR spectroscopic analysis was applied successfully to monitor the optical purity of the crystalline salt while undertaking optical resolution.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Thaliporphine (5a) was demonstrated to possess better positive inotropic and less negative chronotropic effects than the left-hand optical isomer and showed the best activity on rat cardiac tissue among the N-homologues prepared.", "output": {"entities": {"chemical": [{"text": "Thaliporphine", "start": 0, "end": 13}, {"text": "N", "start": 207, "end": 208}]}}, "schema": []}
{"input": "Surface transformations of Bioglass 45S5 during scaffold synthesis for bone tissue engineering.", "output": {"entities": {"chemical": [{"text": "Bioglass 45S5", "start": 27, "end": 40}]}}, "schema": []}
{"input": "In physiological fluid, a layer of hydroxycarbonate apatite, similar to bone mineral, develops on the surface of Bioglass 45S5.", "output": {"entities": {"chemical": [{"text": "hydroxycarbonate apatite", "start": 35, "end": 59}, {"text": "Bioglass 45S5", "start": 113, "end": 126}]}}, "schema": []}
{"input": "Collagen from the surrounding tissue is adsorbed on this layer that attracts osteoblasts, and favors bone regrowth.", "output": {"entities": {}}, "schema": []}
{"input": "Bioglass is therefore an osteoinductive material.", "output": {"entities": {}}, "schema": []}
{"input": "Still, due to its brittleness, the glass alone cannot be used to heal large bone defects.", "output": {"entities": {}}, "schema": []}
{"input": "To overcome this issue, Bioglass is used to form a composite scaffold with poly (D, L-lactide) (PDLLA), a biodegradable polymer.", "output": {"entities": {"chemical": [{"text": "poly (D, L-lactide)", "start": 75, "end": 94}, {"text": "PDLLA", "start": 96, "end": 101}]}}, "schema": []}
{"input": "The goal of this work is to understand Bioglass reactivity throughout scaffold fabrication via a low-temperature route, the solvent casting and particulate leaching technique.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in Bioglass (especially its surface) are susceptible to occur both while in contact with the processing fluids and potentially through a reaction with the surrounding polymeric matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Here we analyzed the surface changes of three different Bioglass samples: (i) as-received, (ii) treated in solutions that parallel those used in scaffold fabrication, and (iii) extracted from the scaffolds.", "output": {"entities": {}}, "schema": []}
{"input": "We showed that extracted, just like treated, Bioglass deviates from the as-received, but to a larger extent.", "output": {"entities": {}}, "schema": []}
{"input": "X-ray photoelectron and infrared spectroscopy support the theory that Bioglass surface was modified not just through contact with the solutions in scaffold fabrication, but upon an interaction with the polymeric matrix.", "output": {"entities": {}}, "schema": []}
{"input": "The polymer network slows down the Na (+)/H (+) exchange between Bioglass and water used to leach salt particles to create pores within the scaffold.", "output": {"entities": {"chemical": [{"text": "Na (+)", "start": 35, "end": 41}, {"text": "H (+)", "start": 42, "end": 47}]}}, "schema": []}
{"input": "Changes in surface properties affect the bioactivity of Bioglass and thus of the composite scaffolds, and are therefore critical to identify.", "output": {"entities": {}}, "schema": []}
{"input": "Plasmonic coupling and long-range transfer of an excitation along a DNA nanowire.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate an excitation transfer along a fluorescently labeled dsDNA nanowire over a length of several micrometers.", "output": {"entities": {}}, "schema": []}
{"input": "Launching of the excitation is done by exciting a localized surface plasmon mode of a 40 nm silver nanoparticle by 800 nm femtosecond laser pulses via two-photon absorption.", "output": {"entities": {"chemical": [{"text": "silver", "start": 92, "end": 98}]}}, "schema": []}
{"input": "The plasmonic mode is subsequently coupled or transformed to excitation in the nanowire in contact with the particle and propagated along it, inducing bleaching of the dyes on its way.", "output": {"entities": {}}, "schema": []}
{"input": "In situ as well as ex situ fluorescence microscopy is utilized to observe the phenomenon.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, transfer of the excitation along the nanowire to another nanoparticle over a separation of 5. 7 mu m was clearly observed.", "output": {"entities": {}}, "schema": []}
{"input": "The nature of the excitation coupling and transfer could not be fully resolved here, but injection of an electron into the DNA from the excited nanoparticle and subsequent coupled transfer of charge (Dexter) and delocalized exciton (Frenkel) is the most probable mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "However, a direct plasmonic or optical coupling and energy transfer along the nanowire cannot be totally ruled out either.", "output": {"entities": {}}, "schema": []}
{"input": "By further studies the observed phenomenon could be utilized in novel molecular systems, providing a long-needed communication method between molecular devices.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure.", "output": {"entities": {"chemical": [{"text": "LY2090314", "start": 88, "end": 97}]}}, "schema": []}
{"input": "LY2090314 (3-[9-fluoro-2-(piperidin-1-ylcarbonyl)-1, 2, 3, 4-tetrahydro [1, 4] diazepino [6, 7, 1-hi] indol-7-yl]-4-imidazo [1, 2-a] pyridin-3-yl-1H-pyrrole-2, 5-dione) is an intravenous glycogen synthase kinase-3 inhibitor in oncology trials.", "output": {"entities": {"chemical": [{"text": "LY2090314", "start": 0, "end": 9}, {"text": "3-[9-fluoro-2-(piperidin-1-ylcarbonyl)-1, 2, 3, 4-tetrahydro [1, 4] diazepino [6, 7, 1-hi] indol-7-yl]-4-imidazo [1, 2-a] pyridin-3-yl-1H-pyrrole-2, 5-dione", "start": 11, "end": 167}]}}, "schema": []}
{"input": "Drug disposition was characterized after intravenous infusion of [(14) C] LY2090314 to rats and dogs, and was related to available clinical data.", "output": {"entities": {"chemical": [{"text": "[(14) C] LY2090314", "start": 65, "end": 83}]}}, "schema": []}
{"input": "LY2090314 exhibited high clearance (approximating hepatic blood flow) and a moderate volume of distribution (~ 1-2 l/kg) resulting in rapid elimination (half-life ~ 0. 4, 0. 7, and 1. 8-3. 4 hours in rats, dogs, and humans, respectively).", "output": {"entities": {"chemical": [{"text": "LY2090314", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Scaled clearance from liver microsomes accurately predicted perfusion-limited clearance across species.", "output": {"entities": {}}, "schema": []}
{"input": "LY2090314 was cleared by extensive metabolism, and the numerous metabolites were rapidly excreted into feces via bile (69-97% of dose; 62-93% within 0-24 hours); urinary recovery of drug-related material was low (<= 3% of dose).", "output": {"entities": {"chemical": [{"text": "LY2090314", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Despite extensive metabolism, in rats and humans the parent compound was the sole identifiable drug-related moiety in plasma.", "output": {"entities": {}}, "schema": []}
{"input": "Even in Mdr1a-, Bcrp-, and Mrp2-knockout rats, LY2090314 metabolites did not appear in circulation, and their urinary excretion was not enhanced, because the hypothesized impaired biliary excretion of metabolites in the absence of these canalicular transporters was not observed.", "output": {"entities": {"chemical": [{"text": "LY2090314", "start": 47, "end": 56}]}}, "schema": []}
{"input": "Canine metabolite disposition was generally similar, with the notable exception of dog-unique LY2090314 glucuronide.", "output": {"entities": {"chemical": [{"text": "LY2090314 glucuronide", "start": 94, "end": 115}]}}, "schema": []}
{"input": "This conjugate was formed in the dog liver and was preferentially excreted into the blood, where it accounted for the majority of circulating radioactivity at later times, and was predominantly recovered in urine (16% of dose).", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, LY2090314 was rapidly cleared by extensive metabolism with negligible circulating metabolite exposures due to biliary excretion of metabolites into feces with no apparent intestinal reabsorption.", "output": {"entities": {"chemical": [{"text": "LY2090314", "start": 15, "end": 24}]}}, "schema": []}
{"input": "Three new phenolic compounds from the roots of Glycyrrhiza yunnanensis.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 10, "end": 18}]}}, "schema": []}
{"input": "Three new phenolic compounds (1-3), together with 16 known compounds (4-19), were isolated from the roots of Glycyrrhiza yunnanensis Cheng f.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 10, "end": 18}]}}, "schema": []}
{"input": "et L.", "output": {"entities": {}}, "schema": []}
{"input": "K.", "output": {"entities": {}}, "schema": []}
{"input": "Dai.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of 1D and 2D NMR, HR-ESI-MS, and circular dichroism (CD) spectroscopic analysis, structures of the new compounds were elucidated as 2-(2'-methoxy-4'-hydroxy)-aryl-3-methy-6-hydroxy-benzofuran (1), (2S)-6, 7-(2, 2-dimethyldihydropyrano)-8-prenyl-4'-hydroxyflavanone (2), and 6-prenyl-7, 3', 4'-trihydroxyflavone (3).", "output": {"entities": {"chemical": [{"text": "2-(2'-methoxy-4'-hydroxy)-aryl-3-methy-6-hydroxy-benzofuran", "start": 145, "end": 204}, {"text": "(2S)-6, 7-(2, 2-dimethyldihydropyrano)-8-prenyl-4'-hydroxyflavanone", "start": 210, "end": 277}, {"text": "6-prenyl-7, 3', 4'-trihydroxyflavone", "start": 287, "end": 323}]}}, "schema": []}
{"input": "Compounds 1, 3, 5, 12, 14, 15 and 16 showed antioxidant activity by an ABTS-based assay.", "output": {"entities": {"chemical": [{"text": "ABTS", "start": 71, "end": 75}]}}, "schema": []}
{"input": "Identification of aldo-keto reductases as NRF2-target marker genes in human cells.", "output": {"entities": {}}, "schema": []}
{"input": "Transcription factor NF-E2-related factor 2 (NRF2) plays a crucial role in the cellular defense against oxidative/electrophilic stress by up-regulating multiple antioxidant genes.", "output": {"entities": {}}, "schema": []}
{"input": "Numerous studies with genetically modified animals have demonstrated that Nrf2 is a sensitivity determining factor upon the exposure to environmental chemicals including carcinogens.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, recent studies have demonstrated that polymorphism in the human NRF2 promoter is associated with higher risks for developing acute lung injury, gastric mucosal inflammation, and nephritis.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the identification of reliable and effective human target genes of NRF2 may allow the monitoring of NRF2 activity and to predict individual sensitivity to environmental stress-induced damage.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, we investigated genes that are tightly controlled by NRF2 to establish markers for NRF2 activity in human cells.", "output": {"entities": {}}, "schema": []}
{"input": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 166, "end": 178}, {"text": "tert-butylhydroquinone", "start": 180, "end": 202}, {"text": "cinnamic aldehyde", "start": 204, "end": 221}, {"text": "hydrogen peroxide", "start": 227, "end": 244}]}}, "schema": []}
{"input": "Accordantly, the basal and inducible expressions of AKRs were significantly attenuated in NRF2-silenced HK-2 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas, cells with stable KEAP1 knockdown, which causes a modest NRF2 activation, demonstrated substantially increased levels of AKR1A1, 1B1, 1B10, 1C1, 1C2, and 1C3.", "output": {"entities": {}}, "schema": []}
{"input": "Secondly, the linkage between NRF2 and the AKRs was confirmed in human monocytic leukemia cell line U937, which can be a model of peripherally available blood cells.", "output": {"entities": {}}, "schema": []}
{"input": "The treatment of U937 cells with NRF2 inducers including sulforaphane effectively elevated the expression of AKR1B1, 1B10, 1C1, 1C2, and 1C3.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 57, "end": 69}]}}, "schema": []}
{"input": "Whereas, the levels of both the basal and sulforaphane-inducible expression of AKR1C1 were significantly reduced in NRF2-silenced stable U937 cells compared to the control cells.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 42, "end": 54}]}}, "schema": []}
{"input": "Similarly, the inducible expression of AKR1C1 was observed in another human monocytic leukemia cell line THP-1 as well as in human primary blood CD14 (+) monocytes.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, together with the high inducibility and NRF2 dependency shown in renal epithelial cells as well as in peripherally available blood cells, current findings suggest that AKRs can be utilized as a marker of NRF2 activity in human cells.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial dysfunction contributes to the cytotoxicity of some 3, 5-bis (benzylidene)-4-piperidone derivatives in colon HCT-116 cells.", "output": {"entities": {"chemical": [{"text": "3, 5-bis (benzylidene)-4-piperidone", "start": 66, "end": 101}]}}, "schema": []}
{"input": "The objectives of this study are to investigate the possible ways by which the curcumin analogs 2a and 2b exert their antiproliferative properties.", "output": {"entities": {}}, "schema": []}
{"input": "The analogs 2a and 2b have submicromolar IC (50) values towards human HCT-116 colon cancer cells but are far less toxic to human non-malignant CRL-1790 colon cells.", "output": {"entities": {}}, "schema": []}
{"input": "Both compounds affected a number of mitochondrial functions in HCT-116 cells namely increasing the intracellular concentrations of reactive oxygen species, inhibiting oxygen consumption and decreasing the mitochondrial membrane potential.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 140, "end": 146}, {"text": "oxygen", "start": 167, "end": 173}]}}, "schema": []}
{"input": "These molecules also produced swelling of isolated rat liver mitochondria, supporting a mitochondrial mechanism of cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Both compounds reacted with glutathione in the presence of glutathione S-transferase pi and hence they may be classified as thiol alkylators.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 28, "end": 39}, {"text": "glutathione S", "start": 59, "end": 72}, {"text": "thiol", "start": 124, "end": 129}]}}, "schema": []}
{"input": "Preparation of apigenin nanocrystals using supercritical antisolvent process for dissolution and bioavailability enhancement.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 15, "end": 23}]}}, "schema": []}
{"input": "The aim of the study was to investigate the potential of nanocrystals to enhance the oral bioavailability of apigenin (AP), a bioactive flavonoid with various pharmacological activities but poor aqueous solubility.", "output": {"entities": {"chemical": [{"text": "apigenin", "start": 109, "end": 117}, {"text": "flavonoid", "start": 136, "end": 145}]}}, "schema": []}
{"input": "In the present investigation, the AP nanocrystals were prepared by the supercritical antisolvent process.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro characterization was performed by scanning electron microscopy, FT-IR, differential scanning calorimetry, X-ray powder diffractometry.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro dissolution of prepared nanocrystals was studied and compared with untreated coarse powder.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the pharmacokinetic study of AP nanocrystals, in comparison to coarse powder, was also performed in rats after a single oral dose.", "output": {"entities": {}}, "schema": []}
{"input": "The prepared AP nanocrystals, without change in crystalline structure, appeared in spherical shape with particle size of about 400-800 nm.", "output": {"entities": {}}, "schema": []}
{"input": "The reduction of particle size resulted in a more rapid dissolution of AP from nanocrystals than from coarse powder.", "output": {"entities": {}}, "schema": []}
{"input": "In comparison to coarse powder, AP nanocrystals exhibited a significantly decreased t (max), a 3. 6-fold higher peak plasma concentration (C (max)) and 3. 4-fold higher area under the curve (AUC).", "output": {"entities": {}}, "schema": []}
{"input": "Effects of tris (1, 3-dichloro-2-propyl) phosphate and triphenyl phosphate on receptor-associated mRNA expression in zebrafish embryos/larvae.", "output": {"entities": {"chemical": [{"text": "tris (1, 3-dichloro-2-propyl) phosphate", "start": 11, "end": 50}, {"text": "triphenyl phosphate", "start": 55, "end": 74}]}}, "schema": []}
{"input": "Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) are frequently detected in biota, including fish.", "output": {"entities": {"chemical": [{"text": "Tris (1, 3-dichloro-2-propyl) phosphate", "start": 0, "end": 39}, {"text": "TDCPP", "start": 41, "end": 46}, {"text": "triphenyl phosphate", "start": 52, "end": 71}, {"text": "TPP", "start": 73, "end": 76}]}}, "schema": []}
{"input": "However, knowledge of the toxicological and molecular effects of these currently used flame retardants is limited.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, an in vivo screening approach was developed to evaluate effects of TDCPP and TPP on developmental endpoints and receptor-associated expression of mRNA in zebrafish embryos/larvae.", "output": {"entities": {"chemical": [{"text": "TDCPP", "start": 89, "end": 94}, {"text": "TPP", "start": 99, "end": 102}]}}, "schema": []}
{"input": "Exposure to TDCPP or TPP resulted in significantly smaller rates of hatching and survival, in dose-and time-dependent manners.", "output": {"entities": {"chemical": [{"text": "TDCPP", "start": 12, "end": 17}, {"text": "TPP", "start": 21, "end": 24}]}}, "schema": []}
{"input": "The median lethal concentration (LC (50)) was 7. 0 mg/L for TDCPP and 29. 6 mg/L for TPP at 120 hour post-fertilization (hpf).", "output": {"entities": {"chemical": [{"text": "TDCPP", "start": 60, "end": 65}, {"text": "TPP", "start": 85, "end": 88}]}}, "schema": []}
{"input": "Real-time PCR revealed alterations in expression of mRNAs involved in aryl hydrocarbon receptors (AhRs)-, peroxisome proliferator-activated receptor alpha (PPAR alpha)-, estrogenic receptors (ERs)-, thyroid hormone receptor alpha (TR alpha)-, glucocorticoid receptor (GR)-, and mineralocorticoid receptor (MR)-centered gene networks.", "output": {"entities": {"chemical": [{"text": "aryl hydrocarbon", "start": 70, "end": 86}, {"text": "thyroid hormone", "start": 199, "end": 214}]}}, "schema": []}
{"input": "Exposure to positive control chemicals significantly altered abundances of mRNA in corresponding receptor-centered gene networks, a result that suggests that it is feasible to use zebrafish embryos/larvae to evaluate effects of chemicals on mRNA expression in these gene networks.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to TDCPP altered transcriptional profiles in all six receptor-centered gene networks, thus exerting multiple toxic effects.", "output": {"entities": {"chemical": [{"text": "TDCPP", "start": 12, "end": 17}]}}, "schema": []}
{"input": "TPP was easily metabolized and its potency to change expression of mRNA involved in receptor-centered gene networks was weaker than that of TDCPP.", "output": {"entities": {"chemical": [{"text": "TPP", "start": 0, "end": 3}, {"text": "TDCPP", "start": 140, "end": 145}]}}, "schema": []}
{"input": "The PPAR alpha-and TR alpha-centered gene networks might be the primary pathways affected by TPP.", "output": {"entities": {"chemical": [{"text": "TPP", "start": 93, "end": 96}]}}, "schema": []}
{"input": "Taken together, these results demonstrated that TDCPP and TPP could alter mRNA expression of genes involved in the six receptor-centered gene networks in zebrafish embryos/larvae, and TDCPP seemed to have higher potency in changing the mRNA expression of these genes.", "output": {"entities": {"chemical": [{"text": "TDCPP", "start": 48, "end": 53}, {"text": "TPP", "start": 58, "end": 61}, {"text": "TDCPP", "start": 184, "end": 189}]}}, "schema": []}
{"input": "Lipid composition of Chlorella vulgaris (Trebouxiophyceae) as a function of different cadmium and phosphate concentrations.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 86, "end": 93}, {"text": "phosphate", "start": 98, "end": 107}]}}, "schema": []}
{"input": "Fatty acids are the fundamental structural components of membrane lipids, and the degree of saturation of the long hydrocarbon chains in microalgae contributes to regulation of growth, biomass production and reproduction of aquatic consumers.", "output": {"entities": {"chemical": [{"text": "Fatty acids", "start": 0, "end": 11}, {"text": "hydrocarbon", "start": 115, "end": 126}]}}, "schema": []}
{"input": "This research aimed at evaluating the effects of cadmium (2 x 10 (-8); 10 (-7) mol L (-1) Cd) on lipid class and fatty acid composition of the microalga Chlorella vulgaris under varying phosphate (PO (4) (3-)) concentrations (6. 0 x 10 (-7) to 2. 3 x 10 (-4) mol L (-1)).", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 49, "end": 56}, {"text": "Cd", "start": 90, "end": 92}, {"text": "fatty acid", "start": 113, "end": 123}, {"text": "phosphate", "start": 186, "end": 195}, {"text": "PO (4) (3-)", "start": 197, "end": 208}]}}, "schema": []}
{"input": "Under PO (4) (3-) limitation and Cd stress, the storage lipid class triacylglycerol (TAG) was the most accumulated among the lipid classes.", "output": {"entities": {"chemical": [{"text": "PO (4) (3-)", "start": 6, "end": 17}, {"text": "Cd", "start": 33, "end": 35}, {"text": "triacylglycerol", "start": 68, "end": 83}, {"text": "TAG", "start": 85, "end": 88}]}}, "schema": []}
{"input": "Fatty acid composition revealed that the degree of saturation increased with increasing Cd stress and PO (4) (3-) limitation.", "output": {"entities": {"chemical": [{"text": "Fatty acid", "start": 0, "end": 10}, {"text": "Cd", "start": 88, "end": 90}, {"text": "PO (4) (3-)", "start": 102, "end": 113}]}}, "schema": []}
{"input": "Decreasing PO (4) (3-) and increasing Cd concentrations resulted in higher saturated fatty acid (SAFA) and monounsaturated FA (MUFA) concentrations.", "output": {"entities": {"chemical": [{"text": "PO (4) (3-)", "start": 11, "end": 22}, {"text": "Cd", "start": 38, "end": 40}, {"text": "saturated fatty acid", "start": 75, "end": 95}, {"text": "SAFA", "start": 97, "end": 101}, {"text": "monounsaturated FA", "start": 107, "end": 125}, {"text": "MUFA", "start": 127, "end": 131}]}}, "schema": []}
{"input": "Total polyunsaturated FA (PUFA) and omega 3 PUFA, and PUFA: SAFA ratios were higher in the control (2. 3 x 10 (-4) mol L (-1) PO (4) (3-)) cells than in either PO (4) (3-) limitation or Cd stress, or in the combination of both stresses.", "output": {"entities": {"chemical": [{"text": "polyunsaturated FA", "start": 6, "end": 24}, {"text": "PUFA", "start": 26, "end": 30}, {"text": "omega 3 PUFA", "start": 36, "end": 48}, {"text": "PUFA", "start": 54, "end": 58}, {"text": "SAFA", "start": 60, "end": 64}, {"text": "PO (4) (3-)", "start": 126, "end": 137}, {"text": "PO (4) (3-)", "start": 160, "end": 171}, {"text": "Cd", "start": 186, "end": 188}]}}, "schema": []}
{"input": "Contrasting with all the other PUFAs, 18: 2n-6 increased as PO (4) (3-) limitation increased.", "output": {"entities": {"chemical": [{"text": "PUFAs", "start": 31, "end": 36}, {"text": "PO (4) (3-)", "start": 60, "end": 71}]}}, "schema": []}
{"input": "A significant positive relationship of PUFAs, acetone mobile polar lipids (AMPL) and phospholipids (PL) with phosphate concentration in the culture media was obtained, while TAG concentrations had a positive association with total MUFA and SAFA.", "output": {"entities": {"chemical": [{"text": "PUFAs", "start": 39, "end": 44}, {"text": "acetone", "start": 46, "end": 53}, {"text": "phosphate", "start": 109, "end": 118}, {"text": "TAG", "start": 174, "end": 177}, {"text": "MUFA", "start": 231, "end": 235}, {"text": "SAFA", "start": 240, "end": 244}]}}, "schema": []}
{"input": "Total SAFA, 14: 0, 18: 1n-9 and 18: 2n-6 were positively correlated with Cd and negatively with PO (4) (3-) concentrations.", "output": {"entities": {"chemical": [{"text": "SAFA", "start": 6, "end": 10}, {"text": "Cd", "start": 73, "end": 75}, {"text": "PO (4) (3-)", "start": 96, "end": 107}]}}, "schema": []}
{"input": "The microalga responded to combined PO (4) (3-) limitation and Cd exposure by increasing its total lipid production and significantly altering its lipid composition.", "output": {"entities": {"chemical": [{"text": "PO (4) (3-)", "start": 36, "end": 47}, {"text": "Cd", "start": 63, "end": 65}]}}, "schema": []}
{"input": "The FA 18: 2n-6 may be considered a stress biomarker for PO (4) (3-) limitation and Cd stress in C. vulgaris.", "output": {"entities": {"chemical": [{"text": "PO (4) (3-)", "start": 57, "end": 68}, {"text": "Cd", "start": 84, "end": 86}]}}, "schema": []}
{"input": "Mammalian complex I pumps 4 protons per 2 electrons at high and physiological proton motive force in living cells.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force.", "output": {"entities": {"chemical": [{"text": "NADH", "start": 65, "end": 69}, {"text": "ubiquinone", "start": 89, "end": 99}]}}, "schema": []}
{"input": "The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H (+)/2e (-)) but it has been suggested that stoichiometry may be 3H (+)/2e (-) based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data.", "output": {"entities": {"chemical": [{"text": "4H (+)", "start": 85, "end": 91}, {"text": "3H (+)", "start": 152, "end": 158}]}}, "schema": []}
{"input": "Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD (+) and ubiquinol/ubiquinone pools.", "output": {"entities": {"chemical": [{"text": "NADH", "start": 209, "end": 213}, {"text": "NAD (+)", "start": 214, "end": 221}, {"text": "ubiquinol", "start": 226, "end": 235}, {"text": "ubiquinone", "start": 236, "end": 246}]}}, "schema": []}
{"input": "Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc (1) complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H (+)/2e (-) in mouse and human cells at high and physiological proton motive force.", "output": {"entities": {"chemical": [{"text": "4H (+)", "start": 229, "end": 235}]}}, "schema": []}
{"input": "Probing circulating tumor cells in microfluidics.", "output": {"entities": {}}, "schema": []}
{"input": "Circulating tumor cells (CTCs) are important targets for study as we strive to better understand, diagnose, and treat cancers.", "output": {"entities": {}}, "schema": []}
{"input": "However, CTCs are found in blood at extremely low concentrations; this makes isolation, enrichment, and characterization of CTCs technically challenging.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, the development of CTC separation devices has grown rapidly in both academia and industry.", "output": {"entities": {}}, "schema": []}
{"input": "Part of this development effort centered on microfluidic platforms, exploiting the advantages of microfluidics to improve CTC separation performance and device integration.", "output": {"entities": {}}, "schema": []}
{"input": "In this Focus article, we highlight some of the recent work in microfluidic CTC separation and detection systems and discuss our appraisal of what the field should do next.", "output": {"entities": {}}, "schema": []}
{"input": "The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage.", "output": {"entities": {"chemical": [{"text": "caffeic acid", "start": 24, "end": 36}, {"text": "rosmarinic acid", "start": 41, "end": 56}, {"text": "t-BHP", "start": 105, "end": 110}]}}, "schema": []}
{"input": "Perilla frutescens leaves are often used in East Asian gourmet food.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated the hepatoprotective effects of caffeic acid (CA), rosmarinic acid (RA), and their combination.", "output": {"entities": {"chemical": [{"text": "caffeic acid", "start": 63, "end": 75}, {"text": "rosmarinic acid", "start": 82, "end": 97}]}}, "schema": []}
{"input": "P. frutescens contains 1. 32 mu g CA/mg dry material (DM) and 26. 84 mu g RA/mg DM analyzed by HPLC-DAD and HPLC-MS.", "output": {"entities": {}}, "schema": []}
{"input": "CA remarkably reduced the oxidative damage than rosmarinic acid in an in vitro study.", "output": {"entities": {"chemical": [{"text": "rosmarinic acid", "start": 48, "end": 63}]}}, "schema": []}
{"input": "Oral intubation with CA or RA alone for five days was conducted prior to treatment with a single dose of tert-butyl hydroperoxide (0. 5mmol/kg b. w., i. p.), which led to a significant reduction of indicators of hepatic toxicity, such as aspartate aminotransferase, alanine aminotransferase, oxidized glutathione, lipid peroxidation and enzyme activities related to antioxidant such as catalase, glutathione peroxidase and superoxide dismutase.", "output": {"entities": {"chemical": [{"text": "tert-butyl hydroperoxide", "start": 105, "end": 129}, {"text": "aspartate", "start": 238, "end": 247}, {"text": "alanine", "start": 266, "end": 273}, {"text": "oxidized glutathione", "start": 292, "end": 312}, {"text": "glutathione", "start": 396, "end": 407}, {"text": "superoxide", "start": 423, "end": 433}]}}, "schema": []}
{"input": "Interestingly, compared to treatment with CA or RA alone, a combination of both compounds more increased the endogenous antioxidant enzymes and glutathione (GSH) and decreased lipid peroxidation in livers.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 144, "end": 155}]}}, "schema": []}
{"input": "These results suggest that CA from perilla leaves plays a role in the increased hepatic GSH concentration, and shows an additive hepatic protection with RA against oxidative hepatic damage.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 88, "end": 91}]}}, "schema": []}
{"input": "Effects of silicon on osteoblast activity and bone mineralization of MC3T3-E1 cells.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 11, "end": 18}]}}, "schema": []}
{"input": "Previous studies have reported that dietary silicon (Si) intake is positively associated with bone health including bone mineral density.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 44, "end": 51}, {"text": "Si", "start": 53, "end": 55}]}}, "schema": []}
{"input": "Although the amount of Si intake is high among trace elements in humans, how dietary Si affects bone formation at the cellular level is not well addressed.", "output": {"entities": {"chemical": [{"text": "Si", "start": 23, "end": 25}, {"text": "Si", "start": 85, "end": 87}]}}, "schema": []}
{"input": "The purpose of this study was to investigate the role of Si in osteoblast activity and bone mineralization.", "output": {"entities": {"chemical": [{"text": "Si", "start": 57, "end": 59}]}}, "schema": []}
{"input": "MC3T3-E1 was cultured as mature osteoblasts and treated with sodium metasilicate (0, 1, 5, 10, 25, 50, and 100 mu M) as a source of Si.", "output": {"entities": {"chemical": [{"text": "sodium metasilicate", "start": 61, "end": 80}, {"text": "Si", "start": 132, "end": 134}]}}, "schema": []}
{"input": "After 7 days of treatment, 5 and 10 mu M of sodium metasilicate significantly increased intracellular alkaline phosphatase activity (p < 0. 05) when compared to the control.", "output": {"entities": {"chemical": [{"text": "sodium metasilicate", "start": 44, "end": 63}]}}, "schema": []}
{"input": "Additionally, all doses of sodium metasilicate (1, 5, 10, 25, 50, and 100 mu M) increased mineralized nodule formation at 14 days of differentiation as evidenced by increased Alizarin Red S staining.", "output": {"entities": {"chemical": [{"text": "sodium metasilicate", "start": 27, "end": 46}, {"text": "Alizarin Red S", "start": 175, "end": 189}]}}, "schema": []}
{"input": "In the analysis of gene expression, 50 mu M of sodium metasilicate upregulated type I collagen (COL-I) compared to the control group.", "output": {"entities": {"chemical": [{"text": "sodium metasilicate", "start": 47, "end": 66}]}}, "schema": []}
{"input": "However, the increase of COL-I gene expression as a result of treatment with 1, 10, 25, and 100 mu M of sodium metasilicate did not reach statistical significance.", "output": {"entities": {"chemical": [{"text": "sodium metasilicate", "start": 104, "end": 123}]}}, "schema": []}
{"input": "mRNA expression of insulin-like growth factor-I and receptor activator of NF-kappa B ligand was not significantly changed at any dose of sodium metasilicate (0, 1, 5, 10, 25, 50, and 100 mu M).", "output": {"entities": {"chemical": [{"text": "sodium metasilicate", "start": 137, "end": 156}]}}, "schema": []}
{"input": "In light of the results, we conclude that Si has a positive effect on bone metabolism by enhancing osteoblast mineralization activity.", "output": {"entities": {"chemical": [{"text": "Si", "start": 42, "end": 44}]}}, "schema": []}
{"input": "Ruxolitinib: a new treatment option for myelofibrosis.", "output": {"entities": {"chemical": [{"text": "Ruxolitinib", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Myelofibrosis is a myeloproliferative neoplasm characterized by bone marrow fibrosis and extramedullary hematopoiesis.", "output": {"entities": {}}, "schema": []}
{"input": "Evolution of myelofibrosis can lead to life-threatening complications, including transformation to leukemia, thrombotic events, and hemorrhagic episodes.", "output": {"entities": {}}, "schema": []}
{"input": "The only curative therapy for myelofibrosis is allogeneic hematopoietic stem cell transplantation.", "output": {"entities": {}}, "schema": []}
{"input": "Because this disease manifests primarily in the older population, many patients diagnosed with myelofibrosis are not considered medically fit for such aggressive therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Other available medical therapies do not halt disease progression; instead, current treatment strategies have focused on targeting specific symptomology, although with limited efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "The lack of effective treatment options for patients with myelofibrosis has rendered this orphan disease state an unmet medical need, and novel approaches to improve outcomes are necessary.", "output": {"entities": {}}, "schema": []}
{"input": "Emerging research has identified numerous molecular mutations in patients with myelofibrosis, making this disease a potential candidate for molecularly targeted therapy.", "output": {"entities": {}}, "schema": []}
{"input": "The most prevalent mutation identified is a gain-of-function mutation in the Janus kinase (JAK) family, JAK2 V617F, which has been identified in more than half of patients with myelofibrosis.", "output": {"entities": {}}, "schema": []}
{"input": "This mutation results in a constitutively active JAK-signal transducer and activator of transcription pathway resulting in dysregulated cellular proliferation and hematopoiesis.", "output": {"entities": {}}, "schema": []}
{"input": "Ruxolitinib is a small-molecule inhibitor of JAK1 and JAK2 and recently became the first drug approved by the United States Food and Drug Administration for the treatment of symptomatic intermediate-or high-risk myelofibrosis.", "output": {"entities": {"chemical": [{"text": "Ruxolitinib", "start": 0, "end": 11}]}}, "schema": []}
{"input": "In clinical trials, ruxolitinib demonstrated promising efficacy in reducing splenomegaly and myelofibrosis-related symptoms.", "output": {"entities": {"chemical": [{"text": "ruxolitinib", "start": 20, "end": 31}]}}, "schema": []}
{"input": "However, ruxolitinib did not demonstrate disease-modifying potential and is not considered a curative therapeutic option.", "output": {"entities": {"chemical": [{"text": "ruxolitinib", "start": 9, "end": 20}]}}, "schema": []}
{"input": "Adverse events associated with ruxolitinib are primarily hematologic, with thrombocytopenia and anemia being the most common toxicologic events identified.", "output": {"entities": {"chemical": [{"text": "ruxolitinib", "start": 31, "end": 42}]}}, "schema": []}
{"input": "Future research will shed light on whether ruxolitinib in combination with other treatments will further enhance outcomes in myelofibrosis.", "output": {"entities": {"chemical": [{"text": "ruxolitinib", "start": 43, "end": 54}]}}, "schema": []}
{"input": "Prevalence of and factors that influence board certification among pharmacy practice faculty at United States colleges and schools of pharmacy.", "output": {"entities": {}}, "schema": []}
{"input": "Board certification is a means of demonstrating expertise above the minimum licensing standards.", "output": {"entities": {}}, "schema": []}
{"input": "For many health care professionals, this credential is a necessity.", "output": {"entities": {}}, "schema": []}
{"input": "As pharmacists become involved in more advanced patient care services, board certification becomes an essential component to ensuring quality care.", "output": {"entities": {}}, "schema": []}
{"input": "The prevalence of United States pharmacy practice faculty members who are board certified, however, is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, to our knowledge, factors that serve to motivate or discourage faculty from obtaining board certification have not been previously described; thus, 900 pharmacy practice faculty members listed in the American Association of Colleges of Pharmacy (AACP) online directory were invited to complete an online survey regarding motivators and barriers for board certification.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, a list of board-certified pharmacists, obtained from the Board of Pharmacy Specialties, was used to check the board certification status of all pharmacy practice faculty members listed in the AACP directory.", "output": {"entities": {}}, "schema": []}
{"input": "In 2011, the prevalence of board certification among the 2867 pharmacy practice faculty members was 37% (1063 pharmacists), with the highest prevalence found among assistant professors (39. 4%). A total of 322 faculty members (36% response rate) completed the survey; of these, 308 self-identified as pharmacy practice faculty, and their responses were included in the analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Current board certification in pharmacy specialties was reported by 163 respondents (52. 9%); 14 (4. 5%) were previously certified.", "output": {"entities": {}}, "schema": []}
{"input": "Among the 308 respondents, the most common perceived reason why pharmacy practice faculty become board certified was the desire to be recognized as an expert in the field (71. 5%).", "output": {"entities": {}}, "schema": []}
{"input": "Those who were currently board certified indicated personal growth as the most important reason (60. 1%).", "output": {"entities": {}}, "schema": []}
{"input": "Those previously certified indicated no perceived benefit as the most common reason for not recertifying (71. 4%).", "output": {"entities": {}}, "schema": []}
{"input": "Among those never certified, no perceived need (52. 0%) or benefit (44. 8%) were the most common reasons for not becoming certified; however, a majority of those never certified (68%) stated that they would become board certified if there was no associated cost and they were confident they would pass.", "output": {"entities": {}}, "schema": []}
{"input": "To increase the prevalence of board certification in pharmacy practice faculty at U. S. schools and colleges of pharmacy, the benefits of this credential must be addressed at each institution.", "output": {"entities": {}}, "schema": []}
{"input": "Steps should be taken to assist and encourage board certification.", "output": {"entities": {}}, "schema": []}
{"input": "Tuning optical properties of Si quantum dots by pi-conjugated capping molecules.", "output": {"entities": {"chemical": [{"text": "Si", "start": 29, "end": 31}]}}, "schema": []}
{"input": "The absorption and photoluminescence (PL) properties of silicon quantum dots (QDs) are greatly influenced by their size and surface chemistry.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 56, "end": 63}]}}, "schema": []}
{"input": "Herein, we examined the optical properties of three Si QDs with increasing sigma-pi conjugation length: octyl-, (trimethylsilyl) vinyl-, and 2-phenylvinyl-capped Si QDs.", "output": {"entities": {"chemical": [{"text": "Si", "start": 52, "end": 54}, {"text": "octyl", "start": 104, "end": 109}, {"text": "(trimethylsilyl) vinyl", "start": 112, "end": 134}, {"text": "2-phenylvinyl", "start": 141, "end": 154}, {"text": "Si", "start": 162, "end": 164}]}}, "schema": []}
{"input": "The PL photon energy obtained from as-prepared samples decreased by 0. 1-0. 3 eV, while the PL excitation (PLE) extended from 360 nm (octyl-capped Si QDs) to 400 nm (2-phenylvinyl-capped Si QDs).", "output": {"entities": {"chemical": [{"text": "octyl", "start": 134, "end": 139}, {"text": "Si", "start": 147, "end": 149}, {"text": "2-phenylvinyl", "start": 166, "end": 179}, {"text": "Si", "start": 187, "end": 189}]}}, "schema": []}
{"input": "A vibrational PL feature was observed in all samples with an energy separation of about 0. 192 +/- 0. 013 eV, which was explained based on electron-phonon coupling.", "output": {"entities": {}}, "schema": []}
{"input": "After soft oxidization through drying, all samples showed blue PL with maxima at approximately 410 nm.", "output": {"entities": {}}, "schema": []}
{"input": "A similar high-energy peak was observed with the bare Si QD sample.", "output": {"entities": {"chemical": [{"text": "Si", "start": 54, "end": 56}]}}, "schema": []}
{"input": "The changes in the optical properties of Si QDs were mainly explained by the formation of additional states arising from the strong sigma-pi conjugation and QD oxidation.", "output": {"entities": {"chemical": [{"text": "Si", "start": 41, "end": 43}]}}, "schema": []}
{"input": "Hypoxia-selective O6-alkylguanine-DNA alkyltransferase inhibitors: design, synthesis, and evaluation of 6-(benzyloxy)-2-(aryldiazenyl)-9H-purines as prodrugs of O6-benzylguanine.", "output": {"entities": {"chemical": [{"text": "O6-alkylguanine", "start": 18, "end": 33}, {"text": "6-(benzyloxy)-2-(aryldiazenyl)-9H-purines", "start": 104, "end": 145}, {"text": "O6-benzylguanine", "start": 161, "end": 177}]}}, "schema": []}
{"input": "O (6)-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein which removes alkyl groups from the O-6 position of guanine, thereby providing strong resistance to anticancer agents which alkylate this position.", "output": {"entities": {"chemical": [{"text": "O (6)-Alkylguanine", "start": 0, "end": 18}, {"text": "guanine", "start": 122, "end": 129}]}}, "schema": []}
{"input": "The clinical usefulness of these anticancer agents would be substantially augmented if AGT could be selectively inhibited in tumor tissue, without a corresponding depletion in normal tissue.", "output": {"entities": {}}, "schema": []}
{"input": "We report the synthesis of a new AGT inhibitor (5c) which selectively depletes AGT in hypoxic tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "Morphological control via chemical and shear forces in block copolymer self-assembly in the lab-on-chip.", "output": {"entities": {}}, "schema": []}
{"input": "We investigate the effects of variation in chemical conditions (solvent composition, water content, polymer concentration, and added salt) on the morphologies formed by PS-b-PAA in DMF/dioxane/water mixtures in a two-phase gas-liquid segmented microfluidic reactor.", "output": {"entities": {"chemical": [{"text": "PS-b-PAA", "start": 169, "end": 177}, {"text": "DMF", "start": 181, "end": 184}, {"text": "dioxane", "start": 185, "end": 192}]}}, "schema": []}
{"input": "The differences in morphologies between off-chip and on-chip self-assembly and on-chip morphological trends for different chemical conditions are explained by the interplay of top-down shear effects (coalescence and breakup) and bottom-up chemical forces.", "output": {"entities": {}}, "schema": []}
{"input": "Using off-chip morphology results, we construct a water content-solvent composition phase diagram showing disordered, sphere, cylinder, and vesicle regions.", "output": {"entities": {}}, "schema": []}
{"input": "On-chip morphologies are found to deviate from off-chip morphologies by three identified shear-induced paths: 1) sphere-to-cylinder, and 2) sphere-to-vesicle transitions, both via shear-induced coalescence when initial micelle sizes are small, and 3) cylinder-to-sphere transitions via shear-induced breakup when initial micelle sizes are large (high capillary number conditions).", "output": {"entities": {}}, "schema": []}
{"input": "These pathways contribute to the generation of large extended bilayer aggregates uniquely on-chip, at either increased polymer or salt concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively these results demonstrate the broad utility of top-down directed molecular self-assembly in conjunction with chemical forces to control morphology and size of polymer colloids at the nanoscale.", "output": {"entities": {}}, "schema": []}
{"input": "Versatile biofunctionalization of polypeptide-based thermosensitive hydrogels via click chemistry.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we report thermosensitive hydrogels based on poly (ethylene glycol)-block-poly (gamma-propargyl-l-glutamate) (PEG-PPLG).", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol)-block-poly (gamma-propargyl-l-glutamate)", "start": 60, "end": 123}, {"text": "PEG-PPLG", "start": 125, "end": 133}]}}, "schema": []}
{"input": "(13) C NMR spectra, DLS, and circular dichroism spectra were employed to study the mechanism of the sol-gel phase transition.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Mouse fibroblast L929 cells were encapsulated and cultured within the hydrogel matrices, and the encapsulated cells were shown to be highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibilities.", "output": {"entities": {}}, "schema": []}
{"input": "The mass loss of the hydrogels in vitro was accelerated by the presence of proteinase K compared to the control group.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo biocompatibility studies revealed that the in situ formed gels in the subcutaneous layer last for ~ 21 days, and H & E staining study suggested acceptable biocompatibility of our materials in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of alkynyl side groups in the PEG-PPLG copolymers allowed convenient further functionalization with azide-modified bioactive molecules, such as biotin and galactose.", "output": {"entities": {"chemical": [{"text": "alkynyl", "start": 16, "end": 23}, {"text": "PEG-PPLG", "start": 43, "end": 51}, {"text": "azide", "start": 113, "end": 118}, {"text": "biotin", "start": 157, "end": 163}, {"text": "galactose", "start": 168, "end": 177}]}}, "schema": []}
{"input": "The biofunctionalized PEG-polypeptide block copolymers showed sol-gel phase transitions similar to the parent copolymers.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 22, "end": 25}]}}, "schema": []}
{"input": "Interestingly, the incorporation of galactose groups into the hydrogels was found to improve cell adhesion, likely due to the adsorption of fibronectin (FN) in cell-extracellular matrix (ECM).", "output": {"entities": {"chemical": [{"text": "galactose", "start": 36, "end": 45}]}}, "schema": []}
{"input": "Because bioactive materials have shown unique advantages in biomedical applications, especially tissue engineering and regenerative medicine applications, we believe our novel functionalizable thermosensitive hydrogels have potential to serve as a versatile platform for the development of new biofunctional materials, for example, bioadhesive and bioresponsive hydrogels.", "output": {"entities": {}}, "schema": []}
{"input": "Surface and tribological behaviors of the bioinspired polydopamine thin films under dry and wet conditions.", "output": {"entities": {"chemical": [{"text": "polydopamine", "start": 54, "end": 66}]}}, "schema": []}
{"input": "Dopamine is a \" sticky \" biomolecule containing the typical functional groups of mussel adhesive proteins.", "output": {"entities": {"chemical": [{"text": "Dopamine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "It can self-polymerize into a nanoscale thin film on various surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the surface, adhesion, friction, and cracking properties of polydopamine (PDA) thin films for their effective transfer to functional devices and biocompatible coatings.", "output": {"entities": {"chemical": [{"text": "polydopamine", "start": 76, "end": 88}, {"text": "PDA", "start": 90, "end": 93}]}}, "schema": []}
{"input": "A series of surface characterizations and mechanical tests were performed to reveal the static and dynamic properties of PDA films coated on glass, polydimethylsiloxane (PDMS), and epoxy.", "output": {"entities": {"chemical": [{"text": "PDA", "start": 121, "end": 124}, {"text": "polydimethylsiloxane", "start": 148, "end": 168}, {"text": "PDMS", "start": 170, "end": 174}, {"text": "epoxy", "start": 181, "end": 186}]}}, "schema": []}
{"input": "We found that PDA films are highly hydrated under wet conditions because of their porous membrane-like nanostructures and hydrophilic functional groups.", "output": {"entities": {"chemical": [{"text": "PDA", "start": 14, "end": 17}]}}, "schema": []}
{"input": "Upon dehydration, the films form cracks when they are coated on soft substrates due to internal stresses and the large mismatch in elastic modulus.", "output": {"entities": {}}, "schema": []}
{"input": "The adhesive pull-off force or the effective work of adhesion increased with the contact time, suggesting dynamic interactions at the interface.", "output": {"entities": {}}, "schema": []}
{"input": "A significant decrease in friction forces in water was observed on all three material surfaces coated with PDA; thus, the film might serve as a water-based lubrication coating.", "output": {"entities": {"chemical": [{"text": "PDA", "start": 107, "end": 110}]}}, "schema": []}
{"input": "We attributed the different behavior of PDA films in air and in water to its hydration effects.", "output": {"entities": {"chemical": [{"text": "PDA", "start": 40, "end": 43}]}}, "schema": []}
{"input": "These research findings provide insight into the stability, mechanical, and adhesive properties of the PDA films, which are critical for their applications.", "output": {"entities": {"chemical": [{"text": "PDA", "start": 103, "end": 106}]}}, "schema": []}
{"input": "Fine Needle Aspiration of Thyroid Nodules with Macrocalcification.", "output": {"entities": {}}, "schema": []}
{"input": "Background: The presence of microcalcification is highly suggestive of malignancy; however, the association of macrocalcification with cancer remains unclear and controversial.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to evaluate the diagnostic yield and accuracy of ultrasound (US)-guided fine needle aspiration (FNA) of thyroid nodules with macrocalcification and to investigate the association between macrocalcification subtype and malignancy risk.", "output": {"entities": {}}, "schema": []}
{"input": "Methods: We retrospectively reviewed sonographic findings and pathologic results of thyroid nodules with macrocalcification in patients who underwent US-guided FNA in our hospital from January 2009 through December 2010.", "output": {"entities": {}}, "schema": []}
{"input": "Inclusion criteria were as follows: (a) malignant or benign nodules confirmed on histologic examination of surgical specimens after US-guided FNA and (b) nodules not histologically confirmed that were subjected to FNA at least twice and follow-up US examinations for 2 years.", "output": {"entities": {}}, "schema": []}
{"input": "Thyroid nodules with macrocalcification were classified into 4 groups: smooth total (eggshell) calcification, smooth partial calcification, irregular calcification, and nodular calcification.", "output": {"entities": {}}, "schema": []}
{"input": "Diagnostic yield of FNA for thyroid nodules with macrocalcification was determined by cytology.", "output": {"entities": {}}, "schema": []}
{"input": "Sensitivity, specificity, and diagnostic accuracy of preoperative FNA cytology were calculated and compared with those of histologic examination of surgical specimens.", "output": {"entities": {}}, "schema": []}
{"input": "Results: There were 188 nodules with macrocalcification in 167 patients; of these, 95 were benign, 80 were malignant, and 13 were nondiagnostic.", "output": {"entities": {}}, "schema": []}
{"input": "Diagnostic yield of FNA for thyroid nodules with macrocalcification was 93. 08%.", "output": {"entities": {}}, "schema": []}
{"input": "Sensitivity, specificity, positive predictive value, and negative predictive value were 98. 51%, 90. 91%, 95. 65%, and 96. 77%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The false-positive value and false-negative value were 9. 09% and 1. 49%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The diagnostic accuracy was 96%.", "output": {"entities": {}}, "schema": []}
{"input": "There was no statistically significant difference in the association between macrocalcification subtype and malignancy risk (P > 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: Macrocalcification associated with thyroid nodules is not a reliable criterion for malignancy.", "output": {"entities": {}}, "schema": []}
{"input": "FNA of thyroid nodules with macrocalcification had significantly high diagnostic yield and reliable accuracy.", "output": {"entities": {}}, "schema": []}
{"input": "Consistency between FNA and histology was almost perfect.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, FNA is a good screening method for malignancy of thyroid nodules with macrocalcification.", "output": {"entities": {}}, "schema": []}
{"input": "Virtual walls based on oil-repellent surfaces for low-surface-tension liquids.", "output": {"entities": {}}, "schema": []}
{"input": "Manipulating and controlling water-based aqueous solutions with the use of virtual walls is relatively simple compared to that of nonaqueous low-surface-tension liquids, which pose greater challenges to microfluidic devices.", "output": {"entities": {}}, "schema": []}
{"input": "This letter reports a novel technique to form a virtual wall for various low-surface-tension liquids.", "output": {"entities": {}}, "schema": []}
{"input": "A microfluidic channel with virtual walls has been made to guide low-surface-tension liquids by using a specially designed oil-repellent surface.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike generic superoleophobic surfaces, our oil-repellent surface exhibited strong repellency to the lateral flow of low-surface-tension liquids such as hexadecane and dodecane.", "output": {"entities": {"chemical": [{"text": "hexadecane", "start": 154, "end": 164}, {"text": "dodecane", "start": 169, "end": 177}]}}, "schema": []}
{"input": "A plasma-assisted surface micromachining process has been utilized to form the oil-repellent surface.", "output": {"entities": {}}, "schema": []}
{"input": "The use of combined features of re-entrant geometries on the surface played an important role in promoting its repellence to the lateral flow of low-surface-tension liquids.", "output": {"entities": {}}, "schema": []}
{"input": "We have successfully demonstrated how low-surface-tension liquids can be well confined by the virtual walls.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of Coumarin and Neoflavone Derivatives as HCV NS5B Polymerase Inhibitors.", "output": {"entities": {"chemical": [{"text": "Coumarin", "start": 14, "end": 22}, {"text": "Neoflavone", "start": 27, "end": 37}]}}, "schema": []}
{"input": "Coumarins and coumestans represent an important family of compounds with diverse pharmacological properties.", "output": {"entities": {"chemical": [{"text": "Coumarins", "start": 0, "end": 9}, {"text": "coumestans", "start": 14, "end": 24}]}}, "schema": []}
{"input": "We recently identified coumestans as novel inhibitors of hepatitis C virus NS5B polymerase and predicted their binding in thumb pocket-1 (TP-1) of NS5B.", "output": {"entities": {"chemical": [{"text": "coumestans", "start": 23, "end": 33}]}}, "schema": []}
{"input": "As the coumarins are structurally related to coumestans by virtue of their common A-and B-rings, we postulated them to also exhibit similar binding interaction with NS5B and inhibit its polymerase function.", "output": {"entities": {"chemical": [{"text": "coumarins", "start": 7, "end": 16}, {"text": "coumestans", "start": 45, "end": 55}]}}, "schema": []}
{"input": "We therefore investigated 24 coumarin and neoflavone derivatives as candidate NS5B inhibitors and identified 14 compounds inhibiting NS5B polymerase activity with IC50 values between 17 and 63 mu m.", "output": {"entities": {"chemical": [{"text": "coumarin", "start": 29, "end": 37}, {"text": "neoflavone", "start": 42, "end": 52}]}}, "schema": []}
{"input": "Of these, the newly synthesized 6, 8-diallyl-5, 7-dihydroxycoumarin (8a) was produced in three steps in high chemical yield from floroglucinol and found to be the most potent of this series, exhibiting activity similar to the reference coumestan LQB-34.", "output": {"entities": {"chemical": [{"text": "6, 8-diallyl-5, 7-dihydroxycoumarin", "start": 32, "end": 67}, {"text": "floroglucinol", "start": 129, "end": 142}, {"text": "coumestan LQB-34", "start": 236, "end": 252}]}}, "schema": []}
{"input": "The binding site of 8a was mapped to TP-1 of NS5B by counter screening against P495L NS5B mutant, employed as a screen for TP-1 site binders.", "output": {"entities": {}}, "schema": []}
{"input": "NS5B-TP-1-8a interaction map provided insight into 8a binding and offered clues for future SAR optimization.", "output": {"entities": {}}, "schema": []}
{"input": "Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation.", "output": {"entities": {"chemical": [{"text": "Trimethylamine-N-oxide", "start": 0, "end": 22}]}}, "schema": []}
{"input": "Circulating trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis.", "output": {"entities": {"chemical": [{"text": "trimethylamine-N-oxide", "start": 12, "end": 34}, {"text": "TMAO", "start": 36, "end": 40}]}}, "schema": []}
{"input": "We now examine genetic, dietary, and hormonal factors regulating TMAO levels.", "output": {"entities": {"chemical": [{"text": "TMAO", "start": 65, "end": 69}]}}, "schema": []}
{"input": "We demonstrate that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO.", "output": {"entities": {"chemical": [{"text": "flavin", "start": 24, "end": 30}, {"text": "trimethylamine", "start": 85, "end": 99}, {"text": "TMA", "start": 101, "end": 104}, {"text": "choline", "start": 144, "end": 151}, {"text": "TMAO", "start": 156, "end": 160}]}}, "schema": []}
{"input": "Further, we show that FMO3 exhibits 10-fold higher specific activity than FMO1.", "output": {"entities": {}}, "schema": []}
{"input": "FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing FMO3 decreases TMAO levels.", "output": {"entities": {"chemical": [{"text": "TMAO", "start": 59, "end": 63}, {"text": "TMAO", "start": 102, "end": 106}]}}, "schema": []}
{"input": "In both humans and mice, hepatic FMO3 expression is reduced in males compared to females.", "output": {"entities": {}}, "schema": []}
{"input": "In mice, this reduction in FMO3 expression is due primarily to downregulation by androgens.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 81, "end": 90}]}}, "schema": []}
{"input": "FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor.", "output": {"entities": {"chemical": [{"text": "bile acids", "start": 38, "end": 48}, {"text": "bile acid", "start": 112, "end": 121}]}}, "schema": []}
{"input": "Analysis of natural genetic variation among inbred strains of mice indicates that FMO3 and TMAO are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis.", "output": {"entities": {"chemical": [{"text": "TMAO", "start": 91, "end": 95}, {"text": "TMAO", "start": 130, "end": 134}]}}, "schema": []}
{"input": "Identification of N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine derivatives and their orally active prodrug esters as dual-acting alpha4-beta1 and alpha4-beta7 receptor antagonists.", "output": {"entities": {"chemical": [{"text": "N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine", "start": 18, "end": 67}, {"text": "esters", "start": 112, "end": 118}]}}, "schema": []}
{"input": "N-Acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine derivatives of type 4 were designed to replace the 2, 6-dichlorobenzoylamine portion of compound 1 in order to identify novel compounds with improved potency against alpha 4-integrins.", "output": {"entities": {"chemical": [{"text": "N-Acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine", "start": 0, "end": 49}, {"text": "2, 6-dichlorobenzoylamine", "start": 101, "end": 126}]}}, "schema": []}
{"input": "Several derivatives were identified as very potent dual-acting alpha 4-integrin, alpha 4 beta 1 and alpha 4 beta 7 antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation of a limited number of prodrug esters led to the discovery of the ethyl ester prodrug 42, which demonstrated good intestinal fluid stability and good permeability.", "output": {"entities": {"chemical": [{"text": "ethyl ester", "start": 80, "end": 91}]}}, "schema": []}
{"input": "Despite low solubility, 42 gave acceptable blood levels of 30 when dosed orally in non-human primates.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, 42 had an overall excellent profile and was selected for clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation of N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine derivatives led to the discovery of several very potent dual-acting alpha 4-integrin antagonists.", "output": {"entities": {"chemical": [{"text": "N-acyl 4-(5-pyrimidine-2, 4-dionyl) phenylalanine", "start": 17, "end": 66}]}}, "schema": []}
{"input": "Ethyl ester prodrug 42 advanced to human clinical trials based on the excellent intestinal fluid stability, good permeability and superior efficacy in non-human primates.", "output": {"entities": {"chemical": [{"text": "Ethyl ester", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Tricycloalternarenes F-H: three new mixed terpenoids produced by an endolichenic fungus Ulocladium sp. using OSMAC method.", "output": {"entities": {"chemical": [{"text": "Tricycloalternarenes F-H", "start": 0, "end": 24}, {"text": "terpenoids", "start": 42, "end": 52}]}}, "schema": []}
{"input": "Three new mixed terpenoids, tricycloalternarenes (TCAs) F-H (1-3), together with ten known tricycloalternarenes (4-13), were isolated from the Czapek' s culture of an endophytic fungus Ulocladium sp.", "output": {"entities": {"chemical": [{"text": "terpenoids", "start": 16, "end": 26}, {"text": "tricycloalternarenes", "start": 28, "end": 48}, {"text": "TCAs", "start": 50, "end": 54}, {"text": "tricycloalternarenes", "start": 91, "end": 111}]}}, "schema": []}
{"input": "Their structures were identified by extensive spectroscopic experiments (NMR and MS) and comparison with literature data.", "output": {"entities": {}}, "schema": []}
{"input": "TCA 1b (5) showed weak activity against the Bacille Calmette-Guerin strain with the MIC of 125 mu g/mL.", "output": {"entities": {"chemical": [{"text": "TCA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "TCA 9b (10) exhibited strong cytotoxic activity against Hela cell line with IC50 of 8. 58 mu M.", "output": {"entities": {"chemical": [{"text": "TCA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Aphagrandinoids A-D, cycloartane triterpenoids with antibacterial activities from Aphanamixis grandifolia.", "output": {"entities": {"chemical": [{"text": "Aphagrandinoids A-D", "start": 0, "end": 19}, {"text": "cycloartane triterpenoids", "start": 21, "end": 46}]}}, "schema": []}
{"input": "Three new cycloartane triterpenoids, aphagrandinoids A-C (1-3), and a new natural product, aphagrandinoid D (4), together with a known compound, were isolated from the leaves and twigs of Aphanamixis grandifolia.", "output": {"entities": {"chemical": [{"text": "cycloartane triterpenoids", "start": 10, "end": 35}, {"text": "aphagrandinoids A-C", "start": 37, "end": 56}, {"text": "aphagrandinoid D", "start": 91, "end": 107}]}}, "schema": []}
{"input": "Their structures were elucidated by extensive NMR and MS techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Aphagrandinoid A (1), a 29-nor-cycloart triterpenoid, features with a sprio ring system at the side chain, while aphagrandinoid C (3) is a pentnortriterpenoid.", "output": {"entities": {"chemical": [{"text": "Aphagrandinoid A", "start": 0, "end": 16}, {"text": "29-nor-cycloart triterpenoid", "start": 24, "end": 52}, {"text": "aphagrandinoid C", "start": 113, "end": 129}, {"text": "pentnortriterpenoid", "start": 139, "end": 158}]}}, "schema": []}
{"input": "Antibacterial activities of these five compounds were also evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1 and 5 showed weak antibacterial activities (MIC values: 1. 57-3. 13 mu g/mL) against Staphylococcus aureus, MRSA 92 (#), and MRSA 98 (#).", "output": {"entities": {}}, "schema": []}
{"input": "What are the physiological estrogens?", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Estradiol (E2) is the principal physiological estrogen in mammals.", "output": {"entities": {"chemical": [{"text": "Estradiol", "start": 0, "end": 9}]}}, "schema": []}
{"input": "E2 and its active metabolites, estrone and estriol have a characteristic phenolic A ring, unlike progesterone, testosterone, cortisol and aldosterone, which have an A ring containing a C3-ketone, a Delta (4) bond and a C19 methyl group.", "output": {"entities": {"chemical": [{"text": "estrone", "start": 31, "end": 38}, {"text": "estriol", "start": 43, "end": 50}, {"text": "progesterone", "start": 97, "end": 109}, {"text": "testosterone", "start": 111, "end": 123}, {"text": "cortisol", "start": 125, "end": 133}, {"text": "aldosterone", "start": 138, "end": 149}, {"text": "ketone", "start": 188, "end": 194}, {"text": "methyl", "start": 223, "end": 229}]}}, "schema": []}
{"input": "Crystal structures of E2 in the estrogen receptor (ER) confirm the importance of the A ring in stabilizing E2 in the ER.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 32, "end": 40}]}}, "schema": []}
{"input": "However, other steroids, including Delta (5)-androstenediol, 5 alpha-androstanediol and 27-hydroxycholesterol, which have a saturated A ring containing a 3 beta-hydroxyl and a C19 methyl group, also mediate physiological responses through binding to estrogen receptor-alpha (ER alpha) and ER beta.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 15, "end": 23}, {"text": "Delta (5)-androstenediol", "start": 35, "end": 59}, {"text": "5 alpha-androstanediol", "start": 61, "end": 83}, {"text": "27-hydroxycholesterol", "start": 88, "end": 109}, {"text": "3 beta-hydroxyl", "start": 154, "end": 169}, {"text": "methyl", "start": 180, "end": 186}, {"text": "estrogen", "start": 250, "end": 258}]}}, "schema": []}
{"input": "Moreover, selective estrogen response modulators (SERMs) with diverse structures also regulate transcription of ER alpha and ER beta.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 20, "end": 28}]}}, "schema": []}
{"input": "Our understanding of the physiological responses mediated by these \" alternative \" estrogens is in its infancy.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 83, "end": 92}]}}, "schema": []}
{"input": "Further studies of the role of these steroids and SERMs in regulating responses mediated by ER alpha and ER beta a variety of tissues, during different stages of development, are likely to uncover additional estrogenic activities.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Perturbation of male sexual behavior in mice (Mus musculus) within a discrete range of perinatal bisphenol-A doses in the context of a high-or low-phytoestrogen diet.", "output": {"entities": {"chemical": [{"text": "bisphenol-A", "start": 97, "end": 108}]}}, "schema": []}
{"input": "Differentiation of masculine and feminine behavior in mammals depends on perinatal sex steroids.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 87, "end": 95}]}}, "schema": []}
{"input": "As bisphenol-A (BPA) can be estrogenic and anti-androgenic, we examined impacts of perinatal exposure upon adult sexual behavior and morphology of male mice.", "output": {"entities": {"chemical": [{"text": "bisphenol-A", "start": 3, "end": 14}, {"text": "BPA", "start": 16, "end": 19}]}}, "schema": []}
{"input": "In Experiment 1, dams were fed either a high-or low-phytoestrogen diet and received daily oral doses of 0, 0. 175, 1. 75, or 17. 5 mu g BPA from gestation day 10 through post-partum day 9.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 136, "end": 139}]}}, "schema": []}
{"input": "Male offspring from the high-phytoestrogen plus 17. 5 mu g BPA condition showed reduced mass of vesicular-coagulating but not other male glands, and showed increased latency to insemination when paired with females.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 59, "end": 62}]}}, "schema": []}
{"input": "In Experiment 2, these procedures were replicated but with all animals fed the high-phytoestrogen diet and perinatal BPA doses of 0, 17. 5, 175, or 1750 mu g/day.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 117, "end": 120}]}}, "schema": []}
{"input": "Adult masses of testes and male-accessory glands and levels of urinary steroids were not significantly affected.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 71, "end": 79}]}}, "schema": []}
{"input": "When males each encountered a sexually receptive female, there were fewer intromissions among those given 17. 5 or 175 mu g and fewer ejaculations among those given 17. 5 mu g, but the 1750 mu g dose had no effect.", "output": {"entities": {}}, "schema": []}
{"input": "Perinatal BPA dosages thus influenced male sexual behavior non-monotonically, with impairment evident in a discrete dose range among males on a high-phytoestrogen diet.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 10, "end": 13}]}}, "schema": []}
{"input": "Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury.", "output": {"entities": {}}, "schema": []}
{"input": "Traumatic brain injury (TBI) induces primary and secondary damage in both the endothelium and the brain parenchyma.", "output": {"entities": {}}, "schema": []}
{"input": "While neurons die quickly by necrosis, a vicious cycle of secondary injury in endothelial cells exacerbates the initial injury.", "output": {"entities": {}}, "schema": []}
{"input": "Thyroid hormones are reported to be decreased in patients with brain injury.", "output": {"entities": {}}, "schema": []}
{"input": "Controlled cortical impact injury (CCI) is a widely used, clinically relevant model of TBI.", "output": {"entities": {}}, "schema": []}
{"input": "Here, using CCI in adult male mice, we set to determine whether 3, 5, 3'-triiodothyronine (T3) attenuates posttraumatic neurodegeneration and neuroinflammation in an experimental model of TBI.", "output": {"entities": {"chemical": [{"text": "3, 5, 3'-triiodothyronine", "start": 64, "end": 89}]}}, "schema": []}
{"input": "Treatment with T3 (1. 2 mu g/100g body weight, i. p.) 1h after TBI resulted in a significant improvement in motor and cognitive recovery after CCI, as well as in marked reduction of lesion volumes.", "output": {"entities": {}}, "schema": []}
{"input": "Mouse model for brain injury showed reactive astrocytes with increased glial fibrillary acidic protein, and formation of inducible nitric oxide synthase (iNOS).", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 131, "end": 143}]}}, "schema": []}
{"input": "Western blot analysis revealed the ability of T3 to reduce brain trauma through modulation of cytoplasmic-nuclear shuttling of nuclear factor-kappa B (NF-kappa B).", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-four hours after brain trauma, T3-treated mice also showed significantly lower number of TUNEL (+) apoptotic neurons and curtailed induction of Bax, compared to vehicle control.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle.", "output": {"entities": {}}, "schema": []}
{"input": "Our data provide an additional mechanism for the anti-inflammatory effects of thyroid hormone with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits.", "output": {"entities": {}}, "schema": []}
{"input": "Lipopolysaccharide-induced acute lung injury in rats: comparative assessment of intratracheal instillation and aerosol inhalation.", "output": {"entities": {}}, "schema": []}
{"input": "Acute lung injury (ALI) has many possible etiopathologies and is characterized by acute diffuse lung damage with poor prognosis.", "output": {"entities": {}}, "schema": []}
{"input": "Lipopolysaccharide (LPS) is widely used as septic model of ALI in pharmacological research.", "output": {"entities": {}}, "schema": []}
{"input": "This study compares intratracheal bolus instillation (IT) with dose-adjusted aerosol inhalation (IH) of LPS in Wistar rats using both non-invasive and terminal endpoints.", "output": {"entities": {}}, "schema": []}
{"input": "The former comprised exhaled nitric oxide (NOE) and' enhanced pause' (Penh) both measured in spontaneous breathing conscious rats.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 29, "end": 41}]}}, "schema": []}
{"input": "Terminal endpoints included lung weights, LDH, protein, total cell counts, and cytodifferentiation in bronchoalveolar lavage (BAL).", "output": {"entities": {}}, "schema": []}
{"input": "Measurements were made 1, 3, 7, and 14 days after IT instillation (5 mg LPS/kg body weight) or 6-hour directed-flow nose-only inhalation exposure to respirable LPS-aerosol at 100 mg/m (3) (thoracic dose: 2. 6 mgLPS/kg body weight).", "output": {"entities": {}}, "schema": []}
{"input": "Controls received saline (IT) or air only (IH).", "output": {"entities": {}}, "schema": []}
{"input": "LDH and protein were significantly different from the control in the LPS-IH group (days 1 and 3) with a somewhat inconclusive outcome in the LPS-IT group due to the effects occurring in the control.", "output": {"entities": {}}, "schema": []}
{"input": "Total cell counts were equally elevated with similar time-course changes in the LPS-IT and-IH groups.", "output": {"entities": {}}, "schema": []}
{"input": "Polymorphonuclear neutrophils (PMNs) were indistinguishable amongst LPS-dosed rats.", "output": {"entities": {}}, "schema": []}
{"input": "Again, IT-dosed control rats displayed markedly higher background levels than those dosed by inhalation.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly NOE was significantly elevated on post-LPS day 1 as was Penh.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, the LPS-aerosol dose delivered by nose-only exposure over 6 h was equally potent as the 2-times higher LPS-IT bolus dose on post-LPS day 1 with somewhat faster recovery thereafter.", "output": {"entities": {}}, "schema": []}
{"input": "The climax and discriminatory power of the non-invasive endpoints matched those determined terminally.", "output": {"entities": {}}, "schema": []}
{"input": "This supports the conclusion that the pharmacological efficacy and side effects of inhalation pharmaceuticals designed to mitigate ALI can better be identified by LPS-aerosol than by LPS-IT.", "output": {"entities": {}}, "schema": []}
{"input": "Non-invasive time-course measurements may deliver apt information both on the efficacious dose as well as the dosing intervals required to maintain the targeted efficacy using a minimum of experimental animals.", "output": {"entities": {}}, "schema": []}
{"input": "The outcome of this comparative study supports the conclusion that the inhalation route produces a more uniform type of injury at lower, more meaningful dosages.", "output": {"entities": {}}, "schema": []}
{"input": "When designing studies for screening of effective drugs this mode of delivery appears to better approximate the human condition with less dosimetric uncertainty, less experimental variability and better characterization of what was actually delivered to the entire respiratory tract.", "output": {"entities": {}}, "schema": []}
{"input": "(-)-Xanthatin up-regulation of the GADD45 gamma tumor suppressor gene in MDA-MB-231 breast cancer cells: role of topoisomerase II alpha inhibition and reactive oxygen species.", "output": {"entities": {"chemical": [{"text": "(-)-Xanthatin", "start": 0, "end": 13}, {"text": "oxygen", "start": 160, "end": 166}]}}, "schema": []}
{"input": "Previously, we reported that (-)-xanthatin, a naturally occurring xanthanolide present in the Cocklebur plant, exhibits potent anti-proliferative effects on human breast cancer cells, accompanied by an induction of the growth arrest and DNA damage-inducible gene 45 gamma (GADD45 gamma), recognized recently as a novel tumor suppressor gene.", "output": {"entities": {"chemical": [{"text": "(-)-xanthatin", "start": 29, "end": 42}, {"text": "xanthanolide", "start": 66, "end": 78}]}}, "schema": []}
{"input": "However, the mechanisms mediating this activation were unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Topoisomerase II alpha (Topo II alpha) inhibition has been reported to produce a cell death response accompanied by an atypical DNA laddering fragmentation profile, similar to that noted previously for (-)-xanthatin.", "output": {"entities": {"chemical": [{"text": "(-)-xanthatin", "start": 202, "end": 215}]}}, "schema": []}
{"input": "Therefore we hypothesized that (-)-xanthatin' s GADD45 gamma activation was mediated through the Topo II alpha pathway.", "output": {"entities": {"chemical": [{"text": "(-)-xanthatin", "start": 31, "end": 44}]}}, "schema": []}
{"input": "Here, we identify that (-)-xanthatin does function as a catalytic inhibitor of Topo II alpha, promoting DNA damage.", "output": {"entities": {"chemical": [{"text": "(-)-xanthatin", "start": 23, "end": 36}]}}, "schema": []}
{"input": "In addition, reactive oxygen species (ROS) were elevated in cells treated with this agent.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 22, "end": 28}]}}, "schema": []}
{"input": "Mechanistically, it was determined that the induced levels of GADD45 gamma mRNA resulting from (-)-xanthatin exposures were stabilized by coordinately produced ROS, and that the consequent induction of GADD45 gamma mRNA, GADD45 gamma protein and ROS generation were abrogated by co-treatment with N-acetyl-l-cysteine.", "output": {"entities": {"chemical": [{"text": "(-)-xanthatin", "start": 95, "end": 108}, {"text": "N-acetyl-l-cysteine", "start": 297, "end": 316}]}}, "schema": []}
{"input": "Taken together, the data support the concept that Topo II alpha inhibition by (-)-xanthatin is a trigger that stimulates expression of DNA damage-inducible GADD45 gamma mRNA and that concomitantly produced ROS act downstream to further enhance the GADD45 gamma mRNA/GADD45 gamma protein induction process, resulting in breast cancer cell death.", "output": {"entities": {"chemical": [{"text": "(-)-xanthatin", "start": 78, "end": 91}]}}, "schema": []}
{"input": "Antioxidant, antimicrobial and anti-proliferative activities of Solanum tuberosum L. var.", "output": {"entities": {}}, "schema": []}
{"input": "Vitelotte.", "output": {"entities": {}}, "schema": []}
{"input": "Solanum tuberosum L. var.", "output": {"entities": {}}, "schema": []}
{"input": "Vitelotte is a potato variety widely used for human consumption.", "output": {"entities": {}}, "schema": []}
{"input": "The pigments responsible for its attractive color belong to the class of anthocyanins.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 73, "end": 85}]}}, "schema": []}
{"input": "The objectives of this study were to characterize and measure the concentration of anthocyanins in pigmented potatoes and to evaluate their antioxidant and antimicrobial activities and their anti-proliferative effects in solid and hematological cancer cell lines.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 83, "end": 95}]}}, "schema": []}
{"input": "Anthocyanins exert anti-bacterial activity against different bacterial strains and a slight activity against three fungal strains.", "output": {"entities": {"chemical": [{"text": "Anthocyanins", "start": 0, "end": 12}]}}, "schema": []}
{"input": "The Gram-positive bacterium Staphylococcus aureus and the fungus Rhyzoctonia solani were the most affected microorganisms.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activities were evaluated by DPPH and FRAP methods; the extract showed a higher reducing capability than anti-radical activity.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 41, "end": 45}]}}, "schema": []}
{"input": "Moreover, we found that in different cancer cell models the anthocyanins cause inhibition of proliferation and apoptosis in a dose dependent manner.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 60, "end": 72}]}}, "schema": []}
{"input": "These biological activities are likely due to the high content of malvidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside and petunidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside.", "output": {"entities": {"chemical": [{"text": "malvidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside", "start": 66, "end": 115}, {"text": "petunidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside", "start": 120, "end": 170}]}}, "schema": []}
{"input": "Asymmetric synthesis and anti-protozoal activity of the 8, 4'-oxyneolignans virolin, surinamensin and analogues.", "output": {"entities": {"chemical": [{"text": "8, 4'-oxyneolignans virolin", "start": 56, "end": 83}, {"text": "surinamensin", "start": 85, "end": 97}]}}, "schema": []}
{"input": "The asymmetric synthesis of 8, 4'-oxyneolignans (-)-virolin, (-)-surinamensin and a number of analogues has been achieved.", "output": {"entities": {"chemical": [{"text": "8, 4'-oxyneolignans (-)-virolin", "start": 28, "end": 59}, {"text": "(-)-surinamensin", "start": 61, "end": 77}]}}, "schema": []}
{"input": "A divergent synthesis was used, with all compounds being elaborated from a single chiral aldehyde derived from ethyl lactate.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 89, "end": 97}, {"text": "ethyl lactate", "start": 111, "end": 124}]}}, "schema": []}
{"input": "In the 15 compounds that were tested, the level of substitution on the A-ring was found to directly influence the activity against Leishmania donovani whilst the activity against Plasmodium falciparum was influenced by numerous substitution and stereochemical factors.", "output": {"entities": {}}, "schema": []}
{"input": "Predictive modeling of insulin release profile from cross-linked chitosan microspheres.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin-loaded microspheres composed of chitosan 3% (w/v), and loading 120 IU insulin were produced by emulsion cross-linking method.", "output": {"entities": {}}, "schema": []}
{"input": "Cross-linking time was 5 h and glutaraldehyde 3. 5% (v/v) was used as cross-linker.", "output": {"entities": {"chemical": [{"text": "glutaraldehyde", "start": 31, "end": 45}]}}, "schema": []}
{"input": "Swelling ratio studies were evaluated to predict release of insulin from chitosan microspheres.", "output": {"entities": {}}, "schema": []}
{"input": "Bacitracin and sodium taurocholate were incorporated in the formulations as proteolytic enzyme inhibitor and absorption enhancer, respectively.", "output": {"entities": {"chemical": [{"text": "Bacitracin", "start": 0, "end": 10}, {"text": "sodium taurocholate", "start": 15, "end": 34}]}}, "schema": []}
{"input": "In vitro insulin release studies were performed in phosphate buffer pH 7. 4 and also in HCl pH 2 with and without trypsin.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 51, "end": 60}, {"text": "HCl", "start": 88, "end": 91}]}}, "schema": []}
{"input": "Activity of bacitracin was also evaluated.", "output": {"entities": {"chemical": [{"text": "bacitracin", "start": 12, "end": 22}]}}, "schema": []}
{"input": "In vitro release showed a controlled profile up to 12 h and the formulation containing 0. 15% (w/v) of bacitracin revealed a maximum biological activity of about 49. 1 +/- 4. 1%.", "output": {"entities": {"chemical": [{"text": "bacitracin", "start": 103, "end": 113}]}}, "schema": []}
{"input": "Mathematical modeling using Higuchi and Korsmeyer-Peppas suggested a non-Fickian diffusion as the mechanism of insulin release.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin-loaded chitosan microspheres for oral delivery showed to be an innovative and reliable delivery system to overcome conventional insulin therapy.", "output": {"entities": {}}, "schema": []}
{"input": "A systematic identification of multiple toxin-target interactions based on chemical, genomic and toxicological data.", "output": {"entities": {}}, "schema": []}
{"input": "Although the assessment of toxicity of various agents,-omics (genomic, proteomic, metabolomic, etc.) data has been accumulated largely, the acquirement of toxicity information of variety of molecules through experimental methods still remains a difficult task.", "output": {"entities": {}}, "schema": []}
{"input": "Presently, a systems toxicology approach that integrates massive diverse chemical, genomic and toxicological information was developed for prediction of the toxin targets and their related networks.", "output": {"entities": {}}, "schema": []}
{"input": "The procedures are: (1) by use of two powerful statistical methods, i. e., support vector machine (SVM) and random forest (RF), a systemic model for prediction of multiple toxin-target interactions using the extracted chemical and genomic features has been developed with its reliability and robustness estimated.", "output": {"entities": {}}, "schema": []}
{"input": "And the qualitative classification of targets according to the phenotypic diseases has been taken into account to further uncover the biological meaning of the targets, as well as to validate the robustness of the in silico models.", "output": {"entities": {}}, "schema": []}
{"input": "(2) Based on the predicted toxin-target interactions, a genome-scale toxin-target-disease network exampled by cardiovascular disease is generated.", "output": {"entities": {}}, "schema": []}
{"input": "(3) A topological analysis of the network is carried out to identify those targets that are most susceptible in human to topical agents including the most critical toxins, as well as to uncover both the toxin-specific mechanisms and pathways.", "output": {"entities": {}}, "schema": []}
{"input": "The methodologies presented herein for systems toxicology will make drug development, toxin environmental risk assessment more efficient, acceptable and cost-effective.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro and ex vivo models of human asthma.", "output": {"entities": {}}, "schema": []}
{"input": "Asthma is an inflammatory disorder of the conducting airways which undergo distinct structural and functional changes leading to non-specific bronchial hyperresponsiveness (BHR) and airflow obstruction that fluctuate over time.", "output": {"entities": {}}, "schema": []}
{"input": "It is a complex disease involving multiple genetic and environmental influences whose multifactorial interactions can result in a range of asthma phenotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Since our understanding of these gene-gene and gene-environment interactions is very poor, this poses a major challenge to the logical development of' models of asthma'.", "output": {"entities": {}}, "schema": []}
{"input": "However, use of cells and tissues from asthmatic donors allows genetic and epigenetic influences to be evaluated and can go some way to reflect the complex interplay between genetic and environmental stimuli that occur in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Current alternative approaches to in vivo animal models involve use of a plethora of systems ranging from very simple models using human cells (e. g. bronchial epithelial cells and fibroblasts) in mono-or co-culture, whole tissue explants (biopsies, muscle strips, bronchial rings) through to in vivo studies in human volunteers.", "output": {"entities": {}}, "schema": []}
{"input": "Asthma research has been greatly facilitated by the introduction of fibreoptic bronchoscopy which is now a commonly used technique in the field of respiratory disease research, allowing collection of biopsy specimens, bronchial brushing samples, and bronchoalveolar lavage fluid enabling use of disease-derived cells and tissues in some of these models.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we will consider the merits and limitations of current models and discuss the potential of tissue engineering approaches through which we aim to advance our understanding of asthma and its treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) on histopathology, oxidative stress, and expression of c-fos, c-jun and p16 in rat stomachs.", "output": {"entities": {"chemical": [{"text": "2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine", "start": 11, "end": 61}, {"text": "PhIP", "start": 63, "end": 67}]}}, "schema": []}
{"input": "2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines (HCAs) generated from overcooking meat at high temperatures.", "output": {"entities": {"chemical": [{"text": "2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine", "start": 0, "end": 50}, {"text": "PhIP", "start": 52, "end": 56}, {"text": "heterocyclic amines", "start": 86, "end": 105}, {"text": "HCAs", "start": 107, "end": 111}]}}, "schema": []}
{"input": "To understand the possible mechanism of PhIP-associated stomach cancer, the effects of PhIP on morphology, oxidative stress, gene expression of c-fos, c-jun and p16 in rat stomachs were investigated.", "output": {"entities": {"chemical": [{"text": "PhIP", "start": 40, "end": 44}, {"text": "PhIP", "start": 87, "end": 91}]}}, "schema": []}
{"input": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control.", "output": {"entities": {"chemical": [{"text": "PhIP", "start": 48, "end": 52}, {"text": "PhIP", "start": 118, "end": 122}, {"text": "superoxide", "start": 167, "end": 177}]}}, "schema": []}
{"input": "With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) PhIP at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control.", "output": {"entities": {"chemical": [{"text": "PhIP", "start": 27, "end": 31}, {"text": "malondialdehyde", "start": 33, "end": 48}, {"text": "MDA", "start": 50, "end": 53}, {"text": "carbonyl", "start": 73, "end": 81}, {"text": "PhIP", "start": 201, "end": 205}]}}, "schema": []}
{"input": "The data indicated that PhIP could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer.", "output": {"entities": {"chemical": [{"text": "PhIP", "start": 24, "end": 28}, {"text": "PhIP", "start": 205, "end": 209}]}}, "schema": []}
{"input": "Diminutive effect on T and B-cell proliferation of non-cytotoxic alpha-santonin derived 1, 2, 3-triazoles: a report.", "output": {"entities": {"chemical": [{"text": "alpha-santonin", "start": 65, "end": 79}, {"text": "1, 2, 3-triazoles", "start": 88, "end": 105}]}}, "schema": []}
{"input": "alpha-Santonin derived new series of 1, 2, 3-triazoles synthesized through Azide-Alkyne Huisgen 1, 3-dipolar cycloaddition reaction between substituted aryl azide and a propargylated alpha-desmotrosantonin were bio-evaluated for their diminutive effect on ConA induced T-cell and LPS induced B-cell proliferation.", "output": {"entities": {"chemical": [{"text": "alpha-Santonin", "start": 0, "end": 14}, {"text": "1, 2, 3-triazoles", "start": 37, "end": 54}, {"text": "Azide-Alkyne", "start": 75, "end": 87}, {"text": "aryl azide", "start": 152, "end": 162}, {"text": "propargylated alpha-desmotrosantonin", "start": 169, "end": 205}]}}, "schema": []}
{"input": "Interestingly, most of the synthesized compounds showed better immunosuppressant activity than alpha-santonin.", "output": {"entities": {"chemical": [{"text": "alpha-santonin", "start": 95, "end": 109}]}}, "schema": []}
{"input": "Triazole derivatives 9, 10, 17, 18, 29, and 30 displayed significant diminutive effect on cell proliferation.", "output": {"entities": {"chemical": [{"text": "Triazole", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Compounds 12 and 13 were found selective against ConA T-cell proliferation exhibiting > 90% inhibition at 1 x 10 (-6) M concentration.", "output": {"entities": {}}, "schema": []}
{"input": "The present study resulted in identification of several triazole derivatives as effective immunosuppressive agents.", "output": {"entities": {"chemical": [{"text": "triazole", "start": 56, "end": 64}]}}, "schema": []}
{"input": "Tributyltin exposure influences predatory behavior, neurotransmitter content and receptor expression in Sebastiscus marmoratus.", "output": {"entities": {"chemical": [{"text": "Tributyltin", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Tributyltin (TBT) is a ubiquitous marine contaminant due to its extensive use as a biocide, fungicide and antifouling agent.", "output": {"entities": {"chemical": [{"text": "Tributyltin", "start": 0, "end": 11}, {"text": "TBT", "start": 13, "end": 16}]}}, "schema": []}
{"input": "However, the neurotoxic effect of TBT has not been extensively studied, especially in marine fish.", "output": {"entities": {"chemical": [{"text": "TBT", "start": 34, "end": 37}]}}, "schema": []}
{"input": "This study was conducted to investigate the effects of TBT (10, 100 and 1000 ng/L) on the predatory behavior of Sebastiscus marmoratus and to look into the mechanism involved.", "output": {"entities": {"chemical": [{"text": "TBT", "start": 55, "end": 58}]}}, "schema": []}
{"input": "The results showed that TBT exposure depressed predatory activity after 50 days exposure.", "output": {"entities": {"chemical": [{"text": "TBT", "start": 24, "end": 27}]}}, "schema": []}
{"input": "Dopamine levels in the fish brains increased in a dose-dependent manner, while 5-hydroxytryptamine and norepinephrine levels decreased significantly in the TBT exposure group compared to the control.", "output": {"entities": {"chemical": [{"text": "Dopamine", "start": 0, "end": 8}, {"text": "5-hydroxytryptamine", "start": 79, "end": 98}, {"text": "norepinephrine", "start": 103, "end": 117}, {"text": "TBT", "start": 156, "end": 159}]}}, "schema": []}
{"input": "The mRNA levels of dopamine receptors, which have functions such as cognition, motor activity, motivation and reward, mood, attention and learning, were significantly down-regulated by TBT exposure.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 19, "end": 27}, {"text": "TBT", "start": 185, "end": 188}]}}, "schema": []}
{"input": "Although the levels of amino acid neurotransmitters, including glutamate, did not show marked alteration, the expression of the glutamatergic signaling pathway such as N-methyl-D-aspartate receptors, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, calmodulin, Ca (2 +)/calmodulin-dependent protein kinases-II and cyclic adenosine monophosphate responsive element binding protein, was significantly reduced by TBT exposure, which indicated that central nerve activities were in a state of depression, thus affecting the predatory activities of the fish.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 23, "end": 33}, {"text": "glutamate", "start": 63, "end": 72}, {"text": "N-methyl-D-aspartate", "start": 168, "end": 188}, {"text": "a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid", "start": 200, "end": 252}, {"text": "Ca (2 +)", "start": 275, "end": 283}, {"text": "cyclic adenosine monophosphate", "start": 328, "end": 358}, {"text": "TBT", "start": 424, "end": 427}]}}, "schema": []}
{"input": "Electrical field stimulation (EFS)-induced relaxations turn into contractions upon removal of extracellular calcium in rat mesenteric artery.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 108, "end": 115}]}}, "schema": []}
{"input": "In the present study, we aimed to examine the effect of blockade of L-type Ca (2 +) channels (LTCC) and in addition the removal of extracellular Ca (2 +), on EFS-induced relaxations in rings of rat mesenteric artery.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 75, "end": 83}, {"text": "Ca (2 +)", "start": 145, "end": 153}]}}, "schema": []}
{"input": "EFS applied to the tissues precontracted with phenylephrine caused relaxations which were markedly inhibited by nifedipine (10 (-7) M) and tetraethylammonium (TEA) (1mM).", "output": {"entities": {"chemical": [{"text": "phenylephrine", "start": 46, "end": 59}, {"text": "nifedipine", "start": 112, "end": 122}, {"text": "tetraethylammonium", "start": 139, "end": 157}, {"text": "TEA", "start": 159, "end": 162}]}}, "schema": []}
{"input": "Addition of LTCC opener BAY K 8644 (10 (-7) M) failed to enhance the relaxations.", "output": {"entities": {"chemical": [{"text": "BAY K 8644", "start": 24, "end": 34}]}}, "schema": []}
{"input": "Upon removal of Ca (2 +), EFS with the same stimulation parameters produced frequency-dependent transient contractions.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 16, "end": 24}]}}, "schema": []}
{"input": "Tetrodotoxin (10 (-6) M), capsaicin (10 (-5) M) and removal of endothelium did not alter these contractions suggesting that they were not neural in origin and endothelium-derived contracting factors were unlikely to be involved.", "output": {"entities": {"chemical": [{"text": "Tetrodotoxin", "start": 0, "end": 12}, {"text": "capsaicin", "start": 26, "end": 35}]}}, "schema": []}
{"input": "However, they were increased by nearly 40% in response to BAY K 8644 (10 (-7) M) and were inhibited by nifedipine (10 (-7) M), indicating that activation of the LTCCs was essential.", "output": {"entities": {"chemical": [{"text": "BAY K 8644", "start": 58, "end": 68}, {"text": "nifedipine", "start": 103, "end": 113}]}}, "schema": []}
{"input": "Inositol triphosphate (InsP3) receptor antagonist 2-APB (10 (-4) M) significantly reduced, and high concentration of caffeine (20mM) almost totally suppressed the contractions.", "output": {"entities": {"chemical": [{"text": "Inositol triphosphate", "start": 0, "end": 21}, {"text": "2-APB", "start": 50, "end": 55}, {"text": "caffeine", "start": 117, "end": 125}]}}, "schema": []}
{"input": "These results suggest that in the absence of extracellular Ca (2 +) EFS through membrane depolarization, evokes the opening of the LTCCs which subsequently leads to the release of Ca (2 +) from internal stores via InsP3 receptors, a phenomenon known as Ca (2 +) channel-induced Ca (2 +) release (CCICR), to trigger vasoconstriction.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 59, "end": 67}, {"text": "Ca (2 +)", "start": 180, "end": 188}, {"text": "Ca (2 +)", "start": 253, "end": 261}, {"text": "Ca (2 +)", "start": 278, "end": 286}]}}, "schema": []}
{"input": "That activation of LTCCs causes arterial relaxation or contraction depending on the Ca (2 +) status apparently exemplifies how the same messenger fulfils opposing physiological functions in a given cell.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 84, "end": 92}]}}, "schema": []}
{"input": "Occupational exposure to pentachlorophenol causing lymphoma and hematopoietic malignancy for two generations.", "output": {"entities": {"chemical": [{"text": "pentachlorophenol", "start": 25, "end": 42}]}}, "schema": []}
{"input": "OBJECTIVE: Pentachlorophenol (PCP) is characterized as likely carcinogen of lymphoma and hematopoietic neoplasm.", "output": {"entities": {"chemical": [{"text": "Pentachlorophenol", "start": 11, "end": 28}, {"text": "PCP", "start": 30, "end": 33}]}}, "schema": []}
{"input": "But the carcinogenicity to human was uncertain based on population studies.", "output": {"entities": {}}, "schema": []}
{"input": "A systematic review was conducted to explore two kinds of associations, one was between the workers exposed to PCP with lymphoma and hematopoietic neoplasm, the other was between childhood lymphoma and leukemia with their parents exposed to PCP.", "output": {"entities": {"chemical": [{"text": "PCP", "start": 111, "end": 114}, {"text": "PCP", "start": 241, "end": 244}]}}, "schema": []}
{"input": "METHODS: Systematic search for epidemiologic studies was carried out and the data were collected from MEDLINE database and from the reference lists of relevant studies.", "output": {"entities": {}}, "schema": []}
{"input": "Data were extracted from 20 included studies published between 1986 and 2012.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The meta-analysis suggested a significant association between lymphoma and workers' occupational exposing to PCP, for the pooled odds ratio = 2. 57 (95% confidence interval (CI) = 1. 52-4. 35).", "output": {"entities": {"chemical": [{"text": "PCP", "start": 118, "end": 121}]}}, "schema": []}
{"input": "The subgroup analysis indicated significant association for non-Hodgkin' s lymphoma, but not for Hodgkin' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "The cohort studies also showed comparatively higher relative risk (RR) and standardized mortality ratio (SMR).", "output": {"entities": {}}, "schema": []}
{"input": "Two of the cohort studies found increased RR as the cumulative exposure time added.", "output": {"entities": {}}, "schema": []}
{"input": "Another cohort study discovered that the white males had significantly elevated non-Hodgkin' s lymphoma mortality (SMR = 1. 98, 95% CI = 1. 15-3. 17), and males of other races had increased leukemia mortality (SMR = 4. 57, 95% CI = 1. 25-11. 7).", "output": {"entities": {}}, "schema": []}
{"input": "For the relationship of childhood leukemia and parental exposure to PCP, three published studies suggested an increased risk of childhood leukemia because of their parental exposure to PCP at the preconception period.", "output": {"entities": {"chemical": [{"text": "PCP", "start": 68, "end": 71}, {"text": "PCP", "start": 185, "end": 188}]}}, "schema": []}
{"input": "CONCLUSION: Our review provided the evidence that occupational exposure of workers to PCP might increase the risk of lymphoma and hematopoietic neoplasm in themselves and in their children.", "output": {"entities": {"chemical": [{"text": "PCP", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Silica nanoparticles-induced cytotoxicity, oxidative stress and apoptosis in cultured A431 and A549 cells.", "output": {"entities": {"chemical": [{"text": "Silica", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In medicine, the use of silica nanoparticles (SiO (2) NPs) offers new perspectives in biosensor, drug delivery and cancer therapy.", "output": {"entities": {"chemical": [{"text": "silica", "start": 24, "end": 30}, {"text": "SiO (2)", "start": 46, "end": 53}]}}, "schema": []}
{"input": "However, questions about potential toxic and deleterious effects of SiO (2) NPs have also been raised.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 68, "end": 75}]}}, "schema": []}
{"input": "The aim of this study was to investigate the induction of cytotoxicity, oxidative stress and apoptosis by SiO (2) NPs (size 15 nm) in human skin epithelial (A431) and human lung epithelial (A549) cells.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 106, "end": 113}]}}, "schema": []}
{"input": "SiO (2) NPs (concentration range 25-200 micro g/ml) induced dose-dependent cytotoxicity in both types of cells, which was demonstrated by cell viability (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide) and lactate dehydrogenase leakage assays.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 0, "end": 7}, {"text": "3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide", "start": 154, "end": 215}, {"text": "lactate", "start": 221, "end": 228}]}}, "schema": []}
{"input": "SiO (2) NPs were also found to induce oxidative stress in a dose-dependent manner, indicated by depletion of glutathione and induction of reactive oxygen species (ROS) generation and lipid peroxidation.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 0, "end": 7}, {"text": "glutathione", "start": 109, "end": 120}, {"text": "oxygen", "start": 147, "end": 153}]}}, "schema": []}
{"input": "Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to SiO (2) NPs, the messenger RNA level of apoptotic genes (caspase-3 and caspase-9) were upregulated in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 105, "end": 112}]}}, "schema": []}
{"input": "Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in both kinds of cells exposed to SiO (2) NPs.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 121, "end": 128}]}}, "schema": []}
{"input": "This study suggested that SiO (2) NPs induce cytotoxicity and apoptosis in A431 and A549 cells, which is likely to be mediated through ROS generation and oxidative stress.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 26, "end": 33}]}}, "schema": []}
{"input": "Decreased RB1 mRNA, Protein, and Activity Reflect Obesity-Induced Altered Adipogenic Capacity in Human Adipose Tissue.", "output": {"entities": {}}, "schema": []}
{"input": "Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice.", "output": {"entities": {}}, "schema": []}
{"input": "No studies have been reported thus far in human adipose tissue or human adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models.", "output": {"entities": {}}, "schema": []}
{"input": "Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPAR gamma and IRS1) in both visceral and subcutaneous human adipose tissue.", "output": {"entities": {}}, "schema": []}
{"input": "BMI increase was the main contributor to adipose RB1 downregulation.", "output": {"entities": {}}, "schema": []}
{"input": "In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss.", "output": {"entities": {}}, "schema": []}
{"input": "RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Complex II of the mitochondrial respiratory chain is the key mediator of divalent manganese-induced hydrogen peroxide production in microglia.", "output": {"entities": {"chemical": [{"text": "divalent manganese", "start": 73, "end": 91}, {"text": "hydrogen peroxide", "start": 100, "end": 117}]}}, "schema": []}
{"input": "Exposure to excessive levels of manganese (Mn) is associated with the development of movement disorders, with symptoms overlapping with Parkinson' s disease.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 32, "end": 41}, {"text": "Mn", "start": 43, "end": 45}]}}, "schema": []}
{"input": "Oxidative damage has been implicated as a key contributor to Mn-induced neurotoxicity.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 61, "end": 63}]}}, "schema": []}
{"input": "We have recently reported that divalent Mn (Mn (2 +)) stimulates brain microglia to produce and release hydrogen peroxide (H2O2), and microglial-free radical generation facilitates Mn (2 +)-induced dopaminergic neurotoxicity.", "output": {"entities": {"chemical": [{"text": "divalent Mn", "start": 31, "end": 42}, {"text": "Mn (2 +)", "start": 44, "end": 52}, {"text": "hydrogen peroxide", "start": 104, "end": 121}, {"text": "H2O2", "start": 123, "end": 127}, {"text": "Mn (2 +)", "start": 181, "end": 189}]}}, "schema": []}
{"input": "The goal of this study was to elucidate the underlying mechanism of the Mn (2 +)-induced H2O2 production in microglia.", "output": {"entities": {"chemical": [{"text": "Mn (2 +)", "start": 72, "end": 80}, {"text": "H2O2", "start": 89, "end": 93}]}}, "schema": []}
{"input": "Exposure to low micromolar concentrations of Mn (2 +), but not divalent copper, cadmium, nickel, cobalt, zinc, and iron, induced a significant production of H2O2 from rat microglial but not astroglial cells.", "output": {"entities": {"chemical": [{"text": "Mn (2 +)", "start": 45, "end": 53}, {"text": "divalent copper, cadmium, nickel, cobalt, zinc, and iron", "start": 63, "end": 119}, {"text": "H2O2", "start": 157, "end": 161}]}}, "schema": []}
{"input": "Subcellular fractionation studies revealed that Mn (2 +) was capable of inducing significant H2O2 production in the mitochondrial but not the cytosolic or nuclear fraction prepared from microglia.", "output": {"entities": {"chemical": [{"text": "Mn (2 +)", "start": 48, "end": 56}, {"text": "H2O2", "start": 93, "end": 97}]}}, "schema": []}
{"input": "Analysis of the relative contribution of mitochondrial respiratory chain complexes indicated that Mn (2 +)-induced mitochondrial H2O2 production required the presence of complex II substrate succinate.", "output": {"entities": {"chemical": [{"text": "Mn (2 +)", "start": 98, "end": 106}, {"text": "H2O2", "start": 129, "end": 133}, {"text": "succinate", "start": 191, "end": 200}]}}, "schema": []}
{"input": "In contrast, complex I substrates malate and glutamate failed to support H2O2 production in the presence of Mn (2 +).", "output": {"entities": {"chemical": [{"text": "malate", "start": 34, "end": 40}, {"text": "glutamate", "start": 45, "end": 54}, {"text": "H2O2", "start": 73, "end": 77}, {"text": "Mn (2 +)", "start": 108, "end": 116}]}}, "schema": []}
{"input": "Furthermore, the succinate-supported Mn (2 +)-induced mitochondrial H2O2 production was abolished by pharmacological inhibition of complex II but not that of complexes I and III, suggesting that mitochondrial complex II is a key mediator in Mn (2 +)-induced H2O2 production.", "output": {"entities": {"chemical": [{"text": "succinate", "start": 17, "end": 26}, {"text": "Mn (2 +)", "start": 37, "end": 45}, {"text": "H2O2", "start": 68, "end": 72}, {"text": "Mn (2 +)", "start": 241, "end": 249}, {"text": "H2O2", "start": 258, "end": 262}]}}, "schema": []}
{"input": "These findings advance our knowledge on the mechanisms by which Mn induces oxidative stress and the potential contribution to Mn neurotoxicity.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 64, "end": 66}]}}, "schema": []}
{"input": "Phenotypic profiling of structural cardiotoxins in vitro reveals dependency on multiple mechanisms of toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Morphological damage to cardiomyocytes or loss of viability (structural cardiotoxicity) is a common cause of attrition in preclinical and clinical drug development.", "output": {"entities": {}}, "schema": []}
{"input": "Currently, no predictive in vitro approaches are available to detect this liability early in drug discovery, and knowledge of the mechanisms involved is limited.", "output": {"entities": {}}, "schema": []}
{"input": "Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and the rat myoblastic H9c2 cell lines were used to phenotypically profile a panel of structural cardiotoxins by live-cell fluorescent imaging of mitochondrial membrane potential, endoplasmic reticulum integrity, Ca (2 +) mobilization, and membrane permeability combined with an assessment of cell viability (ATP depletion).", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 273, "end": 281}, {"text": "ATP", "start": 369, "end": 372}]}}, "schema": []}
{"input": "Assay results were normalized to known therapeutically relevant concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "By comparing the outcome of each assay to the known in vivo effects, hESC-CMs offered an improved model over H9c2 cells for the detection of structural cardiotoxicity at therapeutically relevant concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of the spontaneously beating phenotype, a feature of stem cell-derived cardiomyocytes, revealed some degree of cardioprotection following 10 out of 13 structural cardiotoxins, illustrating the intricate relationship between the function and structure of cardiomyocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Classification of structural cardiotoxins into mechanistic themes revealed mitochondria and calcium mobilization to be major distal targets, with only 4 out of 15 compounds affecting contractile function in freshly isolated canine cardiomyocytes at therapeutically relevant concentrations.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 92, "end": 99}]}}, "schema": []}
{"input": "Our data demonstrate the utility of hESC-CMs during drug development to support structural cardiotoxicity hazard identification and to gain insight into the intricate mechanisms implicated in structural cardiotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction: A case-control study.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEFathers of low-birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth-restricted offspring were born. RESEARCH DESIGN AND METHODSWe carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who fathered normal-birth weight offspring (n = 77).", "output": {"entities": {}}, "schema": []}
{"input": "All mothers were healthy, nonsmoking, and similar in age, BMI, ethnicity, and parity.", "output": {"entities": {}}, "schema": []}
{"input": "Within 4 weeks of offspring birth, all fathers had measures of insulin resistance (HOMA index), blood pressure, waist circumference, endothelial function (flow-mediated dilatation), lipid profile, weight, and smoking habit.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison was made using multivariable logistical regression analysis. RESULTSFathers of fetal growth-restricted offspring [mean (SD) 1. 8th (2. 2) customized birth centile] were more likely to have insulin resistance, hypertension, central adiposity, and endothelial dysfunction and to smoke cigarettes compared with fathers of normal grown offspring.", "output": {"entities": {}}, "schema": []}
{"input": "After multivariable analysis, paternal insulin resistance and smoking remained different between the groups.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with fathers of normal grown offspring, men who fathered pregnancies affected by fetal growth restriction had an OR 7. 68 (95% CI 2. 63-22. 40; P < 0. 0001) of having a 1-unit higher log HOMA-IR value and 3. 39 (1. 26-9. 16; P = 0. 016) of being a smoker. CONCLUSIONSMen who recently fathered growth-restricted offspring have preclinical evidence of the insulin resistance syndrome and are more likely to smoke than fathers of normal grown offspring.", "output": {"entities": {}}, "schema": []}
{"input": "Paternal lifestyle may influence heritable factors important for fetal growth.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of four new mouse cytochrome P450 enzymes of the CYP2J subfamily.", "output": {"entities": {}}, "schema": []}
{"input": "The cytochrome P450 superfamily encompasses a diverse group of enzymes that catalyze the oxidation of various substrates.", "output": {"entities": {}}, "schema": []}
{"input": "The mouse CYP2J subfamily includes members that have wide tissue distribution and are active in the metabolism of arachidonic acid (AA), linoleic acid (LA), and other lipids and xenobiotics.", "output": {"entities": {"chemical": [{"text": "arachidonic acid", "start": 114, "end": 130}, {"text": "linoleic acid", "start": 137, "end": 150}]}}, "schema": []}
{"input": "The mouse Cyp2j locus contains seven genes and three pseudogenes located in a contiguous 0. 62 megabase cluster on chromosome 4.", "output": {"entities": {}}, "schema": []}
{"input": "We describe four new mouse CYP2J isoforms (designated CYP2J8, CYP2J11, CYP2J12, and CYP2J13).", "output": {"entities": {}}, "schema": []}
{"input": "The four cDNAs contain open reading frames that encode polypeptides with 62-84% identity with the three previously identified mouse CYP2Js.", "output": {"entities": {}}, "schema": []}
{"input": "All four new CYP2J proteins were expressed in Sf21 insect cells.", "output": {"entities": {}}, "schema": []}
{"input": "Each recombinant protein metabolized AA and LA to epoxides and hydroxy derivatives.", "output": {"entities": {"chemical": [{"text": "epoxides", "start": 50, "end": 58}, {"text": "hydroxy", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Specific antibodies, mRNA probes, and polymerase chain reaction primer sets were developed for each mouse CYP2J to examine their tissue distribution.", "output": {"entities": {}}, "schema": []}
{"input": "CYP2J8 transcripts were found in the kidney, liver, and brain, and protein expression was confirmed in the kidney and brain (neuropil).", "output": {"entities": {}}, "schema": []}
{"input": "CYP2J11 transcripts were most abundant in the kidney and heart, with protein detected primarily in the kidney (proximal convoluted tubules), liver, and heart (cardiomyocytes).", "output": {"entities": {}}, "schema": []}
{"input": "CYP2J12 transcripts were prominently present in the brain, and CYP2J13 transcripts were detected in multiple tissues, with the highest expression in the kidney.", "output": {"entities": {}}, "schema": []}
{"input": "CYP2J12 and CYP2J13 protein expression could not be determined because the antibodies developed were not immunospecific.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that the four new CYP2J isoforms might be involved in the metabolism of AA and LA to bioactive lipids in mouse hepatic and extrahepatic tissues.", "output": {"entities": {}}, "schema": []}
{"input": "An Anti-angiogenic Reverse Thermal Gel as a Drug-Delivery System for Age-Related Wet Macular Degeneration.", "output": {"entities": {}}, "schema": []}
{"input": "Reverse thermal gels have numerous biomedical implications, as they undergo physical gelation upon temperature increases and can incorporate biomolecules to promote tissue repair.", "output": {"entities": {}}, "schema": []}
{"input": "Such a material is developed for the sustained release of bevacizumab (Avastin), a drug used to treat age-related macular degeneration.", "output": {"entities": {}}, "schema": []}
{"input": "The polymer, poly (ethylene glycol)-poly (serinol hexamethylene urethane) (ESHU), forms a physical gel when heated to 37 degrees C and shows good cytocompatibility with ocular cells.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol)-poly (serinol hexamethylene urethane)", "start": 13, "end": 73}, {"text": "ESHU", "start": 75, "end": 79}]}}, "schema": []}
{"input": "ESHU is capable of sustaining bevacizumab release over 17 weeks in vitro, and the release kinetics can be altered by changing the drug dose and the ESHU concentration.", "output": {"entities": {"chemical": [{"text": "ESHU", "start": 0, "end": 4}, {"text": "ESHU", "start": 148, "end": 152}]}}, "schema": []}
{"input": "These results suggest that ESHU is biologically safe, and suitable for ocular drug delivery.", "output": {"entities": {"chemical": [{"text": "ESHU", "start": 27, "end": 31}]}}, "schema": []}
{"input": "Innovation and originality in the strategies developed by bacteria to get access to iron.", "output": {"entities": {"chemical": [{"text": "iron", "start": 84, "end": 88}]}}, "schema": []}
{"input": "Pumping iron: Raymond' s group has identified and described the molecular details of an ABC transporter.", "output": {"entities": {}}, "schema": []}
{"input": "Together with a binding protein at the cell surface, it is able to extract an unstable form of ferricitrate.", "output": {"entities": {}}, "schema": []}
{"input": "Structure and dynamic regulation of Abl kinases.", "output": {"entities": {}}, "schema": []}
{"input": "The c-abl proto-oncogene encodes a unique protein-tyrosine kinase (Abl) distinct from c-Src, c-Fes, and other cytoplasmic tyrosine kinases.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 50, "end": 58}, {"text": "tyrosine", "start": 122, "end": 130}]}}, "schema": []}
{"input": "In normal cells, Abl plays prominent roles in cellular responses to genotoxic stress as well as in the regulation of the actin cytoskeleton.", "output": {"entities": {}}, "schema": []}
{"input": "Abl is also well known in the context of Bcr-Abl, the oncogenic fusion protein characteristic of chronic myelogenous leukemia.", "output": {"entities": {}}, "schema": []}
{"input": "Selective inhibitors of Bcr-Abl, of which imatinib is the prototype, have had a tremendous impact on clinical outcomes in chronic myelogenous leukemia and revolutionized the field of targeted cancer therapy.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 42, "end": 50}]}}, "schema": []}
{"input": "In this minireview, we focus on the structural organization and dynamics of Abl kinases and how these features influence inhibitor sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "Extraction of essential oil from Cupressus sempervirens: comparison of global yields, chemical composition and antioxidant activity obtained by hydrodistillation and supercritical extraction (+).", "output": {"entities": {}}, "schema": []}
{"input": "In this study, supercritical fluid extraction (SFE) with CO (2) and hydrodistillation (HD) were compared as methods to isolate the essential oil from Cupressus sempervirens.", "output": {"entities": {"chemical": [{"text": "CO (2)", "start": 57, "end": 63}]}}, "schema": []}
{"input": "The odour of the oil obtained by SFE at 90 bar and 40 degrees C was very close to the odour of the leaves of C. sempervirens before the extraction.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds extracted by both SFE and HD were identified by GC-FID and GC-MS.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the difference in the chemical composition obtained by SFE and HD was quite noticeable qualitatively and quantitatively.", "output": {"entities": {}}, "schema": []}
{"input": "Phenolic composition and antioxidant activity were also determined.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to HD, the SFE method presents some advantages: the extraction was completed after 1 h in SFE, although 4 h is necessary for HD, and the yield was improved by 34%.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, it has also been shown that SFE is very selective towards some specific components such as manoyl oxide, trans-totarol and alpha-acoradiene.", "output": {"entities": {"chemical": [{"text": "manoyl oxide", "start": 100, "end": 112}, {"text": "trans-totarol", "start": 114, "end": 127}, {"text": "alpha-acoradiene", "start": 132, "end": 148}]}}, "schema": []}
{"input": "Targeting adenosine signaling to treatment of diabetic nephropathy.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 10, "end": 19}]}}, "schema": []}
{"input": "Diabetic nephropathy (DN) continues being the primary cause of chronic hemodialysis and terminal renal disease worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "At tissue levels the DN occurs with glomerulopathy affecting the integrity of the filtration barrier and with an extensive glomerular and tubule-interstitial fibrosis.", "output": {"entities": {}}, "schema": []}
{"input": "Current available therapeutic approaches have only demonstrated a modest effect on progression of kidney injury.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, more research concerning the pathomechanisms and possible interventions are needed.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, in the last years it has been documented that DN progresses with growing levels of the nucleoside adenosine.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 113, "end": 122}]}}, "schema": []}
{"input": "This finding increased the interest in the events controlling the extracellular levels of the nucleoside.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 94, "end": 104}]}}, "schema": []}
{"input": "While the metabolism of extracellular ATP and cyclic AMP are well recognized sources, evidences regarding the role of the equilibrative nucleoside transporters in controlling adenosine availability and promoting diabetic glomerulopathy have recently acquired a pivotal role.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 38, "end": 41}, {"text": "cyclic AMP", "start": 46, "end": 56}, {"text": "nucleoside", "start": 136, "end": 146}, {"text": "adenosine", "start": 175, "end": 184}]}}, "schema": []}
{"input": "The physiological effects of nucleoside are mediated by the P1 family of adenosine receptors.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 29, "end": 39}, {"text": "adenosine", "start": 73, "end": 82}]}}, "schema": []}
{"input": "It has been shown in vivo that the use of an antagonist of the A2B receptor subtype can block the most remarkable early alterations seen in diabetic glomerulopathy.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, using models of chronic kidney injury it was demonstrated that fibrosis can also be blocked using treatment with the antagonist of A2B receptor subtype.", "output": {"entities": {}}, "schema": []}
{"input": "This review highlights these findings that correlate the activity of a low affinity adenosine receptor with an increase in the ligand availability in the pathological state.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 84, "end": 93}]}}, "schema": []}
{"input": "In addition, we discuss the possible therapeutic interventions of adenosine signaling with regards to DN treatment.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 66, "end": 75}]}}, "schema": []}
{"input": "Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins.", "output": {"entities": {}}, "schema": []}
{"input": "Varicose veins (VVs) are a common venous disease of the lower extremity characterized by incompetent valves, venous reflux, and dilated and tortuous veins.", "output": {"entities": {}}, "schema": []}
{"input": "If untreated, VVs could lead to venous thrombosis, thrombophlebitis and chronic venous leg ulcers.", "output": {"entities": {}}, "schema": []}
{"input": "Various genetic, hormonal and environmental factors may lead to structural changes in the vein valves and make them incompetent, leading to venous reflux, increased venous pressure and vein wall dilation.", "output": {"entities": {}}, "schema": []}
{"input": "Prolonged increases in venous pressure and vein wall tension are thought to increase the expression/activity of matrix metalloproteinases (MMPs).", "output": {"entities": {}}, "schema": []}
{"input": "Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs and others.", "output": {"entities": {}}, "schema": []}
{"input": "MMPs are known to degrade various components of the extracellular matrix (ECM).", "output": {"entities": {}}, "schema": []}
{"input": "MMPs may also affect the endothelium and vascular smooth muscle, causing changes in the vein relaxation and contraction mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Endothelial cell injury also triggers leukocyte infiltration, activation and inflammation, which lead to further vein wall damage.", "output": {"entities": {}}, "schema": []}
{"input": "The vein wall dilation and valve dysfunction, and the MMP activation and superimposed inflammation and fibrosis would lead to progressive venous dilation and VVs formation.", "output": {"entities": {}}, "schema": []}
{"input": "Surgical ablation is an effective treatment for VVs, but may be associated with high recurrence rate, and other less invasive approaches that target the cause of the disease are needed.", "output": {"entities": {}}, "schema": []}
{"input": "MMP inhibitors including endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as zinc chelators, doxycycline, batimastat and marimastat, have been used as diagnostic and therapeutic tools in cancer, autoimmune and cardiovascular disease.", "output": {"entities": {"chemical": [{"text": "zinc", "start": 101, "end": 105}, {"text": "doxycycline", "start": 117, "end": 128}, {"text": "batimastat", "start": 130, "end": 140}, {"text": "marimastat", "start": 145, "end": 155}]}}, "schema": []}
{"input": "However, MMP inhibitors may have side effects especially on the musculoskeletal system.", "output": {"entities": {}}, "schema": []}
{"input": "With the advent of new genetic and pharmacological tools, specific MMP inhibitors with fewer undesirable effects could be useful to retard the progression and prevent the recurrence of VVs.", "output": {"entities": {}}, "schema": []}
{"input": "Solphenazines A-F, glycosylated phenazines from Streptomyces sp. strain DL-93.", "output": {"entities": {"chemical": [{"text": "Solphenazines A-F", "start": 0, "end": 17}, {"text": "glycosylated phenazines", "start": 19, "end": 42}]}}, "schema": []}
{"input": "During a survey of actinobacteria known to suppress the growth of Streptomyces scabies (the causative agent of potato scab disease) in vivo, six new rhamnosylated alkaloids, the solphenazines A-F (1-6), were isolated from a biological control strain of Streptomyces (DL-93).", "output": {"entities": {"chemical": [{"text": "solphenazines A-F", "start": 178, "end": 195}]}}, "schema": []}
{"input": "The known rhamnosyl analogue of paraben (9) was also isolated along with a new rhamnosylated derivative of N-methyl-p-aminobenzoic acid (10).", "output": {"entities": {"chemical": [{"text": "rhamnosyl", "start": 10, "end": 19}, {"text": "paraben", "start": 32, "end": 39}, {"text": "N-methyl-p-aminobenzoic acid", "start": 107, "end": 135}]}}, "schema": []}
{"input": "None of the compounds exhibited any antibacterial or antifungal activity against a standard panel of microorganisms, but compounds 1, 2, and 6 displayed some cytotoxicity against HCT-116 cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Additional in vitro testing provided data suggesting that the cytotoxic activity is not due to DNA intercalation or topoisomerase inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological evaluation as microtubule-active agents of several tetrahydrofuran and spiroacetal derivatives.", "output": {"entities": {"chemical": [{"text": "tetrahydrofuran", "start": 76, "end": 91}, {"text": "spiroacetal", "start": 96, "end": 107}]}}, "schema": []}
{"input": "The stereoselective preparation of several molecules containing structural fragments of the tetrahydrofuran and spiroacetal type is described.", "output": {"entities": {"chemical": [{"text": "tetrahydrofuran", "start": 92, "end": 107}, {"text": "spiroacetal", "start": 112, "end": 123}]}}, "schema": []}
{"input": "Their degree of cytotoxicity and their interactions with tubulin have been investigated.", "output": {"entities": {}}, "schema": []}
{"input": "It has been confirmed that the tetrahydrofuran derivatives are cytotoxic but, in contrast to previous reports, it has been found that the cytoxicity is not due to interactions with the microtubule network.", "output": {"entities": {"chemical": [{"text": "tetrahydrofuran", "start": 31, "end": 46}]}}, "schema": []}
{"input": "Furthermore, and also in contrast to a previous report on closely related compounds, the spiroacetal derivatives do show interactions with tubulin, even though the precise mechanism and the binding site still remain to be established.", "output": {"entities": {"chemical": [{"text": "spiroacetal", "start": 89, "end": 100}]}}, "schema": []}
{"input": "The oxygen therapy.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 4, "end": 10}]}}, "schema": []}
{"input": "Oxygen (O (2)) is a vital element.", "output": {"entities": {"chemical": [{"text": "Oxygen", "start": 0, "end": 6}, {"text": "O (2)", "start": 8, "end": 13}]}}, "schema": []}
{"input": "Shortage of O (2) results in deranged metabolism and important changes in vascular tone with opposite effects on the systemic and pulmonary circulation.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 12, "end": 17}]}}, "schema": []}
{"input": "During hypoxemia, oxidative stress exposes the organism to a sort of accelerated senescence as well as to several acute untoward effects.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, hypoxemia should be promptly recognized and treated, hopefully by measures tailored to the pathophysiological mechanisms underlying hypoxemia.", "output": {"entities": {}}, "schema": []}
{"input": "However, O (2) therapy remains the most common therapy of hypoxemia, but it must be carefully tailored to relieve hypoxemia without provoking hyperoxia or hypercarbia.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 9, "end": 14}]}}, "schema": []}
{"input": "Then, the individual response to O (2) as well as changing needs of O (2) during sleep or exercise must be evaluated to provide the best O (2) therapy.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 33, "end": 38}, {"text": "O (2)", "start": 68, "end": 73}, {"text": "O (2)", "start": 137, "end": 142}]}}, "schema": []}
{"input": "Hyperoxia, the effect of overcorrection of hypoxia, can dramatically impact the health status and threaten the survival of the newborn and, through different mechanisms and effects, the adult.", "output": {"entities": {}}, "schema": []}
{"input": "A thorough knowledge of the pathophysiological bases of hypoxemia and O (2) storage and delivery devices is then mandatory to administer O (2) therapy guaranteeing for optimal correction of hypoxemia and minimizing the risk of hyperoxia.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 70, "end": 75}, {"text": "O (2)", "start": 137, "end": 142}]}}, "schema": []}
{"input": "Consistent with this aim also is a careful scrutiny of instruments and procedures for monitoring the individual response to O (2) over time.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 124, "end": 129}]}}, "schema": []}
{"input": "Thus, at variance from classical pharmacological therapy, performing O (2) therapy requires a vast array of clinical and technical competences.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 69, "end": 74}]}}, "schema": []}
{"input": "The optimal integration of these competences is needed to optimize O (2) therapy on individual bases.", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 67, "end": 72}]}}, "schema": []}
{"input": "Recent Developments of p38 alpha MAP Kinase Inhibitors as Antiinflammatory Agents Based on the Imidazole Scaffolds.", "output": {"entities": {"chemical": [{"text": "Imidazole", "start": 95, "end": 104}]}}, "schema": []}
{"input": "Rheumatoid arthritis (RA) and other chronic inflammatory diseases are always the major therapeutic challenges.", "output": {"entities": {}}, "schema": []}
{"input": "Recent research efforts provided new insights into the molecular basis of these diseases and new opportunities for developing improved anti-inflammatory drugs.", "output": {"entities": {}}, "schema": []}
{"input": "The p38 mitogen-activated protein (MAP) kinase plays a central role in the regulation of the biosynthesis and release of several proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta).", "output": {"entities": {}}, "schema": []}
{"input": "Hence, inhibition of the p38 MAP kinase is regarded as a promising therapeutic strategy for controlling inflammatory diseases.", "output": {"entities": {}}, "schema": []}
{"input": "A diverse range of p38 alpha MAP kinase inhibitors have been developed as potential anti-inflammatory agents, and some of them have entered the phase II clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "The imidazole derivatives are known as competitive inhibitors at the ATP binding site of the p38 alpha MAP kinase.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 4, "end": 13}, {"text": "ATP", "start": 69, "end": 72}]}}, "schema": []}
{"input": "Modifications on the imidazole scaffold have led to a large amount of potent p38 alpha MAP kinase inhibitors.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 21, "end": 30}]}}, "schema": []}
{"input": "This review will summarize the developments of small molecule p38 alpha MAP kinase inhibitors based on the imidazole core scaffolds in recent 10 years.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 107, "end": 116}]}}, "schema": []}
{"input": "Variations at the N1, C2, C4 and C5 positions of imidazole were introduced, and the structure-activity relationships of these imidazole inhibitors were also discussed.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 49, "end": 58}, {"text": "imidazole", "start": 126, "end": 135}]}}, "schema": []}
{"input": "What happens to the thiolates created by reductively desorbing SAMs?", "output": {"entities": {"chemical": [{"text": "thiolates", "start": 20, "end": 29}]}}, "schema": []}
{"input": "An in situ study using fluorescence microscopy and electrochemistry.", "output": {"entities": {}}, "schema": []}
{"input": "In situ examination of the reductive desorption process for Au microelectrodes modified with a thiol self-assembled monolayer (SAM) using fluorescence microscopy enabled the study of the fate of the desorbed thiolate species.", "output": {"entities": {"chemical": [{"text": "Au", "start": 60, "end": 62}, {"text": "thiol", "start": 95, "end": 100}, {"text": "thiolate", "start": 208, "end": 216}]}}, "schema": []}
{"input": "The Bodipy labeled alkyl-thiol SAM, when adsorbed, is not fluorescent due to quenching by the Au surface.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 25, "end": 30}, {"text": "Au", "start": 94, "end": 96}]}}, "schema": []}
{"input": "Once reductively desorbed, the thiolate molecules fluoresce and their direction and speed are monitored.", "output": {"entities": {"chemical": [{"text": "thiolate", "start": 31, "end": 39}]}}, "schema": []}
{"input": "At moderately negative reduction potentials, the thiolate species hemispherically diffuse away from the microelectrode.", "output": {"entities": {"chemical": [{"text": "thiolate", "start": 49, "end": 57}]}}, "schema": []}
{"input": "Also observed is the influence of a closely positioned counter electrode on the direction of the desorbed thiolate movement.", "output": {"entities": {"chemical": [{"text": "thiolate", "start": 106, "end": 114}]}}, "schema": []}
{"input": "As the potential becomes more negative, the molecules move in an upward direction, with a speed that depends on the amount of dissolved H (2) produced by water reduction.", "output": {"entities": {"chemical": [{"text": "H (2)", "start": 136, "end": 141}]}}, "schema": []}
{"input": "Shown is that this motion is controlled, in large part, by the change in the electrolyte density near the electrode due to dissolved H (2).", "output": {"entities": {"chemical": [{"text": "H (2)", "start": 133, "end": 138}]}}, "schema": []}
{"input": "These results should help in explaining the extent of readsorption at oxidative potentials observed in cyclic voltammetry (CV) reductive desorption measurements, as well as improving the general understanding of the SAM removal process by reductive desorption.", "output": {"entities": {}}, "schema": []}
{"input": "The electrogenerated H (2) was also shown to be able to reductively remove the thiol SAM from the Pt/Ir particles that decorate the microelectrode glass sheath.", "output": {"entities": {"chemical": [{"text": "H (2)", "start": 21, "end": 26}, {"text": "Pt", "start": 98, "end": 100}, {"text": "Ir", "start": 101, "end": 103}]}}, "schema": []}
{"input": "Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors.", "output": {"entities": {"chemical": [{"text": "pyridine-carboxamide", "start": 23, "end": 43}]}}, "schema": []}
{"input": "The structure-activity relationship studies of a novel series of carboxylic acid derivatives of pyridine-carboxamides as DGAT-1 inhibitors is described.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 65, "end": 80}, {"text": "pyridine-carboxamides", "start": 96, "end": 117}]}}, "schema": []}
{"input": "The optimization of the initial lead compound 6 based on in vitro and in vivo activity led to the discovery of key compounds 10j and 17h.", "output": {"entities": {}}, "schema": []}
{"input": "Atomic pair distribution functions analysis of disordered low-Z materials.", "output": {"entities": {}}, "schema": []}
{"input": "Results of high-energy X-ray diffraction experiments coupled to atomic pair distribution function analysis of disordered low-Z materials are presented.", "output": {"entities": {}}, "schema": []}
{"input": "Several scientifically and technologically important classes of disordered low-Z materials such as small and large organic molecules, graphitic powders, polymers and liquids are intentionally explored to certify the technique' s performance.", "output": {"entities": {"chemical": [{"text": "graphitic", "start": 134, "end": 143}]}}, "schema": []}
{"input": "Results clearly show that disordered low-Z materials can be well characterized in terms of material' s phase identity, relative abundance in mixtures and atomic-scale structure.", "output": {"entities": {}}, "schema": []}
{"input": "The demonstrated efficiency of the technique provides the scientific community with much needed confidence to apply it more often than now.", "output": {"entities": {}}, "schema": []}
{"input": "ErbB2, FoxM1 and 14-3-3 zeta prime breast cancer cells for invasion in response to ionizing radiation.", "output": {"entities": {}}, "schema": []}
{"input": "ErbB2 is frequently highly expressed in premalignant breast cancers, including ductal carcinoma in situ (DCIS); however, little is known about the signals or pathways it contributes to progression into the invasive/malignant state.", "output": {"entities": {}}, "schema": []}
{"input": "Radiotherapy is often used to treat early premalignant lesions regardless of ErbB2 status.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that clinically relevant doses of ionizing radiation (IR)-induce cellular invasion of ErbB2-expressing breast cancer cells, as well as MCF10A cells overexpressing ErbB2.", "output": {"entities": {}}, "schema": []}
{"input": "ErbB2-negative breast cancer cells, such as MCF7 and T47D, do not invade following treatment with IR nor do MCF10A cells overexpressing epidermal growth factor receptor.", "output": {"entities": {}}, "schema": []}
{"input": "ErbB2 becomes phosphorylated at tyrosine 877 in a dose-and time-dependent manner following exposure to X-rays, and activates downstream signaling cascades including PI3K/Akt.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 32, "end": 40}]}}, "schema": []}
{"input": "Inhibition of these pathways, as well as inhibition of reactive oxygen species (ROS) with antioxidants, prevents IR-induced invasion.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 64, "end": 70}]}}, "schema": []}
{"input": "Activation of ErbB2-dependent signaling results in upregulation of the forkhead family transcription factor, FoxM1, and its transcriptional targets, including matrix metalloproteinase 2 (MMP2).", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of FoxM1 by RNA interference prevented induction of invasion by IR, and overexpression of FoxM1 in MCF10A cells was sufficient to promote IR-induced invasion.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, we found that 14-3-3 zeta is also upregulated by IR in cancer cells in a ROS-dependent manner, is required for IR-induced invasion in ErbB2-positive breast cancer cells and together with FoxM1 is sufficient for invasion in ErbB2-negative breast cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, our data show that IR-mediated activation of ErbB2 and induction of 14-3-3 zeta collaborate to regulate FoxM1 and promote invasion of breast cancer cells and furthermore, may serve as therapeutic targets to enhance radiosensitivity of breast cancers. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 629.", "output": {"entities": {}}, "schema": []}
{"input": "TRIM3, a tumor suppressor linked to regulation of p21 (Waf1/Cip1).", "output": {"entities": {}}, "schema": []}
{"input": "The TRIM family of genes is largely studied because of their roles in development, differentiation and host cell antiviral defenses; however, roles in cancer biology are emerging.", "output": {"entities": {}}, "schema": []}
{"input": "Loss of heterozygosity of the TRIM3 locus in ~ 20% of human glioblastomas raised the possibility that this NHL-domain containing member of the TRIM gene family might be a mammalian tumor suppressor.", "output": {"entities": {}}, "schema": []}
{"input": "Consistent with this, reducing TRIM3 expression increased the incidence of and accelerated the development of platelet-derived growth factor-induced glioma in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, TRIM3 can bind to the cdk inhibitor p21 (WAF1/CIP1).", "output": {"entities": {}}, "schema": []}
{"input": "Thus, we conclude that TRIM3 is a tumor suppressor mapping to chromosome 11p15. 5 and that it might block tumor growth by sequestering p21 and preventing it from facilitating the accumulation of cyclin D1-cdk4. Oncogene advance online publication, 14 January 2013; doi: 10. 1038/onc. 2012. 596.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 56, "end": 63}, {"text": "glucose", "start": 109, "end": 116}]}}, "schema": []}
{"input": "The liver plays an important role in maintaining glucose homeostasis in the body.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 49, "end": 56}]}}, "schema": []}
{"input": "In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 35, "end": 42}]}}, "schema": []}
{"input": "In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 32, "end": 39}]}}, "schema": []}
{"input": "Thus, the liver contributes to maintaining blood glucose level within normoglycemic range.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 49, "end": 56}]}}, "schema": []}
{"input": "Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 156, "end": 163}]}}, "schema": []}
{"input": "In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected.", "output": {"entities": {}}, "schema": []}
{"input": "We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 94, "end": 101}, {"text": "glucose", "start": 160, "end": 167}, {"text": "glucose", "start": 193, "end": 200}]}}, "schema": []}
{"input": "On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 12, "end": 19}, {"text": "glucose", "start": 77, "end": 84}, {"text": "catecholamine", "start": 239, "end": 252}]}}, "schema": []}
{"input": "These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 106, "end": 113}, {"text": "glucose", "start": 226, "end": 233}]}}, "schema": []}
{"input": "Butein protects human dental pulp cells from hydrogen peroxide-induced oxidative toxicity via Nrf2 pathway-dependent heme oxygenase-1 expressions.", "output": {"entities": {"chemical": [{"text": "Butein", "start": 0, "end": 6}, {"text": "hydrogen peroxide", "start": 45, "end": 62}]}}, "schema": []}
{"input": "Rhus verniciflua Stokes is a plant that is native to East Asian countries, such as Korea, China, and Japan.", "output": {"entities": {}}, "schema": []}
{"input": "Butein, a plant polyphenol, is one of the major active components of R. verniciflua.", "output": {"entities": {"chemical": [{"text": "Butein", "start": 0, "end": 6}, {"text": "polyphenol", "start": 16, "end": 26}]}}, "schema": []}
{"input": "Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 9, "end": 15}]}}, "schema": []}
{"input": "Here, we found that butein possesses cytoprotective effects on hydrogen peroxide (H2O2)-induced dental cell death.", "output": {"entities": {"chemical": [{"text": "butein", "start": 20, "end": 26}, {"text": "hydrogen peroxide", "start": 63, "end": 80}, {"text": "H2O2", "start": 82, "end": 86}]}}, "schema": []}
{"input": "H2O2 is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 0, "end": 4}]}}, "schema": []}
{"input": "H2O2-induced cytotoxicity and production of ROS were blocked in the presence of butein, and these effects were dose dependent.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 0, "end": 4}, {"text": "butein", "start": 80, "end": 86}]}}, "schema": []}
{"input": "Butein also increased heme oxygenase-1 (HO-1) protein expression and HO activity.", "output": {"entities": {"chemical": [{"text": "Butein", "start": 0, "end": 6}, {"text": "heme", "start": 22, "end": 26}]}}, "schema": []}
{"input": "In addition, butein-dependent HO-1 expression was required for the inhibition of H2O2-induced cell death and ROS generation.", "output": {"entities": {"chemical": [{"text": "butein", "start": 13, "end": 19}, {"text": "H2O2", "start": 81, "end": 85}]}}, "schema": []}
{"input": "Furthermore, butein treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (AREs).", "output": {"entities": {"chemical": [{"text": "butein", "start": 13, "end": 19}]}}, "schema": []}
{"input": "Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and butein treatment led to increased JNK phosphorylation.", "output": {"entities": {"chemical": [{"text": "NH2", "start": 36, "end": 39}, {"text": "butein", "start": 85, "end": 91}, {"text": "butein", "start": 121, "end": 127}]}}, "schema": []}
{"input": "These results indicate that butein may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.", "output": {"entities": {"chemical": [{"text": "butein", "start": 28, "end": 34}]}}, "schema": []}
{"input": "Oxidative and nitrosative stress and apoptosis in oral mucosa cells after ex vivo exposure to lead and benzo [a] pyrene.", "output": {"entities": {"chemical": [{"text": "benzo [a] pyrene", "start": 103, "end": 119}]}}, "schema": []}
{"input": "Exposure of human oral mucosa to lead (Pb) and benzo [a] pyrene (BaP) by inhalation and ingestion can lead to pathological conditions via apoptosis and oxidative and nitrosative stress.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 39, "end": 41}, {"text": "benzo [a] pyrene", "start": 47, "end": 63}, {"text": "BaP", "start": 65, "end": 68}]}}, "schema": []}
{"input": "However, few studies have investigated the effects of Pb and BaP on oral mucosa cells.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 54, "end": 56}, {"text": "BaP", "start": 61, "end": 64}]}}, "schema": []}
{"input": "Furthermore, previous studies focused on chronic Pb and BaP exposure.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 49, "end": 51}, {"text": "BaP", "start": 56, "end": 59}]}}, "schema": []}
{"input": "Therefore, we evaluated important markers of apoptosis and oxidative and nitrosative stress in oral mucosa cells by incubating the cells with Pb and BaP for 5-360 min.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 142, "end": 144}, {"text": "BaP", "start": 149, "end": 152}]}}, "schema": []}
{"input": "Ex vivo samples of human oral mucosa were exposed to Pb or BaP, and immunohistochemical staining was performed to evaluate active caspase-3, 8-epi-prostaglandin F2 alpha (8-epi-PGF2a), and 3-nitrotyrosine (3-NT).", "output": {"entities": {"chemical": [{"text": "Pb", "start": 53, "end": 55}, {"text": "BaP", "start": 59, "end": 62}, {"text": "8-epi-prostaglandin F2 alpha", "start": 141, "end": 169}, {"text": "8-epi-PGF2a", "start": 171, "end": 182}, {"text": "3-nitrotyrosine", "start": 189, "end": 204}, {"text": "3-NT", "start": 206, "end": 210}]}}, "schema": []}
{"input": "Pb and BaP treatments significantly increased active caspase-3 levels in a time-dependent manner.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 0, "end": 2}, {"text": "BaP", "start": 7, "end": 10}]}}, "schema": []}
{"input": "Furthermore, the treatments induced an early increase in 3-NT level, which ceased with longer incubation times.", "output": {"entities": {"chemical": [{"text": "3-NT", "start": 57, "end": 61}]}}, "schema": []}
{"input": "8-Epi-PGF2a level increased only after prolonged incubation with Pb, and this elevation was irrespective of BaP incubation duration.", "output": {"entities": {"chemical": [{"text": "8-Epi-PGF2a", "start": 0, "end": 11}, {"text": "Pb", "start": 65, "end": 67}, {"text": "BaP", "start": 108, "end": 111}]}}, "schema": []}
{"input": "Smokers' samples had significantly lower levels of markers of oxidative and nitrosative stress than did nonsmokers' samples.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, single, short-term exposure to Pb or BaP increases the levels of apoptosis markers and markers of oxidative and nitrosative stress.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 37, "end": 39}, {"text": "BaP", "start": 43, "end": 46}]}}, "schema": []}
{"input": "GC-MS analysis of Eucalyptus citriodora leaf extract and its role on the dietary supplementation in transgenic Drosophila model of Parkinson' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "The role of Eucalyptus citriodora L. leaf extract was studied on the transgenic Drosophila model of flies expressing normal human alpha synuclein (h-alpha S) in the neurons.", "output": {"entities": {}}, "schema": []}
{"input": "These flies exhibit locomotor dysfunction as the age progresses.", "output": {"entities": {}}, "schema": []}
{"input": "The leaf extract was prepared in acetone and was subjected to GC-MS analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The GC-MS analysis revealed the presence of nine major compounds.", "output": {"entities": {}}, "schema": []}
{"input": "E. citriodora extract at final concentration of 0. 25, 0. 50 and 1. 0 mu l/ml was supplemented with the diet and the flies were allowed to feed for 21days.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of extract was studied on the climbing ability and the oxidative stress on the PD model Drosophila expressing normal human alpha synuclein (h-alpha S) in the neurons.", "output": {"entities": {}}, "schema": []}
{"input": "The supplementation of 0. 25, 0. 50 and 1. 0 mu l/ml of E. citriodora extract showed a dose dependent significant delay in the loss of climbing ability and reduction in the oxidative stress in the brain of PD model flies.", "output": {"entities": {}}, "schema": []}
{"input": "The results also support the utility of this model in studying PD symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of enzymatically modified isoquercitrin on preneoplastic liver cell lesions induced by thioacetamide promotion in a two-stage hepatocarcinogenesis model using rats.", "output": {"entities": {"chemical": [{"text": "isoquercitrin", "start": 33, "end": 46}, {"text": "thioacetamide", "start": 94, "end": 107}]}}, "schema": []}
{"input": "To investigate the protective effect of enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and thioacetamide (TAA)-promoted rats.", "output": {"entities": {"chemical": [{"text": "isoquercitrin", "start": 63, "end": 76}, {"text": "N-diethylnitrosamine", "start": 169, "end": 189}, {"text": "thioacetamide", "start": 204, "end": 217}, {"text": "TAA", "start": 219, "end": 222}]}}, "schema": []}
{"input": "We examined the modifying effect of co-administration with EMIQ on the liver tissue environment including hepatic macrophages and lymphocytes and on the induction mechanism of preneoplastic cell apoptosis during early stages of hepatocellular tumor promotion.", "output": {"entities": {}}, "schema": []}
{"input": "TAA increased the number and area of glutathione S-transferase placental form (GST-P) (+) liver cell foci and the numbers of proliferating and apoptotic cells in randomly selected areas in liver sections.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 0, "end": 3}, {"text": "glutathione S", "start": 37, "end": 50}]}}, "schema": []}
{"input": "Co-administration with EMIQ suppressed these effects.", "output": {"entities": {}}, "schema": []}
{"input": "TAA also increased the numbers of ED2 (+), cyclooxygenase-2 (+), and heme oxygenase-1 (+) liver cells, as well as the number of CD3 (+) lymphocytes.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 0, "end": 3}, {"text": "heme", "start": 69, "end": 73}]}}, "schema": []}
{"input": "These effects were also suppressed by EMIQ.", "output": {"entities": {}}, "schema": []}
{"input": "EMIQ increased liver levels of thiobarbituric acid-reactive substance and 8-hydroxydeoxyguanosine, and TUNEL (+) apoptotic cells, death receptor 5 (DR5) (+) cells and 4-hydroxy-2-nonenal (+) cells within GST-P (+) foci.", "output": {"entities": {"chemical": [{"text": "thiobarbituric acid", "start": 31, "end": 50}, {"text": "8-hydroxydeoxyguanosine", "start": 74, "end": 97}, {"text": "4-hydroxy-2-nonenal", "start": 167, "end": 186}]}}, "schema": []}
{"input": "Outside the GST-P (+) foci, EMIQ decreased the numbers of apoptotic cells and DR5 (+) cells.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that TAA-induced tumor promotion involves activation of hepatic macrophages producing proinflammatory factors.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 27, "end": 30}]}}, "schema": []}
{"input": "EMIQ may suppress the TAA-induced tumor-promoting activity by an anti-inflammatory mechanism mediated by suppressing the activation of these macrophages.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 22, "end": 25}]}}, "schema": []}
{"input": "Furthermore, EMIQ may suppress tumor-promoting activity differentially between the inside and outside of GST-P (+) foci.", "output": {"entities": {}}, "schema": []}
{"input": "Within GST-P (+) foci, EMIQ facilitates the apoptosis of preneoplastic cells through the upregulation of DR5.", "output": {"entities": {}}, "schema": []}
{"input": "Outside the GST-P (+) foci, EMIQ suppresses apoptosis and the subsequent regeneration of non-transformed liver cells.", "output": {"entities": {}}, "schema": []}
{"input": "Bioavailability and intravenous toxicokinetic parameters for Pacific ciguatoxin P-CTX-1 in rats.", "output": {"entities": {"chemical": [{"text": "ciguatoxin", "start": 69, "end": 79}, {"text": "CTX-1", "start": 82, "end": 87}]}}, "schema": []}
{"input": "Ciguatoxins are sodium channel activator toxins responsible for ciguatera fish poisoning.", "output": {"entities": {"chemical": [{"text": "Ciguatoxins", "start": 0, "end": 11}, {"text": "sodium", "start": 16, "end": 22}]}}, "schema": []}
{"input": "In this study, we determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0. 13 ng P-CTX-1 per g of body weight.", "output": {"entities": {"chemical": [{"text": "ciguatoxin", "start": 73, "end": 83}, {"text": "CTX-1", "start": 86, "end": 91}, {"text": "CTX-1", "start": 145, "end": 150}]}}, "schema": []}
{"input": "The ciguatoxin activity was assessed over time in blood using the sensitive functional Neuro2a assay.", "output": {"entities": {"chemical": [{"text": "ciguatoxin", "start": 4, "end": 14}]}}, "schema": []}
{"input": "The data were analyzed with a two-compartmental model.", "output": {"entities": {}}, "schema": []}
{"input": "After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7. 8 L).", "output": {"entities": {"chemical": [{"text": "ciguatoxin", "start": 20, "end": 30}]}}, "schema": []}
{"input": "Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35. 5 h.", "output": {"entities": {"chemical": [{"text": "Ciguatoxin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The toxicokinetic parameters determined from this study were compared to data previously obtained after oral and intraperitoneal exposure of rats to 0. 26 ng P-CTX-1 per g of body weight.", "output": {"entities": {"chemical": [{"text": "CTX-1", "start": 160, "end": 165}]}}, "schema": []}
{"input": "Maximal bioavailability was determined by the area under the concentration curve, and was used to calculate the absolute P-CTX-1 bioavailabilities for oral and intraperitoneal routes of exposures of 39% and 75%, respectively.", "output": {"entities": {"chemical": [{"text": "CTX-1", "start": 123, "end": 128}]}}, "schema": []}
{"input": "Identification of alpha 2 beta 1 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae.", "output": {"entities": {}}, "schema": []}
{"input": "Integrins are receptors of the extracellular matrix (ECM), playing a vital role in pathophysiological processes.", "output": {"entities": {}}, "schema": []}
{"input": "They bind to ECM ligands like collagens and can mediate wound healing as well as tumor metastasis and thrombosis, thus being a part of cell adhesion and migration as well as platelet aggregation.", "output": {"entities": {}}, "schema": []}
{"input": "For this reason, identifying alpha 2 beta 1 integrin-specific antagonists can assist in the development of drugs to treat tumor progression, angiogenesis, and cardiovascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Snake venoms have been shown to contain antagonists which target collagen-binding integrins.", "output": {"entities": {}}, "schema": []}
{"input": "EMS16, rhodocetin, and VP12 are three toxins belonging to the C-type lectin-related protein family and have been proven to inhibit the alpha 2 beta 1 integrin, specifically the alpha 2 integrin A domain.", "output": {"entities": {}}, "schema": []}
{"input": "To specifically isolate antagonists targeting the alpha 2 beta 1 integrin A domain, we developed a protocol based on affinity chromatography.", "output": {"entities": {}}, "schema": []}
{"input": "Using this novel approach, the toxin VP-i was isolated from Vipera palaestinae venom.", "output": {"entities": {}}, "schema": []}
{"input": "We show that VP-i binds to the alpha 2 integrin A domain and that it successfully inhibits adhesion of various cells to type I collagen as well as cell migration.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, our results indicate that VP-i differs structurally from the previously purified VP12, although not functionally, and therefore is a further venom compound which can be utilized for drug development.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanical characteristics of human red blood cell membrane change due to C60 nanoparticle infiltration.", "output": {"entities": {"chemical": [{"text": "C60", "start": 74, "end": 77}]}}, "schema": []}
{"input": "The mechanical characteristics of human red blood cell (RBC) membrane change due to C (60) nanoparticle (NP) infiltration have been investigated in the present work.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 84, "end": 90}]}}, "schema": []}
{"input": "Using experimental approaches, including optical tweezer (OT) stretching and atomic force microscopy (AFM) indentation, we found that RBCs in the presence of C (60) NPs are softer than normal RBCs.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 158, "end": 164}]}}, "schema": []}
{"input": "The strain-stress relations of both normal and C (60) infiltrated RBC membranes are extracted from the data of AFM indentation, from which we proved that C (60) NP infiltration can affect the mechanical properties of RBC membrane and tend to weaken the tensile resistance of lipids bilayers.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 47, "end": 53}, {"text": "C (60)", "start": 154, "end": 160}]}}, "schema": []}
{"input": "In order to explain this experimental phenomenon, a mechanical model has been developed.", "output": {"entities": {}}, "schema": []}
{"input": "Based on this model, the strain-stress relations of both normal and C (60) infiltrated lipid bilayers are calculated with consideration of intermolecular interactions.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 68, "end": 74}]}}, "schema": []}
{"input": "The theoretical results are in great agreement with the experimental results.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of C (60) NP concentration on the mechanical properties of RBC membrane is successfully predicted.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 17, "end": 23}]}}, "schema": []}
{"input": "Higher concentrations of C (60) NPs in the lipid bilayers will lead to increased damage to the cell membrane, implying that the dosage of C (60) NPs should be controlled in medical applications.", "output": {"entities": {"chemical": [{"text": "C (60)", "start": 25, "end": 31}, {"text": "C (60)", "start": 138, "end": 144}]}}, "schema": []}
{"input": "Steady and out-of-equilibrium phase diagram of a complex fluid at the nanolitre scale: combining microevaporation, confocal Raman imaging and small angle X-ray scattering.", "output": {"entities": {}}, "schema": []}
{"input": "We engineered specific microfluidic devices based on the pervaporation of water through a PDMS membrane, to formulate continuous and steady concentration gradients of a binary aqueous molecular mixture at the nanolitre scale.", "output": {"entities": {"chemical": [{"text": "PDMS", "start": 90, "end": 94}]}}, "schema": []}
{"input": "In the case of a model complex fluid (a triblock copolymer solution), we demonstrate that such a steady gradient crosses the phase diagram from pure water up to a succession of highly viscous mesophases.", "output": {"entities": {}}, "schema": []}
{"input": "We then performed in situ spatially resolved measurements (confocal spectroscopy and small-angle X-ray scattering) to quantitatively measure the concentration profile and to determine the microstructure of the different textures.", "output": {"entities": {}}, "schema": []}
{"input": "Within a single microfluidic channel, we thus screen quantitatively and continuously the phase diagram of a complex fluid.", "output": {"entities": {}}, "schema": []}
{"input": "Beside, as such a gradient corresponds to an out-of-equilibrium regime, we also extract from the concentration measurement a precise estimate of the collective diffusion coefficient of the mixture as a function of the concentration.", "output": {"entities": {}}, "schema": []}
{"input": "In the present case of the triblock copolymer, this transport coefficient features discontinuities at some phase boundaries, which have never been observed before.", "output": {"entities": {}}, "schema": []}
{"input": "An N-terminal nuclear export signal regulates trafficking and aggregation of Huntingtin (Htt) protein exon 1.", "output": {"entities": {"chemical": [{"text": "N", "start": 3, "end": 4}]}}, "schema": []}
{"input": "Huntington disease is a dominantly inherited neurodegenerative condition caused by polyglutamine expansion in the N terminus of the huntingtin protein (Htt).", "output": {"entities": {"chemical": [{"text": "polyglutamine", "start": 83, "end": 96}, {"text": "N", "start": 114, "end": 115}]}}, "schema": []}
{"input": "The first 17 amino acids (N17) of Htt play a key role in regulating its toxicity and aggregation.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 13, "end": 24}]}}, "schema": []}
{"input": "Both nuclear export and cytoplasm retention functions have been ascribed to N17.", "output": {"entities": {}}, "schema": []}
{"input": "We have determined that N17 acts as a nuclear export sequence (NES) within Htt exon and when fused to yellow fluorescent protein.", "output": {"entities": {}}, "schema": []}
{"input": "We have defined amino acids within N17 that constitute the nuclear export sequence (NES).", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 16, "end": 27}]}}, "schema": []}
{"input": "Mutation of any of the conserved residues increases nuclear accumulation of Htt exon 1.", "output": {"entities": {}}, "schema": []}
{"input": "Nuclear export of Htt is sensitive to leptomycin B and is reduced by knockdown of exportin 1.", "output": {"entities": {"chemical": [{"text": "leptomycin B", "start": 38, "end": 50}]}}, "schema": []}
{"input": "In HEK293 cells, NES mutations decrease overall Htt aggregation but increase the fraction of cells with nuclear inclusions.", "output": {"entities": {}}, "schema": []}
{"input": "In primary cultured neurons, NES mutations increase nuclear accumulation and increase overall aggregation.", "output": {"entities": {}}, "schema": []}
{"input": "This work defines a bona fide nuclear export sequence within N17 and links it to effects on protein aggregation.", "output": {"entities": {}}, "schema": []}
{"input": "This may help explain the important role of N17 in controlling Htt toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Single-molecule catalysis mapping quantifies site-specific activity and uncovers radial activity gradient on single 2D nanocrystals.", "output": {"entities": {}}, "schema": []}
{"input": "Shape-controlled metal nanocrystals are a new generation of nanoscale catalysts.", "output": {"entities": {}}, "schema": []}
{"input": "Depending on their shapes, these nanocrystals exhibit various surface facets, and the assignments of their surface facets have routinely been used to rationalize or predict their catalytic activity in a variety of chemical transformations.", "output": {"entities": {}}, "schema": []}
{"input": "Recently we discovered that for 1-dimensional (1D) nanocrystals (Au nanorods), the catalytic activity is not constant along the same side facets of single nanorods but rather differs significantly and further shows a gradient along its length, which we attributed to an underlying gradient of surface defect density resulting from their linear decay in growth rate during synthesis (Nat. Nanotechnol. 2012, 7, 237-241).", "output": {"entities": {"chemical": [{"text": "Au", "start": 65, "end": 67}]}}, "schema": []}
{"input": "Here we report that this behavior also extends to 2D nanocrystals, even for a different catalytic reaction.", "output": {"entities": {}}, "schema": []}
{"input": "By using super-resolution fluorescence microscopy to map out the locations of catalytic events within individual triangular and hexagonal Au nanoplates in correlation with scanning electron microscopy, we find that the catalytic activity within the flat {111} surface facet of a Au nanoplate exhibits a 2D radial gradient from the center toward the edges.", "output": {"entities": {"chemical": [{"text": "Au", "start": 138, "end": 140}, {"text": "Au", "start": 279, "end": 281}]}}, "schema": []}
{"input": "We propose that this activity gradient results from a growth-dependent surface defect distribution.", "output": {"entities": {}}, "schema": []}
{"input": "We also quantify the site-specific activity at different regions within a nanoplate: The corner regions have the highest activity, followed by the edge regions and then the flat surface facets.", "output": {"entities": {}}, "schema": []}
{"input": "These discoveries highlight the spatial complexity of catalytic activity at the nanoscale as well as the interplay amid nanocrystal growth, morphology, and surface defects in determining nanocatalyst properties.", "output": {"entities": {}}, "schema": []}
{"input": "Evidence for self-association of the alternative sigma factor sigma 54.", "output": {"entities": {}}, "schema": []}
{"input": "Sigma factor sigma (54) has a distinct modus operandi for mediating the activation of bacterial RNA polymerase (RNAP) at promoter recognition motifs 12 and 24 bp upstream from transcription start sites.", "output": {"entities": {}}, "schema": []}
{"input": "sigma (54) was thought to act as monomer in all transcription steps.", "output": {"entities": {}}, "schema": []}
{"input": "However, we provide evidence that sigma (54) of Pseudomonas putida interacts stably with itself.", "output": {"entities": {}}, "schema": []}
{"input": "The interface between monomers involves contacts in sigma (54) regions I and III, sequences that play key roles in the transcription activation of sigma (54)-RNAP holoenzyme.", "output": {"entities": {}}, "schema": []}
{"input": "These roles include interactions with activator proteins and the-12 and-24 motifs.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, we detected inter-monomer contacts between region I, and between region I and the C-terminal portion of region III.", "output": {"entities": {"chemical": [{"text": "C", "start": 97, "end": 98}]}}, "schema": []}
{"input": "Our results suggest a new auto-antagonistic regulatory state of sigma (54).", "output": {"entities": {}}, "schema": []}
{"input": "Determinants of regioselectivity and chemoselectivity in fosfomycin resistance protein FosA from QM/MM calculations.", "output": {"entities": {"chemical": [{"text": "fosfomycin", "start": 57, "end": 67}]}}, "schema": []}
{"input": "FosA is a manganese-dependent enzyme that utilizes a Mn (2 +) ion to catalyze the inactivation of the fosfomycin antibiotic by glutathione (GSH) addition.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 10, "end": 19}, {"text": "Mn (2 +)", "start": 53, "end": 61}, {"text": "fosfomycin", "start": 102, "end": 112}, {"text": "glutathione", "start": 127, "end": 138}, {"text": "GSH", "start": 140, "end": 143}]}}, "schema": []}
{"input": "We report a theoretical study on the catalytic mechanism and the factors governing the regioselectivity and chemoselectivity of FosA.", "output": {"entities": {}}, "schema": []}
{"input": "Density functional theory (DFT) calculations on the uncatalyzed reaction give high barriers and almost no regioselectivity even when adding two water molecules to assist the proton transfer.", "output": {"entities": {}}, "schema": []}
{"input": "According to quantum mechanics/molecular mechanics (QM/MM) calculations on the full solvated protein, the enzyme-catalyzed glutathione addition reaction involves two major chemical steps that both proceed in the sextet state: proton transfer from the GSH thiol group to the Tyr39 anion and nucleophilic attack by the GSH thiolate leading to epoxide ring-opening.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 123, "end": 134}, {"text": "GSH thiol", "start": 251, "end": 260}, {"text": "Tyr39", "start": 274, "end": 279}, {"text": "GSH thiolate", "start": 317, "end": 329}, {"text": "epoxide", "start": 341, "end": 348}]}}, "schema": []}
{"input": "The second step is rate-limiting and is facilitated by the presence of the high-spin Mn (2 +) ion that functions as a Lewis acid and stabilizes the leaving oxyanion through direct coordination.", "output": {"entities": {"chemical": [{"text": "Mn (2 +)", "start": 85, "end": 93}, {"text": "Lewis acid", "start": 118, "end": 128}]}}, "schema": []}
{"input": "The barrier for C1 attack is computed to be 8. 9 kcal/mol lower than that for C2 attack, in agreement with the experimentally observed regioselectivity of the enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Further QM/MM calculations on the alternative water attack predict a concerted mechanism for this reaction, where the deprotonation of water, nucleophilic attack, and epoxide ring-opening take place via the same transition state.", "output": {"entities": {"chemical": [{"text": "epoxide", "start": 167, "end": 174}]}}, "schema": []}
{"input": "The calculated barrier is 8. 3 kcal/mol higher than that for GSH attack, in line with the observed chemoselectivity of the enzyme, which manages to catalyze the addition of GSH in the presence of water molecules around its active site.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 61, "end": 64}, {"text": "GSH", "start": 173, "end": 176}]}}, "schema": []}
{"input": "The catalytic efficiency, regioselectivity, and chemoselectivity of FosA are rationalized in terms of the influence of the active-site protein environment and the different stabilization of the distorted substrates in the relevant transition states.", "output": {"entities": {}}, "schema": []}
{"input": "What is the contact angle of water on graphene?", "output": {"entities": {"chemical": [{"text": "graphene", "start": 38, "end": 46}]}}, "schema": []}
{"input": "Although experimental and theoretical studies have addressed the question of the wetting properties of graphene, the actual value of the contact angle of water on an isolated graphene monolayer remains unknown.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 103, "end": 111}, {"text": "graphene", "start": 175, "end": 183}]}}, "schema": []}
{"input": "While recent experimental literature indicates that the contact angle of water on graphite is in the range 90-95 degrees, it has been suggested that the contact angle on graphene may either be as high as 127 degrees or moderately enhanced in comparison with graphite.", "output": {"entities": {"chemical": [{"text": "graphite", "start": 82, "end": 90}, {"text": "graphene", "start": 170, "end": 178}, {"text": "graphite", "start": 258, "end": 266}]}}, "schema": []}
{"input": "With the support of classical molecular dynamics simulations using empirical force-fields, we develop an argumentation to show that the value of 127 degrees is an unrealistic estimate and that a value of the order of 95-100 degrees should be expected.", "output": {"entities": {}}, "schema": []}
{"input": "Our study establishes a connection between the variation of the work of adhesion of water on graphene-based surfaces and the interaction potential between individual water molecules and these surfaces.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 93, "end": 101}]}}, "schema": []}
{"input": "We show that a variation of the contact angle from 90 degrees on graphite to 127 degrees on graphene would imply that both of the first two carbon layers of graphite contribute approximately the same interaction energy with water.", "output": {"entities": {"chemical": [{"text": "graphite", "start": 65, "end": 73}, {"text": "graphene", "start": 92, "end": 100}, {"text": "carbon", "start": 140, "end": 146}, {"text": "graphite", "start": 157, "end": 165}]}}, "schema": []}
{"input": "Such a situation is incompatible with the short-range nature of the interaction between water and this substrate.", "output": {"entities": {}}, "schema": []}
{"input": "We also show that the interaction potential energy between water and the graphene-based substrates is the main contribution to the work of adhesion of water with a relative magnitude that is independent of the number of graphene layers.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 73, "end": 81}, {"text": "graphene", "start": 220, "end": 228}]}}, "schema": []}
{"input": "We introduce the idea that the remaining contribution is entropic in nature and is connected to the fluctuations in the water-substrate interaction energy.", "output": {"entities": {}}, "schema": []}
{"input": "Lessons on conditional gene targeting in mouse adipose tissue.", "output": {"entities": {}}, "schema": []}
{"input": "Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation.", "output": {"entities": {}}, "schema": []}
{"input": "To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter.", "output": {"entities": {"chemical": [{"text": "tamoxifen", "start": 234, "end": 243}]}}, "schema": []}
{"input": "All three Cre lines demonstrated recombination in the brown and white fat pads.", "output": {"entities": {}}, "schema": []}
{"input": "Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat.", "output": {"entities": {}}, "schema": []}
{"input": "The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, nonmyocyte cells in the skeletal muscle.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in ~ 2% of spermatozoa.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, different \" adipocyte-specific \" Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology.", "output": {"entities": {}}, "schema": []}
{"input": "Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.", "output": {"entities": {}}, "schema": []}
{"input": "Morphine and related micro-opioid receptor (MOR) agonists remain among the most effective drugs known for acute relief of severe pain.", "output": {"entities": {"chemical": [{"text": "Morphine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "A major problem in treating painful conditions is that tolerance limits the long-term utility of opioid agonists.", "output": {"entities": {}}, "schema": []}
{"input": "Considerable effort has been expended on developing an understanding of the molecular and cellular processes that underlie acute MOR signaling, short-term receptor regulation, and the progression of events that lead to tolerance for different MOR agonists.", "output": {"entities": {}}, "schema": []}
{"input": "Although great progress has been made in the past decade, many points of contention and controversy cloud the realization of this progress.", "output": {"entities": {}}, "schema": []}
{"input": "This review attempts to clarify some confusion by clearly defining terms, such as desensitization and tolerance, and addressing optimal pharmacological analyses for discerning relative importance of these cellular mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular and molecular mechanisms regulating MOR function by phosphorylation relative to receptor desensitization and endocytosis are comprehensively reviewed, with an emphasis on agonist-biased regulation and areas where knowledge is lacking or controversial.", "output": {"entities": {}}, "schema": []}
{"input": "The implications of these mechanisms for understanding the substantial contribution of MOR signaling to opioid tolerance are then considered in detail.", "output": {"entities": {}}, "schema": []}
{"input": "While some functional MOR regulatory mechanisms contributing to tolerance are clearly understood, there are large gaps in understanding the molecular processes responsible for loss of MOR function after chronic exposure to opioids.", "output": {"entities": {}}, "schema": []}
{"input": "Further elucidation of the cellular mechanisms that are regulated by opioids will be necessary for the successful development of MOR-based approaches to new pain therapeutics that limit the development of tolerance.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of a Self-Administered Oral Glucose Tolerance Test.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 39, "end": 46}]}}, "schema": []}
{"input": "OBJECTIVETo assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODSEighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0-and 120-min venous plasma samples (twice).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 107, "end": 114}, {"text": "glucose", "start": 448, "end": 455}]}}, "schema": []}
{"input": "The device displayed no results.", "output": {"entities": {}}, "schema": []}
{"input": "A detachable data recorder returned to the clinic provided plasma-equivalent 0-and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTSThe device was universally popular with participants, was perceived as easy to use, and the ability to test at home was well-liked.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 91, "end": 98}, {"text": "glucose", "start": 198, "end": 205}]}}, "schema": []}
{"input": "Device failures meant that 0-and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 41, "end": 48}]}}, "schema": []}
{"input": "Device glucose measurements showed a mean bias compared with laboratory-measured values of + 0. 9 at 5. 0 mmol/L increasing to + 4. 4 at 15. 0 mmol/L.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 7, "end": 14}]}}, "schema": []}
{"input": "Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONSSelf-administered OGTTs can be performed successfully by untrained individuals in a community setting.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 14, "end": 21}]}}, "schema": []}
{"input": "With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 200, "end": 207}]}}, "schema": []}
{"input": "Synthesis and evaluation of antibacterial activity of 7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline derivatives.", "output": {"entities": {"chemical": [{"text": "7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline", "start": 54, "end": 104}]}}, "schema": []}
{"input": "In this study, a series of 7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline derivatives was synthesized and tested for their antibacterial activity against various bacterial strains.", "output": {"entities": {"chemical": [{"text": "7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline", "start": 27, "end": 77}]}}, "schema": []}
{"input": "Most of the compounds exhibited potential antibacterial activity against gram-negative and gram-positive bacteria.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 7p (7-heptyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline) was found to be the most potent inhibitor.", "output": {"entities": {"chemical": [{"text": "7-heptyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline", "start": 13, "end": 64}]}}, "schema": []}
{"input": "The minimum inhibitory concentration (MIC) of compound 7p against Escherichia coli was 0. 5 mu g/mL, better than that of reference agent ciprofloxacin and amoxicillin.", "output": {"entities": {"chemical": [{"text": "ciprofloxacin", "start": 137, "end": 150}, {"text": "amoxicillin", "start": 155, "end": 166}]}}, "schema": []}
{"input": "Furthermore, compound 7p exhibited a modest activity against several gram-negative bacterial strains at a dose range of 2-64 mu g/mL.", "output": {"entities": {}}, "schema": []}
{"input": "A common LRP4 haplotype is associated with bone mineral density and hip geometry in men-data from the Odense Androgen Study (OAS).", "output": {"entities": {}}, "schema": []}
{"input": "Osteoporosis is a common disease characterized by an increased susceptibility to fracture.", "output": {"entities": {}}, "schema": []}
{"input": "It is a complex disorder resulting from the interaction of several polymorphisms in different genes and environmental factors.", "output": {"entities": {}}, "schema": []}
{"input": "Since we recently reported a role for low density lipoprotein-related protein (LRP)-4 in monogenic disorders with bone overgrowth, we now wanted to evaluate whether genetic variation in the LRP4 gene has an effect on the susceptibility to osteoporosis in a population based cohort from the Odense Androgen Study.", "output": {"entities": {"chemical": [{"text": "Androgen", "start": 297, "end": 305}]}}, "schema": []}
{"input": "We chose to genotype four common (minor allele frequency (MAF) >= 0. 05) and non-synonymous coding polymorphisms located in the extracellular region of the LRP4 protein: rs3816614 (A/g), rs2306029 (G/a), rs2306033 (C/t) and rs6485702 (G/a) (large and small characters indicate major and minor alleles, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "Bone mineral density (BMD) measurements of the hip, the spine and whole body as well as different hip geometry parameters were available for a total of 1404 Danish men from two age groups ([20-29 years]: n = 804; [60-74 years]: n = 600).", "output": {"entities": {}}, "schema": []}
{"input": "Using linear regression analysis adjusted for age, height and weight, we found significant associations between both rs2306029 and rs6485702 and BMD at all sites except the lumbar spine.", "output": {"entities": {}}, "schema": []}
{"input": "The most significant association was found with whole body BMD (p = 4. 7 x 10 (-5)).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we found these two polymorphisms to be associated with different geometry parameters especially of the femoral shaft.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of the two associated SNPs in the separate age groups demonstrated that most associations are only present in the youngest group of Danish men.", "output": {"entities": {}}, "schema": []}
{"input": "In the group of elderly men, one Bonferroni corrected association between whole body BMD and rs6485702 was found to be significant.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, all polymorphisms were included in haplotype analyses using the PLINK software (v1. 07).", "output": {"entities": {}}, "schema": []}
{"input": "After adjusting for age, height and weight, two out of five common haplotypes (MAF >= 0. 01) were found to be of particular interest in the regulation of hip and whole body BMD (AGCG, AACA).", "output": {"entities": {}}, "schema": []}
{"input": "Additional analysis suggested that these latter associations are driven by the association of rs6485702.", "output": {"entities": {}}, "schema": []}
{"input": "We suggest, based on these results and the localisation of the variant in the third beta-propeller domain of LRP4, that the variant has possibly a functional effect.", "output": {"entities": {}}, "schema": []}
{"input": "Hereby, we conclude that common variation in the LRP4 gene determines hip and whole body BMD and thus confirm previous results from different GWAs.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, our data proves an additional role for LRP4 in regulating hip structure.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, interaction analysis for LRP4 with SOST and LRP5 showed interaction with LRP5 for femoral shaft geometry.", "output": {"entities": {}}, "schema": []}
{"input": "Cardioprotective potential of N, alpha-L-rhamnopyranosyl vincosamide, an indole alkaloid, isolated from the leaves of Moringa oleifera in isoproterenol induced cardiotoxic rats: in vivo and in vitro studies.", "output": {"entities": {"chemical": [{"text": "N, alpha-L-rhamnopyranosyl vincosamide", "start": 30, "end": 68}, {"text": "indole alkaloid", "start": 73, "end": 88}, {"text": "isoproterenol", "start": 138, "end": 151}]}}, "schema": []}
{"input": "Hitherto unknown protective effect of N, alpha-L-rhamnopyranosyl vincosamide (VR), isolated from Moringa oleifera leaves in isoproterenol (ISO)-induced cardiac toxicity was evaluated in rats.", "output": {"entities": {"chemical": [{"text": "N, alpha-L-rhamnopyranosyl vincosamide", "start": 38, "end": 76}, {"text": "isoproterenol", "start": 124, "end": 137}, {"text": "ISO", "start": 139, "end": 142}]}}, "schema": []}
{"input": "Oral administration of VR at 40 mg/kg for 7 days markedly reduced the ISO-induced increase in the levels of serum cardiac markers such as troponin-T, creatine kinase-MB, lactate dehydrogenase and glutamate pyruvate transaminase as well as cardiac lipid peroxidation with a parallel increase in the cellular antioxidants suggesting its cardio-protective and free radical scavenging potential, which was latter confirmed by in vitro study.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 70, "end": 73}, {"text": "creatine", "start": 150, "end": 158}, {"text": "lactate", "start": 170, "end": 177}, {"text": "glutamate pyruvate", "start": 196, "end": 214}]}}, "schema": []}
{"input": "Rats treated with test compound also improved the ISO-induced abnormal changes in ECG as well as in cardiac histology.", "output": {"entities": {"chemical": [{"text": "ISO", "start": 50, "end": 53}]}}, "schema": []}
{"input": "A reduction in myocardial necrosis was further evidenced by the tri-phenyl tetrazolium chloride (TTC) stain in isolated test drug pretreated rats.", "output": {"entities": {"chemical": [{"text": "tri-phenyl tetrazolium chloride", "start": 64, "end": 95}, {"text": "TTC", "start": 97, "end": 100}]}}, "schema": []}
{"input": "These findings suggest the cardio-protective potential of the isolated alkaloid and possibly the beneficial action is mediated through its free radical scavenging property.", "output": {"entities": {}}, "schema": []}
{"input": "Indenoindolone derivatives as topoisomerase II-inhibiting anticancer agents.", "output": {"entities": {"chemical": [{"text": "Indenoindolone", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Based on known heterocyclic topoisomerase II inhibitors and anticancer agents, various indenoindolone derivatives were predicted as potential topoisomerase II-inhibiting anticancer agents.", "output": {"entities": {"chemical": [{"text": "indenoindolone", "start": 87, "end": 101}]}}, "schema": []}
{"input": "They are hydrazones, (thio) semicarbazones, and oximes of indenoindolones, and indenoindolols.", "output": {"entities": {"chemical": [{"text": "hydrazones", "start": 9, "end": 19}, {"text": "(thio) semicarbazones", "start": 21, "end": 42}, {"text": "oximes of indenoindolones", "start": 48, "end": 73}, {"text": "indenoindolols", "start": 79, "end": 93}]}}, "schema": []}
{"input": "These derivatives with suitable substitutions exhibited potent specific inhibition of human DNA TopoII alpha while not showing inhibition of topoisomerase I and DNA intercalation, despite the fact that parent indenoindolones are known poor/moderate inhibitors of topoisomerase II.", "output": {"entities": {"chemical": [{"text": "indenoindolones", "start": 209, "end": 224}]}}, "schema": []}
{"input": "The potent topoisomerase II inhibitor indenoindolone derivatives exhibited good anticancer activities compared to etoposide and 5-fluorouracil, and relatively low toxicity to normal cells.", "output": {"entities": {"chemical": [{"text": "indenoindolone", "start": 38, "end": 52}, {"text": "etoposide", "start": 114, "end": 123}, {"text": "5-fluorouracil", "start": 128, "end": 142}]}}, "schema": []}
{"input": "These derivatizations of indenoindolones were found to result in enhancement of anticancer activities.", "output": {"entities": {"chemical": [{"text": "indenoindolones", "start": 25, "end": 40}]}}, "schema": []}
{"input": "Empirical power of very rare variants for common traits and disease: results from sanger sequencing 1998 individuals.", "output": {"entities": {}}, "schema": []}
{"input": "The optimal study design for identifying rare variants associated with common disease is not yet clear and researchers have to decide whether to prioritize lower sequencing coverage on larger sample sizes, or higher coverage on smaller sample sizes.", "output": {"entities": {}}, "schema": []}
{"input": "High-coverage sequencing affords several advantages, such as genotype accuracy and improved identification of very rare variants, but this comes at increased cost.", "output": {"entities": {}}, "schema": []}
{"input": "However, the magnitude of the contribution of very rare variants to the statistical power of gene-based association tests is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "By using Sanger sequence data on seven genes from 1998 subjects with simulated phenotypes, we provide evidence that excluding very rare variants, in general, reduces the statistical power of rare variant association tests only modestly.", "output": {"entities": {}}, "schema": []}
{"input": "However, if the probability of being causal and the effect size of the causal variants are inversely related to the minor allele frequency, then very rare variants do contribute to some power, however the absolute power remains low.", "output": {"entities": {}}, "schema": []}
{"input": "As very rare variants constitute the majority of variants identified in sequencing studies, these findings suggest that careful attention need to be placed on the plausible relationship that exist between very rare variants and common disease. European Journal of Human Genetics advance online publication, 16 January 2013; doi: 10. 1038/ejhg. 2012. 284.", "output": {"entities": {}}, "schema": []}
{"input": "The first self-sustainable microbial fuel cell stack.", "output": {"entities": {}}, "schema": []}
{"input": "This study reports for the first time on the development of a self-sustainable microbial fuel cell stack capable of self-maintenance (feeding, hydration, sensing & reporting).", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the stack system is producing excess energy, which can be used for improved functionality.", "output": {"entities": {}}, "schema": []}
{"input": "The self-maintenance is performed by the stack powering single and multi-channel peristaltic pumps.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of the alpha 7 nicotinic ACh receptor induces anxiogenic effects in rats which is blocked by a 5-HT1a receptor antagonist.", "output": {"entities": {}}, "schema": []}
{"input": "The alpha 7 nicotinic acetylcholine receptor (nAChR) is highly expressed in different regions of the brain and is associated with cognitive function as well as anxiety.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 22, "end": 35}]}}, "schema": []}
{"input": "Agonists and positive allosteric modulators (PAMs) of the alpha 7 subtype of nAChRs have been shown to improve cognition.", "output": {"entities": {}}, "schema": []}
{"input": "Previously nicotine, which activates both alpha 7 and non-alpha 7 subtypes of nAChRs, has been shown to have an anxiogenic effect in behavioral tests.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 11, "end": 19}]}}, "schema": []}
{"input": "In this study, we compared the effects of the alpha 7-selective agonist (PNU-282987) and PAM (PNU-120596) in a variety of behavioral tests in Sprague Dawley rats to look at their effects on learning and memory as well as anxiety.", "output": {"entities": {"chemical": [{"text": "PNU-282987", "start": 73, "end": 83}, {"text": "PNU-120596", "start": 94, "end": 104}]}}, "schema": []}
{"input": "We found that neither PNU-282987 nor PNU-120596 improved spatial-learning or episodic memory by themselves.", "output": {"entities": {"chemical": [{"text": "PNU-282987", "start": 22, "end": 32}, {"text": "PNU-120596", "start": 37, "end": 47}]}}, "schema": []}
{"input": "However when cognitive impairment was induced in the rats with scopolamine (1 mg/kg), both PNU-120596 and PNU-282987 were able to reverse this memory impairment and restore it back to normal levels.", "output": {"entities": {"chemical": [{"text": "scopolamine", "start": 63, "end": 74}, {"text": "PNU-120596", "start": 91, "end": 101}, {"text": "PNU-282987", "start": 106, "end": 116}]}}, "schema": []}
{"input": "While PNU-120596 reversed the scopolamine-induced cognitive impairment, it did not have any adverse effect on anxiety.", "output": {"entities": {"chemical": [{"text": "PNU-120596", "start": 6, "end": 16}]}}, "schema": []}
{"input": "PNU-282987 on the other hand displayed an increase in anxiety-like behavior at a higher dose (10 mg/kg) that was significantly reduced by the serotonin 5-HT1a receptor antagonist WAY-100135.", "output": {"entities": {"chemical": [{"text": "PNU-282987", "start": 0, "end": 10}, {"text": "WAY-100135", "start": 179, "end": 189}]}}, "schema": []}
{"input": "However the alpha 7 receptor antagonist methyllycaconitine was unable to reverse these anxiety-like effects seen with PNU-282987.", "output": {"entities": {"chemical": [{"text": "methyllycaconitine", "start": 40, "end": 58}, {"text": "PNU-282987", "start": 118, "end": 128}]}}, "schema": []}
{"input": "These results suggest that alpha 7 nAChR PAMs are pharmacologically advantageous over agonists, and should be considered for further development as therapeutic drugs targeting the alpha 7 receptors.", "output": {"entities": {}}, "schema": []}
{"input": "Microwave absorption in powders of small conducting particles for heating applications.", "output": {"entities": {}}, "schema": []}
{"input": "In microwave chemistry there is a common misconception that small, highly conducting particles heat profusely when placed in a large microwave electric field.", "output": {"entities": {}}, "schema": []}
{"input": "However, this is not the case; with the simple physical explanation that the electric field (which drives the heating) within a highly conducting particle is highly screened.", "output": {"entities": {}}, "schema": []}
{"input": "Instead, it is the magnetic absorption associated with induction that accounts for the large experimental heating rates observed for small metal particles.", "output": {"entities": {}}, "schema": []}
{"input": "We present simple principles for the effective heating of particles in microwave fields from calculations of electric and magnetic dipole absorptions for a range of practical values of particle size and conductivity.", "output": {"entities": {}}, "schema": []}
{"input": "For highly conducting particles, magnetic absorption dominates electric absorption over a wide range of particle radii, with an optimum absorption set by the ratio of mean particle radius a to the skin depth delta (specifically, by the condition a = 2. 41 delta).", "output": {"entities": {}}, "schema": []}
{"input": "This means that for particles of any conductivity, optimized magnetic absorption (and hence microwave heating by magnetic induction) can be achieved by simple selection of the mean particle size.", "output": {"entities": {}}, "schema": []}
{"input": "For weakly conducting samples, electric dipole absorption dominates, and is maximized when the conductivity is approximately sigma =~ 3 omega epsilon (0) =~ 0. 4 S m (-1), independent of particle radius.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, although electric dipole heating can be as effective as magnetic dipole heating for a powder sample of the same volume, it is harder to obtain optimized conditions at a fixed frequency of microwave field.", "output": {"entities": {}}, "schema": []}
{"input": "The absorption of sub-micron particles is ineffective in both magnetic and electric fields.", "output": {"entities": {}}, "schema": []}
{"input": "However, if the particles are magnetic, with a lossy part to their complex permeability, then magnetic dipole losses are dramatically enhanced compared to their values for non-magnetic particles.", "output": {"entities": {}}, "schema": []}
{"input": "An interesting application of this is the use of very small magnetic particles for the selective microwave heating of biological samples.", "output": {"entities": {}}, "schema": []}
{"input": "LPA1-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "There has been much recent interest in lysophosphatidic acid (LPA) signaling through one of its receptors, LPA1, in fibrotic diseases, but the mechanisms by which LPA-LPA1 signaling promotes pathological fibrosis remain to be fully elucidated.", "output": {"entities": {"chemical": [{"text": "lysophosphatidic acid", "start": 39, "end": 60}, {"text": "LPA", "start": 62, "end": 65}, {"text": "LPA1", "start": 107, "end": 111}]}}, "schema": []}
{"input": "Using a mouse peritoneal fibrosis model, we demonstrate central roles for LPA and LPA1 in fibroblast proliferation.", "output": {"entities": {"chemical": [{"text": "LPA", "start": 74, "end": 77}]}}, "schema": []}
{"input": "Genetic deletion or pharmacological antagonism of LPA1 protected mice from peritoneal fibrosis, blunting the increases in peritoneal collagen by 65. 4 and 52. 9%, respectively, compared to control animals and demonstrated that peritoneal fibroblast proliferation was highly LPA1 dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of LPA1 on mesothelial cells induced these cells to express connective tissue growth factor (CTGF), driving fibroblast proliferation in a paracrine fashion.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of mesothelial cell LPA1 induced CTGF expression by inducing cytoskeleton reorganization in these cells, causing nuclear translocation of myocardin-related transcription factor (MRTF)-A and MRTF-B.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacological inhibition of MRTF-induced transcription also diminished CTGF expression and fibrosis in the peritoneal fibrosis model, mitigating the increase in peritoneal collagen content by 57. 9% compared to controls.", "output": {"entities": {}}, "schema": []}
{"input": "LPA1-induced cytoskeleton reorganization therefore makes a previously unrecognized but critically important contribution to the profibrotic activities of LPA by driving MRTF-dependent CTGF expression, which, in turn, drives fibroblast proliferation.-Sakai, N., Chun, J., Duffield, J.", "output": {"entities": {"chemical": [{"text": "LPA1", "start": 0, "end": 4}]}}, "schema": []}
{"input": "S., Wada, T., Luster, A.", "output": {"entities": {}}, "schema": []}
{"input": "D., Tager, A.", "output": {"entities": {}}, "schema": []}
{"input": "M.", "output": {"entities": {}}, "schema": []}
{"input": "LPA1-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin resistance is a very common associate of polycystic ovary syndrome (PCOS).", "output": {"entities": {}}, "schema": []}
{"input": "Pathophysiology in relation with the essential elements including copper, magnesium, zinc, manganese, chromium, and calcium has been reported in women with insulin resistance.", "output": {"entities": {"chemical": [{"text": "copper", "start": 66, "end": 72}, {"text": "magnesium", "start": 74, "end": 83}, {"text": "zinc", "start": 85, "end": 89}, {"text": "manganese", "start": 91, "end": 100}, {"text": "chromium", "start": 102, "end": 110}, {"text": "calcium", "start": 116, "end": 123}]}}, "schema": []}
{"input": "This prospective study was designed to explore whether the women with PCOS do exhibit altered serum element levels in association with/without insulin resistance.", "output": {"entities": {}}, "schema": []}
{"input": "One hundred and thirty-two women with PCOS and forty-six control women were studied.", "output": {"entities": {}}, "schema": []}
{"input": "Women with PCOS were further divided based on the presence of insulin resistance (insulin resistant: n = 50; non-insulin resistant: n = 82).", "output": {"entities": {}}, "schema": []}
{"input": "In all women, basal levels of gonadotropins, prolactin, testosterone, insulin, glucose, and the six different elements were measured.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 56, "end": 68}, {"text": "glucose", "start": 79, "end": 86}]}}, "schema": []}
{"input": "Serum levels of testosterone (p < 0. 001), luteinizing hormone (p < 0. 05), and fasting insulin (p < 0. 004) were significantly higher in the PCOS population compared to controls as well as PCOS women without insulin resistance.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 16, "end": 28}]}}, "schema": []}
{"input": "Women with PCOS exhibited a significantly high calcium (p < 0. 04) and lower manganese levels (p < 0. 002) when compared to controls.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 47, "end": 54}, {"text": "manganese", "start": 77, "end": 86}]}}, "schema": []}
{"input": "However, the PCOS women with insulin resistance exhibited significantly lower serum levels of magnesium and chromium (p < 0. 04), in addition to higher levels of zinc and copper (p < 0. 04).", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 94, "end": 103}, {"text": "chromium", "start": 108, "end": 116}, {"text": "zinc", "start": 162, "end": 166}, {"text": "copper", "start": 171, "end": 177}]}}, "schema": []}
{"input": "The differences in calcium (p < 0. 03) and manganese levels (p < 0. 0001) became aggravated with the presence of insulin resistance when compared to control as well as PCOS women without insulin resistance.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 19, "end": 26}, {"text": "manganese", "start": 43, "end": 52}]}}, "schema": []}
{"input": "In PCOS-associated insulin resistance, circulating serum magnesium (r =-0. 31; p < 0. 03) and chromium (r =-0. 38; p < 0. 006) status significantly correlated with fasting insulin levels.", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 57, "end": 66}, {"text": "chromium", "start": 94, "end": 102}]}}, "schema": []}
{"input": "We conclude that imbalanced element status may be a key foundation for insulin resistance in PCOS.", "output": {"entities": {}}, "schema": []}
{"input": "The findings in this study should be investigated with further trials in order to obtain new insights into PCOS.", "output": {"entities": {}}, "schema": []}
{"input": "Insights into TIM-barrel prenyl transferase mechanisms: crystal structures of PcrB from Bacillus subtilis and Staphylococcus aureus.", "output": {"entities": {}}, "schema": []}
{"input": "Well structured: As a new triose phosphate isomerase (TIM) barrel-fold prenyl transferase, PcrB catalyzes the production of heptaprenylglyceryl phosphate from heptaprenyl diphosphate and glycerol-1-phosphate.", "output": {"entities": {"chemical": [{"text": "triose phosphate", "start": 26, "end": 42}, {"text": "heptaprenylglyceryl phosphate", "start": 124, "end": 153}, {"text": "heptaprenyl diphosphate", "start": 159, "end": 182}, {"text": "glycerol-1-phosphate", "start": 187, "end": 207}]}}, "schema": []}
{"input": "Crystal structures of PcrB from Bacillus subtilis and Staphylococcus aureus in complex with ligands were solved, and together with site-directed mutagenesis and bioinformatics analyses, clearly reveal the catalytic mechanism of the enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Cross-tolerance in amphibians: wood frog mortality when exposed to three insecticides with a common mode of action.", "output": {"entities": {}}, "schema": []}
{"input": "Insecticide tolerance and cross-tolerance in nontarget organisms is often overlooked despite its potential to buffer natural systems from anthropogenic influence.", "output": {"entities": {}}, "schema": []}
{"input": "We exposed wood frog tadpoles from 15 populations to three acetylcholine esterase-inhibiting insecticides and found widespread variation in insecticide tolerance and evidence for cross-tolerance to these insecticides.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 59, "end": 72}]}}, "schema": []}
{"input": "Our results demonstrate that amphibian populations with tolerance to one pesticide may be tolerant to many other pesticides.", "output": {"entities": {}}, "schema": []}
{"input": "Associations between perfluoroalkyl compounds and immune and clinical chemistry parameters in highly exposed bottlenose dolphins (Tursiops truncatus).", "output": {"entities": {"chemical": [{"text": "perfluoroalkyl", "start": 21, "end": 35}]}}, "schema": []}
{"input": "Perfluoroalkyl compounds (PFCs) are ubiquitous, persistent chemical contaminants found in the environment, wildlife, and humans.", "output": {"entities": {"chemical": [{"text": "Perfluoroalkyl", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Despite the widespread occurrence of PFCs, little is known about the impact these contaminants have on the health of wildlife populations.", "output": {"entities": {}}, "schema": []}
{"input": "The authors investigated the relationship between PFCs (including sum perfluorocarboxylates, sum perfluoroalkyl sulfonates, perfluorooctane sulfonate, perfluorooctanoic acid, and perfluorodecanoic acid) and the clinocopathologic and immune parameters in a highly exposed population (n = 79) of Atlantic bottlenose dolphins (mean sum PFCs = 1970 ng/ml; range 574-8670 ng/ml) sampled from 2003 to 2005 near Charleston, South Carolina, USA.", "output": {"entities": {"chemical": [{"text": "perfluorocarboxylates", "start": 70, "end": 91}, {"text": "perfluoroalkyl sulfonates", "start": 97, "end": 122}, {"text": "perfluorooctane sulfonate", "start": 124, "end": 149}, {"text": "perfluorooctanoic acid", "start": 151, "end": 173}, {"text": "perfluorodecanoic acid", "start": 179, "end": 201}]}}, "schema": []}
{"input": "Age-adjusted linear regression models showed statistically significant positive associations between exposure to one or more of the PFC totals and/or individual analytes and the following immunological parameters: absolute numbers of CD2 + T cells, CD4 + helper T cells, CD19 + immature B cells, CD21 + mature B cells, CD2/CD21 ratio, MHCII + cells, B cell proliferation, serum IgG1, granulocytic, and monocytic phagocytosis.", "output": {"entities": {}}, "schema": []}
{"input": "Several PFC analyte groups were also positively associated with serum alanine aminotransferase, gamma-glutamyltransferase, creatinine, phosphorus, amylase, and anion gap and negatively associated with cholesterol levels, creatinine phosphokinase, eosinophils, and monocytes.", "output": {"entities": {"chemical": [{"text": "alanine", "start": 70, "end": 77}, {"text": "creatinine", "start": 123, "end": 133}, {"text": "phosphorus", "start": 135, "end": 145}, {"text": "cholesterol", "start": 201, "end": 212}, {"text": "creatinine", "start": 221, "end": 231}]}}, "schema": []}
{"input": "Based on these relationships, the authors suggest that the PFC concentrations found in Charleston dolphins may have effects on immune, hematopoietic, kidney, and liver function.", "output": {"entities": {}}, "schema": []}
{"input": "The results contribute to the emerging data on PFC health effects in this first study to describe associations between PFCs and health parameters in dolphins.", "output": {"entities": {}}, "schema": []}
{"input": "Potential for metal contamination by direct sonication of nanoparticle suspensions.", "output": {"entities": {}}, "schema": []}
{"input": "While conducting toxicity tests with nano titanium dioxide, the authors found that test suspensions were being contaminated with aluminum and titanium from tip erosion during direct sonication.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 42, "end": 58}, {"text": "aluminum", "start": 129, "end": 137}, {"text": "titanium", "start": 142, "end": 150}]}}, "schema": []}
{"input": "The contaminating alloy particles had a measurable size distribution and zeta potential using dynamic light scattering, which changed the measured characteristics of the suspensions.", "output": {"entities": {}}, "schema": []}
{"input": "Caution should be used when employing direct sonication for preparing test suspensions due to potential interferences of these particles in toxicological assessments.", "output": {"entities": {}}, "schema": []}
{"input": "Korean guidelines for pharmacoeconomic evaluation (second and updated version): consensus and compromise.", "output": {"entities": {}}, "schema": []}
{"input": "The first version of the Korean guidelines for pharmacoeconomic evaluation was published by Health Insurance Review and Assessment Service (HIRA) in 2006.", "output": {"entities": {}}, "schema": []}
{"input": "Since the introduction of the first version, domestic experience with the application of the recommendations has accumulated, and methodologies in certain areas have progressed considerably.", "output": {"entities": {}}, "schema": []}
{"input": "Based on these experiences, HIRA initiated a guidelines revision project to address the need for revisions.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study is to share the process used to complete these guideline revisions and to provide the contents of the revised guidelines.", "output": {"entities": {}}, "schema": []}
{"input": "In developing the current revision, meetings with the advisory committee and working-level meetings with pharmaceutical companies were held several times to reach as much of a consensus as possible, and the results of a survey of pharmaceutical companies and decision makers regarding the existing guidelines were considered.", "output": {"entities": {}}, "schema": []}
{"input": "The second version of the guidelines clarified the level of data requirement (' must',' recommended',' preferred') based on the data availability, the information needs of the decision makers and the strength of the evidence.", "output": {"entities": {}}, "schema": []}
{"input": "The recommended perspective economic studies should take has been modified and additional guidance has been provided on QALY measurement.", "output": {"entities": {}}, "schema": []}
{"input": "Manuals for systematic reviews and indirect comparisons have been published, and a standardized reporting format for expert opinions has been added.", "output": {"entities": {}}, "schema": []}
{"input": "Sections on preferred methods for evaluations, sensitivity analysis, modelling and time horizon have been elucidated.", "output": {"entities": {}}, "schema": []}
{"input": "The revised guidelines clarify the expression of the recommendations, making them more user-friendly, and provide more specific guidance to improve the quality and comparability across submissions.", "output": {"entities": {}}, "schema": []}
{"input": "Heterocycles as nonclassical bioisosteres of alpha-amino acids.", "output": {"entities": {"chemical": [{"text": "alpha-amino acids", "start": 45, "end": 62}]}}, "schema": []}
{"input": "Bioisosterism of alpha-amino acids is often accomplished by replacing the alpha-carboxylate with one of the many known carboxylic acid bioisosteres.", "output": {"entities": {"chemical": [{"text": "alpha-amino acids", "start": 17, "end": 34}, {"text": "alpha-carboxylate", "start": 74, "end": 91}, {"text": "carboxylic acid", "start": 119, "end": 134}]}}, "schema": []}
{"input": "However, bioisosterism of the whole alpha-amino acid moiety is accomplished with heterocyclic bioisosteres that often display an acidic function.", "output": {"entities": {"chemical": [{"text": "alpha-amino acid", "start": 36, "end": 52}]}}, "schema": []}
{"input": "In this Minireview, we summarized the reported heterocycles as nonclassical bioisosteres of alpha-amino acids, which include quinoxaline-2, 4 (1H)-dione, quinoxaline-2, 3 (1H)-dione and quinolin-2 (1H)-one, azagrevellin and azepine-derived structures.", "output": {"entities": {"chemical": [{"text": "alpha-amino acids", "start": 92, "end": 109}, {"text": "quinoxaline-2, 4 (1H)-dione", "start": 125, "end": 152}, {"text": "quinoxaline-2, 3 (1H)-dione", "start": 154, "end": 181}, {"text": "quinolin-2 (1H)-one", "start": 186, "end": 205}, {"text": "azagrevellin", "start": 207, "end": 219}, {"text": "azepine", "start": 224, "end": 231}]}}, "schema": []}
{"input": "The binding mode of the crystalized bioisosteres were compared with those of the crystalized alpha-amino acids that bind in the same domain, and where no data on the crystal structure were available, the displacement studies of known orthosteric ligands were used.", "output": {"entities": {"chemical": [{"text": "alpha-amino acids", "start": 93, "end": 110}]}}, "schema": []}
{"input": "The reported bioisosteres share the following essential structural features for mimicking alpha-amino acids: an aromatic ring system joined to a lactam ring system with an acidic feature next to the lactam carbonyl, where this acidic feature together with the lactam carbonyl can mimic the alpha-carboxylate, and the lactam nitrogen together with the aromatic ring system can mimic the alpha-ammonium.", "output": {"entities": {"chemical": [{"text": "alpha-amino acids", "start": 90, "end": 107}, {"text": "lactam carbonyl", "start": 199, "end": 214}, {"text": "lactam carbonyl", "start": 260, "end": 275}, {"text": "alpha-ammonium", "start": 386, "end": 400}]}}, "schema": []}
{"input": "The majority of these heterocycles can be prepared from three common corresponding starting materials: the corresponding anilines, isatins or anthranilic esters.", "output": {"entities": {"chemical": [{"text": "anilines", "start": 121, "end": 129}, {"text": "isatins", "start": 131, "end": 138}, {"text": "anthranilic esters", "start": 142, "end": 160}]}}, "schema": []}
{"input": "The data collected here show the potential of this class of bioisosteres in the design of glutamate receptor ligands and beyond.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 90, "end": 99}]}}, "schema": []}
{"input": "Effects of antiresorptive therapies on glucose metabolism: Results from the FIT, HORIZON-PFT and FREEDOM trials.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 39, "end": 46}]}}, "schema": []}
{"input": "In rodent models undercarboxylated osteocalcin (ucOC) acts as a hormone promoting insulin sensitivity and secretion.", "output": {"entities": {}}, "schema": []}
{"input": "If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post-hoc analyses of three randomized, placebo-controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N = 6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) (N = 7113) of zoledronic acid (3 years), and Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N = 7076) of denosumab (3 years).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 68, "end": 75}, {"text": "alendronate", "start": 266, "end": 277}, {"text": "Zoledronic Acid", "start": 332, "end": 347}, {"text": "zoledronic acid", "start": 411, "end": 426}]}}, "schema": []}
{"input": "Fasting glucose was measured annually in FIT and HORIZON in a subset of women, and every 6 months in FREEDOM on all participants.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 8, "end": 15}]}}, "schema": []}
{"input": "Weight was measured annually in all trials.", "output": {"entities": {}}, "schema": []}
{"input": "Incident diabetes was identified from adverse event reports, initiation of diabetes medication, or elevated fasting glucose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 116, "end": 123}]}}, "schema": []}
{"input": "Differences in fasting glucose changes from randomization to trial conclusion between treatment and placebo groups were not statistically significant:-0. 47 mg/dL in FIT, 0. 20 mg/dL in HORIZON-PFT and 0. 09 mg/dL in FREEDOM, all p > 0. 6.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 23, "end": 30}]}}, "schema": []}
{"input": "Weight change differed between treatment and placebo groups in FIT (0. 32 kg, p = 0. 003) and FREEDOM (0. 31 kg, p = 0. 023), but not in HORIZON-PFT (0. 15 kg, p = 0. 132).", "output": {"entities": {}}, "schema": []}
{"input": "In the three trials combined, diabetes occurred in 203 and 225 women assigned to treatment or placebo, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetes incidence was not increased in any of the treatment groups or in the pooled estimate (Pooled RR = 0. 90; 95% CI 0. 74, 1. 10).", "output": {"entities": {}}, "schema": []}
{"input": "Antiresorptive therapy does not have a clinically important effect on fasting glucose, weight or diabetes risk in postmenopausal women.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 78, "end": 85}]}}, "schema": []}
{"input": "Contrary to predictions from mouse models, reduced bone turnover does not appear to play a significant role in glucose metabolism in humans.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 111, "end": 118}]}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Single-walled carbon nanotube/polyaniline/n-silicon solar cells: fabrication, characterization, and performance measurements.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 14, "end": 20}, {"text": "polyaniline", "start": 30, "end": 41}, {"text": "silicon", "start": 44, "end": 51}]}}, "schema": []}
{"input": "Carbon nanotube-silicon solar cells are a recently investigated photovoltaic architecture with demonstrated high efficiencies.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}, {"text": "silicon", "start": 16, "end": 23}]}}, "schema": []}
{"input": "Silicon solar-cell devices fabricated with a thin film of conductive polymer (polyaniline) have been reported, but these devices can suffer from poor performance due to the limited lateral current-carrying capacity of thin polymer films.", "output": {"entities": {"chemical": [{"text": "Silicon", "start": 0, "end": 7}, {"text": "polyaniline", "start": 78, "end": 89}]}}, "schema": []}
{"input": "Herein, hybrid solar-cell devices of a thin film of polyaniline deposited on silicon and covered by a single-walled carbon nanotube film are fabricated and characterized.", "output": {"entities": {"chemical": [{"text": "polyaniline", "start": 52, "end": 63}, {"text": "silicon", "start": 77, "end": 84}, {"text": "carbon", "start": 116, "end": 122}]}}, "schema": []}
{"input": "These hybrid devices combine the conformal coverage given by the polymer and the excellent electrical properties of single-walled carbon nanotube films and significantly outperform either of their component counterparts.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 130, "end": 136}]}}, "schema": []}
{"input": "Treatment of the silicon base and carbon nanotubes with hydrofluoric acid and a strong oxidizer (thionyl chloride) leads to a significant improvement in performance.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 17, "end": 24}, {"text": "carbon", "start": 34, "end": 40}, {"text": "hydrofluoric acid", "start": 56, "end": 73}, {"text": "thionyl chloride", "start": 97, "end": 113}]}}, "schema": []}
{"input": "The regulation of Runx2 by FGF2 and connexin43 requires the inositol polyphosphate/protein kinase C delta cascade.", "output": {"entities": {"chemical": [{"text": "inositol polyphosphate", "start": 60, "end": 82}]}}, "schema": []}
{"input": "Connexin43 (Cx43) plays a critical role in osteoblast function and bone mass accrual, yet the identity of the second messengers communicated by Cx43 gap junctions, the targets of these second messengers and how they regulate osteoblast function remain largely unknown.", "output": {"entities": {}}, "schema": []}
{"input": "We have shown that alterations of Cx43 expression in osteoblasts can impact the responsiveness to fibroblast growth factor-2 (FGF2), by modulating the transcriptional activity of Runx2.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we examined the contribution of the phospholipase C gamma 1/inositol polyphosphate/PKC delta cascade to the Cx43-dependent transcriptional response of MC3T3 osteoblasts to FGF2.", "output": {"entities": {"chemical": [{"text": "inositol polyphosphate", "start": 75, "end": 97}]}}, "schema": []}
{"input": "Knockdown of expression and/or inhibition of function of phospholipase C gamma 1, inositol polyphosphate multikinase, which generates InsP (4) and InsP (5), and inositol hexakisphosphate kinase 1/2, which generates inositol pyrophosphates, prevented the ability of Cx43 to potentiate FGF2-induced signaling through Runx2.", "output": {"entities": {"chemical": [{"text": "inositol polyphosphate", "start": 82, "end": 104}, {"text": "inositol hexakisphosphate", "start": 161, "end": 186}, {"text": "inositol pyrophosphates", "start": 215, "end": 238}]}}, "schema": []}
{"input": "Conversely, overexpression of phospholipase C gamma 1 and inositol hexakisphosphate kinase 1/2 enhanced FGF2 activation of Runx2 and the effect of Cx43 overexpression on this response.", "output": {"entities": {"chemical": [{"text": "inositol hexakisphosphate", "start": 58, "end": 83}]}}, "schema": []}
{"input": "Disruption of these pathways blocked the nuclear accumulation of PKC delta and the FGF2-dependent interaction of PKC delta and Runx2, reducing Runx2 transcriptional activity.", "output": {"entities": {}}, "schema": []}
{"input": "These data reveal that FGF2-signaling involves the inositol polyphosphate cascade, including IP6K, and demonstrate that IP6K regulates Runx2 and osteoblast gene expression.", "output": {"entities": {"chemical": [{"text": "inositol polyphosphate", "start": 51, "end": 73}]}}, "schema": []}
{"input": "Additionally, these data implicate the water-soluble inositol polyphosphates as mediators of the Cx43-dependent amplification of the osteoblast response to FGF2, and suggest that these low molecular weight second messengers may be biologically relevant mediators of osteoblast function that are communicated by Cx43-gap junctions.", "output": {"entities": {"chemical": [{"text": "inositol polyphosphates", "start": 53, "end": 76}]}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Betaglycan alters NF kappa B-TGF beta 2 cross talk to reduce survival of human granulosa tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "The molecular pathways controlling granulosa cell tumor (GCT) survival are poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "In many cell types, nuclear factor-kappa B (NF kappa B) and TGF beta coordinately regulate cell survival to maintain tissue homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Because GCT cell lines exhibit constitutively activated NF kappa B, we hypothesized that NF kappa B blocks TGF beta-mediated cell death in GCT cells.", "output": {"entities": {}}, "schema": []}
{"input": "To test this hypothesis, we used the human GCT cell line KGN, which exhibits loss of betaglycan, a TGF beta co-receptor.", "output": {"entities": {}}, "schema": []}
{"input": "After inhibition of NF kappa B in KGN cells, re-expression of betaglycan resulted in a decrease in cell viability, which was further decreased by TGF beta 2.", "output": {"entities": {}}, "schema": []}
{"input": "Intriguingly, TGF beta 2 increased NF kappa B reporter activity in control cells, but betaglycan expression suppressed both basal and TGF beta 2-stimulated NF kappa B activity.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical inhibition of Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signaling or SMAD2/3 gene silencing revealed that both SMADs contributed to cell survival.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, inhibiting NF kappa B activity resulted in a specific reduction in SMAD3 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, overexpression of SMAD3 increased basal NF kappa B activity and countered betaglycan-mediated suppression of NF kappa B activity.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, ERK1/2 activation emerged as the point of convergence of NF kappa B, SMAD3, and TGF beta 2/betaglycan governance of GCT cell viability.", "output": {"entities": {}}, "schema": []}
{"input": "Key findings in KGN cells were reproduced in a second GCT cell line, COV434.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, our data establish that both SMAD2/3 and NF kappa B signaling pathways support GCT cell viability and suggest the existence of a positive feedback loop between NF kappa B and SMAD3 signaling in late-stage GCT.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, our data suggest that loss of betaglycan during tumor progression in GCT alters the functional outcomes generated by NF kappa B and TGF beta pathway cross talk.", "output": {"entities": {}}, "schema": []}
{"input": "Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.", "output": {"entities": {}}, "schema": []}
{"input": "Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 18, "end": 29}]}}, "schema": []}
{"input": "Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 22, "end": 33}]}}, "schema": []}
{"input": "Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 104, "end": 115}]}}, "schema": []}
{"input": "Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 90, "end": 101}]}}, "schema": []}
{"input": "Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation.", "output": {"entities": {}}, "schema": []}
{"input": "Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21, 789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I.", "output": {"entities": {}}, "schema": []}
{"input": "Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest.", "output": {"entities": {}}, "schema": []}
{"input": "The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function.", "output": {"entities": {}}, "schema": []}
{"input": "Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes.", "output": {"entities": {"chemical": [{"text": "manumycin A", "start": 75, "end": 86}, {"text": "cholesterol ester", "start": 189, "end": 206}]}}, "schema": []}
{"input": "In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembly of ordered epitaxial nanostructures on polygonal nanowires.", "output": {"entities": {}}, "schema": []}
{"input": "We study the self-assembly of ordered nanostructures, that is, nanorings (NRs) and quantum dots (QDs), epitaxially grown on a polygonal cross-section nanowire (PCS-NW) using both theoretical and phase-field modeling.", "output": {"entities": {}}, "schema": []}
{"input": "Our studies show that, by increasing the PCS-NW size, transitions from ordered NRs to ordered QDs on facets and further to ordered QDs on ridges occur.", "output": {"entities": {}}, "schema": []}
{"input": "The predicted morphologies and their transitions are in excellent agreement with existing experiments.", "output": {"entities": {}}, "schema": []}
{"input": "Our study suggests a novel approach to fabricate ordered nanostructures on nanowires.", "output": {"entities": {}}, "schema": []}
{"input": "Optimization of Non-ATP Competitive CDK/Cyclin Groove Inhibitors through REPLACE-Mediated Fragment Assembly.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 20, "end": 23}]}}, "schema": []}
{"input": "A major challenge in drug discovery is to develop and improve methods for targeting protein-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Further exemplification of the REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) strategy for generating inhibitors of protein-protein interactions demonstrated that it can be used to optimize fragment alternatives of key determinants, to combine these in an effective way, and this was achieved for compounds targeting the cyclin-dependent kinase 2 (CDK2) substrate recruitment site on the cyclin regulatory subunit.", "output": {"entities": {}}, "schema": []}
{"input": "Phenylheterocyclic isosteres replacing a critical charge-charge interaction provided new structural insights for binding to the cyclin groove.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, these results shed light onto the key contributions of a H-bond observed in crystal structures of N-terminally capped peptides.", "output": {"entities": {"chemical": [{"text": "H", "start": 72, "end": 73}, {"text": "N", "start": 113, "end": 114}]}}, "schema": []}
{"input": "Furthermore, the structure-activity relationship of a bis (aryl) ether C-terminal capping group mimicking dipeptide interactions was probed through ring substitutions, allowing increased complementarity with the primary hydrophobic pocket.", "output": {"entities": {"chemical": [{"text": "bis (aryl) ether C", "start": 54, "end": 72}, {"text": "dipeptide", "start": 106, "end": 115}]}}, "schema": []}
{"input": "This study further validates REPLACE as an effective strategy for converting peptidic compounds to more pharmaceutically relevant compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The volume of distribution is an indicator of poor in vitro-in vivo extrapolation of clearance for acidic drugs in the rat.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "We applied the regression offset approach to predict rat in vivo intrinsic clearance (CLint) for 54 new chemical acid entities with high plasma protein binding values and low renal clearance (CL).", "output": {"entities": {}}, "schema": []}
{"input": "The prediction success was correlated to volume of distribution (Vd), molecular weight (Mw) and CL.", "output": {"entities": {}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "A correlation between poor in vitro-in vivo extrapolation (IVIVE) and Vd values distinct from the Vd of albumin (0. 1-0. 2 L/kg) was revealed.", "output": {"entities": {}}, "schema": []}
{"input": "For compounds with a Vd value above 0. 5 L/kg, 0% of the predictions of in vivo CLint was within twofold of the observed value, compared to 69% for compounds with a Vd value below 0. 5 L/kg.", "output": {"entities": {}}, "schema": []}
{"input": "3. Compounds with a Mw below 450 g/mol demonstrated more accurate in vivo CLint predictions than compounds with a Mw above 450 g/mol, i. e. 63% compared to 21% within twofold.", "output": {"entities": {}}, "schema": []}
{"input": "For compounds with in vivo CL below 30% of the liver blood flow (LBF), 53% of the predictions was within twofold of the observed value, compared to 0% for compounds with CL above 30% of the LBF.", "output": {"entities": {}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "We show that accurate IVIVE for acidic compounds with high plasma protein binding and low renal CL can be associated with a low Vd (i. e. around the Vd of albumin) and with a low in vivo CL, and that Mw is an important optimization parameter for pharmacokinetic.", "output": {"entities": {}}, "schema": []}
{"input": "This study also further demonstrates the advantages of the application of the regression method for identifying cases when metabolic CL is not the single major elimination pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Four new koumine metabolites in rat liver microsomes.", "output": {"entities": {"chemical": [{"text": "koumine", "start": 9, "end": 16}]}}, "schema": []}
{"input": "Four new metabolites M-1 [1, 2, 18, 19-tetradehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan], M-2 [1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan], M-3 [1, 2, 18, 19-tetradehydro-4-demethyl-4-formaldehyde-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan], and M-4 [1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-4-oxy-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan] were isolated from the chloroform extract of koumine incubated with phenobarbital-treated rat liver microsomes.", "output": {"entities": {"chemical": [{"text": "1, 2, 18, 19-tetradehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan", "start": 26, "end": 103}, {"text": "1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan", "start": 111, "end": 194}, {"text": "1, 2, 18, 19-tetradehydro-4-demethyl-4-formaldehyde-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan", "start": 202, "end": 294}, {"text": "1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-4-oxy-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan", "start": 306, "end": 395}, {"text": "chloroform", "start": 420, "end": 430}, {"text": "koumine", "start": 442, "end": 449}, {"text": "phenobarbital", "start": 465, "end": 478}]}}, "schema": []}
{"input": "The structures of M-1, M-2, M-3, and M-4 were elucidated by spectroscopic methods including ESI-TOF-MS, 1D, and 2D NMR experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The metabolic pathway of koumine was proposed.", "output": {"entities": {"chemical": [{"text": "koumine", "start": 25, "end": 32}]}}, "schema": []}
{"input": "The cytotoxic activities between koumine and its metabolites were also compared in the A549 cell line.", "output": {"entities": {"chemical": [{"text": "koumine", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Polymorphism of GeSbTe superlattice nanowires.", "output": {"entities": {"chemical": [{"text": "GeSbTe", "start": 16, "end": 22}]}}, "schema": []}
{"input": "Scaling-down of phase change materials to a nanowire (NW) geometry is critical to a fast switching speed of nonvolatile memory devices.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we report novel composition-phase-tuned GeSbTe NWs, synthesized by a chemical vapor transport method, which guarantees promising applications in the field of nanoscale electric devices.", "output": {"entities": {"chemical": [{"text": "GeSbTe", "start": 48, "end": 54}]}}, "schema": []}
{"input": "As the Sb content increased, they showed a distinctive rhombohedral-cubic-rhombohedral phase evolution.", "output": {"entities": {"chemical": [{"text": "Sb", "start": 7, "end": 9}]}}, "schema": []}
{"input": "Remarkable superlattice structures were identified for the Ge (8) Sb (2) Te (11), Ge (3) Sb (2) Te (6), Ge (3) Sb (8) Te (6), and Ge (2) Sb (7) Te (4) NWs.", "output": {"entities": {"chemical": [{"text": "Ge (8) Sb (2) Te (11)", "start": 59, "end": 80}, {"text": "Ge (3) Sb (2) Te (6)", "start": 82, "end": 102}, {"text": "Ge (3) Sb (8) Te (6)", "start": 104, "end": 124}, {"text": "Ge (2) Sb (7) Te (4)", "start": 130, "end": 150}]}}, "schema": []}
{"input": "The coexisting cubic-rhombohedral phase Ge (3) Sb (2) Te (6) NWs exhibited an exclusively uniform superlattice structure consisting of 2. 2 nm period slabs.", "output": {"entities": {"chemical": [{"text": "Ge (3) Sb (2) Te (6)", "start": 40, "end": 60}]}}, "schema": []}
{"input": "The rhombohedral phase Ge (3) Sb (8) Te (6) and Ge (2) Sb (7) Te (4) NWs adopted an innovative structure; 3Sb (2) layers intercalated the Ge (3) Sb (2) Te (6) and Ge (2) Sb (1) Te (4) domains, respectively, producing 3. 4 and 2. 7 nm period slabs.", "output": {"entities": {"chemical": [{"text": "Ge (3) Sb (8) Te (6)", "start": 23, "end": 43}, {"text": "Ge (2) Sb (7) Te (4)", "start": 48, "end": 68}, {"text": "3Sb (2)", "start": 106, "end": 113}, {"text": "Ge (3) Sb (2) Te (6)", "start": 138, "end": 158}, {"text": "Ge (2) Sb (1) Te (4)", "start": 163, "end": 183}]}}, "schema": []}
{"input": "The current-voltage measurement of the individual NW revealed that the vacancy layers of Ge (8) Sb (2) Te (11) and Ge (3) Sb (2) Te (6) decreased the electrical conductivity.", "output": {"entities": {"chemical": [{"text": "Ge (8) Sb (2) Te (11)", "start": 89, "end": 110}, {"text": "Ge (3) Sb (2) Te (6)", "start": 115, "end": 135}]}}, "schema": []}
{"input": "A new flavonoid with 6-phenyl substituent from Selaginella uncinata.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 6, "end": 15}, {"text": "6-phenyl", "start": 21, "end": 29}]}}, "schema": []}
{"input": "A new flavonoid, 6-(5-acetyl-2-methoxyphenyl)-apigenin (1), together with nine known compounds (2-10), was isolated from Selaginella uncinata (Desv.) Spring.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 6, "end": 15}, {"text": "6-(5-acetyl-2-methoxyphenyl)-apigenin", "start": 17, "end": 54}]}}, "schema": []}
{"input": "This is the first report of the spectroscopic data of compound 3.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 2 was first reported from this species.", "output": {"entities": {}}, "schema": []}
{"input": "The structure of the new compound was elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR as well as HR-EI-MS analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Controlled assembly and release of retinoic acid based on the layer-by-layer method.", "output": {"entities": {"chemical": [{"text": "retinoic acid", "start": 35, "end": 48}]}}, "schema": []}
{"input": "All-trans retinoic acid (RA) has been proved to play important roles in regulating cell growth in various types of cells.", "output": {"entities": {"chemical": [{"text": "All-trans retinoic acid", "start": 0, "end": 23}]}}, "schema": []}
{"input": "Yet most experiments were performed by adding RA in solution previously.", "output": {"entities": {}}, "schema": []}
{"input": "In this Article, we focus on the incorporation of RA, as a negatively charged moiety, into layered polyelectrolyte films on surfaces by means of layer-by-layer (LbL) deposition, followed by adding of capping layers to regulate the release of RA from the films.", "output": {"entities": {}}, "schema": []}
{"input": "The incorporated RA was designed to release over 5 days in buffer solution.", "output": {"entities": {}}, "schema": []}
{"input": "The assembly and release of RA were verified by UV and QCM results.", "output": {"entities": {}}, "schema": []}
{"input": "The controlled release of RA from multilayer films can serve as a model system to study the influence of small molecules on cell growth.", "output": {"entities": {}}, "schema": []}
{"input": "Phase separation induced by Au catalysts in ternary InGaAs nanowires.", "output": {"entities": {"chemical": [{"text": "Au", "start": 28, "end": 30}, {"text": "InGaAs", "start": 52, "end": 58}]}}, "schema": []}
{"input": "We report a novel phase separation phenomenon observed in the growth of ternary In (x) Ga (1-x) As nanowires by metalorganic chemical vapor deposition.", "output": {"entities": {"chemical": [{"text": "In (x) Ga (1-x) As", "start": 80, "end": 98}]}}, "schema": []}
{"input": "A spontaneous formation of core-shell nanowires is investigated by cross-sectional transmission electron microscopy, revealing the compositional complexity within the ternary nanowires.", "output": {"entities": {}}, "schema": []}
{"input": "It has been found that for In (x) Ga (1-x) As nanowires high precursor flow rates generate ternary In (x) Ga (1-x) As cores with In-rich shells, while low precursor flow rates produce binary GaAs cores with ternary In (x) Ga (1-x) As shells.", "output": {"entities": {"chemical": [{"text": "In (x) Ga (1-x) As", "start": 27, "end": 45}, {"text": "In (x) Ga (1-x) As", "start": 99, "end": 117}, {"text": "GaAs", "start": 191, "end": 195}, {"text": "In (x) Ga (1-x) As", "start": 215, "end": 233}]}}, "schema": []}
{"input": "First-principle calculations combined with thermodynamic considerations suggest that this phenomenon is due to competitive alloying of different group-III elements with Au catalysts, and variations in elemental concentrations of group-III materials in the catalyst under different precursor flow rates.", "output": {"entities": {"chemical": [{"text": "Au", "start": 169, "end": 171}]}}, "schema": []}
{"input": "This study shows that precursor flow rates are critical factors for manipulating Au catalysts to produce nanowires of desired composition.", "output": {"entities": {"chemical": [{"text": "Au", "start": 81, "end": 83}]}}, "schema": []}
{"input": "Synthesis and antibacterial evaluation of typharin analog: 6, 8-dihydroxy-7-methyl-3-styryl-3, 4-dihydroisocoumarin.", "output": {"entities": {"chemical": [{"text": "typharin", "start": 42, "end": 50}, {"text": "6, 8-dihydroxy-7-methyl-3-styryl-3, 4-dihydroisocoumarin", "start": 59, "end": 115}]}}, "schema": []}
{"input": "Synthesis of the 6-hydroxy-7-methyl analog of typharin (8-dihydroxy-3-styryl-3, 4-dihydroisocoumarin) isolated from the rhizomes of Typha capensis has been described.", "output": {"entities": {"chemical": [{"text": "6-hydroxy-7-methyl", "start": 17, "end": 35}, {"text": "typharin", "start": 46, "end": 54}, {"text": "8-dihydroxy-3-styryl-3, 4-dihydroisocoumarin", "start": 56, "end": 100}]}}, "schema": []}
{"input": "Direct condensation of 3, 5-dimethoxy-4-methylhomophthalic acid (1) with cinnamoyl chloride at elevated temperature under inert conditions afforded 6, 8-dihydroxy-7-methyl-3-styrylisocoumarin (2).", "output": {"entities": {"chemical": [{"text": "3, 5-dimethoxy-4-methylhomophthalic acid", "start": 23, "end": 63}, {"text": "cinnamoyl chloride", "start": 73, "end": 91}, {"text": "6, 8-dihydroxy-7-methyl-3-styrylisocoumarin", "start": 148, "end": 191}]}}, "schema": []}
{"input": "Hydrolysis of isocoumarin to keto acid (3) followed by reduction and cyclodehydration of hydroxy acid analog (4) afforded (+/-)-6, 8-dimethoxy-3-(4-methoxyphenyl)-3, 4-dihydroisocoumarin (5).", "output": {"entities": {"chemical": [{"text": "isocoumarin", "start": 14, "end": 25}, {"text": "keto acid", "start": 29, "end": 38}, {"text": "hydroxy acid", "start": 89, "end": 101}, {"text": "(+/-)-6, 8-dimethoxy-3-(4-methoxyphenyl)-3, 4-dihydroisocoumarin", "start": 122, "end": 186}]}}, "schema": []}
{"input": "Demethylation of the latter using anhydrous aluminum chloride/ethane thiol furnished the title isocoumarin (6).", "output": {"entities": {"chemical": [{"text": "aluminum chloride", "start": 44, "end": 61}, {"text": "ethane thiol", "start": 62, "end": 74}, {"text": "isocoumarin", "start": 95, "end": 106}]}}, "schema": []}
{"input": "Compounds (1-6) were screened for in vitro antibacterial activity against a representative panel of Gram-positive and Gram-negative bacteria using levofloxacin as the reference drug.", "output": {"entities": {"chemical": [{"text": "levofloxacin", "start": 147, "end": 159}]}}, "schema": []}
{"input": "Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles.", "output": {"entities": {"chemical": [{"text": "methylprednisolone", "start": 52, "end": 70}]}}, "schema": []}
{"input": "Due to their crystalline nature, the encapsulation of hydrophobic corticosteroids within polymeric nanoparticles by o/w solvent evaporation method is often difficult to achieve.", "output": {"entities": {"chemical": [{"text": "corticosteroids", "start": 66, "end": 81}]}}, "schema": []}
{"input": "The aim of this study was to evaluate the effect of both process and formulation parameters on the encapsulation of a model corticosteroid: methylprednisolone (MP).", "output": {"entities": {"chemical": [{"text": "corticosteroid", "start": 124, "end": 138}, {"text": "methylprednisolone", "start": 140, "end": 158}]}}, "schema": []}
{"input": "For this purpose, a 3 (2) factorial design was performed evaluating the effects of the concentration of emulsifiers and sonication time on the manufactured nanoparticles, followed by a multiresponse optimization.", "output": {"entities": {}}, "schema": []}
{"input": "The study also included the evaluation of other parameters such as the type of organic solvent used, polymer characteristics and the initial mass of drug.", "output": {"entities": {}}, "schema": []}
{"input": "The optimal nanoparticle formulation using 0. 25% (w/v) of emulsifying agent (Polyvinyl-alcohol, PVA) and 5 min of sonication was then characterized.", "output": {"entities": {"chemical": [{"text": "Polyvinyl-alcohol", "start": 78, "end": 95}, {"text": "PVA", "start": 97, "end": 100}]}}, "schema": []}
{"input": "The highest encapsulation was obtained with an organic phase consisting of acetone: dichloromethane (1: 1), polyD, L-lactide-co-glycolide (PLGA) 50: 50 as polymer and an initial mass of 6. 6 mg of methylprednisolone.", "output": {"entities": {"chemical": [{"text": "acetone", "start": 75, "end": 82}, {"text": "dichloromethane", "start": 84, "end": 99}, {"text": "polyD, L-lactide-co-glycolide", "start": 108, "end": 137}, {"text": "PLGA", "start": 139, "end": 143}, {"text": "methylprednisolone", "start": 197, "end": 215}]}}, "schema": []}
{"input": "Nanoparticles size and zeta potential of optimized formulation were respectively around 230 nm and-14 mV.", "output": {"entities": {}}, "schema": []}
{"input": "Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "Release study showed that MP-loaded nanoparticles sustained drug release for up to 120 h.", "output": {"entities": {}}, "schema": []}
{"input": "This study reflects the importance of factorial design to optimize the manufacture of nanoparticles encapsulating hydrophobic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Fasciospyrinadine, a novel sesquiterpene pyridine alkaloid from a Guangxi sponge Fasciospongia sp.", "output": {"entities": {"chemical": [{"text": "Fasciospyrinadine", "start": 0, "end": 17}, {"text": "sesquiterpene pyridine alkaloid", "start": 27, "end": 58}]}}, "schema": []}
{"input": "Fasciospyrinadine (1), a novel sesquiterpene pyridine alkaloid with a previously unreported skeleton featuring a monocyclicfarnesane moiety attached to a 3-methylenepyridine residue, was isolated from the sponge Fasciospongia sp. from Weizhou Island, Guangxi Autonomous Region.", "output": {"entities": {"chemical": [{"text": "Fasciospyrinadine", "start": 0, "end": 17}, {"text": "sesquiterpene pyridine alkaloid", "start": 31, "end": 62}, {"text": "monocyclicfarnesane", "start": 113, "end": 132}, {"text": "3-methylenepyridine", "start": 154, "end": 173}]}}, "schema": []}
{"input": "The structure and the relative stereochemistry of 1 were elucidated on the basis of extensive analysis of its 1D and 2D NMR spectroscopic techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Fundamental and Torsional Combination Bands of Two Isomers of the OCS-CO (2) Complex in the CO (2) nu (3) Region.", "output": {"entities": {"chemical": [{"text": "OCS", "start": 66, "end": 69}, {"text": "CO (2)", "start": 70, "end": 76}, {"text": "CO (2)", "start": 92, "end": 98}]}}, "schema": []}
{"input": "Spectra of two isomers of the weakly bound complex OCS-CO (2) are observed in the region of the CO (2) nu (3) fundamental vibration (~ 2349 cm (-1)), using an infrared tunable diode laser to probe a pulsed supersonic slit-jet expansion.", "output": {"entities": {"chemical": [{"text": "OCS", "start": 51, "end": 54}, {"text": "CO (2)", "start": 55, "end": 61}, {"text": "CO (2)", "start": 96, "end": 102}]}}, "schema": []}
{"input": "Two bands are measured and analyzed for each isomer, the fundamental asymmetric stretch of the CO (2) component and a combination band involving this fundamental plus the intermolecular out-of-plane torsional mode.", "output": {"entities": {"chemical": [{"text": "CO (2)", "start": 95, "end": 101}]}}, "schema": []}
{"input": "For one isomer, the corresponding torsional combination band is also detected in the OCS nu (1) stretching region (~ 2060 cm (-1)).", "output": {"entities": {"chemical": [{"text": "OCS", "start": 85, "end": 88}]}}, "schema": []}
{"input": "The resulting torsional frequencies are found to be 18. 8 and 15. 9 cm (-1) for isomers a and b of OCS-CO (2), respectively.", "output": {"entities": {"chemical": [{"text": "OCS", "start": 99, "end": 102}, {"text": "CO (2)", "start": 103, "end": 109}]}}, "schema": []}
{"input": "This may be the first time that such a combination band is observed for a higher-energy isomer of a weakly bound complex.", "output": {"entities": {}}, "schema": []}
{"input": "The resolution of aglinin A epimers and their NMR assignments.", "output": {"entities": {"chemical": [{"text": "aglinin A", "start": 18, "end": 27}]}}, "schema": []}
{"input": "Aglinin A (1) is a mixture of C (24)-epimeric 20S, 24-epoxy-24, 25-dihydroxy-3, 4-secodammar-4 (28)-en-3-oic acid and present in plants of the family Meliaceae.", "output": {"entities": {"chemical": [{"text": "Aglinin A", "start": 0, "end": 9}, {"text": "20S, 24-epoxy-24, 25-dihydroxy-3, 4-secodammar-4 (28)-en-3-oic acid", "start": 46, "end": 113}]}}, "schema": []}
{"input": "The two epimers of 1 were resolved through an acetonide reaction, and the absolute configurations of two derivatives were deduced by the analysis of their (13) C NMR differences induced by gamma-gauche or steric effect.", "output": {"entities": {"chemical": [{"text": "acetonide", "start": 46, "end": 55}, {"text": "(13) C", "start": 155, "end": 161}]}}, "schema": []}
{"input": "Based on it, the (13) C NMR assignment of 24R-1 and 24S-1 was also established.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 17, "end": 23}]}}, "schema": []}
{"input": "Phthalazinone inhibitors of inosine-5'-monophosphate dehydrogenase from Cryptosporidium parvum.", "output": {"entities": {"chemical": [{"text": "Phthalazinone", "start": 0, "end": 13}, {"text": "inosine-5'-monophosphate", "start": 28, "end": 52}]}}, "schema": []}
{"input": "Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition.", "output": {"entities": {}}, "schema": []}
{"input": "This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides.", "output": {"entities": {"chemical": [{"text": "inosine 5'-monophosphate", "start": 34, "end": 58}, {"text": "guanine nucleotides", "start": 103, "end": 122}]}}, "schema": []}
{"input": "A CpIMPDH-selective N-aryl-3, 4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign.", "output": {"entities": {"chemical": [{"text": "N-aryl-3, 4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide", "start": 20, "end": 77}]}}, "schema": []}
{"input": "Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH.", "output": {"entities": {"chemical": [{"text": "phthalazinone", "start": 65, "end": 78}, {"text": "benzofuranamide", "start": 126, "end": 141}]}}, "schema": []}
{"input": "In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary composition of carbohydrates contributes to the development of experimental type 2 diabetes.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 23, "end": 36}]}}, "schema": []}
{"input": "Evidence has emerged supporting a link between high glycaemic index (GI) diets and type 2 diabetes (T2D).", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to determine if dietary GI influences the development of hyperglycaemia in C57BL/6 mice to more closely reflect T2D.", "output": {"entities": {}}, "schema": []}
{"input": "Male C57BL/6 mice (n = 30) were randomly divided into 3 dietary groups consisting of either standard rodent chow (4. 8% fat, 20% protein), or a high fat (HF) diet (21-23% fat, 19% protein) with low GI (15. 4% starch; HF-LG) or high GI (50. 5% dextrose; HF-HG) ad libitum for 10 weeks.", "output": {"entities": {"chemical": [{"text": "dextrose", "start": 243, "end": 251}]}}, "schema": []}
{"input": "Body weight, blood glucose, glucose tolerance, and circulating cholesterol and triglyceride levels were measured for the duration of the study.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 19, "end": 26}, {"text": "glucose", "start": 28, "end": 35}, {"text": "cholesterol", "start": 63, "end": 74}, {"text": "triglyceride", "start": 79, "end": 91}]}}, "schema": []}
{"input": "We found that increasing the GI of a moderately HF diet induces severe hyperglycaemia and insulin resistance in C57BL/6 mice, reflective of criteria for diagnosis of T2D, whilst littermates consuming an equivalent low GI diet maintain glucose homeostasis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 235, "end": 242}]}}, "schema": []}
{"input": "This study demonstrates the significant contribution of both dietary carbohydrate and fat composition in the aetiopathogenesis of T2D.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 69, "end": 81}]}}, "schema": []}
{"input": "The high harm score of alcohol.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 23, "end": 30}]}}, "schema": []}
{"input": "Time for drug policy to be revisited?", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this paper is to create awareness of the negative health impact and economic burden and benefits associated to alcohol consumption.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 122, "end": 129}]}}, "schema": []}
{"input": "Worldwide about two billion people consume alcohol.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 43, "end": 50}]}}, "schema": []}
{"input": "Low intake of alcohol has a minor protective cardiovascular effect.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 14, "end": 21}]}}, "schema": []}
{"input": "On the other hand, even moderate alcohol consumption appears to be weakly, but significantly, associated to a limited number of chronic diseases.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Alcohol causes a considerable economic burden to society due to the high absolute number of alcohol consumers.", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 0, "end": 7}, {"text": "alcohol", "start": 92, "end": 99}]}}, "schema": []}
{"input": "As such, alcohol abuse is more harmful for public health and society than illicit drug use.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 9, "end": 16}]}}, "schema": []}
{"input": "Some 3. 7% of alcohol consumers (worldwide 76 million people) have an alcohol use disorder leading to 60-70% of the societal costs related to alcohol.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 14, "end": 21}, {"text": "alcohol", "start": 70, "end": 77}, {"text": "alcohol", "start": 142, "end": 149}]}}, "schema": []}
{"input": "Therefore, policy measures should, in addition to regulatory measures to reduce alcohol use, aim at closing the treatment gap and improving treatment effectiveness of people with an alcohol use disorder.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 80, "end": 87}, {"text": "alcohol", "start": 182, "end": 189}]}}, "schema": []}
{"input": "The key message is that policy-makers unjustifiably focus on the harm of illicit drugs, whereas they underestimate the harm of alcohol use.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 127, "end": 134}]}}, "schema": []}
{"input": "Policy makers should therefore consider alcohol to be at least as harmful as illicit drugs and invest more in prevention and harm reduction strategies for alcohol abuse and dependence.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 40, "end": 47}, {"text": "alcohol", "start": 155, "end": 162}]}}, "schema": []}
{"input": "Adjunctive aripiprazole therapy with escitalopram in patients with co-morbid major depressive disorder and alcohol dependence: clinical and neuroimaging evidence.", "output": {"entities": {"chemical": [{"text": "aripiprazole", "start": 11, "end": 23}, {"text": "escitalopram", "start": 37, "end": 49}, {"text": "alcohol", "start": 107, "end": 114}]}}, "schema": []}
{"input": "The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 82, "end": 89}]}}, "schema": []}
{"input": "We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone.", "output": {"entities": {"chemical": [{"text": "escitalopram", "start": 45, "end": 57}, {"text": "aripiprazole", "start": 63, "end": 75}, {"text": "alcohol", "start": 140, "end": 147}, {"text": "alcohol", "start": 206, "end": 213}, {"text": "escitalopram", "start": 285, "end": 297}]}}, "schema": []}
{"input": "Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 56, "end": 63}, {"text": "aripiprazole", "start": 120, "end": 132}, {"text": "escitalopram", "start": 135, "end": 147}, {"text": "escitalopram", "start": 155, "end": 167}]}}, "schema": []}
{"input": "At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 86, "end": 93}]}}, "schema": []}
{"input": "During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups.", "output": {"entities": {"chemical": [{"text": "aripiprazole", "start": 136, "end": 148}, {"text": "escitalopram", "start": 151, "end": 163}, {"text": "escitalopram", "start": 168, "end": 180}]}}, "schema": []}
{"input": "In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23. 3 +/- 8. 4 to 14. 3 +/- 4. 9, compared with those of the escitalopram group of from 21. 6 +/- 8. 4 to 19. 3 +/- 7. 1 (F = 13. 1, p < 0. 01).", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 56, "end": 63}, {"text": "aripiprazole", "start": 97, "end": 109}, {"text": "escitalopram", "start": 112, "end": 124}, {"text": "escitalopram", "start": 210, "end": 222}]}}, "schema": []}
{"input": "The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 92, "end": 99}, {"text": "aripiprazole", "start": 143, "end": 155}, {"text": "escitalopram", "start": 158, "end": 170}]}}, "schema": []}
{"input": "The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 101, "end": 108}, {"text": "alcohol", "start": 207, "end": 214}]}}, "schema": []}
{"input": "These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder.", "output": {"entities": {"chemical": [{"text": "aripiprazole", "start": 43, "end": 55}, {"text": "alcohol", "start": 127, "end": 134}]}}, "schema": []}
{"input": "A functional NPSR1 gene variant and environment shape personality and impulsive action: A longitudinal study.", "output": {"entities": {}}, "schema": []}
{"input": "Neuropeptide S and its receptor NPSR1 are involved in the regulation of arousal, attention and anxiety.", "output": {"entities": {}}, "schema": []}
{"input": "We examined whether the NPSR1 gene functional polymorphism Asn (107) Ile (rs324981, A > T) influences personality, impulsivity, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in a population-representative sample, and whether any eventual associations depend on age, sex, family relations and stressful life events (SLE).", "output": {"entities": {}}, "schema": []}
{"input": "We used self-reports or teachers' ratings for both the younger (n = 593) and older (n = 583) cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study.", "output": {"entities": {}}, "schema": []}
{"input": "Males with the TT genotype displayed more ADHD-related symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "Adaptive impulsivity and Extraversion increased the most from age 18 to 25.", "output": {"entities": {}}, "schema": []}
{"input": "While highest increases were observed in AA men, TT women exhibited the largest decreases.", "output": {"entities": {}}, "schema": []}
{"input": "For participants with the AA genotype, Warmth in family was inversely associated with Neuroticism, and positively associated with Extraversion and Adaptive impulsivity.", "output": {"entities": {}}, "schema": []}
{"input": "High exposure to SLE increased impulsivity and ADHD scores in TT genotype subjects.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that the NPSR1 A/T polymorphism is associated with impulsivity, ADHD symptoms and personality, mirroring the activity-and anxiety-mediating role of NPSR1.", "output": {"entities": {}}, "schema": []}
{"input": "Heterozygous individuals were the least sensitive to environmental factors, whereas subjects with the AA genotype and TT genotype reacted to different types of environmental adversities.", "output": {"entities": {}}, "schema": []}
{"input": "Losmapimod concentration-QT relationship in healthy volunteers: meta-analysis of data from six clinical trials.", "output": {"entities": {"chemical": [{"text": "Losmapimod", "start": 0, "end": 10}]}}, "schema": []}
{"input": "PURPOSE: The objective of this work was to describe the losmapimod concentration-QT relationship using meta-analysis of data from clinical trials with healthy volunteers and to evaluate the covariates that have significant impact on the QT prolongation.", "output": {"entities": {"chemical": [{"text": "losmapimod", "start": 56, "end": 66}]}}, "schema": []}
{"input": "METHODS: Losmapimod plasma concentration and QT interval data were collected from six early clinical studies with healthy volunteers.", "output": {"entities": {"chemical": [{"text": "Losmapimod", "start": 9, "end": 19}]}}, "schema": []}
{"input": "The electrocardiograms (ECGs) were collected at baseline and at a number of post-dose time points (losmapimod or placebo).", "output": {"entities": {"chemical": [{"text": "losmapimod", "start": 99, "end": 109}]}}, "schema": []}
{"input": "The population pharmacokinetic/pharmacodynamic (PK/PD) modelling approach was applied to investigate the relationship between losmapimod concentration and QT prolongation.", "output": {"entities": {"chemical": [{"text": "losmapimod", "start": 126, "end": 136}]}}, "schema": []}
{"input": "RESULTS: The dataset for analysis comprised 190 healthy adults who took at least one dose of losmapimod or placebo.", "output": {"entities": {"chemical": [{"text": "losmapimod", "start": 93, "end": 103}]}}, "schema": []}
{"input": "Of the 2, 494 QT observations collected, 1, 532 observations had matched QT and losmapimod plasma concentration data.", "output": {"entities": {"chemical": [{"text": "losmapimod", "start": 80, "end": 90}]}}, "schema": []}
{"input": "Population PK/PD analyses indicated that the model with the individual heart rate correction factor (alpha) fitted the data better than those using fixed alpha (0. 33 for Fridericia' s correction or 0. 5 for Bazett' s correction) and that there was no relationship between losmapimod concentration and QT interval.", "output": {"entities": {"chemical": [{"text": "losmapimod", "start": 273, "end": 283}]}}, "schema": []}
{"input": "Female volunteers had about a 3% higher QT interval at baseline than the male volunteers.", "output": {"entities": {}}, "schema": []}
{"input": "No other covariates had a significant effect on the QT interval.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: It is appropriate to apply population PK/PD analysis to investigate the effect of drug concentration on QT prolongation.", "output": {"entities": {}}, "schema": []}
{"input": "Our meta-analysis of healthy volunteer data indicated no relationship between systemic losmapimod concentration and QT interval in healthy volunteers.", "output": {"entities": {"chemical": [{"text": "losmapimod", "start": 87, "end": 97}]}}, "schema": []}
{"input": "Activation of AMP-activated Protein Kinase and Phosphorylation of Glycogen Synthase Kinase3 beta Mediate Ursolic Acid Induced Apoptosis in HepG2 Liver Cancer Cells.", "output": {"entities": {"chemical": [{"text": "AMP", "start": 14, "end": 17}, {"text": "Ursolic Acid", "start": 105, "end": 117}]}}, "schema": []}
{"input": "Despite the antitumour effect of ursolic acid observed in several cancers, the underlying mechanism remains unclear.", "output": {"entities": {"chemical": [{"text": "ursolic acid", "start": 33, "end": 45}]}}, "schema": []}
{"input": "Thus, in the present study, the roles of AMP-activated protein kinase (AMPK) and glycogen synthase kinase 3 beta (GSK3 beta) were examined in ursolic acid induced apoptosis in HepG2 hepatocellular carcinoma cells.", "output": {"entities": {"chemical": [{"text": "AMP", "start": 41, "end": 44}]}}, "schema": []}
{"input": "Ursolic acid significantly exerted cytotoxicity, increased the sub-G1 population and the number of ethidium homodimer and terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labeling positive cells in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "Ursolic acid", "start": 0, "end": 12}, {"text": "ethidium", "start": 99, "end": 107}, {"text": "dUTP", "start": 175, "end": 179}]}}, "schema": []}
{"input": "Also, ursolic acid enhanced the cleavages of poly-ADP-ribose polymerase (PARP) and caspase3, attenuated the expression of astrocyte elevated gene (AEG1) and survivin in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "poly-ADP-ribose", "start": 45, "end": 60}]}}, "schema": []}
{"input": "Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3 beta at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "ursolic acid", "start": 15, "end": 27}, {"text": "serine", "start": 157, "end": 163}, {"text": "ursolic acid", "start": 175, "end": 187}]}}, "schema": []}
{"input": "Conversely, AMPK inhibitor compound C or GSK3 beta inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "compound C", "start": 27, "end": 37}, {"text": "SB216763", "start": 61, "end": 69}, {"text": "ursolic acid", "start": 125, "end": 137}]}}, "schema": []}
{"input": "Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3 beta phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "MG132", "start": 35, "end": 40}, {"text": "ursolic acid", "start": 139, "end": 151}]}}, "schema": []}
{"input": "Overall, our findings suggest that ursolic acid induced apoptosis in HepG2 cells via AMPK activation and GSK3 beta phosphorylation as a potent chemopreventive agent.", "output": {"entities": {"chemical": [{"text": "ursolic acid", "start": 35, "end": 47}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis, in vitro MAO-B inhibitory evaluation, and computational studies of some 6-nitrobenzothiazole-derived semicarbazones.", "output": {"entities": {"chemical": [{"text": "6-nitrobenzothiazole", "start": 91, "end": 111}, {"text": "semicarbazones", "start": 120, "end": 134}]}}, "schema": []}
{"input": "Monoamine oxidase B (MAO-B) is an important drug target for the treatment of neurological disorders.", "output": {"entities": {}}, "schema": []}
{"input": "A series of 6-nitrobenzothiazole-derived semicarbazones were designed, synthesized, and evaluated as inhibitors of the rat brain MAO-B isoenzyme.", "output": {"entities": {"chemical": [{"text": "6-nitrobenzothiazole", "start": 12, "end": 32}, {"text": "semicarbazones", "start": 41, "end": 55}]}}, "schema": []}
{"input": "Most of the compounds were found to be potent inhibitors of MAO-B, with IC (50) values in the nanomolar to micromolar range.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular docking studies were performed with AutoDock 4. 2 to deduce the affinity and binding mode of these inhibitors toward the MAO-B active site.", "output": {"entities": {}}, "schema": []}
{"input": "The free energies of binding (Delta G) and inhibition constants (K (i)) of the docked compounds were calculated by the Lamarckian genetic algorithm (LGA) of AutoDock 4. 2.", "output": {"entities": {}}, "schema": []}
{"input": "Good correlations between the calculated and experimental results were obtained.", "output": {"entities": {}}, "schema": []}
{"input": "1-[(4-Chlorophenyl) (phenyl) methylene]-4-(6-nitrobenzothiazol-2-yl) semicarbazide emerged as the lead MAO-B inhibitor, with top ranking in both the experimental MAO-B assay (IC (50): 0. 004 +/- 0. 001 mu M) and in computational docking studies (K (i): 1. 08 mu M).", "output": {"entities": {"chemical": [{"text": "1-[(4-Chlorophenyl) (phenyl) methylene]-4-(6-nitrobenzothiazol-2-yl) semicarbazide", "start": 0, "end": 82}]}}, "schema": []}
{"input": "Binding mode analysis of potent inhibitors suggests that these compounds are well accommodated by the MAO-B active site through stable hydrophobic and hydrogen bonding interactions.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 151, "end": 159}]}}, "schema": []}
{"input": "Interestingly, the 6-nitrobenzothiazole moiety is stabilized in the substrate cavity with the aryl or diaryl residues extending up into the entrance cavity of the active site.", "output": {"entities": {"chemical": [{"text": "6-nitrobenzothiazole", "start": 19, "end": 39}]}}, "schema": []}
{"input": "According to our results, docking experiments could be an interesting approach for predicting the activity and binding interactions of this class of semicarbazones against MAO-B.", "output": {"entities": {"chemical": [{"text": "semicarbazones", "start": 149, "end": 163}]}}, "schema": []}
{"input": "Thus, a binding site model consisting of three essential pharmacophoric features is proposed, and this can be used for the design of future MAO-B inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Mutational analysis of the ribosome assembly GTPase RbgA provides insight into ribosome interaction and ribosome-stimulated GTPase activation.", "output": {"entities": {}}, "schema": []}
{"input": "Ribosome biogenesis GTPase A protein (RbgA) is an essential GTPase required for the biogenesis of the 50S subunit in Bacillus subtilis.", "output": {"entities": {}}, "schema": []}
{"input": "Homologs of RbgA are widely distributed in bacteria and eukaryotes and are implicated in ribosome assembly in the mitochondria, chloroplast and cytoplasm.", "output": {"entities": {}}, "schema": []}
{"input": "Cells depleted of RbgA accumulate an immature large subunit that is missing key ribosomal proteins.", "output": {"entities": {}}, "schema": []}
{"input": "RbgA, unlike many members of the Ras superfamily of GTPases, lacks a defined catalytic residue for carrying out guanosine triphosphate (GTP) hydrolysis.", "output": {"entities": {"chemical": [{"text": "guanosine triphosphate", "start": 112, "end": 134}, {"text": "GTP", "start": 136, "end": 139}]}}, "schema": []}
{"input": "To probe RbgA function in ribosome assembly, we used a combined bioinformatics, genetic and biochemical approach.", "output": {"entities": {}}, "schema": []}
{"input": "We identified a RNA-binding domain within the C-terminus of RbgA that is structurally similar to AmiR-NasR Transcription Anti-termination Regulator (ANTAR) domains, which are known to bind structured RNA.", "output": {"entities": {"chemical": [{"text": "C", "start": 46, "end": 47}]}}, "schema": []}
{"input": "Mutation of key residues in the ANTAR domain altered RbgA association with the ribosome.", "output": {"entities": {}}, "schema": []}
{"input": "We identified a putative catalytic residue within a highly conserved region of RbgA, His9, which is contained within a similar PGH motif found in elongation factor Tu (EF-Tu) that is required for GTP hydrolysis on interaction with the ribosome.", "output": {"entities": {"chemical": [{"text": "GTP", "start": 196, "end": 199}]}}, "schema": []}
{"input": "Finally, our results support a model in which the GTPase activity of RbgA directly participates in the maturation of the large subunit rather than solely promoting dissociation of RbgA from the 50S subunit.", "output": {"entities": {}}, "schema": []}
{"input": "Covalently functionalized double-walled carbon nanotubes combine high sensitivity and selectivity in the electrical detection of small molecules.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 40, "end": 46}]}}, "schema": []}
{"input": "Atom-thick materials such as single-walled carbon nanotubes (SWCNTs) and graphene exhibit ultrahigh sensitivity to chemical perturbation partly because all of the constituent atoms are surface atoms.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 43, "end": 49}, {"text": "graphene", "start": 73, "end": 81}]}}, "schema": []}
{"input": "However, low selectivity due to nonspecific binding on the graphitic surface is a challenging issue to many applications including chemical sensing.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrated simultaneous attainment of high sensitivity and selectivity in thin-film field effect transistors (TFTs) based on outer-wall selectively functionalized double-walled carbon nanotubes (DWCNTs).", "output": {"entities": {"chemical": [{"text": "carbon", "start": 188, "end": 194}]}}, "schema": []}
{"input": "With carboxylic acid functionalized DWCNT TFTs, we obtained excellent gate modulation (on/off ratio as high as 4000) with relatively high ON currents at a CNT areal density as low as 35 ng/cm (2).", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 5, "end": 20}]}}, "schema": []}
{"input": "The devices displayed an NH (3) sensitivity of 60 nM (or ~ 1 ppb), which is comparable to small molecule aqueous solution detection using state-of-the-art SWCNT TFT sensors while concomitantly achieving 6000 times higher chemical selectivity toward a variety of amine-containing analyte molecules over that of other small molecules.", "output": {"entities": {"chemical": [{"text": "NH (3)", "start": 25, "end": 31}, {"text": "amine", "start": 262, "end": 267}]}}, "schema": []}
{"input": "These results highlight the potential of using covalently functionalized double-walled carbon nanotubes for simultaneous ultrahigh selective and sensitive detection of chemicals and illustrate some of the structural advantages of this double-wall materials strategy to nanoelectronics.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 87, "end": 93}]}}, "schema": []}
{"input": "A thermoplastic elastomer patch matrix for traditional Chinese medicine: design and evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Objective: To design and evaluate a novel pressure sensitive adhesive (PSA) patch containing traditional Chinese medicine (TCM) using styrene-isoprene-styrene (SIS) copolymer.", "output": {"entities": {"chemical": [{"text": "styrene-isoprene-styrene", "start": 143, "end": 167}, {"text": "SIS", "start": 169, "end": 172}]}}, "schema": []}
{"input": "Method: A mixture D-optimal design with ternary response surface diagram was employed in the optimization process.", "output": {"entities": {}}, "schema": []}
{"input": "The proportions of SIS copolymer, tackifying resin and plasticizer were selected as the independent variables while tack force, peel strength of the patch and skin penetrability of methyl salicylate were selected as the dependent variables.", "output": {"entities": {"chemical": [{"text": "SIS", "start": 19, "end": 22}, {"text": "methyl salicylate", "start": 181, "end": 198}]}}, "schema": []}
{"input": "The optimized patch was then evaluated including in vivo absorption, pharmacological activities and skin irritation, by comparing with a commercial patch based on natural rubber.", "output": {"entities": {}}, "schema": []}
{"input": "Results: The optimized patch, which comprised 30. 0% SIS copolymer, 26. 6% tackifying resin and 43. 4% plasticizer, was superior to commercial patch in skin permeation, pharmacological activities and skin biocompatibility.", "output": {"entities": {"chemical": [{"text": "SIS", "start": 53, "end": 56}]}}, "schema": []}
{"input": "Conclusion: SIS copolymer was a suitable substitute to natural rubber in producing patches containing TCM formula.", "output": {"entities": {"chemical": [{"text": "SIS", "start": 12, "end": 15}]}}, "schema": []}
{"input": "High-contrast electrooptic modulation of a photonic crystal nanocavity by electrical gating of graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 95, "end": 103}]}}, "schema": []}
{"input": "We demonstrate high-contrast electro-optic modulation of a photonic crystal nanocavity integrated with an electrically gated monolayer graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 135, "end": 143}]}}, "schema": []}
{"input": "A silicon air-slot nanocavity provides strong overlap between the resonant optical field and graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Tuning the Fermi energy of the graphene layer to 0. 85 eV enables strong control of its optical conductivity at telecom wavelengths, which allows modulation of cavity reflection in excess of 10 dB for a swing voltage of only 1. 5 V.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 31, "end": 39}]}}, "schema": []}
{"input": "The cavity resonance at 1570 nm is found to undergo a shift in wavelength of nearly 2 nm, together with a 3-fold increase in quality factor.", "output": {"entities": {}}, "schema": []}
{"input": "These observations enable a cavity-enhanced determination of graphene' s complex optical sheet conductivity at different doping levels.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 61, "end": 69}]}}, "schema": []}
{"input": "Our simple device demonstrates the feasibility of high-contrast, low-power, and frequency-selective electro-optic modulators in graphene-integrated silicon photonic integrated circuits.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 128, "end": 136}, {"text": "silicon", "start": 148, "end": 155}]}}, "schema": []}
{"input": "Species-dependent metabolism of a novel selective alpha 7 neuronal acetylcholine receptor agonist ABT-107.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 67, "end": 80}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism of ABT-107 was investigated in in vitro hepatic systems, in rat and monkey receiving [(14) C] ABT-107, and in vivo plasma in rat, dog, monkey and human.", "output": {"entities": {"chemical": [{"text": "ABT-107", "start": 14, "end": 21}, {"text": "[(14) C] ABT-107", "start": 96, "end": 112}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "In in vitro hepatic systems, ABT-107 was primarily cleared via oxidative metabolism, and proceeded via two parallel pathways.", "output": {"entities": {"chemical": [{"text": "ABT-107", "start": 29, "end": 36}]}}, "schema": []}
{"input": "Pathway 1, ABT-107 was oxidized at the nitrogen of quinuclidine moiety to form M1.", "output": {"entities": {"chemical": [{"text": "ABT-107", "start": 11, "end": 18}, {"text": "nitrogen", "start": 39, "end": 47}, {"text": "quinuclidine", "start": 51, "end": 63}]}}, "schema": []}
{"input": "Pathway 2, oxidation occurred at indole-containing moiety to form M2.", "output": {"entities": {"chemical": [{"text": "indole", "start": 33, "end": 39}]}}, "schema": []}
{"input": "Metabolism via N-oxidation was predominant in dog and rat, while in monkey and human, metabolism proceeded primarily via oxidation of indole-containing moiety.", "output": {"entities": {"chemical": [{"text": "N", "start": 15, "end": 16}, {"text": "indole", "start": 134, "end": 140}]}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "ABT-107 was extensively metabolized in vivo in rat and monkey.", "output": {"entities": {"chemical": [{"text": "ABT-107", "start": 0, "end": 7}]}}, "schema": []}
{"input": "M1 was primarily found in rat urine and bile; whereas, M2 was the major metabolite in monkey urine and feces.", "output": {"entities": {}}, "schema": []}
{"input": "M1 was the predominant circulating metabolite in dog and rat.", "output": {"entities": {}}, "schema": []}
{"input": "M2 was the primary circulating metabolite in monkey and human.", "output": {"entities": {}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "Enzymatic studies suggested M1 formation was primarily mediated by renal FMO1.", "output": {"entities": {}}, "schema": []}
{"input": "CYP3A4, 1A2, 2J2 and 2D6 were primary enzymes catalyzing M2 formation.", "output": {"entities": {}}, "schema": []}
{"input": "5.", "output": {"entities": {}}, "schema": []}
{"input": "Biotransformation of ABT-107 in human and monkey is markedly different from that in dog and rat, suggesting that monkey is an appropriate model for predicting human biotransformation and toxicology of ABT-107.", "output": {"entities": {"chemical": [{"text": "ABT-107", "start": 21, "end": 28}, {"text": "ABT-107", "start": 201, "end": 208}]}}, "schema": []}
{"input": "Unprecedented transformation of tetrathienoanthracene into pentacene on Ni (111).", "output": {"entities": {"chemical": [{"text": "tetrathienoanthracene", "start": 32, "end": 53}, {"text": "pentacene", "start": 59, "end": 68}, {"text": "Ni (111)", "start": 72, "end": 80}]}}, "schema": []}
{"input": "The imaging and characterization of single-molecule reaction events is essential to both extending our basic understanding of chemistry and applying this understanding to challenges at the frontiers of technology, for example, in nanoelectronics.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, understanding the behavior of individual molecules can elucidate processes critical to the controlled synthesis of materials for applications in multiple nanoscale technologies.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report the synthesis of an important semiconducting organic molecule through an unprecedented reaction observed with submolecular resolution by scanning tunneling microscopy (STM) under ultrahigh vacuum (UHV) conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Our images reveal a sulfur abstraction and cyclization reaction that converts tetrathienoanthracene precursors into pentacene on the Ni (111) surface.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 20, "end": 26}, {"text": "tetrathienoanthracene", "start": 78, "end": 99}, {"text": "pentacene", "start": 116, "end": 125}, {"text": "Ni (111)", "start": 133, "end": 141}]}}, "schema": []}
{"input": "The identity of the final reaction product was confirmed by time-of-flight secondary ion mass spectrometry (TOF-SIMS).", "output": {"entities": {}}, "schema": []}
{"input": "This reaction has no known literature analogue, and highlights the power of local-probe techniques for exploring new chemical pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Endometrial thickness in women with ovulatory dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "This study is designed to evaluate the relationship between endometrial thickness and clinical/biochemical parameters in women with chronic anovulation.", "output": {"entities": {}}, "schema": []}
{"input": "One hundred and twenty women with ovulatory dysfunction were prospective included, endometrial thickness and endocrine and metabolic parameters were measured.", "output": {"entities": {}}, "schema": []}
{"input": "The interval between the examination day and the day of the most recent menstrual bleeding (the anovulatory interval) for the studied subject was an average of 145 +/- 186 days.", "output": {"entities": {}}, "schema": []}
{"input": "The endometrial thickness averaged 7. 1 +/- 3. 2 mm.", "output": {"entities": {}}, "schema": []}
{"input": "Correlation analyses revealed that the endometrial thickness was positively correlated with body mass index but was not correlated with age, serum androgens, or estradiol (E2) levels.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 147, "end": 156}, {"text": "estradiol", "start": 161, "end": 170}]}}, "schema": []}
{"input": "We further classified the subjects into two groups based on endometrial thickness: Group A, endometrial thickness < 7 mm and Group B, endometrial thickness >= 7 mm.", "output": {"entities": {}}, "schema": []}
{"input": "The anovulatory interval, follicle-stimulating hormone, luteinizing hormone, E2 and androgen levels were not significantly different between Groups A and B.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 84, "end": 92}]}}, "schema": []}
{"input": "Group B had higher body weight and more risk for metabolic syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "We concluded that endometrial thickness in women with ovulatory dysfunction is positively correlated with body weight status but is not correlated with serum androgens or E2 levels.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 158, "end": 167}]}}, "schema": []}
{"input": "The macrocyclic peptide natural product CJ-15, 208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior.", "output": {"entities": {"chemical": [{"text": "CJ-15, 208", "start": 40, "end": 50}, {"text": "cocaine", "start": 111, "end": 118}]}}, "schema": []}
{"input": "The macrocyclic tetrapeptide natural product CJ-15, 208 (cyclo [Phe-d-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration.", "output": {"entities": {"chemical": [{"text": "macrocyclic tetrapeptide", "start": 4, "end": 28}, {"text": "CJ-15, 208", "start": 45, "end": 55}, {"text": "cyclo [Phe-d-Pro-Phe-Trp]", "start": 57, "end": 82}]}}, "schema": []}
{"input": "CJ-15, 208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS.", "output": {"entities": {"chemical": [{"text": "CJ-15, 208", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Orally administered CJ-15, 208 also prevented both cocaine-and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time-and dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "CJ-15, 208", "start": 20, "end": 30}, {"text": "cocaine", "start": 51, "end": 58}, {"text": "cocaine", "start": 108, "end": 115}]}}, "schema": []}
{"input": "Thus, CJ-15, 208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.", "output": {"entities": {"chemical": [{"text": "CJ-15, 208", "start": 6, "end": 16}]}}, "schema": []}
{"input": "Levels of thrombin activatable fibrinolysis inhibitor in gestational diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase, which is synthesised in liver and activated by thrombin and the thrombin-thrombomodulin complex.", "output": {"entities": {}}, "schema": []}
{"input": "TAFI suppresses fibrinolysis by removing carboxy-terminal lysine residues from partially degraded fibrin.", "output": {"entities": {"chemical": [{"text": "carboxy", "start": 41, "end": 48}, {"text": "lysine", "start": 58, "end": 64}]}}, "schema": []}
{"input": "In this study we aimed to assess the circulating levels of TAFI antigen,' a fibrinolytic parameter' in women with gestational diabetes (GDM).", "output": {"entities": {}}, "schema": []}
{"input": "Thirty-four pregnant women with GDM and 50 pregnant women with normal glucose tolerance were included in the study.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma TAFI antigen levels were significantly higher in pregnant women with GDM when compared with controls.", "output": {"entities": {}}, "schema": []}
{"input": "Increased TAFI levels may contribute to the decreased fibrinolytic potency, causing a thrombophilic state.", "output": {"entities": {}}, "schema": []}
{"input": "GDM is regarded as a specific form of diabetes, and it could in addition be a predictor of type 2 diabetes mellitus in the future and the risk of complications due to hypercoagulability increases in this disease.", "output": {"entities": {}}, "schema": []}
{"input": "Increased TAFI levels may also have a role in increased risk of hypercoagulability.", "output": {"entities": {}}, "schema": []}
{"input": "Embelin accelerates cutaneous wound healing in diabetic rats.", "output": {"entities": {"chemical": [{"text": "Embelin", "start": 0, "end": 7}]}}, "schema": []}
{"input": "This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats.", "output": {"entities": {"chemical": [{"text": "embelin", "start": 33, "end": 40}, {"text": "streptozotocin", "start": 67, "end": 81}, {"text": "STZ", "start": 83, "end": 86}]}}, "schema": []}
{"input": "The effect was studied using excision, incision, and dead space models.", "output": {"entities": {}}, "schema": []}
{"input": "In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing.", "output": {"entities": {"chemical": [{"text": "embelin", "start": 41, "end": 48}]}}, "schema": []}
{"input": "Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models.", "output": {"entities": {"chemical": [{"text": "Embelin", "start": 0, "end": 7}]}}, "schema": []}
{"input": "In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined.", "output": {"entities": {"chemical": [{"text": "hydroxyproline", "start": 98, "end": 112}, {"text": "hexosamine", "start": 114, "end": 124}]}}, "schema": []}
{"input": "In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents.", "output": {"entities": {"chemical": [{"text": "STZ", "start": 3, "end": 6}, {"text": "embelin", "start": 55, "end": 62}, {"text": "hydroxyproline", "start": 85, "end": 99}, {"text": "hexosamine", "start": 101, "end": 111}]}}, "schema": []}
{"input": "It also showed a significant increase in wound breaking strength.", "output": {"entities": {}}, "schema": []}
{"input": "Embelin significantly increased granuloma tissue weight and breaking strength in dead space model.", "output": {"entities": {"chemical": [{"text": "Embelin", "start": 0, "end": 7}]}}, "schema": []}
{"input": "These results indicated that embelin accelerated wound healing in diabetic rat.", "output": {"entities": {"chemical": [{"text": "embelin", "start": 29, "end": 36}]}}, "schema": []}
{"input": "Jatropholane-type diterpenes from Euphorbia sikkimensis.", "output": {"entities": {"chemical": [{"text": "Jatropholane", "start": 0, "end": 12}, {"text": "diterpenes", "start": 18, "end": 28}]}}, "schema": []}
{"input": "Four new jatropholane-type diterpenes (1-4), named sikkimenoids A-D, were isolated from the aerial parts of Euphorbia sikkimensis.", "output": {"entities": {"chemical": [{"text": "jatropholane", "start": 9, "end": 21}, {"text": "diterpenes", "start": 27, "end": 37}, {"text": "sikkimenoids A-D", "start": 51, "end": 67}]}}, "schema": []}
{"input": "The structural elucidations of 1-4 were accomplished by extensive NMR analyses, and their absolute configurations were established by ECD calculations.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 2 exhibited weak antiangiogenic activity with an IC (50) value of 43. 0 mu M when evaluated using a zebrafish model.", "output": {"entities": {}}, "schema": []}
{"input": "Significant interaction between RETN-420 G/G genotype and lower BMI on decreased risk of type 2 diabetes mellitus (T2DM) in Japanese--the J-MICC Study.", "output": {"entities": {}}, "schema": []}
{"input": "We examined the association of the RETN (resistin)-420 C > G polymorphism (rs1862513) with risk of diabetes mellitus (DM), considering lifestyle factors, in Japanese.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects were participants of J-MICC Study, where 2, 651 participants aged 35-69 years provided their blood for genotyping and lifestyle data after informed consent.", "output": {"entities": {}}, "schema": []}
{"input": "Odds ratio (OR) of DM for RETN-420 G/G genotype was estimated using unconditional logistic regression model.", "output": {"entities": {}}, "schema": []}
{"input": "Statistically significant interaction on risk of DM was observed between RETN-420 G/G genotype and BMI < 25 (OR for interaction = 0. 12; P = 0. 046), and when subjects with RETN-420 C/C + C/G and BMI >= 25 (n = 69 for DM and 544 for non-DM) were defined as the reference, the adjusted ORs for subjects with RETN-420 G/G genotype and BMI > 25 (n = 10 for DM and 111 for non-DM), RETN-420 C/C + C/G and BMI < 25 (n = 81 for DM and 1, 605 for non-DM), and RETN-420 G/G and BMI < 25 (n = 1 for DM and 230 for non-DM) were demonstrated to be 0. 72 (95% confidence interval: 0. 36-1. 46), 0. 40 (0. 28-0. 56) and 0. 03 (0. 005-0. 25), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The present study revealed the significant interaction of RETN-420 G/G genotype with lower BMI on the decreased risk of DM, but the direction was opposite to the reported ones in Japanese.", "output": {"entities": {}}, "schema": []}
{"input": "We should be careful in interpretation of the present study results because of the limited sample sizes.", "output": {"entities": {}}, "schema": []}
{"input": "Further investigation of this association as well as of the actual biological roles of RETN in the genesis of human metabolic disorders including DM will be required.", "output": {"entities": {}}, "schema": []}
{"input": "Nucleophosmin mutations alter its nucleolar localization by impairing G-quadruplex binding at ribosomal DNA.", "output": {"entities": {}}, "schema": []}
{"input": "Nucleophosmin (NPM1) is an abundant nucleolar protein implicated in ribosome maturation and export, centrosome duplication and response to stress stimuli.", "output": {"entities": {}}, "schema": []}
{"input": "NPM1 is the most frequently mutated gene in acute myeloid leukemia.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations at the C-terminal domain led to variant proteins that aberrantly and stably translocate to the cytoplasm.", "output": {"entities": {"chemical": [{"text": "C", "start": 17, "end": 18}]}}, "schema": []}
{"input": "We have previously shown that NPM1 C-terminal domain binds with high affinity G-quadruplex DNA.", "output": {"entities": {"chemical": [{"text": "C", "start": 35, "end": 36}]}}, "schema": []}
{"input": "Here, we investigate the structural determinants of NPM1 nucleolar localization.", "output": {"entities": {}}, "schema": []}
{"input": "We show that NPM1 interacts with several G-quadruplex regions found in ribosomal DNA, both in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the most common leukemic NPM1 variant completely loses this activity.", "output": {"entities": {}}, "schema": []}
{"input": "This is the consequence of G-quadruplex-binding domain destabilization, as mutations aimed at refolding the leukemic variant also result in rescuing the G-quadruplex-binding activity and nucleolar localization.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we show that treatment of cells with a G-quadruplex selective ligand results in wild-type NPM1 dislocation from nucleoli into nucleoplasm.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, this work establishes a direct correlation between NPM1 G-quadruplex binding at rDNA and its nucleolar localization, which is impaired in the acute myeloid leukemia-associated protein variants.", "output": {"entities": {}}, "schema": []}
{"input": "Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?", "output": {"entities": {}}, "schema": []}
{"input": "There is increasing evidence that pregnancy alters the function of drug-metabolizing enzymes and drug transporters in a gestational-stage and tissue-specific manner.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo probe studies have shown that the activity of several hepatic cytochrome P450 enzymes, such as CYP2D6 and CYP3A4, is increased during pregnancy, whereas the activity of others, such as CYP1A2, is decreased.", "output": {"entities": {}}, "schema": []}
{"input": "The activity of some renal transporters, including organic cation transporter and P-glycoprotein, also appears to be increased during pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Although much has been learned, significant gaps still exist in our understanding of the spectrum of drug metabolism and transport genes affected, gestational age-dependent changes in the activity of encoded drug metabolizing and transporting processes, and the mechanisms of pregnancy-induced alterations.", "output": {"entities": {}}, "schema": []}
{"input": "In this issue of Drug Metabolism and Disposition, a series of articles is presented that address the predictability, mechanisms, and magnitude of changes in drug metabolism and transport processes during pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "The articles highlight state-of-the-art approaches to studying mechanisms of changes in drug disposition during pregnancy, and illustrate the use and integration of data from in vitro models, animal studies, and human clinical studies.", "output": {"entities": {}}, "schema": []}
{"input": "The findings presented show the complex inter-relationships between multiple regulators of drug metabolism and transport genes, such as estrogens, progesterone, and growth hormone, and their effects on enzyme and transporter expression in different tissues.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 136, "end": 145}, {"text": "progesterone", "start": 147, "end": 159}]}}, "schema": []}
{"input": "The studies provide the impetus for a mechanism-and evidence-based approach to optimally managing drug therapies during pregnancy and improving treatment outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Environmental Survey Meta-analysis Reveals Hidden Diversity among Unicellular Opisthokonts.", "output": {"entities": {}}, "schema": []}
{"input": "The Opisthokonta clade includes Metazoa, Fungi, and several unicellular lineages, such as choanoflagellates, filastereans, ichthyosporeans, and nucleariids.", "output": {"entities": {}}, "schema": []}
{"input": "To date, studies of the evolutionary diversity of opisthokonts have focused exclusively on metazoans, fungi, and, very recently, choanoflagellates.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, very little is known about diversity among the filastereans, ichthyosporeans, and nucleariids.", "output": {"entities": {}}, "schema": []}
{"input": "To better understand the evolutionary diversity and ecology of the opisthokonts, here we analyze published environmental data from nonfungal unicellular opisthokonts and report 18S ribosomal DNA phylogenetic analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Our data reveal extensive diversity among all unicellular opisthokonts, except for the filastereans.", "output": {"entities": {}}, "schema": []}
{"input": "We identify several clades that consist exclusively of environmental sequences, especially among ichthyosporeans and choanoflagellates.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, we show that the ichthyosporeans represent a significant percentage of overall unicellular opisthokont diversity, with a greater ecological role in marine environments than previously believed.", "output": {"entities": {}}, "schema": []}
{"input": "Our results provide a useful phylogenetic framework for future ecological and evolutionary studies of these poorly known lineages.", "output": {"entities": {}}, "schema": []}
{"input": "Lack of dosage compensation accompanies the arrested stage of sex chromosome evolution in ostriches.", "output": {"entities": {}}, "schema": []}
{"input": "Sex chromosome evolution is usually seen as a process that, once initiated, will inevitably progress toward an advanced stage of degeneration of the nonrecombining chromosome.", "output": {"entities": {}}, "schema": []}
{"input": "However, despite evidence that avian sex chromosome evolution was initiated > 100 Ma, ratite birds have been trapped in an arrested stage of sex chromosome divergence.", "output": {"entities": {}}, "schema": []}
{"input": "We performed RNA sequencing of several tissues from male and female ostriches and assembled the transcriptome de novo.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 315 Z-linked genes fell into two categories: those that have equal expression level in the two sexes (for which Z-W recombination still occurs) and those that have a 2-fold excess of male expression (for which Z-W recombination has ceased).", "output": {"entities": {}}, "schema": []}
{"input": "We suggest that failure to evolve dosage compensation has constrained sex chromosome divergence in this basal avian lineage.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that dosage compensation is a prerequisite for, not only a consequence of, sex chromosome evolution.", "output": {"entities": {}}, "schema": []}
{"input": "Managing scientific, technical and regulatory innovation in regulated bioanalysis: a discussion paper from the European Bioanalysis Forum.", "output": {"entities": {}}, "schema": []}
{"input": "On 12-13 June 2012, the European Bioanalysis Forum hosted its third Focus Meeting in Brussels (Belgium).", "output": {"entities": {}}, "schema": []}
{"input": "At the meeting, a panel discussion was held on the hurdles that the bioanalytical community encounters when adopting new technologies or managing regulated bioanalysis expectations around emerging technologies.", "output": {"entities": {}}, "schema": []}
{"input": "Over the last few years, the industry has seen many new technologies maturing.", "output": {"entities": {}}, "schema": []}
{"input": "As they became available, the bioanalytical scientist has observed that implementing these technologies in the regulated environment has become increasingly challenging.", "output": {"entities": {}}, "schema": []}
{"input": "For one, scientific developments and regulatory expectations may not go hand in hand.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, the pharmaceutical industry has become increasingly risk averse in their response to these real or perceived higher expectations in regulated bioanalysis.", "output": {"entities": {}}, "schema": []}
{"input": "As a downstream consequence, the potential result of overinterpretation of guidance or occasional widespread and premature implementation of responses to health authority inspections, industry may be contributing significantly to raising the bar on some processes related to day-to-day practices in the bioanalytical laboratory.", "output": {"entities": {}}, "schema": []}
{"input": "Last but not least, with the community being satisfied with the performance of the current tools, potential complacency can be observed in the regulated bioanalytical community because existing technologies, such as LC-MS/MS and ligand-binding assays, have served and still are serving them extremely well.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, the question' what' s next after LC-MS/MS or ELISA?' is not resonating with many scientists as pertinently compared with' What' s next after RIA, GC or LC-UV?', which was the key question in the 1990s, certainly in the context of an increasing effort needed to validate these new tools.", "output": {"entities": {}}, "schema": []}
{"input": "With this article, the European Bioanalysis Forum aims to stimulate an open dialogue between all stakeholders in regulated bioanalysis to positively influence how we balance science, process and regulations in day-to-day work.", "output": {"entities": {}}, "schema": []}
{"input": "This discussion should facilitate the evaluation and the subsequent implementation of innovative techniques for the benefit of the patient, while stimulating our community to raise the bar on added-value science, but at the same time removing the bar on processes with limited or no added value.", "output": {"entities": {}}, "schema": []}
{"input": "Semi-Synthetic Mithramycin SA Derivatives with Improved AntiCancer Activity.", "output": {"entities": {"chemical": [{"text": "Mithramycin SA", "start": 15, "end": 29}]}}, "schema": []}
{"input": "Mithramycin (MTM) is a potent anti-cancer agent that has recently garnered renewed attention.", "output": {"entities": {"chemical": [{"text": "Mithramycin", "start": 0, "end": 11}, {"text": "MTM", "start": 13, "end": 16}]}}, "schema": []}
{"input": "This manuscript describes the design and development of mithramycin derivatives through a combinational approach of biosynthetic analogue generation followed by synthetic manipulation for further derivatization.", "output": {"entities": {"chemical": [{"text": "mithramycin", "start": 56, "end": 67}]}}, "schema": []}
{"input": "Mithramycin SA is a previously discovered analogue produced by the M7W1 mutant strain alongside the improved mithramycin analogues mithramycin SK and mithramycin SDK.", "output": {"entities": {"chemical": [{"text": "Mithramycin SA", "start": 0, "end": 14}, {"text": "mithramycin", "start": 109, "end": 120}, {"text": "mithramycin SK", "start": 131, "end": 145}, {"text": "mithramycin SDK", "start": 150, "end": 165}]}}, "schema": []}
{"input": "Mithramycin SA shows decreased anti-cancer activity compared to mithramycin and has a shorter, two carbon aglycon side chain that is terminated in a carboxylic acid.", "output": {"entities": {"chemical": [{"text": "Mithramycin SA", "start": 0, "end": 14}, {"text": "mithramycin", "start": 64, "end": 75}, {"text": "carbon", "start": 99, "end": 105}, {"text": "carboxylic acid", "start": 149, "end": 164}]}}, "schema": []}
{"input": "The aglycon side chain is responsible for an interaction with the DNA-phosphate backbone as mithramycin interacts with its target DNA.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 70, "end": 79}, {"text": "mithramycin", "start": 92, "end": 103}]}}, "schema": []}
{"input": "It was therefore decided to further functionalize this side chain through reactions with the terminal carboxylic acid in an effort to enhance the interaction with the DNA phosphate backbone and improve the anti-cancer activity.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 102, "end": 117}, {"text": "phosphate", "start": 171, "end": 180}]}}, "schema": []}
{"input": "This side chain was modified with a variety of molecules increasing the anti-cancer activity to a comparable level to mithramycin SK.", "output": {"entities": {"chemical": [{"text": "mithramycin SK", "start": 118, "end": 132}]}}, "schema": []}
{"input": "This work shows the ability to transform the previously useless mithramycin SA into a valuable molecule and opens the door to further functionalization and semi-synthetic modification for the development of molecules with increased specificity and/or drug formulation.", "output": {"entities": {"chemical": [{"text": "mithramycin SA", "start": 64, "end": 78}]}}, "schema": []}
{"input": "Oxytocin in the central amygdaloid nucleus modulates the neuroendocrine responses induced by hypertonic volume expansion in the rat.", "output": {"entities": {"chemical": [{"text": "Oxytocin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The present study investigated the involvement of the oxytocinergic neurones that project into the central amygdala (CeA) in the control of electrolyte excretion and hormone secretion in unanaesthetised rats subjected to acute hypertonic blood volume expansion (BVE; 0. 3 M NaCl, 2 ml/100 g of body weight over 1 min).", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 274, "end": 278}]}}, "schema": []}
{"input": "Oxytocin and vasopressin mRNA expression in the paraventricular (Pa) and supraoptic nucleus (SON) of the hypothalamus were also determined using the real time-polymerase chain reaction and in situ hybridisation.", "output": {"entities": {"chemical": [{"text": "Oxytocin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Male Wistar rats with unilaterally implanted stainless steel cannulas in the CeA were used.", "output": {"entities": {}}, "schema": []}
{"input": "Oxytocin (1 mu g/0. 2 mu l), vasotocin, an oxytocin antagonist (1 mu g/0. 2 mu l) or vehicle was injected into the CeA 20 min before the BVE.", "output": {"entities": {"chemical": [{"text": "Oxytocin", "start": 0, "end": 8}, {"text": "vasotocin", "start": 29, "end": 38}, {"text": "oxytocin", "start": 43, "end": 51}]}}, "schema": []}
{"input": "In rats treated with vehicle in the CeA, hypertonic BVE increased urinary volume, sodium excretion, plasma oxytocin (OT), vasopressin (AVP) and atrial natriuretic peptide (ANP) levels and also increased the expression of OT and AVP mRNA in the Pa and SON.", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 107, "end": 115}]}}, "schema": []}
{"input": "In rats pre-treated with OT in the CeA, previously to the hypertonic BVE, there were further significant increases in plasma AVP, OT and ANP levels, urinary sodium and urine output, as well as in gene expression (AVP and OT mRNA) in the Pa and SON compared to BVE alone.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 157, "end": 163}]}}, "schema": []}
{"input": "Vasotocin reduced sodium, urine output and ANP levels, although no changes were observed in plasma AVP and OT levels or in the expression of the AVP and OT genes in both hypothalamic nuclei.", "output": {"entities": {"chemical": [{"text": "Vasotocin", "start": 0, "end": 9}, {"text": "sodium", "start": 18, "end": 24}]}}, "schema": []}
{"input": "The results of the present study suggest that oxytocin in the CeA exerts a facilitatory role in the maintenance of hydroelectrolyte balance in response to changes in extracellular volume and osmolality.", "output": {"entities": {}}, "schema": []}
{"input": "Testosterone deficiency induces markedly decreased serum triglycerides, increased small dense LDL, and hepatic steatosis mediated by dysregulation of lipid assembly and secretion in mice fed a high-fat diet.", "output": {"entities": {"chemical": [{"text": "Testosterone", "start": 0, "end": 12}, {"text": "triglycerides", "start": 57, "end": 70}]}}, "schema": []}
{"input": "OBJECTIVE: Although low serum testosterone (T) is associated with metabolic disorders, the mechanism of this association is unclear.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 30, "end": 42}]}}, "schema": []}
{"input": "The objective of the present study was to investigate the combined effects of T deficiency and a high-fat diet (HFD) on hepatic lipid homeostasis in mice.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS/METHODS: Orchiectomized (ORX) mice and sham-operated (SHAM) mice were randomly divided into five groups: SHAM mice fed a standard diet (SD), SHAM mice fed HFD, ORX mice fed SD, ORX mice fed HFD, and ORX mice fed HFD with T supplementation.", "output": {"entities": {}}, "schema": []}
{"input": "After 4weeks of treatment, we investigated the synthesis and secretion of lipids in the liver and detailed serum lipoprotein profiles in each group.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: ORX mice fed HFD showed increased hepatic steatosis, markedly decreased serum triglyceride (TG) and TG-VLDL content, and increased serum very small-LDL content.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 87, "end": 99}]}}, "schema": []}
{"input": "Gene expression analysis revealed that ORX mice fed HFD showed significantly decreased expression of microsomal triglyceride transfer protein, lipin-1, peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma coactivator 1-alpha, and significantly increased sterol regulatory element-binding protein-1, diacylglycerol acyltransferase-2 and fatty acid synthase.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 112, "end": 124}, {"text": "sterol", "start": 272, "end": 278}, {"text": "diacylglycerol", "start": 317, "end": 331}, {"text": "fatty acid", "start": 354, "end": 364}]}}, "schema": []}
{"input": "Reduction of hepatic AMPK phosphorylation was observed in ORX mice fed HFD.", "output": {"entities": {}}, "schema": []}
{"input": "These perturbations in ORX mice fed HFD were normalized to the levels of SHAM mice fed HFD by T supplementation.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: T deficiency is associated with failure of lipid homeostasis mediated by altered expression of genes involved in hepatic assembly and secretion of lipids.", "output": {"entities": {}}, "schema": []}
{"input": "Novel anticoagulants in the therapy of peripheral arterial and coronary artery disease.", "output": {"entities": {}}, "schema": []}
{"input": "Anticoagulant and antiplatelet drugs are used and studied in numerous trials for primary and secondary prevention of atherothrombosis since decades.", "output": {"entities": {}}, "schema": []}
{"input": "The annual rate for cardiovascular morbidity and mortality is high in patients following an acute coronary syndrome and in patients with peripheral arterial disease (PAD) due to concomitant cardiac and cerebrovascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Plaque rupture and subsequent thrombosis involves activation of both platelets and coagulation factors.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore the combination of aspirin and warfarin to improve prevention of atherothrombosis compared to antiplatelet therapy alone was studied but could not be established due to significantly increased risk of major bleeding compared to a nonsignificant reduction in ischemic events.", "output": {"entities": {"chemical": [{"text": "aspirin", "start": 29, "end": 36}, {"text": "warfarin", "start": 41, "end": 49}]}}, "schema": []}
{"input": "During the past two decades, clinical trials focused on combined antiplatelet therapies for the prevention of secondary events following acute coronary syndromes and very recently on the new oral anticoagulants in combination with antiplatelet therapy.", "output": {"entities": {}}, "schema": []}
{"input": "This review discusses the role of the new oral anticoagulants such as Factor IIa (thrombin) and Factor Xa inhibitors in atherothrombosis, their pharmacological properties and recently published clinical data in secondary prevention of atherothrombotic events and potential implications for patients with PAD.", "output": {"entities": {}}, "schema": []}
{"input": "Mineralocorticoid receptor antagonists for therapy of coronary artery disease and related complications.", "output": {"entities": {}}, "schema": []}
{"input": "The perception of aldosterone action to be restricted to regulation of fluid balance via sodium reabsorption and potassium excretion is incomplete; plenty of experimental and clinical studies have shown that aldosterone plays a pivotal role in a variety of (patho-) physiologic conditions within the cardiovascular continuum.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 18, "end": 29}, {"text": "sodium", "start": 89, "end": 95}, {"text": "potassium", "start": 113, "end": 122}, {"text": "aldosterone", "start": 208, "end": 219}]}}, "schema": []}
{"input": "Deleterious effects include cardiovascular inflammation, endothelial dysfunction, structural and electrical remodelling.", "output": {"entities": {}}, "schema": []}
{"input": "Mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, prevent some of these maladaptive effects on the cardiovascular system and have proven to be a highly efficacious pharmacological therapy.", "output": {"entities": {"chemical": [{"text": "spironolactone", "start": 55, "end": 69}, {"text": "eplerenone", "start": 74, "end": 84}]}}, "schema": []}
{"input": "In this article we review the current clinical impact of MRAs in the treatment of coronary artery disease (CAD) and its related complications, for example, acute myocardial infarction (MI) and chronic heart failure.", "output": {"entities": {}}, "schema": []}
{"input": "Design and synthesis of D 1 agonist/D 2 antagonist for treatment of schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "A series of tetrahydroisoquinolines were designed, synthesized and evaluated as the first non-natural product type of compounds with dual D (1) receptor (D (1) R) agonism and D (2) receptor (D (2) R) antagonism properties for treatment of schizophrenia.", "output": {"entities": {"chemical": [{"text": "tetrahydroisoquinolines", "start": 12, "end": 35}]}}, "schema": []}
{"input": "The initial SAR of the series was explored.", "output": {"entities": {}}, "schema": []}
{"input": "The lead in the series, 3g, exhibited high affinity and good potency.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 3g displayed 95% of D (1) R occupancy (10 mg/kg, sc) and 75% of D (2) R occupancy (10 mg/kg, sc) in the striatum of male CD-1 mice.", "output": {"entities": {}}, "schema": []}
{"input": "The series exhibited unique pharmacology and merit as tool compounds for target validation and future optimizations.", "output": {"entities": {}}, "schema": []}
{"input": "RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection.", "output": {"entities": {}}, "schema": []}
{"input": "The appropriate execution of DNA double-strand break (DSB) repair is critical for genome stability and tumor avoidance.", "output": {"entities": {}}, "schema": []}
{"input": "53BP1 and BRCA1 directly influence DSB repair pathway choice by regulating 5' end resection, but how this is achieved remains uncertain.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report that Rif1 (-/-) mice are severely compromised for 53BP1-dependent class switch recombination (CSR) and fusion of dysfunctional telomeres.", "output": {"entities": {}}, "schema": []}
{"input": "The inappropriate accumulation of RIF1 at DSBs in S phase is antagonized by BRCA1, and deletion of Rif1 suppresses toxic nonhomologous end joining (NHEJ) induced by PARP inhibition in Brca1-deficient cells.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistically, RIF1 is recruited to DSBs via the N-terminal phospho-SQ/TQ domain of 53BP1, and DSBs generated by ionizing radiation or during CSR are hyperresected in the absence of RIF1.", "output": {"entities": {"chemical": [{"text": "N", "start": 51, "end": 52}, {"text": "phospho", "start": 62, "end": 69}]}}, "schema": []}
{"input": "Thus, RIF1 and 53BP1 cooperate to block DSB resection to promote NHEJ in G1, which is antagonized by BRCA1 in S phase to ensure a switch of DSB repair mode to homologous recombination.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial electron transport is inhibited by disappearance of metallothionein in human bronchial epithelial cells following exposure to silver nitrate.", "output": {"entities": {"chemical": [{"text": "silver nitrate", "start": 140, "end": 154}]}}, "schema": []}
{"input": "Silver (Ag) possesses antibacterial activity and has been used in wound dressings and deodorant powders worldwide.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}, {"text": "Ag", "start": 8, "end": 10}]}}, "schema": []}
{"input": "However, the metabolic behavior and biological roles of Ag in mammals have not been well characterized.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 56, "end": 58}]}}, "schema": []}
{"input": "In the present study, we exposed human bronchial epithelial cells (BEAS-2B) to AgNO3 and investigated uptake and intracellular distribution of Ag, expression of metallothionein (MT), generation of reactive oxygen species (ROS), and changes in mitochondrial respiration.", "output": {"entities": {"chemical": [{"text": "AgNO3", "start": 79, "end": 84}, {"text": "Ag", "start": 143, "end": 145}, {"text": "oxygen", "start": 206, "end": 212}]}}, "schema": []}
{"input": "The culture medium concentration of Ag decreased with time and stabilized at 12h.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 36, "end": 38}]}}, "schema": []}
{"input": "The concentration of both Ag and MT in the soluble cellular fraction increased up to 3h and then decreased, indicating that cytosolic Ag relocated to the insoluble fraction of the cells.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 26, "end": 28}, {"text": "Ag", "start": 134, "end": 136}]}}, "schema": []}
{"input": "The levels of mRNAs for the major human MT isoforms MT-I and MT-II paralleled with the protein levels of Ag-MT.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 105, "end": 107}]}}, "schema": []}
{"input": "The intensity of fluorescence derived from ROS was elevated in the mitochondrial region at 24h.", "output": {"entities": {}}, "schema": []}
{"input": "Ag decreased mitochondrial oxygen consumption in a dose-dependent manner and the activity of mitochondrial complex I-IV enzymes was significantly inhibited following exposure to Ag.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 0, "end": 2}, {"text": "oxygen", "start": 27, "end": 33}, {"text": "Ag", "start": 178, "end": 180}]}}, "schema": []}
{"input": "In a separate experiment, we found that hydrogen peroxide (H2O2) at concentrations as low as 0. 001% (equivalent to the concentration of H2O2 in Ag-exposed cells) removed Ag from MT.", "output": {"entities": {"chemical": [{"text": "hydrogen peroxide", "start": 40, "end": 57}, {"text": "H2O2", "start": 59, "end": 63}, {"text": "H2O2", "start": 137, "end": 141}, {"text": "Ag", "start": 145, "end": 147}, {"text": "Ag", "start": 171, "end": 173}]}}, "schema": []}
{"input": "These results suggest MT was decomposed by cytosolic H2O2, and then Ag released from MT relocated to insoluble cellular fractions and inhibited electron chain transfer of mitochondrial complexes, which eventually led to cell damage.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 53, "end": 57}, {"text": "Ag", "start": 68, "end": 70}]}}, "schema": []}
{"input": "Nitric oxide generated by the compound RuBPY promotes the vascular smooth cell membrane hyperpolarization.", "output": {"entities": {"chemical": [{"text": "Nitric oxide", "start": 0, "end": 12}, {"text": "RuBPY", "start": 39, "end": 44}]}}, "schema": []}
{"input": "The cis-[Ru (bpy) (2) (py) NO (2)] (PF (6)) specie (RuBPY) has been used as nitric oxide (NO) delivery agent.", "output": {"entities": {"chemical": [{"text": "cis-[Ru (bpy) (2) (py) NO (2)] (PF (6))", "start": 4, "end": 43}, {"text": "RuBPY", "start": 52, "end": 57}, {"text": "nitric oxide", "start": 76, "end": 88}, {"text": "NO", "start": 90, "end": 92}]}}, "schema": []}
{"input": "It is an NO reservoir and it is thermodynamically stable in aqueous solution.", "output": {"entities": {"chemical": [{"text": "NO", "start": 9, "end": 11}]}}, "schema": []}
{"input": "This study aimed to evaluate the NO specie generated by RuBPY as compared to NO released from sodium nitroprusside (SNP) and to study the cellular mechanisms specially focusing the activation of soluble guanylyl-cyclase (sGC), K (+) channels and the cell membrane hyperpolarization, which are the main targets for NO-inducing vascular relaxation.", "output": {"entities": {"chemical": [{"text": "NO", "start": 33, "end": 35}, {"text": "RuBPY", "start": 56, "end": 61}, {"text": "NO", "start": 77, "end": 79}, {"text": "sodium nitroprusside", "start": 94, "end": 114}, {"text": "SNP", "start": 116, "end": 119}, {"text": "guanylyl", "start": 203, "end": 211}, {"text": "K (+)", "start": 227, "end": 232}, {"text": "NO", "start": 314, "end": 316}]}}, "schema": []}
{"input": "NO generated by RuBPY and the vascular smooth muscle cell (VSMC) membrane potential were measured by confocal microscopy.", "output": {"entities": {"chemical": [{"text": "NO", "start": 0, "end": 2}, {"text": "RuBPY", "start": 16, "end": 21}]}}, "schema": []}
{"input": "The cellular mechanisms of aorta relaxation were investigated using K (+) channel blockers and sGC inhibitor.", "output": {"entities": {"chemical": [{"text": "K (+)", "start": 68, "end": 73}]}}, "schema": []}
{"input": "NO released from RuBPY was higher than NO released from SNP.", "output": {"entities": {"chemical": [{"text": "NO", "start": 0, "end": 2}, {"text": "RuBPY", "start": 17, "end": 22}, {"text": "NO", "start": 39, "end": 41}, {"text": "SNP", "start": 56, "end": 59}]}}, "schema": []}
{"input": "RuBPY released only radicalar NO (0) and SNP released both NO (-) and NO (0).", "output": {"entities": {"chemical": [{"text": "RuBPY", "start": 0, "end": 5}, {"text": "radicalar NO", "start": 20, "end": 32}, {"text": "SNP", "start": 41, "end": 44}, {"text": "NO (-)", "start": 59, "end": 65}, {"text": "NO", "start": 70, "end": 72}]}}, "schema": []}
{"input": "The concentration-effect curves for RuBPY-induced relaxation was shifted to the right by inhibition of sGC with ODQ and by the non-selective blockade of K (+) channels with TEA.", "output": {"entities": {"chemical": [{"text": "RuBPY", "start": 36, "end": 41}, {"text": "ODQ", "start": 112, "end": 115}, {"text": "K (+)", "start": 153, "end": 158}, {"text": "TEA", "start": 173, "end": 176}]}}, "schema": []}
{"input": "The simultaneous combination of ODQ and TEA abolished the vasorelaxation induced by RuBPY.", "output": {"entities": {"chemical": [{"text": "ODQ", "start": 32, "end": 35}, {"text": "TEA", "start": 40, "end": 43}, {"text": "RuBPY", "start": 84, "end": 89}]}}, "schema": []}
{"input": "The membrane potential measured by the sensitive dye 4-Di-ANNEPS demonstrated that RuBPY induces cell membrane hyperpolarization.", "output": {"entities": {"chemical": [{"text": "4-Di-ANNEPS", "start": 53, "end": 64}, {"text": "RuBPY", "start": 83, "end": 88}]}}, "schema": []}
{"input": "Taken together, our results indicate that the large amount of NO (0) specie generated by RuBPY induces vasorelaxation due to activation of sGC, K (+) channels sensitive to TEA, and cell membrane hyperpolarization.", "output": {"entities": {"chemical": [{"text": "NO", "start": 62, "end": 64}, {"text": "RuBPY", "start": 89, "end": 94}, {"text": "K (+)", "start": 144, "end": 149}, {"text": "TEA", "start": 172, "end": 175}]}}, "schema": []}
{"input": "These results indicate that NO (0) generated from RuBPY can also directly activate the K (+) channels in an independent way of sGC.", "output": {"entities": {"chemical": [{"text": "NO", "start": 28, "end": 30}, {"text": "RuBPY", "start": 50, "end": 55}, {"text": "K (+)", "start": 87, "end": 92}]}}, "schema": []}
{"input": "The inhibition of HIF-2 alpha on the ATM/Chk-2 pathway is involved in the promotion effect of arsenite on benzo (a) pyrene-induced cell transformation.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 94, "end": 102}, {"text": "benzo (a) pyrene", "start": 106, "end": 122}]}}, "schema": []}
{"input": "Both arsenite and benzo (a) pyrene (BaP) are known human carcinogens.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 5, "end": 13}, {"text": "benzo (a) pyrene", "start": 18, "end": 34}, {"text": "BaP", "start": 36, "end": 39}]}}, "schema": []}
{"input": "Studies on the mode-of-action of arsenite indicate that it can also act as co-carcinogen or as a cancer promoter, and that it can facilitate progression of cancers.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 33, "end": 41}]}}, "schema": []}
{"input": "Some studies on development of lung cancers have suggested a synergism between arsenite exposure and cigarette smoking.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 79, "end": 87}]}}, "schema": []}
{"input": "The mechanism of action for such an effect, however, remains obscure.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we investigated the effects of HIF-2 alpha on arsenite-and BaP-induced cell malignant transformation as well as on signal transduction pathways in human bronchial epithelial (HBE) cells.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 68, "end": 76}, {"text": "BaP", "start": 81, "end": 84}]}}, "schema": []}
{"input": "The results show that arsenite accelerates the neoplastic transformation and migration of cells and enhances chromosomal aberrations induced by BaP.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 22, "end": 30}, {"text": "BaP", "start": 144, "end": 147}]}}, "schema": []}
{"input": "HIF-2 alpha is involved in blocking the effects of arsenite in activating the ATM/Chk-2 pathway and in repair of DNA damage induced by BaP.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 51, "end": 59}, {"text": "BaP", "start": 135, "end": 138}]}}, "schema": []}
{"input": "Moreover, blocking of HIF-2 alpha prevents the effects of arsenite on the neoplastic transformation, cell migration, and chromosomal aberrations caused by BaP.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 58, "end": 66}, {"text": "BaP", "start": 155, "end": 158}]}}, "schema": []}
{"input": "These results indicate that the repressive effect of HIF-2 alpha on the ATM/Chk-2 pathway leads to genomic instability, which is involved in arsenite-accelerated, BaP-induced malignant transformation of HBE cells.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 141, "end": 149}, {"text": "BaP", "start": 163, "end": 166}]}}, "schema": []}
{"input": "Cryptotanshinone and dihydrotanshinone I exhibit strong inhibition towards human liver microsome (HLM)-catalyzed propofol glucuronidation.", "output": {"entities": {"chemical": [{"text": "Cryptotanshinone", "start": 0, "end": 16}, {"text": "dihydrotanshinone I", "start": 21, "end": 40}, {"text": "propofol", "start": 113, "end": 121}]}}, "schema": []}
{"input": "Danshen is one of the most famous herbs in the world, and more and more danshen-prescribed drugs interactions have been reported in recent years.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of inhibition potential of danshen' s major ingredients towards UDP-glucuronosyltransferases (UGTs) will be helpful for understanding detailed mechanisms for danshen-drugs interaction.", "output": {"entities": {"chemical": [{"text": "UDP", "start": 75, "end": 78}]}}, "schema": []}
{"input": "Therefore, the aim of the present study is to investigate the inhibitory situation of cryptotanshinone and dihydrotanshinone I towards UGT enzyme-catalyzed propofol glucuronidation.", "output": {"entities": {"chemical": [{"text": "cryptotanshinone", "start": 86, "end": 102}, {"text": "dihydrotanshinone I", "start": 107, "end": 126}, {"text": "propofol", "start": 156, "end": 164}]}}, "schema": []}
{"input": "In vitro the human liver microsome (HLM) incubation system was used, and the results showed that cryptotanshinone and dihydrotanshinone I exhibited dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation.", "output": {"entities": {"chemical": [{"text": "cryptotanshinone", "start": 97, "end": 113}, {"text": "dihydrotanshinone I", "start": 118, "end": 137}, {"text": "propofol", "start": 196, "end": 204}]}}, "schema": []}
{"input": "Dixon plot and Lineweaver-Burk plot showed that the inhibition type was best fit to competitive inhibition type for both cryptotanshinone and dihydrotanshinone I.", "output": {"entities": {"chemical": [{"text": "cryptotanshinone", "start": 121, "end": 137}, {"text": "dihydrotanshinone I", "start": 142, "end": 161}]}}, "schema": []}
{"input": "The second plot using the slopes from the Lineweaver-Burk plot versus the concentrations of cryptotanshinone or dihydrotanshinone I was employed to calculate the inhibition parameters (Ki) to be 0. 4 and 1. 7 mu M, respectively.", "output": {"entities": {"chemical": [{"text": "cryptotanshinone", "start": 92, "end": 108}, {"text": "dihydrotanshinone I", "start": 112, "end": 131}]}}, "schema": []}
{"input": "Using the reported maximum plasma concentration (Cmax), the altered in vivo exposure of propofol increased by 10% and 8. 2% for the co-administration of dihydrotanshinone I and cryptotanshinone, respectively.", "output": {"entities": {"chemical": [{"text": "propofol", "start": 88, "end": 96}, {"text": "dihydrotanshinone I", "start": 153, "end": 172}, {"text": "cryptotanshinone", "start": 177, "end": 193}]}}, "schema": []}
{"input": "All these results indicated the possible danshen-propofol interaction due to the inhibition of dihydrotanshinone I and cryptotanshinone towards the glucuronidation reaction of propofol.", "output": {"entities": {"chemical": [{"text": "propofol", "start": 49, "end": 57}, {"text": "dihydrotanshinone I", "start": 95, "end": 114}, {"text": "cryptotanshinone", "start": 119, "end": 135}, {"text": "propofol", "start": 176, "end": 184}]}}, "schema": []}
{"input": "A new method of segmentation of compact-appearing, transitional and trabecular compartments and quantification of cortical porosity from high resolution peripheral quantitative computed tomographic images.", "output": {"entities": {}}, "schema": []}
{"input": "A transitional or cortico-trabecular junctional zone exists at any location composed of both cortical and trabecular bones such as the metaphyses of tubular bones and short bones like the femoral neck.", "output": {"entities": {}}, "schema": []}
{"input": "The transitional zone comprises the inner cortex adjacent to the medullary canal and trabeculae abutting against the cortex contiguous with the endocortical surface.", "output": {"entities": {}}, "schema": []}
{"input": "This is a site of vigorous remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Intracortical remodeling cavitates the inner cortex expanding this transitional zone at the price of compact-appearing cortex so that it contains porosity, cortical fragments that resemble trabeculae, and trabeculae abutting the eroding cortex.", "output": {"entities": {}}, "schema": []}
{"input": "The porosity of the transitional zone is an important source of bone loss.", "output": {"entities": {}}, "schema": []}
{"input": "It reduces bone strength exponentially and is a quantifiable `fingerprint' of structural deterioration.", "output": {"entities": {}}, "schema": []}
{"input": "A new automated method of segmentation of bone from background and bone into its compact-appearing cortex, transitional zone, and trabecular compartment is described, with a new approach to quantification of cortical porosity.", "output": {"entities": {}}, "schema": []}
{"input": "Segmentation is achieved by automatically selecting attenuation profile curves perpendicular to the periosteal surface.", "output": {"entities": {}}, "schema": []}
{"input": "Local bone edges are identified as the beginning and the end of the rising and falling S-shaped portions of the curve enabling the delineation of the compartments.", "output": {"entities": {}}, "schema": []}
{"input": "Analyzing ~ 3600 consecutive overlapping profiles around the perimeter of each cross-sectional slice segments the compartments.", "output": {"entities": {}}, "schema": []}
{"input": "Porosity is quantified as the average void volume fraction of all voxels within each compartment.", "output": {"entities": {}}, "schema": []}
{"input": "To assess accuracy at the distal radius and tibia, mu CT images of cadaveric specimens imaged at 19 mu m voxel size served as the gold standard.", "output": {"entities": {}}, "schema": []}
{"input": "To assess accuracy at the proximal femur, scanning electron microscopy (SEM) images of specimens collected at 2. 5 mu m resolution served as the gold standard.", "output": {"entities": {}}, "schema": []}
{"input": "Agreement between HRpQCT and the gold standards for segmentation and quantification of porosity at the distal radius and tibia ranged from R (2) = 0. 87 to 0. 99, and for the proximal femur ranged from 0. 93 to 0. 99.", "output": {"entities": {}}, "schema": []}
{"input": "The precision error in vivo for segmentation and quantification of porosity in HRpQCT images at the distal radius, given by the root mean square error of the coefficient of variation, ranged from 0. 54% for porosity of the transitional zone to 3. 98% for area of the compact-appearing cortex.", "output": {"entities": {}}, "schema": []}
{"input": "Segmentation of the transitional zone minimizes errors in apportioning cortical fragments and cortical porosity to the medullary compartment and so is likely to allow accurate assessment of fracture risk and the morphological effects of growth, aging, diseases and therapies.", "output": {"entities": {}}, "schema": []}
{"input": "Investigations of dipeptide structures containing pyrrolysine as N-terminal residues: a DFT study in gas and aqueous phase.", "output": {"entities": {"chemical": [{"text": "dipeptide", "start": 18, "end": 27}, {"text": "pyrrolysine", "start": 50, "end": 61}, {"text": "N", "start": 65, "end": 66}]}}, "schema": []}
{"input": "A set of six dipeptides containing pyrrolysine invariably at their N-terminal positions is studied in gas and aqueous phase using a polarizable continuum model (PCM).", "output": {"entities": {"chemical": [{"text": "dipeptides", "start": 13, "end": 23}, {"text": "pyrrolysine", "start": 35, "end": 46}, {"text": "N", "start": 67, "end": 68}]}}, "schema": []}
{"input": "The molecular geometries of the dipeptides are fully optimized at B3LYP/6-31 + + G (d, p) level of theory and a second derivative (frequency) analysis confirms that all the optimized geometries are true minima.", "output": {"entities": {"chemical": [{"text": "dipeptides", "start": 32, "end": 42}]}}, "schema": []}
{"input": "The effects of solvation and identity of the varying C-terminal residue on the energetics, structural features of the peptide planes, values of the psi and phi dihedrals, geometry around the alpha-carbon atoms and theoretically predicted vibrational spectra of the dipeptides are thoroughly analyzed.", "output": {"entities": {"chemical": [{"text": "C", "start": 53, "end": 54}, {"text": "alpha-carbon", "start": 191, "end": 203}, {"text": "dipeptides", "start": 265, "end": 275}]}}, "schema": []}
{"input": "Solvation effects are found to modify the gas phase conformation of the dipeptides around psi dihedrals while the identity of the varying C-terminal residue affect the values of phi, planarity of the peptide planes and geometry around the alpha-carbon atoms.", "output": {"entities": {"chemical": [{"text": "dipeptides", "start": 72, "end": 82}, {"text": "C", "start": 138, "end": 139}, {"text": "alpha-carbon", "start": 239, "end": 251}]}}, "schema": []}
{"input": "The presence or absence of three types of intramolecular H-bonds, namely O... H-N, N... H-N and O... H-C that leave noticeable signatures in the IR spectra, play crucial roles in influencing the geometry of the peptide planes and in determining the energetics of the dipeptides.", "output": {"entities": {"chemical": [{"text": "H", "start": 57, "end": 58}, {"text": "O", "start": 73, "end": 74}, {"text": "H-N", "start": 78, "end": 81}, {"text": "N", "start": 83, "end": 84}, {"text": "H-N", "start": 88, "end": 91}, {"text": "O", "start": 96, "end": 97}, {"text": "H-C", "start": 101, "end": 104}, {"text": "dipeptides", "start": 267, "end": 277}]}}, "schema": []}
{"input": "NMR investigation on the DNA binding and B-Z transition pathway of the Z alpha domain of human ADAR1.", "output": {"entities": {}}, "schema": []}
{"input": "Human ADAR1, which has two left-handed Z-DNA binding domains, preferentially binds Z-DNA rather than B-DNA with a high binding affinity.", "output": {"entities": {}}, "schema": []}
{"input": "Z-DNA can be induced in long genomic DNA by Z-DNA binding proteins through the formation of two B-Z junctions with the extrusion of one base pair from each junction.", "output": {"entities": {}}, "schema": []}
{"input": "We performed NMR experiments on complexes of Z alpha (ADAR1) with three DNA duplexes at a variety of protein-to-DNA molar ratios.", "output": {"entities": {}}, "schema": []}
{"input": "This study confirmed that the Z alpha (ADAR1) first binds to an 8-bp CG-rich DNA segment via a unique conformation during B-Z transition and the neighboring AT-rich region becomes destabilized.", "output": {"entities": {}}, "schema": []}
{"input": "We also found that, when DNA duplexes have only 6-bp CG-rich segment, the interaction with Z alpha (ADAR1) did not affect the thermal stabilities of the 6-bp CG-rich segment as well as the neighboring two A. T base pairs.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that four Z alpha (ADAR1) proteins interact with the 8-bp DNA sequence containing a 6-bp CG-repeat segment as well as a dinucleotide step, even though the dinucleotid step contains A. T base pairs.", "output": {"entities": {}}, "schema": []}
{"input": "Thus this study suggests that the length of the CG-rich region is more important than the specific DNA sequence for determining which base-pair is extruded from the B-Z junction structure.", "output": {"entities": {}}, "schema": []}
{"input": "This study also found that the Z alpha (ADAR1) in complex with a 11-bp DNA duplex exhibits a Z-DNA-bound conformation distinct from that of free Z alpha (ADAR1) and the initial contact conformations of Z alpha (ADAR1) complexed with 13-bp DNA duplexes.", "output": {"entities": {}}, "schema": []}
{"input": "Electrochemical synthesis of CdTe/SWNT hybrid nanostructures and their tunable electrical and optoelectrical properties.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 29, "end": 33}]}}, "schema": []}
{"input": "A facile electrodeposition technique was utilized to deposit single-walled carbon nanotubes (SWNTs) with cadmium telluride (CdTe) with well-controlled size, density, surface morphology, and composition.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 75, "end": 81}, {"text": "cadmium telluride", "start": 105, "end": 122}, {"text": "CdTe", "start": 124, "end": 128}]}}, "schema": []}
{"input": "By controlling the applied charge, the morphology of these hybrid nanostructures was altered from CdTe nanoparticles on SWNTs to SWNT/CdTe core/shell nanostructures and the composition of the CdTe nanoparticles was altered from Te-rich (29 at% Cd) to Cd-rich (79 at% Cd) CdTe by adjusting the deposition potential.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 98, "end": 102}, {"text": "CdTe", "start": 134, "end": 138}, {"text": "CdTe", "start": 192, "end": 196}, {"text": "Te", "start": 228, "end": 230}, {"text": "Cd", "start": 244, "end": 246}, {"text": "Cd", "start": 251, "end": 253}, {"text": "Cd", "start": 267, "end": 269}, {"text": "CdTe", "start": 271, "end": 275}]}}, "schema": []}
{"input": "The electrical and optoelectrical properties of these hybrid nanostructures showed that photo-induced current can be tuned by tailoring the conductivity type (n-type or p-type), morphology, and size of the CdTe nanostructures, with a maximum photosensitivity (Delta I/I (0)) of about 30% for SWNT/Cd-rich CdTe (n-type) core/shell nanostructures.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 206, "end": 210}, {"text": "Cd", "start": 297, "end": 299}, {"text": "CdTe", "start": 305, "end": 309}]}}, "schema": []}
{"input": "This work demonstrates a novel approach for synthesizing metal chalcogenide/SWNT hybrid nanostructures for various electrical and optoelectrical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Cloning and functional analysis of three genes encoding polygalacturonase-inhibiting proteins from Capsicum annuum and transgenic CaPGIP1 in tobacco in relation to increased resistance to two fungal pathogens.", "output": {"entities": {}}, "schema": []}
{"input": "Polygalacturonase-inhibiting proteins (PGIPs) are plant cell wall glycoproteins that can inhibit fungal endopolygalacturonases (PGs).", "output": {"entities": {}}, "schema": []}
{"input": "The PGIPs directly reduce the aggressive potential of PGs.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we isolated and functionally characterized three members of the pepper (Capsicum annuum) PGIP gene family.", "output": {"entities": {}}, "schema": []}
{"input": "Each was up-regulated at a different time following stimulation of the pepper leaves by Phytophthora capcisi and abiotic stresses including salicylic acid, methyl jasmonate, abscisic acid, wounding and cold treatment.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 140, "end": 154}, {"text": "methyl jasmonate", "start": 156, "end": 172}, {"text": "abscisic acid", "start": 174, "end": 187}]}}, "schema": []}
{"input": "Purified recombinant proteins individually inhibited activity of PGs produced by Alternaria alternata and Colletotrichum nicotianae, respectively, and virus-induced gene silencing in pepper conferred enhanced susceptibility to P. capsici.", "output": {"entities": {}}, "schema": []}
{"input": "Because three PGIP genes acted similarily in conferring resistance to infection by P. capsici, and because individually purified proteins showed consistent inhibition against PG activity of both pathogens, CaPGIP1 was selected for manipulating transgenic tobacco.", "output": {"entities": {}}, "schema": []}
{"input": "The crude proteins from transgenic tobacco exhibited distinct enhanced resistance to PG activity of both fungi.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the transgenic tobacco showed effective resistance to infection and a significant reduction in the number of infection sites, number of lesions and average size of lesions in the leaves.", "output": {"entities": {}}, "schema": []}
{"input": "All results suggest that CaPGIPs may be involved in plant defense response and play an important role in a plant' s resistance to disease.", "output": {"entities": {}}, "schema": []}
{"input": "Iron overload inhibits osteoblast biological activity through oxidative stress.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Iron overload has recently been connected with bone mineral density in osteoporosis.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}]}}, "schema": []}
{"input": "However, to date, the effect of iron overload on osteoblasts remains poorly understood.", "output": {"entities": {"chemical": [{"text": "iron", "start": 32, "end": 36}]}}, "schema": []}
{"input": "The purpose of this study is to examine osteoblast biological activity under iron overload.", "output": {"entities": {"chemical": [{"text": "iron", "start": 77, "end": 81}]}}, "schema": []}
{"input": "The osteoblast cells (hFOB1. 19) were cultured in a medium supplemented with different concentrations (50, 100, and 200 mu M) of ferric ammonium citrate as a donor of ferric ion.", "output": {"entities": {"chemical": [{"text": "ferric ammonium citrate", "start": 129, "end": 152}, {"text": "ferric", "start": 167, "end": 173}]}}, "schema": []}
{"input": "Intracellular iron was measured with a confocal laser scanning microscope.", "output": {"entities": {"chemical": [{"text": "iron", "start": 14, "end": 18}]}}, "schema": []}
{"input": "Reactive oxygen species (ROS) were detected by 2, 7-dichlorofluorescin diacetate fluorophotometry.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 9, "end": 15}, {"text": "2, 7-dichlorofluorescin diacetate", "start": 47, "end": 80}]}}, "schema": []}
{"input": "Osteoblast biological activities were evaluated by measuring the activity of alkaline phosphatase (ALP) and mineralization function.", "output": {"entities": {}}, "schema": []}
{"input": "Results indicated that iron overload could consequently increase intracellular iron concentration and intracellular ROS levels in a concentration-dependent manner.", "output": {"entities": {"chemical": [{"text": "iron", "start": 23, "end": 27}, {"text": "iron", "start": 79, "end": 83}]}}, "schema": []}
{"input": "Additionally, ALP activity was suppressed, and a decline in the number of mineralized nodules was observed in in vitro cultured osteoblast cells.", "output": {"entities": {}}, "schema": []}
{"input": "According to these results, it seems that iron overload probably inhibits osteoblast function through higher oxidative stress following increased intracellular iron concentrations.", "output": {"entities": {"chemical": [{"text": "iron", "start": 42, "end": 46}, {"text": "iron", "start": 160, "end": 164}]}}, "schema": []}
{"input": "A novel canine model for prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: No existing animal model fully recapitulates all features of human prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The dog is the only large mammal, besides humans, that commonly develops spontaneous prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Canine prostate cancer features many similarities with its human counterpart.", "output": {"entities": {}}, "schema": []}
{"input": "We sought to develop a canine model of prostate cancer that would more fully represent the features of human prostate cancer than existing models.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: The Ace-1 canine prostate cancer cell line was injected transabdominally under transrectal ultrasound (TRUS) guidance into the prostates of immunosuppressed, intact, adult male dogs.", "output": {"entities": {}}, "schema": []}
{"input": "Tumor progression was monitored by TRUS imaging.", "output": {"entities": {}}, "schema": []}
{"input": "Some dogs were subjected to positron emission tomography (PET) for tumor detection.", "output": {"entities": {}}, "schema": []}
{"input": "Time of euthanasia was determined based on tumor size, impingement on urethra, and general well-being.", "output": {"entities": {}}, "schema": []}
{"input": "Euthanasia was followed by necropsy and histopathology.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Ace-1 tumor cells grew robustly in every dog injected.", "output": {"entities": {}}, "schema": []}
{"input": "Tumors grew in subcapsular and parenchymal regions of the prostate.", "output": {"entities": {}}, "schema": []}
{"input": "Tumor tissue could be identified using PET.", "output": {"entities": {}}, "schema": []}
{"input": "Histological findings were similar to those observed in human prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Metastases to lungs and lymph nodes were detected, predominantly in dogs with intraprostatic tumors.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: We have established a minimally invasive dog model of prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "This model may be valuable for studying prostate cancer progression and distant metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "Prostate (c) 2013 Wiley Periodicals, Inc.", "output": {"entities": {}}, "schema": []}
{"input": "Chemopreventive effects of Ginkgo biloba extract in estrogen-negative human breast cancer cells.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 52, "end": 60}]}}, "schema": []}
{"input": "Excessive level of estrogen is considered as a main cause of breast cancer, therefore, many studies have focused on estrogen receptor (ER)-positive breast cancer, even though ER-negative cancer has a poor prognosis than ER-positive breast cancer.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 19, "end": 27}, {"text": "estrogen", "start": 116, "end": 124}]}}, "schema": []}
{"input": "We evaluated the anti-cancer effects of Ginkgo biloba extract (GBE) in estrogen-independent breast cancer.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 71, "end": 79}]}}, "schema": []}
{"input": "GBE has been traditionally used as a platelet activating factor, a circulatory stimulant, a tonic, and anti-asthmatic drug, and anti-cancer agent. However, anti-cancer effects of GBE on ER-negative breast cancer have not been proved yet.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we tested chemotherapeutic potential of GBE in the MDA-MB-231 (ER-negative) human breast cancer cell line. Our results showed that cytotoxicity effects of GBE in MDA-MB-231 lead to DNA fragmentation at high concentrations (500 and 1, 000 mu g/ml).", "output": {"entities": {}}, "schema": []}
{"input": "Caspase-3 was significantly activated and mRNA levels of apoptosis-related genes (Bcl-2 and Bax) were altered.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that GBE induces apoptosis in MDA-MB-231 cells.", "output": {"entities": {}}, "schema": []}
{"input": "It is presumed that GBE has chemopreventive effects in ER-independent breast cancer through anti-proliferation and apoptosis-inducing activities.", "output": {"entities": {}}, "schema": []}
{"input": "Room-temperature ferromagnetism in ZnO-encapsulated 1. 9 nm FePt3 nanoparticle-composite thin films with giant interfacial anisotropy.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 35, "end": 38}, {"text": "FePt3", "start": 60, "end": 65}]}}, "schema": []}
{"input": "As synthesized 1. 9-nm FePt3 nanoparticles are superparamagnetic at room temperature.", "output": {"entities": {"chemical": [{"text": "FePt3", "start": 23, "end": 28}]}}, "schema": []}
{"input": "Coating those nanoparticles with ZnO renders them permanently ferromagnetic with coercivity field of 650 Oe at room temperature.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 33, "end": 36}]}}, "schema": []}
{"input": "First-principles calculations indicate that giant interfacial anisotropy, induced by the strong spin-orbit interaction of enhanced orbit momentum of Fe, overcomes the superparamagnetic limit, leading to exceptional room-temperature permanent ferromagnetism.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 149, "end": 151}]}}, "schema": []}
{"input": "The findings are important for the understanding of the origin of permanent ferromagnetism at ultrasmall size and critical for ultrahigh density recording and information processing.", "output": {"entities": {}}, "schema": []}
{"input": "Fast, reversible, and general photomechanical motion in single crystals of various azo compounds using visible light.", "output": {"entities": {"chemical": [{"text": "azo", "start": 83, "end": 86}]}}, "schema": []}
{"input": "Pseudostilbene-type single crystals exhibit ubiquitous, fast, and reversible photomechanical motion under visible-light irradiation.", "output": {"entities": {}}, "schema": []}
{"input": "Push-pull substituents impart extremely rapid switching using just one wavelength of light by shortening the lifetime of the cis-form.", "output": {"entities": {}}, "schema": []}
{"input": "This results in a bending motion in the microsecond regime.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of crystal density, thickness, and molecular orientation on optimization of the photomechanical effect is investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Studies of enantiomeric degradation of the triazole fungicide hexaconazole in tomato, cucumber, and field soil by chiral liquid chromatography-tandem mass spectrometry.", "output": {"entities": {"chemical": [{"text": "triazole", "start": 43, "end": 51}, {"text": "hexaconazole", "start": 62, "end": 74}]}}, "schema": []}
{"input": "Chiral pesticide enantiomers often show different bioactivity and toxicity; however, this property is usually ignored when evaluating their environmental and public health risks.", "output": {"entities": {}}, "schema": []}
{"input": "Hexaconazole is a chiral fungicide used on a variety of crops for the control of many fungal diseases.", "output": {"entities": {"chemical": [{"text": "Hexaconazole", "start": 0, "end": 12}]}}, "schema": []}
{"input": "This use provides opportunities for the pollution of food and soil.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, a sensitive and convenient chiral liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for measuring hexaconazole enantiomers in tomato, cucumber, and soil.", "output": {"entities": {"chemical": [{"text": "hexaconazole", "start": 169, "end": 181}]}}, "schema": []}
{"input": "Separation was by a reversed-phase Chiralcel OD-RH column, under isocratic conditions using a mixture of acetonitrile-2 mM ammonium acetate in water (60/40, v/v) as the mobile phase at a flow rate of 0. 4 mL/min.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 105, "end": 117}, {"text": "ammonium acetate", "start": 123, "end": 139}]}}, "schema": []}
{"input": "Parameters including the matrix effect, linearity, precision, accuracy and stability were undertaken.", "output": {"entities": {}}, "schema": []}
{"input": "Then the proposed method was successfully applied to investigate the possible enantioselective degradation of rac-hexaconazole in plants (tomato and cucumber) and soil under field conditions.", "output": {"entities": {"chemical": [{"text": "rac-hexaconazole", "start": 110, "end": 126}]}}, "schema": []}
{"input": "The degradation of the two enantiomers of hexaconazole proved to be enantioselective and dependent on the media: The (+)-enantiomer showed a faster degradation in plants, while the (-)-enantiomer dissipated faster than the (+)-form in field soil, resulting in relative enrichment of the opposite enantiomer.", "output": {"entities": {"chemical": [{"text": "hexaconazole", "start": 42, "end": 54}]}}, "schema": []}
{"input": "The results of this work demonstrate that both the environmental media and environmental conditions influenced the direction and rate of enantioselective degradation of hexaconazole.", "output": {"entities": {"chemical": [{"text": "hexaconazole", "start": 169, "end": 181}]}}, "schema": []}
{"input": "Electron transfer dissociation (ETD): the mass spectrometric breakthrough essential for O-GlcNAc protein site assignments-a study of the O-GlcNAcylated protein host cell factor C1.", "output": {"entities": {"chemical": [{"text": "O-GlcNAc", "start": 88, "end": 96}, {"text": "O", "start": 137, "end": 138}]}}, "schema": []}
{"input": "The development of electron-based, unimolecular dissociation MS, i. e. electron capture and electron transfer dissociation (ECD and ETD, respectively), has greatly increased the speed and reliability of labile PTM site assignment.", "output": {"entities": {}}, "schema": []}
{"input": "The field of intracellular O-GlcNAc (O-linked N-acetylglucosamine) signaling has especially advanced with the advent of ETD MS.", "output": {"entities": {"chemical": [{"text": "O-GlcNAc", "start": 27, "end": 35}, {"text": "O", "start": 37, "end": 38}, {"text": "N-acetylglucosamine", "start": 46, "end": 65}]}}, "schema": []}
{"input": "Only within the last five years have proteomic-scale experiments utilizing ETD allowed the assignment of hundreds of O-GlcNAc sites within cells and subcellular structures.", "output": {"entities": {"chemical": [{"text": "O-GlcNAc", "start": 117, "end": 125}]}}, "schema": []}
{"input": "Our ability to identify and unambiguously assign the site of O-GlcNAc modifications using ETD is rapidly increasing our understanding of this regulatory glycosylation and its potential interaction with other PTMs.", "output": {"entities": {"chemical": [{"text": "O-GlcNAc", "start": 61, "end": 69}]}}, "schema": []}
{"input": "Here, we discuss the advantages of using ETD, complimented with collisional-activation MS, in a study of the extensively O-GlcNAcylated protein Host Cell Factor C1 (HCF-1).", "output": {"entities": {"chemical": [{"text": "O", "start": 121, "end": 122}]}}, "schema": []}
{"input": "HCF-1 is a transcriptional coregulator that forms a stable complex with O-GlcNAc transferase and controls cell cycle progression.", "output": {"entities": {"chemical": [{"text": "O-GlcNAc", "start": 72, "end": 80}]}}, "schema": []}
{"input": "ETD, along with higher energy collisional dissociation (HCD) MS, was employed to assign the PTMs of the HCF-1 protein isolated from HEK293T cells.", "output": {"entities": {}}, "schema": []}
{"input": "These include 19 sites of O-GlcNAcylation, two sites of phosphorylation, and two sites bearing dimethylarginine, and showcase the residue-specific, PTM complexity of this regulator of cell proliferation.", "output": {"entities": {"chemical": [{"text": "O", "start": 26, "end": 27}, {"text": "dimethylarginine", "start": 95, "end": 111}]}}, "schema": []}
{"input": "ZnO is a CO (2)-selective steam reforming catalyst.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 0, "end": 3}, {"text": "CO (2)", "start": 9, "end": 15}]}}, "schema": []}
{"input": "ZnO was tested as possible methanol and-since formaldehyde is one of the key intermediates in methanol conversion reactions-also as formaldehyde steam reforming catalyst.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 0, "end": 3}, {"text": "methanol", "start": 27, "end": 35}, {"text": "formaldehyde", "start": 46, "end": 58}, {"text": "methanol", "start": 94, "end": 102}, {"text": "formaldehyde", "start": 132, "end": 144}]}}, "schema": []}
{"input": "Catalytic experiments in a batch as well as a flow reactor resulted in highly selective steam reforming, though at low specific activities, of formaldehyde and methanol over ZnO toward CO (2) (selectivity of 95-99. 6%).", "output": {"entities": {"chemical": [{"text": "formaldehyde", "start": 143, "end": 155}, {"text": "methanol", "start": 160, "end": 168}, {"text": "ZnO", "start": 174, "end": 177}, {"text": "CO (2)", "start": 185, "end": 191}]}}, "schema": []}
{"input": "Comparison of the behavior of ZnPd near-surface intermetallic phases, unsupported intermetallic ZnPd and supported ZnPd/ZnO catalysts reveals that formaldehyde is formed from methanol in parallel with CO (2) on the former, while on unsupported intermetallic ZnPd and ZnO-supported ZnPd, it is efficiently reacted toward CO (2), thus, a beneficial role of ZnO in oxidizing formaldehyde-derived intermediates toward CO (2) is evident.", "output": {"entities": {"chemical": [{"text": "ZnPd", "start": 30, "end": 34}, {"text": "ZnPd", "start": 96, "end": 100}, {"text": "ZnPd", "start": 115, "end": 119}, {"text": "ZnO", "start": 120, "end": 123}, {"text": "formaldehyde", "start": 147, "end": 159}, {"text": "methanol", "start": 175, "end": 183}, {"text": "CO (2)", "start": 201, "end": 207}, {"text": "ZnPd", "start": 258, "end": 262}, {"text": "ZnO", "start": 267, "end": 270}, {"text": "ZnPd", "start": 281, "end": 285}, {"text": "CO (2)", "start": 320, "end": 326}, {"text": "ZnO", "start": 355, "end": 358}, {"text": "formaldehyde", "start": 372, "end": 384}, {"text": "CO (2)", "start": 414, "end": 420}]}}, "schema": []}
{"input": "Novel anti-inflammatory phytoconstituents from Desmodium gangeticum.", "output": {"entities": {}}, "schema": []}
{"input": "A new aliphatic enone, (17Z, 20Z)-hexacosa-17, 20-dien-9-one (3), and one new bisindole alkaloid, gangenoid (6), together with seven known compounds were isolated from the roots and aerial parts of Desmodium gangeticum (family: Leguminosae).", "output": {"entities": {"chemical": [{"text": "(17Z, 20Z)-hexacosa-17, 20-dien-9-one", "start": 23, "end": 60}, {"text": "bisindole alkaloid", "start": 78, "end": 96}, {"text": "gangenoid", "start": 98, "end": 107}]}}, "schema": []}
{"input": "All the compounds except 2 and 7 were isolated from this plant for the first time, which may be of chemotaxonomic importance.", "output": {"entities": {}}, "schema": []}
{"input": "Structures of compounds 3 and 6 were determined on the basis of their detailed spectroscopic analyses (NMR, IR and mass).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, compounds 3 and 6 were investigated for their effects on lipopolysaccharide-stimulated macrophages for the production of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-6.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoscale mapping of lithium-ion diffusion in a cathode within an all-solid-state lithium-ion battery by advanced scanning probe microscopy techniques.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 21, "end": 28}, {"text": "lithium", "start": 82, "end": 89}]}}, "schema": []}
{"input": "High-resolution real-space mapping of Li-ion diffusion in the LiNi (1/3) Co (1/3) Mn (1/3) O 2 cathode within an all-solid-state thin film Li-ion battery has been conducted using advanced scanning probe microscopy techniques, namely, band excitation electrochemical strain microscopy (BE-ESM) and conductive atomic force microscopy.", "output": {"entities": {"chemical": [{"text": "Li", "start": 38, "end": 40}, {"text": "LiNi (1/3) Co (1/3) Mn (1/3) O 2", "start": 62, "end": 94}, {"text": "Li", "start": 139, "end": 141}]}}, "schema": []}
{"input": "In addition, local variations of the electrochemical response in the LiNi (1/3) Co (1/3) Mn (1/3) O 2 thin film cathode at different cycling stages have been investigated.", "output": {"entities": {"chemical": [{"text": "LiNi (1/3) Co (1/3) Mn (1/3) O 2", "start": 69, "end": 101}]}}, "schema": []}
{"input": "This work demonstrates the unique feature and applications of the BE-ESM technique on battery research.", "output": {"entities": {}}, "schema": []}
{"input": "The results allow us to establish a direct relationship of the changes in ionic mobility as well as the electrochemical activity at the nanoscale with the numbers of charge/discharge cycles.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, various factors influencing the BE-ESM measurements, including sample mechanical properties (e. g., elastic and dissipative properties) as well as surface electrical properties, have also been studied to investigate the coupling effects on the electrochemical strain.", "output": {"entities": {}}, "schema": []}
{"input": "The study on the relationships between the Li-ion redistribution and microstructure of the electrode materials within thin film Li-ion battery will provide further understanding of the electrochemical degradation mechanisms of Li-ion rechargeable batteries at the nanoscale.", "output": {"entities": {"chemical": [{"text": "Li", "start": 43, "end": 45}, {"text": "Li", "start": 128, "end": 130}, {"text": "Li", "start": 227, "end": 229}]}}, "schema": []}
{"input": "Paradoxical Sost gene expression response to mechanical unloading in metaphyseal bone.", "output": {"entities": {}}, "schema": []}
{"input": "The Sost gene encodes Sclerostin, an inhibitor of Wnt-signaling, generally considered a main response gene to mechanical loading in bone.", "output": {"entities": {}}, "schema": []}
{"input": "Several papers describe that unloading leads to upregulation of Sost, which in turn may lead to loss of bone.", "output": {"entities": {}}, "schema": []}
{"input": "These studies were based on whole bone homogenates or cortical bone.", "output": {"entities": {}}, "schema": []}
{"input": "By serendipity, we noted an opposite response to unloading in the proximal rat tibia.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we hypothesized that Sost-expression in response to changes in mechanical load is bone site specific.", "output": {"entities": {}}, "schema": []}
{"input": "One hind limb of male, 3 month old rats was unloaded by paralyzing the extensors with Botulinium toxin A (Botox) injections.", "output": {"entities": {}}, "schema": []}
{"input": "A series of experiments compared the expression of Sost mRNA in the unloaded and contralateral, loaded limbs, after 3 or 10 days, in metaphyseal cancellous bone, metaphyseal cortical bone, and diaphyseal cortical bone.", "output": {"entities": {}}, "schema": []}
{"input": "We also conducted mu CT to confirm changes in bone volume density related to unloading.", "output": {"entities": {}}, "schema": []}
{"input": "Sost mRNA expression in the cancellous metaphyseal bone was downregulated almost 2-fold, both 3 days and 10 days after unloading (P < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "A similar tendency was seen in the metaphyseal cortical bone, in which Sost was 1. 5-fold downregulated (P < 0. 05) after 10days, but not significantly changed after 3days.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, diaphyseal cortical Sost expression was instead upregulated 1. 4-fold (P < 0. 05) following 3-day unloading, while there was no significant change after 10days.", "output": {"entities": {}}, "schema": []}
{"input": "Cancellous bone volume density was 58% lower (P < 0. 001, compared to cage controls) in the unloaded limb but not significantly affected in the loaded limb.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest that Sost mRNA expression in metaphyseal bone responds to mechanical unloading in an opposite direction to that observed in diaphyseal cortical bone.", "output": {"entities": {}}, "schema": []}
{"input": "This proposes a more complex expression pattern for Sost in response to unloading.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutics that target Sclerostin during altered loading conditions may result in local bone mass changes that are difficult to predict.", "output": {"entities": {}}, "schema": []}
{"input": "Polyphosphates inhibit extracellular matrix mineralization in MC3T3-E1 osteoblast cultures.", "output": {"entities": {"chemical": [{"text": "Polyphosphates", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Studies on various compounds of inorganic phosphate, as well as on organic phosphate added by post-translational phosphorylation of proteins, all demonstrate a central role for phosphate in biomineralization processes.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 42, "end": 51}, {"text": "phosphate", "start": 75, "end": 84}, {"text": "phosphate", "start": 177, "end": 186}]}}, "schema": []}
{"input": "Inorganic polyphosphates are chains of orthophosphates linked by phosphoanhydride bonds that can be up to hundreds of orthophosphates in length.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 10, "end": 24}, {"text": "orthophosphates", "start": 39, "end": 54}, {"text": "phosphoanhydride", "start": 65, "end": 81}, {"text": "orthophosphates", "start": 118, "end": 133}]}}, "schema": []}
{"input": "The role of polyphosphates in mammalian systems, where they are ubiquitous in cells, tissues and bodily fluids, and are at particularly high levels in osteoblasts, is not well understood.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 12, "end": 26}]}}, "schema": []}
{"input": "In cell-free systems, polyphosphates inhibit hydroxyapatite nucleation, crystal formation and growth, and solubility.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 22, "end": 36}]}}, "schema": []}
{"input": "In animal studies, polyphosphate injections inhibit induced ectopic calcification.", "output": {"entities": {}}, "schema": []}
{"input": "While recent work has proposed an integrated view of polyphosphate function in bone, little experimental data for bone are available.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate in osteoblast cultures producing an abundant collagenous matrix that normally show robust mineralization, that two polyphosphates (PolyP5 and PolyP65, polyphosphates of 5 and 65 phosphate residues in length) are potent mineralization inhibitors.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 135, "end": 149}, {"text": "PolyP5", "start": 151, "end": 157}, {"text": "PolyP65", "start": 162, "end": 169}, {"text": "polyphosphates", "start": 171, "end": 185}, {"text": "phosphate", "start": 198, "end": 207}]}}, "schema": []}
{"input": "Twelve-day MC3T3-E1 osteoblast cultures with added ascorbic acid (for collagen matrix assembly) and beta-glycerophosphate (a source of phosphate for mineralization) were treated with either PolyP5 or PolyP65.", "output": {"entities": {"chemical": [{"text": "beta-glycerophosphate", "start": 100, "end": 121}, {"text": "phosphate", "start": 135, "end": 144}, {"text": "PolyP5", "start": 190, "end": 196}, {"text": "PolyP65", "start": 200, "end": 207}]}}, "schema": []}
{"input": "Von Kossa staining and calcium quantification revealed that mineralization was inhibited in a dose-dependent manner by both polyphosphates, with complete mineralization inhibition at 10 mu M.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 124, "end": 138}]}}, "schema": []}
{"input": "Cell proliferation and collagen assembly were unaffected by polyphosphate treatment, indicating that polyphosphate inhibition of mineralization results not from cell and matrix effects but from direct inhibition of mineralization.", "output": {"entities": {}}, "schema": []}
{"input": "This was confirmed by showing that PolyP5 and PolyP65 bound to synthetic hydroxyapatite in a concentration-dependent manner.", "output": {"entities": {"chemical": [{"text": "PolyP5", "start": 35, "end": 41}, {"text": "PolyP65", "start": 46, "end": 53}, {"text": "hydroxyapatite", "start": 73, "end": 87}]}}, "schema": []}
{"input": "Tissue-nonspecific alkaline phosphatase (TNAP, ALPL) efficiently hydrolyzed the two PolyPs as measured by Pi release.", "output": {"entities": {"chemical": [{"text": "PolyPs", "start": 84, "end": 90}]}}, "schema": []}
{"input": "Importantly, at the concentrations of polyphosphates used in this study which inhibited bone cell culture mineralization, the polyphosphates competitively saturated TNAP, thus potentially interfering with its ability to hydrolyze mineralization-inhibiting pyrophosphate (PPi) and mineralizing-promoting beta-glycerophosphate (in cell culture).", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 38, "end": 52}, {"text": "polyphosphates", "start": 126, "end": 140}, {"text": "pyrophosphate", "start": 256, "end": 269}, {"text": "PPi", "start": 271, "end": 274}, {"text": "beta-glycerophosphate", "start": 303, "end": 324}]}}, "schema": []}
{"input": "In the biological setting, polyphosphates may regulate mineralization by shielding the essential inhibitory substrate pyrophosphate from TNAP degradation, and in the same process, delay the release of phosphate from this source.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 27, "end": 41}, {"text": "pyrophosphate", "start": 118, "end": 131}, {"text": "phosphate", "start": 201, "end": 210}]}}, "schema": []}
{"input": "In conclusion, the inhibition of mineralization by polyphosphates is shown to occur via direct binding to apatitic mineral and by mixed inhibition of TNAP.", "output": {"entities": {"chemical": [{"text": "polyphosphates", "start": 51, "end": 65}]}}, "schema": []}
{"input": "Sex differences in the antidepressant-like effects of ketamine.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 54, "end": 62}]}}, "schema": []}
{"input": "Current medications for major depression suffer from numerous limitations.", "output": {"entities": {}}, "schema": []}
{"input": "Once the right drug for treatment has been determined, it still takes several weeks for it to take effect and improve mood.", "output": {"entities": {}}, "schema": []}
{"input": "This time lag is a serious concern for the healthcare community when dealing with patients with suicidal thoughts.", "output": {"entities": {}}, "schema": []}
{"input": "However, recent clinical studies have shown that a single low-dose injection of ketamine, an N-methyl d-aspartate receptor (NMDAR) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 80, "end": 88}, {"text": "N-methyl d-aspartate", "start": 93, "end": 113}]}}, "schema": []}
{"input": "Although major depression affects twice as many women as men, all studies examining the rapid antidepressant effects of ketamine have focused on male subjects.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 120, "end": 128}]}}, "schema": []}
{"input": "Thus, we have investigated the behavioral and molecular effects of ketamine in both male and female rats and demonstrated greater sensitivity in female rats at a low dose of ketamine, a dose does not have antidepressant-like effects in male rats.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 67, "end": 75}, {"text": "ketamine", "start": 174, "end": 182}]}}, "schema": []}
{"input": "The antidepressant-like effects of this low dose of ketamine were completely abolished when female rats were ovariectomized (OVX), and restored when physiological levels of estrogen and progesterone were supplemented, suggesting a critical role for gonadal hormones in enhancing the antidepressant-like effects of ketamine in female rats.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 52, "end": 60}, {"text": "estrogen", "start": 173, "end": 181}, {"text": "progesterone", "start": 186, "end": 198}, {"text": "ketamine", "start": 314, "end": 322}]}}, "schema": []}
{"input": "In preclinical studies, the mammalian target of rapamycin (mTOR) in the medial prefrontal cortex and the eukaryotic elongation factor (eEF2) in the hippocampus have been proposed as critical mediators of ketamine' s rapid antidepressant actions.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 48, "end": 57}, {"text": "ketamine", "start": 204, "end": 212}]}}, "schema": []}
{"input": "In our hands, the increased sensitivity of female rats to a low dose of ketamine was not mediated through phosphorylation of mTOR or eEF2.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 72, "end": 80}]}}, "schema": []}
{"input": "Differential contribution of mesoaccumbens and mesohabenular dopamine to intracranial self-stimulation.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 61, "end": 69}]}}, "schema": []}
{"input": "The contribution of mesoaccumbens dopamine transmission to intracranial self-stimulation is well-established.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 34, "end": 42}]}}, "schema": []}
{"input": "However, although the nucleus accumbens comprises two main subregions, the shell and the core, little is known of the contribution of each to this behaviour.", "output": {"entities": {}}, "schema": []}
{"input": "Our first aim was to study the effects of d-amphetamine infusions into the shell and core in order to understand their relative importance to reward and operant responding.", "output": {"entities": {"chemical": [{"text": "d-amphetamine", "start": 42, "end": 55}]}}, "schema": []}
{"input": "Our second aim was to examine the contribution of a lesser studied group of dopamine neurons, those within the mesohabenular pathway, to intracranial self-stimulation.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 76, "end": 84}]}}, "schema": []}
{"input": "Male Sprague-Dawley rats were implanted with bilateral cannulae in the nucleus accumbens shell, core or in the lateral habenula and a monopolar stimulation electrode in the posterior mesencephalon, a brain site that is sensitive to changes in dopamine transmission.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 243, "end": 251}]}}, "schema": []}
{"input": "Using curve-shift scaling, we measured the reward-and performance-enhancing effects of intra-accumbens (1-20 mu g) and intra-habenular (10-40 mu g) infusions of d-amphetamine or vehicle.", "output": {"entities": {"chemical": [{"text": "d-amphetamine", "start": 161, "end": 174}]}}, "schema": []}
{"input": "Within the nucleus accumbens, the use of multiple doses and long test sessions allowed us to observe an interaction between drug effect and infusion site.", "output": {"entities": {}}, "schema": []}
{"input": "We show, for the first time, differences in the minimal doses necessary to enhance rewarding effectiveness and operant responding, in the magnitude of these enhancements as well as in their duration.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, regardless of dose, intra-habenular d-amphetamine did not alter rewarding effectiveness or operant rate, highlighting the differential contribution of mesoaccumbens and mesohabenular dopamine pathways to intracranial self-stimulation.", "output": {"entities": {"chemical": [{"text": "d-amphetamine", "start": 48, "end": 61}, {"text": "dopamine", "start": 195, "end": 203}]}}, "schema": []}
{"input": "The hidden quality gap in discovery.", "output": {"entities": {}}, "schema": []}
{"input": "Progress made through technological advances in drug discovery can be undermined by problems with measurement equipment, but it is often difficult to detect the issues without a specific investigation.", "output": {"entities": {}}, "schema": []}
{"input": "This article describes the fundamentals of measurement systems analysis and focuses on the issue of precision.", "output": {"entities": {}}, "schema": []}
{"input": "Three case studies are given where measurement systems were found to be flawed when subjected to a systematic analysis, and examples of the approaches needed for correction are described.", "output": {"entities": {}}, "schema": []}
{"input": "Economic and technological drivers of generic sterile injectable drug shortages.", "output": {"entities": {}}, "schema": []}
{"input": "Over the past few years, an increasing number of critically needed medicines have been in short supply.", "output": {"entities": {}}, "schema": []}
{"input": "Using economic theory to frame the drug-shortage problem, this paper explores why and how manufacturing-quality problems could combine with other economic and technological factors to result in shortages of generic sterile injectable drugs.", "output": {"entities": {}}, "schema": []}
{"input": "The fundamental problem we identify is the inability of the market to observe and reward quality.", "output": {"entities": {}}, "schema": []}
{"input": "This lack of reward for quality can reinforce price competition and encourage manufacturers to keep costs down by minimizing quality investments.", "output": {"entities": {}}, "schema": []}
{"input": "The US Food and Drug Administration' s (FDA' s) need to use its regulatory flexibility, on behalf of patients, to avoid shortages of medically necessary drugs may further strengthen the incentive to \" push the envelope \" on quality.", "output": {"entities": {}}, "schema": []}
{"input": "These dynamics may have produced a market situation in which quality problems have become sufficiently common and severe to result in drug shortages.", "output": {"entities": {}}, "schema": []}
{"input": "Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats.", "output": {"entities": {}}, "schema": []}
{"input": "Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS).", "output": {"entities": {}}, "schema": []}
{"input": "The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport.", "output": {"entities": {}}, "schema": []}
{"input": "Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD).", "output": {"entities": {}}, "schema": []}
{"input": "After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18).", "output": {"entities": {}}, "schema": []}
{"input": "The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group.", "output": {"entities": {}}, "schema": []}
{"input": "Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats.", "output": {"entities": {}}, "schema": []}
{"input": "Fasting cerebrospinal fluid insulin was higher in DIO than Con animals.", "output": {"entities": {}}, "schema": []}
{"input": "However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group.", "output": {"entities": {}}, "schema": []}
{"input": "These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin' s transport to the CNS.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.", "output": {"entities": {}}, "schema": []}
{"input": "Osteoblasts survive the arsenic trioxide treatment by activation of ATM-mediated pathway.", "output": {"entities": {"chemical": [{"text": "arsenic trioxide", "start": 24, "end": 40}]}}, "schema": []}
{"input": "Arsenic trioxide (ATO) is widely used in tumor treatment, but excessive arsenic exposure can have adverse effects.", "output": {"entities": {"chemical": [{"text": "Arsenic trioxide", "start": 0, "end": 16}, {"text": "ATO", "start": 18, "end": 21}, {"text": "arsenic", "start": 72, "end": 79}]}}, "schema": []}
{"input": "We recently found that, in primary osteoblasts, ATO produces oxidative stress and causes DNA tailing, but does not induce apoptosis.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 48, "end": 51}]}}, "schema": []}
{"input": "We further examined the signaling pathway by which osteoblasts survive ATO treatment, and found that they were arrested at G2/M phase of the cell cycle at 30h and overrode the G2/M boundary at 48h.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 71, "end": 74}]}}, "schema": []}
{"input": "After treatment for 30h, there was increased Cdc2 phosphorylation and expression of Wee1, a Cdc2 kinase, and expression of the cell cycle inhibitor, p21 (waf1/cip1), which interacts with Cdc2.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, levels of the phosphatase Cdc25C, which activates Cdc2, were decreased, while the ratio of its phosphorylated/inactivated form to the total amount was increased.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, phosphorylation/activation of the checkpoint kinases Chk1, Chk2 and p53 levels were increased, as were levels of activated ATM and gamma-H2AX.", "output": {"entities": {}}, "schema": []}
{"input": "The cell viability was decreased as an ATM inhibitor was added.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, these effects of ATO on gamma-H2AX, Chk1, Chk2, p53, and p21 (waf1/cip1) were reduced by an ATM inhibitor.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 31, "end": 34}]}}, "schema": []}
{"input": "These findings suggest that G2/M phase arrest of osteoblasts is mediated by Chk1/Chk2 activation via an ATM-dependent pathway by which osteoblasts survive.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-obesity effects of 3-hydroxychromone derivative, a novel small-molecule inhibitor of glycogen synthase kinase-3.", "output": {"entities": {"chemical": [{"text": "3-hydroxychromone", "start": 24, "end": 41}]}}, "schema": []}
{"input": "Glycogen synthase kinase 3 (GSK-3) plays a central role in cellular energy metabolism, and dysregulation of GSK-3 activity is implicated in a variety of metabolic disorders, including obesity, type 2 diabetes, and cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, GSK-3 has emerged as an attractive target molecule for the treatment of metabolic disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, this research focused on identification and characterization of a novel small-molecule GSK-3 inhibitor.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 1a, a structure based on 3-hydroxychromone bearing isothiazolidine-1, 1-dione, was identified from chemical library as a highly potent GSK-3 inhibitor.", "output": {"entities": {"chemical": [{"text": "3-hydroxychromone", "start": 34, "end": 51}, {"text": "isothiazolidine-1, 1-dione", "start": 60, "end": 86}]}}, "schema": []}
{"input": "An in vitro kinase assay utilizing a panel of kinases demonstrated that compound 1a strongly inhibits GSK-3 beta.", "output": {"entities": {}}, "schema": []}
{"input": "The potential effects of compound 1a on the inactivation of GSK-3 were confirmed in human liver HepG2 and human embryonic kidney HEK293 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Stabilization of glycogen synthase and beta-catenin, which are direct targets of GSK-3, by compound 1a was assessed in comparison with two other GSK-3 inhibitors: LiCl and SB-415286.", "output": {"entities": {"chemical": [{"text": "LiCl", "start": 163, "end": 167}, {"text": "SB-415286", "start": 172, "end": 181}]}}, "schema": []}
{"input": "In mouse 3T3-L1 preadipocytes, compound 1a markedly blocked adipocyte differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Consistently, intraperitoneal administration of compound 1a to diet-induced obese mice significantly ameliorated their key symptoms such as body weight gain, increased adiposity, dyslipidemia, and hepatic steatosis due to the marked reduction of whole-body lipid level.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro and in vivo effects were accompanied by upregulation of beta-catenin stability and downregulation of the expression of several critical genes related to lipid metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "From these results, it can be concluded that compound 1a, a novel small-molecule inhibitor of GSK-3, has potential as a new class of therapeutic agent for obesity treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding drugs and diseases by systems biology?", "output": {"entities": {}}, "schema": []}
{"input": "Systems biology aims to provide a holistic and in many cases dynamic picture of biological function and malfunction, in case of disease.", "output": {"entities": {}}, "schema": []}
{"input": "Technology developments in the generation of genome-wide datasets and massive improvements in computer power now allow to obtain new insights into complex biological networks and to copy nature by computing these interactions and their kinetics and by generating in silico models of cells, tissues and organs.", "output": {"entities": {}}, "schema": []}
{"input": "The expectations are high that systems biology will pave the way to the identification of novel disease genes, to the selection of successful drug candidates--that do not fail in clinical studies due to toxicity or lack of human efficacy--and finally to a more successful discovery of novel therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "However, further research is necessary to fully unleash the potential of systems biology.", "output": {"entities": {}}, "schema": []}
{"input": "Within this review we aim to highlight the most important and promising top-down and bottom-up systems biology applications in drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "Polyoxometalate-biomolecule conjugates: a new approach to create hybrid drugs for cancer therapeutics.", "output": {"entities": {"chemical": [{"text": "Polyoxometalate", "start": 0, "end": 15}]}}, "schema": []}
{"input": "Some polyoxometalate (POM) clusters have demonstrated attractive anticancer properties.", "output": {"entities": {"chemical": [{"text": "polyoxometalate", "start": 5, "end": 20}, {"text": "POM", "start": 22, "end": 25}]}}, "schema": []}
{"input": "Unfortunately, their cytotoxicity upon normal cell is one of fateful side effects obstructing their further clinic application as inorganic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "In this communication, we report a new approach to create hybrid drugs potentially for cancer therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "At first, the POM cluster bioconjugates were created by attaching the bioactive ligands on an amine grafted POM via simple amidation reaction.", "output": {"entities": {"chemical": [{"text": "POM", "start": 14, "end": 17}, {"text": "amine", "start": 94, "end": 99}]}}, "schema": []}
{"input": "The cytotoxicity study with breast cancer cells (MCF-7 and MDA-MB-231) and non-cancerous breast epithelial cell (MCF-10A) showed that rationally selected ligands with cancer-cell targeting ability on POM-biomolecule conjugates can impart enhanced anti-tumor activity and selectivity, thus representing a new concept to develop novel POM-biomolecule hybrid drugs with the potential synergistic effect: increased bioactivity and lower side effect.", "output": {"entities": {"chemical": [{"text": "POM", "start": 200, "end": 203}, {"text": "POM", "start": 333, "end": 336}]}}, "schema": []}
{"input": "Novel naphthoquinone derivatives: synthesis and activity against human African trypanosomiasis.", "output": {"entities": {"chemical": [{"text": "naphthoquinone", "start": 6, "end": 20}]}}, "schema": []}
{"input": "A series of naphthoquinone derivatives has been synthesized and tested for its biological activity against human African trypanosomiasis.", "output": {"entities": {"chemical": [{"text": "naphthoquinone", "start": 12, "end": 26}]}}, "schema": []}
{"input": "The use of reverse micellar medium not only enhanced the conversion rate, but also showed selectivity towards mono-coupled product in aryl chloride-aniline coupling reactions.", "output": {"entities": {"chemical": [{"text": "aryl chloride", "start": 134, "end": 147}, {"text": "aniline", "start": 148, "end": 155}]}}, "schema": []}
{"input": "Two derivatives of naphthoquinone (9b and 9c) exhibited potent activity against Trypanosoma brucei in vitro with low cytotoxicity.", "output": {"entities": {"chemical": [{"text": "naphthoquinone", "start": 19, "end": 33}]}}, "schema": []}
{"input": "3H-1, 2, 4-Dithiazol-3-one compounds as novel potential affordable antitubercular agents.", "output": {"entities": {"chemical": [{"text": "3H-1, 2, 4-Dithiazol-3-one", "start": 0, "end": 26}]}}, "schema": []}
{"input": "Small molecules with oxathiazol-2-one moiety were recently reported as potent inhibitors of Mycobacterium bovis var. bacilli Calmette-Gu e rin (BCG), among which HT1171 was the most potent and selective proteasome inhibitor.", "output": {"entities": {"chemical": [{"text": "oxathiazol-2-one", "start": 21, "end": 37}, {"text": "HT1171", "start": 162, "end": 168}]}}, "schema": []}
{"input": "Herein we synthesized a series of novel compounds by bioisosteric replacement of the oxathiazol-2-one ring with 3H-1, 2, 4-dithiazol-3-one, and also fifteen 1, 3, 4-oxathiazol-2-one molecules in order for potency comparison and structure-activity relationship elucidation since their antibacterial effects on the virulent strains were not evaluated before.", "output": {"entities": {"chemical": [{"text": "oxathiazol-2-one", "start": 85, "end": 101}, {"text": "3H-1, 2, 4-dithiazol-3-one", "start": 112, "end": 138}, {"text": "1, 3, 4-oxathiazol-2-one", "start": 157, "end": 181}]}}, "schema": []}
{"input": "All the compounds were assessed for antitubercular activities on the virulent H37Rv strain by a serial dilution method.", "output": {"entities": {}}, "schema": []}
{"input": "Among the tested compounds, 3H-1, 2, 4-dithiazol-3-one compound 4n was found to be the most active with a lowest MIC (90) value of 1 mu g/mL.", "output": {"entities": {"chemical": [{"text": "3H-1, 2, 4-dithiazol-3-one", "start": 28, "end": 54}]}}, "schema": []}
{"input": "Furthermore, the cytotoxicities of all the compounds against normal human liver cell line L02 were determined by an MTT method.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 116, "end": 119}]}}, "schema": []}
{"input": "Compound 4n displayed a lower inhibitory ratio than HT1171 at the concentration of 100 mu M, indicating its better safety profile.", "output": {"entities": {"chemical": [{"text": "HT1171", "start": 52, "end": 58}]}}, "schema": []}
{"input": "Toxicity assessment on trophoblast cells for some environment polluting chemicals and 17 beta-estradiol.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 86, "end": 103}]}}, "schema": []}
{"input": "The identification of reproductive toxicants is a major scientific challenge for human health.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the effects of a selected group of environmental polluting chemicals mostly provided with estrogenic activity on the human trophoblast cell lines BeWo and HTR-8/SVneo.", "output": {"entities": {}}, "schema": []}
{"input": "Cells were exposed for 24h to various concentrations (from 0. 1 pM to 1 mM) of atrazine (ATR), diethylstilbestrol (DES), para-nonylphenol (p-NP), resveratrol (RES) and 17 beta-estradiol (E2) and assayed for cell viability and human beta-Chorionic Gonadotropin (beta-hCG) secretion.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 79, "end": 87}, {"text": "ATR", "start": 89, "end": 92}, {"text": "diethylstilbestrol", "start": 95, "end": 113}, {"text": "DES", "start": 115, "end": 118}, {"text": "para-nonylphenol", "start": 121, "end": 137}, {"text": "p-NP", "start": 139, "end": 143}, {"text": "resveratrol", "start": 146, "end": 157}, {"text": "RES", "start": 159, "end": 162}, {"text": "17 beta-estradiol", "start": 168, "end": 185}]}}, "schema": []}
{"input": "Decrease of cell viability as respect to control, vehicle-treated, cultures was obtained for all chemicals in the concentration range of 1 mu M-1 mM in both cell types.", "output": {"entities": {}}, "schema": []}
{"input": "A parallel decrease of beta-hCG secretion was observed in BeWo cells, at 1 mu M-1 mM concentrations, with the only exception of ATR which caused an increase at concentrations up to 1mM.", "output": {"entities": {"chemical": [{"text": "ATR", "start": 128, "end": 131}]}}, "schema": []}
{"input": "beta-hCG release was also unexpectedly inhibited by ATR, DES, p-NP and RES at non-toxic (pM-nM) concentrations.", "output": {"entities": {"chemical": [{"text": "ATR", "start": 52, "end": 55}, {"text": "DES", "start": 57, "end": 60}, {"text": "p-NP", "start": 62, "end": 66}, {"text": "RES", "start": 71, "end": 74}]}}, "schema": []}
{"input": "These findings raise concern about the negative, potential effects of various environmental polluting chemicals on pregnancy success and fetal health.", "output": {"entities": {}}, "schema": []}
{"input": "Electronic and EPR spectra of the species involved in [W10O32] 4-photocatalysis.", "output": {"entities": {"chemical": [{"text": "[W10O32] 4-", "start": 54, "end": 65}]}}, "schema": []}
{"input": "A relativistic DFT investigation.", "output": {"entities": {}}, "schema": []}
{"input": "The decatungstate anion [W (10) O (32)] (4-) is widely used as a photocatalyst in different transformations, during which it undergoes one-electron reduction to [W (10) O (32)] (5-), possibly protonated; the bi-reduced species [W (10) O (32)] (6-) is obtained by ensuing disproportionation.", "output": {"entities": {"chemical": [{"text": "[W (10) O (32)] (4-)", "start": 24, "end": 44}, {"text": "[W (10) O (32)] (5-)", "start": 161, "end": 181}, {"text": "[W (10) O (32)] (6-)", "start": 227, "end": 247}]}}, "schema": []}
{"input": "Relativistic DFT calculations were used to predict the UV-VIS spectra and EPR parameters of all such species.", "output": {"entities": {}}, "schema": []}
{"input": "Differentiating factors between erythropoiesis-stimulating agents: an update to selection for anaemia of chronic kidney disease.", "output": {"entities": {}}, "schema": []}
{"input": "Erythropoiesis-stimulating agents (ESAs) have become a hallmark of anaemia therapy in patients with chronic kidney disease (CKD).", "output": {"entities": {}}, "schema": []}
{"input": "Although different ESAs are available for the treatment of renal anaemia, each nephrologist should select a single ESA for an individual patient.", "output": {"entities": {}}, "schema": []}
{"input": "Epoetin alfa and epoetin beta have been used 1-3 times weekly but extended-interval dosing up to every 4 weeks is also effective in a substantial majority of CKD patients.", "output": {"entities": {}}, "schema": []}
{"input": "However, the epoetin dose necessary to achieve or maintain target haemoglobin (Hb) levels increases substantially as the dosing interval increases.", "output": {"entities": {}}, "schema": []}
{"input": "Subcutaneous administration of short-acting ESAs is more effective than the intravenous route of administration.", "output": {"entities": {}}, "schema": []}
{"input": "Darbepoetin alfa and the continuous erythropoietin receptor activator (CERA) have been developed as a treatment for anaemia with extended administration intervals (every 2 weeks and every 4 weeks, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "Dose requirements for these long-acting ESAs are independent of the route of administration.", "output": {"entities": {}}, "schema": []}
{"input": "Patents of short-acting ESAs have expired, which has opened the field for biosimilars.", "output": {"entities": {}}, "schema": []}
{"input": "Epoetin biosimilars approved by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) have been shown to have a comparable efficacy and safety profile to their originators.", "output": {"entities": {}}, "schema": []}
{"input": "An alarming increase in pure red cell aplasia (PRCA) in Thailand with follow-on epoetins manufactured in Asia (but also those manufactured in Latin America) indicates that stringent country-specific approval and pharmacovigilance protocols for ESAs manufactured in non-North American and non-EU European countries are urgently needed.", "output": {"entities": {}}, "schema": []}
{"input": "Two PRCA cases occurring with subcutaneous HX575 (one certain, one likely) indicate that chances of inducing a more immunogenic product are unpredictable, even with a biosimilar epoetin approved under the EMA biosimilar approval pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Phase III clinical trials with peginesatide, a pegylated synthetic peptide-based ESA without any homology to erythropoietin raised safety concerns in non-dialysis CKD patients but not in dialysis patients.", "output": {"entities": {}}, "schema": []}
{"input": "Subcutaneous bortezomib: in multiple myeloma.", "output": {"entities": {"chemical": [{"text": "bortezomib", "start": 13, "end": 23}]}}, "schema": []}
{"input": "A subcutaneous formulation of bortezomib is now indicated in the EU and the US for the treatment of patients with multiple myeloma.", "output": {"entities": {"chemical": [{"text": "bortezomib", "start": 30, "end": 40}]}}, "schema": []}
{"input": "This article reviews pharmacological, therapeutic efficacy and tolerability data relevant to the utilization of subcutaneous bortezomib (Velcade ((R))) in the treatment of patients with multiple myeloma.", "output": {"entities": {"chemical": [{"text": "bortezomib", "start": 125, "end": 135}, {"text": "Velcade", "start": 137, "end": 144}]}}, "schema": []}
{"input": "In a randomized, nonblind, phase III study, subcutaneous bortezomib was noninferior to intravenous bortezomib in the treatment of adults with relapsed multiple myeloma, as determined by the overall response rate after four cycles of therapy (primary endpoint).", "output": {"entities": {"chemical": [{"text": "bortezomib", "start": 57, "end": 67}, {"text": "bortezomib", "start": 99, "end": 109}]}}, "schema": []}
{"input": "No significant differences between the subcutaneous and intravenous bortezomib formulations were observed in the median time to first response, median progression-free survival, median time to progression and 1-year overall survival.", "output": {"entities": {"chemical": [{"text": "bortezomib", "start": 68, "end": 78}]}}, "schema": []}
{"input": "Compared with intravenous bortezomib, subcutaneous bortezomib confers a significant advantage with respect to the incidence of peripheral neuropathy (all grades, grade >= 2 and grade >= 3).", "output": {"entities": {"chemical": [{"text": "bortezomib", "start": 26, "end": 36}, {"text": "bortezomib", "start": 51, "end": 61}]}}, "schema": []}
{"input": "As a consequence, it provides a new treatment option for patients with multiple myeloma, particularly those with pre-existing neuropathy or at a high risk of developing peripheral neuropathy.", "output": {"entities": {}}, "schema": []}
{"input": "Local deposition of anisotropic nanoparticles using scanning electrochemical microscopy (SECM).", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate localized electrodeposition of anisotropic metal nanoobjects, namely Au nanorods (GNR), on indium tin oxide (ITO) using scanning electrochemical microscopy (SECM).", "output": {"entities": {"chemical": [{"text": "Au", "start": 84, "end": 86}, {"text": "indium tin oxide", "start": 106, "end": 122}, {"text": "ITO", "start": 124, "end": 127}]}}, "schema": []}
{"input": "A gold microelectrode was the source of the gold ions whereby double pulse chronoamperometry was employed to generate initially Au seeds which were further grown under controlled conditions.", "output": {"entities": {"chemical": [{"text": "Au", "start": 128, "end": 130}]}}, "schema": []}
{"input": "The distance between the microelectrode and the ITO surface as well as the different experimental parameters (electrodeposition regime, solution composition and temperature) were optimized to produce faceted gold seeds with the required characteristics (size and distribution).", "output": {"entities": {"chemical": [{"text": "ITO", "start": 48, "end": 51}]}}, "schema": []}
{"input": "Colloidal chemical synthesis was successfully exploited for better understanding the role of the surfactant and different additives in breaking the crystallographic symmetry and anisotropic growth of GNR.", "output": {"entities": {}}, "schema": []}
{"input": "Experiments performed in a conventional three-electrode cell revealed the most appropriate electrochemical conditions allowing high yield synthesis of nanorods with well-defined shape as well as nanocubes and bipyramids.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of long-circulating, backbone degradable HPMA copolymer-doxorubicin conjugates and evaluation of molecular-weight-dependent antitumor efficacy.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 51, "end": 55}, {"text": "doxorubicin", "start": 66, "end": 77}]}}, "schema": []}
{"input": "Backbone degradable, linear, multiblock N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-doxorubicin (DOX) conjugates are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by chain extension via thiol-ene click reaction.", "output": {"entities": {"chemical": [{"text": "N-(2-hydroxypropyl) methacrylamide", "start": 40, "end": 74}, {"text": "HPMA", "start": 76, "end": 80}, {"text": "doxorubicin", "start": 92, "end": 103}, {"text": "DOX", "start": 105, "end": 108}, {"text": "thiol", "start": 243, "end": 248}]}}, "schema": []}
{"input": "The examination of molecular-weight-dependent antitumor activity toward human ovarian A2780/AD carcinoma in nude mice reveals enhanced activity of multiblock, second-generation, higher molecular weight conjugates when compared with traditional HPMA copolymer-DOX conjugates.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 244, "end": 248}, {"text": "DOX", "start": 259, "end": 262}]}}, "schema": []}
{"input": "The examination of body weight changes during treatment indicates the absence of non-specific adverse effects.", "output": {"entities": {}}, "schema": []}
{"input": "Structure prediction of binary pernitride MN2 compounds (M = Ca, Sr, Ba, La, and Ti).", "output": {"entities": {"chemical": [{"text": "pernitride MN2", "start": 31, "end": 45}, {"text": "Ca", "start": 61, "end": 63}, {"text": "Sr", "start": 65, "end": 67}, {"text": "Ba", "start": 69, "end": 71}, {"text": "La", "start": 73, "end": 75}, {"text": "Ti", "start": 81, "end": 83}]}}, "schema": []}
{"input": "Metal-pernitride compounds belong to a class of chemical systems in which both the complex ions and the non-bonding electrons may play roles in the formation of their modified crystalline structures.", "output": {"entities": {"chemical": [{"text": "Metal-pernitride", "start": 0, "end": 16}]}}, "schema": []}
{"input": "To investigate this issue, the energy landscapes of pernitrides of metals with different maximum valence (M = Ca, Sr, Ba, La, and Ti) were globally explored on the ab initio level at standard and high pressures, thereby yielding possible (meta) stable modifications in these systems together with information on how the landscape changed as function of the valence of the metal cation.", "output": {"entities": {"chemical": [{"text": "pernitrides", "start": 52, "end": 63}, {"text": "Ca", "start": 110, "end": 112}, {"text": "Sr", "start": 114, "end": 116}, {"text": "Ba", "start": 118, "end": 120}, {"text": "La", "start": 122, "end": 124}, {"text": "Ti", "start": 130, "end": 132}]}}, "schema": []}
{"input": "For all of the systems in which no compounds had been synthesized so far, we predicted the existence of kinetically stable modifications that should, in principle, be experimentally accessible.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, TiN2 should crystallize in a new structure type, TiN2-I.", "output": {"entities": {"chemical": [{"text": "TiN2", "start": 15, "end": 19}, {"text": "TiN2", "start": 64, "end": 68}]}}, "schema": []}
{"input": "Inhibition pathways of the potent organophosphate CBDP with cholinesterases revealed by X-ray crystallographic snapshots and mass spectrometry.", "output": {"entities": {"chemical": [{"text": "organophosphate CBDP", "start": 34, "end": 54}]}}, "schema": []}
{"input": "Tri-o-cresyl-phosphate (TOCP) is a common additive in jet engine lubricants and hydraulic fluids suspected to have a role in aerotoxic syndrome in humans.", "output": {"entities": {"chemical": [{"text": "Tri-o-cresyl-phosphate", "start": 0, "end": 22}, {"text": "TOCP", "start": 24, "end": 28}]}}, "schema": []}
{"input": "TOCP is metabolized to cresyl saligenin phosphate (CBDP), a potent irreversible inhibitor of butyrylcholinesterase (BChE), a natural bioscavenger present in the bloodstream, and acetylcholinesterase (AChE), the off-switch at cholinergic synapses.", "output": {"entities": {"chemical": [{"text": "TOCP", "start": 0, "end": 4}, {"text": "cresyl saligenin phosphate", "start": 23, "end": 49}, {"text": "CBDP", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Mechanistic details of cholinesterase (ChE) inhibition have, however, remained elusive.", "output": {"entities": {}}, "schema": []}
{"input": "Also, the inhibition of AChE by CBDP is unexpected, from a structural standpoint, i. e., considering the narrowness of AChE active site and the bulkiness of CBDP.", "output": {"entities": {"chemical": [{"text": "CBDP", "start": 32, "end": 36}, {"text": "CBDP", "start": 157, "end": 161}]}}, "schema": []}
{"input": "In the following, we report on kinetic X-ray crystallography experiments that provided 2. 7-3. 3 A snapshots of the reaction of CBDP with mouse AChE and human BChE.", "output": {"entities": {"chemical": [{"text": "CBDP", "start": 128, "end": 132}]}}, "schema": []}
{"input": "The series of crystallographic snapshots reveals that AChE and BChE react with the opposite enantiomers and that an induced-fit rearrangement of Phe297 enlarges the active site of AChE upon CBDP binding.", "output": {"entities": {"chemical": [{"text": "Phe297", "start": 145, "end": 151}, {"text": "CBDP", "start": 190, "end": 194}]}}, "schema": []}
{"input": "Mass spectrometry analysis of aging in either H (2) (16) O or H (2) (18) O furthermore allowed us to identify the inhibition steps, in which water molecules are involved, thus providing insights into the mechanistic details of inhibition.", "output": {"entities": {"chemical": [{"text": "H (2) (16) O", "start": 46, "end": 58}, {"text": "H (2) (18) O", "start": 62, "end": 74}]}}, "schema": []}
{"input": "X-ray crystallography and mass spectrometry show the formation of an aged end product formed in both AChE and BChE that cannot be reactivated by current oxime-based therapeutics.", "output": {"entities": {"chemical": [{"text": "oxime", "start": 153, "end": 158}]}}, "schema": []}
{"input": "Our study thus shows that only prophylactic and symptomatic treatments are viable to counter the inhibition of AChE and BChE by CBDP.", "output": {"entities": {"chemical": [{"text": "CBDP", "start": 128, "end": 132}]}}, "schema": []}
{"input": "From isolated metaatoms to photonic metamaterials: evolution of the plasmonic near-field.", "output": {"entities": {}}, "schema": []}
{"input": "Metamaterials are artificial media which can provide optical properties not available from natural materials.", "output": {"entities": {}}, "schema": []}
{"input": "These properties often result from the resonant excitation of plasmonic modes in the metallic building blocks (\" metaatoms \") of the metamaterial.", "output": {"entities": {}}, "schema": []}
{"input": "Electromagnetic interactions between the metaatoms significantly modify the resonances of the individual metaatoms and influence the optical properties of the whole metamaterial.", "output": {"entities": {}}, "schema": []}
{"input": "To better understand these interactions, we study in this Letter the evolution of the plasmonic near-field in the course of the transition from an isolated metaatom, in our case a split-ring resonator (SRR), to a photonic metamaterial via electron energy-loss spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "For small SRR ensembles, we observe the formation of discrete optical bright and dark modes due to coupling of the metaatoms.", "output": {"entities": {}}, "schema": []}
{"input": "Large SRR arrays reveal a quasi-continuum of modes in the interior and distinct edge modes at the boundaries of the array.", "output": {"entities": {}}, "schema": []}
{"input": "Our experimental results are in excellent agreement with numerical calculations.", "output": {"entities": {}}, "schema": []}
{"input": "Single molecule characterization of the interactions between amyloid-beta peptides and the membranes of hippocampal cells.", "output": {"entities": {}}, "schema": []}
{"input": "Oligomers of the 40 and 42 residue amyloid-beta peptides (A beta 40 and A beta 42) have been implicated in the neuronal damage and impaired cognitive function associated with Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "However, little is known about the specific mechanisms by which these misfolded species induce such detrimental effects on cells.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we use single-molecule imaging techniques to examine the initial interactions between A beta monomers and oligomers and the membranes of live cells.", "output": {"entities": {}}, "schema": []}
{"input": "This highly sensitive method enables the visualization of individual A beta species on the cell surface and characterization of their oligomerization state, all at biologically relevant, nanomolar concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that oligomers preferentially interact with cell membranes, relative to monomers and that the oligomers become immobilized on the cell surface.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, we observe that the interaction of A beta species with the cell membrane is inhibited by the presence of ATP-independent molecular chaperones.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 119, "end": 122}]}}, "schema": []}
{"input": "This study demonstrates the power of this methodology for characterizing the interactions between protein aggregates and the membranes of live neuronal cells at physiologically relevant concentrations and opens the door to quantitative studies of the cellular responses to potentially pathogenic oligomers.", "output": {"entities": {}}, "schema": []}
{"input": "Thyroid hormone levels within reference range are associated with heart rate, cardiac structure and function in middle-aged men and women.", "output": {"entities": {"chemical": [{"text": "Thyroid hormone", "start": 0, "end": 15}]}}, "schema": []}
{"input": "Background Triiodothyronine (T3) has many effects on the heart and marked changes in cardiac function and structure occur in patients with (subclinical) thyroid disease.", "output": {"entities": {"chemical": [{"text": "Triiodothyronine", "start": 11, "end": 27}]}}, "schema": []}
{"input": "We investigated whether between-subject variation in thyroid hormone levels within the euthyroid range is also associated with heart rate and echocardiographic heart function and structure.", "output": {"entities": {"chemical": [{"text": "thyroid hormone", "start": 53, "end": 68}]}}, "schema": []}
{"input": "Methods Subjects were selected from the Asklepios study (n = 2524), a population-representative random sample between 35 and 55 yrs, free from overt cardiovascular disease at baseline.", "output": {"entities": {}}, "schema": []}
{"input": "Analyses were restricted to 2078 subjects (1013 women and 1065 men), not using antihypertensive or thyroid medication nor having anti-TPO levels above clinical cut-off or TSH levels outside the reference range.", "output": {"entities": {}}, "schema": []}
{"input": "All subjects were phenotyped in-depth and underwent comprehensive echocardiography, including diastolic evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "Thyroid function parameters were determined by automated electrochemiluminescence.", "output": {"entities": {}}, "schema": []}
{"input": "Results Heart rate was robustly positively associated with (quartiles of) (F) T3, both in subjects with TSH levels within reference (0. 27-4. 2 micro U/l) as in narrow TSH-range (0. 5-2. 5 micro U/l) (p <= 0. 0001).", "output": {"entities": {}}, "schema": []}
{"input": "(F) T3 was negatively associated with LV (left ventricular) end-diastolic volume but positively with relative wall thickness.", "output": {"entities": {}}, "schema": []}
{"input": "TT3 was associated with enhanced ventricular contraction (as assessed by tissue Doppler imaging).", "output": {"entities": {}}, "schema": []}
{"input": "FT4, FT3 and TT3 were positively associated with late ventricular filling, and TT3 was associated with early ventricular filling.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion We have demonstrated a strong positive association between thyroid hormone levels within the euthyroid range and heart rate, and more subtle effects on cardiac function and structure.", "output": {"entities": {"chemical": [{"text": "thyroid hormone", "start": 70, "end": 85}]}}, "schema": []}
{"input": "More specifically, we suggest smaller LV cavity size (with increased relative wall thickness), an enhanced atrial and ventricular contraction and LV relaxation with higher circulating thyroid hormones.", "output": {"entities": {"chemical": [{"text": "thyroid hormones", "start": 184, "end": 200}]}}, "schema": []}
{"input": "These results illustrate that variation of thyroid hormone levels even within the reference range exerts effects on the heart.", "output": {"entities": {"chemical": [{"text": "thyroid hormone", "start": 43, "end": 58}]}}, "schema": []}
{"input": "Disorder imposed limits of mono-and bilayer graphene electronic modification using covalent chemistry.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 44, "end": 52}]}}, "schema": []}
{"input": "A central question in graphene chemistry is to what extent chemical modification can control an electronically accessible band gap in monolayer and bilayer graphene (MLG and BLG).", "output": {"entities": {"chemical": [{"text": "graphene", "start": 22, "end": 30}, {"text": "graphene", "start": 156, "end": 164}]}}, "schema": []}
{"input": "Density functional theory predicts gaps in covalently functionalized graphene as high as 2 eV, while this approach neglects the fact that lattice symmetry breaking occurs over only a prescribed radius of nanometer dimension, which we label the S-region.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 69, "end": 77}]}}, "schema": []}
{"input": "Therefore, high chemical conversion is central to observing this band gap in transport.", "output": {"entities": {}}, "schema": []}
{"input": "We use an electrochemical approach involving phenyl-diazonium salts to systematically probe electronic modification in MLG and BLG with increasing functionalization for the first time, obtaining the highest conversion values to date.", "output": {"entities": {"chemical": [{"text": "phenyl-diazonium salts", "start": 45, "end": 67}]}}, "schema": []}
{"input": "We find that both MLG and BLG retain their relatively high conductivity after functionalization even at high conversion, as mobility losses are offset by increases in carrier concentration.", "output": {"entities": {}}, "schema": []}
{"input": "For MLG, we find that band gap opening as measured during transport is linearly increased with respect to the I (D)/I (G) ratio but remains below 0. 1 meV in magnitude for SiO (2) supported graphene.", "output": {"entities": {"chemical": [{"text": "SiO (2)", "start": 172, "end": 179}, {"text": "graphene", "start": 190, "end": 198}]}}, "schema": []}
{"input": "The largest transport band gap obtained in a suspended, highly functionalized (I (D)/I (G) = 4. 5) graphene is about 1 meV, lower than our theoretical predictions considering the quantum interference effect between two neighboring S-regions and attributed to its population with midgap states.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 99, "end": 107}]}}, "schema": []}
{"input": "On the other hand, heavily functionalized BLG (I (D)/I (G) = 1. 8) still retains its signature dual-gated band gap opening due to electric-field symmetry breaking.", "output": {"entities": {}}, "schema": []}
{"input": "We find a notable asymmetric deflection of the charge neutrality point (CNP) under positive bias which increases the apparent on/off current ratio by 50%, suggesting that synergy between symmetry breaking, disorder, and quantum interference may allow the observation of new transistor phenomena.", "output": {"entities": {}}, "schema": []}
{"input": "These important observations set definitive limits on the extent to which chemical modification can control graphene electronically.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 108, "end": 116}]}}, "schema": []}
{"input": "5-((1-Aroyl-1H-indol-3-yl) methylene)-2-thioxodihydropyrimidine-4, 6 (1H, 5H)-diones as potential anticancer agents with anti-inflammatory properties.", "output": {"entities": {"chemical": [{"text": "5-((1-Aroyl-1H-indol-3-yl) methylene)-2-thioxodihydropyrimidine-4, 6 (1H, 5H)-diones", "start": 0, "end": 84}]}}, "schema": []}
{"input": "A series of novel 5-((1-aroyl-1H-indol-3-yl) methylene)-2-thioxodihydropyrimidine-4, 6 (1H, 5H)-diones (3a-z) have been evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines.", "output": {"entities": {"chemical": [{"text": "5-((1-aroyl-1H-indol-3-yl) methylene)-2-thioxodihydropyrimidine-4, 6 (1H, 5H)-diones", "start": 18, "end": 102}]}}, "schema": []}
{"input": "Compound 3k exhibited the most potent growth inhibition against melanoma MDA-MB-435 cells (GI (50) = 850 nM), against leukemia SR cancer cells (GI (50) = 1. 45 mu M), and OVCAR-3 (GI (50) = 1. 26 mu M) ovarian cancer cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "The structurally related compound 3s had a GI (50) value of 1. 77 mu M against MDA-MB-435 cells.", "output": {"entities": {}}, "schema": []}
{"input": "The N-naphthoyl analogue 3t had GI (50) values of 1. 30 and 1. 91 mu M against HOP-92 non-small cell lung cancer and MDA-MB-435 melanoma cell lines, respectively.", "output": {"entities": {"chemical": [{"text": "N", "start": 4, "end": 5}, {"text": "naphthoyl", "start": 6, "end": 15}]}}, "schema": []}
{"input": "The related analogue 3w had GI (50) values of 1. 09 mu M against HOP-92 non-small cell lung cancer cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, docking of the two active molecules 3k and 3w into the active site of COX-2 indicates that these compounds are COX-2 ligands with strong hydrophobic and hydrogen bonding interactions.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 168, "end": 176}]}}, "schema": []}
{"input": "Thus, compounds 3k, 3t, 3s, and 3w constitute a new class of anticancer/anti-inflammatory agents that may have unique potential for cancer therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Impact of cooking and handling conditions on furanic compounds in breaded fish products.", "output": {"entities": {"chemical": [{"text": "furanic", "start": 45, "end": 52}]}}, "schema": []}
{"input": "This study evaluates the influence of cooking and handling conditions on the quantity of furanic compounds (furan, 2-furfural, furfuryl alcohol, 2-pentylfuran, 5-hydroxymethylfurfural) in breaded fish products.", "output": {"entities": {"chemical": [{"text": "furanic", "start": 89, "end": 96}, {"text": "furan", "start": 108, "end": 113}, {"text": "2-furfural", "start": 115, "end": 125}, {"text": "furfuryl alcohol", "start": 127, "end": 143}, {"text": "2-pentylfuran", "start": 145, "end": 158}, {"text": "5-hydroxymethylfurfural", "start": 160, "end": 183}]}}, "schema": []}
{"input": "Oven-baking and reheating in the microwave lead to low furanic compounds formation in comparison with deep-frying.", "output": {"entities": {"chemical": [{"text": "furanic", "start": 55, "end": 62}]}}, "schema": []}
{"input": "The use of olive oil for deep-frying promoted higher levels of furanic compounds than sunflower oil.", "output": {"entities": {"chemical": [{"text": "furanic", "start": 63, "end": 70}]}}, "schema": []}
{"input": "The amounts of these compounds diminished as the temperature and time of deep-frying decreased as well as after a delay after deep-frying.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the generation of furanic compounds can be minimized by adjusting the cooking method and conditions, such as using an electric oven, deep-frying in sunflower oil at 160 degrees C during 4min, or waiting 10min after cooking.", "output": {"entities": {"chemical": [{"text": "furanic", "start": 24, "end": 31}]}}, "schema": []}
{"input": "However, these conditions that reduce furanic compounds levels also reduce the content of volatile compounds related to the aroma and flavour of fried foods.", "output": {"entities": {"chemical": [{"text": "furanic", "start": 38, "end": 45}]}}, "schema": []}
{"input": "In this sense, new efforts should be done to reduce the formation of furanic compounds without being detrimental to the volatile profile.", "output": {"entities": {"chemical": [{"text": "furanic", "start": 69, "end": 76}]}}, "schema": []}
{"input": "Shifting from the single to the multitarget paradigm in drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "Increasing evidence that several drug compounds exert their effects through interactions with multiple targets is boosting the development of research fields that challenge the data reductionism approach.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we review and discuss the concepts of drug repurposing, polypharmacology, chemogenomics, phenotypic screening and high-throughput in vivo testing of mixture-based libraries in an integrated manner.", "output": {"entities": {}}, "schema": []}
{"input": "These research fields offer alternatives to the current paradigm of drug discovery, from a one target-one drug model to a multiple-target approach.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the goals of lead identification are being expanded accordingly to identify not only' key' compounds that fit with a single-target' lock', but also' master key' compounds that favorably interact with multiple targets (i. e. operate a set of desired locks to gain access to the expected clinical effects).", "output": {"entities": {}}, "schema": []}
{"input": "Impaired fertility and FSH synthesis in gonadotrope-specific Foxl2 knockout mice.", "output": {"entities": {}}, "schema": []}
{"input": "Impairments in pituitary FSH synthesis or action cause infertility.", "output": {"entities": {}}, "schema": []}
{"input": "However, causes of FSH dysregulation are poorly described, in part because of our incomplete understanding of mechanisms controlling FSH synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, we discovered a critical role for forkhead protein L2 (FOXL2) in activin-stimulated FSH beta-subunit (Fshb) transcription in immortalized cells in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we tested the hypothesis that FOXL2 is required for FSH synthesis in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Using a Cre/lox approach, we selectively ablated Foxl2 in murine anterior pituitary gonadotrope cells.", "output": {"entities": {}}, "schema": []}
{"input": "Conditional knockout (cKO) mice developed overtly normally but were subfertile in adulthood.", "output": {"entities": {}}, "schema": []}
{"input": "Testis size and spermatogenesis were significantly impaired in cKO males.", "output": {"entities": {}}, "schema": []}
{"input": "cKO females exhibited reduced ovarian weight and ovulated fewer oocytes in natural estrous cycles compared with controls.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, ovaries of juvenile cKO females showed normal responses to exogenous gonadotropin stimulation.", "output": {"entities": {}}, "schema": []}
{"input": "Both male and female cKO mice were FSH deficient, secondary to diminished pituitary Fshb mRNA production.", "output": {"entities": {}}, "schema": []}
{"input": "Basal and activin-stimulated Fshb expression was similarly impaired in Foxl2 depleted primary pituitary cultures.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these data definitively establish FOXL2 as the first identified gonadotrope-restricted transcription factor required for selective FSH synthesis in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "The endocrine disrupting chemical tolylfluanid alters adipocyte metabolism via glucocorticoid receptor activation.", "output": {"entities": {"chemical": [{"text": "tolylfluanid", "start": 34, "end": 46}]}}, "schema": []}
{"input": "Glucocorticoid signaling plays a critical role in regulating energy metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "Emerging data implicate environmental endocrine-disrupting chemicals as contributors to the obesity and diabetes epidemics.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies have shown that the phenylsulfamide fungicide tolylfluanid (TF) augments glucocorticoid receptor (GR)-dependent luciferase expression in 3T3-L1 preadipocytes while modulating insulin action in primary murine and human adipocytes.", "output": {"entities": {"chemical": [{"text": "phenylsulfamide", "start": 37, "end": 52}, {"text": "tolylfluanid", "start": 63, "end": 75}]}}, "schema": []}
{"input": "Studies were performed to interrogate glucocorticoid signaling in primary adipocytes exposed to TF.", "output": {"entities": {}}, "schema": []}
{"input": "TF mimicked the gene transcription profile of the murine glucocorticoid corticosterone (Cort).", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 72, "end": 86}, {"text": "Cort", "start": 88, "end": 92}]}}, "schema": []}
{"input": "Cellular fractionation assays demonstrated that TF treatment promoted the activating serine phosphorylation of GR, augmenting its cytoplasmic-to-nuclear translocation as well as its enrichment at glucocorticoid response elements on the glucocorticoid-induced leucine zipper gene promoter.", "output": {"entities": {"chemical": [{"text": "serine", "start": 85, "end": 91}, {"text": "leucine", "start": 259, "end": 266}]}}, "schema": []}
{"input": "After acute treatment, Cort or TF promoted insulin receptor substrate-1 (IRS-1) gene and protein expression.", "output": {"entities": {"chemical": [{"text": "Cort", "start": 23, "end": 27}]}}, "schema": []}
{"input": "Either treatment also enriched GR binding at an identified glucocorticoid response element in the IRS-1 gene.", "output": {"entities": {}}, "schema": []}
{"input": "TF or Cort each increased insulin-stimulated lipogenesis, an effect resulting from increased lipogenic gene expression and enhanced insulin-stimulated dephosphorylation of acetyl-coenzyme A carboxylase.", "output": {"entities": {"chemical": [{"text": "Cort", "start": 6, "end": 10}, {"text": "acetyl-coenzyme A", "start": 172, "end": 189}]}}, "schema": []}
{"input": "The augmentation of insulin-stimulated lipogenesis was mediated through a specific enhancement of Akt phosphorylation at T308.", "output": {"entities": {}}, "schema": []}
{"input": "These findings support modulation of IRS-1 levels as a mechanism for glucocorticoid-mediated changes in insulin action in primary adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Albeit with less affinity than Cort, in silico analysis suggests that TF can interact with the ligand binding pocket of GR.", "output": {"entities": {"chemical": [{"text": "Cort", "start": 31, "end": 35}]}}, "schema": []}
{"input": "Collectively, these studies identify TF as a structurally unique environmental glucocorticoid.", "output": {"entities": {}}, "schema": []}
{"input": "Glucocorticoid signaling may thus represent a novel pathway by which environmental toxicants promote the development of metabolic diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Perfluoroalkylated compounds induce cell death and formation of reactive oxygen species in cultured cerebellar granule cells.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 73, "end": 79}]}}, "schema": []}
{"input": "The present communication investigates the effects of different perfluoroalkylated compounds (PFCs) on formation of reactive oxygen species (ROS) and cell death in cultured cerebellar granule cells.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 125, "end": 131}]}}, "schema": []}
{"input": "This allows direct comparison with similar effects found for other environmental contaminants like polychlorinated biphenyls and brominated flame-retardants.", "output": {"entities": {"chemical": [{"text": "polychlorinated biphenyls", "start": 99, "end": 124}]}}, "schema": []}
{"input": "The increase in ROS formation and cell death was assayed using the fluorescent probe 2, 7-dichlorofluorescin diacetate (DCFH-DA) and the trypan blue exclusion assay.", "output": {"entities": {"chemical": [{"text": "2, 7-dichlorofluorescin diacetate", "start": 85, "end": 118}, {"text": "DCFH-DA", "start": 120, "end": 127}, {"text": "trypan blue", "start": 137, "end": 148}]}}, "schema": []}
{"input": "The effects of the PFCs were structure dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Cell death was induced at relatively low concentrations by perfluorooctyl sulfonate (PFOS), perfluorooctane sulfonylamide (PFOSA) and the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorodecanol (FTOH 8: 2) with EC (50)-values of 62 +/- 7. 6, 13 +/- 1. 8 and 15 +/- 4. 2 mu M (mean +/- SD) respectively.", "output": {"entities": {"chemical": [{"text": "perfluorooctyl sulfonate", "start": 59, "end": 83}, {"text": "PFOS", "start": 85, "end": 89}, {"text": "perfluorooctane sulfonylamide", "start": 92, "end": 121}, {"text": "PFOSA", "start": 123, "end": 128}, {"text": "fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorodecanol", "start": 138, "end": 191}, {"text": "FTOH 8: 2", "start": 193, "end": 202}]}}, "schema": []}
{"input": "PFOS, perfluorooctanoic acid (PFOA) and PFOSA induced a concentration dependent increase in ROS formation with EC (50)-values of 27 +/- 9. 0, 25 +/- 11 and 57 +/- 19 mu M respectively.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 0, "end": 4}, {"text": "perfluorooctanoic acid", "start": 6, "end": 28}, {"text": "PFOA", "start": 30, "end": 34}, {"text": "PFOSA", "start": 40, "end": 45}]}}, "schema": []}
{"input": "Reduced cell viability and ROS formation were observed at concentration level close to what is found in serum of occupationally exposed workers.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of PFCs on ROS formation and cell viability was compared with other halogenated compounds and future investigations should emphasize effects of mixtures and how physical chemical properties of the compounds influence their toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Drug shortages: the cycle of quantity and quality.", "output": {"entities": {}}, "schema": []}
{"input": "Shortages of pharmaceutical drugs pose a serious and growing threat to public health.", "output": {"entities": {}}, "schema": []}
{"input": "Although the number of drugs in shortage in the United States in any given year is very small, the number of prescription drug shortages in the country nearly tripled between 2005 and 2010.", "output": {"entities": {}}, "schema": []}
{"input": "Drug shortages are becoming more severe as well as more frequent.", "output": {"entities": {}}, "schema": []}
{"input": "The affected medicines include cancer treatments, anesthesia drugs, and other drugs that are critical to the treatment and prevention of serious diseases and life-threatening conditions.", "output": {"entities": {}}, "schema": []}
{"input": "(The White House, Office of the Press Secretary, Executive Order 13588-Reducing Prescription Drug Shortages (http://www. whitehouse. gov/the-press-office/2011/10/31/executive-order-reducing-prescription-drug-shortages)).", "output": {"entities": {}}, "schema": []}
{"input": "Membrane tethered bursicon constructs as heterodimeric modulators of the Drosophila G protein-coupled receptor rickets.", "output": {"entities": {}}, "schema": []}
{"input": "The study of complex heterodimeric peptide ligands has been hampered by a paucity of pharmacological tools.", "output": {"entities": {}}, "schema": []}
{"input": "To facilitate such investigations, we have explored the utility of membrane tethered ligands (MTLs).", "output": {"entities": {}}, "schema": []}
{"input": "Feasibility of this recombinant approach was explored with a focus on Drosophila bursicon, a heterodimeric cystine-knot protein that activates the G protein-coupled receptor rickets (rk).", "output": {"entities": {"chemical": [{"text": "cystine", "start": 107, "end": 114}]}}, "schema": []}
{"input": "Rk/bursicon signaling is an evolutionarily conserved pathway in insects required for wing expansion, cuticle hardening, and melanization during development.", "output": {"entities": {}}, "schema": []}
{"input": "We initially engineered two distinct MTL constructs, each composed of a type II transmembrane domain, a peptide linker, and a C terminal extracellular ligand that corresponded to either the alpha or beta bursicon subunit.", "output": {"entities": {"chemical": [{"text": "C", "start": 126, "end": 127}]}}, "schema": []}
{"input": "Coexpression of the two complementary bursicon MTLs triggered rk-mediated signaling in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "We were then able to generate functionally active bursicon MTLs in which the two subunits were fused into a single heterodimeric peptide, oriented as either alpha-beta or beta-alpha.", "output": {"entities": {}}, "schema": []}
{"input": "Carboxy-terminal deletion of 32 amino acids in the beta-alpha MTL construct resulted in loss of agonist activity.", "output": {"entities": {"chemical": [{"text": "Carboxy", "start": 0, "end": 7}, {"text": "amino acids", "start": 32, "end": 43}]}}, "schema": []}
{"input": "Coexpression of this construct with rk inhibited receptor-mediated signaling by soluble bursicon.", "output": {"entities": {}}, "schema": []}
{"input": "We have thus generated membrane-anchored bursicon constructs that can activate or inhibit rk signaling.", "output": {"entities": {}}, "schema": []}
{"input": "These probes can be used in future studies to explore the tissue and/or developmental stage-dependent effects of bursicon in the genetically tractable Drosophila model organism.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, our success in generating functionally diverse bursicon MTLs offers promise that such technology can be broadly applied to other complex ligands, including the family of mammalian cystine-knot proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Exploring resources for intrafamilial communication of cancer genetic risk: we still need to talk.", "output": {"entities": {}}, "schema": []}
{"input": "While the importance of intrafamilial communication of hereditary cancer risk has been acknowledged, the factors that promote and act as barriers to patients disclosing their information to their families are complex and emerging.", "output": {"entities": {}}, "schema": []}
{"input": "This raises the question: How are patients guided in practice to contemplate intrafamilial communication?", "output": {"entities": {}}, "schema": []}
{"input": "Focusing on breast cancer, we conducted an exploratory study examining current resources supporting patients and health-care professionals, and isolated the messages surrounding intrafamilial communication of cancer risk.", "output": {"entities": {}}, "schema": []}
{"input": "We find the duty for health-care professionals to counsel patients regarding intrafamilial communication is acknowledged to varying degrees by multiple actors in the cancer care delivery landscape, including health-care professional associations, health service organizations, and patient groups.", "output": {"entities": {}}, "schema": []}
{"input": "A range of medical, psychosocial, and other factors underlying intrafamilial communication are acknowledged in messages to patients.", "output": {"entities": {}}, "schema": []}
{"input": "Patients, however, are often referred to a single group of health-care professionals to discuss their diverse and complex needs.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, messages aimed at patients appear to place the emphasis on barriers that could exist for patients contemplating intrafamilial communication, while highlighting the benefits families derive from such communication.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, this points to a lack of coherence within materials directed to patients and suggests the need to do coordinated research among stakeholders to address two related issues: (1) determining who are the actors best positioned to send messages surrounding intrafamilial communication to patients and (2) addressing the content of messages conveyed in patient materials. European Journal of Human Genetics advance online publication, 23 January 2013; doi: 10. 1038/ejhg. 2012. 286.", "output": {"entities": {}}, "schema": []}
{"input": "Induction of heat shock protein 70 ameliorates ultraviolet-induced photokeratitis in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Acute ultraviolet (UV) B exposure causes photokeratitis and induces apoptosis in corneal cells.", "output": {"entities": {}}, "schema": []}
{"input": "Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP) 70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions.", "output": {"entities": {"chemical": [{"text": "Geranylgeranylacetone", "start": 0, "end": 21}, {"text": "GGA", "start": 23, "end": 26}, {"text": "acyclic polyisoprenoid", "start": 34, "end": 56}]}}, "schema": []}
{"input": "We examined whether induction of HSP70 has therapeutic effects on UV-photokeratitis in mice.", "output": {"entities": {}}, "schema": []}
{"input": "C57 BL/6 mice were divided into four groups, GGA-treated (500 mg/kg/mouse) and UVB-exposed (400 mJ/cm2), GGA-untreated UVB-exposed (400 mJ/cm2), GGA-treated (500 mg/kg/mouse) but not exposed and naive controls.", "output": {"entities": {"chemical": [{"text": "GGA", "start": 45, "end": 48}, {"text": "GGA", "start": 105, "end": 108}, {"text": "GGA", "start": 145, "end": 148}]}}, "schema": []}
{"input": "Eyeballs were collected 24 h after irradiation, and corneas were stained with hematoxylin and eosin (H & amp; E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).", "output": {"entities": {"chemical": [{"text": "hematoxylin", "start": 78, "end": 89}, {"text": "eosin", "start": 94, "end": 99}, {"text": "dUTP", "start": 155, "end": 159}]}}, "schema": []}
{"input": "HSP70, reactive oxygen species (ROS) production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) and protein kinase B (Akt) expression were also evaluated.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 16, "end": 22}]}}, "schema": []}
{"input": "Irradiated corneal epithelium was significantly thicker in the eyes of mice treated with GGA compared with those given the vehicle alone (p < 0. 01).", "output": {"entities": {"chemical": [{"text": "GGA", "start": 89, "end": 92}]}}, "schema": []}
{"input": "Significantly fewer TUNEL-positive cells were observed in the eyes of GGA-treated mice than controls after irradiation (p < 0. 01).", "output": {"entities": {"chemical": [{"text": "GGA", "start": 70, "end": 73}]}}, "schema": []}
{"input": "Corneal HSP70 levels were significantly elevated in corneas of mice treated with GGA (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "GGA", "start": 81, "end": 84}]}}, "schema": []}
{"input": "ROS signal was not affected by GGA.", "output": {"entities": {"chemical": [{"text": "GGA", "start": 31, "end": 34}]}}, "schema": []}
{"input": "NF-kappa B activation was reduced but phospho-(Ser/Ther) Akt substrate expression was increased in corneas after irradiation when treated with GGA.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 47, "end": 50}, {"text": "Ther", "start": 51, "end": 55}, {"text": "GGA", "start": 143, "end": 146}]}}, "schema": []}
{"input": "GGA-treatment induced HSP70 expression and ameliorated UV-induced corneal damage through the reduced NF-kappa B activation and possibly increased Akt phosphorilation.", "output": {"entities": {"chemical": [{"text": "GGA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "NMR crystallography of alpha-poly (L-lactide).", "output": {"entities": {"chemical": [{"text": "alpha-poly (L-lactide)", "start": 23, "end": 45}]}}, "schema": []}
{"input": "A complementary approach that combines NMR measurements, analysis of X-ray and neutron powder diffraction data and advanced quantum mechanical calculations was employed to study the alpha-polymorph of L-polylactide.", "output": {"entities": {"chemical": [{"text": "L-polylactide", "start": 201, "end": 214}]}}, "schema": []}
{"input": "Such a strategy, which is known as NMR crystallography, to the best of our knowledge, is used here for the first time for the fine refinement of the crystal structure of a synthetic polymer.", "output": {"entities": {}}, "schema": []}
{"input": "The GIPAW method was used to compute the NMR shielding parameters for the different models, which included the alpha-PLLA structure obtained by 2-dimensional wide-angle X-ray diffraction (WAXD) at-150 degrees C (model M1) and at 25 degrees C (model M2), neutron diffraction (WAND) measurements (model M3) and the fully optimized geometry of the PLLA chains in the unit cell with defined size (model M4).", "output": {"entities": {"chemical": [{"text": "alpha-PLLA", "start": 111, "end": 121}]}}, "schema": []}
{"input": "The influence of changes in the chain conformation on the (13) C sigma (ii) NMR shielding parameters is shown.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 58, "end": 64}]}}, "schema": []}
{"input": "The correlation between the sigma (ii) and delta (ii) values for the M1-M4 models revealed that the M4 model provided the best fit.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, a comparison of the experimental (13) C NMR spectra with the spectra calculated using the M1-M4 models strongly supports the data for the M4 model.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 43, "end": 49}]}}, "schema": []}
{"input": "The GIPAW method, via verification using NMR measurements, was shown to be capable of the fine refinement of the crystal structures of polymers when coarse X-ray diffraction data for powdered samples are available.", "output": {"entities": {}}, "schema": []}
{"input": "Photoelectron imaging of small aluminum clusters: quantifying s-p hybridization.", "output": {"entities": {"chemical": [{"text": "aluminum", "start": 31, "end": 39}]}}, "schema": []}
{"input": "Photoelectron imaging experiments and detailed calculations are conducted on Al (n) (-) clusters (n = 3-6) and a calibration method is developed for connecting experimental observations of photoelectron angular distributions to theoretical predictions.", "output": {"entities": {"chemical": [{"text": "Al (n) (-)", "start": 77, "end": 87}]}}, "schema": []}
{"input": "It is shown that this method can be used to quantify the degree to which the molecular orbitals are built from s-or p-like atomic orbitals.", "output": {"entities": {}}, "schema": []}
{"input": "The highest occupied molecular orbitals of these small aluminum clusters are found to contain varying degrees of s-p mixing, with Al (3) (-) containing the \" most hybridized \" orbital and Al (4) (-) containing the \" least hybridized \" orbital.", "output": {"entities": {"chemical": [{"text": "aluminum", "start": 55, "end": 63}, {"text": "Al (3) (-)", "start": 130, "end": 140}, {"text": "Al (4) (-)", "start": 188, "end": 198}]}}, "schema": []}
{"input": "It is shown experimentally that s-p hybridization is already present for the trimer species and, similar to other properties of small metal clusters, oscillates with cluster size.", "output": {"entities": {}}, "schema": []}
{"input": "A \" clickable \" MTX reagent as a practical tool for profiling small-molecule-intracellular target interactions via MASPIT.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 16, "end": 19}]}}, "schema": []}
{"input": "We present a scalable synthesis of a versatile MTX reagent with an azide ligation handle that allows rapid gamma-selective conjugation to yield MTX fusion compounds (MFCs) appropriate for MASPIT, a three-hybrid system that enables the identification of mammalian cytosolic proteins that interact with a small molecule of interest.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 47, "end": 50}, {"text": "azide", "start": 67, "end": 72}, {"text": "MTX", "start": 144, "end": 147}]}}, "schema": []}
{"input": "We selected three structurally diverse pharmacologically active compounds (tamoxifen, reversine, and FK506) as model baits.", "output": {"entities": {"chemical": [{"text": "tamoxifen", "start": 75, "end": 84}, {"text": "reversine", "start": 86, "end": 95}, {"text": "FK506", "start": 101, "end": 106}]}}, "schema": []}
{"input": "After acetylene functionalization of these baits, MFCs were synthesized via a CuAAC reaction, demonstrating the general applicability of the MTX reagent.", "output": {"entities": {"chemical": [{"text": "acetylene", "start": 6, "end": 15}, {"text": "MTX", "start": 141, "end": 144}]}}, "schema": []}
{"input": "In analytical mode, MASPIT was able to give concentration-dependent reporter signals for the established target proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we demonstrate that the sensitivity obtained with the new MTX reagent was significantly stronger than that of a previously used non-regiomeric conjugate mixture.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 71, "end": 74}]}}, "schema": []}
{"input": "Finally, the FK506 MFC was explored in a cellular array screen for targets of FK506.", "output": {"entities": {"chemical": [{"text": "FK506", "start": 13, "end": 18}, {"text": "FK506", "start": 78, "end": 83}]}}, "schema": []}
{"input": "Out of a pilot collection of nearly 2000 full-length human ORF preys, FKBP12, the established target of FK506, emerged as the prey protein that gave the highest increase in luciferase activity.", "output": {"entities": {"chemical": [{"text": "FK506", "start": 104, "end": 109}]}}, "schema": []}
{"input": "This indicates that our newly developed synthetic strategy for the straightforward generation of MFCs is a promising asset to uncover new intracellular targets using MASPIT cellular array screening.", "output": {"entities": {}}, "schema": []}
{"input": "The role of silver and vanadium release in the toxicity of silver vanadate nanowires toward Daphnia similis.", "output": {"entities": {"chemical": [{"text": "silver", "start": 12, "end": 18}, {"text": "vanadium", "start": 23, "end": 31}, {"text": "silver vanadate", "start": 59, "end": 74}]}}, "schema": []}
{"input": "Nanomaterials are used in a wide spectrum of applications, including nanowires that are objects with at least one of its dimensions in the range of 1 to 100 nm.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, a new type of silver vanadate nanowire decorated with silver nanoparticles (SVSN-LQES1) with promising antimicrobial activity against different pathogenic bacteria was described.", "output": {"entities": {"chemical": [{"text": "silver vanadate", "start": 24, "end": 39}, {"text": "silver", "start": 64, "end": 70}]}}, "schema": []}
{"input": "The objective of the present study was to evaluate the role of silver and vanadium release in the acute toxicity of this material using Daphnia similis.", "output": {"entities": {"chemical": [{"text": "silver", "start": 63, "end": 69}, {"text": "vanadium", "start": 74, "end": 82}]}}, "schema": []}
{"input": "To verify the effect of the presence of the nanowires in the test solution, tests were performed before and after filtration.", "output": {"entities": {}}, "schema": []}
{"input": "Total silver release to the testing media was determined using the method of inductively coupled plasma atomic emission spectroscopy (ICP-AES).", "output": {"entities": {"chemical": [{"text": "silver", "start": 6, "end": 12}]}}, "schema": []}
{"input": "Silver vanadate nanowires decorated with silver nanoparticles (SVSN-LQES1) are acutely toxic to D. similis.", "output": {"entities": {"chemical": [{"text": "Silver vanadate", "start": 0, "end": 15}, {"text": "silver", "start": 41, "end": 47}]}}, "schema": []}
{"input": "The release of silver from the nanomaterial trapped in the gut along with the silver released to the test media seems to be responsible for the observed toxicity.", "output": {"entities": {"chemical": [{"text": "silver", "start": 15, "end": 21}, {"text": "silver", "start": 78, "end": 84}]}}, "schema": []}
{"input": "Although toxic to Daphnia, vanadium does not contribute to the toxicity of SVSN-LQES1.", "output": {"entities": {"chemical": [{"text": "vanadium", "start": 27, "end": 35}]}}, "schema": []}
{"input": "The observed increase in lipid droplets appears to be related to the exposure of the organisms to the nanomaterials, but the significance of this response needs further investigation.", "output": {"entities": {}}, "schema": []}
{"input": "Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic stressors promote metabolic disturbances, including obesity and metabolic syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Ghrelin, a peptide that promotes appetite and the accumulation of adipose tissue, is also secreted in response to stressors to protect the brain and peripheral tissues from the effects of these stressors.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that elevated ghrelin levels produced by chronic exposure to social stress are associated with increased caloric intake and body weight gain in male C57BL mice.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, stressed mice lacking ghrelin receptors (GHSR KO mice) or C57BL mice receiving chronic intracerebroventricular delivery of the ghrelin receptor antagonist [d-Lys (3)]-GHRP-6 show attenuated weight gain and feeding responses under the same social stress paradigm.", "output": {"entities": {"chemical": [{"text": "Lys", "start": 171, "end": 174}]}}, "schema": []}
{"input": "Interestingly, stressed GHSR KO mice showed depleted sc and intrascapular brown fat depots, whereas stressed young wild-type mice did not.", "output": {"entities": {}}, "schema": []}
{"input": "In old wild-type mice, chronic social defeat increased visceral and intrascapular brown fat depots in association with increases in obesity markers like hyperleptinemia and hyperinsulinemia along with increased hypothalamic expression of neuropeptide Y and Agouti related peptide.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, the elevated expression of these peptides persisted least for 2 weeks after cessation of the stressor regimen.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, old GHSR KO mice did not show these alterations after chronic social defeat.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that ghrelin plays an important role in the metabolic adaptations necessary to meet the energetic demands posed by stressors, but chronic exposure to stress-induced ghrelin elevations ultimately could lead to long lasting metabolic dysfunctions.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical variability of Algerian Myrtus communis L.", "output": {"entities": {}}, "schema": []}
{"input": "The composition of 55 samples of essential oil isolated from the aerial parts of wild growing Myrtus communis L. harvested in 16 locations from East to West Algeria were investigated by GC (determination of retention indices) and (13) C-NMR analyses.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 230, "end": 236}]}}, "schema": []}
{"input": "The essential oils consisted mainly of monoterpenes, alpha-pinene (27. 4-59. 2%) and 1, 8-cineole (6. 1-34. 3%) being the major components.", "output": {"entities": {"chemical": [{"text": "monoterpenes", "start": 39, "end": 51}, {"text": "alpha-pinene", "start": 53, "end": 65}, {"text": "1, 8-cineole", "start": 85, "end": 97}]}}, "schema": []}
{"input": "They were also characterized by the absence of myrtenyl acetate.", "output": {"entities": {"chemical": [{"text": "myrtenyl acetate", "start": 47, "end": 63}]}}, "schema": []}
{"input": "The compositions of the 55 oils were submitted to k-means partitioning and principal component analysis, which allowed the distinction of two groups within the oil samples, which could be subdivided into two subgroups each.", "output": {"entities": {}}, "schema": []}
{"input": "Groups I (78% of the samples) and II were differentiated on the basis of the contents of alpha-pinene, linalool, and linalyl acetate.", "output": {"entities": {"chemical": [{"text": "alpha-pinene", "start": 89, "end": 101}, {"text": "linalool", "start": 103, "end": 111}, {"text": "linalyl acetate", "start": 117, "end": 132}]}}, "schema": []}
{"input": "Subgroups IA and IB could be distinguished by their contents of alpha-pinene and 1, 8-cineole.", "output": {"entities": {"chemical": [{"text": "alpha-pinene", "start": 64, "end": 76}, {"text": "1, 8-cineole", "start": 81, "end": 93}]}}, "schema": []}
{"input": "Subgroups IIA and IIB differed substantially in their contents of 1, 8-cineole and limonene.", "output": {"entities": {"chemical": [{"text": "1, 8-cineole", "start": 66, "end": 78}, {"text": "limonene", "start": 83, "end": 91}]}}, "schema": []}
{"input": "All the samples contained 3, 3, 5, 5, 8, 8-hexamethyl-7-oxabicyclo [4. 3. 0] non-1 (6)-ene-2, 4-dione (up to 4. 9%).", "output": {"entities": {"chemical": [{"text": "3, 3, 5, 5, 8, 8-hexamethyl-7-oxabicyclo [4. 3. 0] non-1 (6)-ene-2, 4-dione", "start": 26, "end": 101}]}}, "schema": []}
{"input": "Accumulation of dietary methylmercury and effects on growth and survival in two estuarine forage fish: Cyprinodon variegatus and Menidia beryllina.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 24, "end": 37}]}}, "schema": []}
{"input": "Dietary methylmercury (MeHg) uptake by fish in relation to life stage, species, and level of exposure is poorly understood in lower trophic levels, particularly in estuarine species.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 8, "end": 21}, {"text": "MeHg", "start": 23, "end": 27}]}}, "schema": []}
{"input": "The authors compared accumulation of dietary MeHg as well as sensitivity (survival and growth) to dietary MeHg exposure in two species of estuarine forage fish, Cyprinodon variegatus and Menidia beryllina.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 45, "end": 49}, {"text": "MeHg", "start": 106, "end": 110}]}}, "schema": []}
{"input": "Fish were fed one of five dietary MeHg concentrations (ranging from 0. 04 to 14 micro g/g dry wt) over a period of 70 d.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 34, "end": 38}]}}, "schema": []}
{"input": "Growth rate and the level of dietary exposure influenced MeHg tissue concentrations in both species.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 57, "end": 61}]}}, "schema": []}
{"input": "Mercury in the diet exhibited a strong linear relationship with fish Hg tissue concentrations.", "output": {"entities": {"chemical": [{"text": "Mercury", "start": 0, "end": 7}, {"text": "Hg", "start": 69, "end": 71}]}}, "schema": []}
{"input": "Additionally, the authors found that M. beryllina was more sensitive to dietary MeHg exposure than C. variegatus.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 80, "end": 84}]}}, "schema": []}
{"input": "Both species showed some decreases in growth related to MeHg exposure, although these patterns were not consistent among treatments.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 56, "end": 60}]}}, "schema": []}
{"input": "Overall, C. variegatus and M. beryllina were found to have a high tolerance for dietary MeHg exposure.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 88, "end": 92}]}}, "schema": []}
{"input": "If fish occupying low trophic levels are capable of surviving with high Hg body burdens, this tolerance has important implications for Hg exposure of organisms occupying higher trophic levels.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 72, "end": 74}, {"text": "Hg", "start": 135, "end": 137}]}}, "schema": []}
{"input": "The factor VII-activating protease (FSAP) enhances the activity of bone morphogenetic protein-2 (BMP-2).", "output": {"entities": {}}, "schema": []}
{"input": "Factor VII-activating protease (FSAP) is a circulating protease involved in the pathogenesis of atherosclerosis, calcification, and fibrotic processes.", "output": {"entities": {}}, "schema": []}
{"input": "To understand how FSAP controls the balance of local growth factors, we have investigated its effect on the regulation of bone morphogenetic proteins (BMPs).", "output": {"entities": {}}, "schema": []}
{"input": "BMP-2 is produced as a large pro-form and secreted as a mature heparin-binding growth factor after intracellular processing by pro-protein convertases (PCs).", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we discovered that FSAP enhances the biological activity of mature BMP-2 as well as its pro-form, as shown by osteogenic differentiation of C2C12 myoblasts.", "output": {"entities": {}}, "schema": []}
{"input": "These findings were complemented by knockdown of FSAP in hepatocytes, which revealed BMP-2 processing by endogenous FSAP.", "output": {"entities": {}}, "schema": []}
{"input": "N-terminal sequencing indicated that pro-BMP-2 was cleaved by FSAP at the canonical PC cleavage site, giving rise to mature BMP-2 (Arg (282) v Gln (283)), as well as in the N-terminal heparin binding region of mature BMP-2, generating a truncated mature BMP-2 peptide (Arg (289) v Lys (290)).", "output": {"entities": {"chemical": [{"text": "N", "start": 0, "end": 1}, {"text": "Arg", "start": 131, "end": 134}, {"text": "Gln", "start": 143, "end": 146}, {"text": "N", "start": 173, "end": 174}, {"text": "Arg", "start": 269, "end": 272}, {"text": "Lys", "start": 281, "end": 284}]}}, "schema": []}
{"input": "Similarly, mature BMP-2 was also cleaved to a truncated peptide within its N-terminal region (Arg (289) v Lys (290)).", "output": {"entities": {"chemical": [{"text": "N", "start": 75, "end": 76}, {"text": "Arg", "start": 94, "end": 97}, {"text": "Lys", "start": 106, "end": 109}]}}, "schema": []}
{"input": "Plasmin exhibited a similar activity, but it was weaker compared with FSAP.", "output": {"entities": {}}, "schema": []}
{"input": "Thrombin, Factor VIIa, Factor Xa, and activated protein C were not effective.", "output": {"entities": {}}, "schema": []}
{"input": "These results were further supported by the observation that the mutation of the heparin binding region of BMP-2 inhibited the processing by FSAP but not by PC.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the proteolysis and activation of pro-BMP-2 and mature BMP-2 by FSAP can regulate cell differentiation and calcification in vasculature and may explain why polymorphisms in the gene encoding for FSAP are related to vascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of doping on the magnetostructural ordered phase of iron arsenides: a comparative study of the resistivity anisotropy in doped BaFe2As2 with doping into three different sites.", "output": {"entities": {"chemical": [{"text": "iron arsenides", "start": 59, "end": 73}, {"text": "BaFe2As2", "start": 134, "end": 142}]}}, "schema": []}
{"input": "To unravel the role of doping in iron-based superconductors, we investigated the in-plane resistivity of BaFe (2) As (2) doped at one of the three different lattice sites, Ba (Fe (1-x) Co (x)) (2) As (2), BaFe (2) (As (1-x) P (x)) (2), and Ba (1-x) K (x) Fe (2) As (2), focusing on the doping effect in the low-temperature antiferromagnetic/orthorhombic (AFO) phase.", "output": {"entities": {"chemical": [{"text": "iron", "start": 33, "end": 37}, {"text": "BaFe (2) As (2)", "start": 105, "end": 120}, {"text": "Ba (Fe (1-x) Co (x)) (2) As (2)", "start": 172, "end": 203}, {"text": "BaFe (2) (As (1-x) P (x)) (2)", "start": 205, "end": 234}, {"text": "Ba (1-x) K (x) Fe (2) As (2)", "start": 240, "end": 268}]}}, "schema": []}
{"input": "A major role of doping in the high-temperature paramagnetic/tetragonal (PT) phase is known to change the Fermi surface by supplying charge carriers or exerting chemical pressure.", "output": {"entities": {}}, "schema": []}
{"input": "In the AFO phase, we found a clear correlation between the magnitude of the residual resistivity and the resistivity anisotropy.", "output": {"entities": {}}, "schema": []}
{"input": "This indicates that the resistivity anisotropy originates from anisotropic impurity scattering due to dopant atoms.", "output": {"entities": {}}, "schema": []}
{"input": "The magnitude of the residual resistivity was also found to be a parameter controlling the suppression rate of the AFO ordering temperature.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the dominant role of doping in the AFO phase is to introduce disorder to the system, distinct from that in the PT phase.", "output": {"entities": {}}, "schema": []}
{"input": "SeDeM expert system a new innovator tool to develop pharmaceutical forms.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Context: The SeDeM expert system is based on the experimental study and quantitative determination of the characterization parameters of powdered substances, the aim being to determine whether a substance is suitable for producing tablets by means of direct compression (DC) technology, thereby reducing the lead time for pre-formulation studies.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, this expert system also provides formulations with a minimum number of excipients.", "output": {"entities": {}}, "schema": []}
{"input": "Objective: We used this system to analyze suitable formulas for the production of orodispersible ibuprofen tablets.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 97, "end": 106}]}}, "schema": []}
{"input": "Method: Twenty-one disintegrants and ibuprophen were characterized using SeDeM methodology.", "output": {"entities": {"chemical": [{"text": "ibuprophen", "start": 37, "end": 47}]}}, "schema": []}
{"input": "Results: The results indicated that production of ibuprofen tablets by DC would require improvements in the dimension and compressibility factors of the active pharmaceutical ingredient.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 50, "end": 59}]}}, "schema": []}
{"input": "The expert system analysis provided the specific percentage of disintegrant needed to blend with ibuprofen and a standardized formula of lubricants in order to obtain a powder mix that would successfully produce tablets by DC.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 97, "end": 106}]}}, "schema": []}
{"input": "The eight formulas proposed by SeDeM were produced and tested in the laboratory.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: All eight formulas successfully produced tablets by DC, but only four of them could be considered suitable for use as an orodispersible tablet and accomplishes all the pharmaceutical quality parameters.", "output": {"entities": {}}, "schema": []}
{"input": "So, in fact, the use of the SeDeM system reduced the time of medicine' s development and therefore the cost of the activity.", "output": {"entities": {}}, "schema": []}
{"input": "Efficient two-electron reduction of dioxygen to hydrogen peroxide with one-electron reductants with a small overpotential catalyzed by a cobalt chlorin complex.", "output": {"entities": {"chemical": [{"text": "dioxygen", "start": 36, "end": 44}, {"text": "hydrogen peroxide", "start": 48, "end": 65}, {"text": "cobalt chlorin", "start": 137, "end": 151}]}}, "schema": []}
{"input": "A cobalt chlorin complex (Co (II) (Ch)) efficiently and selectively catalyzed two-electron reduction of dioxygen (O (2)) by one-electron reductants (ferrocene derivatives) to produce hydrogen peroxide (H (2) O (2)) in the presence of perchloric acid (HClO (4)) in benzonitrile (PhCN) at 298 K.", "output": {"entities": {"chemical": [{"text": "cobalt chlorin", "start": 2, "end": 16}, {"text": "Co (II) (Ch)", "start": 26, "end": 38}, {"text": "dioxygen", "start": 104, "end": 112}, {"text": "O (2)", "start": 114, "end": 119}, {"text": "ferrocene", "start": 149, "end": 158}, {"text": "hydrogen peroxide", "start": 183, "end": 200}, {"text": "H (2) O (2)", "start": 202, "end": 213}, {"text": "perchloric acid", "start": 234, "end": 249}, {"text": "HClO (4)", "start": 251, "end": 259}, {"text": "benzonitrile", "start": 264, "end": 276}, {"text": "PhCN", "start": 278, "end": 282}]}}, "schema": []}
{"input": "The catalytic reactivity of Co (II) (Ch) was much higher than that of a cobalt porphyrin complex (Co (II) (OEP), OEP (2-) = octaethylporphyrin dianion), which is a typical porphyrinoid complex.", "output": {"entities": {"chemical": [{"text": "Co (II) (Ch)", "start": 28, "end": 40}, {"text": "cobalt porphyrin", "start": 72, "end": 88}, {"text": "Co (II) (OEP)", "start": 98, "end": 111}, {"text": "OEP (2-)", "start": 113, "end": 121}, {"text": "octaethylporphyrin", "start": 124, "end": 142}]}}, "schema": []}
{"input": "The two-electron reduction of O (2) by 1, 1'-dibromoferrocene (Br (2) Fc) was catalyzed by Co (II) (Ch), whereas virtually no reduction of O (2) occurred with Co (II) (OEP).", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 30, "end": 35}, {"text": "1, 1'-dibromoferrocene", "start": 39, "end": 61}, {"text": "Br (2) Fc", "start": 63, "end": 72}, {"text": "Co (II) (Ch)", "start": 91, "end": 103}, {"text": "O (2)", "start": 139, "end": 144}, {"text": "Co (II) (OEP)", "start": 159, "end": 172}]}}, "schema": []}
{"input": "In addition, Co (II) (Ch) is more stable than Co (II) (OEP), where the catalytic turnover number (TON) of the two-electron reduction of O (2) catalyzed by Co (II) (Ch) exceeded 30000.", "output": {"entities": {"chemical": [{"text": "Co (II) (Ch)", "start": 13, "end": 25}, {"text": "Co (II) (OEP)", "start": 46, "end": 59}, {"text": "O (2)", "start": 136, "end": 141}, {"text": "Co (II) (Ch)", "start": 155, "end": 167}]}}, "schema": []}
{"input": "The detailed kinetic studies have revealed that the rate-determining step in the catalytic cycle is the proton-coupled electron transfer reduction of O (2) with the protonated Co (II) (Ch) ([Co (II) (ChH)] (+)) that is produced by facile electron-transfer reduction of [Co (III) (ChH)] (2 +) by ferrocene derivative in the presence of HClO (4).", "output": {"entities": {"chemical": [{"text": "O (2)", "start": 150, "end": 155}, {"text": "Co (II) (Ch)", "start": 176, "end": 188}, {"text": "[Co (II) (ChH)] (+)", "start": 190, "end": 209}, {"text": "[Co (III) (ChH)] (2 +)", "start": 269, "end": 291}, {"text": "ferrocene", "start": 295, "end": 304}, {"text": "HClO (4)", "start": 335, "end": 343}]}}, "schema": []}
{"input": "The one-electron-reduction potential of [Co (III) (Ch)] (+) was positively shifted from 0. 37 V (vs SCE) to 0. 48 V by the addition of HClO (4) due to the protonation of [Co (III) (Ch)] (+).", "output": {"entities": {"chemical": [{"text": "[Co (III) (Ch)] (+)", "start": 40, "end": 59}, {"text": "HClO (4)", "start": 135, "end": 143}, {"text": "[Co (III) (Ch)] (+)", "start": 170, "end": 189}]}}, "schema": []}
{"input": "Such a positive shift of [Co (III) (Ch)] (+) by protonation resulted in enhancement of the catalytic reactivity of [Co (III) (ChH)] (2 +) for the two-electron reduction of O (2) with a lower overpotential as compared with that of [Co (III) (OEP)] (+).", "output": {"entities": {"chemical": [{"text": "[Co (III) (Ch)] (+)", "start": 25, "end": 44}, {"text": "[Co (III) (ChH)] (2 +)", "start": 115, "end": 137}, {"text": "O (2)", "start": 172, "end": 177}, {"text": "[Co (III) (OEP)] (+)", "start": 230, "end": 250}]}}, "schema": []}
{"input": "Binary diffusion coefficients for mixtures of ionic liquids [EMIM] [N (CN) 2], [EMIM] [NTf2], and [HMIM] [NTf2] with acetone and ethanol by dynamic light scattering (DLS).", "output": {"entities": {"chemical": [{"text": "[EMIM] [N (CN) 2]", "start": 60, "end": 77}, {"text": "[EMIM] [NTf2]", "start": 79, "end": 92}, {"text": "[HMIM] [NTf2]", "start": 98, "end": 111}, {"text": "acetone", "start": 117, "end": 124}, {"text": "ethanol", "start": 129, "end": 136}]}}, "schema": []}
{"input": "Mutual diffusivities for binary mixtures of the ionic liquids (ILs) [EMIM] [N (CN) 2] (1-ethyl-3-methylimidazolium dicyanimide), [EMIM] [NTf2] (1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide), and [HMIM] [NTf2] (1-hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide) with acetone and ethanol were studied in dependence on composition in the temperature range from 283. 15 to 323. 15 K, applying dynamic light scattering (DLS).", "output": {"entities": {"chemical": [{"text": "[EMIM] [N (CN) 2]", "start": 68, "end": 85}, {"text": "1-ethyl-3-methylimidazolium dicyanimide", "start": 87, "end": 126}, {"text": "[EMIM] [NTf2]", "start": 129, "end": 142}, {"text": "1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide", "start": 144, "end": 207}, {"text": "[HMIM] [NTf2]", "start": 214, "end": 227}, {"text": "1-hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide", "start": 229, "end": 292}, {"text": "acetone", "start": 299, "end": 306}, {"text": "ethanol", "start": 311, "end": 318}]}}, "schema": []}
{"input": "The influence of experimental parameters on the achievable uncertainties was analyzed to ensure the acquisition of accurate data in adequate measurement times.", "output": {"entities": {}}, "schema": []}
{"input": "For all probed systems, increasing binary diffusion coefficients were found for increasing temperatures.", "output": {"entities": {}}, "schema": []}
{"input": "The systematic variation of anion and cation of the investigated ILs as well as a comparison with the literature data demonstrates the considerable influence of different ions on the resulting binary diffusion coefficients.", "output": {"entities": {}}, "schema": []}
{"input": "Mutual diffusivities were found to be lower for the mixtures with ethanol than for those with acetone, which could be related to the formation of hydrogen bonds between ethanol and the ions.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 66, "end": 73}, {"text": "acetone", "start": 94, "end": 101}, {"text": "hydrogen", "start": 146, "end": 154}, {"text": "ethanol", "start": 169, "end": 176}]}}, "schema": []}
{"input": "Most of the investigated IL solvent mixtures show increasing binary diffusion coefficients with increasing solvent concentration.", "output": {"entities": {}}, "schema": []}
{"input": "For the mixtures of [EMIM] [NTf2] with ethanol, however, a minimum of the mutual diffusivities was found in the ethanol mole fraction range from 0. 7 to 0. 8, which may hint at the vicinity of a critical demixing point.", "output": {"entities": {"chemical": [{"text": "[EMIM] [NTf2]", "start": 20, "end": 33}, {"text": "ethanol", "start": 39, "end": 46}, {"text": "ethanol", "start": 112, "end": 119}]}}, "schema": []}
{"input": "The viscosity of the pure ILs turned out to be no reliable indicator for the mutual diffusivity in mixtures with the same solvent.", "output": {"entities": {}}, "schema": []}
{"input": "Generic legislation of new psychoactive drugs.", "output": {"entities": {}}, "schema": []}
{"input": "New psychoactive drugs (NPDs, new psychoactive substances) enter the market all the time.", "output": {"entities": {}}, "schema": []}
{"input": "However, it takes several months to ban these NPDs and immediate action is generally not possible.", "output": {"entities": {}}, "schema": []}
{"input": "Several European countries and drug enforcement officers insist on a faster procedure to ban NPDs.", "output": {"entities": {}}, "schema": []}
{"input": "Introduction of generic legislation, in which clusters of psychotropic drugs are banned in advance, has been mentioned as a possible solution.", "output": {"entities": {}}, "schema": []}
{"input": "Here we discuss the pros and cons of such an approach.", "output": {"entities": {}}, "schema": []}
{"input": "First, generic legislation could unintentionally increase the expenditures of enforcement, black market practices, administrative burden and health risks for users.", "output": {"entities": {}}, "schema": []}
{"input": "Second, it may have a negative impact on research and the development of new treatments.", "output": {"entities": {}}, "schema": []}
{"input": "Third, due to the complexity of generic legislation, problems in the enforcement are anticipated due to lack of knowledge about the chemical nomenclature.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, various legal options are already available to ban the use, sale and trade of NPDs.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore conclude that the currently used scientific benefit-risk evaluation should be continued to limit the adverse health effects of NPDs.", "output": {"entities": {}}, "schema": []}
{"input": "Only in emergency cases, where fatal incidents (may) occur, should this approach be overruled.", "output": {"entities": {}}, "schema": []}
{"input": "Aqueous self-sorting in extended supramolecular aggregates.", "output": {"entities": {}}, "schema": []}
{"input": "Self-organization and self-sorting processes are responsible for the regulation and control of the vast majority of biological processes that eventually sustain life on our planet.", "output": {"entities": {}}, "schema": []}
{"input": "Attempts to unveil the complexity of these systems have been devoted to the investigation of the binding processes between artificial molecules, complexes or aggregates within multicomponent mixtures, which has facilitated the emergence of the field of self-sorting in the last decade.", "output": {"entities": {}}, "schema": []}
{"input": "Since, artificial systems involving discrete supramolecular structures, extended supramolecular aggregates or gel-phase materials in organic solvents or-to a lesser extent-in water have been investigated.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we have collected diverse strategies employed in recent years to construct extended supramolecular aggregates in water upon self-sorting of small synthetic molecules.", "output": {"entities": {}}, "schema": []}
{"input": "We have made particular emphasis on co-assembly processes in binary mixtures leading to supramolecular structures of remarkable complexity and the influence of different external variables such as solvent and concentration to direct recognition or discrimination processes between these species.", "output": {"entities": {}}, "schema": []}
{"input": "The comprehension of such recognition phenomena will be crucial for the organization and evolution of complex matter.", "output": {"entities": {}}, "schema": []}
{"input": "Beneficial effects of marine algal compounds in cosmeceuticals.", "output": {"entities": {}}, "schema": []}
{"input": "The name \" cosmeceuticals \" is derived from \" cosmetics and pharmaceuticals \", indicating that a specific product contains active ingredients.", "output": {"entities": {}}, "schema": []}
{"input": "Marine algae have gained much importance in cosmeceutical product development due to their rich bioactive compounds.", "output": {"entities": {}}, "schema": []}
{"input": "In the present review, marine algal compounds (phlorotannins, sulfated polysaccharides and tyrosinase inhibitors) have been discussed toward cosmeceutical application.", "output": {"entities": {"chemical": [{"text": "phlorotannins", "start": 47, "end": 60}]}}, "schema": []}
{"input": "In addition, atopic dermatitis and the possible role of matrix metalloproteinase (MMP) in skin-related diseases have been explored extensively for cosmeceutical products.", "output": {"entities": {}}, "schema": []}
{"input": "The proper development of marine algae compounds will be helpful in cosmeceutical product development and in the development of the cosmeceutical industry.", "output": {"entities": {}}, "schema": []}
{"input": "A divergent approach to the synthesis of the yohimbinoid alkaloids venenatine and alstovenine.", "output": {"entities": {"chemical": [{"text": "yohimbinoid alkaloids venenatine", "start": 45, "end": 77}, {"text": "alstovenine", "start": 82, "end": 93}]}}, "schema": []}
{"input": "The yohimbinoid alkaloids continue to receive considerable attention from the synthetic community because of their interesting chemical structures and varied biological activity.", "output": {"entities": {"chemical": [{"text": "yohimbinoid alkaloids", "start": 4, "end": 25}]}}, "schema": []}
{"input": "Although there are several elegant syntheses of certain members of this group of alkaloids, a truly unified approach has yet to be developed.", "output": {"entities": {}}, "schema": []}
{"input": "In short, general approaches to this compound class are hampered by a lack of complete control in setting the C (3) stereocentre at a late stage.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we report that a functionalized hydrindanone enables a divergent strategy that builds on existing precedent to address this long-standing challenge.", "output": {"entities": {"chemical": [{"text": "hydrindanone", "start": 40, "end": 52}]}}, "schema": []}
{"input": "Utilizing an aminonitrile intermediate, the stereochemistry at C (3) of the yohimbinoid skeleton can be controlled effectively in a Pictet-Spengler reaction.", "output": {"entities": {"chemical": [{"text": "aminonitrile", "start": 13, "end": 25}]}}, "schema": []}
{"input": "We applied this approach to the first total syntheses of the C (3) epimeric natural products venenatine and alstovenine.", "output": {"entities": {"chemical": [{"text": "venenatine", "start": 93, "end": 103}, {"text": "alstovenine", "start": 108, "end": 119}]}}, "schema": []}
{"input": "Organic anion transporter 3 interacts selectively with lipophilic beta-lactam antibiotics.", "output": {"entities": {"chemical": [{"text": "beta-lactam", "start": 66, "end": 77}]}}, "schema": []}
{"input": "Transporters are major determinants of the disposition of xenobiotics and endogenous chemicals in the body.", "output": {"entities": {}}, "schema": []}
{"input": "Organic anion transporter 3 (Oat3) functions in the kidney and brain to remove metabolic waste, toxins, and drugs, and thus transports diverse chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Some beta-lactam antibiotics interact with Oat3, and penicillin G exhibits a strong dependence on Oat3 for renal elimination.", "output": {"entities": {"chemical": [{"text": "beta-lactam", "start": 5, "end": 16}, {"text": "penicillin G", "start": 53, "end": 65}]}}, "schema": []}
{"input": "However, over 80 beta-lactams exist, and many have not been assessed for an interaction with Oat3.", "output": {"entities": {"chemical": [{"text": "beta-lactams", "start": 17, "end": 29}]}}, "schema": []}
{"input": "Moreover, beta-lactams continue to receive U. S.", "output": {"entities": {"chemical": [{"text": "beta-lactams", "start": 10, "end": 22}]}}, "schema": []}
{"input": "Food and Drug Administration approval.", "output": {"entities": {}}, "schema": []}
{"input": "This study identified new beta-lactam-Oat3 interactions, provided a head-to-head comparison with Oat1, and characterized the physicochemical determinants of affinity for Oat3.", "output": {"entities": {"chemical": [{"text": "beta-lactam", "start": 26, "end": 37}]}}, "schema": []}
{"input": "Cells expressing mouse Oat3 (mOat3) and Oat1 (mOat1), and human OAT3 (hOAT3) were used to test inhibitors, and high-performance liquid chromatography (HPLC) was used to measure transport.", "output": {"entities": {}}, "schema": []}
{"input": "Of 26 beta-lactams tested, 12 were clear inhibitors of Oat3, and 14 exhibited poor interactions.", "output": {"entities": {"chemical": [{"text": "beta-lactams", "start": 6, "end": 18}]}}, "schema": []}
{"input": "Inhibitors exhibited a nearly identical rank-order of potency against mOat3 and hOAT3.", "output": {"entities": {}}, "schema": []}
{"input": "Oat1 demonstrated a poor interaction with most beta-lactams.", "output": {"entities": {"chemical": [{"text": "beta-lactams", "start": 47, "end": 59}]}}, "schema": []}
{"input": "The majority of Oat3 inhibitors were substrates, and there were clear physicochemical differences between inhibitors and noninhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "That is, inhibitors had nearly 40% fewer hydrogen bond donors (P < 0. 001), a lower total polar surface area (P < 0. 05), and greater lipophilicity (LogP of inhibitors, + 1. 41; noninhibitors,-1. 54; P < 0. 001).", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 41, "end": 49}]}}, "schema": []}
{"input": "Pharmacophore mapping revealed a prohibitive hydrogen bond donor group in noninhibitors adjacent to a hydrophobic moiety that was important for binding to Oat3.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 45, "end": 53}]}}, "schema": []}
{"input": "These findings indicate that Oat3 recognizes lipophilic beta-lactams more readily.", "output": {"entities": {"chemical": [{"text": "beta-lactams", "start": 56, "end": 68}]}}, "schema": []}
{"input": "Moreover, this study has potential implications for designing beta-lactams to avoid renal accumulation or brain efflux via Oat3.", "output": {"entities": {"chemical": [{"text": "beta-lactams", "start": 62, "end": 74}]}}, "schema": []}
{"input": "Theoretical design and experimental implementation of Ag/Au electrodes for the electrochemical reduction of nitrate.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 54, "end": 56}, {"text": "Au", "start": 57, "end": 59}, {"text": "nitrate", "start": 108, "end": 115}]}}, "schema": []}
{"input": "The current imbalance in the biogeochemical cycle of nitrogen is as serious as that of carbon.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 53, "end": 61}, {"text": "carbon", "start": 87, "end": 93}]}}, "schema": []}
{"input": "One way to mitigate this problem is through the electrochemical reduction of nitrates under mild conditions, which is an appealing though not fully understood process.", "output": {"entities": {"chemical": [{"text": "nitrates", "start": 77, "end": 85}]}}, "schema": []}
{"input": "Therefore, deeper insight into the electrocatalytic reaction mechanism is needed to optimize this process.", "output": {"entities": {}}, "schema": []}
{"input": "Here we thoroughly analyse the adsorption energy of nitrate with DFT calculations on various surface facets of pure Au, Ag, and their near-surface and surface alloys, as the adsorption and subsequent reduction of nitrate are thought to be rate limiting in the electrocatalytic reaction.", "output": {"entities": {"chemical": [{"text": "nitrate", "start": 52, "end": 59}, {"text": "Au", "start": 116, "end": 118}, {"text": "Ag", "start": 120, "end": 122}, {"text": "nitrate", "start": 213, "end": 220}]}}, "schema": []}
{"input": "The observed systematic trends allow prediction of the surface with highest electrocatalytic activity for the reduction of nitrate.", "output": {"entities": {"chemical": [{"text": "nitrate", "start": 123, "end": 130}]}}, "schema": []}
{"input": "This prediction was verified experimentally by depositing sub-monolayer amounts of Ag on polycrystalline Au electrodes.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 83, "end": 85}, {"text": "Au", "start": 105, "end": 107}]}}, "schema": []}
{"input": "We observe a well-defined volcano curve which correlates the amount of Ag deposited on the surface with the current density at a fixed potential, with the peak activity around 2/3 ML Ag surface coverage.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 71, "end": 73}, {"text": "Ag", "start": 183, "end": 185}]}}, "schema": []}
{"input": "The electrocatalytic activity and stability of the bimetallic Ag-Au systems, found through the interplay of theoretical modelling and empirical observations, serve as a clear example for the rational design of novel catalytic materials and confirm the key role that the adsorption of nitrate plays in the overall nitrate reduction rate.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 62, "end": 64}, {"text": "Au", "start": 65, "end": 67}, {"text": "nitrate", "start": 284, "end": 291}, {"text": "nitrate", "start": 313, "end": 320}]}}, "schema": []}
{"input": "Tissue accumulation and species-specific metabolism of technical pentabrominated diphenyl ether (DE-71) in two predator fish.", "output": {"entities": {"chemical": [{"text": "pentabrominated diphenyl ether", "start": 65, "end": 95}, {"text": "DE-71", "start": 97, "end": 102}]}}, "schema": []}
{"input": "The tissue-specific accumulation and species-specific metabolism of polybrominated diphenyl ethers (PBDEs) in two predator fish species (redtail catfish and oscar fish) feeding on the same prey (tiger barb) that was exposed to technical pentabrominated diphenyl ether (DE-71) in the laboratory were investigated.", "output": {"entities": {"chemical": [{"text": "polybrominated diphenyl ethers", "start": 68, "end": 98}, {"text": "PBDEs", "start": 100, "end": 105}, {"text": "pentabrominated diphenyl ether", "start": 237, "end": 267}, {"text": "DE-71", "start": 269, "end": 274}]}}, "schema": []}
{"input": "The trends in the wet-weight tissue concentration of PBDEs in two predatory fish species suggested that the tissue distribution of PBDEs occurs through a series of events involving passive diffusion to the lipid compartment.", "output": {"entities": {"chemical": [{"text": "PBDEs", "start": 53, "end": 58}, {"text": "PBDEs", "start": 131, "end": 136}]}}, "schema": []}
{"input": "A comparison of the fugacities of PBDEs in various tissues and in the serum revealed that the liver, gill, and perivisceral adipose tissue readily achieved equilibrium with the serum, but the muscle, kidney, and intestine exhibited the potential to accumulate PBDEs.", "output": {"entities": {"chemical": [{"text": "PBDEs", "start": 34, "end": 39}, {"text": "PBDEs", "start": 260, "end": 265}]}}, "schema": []}
{"input": "The lower fugacities of PBDEs in the intestine may have significance in the transportation of PBDEs from prey to predatory fish.", "output": {"entities": {"chemical": [{"text": "PBDEs", "start": 24, "end": 29}, {"text": "PBDEs", "start": 94, "end": 99}]}}, "schema": []}
{"input": "No tissue-specific differences in PBDE congener profiles were found, while interspecies differences in PBDE profiles were evident.", "output": {"entities": {"chemical": [{"text": "PBDE", "start": 34, "end": 38}, {"text": "PBDE", "start": 103, "end": 107}]}}, "schema": []}
{"input": "The difference in profiles between two species could be attributed to species-specific debromination of PBDE.", "output": {"entities": {"chemical": [{"text": "PBDE", "start": 104, "end": 108}]}}, "schema": []}
{"input": "No metabolic debromination of PBDE was observed in redtail catfish, but extensive debromination of PBDEs occurred in oscar fish.", "output": {"entities": {"chemical": [{"text": "PBDE", "start": 30, "end": 34}, {"text": "PBDEs", "start": 99, "end": 104}]}}, "schema": []}
{"input": "Several hydroxylated PBDEs (OH-PBDEs) were detected in serum samples from the two fish species, but no methoxylated PBDEs were found.", "output": {"entities": {"chemical": [{"text": "hydroxylated PBDEs", "start": 8, "end": 26}, {"text": "OH-PBDEs", "start": 28, "end": 36}, {"text": "PBDEs", "start": 116, "end": 121}]}}, "schema": []}
{"input": "The similarities in the OH-PBDE congener profile and the ratio of OH-PBDEs to total PBDEs between the two fish species indicated that the hydroxylation of PBDEs might not be species-specific.", "output": {"entities": {"chemical": [{"text": "OH-PBDE", "start": 24, "end": 31}, {"text": "OH-PBDEs", "start": 66, "end": 74}, {"text": "PBDEs", "start": 84, "end": 89}, {"text": "PBDEs", "start": 155, "end": 160}]}}, "schema": []}
{"input": "The CXCL12/CXCR4/CXCR7 ligand-receptor system regulates neuro-glio-vascular interactions and vessel growth during human brain development.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigates glio-vascular interactions in human fetal brain at midgestation, specifically examining the expression and immunolocalization of the CXCL12/CXCR4/CXCR7 ligand-receptor axis and its possible role in the vascular patterning of the developing brain.", "output": {"entities": {}}, "schema": []}
{"input": "At midgestation, the telencephalic vesicles are characterized by well developed radial glia cells (RGCs), the first differentiated astrocytes and a basic vascular network mainly built of radial vessels.", "output": {"entities": {}}, "schema": []}
{"input": "RGCs have been recognized to contribute to cerebral cortex neuro-vascular architecture and have also been demonstrated to act as a significant source of neural cells (Rakic, Brain Res 33: 471-476, 1971; Malatesta et al, Development 127: 5253-5263, 2000).", "output": {"entities": {}}, "schema": []}
{"input": "According to our hypothesis CXCL12, a potent migration and differentiation chemokine released by RGCs, may act as a linking factor coordinating neuroblast migration with vessel growth and patterning through the activation of different ligand/receptor axes.", "output": {"entities": {}}, "schema": []}
{"input": "The obtained results support this hypothesis showing that together with CXCR4/CXCR7-reactive neuroblasts, which migrate in close association with CXCL12 RGCs, layer-specific subsets of CXCL12 RGCs and astrocytes specifically contact the microvessel wall.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the CXCL12/CXCR4/CXCR7 system appears to be directly involved in microvessel growth, its members being differentially expressed in angiogenically activated microvessels and vascular sprouts.", "output": {"entities": {}}, "schema": []}
{"input": "Using a fragment-based approach to target protein-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "The ability to identify inhibitors of protein-protein interactions represents a major challenge in modern drug discovery and in the development of tools for chemical biology.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years, fragment-based approaches have emerged as a new methodology in drug discovery; however, few examples of small molecules that are active against chemotherapeutic targets have been published.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we describe the fragment-based approach of targeting the interaction between the tumour suppressor BRCA2 and the recombination enzyme RAD51; it makes use of a screening pipeline of biophysical techniques that we expect to be more generally applicable to similar targets.", "output": {"entities": {}}, "schema": []}
{"input": "Disruption of this interaction in vivo is hypothesised to give rise to cellular hypersensitivity to radiation and genotoxic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "We have used protein engineering to create a monomeric form of RAD51 by humanising a thermostable archaeal orthologue, RadA, and used this protein for fragment screening.", "output": {"entities": {}}, "schema": []}
{"input": "The initial fragment hits were thoroughly validated biophysically by isothermal titration calorimetry (ITC) and NMR techniques and observed by X-ray crystallography to bind in a shallow surface pocket that is occupied in the native complex by the side chain of a phenylalanine from the conserved FxxA interaction motif found in BRCA2.", "output": {"entities": {"chemical": [{"text": "phenylalanine", "start": 263, "end": 276}]}}, "schema": []}
{"input": "This represents the first report of fragments or any small molecule binding at this protein-protein interaction site.", "output": {"entities": {}}, "schema": []}
{"input": "Expression of immunoregulatory genes and its relationship to lead exposure and lead-mediated oxidative stress in wild ungulates from an abandoned mining area.", "output": {"entities": {}}, "schema": []}
{"input": "Lead (Pb) is a highly toxic metal that can induce oxidative stress and affect the immune system by modifying the expression of immunomodulator-related genes.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 6, "end": 8}]}}, "schema": []}
{"input": "The aim of the present study was to investigate the association between Pb exposure and the transcriptional profiles of some cytokines, as well as the relationship between Pb exposure and changes in oxidative stress biomarkers observed in the spleen of wild ungulates exposed to mining pollution.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 72, "end": 74}, {"text": "Pb", "start": 172, "end": 174}]}}, "schema": []}
{"input": "Red deer and wild boar from the mining area studied had higher spleen, liver, and bone Pb levels than controls, indicating a chronic exposure to Pb pollution.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 87, "end": 89}, {"text": "Pb", "start": 145, "end": 147}]}}, "schema": []}
{"input": "Such exposure caused a depletion of spleen glutathione levels in both species and disrupted the activity of antioxidant enzymes, suggesting the generation of oxidative stress conditions.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 43, "end": 54}]}}, "schema": []}
{"input": "Deer from the mining area also showed an induced T-helper (Th)-dependent immune response toward the Th 2 pathway, whereas boar from the mining area showed a cytokine profile suggesting an inclination of the immune response toward the Th 1 pathway.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that environmental exposure to Pb may alter immune responses in wild ungulates exposed to mining pollution.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 54, "end": 56}]}}, "schema": []}
{"input": "However, evidence of direct relationships between Pb-mediated oxidative stress and the changes detected in immune responses were not found.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 50, "end": 52}]}}, "schema": []}
{"input": "Further research is needed to evaluate the immunotoxic potential of Pb pollution, also considering the prevalence of chronic infectious diseases in wildlife in environments affected by mining activities.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 68, "end": 70}]}}, "schema": []}
{"input": "Electrocatalytic hydrogenation and deoxygenation of glucose on solid metal electrodes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 52, "end": 59}]}}, "schema": []}
{"input": "This Full Paper addresses the electrocatalytic hydrogenation of glucose to sorbitol or 2-deoxysorbitol on solid metal electrodes in neutral media.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 64, "end": 71}, {"text": "sorbitol", "start": 75, "end": 83}, {"text": "2-deoxysorbitol", "start": 87, "end": 102}]}}, "schema": []}
{"input": "Combining voltammetry and online product analysis with high-performance liquid chromatography (HPLC), provides both qualitative and quantitative information regarding the reaction products as a function of potential.", "output": {"entities": {}}, "schema": []}
{"input": "Three groups of catalysts clearly show affinities toward: (1) hydrogen formation [on early transition metals (Ti, V, Cr, Mn, Zr, Nb, Mo, Hf, Ta, We, and Re) and platinum group metals (Ru, Rh, Ir, and Pt)], (2) sorbitol formation [on late transition metals (Fe, Co, Ni, Cu, Pd, Au, and Ag) and Al (sp metal)], and (3) sorbitol and 2-deoxysorbitol formation [on post-transition metals (In, Sn, Sb, Pb, and Bi), as well as Zn and Cd (d metals)].", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 62, "end": 70}, {"text": "transition metals", "start": 91, "end": 108}, {"text": "Ti", "start": 110, "end": 112}, {"text": "V", "start": 114, "end": 115}, {"text": "Cr", "start": 117, "end": 119}, {"text": "Mn", "start": 121, "end": 123}, {"text": "Zr", "start": 125, "end": 127}, {"text": "Nb", "start": 129, "end": 131}, {"text": "Mo", "start": 133, "end": 135}, {"text": "Hf", "start": 137, "end": 139}, {"text": "Ta", "start": 141, "end": 143}, {"text": "We", "start": 145, "end": 147}, {"text": "Re", "start": 153, "end": 155}, {"text": "platinum", "start": 161, "end": 169}, {"text": "Ru", "start": 184, "end": 186}, {"text": "Rh", "start": 188, "end": 190}, {"text": "Ir", "start": 192, "end": 194}, {"text": "Pt", "start": 200, "end": 202}, {"text": "sorbitol", "start": 210, "end": 218}, {"text": "transition metals", "start": 238, "end": 255}, {"text": "Fe", "start": 257, "end": 259}, {"text": "Co", "start": 261, "end": 263}, {"text": "Ni", "start": 265, "end": 267}, {"text": "Cu", "start": 269, "end": 271}, {"text": "Pd", "start": 273, "end": 275}, {"text": "Au", "start": 277, "end": 279}, {"text": "Ag", "start": 285, "end": 287}, {"text": "Al", "start": 293, "end": 295}, {"text": "sorbitol", "start": 317, "end": 325}, {"text": "2-deoxysorbitol", "start": 330, "end": 345}, {"text": "transition metals", "start": 365, "end": 382}, {"text": "In", "start": 384, "end": 386}, {"text": "Sn", "start": 388, "end": 390}, {"text": "Sb", "start": 392, "end": 394}, {"text": "Pb", "start": 396, "end": 398}, {"text": "Bi", "start": 404, "end": 406}, {"text": "Zn", "start": 420, "end": 422}, {"text": "Cd", "start": 427, "end": 429}]}}, "schema": []}
{"input": "Ni shows the lowest overpotential for the onset of sorbitol formation (-0. 25 V) whereas Pb generates sorbitol with the highest yield (< 0. 7 mM cm (-2)).", "output": {"entities": {"chemical": [{"text": "Ni", "start": 0, "end": 2}, {"text": "sorbitol", "start": 51, "end": 59}, {"text": "Pb", "start": 89, "end": 91}, {"text": "sorbitol", "start": 102, "end": 110}]}}, "schema": []}
{"input": "Different from a smooth Pt electrode, a large-surface-area Pt/C electrode hydrogenates glucose to sorbitol from-0. 21 V with relatively low current.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 24, "end": 26}, {"text": "Pt", "start": 59, "end": 61}, {"text": "C", "start": 62, "end": 63}, {"text": "glucose", "start": 87, "end": 94}, {"text": "sorbitol", "start": 98, "end": 106}]}}, "schema": []}
{"input": "This emphasizes the importance of the active sites and the surface area of the catalyst.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism to form 2-deoxysorbitol from glucose and/or fructose is discussed according to the observed reaction products.", "output": {"entities": {"chemical": [{"text": "2-deoxysorbitol", "start": 22, "end": 37}, {"text": "glucose", "start": 43, "end": 50}, {"text": "fructose", "start": 58, "end": 66}]}}, "schema": []}
{"input": "The yield and selectivity of hydrogenated products are highly sensitive to the chemical nature and state of the catalyst surface.", "output": {"entities": {}}, "schema": []}
{"input": "Characterisation of Nox4 inhibitors from edible plants.", "output": {"entities": {}}, "schema": []}
{"input": "NADPH oxidases transport electrons from cytosolic NADPH through biological membranes to generate reactive oxygen species.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 0, "end": 5}, {"text": "NADPH", "start": 50, "end": 55}, {"text": "oxygen", "start": 106, "end": 112}]}}, "schema": []}
{"input": "NADPH oxidase 4, broadly expressed in humans, is an interesting pharmacological target, since its activity is deregulated in several diseases, including pulmonary fibrosis, diabetic nephropathy, and cardiac hypertrophy.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Whereas several candidate NADPH oxidase 4 inhibitors were recently described, most of these compounds are either unspecific or toxic.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 26, "end": 31}]}}, "schema": []}
{"input": "Here we set out to identify new NADPH oxidase 4 inhibitors from edible plants, in an attempt to decrease the number of hits with toxic side effects.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 32, "end": 37}]}}, "schema": []}
{"input": "We screened a compound library prepared from edible plants for new bioactives with the ability to inhibit the activity of NADPH oxidase 4.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 122, "end": 127}]}}, "schema": []}
{"input": "Using both cell-based and cell-free assays, we identified several compounds with significant inhibitory activity towards NADPH oxidase 4.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 121, "end": 126}]}}, "schema": []}
{"input": "For selected compounds, the activity profile towards NADPH oxidase 2 and NADPH oxidase 5 was established, and controls were carried out to exclude general reactive oxygen species scavengers.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 53, "end": 58}, {"text": "NADPH", "start": 73, "end": 78}, {"text": "oxygen", "start": 164, "end": 170}]}}, "schema": []}
{"input": "A number of promising NADPH oxidase 4 inhibitors from edible plants was identified and characterised.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 22, "end": 27}]}}, "schema": []}
{"input": "Several new chemical entities are disclosed which act as NADPH oxidase 4 inhibitors, and the efficacies of our best hits, in particular several diarylheptanoids and lignans, are comparable to the best available pharmacological NADPH oxidase 4 inhibitors.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 57, "end": 62}, {"text": "diarylheptanoids", "start": 144, "end": 160}, {"text": "lignans", "start": 165, "end": 172}, {"text": "NADPH", "start": 227, "end": 232}]}}, "schema": []}
{"input": "These findings will provide valuable tools to study mechanisms of NADPH oxidase inhibition.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 66, "end": 71}]}}, "schema": []}
{"input": "Controlled synthesis of amino acid-based pH-responsive chiral polymers and self-assembly of their block copolymers.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 24, "end": 34}]}}, "schema": []}
{"input": "Leucine/isoleucine side chain polymers are of interest due to their hydrophobicity and reported role in the formation of alpha-helical structures.", "output": {"entities": {"chemical": [{"text": "Leucine", "start": 0, "end": 7}, {"text": "isoleucine", "start": 8, "end": 18}]}}, "schema": []}
{"input": "The synthesis and reversible addition-fragmentation chain transfer (RAFT) polymerization of amino acid-based chiral monomers, namely Boc-L-leucine methacryloyloxyethyl ester (Boc-L-Leu-HEMA, 1a), Boc-L-leucine acryloyloxyethyl ester (Boc-L-Leu-HEA, 1b), Boc-L-isoleucine methacryloyloxyethyl ester (Boc-L-Ile-HEMA, 1c), and Boc-L-isoleucine acryloyloxyethyl ester (Boc-L-Ile-HEA, 1d), are reported.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 92, "end": 102}, {"text": "Boc-L-leucine methacryloyloxyethyl ester", "start": 133, "end": 173}, {"text": "Boc-L-Leu-HEMA", "start": 175, "end": 189}, {"text": "Boc-L-leucine acryloyloxyethyl ester", "start": 196, "end": 232}, {"text": "Boc-L-Leu-HEA", "start": 234, "end": 247}, {"text": "Boc-L-isoleucine methacryloyloxyethyl ester", "start": 254, "end": 297}, {"text": "Boc-L-Ile-HEMA", "start": 299, "end": 313}, {"text": "Boc-L-isoleucine acryloyloxyethyl ester", "start": 324, "end": 363}, {"text": "Boc-L-Ile-HEA", "start": 365, "end": 378}]}}, "schema": []}
{"input": "The controlled nature of the polymerization of the said chiral monomers in N, N-dimethylformamide (DMF) at 70 degrees C is evident from the formation of narrow polydisperse polymers, the molecular weight controlled by the monomer/chain transfer agent (CTA) molar ratio and the linear relationship between molecular weight and monomer conversion.", "output": {"entities": {"chemical": [{"text": "N, N-dimethylformamide", "start": 75, "end": 97}, {"text": "DMF", "start": 99, "end": 102}]}}, "schema": []}
{"input": "The resulting well-defined polymers were used as macro-CTAs to prepare corresponding diblock copolymers by RAFT polymerization of methyl (meth) acrylate monomers.", "output": {"entities": {"chemical": [{"text": "methyl (meth) acrylate", "start": 130, "end": 152}]}}, "schema": []}
{"input": "Deprotection of Boc groups in the homopolymers and block copolymers under acidic conditions produced cationic, pH-responsive polymers with primary amine moieties at the side chains.", "output": {"entities": {"chemical": [{"text": "Boc", "start": 16, "end": 19}, {"text": "primary amine", "start": 139, "end": 152}]}}, "schema": []}
{"input": "The optical activity of the homopolymers and block copolymers were studied using circular dichroism (CD) spectroscopy and specific rotation measurements.", "output": {"entities": {}}, "schema": []}
{"input": "The self-assembling nature of the block copolymers to produce highly ordered structures was illustrated through dynamic light scattering (DLS) and atomic force microscopy (AFM) studies.", "output": {"entities": {}}, "schema": []}
{"input": "The side chain amine functionality instills pH-responsive behavior, which makes these cationic polymers attractive candidates for drug delivery applications, as well as for conjugation of biomolecules.", "output": {"entities": {"chemical": [{"text": "amine", "start": 15, "end": 20}]}}, "schema": []}
{"input": "Quantum-dot-sensitized solar cells: understanding linker molecules through theory and experiment.", "output": {"entities": {}}, "schema": []}
{"input": "We have investigated the role of linker molecules in quantum-dot-sensitized solar cells (QDSSCs) using density-functional theory (DFT) and experiments.", "output": {"entities": {}}, "schema": []}
{"input": "Linkers not only govern the number of attached QDs but also influence charge separation, recombination, and transport.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding their behavior is therefore not straightforward.", "output": {"entities": {}}, "schema": []}
{"input": "DFT calculations show that mercaptopropionic acid (MPA) and cysteine (Cys) exhibit characteristic binding configurations on TiO (2) surfaces.", "output": {"entities": {"chemical": [{"text": "mercaptopropionic acid", "start": 27, "end": 49}, {"text": "MPA", "start": 51, "end": 54}, {"text": "cysteine", "start": 60, "end": 68}, {"text": "Cys", "start": 70, "end": 73}, {"text": "TiO (2)", "start": 124, "end": 131}]}}, "schema": []}
{"input": "This information is used to optimize the cell assembly process, yielding Cys-based cells that significantly outperform MPA cells, and reach power conversion efficiencies (PCE) as high as 2. 7% under AM 1. 5 illumination.", "output": {"entities": {"chemical": [{"text": "Cys", "start": 73, "end": 76}, {"text": "MPA", "start": 119, "end": 122}]}}, "schema": []}
{"input": "Importantly, the structural information from theory also helps understand the cause for this improved performance.", "output": {"entities": {}}, "schema": []}
{"input": "Stepwise colonization of the Andes by ruddy ducks and the evolution of novel beta-globin variants.", "output": {"entities": {}}, "schema": []}
{"input": "Andean uplift played a key role in Neotropical bird diversification, yet past dispersal and genetic adaptation to high-altitude environments remain little understood.", "output": {"entities": {}}, "schema": []}
{"input": "Here we use multilocus population genetics to study population history and historical demographic processes in the ruddy duck (Oxyura jamaicensis), a stiff-tailed diving duck comprising three subspecies distributed from Canada to Tierra del Fuego and inhabiting wetlands from sea level to 4500 m in the Andes.", "output": {"entities": {}}, "schema": []}
{"input": "We sequenced the mitochondrial DNA, four autosomal introns and three haemoglobin genes (alpha (A), alpha (D), beta (A)) and used isolation-with-migration (IM) models to study gene flow between North America and South America, and between the tropical and southern Andes.", "output": {"entities": {}}, "schema": []}
{"input": "Our analyses indicated that ruddy ducks dispersed first from North America to the tropical Andes, then from the tropical Andes to the southern Andes.", "output": {"entities": {}}, "schema": []}
{"input": "While no nonsynonymous substitutions were found in either alpha globin gene, three amino acid substitutions were observed in the beta (A) globin.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 83, "end": 93}]}}, "schema": []}
{"input": "Based on phylogenetic reconstruction and power analysis, the first beta (A) substitution, found in all Andean individuals, was acquired when ruddy ducks dispersed from low altitude in North America to high altitude in the tropical Andes, whereas the two additional substitutions occurred more recently, when ruddy ducks dispersed from high altitude in the tropical Andes to low altitude in the southern Andes.", "output": {"entities": {}}, "schema": []}
{"input": "This stepwise colonization pattern accompanied by polarized beta (A) globin amino acid replacements suggest that ruddy ducks first acclimatized or adapted to the Andean highlands and then again to the lowlands.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 76, "end": 86}]}}, "schema": []}
{"input": "In addition, ruddy ducks colonized the Andean highlands via a less common route as compared to other waterbird species that colonized the Andes northwards from the southern cone of South America.", "output": {"entities": {}}, "schema": []}
{"input": "Biotransformation and pharmacokinetics of inositol hexanicotinate in rats.", "output": {"entities": {"chemical": [{"text": "inositol hexanicotinate", "start": 42, "end": 65}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "Inositol hexanicotinate (IHN) is an ester of the anti-hyperlipidemic drug nicotinic acid (NA).", "output": {"entities": {"chemical": [{"text": "Inositol hexanicotinate", "start": 0, "end": 23}, {"text": "IHN", "start": 25, "end": 28}, {"text": "nicotinic acid", "start": 74, "end": 88}]}}, "schema": []}
{"input": "This study assessed the hydrolysis rate of IHN in human and rat plasma, and pharmacokinetics of the drug using a rat animal model.", "output": {"entities": {}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "IHN (10 or 50 micro g/mL) was incubated in plasma at 37 degrees C for 72 h.", "output": {"entities": {"chemical": [{"text": "IHN", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Kinetic parameters were determined based on the disappearance of IHN and the appearance of NA.", "output": {"entities": {"chemical": [{"text": "IHN", "start": 65, "end": 68}]}}, "schema": []}
{"input": "The mean IHN disappearance and NA appearance half-lives were 1. 07 and 3. 93 h in human plasma, and 0. 152 and 2. 68 h in rat plasma.", "output": {"entities": {"chemical": [{"text": "IHN", "start": 9, "end": 12}]}}, "schema": []}
{"input": "Increasing the initial plasma concentration to 50 micro g/mL increased the NA appearance half-life in human and rat plasma to 4. 66 and 6. 47 h, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "After single 50 or 100 mg/kg intravenous dose of IHN to Sprague-Dawley rats, the drug showed statistically significant dose-dependent alterations in systemic clearance, suggesting a non-linear saturable elimination of IHN.", "output": {"entities": {"chemical": [{"text": "IHN", "start": 49, "end": 52}, {"text": "IHN", "start": 218, "end": 221}]}}, "schema": []}
{"input": "Dose-normalized mean plasma levels of NA increased by 30% with increasing IHN dose (p < 0. 02).", "output": {"entities": {"chemical": [{"text": "IHN", "start": 74, "end": 77}]}}, "schema": []}
{"input": "The mean metabolic ratio (i. e. NA/IHN AUC ratio) significantly increased with increasing IHN dose (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "IHN", "start": 35, "end": 38}, {"text": "IHN", "start": 90, "end": 93}]}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "The results provide first indication of saturable elimination and rapid disappearance of IHN, while niacin was slowly formed.", "output": {"entities": {"chemical": [{"text": "IHN", "start": 89, "end": 92}, {"text": "niacin", "start": 100, "end": 106}]}}, "schema": []}
{"input": "Structural and mechanical heterogeneity of the erythrocyte membrane reveals hallmarks of membrane stability.", "output": {"entities": {}}, "schema": []}
{"input": "The erythrocyte membrane, a metabolically regulated active structure that comprises lipid molecules, junctional complexes, and the spectrin network, enables the cell to undergo large passive deformations when passing through the microvascular system.", "output": {"entities": {}}, "schema": []}
{"input": "Here we use atomic force microscopy (AFM) imaging and quantitative mechanical mapping at nanometer resolution to correlate structure and mechanics of key components of the erythrocyte membrane, crucial for cell integrity and function.", "output": {"entities": {}}, "schema": []}
{"input": "Our data reveal structural and mechanical heterogeneity modulated by the metabolic state at unprecedented nanometer resolution.", "output": {"entities": {}}, "schema": []}
{"input": "ATP-depletion, reducing skeletal junction phosphorylation in RBC cells, leads to membrane stiffening.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Analysis of ghosts and shear-force opened erythrocytes show that, in the absence of cytosolic kinases, spectrin phosphorylation results in membrane stiffening at the extracellular face and a reduced junction remodeling in response to loading forces.", "output": {"entities": {}}, "schema": []}
{"input": "Topography and mechanical mapping of single components at the cytoplasmic face reveal that, surprisingly, spectrin phosphorylation by ATP softens individual filaments.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 134, "end": 137}]}}, "schema": []}
{"input": "Our findings suggest that, besides the mechanical signature of each component, the RBC membrane mechanics is regulated by the metabolic state and the assembly of its structural elements.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of endocrine disruptors in a selected population of infertile women.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Several studies report that endocrine disrupting chemicals (EDC) able to interfere with endocrine homeostasis may affect women' s reproductive health.", "output": {"entities": {}}, "schema": []}
{"input": "We analyzed EDC serum levels and nuclear receptors (NRs) expression in order to have an indication of the internal dose of biologically active compounds and a measurement of indicators of their effects, as a result of the repeated uptake from environmental source.", "output": {"entities": {}}, "schema": []}
{"input": "The percentage of patients with detectable bisphenol A (BPA) concentrations was significantly higher in the infertile patients compared with fertile subjects.", "output": {"entities": {"chemical": [{"text": "bisphenol A", "start": 43, "end": 54}, {"text": "BPA", "start": 56, "end": 59}]}}, "schema": []}
{"input": "No significant difference was found between the groups with regard to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), mono-ethylhexyl phthalate (MEHP) and di-(2-ethylhexyl) phthalate (DEHP) concentrations.", "output": {"entities": {"chemical": [{"text": "perfluorooctane sulfonate", "start": 70, "end": 95}, {"text": "PFOS", "start": 97, "end": 101}, {"text": "perfluorooctanoic acid", "start": 104, "end": 126}, {"text": "PFOA", "start": 128, "end": 132}, {"text": "mono-ethylhexyl phthalate", "start": 135, "end": 160}, {"text": "MEHP", "start": 162, "end": 166}, {"text": "di-(2-ethylhexyl) phthalate", "start": 172, "end": 199}, {"text": "DEHP", "start": 201, "end": 205}]}}, "schema": []}
{"input": "Among infertile women, the mean expression of estrogen receptor alpha (ER alpha) and beta (Er beta), androgen receptor (AR) and pregnane X receptor (PXR) was significantly higher than fertile patients.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 46, "end": 54}, {"text": "androgen", "start": 101, "end": 109}, {"text": "pregnane", "start": 128, "end": 136}]}}, "schema": []}
{"input": "The mean expression of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPAR gamma) did not show significant differences between two groups.", "output": {"entities": {"chemical": [{"text": "aryl hydrocarbon", "start": 23, "end": 39}]}}, "schema": []}
{"input": "Patients with endometriosis had higher levels of PPAR gamma than all women with other causes of infertility.", "output": {"entities": {}}, "schema": []}
{"input": "This study led further support to EDC exposure as a risk factor for women' s fertility.", "output": {"entities": {}}, "schema": []}
{"input": "Masked mycotoxins are efficiently hydrolyzed by human colonic microbiota releasing their aglycones.", "output": {"entities": {}}, "schema": []}
{"input": "Fusarium mycotoxins are secondary metabolites produced by Fusarium spp. in cereals.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, deoxynivalenol (DON) and zearalenone (ZEN) are widespread worldwide contaminants of cereal commodities and are ranked as the most important chronic dietary risk factors.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 12, "end": 26}, {"text": "DON", "start": 28, "end": 31}, {"text": "zearalenone", "start": 37, "end": 48}, {"text": "ZEN", "start": 50, "end": 53}]}}, "schema": []}
{"input": "Their conjugates, known as masked mycotoxins, have been described but are still not accounted for in risk assessment studies.", "output": {"entities": {}}, "schema": []}
{"input": "This study demonstrates for the first time that DON and ZEN are effectively deconjugated by the human colonic microbiota, releasing their toxic aglycones and generating yet unidentified catabolites.", "output": {"entities": {"chemical": [{"text": "DON", "start": 48, "end": 51}, {"text": "ZEN", "start": 56, "end": 59}]}}, "schema": []}
{"input": "For this reason, masked mycotoxins should be considered when evaluating population exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-inflammatory diterpenoids from Croton tonkinensis.", "output": {"entities": {"chemical": [{"text": "diterpenoids", "start": 18, "end": 30}]}}, "schema": []}
{"input": "Phytochemical investigation of the methanolic extract of Croton tonkinensis afforded two known kauranes (1, 2), eight new ent-kauranes (3-10), and 16 known ent-kaurane-type diterpenoids (12-27).", "output": {"entities": {"chemical": [{"text": "kauranes", "start": 95, "end": 103}, {"text": "ent-kauranes", "start": 122, "end": 134}, {"text": "ent-kaurane", "start": 156, "end": 167}, {"text": "diterpenoids", "start": 173, "end": 185}]}}, "schema": []}
{"input": "In addition, 30 known compounds were identified by comparison of their physical and spectroscopic data with reported data.", "output": {"entities": {}}, "schema": []}
{"input": "Among the isolated compounds, ent-18-acetoxykaur-16-en-15-one (20) displayed the most significant inhibition of superoxide anion generation and elastase release.", "output": {"entities": {"chemical": [{"text": "ent-18-acetoxykaur-16-en-15-one", "start": 30, "end": 61}, {"text": "superoxide", "start": 112, "end": 122}]}}, "schema": []}
{"input": "H1152 promotes the degradation of polyglutamine-expanded ataxin-3 or ataxin-7 independently of its ROCK-inhibiting effect and ameliorates mutant ataxin-3-induced neurodegeneration in the SCA3 transgenic mouse.", "output": {"entities": {"chemical": [{"text": "H1152", "start": 0, "end": 5}, {"text": "polyglutamine", "start": 34, "end": 47}]}}, "schema": []}
{"input": "Spinocerebellar ataxia type 3 (SCA3) caused by polyglutamine-expanded ataxin-3 is the most prevalent subtype of spinocerebellar ataxias.", "output": {"entities": {"chemical": [{"text": "polyglutamine", "start": 47, "end": 60}]}}, "schema": []}
{"input": "A compound, which decreases protein level of mutant ataxin-3 in SCA3 affected CNS regions, should be a promising therapeutic agent for SCA3.", "output": {"entities": {}}, "schema": []}
{"input": "SCA3 and Huntington' s disease (HD) belong to a family of polyglutamine neurodegenerative diseases.", "output": {"entities": {"chemical": [{"text": "polyglutamine", "start": 58, "end": 71}]}}, "schema": []}
{"input": "Rho-kinase (ROCK) inhibitor Y27632 reduced brain level of polyglutamine-expanded huntingtin in HD transgenic mouse.", "output": {"entities": {"chemical": [{"text": "Y27632", "start": 28, "end": 34}, {"text": "polyglutamine", "start": 58, "end": 71}]}}, "schema": []}
{"input": "Therefore, we tested the possibility that ROCK inhibitors, Y27632, H1152 and GSK429286, downregulate protein expression of polyglutamine-expanded ataxin-3-Q79.", "output": {"entities": {"chemical": [{"text": "Y27632", "start": 59, "end": 65}, {"text": "H1152", "start": 67, "end": 72}, {"text": "GSK429286", "start": 77, "end": 86}, {"text": "polyglutamine", "start": 123, "end": 136}]}}, "schema": []}
{"input": "Y27632 or H1152 reduced protein level of HA-tagged ataxin-3-Q79 (ATX-3-Q79HA) expressed in HEK 293 cells.", "output": {"entities": {"chemical": [{"text": "Y27632", "start": 0, "end": 6}, {"text": "H1152", "start": 10, "end": 15}]}}, "schema": []}
{"input": "Compared to Y27632, H1152 decreased ATX-3-Q79HA protein level with a significantly more potency and efficacy.", "output": {"entities": {"chemical": [{"text": "Y27632", "start": 12, "end": 18}, {"text": "H1152", "start": 20, "end": 25}]}}, "schema": []}
{"input": "H1152 also reduced protein level of HA-tagged polyglutamine-expanded ataxin-7-Q52 (ATX-7-Q52HA), which causes spinocerebellar ataxia type 7 (SCA7).", "output": {"entities": {"chemical": [{"text": "H1152", "start": 0, "end": 5}, {"text": "polyglutamine", "start": 46, "end": 59}]}}, "schema": []}
{"input": "H1152 decreased ATX-3-Q79HA or ATX-7-Q52HA protein level in vitro by augmenting proteasome activity and promoting ATX-3-Q79HA or ATX-7-Q52HA degradation.", "output": {"entities": {"chemical": [{"text": "H1152", "start": 0, "end": 5}]}}, "schema": []}
{"input": "GSK429286, which is structurally different from H1152 but equally inhibits ROCK, failed to affect protein level of ATX-3-Q79HA or ATX-7-Q52HA.", "output": {"entities": {"chemical": [{"text": "GSK429286", "start": 0, "end": 9}, {"text": "H1152", "start": 48, "end": 53}]}}, "schema": []}
{"input": "Furthermore, shRNA-mediated suppression of ROCK1 or ROCK2 expression in 293 cells did not affect protein level of ATX-3-Q79HA or ATX-7-Q52HA and H1152 reduction of ATX-3-Q79HA.", "output": {"entities": {"chemical": [{"text": "H1152", "start": 145, "end": 150}]}}, "schema": []}
{"input": "Daily intraperitoneal administration of H1152 significantly decreased protein level of ATX-3-Q79HA in the cerebellum, pontine nuclei and spinal cord of SCA3 transgenic mice.", "output": {"entities": {"chemical": [{"text": "H1152", "start": 40, "end": 45}]}}, "schema": []}
{"input": "H1152 also ameliorated pontine neuronal death and neurological phenotype of SCA3 transgenic mice.", "output": {"entities": {"chemical": [{"text": "H1152", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Our results suggest that H1152 might be an effective therapeutic agent for SCA3 or SCA7.", "output": {"entities": {"chemical": [{"text": "H1152", "start": 25, "end": 30}]}}, "schema": []}
{"input": "Quercetin ameliorate insulin resistance and up-regulates cellular antioxidants during oleic acid induced hepatic steatosis in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "oleic acid", "start": 86, "end": 96}]}}, "schema": []}
{"input": "Hepatic lipid accumulation and oxidative stress contribute to non-alcoholic fatty liver disease (NAFLD).", "output": {"entities": {}}, "schema": []}
{"input": "Thus, we hypothesized that the hypolipidemic and antioxidant activity of quercetin would attenuate events leading to NAFLD.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 73, "end": 82}]}}, "schema": []}
{"input": "Addition of 2. 0mM oleic acid (OA) into the culture media induced fatty liver condition in HepG2 cells by 24h.", "output": {"entities": {"chemical": [{"text": "oleic acid", "start": 19, "end": 29}]}}, "schema": []}
{"input": "It was marked by significant accumulation of lipid droplets as determined by Oil-Red-O (ORO) based colorimetric assay, increased triacylglycerol (TAG) and increased lipid peroxidation.", "output": {"entities": {"chemical": [{"text": "Oil-Red-O", "start": 77, "end": 86}, {"text": "ORO", "start": 88, "end": 91}, {"text": "triacylglycerol", "start": 129, "end": 144}, {"text": "TAG", "start": 146, "end": 149}]}}, "schema": []}
{"input": "The inflammatory cytokines TNF-alpha and IL-8 levels were significantly increased with decreased antioxidant molecules.", "output": {"entities": {}}, "schema": []}
{"input": "OA induced insulin resistance which was evident by inhibition of glucose uptake and cell proliferation.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 65, "end": 72}]}}, "schema": []}
{"input": "Quercetin (10 mu M) increased cell proliferation by 3. 05 folds with decreased TAG content (45%) and was effective in increasing insulin mediated glucose uptake by 2. 65 folds.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "TAG", "start": 79, "end": 82}, {"text": "glucose", "start": 146, "end": 153}]}}, "schema": []}
{"input": "The intracellular glutathione content was increased by 2. 0 folds without substantial increase in GSSG content.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 18, "end": 29}, {"text": "GSSG", "start": 98, "end": 102}]}}, "schema": []}
{"input": "Quercetin (10 mu M) decreased TNF-alpha and IL-8 by 59. 74% and 41. 11% respectively and inhibited generation of lipid peroxides by 50. 5%.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "peroxides", "start": 119, "end": 128}]}}, "schema": []}
{"input": "In addition, RT-PCR results confirmed quercetin (10 mu M) inhibited TNF-alpha gene expression.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 38, "end": 47}]}}, "schema": []}
{"input": "Further, superoxide dismutase, catalase and glutathione peroxidase activities were increased by 1. 68, 2. 19 and 1. 71 folds respectively.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 9, "end": 19}, {"text": "glutathione", "start": 44, "end": 55}]}}, "schema": []}
{"input": "Albumin and urea content was increased while the alanine aminotransferase (ALAT) activity was significantly decreased by quercetin.", "output": {"entities": {"chemical": [{"text": "urea", "start": 12, "end": 16}, {"text": "alanine", "start": 49, "end": 56}, {"text": "quercetin", "start": 121, "end": 130}]}}, "schema": []}
{"input": "Hence, quercetin effectively reversed NAFLD symptoms by decreased triacyl glycerol accumulation, insulin resistance, inflammatory cytokine secretion and increased cellular antioxidants in OA induced hepatic steatosis in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 7, "end": 16}, {"text": "triacyl glycerol", "start": 66, "end": 82}]}}, "schema": []}
{"input": "The male mammary gland: a target for the xenoestrogen bisphenol A.", "output": {"entities": {"chemical": [{"text": "bisphenol A", "start": 54, "end": 65}]}}, "schema": []}
{"input": "Males of some strains of mice retain their mammary epithelium even in the absence of nipples.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections.", "output": {"entities": {}}, "schema": []}
{"input": "We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland.", "output": {"entities": {"chemical": [{"text": "bisphenol A", "start": 32, "end": 43}, {"text": "BPA", "start": 45, "end": 48}, {"text": "estrogen", "start": 54, "end": 62}]}}, "schema": []}
{"input": "BPA was administered at a range of environmentally relevant doses (0. 25-250 mu g/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "We observed age-and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 97, "end": 100}]}}, "schema": []}
{"input": "These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement.", "output": {"entities": {}}, "schema": []}
{"input": "A novel coating concept for ileo-colonic drug targeting: Proof of concept in humans using scintigraphy.", "output": {"entities": {}}, "schema": []}
{"input": "The in vivo proof of concept of a novel double-coating system, based on enteric polymers, which accelerated drug release in the ileo-colonic region, was investigated in humans.", "output": {"entities": {}}, "schema": []}
{"input": "Prednisolone tablets were coated with a double-coating formulation by applying an inner layer composed of EUDRAGIT (R) S neutralised to pH 8. 0 and a buffer salt (10% KH (2) PO (4)), which was overcoated with layer of standard EUDRAGIT (R) S organic solution.", "output": {"entities": {"chemical": [{"text": "Prednisolone", "start": 0, "end": 12}, {"text": "EUDRAGIT", "start": 106, "end": 114}, {"text": "KH (2) PO (4)", "start": 167, "end": 180}, {"text": "EUDRAGIT", "start": 227, "end": 235}]}}, "schema": []}
{"input": "For comparison, a single coating system was produced by applying the same amount of EUDRAGIT (R) S organic solution on the tablet cores.", "output": {"entities": {"chemical": [{"text": "EUDRAGIT", "start": 84, "end": 92}]}}, "schema": []}
{"input": "Dissolution tests on the tablets were carried out using USP II apparatus in 0. 1N HCl for 2h and subsequently in pH 7. 4 Krebs bicarbonate buffer.", "output": {"entities": {"chemical": [{"text": "HCl", "start": 82, "end": 85}]}}, "schema": []}
{"input": "For comparison, tablets were also tested under the USP method established for modified release mesalamine formulations.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 95, "end": 105}]}}, "schema": []}
{"input": "Ten fasted volunteers received the double-coated and single-coated tablets in a two-way crossover study.", "output": {"entities": {}}, "schema": []}
{"input": "The formulations were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded.", "output": {"entities": {}}, "schema": []}
{"input": "There was no drug release from the single-coated or double-coated tablets in 0. 1N HCl for 2h.", "output": {"entities": {"chemical": [{"text": "HCl", "start": 83, "end": 86}]}}, "schema": []}
{"input": "The single-coated tablets showed slow release in subsequent Krebs bicarbonate buffer with a lag time of 120min, while in contrast drug release from the double-coated tablets was initiated at 60min.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, using the USP dissolution method, normally employed for modified release mesalamine products, no discrimination was attained.", "output": {"entities": {"chemical": [{"text": "mesalamine", "start": 86, "end": 96}]}}, "schema": []}
{"input": "The in vivo disintegration of the single-coated EUDRAGIT (R) S tablets in the large intestine was erratic.", "output": {"entities": {"chemical": [{"text": "EUDRAGIT", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Furthermore, in 2 volunteers, the single-coated tablet was voided intact.", "output": {"entities": {}}, "schema": []}
{"input": "Double-coated tablets disintegrated in a more consistent way, mainly in the ileo-caecal junction or terminal ileum.", "output": {"entities": {}}, "schema": []}
{"input": "The accelerated in vivo disintegration of the double-coating EUDRAGIT (R) S system can overcome the limitations of conventional enteric coatings targeting the colon and avoid the pass-through of intact tablets.", "output": {"entities": {"chemical": [{"text": "EUDRAGIT", "start": 61, "end": 69}]}}, "schema": []}
{"input": "Moreover, Krebs bicarbonate buffer has the ability to discriminate between formulations designed to target the ileo-colonic region.", "output": {"entities": {"chemical": [{"text": "bicarbonate", "start": 16, "end": 27}]}}, "schema": []}
{"input": "Dietary relevant mixtures of phytoestrogens inhibit adipocyte differentiation in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Phytoestrogens (PEs) are naturally occurring plant components, with the ability to induce biological responses in vertebrates by mimicking or modulating the action of endogenous hormones.", "output": {"entities": {}}, "schema": []}
{"input": "Single isoflavones have been shown to affect adipocyte differentiation, but knowledge on the effect of dietary relevant mixtures of PEs, including for instance lignans, is lacking.", "output": {"entities": {"chemical": [{"text": "isoflavones", "start": 7, "end": 18}]}}, "schema": []}
{"input": "In the current study dietary relevant mixtures of isoflavones and their metabolites, lignans and their metabolites, coumestrol, and a mixture containing all of them, were examined for effects on adipogenesis in 3T3-L1 adipocytes, as well as tested for their PPAR gamma activating abilities.", "output": {"entities": {"chemical": [{"text": "isoflavones", "start": 50, "end": 61}, {"text": "lignans", "start": 85, "end": 92}, {"text": "coumestrol", "start": 116, "end": 126}]}}, "schema": []}
{"input": "The results showed that mixtures of isoflavonoid parent compounds and metabolites, respectively, a mixture of lignan metabolites, as well as coumestrol concentration-dependently inhibited adipocyte differentiation.", "output": {"entities": {"chemical": [{"text": "isoflavonoid", "start": 36, "end": 48}, {"text": "lignan", "start": 110, "end": 116}, {"text": "coumestrol", "start": 141, "end": 151}]}}, "schema": []}
{"input": "Furthermore, a mixture of isoflavonoid parent compounds, and a mixture of isoflavonoid metabolites were found to have PPAR gamma activating abilities.", "output": {"entities": {"chemical": [{"text": "isoflavonoid", "start": 26, "end": 38}, {"text": "isoflavonoid", "start": 74, "end": 86}]}}, "schema": []}
{"input": "These results suggest that PEs can affect pathways known to play a role in obesity development, and indicate that the inhibitory effect on adipocyte differentiation does not appear to be strictly associated with PPAR gamma activation/inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "The current study support the hypothesis that compounds with endocrine activity can affect pathways playing a role in the development obesity and obesity related diseases.", "output": {"entities": {}}, "schema": []}
{"input": "A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 21, "end": 30}]}}, "schema": []}
{"input": "Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 13, "end": 22}]}}, "schema": []}
{"input": "Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term potentiation (LTP), which is thought to be involved in cognition.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple mGlu5-positive allosteric modulators (PAMs) have been developed from a variety of different scaffolds.", "output": {"entities": {}}, "schema": []}
{"input": "Previous work has extensively characterized a common allosteric site on mGlu5, termed the MPEP (2-Methyl-6-(phenylethynyl) pyridine) binding site.", "output": {"entities": {"chemical": [{"text": "MPEP", "start": 90, "end": 94}, {"text": "2-Methyl-6-(phenylethynyl) pyridine", "start": 96, "end": 131}]}}, "schema": []}
{"input": "However, one mGlu5 PAM, CPPHA (N-(4-chloro-2-[(1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) methyl] phenyl)-2-hydroxybenzamide), interacts with a separate allosteric site on mGlu5.", "output": {"entities": {"chemical": [{"text": "CPPHA", "start": 24, "end": 29}, {"text": "N-(4-chloro-2-[(1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) methyl] phenyl)-2-hydroxybenzamide", "start": 31, "end": 123}]}}, "schema": []}
{"input": "Using cell-based assays and brain slice preparations, we characterized the interaction of a potent and efficacious mGlu5 PAM from the CPPHA series termed NCFP (N-(4-chloro-2-((4-fluoro-1, 3-dioxoisoindolin-2-yl) methyl) phenyl) picolinamide).", "output": {"entities": {"chemical": [{"text": "CPPHA", "start": 134, "end": 139}, {"text": "NCFP", "start": 154, "end": 158}, {"text": "N-(4-chloro-2-((4-fluoro-1, 3-dioxoisoindolin-2-yl) methyl) phenyl) picolinamide", "start": 160, "end": 240}]}}, "schema": []}
{"input": "NCFP binds to the CPPHA site on mGlu5 and potentiates mGlu5-mediated responses in both recombinant and native systems.", "output": {"entities": {"chemical": [{"text": "NCFP", "start": 0, "end": 4}, {"text": "CPPHA", "start": 18, "end": 23}]}}, "schema": []}
{"input": "However, NCFP provides greater mGlu5 subtype selectivity than does CPPHA, making it more suitable for studies of effects on mGlu5 in CNS preparations.", "output": {"entities": {"chemical": [{"text": "NCFP", "start": 9, "end": 13}, {"text": "CPPHA", "start": 67, "end": 72}]}}, "schema": []}
{"input": "Of interest, NCFP does not potentiate responses involved in hippocampal synaptic plasticity (LTD/LTP), setting it apart from other previously characterized MPEP site PAMs.", "output": {"entities": {"chemical": [{"text": "NCFP", "start": 13, "end": 17}, {"text": "MPEP", "start": 156, "end": 160}]}}, "schema": []}
{"input": "This suggests that although mGlu5 PAMs may have similar responses in some systems, they can induce differential effects on mGlu5-mediated physiologic responses in the CNS.", "output": {"entities": {}}, "schema": []}
{"input": "Such stimulus bias by mGlu5 PAMs may complicate drug discovery efforts but would also allow for specifically tailored therapies, if pharmacological biases can be attributed to different therapeutic outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Targeting the epithelial cells in fibrosis: a new concept for an old disease.", "output": {"entities": {}}, "schema": []}
{"input": "Fibrosis, which affects millions of individuals worldwide, is a leading cause of organ failure.", "output": {"entities": {}}, "schema": []}
{"input": "For 40 years myofibroblasts have been recognized to be the key cellular players in fibrosis.", "output": {"entities": {}}, "schema": []}
{"input": "Currently, several pharmaceutical targets are under investigation that may contribute to the activation of myofibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Recent preclinical and clinical evidence suggests that other components in the fibrotic microenvironment can trigger myofibroblast activation, providing new targets for pharmaceutical intervention.", "output": {"entities": {}}, "schema": []}
{"input": "Epithelial cells may represent the most promising cellular phenotype that could be exploited in the design of new anti-fibrotic medicines through their paracrine action on myofibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "The present review briefly highlights this hypothesis and discusses some interesting related pharmacological targets.", "output": {"entities": {}}, "schema": []}
{"input": "The stereoisomer (+)-naloxone potentiates G-protein coupling and feeding associated with stimulation of mu opioid receptors in the parabrachial nucleus.", "output": {"entities": {"chemical": [{"text": "(+)-naloxone", "start": 17, "end": 29}]}}, "schema": []}
{"input": "Classically, opioids produce their effects by activating Gi-proteins that inhibit adenylate cyclase activity.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies proposed that mu-opioid receptors can also stimulate adenylate cyclase due to an initial transient coupling to Gs-proteins.", "output": {"entities": {"chemical": [{"text": "adenylate", "start": 70, "end": 79}]}}, "schema": []}
{"input": "Treatment with ultra-low doses of the nonselective opioid antagonist (-)-naloxone or its inactive enantiomer (+)-naloxone blocks this excitatory effect and enhances Gi-coupling.", "output": {"entities": {"chemical": [{"text": "(-)-naloxone", "start": 69, "end": 81}, {"text": "(+)-naloxone", "start": 109, "end": 121}]}}, "schema": []}
{"input": "Previously we reported that infusion of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Glycinol5]-Enkephalin (DAMGO) into the mu-opioid receptor expressing lateral parabrachial nucleus increases feeding.", "output": {"entities": {"chemical": [{"text": "[D-Ala2, N-Me-Phe4, Glycinol5]-Enkephalin", "start": 71, "end": 112}, {"text": "DAMGO", "start": 114, "end": 119}]}}, "schema": []}
{"input": "Pretreatment with (-)-naloxone blocks this effect.", "output": {"entities": {"chemical": [{"text": "(-)-naloxone", "start": 18, "end": 30}]}}, "schema": []}
{"input": "We used this parabrachial circuit as a model to assess cellular actions of ultra-low doses of (-)-naloxone and (+)-naloxone in modifying the effects of DAMGO.", "output": {"entities": {"chemical": [{"text": "(-)-naloxone", "start": 94, "end": 106}, {"text": "(+)-naloxone", "start": 111, "end": 123}, {"text": "DAMGO", "start": 152, "end": 157}]}}, "schema": []}
{"input": "Our results showed that an ultra-low concentration of (-)-naloxone (0. 001 nM) and several concentrations of (+)-naloxone (0. 01-10 nM) enhanced DAMGO-stimulated guanosine-5'-0-(gamma-thio)-triphosphate incorporation in parabrachial sections in vitro.", "output": {"entities": {"chemical": [{"text": "(-)-naloxone", "start": 54, "end": 66}, {"text": "(+)-naloxone", "start": 109, "end": 121}, {"text": "DAMGO", "start": 145, "end": 150}, {"text": "guanosine-5'-0-(gamma-thio)-triphosphate", "start": 162, "end": 202}]}}, "schema": []}
{"input": "Further, we analyzed the relevance of these effects in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we show that (+)-naloxone can potentiate DAMGO-induced feeding at doses at which (-)-naloxone was an antagonist.", "output": {"entities": {"chemical": [{"text": "(+)-naloxone", "start": 35, "end": 47}, {"text": "DAMGO", "start": 63, "end": 68}, {"text": "(-)-naloxone", "start": 103, "end": 115}]}}, "schema": []}
{"input": "These results implicated (+)-naloxone as a novel tool for studying mu-opioid receptor functions and suggest that (+)-naloxone may have therapeutic value to enhance clinical actions of opiate drugs.", "output": {"entities": {"chemical": [{"text": "(+)-naloxone", "start": 25, "end": 37}, {"text": "(+)-naloxone", "start": 113, "end": 125}]}}, "schema": []}
{"input": "Disruption of the cereblon gene enhances hepatic AMPK activity and prevents high fat diet-induced obesity and insulin resistance in mice.", "output": {"entities": {}}, "schema": []}
{"input": "A nonsense mutation in cereblon (CRBN) causes a mild type of mental retardation in humans.", "output": {"entities": {}}, "schema": []}
{"input": "An earlier study showed that CRBN negatively regulates the functional activity of AMP-activated protein kinase (AMPK) in vitro by binding directly to the alpha 1 subunit of the AMPK complex.", "output": {"entities": {"chemical": [{"text": "AMP", "start": 82, "end": 85}]}}, "schema": []}
{"input": "However, the in vivo role of CRBN was not studied.", "output": {"entities": {}}, "schema": []}
{"input": "To elucidate the physiological functions of Crbn, a mouse strain was generated in which the Crbn gene was deleted throughout the whole body.", "output": {"entities": {}}, "schema": []}
{"input": "In Crbn-deficient mice fed a normal diet, AMPK in the liver showed hyper-phosphorylation, which indicated the constitutive activation of AMPK.", "output": {"entities": {}}, "schema": []}
{"input": "Since Crbn-deficient mice showed significantly less weight gain when fed a high fat diet and their insulin sensitivity was considerably improved, the functions of Crbn in the liver were primarily investigated.", "output": {"entities": {}}, "schema": []}
{"input": "These results provide the first in vivo evidence that Crbn is a negative modulator of AMPK, which suggests that Crbn may be a potential target for metabolic disorders of the liver.", "output": {"entities": {}}, "schema": []}
{"input": "beta-Cells Are Not Generated in Pancreatic Duct Ligation-Induced Injury in Adult Mice.", "output": {"entities": {}}, "schema": []}
{"input": "The existence of adult beta-cell progenitors remains the most controversial developmental biology topic in diabetes research.", "output": {"entities": {}}, "schema": []}
{"input": "It has been reported that beta-cell progenitors can be activated by ductal ligation-induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional beta-cell mass within a week by differentiation and proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to beta-cell mass expansion.", "output": {"entities": {}}, "schema": []}
{"input": "Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of beta-cell content via traditional morphometry methodologies that superficially sample the pancreas.", "output": {"entities": {}}, "schema": []}
{"input": "To overcome this potential bias, we quantified beta-cells from the entire pancreas and observed that beta-cell mass and insulin content are totally unchanged by PDL-induced injury.", "output": {"entities": {}}, "schema": []}
{"input": "Lineage-tracing studies using sequential administration of thymidine analogs, rat insulin 2 promoter-driven cre-lox, and low-frequency ubiquitous cre-lox reveal that PDL does not convert progenitors to the beta-cell lineage.", "output": {"entities": {"chemical": [{"text": "thymidine", "start": 59, "end": 68}]}}, "schema": []}
{"input": "Thus, we conclude that beta-cells are not generated in injured adult mouse pancreas.", "output": {"entities": {}}, "schema": []}
{"input": "Galectin-3 Deficiency Accelerates High-Fat Diet Induced Obesity and Amplifies Inflammation in Adipose Tissue and Pancreatic Islets.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity-induced diabetes is associated with low-grade inflammation in adipose tissue and macrophage infiltration of islets.", "output": {"entities": {}}, "schema": []}
{"input": "We show that ablation of Galectin-3, a galactoside-binding lectin, accelerates high-fat diet-induced obesity and diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Obese LGALS3 (-/-) mice have increased body weight, amount of total visceral adipose tissue, fasting blood glucose and insulin levels, HOMA-IR and markers of systemic inflammation compared to diet-matched WT animals.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 107, "end": 114}]}}, "schema": []}
{"input": "Obese LGALS3 (-/-) visceral adipose tissue exhibited increased incidence of Type-1 T and NKT lymphocytes and pro-inflammatory CD11c + CD11b macrophages and decreased CD4 + CD25 + FoxP3 + Tregs and M2 macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and IL-1 beta in macrophages and increased accumulation of advanced glycation endproducts (AGE) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3 (-/-) animals accompanied with elevated phosphorilated NF kappa B p65 and mature Caspase-1 protein expression in pancreatic and visceral adipose tissue.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro stimulation of LGALS3 (-/-) peritoneal macrophages with lypopolysaccharide (LPS) and saturated fatty acid palmitate caused increased Caspase-1 dependent IL-1 beta production and increased phosphorilation of NF kappa B p65 compared to WT cells.", "output": {"entities": {"chemical": [{"text": "palmitate", "start": 115, "end": 124}]}}, "schema": []}
{"input": "Transfection of LGALS3 (-/-) macrophages with NLRP3 siRNA attenuated IL-1 beta production in response to palmitate and LPS plus palmitate.", "output": {"entities": {"chemical": [{"text": "palmitate", "start": 105, "end": 114}, {"text": "palmitate", "start": 128, "end": 137}]}}, "schema": []}
{"input": "Obtained results suggest important protective roles for Gal-3 in obesity-induced inflammation and diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "TSG-6 produced by hMSCs delays the onset of autoimmune diabetes by suppressing Th1 development and enhancing tolerogenicity.", "output": {"entities": {}}, "schema": []}
{"input": "Genetic and immunological screening for type 1 diabetes has led to the possibility of preventing disease in susceptible individuals.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that human Mesenchymal Stem/Stromal Cells (hMSCs) and TNF-alpha-stimulated gene 6 (TSG-6), a protein produced by hMSCs in response to signals from injured tissues, delayed the onset of spontaneous autoimmune diabetes in NOD mice by inhibiting insulitis and augmenting regulatory T cells (Tregs) within the pancreas.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, hMSCs with a knockdown of tsg-6 were ineffective at delaying insulitis and the onset of diabetes in mice.", "output": {"entities": {}}, "schema": []}
{"input": "TSG-6 inhibited the activation of both T cell and antigen presenting cells (APCs) in a CD44-dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, multiple treatments of TSG-6 rendered APCs more tolerogenic, capable of enhancing Treg generation and delaying diabetes in an adoptive transfer model.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, these results could provide the basis for a novel therapy for the prevention of type 1 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "The role of GH in adipose tissue: lessons from adipose-specific GH receptor gene-disrupted mice.", "output": {"entities": {}}, "schema": []}
{"input": "GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH.", "output": {"entities": {}}, "schema": []}
{"input": "Many of these discoveries highlight the importance of GH in adipose tissue.", "output": {"entities": {}}, "schema": []}
{"input": "For example GHR-/-mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot.", "output": {"entities": {}}, "schema": []}
{"input": "GHR-/-mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines.", "output": {"entities": {}}, "schema": []}
{"input": "To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice.", "output": {"entities": {}}, "schema": []}
{"input": "Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/-mice.", "output": {"entities": {}}, "schema": []}
{"input": "Like the GHR-/-mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size.", "output": {"entities": {}}, "schema": []}
{"input": "However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 95, "end": 102}]}}, "schema": []}
{"input": "Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/-mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin.", "output": {"entities": {}}, "schema": []}
{"input": "However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 131, "end": 138}]}}, "schema": []}
{"input": "Mineralocorticoid receptor-mediated vascular insulin resistance: an early contributor to diabetes-related vascular disease?", "output": {"entities": {}}, "schema": []}
{"input": "Two-thirds of adults in the U. S. are overweight or obese, and another 26 million have type 2 diabetes (T2D).", "output": {"entities": {}}, "schema": []}
{"input": "Patients with diabetes and/or the metabolic syndrome have a significantly increased risk of heart attack and stroke compared with people with normal insulin sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "Decreased insulin sensitivity in cardiovascular tissues as well as in traditional targets of insulin metabolic signaling, such as skeletal muscle, is an underlying abnormality in obesity, hypertension, and T2D.", "output": {"entities": {}}, "schema": []}
{"input": "In the vasculature, insulin signaling plays a critical role in normal vascular function via endothelial cell nitric oxide production and modulation of Ca (2 +) handling and sensitivity in vascular smooth muscle cells.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 109, "end": 121}, {"text": "Ca (2 +)", "start": 151, "end": 159}]}}, "schema": []}
{"input": "Available evidence suggests that impaired vascular insulin sensitivity may be an early, perhaps principal, defect of vascular function and contributor to the pathogenesis of vascular disease in persons with obesity, hypertension, and T2D.", "output": {"entities": {}}, "schema": []}
{"input": "In the overweight and obese individual, as well as in persons with hypertension, systemic and vascular insulin resistance often occur in concert with elevations in plasma aldosterone.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 171, "end": 182}]}}, "schema": []}
{"input": "Indeed, basic and clinical studies have demonstrated that elevated plasma aldosterone levels predict the development of insulin resistance and that aldosterone directly interferes with insulin signaling in vascular tissues.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 74, "end": 85}, {"text": "aldosterone", "start": 148, "end": 159}]}}, "schema": []}
{"input": "Furthermore, elevated plasma aldosterone levels are associated with increased heart attack and stroke risk.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 29, "end": 40}]}}, "schema": []}
{"input": "Conversely, renin-angiotensin-aldosterone system and mineralocorticoid receptor (MR) antagonism reduces cardiovascular risk in these patient populations.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 30, "end": 41}]}}, "schema": []}
{"input": "Recent and accumulating evidence in this area has implicated excessive Ser phosphorylation and proteosomal degradation of the docking protein, insulin receptor substrate, and enhanced signaling through hybrid insulin/IGF-1 receptor as important mechanisms underlying aldosterone-mediated interruption of downstream vascular insulin signaling.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 71, "end": 74}, {"text": "aldosterone", "start": 267, "end": 278}]}}, "schema": []}
{"input": "Prevention or restoration of these changes via blockade of aldosterone action in the vascular wall with MR antagonists (i. e., spironolactone, eplerenone) may therefore account for the clinical benefit of these compounds in obese and diabetic patients with cardiovascular disease.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 59, "end": 70}, {"text": "spironolactone", "start": 127, "end": 141}, {"text": "eplerenone", "start": 143, "end": 153}]}}, "schema": []}
{"input": "This review will highlight recent evidence supporting the hypothesis that aldosterone and MR signaling represent an ideal candidate pathway linking early promoters of diabetes, especially overnutrition and obesity, to vascular insulin resistance, dysfunction, and disease.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 74, "end": 85}]}}, "schema": []}
{"input": "Photocatalytic properties of graphdiyne and graphene modified TiO 2: from theory to experiment.", "output": {"entities": {"chemical": [{"text": "graphdiyne", "start": 29, "end": 39}, {"text": "graphene", "start": 44, "end": 52}, {"text": "TiO 2", "start": 62, "end": 67}]}}, "schema": []}
{"input": "The chemical structure and electronic properties of two-dimensional (2D) carbon-supported TiO 2, TiO 2-graphdiyne, and TiO 2-graphene composites have been studied by first-principles density functional theory.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 73, "end": 79}, {"text": "TiO 2", "start": 90, "end": 95}, {"text": "TiO 2-graphdiyne", "start": 97, "end": 113}, {"text": "TiO 2-graphene", "start": 119, "end": 133}]}}, "schema": []}
{"input": "Calculation results show that TiO 2 (001)-graphdiyne composites possess superior charge separation and oxidation properties, having the longest lifetimes of photoexcited carriers among all of the 2D composites containing TiO 2 of different facets.", "output": {"entities": {"chemical": [{"text": "TiO 2", "start": 30, "end": 35}, {"text": "graphdiyne", "start": 42, "end": 52}, {"text": "TiO 2", "start": 221, "end": 226}]}}, "schema": []}
{"input": "Our experimental results further proved that TiO 2 (001)-graphdiyne composites could be a promising photocatalyst.", "output": {"entities": {"chemical": [{"text": "TiO 2", "start": 45, "end": 50}, {"text": "graphdiyne", "start": 57, "end": 67}]}}, "schema": []}
{"input": "For photocatalytic degradation of methylene blue, the rate constant of the TiO 2 (001)-graphdiyne composite is 1. 63 +/- 0. 15 times that of the pure TiO 2 (001) and 1. 27 +/- 0. 12 times that of the TiO 2 (001)-graphene composite.", "output": {"entities": {"chemical": [{"text": "methylene blue", "start": 34, "end": 48}, {"text": "TiO 2", "start": 75, "end": 80}, {"text": "graphdiyne", "start": 87, "end": 97}, {"text": "TiO 2", "start": 150, "end": 155}, {"text": "TiO 2", "start": 200, "end": 205}, {"text": "graphene", "start": 212, "end": 220}]}}, "schema": []}
{"input": "In vivo microdialysis for the evaluation of transfersomes as a novel transdermal delivery vehicle for cinnamic acid.", "output": {"entities": {"chemical": [{"text": "cinnamic acid", "start": 102, "end": 115}]}}, "schema": []}
{"input": "Abstract In this study, cinnamic acid-loaded transfersomes were prepared and dermal microdialysis sampling was used in Sprague-Dawley rats to compare the amount of drug released into the skin using transfersomes as transdermal carriers with that released on using conventional liposomes.", "output": {"entities": {"chemical": [{"text": "cinnamic acid", "start": 24, "end": 37}]}}, "schema": []}
{"input": "The formulation of cinnamic acid-loaded transfersomes was optimized by a uniform design through in vitro transdermal permeation studies.", "output": {"entities": {"chemical": [{"text": "cinnamic acid", "start": 19, "end": 32}]}}, "schema": []}
{"input": "Hydration time was confirmed as a significant factor influencing the entrapment efficiency of transfersomes, further affecting their transdermal flux in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "The fluxes of cinnamic acid from transfersomes were all higher than those from conventional liposomes, and the flux from the optimal transfersome formulation was 3. 01-fold higher than that from the conventional liposomes (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "cinnamic acid", "start": 14, "end": 27}]}}, "schema": []}
{"input": "An in vivo microdialysis sampling method revealed that the dermal drug concentrations from transfersomes applied on various skin regions were much lower than those required with conventional liposomes.", "output": {"entities": {}}, "schema": []}
{"input": "After the administration of drug-containing transfersomes and liposomes on abdominal skin regions of rats for a period of 10 h, the C (max) of cinnamic acid from the compared liposomes was 3. 21 +/- 0. 25 mu g/mL and that from the transfersomes was merely 0. 59 +/- 0. 02 mu g/mL.", "output": {"entities": {"chemical": [{"text": "cinnamic acid", "start": 143, "end": 156}]}}, "schema": []}
{"input": "The results suggest that transfersomes can be used as carriers to enhance the transdermal delivery of cinnamic acid, and that these vehicles may penetrate the skin in the complete form, given their significant deformability.", "output": {"entities": {"chemical": [{"text": "cinnamic acid", "start": 102, "end": 115}]}}, "schema": []}
{"input": "Iontophoresis of amoxicillin and cefuroxime: rapid therapeutic concentrations in skin.", "output": {"entities": {"chemical": [{"text": "amoxicillin", "start": 17, "end": 28}, {"text": "cefuroxime", "start": 33, "end": 43}]}}, "schema": []}
{"input": "Abstract Context: Amoxicillin (AMX) and cefuroxime (CFX) are antibiotics used often to treat skin bacterial infections.", "output": {"entities": {"chemical": [{"text": "Amoxicillin", "start": 18, "end": 29}, {"text": "AMX", "start": 31, "end": 34}, {"text": "cefuroxime", "start": 40, "end": 50}, {"text": "CFX", "start": 52, "end": 55}]}}, "schema": []}
{"input": "Typically, high oral doses are required to achieve minimum inhibitory concentration (MIC) at the site of infection that may affect only a very small area of skin.", "output": {"entities": {}}, "schema": []}
{"input": "Objectives: To lower side effects and increase therapeutic effectiveness, the percutaneous absorption and retention of AMX and CFX administered by iontophoresis was investigated in a rabbit model by measuring dermis concentrations via microdialysis.", "output": {"entities": {"chemical": [{"text": "AMX", "start": 119, "end": 122}, {"text": "CFX", "start": 127, "end": 130}]}}, "schema": []}
{"input": "Methods: Iontophoresis was performed using a stainless steel electrode and a non-woven polypropylene pad.", "output": {"entities": {"chemical": [{"text": "polypropylene", "start": 87, "end": 100}]}}, "schema": []}
{"input": "The cartridge pad was soaked with a solution of AMX in glycerin or of CFX in glycerin/water (60: 40).", "output": {"entities": {"chemical": [{"text": "AMX", "start": 48, "end": 51}, {"text": "CFX", "start": 70, "end": 73}]}}, "schema": []}
{"input": "Constant current density of 0, 100, 200 or 300 micro A/cm (2) was applied for 60 min.", "output": {"entities": {}}, "schema": []}
{"input": "Results: For AMX, therapeutically effective skin concentrations were detected immediately after the application of electrical current for any of the current density tested and remained above it for at least 2 h from the end of iontophoresis.", "output": {"entities": {"chemical": [{"text": "AMX", "start": 13, "end": 16}]}}, "schema": []}
{"input": "For CFX, skin concentrations rose above MIC only at the higher current densities and fell below the MIC by the end of the experiment.", "output": {"entities": {"chemical": [{"text": "CFX", "start": 4, "end": 7}]}}, "schema": []}
{"input": "Conclusion: Iontophoresis is a promising method to obtain a fast and sustained concentration of AMX and CFX in skin.", "output": {"entities": {"chemical": [{"text": "AMX", "start": 96, "end": 99}, {"text": "CFX", "start": 104, "end": 107}]}}, "schema": []}
{"input": "Potent elastase inhibitors from cyanobacteria: structural basis and mechanisms mediating cytoprotective and anti-inflammatory effects in bronchial epithelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "We discovered new structural diversity to a prevalent, yet medicinally underappreciated, cyanobacterial protease inhibitor scaffold and undertook comprehensive protease profiling to reveal potent and selective elastase inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Structure-activity relationship (SAR) studies and X-ray cocrystal structure analysis allowed a detailed assessment of critical and tunable structural elements.", "output": {"entities": {}}, "schema": []}
{"input": "To realize the therapeutic potential of these cyclodepsipeptides, we probed the cellular effects of a novel and representative family member, symplostatin 5 (1), which attenuated the downstream cellular effects of elastase in an epithelial lung airway model system, alleviating clinical hallmarks of chronic pulmonary diseases such as cell death, cell detachment, and inflammation.", "output": {"entities": {"chemical": [{"text": "symplostatin 5", "start": 142, "end": 156}]}}, "schema": []}
{"input": "This compound attenuated the effects of elastase on receptor activation, proteolytic processing of the adhesion protein ICAM-1, NF-kappa B activation, and transcriptomic changes, including the expression of pro-inflammatory cytokines IL1A, IL1B, and IL8.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 1 exhibited activity comparable to the clinically approved elastase inhibitor sivelestat in short-term assays and demonstrated superior sustained activity in longer-term assays.", "output": {"entities": {"chemical": [{"text": "sivelestat", "start": 87, "end": 97}]}}, "schema": []}
{"input": "A novel approach to active compounds identification based on support vector regression model and mean impact value.", "output": {"entities": {}}, "schema": []}
{"input": "Traditionally, active compounds were discovered from natural product extracts by bioassay-guided fractionation, which was with high cost and low efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "A well-trained support vector regression model based on mean impact value was used to identify lead active compounds on inhibiting the proliferation of the HeLa cells in curcuminoids from Curcuma longa L.", "output": {"entities": {"chemical": [{"text": "curcuminoids", "start": 170, "end": 182}]}}, "schema": []}
{"input": "Eight constituents possessing the high absolute mean impact value were identified to have significant cytotoxicity, and the cytotoxic effect of these constituents was partly confirmed by subsequent MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays and previous reports.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 198, "end": 201}, {"text": "3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide", "start": 203, "end": 265}]}}, "schema": []}
{"input": "In the dosage range of 0. 2-211. 2, 0. 1-140. 2, 0. 2-149. 9 mu m, 50% inhibiting concentrations (IC50) of curcumin, demethoxycurcumin, and bisdemethoxycurcumin were 26. 99 +/- 1. 11, 19. 90 +/- 1. 22, and 35. 51 +/- 7. 29 mu m, respectively.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 107, "end": 115}, {"text": "demethoxycurcumin", "start": 117, "end": 134}, {"text": "bisdemethoxycurcumin", "start": 140, "end": 160}]}}, "schema": []}
{"input": "It was demonstrated that our method could successfully identify lead active compounds in curcuminoids from Curcuma longa L. prior to bioassay-guided separation.", "output": {"entities": {"chemical": [{"text": "curcuminoids", "start": 89, "end": 101}]}}, "schema": []}
{"input": "The use of a support vector regression model combined with mean impact value analysis could provide an efficient and economical approach for drug discovery from natural products.", "output": {"entities": {}}, "schema": []}
{"input": "Complementary and Alternative Medicine Use Among Patients with Thyroid Cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Background: To report on the incidence and predictors of use of complementary and alternative medicine (CAM) among patients with thyroid cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Methods: Data were collected using a web-based online anonymous survey under IRB approval from Boston University.", "output": {"entities": {}}, "schema": []}
{"input": "This report is based on 1327 responses from subjects with thyroid cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Patient factors were compared by univariate and multivariate analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Results: After excluding multivitamin and prayer use, 74% (n = 941) used CAM.", "output": {"entities": {}}, "schema": []}
{"input": "Respondents were primarily over age 40, White, female and hold a college degree.", "output": {"entities": {}}, "schema": []}
{"input": "The top five modalities were massage therapy, chiropraxy, special diets, herbal tea and yoga.", "output": {"entities": {}}, "schema": []}
{"input": "Few patients reported perceiving a particular modality had a negative effect on treatment.", "output": {"entities": {}}, "schema": []}
{"input": "CAM was more often used for treatment of symptoms (73%) than as part of thyroid cancer treatment (27%).", "output": {"entities": {}}, "schema": []}
{"input": "Multivariable logistic regression demonstrated that patients reporting a poor health status, higher education, cardiovascular disease, pulmonary symptoms, or persistent, recurrent or metastatic disease were more likely to use CAM for treatment of thyroid cancer symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "Nearly 1/3 of respondents reported their CAM use was neither known, prescribed nor asked about by their physicians.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: In comparison to national surveys of the general U. S. population, patients with thyroid cancer use CAM therapies twice as often and report their use far less often.", "output": {"entities": {}}, "schema": []}
{"input": "Physicians who treat patients with thyroid cancer should be aware of these data to further assist in their assessment and care.", "output": {"entities": {}}, "schema": []}
{"input": "Cleavage of DNA by proton-coupled electron transfer to a photoexcited, hydrated Ru (II) 1, 10-phenanthroline-5, 6-dione complex.", "output": {"entities": {"chemical": [{"text": "hydrated Ru (II) 1, 10-phenanthroline-5, 6-dione", "start": 71, "end": 119}]}}, "schema": []}
{"input": "Visible light irradiation of a ruthenium (II) quinone-containing complex, [(phen) (2) Ru (phendione)] (2 +) (1 (2 +)), where phendione = 1, 10-phenanthroline-5, 6-dione, leads to DNA cleavage in an oxygen independent manner.", "output": {"entities": {"chemical": [{"text": "ruthenium (II) quinone", "start": 31, "end": 53}, {"text": "[(phen) (2) Ru (phendione)] (2 +)", "start": 74, "end": 107}, {"text": "phendione", "start": 125, "end": 134}, {"text": "1, 10-phenanthroline-5, 6-dione", "start": 137, "end": 168}, {"text": "oxygen", "start": 198, "end": 204}]}}, "schema": []}
{"input": "A combination of NMR analyses, transient absorption spectroscopy, and fluorescence measurements in water and acetonitrile reveal that complex 1 (2 +) must be hydrated at the quinone functionality, giving [(phen) (2) Ru (phenH (2) O)] (2 +) (1H (2) O (2 +), where phenH (2) O = 1, 10-phenanthroline-6-one-5-diol), in order to access a long-lived (3) MLCT (hydrate) state (tau ~ 360 ns in H (2) O) which is responsible for DNA cleavage.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 109, "end": 121}, {"text": "quinone", "start": 174, "end": 181}, {"text": "[(phen) (2) Ru (phenH (2) O)] (2 +)", "start": 204, "end": 239}, {"text": "1H (2) O (2 +)", "start": 241, "end": 255}, {"text": "phenH (2) O", "start": 263, "end": 274}, {"text": "1, 10-phenanthroline-6-one-5-diol", "start": 277, "end": 310}, {"text": "hydrate", "start": 355, "end": 362}, {"text": "H (2) O", "start": 387, "end": 394}]}}, "schema": []}
{"input": "In effect, hydration at one of the carbonyl functions effectively eliminates the low-energy (3) MLCT (SQ) state (Ru (III) phen-semiquinone radical anion) as the predominant nonradiative decay pathway.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 35, "end": 43}, {"text": "Ru (III) phen-semiquinone", "start": 113, "end": 138}]}}, "schema": []}
{"input": "This (3) MLCT (SQ) state is very short-lived (< 1 ns) as expected from the energy gap law for nonradiative decay, (1) and too short-lived to be the photoactive species.", "output": {"entities": {}}, "schema": []}
{"input": "The resulting excited state in 1H (2) O (2 +) * has photophysical properties similar to the (3) MLCT state in [Ru (phen) (3)] (2 +) * with the added functionality of basic sites at the ligand periphery.", "output": {"entities": {"chemical": [{"text": "1H (2) O (2 +)", "start": 31, "end": 45}, {"text": "[Ru (phen) (3)] (2 +)", "start": 110, "end": 131}]}}, "schema": []}
{"input": "Whereas [Ru (phen) (3)] (2 +) * does not show direct DNA cleavage, the deprotonated form of 1H (2) O (2 +) * does via a proton-coupled electron transfer (PCET) mechanism where the peripheral basic oxygen sites act as the proton acceptor.", "output": {"entities": {"chemical": [{"text": "[Ru (phen) (3)] (2 +)", "start": 8, "end": 29}, {"text": "1H (2) O (2 +)", "start": 92, "end": 106}, {"text": "oxygen", "start": 197, "end": 203}]}}, "schema": []}
{"input": "Analysis of the small molecule byproducts of DNA scission supports the conclusion that cleavage occurs via H-atom abstraction from the sugar moieties, consistent with a PCET mechanism.", "output": {"entities": {"chemical": [{"text": "H", "start": 107, "end": 108}, {"text": "sugar", "start": 135, "end": 140}]}}, "schema": []}
{"input": "Complex 1 (2 +) is a rare example of a ruthenium complex which' turns on' both reactivity and luminescence upon switching to a hydrated state.", "output": {"entities": {"chemical": [{"text": "ruthenium", "start": 39, "end": 48}]}}, "schema": []}
{"input": "Letter to the Editor: Prescience of a Surgeon in 1980.", "output": {"entities": {}}, "schema": []}
{"input": "A photo copy of a page from an unpublished document written in 1980 by the surgeon Mr. Selwyn Taylor and entitled \" The Thyroid and the Thymus \", provides remarkable prescience concerning thyroid lymphocytic infiltrates in Graves' disease and the implications for treating or resolving exophthalmos.", "output": {"entities": {}}, "schema": []}
{"input": "Nano-optomechanical actuator and pull-back instability.", "output": {"entities": {}}, "schema": []}
{"input": "This paper studies the nonlinear behavior of a nano-optomechanical actuator, consisting of a free-standing arc in a ring resonator that is coupled to a bus waveguide through evanescent waves.", "output": {"entities": {}}, "schema": []}
{"input": "The arc deflects when a control light of a fixed wavelength and optical power is pumped into the bus waveguide, while the amount of deflection is monitored by measuring the transmission spectrum of a broadband probe light.", "output": {"entities": {}}, "schema": []}
{"input": "This nanoactuator achieves a maximal deflection of 43. 1 nm, with a resolution of 0. 28 nm.", "output": {"entities": {}}, "schema": []}
{"input": "The optical force is a nonlinear function of the deflection of the arc, leading to pull-back instability when the control light is red-tuned.", "output": {"entities": {}}, "schema": []}
{"input": "This instability is studied by a combination of experiment and modeling.", "output": {"entities": {}}, "schema": []}
{"input": "Potential applications of the nanoactuator include bio-nanomotor, optical switches, and optomechanical memories.", "output": {"entities": {}}, "schema": []}
{"input": "Increased protein sorption in poly (acrylic acid)-containing films through incorporation of comb-like polymers and film adsorption at low pH and high ionic strength.", "output": {"entities": {"chemical": [{"text": "poly (acrylic acid)", "start": 30, "end": 49}]}}, "schema": []}
{"input": "In principle, incorporation of comb-like block copolymers in multilayer polyelectrolyte films can both increase film thickness relative to coatings containing linear polymers and provide more swollen films for increased sorption of proteins.", "output": {"entities": {}}, "schema": []}
{"input": "In the absence of added salt, alternating adsorption of 5 bilayers of protonated poly (allylamine) (PAH) and comb-like poly (2-hydroxyethyl methacrylate)-graft-poly (acrylic acid) (PHEMA-g-PAA) leads to ~ 2-fold thicker coatings than adsorption of PAH and linear PAA, and the difference in the thicknesses of the two coatings increases with the number of bilayers.", "output": {"entities": {"chemical": [{"text": "poly (allylamine)", "start": 81, "end": 98}, {"text": "PAH", "start": 100, "end": 103}, {"text": "poly (2-hydroxyethyl methacrylate)-graft-poly (acrylic acid)", "start": 119, "end": 179}, {"text": "PHEMA-g-PAA", "start": 181, "end": 192}, {"text": "PAH", "start": 248, "end": 251}, {"text": "PAA", "start": 263, "end": 266}]}}, "schema": []}
{"input": "Moreover, the (PAH/PHEMA-g-PAA) n films sorb 2-to 4-fold more protein than corresponding films prepared with linear PAA, and coatings deposited at pH 3. 0 sorb more protein than coatings adsorbed at pH 5. 0, 7. 0, or 9. 0.", "output": {"entities": {"chemical": [{"text": "PAH", "start": 15, "end": 18}, {"text": "PHEMA-g-PAA", "start": 19, "end": 30}, {"text": "PAA", "start": 116, "end": 119}]}}, "schema": []}
{"input": "In fact changes in deposition pH and addition of 0. 5 M NaCl to polyelectrolyte adsorption solutions alter protein sorption more dramatically than variations in the constituent polymer architecture.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 56, "end": 60}]}}, "schema": []}
{"input": "When deposited from 0. 5 M NaCl at pH 3. 0, both (PAH/PHEMA-g-PAA) 5 and (PAH/PAA) 5 films increase in thickness more than 400% upon adsorption of lysozyme.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 27, "end": 31}, {"text": "PAH", "start": 50, "end": 53}, {"text": "PHEMA-g-PAA", "start": 54, "end": 65}, {"text": "PAH", "start": 74, "end": 77}, {"text": "PAA", "start": 78, "end": 81}]}}, "schema": []}
{"input": "These films contain a high concentration of free-COOH groups, and subsequent deprotonation of these groups at neutral pH likely contributes to increased protein binding.", "output": {"entities": {"chemical": [{"text": "COOH", "start": 49, "end": 53}]}}, "schema": []}
{"input": "Lysozyme sorption stabilizes these films, as without lysozyme films deposited at pH 3. 0 from 0. 5 M NaCl desorb at neutral pH.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 101, "end": 105}]}}, "schema": []}
{"input": "Films deposited at pH 9. 0 from 0. 5 M NaCl are more stable and also bind large amounts of lysozyme.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 39, "end": 43}]}}, "schema": []}
{"input": "The high binding capacities of these films make them attractive for potential applications in protein isolation or immobilization of enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "Denaturation-resistant bifunctional colloidal superstructures assembled via the proteinaceous barnase-barstar interface.", "output": {"entities": {}}, "schema": []}
{"input": "To date, a number of biomolecule-mediated nanoparticle self-assembly systems have been developed that are amenable to controllable disassembly under relatively gentle conditions.", "output": {"entities": {}}, "schema": []}
{"input": "However, for some applications such as design of self-assembled multifunctional theragnostic agents, high stability of the assembled structures can be of primary importance.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report extraordinarily high durability of protein-assisted nanoparticle self-assembly systems yielding bifunctional colloidal superstructures resistant to extreme denaturing conditions intolerable for most proteins (e. g., high concentrations of chaotropic agents, high temperature).", "output": {"entities": {}}, "schema": []}
{"input": "Among the tested systems (barnase-barstar (BBS), streptavidin-biotin, antibody-antigen, and protein A-immunoglobulin), the BBS is notable due to the combination of its high resistance to severe chemical perturbation and unique advantages offered by genetic engineering of this entirely protein-based system.", "output": {"entities": {"chemical": [{"text": "streptavidin", "start": 49, "end": 61}, {"text": "biotin", "start": 62, "end": 68}]}}, "schema": []}
{"input": "Comparison of the self-assembly systems shows that whereas in all cases the preassembled structures proved essentially resistant to extreme conditions, the ability of the complementary biomolecular pairs to mediate assembly of the initial biomolecule-particle conjugates differs substantially in these conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxic constituents of ethyl acetate fraction from Dianthus superbus.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 26, "end": 39}]}}, "schema": []}
{"input": "The ethyl acetate fraction (EE-DS) from Dianthus superbus was found to possess the cytotoxic activity against cancer cells in previous study.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 4, "end": 17}]}}, "schema": []}
{"input": "To investigate cytotoxic constituents, the bioassay-guided isolation of compounds from EE-DS was performed.", "output": {"entities": {}}, "schema": []}
{"input": "Two dianthramides (1 and 2), three flavonoids (3-5), two coumarins (6 and 7) and three other compounds (8-10) were obtained.", "output": {"entities": {"chemical": [{"text": "dianthramides", "start": 4, "end": 17}, {"text": "flavonoids", "start": 35, "end": 45}, {"text": "coumarins", "start": 57, "end": 66}]}}, "schema": []}
{"input": "Structures of isolated compounds were identified by spectroscopic analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxicity of the compounds against HepG2 cells was evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 1 showed the strongest cytotoxicity, compounds 10, 4, 3 and 5 had moderate cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Biosynthesis and characterization of diblock copolymer of p (3-Hydroxypropionate)-block-p (4-hydroxybutyrate) from recombinant Escherichia coli.", "output": {"entities": {"chemical": [{"text": "p (3-Hydroxypropionate)-block-p (4-hydroxybutyrate)", "start": 58, "end": 109}]}}, "schema": []}
{"input": "Poly (4-hydroxybutyrate) (P4HB) is a highly elastic polymer, whereas poly (3-hydroxypropionate) (P3HP) is a polymer with enormous tensile strength.", "output": {"entities": {"chemical": [{"text": "Poly (4-hydroxybutyrate)", "start": 0, "end": 24}, {"text": "P4HB", "start": 26, "end": 30}, {"text": "poly (3-hydroxypropionate)", "start": 69, "end": 95}, {"text": "P3HP", "start": 97, "end": 101}]}}, "schema": []}
{"input": "This study aimed to biosynthesize a block copolymer consisting of soft P4HB block with a strong P3HP block to gain unique and excellent material properties.", "output": {"entities": {"chemical": [{"text": "P4HB", "start": 71, "end": 75}, {"text": "P3HP", "start": 96, "end": 100}]}}, "schema": []}
{"input": "A recombinant Escherichia coli strain that produces homopolymers of P3HP and P4HB was employed for the block copolymer synthesis.", "output": {"entities": {"chemical": [{"text": "P3HP", "start": 68, "end": 72}, {"text": "P4HB", "start": 77, "end": 81}]}}, "schema": []}
{"input": "When the strain was grown in the presence of 1, 4-butanediol (BDO) as a 4HB precursor, P4HB block was formed.", "output": {"entities": {"chemical": [{"text": "1, 4-butanediol", "start": 45, "end": 60}, {"text": "BDO", "start": 62, "end": 65}, {"text": "4HB", "start": 72, "end": 75}, {"text": "P4HB", "start": 87, "end": 91}]}}, "schema": []}
{"input": "Sequential supplementation of 1, 3-propanediol (PDO) as a 3HP precursor allowed the strain to produce P3HP block.", "output": {"entities": {"chemical": [{"text": "1, 3-propanediol", "start": 30, "end": 46}, {"text": "PDO", "start": 48, "end": 51}, {"text": "3HP", "start": 58, "end": 61}, {"text": "P3HP", "start": 102, "end": 106}]}}, "schema": []}
{"input": "Thermal, NMR, fractionation, and mechanical characterizations confirmed the resulting polymer as a block copolymer of P3HP-b-P4HB.", "output": {"entities": {"chemical": [{"text": "P3HP-b-P4HB", "start": 118, "end": 129}]}}, "schema": []}
{"input": "Two block copolymers were formed from this study, including the P3HP-b-29% P4HB and P3HP-b-37% P4HB, they showed superior properties over random copolymers P (3HP-co-4HB).", "output": {"entities": {"chemical": [{"text": "P3HP", "start": 64, "end": 68}, {"text": "P4HB", "start": 75, "end": 79}, {"text": "P3HP", "start": 84, "end": 88}, {"text": "P4HB", "start": 95, "end": 99}, {"text": "P (3HP-co-4HB)", "start": 156, "end": 170}]}}, "schema": []}
{"input": "The block copolymers had two glass transition temperatures (Tg) and two melting temperatures (Tm).", "output": {"entities": {}}, "schema": []}
{"input": "In comparison to the homopolymers P3HP and P4HB, incorporation of block microstructure resulted in the lowering of Tm, block copolymers were revealed with higher Young' s modulus, yield strengths, and tension strengths much better than the previously reported random copolymers of similar compositions.", "output": {"entities": {"chemical": [{"text": "P3HP", "start": 34, "end": 38}, {"text": "P4HB", "start": 43, "end": 47}]}}, "schema": []}
{"input": "Block copolymerization of P3HP and P4HB adds a new vision on PHA polymerization by generation of new polymers with superior properties.", "output": {"entities": {"chemical": [{"text": "P3HP", "start": 26, "end": 30}, {"text": "P4HB", "start": 35, "end": 39}, {"text": "PHA", "start": 61, "end": 64}]}}, "schema": []}
{"input": "Neuroprotective effects of inhaled lavender oil on scopolamine-induced dementia via anti-oxidative activities in rats.", "output": {"entities": {"chemical": [{"text": "scopolamine", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Lavender is used in traditional medicines in Asia, Europe, ancient Greece and Rome, and was mentioned in the Bible and in ancient Jewish texts.", "output": {"entities": {}}, "schema": []}
{"input": "Also, lavender is reported to be an effective medical plant in treating inflammation, depression, stress and headache.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was undertaken in order to investigate the antioxidant and antiapoptotic activities of the lavender essential oils from Lavandula angustifolia ssp. angustifolia Mill. and Lavandula hybrida Rev. using superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) specific activities, total content of reduced glutathione (GSH), malondialdehyde (MDA) level (lipid peroxidation) and DNA fragmentation assays in male Wistar rats subjected to scopolamine-induced dementia rat model.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 218, "end": 228}, {"text": "glutathione", "start": 246, "end": 257}, {"text": "reduced glutathione", "start": 332, "end": 351}, {"text": "GSH", "start": 353, "end": 356}, {"text": "malondialdehyde", "start": 359, "end": 374}, {"text": "MDA", "start": 376, "end": 379}, {"text": "scopolamine", "start": 470, "end": 481}]}}, "schema": []}
{"input": "In scopolamine-treated rats, lavender essential oils showed potent antioxidant and antiapoptotic activities.", "output": {"entities": {"chemical": [{"text": "scopolamine", "start": 3, "end": 14}]}}, "schema": []}
{"input": "Subacute exposures (daily, for 7 continuous days) to lavender oils significantly increased antioxidant enzyme activities (SOD, GPX and CAT), total content of reduced GSH and reduced lipid peroxidation (MDA level) in rat temporal lobe homogenates, suggesting antioxidant potential.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 166, "end": 169}, {"text": "MDA", "start": 202, "end": 205}]}}, "schema": []}
{"input": "Also, DNA cleavage patterns were absent in the lavender groups, suggesting antiapoptotic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our results suggest that antioxidant and antiapoptotic activities of the lavender essential oils are the major mechanisms for their potent neuroprotective effects against scopolamine-induced oxidative stress in the rat brain.", "output": {"entities": {"chemical": [{"text": "scopolamine", "start": 187, "end": 198}]}}, "schema": []}
{"input": "Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats.", "output": {"entities": {"chemical": [{"text": "crocin", "start": 27, "end": 33}, {"text": "streptozotocin", "start": 66, "end": 80}]}}, "schema": []}
{"input": "Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, associated with free radical generation.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 30, "end": 44}, {"text": "STZ", "start": 46, "end": 49}]}}, "schema": []}
{"input": "In this study, we evaluated the effects of crocin on cognitive performance in ICV STZ-lesioned rats (3mg/kg bilaterally, on day 1 and 3).", "output": {"entities": {"chemical": [{"text": "crocin", "start": 43, "end": 49}, {"text": "STZ", "start": 82, "end": 85}]}}, "schema": []}
{"input": "Crocin (100mg/kg, p. o.) was administered for 21 consecutive days, starting 1h prior to the first dose of STZ.", "output": {"entities": {"chemical": [{"text": "Crocin", "start": 0, "end": 6}, {"text": "STZ", "start": 106, "end": 109}]}}, "schema": []}
{"input": "Cognitive performance was assessed using Morris water maze task while the parameters of oxidative stress assessed, were malondialdehyde (MDA) and total thiol levels besides glutathione peroxidase (GPx) activity.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 120, "end": 135}, {"text": "MDA", "start": 137, "end": 140}, {"text": "thiol", "start": 152, "end": 157}, {"text": "glutathione", "start": 173, "end": 184}]}}, "schema": []}
{"input": "STZ-lesioned rats showed a severe deficit in memory associated with elevated MDA levels, reduced GPx activity and total thiol content.", "output": {"entities": {"chemical": [{"text": "STZ", "start": 0, "end": 3}, {"text": "MDA", "start": 77, "end": 80}]}}, "schema": []}
{"input": "Crocin treatment improved cognitive performance and resulted in a significant reduction in MDA levels and elevation in total thiol content and GPx activity.", "output": {"entities": {"chemical": [{"text": "Crocin", "start": 0, "end": 6}, {"text": "MDA", "start": 91, "end": 94}, {"text": "thiol", "start": 125, "end": 130}]}}, "schema": []}
{"input": "This study demonstrates that crocin may have beneficial effects in the treatment of neurodegenerative disorders such as Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "crocin", "start": 29, "end": 35}]}}, "schema": []}
{"input": "C16 peptide shown to prevent leukocyte infiltration and alleviate detrimental inflammation in acute allergic encephalomyelitis model.", "output": {"entities": {}}, "schema": []}
{"input": "Integrins are important adhesion receptors for leukocytes binding to endothelial cellular adhesion molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies have suggested that blocking relevant integrins might prevent leukocyte infiltration and suppress clinical and pathological features of neuroinflammatory disease.", "output": {"entities": {}}, "schema": []}
{"input": "Experimental autoimmune encephalomyelitis (EAE), a rodent model of Multiple sclerosis (MS), is characterized by chronic inflammatory disorder of the central nervous system in which circulating leukocytes enter the brain and spinal cord leading to inflammation, myelin damage and subsequent paralysis.", "output": {"entities": {}}, "schema": []}
{"input": "To prove this hypothesis and explore a promising application for MS treatment, the effects of C16, an alpha nu beta 3 integrin-binding peptide, were tested in vitro and in vivo by transendothelial assay, electron microscopy observation, multiple histological and immunohistochemical staining.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed C16 inhibited transendothelial migration of the C8166-CD4 lymphoblast cells, and alleviated extensive spinal cord and brain infiltration of leukocytes and macrophages in the EAE model.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, a significant amelioration of astrogliosis and a dramatic decrease in demyelination and axonal loss were observed in C16 treated animals.", "output": {"entities": {}}, "schema": []}
{"input": "The attenuating inflammatory progression may improve the regional environment and trigger further neuroprotective effects on myelin and axons, all this suggests that C16 peptide may be a promising therapeutic agent for multiple sclerosis.", "output": {"entities": {}}, "schema": []}
{"input": "New imidazo [1, 2-a] pyridines carrying active pharmacophores: synthesis and anticonvulsant studies.", "output": {"entities": {"chemical": [{"text": "imidazo [1, 2-a] pyridines", "start": 4, "end": 30}]}}, "schema": []}
{"input": "Five new series of imidazo [1, 2-a] pyridines carrying biologically active pyrazoline (4a-e), cyanopyridone (5a, b), cyanopyridine (6a-f), 2-aminopyrimidine (7a-f) and pyrimidine-2-thione (8a-d) systems were designed and synthesized as prominent anticonvulsant agents.", "output": {"entities": {"chemical": [{"text": "imidazo [1, 2-a] pyridines", "start": 19, "end": 45}, {"text": "pyrazoline", "start": 75, "end": 85}, {"text": "cyanopyridone", "start": 94, "end": 107}, {"text": "cyanopyridine", "start": 117, "end": 130}, {"text": "2-aminopyrimidine", "start": 139, "end": 156}, {"text": "pyrimidine-2-thione", "start": 168, "end": 187}]}}, "schema": []}
{"input": "The target compounds were screened for their in vivo anticonvulsant activity following maximal electroshock (MES) and subcutaneous pentylene tetrazole (scPTZ) methods at a small test dose of 10 mg/kg.", "output": {"entities": {"chemical": [{"text": "pentylene tetrazole", "start": 131, "end": 150}]}}, "schema": []}
{"input": "Further, Rotarod toxicity method was used to study the toxicity profile of selected compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 4b, 5a, 5b, 6a, 7e and 8d possessing 4-fluorophenyl substituent at 2nd position of imidazo [1, 2-a] pyridine ring displayed potent anticonvulsant activity without displaying any toxicity.", "output": {"entities": {"chemical": [{"text": "4-fluorophenyl", "start": 47, "end": 61}, {"text": "imidazo [1, 2-a] pyridine", "start": 93, "end": 118}]}}, "schema": []}
{"input": "Enhanced activity profile was observed for new compounds in PTZ method over MES method.", "output": {"entities": {"chemical": [{"text": "PTZ", "start": 60, "end": 63}]}}, "schema": []}
{"input": "Sensitizing capacity and allergenicity of enzymatically cross-linked sodium caseinate in comparison to sodium caseinate in a mouse model for cow' s milk allergy.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 69, "end": 75}, {"text": "sodium", "start": 103, "end": 109}]}}, "schema": []}
{"input": "A transglutaminase cross-linked caseinate was designed for use in dairy products to increase the viscosity of food matrices.", "output": {"entities": {}}, "schema": []}
{"input": "The difference in structure of cross-linked caseinate might have implications for the risk of developing cow' s milk allergy.", "output": {"entities": {}}, "schema": []}
{"input": "The sensitizing capacity and the allergenicity (the potency to induce an allergic effector response) of cross-linked sodium caseinate was investigated using a mouse model for cow' s milk allergy.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 117, "end": 123}]}}, "schema": []}
{"input": "Mice were orally sensitized with cross-linked caseinate or caseinate using cholera toxin as adjuvant.", "output": {"entities": {}}, "schema": []}
{"input": "Anaphylactic shock reactions, change in body temperature, acute allergic skin response, caseinate-, cross-linked caseinate-IgE and mMCP-1 concentrations were determined after challenge with cross-linked caseinate or caseinate.", "output": {"entities": {}}, "schema": []}
{"input": "Sensitization with cross-linked caseinate did not result in anaphylactic shock symptoms, drop in body temperature or release of serum mMCP-1.", "output": {"entities": {}}, "schema": []}
{"input": "A tendency toward decreased casein-specific IgE levels was observed.", "output": {"entities": {}}, "schema": []}
{"input": "The allergenicity did not differ between both products.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that in already caseinate-sensitized mice, cross-linked caseinate did not provoke more pronounced allergenic reactions compared to sodium caseinate.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 154, "end": 160}]}}, "schema": []}
{"input": "On top of that, reduced sensitization to cross-linked caseinate was observed.", "output": {"entities": {}}, "schema": []}
{"input": "Cross-linked caseinate might therefore be an interesting new dietary concept for humans at risk for food allergy although more mechanistic studies and clinical trials are needed for validation.", "output": {"entities": {}}, "schema": []}
{"input": "Poly (styrene oxide)-poly (ethylene oxide) block copolymers: From \" classical \" chemotherapeutic nanocarriers to active cell-response inducers.", "output": {"entities": {"chemical": [{"text": "Poly (styrene oxide)-poly (ethylene oxide)", "start": 0, "end": 42}]}}, "schema": []}
{"input": "Two poly (styrene oxide)-poly (ethylene oxide) (PSO-PEO) triblock copolymers with different chain lengths were analyzed as potential chemotherapeutic nanocarriers, and their ability to inhibit the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line were measured in order to establish possible cell-responses induced by the presence of the copolymer molecules.", "output": {"entities": {"chemical": [{"text": "poly (styrene oxide)-poly (ethylene oxide)", "start": 4, "end": 46}, {"text": "PSO-PEO", "start": 48, "end": 55}]}}, "schema": []}
{"input": "Thus, EO33SO14EO33 and EO38SO10EO38 polymeric micelles were tested regarding doxorubicin (DOXO) entrapment efficiency (solubilization test), physical stability (DLS), cytocompatibility (fibroblasts), release profiles at various pHs (in vitro tests), as well as P-gp inhibition and evasion and cytotoxicity of the DOXO-loaded micelles in an ovarian MDR NCI-ADR/RES cell line and in DOXO-sensitive MCF-7 cells.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 77, "end": 88}, {"text": "DOXO", "start": 90, "end": 94}, {"text": "DOXO", "start": 313, "end": 317}, {"text": "DOXO", "start": 381, "end": 385}]}}, "schema": []}
{"input": "EO33SO14EO33 and EO38SO10EO38 formed spherical micelles (~ 13nm) at lower concentration than other copolymers under clinical evaluation (e. g. Pluronic (R)), exhibited 0. 2% to 1. 8% loading capacity, enhancing more than 60 times drug apparent solubility, and retained the cargo for long time.", "output": {"entities": {"chemical": [{"text": "Pluronic", "start": 143, "end": 151}]}}, "schema": []}
{"input": "The copolymer unimers inhibited P-gp ATPase activity in a similar way as Pluronic P85, favoring DOXO accumulation in the resistant cell line, but not in the sensitive cell line.", "output": {"entities": {"chemical": [{"text": "Pluronic P85", "start": 73, "end": 85}, {"text": "DOXO", "start": 96, "end": 100}]}}, "schema": []}
{"input": "DOXO loaded in the micelles accumulated more slowly inside the cells, but caused greater cytotoxicity than free drug solutions in the NCI-ADR-RES cell line, which overexpressed P-gp.", "output": {"entities": {"chemical": [{"text": "DOXO", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Hence, PSO-PEO block copolymers offer interesting features as new biological response modifiers to be used in the design of efficient nanocarriers for cancer chemotherapy.", "output": {"entities": {"chemical": [{"text": "PSO-PEO", "start": 7, "end": 14}]}}, "schema": []}
{"input": "Encapsulation of Nod1 and Nod2 receptor ligands into poly (lactic acid) nanoparticles potentiates their immune properties.", "output": {"entities": {"chemical": [{"text": "poly (lactic acid)", "start": 53, "end": 71}]}}, "schema": []}
{"input": "Most successful vaccines are able to induce persistent antibody responses that can last a lifetime.", "output": {"entities": {}}, "schema": []}
{"input": "Emerging evidences indicate that activation of immune cells through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) or Nod-like receptors (NLRs) may be critical mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Among PRRs, the use of TLR ligands as adjuvants is already largely described whereas the use of NLRs ligands remains largely unexplored.", "output": {"entities": {}}, "schema": []}
{"input": "As activation of intracytoplasmic NLRs is able to induce proinflammatory molecules, the added value of encapsulation of Nod1 and Nod2 receptor ligands into Poly (Lactic Acid) (PLA) biodegradable nanocarriers to modulate their immune properties on human dendritic cells (DCs) maturation has been evaluated.", "output": {"entities": {"chemical": [{"text": "Poly (Lactic Acid)", "start": 156, "end": 174}, {"text": "PLA", "start": 176, "end": 179}]}}, "schema": []}
{"input": "Their ability to induce systemic immune responses in mice was also measured and compared to free ligands and the Alum adjuvant.", "output": {"entities": {}}, "schema": []}
{"input": "Nod ligands encapsulated into PLA NPs were efficiently taken up by DCs and subsequently induced a strong up-regulation of maturation markers and the enhancement of proinflammatory cytokine secretion by DCs.", "output": {"entities": {"chemical": [{"text": "PLA", "start": 30, "end": 33}]}}, "schema": []}
{"input": "Furthermore, co-injection of encapsulated Nod-ligands with PLA particles carrying Gag p24 HIV-1 antigen allowed a 100 fold increase in antibody responses in comparison to Alum.", "output": {"entities": {"chemical": [{"text": "PLA", "start": 59, "end": 62}]}}, "schema": []}
{"input": "These results suggest that encapsulation of Nod ligands into PLA-NPs could be an effective way to improve vaccine efficiency.", "output": {"entities": {"chemical": [{"text": "PLA", "start": 61, "end": 64}]}}, "schema": []}
{"input": "PIM1 kinase inhibitors induce radiosensitization in non-small cell lung cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Radiotherapy plays a critical role in the treatment of non-small cell lung cancer (NSCLC).", "output": {"entities": {}}, "schema": []}
{"input": "However, radioresistance is a major barrier against increasing the efficiency of radiotherapy for NSCLC.", "output": {"entities": {}}, "schema": []}
{"input": "To understand the mechanisms underlying NSCLC radioresistance, we previously focused on the potential involvement of PIM1, PRAS40, FOXO3a, 14-3-3, and protein phosphatases.", "output": {"entities": {}}, "schema": []}
{"input": "Among these proteins, PIM1 functioned as an oncogene and was found to act as a crucial mediator in radioresistant NSCLC cells.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we investigated the use of PIM1-specific inhibitors as novel therapeutic drugs to regulate radiosensitivity in NSCLC.", "output": {"entities": {}}, "schema": []}
{"input": "After structure-based drug selection, SGI-1776, ETP-45299, and tryptanthrin were selected as candidates of PIM1 inhibitors that act as radiosensitizers.", "output": {"entities": {"chemical": [{"text": "SGI-1776", "start": 38, "end": 46}, {"text": "ETP-45299", "start": 48, "end": 57}, {"text": "tryptanthrin", "start": 63, "end": 75}]}}, "schema": []}
{"input": "With irradiation, these drugs inhibited only PIM1 kinase activity without affecting PIM1 mRNA/protein levels or cellular localization.", "output": {"entities": {}}, "schema": []}
{"input": "When PIM1 kinase activity was suppressed by these inhibitors, PRAS40 was not phosphorylated.", "output": {"entities": {}}, "schema": []}
{"input": "Consequently, unphosphorylated PRAS40 did not form trimeric complexes with 14-3-3 and FOXO3a, leading to increased nuclear localization of FOXO3a.", "output": {"entities": {}}, "schema": []}
{"input": "Nuclear FOXO3a promoted the expression of pro-apoptotic proteins such as Bim and FasL, resulting in a radiosensitizing effect on radioresistant NSCLC cells.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, an in vivo xenograft mouse model confirmed this radiosensitizing effect induced by PIM1 inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "In these model systems, tumor volume was significantly reduced by a combinational treatment with irradiation and PIM1 inhibitors compared to irradiation alone.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our findings provided evidence that PIM1-specific inhibitors, SGI-1776, ETP-45299, and tryptanthrin, can act as novel radiosensitizers to enhance the efficacy of radiotherapy by inhibiting irradiation-induced signaling pathway associated with radioresistance.", "output": {"entities": {"chemical": [{"text": "SGI-1776", "start": 78, "end": 86}, {"text": "ETP-45299", "start": 88, "end": 97}, {"text": "tryptanthrin", "start": 103, "end": 115}]}}, "schema": []}
{"input": "Differential regulation of drug transporter expression by all-trans retinoic acid in hepatoma HepaRG cells and human hepatocytes.", "output": {"entities": {"chemical": [{"text": "all-trans retinoic acid", "start": 58, "end": 81}]}}, "schema": []}
{"input": "All-trans retinoic acid (atRA) is the active form of vitamin A, known to activate retinoid receptors, especially the heterodimer retinoid X receptor (RXR): retinoic acid receptor (RAR) that otherwise may play a role in regulation of some drug transporters.", "output": {"entities": {"chemical": [{"text": "All-trans retinoic acid", "start": 0, "end": 23}, {"text": "atRA", "start": 25, "end": 29}, {"text": "vitamin A", "start": 53, "end": 62}, {"text": "retinoic acid", "start": 156, "end": 169}]}}, "schema": []}
{"input": "The present study was designed to characterize the nature of human hepatic transporters that may be targeted by atRA and the heterodimer RXR: RAR.", "output": {"entities": {"chemical": [{"text": "atRA", "start": 112, "end": 116}]}}, "schema": []}
{"input": "Exposure of human hepatoma HepaRG cells and primary human hepatocytes to 5 mu M atRA down-regulated mRNA levels of various sinusoidal solute carrier (SLC) influx transporters, including organic anion transporting polypeptide (OATP) 2B1, OATP1B1, organic cation transporter (OCT) 1 and organic anion transporter (OAT) 2, and induced those of the canalicular breast cancer resistance protein (BCRP).", "output": {"entities": {"chemical": [{"text": "atRA", "start": 80, "end": 84}]}}, "schema": []}
{"input": "The retinoid concomitantly reduced protein expression of OATP2B1 and OATP1B1 and activity of OATPs and OCT1 and induced BCRP protein expression in HepaRG cells.", "output": {"entities": {}}, "schema": []}
{"input": "Some transporters such as OATP1B3 and the bile salt export pump (BSEP) were however down-regulated by atRA in primary human hepatocytes, but induced in HepaRG cells, thus pointing out discrepancies between these two liver cell models in terms of detoxifying protein regulation.", "output": {"entities": {"chemical": [{"text": "atRA", "start": 102, "end": 106}]}}, "schema": []}
{"input": "atRA-mediated repressions of OATP2B1, OATP1B1, OAT2 and OCT1 mRNA expression were finally shown to be counteracted by knocking-down expression of RAR alpha and RXR alpha through siRNA transfection in HepaRG cells.", "output": {"entities": {"chemical": [{"text": "atRA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "atRA thus differentially regulated human hepatic drug transporters, mainly in a RXR: RAR-dependent manner, therefore establishing retinoids and retinoid receptors as modulators of liver drug transporter expression.", "output": {"entities": {"chemical": [{"text": "atRA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "1, 2, 3, 4, 6 Penta-O-galloyl-beta-d-glucose, a bioactivity guided isolated compound from Mangifera indica inhibits 11 beta-HSD-1 and ameliorates high fat diet-induced diabetes in C57BL/6 mice.", "output": {"entities": {"chemical": [{"text": "1, 2, 3, 4, 6 Penta-O-galloyl-beta-d-glucose", "start": 0, "end": 44}]}}, "schema": []}
{"input": "Methanolic leaf extract of Mangifera indica (MEMI) was subjected to bioactivity guided fractionation in order to identify the active antidiabetic constituent.", "output": {"entities": {}}, "schema": []}
{"input": "32 fractions were evaluated for possible 11 beta-HSD-1 inhibition activity under in vitro conditions.", "output": {"entities": {}}, "schema": []}
{"input": "The EA-7/8-9/10-4 fraction was evolved as a most potent fraction among all the fractions and it was identified as well known gallotannin compound 1, 2, 3, 4, 6 penta-O-galloyl-beta-d-glucose (PGG) by spectral analysis.", "output": {"entities": {"chemical": [{"text": "gallotannin", "start": 125, "end": 136}, {"text": "1, 2, 3, 4, 6 penta-O-galloyl-beta-d-glucose", "start": 146, "end": 190}, {"text": "PGG", "start": 192, "end": 195}]}}, "schema": []}
{"input": "Based on these results the PGG was further evaluated in ex vivo 11 beta-HSD-1 inhibition assay and high fat diet (HFD)-induced diabetes in male C57BL/6 mice.", "output": {"entities": {"chemical": [{"text": "PGG", "start": 27, "end": 30}]}}, "schema": []}
{"input": "Single dose (10, 25, 50 and 100mg/kg) of PGG and carbenoxolone (CBX) have dose dependently inhibited the 11 beta-HSD-1 activity in liver and adipose tissue.", "output": {"entities": {"chemical": [{"text": "PGG", "start": 41, "end": 44}, {"text": "carbenoxolone", "start": 49, "end": 62}, {"text": "CBX", "start": 64, "end": 67}]}}, "schema": []}
{"input": "Furthermore, HFD appraisal to male C57BL/6 mice caused severe hyperglycemia, hypertriglyceridemia, elevated levels of plasma corticosterone and insulin, increased liver and white adipose mass with increase in body weight was observed compare to normal control.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 125, "end": 139}]}}, "schema": []}
{"input": "Also, oral glucose tolerance was significantly impaired compare to normal control.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 11, "end": 18}]}}, "schema": []}
{"input": "Interestingly, post-treatment with PGG for 21 days had alleviated the HFD-induced biochemical alterations and improved oral glucose tolerance compare to HFD-control.", "output": {"entities": {"chemical": [{"text": "PGG", "start": 35, "end": 38}, {"text": "glucose", "start": 124, "end": 131}]}}, "schema": []}
{"input": "In conclusion, the PGG isolated from MEMI inhibits 11 beta-HSD-1 activity and ameliorates HFD-induced diabetes in male C57BL/6 mice.", "output": {"entities": {"chemical": [{"text": "PGG", "start": 19, "end": 22}]}}, "schema": []}
{"input": "History of scorpion antivenom: One Arizonan' s view.", "output": {"entities": {}}, "schema": []}
{"input": "This paper was originally presented as the Elsevier Lecture in July, 2012 at the International Society on Toxinology/Venom Week combined meeting in Honolulu, Hawaii.", "output": {"entities": {}}, "schema": []}
{"input": "In it, the author addresses the ancient history of venom and immunity, from the Silurian Era to the 1890s; the development of the first antivenoms; the impact of shifting political and economic pressures; the special case of Arizona; the relative stability of the 1960s through 1990s; the transition to regulatory compliance that took place at the time of the author' s own research; and concluding thoughts regarding the instability of apparent success.", "output": {"entities": {}}, "schema": []}
{"input": "Labdane diterpenoids and lignans from Calocedrus macrolepis.", "output": {"entities": {"chemical": [{"text": "Labdane diterpenoids", "start": 0, "end": 20}, {"text": "lignans", "start": 25, "end": 32}]}}, "schema": []}
{"input": "Three new labdane diterpenoids, calomacrins A-C (1-3), and a new diaryl butyrolactone-type lignan, calomacrol A (8), as well as four known labdane diterpenoids and six known lignans, were isolated from the twigs and leaves of Calocedrus macrolepis.", "output": {"entities": {"chemical": [{"text": "labdane diterpenoids", "start": 10, "end": 30}, {"text": "calomacrins A-C", "start": 32, "end": 47}, {"text": "diaryl butyrolactone", "start": 65, "end": 85}, {"text": "lignan", "start": 91, "end": 97}, {"text": "calomacrol A", "start": 99, "end": 111}, {"text": "labdane diterpenoids", "start": 139, "end": 159}, {"text": "lignans", "start": 174, "end": 181}]}}, "schema": []}
{"input": "Structures of the new compounds were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 3-14 were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Tamoxifen magnifies therapeutic impact of ceramide in human colorectal cancer cells independent of p53.", "output": {"entities": {"chemical": [{"text": "Tamoxifen", "start": 0, "end": 9}, {"text": "ceramide", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Poor prognosis in patients with later stage colorectal cancer (CRC) necessitates the search for new treatment strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Ceramide, because of its role in orchestrating death cascades in cancer cells, is a versatile alternative.", "output": {"entities": {"chemical": [{"text": "Ceramide", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Ceramide can be generated by exposure to chemotherapy or ionizing radiation, or it can be administered in the form of short-chain analogs (C6-ceramide).", "output": {"entities": {"chemical": [{"text": "Ceramide", "start": 0, "end": 8}, {"text": "C6-ceramide", "start": 139, "end": 150}]}}, "schema": []}
{"input": "Because intracellular P-glycoprotein (P-gp) plays a role in catalyzing the conversion of ceramide to higher sphingolipids, we hypothesized that administration of P-gp antagonists with C6-ceramide would magnify cell death cascades.", "output": {"entities": {"chemical": [{"text": "ceramide", "start": 89, "end": 97}, {"text": "sphingolipids", "start": 108, "end": 121}, {"text": "C6-ceramide", "start": 184, "end": 195}]}}, "schema": []}
{"input": "Human CRC cell lines were employed, HCT-15, HT-29, and LoVo.", "output": {"entities": {}}, "schema": []}
{"input": "The addition of either tamoxifen, VX-710, verapamil, or cyclosporin A, antagonists of P-gp, enhanced C6-ceramide cytotoxicity in all cell lines.", "output": {"entities": {"chemical": [{"text": "tamoxifen", "start": 23, "end": 32}, {"text": "VX-710", "start": 34, "end": 40}, {"text": "verapamil", "start": 42, "end": 51}, {"text": "cyclosporin A", "start": 56, "end": 69}, {"text": "C6-ceramide", "start": 101, "end": 112}]}}, "schema": []}
{"input": "In depth studies with C6-ceramide and tamoxifen in LoVo cells showed the regimen induced PARP cleavage, caspase-dependent apoptosis, mitochondrial membrane permeabilization (MMP), and cell cycle arrest at G1 and G2.", "output": {"entities": {"chemical": [{"text": "C6-ceramide", "start": 22, "end": 33}, {"text": "tamoxifen", "start": 38, "end": 47}]}}, "schema": []}
{"input": "At the molecular level, the regimen, but not single agents, induced time-dependent upregulation of tumor suppressor protein p53; however, introduction of a p53 inhibitor staved neither MMP nor apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoliposomal formulations of C6-ceramide and tamoxifen were also effective, yielding synergistic cell kill.", "output": {"entities": {"chemical": [{"text": "C6-ceramide", "start": 30, "end": 41}, {"text": "tamoxifen", "start": 46, "end": 55}]}}, "schema": []}
{"input": "We conclude that tamoxifen is a favorable adjuvant for enhancing C6-ceramide cytotoxicity in CRC, and demonstrates uniquely integrated effects.", "output": {"entities": {"chemical": [{"text": "tamoxifen", "start": 17, "end": 26}, {"text": "C6-ceramide", "start": 65, "end": 76}]}}, "schema": []}
{"input": "The high frequency of expression of P-gp in CRC presents an adventitious target for complementing ceramide-based therapies, a strategy that could hold promise for treatment of resistant disease.", "output": {"entities": {"chemical": [{"text": "ceramide", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Involvement of Src and the actin cytoskeleton in the antitumorigenic action of adenosine dialdehyde.", "output": {"entities": {"chemical": [{"text": "adenosine dialdehyde", "start": 79, "end": 99}]}}, "schema": []}
{"input": "Transmethylation is an important reaction that transfers a methyl group in S-adenosylmethionine (SAM) to substrates such as DNA, RNA, and proteins.", "output": {"entities": {"chemical": [{"text": "S-adenosylmethionine", "start": 75, "end": 95}, {"text": "SAM", "start": 97, "end": 100}]}}, "schema": []}
{"input": "It is known that transmethylation plays critical roles in various cellular responses.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we examined the effects of transmethylation on tumorigenic responses and its regulatory mechanism using an upregulation strategy of adenosylhomocysteine (SAH) acting as a negative feedback inhibitor.", "output": {"entities": {"chemical": [{"text": "adenosylhomocysteine", "start": 147, "end": 167}, {"text": "SAH", "start": 169, "end": 172}]}}, "schema": []}
{"input": "Treatment with adenosine dialdehyde (AdOx), an inhibitor of transmethylation-suppressive adenosylhomocysteine (SAH) hydrolase (SAHH), enhanced the level of SAH and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "adenosine dialdehyde", "start": 15, "end": 35}, {"text": "AdOx", "start": 37, "end": 41}, {"text": "adenosylhomocysteine", "start": 89, "end": 109}, {"text": "SAH", "start": 111, "end": 114}, {"text": "SAHH", "start": 127, "end": 131}]}}, "schema": []}
{"input": "Through immunoblotting analysis, it was found that AdOx was capable of indirectly diminishing the phosphorylation of oncogenic Src and its kinase activity.", "output": {"entities": {"chemical": [{"text": "AdOx", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Interestingly, AdOx disrupted actin cytoskeleton structures, leading to morphological changes, and suppressed the formation of a signaling complex composed of Src and p85/PI3K, which is linked to various tumorigenic responses.", "output": {"entities": {"chemical": [{"text": "AdOx", "start": 15, "end": 19}]}}, "schema": []}
{"input": "In agreement with these data, the exogenous treatment of SAH or inhibition of SAHH by specific siRNA or another type of inhibitor, 3-deazaadenosine (DAZA), similarly resulted in antitumorigenic responses, suppressive activity on Src, the alteration of actin cytoskeleton, and a change of the colocalization pattern between actin and Src.", "output": {"entities": {"chemical": [{"text": "SAH", "start": 57, "end": 60}, {"text": "3-deazaadenosine", "start": 131, "end": 147}, {"text": "DAZA", "start": 149, "end": 153}]}}, "schema": []}
{"input": "Taken together, these results suggest that SAH/SAHH-mediated transmethylation could be linked to the tumorigenic processes through cross-regulation between the actin cytoskeleton and Src kinase activity.", "output": {"entities": {"chemical": [{"text": "SAH", "start": 43, "end": 46}]}}, "schema": []}
{"input": "Synthesis of derivatives of methyl rosmarinate and their inhibitory activities against matrix metalloproteinase-1 (MMP-1).", "output": {"entities": {"chemical": [{"text": "methyl rosmarinate", "start": 28, "end": 46}]}}, "schema": []}
{"input": "A series of MMP-1 inhibitors have been identified based upon a methyl rosmarinate scaffold using structure-based drug design methods.", "output": {"entities": {"chemical": [{"text": "methyl rosmarinate", "start": 63, "end": 81}]}}, "schema": []}
{"input": "The best compound in the series showed an IC50 value of 0. 4 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "A docking study was conducted for compound (S)-10n in order to investigate its binding interactions with MMP-1.", "output": {"entities": {}}, "schema": []}
{"input": "The structure-activity relationships (SAR) were also briefly discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Useful SAR was established which provides important guidelines for the design of future generations of potent inhibitors against MMP-1.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis and anticancer properties of 5-arylbenzoxepins as conformationally restricted isocombretastatin A-4 analogs.", "output": {"entities": {"chemical": [{"text": "5-arylbenzoxepins", "start": 47, "end": 64}, {"text": "isocombretastatin A-4", "start": 96, "end": 117}]}}, "schema": []}
{"input": "A series of novel benzoxepins 6 was designed and prepared as rigid-isoCA-4 analogs according to a convergent strategy using the coupling of N-tosylhydrazones with aryl iodides under palladium catalysis.", "output": {"entities": {"chemical": [{"text": "benzoxepins", "start": 18, "end": 29}, {"text": "isoCA-4", "start": 67, "end": 74}, {"text": "N-tosylhydrazones", "start": 140, "end": 157}, {"text": "aryl iodides", "start": 163, "end": 175}, {"text": "palladium", "start": 182, "end": 191}]}}, "schema": []}
{"input": "The most potent compound 6b, having the greatest resemblance to CA-4 and isoCA-4 displayed antiproliferative activity at nanomolar concentrations against various cancer cell lines and inhibited tubulin assembly at a micromolar range.", "output": {"entities": {"chemical": [{"text": "CA-4", "start": 64, "end": 68}, {"text": "isoCA-4", "start": 73, "end": 80}]}}, "schema": []}
{"input": "In addition, benzoxepin 6b led to the arrest of HCT116, K562, H1299 and MDA-MB231 cancer cell lines in the G2/M phase of the cell cycle, and strongly induced apoptosis at low concentrations.", "output": {"entities": {"chemical": [{"text": "benzoxepin", "start": 13, "end": 23}]}}, "schema": []}
{"input": "Docking studies demonstrated that benzoxepin 6b adopt an orientation similar to that of isoCA-4 at the colchicine binding site on beta-tubulin.", "output": {"entities": {"chemical": [{"text": "benzoxepin", "start": 34, "end": 44}, {"text": "isoCA-4", "start": 88, "end": 95}]}}, "schema": []}
{"input": "Cytotoxicity of lapachol, beta-lapachone and related synthetic 1, 4-naphthoquinones against oesophageal cancer cells.", "output": {"entities": {"chemical": [{"text": "lapachol", "start": 16, "end": 24}, {"text": "beta-lapachone", "start": 26, "end": 40}, {"text": "1, 4-naphthoquinones", "start": 63, "end": 83}]}}, "schema": []}
{"input": "Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells.", "output": {"entities": {"chemical": [{"text": "Naphthoquinones", "start": 0, "end": 15}]}}, "schema": []}
{"input": "The secondary metabolites lapachol, alpha-and beta-lapachone and a series of 25 related synthetic 1, 4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1).", "output": {"entities": {"chemical": [{"text": "alpha-and beta-lapachone", "start": 36, "end": 60}, {"text": "1, 4-naphthoquinones", "start": 98, "end": 118}]}}, "schema": []}
{"input": "Most of the compounds exhibited enhanced cytotoxicity (IC50 1. 6-11. 7 mu M) compared to the current drug of choice cisplatin (IC50 = 16. 5 mu M).", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 116, "end": 125}]}}, "schema": []}
{"input": "This study also established that the two new synthetic halogenated compounds 12a and 16a (IC50 = 3. 0 and 7. 3 mu M) and the previously reported compound 11a (IC50 = 3. 9 mu M), were non-toxic to NIH3T3 normal fibroblast cells.", "output": {"entities": {}}, "schema": []}
{"input": "Cell death of oesophageal cancer cells by processes involving PARP cleavage caused by 11a was shown to be associated with elevated c-Jun levels, suggesting a role for this pathway in the mechanism of action of this cohort of naphthoquinone compounds.", "output": {"entities": {"chemical": [{"text": "naphthoquinone", "start": 225, "end": 239}]}}, "schema": []}
{"input": "Synthesis of an MIF-1 analogue containing enantiopure (S)-alpha-trifluoromethyl-proline and biological evaluation on nociception.", "output": {"entities": {"chemical": [{"text": "MIF-1", "start": 16, "end": 21}, {"text": "(S)-alpha-trifluoromethyl-proline", "start": 54, "end": 87}]}}, "schema": []}
{"input": "The synthesis and the effect of a novel MIF-1 analogue on nociception during acute pain in rat model are reported.", "output": {"entities": {"chemical": [{"text": "MIF-1", "start": 40, "end": 45}]}}, "schema": []}
{"input": "The synthesis of this enantiopure trifluoromethyl group containing tripeptide was performed through a peptide coupling reaction between the HCl.", "output": {"entities": {"chemical": [{"text": "trifluoromethyl", "start": 34, "end": 49}, {"text": "tripeptide", "start": 67, "end": 77}]}}, "schema": []}
{"input": "Leu-Gly-NH2 and the (S)-alpha-Tfm-proline.", "output": {"entities": {"chemical": [{"text": "Leu-Gly-NH2", "start": 0, "end": 11}, {"text": "(S)-alpha-Tfm-proline", "start": 20, "end": 41}]}}, "schema": []}
{"input": "The analgesic effect of the CF3-(MIF-1) 2 has been evaluated in vivo on rat model by paw pressure (PP) and hot plate (HP) tests and compared to the native peptide MIF-1.", "output": {"entities": {"chemical": [{"text": "CF3-(MIF-1)", "start": 28, "end": 39}, {"text": "MIF-1", "start": 163, "end": 168}]}}, "schema": []}
{"input": "Highest analgesic effect was observed with CF3-(MIF-1) 2 only in PP test.", "output": {"entities": {"chemical": [{"text": "CF3-(MIF-1)", "start": 43, "end": 54}]}}, "schema": []}
{"input": "In order to study the mechanisms of nociception induced by the studied peptides, the involvement of the opioid and the nitric oxideergic systems was investigated.", "output": {"entities": {"chemical": [{"text": "nitric", "start": 119, "end": 125}]}}, "schema": []}
{"input": "The results are in favor of a participation of both system since pretreatment, 20 min before injection of the CF3-(MIF-1) 2, with the non-competitive antagonist of opiate receptors naloxone, the nitric oxide synthase (NOS) inhibitor l-N (G)-nitroarginine ester (l-NAME) or the nitric oxide (NO) donor l-arginine (l-Arg) significantly decreased the pain perception in PP and HP tests.", "output": {"entities": {"chemical": [{"text": "CF3-(MIF-1)", "start": 110, "end": 121}, {"text": "naloxone", "start": 181, "end": 189}, {"text": "nitric oxide", "start": 195, "end": 207}, {"text": "l-N (G)-nitroarginine ester", "start": 233, "end": 260}, {"text": "l-NAME", "start": 262, "end": 268}, {"text": "nitric oxide", "start": 277, "end": 289}, {"text": "NO", "start": 291, "end": 293}, {"text": "l-arginine", "start": 301, "end": 311}, {"text": "l-Arg", "start": 313, "end": 318}]}}, "schema": []}
{"input": "Synthesis, characterization, cytotoxicity and antimicrobial studies on bis (N-furfuryl-N-(2-phenylethyl) dithiocarbamato-S, S') zinc (II) and its nitrogen donor adducts.", "output": {"entities": {"chemical": [{"text": "bis (N-furfuryl-N-(2-phenylethyl) dithiocarbamato-S, S') zinc (II)", "start": 71, "end": 137}, {"text": "nitrogen", "start": 146, "end": 154}]}}, "schema": []}
{"input": "[Zn (fpedtc) 2] (1), [Zn (fpedtc) 2 (py)] (2), [Zn (fpedtc) 2 (1, 10-phen)] (3) and [Zn (fpedtc) 2 (2, 2'-bipy)] (4) (where fpedtc = N-furfuryl-N-(2-phenylethyl) dithiocarbamate, py = pyridine, 1, 10-phen = 1, 10-phenanthroline and 2, 2'-bipy = 2, 2'-bipyridine) were synthesized.", "output": {"entities": {"chemical": [{"text": "Zn (fpedtc) 2", "start": 1, "end": 14}, {"text": "Zn (fpedtc) 2 (py)", "start": 22, "end": 40}, {"text": "Zn (fpedtc) 2 (1, 10-phen)", "start": 48, "end": 74}, {"text": "Zn (fpedtc) 2 (2, 2'-bipy)", "start": 85, "end": 111}, {"text": "fpedtc", "start": 124, "end": 130}, {"text": "N-furfuryl-N-(2-phenylethyl) dithiocarbamate", "start": 133, "end": 177}, {"text": "pyridine", "start": 184, "end": 192}, {"text": "1, 10-phen", "start": 194, "end": 204}, {"text": "1, 10-phenanthroline", "start": 207, "end": 227}, {"text": "2, 2'-bipy", "start": 232, "end": 242}, {"text": "2, 2'-bipyridine", "start": 245, "end": 261}]}}, "schema": []}
{"input": "Characterization of the complexes were achieved by IR and NMR ((1) H and (13) C) spectra and in addition, for 2 and 3, by X-ray crystallography.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 63, "end": 68}, {"text": "(13) C", "start": 73, "end": 79}]}}, "schema": []}
{"input": "Single crystal X-ray structural analysis of 2 and 3 showed that complex 2 is almost half way between trigonal bipyramidal and square pyramidal and complex 3 has a distorted octahedral geometry.", "output": {"entities": {}}, "schema": []}
{"input": "Zn-N distances in 2 is shorter than that found in a six coordinate complex 3 due to the change in coordination number.", "output": {"entities": {"chemical": [{"text": "Zn", "start": 0, "end": 2}, {"text": "N", "start": 3, "end": 4}]}}, "schema": []}
{"input": "These complexes were also screened for in vitro antibacterial and antifungal activities and significant activities have been found.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro cytotoxic activity of all the synthesized complexes was evaluated on HeLa cell line.", "output": {"entities": {}}, "schema": []}
{"input": "Complex 1 exhibits maximum inhibitory effect at a concentration of 40 mu g mL (-1) on HeLa cell line.", "output": {"entities": {}}, "schema": []}
{"input": "Novel agmatine dipeptide inhibitors against the West Nile virus NS2B/NS3 protease: A P3 and N-cap optimization study.", "output": {"entities": {"chemical": [{"text": "agmatine dipeptide", "start": 6, "end": 24}]}}, "schema": []}
{"input": "This communication describes the synthesis and inhibitory activities of thirty-seven novel C-terminal agmatine dipeptides used as screening compounds to study the structure-activity relationship between active-site peptidomimetics and the West Nile virus (WNV) NS2B/NS3 serine protease.", "output": {"entities": {"chemical": [{"text": "C", "start": 91, "end": 92}, {"text": "agmatine dipeptides", "start": 102, "end": 121}, {"text": "serine", "start": 270, "end": 276}]}}, "schema": []}
{"input": "Our efforts lead to the discovery of a novel agmatine dipeptide inhibitor (compound 33, IC50 2. 6 +/- 0. 3 mu M) with improved inhibitory activity in comparison to the most potent inhibitor described in our recent report [IC50 4. 7 +/- 1. 2 mu M; Lim et al., Eur. J. Med. Chem. 46 (2011) 3130-3134].", "output": {"entities": {"chemical": [{"text": "agmatine dipeptide", "start": 45, "end": 63}]}}, "schema": []}
{"input": "In addition, our study cleared the contention surrounding the previous X-ray co-crystallization study and an enzyme inhibition report on the binding conformation adopted by active-site peptide aldehydes.", "output": {"entities": {"chemical": [{"text": "aldehydes", "start": 193, "end": 202}]}}, "schema": []}
{"input": "Our data should provide valuable insights into the design of future peptidomimetic antivirals against WNV infections.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, pharmacological evaluation and QSAR modeling of mono-substituted 4-phenylpiperidines and 4-phenylpiperazines.", "output": {"entities": {"chemical": [{"text": "4-phenylpiperidines", "start": 76, "end": 95}, {"text": "4-phenylpiperazines", "start": 100, "end": 119}]}}, "schema": []}
{"input": "A series of mono-substituted 4-phenylpiperidines and-piperazines have been synthesized and their effects on the dopaminergic system tested in vivo.", "output": {"entities": {"chemical": [{"text": "mono-substituted 4-phenylpiperidines and-piperazines", "start": 12, "end": 64}]}}, "schema": []}
{"input": "The structure activity relationship (SAR) revealed that the position and physicochemical character of the aromatic substituent proved to be critical for the levels of 3, 4-dihydroxyphenylacetic acid (DOPAC) in the brain of freely moving rats.", "output": {"entities": {"chemical": [{"text": "3, 4-dihydroxyphenylacetic acid", "start": 167, "end": 198}, {"text": "DOPAC", "start": 200, "end": 205}]}}, "schema": []}
{"input": "In order to investigate how the structural properties of these compounds affect the response, a set of tabulated and calculated physicochemical descriptors were modeled against the in vivo effects using partial least square (PLS) regression.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the binding affinities to the dopamine D2 (DA D2) receptor and monoamine oxidase A (MAO A) enzyme were determined for a chosen subset and QSAR models using the same descriptors as in the in vivo model were produced to investigate the mechanisms leading to the observed DOPAC response.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 43, "end": 51}, {"text": "monoamine", "start": 76, "end": 85}, {"text": "DOPAC", "start": 282, "end": 287}]}}, "schema": []}
{"input": "These models, in combination with a strong correlation between the levels of striatal DOPAC and the affinities to DA D2 and MAO A, provides a comprehensive understanding of the biological response for compounds in this class.", "output": {"entities": {"chemical": [{"text": "DOPAC", "start": 86, "end": 91}]}}, "schema": []}
{"input": "Magnetic field triggered drug release from polymersomes for cancer therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Local and temporal control of drug release has for long been a main focus in the development of novel drug carriers.", "output": {"entities": {}}, "schema": []}
{"input": "Polymersomes, which can load both hydrophilic and hydrophobic species and, at the same time, be tailored to respond to a desired stimulus, have drawn much attention over the last decade.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe polymersomes able to encapsulate up to 6% (w/w) of doxorubicin (DOX) together with 30% (w/w) of superparamagnetic iron oxide nanoparticles (USPIO; gamma-Fe (2) O (3)).", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 68, "end": 79}, {"text": "DOX", "start": 81, "end": 84}, {"text": "iron oxide", "start": 131, "end": 141}, {"text": "gamma-Fe (2) O (3)", "start": 164, "end": 182}]}}, "schema": []}
{"input": "Upon internalization in HeLa cells and when a high frequency AC magnetic field (14mT at 750kHz) was applied, the developed delivery system elicited an 18% increase in cell toxicity, associated with augmented DOX release kinetics.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 208, "end": 211}]}}, "schema": []}
{"input": "In order to ensure that the observed cytotoxicity arose from the increased doxorubicin release and not from a pure magnetic hyperthermia effect, polymersomes loaded with magnetic nanoparticles alone were also tested.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 75, "end": 86}]}}, "schema": []}
{"input": "In this case, no increased toxicity was observed.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesize that the magnetic field is inducing a very local hyperthermia effect at the level of the polymersome membrane, increasing drug release.", "output": {"entities": {}}, "schema": []}
{"input": "This approach opens new perspectives in the development of smart delivery systems able to release drug upon demand and therefore, improving treatment control.", "output": {"entities": {}}, "schema": []}
{"input": "Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertension.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 10, "end": 17}]}}, "schema": []}
{"input": "Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH.", "output": {"entities": {}}, "schema": []}
{"input": "However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 99, "end": 106}, {"text": "HA-1077", "start": 108, "end": 115}]}}, "schema": []}
{"input": "Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 62, "end": 69}, {"text": "ammonium sulfate", "start": 84, "end": 100}]}}, "schema": []}
{"input": "Liposomes were then characterized for various physicochemical properties.", "output": {"entities": {}}, "schema": []}
{"input": "Optimized formulations were tested for pulmonary absorption and their pharmacological efficacy in a monocrotaline (MCT) induced rat model of PAH.", "output": {"entities": {"chemical": [{"text": "monocrotaline", "start": 100, "end": 113}, {"text": "MCT", "start": 115, "end": 118}]}}, "schema": []}
{"input": "The entrapment efficiency of optimized liposomal fasudil formulations was between 68. 1 +/- 0. 8% and 73. 6 +/- 2. 3%, and the cumulative release at 37 degrees C was 98-99% over a period of 5 days.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 49, "end": 56}]}}, "schema": []}
{"input": "Compared to intravenous (IV) fasudil, a ~ 10 fold increase in the terminal plasma half-life was observed when liposomal fasudil was administered as aerosols.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 29, "end": 36}, {"text": "fasudil", "start": 120, "end": 127}]}}, "schema": []}
{"input": "The t1/2 of IV fasudil was 0. 39 +/- 0. 12 h. and when given as liposomes via pulmonary route, the t1/2 extended to 4. 71 +/- 0. 72 h.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 15, "end": 22}]}}, "schema": []}
{"input": "One h after intratracheal instillation of liposomal fasudil, mean pulmonary arterial pressure (MPAP) was reduced by 37. 6 +/- 5. 7% and continued to decrease for about 3 h, suggesting that liposomal formulations produced pulmonary preferential vasodilation in MCT induced PAH rats.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 52, "end": 59}, {"text": "MCT", "start": 260, "end": 263}]}}, "schema": []}
{"input": "Overall, this study established the proof-of-principle that aerosolized liposomal fasudil is a feasible option for a non-invasive, controlled release and pulmonary preferential treatment of PAH.", "output": {"entities": {"chemical": [{"text": "fasudil", "start": 82, "end": 89}]}}, "schema": []}
{"input": "Cystathionase mediates senescence evasion in melanocytes and melanoma cells.", "output": {"entities": {}}, "schema": []}
{"input": "The development of malignant melanoma is a highly complex process, which is still poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "A majority of human melanomas are found to express a few oncogenic proteins, such as mutant RAS and BRAF variants.", "output": {"entities": {}}, "schema": []}
{"input": "However, these oncogenes are also found in nevi, and it is now a well-accepted fact that their expression alone leads to senescence.", "output": {"entities": {}}, "schema": []}
{"input": "This renders the understanding of senescence escape mechanisms an important point to understand tumor development.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we approached the question of senescence evasion by expressing the transcription factor v-myc myelocytomatosis viral oncogene homolog (c-MYC), which is known to act synergistically with many oncogenes, in melanocytes.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that MYC drives the evasion of reactive-oxygen stress-induced melanocyte senescence, caused by activated receptor tyrosine kinase signaling.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 52, "end": 58}, {"text": "tyrosine", "start": 126, "end": 134}]}}, "schema": []}
{"input": "Conversely, MIZ1, the growth suppressing interaction partner of MYC, is involved in mediating melanocyte senescence.", "output": {"entities": {}}, "schema": []}
{"input": "Both, MYC overexpression and Miz1 knockdown led to a strong reduction of endogenous reactive-oxygen species (ROS), DNA damage and senescence.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 93, "end": 99}]}}, "schema": []}
{"input": "We identified the cystathionase (CTH) gene product as mediator of the ROS-related MYC and MIZ1 effects.", "output": {"entities": {}}, "schema": []}
{"input": "Blocking CTH enzymatic activity in MYC-overexpressing and Miz1 knockdown cells increased intracellular stress and senescence.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, pharmacological inhibition of CTH in human melanoma cells also reconstituted senescence in the majority of cell lines, and CTH knockdown reduced tumorigenic effects such as proliferation, H (2) O (2) resistance and soft agar growth.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 201, "end": 212}]}}, "schema": []}
{"input": "Thus, we identified CTH as new MYC target gene with an important function in senescence evasion. Oncogene advance online publication, 28 January 2013; doi: 10. 1038/onc. 2012. 641.", "output": {"entities": {}}, "schema": []}
{"input": "Support for 5-HT2C receptor functional selectivity in vivo utilizing structurally diverse, selective 5-HT2C receptor ligands and the 2, 5-dimethoxy-4-iodoamphetamine elicited head-twitch response model.", "output": {"entities": {"chemical": [{"text": "2, 5-dimethoxy-4-iodoamphetamine", "start": 133, "end": 165}]}}, "schema": []}
{"input": "There are seemingly conflicting data in the literature regarding the role of serotonin (5-HT) 5-HT2C receptors in the mouse head-twitch response (HTR) elicited by the hallucinogenic 5-HT2A/2B/2C receptor agonist 2, 5-dimethoxy-4-iodoamphetamine (DOI).", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 77, "end": 86}, {"text": "5-HT", "start": 88, "end": 92}, {"text": "2, 5-dimethoxy-4-iodoamphetamine", "start": 212, "end": 244}, {"text": "DOI", "start": 246, "end": 249}]}}, "schema": []}
{"input": "Namely, both 5-HT2C receptor agonists and antagonists, regarding 5-HT2C receptor-mediated Gq-phospholipase C (PLC) signaling, reportedly attenuate the HTR response.", "output": {"entities": {}}, "schema": []}
{"input": "The present experiments tested the hypothesis that both classes of 5-HT2C receptor compounds could attenuate the DOI-elicited-HTR in a single strain of mice, C57Bl/6J.", "output": {"entities": {"chemical": [{"text": "DOI", "start": 113, "end": 116}]}}, "schema": []}
{"input": "The expected results were considered in accordance with ligand functional selectivity.", "output": {"entities": {}}, "schema": []}
{"input": "Commercially-available 5-HT2C agonists (CP 809101, Ro 60-0175, WAY 161503, mCPP, and 1-methylpsilocin), novel 4-phenyl-2-N, N-dimethyl-aminotetralin (PAT)-type 5-HT2C agonists (with 5-HT2A/2B antagonist activity), and antagonists selective for 5-HT2A (M100907), 5-HT2C (SB-242084), and 5-HT2B/2C (SB-206553) receptors attenuated the DOI-elicited-HTR.", "output": {"entities": {"chemical": [{"text": "CP 809101", "start": 40, "end": 49}, {"text": "Ro 60-0175", "start": 51, "end": 61}, {"text": "WAY 161503", "start": 63, "end": 73}, {"text": "mCPP", "start": 75, "end": 79}, {"text": "1-methylpsilocin", "start": 85, "end": 101}, {"text": "4-phenyl-2-N, N-dimethyl-aminotetralin", "start": 110, "end": 148}, {"text": "PAT", "start": 150, "end": 153}, {"text": "M100907", "start": 252, "end": 259}, {"text": "SB-242084", "start": 270, "end": 279}, {"text": "SB-206553", "start": 297, "end": 306}, {"text": "DOI", "start": 333, "end": 336}]}}, "schema": []}
{"input": "In contrast, there were differential effects on locomotion across classes of compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The 5-HT2C agonists and M100907 decreased locomotion, SB-242084 increased locomotion, SB-206553 resulted in dose-dependent biphasic effects on locomotion, and the PATs did not alter locomotion.", "output": {"entities": {"chemical": [{"text": "M100907", "start": 24, "end": 31}, {"text": "SB-242084", "start": 54, "end": 63}, {"text": "SB-206553", "start": 86, "end": 95}]}}, "schema": []}
{"input": "In vitro molecular pharmacology studies showed that 5-HT2C agonists potent for attenuating the DOI-elicited-HTR also reduced the efficacy of DOI to activate mouse 5-HT2C receptor-mediated PLC signaling in HEK cells.", "output": {"entities": {"chemical": [{"text": "DOI", "start": 95, "end": 98}, {"text": "DOI", "start": 141, "end": 144}]}}, "schema": []}
{"input": "Although there were differences in affinities of a few compounds at mouse compared to human 5-HT2A or 5-HT2C receptors, all compounds tested retained their selectivity for either receptor, regardless of receptor species.", "output": {"entities": {}}, "schema": []}
{"input": "Results indicate that 5-HT2C receptor agonists and antagonists attenuate the DOI-elicited-HTR in C57Bl/6J mice, and suggest that structurally diverse 5-HT2C ligands result in different 5-HT2C receptor signaling outcomes compared to DOI.", "output": {"entities": {"chemical": [{"text": "DOI", "start": 77, "end": 80}, {"text": "DOI", "start": 232, "end": 235}]}}, "schema": []}
{"input": "Drug \" supersaturation \" states induced by polymeric micelles and liposomes: a mechanistic investigation into permeability enhancements.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to investigate if the increase in apparent solubility induced by liposomalization or micellization of the poorly soluble drug hydrocortisone (HC) would lead to an enhancement of its permeability through biological membranes.", "output": {"entities": {"chemical": [{"text": "hydrocortisone", "start": 158, "end": 172}]}}, "schema": []}
{"input": "For this purpose phosphatidylcholine liposome formulations as well as d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) micelle dispersions and polyvinylpyrrolidone (PVP) supersaturated solutions were prepared in order to increase the apparent solubility of HC.", "output": {"entities": {"chemical": [{"text": "phosphatidylcholine", "start": 17, "end": 36}, {"text": "d-alpha-tocopheryl polyethylene glycol 1000 succinate", "start": 70, "end": 123}, {"text": "TPGS", "start": 125, "end": 129}, {"text": "polyvinylpyrrolidone", "start": 155, "end": 175}, {"text": "PVP", "start": 177, "end": 180}]}}, "schema": []}
{"input": "Both the apparent solubility of hydrocortisone (i. e. amount of drug entrapped plus non-entrapped in the carriers) as well as the concentration of molecularly dissolved drug (i. e. fraction non-entrapped into carriers, truly molecularly dissolved fraction) were characterized.", "output": {"entities": {"chemical": [{"text": "hydrocortisone", "start": 32, "end": 46}]}}, "schema": []}
{"input": "Subsequently, the permeability of hydrocortisone was assessed for each type of formulation using the in vitro sheep nasal mucosa permeability assay.", "output": {"entities": {"chemical": [{"text": "hydrocortisone", "start": 34, "end": 48}]}}, "schema": []}
{"input": "In all formulations where solubilizing agents are present, an enhanced flux of HC (compared to the pure drug powder suspension) is observed.", "output": {"entities": {}}, "schema": []}
{"input": "The expected linear correlation between apparent solubilities and fluxes was not found, whereas, the concentrations of molecularly dissolved HC were found to be directly proportional to the respective fluxes.", "output": {"entities": {}}, "schema": []}
{"input": "This is an experimental proof for the hypothesis that, of all the strategies to increase the apparent solubility of poorly soluble drugs, enhancement of the molecularly dissolved drug concentration (induction of true supersaturation) would lead to better permeation though membranes.", "output": {"entities": {}}, "schema": []}
{"input": "Pesticides and oncogenic modulation.", "output": {"entities": {}}, "schema": []}
{"input": "Pesticides constitute a diverse class of chemicals used for the protection of agricultural products.", "output": {"entities": {}}, "schema": []}
{"input": "Several lines of evidence demonstrate that organochlorine and organophosphate pesticides can cause malignant transformation of cells in in vitro and in vivo models.", "output": {"entities": {"chemical": [{"text": "organochlorine", "start": 43, "end": 57}, {"text": "organophosphate", "start": 62, "end": 77}]}}, "schema": []}
{"input": "In the current minireview a comprehensive summary of recent in vitro findings is presented along with data reported from human population studies, regarding the impact of pesticide exposure on activation or dysregulation of oncogenes and tumor suppressor genes.", "output": {"entities": {}}, "schema": []}
{"input": "Substantial mechanistic work suggests that pesticides are capable of inducing mutations in oncogenes and increase their transcriptional expression in vitro, whereas human population studies indicate associations between pesticide exposure levels and mutation occurrence in cancer-related genes.", "output": {"entities": {}}, "schema": []}
{"input": "Further work is required to fully explore the exact mechanisms by which pesticide exposure affects the integrity and normal function of oncogenes and tumor suppressor genes in human populations.", "output": {"entities": {}}, "schema": []}
{"input": "Caffeine increases liking and consumption of novel-flavored yogurt.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "RATIONALE: Caffeine has been shown to increase preference for beverages with which it is paired; however, it is not known if caffeine alters liking for foods with which it is paired indirectly.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 11, "end": 19}, {"text": "caffeine", "start": 125, "end": 133}]}}, "schema": []}
{"input": "OBJECTIVES: The purpose of the current experiment was to test the hypothesis that a caffeinated beverage paired with a novel-flavored yogurt will increase preference for that yogurt compared to one paired with placebo.", "output": {"entities": {}}, "schema": []}
{"input": "We also tested the hypothesis that liking would increase more when caffeine was paired with high energy density yogurt.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 67, "end": 75}]}}, "schema": []}
{"input": "METHODS: Men and women (n = 62) were randomized to receive a beverage containing placebo (PLA) or caffeine (CAF) and to consume a low (LED) or high energy density (HED), novel-flavored yogurt.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 98, "end": 106}, {"text": "CAF", "start": 108, "end": 111}]}}, "schema": []}
{"input": "Participants rated, ranked, and consumed seven novel-flavored yogurts and then had a target yogurt paired with either PLA or CAF over four consecutive days.", "output": {"entities": {"chemical": [{"text": "CAF", "start": 125, "end": 128}]}}, "schema": []}
{"input": "RESULTS: In general, yogurt liking increased over time, the HED yogurt was liked more than the LED yogurt, and yogurt paired with caffeine was liked more than yogurt paired with placebo.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 130, "end": 138}]}}, "schema": []}
{"input": "Participants showed a significant increase in liking of LED yogurt paired with caffeine compared to those with LED yogurt paired with placebo.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 79, "end": 87}]}}, "schema": []}
{"input": "CONCLUSIONS: Caffeine administration may increase liking and consumption of novel-flavored foods, particularly if the food is not highly liked at baseline.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 13, "end": 21}]}}, "schema": []}
{"input": "This suggests that caffeine pairing may be a way to increase liking of LED foods, such as vegetables and fruit.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 19, "end": 27}]}}, "schema": []}
{"input": "Effects of repeated exposure to MDMA on 5HT1a autoreceptor function: behavioral and neurochemical responses to 8-OHDPAT.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 32, "end": 36}, {"text": "8-OHDPAT", "start": 111, "end": 119}]}}, "schema": []}
{"input": "A consistent effect of repeated exposure to 3, 4 methylenedioxymethamphetamine (MDMA) is a decrease in the tissue levels of serotonin (5-HT).", "output": {"entities": {"chemical": [{"text": "3, 4 methylenedioxymethamphetamine", "start": 44, "end": 78}, {"text": "MDMA", "start": 80, "end": 84}, {"text": "serotonin", "start": 124, "end": 133}, {"text": "5-HT", "start": 135, "end": 139}]}}, "schema": []}
{"input": "A variety of behavioural and neurochemical tests were conducted to determine whether the tissue deficits were accompanied by an increased sensitivity of the 5-HT1a autoreceptor.", "output": {"entities": {}}, "schema": []}
{"input": "Tests were conducted 2 weeks following MDMA exposure (four injections of 10. 0 mg/kg, IP, administered at 2-h intervals in a single day).", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 39, "end": 43}]}}, "schema": []}
{"input": "The response to the 5-HT1a agonist, 8-OHDPAT (0. 003-0. 5 mg/kg, SC), was assessed using lower lip retraction (LLR), hypoactivity, and 5-hydroxytryptophan (5-HTP) accumulation following decarboxylase inhibition.", "output": {"entities": {"chemical": [{"text": "8-OHDPAT", "start": 36, "end": 44}, {"text": "5-hydroxytryptophan", "start": 135, "end": 154}, {"text": "5-HTP", "start": 156, "end": 161}]}}, "schema": []}
{"input": "The 8-OHDPAT produced a dose-dependent increase in LLR and hypoactivity, but these effects were comparable for MDMA and saline pretreated groups.", "output": {"entities": {"chemical": [{"text": "8-OHDPAT", "start": 4, "end": 12}, {"text": "MDMA", "start": 111, "end": 115}]}}, "schema": []}
{"input": "MDMA decreased tissue levels of 5-HT and the accumulation of 5-HTP, but these effects were not reflected in the changes in autoreceptor sensitivity.", "output": {"entities": {"chemical": [{"text": "MDMA", "start": 0, "end": 4}, {"text": "5-HT", "start": 32, "end": 36}, {"text": "5-HTP", "start": 61, "end": 66}]}}, "schema": []}
{"input": "The data suggest that the decrease in tissue levels of 5-HT produced by MDMA is accompanied by a decrease in tryptophan hydroxylase activity but cannot be explained by supersensitivity of the 5-HT1a autoreceptor.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 55, "end": 59}, {"text": "MDMA", "start": 72, "end": 76}, {"text": "tryptophan", "start": 109, "end": 119}]}}, "schema": []}
{"input": "Age-related differences and relationships between elements in human amygdala and other limbic system or Basal Ganglia.", "output": {"entities": {}}, "schema": []}
{"input": "To elucidate the compositional changes of the amygdala with aging, the authors investigated age-related differences of elements in human amygdalae.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the relationships between the amygdala and other brain regions were investigated from a viewpoint of elements.", "output": {"entities": {}}, "schema": []}
{"input": "After ordinary dissections at Nara Medical University were finished, the amygdalae were removed from the cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the hippocampus, dentate gyrus, mammillary body of the limbic system and the caudate nucleus, putamen, and globus pallidus of the basal ganglia were also removed from the identical cerebra.", "output": {"entities": {}}, "schema": []}
{"input": "After the brain samples were incinerated with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry.", "output": {"entities": {"chemical": [{"text": "nitric acid", "start": 46, "end": 57}, {"text": "perchloric acid", "start": 62, "end": 77}]}}, "schema": []}
{"input": "It was found that both the Ca and Mg contents increased significantly in the amygdalae with aging, but the other five element contents (P, S, Zn, Fe, and Na) did not change significantly in the amygdalae with aging.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 27, "end": 29}, {"text": "Mg", "start": 34, "end": 36}, {"text": "P", "start": 136, "end": 137}, {"text": "S", "start": 139, "end": 140}, {"text": "Zn", "start": 142, "end": 144}, {"text": "Fe", "start": 146, "end": 148}, {"text": "Na", "start": 154, "end": 156}]}}, "schema": []}
{"input": "Regarding the relationships among elements, very significant or significant direct correlations were found among the Ca, P, and Mg contents in the amygdalae.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 117, "end": 119}, {"text": "P", "start": 121, "end": 122}, {"text": "Mg", "start": 128, "end": 130}]}}, "schema": []}
{"input": "To explore the relationships between the amygdala and either other limbic system or basal ganglia, the correlations between seven elements of the amygdala and hippocampus, dentate gyrus, or mammillary body, and between those of the amygdala and caudate nucleus, putamen, or globus pallidus which derived from the identical cerebra, were analyzed with Pearson' s correlation.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that regarding the four elements of Ca, P, Mg, and Fe, a close relationship existed between the amygdala and hippocampus, globus pallidus, or mammillary body.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 49, "end": 51}, {"text": "P", "start": 53, "end": 54}, {"text": "Mg", "start": 56, "end": 58}, {"text": "Fe", "start": 64, "end": 66}]}}, "schema": []}
{"input": "Investigational anti-hyperglycemic agents: the future of type 2 diabetes therapy?", "output": {"entities": {}}, "schema": []}
{"input": "As the pandemic of type 2 diabetes spreads globally, clinicians face many challenges in treating an increasingly diverse patient population varying in age, comorbidities, and socioeconomic status.", "output": {"entities": {}}, "schema": []}
{"input": "Current therapies for type 2 diabetes are often unable to alter the natural course of the disease and provide durable glycemic control, and side effects in the context of individual patient characteristics often limit treatment choices.", "output": {"entities": {}}, "schema": []}
{"input": "This often results in the progression to insulin use and complex regimens that are difficult to maintain.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, a number of agents are being developed to better address the pathogenesis of type 2 diabetes and to overcome limitations of current therapies.", "output": {"entities": {}}, "schema": []}
{"input": "The hope is to provide more options for glucose lowering and complication reduction with less risk for hypoglycemia and other adverse effects.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 40, "end": 47}]}}, "schema": []}
{"input": "These agents include newer incretin-based therapies and PPAR agonists, as well as new therapeutic classes such as sodium-coupled glucose cotransporter 2 inhibitors, free fatty acid receptor agonists, 11-beta-hydroxysteroid dehydrogenase type 1 inhibitors, glucokinase activators, and several others that may enter clinical use over the next decade.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 114, "end": 120}, {"text": "glucose", "start": 129, "end": 136}, {"text": "fatty acid", "start": 170, "end": 180}, {"text": "11-beta-hydroxysteroid", "start": 200, "end": 222}]}}, "schema": []}
{"input": "Herein we review these agents that are advancing through clinical trials and describe the rationale behind their use, mechanisms of action, and potential for glucose lowering, as well as what is known of their limitations.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 158, "end": 165}]}}, "schema": []}
{"input": "Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 31, "end": 43}, {"text": "tazobactam", "start": 44, "end": 54}]}}, "schema": []}
{"input": "OBJECTIVES: To develop population pharmacokinetic (PK) models for piperacillin/tazobactam in neonates and infants of less than 2 months of age in order to determine the appropriate dosing regimen and provide a rational basis for the development of preliminary dosing guidelines suitable for this population.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 66, "end": 78}, {"text": "tazobactam", "start": 79, "end": 89}]}}, "schema": []}
{"input": "METHODS: A two-stage, open-label study was conducted in neonates and infants less than 2 months of age in the neonatal intensive care unit (NICU).", "output": {"entities": {}}, "schema": []}
{"input": "A total of 207 piperacillin and 204 tazobactam concentration-time data sets from 71 patients were analyzed using a nonlinear mixed-effect modeling approach (NONMEM VII).", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 15, "end": 27}, {"text": "tazobactam", "start": 36, "end": 46}]}}, "schema": []}
{"input": "PK models were developed for piperacillin and tazobactam.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 29, "end": 41}, {"text": "tazobactam", "start": 46, "end": 56}]}}, "schema": []}
{"input": "The final models were evaluated using both bootstrap and visual predictive checks.", "output": {"entities": {}}, "schema": []}
{"input": "External model evaluations were made in 20 additional patients.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: For neonates and young infants less than 2 months of age, the median central clearance was 0. 133 and 0. 149 L/h/kg for piperacillin and tazobactam, respectively.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 129, "end": 141}, {"text": "tazobactam", "start": 146, "end": 156}]}}, "schema": []}
{"input": "Postmenstrual age (PMA) was identified as the most significant covariate on central clearance of piperacillin and tazobactam.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 97, "end": 109}, {"text": "tazobactam", "start": 114, "end": 124}]}}, "schema": []}
{"input": "However, the combination of current bodyweight (BW) and postnatal age proved to be superior to PMA alone.", "output": {"entities": {}}, "schema": []}
{"input": "BW was the most important covariate for apparent central volume of distribution.", "output": {"entities": {}}, "schema": []}
{"input": "Both internal and external evaluations supported the prediction of the final piperacillin and tazobactam PK models.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 77, "end": 89}, {"text": "tazobactam", "start": 94, "end": 104}]}}, "schema": []}
{"input": "The dosing strategy 44. 44/5. 56 mg/kg/dose piperacillin/tazobactam every 8 or 12 h evaluated in this study achieved the pharmacodynamic target (free piperacillin concentrations > 4 mg/L for more than 50% of the dosing interval) in about 67% of infants.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 44, "end": 56}, {"text": "tazobactam", "start": 57, "end": 67}, {"text": "piperacillin", "start": 150, "end": 162}]}}, "schema": []}
{"input": "CONCLUSIONS: Population PK models accurately described the PK profiles of piperacillin/tazobactam in infants less than 2 months of age.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 74, "end": 86}, {"text": "tazobactam", "start": 87, "end": 97}]}}, "schema": []}
{"input": "The results indicated that higher doses or more frequent dosing regimens may be required for controlling infection in this population in NICU.", "output": {"entities": {}}, "schema": []}
{"input": "Decoupling cell and matrix mechanics in engineered microtissues using magnetically actuated microcantilevers.", "output": {"entities": {}}, "schema": []}
{"input": "A novel bio-magnetomechanical microtissue system is described for magnetic actuation of arrays of 3D microtissues using microcantilevers.", "output": {"entities": {}}, "schema": []}
{"input": "This system enables both in situ measurements of fundamental mechanical properties of engineered tissue, such as contractility and stiffness, as well as dynamic stimulation of the microtissues.", "output": {"entities": {}}, "schema": []}
{"input": "Using this system, cell and extracellular matrix contributions to the tissue mechanical properties are decoupled for the first time under both static and dynamic loading conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Evaporation-induced self-alignment and transfer of semiconductor nanowires by wrinkled elastomeric templates.", "output": {"entities": {}}, "schema": []}
{"input": "The evaporation-induced self-alignment of semiconductor nanowires is achieved using wrinkled elastomeric templates.", "output": {"entities": {}}, "schema": []}
{"input": "The wrinkled templates, which have a surface topography that can be tuned via changes in the mechanical strain, are used as both a template to align the nanowires and as a stamp to transfer the aligned nanowires to target substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Self-healing polymer coatings based on crosslinked metallosupramolecular copolymers.", "output": {"entities": {}}, "schema": []}
{"input": "Self-healing coating based on metallopolymers are prepared and fully characterized.", "output": {"entities": {}}, "schema": []}
{"input": "Iron bisterpyridine complexes are incorporated into a polymer network based on methacrylates, resulting in self-healing properties of these materials.", "output": {"entities": {"chemical": [{"text": "Iron bisterpyridine", "start": 0, "end": 19}, {"text": "methacrylates", "start": 79, "end": 92}]}}, "schema": []}
{"input": "Moreover, the influence of the comonomers on the thermal properties is studied in detail.", "output": {"entities": {}}, "schema": []}
{"input": "The discovery of phenylbenzamide derivatives as Grb7-based antitumor agents.", "output": {"entities": {"chemical": [{"text": "phenylbenzamide", "start": 17, "end": 32}]}}, "schema": []}
{"input": "Grb7 is a non-catalytic protein, the overexpression of which has been associated with the proliferative and migratory potentials of cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Virtual screening strategies involving a shape-based similarity search, molecular docking, and 2D-similarity searches complemented by experimental binding studies (Thermofluor and isothermal titration calorimetry) resulted in the identification of nine novel phenylbenzamide-based antagonists of the Grb7 SH2 domain.", "output": {"entities": {"chemical": [{"text": "phenylbenzamide", "start": 259, "end": 274}]}}, "schema": []}
{"input": "Moderate binding affinities were observed, ranging from K (d) = 32. 3 mu M for lead phenylbenzamide NSC 104999 (1) to K (d) = 1. 1 mu M for a structurally related compound, NSC 57148 (2).", "output": {"entities": {"chemical": [{"text": "phenylbenzamide NSC 104999", "start": 84, "end": 110}, {"text": "NSC 57148", "start": 173, "end": 182}]}}, "schema": []}
{"input": "Deconvolution of the affinity data into its components revealed differences in lead binding, from being entropy based (lead 1) to enthalpically driven (NSC 100874 (3), NSC 55158 (4), and compound 2).", "output": {"entities": {"chemical": [{"text": "NSC 100874", "start": 152, "end": 162}, {"text": "NSC 55158", "start": 168, "end": 177}]}}, "schema": []}
{"input": "Finally, the lead compound 1 was found to decrease the growth of MDA-MB-468 breast cancer cells, with an IC (50) value of 39. 9 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "It is expected that these structures will serve as novel leads in the development of Grb7-based anticancer therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Structural Basis of Signaling Blockade by Anti-IL-13 Antibody Lebrikizumab.", "output": {"entities": {}}, "schema": []}
{"input": "The cytokine interleukin 13 (IL-13) is a major effector molecule for T-helper type 2 inflammation and is pathogenic in allergic diseases such as asthma.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of IL-13 are mediated via a pathway that is initiated by binding to a heterodimeric receptor consisting of IL-13R alpha 1 and IL-4R alpha.", "output": {"entities": {}}, "schema": []}
{"input": "Antibodies raised against IL-13 can block its inflammatory effects by interfering with binding to either of the two receptor polypeptides.", "output": {"entities": {}}, "schema": []}
{"input": "Lebrikizumab is a monoclonal anti-IL-13 antibody that has shown clinical benefit in a phase II study for the treatment of moderate-to-severe uncontrolled asthma.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report the molecular structure of IL-13 in complex with the Fab from lebrikizumab by X-ray crystallography at 1. 9 A resolution.", "output": {"entities": {}}, "schema": []}
{"input": "We show that lebrikizumab inhibits IL-13 signaling by binding to IL-13 with very high affinity and blocking IL-13 binding to IL-4R alpha.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we use site-directed mutations to identify the most important antibody contributors to binding.", "output": {"entities": {}}, "schema": []}
{"input": "Our studies define key features of lebrikizumab binding and its mechanism of action that may contribute to its clinical effects.", "output": {"entities": {}}, "schema": []}
{"input": "The role of phosphodiesterases in hippocampal synaptic plasticity.", "output": {"entities": {}}, "schema": []}
{"input": "Phosphodiesterases (PDEs) degrade cyclic nucleotides, signalling molecules that play important roles in synaptic plasticity and memory.", "output": {"entities": {"chemical": [{"text": "cyclic nucleotides", "start": 34, "end": 52}]}}, "schema": []}
{"input": "Inhibition of PDEs may therefore enhance synaptic plasticity and memory as a result of elevated levels of these signalling molecules, and this has led to interest in PDE inhibitors as cognitive enhancers.", "output": {"entities": {}}, "schema": []}
{"input": "The development of new mouse models in which PDE subtypes have been selectively knocked out and increasing selectivity of PDE antagonists means that this field is currently expanding.", "output": {"entities": {}}, "schema": []}
{"input": "Roles for PDE2, 4, 5 and 9 in synaptic plasticity have so far been demonstrated and we review these studies here in the context of cyclic nucleotide signalling more generally.", "output": {"entities": {"chemical": [{"text": "cyclic nucleotide", "start": 131, "end": 148}]}}, "schema": []}
{"input": "The role of other PDE families in synaptic plasticity has not yet been investigated, and this area promises to advance our understanding of cyclic nucleotide signalling in synaptic plasticity in the future.", "output": {"entities": {"chemical": [{"text": "cyclic nucleotide", "start": 140, "end": 157}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.", "output": {"entities": {}}, "schema": []}
{"input": "beta-Asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression.", "output": {"entities": {"chemical": [{"text": "beta-Asarone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Colorectal cancer is a leading cause of cancer mortality with a complex carcinogenesis that includes reduced cellular senescence.", "output": {"entities": {}}, "schema": []}
{"input": "Lamin proteins are decreased in senescing cells, and frequently decreased in malignancies.", "output": {"entities": {}}, "schema": []}
{"input": "This study identified a new drug candidate for colorectal cancer that appears to target cell senescence via a lamin protein.", "output": {"entities": {}}, "schema": []}
{"input": "beta-Asarone (1-propenyl-2, 4, 5-methoxybenzol) is a compound from the traditional medical herb Acorus calamus Linn.", "output": {"entities": {"chemical": [{"text": "beta-Asarone", "start": 0, "end": 12}, {"text": "1-propenyl-2, 4, 5-methoxybenzol", "start": 14, "end": 46}]}}, "schema": []}
{"input": "This study tested the in vitro and in vivo effects of beta-asarone on colorectal cancer cells by testing cell viability using human colorectal cell lines HT29 and SW480 in MTT assays; tumorigenesis using xenografts in nude mice and a mouse model of colorectal cancer; cell senescence using senescence-associated beta-galactosidase activity; and expression of cancer and senescence-related proteins, specifically lamins, Oct-1, p53, p21, and p15, by Western blot.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 54, "end": 66}, {"text": "MTT", "start": 172, "end": 175}]}}, "schema": []}
{"input": "beta-Asarone appeared to increase expression of lamin B1, p53, p21, but not lamin A/C.", "output": {"entities": {"chemical": [{"text": "beta-Asarone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "beta-Asarone regulates p15 expression by regulation of Oct-1 binding.", "output": {"entities": {"chemical": [{"text": "beta-Asarone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Collectively, the results suggested that beta-asarone inhibits colon cancer formation in vivo and in vitro by inducing senescence.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 41, "end": 53}]}}, "schema": []}
{"input": "Since beta-asarone induced lamin B1 expression, a model is proposed in which beta-asarone inhibits colorectal cancer by inducing senescence through lamin B1.", "output": {"entities": {"chemical": [{"text": "beta-asarone", "start": 6, "end": 18}, {"text": "beta-asarone", "start": 77, "end": 89}]}}, "schema": []}
{"input": "Inhibitory effect on NO production of triterpenes from the fruiting bodies of Ganoderma lucidum.", "output": {"entities": {"chemical": [{"text": "NO", "start": 21, "end": 23}, {"text": "triterpenes", "start": 38, "end": 49}]}}, "schema": []}
{"input": "Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D (2) (2), butyl lucidenate E (2) (3) and butyl lucidenate Q (4) along with 11 known compounds (5-15) were isolated from the fruiting bodies of Ganoderma lucidum.", "output": {"entities": {"chemical": [{"text": "lanostane triterpenes", "start": 9, "end": 30}, {"text": "butyl lucidenate P", "start": 32, "end": 50}, {"text": "butyl lucidenate D (2)", "start": 56, "end": 78}, {"text": "butyl lucidenate E (2)", "start": 84, "end": 106}, {"text": "butyl lucidenate Q", "start": 115, "end": 133}]}}, "schema": []}
{"input": "Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW 264. 7 cells.", "output": {"entities": {"chemical": [{"text": "NO", "start": 67, "end": 69}]}}, "schema": []}
{"input": "Compounds 1, 3, 4, 9, 10 and 15 showed inhibitory potency with IC (50) values of 7. 4, 6. 4, 4. 3, 9. 4, 9. 2 and 4. 5 mu M, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1, 3 and 15 dose-dependently reduced the LPS-induced iNOS expressions.", "output": {"entities": {}}, "schema": []}
{"input": "Preincubation of cell with 1, 3 and 15 significantly suppressed LPS-induced expression of COX-2 protein.", "output": {"entities": {}}, "schema": []}
{"input": "Constitutively active group I mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal cortex.", "output": {"entities": {}}, "schema": []}
{"input": "Synaptic transmission is essential for early development of the central nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "However, the mechanisms that regulate early synaptic transmission in the cerebral cortex are unclear.", "output": {"entities": {}}, "schema": []}
{"input": "PKM zeta is a kinase essential for the maintenance of LTP.", "output": {"entities": {}}, "schema": []}
{"input": "We show for the first time that inhibition of PKM zeta produces a profound depression of basal synaptic transmission in neonatal, but not adult, rat perirhinal cortex.", "output": {"entities": {}}, "schema": []}
{"input": "This suggests that synapses in early development are in a constitutive LTP-like state.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, basal synaptic transmission in immature, but not mature, perirhinal cortex relies on persistent activity of metabotropic glutamate (mGlu) receptor, PI3Kinase and mammalian target of rapamycin (mTOR).", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 134, "end": 143}, {"text": "rapamycin", "start": 195, "end": 204}]}}, "schema": []}
{"input": "Thus early in development, cortical synapses exist in an LTP-like state maintained by tonically active mGlu receptor-, mTOR-and PKM zeta-dependent cascades.", "output": {"entities": {}}, "schema": []}
{"input": "These results provide new understanding of the molecular mechanisms that control synapses during development and may aid our understanding of developmental disorders such as autism and schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Relative impact of incorporating pharmacokinetics on predicting in vivo hazard and mode of action from high-throughput in vitro toxicity assays.", "output": {"entities": {}}, "schema": []}
{"input": "The use of high-throughput in vitro assays has been proposed to play a significant role in the future of toxicity testing.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, rat hepatic metabolic clearance and plasma protein binding were measured for 59 ToxCast phase I chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Computational in vitro-to-in vivo extrapolation was used to estimate the daily dose in a rat, called the oral equivalent dose, which would result in steady-state in vivo blood concentrations equivalent to the AC 50 or lowest effective concentration (LEC) across more than 600 ToxCast phase I in vitro assays.", "output": {"entities": {}}, "schema": []}
{"input": "Statistical classification analysis was performed using either oral equivalent doses or unadjusted AC 50/LEC values for the in vitro assays to predict the in vivo effects of the 59 chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Adjusting the in vitro assays for pharmacokinetics did not improve the ability to predict in vivo effects as either a discrete (yes or no) response or a low effect level (LEL) on a continuous dose scale.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, a comparison of the in vitro assay with the lowest oral equivalent dose with the in vivo endpoint with the lowest LEL suggested that the lowest oral equivalent dose may provide a conservative estimate of the point of departure for a chemical in a dose-response assessment.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, comparing the oral equivalent doses for the in vitro assays with the in vivo dose range that resulted in adverse effects identified more coincident in vitro assays across chemicals than expected by chance, suggesting that the approach may also be used to identify potential molecular initiating events leading to adversity.", "output": {"entities": {}}, "schema": []}
{"input": "The spectrum of circulating RNA: a window into systems toxicology.", "output": {"entities": {}}, "schema": []}
{"input": "Adverse effects caused by therapeutic drugs are a serious and costly health concern.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the body' s systemic responses to therapeutics, the liver is often the focus of damage and is usually the focus of studies of toxic effects due to its active roles in the metabolism of xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "It is extremely difficult, however, to assess systemic responses with currently available methods.", "output": {"entities": {}}, "schema": []}
{"input": "Comprehensive cataloging of cell-free circulating RNAs using next-generation sequencing technology may open a window to assess drug-associated adverse effects at the systems level.", "output": {"entities": {}}, "schema": []}
{"input": "To explore this potential, we conducted an RNA profiling study using the well-characterized acetaminophen overdose mouse model on liver and plasma with microarray and next-generation sequencing platforms, respectively.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 92, "end": 105}]}}, "schema": []}
{"input": "After drug treatment, the levels of a number of transcripts, both endogenous and exogenous RNAs, showed significant changes in plasma, reflecting not only the classical liver injury induced by acetaminophen overdose but also damage in tissues other than the liver.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 193, "end": 206}]}}, "schema": []}
{"input": "The changes in exogenous RNAs also reflect alteration on dieting behavior after acetaminophen overdose.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 80, "end": 93}]}}, "schema": []}
{"input": "Besides reporting an extensive list of circulating RNA-based biomarker candidates, this study illustrates the possibility of using circulating RNAs to assess global effects of therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "This could also lead to a new approach for a more comprehensive assessment of the efficacy and safety of therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of p-glycoprotein mediated multidrug resistance by stemofoline derivatives.", "output": {"entities": {"chemical": [{"text": "stemofoline", "start": 62, "end": 73}]}}, "schema": []}
{"input": "Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATP-binding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 95, "end": 98}]}}, "schema": []}
{"input": "We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp.", "output": {"entities": {"chemical": [{"text": "stemofoline", "start": 58, "end": 69}]}}, "schema": []}
{"input": "Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay were determined.", "output": {"entities": {"chemical": [{"text": "Didehydrostemofoline", "start": 0, "end": 20}, {"text": "doxorubicin", "start": 109, "end": 120}, {"text": "vinblastine", "start": 122, "end": 133}, {"text": "paclitaxel", "start": 138, "end": 148}, {"text": "3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide", "start": 253, "end": 315}, {"text": "MTT", "start": 317, "end": 320}]}}, "schema": []}
{"input": "We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562).", "output": {"entities": {"chemical": [{"text": "stemofoline", "start": 38, "end": 49}, {"text": "OH-A1", "start": 72, "end": 77}, {"text": "NH-B6", "start": 79, "end": 84}, {"text": "NH-D6", "start": 89, "end": 94}, {"text": "doxorubicin", "start": 151, "end": 162}, {"text": "vinblastine", "start": 164, "end": 175}, {"text": "paclitaxel", "start": 180, "end": 190}, {"text": "doxorubicin", "start": 234, "end": 245}, {"text": "paclitaxel", "start": 251, "end": 261}]}}, "schema": []}
{"input": "These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers.", "output": {"entities": {"chemical": [{"text": "stemofoline", "start": 28, "end": 39}]}}, "schema": []}
{"input": "The molecular mechanism of modulation of P-gp would be further determined.", "output": {"entities": {}}, "schema": []}
{"input": "Partial peptide of alpha-synuclein modified with small-molecule inhibitors specifically inhibits amyloid fibrillation of alpha-synuclein.", "output": {"entities": {}}, "schema": []}
{"input": "We have previously reported that pyrroloquinoline quinone (PQQ) prevents the amyloid formation of alpha-synuclein, amyloid beta (1-42) (A beta (1-42)), and mouse prion protein.", "output": {"entities": {"chemical": [{"text": "pyrroloquinoline quinone", "start": 33, "end": 57}, {"text": "PQQ", "start": 59, "end": 62}]}}, "schema": []}
{"input": "Moreover, PQQ-modified alpha-synuclein and a proteolytic fragment of the PQQ-modified alpha-synuclein are able to inhibit the amyloid formation of alpha-synuclein.", "output": {"entities": {"chemical": [{"text": "PQQ", "start": 10, "end": 13}, {"text": "PQQ", "start": 73, "end": 76}]}}, "schema": []}
{"input": "Here, we identified the peptide sequences that play an important role as PQQ-modified specific peptide inhibitors of alpha-synuclein.", "output": {"entities": {"chemical": [{"text": "PQQ", "start": 73, "end": 76}]}}, "schema": []}
{"input": "We demonstrate that the PQQ-modified alpha-Syn (36-46) peptide, which is a partial sequence of alpha-synuclein, prevented alpha-synuclein amyloid fibril formation but did not inhibit A beta (1-42) fibril formation.", "output": {"entities": {"chemical": [{"text": "PQQ", "start": 24, "end": 27}]}}, "schema": []}
{"input": "In addition, the alpha-synuclein partial peptide modified with other small-molecule inhibitors, Baicalein and epigallocatechin gallate (EGCG), prevented alpha-synuclein fibril formation.", "output": {"entities": {"chemical": [{"text": "Baicalein", "start": 96, "end": 105}, {"text": "epigallocatechin gallate", "start": 110, "end": 134}, {"text": "EGCG", "start": 136, "end": 140}]}}, "schema": []}
{"input": "Currently reported quinone amyloid inhibitors do not have selectivity toward protein molecules.", "output": {"entities": {"chemical": [{"text": "quinone", "start": 19, "end": 26}]}}, "schema": []}
{"input": "Therefore, our achievements provide a novel strategy for the development of targeted specific amyloid formation inhibitors: the combination of quinone compounds with specific peptide sequence from target proteins involved in amyloid formation.", "output": {"entities": {"chemical": [{"text": "quinone", "start": 143, "end": 150}]}}, "schema": []}
{"input": "Synthesis and biological evaluation of xanthine derivatives on dipeptidyl peptidase 4.", "output": {"entities": {"chemical": [{"text": "xanthine", "start": 39, "end": 47}]}}, "schema": []}
{"input": "A series of xanthine derivatives in which a methylene was inserted at position 8 of xanthine scaffold was synthesized and evaluated as inhibitors of dipeptidyl peptidase 4 (DPP-4) for the treatment of type 2 diabetes.", "output": {"entities": {"chemical": [{"text": "xanthine", "start": 12, "end": 20}, {"text": "methylene", "start": 44, "end": 53}, {"text": "xanthine", "start": 84, "end": 92}]}}, "schema": []}
{"input": "As the results of structure-activity relationship (SAR) study of the series, the compounds with 4-methyl-quinazoline-2-yl-methyl group at N-1 position and 2-aminoethylaminomethyl group gave better activities.", "output": {"entities": {"chemical": [{"text": "4-methyl-quinazoline-2-yl-methyl", "start": 96, "end": 128}, {"text": "2-aminoethylaminomethyl", "start": 155, "end": 178}]}}, "schema": []}
{"input": "Compounds H4 and H9 showed good DPP-4 inhibition and more than 100-fold selectivity over DPP-7 and DPP-8.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, DNA binding and antitumor evaluation of styelsamine and cystodytin analogues.", "output": {"entities": {"chemical": [{"text": "styelsamine", "start": 51, "end": 62}, {"text": "cystodytin", "start": 67, "end": 77}]}}, "schema": []}
{"input": "A series of N-14 sidechain substituted analogues of styelsamine (pyrido [4, 3, 2-mn] acridine) and cystodytin (pyrido [4, 3, 2-mn] acridin-4-one) alkaloids have been prepared and evaluated for their DNA binding affinity and antiproliferative activity towards a panel of human tumor cell lines.", "output": {"entities": {"chemical": [{"text": "styelsamine", "start": 52, "end": 63}, {"text": "pyrido [4, 3, 2-mn] acridine", "start": 65, "end": 93}, {"text": "cystodytin", "start": 99, "end": 109}, {"text": "pyrido [4, 3, 2-mn] acridin-4-one", "start": 111, "end": 144}]}}, "schema": []}
{"input": "Overall it was found that styelsamine analogues were stronger DNA binders, with the natural products styelsamines B and D having particularly high affinity (K (app) 5. 33 x 10 (6) and 3. 64 x 10 (6) M (-1), respectively).", "output": {"entities": {"chemical": [{"text": "styelsamine", "start": 26, "end": 37}, {"text": "styelsamines B and D", "start": 101, "end": 121}]}}, "schema": []}
{"input": "In comparison, the cystodytin iminoquinone alkaloids showed lower affinity for DNA, but were typically just as active as styelsamine analogues at inhibiting proliferation of tumor cells in vitro.", "output": {"entities": {"chemical": [{"text": "cystodytin iminoquinone alkaloids", "start": 19, "end": 52}, {"text": "styelsamine", "start": 121, "end": 132}]}}, "schema": []}
{"input": "Sub-panel selectivity towards non-small cell lung, melanoma and renal cancer cell lines were observed for a number of the analogues.", "output": {"entities": {}}, "schema": []}
{"input": "Correlation was observed between whole cell activity and clogP, with the most potent antiproliferative activity being observed for 3-phenylpropanamide analogues 37 and 41 (NCI panel average GI (50) 0. 4 mu M and 0. 32 mu M, respectively) with clogP ~ 4. 0-4. 5.", "output": {"entities": {"chemical": [{"text": "3-phenylpropanamide", "start": 131, "end": 150}]}}, "schema": []}
{"input": "Variation in the alpha 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 35, "end": 48}, {"text": "nicotine", "start": 125, "end": 133}]}}, "schema": []}
{"input": "A single-nucleotide polymorphism (SNP) in the alpha 5 nicotinic acetylcholine receptor subunit gene, rs16969968, has been repeatedly associated with both smoking and respiratory health phenotypes.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 64, "end": 77}]}}, "schema": []}
{"input": "However, there remains considerable debate as to whether associations with lung cancer are mediated through effects on smoking behavior.", "output": {"entities": {}}, "schema": []}
{"input": "Preclinical studies suggest that alpha 5 receptor subunit expression and function may have a direct role in nicotine titration during self administration.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 108, "end": 116}]}}, "schema": []}
{"input": "The present study investigated the association of CHRNA5 polymorphisms and smoking topography in 66 smokers asked to smoke four nicotine-containing (nicotine yield = 0. 60 mg) and four placebo (nicotine yield < 0. 05 mg) cigarettes, during separate experimental sessions.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 128, "end": 136}, {"text": "nicotine", "start": 149, "end": 157}, {"text": "nicotine", "start": 194, "end": 202}]}}, "schema": []}
{"input": "Genotype at rs16969968 predicted nicotine titration, with homozygotes for the major allele (G: G) displaying significantly reduced puff volume in response to nicotine, whereas minor allele carriers (A: G or A: A) produced equivalent puff volumes for placebo and nicotine cigarettes.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 33, "end": 41}, {"text": "nicotine", "start": 158, "end": 166}, {"text": "nicotine", "start": 262, "end": 270}]}}, "schema": []}
{"input": "The present results suggest that puff volume may be a more powerful objective phenotype of smoking behavior than self-reported cigarettes per day and nicotine dependence.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 150, "end": 158}]}}, "schema": []}
{"input": "Further, these results suggest that the association between rs16969968 and lung cancer may be mediated by the quantity of smoke inhaled. The Pharmacogenomics Journal advance online publication, 29 January 2013; doi: 10. 1038/tpj. 2012. 50.", "output": {"entities": {}}, "schema": []}
{"input": "Dynamic pH mapping in microfluidic devices by integrating adaptive coatings based on polyaniline with colorimetric imaging techniques.", "output": {"entities": {"chemical": [{"text": "polyaniline", "start": 85, "end": 96}]}}, "schema": []}
{"input": "In this paper we present a microfluidic device that has integrated pH optical sensing capabilities based on polyaniline.", "output": {"entities": {"chemical": [{"text": "polyaniline", "start": 108, "end": 119}]}}, "schema": []}
{"input": "The optical properties of polyaniline coatings change in response to the pH of the solution that is flushed inside the microchannel offering the possibility of monitoring pH in continuous flow over a wide pH range throughout the entire channel length.", "output": {"entities": {"chemical": [{"text": "polyaniline", "start": 26, "end": 37}]}}, "schema": []}
{"input": "This work also features an innovative detection system for spatial localisation of chemical pH gradients along microfluidic channels through the use of a low cost optical device.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, the use of a microfluidic channel coated with polyaniline is shown to respond colorimetrically to pH and that effect is detected by the detection system, even when pH gradients are induced within the channel.", "output": {"entities": {"chemical": [{"text": "polyaniline", "start": 60, "end": 71}]}}, "schema": []}
{"input": "This study explores the capability of detecting this gradient by means of imaging techniques and the mapping of the camera' s response to its corresponding pH after a successful calibration process.", "output": {"entities": {}}, "schema": []}
{"input": "The provision of an inherently responsive channel means that changes in the pH of a sample moving through the system can be detected dynamically using digital imaging along the entire channel length in real time, without the need to add reagents to the sample.", "output": {"entities": {}}, "schema": []}
{"input": "This approach is generic and can be applied to other chemically responsive coatings immobilised on microchannels.", "output": {"entities": {}}, "schema": []}
{"input": "Agrochemicals in field margins-assessing the impacts of herbicides, insecticides, and fertilizer on the common buttercup (ranunculus acris).", "output": {"entities": {}}, "schema": []}
{"input": "The effects of herbicide, insecticide, and fertilizer inputs on the common buttercup Ranunculus acris in field margins were studied in an experimental field study.", "output": {"entities": {}}, "schema": []}
{"input": "The test design allowed us to investigate the single and combined effects of repeated herbicide, insecticide, and fertilizer applications in successive growing seasons.", "output": {"entities": {}}, "schema": []}
{"input": "To assess the effects of the agrochemical applications on R. acris, plant community assessments were carried out and a photodocumentation of the flowering intensity was performed over two years.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the authors conducted a monitoring survey of R. acris in field margins in the proximity of the study site.", "output": {"entities": {}}, "schema": []}
{"input": "In the field experiment, R. acris plant density decreased significantly with treatments including fertilizer.", "output": {"entities": {}}, "schema": []}
{"input": "The herbicide caused a sublethal effect by reducing flower intensity by 85%.", "output": {"entities": {}}, "schema": []}
{"input": "In the long run, both effects will result in a decline of R. acris and lead to shifts in plant communities in field margins.", "output": {"entities": {}}, "schema": []}
{"input": "This was confirmed by the monitoring survey, where R. acris could hardly be observed in field margins directly adjacent to cereal fields, whereas in margins next to meadows the species was recorded frequently.", "output": {"entities": {}}, "schema": []}
{"input": "Besides the implications for the plants, the sublethal effects may also affect many flower-visiting insects.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that the current risk assessment for nontarget plants is insufficiently protective for wild plant species in field margins and that consideration of sublethal effects is crucial to preserve biodiversity in agricultural landscapes.", "output": {"entities": {}}, "schema": []}
{"input": "Environ.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicol.", "output": {"entities": {}}, "schema": []}
{"input": "Chem.", "output": {"entities": {}}, "schema": []}
{"input": "2013; 32: 1124-1131.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Effect propagation in a toxicokinetic/toxicodynamic model explains delayed effects on the growth of unicellular green algae scenedesmus vacuolatus.", "output": {"entities": {}}, "schema": []}
{"input": "Ecotoxicological standard tests assess toxic effects by exposing an organism to high concentrations over defined periods of time.", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate toxicity under field conditions such as fluctuating and pulsed exposures, process-based toxicokinetic/toxicodynamic (TK/TD) models may be used for extrapolation from the existing evidence.", "output": {"entities": {}}, "schema": []}
{"input": "A TK/TD model was developed that simulates the effect on growth of the green algae Scenedesmus vacuolatus continuously exposed to the model chemicals norflurazon, triclosan, and N-phenyl-2-naphthylamine.", "output": {"entities": {"chemical": [{"text": "norflurazon", "start": 150, "end": 161}, {"text": "triclosan", "start": 163, "end": 172}, {"text": "N-phenyl-2-naphthylamine", "start": 178, "end": 202}]}}, "schema": []}
{"input": "A pharmacological time-response model describing the effects of anticancer treatments on cancer cell growth was adapted and modified to model the affected growth of synchronized algae cells.", "output": {"entities": {}}, "schema": []}
{"input": "The TK/TD model simulates the temporal effect course by linking the ambient concentration of a chemical to the observable adverse effect via an internal concentration and a sequence of biological events in the organism.", "output": {"entities": {}}, "schema": []}
{"input": "The parameters of the toxicodynamic model are related to the growth characteristics of algae cells, a no effect concentration, the chemical efficacy as well as the ability of recovery and repair, and the delay during damage propagation.", "output": {"entities": {}}, "schema": []}
{"input": "The TK/TD model fits well to the observed algae growth.", "output": {"entities": {}}, "schema": []}
{"input": "The effect propagation through cumulative cell damage explained the observed delayed responses better than just the toxicokinetics.", "output": {"entities": {}}, "schema": []}
{"input": "The TK/TD model could facilitate the link between several effect levels within damage propagation, which prospectively may be helpful to model adverse outcome pathways and time-dependent mixture effects.", "output": {"entities": {}}, "schema": []}
{"input": "Environ.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicol.", "output": {"entities": {}}, "schema": []}
{"input": "Chem.", "output": {"entities": {}}, "schema": []}
{"input": "2013; 32: 1161-1172.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacologic therapy for nonalcoholic fatty liver disease in adults.", "output": {"entities": {}}, "schema": []}
{"input": "Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH).", "output": {"entities": {"chemical": [{"text": "triglycerides", "start": 81, "end": 94}, {"text": "alcohol", "start": 138, "end": 145}]}}, "schema": []}
{"input": "Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma.", "output": {"entities": {}}, "schema": []}
{"input": "NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere.", "output": {"entities": {}}, "schema": []}
{"input": "Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH.", "output": {"entities": {}}, "schema": []}
{"input": "The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise.", "output": {"entities": {}}, "schema": []}
{"input": "There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy.", "output": {"entities": {}}, "schema": []}
{"input": "A PubMed search was conducted using the medical subject heading terms \" fatty liver \" and \" steatohepatitis. \" This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH.", "output": {"entities": {}}, "schema": []}
{"input": "Continued investigation of drugs or combinations that improve NAFLD progression is crucial.", "output": {"entities": {}}, "schema": []}
{"input": "Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.", "output": {"entities": {}}, "schema": []}
{"input": "PEG-Modified Macroporous Poly (Glycidyl Methacrylate) and Poly (2-Hydroxyethyl Methacrylate) Microspheres to Reduce Non-Specific Protein Adsorption.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 0, "end": 3}, {"text": "Poly (Glycidyl Methacrylate)", "start": 25, "end": 53}, {"text": "Poly (2-Hydroxyethyl Methacrylate)", "start": 58, "end": 92}]}}, "schema": []}
{"input": "To minimize non-specific protein adsorption on macroporous poly (glycidyl methacrylate) and poly (2-hydroxyethyl methacrylate) microspheres containing amino and/or carboxyl groups, the microspheres are coated with alpha, omega-bis-carboxy poly (ethylene glycol) and amino-terminated poly (ethylene glycol-co-propylene glycol) or alpha-methoxy-omega-amino poly (ethylene glycol).", "output": {"entities": {"chemical": [{"text": "poly (glycidyl methacrylate)", "start": 59, "end": 87}, {"text": "poly (2-hydroxyethyl methacrylate)", "start": 92, "end": 126}, {"text": "amino", "start": 151, "end": 156}, {"text": "carboxyl", "start": 164, "end": 172}, {"text": "alpha, omega-bis-carboxy poly (ethylene glycol)", "start": 214, "end": 261}, {"text": "amino", "start": 266, "end": 271}, {"text": "poly (ethylene glycol-co-propylene glycol)", "start": 283, "end": 325}, {"text": "alpha-methoxy-omega-amino poly (ethylene glycol)", "start": 329, "end": 377}]}}, "schema": []}
{"input": "Adsorption of bovine serum albumin (BSA), gamma-globulin, (125) I-BSA, pepsin, and chymotrypsin on neat and PEGylated microspheres is determined by UV-VIS spectroscopy of supernatants and eluates or by measurement of radioactivity in an ionization chamber.", "output": {"entities": {"chemical": [{"text": "(125) I", "start": 58, "end": 65}]}}, "schema": []}
{"input": "Neat and PEGylated microspheres adsorb 0. 8-70% and 0. 02-44% of protein, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Electronic structure of individual hybrid colloid particles studied by near-edge X-ray absorption fine structure (NEXAFS) spectroscopy in the X-ray microscope.", "output": {"entities": {}}, "schema": []}
{"input": "The electronic structure of individual hybrid particles was studied by nanoscale near-edge X-ray absorption spectromicroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "The colloidal particles consist of a solid polystyrene core and a cross-linked poly-N-(isopropylacrylamide) shell with embedded crystalline titanium dioxide (TiO (2)) nanoparticles (d = 6 +/- 3 nm).", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 43, "end": 54}, {"text": "poly-N-(isopropylacrylamide)", "start": 79, "end": 107}, {"text": "titanium dioxide", "start": 140, "end": 156}, {"text": "TiO (2)", "start": 158, "end": 165}]}}, "schema": []}
{"input": "The TiO (2) particles are generated in the carrier network by a sol-gel process at room temperature.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 4, "end": 11}]}}, "schema": []}
{"input": "The hybrid particles were imaged with photon energy steps of 0. 1 eV in their hydrated environment with a cryo transmission X-ray microscope (TXM) at the Ti L (2, 3)-edge.", "output": {"entities": {"chemical": [{"text": "Ti", "start": 154, "end": 156}]}}, "schema": []}
{"input": "By analyzing the image stacks, the obtained near-edge X-ray absorption fine structure (NEXAFS) spectra of our individual hybrid particles show clearly that our synthesis generates TiO (2) in the anastase phase.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 180, "end": 187}]}}, "schema": []}
{"input": "Additionally, our spectromicroscopy method permits the determination of the density distribution of TiO (2) in single carrier particles.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 100, "end": 107}]}}, "schema": []}
{"input": "Therefore, NEXAFS spectroscopy combined with TXM presents a unique method to get in-depth insight into the electronic structure of hybrid materials.", "output": {"entities": {}}, "schema": []}
{"input": "Assessing the regioselectivity of OleD-catalyzed glycosylation with a diverse set of acceptors.", "output": {"entities": {}}, "schema": []}
{"input": "To explore the acceptor regioselectivity of OleD-catalyzed glucosylation, the products of OleD-catalyzed reactions with six structurally diverse acceptors flavones-(daidzein), isoflavones (flavopiridol), stilbenes (resveratrol), indole alkaloids (10-hydroxycamptothecin), and steroids (2-methoxyestradiol)-were determined.", "output": {"entities": {"chemical": [{"text": "flavones", "start": 155, "end": 163}, {"text": "daidzein", "start": 165, "end": 173}, {"text": "isoflavones", "start": 176, "end": 187}, {"text": "flavopiridol", "start": 189, "end": 201}, {"text": "stilbenes", "start": 204, "end": 213}, {"text": "resveratrol", "start": 215, "end": 226}, {"text": "indole alkaloids", "start": 229, "end": 245}, {"text": "10-hydroxycamptothecin", "start": 247, "end": 269}, {"text": "steroids", "start": 276, "end": 284}, {"text": "2-methoxyestradiol", "start": 286, "end": 304}]}}, "schema": []}
{"input": "This study highlights the first synthesis of flavopiridol and 2-methoxyestradiol glucosides and confirms the ability of OleD to glucosylate both aromatic and aliphatic nucleophiles.", "output": {"entities": {"chemical": [{"text": "flavopiridol", "start": 45, "end": 57}, {"text": "2-methoxyestradiol glucosides", "start": 62, "end": 91}, {"text": "glucosylate", "start": 128, "end": 139}]}}, "schema": []}
{"input": "In all cases, molecular dynamics simulations were consistent with the determined product distribution and suggest the potential to develop a virtual screening model to identify additional OleD substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Nonhuman targets in allergic lung conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Existing therapies for allergic asthma are far from perfect: the global prevalence of disease increases despite them and they are poorly effective in dealing with the exacerbations that account for hospitalization and asthma deaths.", "output": {"entities": {}}, "schema": []}
{"input": "Commercially, there are pressures on these existing medicines too-a growing threat from generics and reluctance by payers to reimburse for increasingly marginal improvements in medicines with precedented mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Experience shows that attempts to devise selective small-molecule interventions directed at the myriad of downstream effector pathways has not been a fertile ground for the development of effective new medicines.", "output": {"entities": {}}, "schema": []}
{"input": "An alternative strategy, exploiting breakthroughs in understanding the molecular basis of allergenicity and the key role of innate immune mechanisms in asthma, is to direct new approaches to the disease triggers themselves: allergens.", "output": {"entities": {}}, "schema": []}
{"input": "This raises interesting possibilities for anti-Lipinski drug design (extracellular nonhuman targets, inhaled delivery) and creates unprecedented pharmacological opportunities in the therapeutic area.", "output": {"entities": {}}, "schema": []}
{"input": "Macroporous silk fibroin cryogels.", "output": {"entities": {}}, "schema": []}
{"input": "Silk fibroin cryogels with remarkable properties were obtained from frozen fibroin solutions (4. 2-12. 6%) at subzero temperatures between-5 and-22 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "This was achieved by the addition of ethylene glycol diglycidyl ether (EGDE) into the cryogelation system.", "output": {"entities": {"chemical": [{"text": "ethylene glycol diglycidyl ether", "start": 37, "end": 69}, {"text": "EGDE", "start": 71, "end": 75}]}}, "schema": []}
{"input": "EGDE triggers the conformational transition of fibroin from random coil to beta-sheet structure and hence fibroin gelation.", "output": {"entities": {"chemical": [{"text": "EGDE", "start": 0, "end": 4}]}}, "schema": []}
{"input": "One of the unique features of fibroin cryogels is their elasticity that allows them to resist complete compression without any crack development, during which water inside the cryogel is removed.", "output": {"entities": {}}, "schema": []}
{"input": "The compressed cryogel immediately swells during unloading to recover its original shape.", "output": {"entities": {}}, "schema": []}
{"input": "The scaffolds obtained by freeze-drying of the cryogels consist of regular, interconnected pores of diameters ranging from 50 to 10 mu m that could be regulated by the synthesis parameters.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanical compressive strength and the modulus of the scaffolds increase with decreasing pore diameter, that is, with decreasing gelation temperature or, with increasing fibroin or EGDE concentrations in the feed.", "output": {"entities": {"chemical": [{"text": "EGDE", "start": 186, "end": 190}]}}, "schema": []}
{"input": "The scaffolds produced at 12. 6% fibroin exhibit a very high compressive modulus (50 MPa) making them good candidates as bone scaffold materials.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of polymer end-group chemistry and order of deposition on controlled protein delivery from layer-by-layer assembly.", "output": {"entities": {}}, "schema": []}
{"input": "Layer-by-layer (LBL) assembly is an attractive platform for controlled release of biologics given its mild fabrication process and versatility in coating substrates of any shape.", "output": {"entities": {}}, "schema": []}
{"input": "Proteins can be incorporated into LBL coatings by sequentially depositing oppositely charged polyelectrolytes, which self-assemble into nanoscale films on medical devices or tissue engineering scaffolds.", "output": {"entities": {}}, "schema": []}
{"input": "However, previously reported LBL platforms often require the use of a few hundred layers to avoid burst release, which hinders their broad translation due to the lengthy fabrication process, cost, and batch-to-batch variability.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report a biodegradable LBL platform composed of only 10 layers with tunable protein release kinetics, which is an order of magnitude less than previously reported LBL platforms.", "output": {"entities": {}}, "schema": []}
{"input": "We performed a combinatorial study to examine the effects of polymer chemistry and order of deposition of poly (beta-amino) esters on protein release kinetics under 81 LBL assembly conditions.", "output": {"entities": {"chemical": [{"text": "poly (beta-amino) esters", "start": 106, "end": 130}]}}, "schema": []}
{"input": "Using the optimal \" polyelectrolyte couples \" for constructing the LBL film, basic fibroblast growth factor (bFGF) was released gradually over 14 days with retained biological activity to stimulate cell proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "The method reported herein is applicable for coating various substrates including metals, polymers, and ceramics and may be used for a broad range of biomedical and tissue engineering applications.", "output": {"entities": {}}, "schema": []}
{"input": "Epitaxial silicon dots self-assembled on aluminum nitride/Si (111).", "output": {"entities": {"chemical": [{"text": "silicon", "start": 10, "end": 17}, {"text": "aluminum nitride", "start": 41, "end": 57}, {"text": "Si (111)", "start": 58, "end": 66}]}}, "schema": []}
{"input": "Si nanoscale dots are synthesized on AlN/Si (111) by molecular beam epitaxy.", "output": {"entities": {"chemical": [{"text": "Si", "start": 0, "end": 2}, {"text": "AlN", "start": 37, "end": 40}, {"text": "Si (111)", "start": 41, "end": 49}]}}, "schema": []}
{"input": "A dot density of 2. 2 x 10 (11) cm (-2) with a mean radius of 5. 6 +/- 2. 8 nm is obtained in Volmer-Weber growth mode.", "output": {"entities": {}}, "schema": []}
{"input": "A double Si coverage leads to a decrease in dot density and increase in dot size.", "output": {"entities": {"chemical": [{"text": "Si", "start": 9, "end": 11}]}}, "schema": []}
{"input": "The dot orientations are [11 [overline] 0] (Si) (or [1 [overline] 10] (Si))//[112 [overline] 0] (AlN) and (111) (Si)//(0001) (AlN), which are similar (or identical) to the orientation of AlN relative to the Si substrate.", "output": {"entities": {"chemical": [{"text": "Si", "start": 44, "end": 46}, {"text": "Si", "start": 71, "end": 73}, {"text": "AlN", "start": 97, "end": 100}, {"text": "(111) (Si)", "start": 106, "end": 116}, {"text": "AlN", "start": 126, "end": 129}, {"text": "AlN", "start": 187, "end": 190}, {"text": "Si", "start": 207, "end": 209}]}}, "schema": []}
{"input": "Safety of posaconazole.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 10, "end": 22}]}}, "schema": []}
{"input": "INTRODUCTION: The increasing number of invasive fungal infections (IFI) among immunocompromised hosts is a significant clinical issue.", "output": {"entities": {}}, "schema": []}
{"input": "Diagnosis of IFI, choosing among the available antifungal drugs, and the high morbidity/mortality associated with IFI pose clinical challenges for healthcare providers.", "output": {"entities": {}}, "schema": []}
{"input": "Besides efficacy, a thorough knowledge of the pharmacokinetics, drug-drug interactions and safety profile of the antifungal drugs is critical for appropriate drug selection.", "output": {"entities": {}}, "schema": []}
{"input": "Among the commonly used triazoles, the recently released posaconazole is relatively less well investigated in terms of its safety.", "output": {"entities": {"chemical": [{"text": "triazoles", "start": 24, "end": 33}, {"text": "posaconazole", "start": 57, "end": 69}]}}, "schema": []}
{"input": "With expanding clinical use of posaconazole, the present review examines the safety of the drug and its propensity for drug-drug interaction.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 31, "end": 43}]}}, "schema": []}
{"input": "AREAS COVERED: This paper mainly discusses the safety profile of posaconazole, its adverse effects and drug-drug interaction.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 65, "end": 77}]}}, "schema": []}
{"input": "EXPERT OPINION: Posaconazole is generally safe and well tolerated.", "output": {"entities": {"chemical": [{"text": "Posaconazole", "start": 16, "end": 28}]}}, "schema": []}
{"input": "Lack of an intravenous formulation and unpredictable bioavailability of the suspension form are significant factors limiting the widespread use of posaconazole.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 147, "end": 159}]}}, "schema": []}
{"input": "Mass transfer and adsorption equilibrium for low volatility alkanes in BPL activated carbon.", "output": {"entities": {"chemical": [{"text": "alkanes", "start": 60, "end": 67}, {"text": "carbon", "start": 85, "end": 91}]}}, "schema": []}
{"input": "The structure of a molecule and its concentration can strongly influence diffusional properties for transport in nanoporous materials.", "output": {"entities": {}}, "schema": []}
{"input": "We study mass transfer of alkanes in BPL activated carbon using the concentration-swing frequency response method, which can easily discriminate among mass transfer mechanisms.", "output": {"entities": {"chemical": [{"text": "alkanes", "start": 26, "end": 33}, {"text": "carbon", "start": 51, "end": 57}]}}, "schema": []}
{"input": "We measure concentration-dependent diffusion rates for n-hexane, n-octane, n-decane, 2, 7-dimethyloctane, and cyclodecane, which have different carbon numbers and geometries: straight chain, branched chain, and cyclic.", "output": {"entities": {"chemical": [{"text": "n-hexane", "start": 55, "end": 63}, {"text": "n-octane", "start": 65, "end": 73}, {"text": "n-decane", "start": 75, "end": 83}, {"text": "2, 7-dimethyloctane", "start": 85, "end": 104}, {"text": "cyclodecane", "start": 110, "end": 121}, {"text": "carbon", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Micropore diffusion is determined to be the controlling mass transfer resistance except at low relative saturation for n-decane, where an external mass transfer resistance also becomes important, showing that the controlling mass transfer mechanism can change with system concentration.", "output": {"entities": {"chemical": [{"text": "n-decane", "start": 119, "end": 127}]}}, "schema": []}
{"input": "Micropore diffusion coefficients are found to be strongly concentration dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Adsorption isotherm slopes obtained from measured isotherms, the concentration-swing frequency response method, and a predictive method show reasonably good agreement.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis, and structure-activity relationship studies of tryptanthrins as antitubercular agents.", "output": {"entities": {"chemical": [{"text": "tryptanthrins", "start": 66, "end": 79}]}}, "schema": []}
{"input": "The natural product tryptanthrin (1a) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb).", "output": {"entities": {"chemical": [{"text": "tryptanthrin", "start": 20, "end": 32}, {"text": "tryptanthrin", "start": 104, "end": 116}]}}, "schema": []}
{"input": "However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB.", "output": {"entities": {}}, "schema": []}
{"input": "Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds.", "output": {"entities": {"chemical": [{"text": "tryptanthrin", "start": 38, "end": 50}]}}, "schema": []}
{"input": "Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB.", "output": {"entities": {}}, "schema": []}
{"input": "The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products.", "output": {"entities": {}}, "schema": []}
{"input": "Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents.", "output": {"entities": {"chemical": [{"text": "tryptanthrin", "start": 47, "end": 59}, {"text": "tryptanthrin", "start": 166, "end": 178}]}}, "schema": []}
{"input": "However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.", "output": {"entities": {"chemical": [{"text": "tryptanthrin", "start": 128, "end": 140}]}}, "schema": []}
{"input": "pi-Conjugated nickel bis (dithiolene) complex nanosheet.", "output": {"entities": {"chemical": [{"text": "nickel bis (dithiolene)", "start": 14, "end": 37}]}}, "schema": []}
{"input": "A pi-conjugated nanosheet comprising planar nickel bis (dithiolene) complexes was synthesized by a bottom-up method.", "output": {"entities": {"chemical": [{"text": "nickel bis (dithiolene)", "start": 44, "end": 67}]}}, "schema": []}
{"input": "A liquid-liquid interfacial reaction using benzenehexathiol in the organic phase and nickel (II) acetate in the aqueous phase produced a semiconducting bulk material with a thickness of several micrometers.", "output": {"entities": {"chemical": [{"text": "benzenehexathiol", "start": 43, "end": 59}, {"text": "nickel (II) acetate", "start": 85, "end": 104}]}}, "schema": []}
{"input": "Powder X-ray diffraction analysis revealed that the crystalline portion of the bulk material comprised a staggered stack of nanosheets.", "output": {"entities": {}}, "schema": []}
{"input": "A single-layer nanosheet was successfully realized using a gas-liquid interfacial reaction.", "output": {"entities": {}}, "schema": []}
{"input": "Atomic force microscopy and scanning tunneling microscopy confirmed that the pi-conjugated nanosheet was single-layered.", "output": {"entities": {}}, "schema": []}
{"input": "Modulation of the oxidation state of the nanosheet was possible using chemical redox reactions.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative surface thermodynamic analysis of new fluid phase formation between a sphere and a flat plate.", "output": {"entities": {}}, "schema": []}
{"input": "This paper investigates the behavior of confined fluid in the gap between a sphere and a flat plate by examining the curve of free energy of the system versus size of the new phase.", "output": {"entities": {}}, "schema": []}
{"input": "Four possible situations corresponding to new phase formation out of confined liquid or vapor at pressures above or below the saturation pressure are studied.", "output": {"entities": {}}, "schema": []}
{"input": "Using surface thermodynamics, the feasible shape of the meniscus (concave/convex), the possibility of phase transition, as well as the number and the nature (unstable/stable) of equilibrium states have been determined for each of these four situations.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of equilibrium contact angle, separation distance of confinement surfaces, and sphere size have been studied.", "output": {"entities": {}}, "schema": []}
{"input": "We show that the number and nature of equilibrium states, along with the effect of different parameters in these four possible situations, can be well described under two categories of new phase formation with (a) concave or (b) convex meniscus.", "output": {"entities": {}}, "schema": []}
{"input": "Our results reveal that in the sphere-plate gap, stable coexistence of the liquid and vapor phases is only possible when the meniscus is concave (which corresponds to either capillary condensation or capillary evaporation), and when the sphere and plate are separated by a distance less than a critical amount (where that critical amount is always less than the Kelvin radius).", "output": {"entities": {}}, "schema": []}
{"input": "With convex menisci, no stable coexistence of liquid and vapor phase is possible.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro and mechanistic studies of an antiamyloidogenic self-assembled cyclic D, L-alpha-peptide architecture.", "output": {"entities": {"chemical": [{"text": "cyclic D, L-alpha-peptide", "start": 72, "end": 97}]}}, "schema": []}
{"input": "Misfolding of the A beta protein and its subsequent aggregation into toxic oligomers are related to Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Although peptides of various sequences can self-assemble into amyloid structures, these structures share common three-dimensional features that may promote their cross-reaction.", "output": {"entities": {}}, "schema": []}
{"input": "Given the significant similarities between amyloids and the architecture of self-assembled cyclic D, L-alpha-peptide, we hypothesized that the latter may bind and stabilize a nontoxic form of A beta, thereby preventing its aggregation into toxic forms.", "output": {"entities": {"chemical": [{"text": "cyclic D, L-alpha-peptide", "start": 91, "end": 116}]}}, "schema": []}
{"input": "By screening a focused library of six-residue cyclic D, L-alpha-peptides and optimizing the activity of a lead peptide, we found one cyclic D, L-alpha-peptide (CP-2) that interacts strongly with A beta and inhibits its aggregation.", "output": {"entities": {"chemical": [{"text": "cyclic D, L-alpha-peptides", "start": 46, "end": 72}, {"text": "cyclic D, L-alpha-peptide", "start": 133, "end": 158}, {"text": "CP-2", "start": 160, "end": 164}]}}, "schema": []}
{"input": "In transmission electron microscopy, optimized thioflavin T and cell survival assays, CP-2 inhibits the formation of A beta aggregates, entirely disassembles preformed aggregated and fibrillar A beta, and protects rat pheochromocytoma PC12 cells from A beta toxicity, without inducing any toxicity by itself.", "output": {"entities": {"chemical": [{"text": "thioflavin T", "start": 47, "end": 59}, {"text": "CP-2", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Using various immunoassays, circular dichroism spectroscopy, photoinduced cross-linking of unmodified proteins (PICUP) combined with SDS/PAGE, and NMR, we probed the mechanisms underlying CP-2' s antiamyloidogenic activity.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 133, "end": 136}, {"text": "CP-2", "start": 188, "end": 192}]}}, "schema": []}
{"input": "NMR spectroscopy indicates that CP-2 interacts with A beta through its self-assembled conformation and induces weak secondary structure in A beta.", "output": {"entities": {"chemical": [{"text": "CP-2", "start": 32, "end": 36}]}}, "schema": []}
{"input": "Upon coincubation, CP-2 changes the aggregation pathway of A beta and alters its oligomer distribution by stabilizing small oligomers (1-3 mers).", "output": {"entities": {"chemical": [{"text": "CP-2", "start": 19, "end": 23}]}}, "schema": []}
{"input": "Our results support studies suggesting that toxic early oligomeric states of A beta may be composed of antiparallel beta-peptide structures and that the interaction of A beta with CP-2 promotes formation of more benign parallel beta-structures.", "output": {"entities": {"chemical": [{"text": "CP-2", "start": 180, "end": 184}]}}, "schema": []}
{"input": "Further studies will show whether these kinds of abiotic cyclic D, L-alpha-peptides are also beneficial as an intervention in related in vivo models.", "output": {"entities": {"chemical": [{"text": "cyclic D, L-alpha-peptides", "start": 57, "end": 83}]}}, "schema": []}
{"input": "Anti-inflammatory effects of a special carbohydrate-whey protein cake after exhaustive cycling in humans.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 39, "end": 51}]}}, "schema": []}
{"input": "Intense exercise induces increased levels of pro-inflammatory and anti-inflammatory cytokines.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the purpose of this study was to examine the effects of a special cake (consisting of carbohydrate to whey protein 3. 5: 1) vs. an isocaloric carbohydrate cake on inflammatory markers after exhaustive cycling in humans.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 92, "end": 104}, {"text": "carbohydrate", "start": 148, "end": 160}]}}, "schema": []}
{"input": "Nine subjects received either the experimental or placebo cake in a counterbalanced fashion using a crossover, double-blind, repeated-measures design.", "output": {"entities": {}}, "schema": []}
{"input": "They performed one trial involving a 2h exercise on a cycle ergometer at 60-65% VO2max followed by a 4h recovery and then a second trial involving an 1h exercise at 60-65% VO2max which was increased at 95% VO2max.", "output": {"entities": {}}, "schema": []}
{"input": "Blood samples were collected pre-exercise, 30min and 4h post-exercise, post-time Trial and 48h post-time Trial.", "output": {"entities": {}}, "schema": []}
{"input": "Cakes were consumed immediately post-exercise and every 1h for the next 3h.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that consumption of the experimental cake reduced significantly (p < 0. 05), 4h post-exercise, the pro-inflammatory protein levels IL-6 and CRP compared to the control group by 50% and 46% respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, in the experimental cake group, the level of the anti-inflammatory cytokine IL-10 was higher by 118%, 4h post-exercise, compared to the control group but not statistically significant.", "output": {"entities": {}}, "schema": []}
{"input": "X-ray absorption spectroscopy and energy storage of Ni-doped cobalt nitride, (Ni (0. 33) Co (0. 67)) N, prepared by a simple synthesis route.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 52, "end": 54}, {"text": "cobalt nitride", "start": 61, "end": 75}, {"text": "(Ni (0. 33) Co (0. 67)) N", "start": 77, "end": 102}]}}, "schema": []}
{"input": "Metal nitride (Ni (0. 33) Co (0. 67)) N nanoparticles are prepared by nitridation using NiCo (2) O (4) as a precursor material by heating at 335 degrees C for 2 h in flowing NH (3) + N (2) gas and characterized by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), high resolution-transmission electron microscopy (HR-TEM), along with selective area electron diffraction (SAED) and X-ray absorption spectroscopy (XAS) techniques.", "output": {"entities": {"chemical": [{"text": "Metal nitride (Ni (0. 33) Co (0. 67)) N", "start": 0, "end": 39}, {"text": "NiCo (2) O (4)", "start": 88, "end": 102}, {"text": "NH (3)", "start": 174, "end": 180}, {"text": "N (2)", "start": 183, "end": 188}]}}, "schema": []}
{"input": "The X-ray absorption near edge structure (XANES) at the Co K-edge showed that the oxidation state of cobalt is close to 3 +.", "output": {"entities": {"chemical": [{"text": "Co", "start": 56, "end": 58}, {"text": "cobalt", "start": 101, "end": 107}]}}, "schema": []}
{"input": "The (Ni (0. 33) Co (0. 67)) N showed a shift in edge energy towards lower values due to Ni-doping to cobalt site.", "output": {"entities": {"chemical": [{"text": "(Ni (0. 33) Co (0. 67)) N", "start": 4, "end": 29}, {"text": "Ni", "start": 88, "end": 90}]}}, "schema": []}
{"input": "The Li-storage behaviour of (Ni (0. 33) Co (0. 67)) N nanoparticles was evaluated by galvanostatic cycling and cyclic voltammetry in the cells with Li-metal as counter electrode in the voltage range of 0. 005-3. 0 V at ambient temperature.", "output": {"entities": {"chemical": [{"text": "Li", "start": 4, "end": 6}, {"text": "(Ni (0. 33) Co (0. 67)) N", "start": 28, "end": 53}, {"text": "Li", "start": 148, "end": 150}]}}, "schema": []}
{"input": "When cycled at 250 mA g (-1), the first-cycle reversible capacity of 700 (+/- 5) mA h g (-1) (~ 1. 9 moles of Li) is obtained.", "output": {"entities": {"chemical": [{"text": "Li", "start": 110, "end": 112}]}}, "schema": []}
{"input": "It showed an initial decrease in capacity until the 10 (th) cycle and a stable capacity of 400 (+/- 5) mA h g (-1) (~ 1. 09 moles of Li) is observed at the end of the 50 (th) cycle.", "output": {"entities": {"chemical": [{"text": "Li", "start": 133, "end": 135}]}}, "schema": []}
{"input": "Excellent rate capability is also shown when cycling at 500 mA g (-1) (up to 50 cycles).", "output": {"entities": {}}, "schema": []}
{"input": "The materials showed excellent Li-ion insertion/extraction, with the coulombic efficiency reaching almost 99% in the range of 10-50 cycles.", "output": {"entities": {"chemical": [{"text": "Li", "start": 31, "end": 33}]}}, "schema": []}
{"input": "The average charge and discharge potentials are ~ 2. 03 and ~ 1. 0 V, respectively for the decomposition/formation of Li (3) N as determined by electroanalytical techniques.", "output": {"entities": {"chemical": [{"text": "Li (3) N", "start": 118, "end": 126}]}}, "schema": []}
{"input": "Self-assembly of mesoporous CuO nanosheets-CNT 3D-network composites for lithium-ion batteries.", "output": {"entities": {"chemical": [{"text": "CuO", "start": 28, "end": 31}, {"text": "lithium", "start": 73, "end": 80}]}}, "schema": []}
{"input": "A facile, flexible and large-scale technique was proposed to prepare a CuO-CNT 3D-network composite with the aid of electrostatic interactions in aqueous solution.", "output": {"entities": {"chemical": [{"text": "CuO", "start": 71, "end": 74}]}}, "schema": []}
{"input": "The composite greatly improves the electrochemical performance.", "output": {"entities": {}}, "schema": []}
{"input": "At a rate of 0. 1 C, the cycling discharge capacity of the optimal composite is more than 2. 3 times of that of unmodified mesoporous CuO nanosheets as the active material in an anode after 40 cycles.", "output": {"entities": {"chemical": [{"text": "CuO", "start": 134, "end": 137}]}}, "schema": []}
{"input": "Adsorbed and near surface structure of ionic liquids at a solid interface.", "output": {"entities": {}}, "schema": []}
{"input": "The structure of solid-ionic liquid (IL) interfaces has been characterised with unprecedented clarity by employing a range of atomic force microscopy (AFM) imaging techniques and tip pressures appropriate for the system under study.", "output": {"entities": {}}, "schema": []}
{"input": "Soft contact and amplitude-modulation (AM) AFM imaging have been used to elucidate the lateral structure of ILs adsorbed onto mica, and in the near surface ion layers.", "output": {"entities": {}}, "schema": []}
{"input": "Data is presented for ethylammonium nitrate (EAN) and 1-ethyl-3-methylimidazolium bis (trifluoro-methylsulfonyl) imide (EMIm TFSI).", "output": {"entities": {"chemical": [{"text": "ethylammonium nitrate", "start": 22, "end": 43}, {"text": "EAN", "start": 45, "end": 48}, {"text": "1-ethyl-3-methylimidazolium bis (trifluoro-methylsulfonyl) imide", "start": 54, "end": 118}, {"text": "EMIm TFSI", "start": 120, "end": 129}]}}, "schema": []}
{"input": "Whereas EAN is a protic IL that forms a nanostructured sponge phase in the bulk, EMIm TFSI is aprotic and has weak (or absent) bulk association structure.", "output": {"entities": {"chemical": [{"text": "EAN", "start": 8, "end": 11}, {"text": "EMIm TFSI", "start": 81, "end": 90}]}}, "schema": []}
{"input": "Comparison of results obtained for the two liquids elucidates how the strength of bulk liquid morphology effects lateral organisation at the surface, and any effect of IL class, i. e. protic versus aprotic.", "output": {"entities": {}}, "schema": []}
{"input": "Imaging reveals EAN self assembles at the solid surface in a worm-like morphology, whereas EMIm cations adsorb in a more isolated fashion, but still in rows templated by the mica surface.", "output": {"entities": {"chemical": [{"text": "EAN", "start": 16, "end": 19}, {"text": "EMIm", "start": 91, "end": 95}]}}, "schema": []}
{"input": "To the authors' knowledge, the wormlike structures present at the EAN-mica interface are the smallest self-assembled aggregates ever imaged on a solid surface.", "output": {"entities": {"chemical": [{"text": "EAN", "start": 66, "end": 69}]}}, "schema": []}
{"input": "Review of clinical trials for mitochondrial disorders: 1997-2012.", "output": {"entities": {}}, "schema": []}
{"input": "Over the last 15 years, some 16 open and controlled clinical trials for potential treatments of mitochondrial diseases have been reported or are in progress, and are summarized and reviewed herein.", "output": {"entities": {}}, "schema": []}
{"input": "These include trials of administering dichloroacetate (an activator of pyruvate dehydrogenase complex), arginine or citrulline (precursors of nitric oxide), coenzyme Q10 (CoQ10; part of the electron transport chain and an antioxidant), idebenone (a synthetic analogue of CoQ10), EPI-743 (a novel oral potent 2-electron redox cycling agent), creatine (a precursor of phosphocreatine), combined administration (of creatine, alpha-lipoate, and CoQ10), and exercise training (to increase muscle mitochondria).", "output": {"entities": {"chemical": [{"text": "dichloroacetate", "start": 38, "end": 53}, {"text": "pyruvate", "start": 71, "end": 79}, {"text": "arginine", "start": 104, "end": 112}, {"text": "citrulline", "start": 116, "end": 126}, {"text": "nitric oxide", "start": 142, "end": 154}, {"text": "coenzyme Q10", "start": 157, "end": 169}, {"text": "CoQ10", "start": 171, "end": 176}, {"text": "idebenone", "start": 236, "end": 245}, {"text": "CoQ10", "start": 271, "end": 276}, {"text": "EPI-743", "start": 279, "end": 286}, {"text": "creatine", "start": 341, "end": 349}, {"text": "phosphocreatine", "start": 366, "end": 381}, {"text": "creatine", "start": 412, "end": 420}, {"text": "alpha-lipoate", "start": 422, "end": 435}, {"text": "CoQ10", "start": 441, "end": 446}]}}, "schema": []}
{"input": "These trials have included patients with various mitochondrial disorders, a selected subcategory of mitochondrial disorders, or specific mitochondrial disorders (Leber hereditary optic neuropathy or mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes).", "output": {"entities": {}}, "schema": []}
{"input": "The trial designs have varied from open-label/uncontrolled, open-label/controlled, or double-blind/placebo-controlled/crossover.", "output": {"entities": {}}, "schema": []}
{"input": "Primary outcomes have ranged from single, clinically-relevant scores to multiple measures.", "output": {"entities": {}}, "schema": []}
{"input": "Eight of these trials have been well-controlled, completed trials.", "output": {"entities": {}}, "schema": []}
{"input": "Of these only 1 (treatment with creatine) showed a significant change in primary outcomes, but this was not reproduced in 2 subsequent trials with creatine with different patients.", "output": {"entities": {"chemical": [{"text": "creatine", "start": 32, "end": 40}]}}, "schema": []}
{"input": "One trial (idebenone treatment of Leber hereditary optic neuropathy) did not show significant improvement in the primary outcome, but there was significant improvement in a subgroup of patients.", "output": {"entities": {"chemical": [{"text": "idebenone", "start": 11, "end": 20}]}}, "schema": []}
{"input": "Despite the paucity of benefits found so far, well-controlled clinical trials are essential building blocks in the continuing search for more effective treatment of mitochondrial disease, and current trials based on information gained from these prior experiences are in progress.", "output": {"entities": {}}, "schema": []}
{"input": "Because of difficulties in recruiting sufficient mitochondrial disease patients and the relatively large expense of conducting such trials, advantageous strategies include crossover designs (where possible), multicenter collaboration, and the selection of very few, clinically relevant, primary outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Antenatal manifestations of mitochondrial disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial respiratory chain diseases are a heterogeneous group of pathologies caused by genetic alterations affecting mitochondrial energy production.", "output": {"entities": {}}, "schema": []}
{"input": "Theoretically, this deficiency may lead to any symptoms, in any organ or tissue, at any age even before birth.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of our study was to identify the frequency and characterize antenatal manifestations identifying possible associations between mitochondrial disease and more specific and earlier manifestation.", "output": {"entities": {}}, "schema": []}
{"input": "We retrospectively review the files of 44 paediatric subjects with genetic and biochemical alterations of respiratory chain identified in the first decade of life and compare data with a control group (n = 88).", "output": {"entities": {}}, "schema": []}
{"input": "Our results show that maternal age was similar in both groups.", "output": {"entities": {}}, "schema": []}
{"input": "The female gender was predominant in patients group.", "output": {"entities": {}}, "schema": []}
{"input": "Gestational age at delivery was similar in both groups.", "output": {"entities": {}}, "schema": []}
{"input": "Concerning birth weight, it was significantly lower (p = 0. 001) in patients (2899. 9 +/- 538. 3 vs. 3246. 6 +/- 460. 2 g).", "output": {"entities": {}}, "schema": []}
{"input": "Fifteen pregnancies of the patients group were considered abnormal.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings show that intrauterine growth restriction was the most frequent antenatal feature observed.", "output": {"entities": {}}, "schema": []}
{"input": "Neonatal morbidity was significantly higher (fivefold) in patients (p < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "The clinical findings are independent of the molecular defect type.", "output": {"entities": {}}, "schema": []}
{"input": "Our results are preliminary and more studies are needed, in order to learn more about mitochondrial physiology and activity in embryological development for the assessment of mitochondrial disease progress in fetal life.", "output": {"entities": {}}, "schema": []}
{"input": "However, the present work is a significant contribution, given the scarcity of information in this field.", "output": {"entities": {}}, "schema": []}
{"input": "Left ventricular noncompaction (LVNC) and low mitochondrial membrane potential are specific for Barth syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Barth syndrome (BTHS) is an X-linked mitochondrial defect characterised by dilated cardiomyopathy, neutropaenia and 3-methylglutaconic aciduria (3-MGCA).", "output": {"entities": {}}, "schema": []}
{"input": "We report on two affected brothers with c. 646G > A (p. G216R) TAZ gene mutations.", "output": {"entities": {}}, "schema": []}
{"input": "The pathogenicity of the mutation, as indicated by the structure-based functional analyses, was further confirmed by abnormal monolysocardiolipin/cardiolipin ratio in dry blood spots of the patients as well as the occurrence of this mutation in another reported BTHS proband.", "output": {"entities": {"chemical": [{"text": "monolysocardiolipin", "start": 126, "end": 145}, {"text": "cardiolipin", "start": 146, "end": 157}]}}, "schema": []}
{"input": "In both brothers, 2D-echocardiography revealed some features of left ventricular noncompaction (LVNC) despite marked differences in the course of the disease; the eldest child presented with isolated cardiomyopathy from late infancy, whereas the youngest showed severe lactic acidosis without 3-MGCA during the neonatal period.", "output": {"entities": {}}, "schema": []}
{"input": "An examination of the patients' fibroblast cultures revealed that extremely low mitochondrial membrane potentials (mt Delta Psi about 50% of the control value) dominated other unspecific mitochondrial changes detected (respiratory chain dysfunction, abnormal ROS production and depressed antioxidant defense).", "output": {"entities": {}}, "schema": []}
{"input": "1) Our studies confirm generalised mitochondrial dysfunction in the skeletal muscle and the fibroblasts of BTHS patients, especially a severe impairment in the mt Delta Psi and the inhibition of complex V activity.", "output": {"entities": {}}, "schema": []}
{"input": "It can be hypothesised that impaired mt Delta Psi and mitochondrial ATP synthase activity may contribute to episodes of cardiac arrhythmia that occurred unexpectedly in BTHS patients.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 68, "end": 71}]}}, "schema": []}
{"input": "2) Severe lactic acidosis without 3-methylglutaconic aciduria in male neonates as well as an asymptomatic mild left ventricular noncompaction may characterise the ranges of natural history of Barth syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Facile solution synthesis of Ag @Pt core-shell nanoparticles with dendritic Pt shells.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 29, "end": 31}, {"text": "Pt", "start": 33, "end": 35}, {"text": "Pt", "start": 76, "end": 78}]}}, "schema": []}
{"input": "Ag @Pt nanoparticles with various dendritic Pt shells were successfully synthesized by using nonionic surfactants at room temperature.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 0, "end": 2}, {"text": "Pt", "start": 4, "end": 6}, {"text": "Pt", "start": 44, "end": 46}]}}, "schema": []}
{"input": "Our recent study demonstrated that the addition of nonionic surfactant plays an important key role in the synthesis of dendritic Pt nanostructures (J. Am. Chem. Soc., 2010, 132, 13636).", "output": {"entities": {"chemical": [{"text": "Pt", "start": 129, "end": 131}]}}, "schema": []}
{"input": "Here we extend this synthetic concept to prepare various Ag @Pt nanoarchitectures.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 57, "end": 59}, {"text": "Pt", "start": 61, "end": 63}]}}, "schema": []}
{"input": "The different nanostructured Pt shells on the Ag core were confirmed by ultraviolet-visible absorption spectroscopy and transmission electron microscopy.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 29, "end": 31}, {"text": "Ag", "start": 46, "end": 48}]}}, "schema": []}
{"input": "As a preliminary electrochemical application, the obtained Ag @Pt nanostructures were applied in the methanol oxidation reaction (MOR) in 0. 5 M H (2) SO (4) solution containing 0. 5 M methanol.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 59, "end": 61}, {"text": "Pt", "start": 63, "end": 65}, {"text": "methanol", "start": 101, "end": 109}, {"text": "H (2) SO (4)", "start": 145, "end": 157}, {"text": "methanol", "start": 185, "end": 193}]}}, "schema": []}
{"input": "The Ag @Pt nanoparticles with thin dendritic Pt shells show superior CO-tolerance performance with a I (f)/I (b) value reaching 3. 71.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 4, "end": 6}, {"text": "Pt", "start": 8, "end": 10}, {"text": "Pt", "start": 45, "end": 47}, {"text": "CO", "start": 69, "end": 71}]}}, "schema": []}
{"input": "Our Ag @Pt nanostructures with good CO tolerant activity will be prominent catalysts for MOR.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 4, "end": 6}, {"text": "Pt", "start": 8, "end": 10}, {"text": "CO", "start": 36, "end": 38}]}}, "schema": []}
{"input": "A mechanistic study of the electrochemical oxygen reduction on the model semiconductor n-Ge (100) by ATR-IR and DFT.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 43, "end": 49}, {"text": "Ge", "start": 89, "end": 91}]}}, "schema": []}
{"input": "The electrochemical oxygen reduction reaction (ORR) on a n-Ge (100) surface in 0. 1 M HClO4 was investigated in situ and operando using a combination of attenuated total reflection infrared (ATR-IR) spectroscopy and density functional (DFT) calculations.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 20, "end": 26}, {"text": "Ge", "start": 59, "end": 61}, {"text": "HClO4", "start": 86, "end": 91}]}}, "schema": []}
{"input": "The vibrational modes of the detected intermediates were assigned based on DFT calculations of solvated model clusters such as Ge-bound superoxides and peroxides.", "output": {"entities": {"chemical": [{"text": "Ge", "start": 127, "end": 129}, {"text": "superoxides", "start": 136, "end": 147}, {"text": "peroxides", "start": 152, "end": 161}]}}, "schema": []}
{"input": "ATR-IR shows the Ge-bound superoxide with a transition dipole moment oriented at (28 +/- 10) degrees with respect to the surface normal.", "output": {"entities": {"chemical": [{"text": "Ge", "start": 17, "end": 19}, {"text": "superoxide", "start": 26, "end": 36}]}}, "schema": []}
{"input": "At slightly negative potentials, the surface-bound peroxide is identified by an OOH bending mode as a further intermediate, oriented at a similar angle.", "output": {"entities": {"chemical": [{"text": "peroxide", "start": 51, "end": 59}, {"text": "OOH", "start": 80, "end": 83}]}}, "schema": []}
{"input": "At strongly negative potentials, a surface-bound perchlorate is found.", "output": {"entities": {}}, "schema": []}
{"input": "The findings indicate a multistep mechanism of the ORR.", "output": {"entities": {}}, "schema": []}
{"input": "The reaction is furthermore coupled with the hydrogen evolution reaction (HER).", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Microfluidic platforms for RNA interference screening of virus-host interactions.", "output": {"entities": {}}, "schema": []}
{"input": "RNA interference (RNAi) is a powerful tool for functional genomics with the capacity to comprehensively analyze host-pathogen interactions.", "output": {"entities": {}}, "schema": []}
{"input": "High-throughput RNAi screening is used to systematically perturb cellular pathways and discover therapeutic targets, but the method can be tedious and requires extensive capital equipment and expensive reagents.", "output": {"entities": {}}, "schema": []}
{"input": "To aid in the development of an inexpensive miniaturized RNAi screening platform, we have developed a two part microfluidic system for patterning and screening gene targets on-chip to examine cellular pathways involved in virus entry and infection.", "output": {"entities": {}}, "schema": []}
{"input": "First, a multilayer polydimethylsiloxane (PDMS)-based spotting device was used to array siRNA molecules into 96 microwells targeting markers of endocytosis, along with siRNA controls.", "output": {"entities": {"chemical": [{"text": "polydimethylsiloxane", "start": 20, "end": 40}, {"text": "PDMS", "start": 42, "end": 46}]}}, "schema": []}
{"input": "By using a PDMS-based spotting device, we remove the need for a microarray printer necessary to perform previously described small scale (e. g. cellular microarrays) and microchip-based RNAi screening, while still minimizing reagent usage tenfold compared to conventional screening.", "output": {"entities": {"chemical": [{"text": "PDMS", "start": 11, "end": 15}]}}, "schema": []}
{"input": "Second, the siRNA spotted array was transferred to a reversibly sealed PDMS-based screening platform containing microchannels designed to enable efficient cell loading and transfection of mammalian cells while preventing cross-contamination between experimental conditions.", "output": {"entities": {"chemical": [{"text": "PDMS", "start": 71, "end": 75}]}}, "schema": []}
{"input": "Validation of the screening platform was examined using Vesicular stomatitis virus and emerging pathogen Rift Valley fever virus, which demonstrated virus entry pathways of clathrin-mediated endocytosis and caveolae-mediated endocytosis, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The techniques here are adaptable to other well-characterized infection pathways with a potential for large scale screening in high containment biosafety laboratories.", "output": {"entities": {}}, "schema": []}
{"input": "Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology.", "output": {"entities": {}}, "schema": []}
{"input": "Deregulation of mini-chromosome maintenance (MCM) proteins is associated with genomic instability and cancer.", "output": {"entities": {}}, "schema": []}
{"input": "MCM complexes are recruited to replication origins for genome duplication.", "output": {"entities": {}}, "schema": []}
{"input": "Paradoxically, MCM proteins are in excess than the number of origins and are associated with chromatin regions away from the origins during G1 and S phases.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report an unusually wide left-handed filament structure for an archaeal MCM, as determined by X-ray and electron microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "The crystal structure reveals that an alpha-helix bundle formed between two neighboring subunits plays a critical role in filament formation.", "output": {"entities": {}}, "schema": []}
{"input": "The filament has a remarkably strong electro-positive surface spiraling along the inner filament channel for DNA binding.", "output": {"entities": {}}, "schema": []}
{"input": "We show that this MCM filament binding to DNA causes dramatic DNA topology change.", "output": {"entities": {}}, "schema": []}
{"input": "This newly identified function of MCM to change DNA topology may imply a wider functional role for MCM in DNA metabolisms beyond helicase function.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, using yeast genetics, we show that the inter-subunit interactions, important for MCM filament formation, play a role for cell growth and survival.", "output": {"entities": {}}, "schema": []}
{"input": "Transcriptional regulators of hepatic gluconeogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Glucose is a primary fuel for generating energy in basic daily activities.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Thus, glucose homeostasis is tightly regulated by counter-regulatory hormones such as glucagon, cortisol, and insulin, which affect key organs including liver, skeletal muscle, pancreas, and adipocytes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 6, "end": 13}]}}, "schema": []}
{"input": "Among metabolic tissues, liver plays a critical role in controlling glucose production under various hormonal and metabolic cues.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 68, "end": 75}]}}, "schema": []}
{"input": "Under fasting, acute activation of both glycogenolysis and gluconeogenesis is achieved by post-translational modification or allosteric activation of key rate-limiting enzymes, thereby enabling enhanced glucose production from the liver to maintain glucose homeostasis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 203, "end": 210}, {"text": "glucose", "start": 249, "end": 256}]}}, "schema": []}
{"input": "More prolonged fasting or starvation leads to the chronic activation of gluconeogenesis that requires increased expression of key enzymes in the pathway, which is turned off under feeding conditions by the molecular events that are initiated by insulin.", "output": {"entities": {}}, "schema": []}
{"input": "This process is normally achieved by the regulation of gene expression at the level of transcription.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, the transcriptional regulators of hepatic gluconeogenesis are considered as potential therapeutic targets for the treatment of type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we would like to discuss the current knowledge regarding the key transcriptional activators and inhibitors of hepatic gluconeogenic program to provide the better insight into the control of glycemia in the disease status.", "output": {"entities": {}}, "schema": []}
{"input": "Role of cytochrome P4502B6 in methadone metabolism and clearance.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 30, "end": 39}]}}, "schema": []}
{"input": "Methadone N-demethylation in vitro is catalyzed by hepatic cytochrome P4502B6 (CYP2B6) and CYP3A4, but clinical disposition is often attributed to CYP3A4.", "output": {"entities": {"chemical": [{"text": "Methadone N", "start": 0, "end": 11}]}}, "schema": []}
{"input": "This investigation tested the hypothesis that CYP2B6 is a prominent CYP isoform responsible for clinical methadone N-demethylation and clearance, using the in vivo mechanism-based CYP2B6 inhibitor ticlopidine, given orally for 4 days.", "output": {"entities": {"chemical": [{"text": "methadone N", "start": 105, "end": 116}, {"text": "ticlopidine", "start": 197, "end": 208}]}}, "schema": []}
{"input": "A preliminary clinical investigation with the CYP3A4/5 substrate probe alfentanil established that ticlopidine did not inhibit intestinal or hepatic CYP3A4/5.", "output": {"entities": {"chemical": [{"text": "alfentanil", "start": 71, "end": 81}, {"text": "ticlopidine", "start": 99, "end": 110}]}}, "schema": []}
{"input": "Subjects received intravenous plus oral (deuterium-labeled) racemic methadone before and after ticlopidine.", "output": {"entities": {"chemical": [{"text": "deuterium", "start": 41, "end": 50}, {"text": "racemic methadone", "start": 60, "end": 77}, {"text": "ticlopidine", "start": 95, "end": 106}]}}, "schema": []}
{"input": "Ticlopidine significantly and stereoselectively (S > R) inhibited methadone N-demethylation, decreasing plasma metabolite/methadone area under the curve ratios and metabolite formation clearances.", "output": {"entities": {"chemical": [{"text": "Ticlopidine", "start": 0, "end": 11}, {"text": "methadone N", "start": 66, "end": 77}, {"text": "methadone", "start": 122, "end": 131}]}}, "schema": []}
{"input": "Ticlopidine also significantly increased the dose-adjusted plasma area under the curve for R-and S-methadone by 20% and 60%, respectively, after both intravenous and oral dosing.", "output": {"entities": {"chemical": [{"text": "Ticlopidine", "start": 0, "end": 11}, {"text": "R-and S-methadone", "start": 91, "end": 108}]}}, "schema": []}
{"input": "CYP2B6 inhibition reduces methadone N-demethylation and clearance, and alters methadone concentrations, demonstrating an important role for CYP2B6 in clinical methadone disposition.", "output": {"entities": {"chemical": [{"text": "methadone N", "start": 26, "end": 37}, {"text": "methadone", "start": 78, "end": 87}, {"text": "methadone", "start": 159, "end": 168}]}}, "schema": []}
{"input": "Carboxylic acid (bio) isosteres in drug design.", "output": {"entities": {"chemical": [{"text": "Carboxylic acid", "start": 0, "end": 15}]}}, "schema": []}
{"input": "The carboxylic acid functional group can be an important constituent of a pharmacophore, however, the presence of this moiety can also be responsible for significant drawbacks, including metabolic instability, toxicity, as well as limited passive diffusion across biological membranes.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 4, "end": 19}]}}, "schema": []}
{"input": "To avoid some of these shortcomings while retaining the desired attributes of the carboxylic acid moiety, medicinal chemists often investigate the use of carboxylic acid (bio) isosteres.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 82, "end": 97}, {"text": "carboxylic acid", "start": 154, "end": 169}]}}, "schema": []}
{"input": "The same type of strategy can also be effective for a variety other purposes, for example, to increase the selectivity of a biologically active compound or to create new intellectual property.", "output": {"entities": {}}, "schema": []}
{"input": "Several carboxylic acid isosteres have been reported, however, the outcome of any isosteric replacement cannot be readily predicted as this strategy is generally found to be dependent upon the particular context (i. e., the characteristic properties of the drug and the drug-target).", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 8, "end": 23}]}}, "schema": []}
{"input": "As a result, screening of a panel of isosteres is typically required.", "output": {"entities": {}}, "schema": []}
{"input": "In this context, the discovery and development of novel carboxylic acid surrogates that could complement the existing palette of isosteres remains an important area of research.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 56, "end": 71}]}}, "schema": []}
{"input": "The goal of this Minireview is to provide an overview of the most commonly employed carboxylic acid (bio) isosteres and to present representative examples demonstrating the use and utility of each isostere in drug design.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 84, "end": 99}]}}, "schema": []}
{"input": "Tumor localization and biochemical response to cure in tumor-induced osteomalacia.", "output": {"entities": {}}, "schema": []}
{"input": "Tumor-induced osteomalacia (TIO) is a rare disorder of phosphate wasting due to fibroblast growth factor-23 (FGF23)-secreting tumors that are often difficult to locate.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 55, "end": 64}]}}, "schema": []}
{"input": "We present a systematic approach to tumor localization and post-operative biochemical changes in 31 subjects with TIO.", "output": {"entities": {}}, "schema": []}
{"input": "All had failed either initial, or re-localization (in case of recurrence or metastases at outside institutions).", "output": {"entities": {}}, "schema": []}
{"input": "Functional imaging with (111) Indium-octreotide with single photon emission computed tomography (octreo-SPECT or SPECT/CT), and (18) fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) were performed, followed by anatomic imaging (CT, MRI).", "output": {"entities": {"chemical": [{"text": "(111) Indium", "start": 24, "end": 36}, {"text": "(18) fluorodeoxyglucose", "start": 128, "end": 151}]}}, "schema": []}
{"input": "Selective venous sampling (VS) was performed when multiple suspicious lesions were identified or high surgical risk was a concern.", "output": {"entities": {}}, "schema": []}
{"input": "Tumors were localized in 20/31 subjects (64. 5%).", "output": {"entities": {}}, "schema": []}
{"input": "Nineteen of 20 subjects underwent octreo-SPECT imaging, and 16/20 FDG-PET/CT imaging.", "output": {"entities": {}}, "schema": []}
{"input": "Eighteen of 19 (95%) were positive on octreo-SPECT, and 14/16 (88%) on FDG-PET/CT.", "output": {"entities": {}}, "schema": []}
{"input": "Twelve of 20 subjects underwent VS; 10/12 (83%) were positive.", "output": {"entities": {}}, "schema": []}
{"input": "Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were: sensitivity = 0. 95, specificity = 0. 64, PPV = 0. 82 and NPV = 0. 88 for octreo-SPECT; sensitivity = 0. 88, specificity = 0. 36, PPV = 0. 62 and NPV = 0. 50 for FDG-PET/CT.", "output": {"entities": {}}, "schema": []}
{"input": "Fifteen subjects had their tumor resected at our institution, and were disease-free at last follow-up.", "output": {"entities": {}}, "schema": []}
{"input": "Serum phosphorus returned to normal in all subjects within 1-5 days.", "output": {"entities": {"chemical": [{"text": "phosphorus", "start": 6, "end": 16}]}}, "schema": []}
{"input": "In 10 subjects who were followed for at least 7 days postoperatively, intact FGF23 (iFGF23) decreased to near undetectable within hours and returned to the normal range within 5 days.", "output": {"entities": {}}, "schema": []}
{"input": "C-terminal FGF23 (cFGF23) decreased immediately but remained elevated, yielding a markedly elevated cFGF23/iFGF23 ratio.", "output": {"entities": {"chemical": [{"text": "C", "start": 0, "end": 1}]}}, "schema": []}
{"input": "Serum 1, 25-dihydroxyvitamin D (3) (1, 25D) rose and exceeded the normal range.", "output": {"entities": {"chemical": [{"text": "1, 25-dihydroxyvitamin D (3)", "start": 6, "end": 34}, {"text": "1, 25D", "start": 36, "end": 42}]}}, "schema": []}
{"input": "In this systematic approach to TIO tumor localization Octreo-SPECT was more sensitive and specific, but in many cases FDG-PET/CT was complementary.", "output": {"entities": {}}, "schema": []}
{"input": "VS can discriminate between multiple suspicious lesions and increase certainty prior to surgery.", "output": {"entities": {}}, "schema": []}
{"input": "Sustained elevations in cFGF23 and 1, 25D were observed, suggesting novel regulation of FGF23 processing and 1, 25D generation.", "output": {"entities": {"chemical": [{"text": "1, 25D", "start": 35, "end": 41}, {"text": "1, 25D", "start": 109, "end": 115}]}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Graphene Oxide-Based Fluorescent Biosensor for Protein Detection via Terminal Protection of Small-Molecule-Linked DNA.", "output": {"entities": {"chemical": [{"text": "Graphene Oxide", "start": 0, "end": 14}]}}, "schema": []}
{"input": "A fluorescence method for protein detection is developed based on terminal protection of small-molecule-linked DNA by target protein and a graphene oxide-assisted DNA assay strategy.", "output": {"entities": {"chemical": [{"text": "graphene oxide", "start": 139, "end": 153}]}}, "schema": []}
{"input": "This design results in fluorescence-enhanced detection that is sensitive and selective for the target protein.", "output": {"entities": {}}, "schema": []}
{"input": "Vemurafenib potently induces endoplasmic reticulum stress-mediated apoptosis in BRAFV600E melanoma cells.", "output": {"entities": {"chemical": [{"text": "Vemurafenib", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients with BRAFV600E-mutated melanoma, its effects are limited by the onset of drug resistance.", "output": {"entities": {"chemical": [{"text": "vemurafenib", "start": 40, "end": 51}]}}, "schema": []}
{"input": "We found that exposure of melanoma cell lines with the BRAFV600E mutation to vemurafenib decreased the abundance of antiapoptotic proteins and induced intrinsic mitochondrial apoptosis.", "output": {"entities": {"chemical": [{"text": "vemurafenib", "start": 77, "end": 88}]}}, "schema": []}
{"input": "Vemurafenib-treated melanoma cells showed increased cytosolic concentration of calcium, a potential trigger for endoplasmic reticulum (ER) stress, which can lead to apoptosis.", "output": {"entities": {"chemical": [{"text": "Vemurafenib", "start": 0, "end": 11}, {"text": "calcium", "start": 79, "end": 86}]}}, "schema": []}
{"input": "Consistent with an ER stress-induced response, vemurafenib decreased the abundance of the ER chaperone protein glucose-regulated protein 78, increased the abundance of the spliced isoform of the transcription factor X-box binding protein 1 (XBP1) (which transcriptionally activates genes involved in ER stress responses), increased the phosphorylation of the translation initiation factor eIF2 alpha (which would be expected to inhibit protein synthesis), and induced the expression of ER stress-related genes.", "output": {"entities": {"chemical": [{"text": "vemurafenib", "start": 47, "end": 58}, {"text": "glucose", "start": 111, "end": 118}]}}, "schema": []}
{"input": "Knockdown of the ER stress response protein activating transcription factor 4 (ATF4) significantly reduced vemurafenib-induced apoptosis.", "output": {"entities": {"chemical": [{"text": "vemurafenib", "start": 107, "end": 118}]}}, "schema": []}
{"input": "Moreover, the ER stress inducer thapsigargin prevented invasive growth of tumors formed from vemurafenib-sensitive melanoma cells in vivo.", "output": {"entities": {"chemical": [{"text": "thapsigargin", "start": 32, "end": 44}, {"text": "vemurafenib", "start": 93, "end": 104}]}}, "schema": []}
{"input": "In melanoma cells with low sensitivity or resistance to vemurafenib, combination treatment with thapsigargin augmented or induced apoptosis.", "output": {"entities": {"chemical": [{"text": "vemurafenib", "start": 56, "end": 67}, {"text": "thapsigargin", "start": 96, "end": 108}]}}, "schema": []}
{"input": "Thus, thapsigargin or other inducers of ER stress may be useful in combination therapies to overcome vemurafenib resistance.", "output": {"entities": {"chemical": [{"text": "thapsigargin", "start": 6, "end": 18}, {"text": "vemurafenib", "start": 101, "end": 112}]}}, "schema": []}
{"input": "Transforming growth factor beta integrates Smad 3 to mechanistic target of rapamycin complexes to arrest deptor abundance for glomerular mesangial cell hypertrophy.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 75, "end": 84}]}}, "schema": []}
{"input": "In many renal diseases, transforming growth factor beta (TGF beta)-stimulated canonical Smad 3 and noncanonical mechanistic target of rapamycin (mTOR) promote increased protein synthesis and mesangial cell hypertrophy.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 134, "end": 143}]}}, "schema": []}
{"input": "The cellular underpinnings involving these signaling molecules to regulate mesangial cell hypertrophy are not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "Deptor has recently been identified as an mTOR interacting protein and functions as an endogenous inhibitor of the kinase activity for both TORC1 and TORC2.", "output": {"entities": {}}, "schema": []}
{"input": "Prolonged incubation of mesangial cells with TGF beta reduced the levels of deptor concomitant with an increase in TORC1 and TORC2 activity.", "output": {"entities": {}}, "schema": []}
{"input": "Sustained TGF beta activation was required to inhibit association of deptor with mTOR, whereas rapid activation had no effect.", "output": {"entities": {}}, "schema": []}
{"input": "Using the mTOR inhibitor PP242, we found that TGF beta-induced both early and sustained activation of TORC1 and TORC2 was necessary for deptor suppression.", "output": {"entities": {"chemical": [{"text": "PP242,", "start": 25, "end": 31}]}}, "schema": []}
{"input": "PP242-induced reversal of deptor suppression by TGF beta was associated with a significant inhibition of TGF beta-stimulated protein synthesis and hypertrophy.", "output": {"entities": {"chemical": [{"text": "PP242", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Interestingly, expression of siRNA against Smad 3 or Smad 7, which blocks TGF beta receptor-specific Smad 3 signaling, prevented TGF beta-induced suppression of deptor abundance and TORC1/2 activities.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, overexpression of Smad 3 decreased deptor expression similar to TGF beta stimulation concomitant with increased TORC1 and TORC2 activities.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, knockdown of deptor reversed Smad 7-mediated inhibition of protein synthesis and mesangial cell hypertrophy induced by TGF beta.", "output": {"entities": {}}, "schema": []}
{"input": "These data reveal the requirement of both early and late activation of mTOR for TGF beta-induced protein synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Our results support that TGF beta-stimulated Smad 3 acts as a key node to instill a feedback loop between deptor down-regulation and TORC1/2 activation in driving mesangial cell hypertrophy.", "output": {"entities": {}}, "schema": []}
{"input": "Tuning the magnetic properties of metal oxide nanocrystal heterostructures by cation exchange.", "output": {"entities": {"chemical": [{"text": "metal oxide", "start": 34, "end": 45}]}}, "schema": []}
{"input": "For three types of colloidal magnetic nanocrystals, we demonstrate that postsynthetic cation exchange enables tuning of the nanocrystal' s magnetic properties and achieving characteristics not obtainable by conventional synthetic routes.", "output": {"entities": {}}, "schema": []}
{"input": "While the cation exchange procedure, performed in solution phase approach, was restricted so far to chalcogenide based semiconductor nanocrystals, here ferrite-based nanocrystals were subjected to a Fe (2 +) to Co (2 +) cation exchange procedure.", "output": {"entities": {"chemical": [{"text": "ferrite", "start": 152, "end": 159}, {"text": "Fe (2 +)", "start": 199, "end": 207}, {"text": "Co (2 +)", "start": 211, "end": 219}]}}, "schema": []}
{"input": "This allows tracing of the compositional modifications by systematic and detailed magnetic characterization.", "output": {"entities": {}}, "schema": []}
{"input": "In homogeneous magnetite nanocrystals and in gold/magnetite core shell nanocrystals the cation exchange increases the coercivity field, the remanence magnetization, as well as the superparamagnetic blocking temperature.", "output": {"entities": {}}, "schema": []}
{"input": "For core/shell nanoheterostructures a selective doping of either the shell or predominantly of the core with Co (2 +) is demonstrated.", "output": {"entities": {"chemical": [{"text": "Co (2 +)", "start": 109, "end": 117}]}}, "schema": []}
{"input": "By applying the cation exchange to FeO/CoFe (2) O (4) core/shell nanocrystals the Ne e l temperature of the core material is increased and exchange-bias effects are enhanced so that vertical shifts of the hysteresis loops are obtained which are superior to those in any other system.", "output": {"entities": {"chemical": [{"text": "FeO", "start": 35, "end": 38}, {"text": "CoFe (2) O (4)", "start": 39, "end": 53}]}}, "schema": []}
{"input": "Attitude of German women towards hormone therapy: results of a lay survey.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Objective: Hormone therapy (HT) use has experienced a substantial change since publication of Women' s Health Initiative (WHI) controlled trial.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to investigate the attitude towards HT in German women aged 45-60 years.", "output": {"entities": {}}, "schema": []}
{"input": "Study design: A questionnaire was sent to 9785 randomly selected women in Germany aged between 45 and 60 years.", "output": {"entities": {}}, "schema": []}
{"input": "Results: Response rate was 19. 3% (n = 1, 893).", "output": {"entities": {}}, "schema": []}
{"input": "Of those, 81% experienced climacteric symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "Vasomotor symptoms were most frequently reported (71. 2%; n = 1332).", "output": {"entities": {}}, "schema": []}
{"input": "Of the respondents, 19. 7% (n = 369) used HT.", "output": {"entities": {}}, "schema": []}
{"input": "The most frequently mentioned benefits of HT were the improvement of climacteric complaints (71. 2%; n = 1346), followed by the relief of osteoporosis (37. 2%; n = 697) and the \" anti-aging \" effect (16. 3%; n = 305).", "output": {"entities": {}}, "schema": []}
{"input": "Breast cancer was stated as the main risk (64. 9%; n = 1215), closely followed by weight gain (53. 4%; n = 1000) and thromboembolism (48%; n = 898).", "output": {"entities": {}}, "schema": []}
{"input": "About 44% of the women who has been advised by gynaecologists choose a HT, whereas this rate dropped down to 14. 3% and 11. 3% for women who have been advised by friends or media.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: German women were generally aware of the main risks and benefits of HT.", "output": {"entities": {}}, "schema": []}
{"input": "\" More informed \" women appear to be more likely to use HT compared to \" less informed \" women.", "output": {"entities": {}}, "schema": []}
{"input": "The media produces negative impression of HT.", "output": {"entities": {}}, "schema": []}
{"input": "Development of Inhibitors of the PAS-B Domain of the HIF-2 alpha Transcription Factor.", "output": {"entities": {}}, "schema": []}
{"input": "Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in a variety of pathophysiological settings, including cancer.", "output": {"entities": {}}, "schema": []}
{"input": "We describe the first detailed structure-activity relationship study of small molecules designed to inhibit HIF-2 alpha-ARNT heterodimerization by binding an internal cavity of the HIF-2 alpha PAS-B domain.", "output": {"entities": {}}, "schema": []}
{"input": "Through a series of biophysical characterizations of inhibitor-protein interactions (NMR and X-ray crystallography), we have established the structural requirements for artificial inhibitors of the HIF-2 alpha-ARNT PAS-B interaction.", "output": {"entities": {}}, "schema": []}
{"input": "These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action.", "output": {"entities": {}}, "schema": []}
{"input": "Adverse effects of wood smoke PM (2. 5) exposure on macrophage functions.", "output": {"entities": {}}, "schema": []}
{"input": "Epidemiological studies have shown a correlation between chronic biomass smoke exposure and increased respiratory infection.", "output": {"entities": {}}, "schema": []}
{"input": "Pulmonary macrophages are instrumental in both the innate and the adaptive immune responses to respiratory infection.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, in vitro systems were utilized where alveolar macrophages (AM) and bone marrow-derived macrophages (BMdM) were exposed to concentrated wood smoke-derived particulate matter (WS-PM) and mice were exposed in vivo to either concentrated WS-PM or inhaled WS.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo studies demonstrated that WS-exposed mice inoculated with Streptococcus pneumoniae had a higher bacterial load 24 h post-exposure, and corresponding AM were found to have decreased lymphocyte activation activity.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, while classic markers of inflammation (cellular infiltration, total protein, neutrophils) were not affected, there were changes in pulmonary macrophages populations, including significant decreases in macrophages expressing markers of activation in WS-exposed mice.", "output": {"entities": {}}, "schema": []}
{"input": "The lymphocyte activation activity of WS-PM-exposed AM was significantly suppressed, but the phagocytic activity appeared unchanged.", "output": {"entities": {}}, "schema": []}
{"input": "In an effort to determine a pathway for WS-induced suppression, RelB activation, assessed by nuclear translocation, was observed in AM exposed to either inhaled WS or instilled WS-PM.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, an analysis of WS-PM fractions determined the presence of 4-5 polycyclic aromatic hydrocarbons (PAHs), and preliminary work suggests a potential role for these PAHs to alter macrophage functions.", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbons", "start": 71, "end": 103}, {"text": "PAHs", "start": 105, "end": 109}, {"text": "PAHs", "start": 169, "end": 173}]}}, "schema": []}
{"input": "These studies show a decreased ability of WS-exposed pulmonary macrophages to effectively mount a defense against infection, the effect lasts at least a week post-exposure, and appears to be mediated via RelB activation.", "output": {"entities": {}}, "schema": []}
{"input": "Association of Inhalation Toxicologists' (AIT) review of regulatory aspects for inhalation toxicology studies.", "output": {"entities": {}}, "schema": []}
{"input": "Regulatory guidelines are intended to provide recommendations on ways to achieve greater harmonization in the interpretation and application of technical procedures and requirements for product registration in order to reduce or obviate replication of the testing carried out during the research and development of new products.", "output": {"entities": {}}, "schema": []}
{"input": "The objectives of such harmonization are more economical use of human, animal and material resources; the elimination of unnecessary delay in the global development and availability of new products while maintaining safeguards on quality, safety and efficacy; and the fulfillment of regulatory obligations to protect public health.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of superconducting nanocables of FeSe encapsulated in carbonaceous shell.", "output": {"entities": {"chemical": [{"text": "FeSe", "start": 43, "end": 47}]}}, "schema": []}
{"input": "The recent discovery of superconductivity in iron selenide has attracted considerable attention due to the simplicity of composition, unconventional nature of superconductivity, and ease of synthesis.", "output": {"entities": {"chemical": [{"text": "iron selenide", "start": 45, "end": 58}]}}, "schema": []}
{"input": "We have synthesized superconducting FeSe nanowires with a simple catalyst-aided vapor transport reaction at 800 degrees C in an inert atmosphere.", "output": {"entities": {"chemical": [{"text": "FeSe", "start": 36, "end": 40}]}}, "schema": []}
{"input": "The precursors were chosen to be elemental Se and iron acetylacetonate [Fe (III) (C 5 H 8 O 2) 3].", "output": {"entities": {"chemical": [{"text": "Se", "start": 43, "end": 45}, {"text": "iron acetylacetonate", "start": 50, "end": 70}, {"text": "Fe (III) (C 5 H 8 O 2) 3", "start": 72, "end": 96}]}}, "schema": []}
{"input": "These vaporized very easily, thereby facilitating transport, and also contributed to the formation of a carbonaceous shell encapsulating the FeSe nanowires.", "output": {"entities": {"chemical": [{"text": "FeSe", "start": 141, "end": 145}]}}, "schema": []}
{"input": "The superconductivity of these nanocables was confirmed through magnetic measurements and a T (c) of =~ 8 K was obtained for an ensemble of nanocables.", "output": {"entities": {}}, "schema": []}
{"input": "The length of FeSe filling inside the carbon nanofibers could be varied by controlling the reaction conditions while the diameter of nanowires was dependent on the thickness of Au-Pd coating used as a catalyst.", "output": {"entities": {"chemical": [{"text": "FeSe", "start": 14, "end": 18}, {"text": "carbon", "start": 38, "end": 44}, {"text": "Au-Pd", "start": 177, "end": 182}]}}, "schema": []}
{"input": "Extensive analysis through high-resolution microscopy revealed that there was considerable lattice contraction of FeSe in the nanocable up to about 3. 6% along the c-direction leading to a reduced spacing between the (001) lattice planes.", "output": {"entities": {"chemical": [{"text": "FeSe", "start": 114, "end": 118}]}}, "schema": []}
{"input": "Interestingly, this compression was more pronounced near the catalyst-FeSe interface and was reduced further along the length of the nanocable.", "output": {"entities": {"chemical": [{"text": "FeSe", "start": 70, "end": 74}]}}, "schema": []}
{"input": "The presence of carbon nanofibers as a shell around the FeSe protected the FeSe nanowires from both atmospheric O 2 and moisture attack, as was evident from the very long ambient condition shelf life of these nanocables, and also makes them more stable under e-beam irradiation.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 16, "end": 22}, {"text": "FeSe", "start": 56, "end": 60}, {"text": "FeSe", "start": 75, "end": 79}, {"text": "O 2", "start": 112, "end": 115}]}}, "schema": []}
{"input": "Genistein, a natural product derived from soybeans, ameliorates polyglutamine-mediated motor neuron disease.", "output": {"entities": {"chemical": [{"text": "Genistein", "start": 0, "end": 9}, {"text": "polyglutamine", "start": 64, "end": 77}]}}, "schema": []}
{"input": "Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor (AR) gene.", "output": {"entities": {"chemical": [{"text": "polyglutamine", "start": 108, "end": 121}, {"text": "polyQ", "start": 123, "end": 128}, {"text": "androgen", "start": 147, "end": 155}]}}, "schema": []}
{"input": "The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem, and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs.", "output": {"entities": {}}, "schema": []}
{"input": "AR-associated coregulator 70 (ARA70) was the first coregulator of AR to be identified, and it has been shown to interact with AR and increase its protein stability.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report that genistein, an isoflavone found in soy, disrupts the interaction between AR and ARA70 and promotes the degradation of mutant AR in neuronal cells and transgenic mouse models of SBMA.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 21, "end": 30}, {"text": "isoflavone", "start": 35, "end": 45}]}}, "schema": []}
{"input": "We also demonstrate that dietary genistein ameliorates behavioral abnormalities, improves spinal cord and muscle pathology, and decreases the amounts of monomeric AR and high-molecular-weight mutant AR protein aggregates in SBMA transgenic mice.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 33, "end": 42}]}}, "schema": []}
{"input": "Thus, genistein treatment may be a potential therapeutic approach for alleviating the symptoms of SBMA by disrupting the interactions between AR and ARA70.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 6, "end": 15}]}}, "schema": []}
{"input": "High T (g) bio-based aliphatic polyesters from bicyclic D-mannitol.", "output": {"entities": {"chemical": [{"text": "polyesters", "start": 31, "end": 41}, {"text": "bicyclic D-mannitol", "start": 47, "end": 66}]}}, "schema": []}
{"input": "The carbohydrate-based diol 2, 4: 3, 5-di-O-methylene-d-mannitol (Manx) has been used to obtain aliphatic polyesters.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 4, "end": 16}, {"text": "diol 2, 4: 3, 5-di-O-methylene-d-mannitol", "start": 23, "end": 64}, {"text": "polyesters", "start": 106, "end": 116}]}}, "schema": []}
{"input": "Manx is a symmetric bicyclic compound consisting of two fused 1, 3-dioxane rings and bearing two primary hydroxyl groups.", "output": {"entities": {"chemical": [{"text": "1, 3-dioxane", "start": 62, "end": 74}, {"text": "hydroxyl", "start": 105, "end": 113}]}}, "schema": []}
{"input": "In terms of stiffness, it is comparable to the widely known isosorbide, but it affords the additional advantages of being much more reactive in polycondensation and capable of producing stereoregular polymers with fairly high molecular weights.", "output": {"entities": {"chemical": [{"text": "isosorbide", "start": 60, "end": 70}]}}, "schema": []}
{"input": "A fully bio-based homopolyester (PManxS) has been synthesized by polycondensation in the melt from dimethyl succinate and Manx.", "output": {"entities": {"chemical": [{"text": "dimethyl succinate", "start": 99, "end": 117}]}}, "schema": []}
{"input": "The high thermal stability of PManxS, its relatively high glass transition temperature (Tg = 68 degrees C) and elastic modulus, and its enhanced sensitivity to the action of lipases point to PManxS as a polyester of exceptional interest for those applications where biodegradability and molecular stiffness are priority requirements.", "output": {"entities": {"chemical": [{"text": "polyester", "start": 203, "end": 212}]}}, "schema": []}
{"input": "In addition, random copolyesters (PBxManxyS) covering a broad range of compositions have been obtained using mixtures of Manx and 1, 4-butanediol in the reaction with dimethyl succinate.", "output": {"entities": {"chemical": [{"text": "1, 4-butanediol", "start": 130, "end": 145}, {"text": "dimethyl succinate", "start": 167, "end": 185}]}}, "schema": []}
{"input": "All PBxManxyS were semicrystalline and displayed Tg values from-29 to + 51 degrees C steadily increasing with the content in Manx units.", "output": {"entities": {}}, "schema": []}
{"input": "The stress-strain behavior of these copolyesters largely depended on their content in Manx and they were enzymatically degraded faster than PBS.", "output": {"entities": {}}, "schema": []}
{"input": "TCDD and corticosterone on testicular steroidogenesis and antioxidant system of epididymal sperm in rats.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}, {"text": "corticosterone", "start": 9, "end": 23}]}}, "schema": []}
{"input": "2, 3, 7, 8-Tetrachloro dibenzo-p-dioxin (TCDD), an endocrine-disrupting environmental pollutant, has been found to cause male reproductive toxicity.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-Tetrachloro dibenzo-p-dioxin", "start": 0, "end": 39}, {"text": "TCDD", "start": 41, "end": 45}]}}, "schema": []}
{"input": "Glucocorticoids have been found to influence the metabolic pathway of TCDD.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 70, "end": 74}]}}, "schema": []}
{"input": "Stress, which affects the male reproductive function, is marked by an increase in the level and activity of glucocorticoids in the body.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was carried out to understand the effect of TCDD on testicular steroidogenesis and sperm antioxidant system under the influence of increased level of corticosterone in the body.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 62, "end": 66}, {"text": "corticosterone", "start": 168, "end": 182}]}}, "schema": []}
{"input": "Adult male rats were treated with either TCDD (100 ng/kg bw/day) or corticosterone (3 mg/kg bw/day) or both for 15 days.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 41, "end": 45}, {"text": "corticosterone", "start": 68, "end": 82}]}}, "schema": []}
{"input": "Treatment with either TCDD or corticosterone was found to suppress the levels of steroidogenic acute regulatory protein and androgen-binding protein and reduce the activities of steroidogenic enzymes in testis while increasing oxidative stress in ventral prostate, seminal vesicles and epididymal sperm.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 22, "end": 26}]}}, "schema": []}
{"input": "In rats treated with both TCDD and corticosterone, the suppression of testicular steroidogenesis and increase in oxidative stress observed in ventral prostate, seminal vesicles and epididymal sperm were significant as compared to TCDD alone treated rats.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 26, "end": 30}, {"text": "corticosterone", "start": 35, "end": 49}, {"text": "TCDD", "start": 230, "end": 234}]}}, "schema": []}
{"input": "The levels of Fas and FasL proteins were also increased in rats subjected to either TCDD or corticosterone treatment.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 84, "end": 88}, {"text": "corticosterone", "start": 92, "end": 106}]}}, "schema": []}
{"input": "In rats treated with both compounds, the increase observed in testicular levels of Fas and FasL was significant as compared to TCDD alone treated rats.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 127, "end": 131}]}}, "schema": []}
{"input": "Effect of TCDD on testicular steroidogenesis and antioxidant system of epididymal sperm may get enhanced under increased level of glucocorticoids in the body.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 10, "end": 14}]}}, "schema": []}
{"input": "The genome-defence gene Tex19. 1 suppresses LINE-1 retrotransposons in the placenta and prevents intra-uterine growth retardation in mice.", "output": {"entities": {}}, "schema": []}
{"input": "DNA methylation plays an important role in suppressing retrotransposon activity in mammalian genomes, yet there are stages of mammalian development where global hypomethylation puts the genome at risk of retrotransposition-mediated genetic instability.", "output": {"entities": {}}, "schema": []}
{"input": "Hypomethylated primordial germ cells appear to limit this risk by expressing a cohort of retrotransposon-suppressing genome-defence genes whose silencing depends on promoter DNA methylation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we investigate whether similar mechanisms operate in hypomethylated trophectoderm-derived components of the mammalian placenta to couple expression of genome-defence genes to the potential for retrotransposon activity.", "output": {"entities": {}}, "schema": []}
{"input": "We show that the hypomethylated state of the mouse placenta results in activation of only one of the hypomethylation-sensitive germline genome-defence genes: Tex19. 1.", "output": {"entities": {}}, "schema": []}
{"input": "Tex19. 1 appears to play an important role in placenta function as Tex19. 1 (-/-) mouse embryos exhibit intra-uterine growth retardation and have small placentas due to a reduction in the number of spongiotrophoblast, glycogen trophoblast and sinusoidal trophoblast giant cells.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we show that retrotransposon mRNAs are derepressed in Tex19. 1 (-/-) placentas and that protein encoded by the LINE-1 retrotransposon is upregulated in hypomethylated trophectoderm-derived cells that normally express Tex19. 1.", "output": {"entities": {}}, "schema": []}
{"input": "This study suggests that post-transcriptional genome-defence mechanisms are operating in the placenta to protect the hypomethylated cells in this tissue from retrotransposons and suggests that imbalances between retrotransposon activity and genome-defence mechanisms could contribute to placenta dysfunction and disease.", "output": {"entities": {}}, "schema": []}
{"input": "Tetrabenzoporphyrins: synthetic developments and applications.", "output": {"entities": {"chemical": [{"text": "Tetrabenzoporphyrins", "start": 0, "end": 20}]}}, "schema": []}
{"input": "Tetrabenzoporphyrins have attracted considerable worldwide attention over the last few decades.", "output": {"entities": {"chemical": [{"text": "Tetrabenzoporphyrins", "start": 0, "end": 20}]}}, "schema": []}
{"input": "Since the discovery of these pigments, chemists, biologists, medical professionals and material scientists have devoted pronounced efforts in order to develop synthetic methods and discover useful applications for these compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Nowadays, tetrabenzoporphyrins occupy a prominent position in porphyrin chemistry, and this review is intended to cover the main synthetic methods and applications of these compounds.", "output": {"entities": {"chemical": [{"text": "tetrabenzoporphyrins", "start": 10, "end": 30}, {"text": "porphyrin", "start": 62, "end": 71}]}}, "schema": []}
{"input": "Engineering a serum-resistant and thermostable vesicular stomatitis virus G glycoprotein for pseudotyping retroviral and lentiviral vectors.", "output": {"entities": {}}, "schema": []}
{"input": "Vesicular stomatitis virus G glycoprotein (VSV-G) is the most widely used envelope protein for retroviral and lentiviral vector pseudotyping; however, serum inactivation of VSV-G pseudotyped vectors is a significant challenge for in vivo gene delivery.", "output": {"entities": {}}, "schema": []}
{"input": "To address this problem, we conducted directed evolution of VSV-G to increase its resistance to human serum neutralization.", "output": {"entities": {}}, "schema": []}
{"input": "After six selection cycles, numerous common mutations were present.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of their location within VSV-G, we analyzed whether substitutions in several surface exposed residues could endow viral vectors with higher resistance to serum.", "output": {"entities": {}}, "schema": []}
{"input": "S162T, T230N and T368A mutations enhanced serum resistance, and additionally K66T, T368A and E380K substitutions increased the thermostability of VSV-G pseudotyped retroviral vectors, an advantageous byproduct of the selection strategy.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of a number of combined mutants revealed that VSV-G harboring T230N + T368A or K66T + S162T + T230N + T368A mutations exhibited both higher in vitro resistance to human serum and higher thermostability, as well as enhanced resistance to rabbit and mouse serum.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, lentiviral vectors pseudotyped with these variants were more resistant to human serum in a murine model.", "output": {"entities": {}}, "schema": []}
{"input": "These serum-resistant and thermostable VSV-G variants may aid the application of retroviral and lentiviral vectors to gene therapy. Gene Therapy advance online publication, 31 January 2013; doi: 10. 1038/gt. 2013. 1.", "output": {"entities": {}}, "schema": []}
{"input": "Predicting metabolic clearance for drugs that are actively transported into hepatocytes: incubational binding as a consequence of in vitro hepatocyte concentration is a key factor.", "output": {"entities": {}}, "schema": []}
{"input": "Incubational binding or the fraction of drug unbound in an in vitro incubation, fuinc, is an important parameter to predict or measure in the pursuit of accurate clearance predictions from in vitro data.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe a method for fuinc determination directly in the hepatocyte intrinsic clearance (CLint) assay with emphasis on compounds that are actively transported into hepatocytes, hypothesizing that for such compounds the typical protocol of 1 million hepatocytes/ml systematically underestimates the maximum attainable unbound intracellular drug concentration.", "output": {"entities": {}}, "schema": []}
{"input": "Using the transporter substrate atorvastatin as a test compound, incubations were performed and a mathematical model applied to describe metabolism, distribution, and binding at different hepatocyte concentrations.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 32, "end": 44}]}}, "schema": []}
{"input": "From these investigations it was evident that, since binding is more extensive intracellularly than in the medium, increased partitioning into the cellular volume, due to active uptake, increases the total amount of atorvastatin bound in the incubation.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 216, "end": 228}]}}, "schema": []}
{"input": "Consequently, a significant lowering of the hepatocyte concentration impacts the free drug concentration in the incubation and increases the observed rate of metabolism and therefore observed CLint (that is, when viewed from the media drug concentration).", "output": {"entities": {}}, "schema": []}
{"input": "The applicability of the findings was tested for a series of 11 actively transported zwitterions for which standard rat hepatocyte metabolic CLint data (1 million cells/ml incubation) poorly predicted in vivo clearance (average fold error of 5. 4).", "output": {"entities": {}}, "schema": []}
{"input": "Using metabolic CLint determined at a lower hepatocyte concentration (0. 125 million cells/ml) considerably improved clearance predictions (average fold error of 2. 3).", "output": {"entities": {}}, "schema": []}
{"input": "Investigation of the toxicokinetics of petroleum hydrocarbon distillates with the earthworm Eisenia andrei.", "output": {"entities": {"chemical": [{"text": "petroleum hydrocarbon", "start": 39, "end": 60}]}}, "schema": []}
{"input": "The Canada-wide standards for petroleum hydrocarbons in soils regulate petroleum hydrocarbons based on four distillate ranges: F1 (C6-C10), F2 (> C10-C16), F3 (> C16-C34), and F4 (> C34).", "output": {"entities": {"chemical": [{"text": "petroleum hydrocarbons", "start": 30, "end": 52}, {"text": "petroleum hydrocarbons", "start": 71, "end": 93}]}}, "schema": []}
{"input": "Previous toxicity tests with earthworms and F2, as well as two subfractions of F3, F3a (> C16-C23) and F3a (> C23-C34), indicate that test durations might not be sufficiently long to reach threshold effect concentrations, likely because of the differing toxicokinetics for each distillate.", "output": {"entities": {}}, "schema": []}
{"input": "A study was conducted to determine the toxicokinetics of both aliphatic and aromatic fractions of F2, F3a, and F3b with the earthworm Eisenia andrei.", "output": {"entities": {}}, "schema": []}
{"input": "Peak accumulation curves were observed for F2 aliphatics and aromatics and F3a aromatics, likely as a result of changes in exposure concentration over the test duration via loss or a decrease in the bioavailable fraction.", "output": {"entities": {}}, "schema": []}
{"input": "Biota-soil accumulation factors were > 1 for total F2 aliphatics and aromatics and F3a aromatics as well as for several individual polyaromatic hydrocarbons for each distillate.", "output": {"entities": {"chemical": [{"text": "polyaromatic hydrocarbons", "start": 131, "end": 156}]}}, "schema": []}
{"input": "Aromatics were disproportionately accumulated over aliphatics and were the main contributors to toxicity; therefore, aromatics and aliphatics should be regulated separately.", "output": {"entities": {}}, "schema": []}
{"input": "The toxicokinetics were used to interpret previous toxicity data.", "output": {"entities": {}}, "schema": []}
{"input": "Higher molecular weight distillates need longer-than-standard test durations to determine toxicity, so toxicity test results from fixed, standard-duration tests are not strictly comparable for these petroleum distillates.", "output": {"entities": {}}, "schema": []}
{"input": "Environ.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicol.", "output": {"entities": {}}, "schema": []}
{"input": "Chem.", "output": {"entities": {}}, "schema": []}
{"input": "2013; 32: 1006-1015.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 6, "end": 17}]}}, "schema": []}
{"input": "This study aimed to examine the acute and sub-chronic effects of cocoa polyphenols on cognition and mood.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 71, "end": 82}]}}, "schema": []}
{"input": "In a randomized, double-blind study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg or 0 mg of polyphenols (placebo) in a parallel-groups design.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 156, "end": 167}]}}, "schema": []}
{"input": "Participants consumed their assigned treatment once daily for 30 days.", "output": {"entities": {}}, "schema": []}
{"input": "Cognition was measured with the Cognitive Drug Research system and self-rated mood with the Bond-Lader Visual Analogue Scale.", "output": {"entities": {}}, "schema": []}
{"input": "Participants were tested at baseline, at 1, 2. 5 and 4 h after a single acute dose and again after receiving 30 days of treatment.", "output": {"entities": {}}, "schema": []}
{"input": "In total, 72 participants completed the trial.", "output": {"entities": {}}, "schema": []}
{"input": "After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to placebo.", "output": {"entities": {}}, "schema": []}
{"input": "Mood was unchanged by treatment acutely while cognition was unaffected by treatment at all time points.", "output": {"entities": {}}, "schema": []}
{"input": "This randomized controlled trial is perhaps the first to demonstrate the positive effects of cocoa polyphenols on mood in healthy participants.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 99, "end": 110}]}}, "schema": []}
{"input": "This provides a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 54, "end": 65}]}}, "schema": []}
{"input": "Opiate agonists and antagonists modulate taste perception in opiate-maintained and recently detoxified subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Heroin addicts consume large quantities of refined sugars.", "output": {"entities": {"chemical": [{"text": "Heroin", "start": 0, "end": 6}, {"text": "sugars", "start": 51, "end": 57}]}}, "schema": []}
{"input": "This study investigated the effect of opiate use and antagonism on sweet taste in opiate-maintained drug users and detoxified former chronic opiate users, using a within-subject design.", "output": {"entities": {}}, "schema": []}
{"input": "Seven opiate users received methadone and seven buprenorphine maintenance.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 28, "end": 37}, {"text": "buprenorphine", "start": 48, "end": 61}]}}, "schema": []}
{"input": "Six detoxified subjects received naltrexone.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 33, "end": 43}]}}, "schema": []}
{"input": "Sucrose recognition thresholds and measurements of pleasantness and intensity were determined before and four hours after 1) a single dose of methadone or buprenorphine or 2) naltrexone.", "output": {"entities": {"chemical": [{"text": "Sucrose", "start": 0, "end": 7}, {"text": "methadone", "start": 142, "end": 151}, {"text": "buprenorphine", "start": 155, "end": 168}, {"text": "naltrexone", "start": 175, "end": 185}]}}, "schema": []}
{"input": "Control data were taken from a cohort of healthy volunteers including smokers.", "output": {"entities": {}}, "schema": []}
{"input": "All measures of sweet and salt taste perception were significantly greater in opiate users and recently detoxified subjects compared to control subjects, with the exception of sweet pleasantness, which returned to control level after detoxification.", "output": {"entities": {}}, "schema": []}
{"input": "Acute methadone administration reduced salt thresholds and unpleasantness to control levels.", "output": {"entities": {"chemical": [{"text": "methadone", "start": 6, "end": 15}]}}, "schema": []}
{"input": "Increased sweet thresholds and salt unpleasantness in detoxified subjects were reversed by acute opioid antagonism, returning to control levels.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that opiate use and antagonism alters taste perception.", "output": {"entities": {}}, "schema": []}
{"input": "Some of the alterations reverse on detoxification (sweet pleasantness), and others can be reversed by opioid antagonism (sweet threshold, salt unpleasantness).", "output": {"entities": {}}, "schema": []}
{"input": "Changes in taste perception may underlie altered consumption of refined sugars in opiate users.", "output": {"entities": {"chemical": [{"text": "sugars", "start": 72, "end": 78}]}}, "schema": []}
{"input": "Heracleifolinosides A-F, new triterpene glycosides from Cimicifuga heracleifolia, and their inhibitory activities against hypoxia and reoxygenation.", "output": {"entities": {"chemical": [{"text": "Heracleifolinosides A-F", "start": 0, "end": 23}, {"text": "triterpene glycosides", "start": 29, "end": 50}]}}, "schema": []}
{"input": "Six new 9, 19-cycloartane triterpene glycosides, heracleifolinosides A-F (1-6), and one new chromone, norkhelloside (7), were isolated from the rhizome of Cimicifuga heracleifolia, together with 15 known compounds (8-22).", "output": {"entities": {"chemical": [{"text": "9, 19-cycloartane triterpene glycosides", "start": 8, "end": 47}, {"text": "heracleifolinosides A-F", "start": 49, "end": 72}, {"text": "norkhelloside", "start": 102, "end": 115}]}}, "schema": []}
{"input": "The structures of the new compounds were elucidated by means of spectroscopic methods including 2D NMR and mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The extracts of C. heracleifolia and all the isolated compounds were tested for activities against hypoxia and reoxygenation injury in human umbilical vein endothelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "Heracleifolinoside B (2) is effectively resistant to hypoxia and reoxygenation-induced human umbilical vein endothelial cell injury, with cell viabilities of 61. 95 +/- 2. 04%, 77. 04 +/- 4. 44%, and 83. 65 +/- 3. 29% at concentrations of 1, 10, and 100 micro M, respectively.", "output": {"entities": {"chemical": [{"text": "Heracleifolinoside B", "start": 0, "end": 20}]}}, "schema": []}
{"input": "Model for conformational relaxation of flexible conjugated polymers: application to p-phenylenevinylene trimers in nonpolar solvents.", "output": {"entities": {"chemical": [{"text": "p-phenylenevinylene trimers", "start": 84, "end": 111}]}}, "schema": []}
{"input": "Photoexcitation of flexible conjugated polymers is invariably followed by a fast conformational/torsional relaxation towards a configuration favouring coplanarity of the conjugated segments.", "output": {"entities": {}}, "schema": []}
{"input": "In general, the experimental relaxation rate constant (k (CR)) depends on the solvent viscosity (eta) and temperature (T), and is not proportional to T/eta.", "output": {"entities": {}}, "schema": []}
{"input": "A theory capable of explaining the observed dependence of k (CR) on T and eta over a wide range of these variables is not available.", "output": {"entities": {}}, "schema": []}
{"input": "This gap is filled here by presenting a stochastic model that includes the participation of the oligomer side chain in storing and dissipating the stresses induced by photoexcitation.", "output": {"entities": {}}, "schema": []}
{"input": "The model is able to account for the softening of solute-solvent interactions and its predictions are found to be in excellent agreement with the observed relaxation rate constants of a series of substituted p-phenylenevinylene trimers [ChemPhysChem 2009, 10, 448-454] on T, eta and the size of the side-chains.", "output": {"entities": {"chemical": [{"text": "p-phenylenevinylene trimers", "start": 208, "end": 235}]}}, "schema": []}
{"input": "A method to predict and understand fish survival under dynamic chemical stress using standard ecotoxicity data.", "output": {"entities": {}}, "schema": []}
{"input": "The authors present a method to predict fish survival under exposure to fluctuating concentrations and repeated pulses of a chemical stressor.", "output": {"entities": {}}, "schema": []}
{"input": "The method is based on toxicokinetic-toxicodynamic modeling using the general unified threshold model of survival (GUTS) and calibrated using raw data from standard fish acute toxicity tests.", "output": {"entities": {}}, "schema": []}
{"input": "The model was validated by predicting fry survival in a fish early life stage test.", "output": {"entities": {}}, "schema": []}
{"input": "Application of the model was demonstrated by using Forum for Co-ordination of Pesticide Fate Models and Their Use surface water (FOCUS-SW) exposure patterns as model input and predicting the survival of fish over 485 d.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure patterns were also multiplied by factors of five and 10 to achieve higher exposure concentrations for fish survival predictions.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the authors quantified how far the exposure profiles were below the onset of mortality by finding the corresponding exposure multiplication factor for each scenario.", "output": {"entities": {}}, "schema": []}
{"input": "The authors calculated organism recovery times as additional characteristic of toxicity as well as number of peaks, interval length between peaks, and mean duration as additional characteristics of the exposure pattern.", "output": {"entities": {}}, "schema": []}
{"input": "The authors also calculated which of the exposure patterns had the smallest and largest inherent potential toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Sensitivity of the model to parameter changes depends on the exposure pattern and differs between GUTS individual tolerance and GUTS stochastic death.", "output": {"entities": {}}, "schema": []}
{"input": "Possible uses of the additional information gained from modeling to inform risk assessment are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitors of JAK2 and JAK3: an update on the patent literature 2010-2012.", "output": {"entities": {}}, "schema": []}
{"input": "INTRODUCTION: Janus kinases (JAKs) comprise a family of four enzymes, JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2), centrally implicated in cell signaling processes important in cancer and immune-inflammatory diseases.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Progression in the field has taken a recent step forward with the approval of ruxolitinib (Jakafi), a selective inhibitor of JAK1/2 and very recently tofacitinib (Xeljanz), a pan-JAK inhibitor.", "output": {"entities": {"chemical": [{"text": "ruxolitinib", "start": 78, "end": 89}, {"text": "Jakafi", "start": 91, "end": 97}, {"text": "tofacitinib", "start": 150, "end": 161}, {"text": "Xeljanz", "start": 163, "end": 170}]}}, "schema": []}
{"input": "There are many new JAK family enzyme inhibitors in the clinic now with a range of selectivity profiles.", "output": {"entities": {}}, "schema": []}
{"input": "More selective JAK2 or JAK3 compounds are now coming through in considerable numbers and this review attempts to provide an update of the recent patent literature of those new compounds.", "output": {"entities": {}}, "schema": []}
{"input": "An overview is given on the diversity of core structures employed for inhibitor design showing that the vast majority of compounds are based on classic ATP-competitive kinase inhibitor heterocycles.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 152, "end": 155}]}}, "schema": []}
{"input": "AREAS COVERED: This review updates new patents claiming JAK2 and/or JAK3 inhibitors published from 2010 to 2012.", "output": {"entities": {}}, "schema": []}
{"input": "Pre-2010 patents have been extensively covered in previous reviews.", "output": {"entities": {}}, "schema": []}
{"input": "Comments on the context of each chemical series are given where applicable to orientate the readers on the bewildering array of molecular designs now available.", "output": {"entities": {}}, "schema": []}
{"input": "This review does not cover JAK1 or TYK2 inhibitors but mention is made of these where they occur within series of JAK2/3 inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Given the overlap between many pharmacophores, it was not possible to completely separate inhibitors of JAK2 from JAK3, hence the material is organized by JAK2, JAK3 and JAK2/3 and within each section by alphabetical order of the patent assignee, some companies having published five or more patents, such as Ambit (10), Incyte (9), Galapagos (7), Almirall (6) and Biocryst (5).", "output": {"entities": {}}, "schema": []}
{"input": "A total of 98 patents are reviewed herein.", "output": {"entities": {}}, "schema": []}
{"input": "EXPERT OPINION: JAK inhibitor therapy is entering a significant new era with the advent on the market of the JAK1/2 inhibitor ruxolitinib and the pan-JAK inhibitor tofacitinib, with unprecedented speed of development.", "output": {"entities": {"chemical": [{"text": "ruxolitinib", "start": 126, "end": 137}, {"text": "tofacitinib", "start": 164, "end": 175}]}}, "schema": []}
{"input": "Selectivity against the four individual JAK family enzymes, JAK1, 2, 3 and TYK2, is now a key goal since they each play subtly different roles in cytokine-induced cell signaling.", "output": {"entities": {}}, "schema": []}
{"input": "The future looks bright for patients as many new drugs are being developed and now combinations of JAK inhibitors with other targeted agents are being studied in the clinic.", "output": {"entities": {}}, "schema": []}
{"input": "These advances are expected to lead to further significant progress improving patient outcomes and quality of life.", "output": {"entities": {}}, "schema": []}
{"input": "Stereochemical control of polymorph transitions in nanoscale reactors.", "output": {"entities": {}}, "schema": []}
{"input": "Crystallization of glycine in the cylindrical nanopores of anodic aluminum oxide (AAO) revealed the formation of metastable beta-glycine in pores having diameters less than 200 nm.", "output": {"entities": {"chemical": [{"text": "glycine", "start": 19, "end": 26}, {"text": "aluminum oxide", "start": 66, "end": 80}, {"text": "AAO", "start": 82, "end": 85}, {"text": "beta-glycine", "start": 124, "end": 136}]}}, "schema": []}
{"input": "Two-dimensional X-ray microdiffraction indicated that the [010] axis of the embedded beta-glycine nanocrystals coincided with the pore direction, identical to behavior observed previously in the cylindrical nanopores of polymer monoliths.", "output": {"entities": {"chemical": [{"text": "beta-glycine", "start": 85, "end": 97}]}}, "schema": []}
{"input": "Whereas the beta-glycine nanocrystals were stable indefinitely in ambient air and persisted upon heating, they transformed to the alpha polymorph upon standing at room temperature and 90% relative humidity (RH).", "output": {"entities": {"chemical": [{"text": "beta-glycine", "start": 12, "end": 24}]}}, "schema": []}
{"input": "The alpha-glycine nanocrystals were oriented with the [010] axis nearly perpendicular to the pore direction, reflecting a nearly 90 degrees rotation of the glycine molecules during the transition.", "output": {"entities": {"chemical": [{"text": "alpha-glycine", "start": 4, "end": 17}, {"text": "glycine", "start": 156, "end": 163}]}}, "schema": []}
{"input": "When the beta-glycine nanocrystals were formed in the AAO cylinders in the presence of small amounts of racemic hydrophobic amino acid auxiliaries, which are known to bind selectively to the (010) and (010) faces on the fast-growing end of beta-glycine enantiomorphs, the beta --> alpha phase transition at 90% RH was suppressed.", "output": {"entities": {"chemical": [{"text": "beta-glycine", "start": 9, "end": 21}, {"text": "AAO", "start": 54, "end": 57}, {"text": "amino acid", "start": 124, "end": 134}, {"text": "beta-glycine", "start": 240, "end": 252}]}}, "schema": []}
{"input": "In contrast, beta-glycine nanocrystals grown in the presence of an enantiopure amino acid auxiliary, which binds to the fast-growing end of only one of the enantiomorphs, thus suppressing its formation and leaving the other enantiomorph unperturbed, transformed into the alpha polymorph under the same conditions.", "output": {"entities": {"chemical": [{"text": "beta-glycine", "start": 13, "end": 25}, {"text": "amino acid", "start": 79, "end": 89}]}}, "schema": []}
{"input": "This observation confirms that binding of an amino acid to the {010} faces is stereoselective and that access of water to these faces is essential for the transition to the alpha polymorph.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 45, "end": 55}]}}, "schema": []}
{"input": "The impact of functionalization on the stability, work function, and photoluminescence of reduced graphene oxide.", "output": {"entities": {"chemical": [{"text": "reduced graphene oxide", "start": 90, "end": 112}]}}, "schema": []}
{"input": "Reduced graphene oxide (rGO) is a promising material for a variety of thin-film optoelectronic applications.", "output": {"entities": {"chemical": [{"text": "Reduced graphene oxide", "start": 0, "end": 22}, {"text": "rGO", "start": 24, "end": 27}]}}, "schema": []}
{"input": "Two main barriers to its widespread use are the lack of (1) fabrication protocols leading to tailored functionalization of the graphene sheet with oxygen-containing chemical groups, and (2) understanding of the impact of such functional groups on the stability and on the optical and electronic properties of rGO.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 127, "end": 135}, {"text": "oxygen", "start": 147, "end": 153}, {"text": "rGO", "start": 309, "end": 312}]}}, "schema": []}
{"input": "We carry out classical molecular dynamics and density functional theory calculations on a large set of realistic rGO structures to decompose the effects of different functional groups on the stability, work function, and photoluminescence.", "output": {"entities": {"chemical": [{"text": "rGO", "start": 113, "end": 116}]}}, "schema": []}
{"input": "Our calculations indicate the metastable nature of carbonyl-rich rGO and its favorable transformation to hydroxyl-rich rGO at room temperature via carbonyl-to-hydroxyl conversion reactions near carbon vacancies and holes.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 51, "end": 59}, {"text": "rGO", "start": 65, "end": 68}, {"text": "hydroxyl", "start": 105, "end": 113}, {"text": "rGO", "start": 119, "end": 122}, {"text": "carbonyl", "start": 147, "end": 155}, {"text": "hydroxyl", "start": 159, "end": 167}, {"text": "carbon", "start": 194, "end": 200}]}}, "schema": []}
{"input": "We demonstrate a significant tunability in the work function of rGO up to 2. 5 eV by altering the composition of oxygen-containing functional groups for a fixed oxygen concentration, and of the photoluminescence emission by modulating the fraction of epoxy and carbonyl groups.", "output": {"entities": {"chemical": [{"text": "rGO", "start": 64, "end": 67}, {"text": "oxygen", "start": 113, "end": 119}, {"text": "oxygen", "start": 161, "end": 167}, {"text": "epoxy", "start": 251, "end": 256}, {"text": "carbonyl", "start": 261, "end": 269}]}}, "schema": []}
{"input": "Taken together, our results guide the application of tailored rGO structures in devices for optoelectronics and renewable energy.", "output": {"entities": {"chemical": [{"text": "rGO", "start": 62, "end": 65}]}}, "schema": []}
{"input": "The contrasting activity of iodido versus chlorido ruthenium and osmium arene azo-and imino-pyridine anticancer complexes: control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway.", "output": {"entities": {"chemical": [{"text": "iodido", "start": 28, "end": 34}, {"text": "chlorido ruthenium", "start": 42, "end": 60}, {"text": "osmium arene azo-and imino-pyridine", "start": 65, "end": 100}]}}, "schema": []}
{"input": "Organometallic half-sandwich complexes [M (p-cymene) (azo/imino-pyridine) X] (+) where M = Ru (II) or Os (II) and X = Cl or I, exhibit potent antiproliferative activity toward a range of cancer cells.", "output": {"entities": {"chemical": [{"text": "[M (p-cymene) (azo/imino-pyridine) X] (+)", "start": 39, "end": 80}, {"text": "M = Ru (II) or Os (II)", "start": 87, "end": 109}, {"text": "X = Cl or I", "start": 114, "end": 125}]}}, "schema": []}
{"input": "Not only are the iodido complexes more potent than the chlorido analogues, but they are not cross-resistant with the clinical platinum drugs cisplatin and oxaliplatin.", "output": {"entities": {"chemical": [{"text": "iodido", "start": 17, "end": 23}, {"text": "chlorido", "start": 55, "end": 63}, {"text": "platinum", "start": 126, "end": 134}, {"text": "cisplatin", "start": 141, "end": 150}, {"text": "oxaliplatin", "start": 155, "end": 166}]}}, "schema": []}
{"input": "They are also more selective for cancer cells versus normal cells (fibroblasts) and show high accumulation in cell membranes.", "output": {"entities": {}}, "schema": []}
{"input": "They arrest cell growth in G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 51, "end": 60}]}}, "schema": []}
{"input": "The iodido complexes retain potency in p53 mutant colon cells.", "output": {"entities": {"chemical": [{"text": "iodido", "start": 4, "end": 10}]}}, "schema": []}
{"input": "All complexes activate caspase 3.", "output": {"entities": {}}, "schema": []}
{"input": "In general, antiproliferative activity is greatly enhanced by low levels of the glutathione synthase inhibitor l-buthionine sulfoxime.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 80, "end": 91}, {"text": "l-buthionine sulfoxime", "start": 111, "end": 133}]}}, "schema": []}
{"input": "The work illustrates how subtle changes to the design of low-spin d (6) metal complexes can lead to major changes in cellular metabolism and to potent complexes with novel mechanisms of anticancer activity.", "output": {"entities": {}}, "schema": []}
{"input": "Metastable Cu (I)-niobate semiconductor with a low-temperature, nanoparticle-mediated synthesis.", "output": {"entities": {"chemical": [{"text": "Cu (I)", "start": 11, "end": 17}]}}, "schema": []}
{"input": "A nanoparticle synthetic strategy for the preparation of a new metastable Cu (I)-niobate is described, and that involves multipored Li 3 NbO 4 nanoparticles as a precursor.", "output": {"entities": {"chemical": [{"text": "Cu (I)", "start": 74, "end": 80}, {"text": "niobate", "start": 81, "end": 88}, {"text": "Li 3 NbO 4", "start": 132, "end": 142}]}}, "schema": []}
{"input": "A hydrothermal reaction of HNbO 3 and LiOH. H 2 O in PEG200 and water at ~ 180 degrees C yields ~ 15-40 nm Li 3 NbO 4 particles.", "output": {"entities": {"chemical": [{"text": "HNbO 3", "start": 27, "end": 33}, {"text": "LiOH. H 2 O", "start": 38, "end": 49}, {"text": "PEG200", "start": 53, "end": 59}, {"text": "Li 3 NbO 4", "start": 107, "end": 117}]}}, "schema": []}
{"input": "These particles are subsequently used in a solvothermal copper (I)-exchange reaction with excess CuCl at 150 degrees C.", "output": {"entities": {"chemical": [{"text": "copper (I)", "start": 56, "end": 66}, {"text": "CuCl", "start": 97, "end": 101}]}}, "schema": []}
{"input": "Heating these products within the used CuCl flux (mp = 430 degrees C) to 450 degrees C for 30 min yields ~ 4-12 nm Cu 2 Nb 8 O 2 1 crystalline nanoparticles, and for a heating time of 24 h yields mu m-sized, rod-shaped crystals.", "output": {"entities": {"chemical": [{"text": "CuCl", "start": 39, "end": 43}, {"text": "Cu 2 Nb 8 O 2 1", "start": 115, "end": 130}]}}, "schema": []}
{"input": "The new structure was characterized by single-crystal X-ray diffraction to have a condensed network consisting of NbO 7 polyhedra and chains of elongated CuO 4 tetrahedra.", "output": {"entities": {"chemical": [{"text": "NbO 7", "start": 114, "end": 119}, {"text": "CuO 4", "start": 154, "end": 159}]}}, "schema": []}
{"input": "The compound thermally decomposes starting at ~ 250 degrees C and higher temperatures, depending on the particle sizes, owing to the loss of the weakly coordinated Cu (I) cations from the structure and a concurrent disproportionation reaction at its surfaces.", "output": {"entities": {"chemical": [{"text": "Cu (I)", "start": 164, "end": 170}]}}, "schema": []}
{"input": "Thus, conventional solid-state reactions involving higher temperatures and bulk reagents have proven unsatisfactory for its synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "The measured bandgap size is ~ 1. 43-1. 65 eV (indirect) and shows a dependence on the particle sizes.", "output": {"entities": {}}, "schema": []}
{"input": "Electronic structure calculations based on density functional theory show that the bandgap transition results from the excitation of electrons at the band edges between filled Cu (I) 3d (1) 0-orbitals and empty Nb (V) 4d 0-orbitals, respectively.", "output": {"entities": {"chemical": [{"text": "Cu (I)", "start": 176, "end": 182}, {"text": "Nb (V)", "start": 211, "end": 217}]}}, "schema": []}
{"input": "The p-type nature of the Cu 2 Nb 8 O 2 1 particles was confirmed in photoelectrochemical measurements on polycrystalline films that show a strong photocathodic current under visible-light irradiation in aqueous solutions.", "output": {"entities": {"chemical": [{"text": "Cu 2 Nb 8 O 2 1", "start": 25, "end": 40}]}}, "schema": []}
{"input": "These results demonstrate the general utility of reactive nanoscale precursors in the synthetic discovery of new Cu (I)-based semiconducting oxides and which also show promise for use in solar energy conversion applications.", "output": {"entities": {"chemical": [{"text": "Cu (I)", "start": 113, "end": 119}, {"text": "oxides", "start": 141, "end": 147}]}}, "schema": []}
{"input": "Self-assembly of symmetric brush diblock copolymers.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembled structures of brush block copolymers (BrBCPs) with polylactide (PLA) and polystyrene (PS) side chains were studied.", "output": {"entities": {"chemical": [{"text": "polylactide", "start": 66, "end": 77}, {"text": "PLA", "start": 79, "end": 82}, {"text": "polystyrene", "start": 88, "end": 99}]}}, "schema": []}
{"input": "The polynorbornene-backbone-based BrBCPs containing approximately equal volume fractions of each block self-assembled into highly ordered lamellae with domain spacing ranging from 20 to 240 nm by varying molecular weight of the backbone in the bulk state, as revealed by small-angle X-ray scattering (SAXS).", "output": {"entities": {"chemical": [{"text": "polynorbornene", "start": 4, "end": 18}]}}, "schema": []}
{"input": "The domain size increased approximately linearly with backbone length, which indicated an extended conformation of the backbone in the ordered state.", "output": {"entities": {}}, "schema": []}
{"input": "In situ SAXS measurements suggested that the BrBCPs self-assemble with an extremely fast manner which could be attributed to a reduced number of entanglements between chains.", "output": {"entities": {}}, "schema": []}
{"input": "The strong segregation theory and Monte Carlo simulation also confirmed this near-linear dependence of the domain spacing on backbone length, rationalizing experimental results.", "output": {"entities": {}}, "schema": []}
{"input": "Structures and cytotoxic evaluation of new and known acyclic Ene-Ynes from an American Samoa Petrosia sp.", "output": {"entities": {}}, "schema": []}
{"input": "Sponge.", "output": {"entities": {}}, "schema": []}
{"input": "Four new compounds, (-)-petrosynoic acids A-D (1-4), and five known congeners, pellynols A (5), C (6), D (7), F (8), and I (9), were isolated from a Petrosia sp. marine sponge collected in American Samoa.", "output": {"entities": {"chemical": [{"text": "(-)-petrosynoic acids A-D", "start": 20, "end": 45}, {"text": "pellynols A (5), C (6), D (7), F (8), and I", "start": 79, "end": 122}]}}, "schema": []}
{"input": "Isolation work was guided by cytotoxicity against human lung cancer cells (H460).", "output": {"entities": {}}, "schema": []}
{"input": "The structures of the C31-C33 polyacetylenes (1-9) were determined on the basis of 1D-and 2D-NMR analysis, mass spectrometry, and comparison of specific rotation values.", "output": {"entities": {"chemical": [{"text": "C31-C33 polyacetylenes", "start": 22, "end": 44}]}}, "schema": []}
{"input": "Compounds 1-9 were found to be broadly cytotoxic with limited selectivity for cancer cells, as they were all moderately active against the A2058 (melanoma), H522-T1 (lung), and H460 (lung) human cancer cell lines as well as IMR-90 quiescent human fibroblast cells.", "output": {"entities": {}}, "schema": []}
{"input": "pH-dependent motion of self-propelled droplets due to Marangoni effect at neutral pH.", "output": {"entities": {}}, "schema": []}
{"input": "Oil droplets loaded with surfactant propel themselves with a velocity up to 6 mm s (-1) when they are placed in an aqueous phase of NaOH solution or buffer solution.", "output": {"entities": {"chemical": [{"text": "NaOH", "start": 132, "end": 136}]}}, "schema": []}
{"input": "The required driving force for such motion is generated on the interface of the droplets by the change in interfacial tension, due to deprotonation of the surfactant.", "output": {"entities": {}}, "schema": []}
{"input": "This force induces Marangoni convection, which gives rise to a circulating flow inside the droplets.", "output": {"entities": {}}, "schema": []}
{"input": "The droplets begin to move when the axis of this circulation deviates from the vertical line.", "output": {"entities": {}}, "schema": []}
{"input": "This motion depends on the pH condition of the aqueous phase.", "output": {"entities": {}}, "schema": []}
{"input": "When the initial value of pH is adjusted such that the pH exceeds the threshold at the equilibrium state, the droplets move spontaneously.", "output": {"entities": {}}, "schema": []}
{"input": "It was seen that the droplets were independent of the material of the solid substrates because the droplets were not directly in contact with the surface of the substrate.", "output": {"entities": {}}, "schema": []}
{"input": "The condition for the onset of this spontaneous motion was verified by comparing the prediction from the linear stability analysis with experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The stability analysis overestimates the value of the driving force, causing instability.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and characterization of a matrix-metalloproteinase responsive silk-elastinlike protein polymer.", "output": {"entities": {}}, "schema": []}
{"input": "Silk-elastinlike protein polymers (SELPs) are recombinant polymers consisting of tandem repeats of silk (GAGAGS) and elastin (GVGVP) units.", "output": {"entities": {}}, "schema": []}
{"input": "By modification of the length and composition of these repeats, the properties of SELP hydrogels can be controlled for specific applications including nucleic acid and virus delivery and tissue engineering.", "output": {"entities": {}}, "schema": []}
{"input": "Here, the structure of SELPs is further modified to include a sequence that is sensitive to matrix-metalloproteinases (MMPs).", "output": {"entities": {}}, "schema": []}
{"input": "MMPs are a ubiquitous family of extracellular matrix-modifying enzymes that are commonly associated with numerous vital processes.", "output": {"entities": {}}, "schema": []}
{"input": "Increased levels of MMPs are found at high levels locally in many types of solid tumors.", "output": {"entities": {}}, "schema": []}
{"input": "By modifying the SELP backbone with MMP-sensitive peptide sequences, a hydrogel that is degradable by MMPs was produced.", "output": {"entities": {}}, "schema": []}
{"input": "The MMP-sensitivity of the polymer was examined by incubation with MMP-2 and MMP-9, which yielded complete cleavage of all full-length polymers by 36 hours and 48 hours, respectively, with no observable effect on unmodified SELP.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrogel sensitivity was tested by exposure to MMP-2 or MMP-9 for 2 weeks, during which samples were taken to analyze protein loss from the hydrogel and release of 100 nm fluorescent beads.", "output": {"entities": {}}, "schema": []}
{"input": "Following the incubation period, hydrogels were tested in mechanical compression to examine the loss of hydrogel stiffness due to degradation.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that MMP-2 and MMP-9 caused 63% and 44% increased protein loss and 65% and 95% increased release from MMP-sensitive hydrogels, while the compressive modulus decreased by 41% and 29%.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest the potential of MMP-responsive SELPs for localized delivery of bioactive agents where MMPs are overexpressed.", "output": {"entities": {}}, "schema": []}
{"input": "Biobased polyesters with composition-dependent thermomechanical properties: synthesis and characterization of poly (butylene succinate-co-butylene azelate).", "output": {"entities": {"chemical": [{"text": "polyesters", "start": 9, "end": 19}, {"text": "poly (butylene succinate-co-butylene azelate)", "start": 110, "end": 155}]}}, "schema": []}
{"input": "Environmentally friendly poly (butylenesuccinate-co-butyleneazelate) (P (BS-co-BAz) s) aliphatic copolyesters with composition-dependent thermomechanical properties were synthesized from succinic acid (SuA), 1, 4-butanediol (BDO), and dimethylazelate (DMAz) through a two-step polycondensation reaction.", "output": {"entities": {"chemical": [{"text": "poly (butylenesuccinate-co-butyleneazelate)", "start": 25, "end": 68}, {"text": "P (BS-co-BAz) s", "start": 70, "end": 85}, {"text": "aliphatic copolyesters", "start": 87, "end": 109}, {"text": "succinic acid", "start": 187, "end": 200}, {"text": "SuA", "start": 202, "end": 205}, {"text": "1, 4-butanediol", "start": 208, "end": 223}, {"text": "BDO", "start": 225, "end": 228}, {"text": "dimethylazelate", "start": 235, "end": 250}, {"text": "DMAz", "start": 252, "end": 256}]}}, "schema": []}
{"input": "The molar SuA/AzA ratio was varied from 4: 1 to 1: 4, and the chemical structure and molecular characteristics of resulting (co) polyesters were characterized by NMR and SEC, whereas thermal properties and crystallinity were studied by differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), and X-ray diffraction (XRD).", "output": {"entities": {"chemical": [{"text": "SuA", "start": 10, "end": 13}, {"text": "AzA", "start": 14, "end": 17}, {"text": "(co) polyesters", "start": 124, "end": 139}]}}, "schema": []}
{"input": "A good agreement between theoretical and experimental SuA/AzA molar ratios in the copolyesters was achieved, together with the recovery of semicrystalline random copolymers of uniform composition along the chains.", "output": {"entities": {"chemical": [{"text": "SuA", "start": 54, "end": 57}, {"text": "AzA", "start": 58, "end": 61}, {"text": "copolyesters", "start": 82, "end": 94}]}}, "schema": []}
{"input": "NMR, DSC, DMTA, and XRD results show that depending on their composition the P (BS-co-BAz) copolyesters might find applications from elastomers to high-impact thermoplastics.", "output": {"entities": {"chemical": [{"text": "P (BS-co-BAz) copolyesters", "start": 77, "end": 103}]}}, "schema": []}
{"input": "Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl.", "output": {"entities": {"chemical": [{"text": "diltiazem HCl", "start": 107, "end": 120}]}}, "schema": []}
{"input": "Abstract Context: Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs.", "output": {"entities": {"chemical": [{"text": "polyethylene oxide", "start": 71, "end": 89}, {"text": "PEO", "start": 91, "end": 94}]}}, "schema": []}
{"input": "Objective: To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ).", "output": {"entities": {"chemical": [{"text": "PEO", "start": 40, "end": 43}, {"text": "Diltiazem hydrochloride", "start": 189, "end": 212}, {"text": "DTZ", "start": 214, "end": 217}]}}, "schema": []}
{"input": "Methods: Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate.", "output": {"entities": {"chemical": [{"text": "sodium bicarbonate", "start": 127, "end": 145}]}}, "schema": []}
{"input": "Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate.", "output": {"entities": {"chemical": [{"text": "PEO", "start": 122, "end": 125}, {"text": "sodium bicarbonate", "start": 130, "end": 148}]}}, "schema": []}
{"input": "Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied.", "output": {"entities": {}}, "schema": []}
{"input": "Results and discussion: The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3-4 min.", "output": {"entities": {}}, "schema": []}
{"input": "Drug release was faster from low molecular weight (MW) PEO as compared to high MW.", "output": {"entities": {"chemical": [{"text": "PEO", "start": 55, "end": 58}]}}, "schema": []}
{"input": "With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO (2) gas formation.", "output": {"entities": {"chemical": [{"text": "sodium bicarbonate", "start": 34, "end": 52}, {"text": "CO (2)", "start": 104, "end": 110}]}}, "schema": []}
{"input": "Drug release followed zero-order and gave a good fit to the Korsmeyer-Peppas model, which suggested that drug release was due to diffusion through polymer swelling.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer.", "output": {"entities": {"chemical": [{"text": "sodium bicarbonate", "start": 132, "end": 150}]}}, "schema": []}
{"input": "The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.", "output": {"entities": {"chemical": [{"text": "DTZ", "start": 51, "end": 54}]}}, "schema": []}
{"input": "Recent progress and challenges in the discovery of new neuraminidase inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "INTRODUCTION: At present, the key public health concern is to define the way in which the next influenza pandemic should be controlled.", "output": {"entities": {}}, "schema": []}
{"input": "While influenza vaccines are available, their effectiveness could be significantly reduced if new strains differ significantly from those of the vaccines.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, antiviral drugs play an important role in the prevention and management of influenza.", "output": {"entities": {}}, "schema": []}
{"input": "The influenza neuraminidase (NA), a surface-glycoprotein enzyme involved in releasing the virus from the host cell, has been considered as an essential therapeutic target for treatment and prophylaxis of influenza infection.", "output": {"entities": {}}, "schema": []}
{"input": "It is a highly conserved feature of the active site across all influenza A and B viruses and is of particular interest because compounds NA inhibitors (NAIs) can be cross-reactive against multiple types and subtypes of influenza.", "output": {"entities": {}}, "schema": []}
{"input": "Currently, there are two NAI drugs which are licensed worldwide: oseltamivir and zanamivir, and two more drugs which have received recent approval in Japan: peramivir and laninamivir.", "output": {"entities": {"chemical": [{"text": "oseltamivir", "start": 65, "end": 76}, {"text": "zanamivir", "start": 81, "end": 90}, {"text": "peramivir", "start": 157, "end": 166}, {"text": "laninamivir", "start": 171, "end": 182}]}}, "schema": []}
{"input": "Sudden changes in NAI susceptibility have stressed the urgent need in searching for novel inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "AREAS COVERED: In this review, a potential pitfall in NA-based assays and the progress in the chemical synthesis of all patented NAIs from February 2006 to July 2012 are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "EXPERT OPINION: Both NA enzyme inhibition and X-ray crystallography data have suggested that the strategy of designing NAIs binding to the highly conserved region of NA can lead to inhibitors that are effective against all influenza NA subtypes.", "output": {"entities": {}}, "schema": []}
{"input": "A number of new synthetic entries having unique structural frameworks that were designed based on computational study of X-ray structures of NA.", "output": {"entities": {}}, "schema": []}
{"input": "They strongly exhibited the activity of NA in the low nanomolar range such as phosphonate congeners of zanamivir and oseltarmivir.", "output": {"entities": {"chemical": [{"text": "phosphonate", "start": 78, "end": 89}, {"text": "zanamivir", "start": 103, "end": 112}, {"text": "oseltarmivir", "start": 117, "end": 129}]}}, "schema": []}
{"input": "Screening strategies based on the chemical diversity of natural products have revealed that flavonoids are the most prominent scaffolds possessing NA inhibitory activity.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 92, "end": 102}]}}, "schema": []}
{"input": "However, these substituted phenyl-benzopyrane compounds have been reported to exert a considerable quenching effect, causing false-positive results in the commonly used method of enzyme-based NA inhibition assays, and thus, reliability of the flavonoid-based NAIs reported in the literature.", "output": {"entities": {"chemical": [{"text": "phenyl-benzopyrane", "start": 27, "end": 45}, {"text": "flavonoid", "start": 243, "end": 252}]}}, "schema": []}
{"input": "Liver, plasma and erythrocyte levels of thiamine and its phosphate esters in rats with acute ethanol intoxication: a comparison of thiamine and benfotiamine administration.", "output": {"entities": {"chemical": [{"text": "thiamine", "start": 40, "end": 48}, {"text": "phosphate esters", "start": 57, "end": 73}, {"text": "ethanol", "start": 93, "end": 100}, {"text": "thiamine", "start": 131, "end": 139}, {"text": "benfotiamine", "start": 144, "end": 156}]}}, "schema": []}
{"input": "Thiamine and benfotiamine are vitamin B1 and pro-vitamin B1 substances, respectively.", "output": {"entities": {"chemical": [{"text": "Thiamine", "start": 0, "end": 8}, {"text": "benfotiamine", "start": 13, "end": 25}, {"text": "vitamin B1", "start": 30, "end": 40}, {"text": "pro-vitamin B1", "start": 45, "end": 59}]}}, "schema": []}
{"input": "Vitamin B1 plays an essential role in energy metabolism, and its deficiency leads to neurologic and cardiovascular pathologies, as seen in alcoholics.", "output": {"entities": {"chemical": [{"text": "Vitamin B1", "start": 0, "end": 10}, {"text": "alcoholics", "start": 139, "end": 149}]}}, "schema": []}
{"input": "This study presents new data about the effects of thiamine hydrochloride or benfotiamine treatment given to rats with acute alcohol intoxication, on the distribution of thiamine and its phosphate esters in liver, plasma and erythrocytes.", "output": {"entities": {"chemical": [{"text": "thiamine hydrochloride", "start": 50, "end": 72}, {"text": "benfotiamine", "start": 76, "end": 88}, {"text": "alcohol", "start": 124, "end": 131}, {"text": "thiamine", "start": 169, "end": 177}, {"text": "phosphate esters", "start": 186, "end": 202}]}}, "schema": []}
{"input": "The treatments were effective in increasing thiamine levels in plasma, erythrocytes and liver cells.", "output": {"entities": {"chemical": [{"text": "thiamine", "start": 44, "end": 52}]}}, "schema": []}
{"input": "The benfotiamine-treated group had its total plasma thiamine increased by 100%.", "output": {"entities": {"chemical": [{"text": "benfotiamine", "start": 4, "end": 16}, {"text": "thiamine", "start": 52, "end": 60}]}}, "schema": []}
{"input": "In erythrocytes, thiamine levels were 4-and 25-fold higher in the groups treated with thiamine and benfotiamine, respectively, compared with the untreated groups.", "output": {"entities": {"chemical": [{"text": "thiamine", "start": 17, "end": 25}, {"text": "thiamine", "start": 86, "end": 94}, {"text": "benfotiamine", "start": 99, "end": 111}]}}, "schema": []}
{"input": "Liver thiamine was increased by 60% in the treated groups compared with the untreated groups.", "output": {"entities": {"chemical": [{"text": "thiamine", "start": 6, "end": 14}]}}, "schema": []}
{"input": "Thus, we verified the high bioavailability especially of benfotiamine within 6h of ethanol administration.", "output": {"entities": {"chemical": [{"text": "benfotiamine", "start": 57, "end": 69}, {"text": "ethanol", "start": 83, "end": 90}]}}, "schema": []}
{"input": "Short-term assessment of toxicological aspects, oxidative and inflammatory response to dietary melon superoxide dismutase in rats.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 101, "end": 111}]}}, "schema": []}
{"input": "The protective effects of SODB, a gastro-resistant encapsulated melon superoxide dismutase, on haematological and biochemical parameters and inflammatory and oxidative status, were evaluated in the blood and liver tissue.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 70, "end": 80}]}}, "schema": []}
{"input": "The study consisted in a 28-day experiment on rats supplemented with three doses (10, 40 and 160USOD/day) of SODB-M, SODB-D or SODB-S, different depending on the nature of the coating (palm oil, shellac or gum Arabic respectively).", "output": {"entities": {}}, "schema": []}
{"input": "No mortality, abnormal clinical signs, behavioural changes or macroscopic findings were observed whatever the groups.", "output": {"entities": {}}, "schema": []}
{"input": "Haematological parameters (total red blood cell count, haemoglobin content, haematocrit, red cell indices, white blood cell count and platelets count) were not modified in SODB treated-groups.", "output": {"entities": {}}, "schema": []}
{"input": "No marked change was recorded in biochemical parameters (plasma urea, creatinine, lipids, electrolytes, bilirubin, transaminases and gamma-glutamyl transferase).", "output": {"entities": {"chemical": [{"text": "urea", "start": 64, "end": 68}, {"text": "creatinine", "start": 70, "end": 80}, {"text": "bilirubin", "start": 104, "end": 113}, {"text": "gamma-glutamyl", "start": 133, "end": 147}]}}, "schema": []}
{"input": "The liver endogenous antioxidant enzymes (copper/zinc and manganese superoxide dismutase) expressions were significantly increased in the rats receiving the highest dose of SODB (160USOD/day) whatever the coating.", "output": {"entities": {"chemical": [{"text": "copper", "start": 42, "end": 48}, {"text": "zinc", "start": 49, "end": 53}, {"text": "manganese superoxide", "start": 58, "end": 78}]}}, "schema": []}
{"input": "Moreover, interleukin-6, a marker of inflammation, was significantly decreased in these high dose-treated-groups.", "output": {"entities": {}}, "schema": []}
{"input": "The present study indicates that dietary supplementation of SODB on rats has no harmful side effects and could be beneficial especially at high doses.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-oxidant and natural killer cell activity of Korean red ginseng (Panax ginseng) and urushiol (Rhus vernicifera Stokes) on non-alcoholic fatty liver disease of rat.", "output": {"entities": {"chemical": [{"text": "urushiol", "start": 88, "end": 96}]}}, "schema": []}
{"input": "Anti-oxidative and immunologic effects of the Korea red ginseng (KRG; Panax ginseng) and urushiol (Rhus vernicifera Stokes) on non-alcoholic fatty liver disease (NAFLD) were evaluated.", "output": {"entities": {"chemical": [{"text": "urushiol", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Forty-five rats (five Long-Evans Tokushima Otsuka and 40 Otsuka Long-Evans Tokushima Fatty [OLETF] rats) received chew diets for 10months; after this period.", "output": {"entities": {}}, "schema": []}
{"input": "The OLETF rats were divided into the following four groups according to diet for 2months: NAFLD (chew), KRG (chew + KRG [200mg/kg/day]), urushiol (chew + urushiol [0. 5mg/kg/day]), and ursodeoxycholic acid (UDCA) (chew + UDCA [15mg/kg/day]) groups.", "output": {"entities": {"chemical": [{"text": "urushiol", "start": 137, "end": 145}, {"text": "urushiol", "start": 154, "end": 162}, {"text": "ursodeoxycholic acid", "start": 185, "end": 205}, {"text": "UDCA", "start": 207, "end": 211}, {"text": "UDCA", "start": 221, "end": 225}]}}, "schema": []}
{"input": "Liver function, lipid profiles and anti-oxidant activity of liver and serum, natural killer (NK) cell activity, and pathology were compared.", "output": {"entities": {}}, "schema": []}
{"input": "In KRG and urushiol groups, the level of serum triglyceride ([302. 0 +/- 70. 4 and 275. 2 +/- 63. 8] vs. 527. 7 +/- 153. 3mg/dL) were lower compared with that of NAFLD group (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "urushiol", "start": 11, "end": 19}, {"text": "triglyceride", "start": 47, "end": 59}]}}, "schema": []}
{"input": "The levels of HDL-cholesterol (liver tissue: [4. 8 +/- 0. 2 and 4. 8 +/- 0. 5] vs. 4. 2 +/- 0. 2mg/g) and NK cell activity ([3485 +/- 910 and 3559 +/- 910] vs. 2486 +/- 619 counts) were significantly higher than those of the NAFLD group (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 18, "end": 29}]}}, "schema": []}
{"input": "Inflammation with neutrophil infiltration was observed in only two rats in the NAFLD group.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that 2months of oral KRG or urushiol administration improves lipid profiles and stimulates NK cell activity, while inhibiting steatohepatitis in OLEFT rats.", "output": {"entities": {"chemical": [{"text": "urushiol", "start": 50, "end": 58}]}}, "schema": []}
{"input": "TNF alpha and Fas/FasL pathways are involved in 9-Methoxycamptothecin-induced apoptosis in cancer cells with oxidative stress and G2/M cell cycle arrest.", "output": {"entities": {"chemical": [{"text": "9-Methoxycamptothecin", "start": 48, "end": 69}]}}, "schema": []}
{"input": "9-Methoxycamptothecin (MCPT) has been recently reported to have a strong anticancer activity.", "output": {"entities": {"chemical": [{"text": "9-Methoxycamptothecin", "start": 0, "end": 21}, {"text": "MCPT", "start": 23, "end": 27}]}}, "schema": []}
{"input": "However, its detailed mechanism of action in human cancer cells has not been well clarified.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that MCPT induced cytotoxicity in seven human cancer cell lines in a dose dependent manner after 72h, with A2780 and Hela cell lines more sensitive, so the two cell lines were chosen to do further studies.", "output": {"entities": {"chemical": [{"text": "MCPT", "start": 24, "end": 28}]}}, "schema": []}
{"input": "MCPT induced strong G2/M arrest in both A2780 cells and Hela cells after 24h, following by substantial sub-G1 arrest (indicating apoptosis).", "output": {"entities": {"chemical": [{"text": "MCPT", "start": 0, "end": 4}]}}, "schema": []}
{"input": "The apoptosis was verified by staining with Annexin V-FITC and propidium iodide.", "output": {"entities": {"chemical": [{"text": "FITC", "start": 54, "end": 58}, {"text": "propidium iodide", "start": 63, "end": 79}]}}, "schema": []}
{"input": "ROS generation increased significantly in MCPT-induced apoptosis.", "output": {"entities": {"chemical": [{"text": "MCPT", "start": 42, "end": 46}]}}, "schema": []}
{"input": "Meanwhile, the apoptosis appeared to be dependent on caspase-3,-8 and-9 in A2780 cells, and caspase-3 in Hela cells.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, MCPT induced up-regulation expression of most of seventeen genes in both cell lines.", "output": {"entities": {"chemical": [{"text": "MCPT", "start": 13, "end": 17}]}}, "schema": []}
{"input": "Western blot verified that changes of TNF alpha, Fas, P53 and P27 protein level were consistent with their gene expression changes.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, MCPT plays an important role in tumor growth suppression by inducing apoptosis in both cell lines via extrinsic and intrinsic apoptotic pathways, and has the potential to be developed into an antitumor agent.", "output": {"entities": {"chemical": [{"text": "MCPT", "start": 16, "end": 20}]}}, "schema": []}
{"input": "Hierarchical organization of osteoblasts reveals the significant role of CD166 in hematopoietic stem cell maintenance and function.", "output": {"entities": {}}, "schema": []}
{"input": "The role of osteoblasts (OB) in maintaining hematopoietic stem cells (HSC) in their niche is well elucidated, but the exact definition, both phenotypically and hierarchically of OB responsible for these functions is not clearly known.", "output": {"entities": {}}, "schema": []}
{"input": "We previously demonstrated that OB maturational status influences HSC function whereby immature OB with high Runx2 expression promote hematopoietic expansion.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that Activated Leukocyte Cell Adhesion Molecule (ALCAM) or CD166 expression on OB is directly correlated with Runx2 expression and high hematopoiesis enhancing activity (HEA).", "output": {"entities": {}}, "schema": []}
{"input": "Fractionation of OB with lineage markers: Sca1, osteopontin (OPN), CD166, CD44, and CD90 revealed that Lin-Sca1-OPN + CD166 + cells (CD166 +) and their subpopulations fractionated with CD44 and CD90 expressed high levels of Runx2 and low levels of osteocalcin (OC) demonstrating the relatively immature status of these cells.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, the majority of the Lin-Sca1-OPN + CD166-cells (CD166-) expressed high OC levels suggesting that CD166-OB are more mature.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro hematopoietic potential of LSK cells co-cultured for 7days with fresh OB or OB pre-cultured for 1, 2, or 3 weeks declined precipitously with increasing culture duration concomitant with loss of CD166 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, LSK cells co-cultured with CD166 + CD44 + CD90 + OB maintained their in vivo repopulating potential through primary and secondary transplantation, suggesting that robust HEA activity is best mediated by immature CD166 + OB with high Runx2 and low OC expression.", "output": {"entities": {}}, "schema": []}
{"input": "These studies begin to define the hierarchical organization of osteoblastic cells and provide a more refined definition of OB that can mediate HEA.", "output": {"entities": {}}, "schema": []}
{"input": "Alteration of proteoglycan sulfation affects bone growth and remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 124, "end": 131}]}}, "schema": []}
{"input": "Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients.", "output": {"entities": {}}, "schema": []}
{"input": "To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans.", "output": {"entities": {}}, "schema": []}
{"input": "X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model.", "output": {"entities": {}}, "schema": []}
{"input": "We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice.", "output": {"entities": {}}, "schema": []}
{"input": "Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates.", "output": {"entities": {"chemical": [{"text": "deoxypyridinoline", "start": 132, "end": 149}, {"text": "C", "start": 198, "end": 199}]}}, "schema": []}
{"input": "Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice.", "output": {"entities": {}}, "schema": []}
{"input": "These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "APE1/Ref-1 prevents oxidative inactivation of ERK for G1-to-S progression following lead acetate exposure.", "output": {"entities": {"chemical": [{"text": "lead acetate", "start": 84, "end": 96}]}}, "schema": []}
{"input": "Apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 is a multifunctional enzyme involved in DNA base excision repair and protein redox regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, we have showed that lead acetate (Pb) elicits EGFR activation to initiate the SFK/PKC alpha/Ras/Raf-1/MKK1/2/ERK signaling cascade functioning against genotoxicity.", "output": {"entities": {"chemical": [{"text": "lead acetate", "start": 32, "end": 44}, {"text": "Pb", "start": 46, "end": 48}]}}, "schema": []}
{"input": "Here, we explore whether APE1 and reactive oxygen species (ROS) affect ERK signaling and cell cycle progression following Pb exposure.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 43, "end": 49}, {"text": "Pb", "start": 122, "end": 124}]}}, "schema": []}
{"input": "We found that Pb induced APE1 expression and ROS generation in CL3 human lung cancer cells.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 14, "end": 16}]}}, "schema": []}
{"input": "The Pb-elicited ROS levels and cytotoxicity were further enhanced by introducing small interfering RNA specific for APE1 (siAPE1).", "output": {"entities": {"chemical": [{"text": "Pb", "start": 4, "end": 6}]}}, "schema": []}
{"input": "E3330, an inhibitor of APE1 redox activity, also augmented the ROS levels and cytotoxicity in Pb-treated cells.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 94, "end": 96}]}}, "schema": []}
{"input": "Intriguingly, the capability of Pb to activate ERK was abolished under siAPE1 or E3330 co-treatments; conversely, forced expression of APE1 up-regulated the ERK activation by Pb or serum in both Cys65-redox activity dependent and independent manners.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 32, "end": 34}, {"text": "Pb", "start": 175, "end": 177}, {"text": "Cys65", "start": 195, "end": 200}]}}, "schema": []}
{"input": "Moreover, APE1 formed complex with ERK2, and its redox activity could rescue ERK oxidative inactivation.", "output": {"entities": {}}, "schema": []}
{"input": "APE1 redox activity also facilitated the Cyclin D1 expression and G1-to-S progression following Pb exposure.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 96, "end": 98}]}}, "schema": []}
{"input": "In summary, the results indicate that APE1 is a direct redox regulator of ERK for maintaining the kinase activity to promote cell proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, quantitative structure-activity relationship and biological evaluation of 1, 3, 4-oxadiazole derivatives possessing diphenylamine moiety as potential anticancer agents.", "output": {"entities": {"chemical": [{"text": "1, 3, 4-oxadiazole", "start": 85, "end": 103}, {"text": "diphenylamine", "start": 127, "end": 140}]}}, "schema": []}
{"input": "Synthesis of 2, 5-disubstituted-1, 3, 4-oxadiazole (2a-c), 3-substituted aminomethyl-5-substituted-1, 3, 4-oxadiazole-2 (3H)-thione (4a-m) and 2-substituted thio-5-substituted-1, 3, 4-oxadiazole (5a, b) had been described.", "output": {"entities": {"chemical": [{"text": "2, 5-disubstituted-1, 3, 4-oxadiazole", "start": 13, "end": 50}, {"text": "3-substituted aminomethyl-5-substituted-1, 3, 4-oxadiazole-2 (3H)-thione", "start": 59, "end": 131}, {"text": "2-substituted thio-5-substituted-1, 3, 4-oxadiazole", "start": 143, "end": 194}]}}, "schema": []}
{"input": "All the synthesized derivatives were screened for anticancer activity against HT29 and MCF7 cancer cell lines using Sulfo-Rodamine B (SRB) standard method.", "output": {"entities": {"chemical": [{"text": "Sulfo-Rodamine B", "start": 116, "end": 132}, {"text": "SRB", "start": 134, "end": 137}]}}, "schema": []}
{"input": "Most of the tested compounds exploited potent antiproliferative activity against HT29 cancer cell line rather than MCF7 cancer cell line.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 2a-c, 4f and 5a exhibited potent cytotoxicity (IC (50) 1. 3-2. 0 micro M) and selectivity against HT29 cancer cell line.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative structure-activity relationship (QSAR) study was applied to find a correlation between the experimental antiproliferative activities of the newly synthesized oxadiazole derivatives with their physicochemical parameter and topological index.", "output": {"entities": {"chemical": [{"text": "oxadiazole", "start": 171, "end": 181}]}}, "schema": []}
{"input": "Statistical modeling, optimization and characterization of spray-dried solid self-microemulsifying drug delivery system using design of experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The present study systematically and simultaneously investigates the influence of process variables of spray-drying on the properties of solid self-microemulsifying drug delivery system (SMEDDS) using design of experiment (DOE) and optimizes them in order to produce solid-SMEDDS satisfying pre-defined powder quality attributes.", "output": {"entities": {}}, "schema": []}
{"input": "Flurbiprofen-loaded liquid-SMEDDS was dispersed in dextran and spray-dried.", "output": {"entities": {"chemical": [{"text": "Flurbiprofen", "start": 0, "end": 12}]}}, "schema": []}
{"input": "After preliminary screening, the independent factors selected according to three-factor, three-level Box-Behnken design were inlet temperature (X (1)), feed rate (X (2)) and carrier concentration (X (3)).", "output": {"entities": {}}, "schema": []}
{"input": "The responses used to compute the effects of independent factors were moisture content (Y (1)), yield (Y (2)), drug content (Y (3)) and droplet size (Y (4)) of the micro-emulsion.", "output": {"entities": {}}, "schema": []}
{"input": "SMEDDS powder characteristics such as morphology, thermal behavior, crystallinity and flowability were also considered.", "output": {"entities": {}}, "schema": []}
{"input": "Models were developed and model fitting analysis showed an adequate fit for all responses, indicating good predictability.", "output": {"entities": {}}, "schema": []}
{"input": "Significant effects of processing parameters on powder characteristics were observed.", "output": {"entities": {}}, "schema": []}
{"input": "The spray-drying process parameters were optimized as inlet temperature (134 degrees C), feed rate (5%) and carrier concentration (0. 6%) to produce solid-SMEDDS with acceptable moisture content (0. 72 +/- 0. 02%), yield (58. 5 +/- 2. 9%), drug content (70. 1 +/- 2. 7 mg/g) and droplet size (166. 8 +/- 13. 8 nm).", "output": {"entities": {}}, "schema": []}
{"input": "Validation of the optimization process in five batches showed experimental value very close to the predicted one, ensuring the reproducibility of the developed models.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, optimized parameters resulted a highly crystalline flurbiprofen changed to an amorphous form.", "output": {"entities": {"chemical": [{"text": "flurbiprofen", "start": 64, "end": 76}]}}, "schema": []}
{"input": "In conclusion, this study demonstrated the applicability of the DOE approach for optimizing the process parameters to manufacture solid-SMEDDS with desired quality attributes.", "output": {"entities": {}}, "schema": []}
{"input": "Organosilicon compounds as adult T-cell leukemia cell proliferation inhibitors.", "output": {"entities": {"chemical": [{"text": "Organosilicon", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Aggressive forms of adult T-cell leukemia (ATL) respond poorly to conventional anticancer chemotherapy, and new lead compounds are required for the development of drugs to treat this fatal disease.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, we developed ATL cell-selective proliferation inhibitors based on a tetrahydrotetramethylnaphthalene (TMN) skeleton 1, and here we report the design and synthesis of silicon analogs of TMN derivatives.", "output": {"entities": {"chemical": [{"text": "tetrahydrotetramethylnaphthalene", "start": 78, "end": 110}, {"text": "TMN", "start": 112, "end": 115}, {"text": "silicon", "start": 176, "end": 183}, {"text": "TMN", "start": 195, "end": 198}]}}, "schema": []}
{"input": "Among them, compound 13 showed the most potent growth-inhibitory activity towards the ATL cell line S1T, though its selectivity for S1T over the non-ATL cell line MOLT-4 was only moderate.", "output": {"entities": {}}, "schema": []}
{"input": "This result, as well as computational studies, suggests that sila-substitution (C/Si exchange) is useful for structure optimization of these inhibitors.", "output": {"entities": {"chemical": [{"text": "C", "start": 80, "end": 81}, {"text": "Si", "start": 82, "end": 84}]}}, "schema": []}
{"input": "Temporal stability of magic-number metal clusters: beyond the shell closing model.", "output": {"entities": {}}, "schema": []}
{"input": "The anomalous stability of magic-number metal clusters has been associated with closed geometric and electronic shells and the opening of HOMO-LUMO gaps.", "output": {"entities": {}}, "schema": []}
{"input": "Despite this enhanced stability, magic-number clusters are known to decay and react in the condensed phase to form other products.", "output": {"entities": {}}, "schema": []}
{"input": "Improving our understanding of their decay mechanisms and developing strategies to control or eliminate cluster instability is a priority, to develop a more complete theory of their stability, to avoid studying mixtures of clusters produced by the decay of purified materials, and to enable technology development.", "output": {"entities": {}}, "schema": []}
{"input": "Silver clusters are sufficiently reactive to facilitate the study of the ambient temporal stability of magic-number metal clusters and to begin to understand their decay mechanisms.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Here, the solution phase stability of a series of silver: glutathione (Ag: SG) clusters was studied as a function of size, pH and chemical environment.", "output": {"entities": {"chemical": [{"text": "silver", "start": 50, "end": 56}, {"text": "glutathione", "start": 58, "end": 69}, {"text": "Ag", "start": 71, "end": 73}]}}, "schema": []}
{"input": "Cluster stability was found to be a non-monotonic function of size.", "output": {"entities": {}}, "schema": []}
{"input": "Electrophoretic separations showed that the dominant mechanism involved the redistribution of mass toward smaller sizes, where the products were almost exclusively previously known cluster sizes.", "output": {"entities": {}}, "schema": []}
{"input": "Optical absorption spectra showed that the smaller clusters evolved toward the two most stable cluster sizes.", "output": {"entities": {}}, "schema": []}
{"input": "The net surface charge was found to play an important role in cluster stabilization although charge screening had no effect on stability, contrary to DLVO theory.", "output": {"entities": {}}, "schema": []}
{"input": "The decay mechanism was found to involve the loss of Ag (+) ions and silver glutathionates.", "output": {"entities": {"chemical": [{"text": "Ag (+)", "start": 53, "end": 59}, {"text": "silver glutathionates", "start": 69, "end": 90}]}}, "schema": []}
{"input": "Clusters could be stabilized by the addition of Ag (+) ions and destabilized by either the addition of glutathione or the removal of Ag (+) ions.", "output": {"entities": {"chemical": [{"text": "Ag (+)", "start": 48, "end": 54}, {"text": "glutathione", "start": 103, "end": 114}, {"text": "Ag (+)", "start": 133, "end": 139}]}}, "schema": []}
{"input": "Clusters were also found to be most stable in near neutral pH, where they had a net negative surface charge.", "output": {"entities": {}}, "schema": []}
{"input": "These results provide new mechanistic insights into the control of post-synthesis stability and chemical decay of magic-number metal clusters, which could be used to develop design principles for synthesizing specific cluster species.", "output": {"entities": {}}, "schema": []}
{"input": "Biomarkers for predicting future metastasis of human gastrointestinal tumors.", "output": {"entities": {}}, "schema": []}
{"input": "The recent advances in surgery and radiation therapy have significantly improved the prognosis of patients with primary cancer, and the major challenge of cancer treatment now is metastatic disease development.", "output": {"entities": {}}, "schema": []}
{"input": "The 5-year survival rate of cancer patients who have distant metastasis at diagnosis is extremely low, suggesting that prediction and early detection of metastasis would definitely improve their prognosis because suitable patient therapeutic management and treatment strategy can be provided.", "output": {"entities": {}}, "schema": []}
{"input": "Cancer cells from a primary site give rise to a metastatic tumor via a number of steps which require the involvement and altered expression of many regulators.", "output": {"entities": {}}, "schema": []}
{"input": "These regulators may serve as biomarkers for predicting metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "Over the past few years, numerous regulators have been found correlating with metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we summarize the findings of a number of potential biomarkers that are involved in cadherin-catenin interaction, integrin signaling, PI3K/Akt/mTOR signaling and cancer stem cell identification in gastrointestinal cancers.", "output": {"entities": {}}, "schema": []}
{"input": "We will also discuss how certain biomarkers are associated with the tumor microenvironment that favors cancer metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "The role of cortisol and psychopathy in the cycle of violence.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 12, "end": 20}]}}, "schema": []}
{"input": "RATIONALE: Child abuse and neglect are universal risk factors for delinquency, violence, and aggression; this phenomenon is known as the cycle of violence.", "output": {"entities": {}}, "schema": []}
{"input": "Additional factors-psychopathy, impulsiveness, and disruptions in the hypothalamic-pituitary-adrenal (HPA) axis-play a role in aggressive behavior but have rarely been examined in the same conceptual and experimental framework.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVES: We sought to examine the above-mentioned risk factors for aggression in a prospective study employing psychopharmacologic and psychometric techniques.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Sixty-seven adult participants were given an acute dose of 20 mg cortisol in a placebo-controlled, within-subject, counter-balanced dosing design.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 74, "end": 82}]}}, "schema": []}
{"input": "Salivary cortisol was measured at baseline and at regular intervals across a 5 h testing period.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 9, "end": 17}]}}, "schema": []}
{"input": "Following dosing, state-aggressive behavior was measured by a laboratory task, the Point-Subtraction Aggression Paradigm.", "output": {"entities": {}}, "schema": []}
{"input": "History of child abuse/neglect, psychopathy, impulsivity, and a trait measure of aggression were assessed through self-report questionnaires.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Using multiple regression, a model including abuse/neglect, psychopathy, impulsivity, and baseline cortisol explained 58% of the variance in trait aggression and 26% of the variance in state aggression.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 108, "end": 116}]}}, "schema": []}
{"input": "Abuse/neglect predicted diminished HPA-axis reactivity and HPA-axis reactivity showed a trend toward predicting state and trait aggression, although it was not a significant mediating variable between abuse/neglect and aggression.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: The results indicate that child maltreatment, psychopathy and HPA-axis reactivity interact to provide a confluence over aggressive behavior, and intervention efforts need to consider all these factors.", "output": {"entities": {}}, "schema": []}
{"input": "One-Pot Facile Synthesis of Double-Shelled SnO2 Yolk-Shell-Structured Powders by Continuous Process as Anode Materials for Li-ion Batteries.", "output": {"entities": {"chemical": [{"text": "SnO2", "start": 43, "end": 47}, {"text": "Li", "start": 123, "end": 125}]}}, "schema": []}
{"input": "Double-shelled SnO2 yolk-shell-structured powders are prepared by applying a new facile one-pot process.", "output": {"entities": {"chemical": [{"text": "SnO2", "start": 15, "end": 19}]}}, "schema": []}
{"input": "Carbon-SnO2 composite powder particles are first formed as an intermediate product inside a tubular reactor.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}, {"text": "SnO2", "start": 7, "end": 11}]}}, "schema": []}
{"input": "Step-by-step combustion of carbon from outside the composite powder particles forms the double-shelled SnO2 yolk-shell-structured powder particles.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 27, "end": 33}, {"text": "SnO2", "start": 103, "end": 107}]}}, "schema": []}
{"input": "The SnO2 yolk-shell-structured powders show excellent electrochemical properties.", "output": {"entities": {"chemical": [{"text": "SnO2", "start": 4, "end": 8}]}}, "schema": []}
{"input": "Selective fluorescence detection of small-molecule-binding proteins by using a dual photoaffinity labeling system.", "output": {"entities": {}}, "schema": []}
{"input": "PHOTO OPPORTUNITY: We have developed a dual photoaffinity labeling system in which an active and an inactive probe bearing orthogonal detection groups are co-reacted in a single photoreaction.", "output": {"entities": {}}, "schema": []}
{"input": "The approach allowed selective fluorescent detection of a model binding protein in cell lysate by either 1D or 2D electrophoresis.", "output": {"entities": {}}, "schema": []}
{"input": "Selective fluorogenic chemosensors for distinct classes of nucleases.", "output": {"entities": {}}, "schema": []}
{"input": "NUCLEASE SENSOR TRIO: Fluorogenic DNA sensors were developed for distinct classes of nucleases: 3'-exonucleases, 5'-exonucleases, and endonucleases.", "output": {"entities": {}}, "schema": []}
{"input": "The highly selective sensors, built from very small modified DNA oligomers containing the unnatural fluorescent base pyrene, and employing thymine as a quencher, were found to function in a variety of complex biological media.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 117, "end": 123}, {"text": "thymine", "start": 139, "end": 146}]}}, "schema": []}
{"input": "Role of autophagy in the progression from obesity to diabetes and in the control of energy balance.", "output": {"entities": {}}, "schema": []}
{"input": "Autophagy plays a crucial role in cellular homeostasis through the degradation and recycling of organelles such as mitochondria or endoplasmic reticulum (ER) that are closely related to the pathogenesis of diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "In pancreatic beta-cells producing insulin, autophagy helps maintain beta-cell mass, structure and function.", "output": {"entities": {}}, "schema": []}
{"input": "In mice with beta-cell-specific deletion of Atg7 (autophagy-related 7), a critical autophagy gene, reduction of beta-cell mass and pancreatic insulin content were observed together with impaired insulin secretory function.", "output": {"entities": {}}, "schema": []}
{"input": "Because of such structural and functional defects, beta-cell-specific Atg7-null mice showed hypoinsulinemia and hyperglycemia.", "output": {"entities": {}}, "schema": []}
{"input": "However, those mice never developed diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity and lipids are physiological ER stressors that can precipitate beta-cell dysfunction and insulin resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies showed that beta-cell-specific Atg7-null mice, when bred with ob/ob mice, developed severe diabetes, suggesting that autophagy-deficient beta-cells can handle basal metabolic stress but have problems dealing with increased metabolic stress.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, autophagy deficiency in beta-cells could be a factor in the progression from obesity to diabetes due to an inappropriate response to obesity-induced ER stress.", "output": {"entities": {}}, "schema": []}
{"input": "Autophagy also appears to play a role in the hypothalamic control of energy expenditure, appetite and body weight.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, autophagy is important to body and nutrient metabolism in many ways, and its dysregulation could contribute to the pathogenesis of metabolic disorders and diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Manganese supplementation protects against diet-induced diabetes in wild type mice by enhancing insulin secretion.", "output": {"entities": {"chemical": [{"text": "Manganese", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Mitochondrial dysfunction is both a contributing mechanism and complication of diabetes, and oxidative stress contributes to that dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondrial manganese-superoxide dismutase (MnSOD) is a metalloenzyme that provides antioxidant protection.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 14, "end": 23}, {"text": "superoxide", "start": 24, "end": 34}]}}, "schema": []}
{"input": "We have previously shown in a mouse model of hereditary iron overload that cytosolic iron levels affected mitochondrial manganese availability, MnSOD activity, and insulin secretion.", "output": {"entities": {"chemical": [{"text": "iron", "start": 56, "end": 60}, {"text": "manganese", "start": 120, "end": 129}, {"text": "MnSOD", "start": 144, "end": 149}]}}, "schema": []}
{"input": "We therefore sought to determine the metallation status of MnSOD in wild-type mice and whether altering that status affected beta-cell function.", "output": {"entities": {"chemical": [{"text": "MnSOD", "start": 59, "end": 64}]}}, "schema": []}
{"input": "129/SvEVTac mice given supplemental manganese exhibited a 73% increase in hepatic MnSOD activity and increased metallation of MnSOD.", "output": {"entities": {"chemical": [{"text": "MnSOD", "start": 82, "end": 87}, {"text": "MnSOD", "start": 126, "end": 131}]}}, "schema": []}
{"input": "To determine whether manganese supplementation offered glucose homeostasis under a situation of beta-cell stress, we challenged C57BL/6J mice, which are more susceptible to diet-induced diabetes, with a high-fat diet for 12 weeks.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 55, "end": 62}]}}, "schema": []}
{"input": "Manganese was supplemented or not for the final 8 weeks on that diet, after which we examined glucose tolerance and the function of isolated islets.", "output": {"entities": {"chemical": [{"text": "Manganese", "start": 0, "end": 9}, {"text": "glucose", "start": 94, "end": 101}]}}, "schema": []}
{"input": "Liver mitochondria from manganese-injected C57BL/6J mice had similar increases in MnSOD activity (81%) and metallation as were seen in 129/SvEVTac mice.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 24, "end": 33}, {"text": "MnSOD", "start": 82, "end": 87}]}}, "schema": []}
{"input": "The manganese-treated group fed high fat had improved glucose tolerance (24% decrease in fasting glucose and 41% decrease in area under the glucose curve), comparable with mice on normal chow and increased serum insulin levels.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 4, "end": 13}, {"text": "glucose", "start": 54, "end": 61}, {"text": "glucose", "start": 97, "end": 104}, {"text": "glucose", "start": 140, "end": 147}]}}, "schema": []}
{"input": "Isolated islets from the manganese-treated group exhibited improved insulin secretion, decreased lipid peroxidation, and improved mitochondrial function.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 25, "end": 34}]}}, "schema": []}
{"input": "In conclusion, MnSOD metallation and activity can be augmented with manganese supplementation in normal mice on normal chow, and manganese treatment can increase insulin secretion to improve glucose tolerance under conditions of dietary stress.", "output": {"entities": {"chemical": [{"text": "MnSOD", "start": 15, "end": 20}, {"text": "manganese", "start": 68, "end": 77}, {"text": "manganese", "start": 129, "end": 138}, {"text": "glucose", "start": 191, "end": 198}]}}, "schema": []}
{"input": "A simple and sensitive method for determination of vitamins D (3) and K (1) in rat plasma: application for an in vivo pharmacokinetic study.", "output": {"entities": {"chemical": [{"text": "vitamins D (3) and K (1)", "start": 51, "end": 75}]}}, "schema": []}
{"input": "Abstract Purpose: To develop and to validate a simple but sensitive method for determination of vitamins D (3) and K (1) in rat plasma.", "output": {"entities": {"chemical": [{"text": "vitamins D (3) and K (1)", "start": 96, "end": 120}]}}, "schema": []}
{"input": "Methods: The sample treatment included protein precipitation by cold acetonitrile, evaporation, reconstitution with methanol and filtration.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 69, "end": 81}, {"text": "methanol", "start": 116, "end": 124}]}}, "schema": []}
{"input": "The chromatography conditions included Xterra RP18 3. 5 micro m 4. 6 x 100 mm column at ambient temperature and mobile phase consisting of methanol/water (93/7, v/v) at 0. 5 mL/min flow rate.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 139, "end": 147}]}}, "schema": []}
{"input": "Vitamin D (3) and probucol were detected at 265 nm and vitamin K (1) at 239 nm.", "output": {"entities": {"chemical": [{"text": "Vitamin D (3)", "start": 0, "end": 13}, {"text": "probucol", "start": 18, "end": 26}, {"text": "vitamin K (1)", "start": 55, "end": 68}]}}, "schema": []}
{"input": "Rats were administered intravenously by 0. 1 mg/kg of vitamin D (3) or K (1) and the blood samples were withdrawn pre-administration and at pre-determined time points post-administration.", "output": {"entities": {"chemical": [{"text": "vitamin D (3) or K (1)", "start": 54, "end": 76}]}}, "schema": []}
{"input": "The pharmacokinetic analysis was performed using a non-compartmental approach.", "output": {"entities": {}}, "schema": []}
{"input": "Results: The calibration curves in rat plasma were linear up to 5000 ng/mL for both vitamins.", "output": {"entities": {"chemical": [{"text": "vitamins", "start": 84, "end": 92}]}}, "schema": []}
{"input": "The limit of quantification (LOQ) was 20 ng/mL for vitamin D (3) and 40 ng/mL for K (1).", "output": {"entities": {"chemical": [{"text": "vitamin D (3)", "start": 51, "end": 64}]}}, "schema": []}
{"input": "Inter-and intra-day precision and accuracy were below 15%.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacokinetic parameters of vitamin D (3) following intravenous administration were: AUC (0-infinity) = 11323 +/- 1081 h x ng/mL, V (d) = 218 +/- 80 mL/kg, CL = 8. 9 +/- 0. 8 mL/h/kg, t (1/2) = 16. 8 +/- 5 h; and of vitamin K (1): AUC (0-infinity) = 2495 +/- 297 h x ng/mL, V (d) = 60 +/- 24 mL/kg, CL = 40. 5 +/- 5. 1 mL/h/kg, t (1/2) = 1. 1 +/- 0. 5 h.", "output": {"entities": {"chemical": [{"text": "vitamin D (3)", "start": 34, "end": 47}, {"text": "vitamin K (1)", "start": 222, "end": 235}]}}, "schema": []}
{"input": "Conclusion: The developed HPLC-UV assay is a simple and sensitive method for the determination of vitamins D (3) and K (1) in rat plasma.", "output": {"entities": {"chemical": [{"text": "vitamins D (3) and K (1)", "start": 98, "end": 122}]}}, "schema": []}
{"input": "A higher dose of vitamin K (1) should be used in future studies for accurate estimation of pharmacokinetic parameters.", "output": {"entities": {"chemical": [{"text": "vitamin K (1)", "start": 17, "end": 30}]}}, "schema": []}
{"input": "The data show the suitability of the assay for pharmacokinetic studies in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of superparamagnetic particles with tunable morphologies: the role of nanoparticle-nanoparticle interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Superparamagnetic microparticles are extensively used in the purification of biomolecules due to the speed and ease of magnetic separation.", "output": {"entities": {}}, "schema": []}
{"input": "It is desirable that the microparticles used in biological affinity separations have both high surface area and high magnetic mobility to facilitate a high binding capacity of target biomolecules and their rapid removal from solution, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Scaling laws for conventional spherical superparamagnetic microparticles are such that increasing the microparticle specific surface area results in a significant decrease in the magnetic mobility.", "output": {"entities": {}}, "schema": []}
{"input": "More favorable combinations of these key parameters can be found if alternative microparticle morphologies are developed for use in affinity separations.", "output": {"entities": {}}, "schema": []}
{"input": "Emulsion-templated self-assembly of iron oxide nanoparticles into microparticles using oil-in-water emulsions was carried out using a modified Couette shear mixer with separate inlet ports for the oil and aqueous phases, enabling high throughput microparticle synthesis.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 36, "end": 46}]}}, "schema": []}
{"input": "By controlling the dissolved nanoparticle concentration and nanoparticle surface activity at the droplet interfaces, the resulting microparticles were tuned to spherical, dimpled, or crumpled morphologies.", "output": {"entities": {}}, "schema": []}
{"input": "The specific binding capacity and magnetic mobility of each type of microparticle were measured by a peroxidase-based colorimetric assay and by their magnetic field-induced motion in a viscous fluid, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Superparamagnetic microparticles with dimpled and crumpled morphologies were found to have higher specific binding capacities compared to spherical microparticles, while maintaining high magnetic field velocities due to their high iron oxide content.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 231, "end": 241}]}}, "schema": []}
{"input": "Superparamagnetic microparticles with these novel morphologies would make excellent tools for affinity-based bioseparations where binding capacity and magnetic mobility are key factors.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation of astatine (III) hydrolyzed species: experiments and relativistic calculations.", "output": {"entities": {"chemical": [{"text": "astatine (III)", "start": 17, "end": 31}]}}, "schema": []}
{"input": "This work aims to resolve some controversies about astatine (III) hydroxide species present in oxidant aqueous solution.", "output": {"entities": {"chemical": [{"text": "astatine (III) hydroxide", "start": 51, "end": 75}]}}, "schema": []}
{"input": "AtO (+) is the dominant species existing under oxidizing and acidic pH conditions.", "output": {"entities": {"chemical": [{"text": "AtO (+)", "start": 0, "end": 7}]}}, "schema": []}
{"input": "This is consistent with high-performance ion-exchange chromatography data showing the existence of one species holding one positive charge.", "output": {"entities": {}}, "schema": []}
{"input": "A change in speciation occurs as the pH changes from 1 to 4, while remaining under oxidizing conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Dynamic experiments with ion-exchange resins evidence the existence of a neutral species witnessed by its elution in the void volume.", "output": {"entities": {}}, "schema": []}
{"input": "Batch-experiments using a competition method show the exchange of one proton indicating the formation of the AtO (OH) species.", "output": {"entities": {"chemical": [{"text": "AtO (OH)", "start": 109, "end": 117}]}}, "schema": []}
{"input": "The hydrolysis thermodynamic constant, extrapolated to zero ionic strength, was determined to be 10 (-1. 9).", "output": {"entities": {}}, "schema": []}
{"input": "This value is supported by two-component relativistic quantum calculations and therefore allows disclosing unambiguously the structure of the formed species.", "output": {"entities": {}}, "schema": []}
{"input": "Polymer therapeutics with a coiled coil motif targeted against murine bcl1 leukemia.", "output": {"entities": {}}, "schema": []}
{"input": "The specificity of polymer conjugates based on N-(2-hydroxypropyl) methacrylamide (HPMA) bearing cytostatic drugs for cancer cells could be significantly increased by the incorporation of a suitable targeting ligand, such as a monoclonal antibody (mAb).", "output": {"entities": {"chemical": [{"text": "N-(2-hydroxypropyl) methacrylamide", "start": 47, "end": 81}, {"text": "HPMA", "start": 83, "end": 87}]}}, "schema": []}
{"input": "However, direct binding of the protein to the polymer carrier could cause considerable problems, such as decreasing the binding capacity of mAb to its target.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we introduce a novel strategy of joining a targeting moiety to a polymeric conjugate with cytostatic drug.", "output": {"entities": {}}, "schema": []}
{"input": "The scFv of B1 mAb (specific for BCL1 leukemia cells) was tagged with peptide K ((VAALKEK) 4).", "output": {"entities": {}}, "schema": []}
{"input": "Peptide E ((VAALEKE) 4), which forms a stable coiled coil structure heterodimer with peptide K, was assembled with the HPMA copolymers bearing doxorubicin.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 119, "end": 123}, {"text": "doxorubicin", "start": 143, "end": 154}]}}, "schema": []}
{"input": "Such targeted polymeric conjugates possess very selective and high binding activity toward BCL1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, targeted polymeric conjugates exert approximately 100 times higher cytostatic activity toward BCL1 cells in comparison to nontargeted conjugates in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, the conjugates have comparable and rather low cytostatic activity for 38C13 cells, which are used as a negative control, in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Dopamine D2 receptor activation leads to an up-regulation of glial cell line-derived neurotrophic factor via G beta gamma-Erk1/2-dependent induction of Zif268.", "output": {"entities": {"chemical": [{"text": "Dopamine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Glial cell line-derived neurotrophic factor (GDNF) is a potent growth factor essential to the development, survival, and function of dopaminergic neurons (Airaksinen and Saarma 2002).", "output": {"entities": {}}, "schema": []}
{"input": "The molecular mechanisms underlying GDNF expression remain elusive; thus, we set out to identify a signaling pathway that governs GDNF levels.", "output": {"entities": {}}, "schema": []}
{"input": "We found that treatment of both differentiated dopaminergic-like SH-SY5Y cells and rat midbrain slices with the dopamine D2 receptor (D2R) agonist, quinpirole, triggered an increase in the expression of GDNF that was temporally preceded by an increase in the levels of zinc-finger protein 268 (Zif268), a DNA-binding transcription factor encoded by an immediate-early gene.", "output": {"entities": {"chemical": [{"text": "dopaminergic", "start": 47, "end": 59}, {"text": "quinpirole", "start": 148, "end": 158}, {"text": "zinc", "start": 269, "end": 273}]}}, "schema": []}
{"input": "Moreover, the D2R inhibitor raclopride blocked the increase of both GDNF and Zif268 expression following potassium-evoked dopamine release in SH-SY5Y cells.", "output": {"entities": {"chemical": [{"text": "raclopride", "start": 28, "end": 38}, {"text": "potassium", "start": 105, "end": 114}, {"text": "dopamine", "start": 122, "end": 130}]}}, "schema": []}
{"input": "We used adenoviral delivery of small hairpin RNA (shRNA) targeting Zif268 to down-regulate its expression and found that Zif268 is specifically required for the D2R-mediated up-regulation of GDNF.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the D2R-mediated induction of GDNF and Zif268 expression was dependent on G beta gamma-mediated signaling and activation of extracellular signal-regulated kinase 1/2.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, using chromatin immunoprecipitation assay, we identified a direct association of Zif268 with the GDNF promoter.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that D2R activation induces a G beta gamma-and extracellular signal-regulated kinase 1/2-dependent increase in the level of Zif268, which functions to directly up-regulate the expression of GDNF.", "output": {"entities": {}}, "schema": []}
{"input": "Fast protein motions are coupled to enzyme H-transfer reactions.", "output": {"entities": {"chemical": [{"text": "H", "start": 43, "end": 44}]}}, "schema": []}
{"input": "Coupling of fast protein dynamics to enzyme chemistry is controversial and has ignited considerable debate, especially over the past 15 years in relation to enzyme-catalyzed H-transfer.", "output": {"entities": {"chemical": [{"text": "H", "start": 174, "end": 175}]}}, "schema": []}
{"input": "H-transfer can occur by quantum tunneling, and the temperature dependence of kinetic isotope effects (KIEs) has emerged as the \" gold standard \" descriptor of these reactions.", "output": {"entities": {"chemical": [{"text": "H", "start": 0, "end": 1}]}}, "schema": []}
{"input": "The anomalous temperature dependence of KIEs is often rationalized by invoking fast motions to facilitate H-transfer, yet crucially, direct evidence for coupled motions is lacking.", "output": {"entities": {"chemical": [{"text": "H", "start": 106, "end": 107}]}}, "schema": []}
{"input": "The fast motions hypothesis underpinning the temperature dependence of KIEs is based on inference.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we have perturbed vibrational motions in pentaerythritol tetranitrate reductase (PETNR) by isotopic substitution where all non-exchangeable atoms were replaced with the corresponding heavy isotope ((13) C, (15) N, and (2) H).", "output": {"entities": {"chemical": [{"text": "pentaerythritol tetranitrate", "start": 47, "end": 75}, {"text": "(13) C", "start": 204, "end": 210}, {"text": "(15) N", "start": 212, "end": 218}, {"text": "(2) H", "start": 224, "end": 229}]}}, "schema": []}
{"input": "The KIE temperature dependence is perturbed by heavy isotope labeling, demonstrating a direct link between (promoting) vibrations in the protein and the observed KIE.", "output": {"entities": {}}, "schema": []}
{"input": "Further we show that temperature-independent KIEs do not necessarily rule out a role for fast dynamics coupled to reaction chemistry.", "output": {"entities": {}}, "schema": []}
{"input": "We show causality between fast motions and enzyme chemistry and demonstrate how this impacts on experimental KIEs for enzyme reactions.", "output": {"entities": {}}, "schema": []}
{"input": "Cis-trans isomerizations of proline residues are key to bradykinin conformations.", "output": {"entities": {"chemical": [{"text": "proline", "start": 28, "end": 35}, {"text": "bradykinin", "start": 56, "end": 66}]}}, "schema": []}
{"input": "A recent ion mobility-mass spectrometry (IM-MS) study of the nonapeptide bradykinin (BK, amino acid sequence Arg (1)-Pro (2)-Pro (3)-Gly (4)-Phe (5)-Ser (6)-Pro (7)-Phe (8)-Arg (9)) found evidence for 10 populations of conformations that depend upon the solution composition [J. Am. Chem. Soc. 2011, 133, 13810].", "output": {"entities": {"chemical": [{"text": "bradykinin", "start": 73, "end": 83}, {"text": "amino acid", "start": 89, "end": 99}, {"text": "Arg", "start": 109, "end": 112}, {"text": "Pro", "start": 117, "end": 120}, {"text": "Pro", "start": 125, "end": 128}, {"text": "Gly", "start": 133, "end": 136}, {"text": "Phe", "start": 141, "end": 144}, {"text": "Ser", "start": 149, "end": 152}, {"text": "Pro", "start": 157, "end": 160}, {"text": "Phe", "start": 165, "end": 168}, {"text": "Arg", "start": 173, "end": 176}]}}, "schema": []}
{"input": "Here, the role of the three proline residues (Pro (2), Pro (3), and Pro (7)) in establishing these conformations is investigated using a series of seven analogue peptides in which combinations of alanine residues are substituted for prolines.", "output": {"entities": {"chemical": [{"text": "proline", "start": 28, "end": 35}, {"text": "Pro", "start": 46, "end": 49}, {"text": "Pro", "start": 55, "end": 58}, {"text": "Pro", "start": 68, "end": 71}, {"text": "alanine", "start": 196, "end": 203}, {"text": "prolines", "start": 233, "end": 241}]}}, "schema": []}
{"input": "IM-MS distributions of the analogue peptides, when compared to the distribution for BK, indicate the multiple structures are associated with different combinations of cis and trans forms of the three proline residues.", "output": {"entities": {"chemical": [{"text": "proline", "start": 200, "end": 207}]}}, "schema": []}
{"input": "These data are used to assign the structures to different peptide populations that are observed under various solution conditions.", "output": {"entities": {}}, "schema": []}
{"input": "The assignments also show the connectivity between structures when collisional activation is used to convert one state into another.", "output": {"entities": {}}, "schema": []}
{"input": "REMNANT UPTAKE AS A POSTOPERATIVE ONCOLOGIC QUALITY INDICATOR.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: The purpose of this study was to examine the utility of remnant uptake on postoperative radioiodine scans as an oncologic indicator after thyroidectomy for differentiated thyroid cancer (DTC).", "output": {"entities": {"chemical": [{"text": "radioiodine", "start": 100, "end": 111}]}}, "schema": []}
{"input": "METHODS: We conducted a retrospective review of patients undergoing total thyroidectomy for DTC and subsequent radioactive iodine (RAI) treatment.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 123, "end": 129}]}}, "schema": []}
{"input": "Of the eight surgeons included, three were considered high volume, performing at least 20 thyroidectomies per year.", "output": {"entities": {}}, "schema": []}
{"input": "Patients with distant metastases at diagnosis or poorly differentiated variants were excluded.", "output": {"entities": {}}, "schema": []}
{"input": "To control for the effect of varying RAI doses, the remnant uptake was analyzed as a ratio of the percentage uptake to the dose received (uptake to dose ratio, UDR).", "output": {"entities": {}}, "schema": []}
{"input": "Multivariate logistic regression was used to determine the influence of UDR on recurrence.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Of the 223 patients who met inclusion criteria, 21 patients (9. 42%) experienced a recurrence.", "output": {"entities": {}}, "schema": []}
{"input": "Those who recurred had a ten-fold higher UDR compared to those who did not recur (0. 030 vs. 0. 003, p = 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, patients with increasing postoperative thyroglobulin measurements (0. 339 vs. 0. 003, p < 0. 001) also had significantly greater UDRs compared to those with stable thyroglobulin.", "output": {"entities": {}}, "schema": []}
{"input": "The UDRs of high volume surgeons were significantly smaller than low volume surgeons (0. 003 vs. 0. 025, p = 0. 002).", "output": {"entities": {}}, "schema": []}
{"input": "When combined with other known predictors for recurrence, UDR (OR 3. 71, C. I 1. 05-13. 10, p = 0. 041) was significantly associated with recurrence.", "output": {"entities": {}}, "schema": []}
{"input": "High volume surgeons maintained a low level of permanent complications across all UDRs whereas low volume surgeons had greater permanent complications associated with higher uptake.", "output": {"entities": {}}, "schema": []}
{"input": "Mdm2 and MdmX inhibitors for the treatment of cancer: a patent review (2011-present).", "output": {"entities": {}}, "schema": []}
{"input": "INTRODUCTION: One of the hallmarks of cancer cells is the inactivation of the p53 pathway either due to mutations in the p53 gene or over-expression of negative regulators, Mdm2 and/or MdmX.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacological disruption of the Mdm2/X-p53 interaction to restore p53 activity is an attractive concept, aiming at a targeted and non-toxic cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "AREAS COVERED: The introduction covers the biological role of p53 pathway and its regulation by Mdm2 and MdmX in normal and cancer cells and the current repertoire and development status of inhibitors of the Mdm2/X-p53 interaction for the treatment of cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The main part of the article covers patents and patent applications describing small molecule inhibitors of the Mdm2/X-p53 interaction published from 2011 until 2012.", "output": {"entities": {}}, "schema": []}
{"input": "EXPERT OPINION: The area of small molecule Mdm2/X-p53 interaction inhibitor development is progressing fast.", "output": {"entities": {}}, "schema": []}
{"input": "Several Phase I clinical studies and preclinical programs are now in progress, however, the clinical proof concept has yet to be demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple available compounds inhibit Mdm2-p53 interaction with nanomolar affinities, but MdmX is still missing such potent binders.", "output": {"entities": {}}, "schema": []}
{"input": "Since research points to a complementary mode of Mdm2 and MdmX action, the future compound classes will possibly want to include dual actions versus Mdm2 and MdmX.", "output": {"entities": {}}, "schema": []}
{"input": "Enter the matrix: shape, signal and superhighway.", "output": {"entities": {}}, "schema": []}
{"input": "Mammalian skeletal muscle is notable for both its highly ordered biophysical structure and its regenerative capacity following trauma.", "output": {"entities": {}}, "schema": []}
{"input": "Critical to both of these features is the specialized muscle extracellular matrix, comprising both the multiple concentric sheaths of connective tissue surrounding structural units from single myofibers to whole muscles and the dense interstitial matrix that occupies the space between them.", "output": {"entities": {}}, "schema": []}
{"input": "Extracellular matrix-dependent interactions affect all activities of the resident muscle stem cell population (the satellite cells), from maintenance of quiescence and stem cell potential to the regulation of proliferation and differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on the role of the extracellular matrix in muscle regeneration, with a particular emphasis on regulation of satellite-cell activity.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological evaluation of 5-nitropyrimidine analogs with azabicyclic substituents as GPR119 agonists.", "output": {"entities": {"chemical": [{"text": "5-nitropyrimidine", "start": 39, "end": 56}, {"text": "azabicyclic", "start": 70, "end": 81}]}}, "schema": []}
{"input": "5-Nitropyrimidine analogs substituted with conformationally restricted azabicyclic amines and alcohols were prepared and evaluated their agonistic activity against human GPR119.", "output": {"entities": {"chemical": [{"text": "5-Nitropyrimidine", "start": 0, "end": 17}, {"text": "azabicyclic amines and alcohols", "start": 71, "end": 102}]}}, "schema": []}
{"input": "The analogs bearing endo-azabicyclic amines and alcohols (7, 8, 11, and 12) exhibited full agonistic activities while the analogs with exo-azabicyclic amines and alcohols were proved as partial agonists (9, 10, 13, and 14) regardless of their EC (50) values.", "output": {"entities": {"chemical": [{"text": "endo-azabicyclic amines and alcohols", "start": 20, "end": 56}, {"text": "exo-azabicyclic amines and alcohols", "start": 135, "end": 170}]}}, "schema": []}
{"input": "5-Nitropyrimidine analogs with (2-fluoro-4-methylsulfonyl) phenylamino group (8, 10, 12, 14) showed more potent GPR119 activation activities than the analogs without fluorine in all cases (7, 9, 11, 13).", "output": {"entities": {"chemical": [{"text": "5-Nitropyrimidine", "start": 0, "end": 17}, {"text": "(2-fluoro-4-methylsulfonyl) phenylamino", "start": 31, "end": 70}, {"text": "fluorine", "start": 166, "end": 174}]}}, "schema": []}
{"input": "2', 4'-BNA/LNA aptamers: CE-SELEX using a DNA-based library of full-length 2'-O, 4'-C-methylene-bridged/linked bicyclic ribonucleotides.", "output": {"entities": {"chemical": [{"text": "2'-O, 4'-C-methylene-bridged/linked bicyclic ribonucleotides", "start": 75, "end": 135}]}}, "schema": []}
{"input": "DNA-based aptamers that contain 2'-O, 4'-C-methylene-bridged/linked bicyclic ribonucleotides (B/L nucleotides) over the entire length were successfully obtained using a capillary electrophoresis systematic evolution of ligands by exponential enrichment (CE-SELEX) method.", "output": {"entities": {"chemical": [{"text": "2'-O, 4'-C-methylene-bridged/linked bicyclic ribonucleotides", "start": 32, "end": 92}, {"text": "nucleotides", "start": 98, "end": 109}]}}, "schema": []}
{"input": "A modified DNA library was prepared with an enzyme mix of KOD Dash and KOD mutant DNA polymerases.", "output": {"entities": {}}, "schema": []}
{"input": "Forty 2'-O, 4'-C-methylene bridged/locked nucleic acid (2', 4'-BNA/LNA) aptamers were isolated from an enriched pool and classified into six groups according to their sequence.", "output": {"entities": {"chemical": [{"text": "methylene", "start": 17, "end": 26}]}}, "schema": []}
{"input": "2', 4'-BNA/LNA aptamers of groups V and VI bound human thrombin with K (d) values in the range of several 10 nanomolar levels.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery and structure-activity relationships of small molecules that block the human immunoglobulin G-human neonatal Fc receptor (hIgG-hFcRn) protein-protein interaction.", "output": {"entities": {}}, "schema": []}
{"input": "The neonatal Fc receptor, FcRn, prolongs the half-life of IgG in the serum and represents a potential therapeutic target for the treatment of autoimmune disease.", "output": {"entities": {}}, "schema": []}
{"input": "Small molecules that block the protein-protein interactions of human IgG-human FcRn may lower pathogenic autoantibodies and provide effective treatment.", "output": {"entities": {}}, "schema": []}
{"input": "A novel class of quinoxalines has been discovered as antagonists of the IgG: FcRn protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen.", "output": {"entities": {"chemical": [{"text": "quinoxalines", "start": 17, "end": 29}]}}, "schema": []}
{"input": "3'-R/S-Hydroxyvoacamine, a potent acetylcholinesterase inhibitor from Tabernaemontana divaricata.", "output": {"entities": {"chemical": [{"text": "3'-R/S-Hydroxyvoacamine", "start": 0, "end": 23}]}}, "schema": []}
{"input": "Guided by the acetylcholinesterase inhibiting activity, the bisindole alkaloid 3'-R/S-hydroxyvoacamine was isolated from a stem extract of Tabernaemontana divaricata, a plant used in Thailand in traditional rejuvenation remedies for improving the memory.", "output": {"entities": {"chemical": [{"text": "bisindole alkaloid 3'-R/S-hydroxyvoacamine", "start": 60, "end": 102}]}}, "schema": []}
{"input": "The structure of the alkaloid was elucidated by extensive use of NMR spectroscopy and the complete assignment of the (1) H and (13) C NMR spectra is reported.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 117, "end": 122}, {"text": "(13) C", "start": 127, "end": 133}]}}, "schema": []}
{"input": "The alkaloid acted as a non-competitive inhibitor against AChE with an IC50 value of 7. 00 +/- 1. 99 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "An HPLC method was developed for the quantitative analysis of the AChE inhibitor.", "output": {"entities": {}}, "schema": []}
{"input": "It suggested that there was 12. 4% (w/w) of 3'-R/S-hydroxyvoacamine in the alkaloid enriched fraction of T. divaricata stem.", "output": {"entities": {"chemical": [{"text": "3'-R/S-hydroxyvoacamine", "start": 44, "end": 67}]}}, "schema": []}
{"input": "Of marsupials and men: \" Backdoor \" dihydrotestosterone synthesis in male sexual differentiation.", "output": {"entities": {"chemical": [{"text": "dihydrotestosterone", "start": 36, "end": 55}]}}, "schema": []}
{"input": "Following development of the fetal bipotential gonad into a testis, male genital differentiation requires testicular androgens.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 117, "end": 126}]}}, "schema": []}
{"input": "Fetal Leydig cells produce testosterone that is converted to dihydrotestosterone in genital skin, resulting in labio-scrotal fusion.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 27, "end": 39}, {"text": "dihydrotestosterone", "start": 61, "end": 80}]}}, "schema": []}
{"input": "An alternative' backdoor' pathway of dihydrotestosterone synthesis that bypasses testosterone has been described in marsupials, but its relevance to human biology has been uncertain.", "output": {"entities": {"chemical": [{"text": "dihydrotestosterone", "start": 37, "end": 56}, {"text": "testosterone", "start": 81, "end": 93}]}}, "schema": []}
{"input": "The classic and backdoor pathways share many enzymes, but a 3 alpha-reductase, AKR1C2, is unique to the backdoor pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Human AKR1C2 mutations cause disordered sexual differentiation, lending weight to the idea that both pathways are required for normal human male genital development.", "output": {"entities": {}}, "schema": []}
{"input": "These observations indicate that fetal dihydrotestosterone acts both as a hormone and as a paracrine factor, substantially revising the classic paradigm for fetal male sexual development.", "output": {"entities": {"chemical": [{"text": "dihydrotestosterone", "start": 39, "end": 58}]}}, "schema": []}
{"input": "Long-range interactions in the alpha subunit of tryptophan synthase help to coordinate ligand binding, catalysis, and substrate channeling.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 48, "end": 58}]}}, "schema": []}
{"input": "The alpha-subunit of tryptophan synthase (alpha TS) catalyzes the conversion of indole-3-glycerol phosphate to d-glyceraldehyde-3-phosphate and indole.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 21, "end": 31}, {"text": "indole-3-glycerol phosphate", "start": 80, "end": 107}, {"text": "d-glyceraldehyde-3-phosphate", "start": 111, "end": 139}, {"text": "indole", "start": 144, "end": 150}]}}, "schema": []}
{"input": "We propose that allosteric networks intrinsic to alpha TS are modulated by the binding of the beta-subunit to regulate alpha TS function.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding these long-range amino acid networks in alpha TS thus gives insight into the coordination of the two active sites within TS.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 31, "end": 41}]}}, "schema": []}
{"input": "In this study, we have used Ala residues as probes for structural and dynamic changes of alpha TS throughout its catalytic cycle, in the absence of the beta-subunit.", "output": {"entities": {"chemical": [{"text": "Ala", "start": 28, "end": 31}]}}, "schema": []}
{"input": "Projection analysis of the chemical shift changes by site-specific amino acid substitutions and ligand titrations indicates that alpha TS has three important conformational states: ligand-free, glyceraldehyde-3-phosphate-bound (like), and the active states.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 67, "end": 77}, {"text": "glyceraldehyde-3-phosphate", "start": 194, "end": 220}]}}, "schema": []}
{"input": "The amino acid networks within these conformations are different, as suggested by chemical shift correlation analysis.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 4, "end": 14}]}}, "schema": []}
{"input": "In particular, there are long-range connections, only in the active state, between Ala47, which reports on structural and dynamic changes associated with the general acid/base Glu49, and residues within the beta 2 alpha 2 loop, which contains the catalytically important Asp60 residue.", "output": {"entities": {"chemical": [{"text": "Ala47", "start": 83, "end": 88}, {"text": "Glu49", "start": 176, "end": 181}, {"text": "Asp60", "start": 271, "end": 276}]}}, "schema": []}
{"input": "These long-range interactions are likely important for coordinating chemical catalysis.", "output": {"entities": {}}, "schema": []}
{"input": "In the free state, but not in the active state, there are connections between the beta 2 alpha 2 and beta 6 alpha 6 loops that likely help to coordinate substrate binding.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in the allosteric networks are also accompanied by protein dynamic changes.", "output": {"entities": {}}, "schema": []}
{"input": "During catalytic turnover, the protein becomes more rigid on the millisecond timescale and the active-site dynamics are driven to a faster nanosecond timescale.", "output": {"entities": {}}, "schema": []}
{"input": "Fibroblast-mediated drug resistance in cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Tumor progression relies upon the dynamic interaction of cancer cells with host fibroblasts, endothelial cells, immune cells and components of the extracellular matrix, collectively known as the tumor microenvironment.", "output": {"entities": {}}, "schema": []}
{"input": "Despite this, relatively little is known about how normal host cells dictate the response of tumors to anti-cancer therapies.", "output": {"entities": {}}, "schema": []}
{"input": "Emerging data suggests that host factors play a critical role in determining risks for tumor progression and decreased therapeutic responses.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, recent findings have provided evidence that the tumor microenvironment provides a protective niche that allows minor populations of cancer cells to escape from the cytotoxic effects of radiation, chemotherapy and targeted therapies.", "output": {"entities": {}}, "schema": []}
{"input": "In this review we will outline the mechanisms by which tumor cells and host fibroblasts co-operate to drive tumor initiation and progression.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, we will focus upon the mechanisms by which tumor cells exposed to targeted therapies co-opt the host leading to therapeutic escape and resistance.", "output": {"entities": {}}, "schema": []}
{"input": "We will end by discussing the idea that long-term responses to targeted anticancer therapies will only be achieved through strategies that target both the tumor and host.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of the mouse promoter region of the acyl-CoA synthetase 4 gene: role of Sp1 and CREB.", "output": {"entities": {"chemical": [{"text": "acyl-CoA", "start": 53, "end": 61}]}}, "schema": []}
{"input": "Acyl-CoA synthetase 4 (Acsl4) is involved in several cellular functions including steroidogenesis, synaptic development and cancer metastasis.", "output": {"entities": {"chemical": [{"text": "Acyl-CoA", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Although the expression of Acsl4 seems to be regulated by tissue-and cell-specific factors as well as pituitary hormones and growth factors, the transcriptional mechanisms involved remain unknown.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrated hCG and cAMP regulation of Acsl4 mRNA in mouse steroidogenic MA-10 Leydig cells.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 24, "end": 28}]}}, "schema": []}
{"input": "We characterized the transcription initiation site and promoter of the Acsl4 mouse gene and identified three alternative splice variants present in MA-10 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Sequence analysis of a 1. 5-kb fragment of the Acsl4 promoter revealed the absence of a TATA box and the presence of many putative binding sites for transcription factors including Sp1 and CREB.", "output": {"entities": {}}, "schema": []}
{"input": "Functional characterization revealed that the specificity protein/Kr u ppel-like factor Sp1 binding site in the proximal promoter is involved in basal activity and that the cAMP response element-binding site is involved in cAMP stimulation of Acsl4 transcription.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 173, "end": 177}, {"text": "cAMP", "start": 223, "end": 227}]}}, "schema": []}
{"input": "Synthesis and biological evaluation of thieno [2', 3': 4, 5] pyrimido [1, 2-b] [1, 2, 4] triazines and thieno [2, 3-d] [1, 2, 4] triazolo [1, 5-a] pyrimidines as anti-inflammatory and analgesic agents.", "output": {"entities": {"chemical": [{"text": "thieno [2', 3': 4, 5] pyrimido [1, 2-b] [1, 2, 4] triazines", "start": 39, "end": 98}, {"text": "thieno [2, 3-d] [1, 2, 4] triazolo [1, 5-a] pyrimidines", "start": 103, "end": 158}]}}, "schema": []}
{"input": "A new series of thieno [2', 3': 4, 5] pyrimido [1, 2-b] [1, 2, 4] triazines and thieno [2, 3-d] [1, 2, 4] triazolo [1, 5-a] pyrimidines was synthesized.", "output": {"entities": {"chemical": [{"text": "thieno [2', 3': 4, 5] pyrimido [1, 2-b] [1, 2, 4] triazines", "start": 16, "end": 75}, {"text": "thieno [2, 3-d] [1, 2, 4] triazolo [1, 5-a] pyrimidines", "start": 80, "end": 135}]}}, "schema": []}
{"input": "The newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activity using diclofenac Na as a reference standard.", "output": {"entities": {"chemical": [{"text": "diclofenac Na", "start": 104, "end": 117}]}}, "schema": []}
{"input": "Additionally, the ulcerogenic effects and acute toxicity (ALD50) values of the active compounds were also determined.", "output": {"entities": {}}, "schema": []}
{"input": "In general, the thieno [2, 3-d] [1, 2, 4] triazolo [1, 5-a] pyrimidine derivatives exhibited better biological activities than the thieno [2', 3': 4, 5] pyrimido [1, 2-b] [1, 2, 4] triazines.", "output": {"entities": {"chemical": [{"text": "thieno [2, 3-d] [1, 2, 4] triazolo [1, 5-a] pyrimidine", "start": 16, "end": 70}, {"text": "thieno [2', 3': 4, 5] pyrimido [1, 2-b] [1, 2, 4] triazines", "start": 131, "end": 190}]}}, "schema": []}
{"input": "Collectively, the thienotriazolopyrimidine derivatives 9, 13 and 14a were proved to display distinctive anti-inflammatory activity at the acute and subacute models as well as good analgesic profile with a delayed onset of action.", "output": {"entities": {"chemical": [{"text": "thienotriazolopyrimidine", "start": 18, "end": 42}]}}, "schema": []}
{"input": "Moreover, they revealed good gastrointestinal safety profile and are well tolerated by experimental animals with high safety margin (ALD50 > 0. 3 g/kg).", "output": {"entities": {}}, "schema": []}
{"input": "Molecular insight into the inhibition mechanism of cyrtominetin to alpha-hemolysin by molecular dynamics simulation.", "output": {"entities": {"chemical": [{"text": "cyrtominetin", "start": 51, "end": 63}]}}, "schema": []}
{"input": "The protein alpha-hemolysin (alpha-HL) is a self-assembling exotoxin that binds to the membrane of a susceptible host cell.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, experimental studies show that cyrtominetin (CTM) can inhibit the hemolytic activity of alpha-HL.", "output": {"entities": {"chemical": [{"text": "cyrtominetin", "start": 46, "end": 58}, {"text": "CTM", "start": 60, "end": 63}]}}, "schema": []}
{"input": "To understand how CTM can affect hemolytic activity, molecular dynamics simulations were carried out for alpha-HL-CTM complex and these results were compared with the crystal structure of monomeric alpha-HL.", "output": {"entities": {"chemical": [{"text": "CTM", "start": 18, "end": 21}, {"text": "CTM", "start": 114, "end": 117}]}}, "schema": []}
{"input": "With this approach, the analysis revealed that the inhibition of CTM involves CTM directly binding to alpha-HL.", "output": {"entities": {"chemical": [{"text": "CTM", "start": 65, "end": 68}, {"text": "CTM", "start": 78, "end": 81}]}}, "schema": []}
{"input": "Due to the binding of CTM, the conformation of the critical \" Loop \" region was restrained.", "output": {"entities": {"chemical": [{"text": "CTM", "start": 22, "end": 25}]}}, "schema": []}
{"input": "This mechanism was confirmed by the experimental data.", "output": {"entities": {}}, "schema": []}
{"input": "These findings indicate that CTM hinders the lysis activity of alpha-HL through a novel mechanism.", "output": {"entities": {"chemical": [{"text": "CTM", "start": 29, "end": 32}]}}, "schema": []}
{"input": "Influence of environmentally relevant concentrations of vinclozolin on quality, DNA integrity, and antioxidant responses of sterlet Acipenser ruthenus spermatozoa.", "output": {"entities": {"chemical": [{"text": "vinclozolin", "start": 56, "end": 67}]}}, "schema": []}
{"input": "The effects of vinclozolin (VIN), an anti-androgenic fungicide, on quality, oxidative stress, DNA integrity, and ATP level of sterlet (Acipenser ruthenus) spermatozoa were investigated in vitro.", "output": {"entities": {"chemical": [{"text": "vinclozolin", "start": 15, "end": 26}, {"text": "VIN", "start": 28, "end": 31}, {"text": "ATP", "start": 113, "end": 116}]}}, "schema": []}
{"input": "Fish spermatozoa were incubated with different concentrations of vinclozolin (0. 5, 2, 10, 15, 20 and 50 mu g/l) for 2h.", "output": {"entities": {"chemical": [{"text": "vinclozolin", "start": 65, "end": 76}]}}, "schema": []}
{"input": "A dose-dependent reduction in spermatozoa motility and velocity was observed at concentrations of 2-50 mu g/l.", "output": {"entities": {}}, "schema": []}
{"input": "A dramatic increase in DNA fragmentation was recorded at concentrations 10 mu g/l and above.", "output": {"entities": {}}, "schema": []}
{"input": "After 2h exposure at higher test concentrations (10-50 mu g/l), oxidative stress was apparent, as reflected by significantly higher levels of protein and lipid oxidation and significantly greater superoxide dismutase activity.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 196, "end": 206}]}}, "schema": []}
{"input": "Intracellular ATP content of spermatozoa decreased with increasing concentrations of VIN.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 14, "end": 17}, {"text": "VIN", "start": 85, "end": 88}]}}, "schema": []}
{"input": "The results demonstrated that VIN can induce reactive oxygen species stress in fish spermatozoa, which could impair the sperm quality, DNA integrity, ATP content, and the antioxidant defense system.", "output": {"entities": {"chemical": [{"text": "VIN", "start": 30, "end": 33}, {"text": "oxygen", "start": 54, "end": 60}, {"text": "ATP", "start": 150, "end": 153}]}}, "schema": []}
{"input": "Elimination and utilization of oxidized guanine nucleotides in the synthesis of RNA and its precursors.", "output": {"entities": {"chemical": [{"text": "guanine nucleotides", "start": 40, "end": 59}]}}, "schema": []}
{"input": "Reactive oxygen species are produced as side products of oxygen utilization and can lead to the oxidation of nucleic acids and their precursor nucleotides.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 9, "end": 15}, {"text": "oxygen", "start": 57, "end": 63}, {"text": "nucleotides", "start": 143, "end": 154}]}}, "schema": []}
{"input": "Among the various oxidized bases, 8-oxo-7, 8-dihydroguanine seems to be the most critical during the transfer of genetic information because it can pair with both cytosine and adenine.", "output": {"entities": {"chemical": [{"text": "8-oxo-7, 8-dihydroguanine", "start": 34, "end": 59}, {"text": "cytosine", "start": 163, "end": 171}, {"text": "adenine", "start": 176, "end": 183}]}}, "schema": []}
{"input": "During the de novo synthesis of guanine nucleotides, GMP is formed first, and it is converted to GDP by guanylate kinase.", "output": {"entities": {"chemical": [{"text": "guanine nucleotides", "start": 32, "end": 51}, {"text": "GMP", "start": 53, "end": 56}, {"text": "GDP", "start": 97, "end": 100}, {"text": "guanylate", "start": 104, "end": 113}]}}, "schema": []}
{"input": "This enzyme hardly acts on an oxidized form of GMP (8-oxo-GMP) formed by the oxidation of GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein.", "output": {"entities": {"chemical": [{"text": "GMP", "start": 47, "end": 50}, {"text": "8-oxo-GMP", "start": 52, "end": 61}, {"text": "GMP", "start": 90, "end": 93}, {"text": "8-oxo-GDP", "start": 116, "end": 125}, {"text": "8-oxo-GTP", "start": 130, "end": 139}]}}, "schema": []}
{"input": "Although the formation of 8-oxo-GDP from 8-oxo-GMP is thus prevented, 8-oxo-GDP itself may be produced by the oxidation of GDP by reactive oxygen species.", "output": {"entities": {"chemical": [{"text": "8-oxo-GDP", "start": 26, "end": 35}, {"text": "8-oxo-GMP", "start": 41, "end": 50}, {"text": "8-oxo-GDP", "start": 70, "end": 79}, {"text": "GDP", "start": 123, "end": 126}, {"text": "oxygen", "start": 139, "end": 145}]}}, "schema": []}
{"input": "The 8-oxo-GDP thus formed can be converted to 8-oxo-GTP because nucleoside-diphosphate kinase and adenylate kinase, both of which catalyze the conversion of GDP to GTP, do not discriminate 8-oxo-GDP from normal GDP.", "output": {"entities": {"chemical": [{"text": "8-oxo-GDP", "start": 4, "end": 13}, {"text": "8-oxo-GTP", "start": 46, "end": 55}, {"text": "nucleoside-diphosphate", "start": 64, "end": 86}, {"text": "adenylate", "start": 98, "end": 107}, {"text": "GDP", "start": 157, "end": 160}, {"text": "GTP", "start": 164, "end": 167}, {"text": "8-oxo-GDP", "start": 189, "end": 198}, {"text": "GDP", "start": 211, "end": 214}]}}, "schema": []}
{"input": "The 8-oxo-GTP produced in this way and by the oxidation of GTP can be used for RNA synthesis.", "output": {"entities": {"chemical": [{"text": "8-oxo-GTP", "start": 4, "end": 13}, {"text": "GTP", "start": 59, "end": 62}]}}, "schema": []}
{"input": "This misincorporation is prevented by MutT protein, which has the potential to cleave 8-oxo-GTP as well as 8-oxo-GDP to 8-oxo-GMP.", "output": {"entities": {"chemical": [{"text": "8-oxo-GTP", "start": 86, "end": 95}, {"text": "8-oxo-GDP", "start": 107, "end": 116}, {"text": "8-oxo-GMP", "start": 120, "end": 129}]}}, "schema": []}
{"input": "When (14) C-labeled 8-oxo-GTP was applied to CaCl2-permeabilized cells of a mutT (-) mutant strain, it could be incorporated into RNA at 4% of the rate for GTP.", "output": {"entities": {"chemical": [{"text": "(14) C-labeled 8-oxo-GTP", "start": 5, "end": 29}, {"text": "CaCl2", "start": 45, "end": 50}, {"text": "GTP", "start": 156, "end": 159}]}}, "schema": []}
{"input": "Escherichia coli cells appear to possess mechanisms to prevent misincorporation of 8-oxo-7, 8-dihydroguanine into RNA.", "output": {"entities": {"chemical": [{"text": "8-oxo-7, 8-dihydroguanine", "start": 83, "end": 108}]}}, "schema": []}
{"input": "Bradykinin modulates spontaneous nerve growth factor production and stretch-induced ATP release in human urothelium.", "output": {"entities": {"chemical": [{"text": "Bradykinin", "start": 0, "end": 10}, {"text": "ATP", "start": 84, "end": 87}]}}, "schema": []}
{"input": "The urothelium plays a crucial role in integrating urinary bladder sensory outputs, responding to mechanical stress and chemical stimulation by producing several diffusible mediators, including ATP and, possibly, neurotrophin nerve growth factor (NGF).", "output": {"entities": {"chemical": [{"text": "ATP", "start": 194, "end": 197}]}}, "schema": []}
{"input": "Such urothelial mediators activate underlying afferents and thus may contribute to normal bladder sensation and possibly to the development of bladder overactivity.", "output": {"entities": {}}, "schema": []}
{"input": "The muscle-contracting and pain-inducing peptide bradykinin is produced in various inflammatory and non-inflammatory pathologies associated with bladder overactivity, but the effect of bradykinin on human urothelial function has not yet been characterized.", "output": {"entities": {"chemical": [{"text": "bradykinin", "start": 49, "end": 59}, {"text": "bradykinin", "start": 185, "end": 195}]}}, "schema": []}
{"input": "The human urothelial cell line UROtsa expresses mRNA for both B1 and B2 subtypes of bradykinin receptors, as determined by real-time PCR.", "output": {"entities": {"chemical": [{"text": "bradykinin", "start": 84, "end": 94}]}}, "schema": []}
{"input": "Bradykinin concentration-dependently (pEC50 = 8. 3, Emax 4434 +/- 277nM) increased urothelial intracellular calcium levels and induced phosphorylation of the mitogen-activated protein kinase (MAPK) ERK1/2.", "output": {"entities": {"chemical": [{"text": "Bradykinin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Activation of both bradykinin-induced signaling pathways was completely abolished by the B2 antagonist icatibant (1 mu M), but not the B1 antagonist R715 (1 mu M).", "output": {"entities": {"chemical": [{"text": "bradykinin", "start": 19, "end": 29}]}}, "schema": []}
{"input": "Bradykinin-induced (100nM) B2 receptor activation markedly increased (192 +/- 13% of control levels) stretch-induced ATP release from UROtsa in hypotonic medium, the effect being dependent on intracellular calcium elevations.", "output": {"entities": {"chemical": [{"text": "Bradykinin", "start": 0, "end": 10}, {"text": "ATP", "start": 117, "end": 120}]}}, "schema": []}
{"input": "UROtsa cells also expressed mRNA and protein for NGF and spontaneously released NGF to the medium in the course of hours (11. 5 +/- 1. 4pgNGF/mgprotein/h).", "output": {"entities": {}}, "schema": []}
{"input": "Bradykinin increased NGF mRNA expression and accelerated urothelial NGF release to 127 +/- 5% in a protein kinase C-and ERK1/2-dependent manner.", "output": {"entities": {"chemical": [{"text": "Bradykinin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Finally, bradykinin up-regulated mRNA for transient-receptor potential vanilloid (TRPV1) sensory ion channel in UROtsa.", "output": {"entities": {"chemical": [{"text": "bradykinin", "start": 9, "end": 19}]}}, "schema": []}
{"input": "In conclusion, we show that bradykinin represents a versatile modulator of human urothelial phenotype, accelerating stretch-induced ATP release, spontaneous release of NGF, as well as expression of sensory ion channel TRPV1.", "output": {"entities": {"chemical": [{"text": "bradykinin", "start": 28, "end": 38}, {"text": "ATP", "start": 132, "end": 135}]}}, "schema": []}
{"input": "Bradykinin-induced changes in urothelial sensory function might contribute to the development of bladder dysfunction.", "output": {"entities": {"chemical": [{"text": "Bradykinin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "3, 3'-Diindolymethane ameliorates adriamycin-induced cardiac fibrosis via activation of a BRCA1-dependent anti-oxidant pathway.", "output": {"entities": {"chemical": [{"text": "3, 3'-Diindolymethane", "start": 0, "end": 21}, {"text": "adriamycin", "start": 34, "end": 44}]}}, "schema": []}
{"input": "The cardiotoxicity of adriamycin greatly limits its application in the treatment of cancer.", "output": {"entities": {"chemical": [{"text": "adriamycin", "start": 22, "end": 32}]}}, "schema": []}
{"input": "Heart failure that is caused by adriamycin-treatment induced cardiac fibrosis is a major cause of death in patients who are treated with this medication.", "output": {"entities": {"chemical": [{"text": "adriamycin", "start": 32, "end": 42}]}}, "schema": []}
{"input": "The severe oxidative stress that is induced by adriamycin is considered to be one of the primary mechanisms by which fibrogenesis of cardiac tissue occurs.", "output": {"entities": {"chemical": [{"text": "adriamycin", "start": 47, "end": 57}]}}, "schema": []}
{"input": "In the present study, we demonstrate that 3, 3'-diindolymethane (DIM) exhibits a significant anti-fibrosis effect on cardiac tissue in an animal model of adriamycin-induced cardiac fibrosis (AICF).", "output": {"entities": {"chemical": [{"text": "3, 3'-diindolymethane", "start": 42, "end": 63}, {"text": "DIM", "start": 65, "end": 68}, {"text": "adriamycin", "start": 154, "end": 164}]}}, "schema": []}
{"input": "Further studies demonstrated that DIM is able to dramatically up-regulate the expression of breast cancer type 1 susceptibility protein (BRCA1) in cardiac tissue and fibroblast, which subsequently activate the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2).", "output": {"entities": {"chemical": [{"text": "DIM", "start": 34, "end": 37}]}}, "schema": []}
{"input": "The upregulation of this transcription factor resulted in the expression of several anti-oxidant genes in the cell.", "output": {"entities": {}}, "schema": []}
{"input": "Because DIM is a safe food additive that has been used for decades, our findings suggest that there is a great potential for this chemical to be developed into a clinical medication for the treatment of adriamycin-induced heart failure during cancer therapy.", "output": {"entities": {"chemical": [{"text": "DIM", "start": 8, "end": 11}, {"text": "adriamycin", "start": 203, "end": 213}]}}, "schema": []}
{"input": "PI3 k/akt inhibition induces apoptosis through p38 activation in neurons.", "output": {"entities": {}}, "schema": []}
{"input": "Accumulating evidence suggests that the PI3K/AKT pathway is a pro-survival signalling system in neurons.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the inhibition of this pathway may be implicated in the degeneration of neurons in Parkinson' s disease (PD), Alzheimer' s disease (AD), and other neurological disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Here we study the participation of the mitogen-activated protein kinase (MAPK) pathway on apoptosis induced by PI3K/AKT inhibition in cultured cerebellar granule cells (CGCs).", "output": {"entities": {}}, "schema": []}
{"input": "LY294002, a specific PI3K/AKT inhibitor, selectively activated the p38 MAPK kinase pathway and enhanced c-Jun phosphorylation, but did not activate JNK.", "output": {"entities": {"chemical": [{"text": "LY294002", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The pharmacological inhibitors SB203580 (p38 inhibitor) and SP600125 (a JNK inhibitor) protected primary cultures of rat CGCs from LY294002-induced apoptosis.", "output": {"entities": {"chemical": [{"text": "SB203580", "start": 31, "end": 39}, {"text": "SP600125", "start": 60, "end": 68}, {"text": "LY294002", "start": 131, "end": 139}]}}, "schema": []}
{"input": "Furthermore, both compounds decreased the phosphorylation of c-Jun and lowered mRNA levels of the pro-apoptotic gene dp5, a direct target of c-Jun.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our data demonstrate that PI3K/AKT inhibition induces neuronal apoptosis, a process that is mediated by the activation of p38 MAPK/c-Jun/dp5.", "output": {"entities": {}}, "schema": []}
{"input": "Gender and strain contributions to the variability of buprenorphine-related respiratory toxicity in mice.", "output": {"entities": {"chemical": [{"text": "buprenorphine", "start": 54, "end": 67}]}}, "schema": []}
{"input": "While most deaths from asphyxia related to buprenorphine (BUP) overdose have been reported in males, higher plasma concentrations of BUP and its toxic metabolite norbuprenorphine (NBUP) have been observed in females.", "output": {"entities": {"chemical": [{"text": "buprenorphine", "start": 43, "end": 56}, {"text": "BUP", "start": 58, "end": 61}, {"text": "BUP", "start": 133, "end": 136}, {"text": "norbuprenorphine", "start": 162, "end": 178}, {"text": "NBUP", "start": 180, "end": 184}]}}, "schema": []}
{"input": "We previously demonstrated that P-glycoprotein (P-gp) modulation at the blood-brain barrier (BBB) contributes highly to BUP-related respiratory toxicity, by limiting NBUP entrance into the brain.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 120, "end": 123}, {"text": "NBUP", "start": 166, "end": 170}]}}, "schema": []}
{"input": "In this work, we sought to investigate the role of P-gp-mediated transport at the BBB in gender and strain-related variability of BUP and NBUP-induced respiratory effects in mice.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 130, "end": 133}, {"text": "NBUP", "start": 138, "end": 142}]}}, "schema": []}
{"input": "Ventilation was studied using plethysmography, P-gp expression using western blot, and transport at the BBB using in situ cerebral perfusion.", "output": {"entities": {}}, "schema": []}
{"input": "In male Fvb and Swiss mice, BUP was responsible for ceiling respiratory effects.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 28, "end": 31}]}}, "schema": []}
{"input": "NBUP-related reduction in minute volume was dose-dependent but more marked in Fvb (p < 0. 01 at 1mg/kg NBUP and p < 0. 001 at 3 and 9mg/kg NBUP) than in Swiss mice (p < 0. 001 at 9mg/kg NBUP).", "output": {"entities": {"chemical": [{"text": "NBUP", "start": 0, "end": 4}, {"text": "NBUP", "start": 103, "end": 107}, {"text": "NBUP", "start": 139, "end": 143}, {"text": "NBUP", "start": 186, "end": 190}]}}, "schema": []}
{"input": "Female Fvb mice were more susceptible to BUP than males with significantly increased inspiratory time (p < 0. 05) and to NBUP with significantly increased expiratory time (p < 0. 01).", "output": {"entities": {"chemical": [{"text": "BUP", "start": 41, "end": 44}, {"text": "NBUP", "start": 121, "end": 125}]}}, "schema": []}
{"input": "Following BUP administration, plasma BUP concentrations were significantly higher (p < 0. 01) and plasma NBUP concentrations significantly lower (p < 0. 001) in Fvb mice compared to Swiss mice.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 10, "end": 13}, {"text": "BUP", "start": 37, "end": 40}, {"text": "NBUP", "start": 105, "end": 109}]}}, "schema": []}
{"input": "Plasma BUP concentrations were significantly higher (p < 0. 05) and plasma NBUP concentrations significantly lower (p < 0. 01) in male compared to female Fvb mice.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 7, "end": 10}, {"text": "NBUP", "start": 75, "end": 79}]}}, "schema": []}
{"input": "In contrast, following NBUP administration, comparable plasma NBUP concentrations were observed in both genders and strains.", "output": {"entities": {"chemical": [{"text": "NBUP", "start": 23, "end": 27}, {"text": "NBUP", "start": 62, "end": 66}]}}, "schema": []}
{"input": "No differences in P-gp expression or BUP and NBUP transport across the BBB were observed between male and female Fvb mice as well as between Swiss and Fvb mice.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 37, "end": 40}, {"text": "NBUP", "start": 45, "end": 49}]}}, "schema": []}
{"input": "Our results suggest that P-gp-mediated transport across the BBB does not play a key-role in gender and strain-related variability in BUP and NBUP-induced respiratory toxicity in mice.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 133, "end": 136}, {"text": "NBUP", "start": 141, "end": 145}]}}, "schema": []}
{"input": "Both gender-and strain-related differences in respiratory effects of BUP could be attributed to BUP itself rather than to its metabolite, NBUP.", "output": {"entities": {"chemical": [{"text": "BUP", "start": 69, "end": 72}, {"text": "BUP", "start": 96, "end": 99}, {"text": "NBUP", "start": 138, "end": 142}]}}, "schema": []}
{"input": "Absence of CC chemokine receptors 2a and 2b from human adipose lineage cells.", "output": {"entities": {}}, "schema": []}
{"input": "Previous results have suggested the existence of receptors for monocyte chemoattractant protein-1 (MCP-1), CC chemokine receptors 2 (CCR2), in human adipocytes and their involvement in mediating effects of MCP-1 on adipocyte functions.", "output": {"entities": {}}, "schema": []}
{"input": "However, the presence of CCR2 present on non-adipose-lineage cells of adipose tissue has not been excluded.", "output": {"entities": {}}, "schema": []}
{"input": "We have used human Simpson-Golabi-Behmel-Syndrome (SGBS) preadipocytes and in-vitro-differentiated mature adipocytes to investigate the expression of CCR2 in human (pre) adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "We found that the cells are devoid of CCR2 receptor protein and mRNA expression and fail to respond to treatment with all known CCR2 chemokine agonists.", "output": {"entities": {}}, "schema": []}
{"input": "CCR2 is also absent from (pre) adipocytes prepared in vitro from human multipotent adipose-derived stem cells, bone-marrow-derived mesenchymal stem cells, or from primary (pre) adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Conditions mimicking proinflammatory changes in adipose tissue did not induce CCR2 receptor expression.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that CCR2 is absent from human adipose lineage cells.", "output": {"entities": {}}, "schema": []}
{"input": "Functional effects previously described for MCP-1 in human adipose tissue may be mediated indirectly through paracrine effects on non-adipose-lineage cells or by a (pre) adipocyte receptor for MCP-1 distinct from CCR2.", "output": {"entities": {}}, "schema": []}
{"input": "FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development.", "output": {"entities": {}}, "schema": []}
{"input": "Developmental signalling pathways are implicated in the formation and maintenance of the adrenal gland, but their roles are currently not well defined.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years it has emerged that Sonic hedgehog (Shh) and Wnt/beta catenin signalling are crucial for the growth and development of the adrenal cortex.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that Fibroblast growth factor receptor (Fgfr) 2 isoforms IIIb and IIIc are expressed mainly in the adrenal subcapsule during embryogenesis and that specific deletion of the Fgfr2 IIIb isoform impairs adrenal development, causing reduced adrenal growth and impaired expression of SF1 and steroidogenic enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "The hypoplastic adrenals also have thicker, disorganised capsules which retain Gli1 expression but no longer express Dlk1.", "output": {"entities": {}}, "schema": []}
{"input": "Fgfr2 ligands were detected in both the capsule and the cortex, suggesting the importance of signalling between the capsule and the cortex in adrenal development.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in skeletal muscle proteolytic gene expression after prophylactic supplementation of EGCG and NAC and eccentric damage.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 93, "end": 97}, {"text": "NAC", "start": 102, "end": 105}]}}, "schema": []}
{"input": "PURPOSE: The impact of prophylactic supplementation of N-acetyl-cysteine (NAC) and epigallocatechin gallate (EGCG) on intramuscular expression of proteolytic genes after unaccustomed eccentric muscle contractions was investigated.", "output": {"entities": {"chemical": [{"text": "N-acetyl-cysteine", "start": 55, "end": 72}, {"text": "NAC", "start": 74, "end": 77}, {"text": "epigallocatechin gallate", "start": 83, "end": 107}, {"text": "EGCG", "start": 109, "end": 113}]}}, "schema": []}
{"input": "METHODS: Thirty apparently healthy males (mean +/- SD: 20. 0 +/- 1. 8years, 175 +/- 7. 1cm, 76. 1 +/- 16. 9kg) ingested daily either 1800mg of NAC or 1800mg of EGCG (98% total polyphenols, 80% total catechins, and 50% EGCG), or 1000mg of a glucomannan placebo (PLA) in a double blind, prophylactic fashion for 14days.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 143, "end": 146}, {"text": "EGCG", "start": 160, "end": 164}, {"text": "polyphenols", "start": 176, "end": 187}, {"text": "catechins", "start": 199, "end": 208}, {"text": "EGCG", "start": 218, "end": 222}]}}, "schema": []}
{"input": "Subjects then completed an unaccustomed eccentric exercise bout (100 repetitions at 30 degrees s (-1)) using the dominant knee extensors.", "output": {"entities": {}}, "schema": []}
{"input": "Skeletal muscle biopsies were collected from the vastus lateralis at baseline and both 6 and 24h after exercise.", "output": {"entities": {}}, "schema": []}
{"input": "The expression of proteolytic genes [i. e., muscle ring-finger 1 (MuRF1), atrogin-1, alpha-type 20S subunit C2 (HC2), alpha-type 20S subunit C3 (HC3), ubiquitin protein ligase 3B (UBE3B), mu-calpain, and m-calpain] was quantified using real-time RT-PCR.", "output": {"entities": {}}, "schema": []}
{"input": "Separate 3 x 3 (group x time) repeated measures ANOVAs were used to analyze changes in gene expression over time between groups.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: No significant group x time interactions were detected between groups for the expression of any of the atrogenes or calpains (p > 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Significant main effects for time identified increases in MuRF1 (6h: 5. 3 +/- 10. 8 fold; p = 0. 046), UBE3B (6h: 5. 3 +/- 7. 7 fold; p = 0. 006; 24h: 3. 3 +/- 4. 5 fold; p = 0. 005), and m-calpain expression (6h: 2. 7 +/- 4. 4 fold; p = 0. 045) in all participants following exercise.", "output": {"entities": {}}, "schema": []}
{"input": "Increases approached significance in HC2 (6h: 1. 9 +/- 2. 4 fold; p = 0. 079; 24h: 1. 6 +/- 1. 9 fold; p = 0. 084) and m-calpain expression (24h: 1. 8 +/- 2. 3 fold; p = 0. 084) following exercise.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: Prophylactic supplementation of NAC and EGCG did not impact acute changes in skeletal muscle proteolytic gene expression following eccentric exercise.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 45, "end": 48}, {"text": "EGCG", "start": 53, "end": 57}]}}, "schema": []}
{"input": "Eccentric muscle contractions elevated MuRF1 and UBE3B, while m-calpain and HC2 mRNA tended to increase.", "output": {"entities": {}}, "schema": []}
{"input": "Lead at 2. 5 and 5. 0 mu M induced aberrant MH-II surface expression through increased MII exocytosis and increased autophagosome formation in Raw 267. 4 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Aberrant major histocompatibility complex class II (MHC-II) surface expression on antigen presenting cells (APCs) is associated with dysregulated immune homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Lead (Pb) is known to increase MHC-II surface expression on murine peritoneal macrophages ex vivo at concentrations exceeding 25 mu M.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 6, "end": 8}]}}, "schema": []}
{"input": "Little data exist examining this effect at physiologically relevant concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "To address this deficit, we examined the effects of Pb on MHC-II surface expression, secondary T-cell activation markers (CD80, CD86, CD40), cell viability, cellular metabolic activity, and beta-hexosaminidase activity in RAW 267. 4 macrophage cell lines, with changes in cell ultrastructure evaluated by electron and confocal microscopy.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 52, "end": 54}]}}, "schema": []}
{"input": "Pb induced an increase in MHC-II, CD86, and lysosome-associated LAMP-1 and LAMP-2 surface mean expression during one doubling cycle (17 h), which was mirrored by increased beta-hexosaminidase activity.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 0, "end": 2}]}}, "schema": []}
{"input": "Although cell viability was unaffected, cellular metabolism was inhibited.", "output": {"entities": {}}, "schema": []}
{"input": "Electron microscopy revealed evidence of lipid vacuolization, macroautophagy and myelin figure formation in cells cultured with either Pb or LPS.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 135, "end": 137}]}}, "schema": []}
{"input": "Confocal microscopy with antibodies against LC3B showed a punctate pattern consistent with the presence of mature autophagosomes.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these data suggest that 2. 5-5. 0 mu M Pb increased MHC-II surface expression by inhibiting metabolic activity, inducing autophagy, and increasing MHC-II trafficking in a macrophage cell line.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 53, "end": 55}]}}, "schema": []}
{"input": "Prenatal developmental toxicity studies on diundecyl and ditridecyl phthalates in Sprague-Dawley rats.", "output": {"entities": {"chemical": [{"text": "diundecyl and ditridecyl phthalates", "start": 43, "end": 78}]}}, "schema": []}
{"input": "This study evaluates the developmental toxicity of two high molecular weight dialkyl phthalate esters, diundecyl phthalate (DUDP) and ditridecyl phthalate (DTDP).", "output": {"entities": {"chemical": [{"text": "dialkyl phthalate esters", "start": 77, "end": 101}, {"text": "diundecyl phthalate", "start": 103, "end": 122}, {"text": "DUDP", "start": 124, "end": 128}, {"text": "ditridecyl phthalate", "start": 134, "end": 154}, {"text": "DTDP", "start": 156, "end": 160}]}}, "schema": []}
{"input": "Sprague-Dawley rats were administered 0, 0. 25, 0. 50, or 1g/kg/day of DUDP or DTDP, by gavage, on gestation days 6-20.", "output": {"entities": {"chemical": [{"text": "DUDP", "start": 71, "end": 75}, {"text": "DTDP", "start": 79, "end": 83}]}}, "schema": []}
{"input": "DUDP and DTDP had no adverse effects on maternal body weight and food consumption.", "output": {"entities": {"chemical": [{"text": "DUDP", "start": 0, "end": 4}, {"text": "DTDP", "start": 9, "end": 13}]}}, "schema": []}
{"input": "The number of live fetuses, percent of post-implantation loss and of resorptions, fetal sex, and fetal body weights were not affected by either phthalate.", "output": {"entities": {"chemical": [{"text": "phthalate", "start": 144, "end": 153}]}}, "schema": []}
{"input": "There was no evidence of teratogenicity, whatever treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Small decreases in the anogenital distance of male fetuses were noted at 0. 5 and 1g DUDP/kg/day.", "output": {"entities": {"chemical": [{"text": "DUDP", "start": 85, "end": 89}]}}, "schema": []}
{"input": "The incidence of fetuses with supernumerary lumbar ribs was significantly higher than control at 0. 5 and 1g DUDP/kg/day.", "output": {"entities": {"chemical": [{"text": "DUDP", "start": 109, "end": 113}]}}, "schema": []}
{"input": "Thus, DTDP was not developmentally toxic up to 1g/kg/day and there were signs of DUDP-induced fetal effects at 0. 5 and 1g/kg/day.", "output": {"entities": {"chemical": [{"text": "DTDP", "start": 6, "end": 10}, {"text": "DUDP", "start": 81, "end": 85}]}}, "schema": []}
{"input": "Optimal dosing of warfarin and other coumarin anticoagulants: the role of genetic polymorphisms.", "output": {"entities": {"chemical": [{"text": "warfarin", "start": 18, "end": 26}, {"text": "coumarin", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Coumarin anticoagulants, which include warfarin, acenocoumarol and phenprocoumon, are among the most widely prescribed drugs worldwide.", "output": {"entities": {"chemical": [{"text": "Coumarin", "start": 0, "end": 8}, {"text": "warfarin", "start": 39, "end": 47}, {"text": "acenocoumarol", "start": 49, "end": 62}, {"text": "phenprocoumon", "start": 67, "end": 80}]}}, "schema": []}
{"input": "There is now a large body of published data showing that genotype for certain common polymorphisms in the genes encoding the target vitamin K epoxide reductase (G-1639A/C1173T) and the main metabolizing enzyme CYP2C9 (CYP2C9 * 2 and * 3 alleles) are important determinants of the individual coumarin anticoagulant dose requirement.", "output": {"entities": {"chemical": [{"text": "vitamin K epoxide", "start": 132, "end": 149}, {"text": "coumarin", "start": 291, "end": 299}]}}, "schema": []}
{"input": "Additional less common polymorphisms in these genes together with polymorphisms in other genes relevant to blood coagulation such as the cytochrome P450 CYP4F2, gamma-glutamyl carboxylase, calumenin and cytochrome P450 oxidoreductase may also be significant predictors of dose, especially in ethnic groups such as Africans where there have been fewer genetic studies compared with European populations.", "output": {"entities": {"chemical": [{"text": "gamma-glutamyl", "start": 161, "end": 175}]}}, "schema": []}
{"input": "Using relevant genotypes to calculate starting dose may improve safety during the initiation period.", "output": {"entities": {}}, "schema": []}
{"input": "Various algorithms for dose calculation, which also take patient age and other characteristics into consideration, have been developed for all three widely used coumarin anticoagulants and are now being tested in ongoing large randomised clinical trials.", "output": {"entities": {"chemical": [{"text": "coumarin", "start": 161, "end": 169}]}}, "schema": []}
{"input": "One recently completed study has provided encouraging results suggesting that calculation of warfarin dose on the basis of individual patient genotype leads to few adverse events and a higher proportion of time within the therapeutic coagulation rate window, but these findings still need confirmation.", "output": {"entities": {"chemical": [{"text": "warfarin", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Effects of caffeine and alcohol on mood and performance changes following consumption of lager.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 11, "end": 19}, {"text": "alcohol", "start": 24, "end": 31}]}}, "schema": []}
{"input": "RATIONALE: The present study examined whether caffeine would modify the behavioural effects of alcohol.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 46, "end": 54}, {"text": "alcohol", "start": 95, "end": 102}]}}, "schema": []}
{"input": "OBJECTIVES: The aim of the study was to determine whether caffeine modifies the effects of alcohol on mood and psychomotor performance and to identify possible dose-response and temporal relationships.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 58, "end": 66}, {"text": "alcohol", "start": 91, "end": 98}]}}, "schema": []}
{"input": "METHODS: A double-blind study examined the effects of three successive lager drinks (330 ml each) in the early afternoon on mood and psychomotor performance assessed at 30-min intervals over a 2-h period.", "output": {"entities": {}}, "schema": []}
{"input": "Participants carried out a baseline session and were then randomly assigned to one of six conditions formed by combining three different doses of caffeine (0, 62. 5 and 125 mg per drink) with either no alcohol or 4. 3% alcohol.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 146, "end": 154}, {"text": "alcohol", "start": 202, "end": 209}, {"text": "alcohol", "start": 219, "end": 226}]}}, "schema": []}
{"input": "One hundred and forty-six young adults (65 male, 81 female; age range 18-30 years) participated in the study.", "output": {"entities": {}}, "schema": []}
{"input": "Mood (alertness, hedonic tone and anxiety) was assessed before and after performing simple reaction time and choice reaction time tasks.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Alcohol was associated with higher hedonic tone (p < 0. 005), reduced anxiety (p < 0. 05) and reduced alertness (p < 0. 005).", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 9, "end": 16}]}}, "schema": []}
{"input": "Caffeine had no modifying effect on hedonic tone or anxiety.", "output": {"entities": {"chemical": [{"text": "Caffeine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "However, the highest dose of caffeine did remove the effect of alcohol on alertness (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 29, "end": 37}, {"text": "alcohol", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Effects of alcohol and caffeine were found on the performance tasks (all p values < 0. 05) but these were independent effects.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 11, "end": 18}, {"text": "caffeine", "start": 23, "end": 31}]}}, "schema": []}
{"input": "CONCLUSIONS: The results from the present study confirm that caffeine does not remove the negative effects of alcohol on performance although high doses counteract the drop in subjective alertness produced by alcohol.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 61, "end": 69}, {"text": "alcohol", "start": 110, "end": 117}, {"text": "alcohol", "start": 209, "end": 216}]}}, "schema": []}
{"input": "3D Organotypic Cultures of Human HepaRG Cells: A Tool for In Vitro Toxicity Studies.", "output": {"entities": {}}, "schema": []}
{"input": "Drug-induced human hepatotoxicity is difficult to predict using the current in vitro systems.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, long-term 3D organotypic cultures of the human hepatoma HepaRG cell line were prepared using a high-throughput hanging drop method.", "output": {"entities": {}}, "schema": []}
{"input": "The organotypic cultures were maintained for 3 weeks and assessed for (1) liver specific functions, including phase I enzyme and transporter activities, (2) expression of liver-specific proteins, and (3) responses to three drugs (acetaminophen, troglitazone, and rosiglitazone).", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 230, "end": 243}, {"text": "troglitazone", "start": 245, "end": 257}, {"text": "rosiglitazone", "start": 263, "end": 276}]}}, "schema": []}
{"input": "Our results show that the organotypic cultures maintain high liver-specific functionality during 3 weeks of culture.", "output": {"entities": {}}, "schema": []}
{"input": "The immunohistochemistry analyses illustrate that the organotypic cultures express liver-specific markers such as albumin, CYP3A4, CYP2E1, and MRP-2 throughout the cultivation period.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, the production rates of albumin and glucose, as well as CYP2E1 activity, were significantly higher in the 3D versus the 2D cultures.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 49, "end": 56}]}}, "schema": []}
{"input": "Toxicity studies show that the organotypic cultures are more sensitive to acetaminophen-and rosiglitazone-induced toxicity but less sensitive to troglitazone-induced toxicity than the 2D cultures.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 74, "end": 87}, {"text": "rosiglitazone", "start": 92, "end": 105}, {"text": "troglitazone", "start": 145, "end": 157}]}}, "schema": []}
{"input": "Furthermore, the EC50 value (2. 7mM) for acetaminophen on the 3D cultures was similar to in vivo toxicity.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 41, "end": 54}]}}, "schema": []}
{"input": "In summary, the results from our study suggest that the 3D organotypic HepaRG culture is a promising in vitro tool for more accurate assessment of acute and also possibly for chronic drug-induced hepatotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Mending leaky blood vessels: the angiopoietin-Tie2 pathway in sepsis.", "output": {"entities": {}}, "schema": []}
{"input": "Sepsis is a systemic inflammatory response to infection.", "output": {"entities": {}}, "schema": []}
{"input": "A common end-feature, these patients regularly suffer from is the so-called multiple organ dysfunction syndrome, an often fatal consequence of organ hypoperfusion, coagulopathy, immune dysregulation, and mitochondrial dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Microvascular dysfunction critically contributes to the morbidity and mortality of this disease.", "output": {"entities": {}}, "schema": []}
{"input": "The angiopoietin (Angpt)/Tie2 system consists of the transmembrane endothelial tyrosine kinase Tie2 and its circulating ligands (Angpt-1,-2, and-3/4).", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 79, "end": 87}]}}, "schema": []}
{"input": "The balance between the canonical agonist Angpt-1 and its competitive inhibitor, Angpt-2, regulates basal endothelial barrier function and the leakage and vascular inflammation that develop in response to pathogens and cytokines.", "output": {"entities": {}}, "schema": []}
{"input": "Here we summarize recent work in mice and men to highlight the therapeutic potential in this pathway to prevent or even reverse microvascular dysfunction in this deadly disease.", "output": {"entities": {}}, "schema": []}
{"input": "Implications of lipid moiety in oligomerization and immunoreactivities of GPI-anchored proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Glycosylphosphatidylinositol (GPI) enriches GPI-anchored proteins (GPI-AP) in lipid rafts by intimate interaction of its lipid moiety with sphingolipids and cholesterol.", "output": {"entities": {"chemical": [{"text": "sphingolipids", "start": 139, "end": 152}, {"text": "cholesterol", "start": 157, "end": 168}]}}, "schema": []}
{"input": "In addition to such lipid-lipid interactions, it has been reported that GPI may interact with protein moiety linked to GPI and affect protein conformations because GPI delipidation reduced immunoreactivities of protein.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report that GPI-APs that have not undergone fatty acid remodeling exhibit reduced immunoreactivities in Western blotting, similar to delipidated proteins, compared with normal remodeled GPI-APs.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 53, "end": 63}]}}, "schema": []}
{"input": "In contrast, immunostaining in flow cytometry and immunoprecipitation did not show significant differences between remodeled and unremodeled GPI-APs.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, detection with premixed primary/secondary antibody complexes or Fab fragments eliminated this difference in Western blotting.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that normally remodeled GPI enhanced oligomerization of GPI-APs and that inefficient oligomerization of unremodeled GPI-APs was responsible for reduced immunoreactivities.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the reduction in immunoreactivities of delipidated GPI-APs was most likely caused by the same effect.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, by chemical cross-linking of surface proteins in living cells and cell killing assay using a pore-forming bacterial toxin, we showed that enhanced oligomerization by GPI-remodeling occurs under a physiological membrane environment.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, this study clarifies the significance of GPI fatty acid remodeling in oligomerization of GPI-APs and provides useful information for technical studies of these cell components.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 51, "end": 61}]}}, "schema": []}
{"input": "Structural Modifications to Tetrahydropyridine-3-carboxylate Esters en Route to the Discovery of M (5)-Preferring Muscarinic Receptor Orthosteric Antagonists.", "output": {"entities": {"chemical": [{"text": "Tetrahydropyridine-3-carboxylate Esters", "start": 28, "end": 67}]}}, "schema": []}
{"input": "The M (5) muscarinic acetylcholine receptor is suggested to be a potential pharmacotherapeutic target for the treatment of drug abuse.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 21, "end": 34}]}}, "schema": []}
{"input": "We describe herein the discovery of a series of M (5)-preferring orthosteric antagonists based on the scaffold of 1, 2, 5, 6-tetrahydropyridine-3-carboxylic acid.", "output": {"entities": {"chemical": [{"text": "1, 2, 5, 6-tetrahydropyridine-3-carboxylic acid", "start": 114, "end": 161}]}}, "schema": []}
{"input": "Compound 56, the most selective compound in this series, possesses an 11-fold selectivity for the M (5) over M (1) receptor and shows little activity at M (2)-M (4).", "output": {"entities": {}}, "schema": []}
{"input": "This compound, although exhibiting modest affinity (K (i) = 2. 24 mu M) for the [(3) H] N-methylscopolamine binding site on the M (5) receptor, is potent (IC (50) = 0. 45 nM) in inhibiting oxotremorine-evoked [(3) H] DA release from rat striatal slices.", "output": {"entities": {"chemical": [{"text": "[(3) H] N-methylscopolamine", "start": 80, "end": 107}, {"text": "oxotremorine", "start": 189, "end": 201}, {"text": "[(3) H] DA", "start": 209, "end": 219}]}}, "schema": []}
{"input": "Further, a homology model of human M (5) receptor based on the crystal structure of the rat M (3) receptor was constructed, and docking studies of compounds 28 and 56 were performed in an attempt to understand the possible binding mode of these novel analogues to the receptor.", "output": {"entities": {}}, "schema": []}
{"input": "Small molecule antivirulents targeting the iron-regulated heme oxygenase (HemO) of P. aeruginosa.", "output": {"entities": {"chemical": [{"text": "iron", "start": 43, "end": 47}, {"text": "heme", "start": 58, "end": 62}]}}, "schema": []}
{"input": "Bacteria require iron for survival and virulence and employ several mechanisms including utilization of the host heme containing proteins.", "output": {"entities": {"chemical": [{"text": "iron", "start": 17, "end": 21}, {"text": "heme", "start": 113, "end": 117}]}}, "schema": []}
{"input": "The final step in releasing iron is the oxidative cleavage of heme by HemO.", "output": {"entities": {"chemical": [{"text": "iron", "start": 28, "end": 32}, {"text": "heme", "start": 62, "end": 66}]}}, "schema": []}
{"input": "A recent computer aided drug design (CADD) study identified several inhibitors of the bacterial HemOs.", "output": {"entities": {}}, "schema": []}
{"input": "Herein we report the near complete HN, N, CO, C alpha, and C beta chemical shift assignment of the P. aeruginosa HemO in the absence and presence of inhibitors (E)-3-(4-(phenylamino) phenylcarbamoyl) acrylic acid (3) and (E)-N'-(4-(dimethylamino) benzylidene) diazenecarboximidhydrazide (5).", "output": {"entities": {"chemical": [{"text": "HN", "start": 35, "end": 37}, {"text": "N", "start": 39, "end": 40}, {"text": "CO", "start": 42, "end": 44}, {"text": "(E)-3-(4-(phenylamino) phenylcarbamoyl) acrylic acid", "start": 160, "end": 212}, {"text": "(E)-N'-(4-(dimethylamino) benzylidene) diazenecarboximidhydrazide", "start": 221, "end": 286}]}}, "schema": []}
{"input": "The NMR data confirm that the inhibitors bind within the heme pocket of HemO consistent with in silico molecular dynamic simulations.", "output": {"entities": {"chemical": [{"text": "heme", "start": 57, "end": 61}]}}, "schema": []}
{"input": "Both inhibitors and the phenoxy derivative of 3 have activity against P. aeruginosa clinical isolates.", "output": {"entities": {"chemical": [{"text": "phenoxy", "start": 24, "end": 31}]}}, "schema": []}
{"input": "Furthermore, 5 showed antimicrobial activity in the in vivo C. elegans curing assay.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, targeting virulence mechanisms required within the host is a viable antimicrobial strategy for the development of novel antivirulants.", "output": {"entities": {}}, "schema": []}
{"input": "Landscape heterogeneity shapes host-parasite interactions and results in apparent plant-virus codivergence.", "output": {"entities": {}}, "schema": []}
{"input": "Knowledge on how landscape heterogeneity shapes host-parasite interactions is central to understand the emergence, dynamics and evolution of infectious diseases.", "output": {"entities": {}}, "schema": []}
{"input": "However, this is an underexplored subject, particularly for plant-virus systems.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we analyse how landscape heterogeneity influences the prevalence, spatial genetic structure, and temporal dynamics of Pepper golden mosaic and Pepper huasteco yellow vein begomoviruses infecting populations of the wild pepper Capsicum annuum glabriusculum (chiltepin) in Mexico.", "output": {"entities": {}}, "schema": []}
{"input": "Environmental heterogeneity occurred at different nested spatial scales (host populations within biogeographical provinces), with levels of human management varying among host population within a province.", "output": {"entities": {}}, "schema": []}
{"input": "Results indicate that landscape heterogeneity affects the epidemiology and genetic structure of chiltepin-infecting begomoviruses in a scale-specific manner, probably related to conditions favouring the viruses' whitefly vector and its dispersion.", "output": {"entities": {}}, "schema": []}
{"input": "Increased levels of human management of the host populations were associated with higher virus prevalence and erased the spatial genetic structure of the virus populations.", "output": {"entities": {}}, "schema": []}
{"input": "Also, environmental heterogeneity similarly shaped the spatial genetic structures of host and viruses.", "output": {"entities": {}}, "schema": []}
{"input": "This resulted in the congruence between host and virus phylogenies, which does not seem to be due to host-virus co-evolution.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, results provide evidence of the key role of landscape heterogeneity in determining plant-virus interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Bifunctional inhibition of HIV-1 reverse transcriptase: a first step in designing a bifunctional triphosphate.", "output": {"entities": {"chemical": [{"text": "triphosphate", "start": 97, "end": 109}]}}, "schema": []}
{"input": "The onset of resistance to approved anti-AIDS drugs by HIV necessitates the search for novel inhibitors of HIV-1 reverse transcriptase (RT).", "output": {"entities": {}}, "schema": []}
{"input": "Developing single molecular agents concurrently occupying the nucleoside and nonnucleoside binding sites in RT is an intriguing idea but the proof of concept has so far been elusive.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 62, "end": 72}]}}, "schema": []}
{"input": "As a first step, we describe molecular modeling to guide focused chemical syntheses of conjugates having nucleoside (d4T) and nonnucleoside (TIBO) moieties tethered by a flexible polyethylene glycol (PEG) linker.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 105, "end": 115}, {"text": "d4T", "start": 117, "end": 120}, {"text": "TIBO", "start": 141, "end": 145}, {"text": "polyethylene glycol", "start": 179, "end": 198}, {"text": "PEG", "start": 200, "end": 203}]}}, "schema": []}
{"input": "A triphosphate of d4T-6PEG-TIBO conjugate was successfully synthesized that is recognized as a substrate by HIV-1 RT and incorporated into a double-stranded DNA.", "output": {"entities": {"chemical": [{"text": "triphosphate", "start": 2, "end": 14}, {"text": "d4T-6PEG-TIBO", "start": 18, "end": 31}]}}, "schema": []}
{"input": "Association of serum proprotein convertase subtilisin/kexin type 9 with carotid intima media thickness in hypertensive subjects.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE: The clinical significance of the measurement of serum PCSK9 (proprotein subtilisin kexin type 9) is not well defined.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigated the association between serum PCSK9 levels and atherosclerosis assessed by carotid intima media thickness (IMT) in hypertensive patients.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: A total of 126 hypertensive patients over the age of 45 were enrolled.", "output": {"entities": {}}, "schema": []}
{"input": "The maximum carotid IMT (max-IMT) and the mean carotid IMT (mean-IMT) were measured at the time of enrollment.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical and laboratory parameters including serum PCSK9 were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Patients were divided into tertiles based on serum PCSK9 levels.", "output": {"entities": {}}, "schema": []}
{"input": "After adjusting for age, sex, total cholesterol, HDL-cholesterol and triglyceride, max-IMT was significantly increased in the highest tertile of serum PCSK9 (0. 969 +/- 0. 033 vs 0. 959 +/- 0. 033 vs 1. 077 +/- 0. 033mm, respectively; P = 0. 026).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 36, "end": 47}, {"text": "triglyceride", "start": 69, "end": 81}]}}, "schema": []}
{"input": "Mean-IMT showed a tendency to increase across the tertile groups (0. 773 +/- 0. 025 vs 0. 790 +/- 0. 026 vs 0. 856 +/- 0. 025mm, respectively; P = 0. 059).", "output": {"entities": {}}, "schema": []}
{"input": "Multivariate regression analysis revealed that serum PCSK9 was independently associated with carotid IMT (max-IMT: beta = 0. 212, P = 0. 016; mean-IMT: beta = 0. 184, P = 0. 04).", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: The present study is the first to report the association between serum PCSK9 levels and carotid IMT in hypertensive patients.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that serum PCSK9 may have a certain role in early pathogenesis of atherosclerosis.", "output": {"entities": {}}, "schema": []}
{"input": "Impairing effect of amphetamine and concomitant ionotropic glutamate receptors blockade in the ventral striatum on spatial learning in mice.", "output": {"entities": {"chemical": [{"text": "amphetamine", "start": 20, "end": 31}, {"text": "glutamate", "start": 59, "end": 68}]}}, "schema": []}
{"input": "RATIONALE: Accumulating evidence supports the involvement of the ventral striatum (VS) in spatial information processing.", "output": {"entities": {}}, "schema": []}
{"input": "The multiple cortical glutamatergic and mesolimbic dopaminergic (DAergic) afferences on the same neurons in the ventral striatum provide the neuroanatomical substrate for glutamate and dopamine functional interaction.", "output": {"entities": {"chemical": [{"text": "glutamatergic", "start": 22, "end": 35}, {"text": "dopaminergic", "start": 51, "end": 63}]}}, "schema": []}
{"input": "However, there is little evidence in the literature on how this interaction affects the ability to encode spatial information.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE: First, we evaluated the effect of intra-VS bilateral infusion of different doses of amphetamine (0. 3, 0. 75, and 1. 5 mu g/side) on the ability to detect spatial novelty in mice.", "output": {"entities": {"chemical": [{"text": "amphetamine", "start": 95, "end": 106}]}}, "schema": []}
{"input": "Next, we examined the impact produced on the same abilities by intra-VS infusion of ineffective doses of amphetamine (0. 3 mu g/side) in association with N-methyl-D-aspartate (NMDA) (3. 125 ng/side) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) (0. 25 ng/side) receptor antagonist.", "output": {"entities": {"chemical": [{"text": "amphetamine", "start": 105, "end": 116}, {"text": "N-methyl-D-aspartate", "start": 154, "end": 174}, {"text": "NMDA", "start": 176, "end": 180}, {"text": "alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid", "start": 202, "end": 258}, {"text": "AMPA", "start": 260, "end": 264}]}}, "schema": []}
{"input": "RESULTS: The results show that infusion of amphetamine impairs detection of spatial novelty, affecting also exploratory activity and marginally the detection of nonspatial novelty.", "output": {"entities": {"chemical": [{"text": "amphetamine", "start": 43, "end": 54}]}}, "schema": []}
{"input": "In contrast, an association of subthreshold doses of amphetamine with NMDA or AMPA receptor antagonists exerted a selective effect on reactivity to a spatial change.", "output": {"entities": {"chemical": [{"text": "amphetamine", "start": 53, "end": 64}, {"text": "NMDA", "start": 70, "end": 74}, {"text": "AMPA", "start": 78, "end": 82}]}}, "schema": []}
{"input": "CONCLUSIONS: These findings demonstrate that enhanced DAergic activity in the VS enhances glutamate receptor antagonist-induced impairment in learning and memory.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 90, "end": 99}]}}, "schema": []}
{"input": "Differential autophagic cell death under stress with ectopic cytoplasmic and mitochondrial-specific PPP2R2B in human neuroblastoma cells.", "output": {"entities": {}}, "schema": []}
{"input": "Protein phosphatase 2A is one of four major classes of serine/threonine phosphatases.", "output": {"entities": {"chemical": [{"text": "serine", "start": 55, "end": 61}, {"text": "threonine", "start": 62, "end": 71}]}}, "schema": []}
{"input": "Overexpression of brain-specific regulatory subunit PPP2R2 in neuron cells is implicated in pathogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "The alternative splicing of PPP2R2B encodes two isoforms.", "output": {"entities": {}}, "schema": []}
{"input": "They are subunit of cytoplasmic specific B beta 1 and mitochondria-targeted B beta 2.", "output": {"entities": {}}, "schema": []}
{"input": "The two constructs were transfected into human neuroblastoma cells, SK-N-SH, respectively, and the stable clones overexpressing either B beta 1 or B beta 2 established.", "output": {"entities": {}}, "schema": []}
{"input": "We have reported that B beta 2 clones are sensitive to reactive oxygen species (ROS) treatment by inducing autophagic cell death.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 64, "end": 70}]}}, "schema": []}
{"input": "To study more on the onset of neuropathogenesis under strain, both clones were exposed to different environmental stress, e. g. starvation and endoplasmic reticulum (ER) stress.", "output": {"entities": {}}, "schema": []}
{"input": "To learn how PPP2R2B overexpression responds to starvation, cells were incubated in Hank' s buffered salt solution of deprived nutrient.", "output": {"entities": {}}, "schema": []}
{"input": "Cell death was induced in B beta 1 clones after 6 h starvation, but not in B beta 2 clones.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacological inhibitor, Bafilomycin A1, rescued the cell death while suppressing autophagy.", "output": {"entities": {"chemical": [{"text": "Bafilomycin A1", "start": 31, "end": 45}]}}, "schema": []}
{"input": "On the other hand, to assess how cells respond to ER stress, the cells were treated with 0. 1 mu M of N-glycosylation inhibitor, tunicamycin (TM).", "output": {"entities": {"chemical": [{"text": "N", "start": 102, "end": 103}, {"text": "tunicamycin", "start": 129, "end": 140}]}}, "schema": []}
{"input": "In contrast with B beta 1, the apoptotic cell death appeared in B beta 2 after 48 h treatment.", "output": {"entities": {}}, "schema": []}
{"input": "The formation of autophagolysosome was detected in B beta 2 following 12 h treatment with TM as evidenced by lysotracker and GFP-LC3 staining for fluorescence microscopy analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The autophagy inhibitor, 3-methyladenine, salvaged the final apoptosis.", "output": {"entities": {"chemical": [{"text": "3-methyladenine", "start": 25, "end": 40}]}}, "schema": []}
{"input": "The stable cell lines with ectopically transfected PPP2R2B genes encoding isoforms of brain-specific regulatory subunit exhibit distinct apoptosis under different stressors.", "output": {"entities": {}}, "schema": []}
{"input": "The induced autophagic apoptotic cell death is related to mitochondrial membrane potential drop and ROS generation.", "output": {"entities": {}}, "schema": []}
{"input": "Disturbance of autophagy alleviates the induced cell death.", "output": {"entities": {}}, "schema": []}
{"input": "The results promised a good model for understanding the onset in pathogenesis under stress in neuron cells with aberrant PPP2R2B expression.", "output": {"entities": {}}, "schema": []}
{"input": "A review of fabrication and applications of carbon nanotube film-based flexible electronics.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 44, "end": 50}]}}, "schema": []}
{"input": "Flexible electronics offer a wide-variety of applications such as flexible circuits, flexible displays, flexible solar cells, skin-like pressure sensors, and conformable RFID tags.", "output": {"entities": {}}, "schema": []}
{"input": "Carbon nanotubes (CNTs) are a promising material for flexible electronics, both as the channel material in field-effect transistors (FETs) and as transparent electrodes, due to their high intrinsic carrier mobility, conductivity, and mechanical flexibility.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In this feature article, we review the recent progress of CNTs in flexible electronics by describing both the processing and the applications of CNT-based flexible devices.", "output": {"entities": {}}, "schema": []}
{"input": "To employ CNTs as the channel material in FETs, single-walled carbon nanotubes (SWNTs) are used.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 62, "end": 68}]}}, "schema": []}
{"input": "There are generally two methods of depositing SWNTs on flexible substrates-transferring CVD-grown SWNTs or solution-depositing SWNTs.", "output": {"entities": {}}, "schema": []}
{"input": "Since CVD-grown SWNTs can be highly aligned, they often outperform solution-processed SWNT films that are typically in the form of random network.", "output": {"entities": {}}, "schema": []}
{"input": "However, solution-based SWNTs can be printed at a large-scale and at low-cost, rendering them more appropriate for manufacturing.", "output": {"entities": {}}, "schema": []}
{"input": "In either case, the removal of metallic SWNTs in an effective and a scalable manner is critical, which must still be developed and optimized.", "output": {"entities": {}}, "schema": []}
{"input": "Nevertheless, promising results demonstrating SWNT-based flexible circuits, displays, RF-devices, and biochemical sensors have been reported by various research groups, proving insight into the exciting possibilities of SWNT-based FETs.", "output": {"entities": {}}, "schema": []}
{"input": "In using carbon nanotubes as transparent electrodes (TEs), two main strategies have been implemented to fabricate highly conductive, transparent, and mechanically compliant films-superaligned films of CNTs drawn from vertically grown CNT forests using the \" dry-drawing \" technique and the deposition or embedding of CNTs onto flexible or stretchable substrates.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 9, "end": 15}]}}, "schema": []}
{"input": "The main challenge for CNT based TEs is to fabricate films that are both highly conductive and transparent.", "output": {"entities": {}}, "schema": []}
{"input": "These CNT based TEs have been used in stretchable and flexible pressure, strain, and chemical and biological sensors.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, they have also been used as the anode and cathode in flexible light emitting diodes, solar cells, and supercapacitors.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, there are a number of challenges yet to overcome to optimize the processing and performance of CNT-based flexible electronics; nonetheless, CNTs remain a highly suitable candidate for various flexible electronic applications in the near future.", "output": {"entities": {}}, "schema": []}
{"input": "A Serum-Resistant Low-Generation Polyamidoamine with PEI 423 Outer Layer for Gene Delivery Vector.", "output": {"entities": {"chemical": [{"text": "Polyamidoamine", "start": 33, "end": 47}, {"text": "PEI 423", "start": 53, "end": 60}]}}, "schema": []}
{"input": "A new derivative of polyamidoamine and polyethylenimine, G2. 5-PEI 423 or G1. 5-PEI 423, is prepared by an amidation reaction of PAMAM G2. 5 or PAMAM G1. 5 using PEI 423.", "output": {"entities": {"chemical": [{"text": "polyamidoamine", "start": 20, "end": 34}, {"text": "polyethylenimine", "start": 39, "end": 55}, {"text": "PEI 423", "start": 63, "end": 70}, {"text": "PEI 423", "start": 80, "end": 87}, {"text": "PAMAM", "start": 129, "end": 134}, {"text": "PAMAM", "start": 144, "end": 149}, {"text": "PEI 423", "start": 162, "end": 169}]}}, "schema": []}
{"input": "The polycations show a great ability to combine with pDNA to form complexes, which protect the pDNA from nuclease degradation.", "output": {"entities": {}}, "schema": []}
{"input": "The polymers display stronger buffer capacity and lower cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The complexes have particle sizes of 120-180 nm and zeta potentials of 20-40 mV.", "output": {"entities": {}}, "schema": []}
{"input": "The G2. 5-PEI 423 complexes display much higher transfection efficiencies than PAMAM G5 and Lipo-2k, and the G1. 5-PEI 423 complexes display higher transfection efficiencies than PAMAM G4 and PEI-25k.", "output": {"entities": {"chemical": [{"text": "PEI 423", "start": 10, "end": 17}, {"text": "PAMAM", "start": 79, "end": 84}, {"text": "PEI 423", "start": 115, "end": 122}, {"text": "PAMAM", "start": 179, "end": 184}, {"text": "PEI", "start": 192, "end": 195}]}}, "schema": []}
{"input": "The complexes possess better serum-resistant capacity.", "output": {"entities": {}}, "schema": []}
{"input": "The G2. 5-PEI 423 has a great potential to be used as a serum-resistant gene vector.", "output": {"entities": {"chemical": [{"text": "PEI 423", "start": 10, "end": 17}]}}, "schema": []}
{"input": "The influence of bypass procedures and other anatomical changes in the gastrointestinal tract on the oral bioavailability of drugs.", "output": {"entities": {}}, "schema": []}
{"input": "The gastrointestinal (GI) tract plays an important role in the absorption of orally administered drugs.", "output": {"entities": {}}, "schema": []}
{"input": "However, in some cases the anatomy of the GI tract is changed due to GI surgery, which has the potential of influencing drug bioavailability.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we aim to compile, review, and comment the existing but sometimes fragmented scientific data regarding the impact of GI surgery on the oral bioavailability of drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Relevant reports were gathered through the PubMed database from database inception through January 2012.", "output": {"entities": {}}, "schema": []}
{"input": "Drugs for which at least one trial or case report suggested a change in oral bioavailability or absorption caused by GI surgery are discussed in detail.", "output": {"entities": {}}, "schema": []}
{"input": "Major methodological differences, such as study design, number of subjects and choice of reference group, were observed in the reported studies.", "output": {"entities": {}}, "schema": []}
{"input": "Predicting the impact of GI surgery on the oral bioavailability was therefore difficult to perform, even the most sophisticated classification systems could not be used for predicting purposes.", "output": {"entities": {}}, "schema": []}
{"input": "Population pharmacokinetics of atorvastatin and its active metabolites in children and adolescents with heterozygous familial hypercholesterolemia: selective use of informative prior distributions from adults.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 31, "end": 43}]}}, "schema": []}
{"input": "The population pharmacokinetics (PPK) of atorvastatin and its principal active metabolite, o-hydroxyatorvastatin, were described in 6-17 years old pediatric hypercholesterolemia patients with a 2-compartment model for both parent and metabolite.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 41, "end": 53}, {"text": "o-hydroxyatorvastatin", "start": 91, "end": 112}]}}, "schema": []}
{"input": "Informative prior distributions on selected parameters, based on adult data, were required to stabilize the model and were implemented using a Bayesian penalty term on the likelihood function in the nonlinear mixed effects model (NONMEM VI with PRIOR).", "output": {"entities": {}}, "schema": []}
{"input": "Concentrations below the limit of quantitation were treated as censored data using a conditional likelihood function.", "output": {"entities": {}}, "schema": []}
{"input": "Atorvastatin apparent oral clearance (CL/F) was described as a function of body weight using an allometric equation.", "output": {"entities": {"chemical": [{"text": "Atorvastatin", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Based on the final model, the typical CL/F estimates for a Tanner Stage 1 patient (35 kg weight) and Tanner Stage >= 2 (50 kg weight), would be 553 and 543 L/hour, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "When scaled allometrically, CL/F was similar to values reported for adults.", "output": {"entities": {}}, "schema": []}
{"input": "Variability in atorvastatin PK was primarily affected by weight.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 15, "end": 27}]}}, "schema": []}
{"input": "Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 21, "end": 32}, {"text": "clarithromycin", "start": 37, "end": 51}, {"text": "sibutramine", "start": 96, "end": 107}]}}, "schema": []}
{"input": "In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 42, "end": 53}, {"text": "clarithromycin", "start": 58, "end": 72}, {"text": "racemic sibutramine", "start": 162, "end": 181}]}}, "schema": []}
{"input": "Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers.", "output": {"entities": {"chemical": [{"text": "Sibutramine", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2. 2-fold versus 4. 1-fold increase in the AUC in S-enantiomer and 1. 8-fold versus 2. 0-fold for the R-enantiomer, respectively.", "output": {"entities": {"chemical": [{"text": "Clopidogrel", "start": 0, "end": 11}, {"text": "clarithromycin", "start": 16, "end": 30}, {"text": "sibutramine", "start": 59, "end": 70}]}}, "schema": []}
{"input": "The AUCs of S-and R-desmethyl metabolites changed significantly during the clopidogrel phase (P <. 001 and P <. 001, respectively) but not during the clarithromycin phase (P =. 099 and P =. 090, respectively).", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 75, "end": 86}, {"text": "clarithromycin", "start": 150, "end": 164}]}}, "schema": []}
{"input": "Exposure to sibutramine was higher in subjects with the CYP2B6 * 6/* 6 genotype, but no statistical difference was observed among the CYP2B6 genotypes.", "output": {"entities": {"chemical": [{"text": "sibutramine", "start": 12, "end": 23}]}}, "schema": []}
{"input": "These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo.", "output": {"entities": {"chemical": [{"text": "sibutramine", "start": 63, "end": 74}]}}, "schema": []}
{"input": "Absence of edge States in covalently bonded zigzag edges of graphene on ir (111).", "output": {"entities": {"chemical": [{"text": "graphene", "start": 60, "end": 68}, {"text": "ir (111)", "start": 72, "end": 80}]}}, "schema": []}
{"input": "The zigzag edges of graphene on Ir (111) are studied by ab initio simulations and low-temperature scanning tunneling spectroscopy, providing information about their structural, electronic, and magnetic properties.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 20, "end": 28}, {"text": "Ir (111)", "start": 32, "end": 40}]}}, "schema": []}
{"input": "No edge state is found to exist, which is explained in terms of the interplay between a strong geometrical relaxation at the edge and a hybridization of the d orbitals of Ir atoms with the graphene orbitals at the edge.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 189, "end": 197}]}}, "schema": []}
{"input": "Characterization of efflux transporters involved in distribution and disposition of apixaban.", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 84, "end": 92}]}}, "schema": []}
{"input": "The studies reported here were conducted to investigate the transport characteristics of apixaban (1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl) phenyl)-4, 5, 6, 7-tetrahydro-1H-pyrazolo [3, 4-c] pyridine-3-carboxamide) and to understand the impact of transporters on apixaban distribution and disposition.", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 89, "end": 97}, {"text": "1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl) phenyl)-4, 5, 6, 7-tetrahydro-1H-pyrazolo [3, 4-c] pyridine-3-carboxamide", "start": 99, "end": 225}]}}, "schema": []}
{"input": "In human permeability glycoprotein (P-gp)-and breast cancer resistance protein (BCRP)-cDNA-transfected cell monolayers as well as Caco-2 cell monolayers, the apparent efflux ratio of basolateral-to-apical (PcB-A) versus apical-to-basolateral permeability (PcA-B) of apixaban was > 10.", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 266, "end": 274}]}}, "schema": []}
{"input": "The P-gp-and BCRP-facilitated transport of apixaban was concentration-and time-dependent and did not show saturation over a wide range of concentrations (1-100 mu M).", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 43, "end": 51}]}}, "schema": []}
{"input": "The efflux transport of apixaban was also demonstrated by the lower mucosal-to-serosal permeability than that of the serosal-to-mucosal direction in isolated rat jejunum segments.", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Apixaban did not inhibit digoxin transport in Caco-2 cells.", "output": {"entities": {"chemical": [{"text": "Apixaban", "start": 0, "end": 8}, {"text": "digoxin", "start": 25, "end": 32}]}}, "schema": []}
{"input": "Ketoconazole decreased the P-gp-mediated apixaban efflux in Caco-2 and the P-gp-cDNA-transfected cell monolayers, but did not affect the apixaban efflux to a meaningful extent in the BCRP-cDNA-transfected cell monolayers.", "output": {"entities": {"chemical": [{"text": "Ketoconazole", "start": 0, "end": 12}, {"text": "apixaban", "start": 41, "end": 49}]}}, "schema": []}
{"input": "Coincubation of a P-gp inhibitor (ketoconazole or cyclosporin A) and a BCRP inhibitor (Ko134) provided more complete inhibition of apixaban efflux in Caco-2 cells than separate inhibition by individual inhibitors.", "output": {"entities": {"chemical": [{"text": "ketoconazole", "start": 34, "end": 46}, {"text": "cyclosporin A", "start": 50, "end": 63}, {"text": "Ko134", "start": 87, "end": 92}]}}, "schema": []}
{"input": "Naproxen inhibited apixaban efflux in Caco-2 cells but showed only a minimal effect on apixaban transport in the BCRP-transfected cells.", "output": {"entities": {"chemical": [{"text": "Naproxen", "start": 0, "end": 8}, {"text": "apixaban", "start": 19, "end": 27}, {"text": "apixaban", "start": 87, "end": 95}]}}, "schema": []}
{"input": "Naproxen was the first nonsteroidal antiinflammatory drug that was demonstrated as a weak P-gp inhibitor.", "output": {"entities": {"chemical": [{"text": "Naproxen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "These results demonstrate that apixaban is a substrate for efflux transporters P-gp and BCRP, which can help explain its low brain penetration, and low fetal exposures and high milk excretion in rats.", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 31, "end": 39}]}}, "schema": []}
{"input": "A large-scale zebrafish gene knockout resource for the genome-wide study of gene function.", "output": {"entities": {}}, "schema": []}
{"input": "With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way.", "output": {"entities": {}}, "schema": []}
{"input": "The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome.", "output": {"entities": {}}, "schema": []}
{"input": "We also report the first 6144 mutagenized and archived F1' s predicted to carry up to 3776 mutations in annotated genes.", "output": {"entities": {}}, "schema": []}
{"input": "Using in vitro fertilization, we have rescued and characterized ~ 0. 5% of the predicted mutations, showing mutation efficacy and a variety of phenotypes relevant to both developmental processes and human genetic diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Mutagenized fish lines are being made freely available to the public through the Zebrafish International Resource Center.", "output": {"entities": {}}, "schema": []}
{"input": "These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome.", "output": {"entities": {}}, "schema": []}
{"input": "High-relaxivity and luminescent silica nanoparticles as multimodal agents for molecular imaging.", "output": {"entities": {"chemical": [{"text": "silica", "start": 32, "end": 38}]}}, "schema": []}
{"input": "The design and synthesis of a new bimodal contrast agent for magnetic resonance imaging and optical imaging is reported.", "output": {"entities": {}}, "schema": []}
{"input": "Tunable-sized silica nanoparticles were synthesized by a microemulsion-mediated pathway and used as carriers for paramagnetic and luminescent probes.", "output": {"entities": {"chemical": [{"text": "silica", "start": 14, "end": 20}]}}, "schema": []}
{"input": "The near-infrared luminescent agent was a ruthenium complex that was directly entrapped in the silica shell to provide photoluminescence enhancement and to make it highly photostable as it was protected from the surrounding environment.", "output": {"entities": {"chemical": [{"text": "ruthenium", "start": 42, "end": 51}, {"text": "silica", "start": 95, "end": 101}]}}, "schema": []}
{"input": "The paramagnetic activity came from a Gd-DTPA derivative that was grafted on the silica surface.", "output": {"entities": {"chemical": [{"text": "Gd-DTPA", "start": 38, "end": 45}, {"text": "silica", "start": 81, "end": 87}]}}, "schema": []}
{"input": "NMRD profiles showed a strong relaxivity enhancement (increase of 432% in the r1 value at 20 MHz) when the paramagnetic complex was grafted at the nanoparticle surface, because of a reduction of its mobility.", "output": {"entities": {}}, "schema": []}
{"input": "Polyethylene glycol was also grafted at the nanoparticle surface to enhance the nanoparticle residence time in the bloodstream.", "output": {"entities": {"chemical": [{"text": "Polyethylene glycol", "start": 0, "end": 19}]}}, "schema": []}
{"input": "A thorough characterization of the material confirmed its potential as a very effective bimodal contrast agent.", "output": {"entities": {}}, "schema": []}
{"input": "Effectiveness of preoperative plasmapheresis in a pregnancy complicated by hyperthyroidism and anti-thyroid drug-associated angioedema.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Hyperthyroidism is not a rare entity in pregnancy and 85% of these cases attributed to Graves' disease (GD).", "output": {"entities": {}}, "schema": []}
{"input": "There is no therapeutic modality for GD considered as totally safe in pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Fetal and neonatal risks of maternal hyperthyroid disease are related to the hyperthyroidism itself and/or to the medical treatment of the disease.", "output": {"entities": {}}, "schema": []}
{"input": "There are no data supporting an association between congenital anomalies in the fetus and propylthiouracil (PTU).", "output": {"entities": {"chemical": [{"text": "propylthiouracil", "start": 90, "end": 106}, {"text": "PTU", "start": 108, "end": 111}]}}, "schema": []}
{"input": "Hepatotoxicity, cytopenias-especially agranulocytosis and quite rarely, angioedema, may be seen as side effects of PTU.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 115, "end": 118}]}}, "schema": []}
{"input": "In this case report, we examine an instance of Graves' hyperthyroidism diagnosed during pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "In this case, a serious side effect during anti-thyroid drug usage was encountered, eventually resulting in surgery in the second trimester.", "output": {"entities": {}}, "schema": []}
{"input": "This intervention was assisted by the use of plasmapheresis to obtain rapid normalization of serum thyroid hormone levels.", "output": {"entities": {"chemical": [{"text": "thyroid hormone", "start": 99, "end": 114}]}}, "schema": []}
{"input": "Frequency and intensity of pain related to thyroid nodule fine needle aspiration cytology.", "output": {"entities": {}}, "schema": []}
{"input": "Background: Quality of life is an important issue in endocrine tumors because of the high prevalence of benign tumors and the indolent course of most malignant tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Objective: To evaluate the frequency and the intensity of pain and anxiety in patients undergoing thyroid nodule fine needle aspiration cytology (FNAC), and to identify factors associated with pain.", "output": {"entities": {}}, "schema": []}
{"input": "Method: Single center prospective study in the setting of a one-stop outpatient diagnostic clinic for thyroid nodules.", "output": {"entities": {}}, "schema": []}
{"input": "Pain was evaluated using a 100-mm visual analogue scale (VAS) immediately following (VAS1) and 30 minutes after (VAS2) FNAC and was considered significant if >= 30.", "output": {"entities": {}}, "schema": []}
{"input": "Anxiety symptoms were assessed prior to FNAC using a self-report measure questionnaire: the state form of Spielberger State-Trait Anxiety Inventory (STAI, form Y-A).", "output": {"entities": {}}, "schema": []}
{"input": "FNAC was performed with a 25-Gauge needle and a moderate aspiration and two passes for each nodule.", "output": {"entities": {}}, "schema": []}
{"input": "Results: 218 consecutive patients (163 females, 55 males; mean age 53 years, range 12-84) undergoing FNAC of 1 to 3 nodules were included.", "output": {"entities": {}}, "schema": []}
{"input": "VAS1 was >= 30 in 24% of the patients and VAS2 was <F0B3> 30 in 13% of the patients.", "output": {"entities": {}}, "schema": []}
{"input": "Independent significant factors correlated to a VAS1 <F0B3> 30 were age under 25 and the number of nodules being biopsied.", "output": {"entities": {}}, "schema": []}
{"input": "Independent significant factors correlated to a VAS2 <F0B3> 30 were VAS1 <F0B3> 30 and female gender.", "output": {"entities": {}}, "schema": []}
{"input": "No correlation was found between pain and nodule size or nodule depth, nor the duration of application of the Eutectic Mixture of Local Anesthetics (EMLA patch) prior to FNAC.", "output": {"entities": {}}, "schema": []}
{"input": "The mean STAI score for anxiety was 37 <F0B1> 12.", "output": {"entities": {}}, "schema": []}
{"input": "The average STAI score was significantly higher in women (39) than in men (33) (p = 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "There was no significant correlation between STAI score and age under 25, previous FNAC, number of nodules biopsied or acetaminophen administration, but the STAI score was significantly correlated to VAS1 and VAS2 Conclusions: FNAC-related pain is frequent and correlates with the number of nodules biopsied, age under 25, female gender and anxiety.", "output": {"entities": {}}, "schema": []}
{"input": "Maximal Raman optical activity in hybrid single molecule-plasmonic nanostructures with multiple dipolar resonances.", "output": {"entities": {}}, "schema": []}
{"input": "We show that a hybrid system built of a plasmonic nanoparticle cluster and a single molecule can attain maximal Raman optical activity (ROA), converting linearly polarized light into purely circularly polarized light at the Raman-scattered frequency.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to standard molecular ROA, the effect described here does not involve magnetic modes and is attributed to off-resonance excitation of electric-dipole plasmon modes of the nanoparticle cluster.", "output": {"entities": {}}, "schema": []}
{"input": "A model based on a combination of harmonic oscillators excited at the frequency of the Raman-scattered light is shown to successfully capture the physics of the effect.", "output": {"entities": {}}, "schema": []}
{"input": "Acitretin affects bioenergetics of liver mitochondria and promotes mitochondrial permeability transition: Potential mechanisms of hepatotoxicity.", "output": {"entities": {"chemical": [{"text": "Acitretin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Acitretin is a synthetic retinoid used for severe extensive psoriasis and it has been shown to be an effective and a safe therapeutic drug for other diseases including cancer when used in combination with other agents.", "output": {"entities": {"chemical": [{"text": "Acitretin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "However, cases of acitretin-associated liver injury have been documented, but the possible mechanisms of acitretin-associated hepatotoxicity and apoptosis are not entirely clarified.", "output": {"entities": {"chemical": [{"text": "acitretin", "start": 18, "end": 27}, {"text": "acitretin", "start": 105, "end": 114}]}}, "schema": []}
{"input": "This study reports that mitochondrial dysfunctions may play an important role in liver injury and apoptosis induced by this retinoid.", "output": {"entities": {"chemical": [{"text": "retinoid", "start": 124, "end": 132}]}}, "schema": []}
{"input": "Acitretin (5-20 mu M) impaired mitochondrial phosphorylation efficiency as demonstrated by the decrease in the state 3 respiration and ATP levels, and by the increase in the lag phase of ADP phosphorylation cycle, without affecting the membrane potential.", "output": {"entities": {"chemical": [{"text": "Acitretin", "start": 0, "end": 9}, {"text": "ATP", "start": 135, "end": 138}, {"text": "ADP", "start": 187, "end": 190}]}}, "schema": []}
{"input": "Acitretin induced Ca (2 +)-mediated mitochondrial permeability transition (MPT) and decreased the adenine nucleotide translocase (ANT) content.", "output": {"entities": {"chemical": [{"text": "Acitretin", "start": 0, "end": 9}, {"text": "Ca (2 +)", "start": 18, "end": 26}, {"text": "adenine nucleotide", "start": 98, "end": 116}]}}, "schema": []}
{"input": "Acitretin-induced MPT was not prevented by thiol group protecting and antioxidant agents, excluding the involvement of oxidative stress mechanisms.", "output": {"entities": {"chemical": [{"text": "Acitretin", "start": 0, "end": 9}, {"text": "thiol", "start": 43, "end": 48}]}}, "schema": []}
{"input": "However, MPT was prevented by ANT ligands ATP, ADP, tamoxifen and 4-hydroxytamoxifen, implying that the MPT induction by acitretin is mediated by the ANT.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 42, "end": 45}, {"text": "ADP", "start": 47, "end": 50}, {"text": "tamoxifen", "start": 52, "end": 61}, {"text": "4-hydroxytamoxifen", "start": 66, "end": 84}]}}, "schema": []}
{"input": "ANT plays a major role in promoting apoptosis and ATP synthesis, and it is still considered as a structural component of the pore with a regulatory role in MPT formation.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 50, "end": 53}]}}, "schema": []}
{"input": "Therefore, our results, including the decrease in the state 3 respiration and the increase in the lag phase of phosphorylation cycle, the ATP depletion and the induction of Ca (2 +)-mediated MPT, indicate that acitretin-associated liver toxicity and apoptosis is possibly related with mitochondrial dysfunctions due to interactions with the ANT.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 138, "end": 141}, {"text": "Ca (2 +)", "start": 173, "end": 181}, {"text": "acitretin", "start": 210, "end": 219}]}}, "schema": []}
{"input": "Additionally, the combination of acitretin with other drugs, such as antiestrogens, which are able to inhibit the MPT, may contribute to decrease the toxicity induced by acitretin.", "output": {"entities": {"chemical": [{"text": "acitretin", "start": 33, "end": 42}, {"text": "acitretin", "start": 170, "end": 179}]}}, "schema": []}
{"input": "Therapeutic potential of neuregulin-1 in cardiovascular disease.", "output": {"entities": {}}, "schema": []}
{"input": "Neuregulin-1 (NRG-1)/ErbB signaling has an indispensable role in cardiac development and in the maintenance of the structural and functional integrity of the human adult heart in health and disease.", "output": {"entities": {}}, "schema": []}
{"input": "Several animal studies have now demonstrated the therapeutic effects of NRG-1 during acute cardiac injury and during chronic heart failure, with improvements in cardiac performance and animal survival.", "output": {"entities": {}}, "schema": []}
{"input": "Phase I and II clinical trials for chronic heart failure in humans are now in progress.", "output": {"entities": {}}, "schema": []}
{"input": "Glucocorticoid-induced suppression of beta-cell proliferation is mediated by Mig6.", "output": {"entities": {}}, "schema": []}
{"input": "Glucocorticoids can cause steroid-induced diabetes or accelerate the progression to diabetes by creating systemic insulin resistance and decreasing functional beta-cell mass, which is influenced by changes in beta-cell function, growth, and death.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 26, "end": 33}]}}, "schema": []}
{"input": "The synthetic glucocorticoid agonist dexamethasone (Dex) is deleterious to functional beta-cell mass by decreasing beta-cell function, survival, and proliferation.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 37, "end": 50}, {"text": "Dex", "start": 52, "end": 55}]}}, "schema": []}
{"input": "However, the mechanism by which Dex decreases beta-cell proliferation is unknown.", "output": {"entities": {"chemical": [{"text": "Dex", "start": 32, "end": 35}]}}, "schema": []}
{"input": "Interestingly, Dex induces the transcription of an antiproliferative factor and negative regulator of epidermal growth factor receptor signaling, Mig6 (also known as gene 33, RALT, and Errfi1).", "output": {"entities": {"chemical": [{"text": "Dex", "start": 15, "end": 18}]}}, "schema": []}
{"input": "We, therefore, hypothesized that Dex impairs beta-cell proliferation by increasing the expression of Mig6 and thereby decreasing downstream signaling of epidermal growth factor receptor.", "output": {"entities": {"chemical": [{"text": "Dex", "start": 33, "end": 36}]}}, "schema": []}
{"input": "We found that Dex induced Mig6 and decreased [(3) H] thymidine incorporation, an index of cellular replication, in mouse, rat, and human islets.", "output": {"entities": {"chemical": [{"text": "Dex", "start": 14, "end": 17}, {"text": "[(3) H] thymidine", "start": 45, "end": 62}]}}, "schema": []}
{"input": "Using adenovirally delivered small interfering RNA targeted to Mig6 in rat islets, we were able to limit the induction of Mig6 upon exposure to Dex, compared with islets treated with a control virus, and completely rescued the Dex-mediated impairment in replication.", "output": {"entities": {"chemical": [{"text": "Dex", "start": 144, "end": 147}, {"text": "Dex", "start": 227, "end": 230}]}}, "schema": []}
{"input": "We demonstrated that both Dex and overexpression of Mig6 attenuated the phosphorylation of ERK1/2 and blocked the G (1)/S transition of the cell cycle.", "output": {"entities": {"chemical": [{"text": "Dex", "start": 26, "end": 29}]}}, "schema": []}
{"input": "In conclusion, Mig6 functions as a molecular brake for beta-cell proliferation during glucocorticoid treatment in beta-cells, and thus, Mig6 may be a novel target for preventing glucocorticoid-induced impairments in functional beta-cell mass.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of cytosolic glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase genes in rainbow trout (Oncorhynchus mykiss) and their modulation by in vitro selenium exposure.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 30, "end": 41}, {"text": "hydroperoxide glutathione", "start": 70, "end": 95}, {"text": "selenium", "start": 185, "end": 193}]}}, "schema": []}
{"input": "Selenium (Se) is an oligonutrient with both essential biological functions and recognized harmful effects.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 0, "end": 8}, {"text": "Se", "start": 10, "end": 12}]}}, "schema": []}
{"input": "As the selenocysteine (SeCys) amino acid, selenium is integrated in several Se-containing proteins (selenoproteins), many of which are fundamental for cell homeostasis.", "output": {"entities": {"chemical": [{"text": "selenocysteine", "start": 7, "end": 21}, {"text": "SeCys", "start": 23, "end": 28}, {"text": "amino acid", "start": 30, "end": 40}, {"text": "selenium", "start": 42, "end": 50}, {"text": "Se", "start": 76, "end": 78}]}}, "schema": []}
{"input": "Nevertheless, selenium may exert toxic effects at levels marginally above those required, mainly through the generation of reactive oxygen species (ROS).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 132, "end": 138}]}}, "schema": []}
{"input": "The selenium chemical speciation can strongly affect the bioavailability of this metal and its impact on metabolism, dictating the levels that can be beneficial or detrimental towards an organism.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 4, "end": 12}]}}, "schema": []}
{"input": "Glutathione peroxidase (GPxs) is the largest and the most studied selenoprotein family.", "output": {"entities": {"chemical": [{"text": "Glutathione", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Cytosolic glutathione peroxidase (cGPx, GPx1) and phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) are widely distributed throughout tissues, and play a pivotal role in regulating the oxidative status in the cell.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 10, "end": 21}, {"text": "hydroperoxide glutathione", "start": 63, "end": 88}]}}, "schema": []}
{"input": "In this study we have cloned GPx1 and GPx4 genes in rainbow trout (Oncorhynchus mykiss).", "output": {"entities": {}}, "schema": []}
{"input": "The constitutive mRNA expression of these GPx genes was examined in 18 trout tissues and their responsiveness to Se availability was analysed using a rainbow trout liver cell line (RTL).", "output": {"entities": {}}, "schema": []}
{"input": "An inorganic (sodium selenite, Na2SeO3) and organic (selenocysteine, Cys-Se-Se-Cys) selenocompound have been used as Se sources.", "output": {"entities": {"chemical": [{"text": "sodium selenite", "start": 14, "end": 29}, {"text": "Na2SeO3", "start": 31, "end": 38}, {"text": "selenocysteine", "start": 53, "end": 67}, {"text": "Cys-Se-Se-Cys", "start": 69, "end": 82}, {"text": "Se", "start": 117, "end": 119}]}}, "schema": []}
{"input": "GPx1 activity was also tested to verify the impact of transcript changes on the enzymatic function of these molecules.", "output": {"entities": {}}, "schema": []}
{"input": "To understand if the results obtained from the transcript expression analysis were due to Se bioavailability or generation of ROS, the cytoxicity of the two selenocompounds was tested by measuring the impact of Se on cell membrane integrity.", "output": {"entities": {"chemical": [{"text": "Se", "start": 90, "end": 92}, {"text": "Se", "start": 211, "end": 213}]}}, "schema": []}
{"input": "Lastly, Se availability was quantified by mass spectrophotometry to determine the amount of Se in the cell culture media, the Se background due to the foetal calf serum supplement and the contribution from the two selenocompounds used in the treatments.", "output": {"entities": {"chemical": [{"text": "Se", "start": 8, "end": 10}, {"text": "Se", "start": 92, "end": 94}, {"text": "Se", "start": 126, "end": 128}]}}, "schema": []}
{"input": "Three isoforms of genes for both GPx1 (GPx1a, 1b1 and 1b2) and GPx4 (GPx4a1, a2 and b) have been identified.", "output": {"entities": {}}, "schema": []}
{"input": "The discovery of a third gene encoding for GPx1 and GPx4 hints that salmonids may have the biggest selenoproteome amongst all vertebrates.", "output": {"entities": {}}, "schema": []}
{"input": "Transcripts of GPx4 genes were more highly expressed in most tissues examined in vivo (except blood, head kidney and spleen), whereas those of the GPx1 genes were more responsive to selenium exposure in vitro, especially to the organic form.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 182, "end": 190}]}}, "schema": []}
{"input": "Interestingly, GPx1a was the most sensitive to selenium availability in non stressful conditions, whereas GPx1b1 and GPx1b2 were highly induced by exposure to selenium levels that had some toxic effects on the cells.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 47, "end": 55}, {"text": "selenium", "start": 159, "end": 167}]}}, "schema": []}
{"input": "Although the different concentrations tested of the two selenocompounds modulate GPx1 transcript expression to various degrees, no significant change of GPx1 enzymatic activity was detectable.", "output": {"entities": {}}, "schema": []}
{"input": "Our results lead us to conclude that trout GPx1 transcripts expression level may represent a sensitive biomarker for selenium intake, helping to evaluate if selenium concentration and chemical speciation impact on cell homeostasis.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 117, "end": 125}, {"text": "selenium", "start": 157, "end": 165}]}}, "schema": []}
{"input": "Application of activated nucleoside analogs for the treatment of drug-resistant tumors by oral delivery of nanogel-drug conjugates.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 25, "end": 35}]}}, "schema": []}
{"input": "A majority of nanoencapsulated drugs that have shown promise in cancer chemotherapy are administered intravenously.", "output": {"entities": {}}, "schema": []}
{"input": "Development of effective oral nanoformulations presents a very challenging medical goal.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we describe successful applications of innovative polymeric nanogels in the form of conjugates with activated nucleoside analogs for oral administration in cancer chemotherapy.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 116, "end": 126}]}}, "schema": []}
{"input": "Previously, we reported the synthesis of amphiphilic polyvinyl alcohol and dextrin-based nanogel conjugates with the phosphorylated 5-FU nucleoside Floxuridine and demonstrated their enhanced activity against regular and drug-resistant cancers (T. H. Senanayake, G. Warren, S. V. Vinogradov, Novel anticancer polymeric conjugates of activated nucleoside analogs, Bioconjug. Chem. 22 (2011) 1983-1993).", "output": {"entities": {"chemical": [{"text": "polyvinyl alcohol", "start": 53, "end": 70}, {"text": "phosphorylated 5-FU nucleoside Floxuridine", "start": 117, "end": 159}, {"text": "nucleoside", "start": 343, "end": 353}]}}, "schema": []}
{"input": "In this study, we synthesized and evaluated oral applications of nanogel conjugates of a protected Gemcitabine, the drug never used in oral therapies.", "output": {"entities": {"chemical": [{"text": "Gemcitabine", "start": 99, "end": 110}]}}, "schema": []}
{"input": "These conjugates were able to quickly release an active form of the drug (Gemcitabine 5'-mono-, di-and triphosphates) by specific enzymatic activities, or slowly during hydrolysis.", "output": {"entities": {"chemical": [{"text": "Gemcitabine 5'-mono-, di-and triphosphates", "start": 74, "end": 116}]}}, "schema": []}
{"input": "Gemcitabine conjugates demonstrated up to 127 times higher in vitro efficacy than the free drug against various cancer cells, including the lines resistant to nucleoside analogs.", "output": {"entities": {"chemical": [{"text": "Gemcitabine", "start": 0, "end": 11}, {"text": "nucleoside", "start": 159, "end": 169}]}}, "schema": []}
{"input": "Surprisingly, these nanogel-drug conjugates were relatively stable in gastric conditions and able to actively penetrate through the gastrointestinal barrier based on permeability studies in Caco-2 cell model.", "output": {"entities": {}}, "schema": []}
{"input": "In tumor xenograft models of several drug-resistant human cancers, we observed an efficient inhibition of tumor growth and extended the life-span of the animals by 3 times that of the control with orally treated Gemcitabine-or Floxuridine-nanogel conjugates.", "output": {"entities": {"chemical": [{"text": "Gemcitabine", "start": 212, "end": 223}, {"text": "Floxuridine", "start": 227, "end": 238}]}}, "schema": []}
{"input": "Thus, we have demonstrated a potential of therapeutic nanogel conjugates with the activated and stabilized Gemcitabine as a successful oral drug form against Gemcitabine-resistant and other drug-resistant tumors.", "output": {"entities": {"chemical": [{"text": "Gemcitabine", "start": 107, "end": 118}, {"text": "Gemcitabine", "start": 158, "end": 169}]}}, "schema": []}
{"input": "Design and synthesis of imidazole and triazole derivatives as Lp-PLA 2 inhibitors and the unexpected discovery of highly potent quaternary ammonium salts.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 24, "end": 33}, {"text": "triazole", "start": 38, "end": 46}, {"text": "quaternary ammonium salts", "start": 128, "end": 153}]}}, "schema": []}
{"input": "New Lp-PLA (2) inhibitors were synthesized by the bioisosteric replacement of the amide group of Darapladib with an imidazole or a triazole.", "output": {"entities": {"chemical": [{"text": "amide", "start": 82, "end": 87}, {"text": "Darapladib", "start": 97, "end": 107}, {"text": "imidazole", "start": 116, "end": 125}, {"text": "triazole", "start": 131, "end": 139}]}}, "schema": []}
{"input": "Unfortunately, the inhibitory activities of these derivatives were lower than that of Darapladib.", "output": {"entities": {"chemical": [{"text": "Darapladib", "start": 86, "end": 96}]}}, "schema": []}
{"input": "But interestingly, a series of quaternary ammonium salts that were isolated as by-products during this synthetic work were found with high potency.", "output": {"entities": {"chemical": [{"text": "quaternary ammonium salts", "start": 31, "end": 56}]}}, "schema": []}
{"input": "Of these by-products, compound 22c showed a similar profile to Darapladib both in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "Darapladib", "start": 63, "end": 73}]}}, "schema": []}
{"input": "Synthesis and antibacterial activities of new piperidine substituted (5R)-[1, 2, 3] triazolylmethyl and (5R)-[(4-F-[1, 2, 3] triazolyl) methyl] oxazolidinones.", "output": {"entities": {"chemical": [{"text": "piperidine", "start": 46, "end": 56}, {"text": "(5R)-[1, 2, 3] triazolylmethyl and (5R)-[(4-F-[1, 2, 3] triazolyl) methyl] oxazolidinones", "start": 69, "end": 158}]}}, "schema": []}
{"input": "A novel series of 5 (R)-[1, 2, 3] triazolylmethyl and (5R)-[(4-F-[1, 2, 3] triazolyl) methyl] oxazolidinones having various piperidine group were synthesized and evaluated antibacterial activity against clinically isolated resistant strains of Gram-positive and Gram-negative bacteria.", "output": {"entities": {"chemical": [{"text": "5 (R)-[1, 2, 3] triazolylmethyl and (5R)-[(4-F-[1, 2, 3] triazolyl) methyl] oxazolidinones", "start": 18, "end": 108}, {"text": "piperidine", "start": 124, "end": 134}]}}, "schema": []}
{"input": "The compound 12a having exo-cyanoethylidene group in the 4-position of piperidine ring was found to be two to threefold more potent than the linezolid against penicillin-resistant Staphylococcus pneumonia and Staphylococcus agalactiae, and also exhibited reduced MAO-B inhibitory activity.", "output": {"entities": {"chemical": [{"text": "exo-cyanoethylidene", "start": 24, "end": 43}, {"text": "piperidine", "start": 71, "end": 81}, {"text": "linezolid", "start": 141, "end": 150}, {"text": "penicillin", "start": 159, "end": 169}]}}, "schema": []}
{"input": "Integrated analysis of transcriptomics and metabonomics profiles in aflatoxin B1-induced hepatotoxicity in rat.", "output": {"entities": {"chemical": [{"text": "aflatoxin B1", "start": 68, "end": 80}]}}, "schema": []}
{"input": "The aim of this work was to identify mechanisms and potential biomarkers for predicting the development and progression of aflatoxin B1 (AFB1)-induced acute hepatotoxicity.", "output": {"entities": {"chemical": [{"text": "aflatoxin B1", "start": 123, "end": 135}, {"text": "AFB1", "start": 137, "end": 141}]}}, "schema": []}
{"input": "In this study, microarray analysis and metabolites profiles were used to identify shifts in gene expression and metabolite levels associated with the affected physiological processes of rats treated with AFB1.", "output": {"entities": {"chemical": [{"text": "AFB1", "start": 204, "end": 208}]}}, "schema": []}
{"input": "Histopathological examinations and serum biochemical analysis were simultaneously performed; the results indicated that hepatotoxicity occurred in higher dosage groups.", "output": {"entities": {}}, "schema": []}
{"input": "However, gene expression analysis and metabolite profiles are more sensitive than general toxicity studies for detecting AFB1-induced acute hepatotoxicity as the patterns of low-dose AFB1-treated rats in these two technique platforms were more similar to the rats in higher dosage groups than to the control rats.", "output": {"entities": {"chemical": [{"text": "AFB1", "start": 121, "end": 125}, {"text": "AFB1", "start": 183, "end": 187}]}}, "schema": []}
{"input": "Integrated analysis of the results from general toxicity studies, transcriptomics and metabonomics profiles suggested that p53 signaling pathway induced by oxidative damage was the crucial step in AFB1-induced acute hepatotoxicity, whereas gluconeogenesis and lipid metabolism disorder were found to be the major metabolic effects after acute AFB1 exposure.", "output": {"entities": {"chemical": [{"text": "AFB1", "start": 197, "end": 201}, {"text": "AFB1", "start": 343, "end": 347}]}}, "schema": []}
{"input": "The genes and metabolites significantly affected in common in rat liver or serum of three doses AFB1 treatments served as potential biomarkers for detecting AFB1-induced acute hepatotoxicity.", "output": {"entities": {"chemical": [{"text": "AFB1", "start": 96, "end": 100}, {"text": "AFB1", "start": 157, "end": 161}]}}, "schema": []}
{"input": "QM/MM simulations of vibrational spectra of bacteriorhodopsin and channelrhodopsin-2.", "output": {"entities": {}}, "schema": []}
{"input": "Channelrhodopsin-2 is a light-gated ion channel, which has been studied intensively over the last decade.", "output": {"entities": {}}, "schema": []}
{"input": "Vibrational spectroscopic experiments started to shed light on the structural changes, that occur during the photocycle, especially in the hydrogen-bonded network surrounding the protonated D156 and C128-the DC gate.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 139, "end": 147}]}}, "schema": []}
{"input": "However, the interpretation of these experiments was only based on homology models.", "output": {"entities": {}}, "schema": []}
{"input": "Since then, an X-ray structure and better computational models became available.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we show that in combination with a recent reparametrization, the approximate DFT method, DFTB, is able to describe the effects of hydrogen bonding on the C [double bond, length as m-dash] O stretch vibration in carboxylic acids reliably and agrees well with full DFT results.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 147, "end": 155}, {"text": "C", "start": 171, "end": 172}, {"text": "O", "start": 205, "end": 206}, {"text": "carboxylic acids", "start": 228, "end": 244}]}}, "schema": []}
{"input": "We apply DFTB in a QM/MM framework to perform vibrational analysis of buried aspartic acids in bacteriorhodopsin and channelrhodopsin-2.", "output": {"entities": {"chemical": [{"text": "aspartic acids", "start": 77, "end": 91}]}}, "schema": []}
{"input": "Using this approach, we can simulate the FTIR spectral difference between D115 in the dark-adapted and K states of bacteriorhodopsin.", "output": {"entities": {}}, "schema": []}
{"input": "The FTIR experiments on the DC gate in channelrhodopsin-2 are well described using an indirect model, where D156 and C128 are bridged via a water molecule.", "output": {"entities": {}}, "schema": []}
{"input": "Preparation and evaluation of sustained-release doxazosin mesylate pellets.", "output": {"entities": {"chemical": [{"text": "doxazosin mesylate", "start": 48, "end": 66}]}}, "schema": []}
{"input": "Doxazosin mesylate (DXM) sustained release pellets were prepared by an extrusion-spheronization and fluid-bed coating technique.", "output": {"entities": {"chemical": [{"text": "Doxazosin mesylate", "start": 0, "end": 18}, {"text": "DXM", "start": 20, "end": 23}]}}, "schema": []}
{"input": "The core pellets containing DXM were prepared by extrusion-spheronization technique, and coated by a fluid-bed coater to control the release of DXM.", "output": {"entities": {"chemical": [{"text": "DXM", "start": 28, "end": 31}, {"text": "DXM", "start": 144, "end": 147}]}}, "schema": []}
{"input": "The factors affecting to properties of pellets, such as diluent content, type and coating level of coating agents and plasticizers were studied in the present study.", "output": {"entities": {}}, "schema": []}
{"input": "Polymethacrylate derivatives (Eudragit (R) RS PO and RL PO) were used for coating agents, and polyethylene glycol 6000 (PEG 6000), triethyl citrate (TEC) and castor oil were as plasticizers.", "output": {"entities": {"chemical": [{"text": "Polymethacrylate", "start": 0, "end": 16}, {"text": "Eudragit", "start": 30, "end": 38}, {"text": "polyethylene glycol 6000", "start": 94, "end": 118}, {"text": "PEG 6000", "start": 120, "end": 128}, {"text": "triethyl citrate", "start": 131, "end": 147}, {"text": "TEC", "start": 149, "end": 152}]}}, "schema": []}
{"input": "To evaluate the properties of prepared pellets, the size of prepared pellets was investigated by sieve analysis technique and the morphology of pellets was evaluated by scanning electron microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Through the dissolution test, factors that have an effect on the dissolution of the drug were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "As the content ratio of microcrystalline cellulose (MCC) had increased, the dissolution was proportionally sustained.", "output": {"entities": {}}, "schema": []}
{"input": "Eudragit (R) RS PO had more marked sustaining effect on the dissolution rate than Eudragit (R) RL PO, and the effect was more pronounced with the increased coating level.", "output": {"entities": {"chemical": [{"text": "Eudragit", "start": 0, "end": 8}, {"text": "Eudragit", "start": 82, "end": 90}]}}, "schema": []}
{"input": "PEG 6000 was an appropriate plasticizer for DXM pellets, and increasing the content of PEG 6000, was also slightly decreasing the dissolution rate.", "output": {"entities": {"chemical": [{"text": "PEG 6000", "start": 0, "end": 8}, {"text": "DXM", "start": 44, "end": 47}, {"text": "PEG 6000", "start": 87, "end": 95}]}}, "schema": []}
{"input": "Nocapyrones H-J, 3, 6-Disubstituted alpha-Pyrones from the Marine Actinomycete Nocardiopsis sp.", "output": {"entities": {"chemical": [{"text": "Nocapyrones H-J", "start": 0, "end": 15}, {"text": "3, 6-Disubstituted alpha-Pyrones", "start": 17, "end": 49}]}}, "schema": []}
{"input": "KMF-001.", "output": {"entities": {}}, "schema": []}
{"input": "Three new 3, 6-disubstituted alpha-pyrones, nocapyrones H-J (1-3), were isolated from the marine actinomycete Nocardiopsis sp.", "output": {"entities": {"chemical": [{"text": "3, 6-disubstituted alpha-pyrones", "start": 10, "end": 42}, {"text": "nocapyrones H-J", "start": 44, "end": 59}]}}, "schema": []}
{"input": "KMF-001.", "output": {"entities": {}}, "schema": []}
{"input": "Their structures were assigned to be 3-alkylated 6-(1-methyl-1-propenyl)-2H-pyran-2-ones on the basis of UV, MS, NMR, and high resolution (HR)-FAB-MS analyses.", "output": {"entities": {"chemical": [{"text": "3-alkylated 6-(1-methyl-1-propenyl)-2H-pyran-2-ones", "start": 37, "end": 88}]}}, "schema": []}
{"input": "Nocapyrone H (1) reduced the pro-inflammatory factor such as nitric oxide (NO), prostaglandin E2 (PGE2) and interleukin-1 beta (IL-1 beta).", "output": {"entities": {"chemical": [{"text": "Nocapyrone H", "start": 0, "end": 12}, {"text": "nitric oxide", "start": 61, "end": 73}, {"text": "NO", "start": 75, "end": 77}, {"text": "prostaglandin E2", "start": 80, "end": 96}, {"text": "PGE2", "start": 98, "end": 102}]}}, "schema": []}
{"input": "Moreover, nocapyrone H showed 5. 82% stronger inhibitory effect on NO production than chrysin at a concentration of 10 micro m in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells.", "output": {"entities": {"chemical": [{"text": "nocapyrone H", "start": 10, "end": 22}, {"text": "NO", "start": 67, "end": 69}]}}, "schema": []}
{"input": "In vitro-in vivo correlation of the inhibition potency of sodium-glucose cotransporter inhibitors in rat: a pharmacokinetic and pharmacodynamic modeling approach.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 58, "end": 64}, {"text": "glucose", "start": 65, "end": 72}]}}, "schema": []}
{"input": "To evaluate the relationship between the in vitro and in vivo potency of sodium-glucose cotransporter (SGLT) inhibitors, a pharmacokinetic and pharmacodynamic (PK-PD) study was performed using normal rats.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 73, "end": 79}, {"text": "glucose", "start": 80, "end": 87}]}}, "schema": []}
{"input": "A highly selective SGLT2 inhibitor, tofogliflozin, and four other inhibitors with different in vitro inhibition potency to SGLT2 and selectivity toward SGLT2, versus SGLT1 were used as test compounds, and the time courses for urinary glucose excretion (UGE) and the plasma glucose and compound concentrations were monitored after administration of the compounds.", "output": {"entities": {"chemical": [{"text": "tofogliflozin", "start": 36, "end": 49}, {"text": "glucose", "start": 234, "end": 241}, {"text": "glucose", "start": 273, "end": 280}]}}, "schema": []}
{"input": "A PK-PD analysis of the UGE caused by SGLT inhibition was performed on the basis of a nonlinear parallel tube model that took into consideration the consecutive reabsorption by different glucose transport properties of SGLT2 and SGLT1.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 187, "end": 194}]}}, "schema": []}
{"input": "The model adequately captured the time course of cumulative UGE caused by SGLT inhibition; then, the in vivo inhibition constants (Ki) of inhibitors for both SGLT1 and SGLT2 were estimated.", "output": {"entities": {}}, "schema": []}
{"input": "The in vivo selectivity toward SGLT2 showed a good correlation with the in vitro data (r = 0. 985; P < 0. 05), with in vivo Ki values for SGLT2 in the range of 0. 3-3. 4-fold the in vitro data.", "output": {"entities": {}}, "schema": []}
{"input": "This suggests that in vitro inhibition potency to both SGLT2 and SGLT1 is reflected in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the complementary role of SGLT1 to SGLT2 and how selectivity toward SGLT2 affects the inhibitory potency for renal glucose reabsorption were discussed using the PK-PD model.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 128, "end": 135}]}}, "schema": []}
{"input": "SnO (2)-Based Nanomaterials: Synthesis and Application in Lithium-Ion Batteries.", "output": {"entities": {"chemical": [{"text": "SnO (2)", "start": 0, "end": 7}, {"text": "Lithium", "start": 58, "end": 65}]}}, "schema": []}
{"input": "The development of new electrode materials for lithium-ion batteries (LIBs) has always been a focal area of materials science, as the current technology may not be able to meet the high energy demands for electronic devices with better performance.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 47, "end": 54}]}}, "schema": []}
{"input": "Among all the metal oxides, tin dioxide (SnO (2)) is regarded as a promising candidate to serve as the anode material for LIBs due to its high theoretical capacity.", "output": {"entities": {"chemical": [{"text": "metal oxides", "start": 14, "end": 26}, {"text": "tin dioxide", "start": 28, "end": 39}, {"text": "SnO (2)", "start": 41, "end": 48}]}}, "schema": []}
{"input": "Here, a thorough survey is provided of the synthesis of SnO (2)-based nanomaterials with various structures and chemical compositions, and their application as negative electrodes for LIBs.", "output": {"entities": {"chemical": [{"text": "SnO (2)", "start": 56, "end": 63}]}}, "schema": []}
{"input": "It covers SnO (2) with different morphologies ranging from 1D nanorods/nanowires/nanotubes, to 2D nanosheets, to 3D hollow nanostructures.", "output": {"entities": {"chemical": [{"text": "SnO (2)", "start": 10, "end": 17}]}}, "schema": []}
{"input": "Nanocomposites consisting of SnO (2) and different carbonaceous supports, e. g., amorphous carbon, carbon nanotubes, graphene, are also investigated.", "output": {"entities": {"chemical": [{"text": "SnO (2)", "start": 29, "end": 36}, {"text": "carbonaceous", "start": 51, "end": 63}, {"text": "carbon", "start": 91, "end": 97}, {"text": "graphene", "start": 117, "end": 125}]}}, "schema": []}
{"input": "The use of Sn-based nanomaterials as the anode material for LIBs will be briefly discussed as well.", "output": {"entities": {"chemical": [{"text": "Sn", "start": 11, "end": 13}]}}, "schema": []}
{"input": "The aim of this review is to provide an in-depth and rational understanding such that the electrochemical properties of SnO (2)-based anodes can be effectively enhanced by making proper nanostructures with optimized chemical composition.", "output": {"entities": {"chemical": [{"text": "SnO (2)", "start": 120, "end": 127}]}}, "schema": []}
{"input": "By focusing on SnO (2), the hope is that such concepts and strategies can be extended to other potential metal oxides, such as titanium dioxide or iron oxides, thus shedding some light on the future development of high-performance metal-oxide based negative electrodes for LIBs.", "output": {"entities": {"chemical": [{"text": "SnO (2)", "start": 15, "end": 22}, {"text": "metal oxides", "start": 105, "end": 117}, {"text": "titanium dioxide", "start": 127, "end": 143}, {"text": "iron oxides", "start": 147, "end": 158}, {"text": "metal-oxide", "start": 231, "end": 242}]}}, "schema": []}
{"input": "Add-on therapy with the DPP-4 inhibitor sitagliptin improves glycemic control in insulin-treated Japanese patients with type 2 diabetes mellitus.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 40, "end": 51}]}}, "schema": []}
{"input": "The effect of add-on therapy with sitagliptin on glycemic control was prospectively investigated in patients with type 2 diabetes mellitus (T2DM) receiving insulin alone or insulin combined with oral antidiabetic drugs.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 34, "end": 45}]}}, "schema": []}
{"input": "Seventy-one patients were evaluated (38 men and 33 women aged 63. 9 +/- 10. 2 years).", "output": {"entities": {}}, "schema": []}
{"input": "They were divided into three groups, which were 45 patients receiving premixed insulin twice daily, 15 patients receiving multiple daily insulin injections, and 11 patients receiving basal insulin with oral antidiabetic drugs (basal insulin therapy).", "output": {"entities": {}}, "schema": []}
{"input": "Concomitant oral drugs included sulfonylureas, alpha-glucosidase inhibitors and metformin.", "output": {"entities": {"chemical": [{"text": "sulfonylureas", "start": 32, "end": 45}, {"text": "metformin", "start": 80, "end": 89}]}}, "schema": []}
{"input": "The hemoglobin A1c (HbA1c) of all patients improved significantly from 8. 1 +/- 1. 2% to 7. 6 +/- 1. 1% after 12 weeks of add-on therapy with sitagliptin (p < 0. 01), and the insulin dosage was reduced from 27. 3 +/- 15. 8 U/day to 24. 5 +/- 16. 5 U/day (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 142, "end": 153}]}}, "schema": []}
{"input": "Body weight did not change after the start of concomitant therapy and severe hypoglycemia was not observed.", "output": {"entities": {}}, "schema": []}
{"input": "The baseline HbA1c and glycated albumin levels were identified as factors that predicted the response to add-on therapy with sitagliptin.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 125, "end": 136}]}}, "schema": []}
{"input": "These findings suggest that add-on therapy with sitagliptin can be expected to achieve improvement of poor glycemic control irrespective of a patient' s demographic profile.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 48, "end": 59}]}}, "schema": []}
{"input": "Stratified analysis based on the insulin regimen revealed a stronger antidiabetic effect and a high efficacy of sitagliptin when it was added to basal insulin therapy.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 112, "end": 123}]}}, "schema": []}
{"input": "The results of this investigation confirmed that add-on therapy with sitagliptin to various insulin regimens could improve glycemic control without severe hypoglycemia and/or weight gain.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 69, "end": 80}]}}, "schema": []}
{"input": "CYP21A2 Mutations in Women with Polycystic Ovary Syndrome (PCOS).", "output": {"entities": {}}, "schema": []}
{"input": "The question of the contribution of CYP21A2 heterozygosity to the development of polycystic ovary syndrome (PCOS) has repeatedly been raised in the literature.", "output": {"entities": {}}, "schema": []}
{"input": "The available data, however, do not offer a satisfactory answer.", "output": {"entities": {}}, "schema": []}
{"input": "The discrepancy must be attributed, primarily, to the small number of subjects in the various studies, the type of selected phenotype, and the number of searched mutations.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the study was to define the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS.", "output": {"entities": {}}, "schema": []}
{"input": "We searched for 14 molecular defects of the CYP21A2 gene in 197 PCOS women, employing allele specific PCR.", "output": {"entities": {}}, "schema": []}
{"input": "Androgen levels were determined at baseline by appropriate methodology in the follicular phase.", "output": {"entities": {"chemical": [{"text": "Androgen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "PCOS women with 17-hydroxyprogesterone (17OHP) basal values > 2 ng/ml and/or post-ACTH > 10 ng/ml were excluded.", "output": {"entities": {"chemical": [{"text": "17-hydroxyprogesterone", "start": 16, "end": 38}, {"text": "17OHP", "start": 40, "end": 45}]}}, "schema": []}
{"input": "Appropriate controls were included.", "output": {"entities": {}}, "schema": []}
{"input": "The frequency of the CYP21A2 heterozygous mutations in PCOS women and in controls was 7. 6% and 5. 9%, respectively [p-value (PCOS vs. controls): 0. 663].", "output": {"entities": {}}, "schema": []}
{"input": "Homozygosity for CYP21A2 gene defects was not detected.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS is not substantiated by our data.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, 17-hydroxyprogesterone values of < 10 ng/ml post-ACTH exclude homozygosity of CYP21A2 mutations.", "output": {"entities": {"chemical": [{"text": "17-hydroxyprogesterone", "start": 10, "end": 32}]}}, "schema": []}
{"input": "Effectiveness of an educational intervention on prescription writing skill of preclerkship medical students in a problem-based learning curriculum.", "output": {"entities": {}}, "schema": []}
{"input": "Medical school training for students in pharmacotherapy is suboptimal and junior doctors are not confident to prescribe drugs.", "output": {"entities": {}}, "schema": []}
{"input": "This study evaluated the effectiveness of an optional educational intervention on prescribing skill of pre-clerkship medical students in a problem-based learning (PBL) program.", "output": {"entities": {}}, "schema": []}
{"input": "Performance was assessed in seven end-unit objective structured practical examinations (OSPE).", "output": {"entities": {}}, "schema": []}
{"input": "Physician-related prescription components (PRCs) and drug-related prescription components (DRCs) were assessed.", "output": {"entities": {}}, "schema": []}
{"input": "The performance of students who attended the intervention sessions (attendees) and non-attendees was compared.", "output": {"entities": {}}, "schema": []}
{"input": "Approximately half of the students attended the sessions.", "output": {"entities": {}}, "schema": []}
{"input": "PRCs were written appropriately by most of the students.", "output": {"entities": {}}, "schema": []}
{"input": "DRCs were written less competently by both attendees and non-attendees, specifically the dosage form, quantity to be dispensed and directions.", "output": {"entities": {}}, "schema": []}
{"input": "Performance on individual DRCs was significantly better for attendees compared to non-attendees.", "output": {"entities": {}}, "schema": []}
{"input": "The mean total score for all prescription components of attendees was significantly greater than that of non-attendees.", "output": {"entities": {}}, "schema": []}
{"input": "The percentage of high achievers was significantly greater for attendees.", "output": {"entities": {}}, "schema": []}
{"input": "A positive correlation was found between student attendance and the total score.", "output": {"entities": {}}, "schema": []}
{"input": "An optional educational intervention during the preclerkship phase is an important determinant of prescribing performance of medical students.", "output": {"entities": {}}, "schema": []}
{"input": "Reversible inhibition of human carboxylesterases by acyl glucuronides.", "output": {"entities": {"chemical": [{"text": "acyl glucuronides", "start": 52, "end": 69}]}}, "schema": []}
{"input": "Carboxylesterases hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively.", "output": {"entities": {"chemical": [{"text": "esters", "start": 28, "end": 34}, {"text": "amides", "start": 36, "end": 42}, {"text": "thioesters", "start": 48, "end": 58}, {"text": "carboxylic acids", "start": 70, "end": 86}, {"text": "alcohols", "start": 101, "end": 109}, {"text": "amines", "start": 111, "end": 117}, {"text": "thiols", "start": 123, "end": 129}]}}, "schema": []}
{"input": "Uridine 5'-diphosphate-glucuronosyltransferases are colocalized with carboxylesterases and have the potential to further metabolize carboxylic acids to acyl glucuronides, but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases.", "output": {"entities": {"chemical": [{"text": "Uridine 5'-diphosphate", "start": 0, "end": 22}, {"text": "carboxylic acids", "start": 132, "end": 148}, {"text": "acyl glucuronides", "start": 152, "end": 169}, {"text": "acyl glucuronides", "start": 202, "end": 219}, {"text": "esters", "start": 227, "end": 233}]}}, "schema": []}
{"input": "Objective: This study explores the ability of acyl glucuronides to act as substrates or inhibitors of human carboxylesterases 1 (hCES1) and 2 (hCES2).", "output": {"entities": {"chemical": [{"text": "acyl glucuronides", "start": 46, "end": 63}]}}, "schema": []}
{"input": "Methods: The stability of six acyl glucuronides in the presence of hCES1, hCES2, and buffer alone (100 mM potassium phosphate, pH 7. 4, 37 degrees C) were investigated.", "output": {"entities": {"chemical": [{"text": "acyl glucuronides", "start": 30, "end": 47}, {"text": "potassium phosphate", "start": 106, "end": 125}]}}, "schema": []}
{"input": "Reversible inhibition of 4-nitrophenyl acetate hydrolysis by the acyl glucuronides was also studied.", "output": {"entities": {"chemical": [{"text": "4-nitrophenyl acetate", "start": 25, "end": 46}, {"text": "acyl glucuronides", "start": 65, "end": 82}]}}, "schema": []}
{"input": "Diclofenac-beta-d-glucuronide was used to explore potential time-dependent inactivation.", "output": {"entities": {"chemical": [{"text": "Diclofenac-beta-d-glucuronide", "start": 0, "end": 29}]}}, "schema": []}
{"input": "Results: The chemical stability half-life values for CGP 47292-beta-d-glucuronide, diclofenac-beta-d-glucuronide, (R)-naproxen-beta-d-glucuronide, (S)-naproxen-beta-d-glucuronide, ibuprofen-beta-d-glucuronide (racemic), clopidogrel-beta-d-glucuronide, and valproate-beta-d-glucuronide were found to be 0. 252, 0. 537, 0. 996, 1. 77, 3. 67, 5. 02, and 15. 2 hours, respectively.", "output": {"entities": {"chemical": [{"text": "CGP 47292-beta-d-glucuronide", "start": 53, "end": 81}, {"text": "diclofenac-beta-d-glucuronide", "start": 83, "end": 112}, {"text": "(R)-naproxen-beta-d-glucuronide", "start": 114, "end": 145}, {"text": "(S)-naproxen-beta-d-glucuronide", "start": 147, "end": 178}, {"text": "ibuprofen-beta-d-glucuronide (racemic)", "start": 180, "end": 218}, {"text": "clopidogrel-beta-d-glucuronide", "start": 220, "end": 250}, {"text": "valproate-beta-d-glucuronide", "start": 256, "end": 284}]}}, "schema": []}
{"input": "Diclofenac-beta-d-glucuronide, clopidogrel-beta-d-glucuronide, ibuprofen-beta-d-glucuronide, (R)-naproxen-beta-d-glucuronide, and (S)-naproxen-beta-d-glucuronide selectively inhibited hCES1, with Ki values of 4. 32 +/- 0. 47, 24. 8 +/- 4. 2, 355 +/- 38, 468 +/- 21, 707 +/- 64 micro M, respectively, but did not significantly inhibit hCES2.", "output": {"entities": {"chemical": [{"text": "Diclofenac-beta-d-glucuronide", "start": 0, "end": 29}, {"text": "clopidogrel-beta-d-glucuronide", "start": 31, "end": 61}, {"text": "ibuprofen-beta-d-glucuronide", "start": 63, "end": 91}, {"text": "(R)-naproxen-beta-d-glucuronide", "start": 93, "end": 124}, {"text": "(S)-naproxen-beta-d-glucuronide", "start": 130, "end": 161}]}}, "schema": []}
{"input": "Valproate-beta-d-glucuronide and CGP 47292-beta-d-glucuronide did not inhibit either hCES.", "output": {"entities": {"chemical": [{"text": "Valproate-beta-d-glucuronide", "start": 0, "end": 28}, {"text": "CGP 47292-beta-d-glucuronide", "start": 33, "end": 61}]}}, "schema": []}
{"input": "Time-dependent inactivation of hCES1 by diclofenac-beta-d-glucuronide was not observed.", "output": {"entities": {"chemical": [{"text": "diclofenac-beta-d-glucuronide", "start": 40, "end": 69}]}}, "schema": []}
{"input": "Lastly, both hCES1 and hCES2 were shown not to catalyze the hydrolysis of the acyl glucuronides studied.", "output": {"entities": {"chemical": [{"text": "acyl glucuronides", "start": 78, "end": 95}]}}, "schema": []}
{"input": "Conclusion: Drug-drug interaction studies may be warranted for drugs that metabolize to acyl glucuronides due to the potential inhibition of hCESs.", "output": {"entities": {"chemical": [{"text": "acyl glucuronides", "start": 88, "end": 105}]}}, "schema": []}
{"input": "Hepatic effects of ketamine administration for 2 weeks in rats.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 19, "end": 27}]}}, "schema": []}
{"input": "The aim of the present study was to investigate the long-term and high-dose application of ketamine on the liver by employing histologic and biochemical methods.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 91, "end": 99}]}}, "schema": []}
{"input": "A total of 30 male rats were randomly assigned to control and four treatment groups (n: 6).", "output": {"entities": {}}, "schema": []}
{"input": "Saline for control group and different doses of ketamine for four treatment groups (40, 60, 80 and 100 mg kg (-1)) were administered intraperitoneal twice a day for 2 weeks.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Immunohistological staining, light and electron microscopy were used to study tissue specimens.", "output": {"entities": {}}, "schema": []}
{"input": "Histopathological changes were more severe and diverse in groups 80 and 100 mg kg (-1) day (-1), and the least significant change was observed in groups 40 and 60 mg kg (-1) day (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The most important ultrastructural changes were seen in mitochondria and in the rough endoplasmic reticulum.", "output": {"entities": {}}, "schema": []}
{"input": "The immunoreactivity of calcineurin was determined as different.", "output": {"entities": {}}, "schema": []}
{"input": "Prolonged use of ketamine caused hepatocellualar toxicity and histological changes in hepatocytes in a dose-dependent manner in all experimental groups.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 17, "end": 25}]}}, "schema": []}
{"input": "Cytotoxic activity of Guettarda pohliana M u ll.", "output": {"entities": {}}, "schema": []}
{"input": "Arg.", "output": {"entities": {}}, "schema": []}
{"input": "(Rubiaceae).", "output": {"entities": {}}, "schema": []}
{"input": "The cytotoxic activity of crude extracts and their fractions from leaves and roots of G. pohliana was assessed against nine human cancer cell lines: melanoma (UACC-62), breast (MCF-7), breast expressing the multidrug resistance phenotype (NCI-ADR), lung (NCI-460), prostate (PCO-3), kidney (786-0), ovarian (OVCAR), colon (HT-29) and leukaemia (K-562).", "output": {"entities": {}}, "schema": []}
{"input": "The hexane fraction from leaves (HL) and ethyl acetate (EAR), chloroform (CR) and hydromethanolic (HMR) fractions from roots were the most active fractions against K-562 with GI (50) values being lower than 1 mu g mL (-1).", "output": {"entities": {"chemical": [{"text": "hexane", "start": 4, "end": 10}, {"text": "ethyl acetate", "start": 41, "end": 54}, {"text": "chloroform", "start": 62, "end": 72}]}}, "schema": []}
{"input": "Also, CR and HMR fractions were active against UACC-62 cell line in the same order of magnitude.", "output": {"entities": {}}, "schema": []}
{"input": "The phytochemical study of the CR fraction allowed identifying the known iridoids secoxyloganin, sweroside and loganin.", "output": {"entities": {"chemical": [{"text": "iridoids secoxyloganin", "start": 73, "end": 95}, {"text": "sweroside", "start": 97, "end": 106}, {"text": "loganin", "start": 111, "end": 118}]}}, "schema": []}
{"input": "Photoelectron and electron momentum spectroscopy of tetrahydrofuran from a molecular dynamical perspective.", "output": {"entities": {"chemical": [{"text": "tetrahydrofuran", "start": 52, "end": 67}]}}, "schema": []}
{"input": "The results of experimental studies of the valence electronic structure of tetrahydrofuran employing He I photoelectron spectroscopy as well as Electron Momentum Spectroscopy (EMS) have been reinterpreted on the basis of Molecular Dynamical simulations employing the classical MM3 force field and large-scale quantum mechanical simulations employing Born-Oppenheimer Molecular Dynamics in conjunction with the dispersion corrected omega B97XD exchange-correlation functional.", "output": {"entities": {"chemical": [{"text": "tetrahydrofuran", "start": 75, "end": 90}, {"text": "He", "start": 101, "end": 103}]}}, "schema": []}
{"input": "Analysis of the produced atomic trajectories demonstrates the importance of thermal deviations from the lowest energy path for pseudorotation, in the form of considerable variations of the ring-puckering amplitude.", "output": {"entities": {}}, "schema": []}
{"input": "These deviations are found to have a significant influence on several outer-valence electron momentum distributions, as well as on the He I photoelectron spectrum.", "output": {"entities": {"chemical": [{"text": "He", "start": 135, "end": 137}]}}, "schema": []}
{"input": "Azaspiracid-1 inhibits the maturation of cathepsin D in mammalian cells.", "output": {"entities": {"chemical": [{"text": "Azaspiracid-1", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Azaspiracid-1 (AZA-1) inhibits endocytosis, but the consequences of this alteration on cellular processes are unknown.", "output": {"entities": {"chemical": [{"text": "Azaspiracid-1", "start": 0, "end": 13}, {"text": "AZA-1", "start": 15, "end": 20}]}}, "schema": []}
{"input": "We hypothesized that the inhibition of endocytosis is a key step of the mode of action of AZA-1, leading to perturbation of cellular processes dependent on proper functioning of endocytic machinery.", "output": {"entities": {"chemical": [{"text": "AZA-1", "start": 90, "end": 95}]}}, "schema": []}
{"input": "We tested this working hypothesis by probing whether AZA-1 can alter the maturation of cathepsin D in MCF-7 epithelial cells, as a model system.", "output": {"entities": {"chemical": [{"text": "AZA-1", "start": 53, "end": 58}]}}, "schema": []}
{"input": "We found that cell treatment with AZA-1 inhibited the conversion of 52 kDa procathepsin D into the mature 30 kDa protein.", "output": {"entities": {"chemical": [{"text": "AZA-1", "start": 34, "end": 39}]}}, "schema": []}
{"input": "The effects induced by AZA-1 were similar to those elicited by chlorpromazine and other agents preventing proper maturation of lysosomal enzymes, indicating that the inhibition of endocytic transfer of proforms to late endosomes/lysosomess is responsible for the effect induced by the toxin.", "output": {"entities": {"chemical": [{"text": "AZA-1", "start": 23, "end": 28}, {"text": "chlorpromazine", "start": 63, "end": 77}]}}, "schema": []}
{"input": "By immunofluorescence microscopy, we found no colocalization of cathepsin D and the early endosomal marker EEA-1 in control cells, where most of cathepsin D resides in late endosomes/lysosomes.", "output": {"entities": {}}, "schema": []}
{"input": "Co-localization of cathepsin D and EEA-1 immunoreactivity, in turn, was found in cells exposed to AZA-1, indicating that the toxin blocks protein maturation at the early steps of endocytosis, causing accumulation of procathepsin D in early endosomes.", "output": {"entities": {"chemical": [{"text": "AZA-1", "start": 98, "end": 103}]}}, "schema": []}
{"input": "The molecular alteration induced by AZA-1 involved both secreted and intracellular pools of procathepsin D, showing that the toxin effect does not result from a general impairment of vesicular trafficking but is the outcome of a perturbed centripetal process.", "output": {"entities": {"chemical": [{"text": "AZA-1", "start": 36, "end": 41}]}}, "schema": []}
{"input": "Furthermore, AZA-1 was found to inhibit procathepsin D maturation also in normal fibroblasts, showing that this molecular response is induced by this toxin in different cell types.", "output": {"entities": {"chemical": [{"text": "AZA-1", "start": 13, "end": 18}]}}, "schema": []}
{"input": "The data we obtained corroborated our hypothesis and provide a unified molecular frame for the mode of action of AZAs in animal models, involving a primary alteration of endocytic processes.", "output": {"entities": {"chemical": [{"text": "AZAs", "start": 113, "end": 117}]}}, "schema": []}
{"input": "Controlled fabrication of hexagonally close-packed Langmuir-Blodgett silica particulate monolayers from binary surfactant and solvent systems.", "output": {"entities": {"chemical": [{"text": "silica", "start": 69, "end": 75}]}}, "schema": []}
{"input": "We describe a controllable method to fabricate hexagonally close-packed Langmuir-Blodgett (LB) monolayers with stearic acid (SA) as co-surfactant and methanol as co-solvent.", "output": {"entities": {"chemical": [{"text": "stearic acid", "start": 111, "end": 123}, {"text": "methanol", "start": 150, "end": 158}]}}, "schema": []}
{"input": "The optimal SA concentrations and volume ratios of chloroform to methanol are 0. 8 mg/mL and 3: 1 for particles of 140 nm, 0. 50 mg/mL and 4: 1 for particles of 300 nm, and 0. 05 mg/mL and 5: 1 for particles of 550 nm, respectively.", "output": {"entities": {"chemical": [{"text": "chloroform", "start": 51, "end": 61}, {"text": "methanol", "start": 65, "end": 73}]}}, "schema": []}
{"input": "Additionally, SEM detections of the monolayers transferred at different surface pressures indicate that the monolayers deposited from the binary systems are more compressible.", "output": {"entities": {}}, "schema": []}
{"input": "The experimental results indicate that the interparticle repulsions and particle-water interactions can be enhanced without decreasing the particle hydrophobicity by adding SA and methanol; thus, particulate monolayers with large hexagonally close-packed domains composed of small silica particles can be successfully fabricated using LB technique.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 180, "end": 188}, {"text": "silica", "start": 281, "end": 287}]}}, "schema": []}
{"input": "We propose that the enhanced interparticle repulsion is attributed to the Columbic repulsion resulting from the attachment of SA molecules to the CTAB modified particles around the three phase contact line.", "output": {"entities": {"chemical": [{"text": "CTAB", "start": 146, "end": 150}]}}, "schema": []}
{"input": "Sesquiterpenes from the rhizomes of Curcuma heyneana.", "output": {"entities": {"chemical": [{"text": "Sesquiterpenes", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Four new germacranes [heyneanones A-D (1-4)], three new guaianes [4, 10-epizedoarondiol (5), 15-hydroxyprocurcumenol (6), 12-hydroxycurcumenol (7)], and two new spirolactones [curcumanolides C (8) and D (9)] were isolated from the rhizomes of Curcuma heyneana together with 13 known sesquiterpenes and two known labdane-type diterpenes.", "output": {"entities": {"chemical": [{"text": "germacranes", "start": 9, "end": 20}, {"text": "heyneanones A-D", "start": 22, "end": 37}, {"text": "guaianes", "start": 56, "end": 64}, {"text": "4, 10-epizedoarondiol", "start": 66, "end": 87}, {"text": "15-hydroxyprocurcumenol", "start": 93, "end": 116}, {"text": "12-hydroxycurcumenol", "start": 122, "end": 142}, {"text": "spirolactones", "start": 161, "end": 174}, {"text": "curcumanolides", "start": 176, "end": 190}, {"text": "sesquiterpenes", "start": 283, "end": 297}, {"text": "labdane", "start": 312, "end": 319}, {"text": "diterpenes", "start": 325, "end": 335}]}}, "schema": []}
{"input": "Among the isolated compounds, heyneanone A (1), heyneanone C (3), 4, 10-epizedoarondiol (5), procurcumenol (16), aerugidiol (17), zerumin A (23), and (E)-15, 16-bisnorlabda-8 (17), 11-dien-13-one (24) inhibited protein tyrosine phosphatase 1B (PTP1B) with IC (50) values of 42. 5, 35. 2, 35. 1, 45. 6, 35. 7, 10. 4, and 14. 7 mu M, respectively.", "output": {"entities": {"chemical": [{"text": "heyneanone A", "start": 30, "end": 42}, {"text": "heyneanone C", "start": 48, "end": 60}, {"text": "4, 10-epizedoarondiol", "start": 66, "end": 87}, {"text": "procurcumenol", "start": 93, "end": 106}, {"text": "aerugidiol", "start": 113, "end": 123}, {"text": "zerumin A", "start": 130, "end": 139}, {"text": "(E)-15, 16-bisnorlabda-8 (17), 11-dien-13-one", "start": 150, "end": 195}, {"text": "tyrosine", "start": 219, "end": 227}]}}, "schema": []}
{"input": "c (RGDfK) decorated micellar drug delivery system for intravesical instilled chemotherapy of superficial bladder cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this work was to develop a targeted drug delivery system with potentials for intravesical instilled chemotherapy of superficial bladder cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The amphiphilic diblock copolymer poly (epsilon-caprolactone)-b-poly (ethylene oxide) (PCL-b-PEO) was first conjugated with the cyclic (Arginine-Glycine-Aspartic acid-d-Phenylalanine-Lysine) (c (RGDfK)) and fluorescein isothiocyannate (FITC) via the functional terminal groups of hydrophilic block, and then assembled into micelles.", "output": {"entities": {"chemical": [{"text": "poly (epsilon-caprolactone)-b-poly (ethylene oxide)", "start": 34, "end": 85}, {"text": "PCL-b-PEO", "start": 87, "end": 96}, {"text": "cyclic (Arginine-Glycine-Aspartic acid-d-Phenylalanine-Lysine)", "start": 128, "end": 190}, {"text": "fluorescein isothiocyannate", "start": 207, "end": 234}, {"text": "FITC", "start": 236, "end": 240}]}}, "schema": []}
{"input": "The interaction between micelles and various model cells was well studied by means of confocal laser scanning microscopy and flow cytometry.", "output": {"entities": {}}, "schema": []}
{"input": "The c (RGDfK) on the surface of the micelle was confirmed by (1) H NMR analysis and cell affinity with human glioblastoma-astrocytoma cells (U87MG).", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 61, "end": 66}]}}, "schema": []}
{"input": "The cell viability of bladder cancer cells (T-24 cells) after incubation with doxorubicin (DOX) loaded polymeric micelles was evaluated by in vitro cytotoxicity assay.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 78, "end": 89}, {"text": "DOX", "start": 91, "end": 94}]}}, "schema": []}
{"input": "The results revealed that c (RGDfK) modified micelles showed strong affinity to T-24 cells and strong inhibitory effect on the proliferation of T-24 cells when doxorubicin drug was loaded, indicating the high affinity of c (RGDfK) to bladder cancer cells.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 160, "end": 171}]}}, "schema": []}
{"input": "The c (RGDfK) modified micelles assembled from PCL-b-PEO diblock copolymers developed in this study are of great potentials as nano-scaled drug delivery system for intravesical instilled chemotherapy of superficial bladder cancer.", "output": {"entities": {"chemical": [{"text": "PCL-b-PEO", "start": 47, "end": 56}]}}, "schema": []}
{"input": "Prolyl-hydroxylase inhibition preserves endothelial cell function in a rat model of vascular ischemia reperfusion injury.", "output": {"entities": {"chemical": [{"text": "Prolyl", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Storage protocols of vascular grafts need further improvement against ischemia-reperfusion (IR) injury.", "output": {"entities": {}}, "schema": []}
{"input": "Hypoxia elicits a variety of complex cellular responses by altering the activity of many signaling pathways, such as the oxygen-dependent prolyl-hyroxylase domain-containing enzyme (PHD).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 121, "end": 127}, {"text": "prolyl", "start": 138, "end": 144}]}}, "schema": []}
{"input": "Reduction of PHD activity during hypoxia leads to stabilization and accumulation of hypoxia inducible factor (HIF) 1 alpha.", "output": {"entities": {}}, "schema": []}
{"input": "We examined the effects of PHD inhibiton by dimethyloxalylglycine on the vasomotor responses of isolated rat aorta and aortic vascular smooth muscle cells (VSMCs) in a model of cold ischemia/warm reperfusion.", "output": {"entities": {"chemical": [{"text": "dimethyloxalylglycine", "start": 44, "end": 65}]}}, "schema": []}
{"input": "Aortic segments underwent 24 hours of cold ischemic preservation in saline or DMOG (dimethyloxalylglycine)-supplemented saline solution.", "output": {"entities": {"chemical": [{"text": "DMOG", "start": 78, "end": 82}, {"text": "dimethyloxalylglycine", "start": 84, "end": 105}]}}, "schema": []}
{"input": "We investigated endothelium-dependent and-independent vasorelaxations.", "output": {"entities": {}}, "schema": []}
{"input": "To simulate IR injury, hypochlorite (NaOCl) was added during warm reperfusion.", "output": {"entities": {"chemical": [{"text": "hypochlorite", "start": 23, "end": 35}, {"text": "NaOCl", "start": 37, "end": 42}]}}, "schema": []}
{"input": "VSMCs were incubated in NaCl or DMOG solution at 4 degrees C for 24 hours after the medium was changed for a supplied standard medium at 37 degrees C for 6 hours.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 24, "end": 28}, {"text": "DMOG", "start": 32, "end": 36}]}}, "schema": []}
{"input": "Apoptosis was assessed using the TUNEL method.", "output": {"entities": {}}, "schema": []}
{"input": "Gene expression analysis was performed using quantitative real-time polymerase chain reaction.", "output": {"entities": {}}, "schema": []}
{"input": "Cold ischemic preservation and NaOCl induced severe endothelial dysfunction, which was significantly improved by DMOG supplementation (maximal relaxation of aortic segments to acetylcholine: control 95% +/- 1% versus NaOCl 44% +/- 4% versus DMOG 68% +/- 5%).", "output": {"entities": {"chemical": [{"text": "NaOCl", "start": 31, "end": 36}, {"text": "DMOG", "start": 113, "end": 117}, {"text": "acetylcholine", "start": 176, "end": 189}, {"text": "NaOCl", "start": 217, "end": 222}, {"text": "DMOG", "start": 241, "end": 245}]}}, "schema": []}
{"input": "Number of TUNEL-positive cell nuclei was significantly higher in the NaOCl group, and DMOG treatment significantly decreased apoptosis.", "output": {"entities": {"chemical": [{"text": "NaOCl", "start": 69, "end": 74}, {"text": "DMOG", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Inducible heme-oxygenase 1 mRNA expressions were significantly higher in the DMOG group.", "output": {"entities": {"chemical": [{"text": "heme", "start": 10, "end": 14}, {"text": "DMOG", "start": 77, "end": 81}]}}, "schema": []}
{"input": "Pharmacological modulation of oxygen sensing system by DMOG in an in vitro model of vascular IR effectively preserved endothelial function.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 30, "end": 36}, {"text": "DMOG", "start": 55, "end": 59}]}}, "schema": []}
{"input": "Inhibition of PHDs could therefore be a new therapeutic avenue for protecting endothelium and vascular muscle cells against IR injury.", "output": {"entities": {}}, "schema": []}
{"input": "Transport of A1 adenosine receptor agonist tecadenoson by human and mouse nucleoside transporters: evidence for blood-brain barrier transport by murine equilibrative nucleoside transporter 1 mENT1.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 16, "end": 25}, {"text": "tecadenoson", "start": 43, "end": 54}, {"text": "nucleoside", "start": 74, "end": 84}, {"text": "nucleoside", "start": 166, "end": 176}]}}, "schema": []}
{"input": "The high density of A1 adenosine receptors in the brain results in significant potential for central nervous system (CNS)-related adverse effects with A1 agonists.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Tecadenoson is a selective A1 adenosine receptor agonist with close similarity to adenosine.", "output": {"entities": {"chemical": [{"text": "Tecadenoson", "start": 0, "end": 11}, {"text": "adenosine", "start": 30, "end": 39}, {"text": "adenosine", "start": 82, "end": 91}]}}, "schema": []}
{"input": "We studied the binding and transmembrane transport of tecadenoson by recombinant human equilibrative nucleoside transporters (hENTs) hENT1 and hENT2, and human concentrative nucleoside transporters (hCNTs) hCNT1, hCNT2, and hCNT3 in vitro and by mouse mENT1 in vivo.", "output": {"entities": {"chemical": [{"text": "tecadenoson", "start": 54, "end": 65}, {"text": "nucleoside", "start": 101, "end": 111}, {"text": "nucleoside", "start": 174, "end": 184}]}}, "schema": []}
{"input": "Binding affinities of the five recombinant human nucleoside transporters for tecadenoson differed (hENT1 > hCNT1 > hCNT3 > hENT2 > hCNT2), and tecadenoson was transported largely by hENT1.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 49, "end": 59}, {"text": "tecadenoson", "start": 77, "end": 88}, {"text": "tecadenoson", "start": 143, "end": 154}]}}, "schema": []}
{"input": "Pretreatment of mice with a phosphorylated prodrug of nitrobenzylmercaptopurine riboside, an inhibitor of mENT1, significantly decreased brain exposure to tecadenoson compared with that of the untreated (control) group, suggesting involvement of mENT1 in transport of tecadenoson across the blood-brain barrier (BBB).", "output": {"entities": {"chemical": [{"text": "nitrobenzylmercaptopurine", "start": 54, "end": 79}, {"text": "tecadenoson", "start": 155, "end": 166}, {"text": "tecadenoson", "start": 268, "end": 279}]}}, "schema": []}
{"input": "In summary, ENT1 was shown to mediate the transport of tecadenoson in vitro with recombinant and native human protein and in vivo with mice.", "output": {"entities": {"chemical": [{"text": "tecadenoson", "start": 55, "end": 66}]}}, "schema": []}
{"input": "The micromolar apparent Km value of tecadenoson for transport by native hENT1 in cultured cells suggests that hENT1 will not be saturated at clinically relevant (i. e., nanomolar) concentrations of tecadenoson, and that hENT1-mediated passage across the BBB may contribute to the adverse CNS effects observed in clinical trials.", "output": {"entities": {"chemical": [{"text": "tecadenoson", "start": 36, "end": 47}, {"text": "tecadenoson", "start": 198, "end": 209}]}}, "schema": []}
{"input": "In contrast, in cases in which a CNS effect is desired, the present results illustrate that synthetic A1 agonists that are transported by hENT1 could be used to target CNS disorders because of enhanced delivery to the brain.", "output": {"entities": {}}, "schema": []}
{"input": "Core oligosaccharide of Plesiomonas shigelloides PCM 2231 (Serotype O17) lipopolysaccharide--structural and serological analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The herein presented complete structure of the core oligosaccharide of lipopolysaccharide (LPS) P. shigelloides Polish Collection of Microorganisms (PCM) 2231 (serotype O17) was investigated by (1) H, (13) C NMR spectroscopy, mass spectrometry, chemical analyses and serological methods.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 194, "end": 199}, {"text": "(13) C", "start": 201, "end": 207}]}}, "schema": []}
{"input": "The core oligosaccharide is composed of an undecasaccharide, which represents the second core type identified for P. shigelloides serotype O17 LPS.", "output": {"entities": {}}, "schema": []}
{"input": "This structure is similar to that of the core oligosaccharide of P. shigelloides strains 302-73 (serotype O1) and 7-63 (serotype O17) and differs from these only by one sugar residue.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 169, "end": 174}]}}, "schema": []}
{"input": "Serological screening of 55 strains of P. shigelloides with the use of serum against identified core oligosaccharide conjugated with bovine serum albumin (BSA) indicated the presence of similar structures in the LPS core region of 28 O-serotypes.", "output": {"entities": {}}, "schema": []}
{"input": "This observation suggests that the core oligosaccharide structure present in strain PCM 2231 could be the most common type among P. shigelloides lipopolysaccharides.", "output": {"entities": {}}, "schema": []}
{"input": "New casbane diterpenoids from a South China Sea soft coral, Sinularia sp.", "output": {"entities": {"chemical": [{"text": "casbane diterpenoids", "start": 4, "end": 24}]}}, "schema": []}
{"input": "Six new casbane diterpenoids, named as sinularcasbanes A-F (1-6), along with six known analogues 7-12, were isolated from a South China Sea soft coral, Sinularia sp.", "output": {"entities": {"chemical": [{"text": "casbane diterpenoids", "start": 8, "end": 28}, {"text": "sinularcasbanes A-F", "start": 39, "end": 58}]}}, "schema": []}
{"input": "The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with data reported in the literature.", "output": {"entities": {}}, "schema": []}
{"input": "All compounds were evaluated for their cytotoxicity against selected cancer cell lines and the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 142, "end": 154}, {"text": "NO", "start": 156, "end": 158}]}}, "schema": []}
{"input": "The effect of magnetically induced linear aggregates on proton transverse relaxation rates of aqueous suspensions of polymer coated magnetic nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "It has been recently reported that for some suspensions of magnetic nanoparticles the transverse proton relaxation rate, R (2), is dependent on the time that the sample is exposed to an applied magnetic field.", "output": {"entities": {}}, "schema": []}
{"input": "This time dependence has been linked to the formation of linear aggregates or chains in an applied magnetic field via numerical modeling.", "output": {"entities": {}}, "schema": []}
{"input": "It is widely known that chain formation occurs in more concentrated ferrofluids systems and that this has an affect on the ferrofluid properties.", "output": {"entities": {}}, "schema": []}
{"input": "In this work we examine the relationships between colloidal stability, the formation of these linear structures, and changes observed in the proton transverse relaxation rate of aqueous suspensions of magnetic particles.", "output": {"entities": {}}, "schema": []}
{"input": "A series of iron oxide nanoparticles with varying stabilizing ligand brush lengths were synthesized.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 12, "end": 22}]}}, "schema": []}
{"input": "These systems were characterized with dynamic light scattering, transmission electron microscopy, dark-field optical microscopy, and proton transverse relaxation rate measurements.", "output": {"entities": {}}, "schema": []}
{"input": "The dark field optical microscopy and R (2) measurements were made in similar magnetic fields over the same time scale so as to correlate the reduction of the transverse relaxivity with the formation of linear aggregates.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that varying the ligand length has a direct effect on the colloidal arrangement of the system in a magnetic field, producing differences in the rate and size of chain formation, and hence systematic changes in transverse relaxation rates over time.", "output": {"entities": {}}, "schema": []}
{"input": "With increasing ligand brush length, attractive inter-particle interactions are reduced, which results in slower aggregate formation and shorter linear aggregate length.", "output": {"entities": {}}, "schema": []}
{"input": "These results have implications for the stabilization, characterization and potentially the toxicity of magnetic nanoparticle systems used in biomedical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Public health challenges and prospects for malaria control and elimination.", "output": {"entities": {}}, "schema": []}
{"input": "The past decade witnessed unprecedented efforts to control malaria, including renewed political and financial commitment and increased availability of both old and new strategies and tools.", "output": {"entities": {}}, "schema": []}
{"input": "However, malaria still represents a major health burden, particularly in Africa.", "output": {"entities": {}}, "schema": []}
{"input": "Important challenges such as the fragility of many health systems, the rise of insecticide and drug resistance, and particularly the expected decline both in funding and in the coverage of key interventions if they are not replaced as needed, urgently need to be addressed.", "output": {"entities": {}}, "schema": []}
{"input": "Further research and development is also becoming increasingly crucial.", "output": {"entities": {}}, "schema": []}
{"input": "Among other needs, common methodologies for estimating and tracking the malaria burden, new strategies to measure transmission, better understanding of immunity, and increased knowledge of the mechanisms and effects of resistance to drugs and insecticides stand out.", "output": {"entities": {}}, "schema": []}
{"input": "The ongoing efforts in research and development for new antimalarial drugs, more sensitive point-of-care rapid diagnostic tests and new insecticides need further innovation and substantial strengthening.", "output": {"entities": {}}, "schema": []}
{"input": "Clearly, efforts should focus not only on Plasmodium falciparum but also and increasingly on Plasmodium vivax, the neglected human malaria parasite.", "output": {"entities": {}}, "schema": []}
{"input": "Addressing these challenges in a comprehensive and timely way will allow us to sustain the gains made so far and make further progress in control and progressive elimination.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of toxicity between the different-type TiO (2) nanowires in vivo and in vitro.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 50, "end": 57}]}}, "schema": []}
{"input": "In this study, we compared their toxicity in vivo and in vitro based on the physicochemical properties of three different types of TiO (2) nanowires, H (2) Ti (3) O (7) nanowires (1HTO), hydrothermal treatment (2HTO), and calcination (3HTO) of 1HTO.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 131, "end": 138}, {"text": "H (2) Ti (3) O (7)", "start": 150, "end": 168}]}}, "schema": []}
{"input": "The surface of 1HTO was smooth, and the surface of 2HTO was much rougher.", "output": {"entities": {}}, "schema": []}
{"input": "The negative charge on the surface increased in the order of 2HTO, 3HTO, and 1HTO, whereas the surface area increased in the order of 3HTO, 1HTO, and 2HTO.", "output": {"entities": {}}, "schema": []}
{"input": "The lung is a main exposure route of nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "On day 28 after a single instillation (1 mg/kg), three nanowires induced a Th2-type inflammatory response together with the relative increase in CD4 (+) T cells, especially by 2HTO.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro, three TiO (2) nanowires (10 mu g/ml) commonly induced the generation of cell debris in eight cell lines which may be the potential target organ of nanoparticles, especially by 2HTO.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 16, "end": 23}]}}, "schema": []}
{"input": "It seemed that the generation of cell debris coincides with the increase in autophagosome-like vacuoles in the cytosol.", "output": {"entities": {}}, "schema": []}
{"input": "In further study using BEAS-2B cells originated from the lung, the protein amount from cells exposed to 2HTO decreased more clearly although the generation of reactive oxygen species (ROS) was less compared to 1HTO and 3HTO.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 168, "end": 174}]}}, "schema": []}
{"input": "Based on these results, we suggest that surface area may act as an important factor depends on the biological response by TiO (2) nanowires.", "output": {"entities": {"chemical": [{"text": "TiO (2)", "start": 122, "end": 129}]}}, "schema": []}
{"input": "Furthermore, the increase in autophagosome-like vacuoles may be an important cause of cell death by nanoparticles with ROS.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of BMY-14802 against L-DOPA-and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat.", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 15, "end": 24}, {"text": "L-DOPA", "start": 33, "end": 39}, {"text": "dopamine", "start": 44, "end": 52}]}}, "schema": []}
{"input": "RATIONALE: L-DOPA continues to be the primary treatment for patients with Parkinson' s disease; however, the benefits of long-term treatment are often accompanied by debilitating side effects known as dyskinesias.", "output": {"entities": {"chemical": [{"text": "L-DOPA", "start": 11, "end": 17}]}}, "schema": []}
{"input": "In recent years, several 5-HT (1A) receptor agonists have been found to reduce dyskinesia in clinical and experimental models of PD.", "output": {"entities": {}}, "schema": []}
{"input": "The purported sigma-1 antagonist, BMY-14802 has been previously demonstrated to reduce L-DOPA induced dyskinesia in a 5-HT (1A) receptor dependent manner.", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 34, "end": 43}, {"text": "L-DOPA", "start": 87, "end": 93}]}}, "schema": []}
{"input": "OBJECTIVE: In the present study, we extend these findings by examining the anti-dyskinetic potential of BMY-14802 against L-DOPA, the D (1) receptor agonist SKF81297 and the D (2) receptor agonist, quinpirole, in the hemi-parkinsonian rat model.", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 104, "end": 113}, {"text": "L-DOPA", "start": 122, "end": 128}, {"text": "SKF81297", "start": 157, "end": 165}, {"text": "quinpirole", "start": 198, "end": 208}]}}, "schema": []}
{"input": "In addition, the receptor specificity of BMY-14802' s effects was evaluated using WAY-100635, a 5-HT (1A) receptor antagonist.", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 41, "end": 50}, {"text": "WAY-100635", "start": 82, "end": 92}]}}, "schema": []}
{"input": "RESULTS: Results confirmed the dose-dependent (20 > 10 > 5 mg/kg) anti-dyskinetic effects of BMY-14802 against L-DOPA with preservation of anti-parkinsonian efficacy at 10 mg/kg.", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 93, "end": 102}, {"text": "L-DOPA", "start": 111, "end": 117}]}}, "schema": []}
{"input": "BMY-14802 at 10 and 20 mg/kg also reduced dyskinesia induced by both D (1) and D (2) receptor agonists.", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Additionally, BMY-14802' s anti-dyskinetic effects against L-DOPA, but not SKF81297 or quinpirole, were reversed by WAY-100635 (0. 5 mg/kg).", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 14, "end": 23}, {"text": "L-DOPA", "start": 59, "end": 65}, {"text": "SKF81297", "start": 75, "end": 83}, {"text": "quinpirole", "start": 87, "end": 97}, {"text": "WAY-100635", "start": 116, "end": 126}]}}, "schema": []}
{"input": "CONCLUSION: Collectively, these findings demonstrate that BMY-14802 provides anti-dyskinetic relief against L-DOPA and direct DA agonist in a preclinical model of PD, acting via multiple receptor systems and supports the utility of such compounds for the improved treatment of PD.", "output": {"entities": {"chemical": [{"text": "BMY-14802", "start": 58, "end": 67}, {"text": "L-DOPA", "start": 108, "end": 114}]}}, "schema": []}
{"input": "Contractile signaling pathways in mouse prostate smooth muscle.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: Prostate smooth muscle plays an important role in the physiological ejection of prostatic fluid and also in the pathogenesis of benign prostate hyperplasia.", "output": {"entities": {}}, "schema": []}
{"input": "Although mouse is the best genetically engineered animal model to identify potential molecular targets for human diseases, only fragmentary information is available for basic mechanism of mouse prostate contraction.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Small smooth muscle tubular rings were excised from four mouse prostate lobes to measure their isometric contractions.", "output": {"entities": {}}, "schema": []}
{"input": "High K (+), noradrenaline (NA), or acetylcholine (ACh) was applied with and without various antagonists and/or inhibitors to examine the contractile signaling pathways.", "output": {"entities": {"chemical": [{"text": "K (+)", "start": 5, "end": 10}, {"text": "noradrenaline", "start": 12, "end": 25}, {"text": "acetylcholine", "start": 35, "end": 48}, {"text": "ACh", "start": 50, "end": 53}]}}, "schema": []}
{"input": "RESULTS: Maximum amplitude of agonist-induced contractions varied greatly with different lobes but not with different locations or orientations within each lobe.", "output": {"entities": {}}, "schema": []}
{"input": "Both NA and ACh produced large contractions in ventral and dorsal rings, whereas only small contractions were elicited in lateral and anterior rings.", "output": {"entities": {"chemical": [{"text": "ACh", "start": 12, "end": 15}]}}, "schema": []}
{"input": "Combination of alpha-1 and muscarinic antagonists suppressed K (+) depolarization-induced contraction potently in ventral rings, but slightly in anterior rings.", "output": {"entities": {"chemical": [{"text": "K (+)", "start": 61, "end": 66}]}}, "schema": []}
{"input": "Blocking of either Ca (2 +)-release or Ca (2 +)-influx reduced agonist-induced contraction of ventral rings, however, a considerable amount of contractility remained even with both blockers.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 19, "end": 27}, {"text": "Ca (2 +)", "start": 39, "end": 47}]}}, "schema": []}
{"input": "Inhibitors of ROCK and PKC partially inhibited NA-induced contractions, whereas a combination of Ca (2 +)-blockers and Ca (2 +)-sensitization inhibitors strongly suppressed the contraction.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 97, "end": 105}, {"text": "Ca (2 +)", "start": 119, "end": 127}]}}, "schema": []}
{"input": "CONCLUSIONS: The ejection of prostatic fluid is differentially regulated in each prostate lobe.", "output": {"entities": {}}, "schema": []}
{"input": "In ventral prostate smooth muscle, Ca (2 +)-release, Ca (2 +)-influx, and ROCK-and PKC-mediated Ca (2 +)-sensitizations are all involved in NA-induced contractions.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 35, "end": 43}, {"text": "Ca (2 +)", "start": 53, "end": 61}, {"text": "Ca (2 +)", "start": 96, "end": 104}]}}, "schema": []}
{"input": "This finding is a useful step toward the understanding of the phenotypic changes in the smooth muscle of BPH prostate.", "output": {"entities": {}}, "schema": []}
{"input": "Prostate (c) 2013 Wiley Periodicals, Inc.", "output": {"entities": {}}, "schema": []}
{"input": "A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: Prostatic inflammation has been linked to a number of prostatic diseases such as benign prostatic hyperplasia (BPH), prostatitis syndromes, and prostate cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Major unanswered questions include what pathogenic mechanisms, such as bacterial infections, may drive the accumulation of inflammatory infiltrates in the human prostate, and how inflammation might contribute to disease.", "output": {"entities": {}}, "schema": []}
{"input": "To study this potential link in an in vivo system, we developed a mouse model of long-term bacteria-induced chronic inflammation of the prostate using a human prostatectomy-derived strain of Propionibacterium acnes.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: C57BL/6J mice were inoculated, via urethral catheterization, with vehicle control or a prostatectomy-derived strain of P. acnes (PA2).", "output": {"entities": {}}, "schema": []}
{"input": "Animals were assessed at 2 days, 1, 2, or 8 weeks post-inoculation via histology and immunohistochemistry (IHC).", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: PA2 inoculation resulted in severe acute and chronic inflammation confined to the dorsal lobe of the prostate.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic inflammation persisted for at least 8 weeks post-inoculation.", "output": {"entities": {}}, "schema": []}
{"input": "Inflammatory lesions were associated with an increase in the Ki-67 proliferative index, and diminished Nkx3. 1 and androgen receptor (AR) production.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 115, "end": 123}]}}, "schema": []}
{"input": "Interestingly, the observed response required live bacteria and both IHC and in situ hybridization assays for P. acnes indicated a potential intracellular presence of P. acnes in prostate epithelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: To our knowledge, this is the first mouse model of long-term prostatic inflammation induced by P. acnes, and more generally, any prostatectomy-derived bacterial isolate.", "output": {"entities": {}}, "schema": []}
{"input": "This model may serve as a valuable preclinical model of chronic prostatic inflammation that can be used to mechanistically study the link between inflammation and prostatic disease.", "output": {"entities": {}}, "schema": []}
{"input": "Prostate (c) 2013 Wiley Periodicals, Inc.", "output": {"entities": {}}, "schema": []}
{"input": "Phosphodiesterase 4 inhibitors augment the ability of formoterol to enhance glucocorticoid-dependent gene transcription in human airway epithelial cells: a novel mechanism for the clinical efficacy of roflumilast in severe chronic obstructive pulmonary disease.", "output": {"entities": {"chemical": [{"text": "formoterol", "start": 54, "end": 64}, {"text": "roflumilast", "start": 201, "end": 212}]}}, "schema": []}
{"input": "Post-hoc analysis of two phase III clinical studies found that the phosphodiesterase 4 (PDE4) inhibitor, roflumilast, reduced exacerbation frequency in patients with severe chronic obstructive pulmonary disease (COPD) who were taking inhaled corticosteroids (ICS) concomitantly, whereas patients not taking ICS derived no such benefit.", "output": {"entities": {"chemical": [{"text": "roflumilast", "start": 105, "end": 116}]}}, "schema": []}
{"input": "In contrast, in two different trials also performed in patients with severe COPD, roflumilast reduced exacerbation rates in the absence of ICS, indicating that PDE4 inhibition alone is sufficient for therapeutic activity to be realized.", "output": {"entities": {"chemical": [{"text": "roflumilast", "start": 82, "end": 93}]}}, "schema": []}
{"input": "Given that roflumilast is recommended as an \" add-on \" medication to patients with severe disease who will inevitably be taking a long-acting beta 2-adrenoceptor agonist (LABA)/ICS combination therapy, we tested the hypothesis that roflumilast augments the ability of glucocorticoids to induce genes with anti-inflammatory activity.", "output": {"entities": {"chemical": [{"text": "roflumilast", "start": 11, "end": 22}, {"text": "roflumilast", "start": 232, "end": 243}]}}, "schema": []}
{"input": "Using a glucocorticoid response element (GRE) luciferase reporter transfected into human airway epithelial cells [both bronchial epithelium + adenovirus 12-SV40 hybrid (BEAS-2B) cells and primary cultures], roflumilast enhanced fluticasone propionate-induced GRE-dependent transcription.", "output": {"entities": {"chemical": [{"text": "roflumilast", "start": 207, "end": 218}, {"text": "fluticasone propionate", "start": 228, "end": 250}]}}, "schema": []}
{"input": "Roflumilast also produced a sinistral displacement of the concentration-response curves that described the augmentation of GRE-dependent transcription by the LABA formoterol.", "output": {"entities": {"chemical": [{"text": "Roflumilast", "start": 0, "end": 11}, {"text": "formoterol", "start": 163, "end": 173}]}}, "schema": []}
{"input": "In BEAS-2B cells and primary airway epithelia, roflumilast interacted with formoterol in a positive cooperative manner to enhance the expression of several glucocorticoid-inducible genes that have anti-inflammatory potential.", "output": {"entities": {"chemical": [{"text": "roflumilast", "start": 47, "end": 58}, {"text": "formoterol", "start": 75, "end": 85}]}}, "schema": []}
{"input": "We suggest that the ability of roflumilast and formoterol to interact in this way supports the concept that these drugs together may impart clinical benefit beyond that achievable by an ICS alone, a PDE4 inhibitor alone, or an ICS/LABA combination therapy.", "output": {"entities": {"chemical": [{"text": "roflumilast", "start": 31, "end": 42}, {"text": "formoterol", "start": 47, "end": 57}]}}, "schema": []}
{"input": "Roflumilast may, therefore, be especially effective in patients with severe COPD.", "output": {"entities": {"chemical": [{"text": "Roflumilast", "start": 0, "end": 11}]}}, "schema": []}
{"input": "FOXO1 binds to the TAU5 motif and inhibits constitutively active androgen receptor splice variants.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 65, "end": 73}]}}, "schema": []}
{"input": "BACKGROUND: Aberrant activation of the androgen receptor (AR) is a major factor highly relevant to castration-resistant progression of prostate cancer (PCa).", "output": {"entities": {"chemical": [{"text": "androgen", "start": 39, "end": 47}]}}, "schema": []}
{"input": "FOXO1, a key downstream effector of PTEN, inhibits androgen-independent activation of the AR.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 51, "end": 59}]}}, "schema": []}
{"input": "However, the underlying mechanism remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: The inhibitory effect of FOXO1 on full-length and constitutively active splice variants of the AR was examined by luciferase reporter assays and real-time reverse transcription polymerase chain reaction (RT-qPCR).", "output": {"entities": {}}, "schema": []}
{"input": "In vitro protein binding assays and western blot analyses were used to determine the regions in FOXO1 and AR responsible for their interaction.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: We found that a putative transcription repression domain in the NH2-terminus of FOXO1 is dispensable for FOXO1 inhibition of the AR.", "output": {"entities": {"chemical": [{"text": "NH2", "start": 73, "end": 76}]}}, "schema": []}
{"input": "In vitro protein binding assays showed that FOXO1 binds to the transcription activation unit 5 (TAU5) motif in the AR NH2-terminal domain (NTD), a region required for recruitment of p160 activators including SRC-1.", "output": {"entities": {"chemical": [{"text": "NH2", "start": 118, "end": 121}]}}, "schema": []}
{"input": "Ectopic expression of SRC-1 augmented transcriptional activity of some, but not all AR splice variants examined.", "output": {"entities": {}}, "schema": []}
{"input": "Forced expression of FOXO1 blocked the effect of SRC-1 on AR variants' transcriptional activity by decreasing the binding of SRC-1 to the AR NTD.", "output": {"entities": {}}, "schema": []}
{"input": "Ectopic expression of FOXO1 inhibited expression of endogenous genes activated primarily by alternatively spliced AR variants in human castration-resistant PCa 22Rv1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: FOXO1 binds to the TAU5 motif in the AR NTD and inhibits ligand-independent activation of AR splice variants, suggesting the PTEN/FOXO1 pathway as a potential therapeutic target for inhibition of aberrant AR activation and castration-resistant PCa growth.", "output": {"entities": {}}, "schema": []}
{"input": "Prostate (c) 2013 Wiley Periodicals, Inc.", "output": {"entities": {}}, "schema": []}
{"input": "Development and characterization of an SMN2-based intermediate mouse model of Spinal Muscular Atrophy.", "output": {"entities": {}}, "schema": []}
{"input": "Spinal Muscular Atrophy (SMA) is due to the loss of the survival motor neuron gene 1 (SMN1), resulting in motor neuron (MN) degeneration, muscle atrophy and loss of motor function.", "output": {"entities": {}}, "schema": []}
{"input": "While SMN2 encodes a protein identical to SMN1, a single nucleotide difference in exon 7 causes most of the SMN2-derived transcripts to be alternatively spliced resulting in a truncated and unstable protein (SMN Delta 7).", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 57, "end": 67}]}}, "schema": []}
{"input": "SMA patients retain at least one SMN2 copy, making it an important target for therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Many of the existing SMA models are very severe, with animals typically living less than 2 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present a novel intermediate mouse model of SMA based upon the human genomic SMN2 gene.", "output": {"entities": {}}, "schema": []}
{"input": "Genetically, this model is similar to the well-characterized SMN Delta 7 model; however, we have manipulated the SMN Delta 7 transgene to encode a modestly more functional protein referred to as SMN read-through (SMN (RT)).", "output": {"entities": {}}, "schema": []}
{"input": "By introducing the SMN (RT) transgene onto the background of a severe mouse model of SMA (SMN2 (+/+); Smn (-/-)), disease severity was significantly decreased based upon a battery of phenotypic parameters, including MN pathology and a significant extension in survival.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, there is not a full phenotypic correction, allowing for the examination of a broad range of therapeutics, including SMN2-dependent and SMN-independent pathways.", "output": {"entities": {}}, "schema": []}
{"input": "This novel animal model serves as an important biological and therapeutic model for less severe forms of SMA and provides an in vivo validation of the SMN (RT) protein.", "output": {"entities": {}}, "schema": []}
{"input": "Superatom paramagnetism enables gold nanocluster heating in applied radiofrequency fields.", "output": {"entities": {}}, "schema": []}
{"input": "The Au102 (pMBA) 44 nanocluster becomes a superatom paramagnet after chemical oxidation.", "output": {"entities": {"chemical": [{"text": "Au102 (pMBA) 44", "start": 4, "end": 19}]}}, "schema": []}
{"input": "Solutions of paramagnetic Au102 (pMBA) 44 heat in an oscillating magnetic field component of an RF field, but not in the electric component.", "output": {"entities": {"chemical": [{"text": "Au102 (pMBA) 44", "start": 26, "end": 41}]}}, "schema": []}
{"input": "Combined, these experiments suggest that paramagnetic Au102 (pMBA) 44 heats through interactions of spin magnetic moment with an external oscillating magnetic field.", "output": {"entities": {"chemical": [{"text": "Au102 (pMBA) 44", "start": 54, "end": 69}]}}, "schema": []}
{"input": "These results may clarify some current controversy regarding gold nanoparticle heating in radiofrequency fields.", "output": {"entities": {}}, "schema": []}
{"input": "Signature of singlet open-shell character on the optically allowed singlet excitation energy and singlet-triplet energy gap.", "output": {"entities": {}}, "schema": []}
{"input": "A signature of singlet open-shell character on the optically allowed singlet excitation energy and singlet-triplet energy gap is theoretically illuminated for open-shell singlet molecules.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of a two-site diradical model with two electrons in two orbitals, the linear dependence of these excitation energies on the transfer integral, which is equivalent to the energy gap between the highest occupied (HOMO) and the lowest unoccupied (LUMO) molecular orbitals in the H u ckel theory, is found to be broken down in the high diradical character region due to an increase in electron correlation in the open-shell singlet ground state.", "output": {"entities": {}}, "schema": []}
{"input": "A series of polyacenes shows the similar behavior of the optically allowed singlet excitation energies obtained by time-dependent spin-flip density functional theory calculations and experiments, which bears testimony to the singlet open-shell character in long polyacenes.", "output": {"entities": {"chemical": [{"text": "polyacenes", "start": 12, "end": 22}]}}, "schema": []}
{"input": "High-resolution zero-field NMR J-spectroscopy of aromatic compounds.", "output": {"entities": {}}, "schema": []}
{"input": "We report the acquisition and interpretation of nuclear magnetic resonance (NMR) J-spectra at zero magnetic field for a series of benzene derivatives, demonstrating the analytical capabilities of zero-field NMR.", "output": {"entities": {"chemical": [{"text": "benzene", "start": 130, "end": 137}]}}, "schema": []}
{"input": "The zeroth-order spectral patterns do not overlap, which allows for straightforward determination of the spin interactions of substituent functional groups.", "output": {"entities": {}}, "schema": []}
{"input": "Higher-order effects cause additional line splittings, revealing additional molecular information.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate resonance linewidths as narrow as 11 mHz, permitting resolution of minute frequency differences and precise determination of long-range J-couplings.", "output": {"entities": {}}, "schema": []}
{"input": "The measurement of J-couplings with the high precision offered by zero-field NMR may allow further refinements in the determination of molecular structure and conformation.", "output": {"entities": {}}, "schema": []}
{"input": "Solvent and pressure effects on the motions of encapsulated guests: tuning the flexibility of a supramolecular host.", "output": {"entities": {}}, "schema": []}
{"input": "The supramolecular host assembly [Ga4L6] (12-) [1; L = 1, 5-bis (2, 3-dihydroxybenzamido) naphthalene] contains a flexible, hydrophobic interior cavity that can encapsulate cationic guest molecules and catalyze a variety of chemical transformations.", "output": {"entities": {"chemical": [{"text": "[Ga4L6] (12-)", "start": 33, "end": 46}, {"text": "1, 5-bis (2, 3-dihydroxybenzamido) naphthalene", "start": 55, "end": 101}]}}, "schema": []}
{"input": "The Ar-CH2 bond rotational barrier for encapsulated ortho-substituted benzyl phosphonium guest molecules is sensitive to the size and shape of the host interior space.", "output": {"entities": {"chemical": [{"text": "Ar-CH2", "start": 4, "end": 10}, {"text": "ortho-substituted benzyl phosphonium", "start": 52, "end": 88}]}}, "schema": []}
{"input": "Here we examine how changes in bulk solvent (water, methanol, or DMF) or applied pressure (up to 150 MPa) affect the rotational dynamics of encapsulated benzyl phosphonium guests, as a way to probe changes in host cavity size or flexibility.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 52, "end": 60}, {"text": "DMF", "start": 65, "end": 68}, {"text": "benzyl phosphonium", "start": 153, "end": 171}]}}, "schema": []}
{"input": "When host 1 is dissolved in organic solvents with large solvent internal pressures (d U/d V) T, we find that the free energy barrier to Ar-CH2 bond rotation increases by 1-2 kcal/mol, compared with that in aqueous solution.", "output": {"entities": {"chemical": [{"text": "Ar-CH2", "start": 136, "end": 142}]}}, "schema": []}
{"input": "Likewise, when external pressure is applied to the host-guest complex in solution, the bond rotational rates for the encapsulated guests decrease.", "output": {"entities": {}}, "schema": []}
{"input": "The magnitude of these rate changes and the volumes of activation obtained using either solvent internal pressure or applied external pressure are very similar.", "output": {"entities": {}}, "schema": []}
{"input": "NOE distance measurements reveal shorter average host-guest distances (~ 0. 3 A) in organic versus aqueous solution.", "output": {"entities": {}}, "schema": []}
{"input": "These experiments demonstrate that increasing solvent internal pressure or applied external pressure reduces the host cavity size or flexibility, resulting in more restricted motions for encapsulated guest molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Changing bulk solvent or external pressure might therefore be used to tune the physical properties or reactivity of guest molecules encapsulated in a flexible supramolecular host.", "output": {"entities": {}}, "schema": []}
{"input": "Allometric scaling and prediction of concentration-time profiles of coagulation factors in humans from animals.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "Allometric scaling is a useful tool in early drug development and can be used for the prediction of human pharmacokinetic (PK) parameters from animal PK parameters.", "output": {"entities": {}}, "schema": []}
{"input": "The main objective of this work was to predict concentration-time profiles of coagulation factors in humans in a multi-compartment system using animal PK parameters.", "output": {"entities": {}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "The prediction of concentration-time profiles in humans in a multi-compartment system was based on the predicted values of clearance and volumes of distribution (V (c), V (ss) and V (beta)) from animals.", "output": {"entities": {}}, "schema": []}
{"input": "Five coagulation factors from the literature were chosen that were described by two-compartment model in both humans and animals.", "output": {"entities": {}}, "schema": []}
{"input": "Clearance and volumes of distribution from animals were allometrically scaled to humans and then were used to predict concentration-time profiles in humans.", "output": {"entities": {}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "The predicted concentration-time profile for a given coagulation factor was accurate for most of the time points.", "output": {"entities": {}}, "schema": []}
{"input": "Percent prediction error range varied across coagulation factors.", "output": {"entities": {}}, "schema": []}
{"input": "The prediction error > 50% was observed either at 1 or a maximum of two time points for a given drug.", "output": {"entities": {}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "The study indicated that the allometric scaling can be useful in the prediction of concentration-time profiles of coagulation factors in humans from animals and may be helpful in designing a first-in-human study.", "output": {"entities": {}}, "schema": []}
{"input": "ADME characterization in rats revealed immediate secretion of AZD7903 into the stomach after IV dosing.", "output": {"entities": {"chemical": [{"text": "AZD7903", "start": 62, "end": 69}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "The distribution of AZD7903 and/or its metabolites was studied in rats following a single p. o. or i. v. dose using quantitative whole-body autoradiography (QWBA).", "output": {"entities": {"chemical": [{"text": "AZD7903", "start": 20, "end": 27}]}}, "schema": []}
{"input": "At 5 min after i. v. administration of the (14) C compound, high levels of radioactivity were observed in the fundus of the stomach compared to blood and plasma and the rest of the stomach, indicating an active secretion of (14) C material into the stomach.", "output": {"entities": {"chemical": [{"text": "(14) C", "start": 43, "end": 49}, {"text": "(14) C", "start": 224, "end": 230}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "Also, excretion and pharmacokinetics were studied following p. o. and i. v. dosage in rats.", "output": {"entities": {}}, "schema": []}
{"input": "The radioactivity was mainly excreted via feces, and even in i. v. administered bile-duct cannulated (BDC) animals a significant part of radioactivity (26% in males and 57% in females) was recovered in the feces in the form of parent compound and two minor metabolic products.", "output": {"entities": {}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "The compound was well absorbed (F% 98 in males and 76 in females), and showed low clearance in plasma (0. 14 L/h/kg in males and 0. 03 L/h/kg in females) and low-intermediate Vd (ss) (0. 7 L/kg).", "output": {"entities": {}}, "schema": []}
{"input": "Clear differences in metabolic pathways (qualitative) and rates (quantitative) and consequently in PK parameters between sexes were observed.", "output": {"entities": {}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, the results indicate AZD7903 being substrate for a transporter protein and support the hypothesis that the differences in disposition between sexes are due to differences in metabolic pathways and rates.", "output": {"entities": {"chemical": [{"text": "AZD7903", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Metabolically obese status with normal weight is associated with both the prevalence and severity of angiographic coronary artery disease.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE: We evaluated prevalence and severity of angiographic coronary artery disease (CAD) according to groups by metabolically obese (MO) and/or weight status.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIAL/METHODS: Normal weight was defined as body mass index (BMI, kg/m (2)) < 25 and obesity was defined as BMI >= 25.", "output": {"entities": {}}, "schema": []}
{"input": "The MO was determined using the National Cholesterol Education Program-Adult Treatment Panel III classification with Korean-specific cutoffs for abdominal obesity.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 41, "end": 52}]}}, "schema": []}
{"input": "Therefore, a total of 856 subjects were categorized as follows: (1) metabolically healthy and normal weight (MHNW); (2) metabolically obese but normal weight (MONW); (3) metabolically healthy but obese (MHO); and (4) metabolically abnormally obese (MAO).", "output": {"entities": {}}, "schema": []}
{"input": "The presence of obstructive lesion >= 50% of coronary artery was considered as an angiographic CAD and the Gensini scoring system was used for the severity.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: MONW or MO showed a higher prevalence of CAD than MHNW or non-MO after adjustment for age and sex, respectively (MONW, odds ratio [OR] = 1. 69, 95% confidence interval [CI]: 1. 13-2. 51 and MO, OR = 1. 44, 95% CI: 1. 09-1. 91).", "output": {"entities": {}}, "schema": []}
{"input": "In subjects without diabetes mellitus (DM), MONW or MO showed a marginally higher prevalence of CAD (MONW, OR = 1. 58, 95% CI: 0. 96-2. 61 and MO, OR = 1. 41, 95% CI: 0. 96-2. 08).", "output": {"entities": {}}, "schema": []}
{"input": "MONW was independently associated with a higher severity of angiographic CAD than MHNW after age, sex, glomerular filtration rate, smoking status, high sensitive C-reactive protein, and use of anti-platelet and anti-angina drugs (beta = 0. 118, P = 0. 005).", "output": {"entities": {}}, "schema": []}
{"input": "And MO was associated with a higher severity of angiographic CAD than non-MO after adjustment for age and sex (beta = 0. 077, P = 0. 024).", "output": {"entities": {}}, "schema": []}
{"input": "The above associations were also consistent in subjects without DM (MONW, beta = 0. 147, P = 0. 003 and MO, beta = 0. 129, P = 0. 005).", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: MONW or MO is associated with both the prevalence and severity of angiographic CAD after adjustment for age and sex and MONW is independently associated with the severity of angiographic CAD irrespective of DM.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, subjects with MO but normal weight (MONW) should be carefully examined for angiographic CAD.", "output": {"entities": {}}, "schema": []}
{"input": "Quasiclassical trajectory and statistical quantum calculations for the C + OH --> CO + H reaction on the first excited 1 (2) A'' potential energy surface.", "output": {"entities": {"chemical": [{"text": "C", "start": 71, "end": 72}, {"text": "OH", "start": 75, "end": 77}, {"text": "CO", "start": 82, "end": 84}, {"text": "H", "start": 87, "end": 88}]}}, "schema": []}
{"input": "We report quasiclassical trajectory dynamical calculations for the C ((3) P) + OH (X (2) Pi) --> CO (a (3) Pi) + H ((2) S) using a recently developed ab initio potential energy surface for the first electronic state of HCO of 1 (2) A'' symmetry.", "output": {"entities": {"chemical": [{"text": "C", "start": 67, "end": 68}, {"text": "OH", "start": 79, "end": 81}, {"text": "CO", "start": 97, "end": 99}, {"text": "H", "start": 113, "end": 114}, {"text": "HCO", "start": 219, "end": 222}]}}, "schema": []}
{"input": "The dependence of integral cross sections on the collision energy was determined.", "output": {"entities": {}}, "schema": []}
{"input": "Product energy and angular distributions have also been calculated.", "output": {"entities": {}}, "schema": []}
{"input": "Integral cross sections show no energy threshold and decrease as the collision energy increases.", "output": {"entities": {}}, "schema": []}
{"input": "The comparison with results obtained from a statistical quantum method seems to confirm that the reaction is mainly dominated by an indirect mechanism in which a long-lived intermediate complex is involved.", "output": {"entities": {}}, "schema": []}
{"input": "Biotransformation pathways of biocides and pharmaceuticals in freshwater crustaceans based on structure elucidation of metabolites using high resolution mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "So far, there is limited information on biotransformation mechanisms and products of polar contaminants in freshwater crustaceans.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, metabolites of biocides and pharmaceuticals formed in Gammarus pulex and Daphnia magna were identified using liquid chromatography-high resolution mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Different confidence levels were assigned to the identification of metabolites without reference standards using a framework based on the background evidence used for structure elucidation.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-five metabolites were tentatively identified for irgarol, terbutryn, tramadol, and venlafaxine in G. pulex (21 via oxidation and 4 via conjugation reactions) and 11 metabolites in D. magna (7 via oxidation and 4 via conjugation reactions), while no evidence of metabolites for clarithromycin and valsartan was found.", "output": {"entities": {"chemical": [{"text": "irgarol", "start": 56, "end": 63}, {"text": "terbutryn", "start": 65, "end": 74}, {"text": "tramadol", "start": 76, "end": 84}, {"text": "venlafaxine", "start": 90, "end": 101}, {"text": "clarithromycin", "start": 284, "end": 298}, {"text": "valsartan", "start": 303, "end": 312}]}}, "schema": []}
{"input": "Of the 360 metabolites predicted for the four parent compounds using pathway prediction systems and expert knowledge, 23 products were true positives, while 2 identified metabolites were unexpected products.", "output": {"entities": {}}, "schema": []}
{"input": "Observed oxidative reactions included N-and O-demethylation, hydroxylation, and N-oxidation.", "output": {"entities": {"chemical": [{"text": "N", "start": 38, "end": 39}, {"text": "O", "start": 44, "end": 45}, {"text": "N", "start": 80, "end": 81}]}}, "schema": []}
{"input": "Glutathione conjugation of selected biocides followed by subsequent reactions forming cysteine conjugates was described for the first time in freshwater invertebrates.", "output": {"entities": {"chemical": [{"text": "Glutathione", "start": 0, "end": 11}, {"text": "cysteine", "start": 86, "end": 94}]}}, "schema": []}
{"input": "Cloning, Characterization, and Sulfonamide and Thiol Inhibition Studies of an alpha-Carbonic Anhydrase from Trypanosoma cruzi, the Causative Agent of Chagas Disease.", "output": {"entities": {"chemical": [{"text": "Sulfonamide", "start": 31, "end": 42}, {"text": "Thiol", "start": 47, "end": 52}]}}, "schema": []}
{"input": "An alpha-carbonic anhydrase (CA, EC 4. 2. 1. 1) has been identified, cloned, and characterized from the unicellular protozoan Trypanosoma cruzi, the causative agent of Chagas disease.", "output": {"entities": {}}, "schema": []}
{"input": "The enzyme (TcCA) has a very high catalytic activity for the CO (2) hydration reaction, being similar kinetically to the human (h) isoform hCA II, although it is devoid of the His64 proton shuttle.", "output": {"entities": {"chemical": [{"text": "CO (2)", "start": 61, "end": 67}, {"text": "His64", "start": 176, "end": 181}]}}, "schema": []}
{"input": "A large number of aromatic/heterocyclic sulfonamides and some 5-mercapto-1, 3, 4-thiadiazoles were investigated as TcCA inhibitors.", "output": {"entities": {"chemical": [{"text": "aromatic/heterocyclic sulfonamides", "start": 18, "end": 52}, {"text": "5-mercapto-1, 3, 4-thiadiazoles", "start": 62, "end": 93}]}}, "schema": []}
{"input": "The aromatic sulfonamides were weak inhibitors (K (I) values of 192 nM to 84 mu M), whereas some heterocyclic compounds inhibited the enzyme with K (I) values in the range 61. 6-93. 6 nM.", "output": {"entities": {"chemical": [{"text": "aromatic sulfonamides", "start": 4, "end": 25}]}}, "schema": []}
{"input": "The thiols were the most potent in vitro inhibitors (K (I) values of 21. 1-79. 0 nM), and some of them also inhibited the epimastigotes growth of two T. cruzi strains in vivo.", "output": {"entities": {"chemical": [{"text": "thiols", "start": 4, "end": 10}]}}, "schema": []}
{"input": "Cell division: kinetochores SKAdaddle.", "output": {"entities": {}}, "schema": []}
{"input": "Accurate chromosome segregation during cell division requires that kinetochores couple microtubule dynamics to chromosome movement.", "output": {"entities": {}}, "schema": []}
{"input": "New research reveals that the kinetochore-associated Ska1 complex hangs on to depolymerizing microtubules and brings some important friends along for the ride.", "output": {"entities": {}}, "schema": []}
{"input": "Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia.", "output": {"entities": {}}, "schema": []}
{"input": "Accumulation of nanoparticles in solid tumors depends on their extravasation.", "output": {"entities": {}}, "schema": []}
{"input": "However, vascular permeability is very heterogeneous within a tumor and among different tumor types, hampering efficient delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Local hyperthermia at a tumor can improve nanoparticle delivery by increasing tumor vasculature permeability, perfusion and interstitial fluid flow.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study is to investigate hyperthermia conditions required to improve tumor vasculature permeability, subsequent liposome extravasation and interstitial penetration in 4 tumor models.", "output": {"entities": {}}, "schema": []}
{"input": "Tumors are implanted in dorsal skin flap window chambers and observed for liposome (~ 85 nm) accumulation by intravital confocal microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Local hyperthermia at 41 degrees C for 30 min initiates liposome extravasation through permeable tumor vasculature in all 4 tumor models.", "output": {"entities": {}}, "schema": []}
{"input": "A further increase in nanoparticle extravasation occurs while continuing heating to 1h, which is a clinically relevant duration.", "output": {"entities": {}}, "schema": []}
{"input": "After hyperthermia, the tumor vasculature remains permeable for 8h.", "output": {"entities": {}}, "schema": []}
{"input": "We visualize gaps in the endothelial lining of up to 10 mu m induced by HT.", "output": {"entities": {}}, "schema": []}
{"input": "Liposomes extravasate through these gaps and penetrate into the interstitial space to at least 27. 5 mu m in radius from the vessel walls.", "output": {"entities": {}}, "schema": []}
{"input": "Whole body optical imaging confirms HT induced extravasation while liposome extravasation was absent at normothermia.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, a thermal dose of 41 degrees C for 1h is effective to induce long-lasting permeable tumor vasculature for liposome extravasation and interstitial penetration.", "output": {"entities": {}}, "schema": []}
{"input": "These findings hold promise for improved intratumoral drug delivery upon application of local mild hyperthermia prior to administration of nanoparticle-based drug delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicological, toxicokinetic and gastroprotective evaluation of the benzaldehyde semicarbazone.", "output": {"entities": {"chemical": [{"text": "benzaldehyde semicarbazone", "start": 68, "end": 94}]}}, "schema": []}
{"input": "Benzaldehyde semicarbazone (BS) has presented positive results in several pharmacological models, including anticonvulsivant and anti-inflammatory models.", "output": {"entities": {"chemical": [{"text": "Benzaldehyde semicarbazone", "start": 0, "end": 26}]}}, "schema": []}
{"input": "The present study evaluated the preclinical toxicity (acute and subchronic), as well as the toxicokinetic and gastroprotective effects of BS against ethanol lesions.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 149, "end": 156}]}}, "schema": []}
{"input": "Oral doses of 300 and 2000mg/kg were used in the preclinical acute toxicity study; 100, 200, and 300mg/kg were used in both the subchronic toxicity evaluation and the gastric study; and 300mg/kg was used in the toxicokinetic study.", "output": {"entities": {}}, "schema": []}
{"input": "No impact from the dose of 300mg/kg could be identified; while, one animal died at 2000mg/kg in the acute toxicity test.", "output": {"entities": {}}, "schema": []}
{"input": "In the subchronic toxicity test, changes in the biochemical parameters of the liver, as well as in the histopatological evaluation, demonstrated that BS is a hepatotoxic drug.", "output": {"entities": {}}, "schema": []}
{"input": "BS proved to be effective for moderate and severe gastric lesions.", "output": {"entities": {}}, "schema": []}
{"input": "In the toxicokinetics study, BS presented a low concentration and rapid plasma disappearance.", "output": {"entities": {}}, "schema": []}
{"input": "Several results also indicate that BS is likely to be mostly eliminated from the liver and may well undergo a first-pass effect after oral absorption.", "output": {"entities": {}}, "schema": []}
{"input": "It was impossible to estimate the noobserved-adverse-effect-levels (NOAEL) and lowest-observed-adverse-effect-levels (LOAEL) due to the presence of hepatotoxicity in all tested doses.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of Li-Mn-O mesocrystals with controlled crystal phases through topotactic transformation of MnCO 3.", "output": {"entities": {"chemical": [{"text": "Li", "start": 13, "end": 15}, {"text": "Mn", "start": 16, "end": 18}, {"text": "O", "start": 19, "end": 20}, {"text": "MnCO 3", "start": 102, "end": 108}]}}, "schema": []}
{"input": "Mesocrystals of Li-Mn-O compounds, such as LiMn2O4, Li2MnO3, and LiMnO2-Li2MnO3, consisting of oriented nanoscale units were selectively produced under hydrothermal conditions from biomimetically prepared MnCO3 mesocrystals.", "output": {"entities": {"chemical": [{"text": "Li", "start": 16, "end": 18}, {"text": "Mn", "start": 19, "end": 21}, {"text": "O", "start": 22, "end": 23}, {"text": "LiMn2O4", "start": 43, "end": 50}, {"text": "Li2MnO3", "start": 52, "end": 59}, {"text": "LiMnO2", "start": 65, "end": 71}, {"text": "Li2MnO3", "start": 72, "end": 79}, {"text": "MnCO3", "start": 205, "end": 210}]}}, "schema": []}
{"input": "Topotactic transformation through the intermediate phase of Mn5O8 inheriting a hierarchical structure of the MnCO3 precursor was essential for the formation of the mesocrystal compounds.", "output": {"entities": {"chemical": [{"text": "Mn5O8", "start": 60, "end": 65}, {"text": "MnCO3", "start": 109, "end": 114}]}}, "schema": []}
{"input": "The crystal phases were successfully controlled by varying the conditions for the hydrothermal reactions.", "output": {"entities": {}}, "schema": []}
{"input": "The Li-Mn-O mesocrystals have considerable potential as cathodes of Li-ion batteries.", "output": {"entities": {"chemical": [{"text": "Li", "start": 4, "end": 6}, {"text": "Mn", "start": 7, "end": 9}, {"text": "O", "start": 10, "end": 11}, {"text": "Li", "start": 68, "end": 70}]}}, "schema": []}
{"input": "Time-of-flight magnetic flow cytometry in whole blood with integrated sample preparation.", "output": {"entities": {}}, "schema": []}
{"input": "Rapid and specific rare cell detection for point-of-care testing requires an integration of the sample preparation for flow cytometry.", "output": {"entities": {}}, "schema": []}
{"input": "To achieve such a challenging goal we have developed a magnetic flow cytometry technique which applies magnetophoresis to perform cell enrichment, focusing, and background elimination in a single step.", "output": {"entities": {}}, "schema": []}
{"input": "Time-of-flight measurements are performed with integrated magnetic sensors to detect specifically cancer cells and cell diameters in whole blood.", "output": {"entities": {}}, "schema": []}
{"input": "Ventral tegmental area GABA neurons and opiate motivation.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 23, "end": 27}]}}, "schema": []}
{"input": "RATIONALE: Past research has demonstrated that when an animal changes from a previously drug-naive to an opiate-dependent and withdrawn state, morphine' s motivational effects are switched from a tegmental pedunculopontine nucleus (TPP)-dependent to a dopamine-dependent pathway.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 143, "end": 151}, {"text": "dopamine", "start": 252, "end": 260}]}}, "schema": []}
{"input": "Interestingly, a corresponding change is observed in ventral tegmental area (VTA) GABA (A) receptors, which change from mediating hyperpolarization of VTA GABA neurons to mediating depolarization.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 82, "end": 86}, {"text": "GABA", "start": 155, "end": 159}]}}, "schema": []}
{"input": "OBJECTIVES: The present study investigated whether pharmacological manipulation of VTA GABA (A) receptor activity could directly influence the mechanisms underlying opiate motivation.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 87, "end": 91}]}}, "schema": []}
{"input": "RESULTS: Using an unbiased place conditioning procedure, we demonstrated that in Wistar rats, intra-VTA administration of furosemide, a Cl (-) cotransporter inhibitor, was able to promote a switch in the mechanisms underlying morphine' s motivational properties, one which is normally observed only after chronic opiate exposure.", "output": {"entities": {"chemical": [{"text": "furosemide", "start": 122, "end": 132}, {"text": "Cl (-)", "start": 136, "end": 142}, {"text": "morphine", "start": 226, "end": 234}]}}, "schema": []}
{"input": "This behavioral switch was prevented by intra-VTA administration of acetazolamide, an inhibitor of the bicarbonate ion-producing carbonic anhydrase enzyme.", "output": {"entities": {"chemical": [{"text": "acetazolamide", "start": 68, "end": 81}, {"text": "bicarbonate", "start": 103, "end": 114}]}}, "schema": []}
{"input": "Electrophysiological recordings of mouse VTA showed that furosemide reduced the sensitivity of VTA GABA neurons to inhibition by the GABA (A) receptor agonist muscimol, instead increasing the firing rate of a significant subset of these GABA neurons.", "output": {"entities": {"chemical": [{"text": "furosemide", "start": 57, "end": 67}, {"text": "GABA", "start": 99, "end": 103}, {"text": "GABA", "start": 133, "end": 137}, {"text": "muscimol", "start": 159, "end": 167}, {"text": "GABA", "start": 237, "end": 241}]}}, "schema": []}
{"input": "CONCLUSIONS: Our results suggest that the carbonic anhydrase enzyme may constitute part of a common VTA GABA neuron-based biological pathway responsible for controlling the mechanisms underlying opiate motivation, supporting the hypothesis that VTA GABA (A) receptor hyperpolarization or depolarization is responsible for selecting TPP-or dopamine-dependent motivational outputs, respectively.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 104, "end": 108}, {"text": "GABA", "start": 249, "end": 253}, {"text": "dopamine", "start": 339, "end": 347}]}}, "schema": []}
{"input": "Effects of monocarboxylate transporter inhibition on the oral toxicokinetics/toxicodynamics of gamma-hydroxybutyrate and gamma-butyrolactone.", "output": {"entities": {"chemical": [{"text": "monocarboxylate", "start": 11, "end": 26}, {"text": "gamma-hydroxybutyrate", "start": 95, "end": 116}, {"text": "gamma-butyrolactone", "start": 121, "end": 140}]}}, "schema": []}
{"input": "Respiratory depression and death secondary to respiratory arrest have occurred after oral overdoses of gamma-hydroxybutyrate (GHB) and its precursor gamma-butyrolactone (GBL).", "output": {"entities": {"chemical": [{"text": "gamma-hydroxybutyrate", "start": 103, "end": 124}, {"text": "GHB", "start": 126, "end": 129}, {"text": "gamma-butyrolactone", "start": 149, "end": 168}, {"text": "GBL", "start": 170, "end": 173}]}}, "schema": []}
{"input": "GHB is a substrate for monocarboxylate transporters (MCTs), and increasing GHB renal clearance or decreasing GHB absorption via MCT inhibition represents a potential treatment strategy for GHB/GBL overdose.", "output": {"entities": {"chemical": [{"text": "GHB", "start": 0, "end": 3}, {"text": "monocarboxylate", "start": 23, "end": 38}, {"text": "GHB", "start": 75, "end": 78}, {"text": "GHB", "start": 109, "end": 112}, {"text": "GHB", "start": 189, "end": 192}, {"text": "GBL", "start": 193, "end": 196}]}}, "schema": []}
{"input": "In these studies, GHB and GBL were administered in doses of 1. 92, 5. 77, and 14. 4 mmol/kg orally with and without MCT inhibition to determine effects of this treatment strategy on the oral toxicokinetics and toxicodynamics of GHB and GBL.", "output": {"entities": {"chemical": [{"text": "GHB", "start": 18, "end": 21}, {"text": "GBL", "start": 26, "end": 29}, {"text": "GHB", "start": 228, "end": 231}, {"text": "GBL", "start": 236, "end": 239}]}}, "schema": []}
{"input": "The competitive MCT inhibitor l-lactate was administered by intravenous infusion starting 1 hour after GHB and GBL administration.", "output": {"entities": {"chemical": [{"text": "l-lactate", "start": 30, "end": 39}, {"text": "GHB", "start": 103, "end": 106}, {"text": "GBL", "start": 111, "end": 114}]}}, "schema": []}
{"input": "Oral administration of l-lactate and the MCT inhibitor luteolin was also evaluated.", "output": {"entities": {"chemical": [{"text": "l-lactate", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Respiratory depression was measured using plethysmography.", "output": {"entities": {}}, "schema": []}
{"input": "Intravenous l-lactate, but not oral treatments, significantly increased GHB renal and/or oral clearances.", "output": {"entities": {"chemical": [{"text": "l-lactate", "start": 12, "end": 21}, {"text": "GHB", "start": 72, "end": 75}]}}, "schema": []}
{"input": "At the low dose of GHB and GBL, i. v. l-lactate increased GHB renal clearance.", "output": {"entities": {"chemical": [{"text": "GHB", "start": 19, "end": 22}, {"text": "GBL", "start": 27, "end": 30}, {"text": "l-lactate", "start": 38, "end": 47}, {"text": "GHB", "start": 58, "end": 61}]}}, "schema": []}
{"input": "Due to the increased contribution of renal clearance to total clearance at the moderate dose, increased renal clearance translated to an increase in oral clearance.", "output": {"entities": {}}, "schema": []}
{"input": "At the highest GHB dose, oral clearance was increased without a significant change in renal clearance.", "output": {"entities": {"chemical": [{"text": "GHB", "start": 15, "end": 18}]}}, "schema": []}
{"input": "The lack of effect of i. v. l-lactate on renal clearance after a high oral GHB dose suggests possible effects of i. v. l-lactate on MCT-mediated absorption.", "output": {"entities": {"chemical": [{"text": "l-lactate", "start": 28, "end": 37}, {"text": "GHB", "start": 75, "end": 78}, {"text": "l-lactate", "start": 119, "end": 128}]}}, "schema": []}
{"input": "The resulting increases in oral clearance improved respiratory depression.", "output": {"entities": {}}, "schema": []}
{"input": "Intravenous l-lactate also reduced mortality with the high GBL dose.", "output": {"entities": {"chemical": [{"text": "l-lactate", "start": 12, "end": 21}, {"text": "GBL", "start": 59, "end": 62}]}}, "schema": []}
{"input": "These data indicate i. v. l-lactate represents a potential treatment strategy in oral overdose of GHB and GBL.", "output": {"entities": {"chemical": [{"text": "l-lactate", "start": 26, "end": 35}, {"text": "GHB", "start": 98, "end": 101}, {"text": "GBL", "start": 106, "end": 109}]}}, "schema": []}
{"input": "Antidepressant treatment and emotional processing: can we dissociate the roles of serotonin and noradrenaline?", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 82, "end": 91}, {"text": "noradrenaline", "start": 96, "end": 109}]}}, "schema": []}
{"input": "The ability to match individual patients to tailored treatments has the potential to greatly improve outcomes for individuals suffering from major depression.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, while the vast majority of antidepressant treatments affect either serotonin or noradrenaline or a combination of these two neurotransmitters, it is not known whether there are particular patients or symptom profiles which respond preferentially to the potentiation of serotonin over noradrenaline or vice versa.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 82, "end": 91}, {"text": "noradrenaline", "start": 95, "end": 108}, {"text": "serotonin", "start": 284, "end": 293}, {"text": "noradrenaline", "start": 299, "end": 312}]}}, "schema": []}
{"input": "Experimental medicine models suggest that the primary mode of action of these treatments may be to remediate negative biases in emotional processing.", "output": {"entities": {}}, "schema": []}
{"input": "Such models may provide a useful framework for interrogating the specific actions of antidepressants.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we therefore review evidence from studies examining the effects of drugs which potentiate serotonin, noradrenaline or a combination of both neurotransmitters on emotional processing.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 96, "end": 105}, {"text": "noradrenaline", "start": 107, "end": 120}]}}, "schema": []}
{"input": "These results suggest that antidepressants targeting serotonin and noradrenaline may have some specific actions on emotion and reward processing which could be used to improve tailoring of treatment or to understand the effects of dual-reuptake inhibition.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 53, "end": 62}, {"text": "noradrenaline", "start": 67, "end": 80}]}}, "schema": []}
{"input": "Specifically, serotonin may be particularly important in alleviating distress symptoms, while noradrenaline may be especially relevant to anhedonia.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 14, "end": 23}, {"text": "noradrenaline", "start": 94, "end": 107}]}}, "schema": []}
{"input": "The data reviewed here also suggest that noradrenergic-based treatments may have earlier effects on emotional memory that those which affect serotonin.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 141, "end": 150}]}}, "schema": []}
{"input": "GnRH pulse frequency-dependent stimulation of FSH beta transcription is mediated via activation of PKA and CREB.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Expression of pituitary FSH and LH, under the control of pulsatile GnRH, is essential for fertility.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 67, "end": 71}]}}, "schema": []}
{"input": "cAMP response element-binding protein (CREB) has been implicated in the regulation of FSH beta gene expression, but the molecular mechanisms by which pulsatile GnRH regulates CREB activation remain poorly understood.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 0, "end": 4}, {"text": "GnRH", "start": 160, "end": 164}]}}, "schema": []}
{"input": "We hypothesized that CREB is activated by a distinct signaling pathway in response to pulsatile GnRH in a frequency-dependent manner to dictate the FSH beta transcriptional response.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 96, "end": 100}]}}, "schema": []}
{"input": "GnRH stimulation of CREB phosphorylation (pCREB) in the gonadotrope-derived L beta T2 cell line was attenuated by a protein kinase A (PKA) inhibitor, H89.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 0, "end": 4}, {"text": "H89", "start": 150, "end": 153}]}}, "schema": []}
{"input": "A dominant negative PKA (DNPKA) reduced GnRH-stimulated pCREB and markedly decreased GnRH stimulation of FSH beta mRNA and FSH beta LUC activity, but had little effect on LH beta LUC activity, indicating relative specificity of this pathway.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 40, "end": 44}, {"text": "GnRH", "start": 85, "end": 89}]}}, "schema": []}
{"input": "In perifusion studies, FSH beta mRNA levels and FSH beta LUC activities were increased by pulsatile GnRH, with significantly greater increases at low compared with high pulse frequencies.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 100, "end": 104}]}}, "schema": []}
{"input": "DNPKA markedly reduced these GnRH-stimulated FSH beta responses at both low and high pulse frequencies.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 29, "end": 33}]}}, "schema": []}
{"input": "Correlating with FSH beta activation, both PKA activity and levels of pCREB were increased to a greater extent by low compared with high GnRH pulse frequencies, and the induction of pCREB was also attenuated by overexpression of DNPKA at both low and high pulse frequencies.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 137, "end": 141}]}}, "schema": []}
{"input": "Taken together, these data indicate that a PKA-mediated signaling pathway mediates GnRH activation of CREB at low-pulse frequencies, playing a significant role in the decoding of the hypothalamic GnRH signal to result in frequency-dependent FSH beta activation.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 83, "end": 87}, {"text": "GnRH", "start": 196, "end": 200}]}}, "schema": []}
{"input": "Regional Primary Care Team to Deliver Best-Practice Diabetes Care: A needs-driven health workforce model reflecting a biopsychosocial construct of health.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEBest-practice diabetes care can reduce the burden of diabetes and associated health care costs.", "output": {"entities": {}}, "schema": []}
{"input": "But this requires access to a multidisciplinary team with the right skill mix.", "output": {"entities": {}}, "schema": []}
{"input": "We applied a needs-driven evidence-based health workforce model to describe the primary care team required to support best practice diabetes care, paying particular attention to diverse clinic populations. RESEARCH DESIGN AND METHODSCare protocols, by number and duration of consultations, were derived for twenty distinct competencies based on clinical practice guidelines and structured input from a multidisciplinary clinical panel.", "output": {"entities": {}}, "schema": []}
{"input": "This was combined with a previously estimated population profile of persons across 26 patient attributes (i. e., type of diabetes, complications, and threats to self-care) to estimate clinician contact hours by competency required to deliver best practice care in the study region. RESULTSA primary care team of 22. 1 full-time-equivalent (FTE) positions was needed to deliver best practice primary care to a catchment of 1, 000 persons with diabetes with the attributes of the Australian population.", "output": {"entities": {}}, "schema": []}
{"input": "Competencies requiring greatest contact time were psychosocial issues and dietary advice at 3. 5 and 3. 3 FTE, respectively (1 FTE/~ 300 persons); home (district) nursing at 3. 2 FTE; and diabetes education at 2. 8 FTE.", "output": {"entities": {}}, "schema": []}
{"input": "The annual cost of delivering care was estimated at just over 2, 000 Australian dollars (~ 2, 090 USD) (2012) per person with diabetes. CONCLUSIONSA needs-driven approach to primary care service planning identified a wider range of competencies in the diabetes primary and community care team than typically described.", "output": {"entities": {}}, "schema": []}
{"input": "Access to psychosocial competences as well as medical management is required if clinical targets are to be met, especially in disadvantaged groups.", "output": {"entities": {}}, "schema": []}
{"input": "Detectable subclinical myocardial necrosis is associated with cardiovascular risk in stable patients with diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE To investigate the relationship between different degrees of subclinical myocardial necrosis, glycemic control, and long-term adverse clinical outcomes within a stable patient population with diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "RESEARCH DESIGN AND METHODS We examined 1, 275 stable patients with diabetes mellitus undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (MI) (< 0. 03 ng/mL).", "output": {"entities": {}}, "schema": []}
{"input": "The relationship of subclinical myocardial necrosis (cTnI 0. 009-0. 029 ng/mL) with incident major adverse cardiovascular events (MACE; defined as any death, MI, or stroke) over 3 years of follow-up was examined.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS Subclinical myocardial necrosis was observed in 22% of patients.", "output": {"entities": {}}, "schema": []}
{"input": "A strong association was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident MACE (hazard ratio, 1. 98; 95% confidence interval, 1. 48-2. 65; P < 0. 001) and remained statistically significant even after adjustment for traditional risk factors, high-sensitivity C-reactive protein, and creatinine clearance.", "output": {"entities": {}}, "schema": []}
{"input": "Only a weak correlation was observed between the presence of subclinical myocardial necrosis and either glycemic control (r = 0. 06; P = 0. 044 for hemoglobin A1c versus cTnI) or insulin resistance (r = 0. 04; P = 0. 094 for glucose-to-insulin ratio versus cTnI).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 225, "end": 232}]}}, "schema": []}
{"input": "CONCLUSIONS The presence of detectable subclinical myocardial necrosis in stable patients with diabetes mellitus is associated with heightened long-term risk for MACE, independent of traditional risk factors and glycemic control.", "output": {"entities": {}}, "schema": []}
{"input": "Removal of Duodenum Elicits GLP-1 Secretion.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVETo evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects. RESEARCH DESIGN AND METHODSFor evaluation of hormonal secretion and insulin sensitivity, 10 overweight patients without type 2 diabetes (age 61 +/- 19. 3 years and BMI 27. 9 +/- 5. 3 kg/m (2)) underwent a mixed-meal test and a hyperinsulinemic-euglycemic clamp before and after pylorus-preserving pancreatoduodenectomy for ampulloma. RESULTSAll patients experienced a reduction in insulin (P = 0. 002), C-peptide (P = 0. 0002), and gastric inhibitory peptide (GIP) secretion (P = 0. 0004), while both fasting and postprandial glucose levels increased (P = 0. 0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0. 02 and 0. 031).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 676, "end": 683}]}}, "schema": []}
{"input": "While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R (2) = 0. 56; P = 0. 012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R (2) = 0. 46; P = 0. 03) and C-peptide (R (2) = 0. 37; P = 0. 04).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 74, "end": 81}]}}, "schema": []}
{"input": "Given that the remaining pancreas presumably has preserved intraislet anatomy, insulin secretory capacity, and alpha-and beta-cell interplay, our data suggest that the increased glucagon secretion is related to decreased systemic insulin. CONCLUSIONSPylorus-preserving pancreatoduodenectomy was associated with a decrease in GIP and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion.", "output": {"entities": {}}, "schema": []}
{"input": "Rather, the hypoinsulinemia may have caused an increase in glucagon secretion.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetic Interactions between Monoamine Oxidase A Inhibitor Harmaline and 5-Methoxy-N, N-Dimethyltryptamine, and the Impact of CYP2D6 Status.", "output": {"entities": {"chemical": [{"text": "Monoamine", "start": 37, "end": 46}, {"text": "Harmaline", "start": 67, "end": 76}, {"text": "5-Methoxy-N, N-Dimethyltryptamine", "start": 81, "end": 114}]}}, "schema": []}
{"input": "5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT or street name \" 5-MEO \") is a newer designer drug belonging to a group of naturally occurring indolealkylamines.", "output": {"entities": {"chemical": [{"text": "5-Methoxy-N, N-dimethyltryptamine", "start": 0, "end": 33}, {"text": "5-MeO-DMT", "start": 35, "end": 44}, {"text": "5-MEO", "start": 62, "end": 67}, {"text": "indolealkylamines", "start": 140, "end": 157}]}}, "schema": []}
{"input": "Our recent study has demonstrated that coadministration of monoamine oxidase A (MAO-A) inhibitor harmaline (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine.", "output": {"entities": {"chemical": [{"text": "monoamine", "start": 59, "end": 68}, {"text": "harmaline", "start": 97, "end": 106}, {"text": "5-MeO-DMT", "start": 148, "end": 157}]}}, "schema": []}
{"input": "This study is aimed at delineating harmaline and 5-MeO-DMT pharmacokinetic (PK) interactions at multiple dose levels, as well as the impact of CYP2D6 that affects harmaline PK and determines 5-MeO-DMT O-demethylation to produce bufotenine.", "output": {"entities": {"chemical": [{"text": "harmaline", "start": 35, "end": 44}, {"text": "5-MeO-DMT", "start": 49, "end": 58}, {"text": "harmaline", "start": 163, "end": 172}, {"text": "5-MeO-DMT O", "start": 191, "end": 202}, {"text": "bufotenine", "start": 228, "end": 238}]}}, "schema": []}
{"input": "Our data revealed that inhibition of MAO-A-mediated metabolic elimination by harmaline (2, 5, and 15 mg/kg) led to a sharp increase in systemic and cerebral exposure to 5-MeO-DMT (2 and 10 mg/kg) at all dose combinations.", "output": {"entities": {"chemical": [{"text": "harmaline", "start": 77, "end": 86}, {"text": "5-MeO-DMT", "start": 169, "end": 178}]}}, "schema": []}
{"input": "A more pronounced effect on 5-MeO-DMT PK was associated with greater exposure to harmaline in wild-type mice than CYP2D6-humanized (Tg-CYP2D6) mice.", "output": {"entities": {"chemical": [{"text": "5-MeO-DMT", "start": 28, "end": 37}, {"text": "harmaline", "start": 81, "end": 90}]}}, "schema": []}
{"input": "Harmaline (5 mg/kg) also increased blood and brain bufotenine concentrations that were generally higher in Tg-CYP2D6 mice.", "output": {"entities": {"chemical": [{"text": "Harmaline", "start": 0, "end": 9}, {"text": "bufotenine", "start": 51, "end": 61}]}}, "schema": []}
{"input": "Surprisingly, greater harmaline dose (15 mg/kg) reduced bufotenine levels.", "output": {"entities": {"chemical": [{"text": "harmaline", "start": 22, "end": 31}, {"text": "bufotenine", "start": 56, "end": 66}]}}, "schema": []}
{"input": "The in vivo inhibitory effect of harmaline on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified CYP2D6.", "output": {"entities": {"chemical": [{"text": "harmaline", "start": 33, "end": 42}, {"text": "bufotenine", "start": 63, "end": 73}]}}, "schema": []}
{"input": "Given these findings, a unified PK model including the inhibition of MAO-A-and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "output": {"entities": {"chemical": [{"text": "5-MeO-DMT", "start": 96, "end": 105}, {"text": "harmaline", "start": 120, "end": 129}, {"text": "harmaline", "start": 162, "end": 171}, {"text": "5-MeO-DMT", "start": 173, "end": 182}, {"text": "bufotenine", "start": 188, "end": 198}]}}, "schema": []}
{"input": "This PK model may be further employed to predict harmaline and 5-MeO-DMT PK interactions at various doses, define the impact of CYP2D6 status, and drive harmaline-5-MeO-DMT pharmacodynamics.", "output": {"entities": {"chemical": [{"text": "harmaline", "start": 49, "end": 58}, {"text": "5-MeO-DMT", "start": 63, "end": 72}, {"text": "harmaline", "start": 153, "end": 162}, {"text": "5-MeO-DMT", "start": 163, "end": 172}]}}, "schema": []}
{"input": "Hyperbranched Polyester Hydrogels with Controlled Drug Release and Cell Adhesion Properties.", "output": {"entities": {"chemical": [{"text": "Polyester", "start": 14, "end": 23}]}}, "schema": []}
{"input": "Hyperbranched polyesters (HPE) have a high efficiency to encapsulate bioactive agents, including drugs, genes, and proteins, due to their globe-like nanostructure.", "output": {"entities": {"chemical": [{"text": "polyesters", "start": 14, "end": 24}]}}, "schema": []}
{"input": "However, the use of these highly branched polymeric systems for tissue engineering applications has not been broadly investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report synthesis and characterization of photocrosslinkable HPE hydrogels with sustained drug release characteristics for cellular therapies.", "output": {"entities": {}}, "schema": []}
{"input": "These HPE can encapsulate hydrophobic drug molecules within the HPE cavities due to the presence of a hydrophobic inner structure that is otherwise difficult to achieve in conventional hydrogels.", "output": {"entities": {}}, "schema": []}
{"input": "The functionalization of HPE with photocrosslinkable acrylate moieties renders the formation of hydrogels with a highly porous interconnected structure and mechanically tough network.", "output": {"entities": {"chemical": [{"text": "acrylate", "start": 53, "end": 61}]}}, "schema": []}
{"input": "The compressive modulus of HPE hydrogels was tunable by changing the crosslinking density.", "output": {"entities": {}}, "schema": []}
{"input": "The feasibility of using these HPE networks for cellular therapies was investigated by evaluating cell adhesion, spreading, and proliferation on hydrogel surface.", "output": {"entities": {}}, "schema": []}
{"input": "Highly crosslinked and mechanically stiff HPE hydrogels have higher cell adhesion, spreading, and proliferation compared to soft and complaint HPE hydrogels.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, we showed that hydrogels made from HPE could be used for biomedical applications that require spatial control of cell adhesion and controlled release of hydrophobic clues.", "output": {"entities": {}}, "schema": []}
{"input": "One-pot, exchange-free, room-temperature synthesis of sub-10 nm aqueous, noninteracting, and stable zwitterated iron oxide nanoparticles.", "output": {"entities": {"chemical": [{"text": "zwitterated iron oxide", "start": 100, "end": 122}]}}, "schema": []}
{"input": "Stable aqueous dispersions of superparamagnetic iron oxide nanoparticles were synthesized in one step in the presence of a zwitterionic siloxane as the stabilizing/capping/solubilizing ligand.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 48, "end": 58}, {"text": "zwitterionic siloxane", "start": 123, "end": 144}]}}, "schema": []}
{"input": "The hydrodynamic diameter of the particles was tuned by controlling the concentration of zwitterion siloxane, which ultimately yielded monodisperse nanoparticles small enough for renal filtration (< 6 nm diameter).", "output": {"entities": {"chemical": [{"text": "zwitterion siloxane", "start": 89, "end": 108}]}}, "schema": []}
{"input": "The zwitterated nanoparticles were readily dispersed and stable in aqueous media in the pH range 6-9 but exhibited lower magnetization values than nonzwitterated materials due to amorphous content and spin canting, typical for particles of such size.", "output": {"entities": {}}, "schema": []}
{"input": "Turbidimetry and light scattering studies revealed no interaction between the particles and proteins, suggesting the materials will circulate well in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Tetracyclic diterpenoids with isomerized isospongian skeleton and labdane diterpenoids from the fruits of Amomum kravanh.", "output": {"entities": {"chemical": [{"text": "Tetracyclic diterpenoids", "start": 0, "end": 24}, {"text": "isospongian", "start": 41, "end": 52}, {"text": "labdane diterpenoids", "start": 66, "end": 86}]}}, "schema": []}
{"input": "Four novel diterpenoids, including three tetracyclic diterpenes with isomerized isospongian skeletons, kravanhins A-C (1-3), and kravanhin D (4), and three new labdane diterpenes (5-7) were isolated from the fruits of Amomum kravanh.", "output": {"entities": {"chemical": [{"text": "diterpenoids", "start": 11, "end": 23}, {"text": "tetracyclic diterpenes", "start": 41, "end": 63}, {"text": "isospongian", "start": 80, "end": 91}, {"text": "kravanhins A-C", "start": 103, "end": 117}, {"text": "kravanhin D", "start": 129, "end": 140}, {"text": "labdane diterpenes", "start": 160, "end": 178}]}}, "schema": []}
{"input": "Compounds 1-4 had unprecedented isospongian diterpene skeletons with a trans-anti-cis fused tricyclic ring system.", "output": {"entities": {"chemical": [{"text": "isospongian diterpene", "start": 32, "end": 53}]}}, "schema": []}
{"input": "The structures of compounds 1-7 were established on the basis of extensive analysis of NMR spectra, CD, and X-ray crystallography.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 2 showed inhibitory activity on nitric oxide production in lipopolysaccharide-induced RAW264. 7 macrophages with an IC (50) value of 36. 2 mu M.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 41, "end": 53}]}}, "schema": []}
{"input": "Methotrexate pharmacogenetics in rheumatoid arthritis: a status report.", "output": {"entities": {"chemical": [{"text": "Methotrexate", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Methotrexate (MTX), an antifolate drug, is the first-line disease-modifying agent for the treatment of rheumatoid arthritis (RA) worldwide.", "output": {"entities": {"chemical": [{"text": "Methotrexate", "start": 0, "end": 12}, {"text": "MTX", "start": 14, "end": 17}]}}, "schema": []}
{"input": "MTX has excellent long-term efficacy, tolerability and safety.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Early initiation of MTX in patients with RA controls joint destruction and slows progression of disease.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 20, "end": 23}]}}, "schema": []}
{"input": "However, the clinical response to MTX and frequency of adverse effects from the drug exhibit marked interpatient variability.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 34, "end": 37}]}}, "schema": []}
{"input": "Over the past decade, there has been a quest to identify genetic markers that reliably predict MTX efficacy and toxicity and help optimize MTX therapy in RA; that is, the field of MTX pharmacogenetics.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 95, "end": 98}, {"text": "MTX", "start": 139, "end": 142}, {"text": "MTX", "start": 180, "end": 183}]}}, "schema": []}
{"input": "This review will summarize key pharmacogenetic studies examining SNPs in the genes encoding enzymes in the MTX cellular pathway and their association with MTX response in RA.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 107, "end": 110}, {"text": "MTX", "start": 155, "end": 158}]}}, "schema": []}
{"input": "As evident from this review, MTX pharmacogenetics in RA remains a muddled field, mostly due to inconsistent results from several small underpowered studies.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 29, "end": 32}]}}, "schema": []}
{"input": "Reversible sol-to-gel transformation of uracil gelators: specific colorimetric and fluorimetric sensor for fluoride ions.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 40, "end": 46}, {"text": "fluoride", "start": 107, "end": 115}]}}, "schema": []}
{"input": "A new type of anthracene organogelator based on uracil was obtained using organic aromatic solvents, cyclohexane, DMSO, ethanol, and ethyl acetate.", "output": {"entities": {"chemical": [{"text": "anthracene", "start": 14, "end": 24}, {"text": "uracil", "start": 48, "end": 54}, {"text": "cyclohexane", "start": 101, "end": 112}, {"text": "DMSO", "start": 114, "end": 118}, {"text": "ethanol", "start": 120, "end": 127}, {"text": "ethyl acetate", "start": 133, "end": 146}]}}, "schema": []}
{"input": "It was further characterized by field-emission scanning electron microscopy and transmission electron microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, the resulting organogels were demonstrated to be promising colorimetric and fluorescent sensors toward fluoride ions with high sensitivity and selectivity, accompanying the disruption of the gelators.", "output": {"entities": {}}, "schema": []}
{"input": "Spectroscopic study and (1) H NMR titration experiment revealed that the deprotonation of the hydrogen atom on the N position of uracil moiety by fluoride ions is responsible for the recognition events, evidenced by immediate transformation from the sol phase to the gel state upon adding a small amount of a proton solvent, methanol.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 24, "end": 29}, {"text": "hydrogen", "start": 94, "end": 102}, {"text": "N", "start": 115, "end": 116}, {"text": "uracil", "start": 129, "end": 135}, {"text": "fluoride", "start": 146, "end": 154}, {"text": "methanol", "start": 325, "end": 333}]}}, "schema": []}
{"input": "The process is reversible, with zero loss in sensing activity and sol-to-gel transformation ability even after five runs.", "output": {"entities": {}}, "schema": []}
{"input": "Statin intolerance: why and what to do-with a focus on diabetic people.", "output": {"entities": {}}, "schema": []}
{"input": "The standards of medical care in diabetes recommend that statin therapy is added to lifestyle therapy for diabetic patients with overt cardiovascular disease (LDL cholesterol goal < 70 mg/dl), or without cardiovascular disease who are over the age of 40 years and who have one or more other cardiovascular disease risk factors (LDL cholesterol goal < 100 mg/dl).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 163, "end": 174}, {"text": "cholesterol", "start": 332, "end": 343}]}}, "schema": []}
{"input": "In order to reach strict LDL targets, high doses of statins may be required.", "output": {"entities": {}}, "schema": []}
{"input": "However, the frequency of statin associated adverse effects and statin intolerance in clinical practice is high (up to 10-15% of statin users) especially at muscle level.", "output": {"entities": {}}, "schema": []}
{"input": "The review overviews: 1) the known or hypothesised mechanisms through which causal and contributing factors are associated with adverse effects in diabetic people, and 2) the rationale of strategies for managing statin intolerant patients.", "output": {"entities": {}}, "schema": []}
{"input": "Thymidylate kinase: an old topic brings new perspectives.", "output": {"entities": {"chemical": [{"text": "Thymidylate", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Thymidylate kinase (TMPK) is a key enzyme for pyrimidine synthesis that catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) in the presence of ATP and Mg (2 +) to form thymidine 5'-diphosphate (dTDP), which is then converted to thymidine 5'-triphosphate (dTTP) by nucleoside-diphosphate kinase (NDK).", "output": {"entities": {"chemical": [{"text": "Thymidylate", "start": 0, "end": 11}, {"text": "pyrimidine", "start": 46, "end": 56}, {"text": "thymidine 5'-monophosphate", "start": 105, "end": 131}, {"text": "dTMP", "start": 133, "end": 137}, {"text": "ATP", "start": 158, "end": 161}, {"text": "Mg (2 +)", "start": 166, "end": 174}, {"text": "thymidine 5'-diphosphate", "start": 183, "end": 207}, {"text": "dTDP", "start": 209, "end": 213}, {"text": "thymidine 5'-triphosphate", "start": 243, "end": 268}, {"text": "dTTP", "start": 270, "end": 274}, {"text": "nucleoside-diphosphate", "start": 279, "end": 301}]}}, "schema": []}
{"input": "TMPK has an important function in cell proliferation and its enzyme kinetics and related structures have been determined in various organisms.", "output": {"entities": {}}, "schema": []}
{"input": "TMPK is well recognized as a potential drug target, with the most notable function being in the activation of anti-HIV nucleoside prodrugs.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 119, "end": 129}]}}, "schema": []}
{"input": "Recent studies have shown that TMPK is a validated target for antibiotic development against gram-positive bacterium of Staphylococcus aureus.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, inhibition of human TMPK increases the potential of anticancer agent doxorubicin toward colon cancer cells regardless of p53 status.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 82, "end": 93}]}}, "schema": []}
{"input": "Following the rapid expanding knowledge on TMPKs and the rising interests in TMPKs as a drug target, in this review we try to describe current research on TMPKs in various organisms of eukaryotes, prokaryotes and viruses and to provide information for designing new potential inhibitors against TMPKs.", "output": {"entities": {}}, "schema": []}
{"input": "Growth of highly fluorescent polyethylene glycol-and zwitterion-functionalized gold nanoclusters.", "output": {"entities": {"chemical": [{"text": "polyethylene glycol", "start": 29, "end": 48}]}}, "schema": []}
{"input": "We have prepared and characterized a new set of highly fluorescent gold nanoclusters (AuNCs) using one-step aqueous reduction of a gold precursor in the presence of bidentate ligands made of lipoic acid anchoring groups, appended with either a poly (ethylene glycol) short chain or a zwitterion group.", "output": {"entities": {"chemical": [{"text": "lipoic acid", "start": 191, "end": 202}, {"text": "poly (ethylene glycol)", "start": 244, "end": 266}]}}, "schema": []}
{"input": "The AuNCs fluoresce in the red to near-infrared region of the optical spectrum with emission centered at ~ 750 nm and a quantum yield of ~ 10-14%, and they exhibit long fluorescence lifetimes (up to ~ 300 ns).", "output": {"entities": {}}, "schema": []}
{"input": "Dispersions of these AuNCs exhibit great long-term colloidal stability, over a wide range of pHs (2-13) and in the presence of high electrolyte concentrations, and a strong resistance to reducing agents such as glutathione.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 211, "end": 222}]}}, "schema": []}
{"input": "The growth strategy further permitted the controlled, in situ functionalization of the NCs with reactive groups (e. g., carboxylic acid or amine), making these nanoclusters compatible with common and simple-to-implement coupling strategies, such as carbodiimide chemistry.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 120, "end": 135}, {"text": "amine", "start": 139, "end": 144}, {"text": "carbodiimide", "start": 249, "end": 261}]}}, "schema": []}
{"input": "These properties combined make these fluorescent NCs greatly promising for use in various imaging and sensing applications where NIR and long-lived excitations are desired.", "output": {"entities": {}}, "schema": []}
{"input": "Correlating superlattice polymorphs to internanoparticle distance, packing density, and surface lattice in assemblies of PbS nanoparticles.", "output": {"entities": {"chemical": [{"text": "PbS", "start": 121, "end": 124}]}}, "schema": []}
{"input": "Assemblies of 3. 5 nm PbS nanoparticles (NPs) nucleate in three dominant superlattice polymorphs: amorphous, body-centered-cubic (bcc) and face-centered-cubic (fcc) phase.", "output": {"entities": {"chemical": [{"text": "PbS", "start": 22, "end": 25}]}}, "schema": []}
{"input": "This superlattice relationship can be controlled by the inter-NP distance without changing the NP size.", "output": {"entities": {}}, "schema": []}
{"input": "Upon increase of inter-NP distance, the packing density decreases, and the capping molecules at NP surfaces change in structure and accordingly modify the surface energy.", "output": {"entities": {}}, "schema": []}
{"input": "The driving force for NP assembly develops from an entropic maximization to a reduction of total free energy through multiple interactions between surface molecules and NPs and resulting variation of surface molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Upon long-term aging and additional thermal treatment, fcc undergoes a tetragonal distortion and subsequently transforms to bcc phase, and simultaneously, the NPs embedded in supercrystals reduce surface energy primarily in {200} facets.", "output": {"entities": {}}, "schema": []}
{"input": "Linking molecule-NP interactions with a series of changes of packing density and surface lattice spacings of NPs allows for an interpretation of principles governing the nucleation, structure stability, and transformation of PbS NP-assembled supercrystals.", "output": {"entities": {"chemical": [{"text": "PbS", "start": 225, "end": 228}]}}, "schema": []}
{"input": "Antiretroviral bioanalysis methods of tissues and body biofluids.", "output": {"entities": {}}, "schema": []}
{"input": "Research in the many areas of HIV treatment, eradication and prevention has necessitated measurement of antiretroviral (ARV) concentrations in nontraditional specimen types.", "output": {"entities": {}}, "schema": []}
{"input": "To determine the knowledgebase of critical details for accurate bioanalysis, a review of the literature was performed and summarized.", "output": {"entities": {}}, "schema": []}
{"input": "Bioanalytical assays for 31 ARVs, including metabolites, were identified in 205 publications measuring various tissues and biofluids.", "output": {"entities": {}}, "schema": []}
{"input": "18 and 30% of tissue or biofluid methods, respectively, analyzed more than one specimen type; 35-37% of the tissue or biofluid methods quantitated more than one ARV.", "output": {"entities": {}}, "schema": []}
{"input": "20 and 76% of tissue or biofluid methods, respectively, were used for the analysis of human specimens.", "output": {"entities": {}}, "schema": []}
{"input": "HPLC methods with UV detection predominated, but chronologically MS detection began to surpass.", "output": {"entities": {}}, "schema": []}
{"input": "40% of the assays provided complete intra-and inter-assay validation data, but only 9% of publications provided any stability data with even less for the prevalent ARV in treatments.", "output": {"entities": {}}, "schema": []}
{"input": "Conundrum of angiotensin II and TGF-beta interactions in aortic aneurysms.", "output": {"entities": {}}, "schema": []}
{"input": "Angiotensin II (AngII) has been invoked as a principal mediator for the development and progression of both thoracic and abdominal aortic aneurysms.", "output": {"entities": {}}, "schema": []}
{"input": "While there is consistency in experimental and clinical studies that overactivation of the renin angiotensin system promotes aortic aneurysm development, there are many unknowns regarding the mechanistic basis underlying AngII-induced aneurysms.", "output": {"entities": {}}, "schema": []}
{"input": "Interactions of AngII with TGF-beta in both thoracic and abdominal aortic aneurysms have been the focus of recent studies.", "output": {"entities": {}}, "schema": []}
{"input": "While these studies have demonstrated profound effects of manipulating TGF-beta activity on AngII-induced aortic aneurysms, they have also led to more questions regarding the interactions between AngII and this multifunctional cytokine.", "output": {"entities": {}}, "schema": []}
{"input": "This review compiled the recent literature to provide insights into understanding the potentially complex interactions between AngII and TGF-beta in the development of aortic aneurysms.", "output": {"entities": {}}, "schema": []}
{"input": "Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 25, "end": 34}, {"text": "tauro-beta-muricholic acid", "start": 72, "end": 98}]}}, "schema": []}
{"input": "Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids.", "output": {"entities": {"chemical": [{"text": "Bile acids", "start": 0, "end": 10}, {"text": "cholesterol", "start": 32, "end": 43}, {"text": "bile acids", "start": 118, "end": 128}]}}, "schema": []}
{"input": "Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver.", "output": {"entities": {"chemical": [{"text": "Bile acid", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 21, "end": 30}]}}, "schema": []}
{"input": "We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice.", "output": {"entities": {"chemical": [{"text": "muricholic acid", "start": 37, "end": 52}, {"text": "cholic acid", "start": 62, "end": 73}]}}, "schema": []}
{"input": "Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7 alpha-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 147, "end": 158}]}}, "schema": []}
{"input": "Importantly, we identified tauro-conjugated beta-and alpha-muricholic acids as FXR antagonists.", "output": {"entities": {"chemical": [{"text": "tauro-conjugated beta-and alpha-muricholic acids", "start": 27, "end": 75}]}}, "schema": []}
{"input": "These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 75, "end": 84}, {"text": "bile acid", "start": 114, "end": 123}]}}, "schema": []}
{"input": "Tmem64 modulates calcium signaling during RANKL-mediated osteoclast differentiation.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 17, "end": 24}]}}, "schema": []}
{"input": "Osteoclast maturation and function primarily depend on receptor activator of NF-kappa B ligand (RANKL)-mediated induction of nuclear factor of activated T cells c1 (NFATc1), which is further activated via increased intracellular calcium ([Ca (2 +)] (i)) oscillation.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 229, "end": 236}, {"text": "Ca (2 +)", "start": 239, "end": 247}]}}, "schema": []}
{"input": "However, the coordination mechanism that mediates Ca (2 +) oscillation during osteoclastogenesis remains ill defined.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 50, "end": 58}]}}, "schema": []}
{"input": "Here, we identified transmembrane protein 64 (Tmem64) as a regulator of Ca (2 +) oscillation during osteoclastogenesis.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 72, "end": 80}]}}, "schema": []}
{"input": "We found that Tmem64-deficient mice exhibit increased bone mass due in part to impaired osteoclast formation.", "output": {"entities": {}}, "schema": []}
{"input": "Using in vitro osteoclast culture systems, we show here that Tmem64 interacts with sarcoplasmic endoplasmic reticulum Ca (2 +) ATPase 2 (SERCA2) and modulates its activity.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 118, "end": 126}]}}, "schema": []}
{"input": "Consequently, Tmem64 deficiency significantly diminishes RANKL-induced [Ca (2 +)] (i) oscillation, which results in reduced Ca (2 +)/calmodulin-dependent protein kinases (CaMK) IV and mitochondrial ROS, both of which contribute to achieving the CREB activity necessary for osteoclast formation.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 72, "end": 80}, {"text": "Ca (2 +)", "start": 124, "end": 132}]}}, "schema": []}
{"input": "These data demonstrate that Tmem64 is a positive modulator of osteoclast differentiation via SERCA2-dependent Ca (2 +) signaling.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 110, "end": 118}]}}, "schema": []}
{"input": "HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis.", "output": {"entities": {"chemical": [{"text": "heme", "start": 22, "end": 26}]}}, "schema": []}
{"input": "Adult humans have about 25 trillion red blood cells (RBCs), and each second we recycle about 5 million RBCs by erythrophagocytosis (EP) in macrophages of the reticuloendothelial system.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the central role for EP in mammalian iron metabolism, the molecules and pathways responsible for heme trafficking during EP remain unknown.", "output": {"entities": {"chemical": [{"text": "iron", "start": 45, "end": 49}, {"text": "heme", "start": 105, "end": 109}]}}, "schema": []}
{"input": "Here, we show that the mammalian homolog of HRG1, a transmembrane heme permease in C. elegans, is essential for macrophage iron homeostasis and transports heme from the phagolysosome to the cytoplasm during EP.", "output": {"entities": {"chemical": [{"text": "heme", "start": 66, "end": 70}, {"text": "iron", "start": 123, "end": 127}, {"text": "heme", "start": 155, "end": 159}]}}, "schema": []}
{"input": "HRG1 is strongly expressed in macrophages of the reticuloendothelial system and specifically localizes to the phagolysosomal membranes during EP.", "output": {"entities": {}}, "schema": []}
{"input": "Depletion of Hrg1 in mouse macrophages causes attenuation of heme transport from the phagolysosomal compartment.", "output": {"entities": {"chemical": [{"text": "heme", "start": 61, "end": 65}]}}, "schema": []}
{"input": "Importantly, missense polymorphisms in human HRG1 are defective in heme transport.", "output": {"entities": {"chemical": [{"text": "heme", "start": 67, "end": 71}]}}, "schema": []}
{"input": "Our results reveal HRG1 as the long-sought heme transporter for heme-iron recycling in macrophages and suggest that genetic variations in HRG1 could be modifiers of human iron metabolism.", "output": {"entities": {"chemical": [{"text": "heme", "start": 43, "end": 47}, {"text": "heme", "start": 64, "end": 68}, {"text": "iron", "start": 69, "end": 73}, {"text": "iron", "start": 171, "end": 175}]}}, "schema": []}
{"input": "Sonication in combination with heat and low pressure as an alternative pasteurization treatment--effect on Escherichia coli K12 inactivation and quality of apple cider.", "output": {"entities": {}}, "schema": []}
{"input": "Escherichia coli K12 cells suspended in apple cider were treated by manothermosonication (MTS, 400 kPa/59 degrees C), thermosonication (TS, 100 kPa/59 degrees C), and manosonication (MS, 400 kPa/55 degrees C) for up to 4 min.", "output": {"entities": {}}, "schema": []}
{"input": "A 5-log reduction was achieved in 1. 4 min by MTS, 3. 8 min by TS, and 2. 5 min by MS.", "output": {"entities": {}}, "schema": []}
{"input": "The inactivation curves of the E. coli exhibited a fast initial reduction followed by a slow inactivation section.", "output": {"entities": {}}, "schema": []}
{"input": "The Weibull, log-logistic, and biphasic linear models showed a good fit of the inactivation data.", "output": {"entities": {}}, "schema": []}
{"input": "Quality analyses were conducted with raw apple cider (control), thermally-pasteurized (TP), and MTS-, TS-, and MS-treated cider samples over a 3-week period at refrigeration temperature.", "output": {"entities": {}}, "schema": []}
{"input": "Titratable acidity and pH did not differ among any of the samples.", "output": {"entities": {}}, "schema": []}
{"input": "During storage, the turbidity value of the control was the highest, followed by TP, TS, MTS and MS.", "output": {"entities": {}}, "schema": []}
{"input": "All color parameters of the TP sample were significantly different from those receiving the other treatments.", "output": {"entities": {}}, "schema": []}
{"input": "The control and sonicated samples showed similar color parameters during storage.", "output": {"entities": {}}, "schema": []}
{"input": "In total, 97 aroma compounds were identified in the control, TS-, MS-, and MTS-treated cider samples, while 95 aroma compounds were found in the TP at Week 0.", "output": {"entities": {}}, "schema": []}
{"input": "Among all the aroma compounds, 9 key ones were identified in all samples, including ethyl 2-methylbutanoate, butyl acetate, 1-butanol, ethyl hexanoate, 1-hexanol, butanoic acid, beta-damascenone, hexanoic acid, and octanoic acid.", "output": {"entities": {"chemical": [{"text": "ethyl 2-methylbutanoate", "start": 84, "end": 107}, {"text": "butyl acetate", "start": 109, "end": 122}, {"text": "1-butanol", "start": 124, "end": 133}, {"text": "ethyl hexanoate", "start": 135, "end": 150}, {"text": "1-hexanol", "start": 152, "end": 161}, {"text": "butanoic acid", "start": 163, "end": 176}, {"text": "beta-damascenone", "start": 178, "end": 194}, {"text": "hexanoic acid", "start": 196, "end": 209}, {"text": "octanoic acid", "start": 215, "end": 228}]}}, "schema": []}
{"input": "The profiles of the key aroma compounds in all sonicated samples were more similar to the control than the TP sample at Weeks 0 and 3.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding metabolic regulation and its influence on cell physiology.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism impacts all cellular functions and plays a fundamental role in biology.", "output": {"entities": {}}, "schema": []}
{"input": "In the last century, our knowledge of metabolic pathway architecture and the genomic landscape of disease has increased exponentially.", "output": {"entities": {}}, "schema": []}
{"input": "Combined with these insights, advances in analytical methods for quantifying metabolites and systems approaches to analyze these data now provide powerful tools to study metabolic regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Here we review the diverse mechanisms cells use to adapt metabolism to specific physiological states and discuss how metabolic flux analyses can be applied to identify important regulatory nodes to understand normal and pathological cell physiology.", "output": {"entities": {}}, "schema": []}
{"input": "Biomedical applications of bisphosphonates.", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 27, "end": 42}]}}, "schema": []}
{"input": "Since their discovery over 100 years ago, bisphosphonates have been used industrially as corrosion inhibitors and complexing agents.", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 42, "end": 57}]}}, "schema": []}
{"input": "With the discovery of their pharmacological activity in the late 1960s, implicating their high affinity for hydroxyapatite, bisphosphonates have been employed in the treatment of bone diseases and as targeting agents for colloids and drugs.", "output": {"entities": {"chemical": [{"text": "hydroxyapatite", "start": 108, "end": 122}, {"text": "bisphosphonates", "start": 124, "end": 139}]}}, "schema": []}
{"input": "They have notably been investigated for the treatment of Paget' s disease, osteoporosis, bone metastases, malignancy-associated hypercalcemia, and pediatric bone diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Currently, they are first-line medications for several of these diseases and are taken by millions of patients worldwide, mostly postmenopausal women.", "output": {"entities": {}}, "schema": []}
{"input": "A major problem associated with their use is their low oral bioavailability.", "output": {"entities": {}}, "schema": []}
{"input": "Several delivery systems have been proposed to improve their absorption and to direct them to sites other than bone tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Beyond their important pharmacological role, the medical applications of bisphosphonates are numerous.", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 73, "end": 88}]}}, "schema": []}
{"input": "In addition, their metal-chelating properties have been exploited to coat and stabilize implants, nanoparticulates, and contrast agents.", "output": {"entities": {}}, "schema": []}
{"input": "In this contribution, we review the pharmacological and clinical uses of bisphosphonates and highlight their novel applications in the pharmaceutical and biomedical fields.", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 73, "end": 88}]}}, "schema": []}
{"input": "Sophocarpine alleviates hepatocyte steatosis through activating AMPK signaling pathway.", "output": {"entities": {"chemical": [{"text": "Sophocarpine", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Sophocarpine, an effective compound derived from foxtail-like sophora herb and seed, has been reported that it can alleviate non-alcoholic steatohepatitis (NASH) in rats and affect adipocytokine synthesis.", "output": {"entities": {"chemical": [{"text": "Sophocarpine", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Meanwhile, adipocytokines could adjust hepatic lipid metabolism through AMPK signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "In the work presented here, primary hepatocytes were isolated from specific pathogen-free male SD rats and incubated with 200 mu mol/L oleic acid for 24h to induce steatotic model, then treated with sophocarpine for 72 h.", "output": {"entities": {"chemical": [{"text": "oleic acid", "start": 135, "end": 145}, {"text": "sophocarpine", "start": 199, "end": 211}]}}, "schema": []}
{"input": "Oil red staining was performed to evaluate steatosis, total RNA and protein of primary hepatocytes were extracted for real-time RT-PCR and western blot analysis.", "output": {"entities": {}}, "schema": []}
{"input": "A cluster of aberrances were observed in the model group, including hepatocyte steatosis, increased leptin and decreased adiponectin mRNA expressions.", "output": {"entities": {}}, "schema": []}
{"input": "While sophocarpine treatment resulted in: significant improvement of steatosis (> 50% decrease), decrease of leptin expression (< 0. 57-fold) and increase of adiponectin expression (> 1. 48-fold).", "output": {"entities": {"chemical": [{"text": "sophocarpine", "start": 6, "end": 18}]}}, "schema": []}
{"input": "Moreover, compared with the model group, sophocarpine could significantly increase P-AMPK alpha (> 5. 82-fold), AMPK alpha (> 1. 29-fold) and ACC (> 3. 27-fold) protein expressions, and reduce P-ACC (< 0. 30-fold) and HNF-4 alpha (< 0. 20-fold) protein expression.", "output": {"entities": {"chemical": [{"text": "sophocarpine", "start": 41, "end": 53}]}}, "schema": []}
{"input": "The mRNA expression of Srebp-1c was downregulated significantly simultaneously (< 0. 68-fold).", "output": {"entities": {}}, "schema": []}
{"input": "We concluded that sophocarpine could alleviate hepatocyte steatosis and the potential mechanism might be the activated signaling pathway of AMPK.", "output": {"entities": {"chemical": [{"text": "sophocarpine", "start": 18, "end": 30}]}}, "schema": []}
{"input": "Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells.", "output": {"entities": {}}, "schema": []}
{"input": "Silymarin inhibits UVB-induced immunosuppression in mouse skin.", "output": {"entities": {}}, "schema": []}
{"input": "To identify the molecular mechanisms underlying this effect, we used an adoptive transfer approach in which dendritic cells (DCs) from the draining lymph nodes of donor mice that had been UVB-exposed and sensitized to 2, 4,-dinitrofluorobenzene (DNFB) were transferred into na i ve recipient mice.", "output": {"entities": {"chemical": [{"text": "2, 4,-dinitrofluorobenzene", "start": 218, "end": 244}, {"text": "DNFB", "start": 246, "end": 250}]}}, "schema": []}
{"input": "The contact hypersensitivity (CHS) response of the recipient mice to DNFB was then measured.", "output": {"entities": {"chemical": [{"text": "DNFB", "start": 69, "end": 73}]}}, "schema": []}
{"input": "When DCs were obtained from UVB-exposed donor mice that were not treated with silymarin, the CHS response was suppressed confirming the role of DCs in the UVB-induced immunosuppression.", "output": {"entities": {}}, "schema": []}
{"input": "Silymarin treatment of UVB-exposed donor mice relieved this suppression of the CHS response in the recipients.", "output": {"entities": {}}, "schema": []}
{"input": "Silymarin treatment was associated with rapid repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in DCs and silymarin treatment did not prevent UV-induced immunosuppression in XPA-deficient mice which are unable to repair UV-induced DNA damage.", "output": {"entities": {"chemical": [{"text": "cyclobutane pyrimidine dimers", "start": 68, "end": 97}, {"text": "CPDs", "start": 99, "end": 103}]}}, "schema": []}
{"input": "The CHS response in mice receiving DCs from silymarin-treated UV-exposed donor mice also was associated with enhanced secretion of Th1-type cytokines and stimulation of T cells.", "output": {"entities": {}}, "schema": []}
{"input": "Adoptive transfer of T cells revealed that transfer of either CD8 (+) or CD4 (+) cells from silymarin-treated, UVB-exposed donors resulted in enhancement of the CHS response.", "output": {"entities": {}}, "schema": []}
{"input": "Cell culture study showed enhanced secretion of IL-2 and IFN gamma by CD8 (+) T cells, and reduced secretion of Th2 cytokines by CD4 (+) T cells, obtained from silymarin-treated UVB-exposed mice.", "output": {"entities": {}}, "schema": []}
{"input": "These data suggest that DNA repair-dependent functional activation of DCs, a reduction in CD4 (+) regulatory T-cell activity, and stimulation of CD8 (+) effector T cells contribute to silymarin-mediated inhibition of UVB-induced immunosuppression.", "output": {"entities": {}}, "schema": []}
{"input": "Methods for oxysterol analysis: Past, present and future.", "output": {"entities": {"chemical": [{"text": "oxysterol", "start": 12, "end": 21}]}}, "schema": []}
{"input": "Oxysterols are oxidised forms of cholesterol or its precursors.", "output": {"entities": {"chemical": [{"text": "Oxysterols", "start": 0, "end": 10}, {"text": "cholesterol", "start": 33, "end": 44}]}}, "schema": []}
{"input": "In this article we will concentrate specifically on those formed in mammalian systems.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidation may be catalysed by endogenous enzymes or through reactive oxygen species forming a myriad of potential products.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 69, "end": 75}]}}, "schema": []}
{"input": "A number of these products are biologically active, and oxysterols may have roles in cholesterol homeostasis, neurogenesis, protein prenylation and in the immune system.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 56, "end": 66}, {"text": "cholesterol", "start": 85, "end": 96}]}}, "schema": []}
{"input": "Oxysterols are also implicated in aetiology of disease states including atherosclerosis, neurodegenerative and inflammatory diseases.", "output": {"entities": {"chemical": [{"text": "Oxysterols", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Reports indicating the levels of oxysterols in plasma, cerebrospinal fluid and various tissues are in many cases unrealistic owing to a lack of attention to the possibility of autoxidation, a process by which oxysterols are formed from cholesterol by oxygen in air.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 33, "end": 43}, {"text": "oxysterols", "start": 209, "end": 219}, {"text": "cholesterol", "start": 236, "end": 247}, {"text": "oxygen", "start": 251, "end": 257}]}}, "schema": []}
{"input": "This article comprises a critical assessment of the technical difficulties of oxysterol analysis, highlights methodologies utilising best practise and discusses newer procedures.", "output": {"entities": {"chemical": [{"text": "oxysterol", "start": 78, "end": 87}]}}, "schema": []}
{"input": "Prolactin regulates transcription of the ion uptake Na +/Cl-cotransporter (ncc) gene in zebrafish gill.", "output": {"entities": {"chemical": [{"text": "Na +", "start": 52, "end": 56}, {"text": "Cl-", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake.", "output": {"entities": {}}, "schema": []}
{"input": "Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na (+)/Cl (-) cotransporter (ncc; slc12a10. 2), Na (+)/H (+) exchanger (nhe3b; slc9a3. 2), and epithelial Ca (2 +) channel (ecac; trpv6) transcripts within the gill.", "output": {"entities": {"chemical": [{"text": "Na (+)", "start": 80, "end": 86}, {"text": "Cl (-)", "start": 87, "end": 93}, {"text": "Na (+)", "start": 128, "end": 134}, {"text": "H (+)", "start": 135, "end": 140}, {"text": "Ca (2 +)", "start": 186, "end": 194}]}}, "schema": []}
{"input": "Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac.", "output": {"entities": {}}, "schema": []}
{"input": "Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Delta 1-9-G129R-hPRL).", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl (-) uptake in zebrafish for the first time.", "output": {"entities": {"chemical": [{"text": "Cl (-)", "start": 167, "end": 173}]}}, "schema": []}
{"input": "Molecular design of a highly selective and strong protein inhibitor against matrix metalloproteinase-2 (MMP-2).", "output": {"entities": {}}, "schema": []}
{"input": "Synthetic inhibitors of matrix metalloproteinases (MMPs), designed previously, as well as tissue inhibitors of metalloproteinases (TIMPs) lack enzyme selectivity, which has been a major obstacle for developing inhibitors into safe and effective MMP-targeted drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Here we designed a fusion protein named APP-IP-TIMP-2, in which the ten amino acid residue sequence of APP-derived MMP-2 selective inhibitory peptide (APP-IP) is added to the N terminus of TIMP-2.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 72, "end": 82}, {"text": "N", "start": 175, "end": 176}]}}, "schema": []}
{"input": "The APP-IP and TIMP-2 regions of the fusion protein are designed to interact with the active site and the hemopexin-like domain of MMP-2, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The reactive site of the TIMP-2 region, which has broad specificity against MMPs, is blocked by the APP-IP adduct.", "output": {"entities": {}}, "schema": []}
{"input": "The recombinant APP-IP-TIMP-2 showed strong inhibitory activity toward MMP-2 (Ki (app) = 0. 68 pm), whereas its inhibitory activity toward MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, or MT1-MMP was six orders of magnitude or more weaker (IC50 > 1 mu m).", "output": {"entities": {}}, "schema": []}
{"input": "The fusion protein inhibited the activation of pro-MMP-2 in the concanavalin A-stimulated HT1080 cells, degradation of type IV collagen by the cells, and the migration of stimulated cells.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with the decapeptide APP-IP (t & frac12; = 30 min), APP-IP-TIMP-2 (t & frac12; >> 96 h) showed a much longer half-life in cultured tumor cells.", "output": {"entities": {"chemical": [{"text": "decapeptide", "start": 18, "end": 29}]}}, "schema": []}
{"input": "Therefore, the fusion protein may be a useful tool to evaluate contributions of proteolytic activity of MMP-2 in various pathophysiological processes.", "output": {"entities": {}}, "schema": []}
{"input": "It may also be developed as an effective anti-tumor drug with restricted side effects.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro activity of scorpiand-like azamacrocycle derivatives in promastigotes and intracellular amastigotes of Leishmania infantum and Leishmania braziliensis.", "output": {"entities": {}}, "schema": []}
{"input": "The activity of a family scorpiand-like azamacrocycles against Leishmania infantum and Leishmania braziliensis was studied using promastigotes, axenic and intracellular amastigotes forms.", "output": {"entities": {}}, "schema": []}
{"input": "All the compounds are more active and less toxic than meglumine antimoniate (Glucantime).", "output": {"entities": {"chemical": [{"text": "meglumine antimoniate", "start": 54, "end": 75}, {"text": "Glucantime", "start": 77, "end": 87}]}}, "schema": []}
{"input": "Moreover, the data on infection rates and amastigotes showed that compounds P2Py, PN and P3Py are the most active against both species of Leishmania.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, studies on the inhibitory effect of these compounds on SOD enzymes showed that while the inhibition of the Fe-SOD enzyme of the promastigote forms of the parasites is remarkable, the inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli is negligible.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 126, "end": 128}, {"text": "CuZn", "start": 222, "end": 226}, {"text": "Mn", "start": 235, "end": 237}]}}, "schema": []}
{"input": "The ultrastructural alterations observed in treated promastigote forms confirmed that the compounds having the highest activity were those causing the largest cell damage.", "output": {"entities": {}}, "schema": []}
{"input": "The modifications observed by (1) H NMR, and the amounts of catabolites excreted by the parasites after treatment with the compounds, suggested that the catabolic mechanism could depend on the structure of the side chains linked to the aza-scorpiand macrocycles.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 30, "end": 35}, {"text": "aza", "start": 236, "end": 239}]}}, "schema": []}
{"input": "Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts.", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 0, "end": 7}, {"text": "methyl CpG", "start": 58, "end": 68}, {"text": "CpG", "start": 70, "end": 73}]}}, "schema": []}
{"input": "Fetal alcohol syndrome (FAS), presenting with a constellation of neuro-/psychological, craniofacial and cardiac abnormalities, occurs frequently in offspring of women who consume alcohol during pregnancy, with a prevalence of 1-3 per 1000 livebirths.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 6, "end": 13}, {"text": "alcohol", "start": 179, "end": 186}]}}, "schema": []}
{"input": "The present study was designed to test the hypothesis that alcohol alters global DNA methylation, and modulates expression of the DNA methyltransferases (DNMTs) and various methyl CpG-binding proteins.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 59, "end": 66}, {"text": "methyl CpG", "start": 173, "end": 183}]}}, "schema": []}
{"input": "Murine embryonic fibroblasts (MEFs), utilized as an in vitro embryonic model system, demonstrated ~ 5% reduction in global DNA methylation following exposure to 200mM ethanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 167, "end": 174}]}}, "schema": []}
{"input": "In addition, ethanol induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 13, "end": 20}, {"text": "methyl CpG", "start": 114, "end": 124}]}}, "schema": []}
{"input": "Such degradation could be completely rescued by pretreatment of MEF cells with the proteasomal inhibitor, MG-132.", "output": {"entities": {"chemical": [{"text": "MG-132", "start": 106, "end": 112}]}}, "schema": []}
{"input": "These data support a potential epigenetic molecular mechanism underlying the pathogenesis of FAS during mammalian development.", "output": {"entities": {}}, "schema": []}
{"input": "Functional expression and regulation of drug transporters in monolayer-and sandwich-cultured mouse hepatocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Primary hepatocyte cultures are now considered as convenient models for in vitro analyzing liver drug transport.", "output": {"entities": {}}, "schema": []}
{"input": "However, if primary human and rat hepatocytes have been well-characterized with respect to drug transporter expression and regulation, much less is known for primary mouse hepatocytes.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was therefore designed to gain insights about this point.", "output": {"entities": {}}, "schema": []}
{"input": "The profile of sinusoidal and canalicular drug transporter mRNA expression in short time (4h)-cultured mouse hepatocytes was found to be highly correlated with that of freshly isolated hepatocytes; by contrast, those of counterparts cultured for a longer time (until 4days) either in monolayer configurations on plastic or collagen or in sandwich configuration with matrigel were profoundly altered: uptake drug transporters such as Oct1, Oatps and Oat2 were thus down-regulated, whereas most of efflux transporters such as Mdr1a/b, Mrp3, Mrp4 and Bcrp were induced.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, short time-cultured hepatocytes exhibited the highest levels of sinusoidal influx transporter activities.", "output": {"entities": {}}, "schema": []}
{"input": "Transporter-mediated drug secretion into canalicular networks was however only observed in sandwich-cultured hepatocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Mouse hepatocytes cultured either in monolayer or sandwich configurations were finally shown to exhibit up-regulation of referent transporters in response to exposure to prototypical activators of the drug sensing receptors pregnane X receptor, aryl hydrocarbon receptor or constitutive androstane receptor.", "output": {"entities": {"chemical": [{"text": "pregnane", "start": 224, "end": 232}, {"text": "aryl hydrocarbon", "start": 245, "end": 261}, {"text": "androstane", "start": 287, "end": 297}]}}, "schema": []}
{"input": "Taken together, these data demonstrate the feasibility of using primary mouse hepatocytes for investigating potential interactions of xenobiotics with hepatic transporter activity or regulation, provided that adequate culture conditions are retained.", "output": {"entities": {}}, "schema": []}
{"input": "AhR-and NF-kappa B-dependent induction of interleukin-6 by co-exposure to the environmental contaminant benzanthracene and the cytokine tumor necrosis factor-alpha in human mammary MCF-7 cells.", "output": {"entities": {"chemical": [{"text": "benzanthracene", "start": 104, "end": 118}]}}, "schema": []}
{"input": "Co-exposure to environmental polycyclic aromatic hydrocarbons (PAHs) and interleukin (IL)-1 beta induces expression of the tumor-promoting cytokine IL-6 in cancer cells.", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbons", "start": 29, "end": 61}, {"text": "PAHs", "start": 63, "end": 67}]}}, "schema": []}
{"input": "The present study was designed to determine whether such an IL-6 up-regulation also occurs in response to co-treatment by PAHs and tumor necrosis factor (TNF)-alpha, an inflammatory cytokine commonly found in tumor microenvironment.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 122, "end": 126}]}}, "schema": []}
{"input": "Co-exposure to the prototypical PAH benzanthracene (BZA) and TNF-alpha was found to markedly induce mRNA expression and secretion of IL-6 in human breast cancer cells MCF-7, whereas exposure to either BZA or TNF-alpha alone was without significant effect.", "output": {"entities": {"chemical": [{"text": "PAH benzanthracene", "start": 32, "end": 50}, {"text": "BZA", "start": 52, "end": 55}, {"text": "BZA", "start": 201, "end": 204}]}}, "schema": []}
{"input": "Co-treatment by BZA and TNF-alpha-containing conditioned media from human inflammatory macrophages similarly up-regulated IL-6 expression in MCF-7 cells.", "output": {"entities": {"chemical": [{"text": "BZA", "start": 16, "end": 19}]}}, "schema": []}
{"input": "BZA/TNF-alpha-mediated IL-6 induction in MCF-7 cells was counteracted by silencing aryl hydrocarbon receptor (AhR), known to mediates most of PAH effects.", "output": {"entities": {"chemical": [{"text": "BZA", "start": 0, "end": 3}, {"text": "aryl hydrocarbon", "start": 83, "end": 99}, {"text": "PAH", "start": 142, "end": 145}]}}, "schema": []}
{"input": "IL-6 up-regulation was moreover associated with NF-kappa B activation and was abolished by using chemical NF-kappa B inhibitors or knocking-down expression of the p65/RelA NF-kappa B subunit.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these data indicate that co-exposure to BZA/TNF-alpha induces IL-6 expression by AhR-and NF-kappa B-dependent pathways in MCF-7 cancer cells.", "output": {"entities": {"chemical": [{"text": "BZA", "start": 56, "end": 59}]}}, "schema": []}
{"input": "This regulation of IL-6 by environmental PAHs, that is dependent of inflammatory cytokine microenvironment, may contribute to the well-known carcinogenic properties of these organic pollutants.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 41, "end": 45}]}}, "schema": []}
{"input": "Quercetin prevents protein nitration and glycolytic block of proliferation in hydrogen peroxide insulted cultured neuronal precursor cells (NPCs): Implications on CNS regeneration.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "hydrogen peroxide", "start": 78, "end": 95}]}}, "schema": []}
{"input": "Survival along with optimal proliferation of neuronal precursors determines the outcomes of the endogenous cellular repair in CNS.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular-oxidation based cell death has been described in several neurodegenerative disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, this study was aimed at the identification of the potent targets of oxidative damage to the neuronal precursors and its effective prevention by a natural flavonoid, Quercetin.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 176, "end": 185}]}}, "schema": []}
{"input": "Neuronal precursor cells (NPCs), Nestin + and GFAP (Glial fibrillary acidic protein) + were isolated and cultured from adult rat SVZ (subventricular zone).", "output": {"entities": {}}, "schema": []}
{"input": "These cells were challenged with a single dose of H2O2 (50 mu M) and/or pre-treated with different concentrations of Quercetin.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 50, "end": 54}, {"text": "Quercetin", "start": 117, "end": 126}]}}, "schema": []}
{"input": "H2O2 severely limited the cellular viability and expansion of the neurospheres.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Cellular-oxidation studies revealed reduction in glutathione dependent redox buffering along with depletion of enzymatic cellular antioxidants that might potentiate the nitrite (NO2 (-)) and superoxide anion (O2 (-)) mediated peroxynitrite (ONOO (-)) formation and irreversible protein nitration.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 49, "end": 60}, {"text": "nitrite", "start": 169, "end": 176}, {"text": "NO2 (-)", "start": 178, "end": 185}, {"text": "superoxide", "start": 191, "end": 201}, {"text": "O2 (-)", "start": 209, "end": 215}, {"text": "peroxynitrite", "start": 226, "end": 239}, {"text": "ONOO (-)", "start": 241, "end": 249}]}}, "schema": []}
{"input": "We identified depleted PK-M2 (M2 isoform of pyruvate kinase) activity and apoptosis of NPCs revealed by the genomic DNA fragmentation and elevated PARP (poly ADP ribose polymerase) activity along with increased Caspase activity initiated by severely depolarised mitochondrial membranes.", "output": {"entities": {"chemical": [{"text": "pyruvate", "start": 44, "end": 52}, {"text": "poly ADP ribose", "start": 153, "end": 168}]}}, "schema": []}
{"input": "However, the pre-treatment of Quercetin in a dose-response manner prevented these changes and restored the expansion of neurospheres preferably by neutralizing the oxidative conditions and thereby reducing peroxynitrite formation, protein nitration and PK-M2 depletion.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 30, "end": 39}, {"text": "peroxynitrite", "start": 206, "end": 219}]}}, "schema": []}
{"input": "Our results unravel the potential interactions of oxidative environment and respiration in the survival and activation of precursors and offer a promise shown by a natural flavonoid in the protective strategy for neuronal precursors of adult brain.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 172, "end": 181}]}}, "schema": []}
{"input": "Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear.", "output": {"entities": {}}, "schema": []}
{"input": "JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus.", "output": {"entities": {}}, "schema": []}
{"input": "To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30).", "output": {"entities": {}}, "schema": []}
{"input": "Radiologists infused low-or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes.", "output": {"entities": {}}, "schema": []}
{"input": "Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses.", "output": {"entities": {}}, "schema": []}
{"input": "JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14. 1 months compared to 6. 7 months on the high and low dose, respectively; hazard ratio 0. 39; P = 0. 020).", "output": {"entities": {}}, "schema": []}
{"input": "JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.", "output": {"entities": {}}, "schema": []}
{"input": "Meta-immunological profiling of children with type 1 diabetes identifies new biomarkers to monitor disease progression.", "output": {"entities": {}}, "schema": []}
{"input": "Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta-cells in genetically susceptible individuals.", "output": {"entities": {}}, "schema": []}
{"input": "Triggers of islet autoimmunity, time course and the precise mechanisms responsible for the progressive beta-cell failure are not completely understood.", "output": {"entities": {}}, "schema": []}
{"input": "The recent escalation of obesity in affluent countries has been suggested to contribute to the increased incidence of type 1 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the link between metabolism and immune tolerance could lead to the identification of new markers for the monitoring of disease onset and progression.", "output": {"entities": {}}, "schema": []}
{"input": "We studied several immune cell subsets and factors with high metabolic impact as markers associated with disease progression in high-risk subjects, type 1 diabetes patients at onset, 12 and 24 months after diagnosis.", "output": {"entities": {}}, "schema": []}
{"input": "A multiple correlation matrix among different parameters was evaluated statistically and assessed visually on two-dimensional graphs.", "output": {"entities": {}}, "schema": []}
{"input": "Markers to predict residual beta-cell function up to one year after diagnosis were identified in multivariate logistic regression models.", "output": {"entities": {}}, "schema": []}
{"input": "The metaimmunological profile changed significantly over time in patients and a specific signature that associated with worsening disease was identified.", "output": {"entities": {}}, "schema": []}
{"input": "A multivariate logistic regression model measuring age, body mass index (BMI), fasting C-peptide, number of circulating CD3 (+) CD16 (+) CD56 (+) cells and the percentage of CD1c (+) CD19 (-) CD14 (-) CD303 (-) type 1 myeloid dendritic cells (mDC1s) at disease onset had a significant predictive value.", "output": {"entities": {}}, "schema": []}
{"input": "The identification of a specific meta-immunological profile associated to disease status may contribute to understand the basis of diabetes progression.", "output": {"entities": {}}, "schema": []}
{"input": "A non-enzymatic function of Golgi glycosyltransferases: Mediation of Golgi fragmentation by interaction with non-muscle myosin IIA.", "output": {"entities": {}}, "schema": []}
{"input": "The Golgi apparatus undergoes morphological changes under stress or malignant transformation, but the precise mechanisms are not known.", "output": {"entities": {}}, "schema": []}
{"input": "We recently showed that non-muscle myosin IIA (NMIIA) binds to the cytoplasmic tail of Core 2 N-acetylglucosaminyltransferase mucus-type (C2GnT-M) and transports it to the endoplasmic reticulum for recycling.", "output": {"entities": {"chemical": [{"text": "NMIIA", "start": 47, "end": 52}]}}, "schema": []}
{"input": "Here, we report that Golgi fragmentation induced by brefeldin A (BFA) or coatomer protein (beta-COP) knockdown (KD) in Panc1-bC2GnT-M (c-Myc) cells is accompanied by the increased association of NMIIA with C2GnT-M and its degradation by proteasomes.", "output": {"entities": {"chemical": [{"text": "brefeldin A", "start": 52, "end": 63}, {"text": "BFA", "start": 65, "end": 68}]}}, "schema": []}
{"input": "Golgi fragmentation is prevented by inhibition or KD of NMIIA.", "output": {"entities": {}}, "schema": []}
{"input": "Using multiple approaches, we have shown that the speed of BFA-induced Golgi fragmentation is positively correlated with the levels of this enzyme in the Golgi.", "output": {"entities": {"chemical": [{"text": "BFA", "start": 59, "end": 62}]}}, "schema": []}
{"input": "The observation is reproduced in LNCaP cells which express high levels of two endogenous glycosyltransferases-C2GnT-L and beta-galactoside alpha 2, 3 sialyltransferase 1.", "output": {"entities": {}}, "schema": []}
{"input": "NMIIA is found to form complexes with these two enzymes but not Golgi matrix proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The KD of both enzymes or the prevention of Golgi glycosyltransferases from exiting endoplasmic reticulum reduced Golgi-associated NMIIA and decreased the BFA-induced fragmentation.", "output": {"entities": {"chemical": [{"text": "BFA", "start": 155, "end": 158}]}}, "schema": []}
{"input": "Interestingly, the fragmented Golgi detected in colon cancer HT-29 cells can be restored to a compact morphology after inhibition or KD of NMIIA.", "output": {"entities": {}}, "schema": []}
{"input": "The Golgi disorganization induced by the microtubule or actin destructive agent is NMIIA-independent and does not affect the levels of glycosyltransferases.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that NMIIA interacts with Golgi residential but not matrix proteins, and this interaction is responsible for Golgi fragmentation induced by beta-COP KD or BFA treatment.", "output": {"entities": {"chemical": [{"text": "BFA", "start": 167, "end": 170}]}}, "schema": []}
{"input": "This is a novel non-enzymatic function of Golgi glycosyltransferases.", "output": {"entities": {}}, "schema": []}
{"input": "Saturable active efflux by p-glycoprotein and breast cancer resistance protein at the blood-brain barrier leads to nonlinear distribution of elacridar to the central nervous system.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 141, "end": 150}]}}, "schema": []}
{"input": "The study objective was to investigate factors that affect the central nervous system (CNS) distribution of elacridar.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 108, "end": 117}]}}, "schema": []}
{"input": "Elacridar inhibits transport mediated by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and has been used to study the influence of transporters on brain distribution of chemotherapeutics.", "output": {"entities": {"chemical": [{"text": "Elacridar", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Adequate distribution of elacridar across the blood-brain barrier (BBB) and into the brain parenchyma is necessary to target tumor cells in the brain that overexpress transporters and reside behind an intact BBB.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 25, "end": 34}]}}, "schema": []}
{"input": "We examined the role of P-gp and Bcrp on brain penetration of elacridar using Friend leukemia virus strain B wild-type, Mdr1a/b (-/-), Bcrp1 (-/-), and Mdr1a/b (-/-) Bcrp1 (-/-) mice.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 62, "end": 71}]}}, "schema": []}
{"input": "Initially, the mice were administered 2. 5 mg/kg of elacridar intravenously, and the plasma and brain concentrations were determined.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 52, "end": 61}]}}, "schema": []}
{"input": "The brain-to-plasma partition coefficient of elacridar in the wild-type mice was 0. 82, as compared with 3. 5 in Mdr1a/b (-/-) mice, 6. 6 in Bcrp1 (-/-) mice, and 15 in Mdr1a/b (-/-) Bcrp1 (-/-) mice, indicating that both P-gp and Bcrp limit the brain distribution of elacridar.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 45, "end": 54}, {"text": "elacridar", "start": 268, "end": 277}]}}, "schema": []}
{"input": "The four genotypes were then administered increasing doses of elacridar, and the CNS distribution of elacridar was determined.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 62, "end": 71}, {"text": "elacridar", "start": 101, "end": 110}]}}, "schema": []}
{"input": "The observed and model predicted maximum brain-to-plasma ratios (Emax) at the highest dose were not significantly different in all genotypes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the ED50 was lower for Mdr1a/b (-/-) mice compared with Bcrp1 (-/-) mice.", "output": {"entities": {}}, "schema": []}
{"input": "These findings correlate with the relative expression of P-gp and Bcrp at the BBB in these mice and demonstrate the quantitative enhancement in elacridar CNS distribution as a function of its dose.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, this study provides useful concepts for future applications of elacridar as an adjuvant therapy to improve targeting of chemotherapeutic agents to tumor cells in the brain parenchyma.", "output": {"entities": {"chemical": [{"text": "elacridar", "start": 72, "end": 81}]}}, "schema": []}
{"input": "HepG2 cells simultaneously expressing five P450 enzymes for the screening of hepatotoxicity: identification of bioactivable drugs and the potential mechanism of toxicity involved.", "output": {"entities": {}}, "schema": []}
{"input": "Use of the HepG2 cell line to assess hepatotoxicity induced by bioactivable compounds is hampered by their low cytochrome P450 expression.", "output": {"entities": {}}, "schema": []}
{"input": "To overcome this limitation, we have used adenoviral transfection to develop upgraded HepG2 cells (ADV-HepG2) expressing the major P450 enzymes involved in drug metabolism (CYP1A2, CYP2D6, CYP2C9, CYP2C19, and CYP3A4) at levels comparable to those of human hepatocytes.", "output": {"entities": {}}, "schema": []}
{"input": "The potential utility of this new cell model for the in vitro screening of bioactivable drugs was assessed using a high-content screening assay that we recently developed to simultaneously measure multiple parameters indicative of cell injury.", "output": {"entities": {}}, "schema": []}
{"input": "To this end, ADV-HepG2 and HepG2 cells, cultured in 96-well plates, were exposed for 24 h to a wide range of concentrations of 12 bioactivable and 3 non-bioactivable compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The cell viability and parameters associated with nuclear morphology, mitochondrial function, intracellular calcium concentration, and oxidative stress indicative of prelethal cytotoxicity and representative of different mechanisms of toxicity were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Bioactivable compounds showed lower IC (50) values in ADV-HepG2 cells than in HepG2 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, significant differences in the other parameters analyzed were observed between both cell models, while similar effects were observed for non-bioactivable compounds (negative controls).", "output": {"entities": {}}, "schema": []}
{"input": "The changes in cell parameters detected in our assay for a given compound are in good agreement with the previously reported toxicity mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, our results indicate that this assay may be a suitable new in vitro approach for early screening of compounds to identify bioactivable hepatotoxins and the mechanism (s) involved in their toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Atomic layer deposition of a submonolayer catalyst for the enhanced photoelectrochemical performance of water oxidation with hematite.", "output": {"entities": {"chemical": [{"text": "hematite", "start": 125, "end": 133}]}}, "schema": []}
{"input": "Hematite photoanodes were coated with an ultrathin cobalt oxide layer by atomic layer deposition (ALD).", "output": {"entities": {"chemical": [{"text": "Hematite", "start": 0, "end": 8}, {"text": "cobalt oxide", "start": 51, "end": 63}]}}, "schema": []}
{"input": "The optimal coating-1 ALD cycle, which amounts to < 1 monolayer of Co (OH) 2/Co3O4-resulted in significantly enhanced photoelectrochemical water oxidation performance.", "output": {"entities": {"chemical": [{"text": "Co (OH) 2", "start": 67, "end": 76}, {"text": "Co3O4", "start": 77, "end": 82}]}}, "schema": []}
{"input": "A stable, 100-200 mV cathodic shift in the photocurrent onset potential was observed that is correlated to an order of magnitude reduction in the resistance to charge transfer at the Fe2O3/H2O interface.", "output": {"entities": {"chemical": [{"text": "Fe2O3", "start": 183, "end": 188}, {"text": "H2O", "start": 189, "end": 192}]}}, "schema": []}
{"input": "Furthermore, the optical transparency of the ultrathin Co (OH) 2/Co3O4 coating establishes it as a particularly advantageous treatment for nanostructured water oxidation photoanodes.", "output": {"entities": {"chemical": [{"text": "Co (OH) 2", "start": 55, "end": 64}, {"text": "Co3O4", "start": 65, "end": 70}]}}, "schema": []}
{"input": "The photocurrent of catalyst-coated nanostructured inverse opal scaffold hematite photoanodes reached 0. 81 and 2. 1 mA/cm (2) at 1. 23 and 1. 53 V, respectively.", "output": {"entities": {"chemical": [{"text": "hematite", "start": 73, "end": 81}]}}, "schema": []}
{"input": "A detailed look at the reaction mechanisms of substituted carbenes with water.", "output": {"entities": {"chemical": [{"text": "carbenes", "start": 58, "end": 66}]}}, "schema": []}
{"input": "Two competitive reaction mechanisms for the gas-phase chemical transformation of singlet chlorocarbene into chloromethanol in the presence of one and two water molecules are examined in detail.", "output": {"entities": {"chemical": [{"text": "chlorocarbene", "start": 89, "end": 102}, {"text": "chloromethanol", "start": 108, "end": 122}]}}, "schema": []}
{"input": "An analysis of bond orders and bond order derivatives as well as of properties of bond critical points in the electron densities along the intrinsic reaction coordinates (IRCs for intermediates --> transition state (TS) --> products) suggests that, from the perspective of bond breaking/formation, both reactions should be considered to be highly nonsynchronous, concerted processes.", "output": {"entities": {}}, "schema": []}
{"input": "Both transition states are early, resembling the intermediates, yielding rate constants whose magnitudes are mostly influenced by structural changes and to a lesser degree by bond breaking/formation.", "output": {"entities": {}}, "schema": []}
{"input": "For the case of one water molecule, most of the energy in the reactants region of the IRC is used for structural changes, while the transition state region encompasses the majority of electron activity, except for the formation of the C-O bond, which extends well into the products region.", "output": {"entities": {"chemical": [{"text": "C-O", "start": 235, "end": 238}]}}, "schema": []}
{"input": "In the case of two water molecules, very little electron flux and comparatively less work required for structural changes is noticed in the reactants region, leading to an earlier transition state and therefore to a smaller activation energy and to a larger rate constant.", "output": {"entities": {}}, "schema": []}
{"input": "This, together with evidence gathered from other sources, allows us to provide plausible explanations for the observed difference in rate constants.", "output": {"entities": {}}, "schema": []}
{"input": "Prediction of micelle/water and liposome/water partition coefficients based on molecular dynamics simulations, COSMO-RS, and COSMOmic.", "output": {"entities": {}}, "schema": []}
{"input": "Liposomes and micelles find various applications as potential solubilizers in extraction processes or in drug delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Thermodynamic and transport processes governing the interactions of different kinds of solutes in liposomes or micelles can be analyzed regarding the free energy profiles of the solutes in the system.", "output": {"entities": {}}, "schema": []}
{"input": "However, free energy profiles in heterogeneous systems such as micelles are experimentally almost not accessible.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the development of predictive methods is desirable.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular dynamics (MD) simulations reliably simulate the structure and dynamics of lipid membranes and micelles, whereas COSMO-RS accurately reproduces solvation free energies in different solvents.", "output": {"entities": {}}, "schema": []}
{"input": "For the first time, free energy profiles in micellar systems, as well as mixed lipid bilayers, are investigated, taking advantage of both methods: MD simulations and COSMO-RS, referred to as COSMOmic (Klamt, A.; Huniar, U.; Spycher, S.; Keldenich, J. COSMOmic: A Mechanistic Approach to the Calculation of Membrane-Water Partition Coefficients and Internal Distributions within Membranes and Micelles. J. Phys. Chem. B 2008, 112, 12148-12157).", "output": {"entities": {}}, "schema": []}
{"input": "All-atom molecular dynamics simulations of the system SDS/water and CTAB/water have been applied in order to retrieve representative micelle structures for further analysis with COSMOmic.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 54, "end": 57}, {"text": "CTAB", "start": 68, "end": 72}]}}, "schema": []}
{"input": "For the system CTAB/water, different surfactant concentrations were considered, which results in different micelle sizes.", "output": {"entities": {"chemical": [{"text": "CTAB", "start": 15, "end": 19}]}}, "schema": []}
{"input": "Free energy profiles of more than 200 solutes were predicted and validated by means of experimental partition coefficients.", "output": {"entities": {}}, "schema": []}
{"input": "To our knowledge, these are the first quantitative predictions of micelle/water partition coefficients, which are based on whole free energy profiles from molecular methods.", "output": {"entities": {}}, "schema": []}
{"input": "Further, the partitioning in lipid bilayer systems containing different hydrophobic tail groups (DOPC (1, 2-dioleoyl-sn-glycero-3-phosphocholine), SOPC (stearoyl-oleoylphosphatidylcholine), DMPC (1, 2-dimyristoyl-sn-glycero-3-phosphocholine), and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)) as well as mixed bilayers was calculated.", "output": {"entities": {"chemical": [{"text": "DOPC", "start": 97, "end": 101}, {"text": "1, 2-dioleoyl-sn-glycero-3-phosphocholine", "start": 103, "end": 144}, {"text": "SOPC", "start": 147, "end": 151}, {"text": "stearoyl-oleoylphosphatidylcholine", "start": 153, "end": 187}, {"text": "DMPC", "start": 190, "end": 194}, {"text": "1, 2-dimyristoyl-sn-glycero-3-phosphocholine", "start": 196, "end": 240}, {"text": "POPC", "start": 247, "end": 251}, {"text": "1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine", "start": 253, "end": 301}]}}, "schema": []}
{"input": "Experimental partition coefficients (log P) were reproduced with a root-mean-square error (RMSE) of 0. 62.", "output": {"entities": {}}, "schema": []}
{"input": "To determine the influence of cholesterol as an important component of cellular membranes, free energy profiles in the presence of cholesterol were calculated and shown to be in good agreement with experimental data.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 30, "end": 41}, {"text": "cholesterol", "start": 131, "end": 142}]}}, "schema": []}
{"input": "Probing adsorption of polyacrylamide-based polymers on anisotropic Basal planes of kaolinite using quartz crystal microbalance.", "output": {"entities": {"chemical": [{"text": "polyacrylamide", "start": 22, "end": 36}, {"text": "kaolinite", "start": 83, "end": 92}, {"text": "quartz", "start": 99, "end": 105}]}}, "schema": []}
{"input": "Quartz crystal microbalance with dissipation (QCM-D) was applied to investigate the adsorption characteristics of polyacrylamide-based polymers (PAMs) on anisotropic basal planes of kaolinite.", "output": {"entities": {"chemical": [{"text": "Quartz", "start": 0, "end": 6}, {"text": "polyacrylamide", "start": 114, "end": 128}, {"text": "PAMs", "start": 145, "end": 149}, {"text": "kaolinite", "start": 182, "end": 191}]}}, "schema": []}
{"input": "Kaolinite basal planes were differentiated by depositing kaolinite nanoparticles (KNPs) on silica and alumina sensors in solutions of controlled pH values.", "output": {"entities": {"chemical": [{"text": "Kaolinite", "start": 0, "end": 9}, {"text": "kaolinite", "start": 57, "end": 66}, {"text": "silica", "start": 91, "end": 97}, {"text": "alumina", "start": 102, "end": 109}]}}, "schema": []}
{"input": "Adsorption of an in-house synthesized organic-inorganic Al (OH) 3-PAM (Al-PAM) as an example of cationic hybrid PAM and a commercially available partially hydrolyzed polyacrylamide (MF1011) as an example of anionic PAM was studied.", "output": {"entities": {"chemical": [{"text": "Al (OH) 3-PAM", "start": 56, "end": 69}, {"text": "Al-PAM", "start": 71, "end": 77}, {"text": "PAM", "start": 112, "end": 115}, {"text": "polyacrylamide", "start": 166, "end": 180}, {"text": "MF1011", "start": 182, "end": 188}, {"text": "anionic PAM", "start": 207, "end": 218}]}}, "schema": []}
{"input": "Cationic Al-PAM was found to adsorb irreversibly and preferentially on tetrahedral silica basal planes of kaolinite.", "output": {"entities": {"chemical": [{"text": "Cationic Al-PAM", "start": 0, "end": 15}, {"text": "silica", "start": 83, "end": 89}, {"text": "kaolinite", "start": 106, "end": 115}]}}, "schema": []}
{"input": "In contrast, anionic MF1011 adsorbed strongly on aluminum-hydroxy basal planes, while its adsorption on tetrahedral silica basal planes was weak and reversible.", "output": {"entities": {"chemical": [{"text": "anionic MF1011", "start": 13, "end": 27}, {"text": "aluminum-hydroxy", "start": 49, "end": 65}, {"text": "silica", "start": 116, "end": 122}]}}, "schema": []}
{"input": "Adsorption study revealed that both electrostatic attraction and hydrogen-bonding mechanisms contribute to adsorption of PAMs on kaolinite.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 65, "end": 73}, {"text": "PAMs", "start": 121, "end": 125}, {"text": "kaolinite", "start": 129, "end": 138}]}}, "schema": []}
{"input": "The adsorbed Al-PAM layer was able to release trapped water overtime and became more compact, while MF1011 film became more dissipative as backbones stretched out from kaolinite surface with minimal overlapping.", "output": {"entities": {"chemical": [{"text": "Al-PAM", "start": 13, "end": 19}, {"text": "MF1011", "start": 100, "end": 106}, {"text": "kaolinite", "start": 168, "end": 177}]}}, "schema": []}
{"input": "Experimental results obtained from this study provide clear insights into the phenomenon that governs flocculation-based solid-liquid separation processes using multicomponent flocculants of anionic and cationic nature.", "output": {"entities": {}}, "schema": []}
{"input": "Strong effects of cluster size and air exposure on oxygen reduction and carbon oxidation electrocatalysis by size-selected Pt (n) (n <= 11) on glassy carbon electrodes.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 51, "end": 57}, {"text": "carbon", "start": 72, "end": 78}, {"text": "Pt (n)", "start": 123, "end": 129}, {"text": "glassy carbon", "start": 143, "end": 156}]}}, "schema": []}
{"input": "Model Pt (n)/glassy carbon electrodes (Pt (n)/GCE) were prepared by deposition of mass-selected Pt (n) (+) (n <= 11) on GCE substrates in ultrahigh vacuum.", "output": {"entities": {"chemical": [{"text": "Pt (n)", "start": 6, "end": 12}, {"text": "glassy carbon", "start": 13, "end": 26}, {"text": "Pt (n)", "start": 39, "end": 45}, {"text": "Pt (n) (+)", "start": 96, "end": 106}]}}, "schema": []}
{"input": "Electrocatalysis under conditions appropriate for the oxygen reduction reaction (ORR) was studied, for samples both in situ with no exposure to laboratory air and with air exposure prior to electrochemical measurements.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 54, "end": 60}]}}, "schema": []}
{"input": "Of the small clusters, only a few cluster sizes show the expected ORR activity, and in those cases, the activity per Pt atom is similar to that seen under identical conditions with a conventionally prepared electrode with Pt nanoparticles grown on a GCE.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 117, "end": 119}, {"text": "Pt", "start": 222, "end": 224}]}}, "schema": []}
{"input": "For other small Pt (n) on GCE, any ORR signal is overwhelmed by large oxidative currents attributed to catalysis of carbon oxidation by water.", "output": {"entities": {"chemical": [{"text": "Pt (n)", "start": 16, "end": 22}, {"text": "carbon", "start": 116, "end": 122}]}}, "schema": []}
{"input": "If the samples are exposed to air prior to electrochemistry, both ORR and carbon oxidation signals are absent, and instead only small capacitive currents or currents attributed to redox chemistry of adventitious organic adsorbates are observed, indicating that air exposure results in passivation of the small Pt clusters.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 74, "end": 80}, {"text": "Pt", "start": 310, "end": 312}]}}, "schema": []}
{"input": "Effects of chronic dietary selenomethionine exposure on repeat swimming performance, aerobic metabolism and methionine catabolism in adult zebrafish (Danio rerio).", "output": {"entities": {"chemical": [{"text": "selenomethionine", "start": 27, "end": 43}, {"text": "methionine", "start": 108, "end": 118}]}}, "schema": []}
{"input": "In a previous study we reported impaired swimming performance and greater stored energy in adult zebrafish (Danio rerio) after chronic dietary exposure to selenomethionine (SeMet).", "output": {"entities": {"chemical": [{"text": "selenomethionine", "start": 155, "end": 171}, {"text": "SeMet", "start": 173, "end": 178}]}}, "schema": []}
{"input": "The goal of the present study was to further investigate effects of chronic exposure to dietary SeMet on repeat swimming performance, oxygen consumption (MO2), metabolic capacities (standard metabolic rate [SMR], active metabolic rate [AMR], factorial aerobic scope [F-AS] and cost of transport [COT]) and gene expression of energy metabolism and methionine catabolism enzymes in adult zebrafish.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 96, "end": 101}, {"text": "oxygen", "start": 134, "end": 140}, {"text": "methionine", "start": 347, "end": 357}]}}, "schema": []}
{"input": "Fish were fed SeMet at measured concentrations of 1. 3, 3. 4, 9. 8 or 27. 5 mu g Se/g dry mass (d. m.) for 90 d.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 14, "end": 19}, {"text": "Se", "start": 81, "end": 83}]}}, "schema": []}
{"input": "At the end of the exposure period, fish from each treatment group were divided into three subgroups: (a) no swim, (b) swim, and (c) repeat swim.", "output": {"entities": {}}, "schema": []}
{"input": "Fish from the no swim group were euthanized immediately at 90 d and whole body triglycerides, glycogen and lactate, and gene expression of energy metabolism and methionine catabolism enzymes were determined.", "output": {"entities": {"chemical": [{"text": "triglycerides", "start": 79, "end": 92}, {"text": "lactate", "start": 107, "end": 114}, {"text": "methionine", "start": 161, "end": 171}]}}, "schema": []}
{"input": "Individual fish from the swim group were placed in a swim tunnel respirometer and swimming performance was assessed by determining the critical swimming speed (U (crit)).", "output": {"entities": {}}, "schema": []}
{"input": "After both Ucrit and MO2 analyses, fish were euthanized and whole body energy stores and lactate were determined.", "output": {"entities": {"chemical": [{"text": "lactate", "start": 89, "end": 96}]}}, "schema": []}
{"input": "Similarly, individual fish from the repeat swim group were subjected to two U (crit) tests (U (crit-1) and U (crit-2)) performed with a 60 min recovery period between tests, followed by determination of energy stores and lactate.", "output": {"entities": {"chemical": [{"text": "lactate", "start": 221, "end": 228}]}}, "schema": []}
{"input": "Impaired swim performance was observed in fish fed SeMet at concentrations greater than 3 mu g Se/g in the diet.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 51, "end": 56}, {"text": "Se", "start": 95, "end": 97}]}}, "schema": []}
{"input": "However, within each dietary Se treatment group, no significant differences between single and repeat U (crits) were observed.", "output": {"entities": {"chemical": [{"text": "Se", "start": 29, "end": 31}]}}, "schema": []}
{"input": "Oxygen consumption, SMR and COT were significantly greater, and F-AS was significantly lesser, in fish fed SeMet.", "output": {"entities": {"chemical": [{"text": "Oxygen", "start": 0, "end": 6}, {"text": "SeMet", "start": 107, "end": 112}]}}, "schema": []}
{"input": "Whole body triglycerides were proportional to the concentration of SeMet in the diet.", "output": {"entities": {"chemical": [{"text": "triglycerides", "start": 11, "end": 24}, {"text": "SeMet", "start": 67, "end": 72}]}}, "schema": []}
{"input": "While swimming resulted in lesser concentrations of glycogen in the body, exposure to SeMet in the diet had no significant effect on glycogen content.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 86, "end": 91}]}}, "schema": []}
{"input": "Exposure to SeMet significantly down-regulated mRNA abundance of protein tyrosine phosphatase 1B (PTP 1B) in muscle, and beta-hydroxyacyl coenzyme A dehydrogenase (HOAD), sterol regulatory element binding protein 1 (SREBP 1) and methionine adenosyltransferase 1 alpha (MAT 1A) in liver of adult zebrafish.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 12, "end": 17}, {"text": "tyrosine", "start": 73, "end": 81}, {"text": "beta-hydroxyacyl coenzyme A", "start": 121, "end": 148}, {"text": "sterol", "start": 171, "end": 177}, {"text": "methionine", "start": 229, "end": 239}]}}, "schema": []}
{"input": "Overall the results of this study suggest chronic exposure of adult zebrafish to SeMet in the diet can cause both cellular and organismal effects that could affect fitness and survivability of fish.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 81, "end": 86}]}}, "schema": []}
{"input": "Electron attachment to the dipeptide dialanine: influence of methylation on site selective dissociation reactions.", "output": {"entities": {"chemical": [{"text": "dialanine", "start": 37, "end": 46}]}}, "schema": []}
{"input": "Gas phase dissociative electron attachment (DEA) measurements with methyl-dialanine, C (7) H (14) N (2) O (3), are performed in a crossed electron-molecular beam experiment at high energy resolution (~ 120 meV).", "output": {"entities": {"chemical": [{"text": "methyl-dialanine", "start": 67, "end": 83}, {"text": "C (7) H (14) N (2) O (3)", "start": 85, "end": 109}]}}, "schema": []}
{"input": "Anion efficiency yields as a function of the incident electron energy are obtained for the most abundant fragments up to electron energies of ~ 15 eV.", "output": {"entities": {}}, "schema": []}
{"input": "There is no evidence of molecular anion formation whereas the dehydrogenated closed shell anion (M-H) (-) is one of the most dominant reaction products.", "output": {"entities": {}}, "schema": []}
{"input": "Quantum chemical calculations are performed to investigate the electron attachment process and to elucidate site selective bond cleavage in the (M-H) (-) DEA-channel.", "output": {"entities": {}}, "schema": []}
{"input": "Previous DEA studies on dialanine have shown that (M-H) (-) formation proceeds through abstraction of a hydrogen atom from the carboxyl and amide groups, contributing to two distinct resonances at 0. 81 and 1. 17 eV, respectively [D. Gschliesser, V. Vizcaino, M. Probst, P. Scheier and S. Denifl, Chem.-Eur. J., 2012, 18, 4613-4619].", "output": {"entities": {"chemical": [{"text": "dialanine", "start": 24, "end": 33}, {"text": "hydrogen", "start": 104, "end": 112}, {"text": "carboxyl", "start": 127, "end": 135}, {"text": "amide", "start": 140, "end": 145}]}}, "schema": []}
{"input": "Here we show that by methylation of the carboxyl group, all (calculated) thresholds for H-loss from the different sites in the dialanine molecule are shifted up to a maximum of 1. 4 eV.", "output": {"entities": {"chemical": [{"text": "carboxyl", "start": 40, "end": 48}, {"text": "H", "start": 88, "end": 89}, {"text": "dialanine", "start": 127, "end": 136}]}}, "schema": []}
{"input": "The lowest lying resonance observed experimentally for (M-H) (-) remains operative from the amide group at the electron energy of 2. 4 eV due to the methylation.", "output": {"entities": {"chemical": [{"text": "amide", "start": 92, "end": 97}]}}, "schema": []}
{"input": "We further study methylation-induced effects on the unimolecular dissociation leading to a variety of negatively charged DEA products.", "output": {"entities": {}}, "schema": []}
{"input": "Probing the dielectric response of graphene via dual-band plasmonic nanoresonators.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 35, "end": 43}]}}, "schema": []}
{"input": "In this article, we use optical transmission spectroscopy to measure the changes in the resonance features of a Au plasmonic nanoresonator array consisting of concentric ring/disc cavity elements, when graphene is introduced as an encapsulating medium.", "output": {"entities": {"chemical": [{"text": "Au", "start": 112, "end": 114}]}}, "schema": []}
{"input": "We show that by using finite element modelling to best reproduce our experimental results the dielectric response of the graphene film can be determined.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 121, "end": 129}]}}, "schema": []}
{"input": "We discuss the potential of such structures for chemical sensing applications.", "output": {"entities": {}}, "schema": []}
{"input": "Chromogenic and fluorogenic chemosensors and reagents for anions.", "output": {"entities": {}}, "schema": []}
{"input": "A comprehensive review of the years 2010-2011.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on examples reported in the years 2010-2011 dealing with the design of chromogenic and fluorogenic chemosensors or reagents for anions.", "output": {"entities": {}}, "schema": []}
{"input": "Feasibility of a breath test for monitoring adherence to vaginal administration of antiretroviral microbicide gels.", "output": {"entities": {}}, "schema": []}
{"input": "Adherence to microbicide gel use is critical to optimizing effectiveness in preventing human immunodeficiency virus transmission.", "output": {"entities": {}}, "schema": []}
{"input": "The authors hypothesized that ester taggants added to vaginal gels would generate exhaled alcohol and ketone metabolites and provide a \" breath test \" for vaginal gel use.", "output": {"entities": {"chemical": [{"text": "ester", "start": 30, "end": 35}, {"text": "alcohol", "start": 90, "end": 97}, {"text": "ketone", "start": 102, "end": 108}]}}, "schema": []}
{"input": "This 2-arm (vaginal and dermal), randomized, participant-blinded, pilot study tested this hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "On 8 visits, healthy women (n = 8) received intravaginal taggant (2-butyl acetate, 2-pentyl acetate, isopropyl butyrate, or 2-pentyl butyrate; 30 mg) formulated in hydroxyethylcellulose or tenofovir placebo gel.", "output": {"entities": {"chemical": [{"text": "2-butyl acetate", "start": 66, "end": 81}, {"text": "2-pentyl acetate", "start": 83, "end": 99}, {"text": "isopropyl butyrate", "start": 101, "end": 119}, {"text": "2-pentyl butyrate", "start": 124, "end": 141}, {"text": "tenofovir", "start": 189, "end": 198}]}}, "schema": []}
{"input": "A second group (n = 4) of women received the same formulations administered dermally on the forearm to determine if skin administration might confound the system.", "output": {"entities": {}}, "schema": []}
{"input": "Breath samples were collected using bags before and after taggant administration for 1 hour.", "output": {"entities": {}}, "schema": []}
{"input": "Samples were measured using a miniature gas chromatograph and/or gas chromatography-mass spectroscopy for ester taggant, alcohol, and ketone concentrations.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 121, "end": 128}, {"text": "ketone", "start": 134, "end": 140}]}}, "schema": []}
{"input": "After vaginal administration, 2-butyl acetate, 2-pentyl acetate, and metabolites were observed in breath, whereas isopropyl butyrate, 2-pentyl butyrate, and metabolites were not.", "output": {"entities": {"chemical": [{"text": "2-butyl acetate", "start": 30, "end": 45}, {"text": "2-pentyl acetate", "start": 47, "end": 63}, {"text": "isopropyl butyrate", "start": 114, "end": 132}, {"text": "2-pentyl butyrate", "start": 134, "end": 151}]}}, "schema": []}
{"input": "Some women reported self-resolving, mild burning (24/64 visits) with vaginal administration or a \" bubblegum \" taste (7/64 visits).", "output": {"entities": {}}, "schema": []}
{"input": "No taggants or metabolites were detected following dermal application.", "output": {"entities": {}}, "schema": []}
{"input": "A \" breath test \" for adherence to antiretroviral vaginal gel application appears physiologically and technically feasible.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetics of intravenous voriconazole in obese patients: implications of CYP2C19 homozygous poor metabolizer genotype.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 32, "end": 44}]}}, "schema": []}
{"input": "There is a paucity of pharmacokinetic studies describing weight-based dosing of intravenous voriconazole in obese patients.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 92, "end": 104}]}}, "schema": []}
{"input": "In this case report, we describe the pharmacokinetics of intravenous voriconazole in an obese CYP2C19 homozygous poor metabolizer and review previously reported data regarding the use of intravenous voriconazole in obese patients.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 69, "end": 81}, {"text": "voriconazole", "start": 199, "end": 211}]}}, "schema": []}
{"input": "A 17-year-old obese Hispanic male patient (body mass index 35 kg/m (2)) received intravenous voriconazole for the treatment of suspected aspergillosis.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 93, "end": 105}]}}, "schema": []}
{"input": "After 2. 5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight, the voriconazole area under the serum concentration-time curve over the course of a single (12-hr) dosing interval and trough concentration were 86, 100 ng. hr/ml and 6. 2 micro g/ml, respectively.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 19, "end": 31}, {"text": "voriconazole", "start": 104, "end": 116}]}}, "schema": []}
{"input": "Six days later, the voriconazole dosage was decreased.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 20, "end": 32}]}}, "schema": []}
{"input": "A trough concentration measured just before the dosage reduction (after 8. 5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight) remained elevated at 5. 8 micro g/ml.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 85, "end": 97}]}}, "schema": []}
{"input": "Genotyping revealed a CYP2C19 homozygous poor metabolizer (CYP2C19 * 2/* 2).", "output": {"entities": {}}, "schema": []}
{"input": "Voriconazole was subsequently discontinued due to QTc prolongation.", "output": {"entities": {"chemical": [{"text": "Voriconazole", "start": 0, "end": 12}]}}, "schema": []}
{"input": "These data and those from two recent publications suggest that voriconazole does not distribute extensively into human adipose tissue and that obese patients should be dosed on an adjusted body weight basis.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 63, "end": 75}]}}, "schema": []}
{"input": "If an obese patient dosed on total body weight is also a CYP2C19 poor metabolizer, serum voriconazole concentrations will be further elevated, potentially leading to drug-induced toxicity.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 89, "end": 101}]}}, "schema": []}
{"input": "Key Articles and Guidelines in the Primary Prevention of Ischemic Stroke.", "output": {"entities": {}}, "schema": []}
{"input": "Ischemic stroke is a prevalent disease with a large burden on the health system.", "output": {"entities": {}}, "schema": []}
{"input": "Preventive strategies, therefore, are paramount.", "output": {"entities": {}}, "schema": []}
{"input": "Primary prevention is aimed at reducing the risk of stroke in asymptomatic people.", "output": {"entities": {}}, "schema": []}
{"input": "The most effective prevention is through control of modifiable risk factors.", "output": {"entities": {}}, "schema": []}
{"input": "Due to the large amount of literature available on this topic, this bibliography (the first of a 2-part series) aims to provide a comprehensive resource for medical practitioners charged with caring for this population.", "output": {"entities": {}}, "schema": []}
{"input": "Arsenic geochemistry in a biostimulated aquifer: An aqueous speciation study.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Stimulating microbial growth through the use of acetate injection wells at the former uranium mill site in Rifle, Colorado, USA, has been shown to decrease dissolved uranium (VI) concentrations through bacterial reduction to immobile uranium (IV).", "output": {"entities": {"chemical": [{"text": "uranium (VI)", "start": 166, "end": 178}, {"text": "uranium (IV)", "start": 234, "end": 246}]}}, "schema": []}
{"input": "Bioreduction also changed the redox chemistry of site groundwater, altering the mobility of several other redox-sensitive elements present in the subsurface, including iron, sulfur, and arsenic.", "output": {"entities": {"chemical": [{"text": "iron", "start": 168, "end": 172}, {"text": "sulfur", "start": 174, "end": 180}, {"text": "arsenic", "start": 186, "end": 193}]}}, "schema": []}
{"input": "Following acetate amendment at the site, elevated concentrations of arsenic in the groundwater were observed.", "output": {"entities": {"chemical": [{"text": "acetate", "start": 10, "end": 17}, {"text": "arsenic", "start": 68, "end": 75}]}}, "schema": []}
{"input": "Ion chromatography-inductively coupled plasma-mass spectrometry was used to determine the aqueous arsenic speciation.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 98, "end": 105}]}}, "schema": []}
{"input": "Upgradient samples, unexposed to acetate, showed low levels of arsenic (=~ 1 mu M), with greater than 90% as arsenate (As [V]) and a small amount of arsenite (As [III]).", "output": {"entities": {"chemical": [{"text": "acetate", "start": 33, "end": 40}, {"text": "arsenic", "start": 63, "end": 70}, {"text": "arsenate", "start": 109, "end": 117}, {"text": "As [V]", "start": 119, "end": 125}, {"text": "arsenite", "start": 149, "end": 157}, {"text": "As [III]", "start": 159, "end": 167}]}}, "schema": []}
{"input": "Downgradient acetate-stimulated water samples had much higher levels of arsenic (up to 8 mu M), and 4 additional thioarsenic species were present under sulfate-reducing conditions.", "output": {"entities": {"chemical": [{"text": "acetate", "start": 13, "end": 20}, {"text": "arsenic", "start": 72, "end": 79}, {"text": "thioarsenic", "start": 113, "end": 124}, {"text": "sulfate", "start": 152, "end": 159}]}}, "schema": []}
{"input": "These thioarsenic species demonstrate a strong correlation between arsenic release and sulfide concentrations in groundwater, and their formation may explain the elevated total arsenic concentrations.", "output": {"entities": {"chemical": [{"text": "thioarsenic", "start": 6, "end": 17}, {"text": "arsenic", "start": 67, "end": 74}, {"text": "sulfide", "start": 87, "end": 94}, {"text": "arsenic", "start": 177, "end": 184}]}}, "schema": []}
{"input": "An alternative remediation approach, enhanced flushing of uranium, was accomplished by addition of bicarbonate and did not result in highly elevated arsenic concentrations.", "output": {"entities": {"chemical": [{"text": "uranium", "start": 58, "end": 65}, {"text": "bicarbonate", "start": 99, "end": 110}, {"text": "arsenic", "start": 149, "end": 156}]}}, "schema": []}
{"input": "Environ Toxicol Chem 2013; 32: 1216-1223.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "The Lignan (-)-Cubebin Inhibits Vascular Contraction and Induces Relaxation Via Nitric Oxide Activation in Isolated Rat Aorta.", "output": {"entities": {"chemical": [{"text": "Lignan (-)-Cubebin", "start": 4, "end": 22}, {"text": "Nitric Oxide", "start": 80, "end": 92}]}}, "schema": []}
{"input": "Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic.", "output": {"entities": {"chemical": [{"text": "Cubebin", "start": 0, "end": 7}, {"text": "lignan", "start": 27, "end": 33}]}}, "schema": []}
{"input": "This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated.", "output": {"entities": {"chemical": [{"text": "(-)-cubebin", "start": 60, "end": 71}, {"text": "phenylephrine", "start": 121, "end": 134}, {"text": "Phe", "start": 136, "end": 139}]}}, "schema": []}
{"input": "Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 47, "end": 60}, {"text": "(-)-cubebin", "start": 65, "end": 76}, {"text": "sodium nitroprusside", "start": 162, "end": 182}, {"text": "(-)-cubebin", "start": 187, "end": 198}]}}, "schema": []}
{"input": "Cumulative concentration-response curves for Phe (10 (-10)-10 (-5) M) were determined for endothelium-intact and endothelium-denuded aortic rings in either the presence or absence of (-)-cubebin.", "output": {"entities": {"chemical": [{"text": "Phe", "start": 45, "end": 48}, {"text": "(-)-cubebin", "start": 183, "end": 194}]}}, "schema": []}
{"input": "Dose-response curves were also constructed for pre-incubation of vascular rings with N omega-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor).", "output": {"entities": {"chemical": [{"text": "N omega-nitro-L-arginine methyl ester", "start": 85, "end": 122}, {"text": "L-NAME", "start": 124, "end": 130}, {"text": "nitric oxide", "start": 148, "end": 160}, {"text": "indomethacin", "start": 182, "end": 194}, {"text": "1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one", "start": 241, "end": 290}, {"text": "ODQ", "start": 292, "end": 295}]}}, "schema": []}
{"input": "(-)-Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L-NAME and ODQ, but not with indomethacin.", "output": {"entities": {"chemical": [{"text": "(-)-Cubebin", "start": 0, "end": 11}, {"text": "L-NAME", "start": 139, "end": 145}, {"text": "ODQ", "start": 150, "end": 153}, {"text": "indomethacin", "start": 168, "end": 180}]}}, "schema": []}
{"input": "In addition, (-)-cubebin was able to reduce Phe contraction in the case of intact rings.", "output": {"entities": {"chemical": [{"text": "(-)-cubebin", "start": 13, "end": 24}, {"text": "Phe", "start": 44, "end": 47}]}}, "schema": []}
{"input": "These results suggest that (-)-cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement.", "output": {"entities": {"chemical": [{"text": "(-)-cubebin", "start": 27, "end": 38}, {"text": "NO", "start": 67, "end": 69}, {"text": "cGMP", "start": 70, "end": 74}, {"text": "prostacyclin", "start": 105, "end": 117}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "[6]-Shogaol Attenuates Neuronal Apoptosis in Hydrogen Peroxide-Treated Astrocytes Through the Up-Regulation of Neurotrophic Factors.", "output": {"entities": {"chemical": [{"text": "[6]-Shogaol", "start": 0, "end": 11}, {"text": "Hydrogen Peroxide", "start": 45, "end": 62}]}}, "schema": []}
{"input": "Neuronal apoptosis induced by oxidative stress is a prominent feature of neurodegenerative disorders.", "output": {"entities": {}}, "schema": []}
{"input": "[6]-shogaol, a bio-active compound in ginger, possesses potent anti-inflammatory actions and has recently emerged as a potential therapeutic agent for neurodegenerative disorders.", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "However, the effects of [6]-shogaol on astroglial apoptosis following exogenously induced oxidative stress has not yet been investigated.", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 24, "end": 35}]}}, "schema": []}
{"input": "Here, we show that the anti-apoptotic activity of [6]-shogaol in astrocytes following exposure to hydrogen peroxide (H (2) O (2)) involves a marked up-regulation of neurotrophic factors such as nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor.", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 50, "end": 61}, {"text": "hydrogen peroxide", "start": 98, "end": 115}, {"text": "H (2) O (2)", "start": 117, "end": 128}]}}, "schema": []}
{"input": "Astrocytes co-treated with [6]-shogaol and H (2) O (2) for 1 h showed decrease in reactive oxygen species production compared with those only treated with H (2) O (2).", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 27, "end": 38}, {"text": "H (2) O (2)", "start": 43, "end": 54}, {"text": "oxygen", "start": 91, "end": 97}, {"text": "H (2) O (2)", "start": 155, "end": 166}]}}, "schema": []}
{"input": "Moreover, [6]-shogaol counteracted the reduced expression of ERK1/2 in H (2) O (2)-treated astrocytes and protected these cells from oxidative stress and apoptosis by attenuating the impairment of mitochondrial function proteins such as Bcl-2 and Bcl-xL.", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 10, "end": 21}, {"text": "H (2) O (2)", "start": 71, "end": 82}]}}, "schema": []}
{"input": "Additionally, [6]-shogaol inhibits the expression of the apoptotic proteins Bax and caspase-3 in H (2) O (2)-treated astrocytes.", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 14, "end": 25}, {"text": "H (2) O (2)", "start": 97, "end": 108}]}}, "schema": []}
{"input": "This data suggest that following oxidative stress, [6]-shogaol protects astrocytes from oxidative damage through the up-regulating levels of neurotrophic factors.", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 51, "end": 62}]}}, "schema": []}
{"input": "These findings provide further support for the use of [6]-shogaol as a therapeutic agent in neurodegenerative disorders.", "output": {"entities": {"chemical": [{"text": "[6]-shogaol", "start": 54, "end": 65}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo Antimalarial Activity of a Labdane Diterpenoid from the Leaves of Otostegia integrifolia Benth.", "output": {"entities": {"chemical": [{"text": "Labdane Diterpenoid", "start": 35, "end": 54}]}}, "schema": []}
{"input": "In Ethiopian traditional medicine, the leaves of Otostegia integrifolia Benth. are used for the treatment of several diseases including malaria.", "output": {"entities": {}}, "schema": []}
{"input": "In an ongoing search for effective, safe and cheap antimalarial agents from plants, the 80% methanol leaf extract O. integrifolia was tested for its in vivo antimalarial activity, in a 4-day suppressive assay against Plasmodium berghei.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 92, "end": 100}]}}, "schema": []}
{"input": "Activity-guided fractionation of this extract which showed potent antiplasmodial activity resulted in the isolation of a labdane diterpenoid identified as otostegindiol.", "output": {"entities": {"chemical": [{"text": "labdane diterpenoid", "start": 121, "end": 140}, {"text": "otostegindiol", "start": 155, "end": 168}]}}, "schema": []}
{"input": "Otostegindiol displayed a significant (P < 0. 001) antimalarial activity at doses of 25, 50 and 100 mg/kg with chemosuppression values of 50. 13, 65. 58 and 73. 16%, respectively.", "output": {"entities": {"chemical": [{"text": "Otostegindiol", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Acute toxicity studies revealed that the crude extract possesses no toxicity in mice up to a maximum dose of 5000 mg/kg suggesting the relative safety of the plant when administered orally.", "output": {"entities": {}}, "schema": []}
{"input": "The results of the present study indicate that otostegindiol is among the antimalarial principles in this medicinal plant, and further support claims for the traditional medicinal use of the plant for the treatment of malaria.", "output": {"entities": {"chemical": [{"text": "otostegindiol", "start": 47, "end": 60}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Exploring the Interplay Between Ligand Derivatisation and Cation Type in the Assembly of Hybrid Polyoxometalate Mn-Andersons.", "output": {"entities": {"chemical": [{"text": "Polyoxometalate Mn", "start": 96, "end": 114}]}}, "schema": []}
{"input": "Herein a library of hybrid Mn-Anderson polyoxometalates anions are presented: 1, [(MnMo (6) O (18)) ((OCH (2)) (3)-C-(CH (2)) (7) CHCH (2)) (2)] (3-); compound 2, [(MnMo (6) O (18)) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (2)] (3-); compound 3, [(MnMo (6) O (18)) ((OCH (2)) (3) C-(CH (2)) (7) CHCH (2)) (1) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (1)] (3-); compound 4, [(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) CH (2) CHCH (2)) (2)] (3-) and compounds 5-9, [(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) (CH (2)) (x) CH (3)) (2)]), where x = 4, 10, 12, 14, and 18 respectively.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 27, "end": 29}, {"text": "polyoxometalates", "start": 39, "end": 55}, {"text": "[(MnMo (6) O (18)) ((OCH (2)) (3)-C-(CH (2)) (7) CHCH (2)) (2)] (3-)", "start": 81, "end": 149}, {"text": "[(MnMo (6) O (18)) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (2)] (3-)", "start": 163, "end": 231}, {"text": "[(MnMo (6) O (18)) ((OCH (2)) (3) C-(CH (2)) (7) CHCH (2)) (1) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (1)] (3-)", "start": 245, "end": 357}, {"text": "[(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) CH (2) CHCH (2)) (2)] (3-)", "start": 371, "end": 441}, {"text": "[(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) (CH (2)) (x) CH (3)) (2)])", "start": 461, "end": 531}]}}, "schema": []}
{"input": "The compounds resulting from the cation exchange of the anions 1-9 to give TBA (a) and DMDOA (b) salts, and additionally for compounds 1, 2 and 3, tetraphenylphosphonium (PPh (4)) (c) salts, are explored at the air/water interface using scanning force microscopy, showing a range of architectures including hexagonal structures, nanofibers and other supramolecular forms.", "output": {"entities": {"chemical": [{"text": "TBA", "start": 75, "end": 78}, {"text": "DMDOA", "start": 87, "end": 92}, {"text": "tetraphenylphosphonium", "start": 147, "end": 169}, {"text": "PPh (4)", "start": 171, "end": 178}]}}, "schema": []}
{"input": "Additionally the solid-state structures for compounds 1c, 2c, 4a, 6a, 9a, are presented for the first time and these investigations demonstrate the delicate interplay between the structure of the covalently derivatised hybrid organo-clusters as well as the ion-exchange cation types.", "output": {"entities": {}}, "schema": []}
{"input": "Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome p450 enzymes in healthy volunteers.", "output": {"entities": {}}, "schema": []}
{"input": "This cocktail study evaluated the interaction potential of the oral lavender oil preparation silexan with major P450 (cytochrome P450) enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects and Methods: Sixteen healthy male or female Caucasians completed this double-blind, randomized, 2-fold crossover study.", "output": {"entities": {}}, "schema": []}
{"input": "Silexan (160 mg) or placebo were administered once daily for 11 days.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, on day 11 of both study periods, 150 mg caffeine (CYP1A2), 125 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan-HBr (CYP2D6), and 2 mg midazolam (CYP3A4) were administered orally.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 54, "end": 62}, {"text": "tolbutamide", "start": 80, "end": 91}, {"text": "omeprazole", "start": 108, "end": 118}, {"text": "dextromethorphan-HBr", "start": 136, "end": 156}, {"text": "midazolam", "start": 176, "end": 185}]}}, "schema": []}
{"input": "Formal interaction was excluded if the 90% confidence interval (CI) for the silexan over placebo ratios for phenotyping metrics (primary: AUC0-t) was within a 0. 70-1. 43 range.", "output": {"entities": {}}, "schema": []}
{"input": "Results: According to the AUC0-t comparisons, silexan had no relevant effect on CYP1A2, 2C9, 2D6, and 3A4 activity.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary phenotyping metrics confirmed this result.", "output": {"entities": {}}, "schema": []}
{"input": "Mean ratios for all omeprazole-derived metrics were close to unity.", "output": {"entities": {"chemical": [{"text": "omeprazole", "start": 20, "end": 30}]}}, "schema": []}
{"input": "The 90% CI for the AUC0-t ratio of omeprazole but not for omeprazole/5-OH-omeprazole plasma ratio 3 hours post-dose or omeprazole/5-OH-omeprazole AUC0-t ratio (secondary CYP2C19 metrics) was above the predefined threshold of 1. 43, probably caused by the inherent high variability of omeprazole pharmacokinetics.", "output": {"entities": {"chemical": [{"text": "omeprazole", "start": 35, "end": 45}, {"text": "omeprazole", "start": 58, "end": 68}, {"text": "5-OH-omeprazole", "start": 69, "end": 84}, {"text": "omeprazole", "start": 119, "end": 129}, {"text": "5-OH-omeprazole", "start": 130, "end": 145}, {"text": "omeprazole", "start": 284, "end": 294}]}}, "schema": []}
{"input": "Silexan and the phenotyping drugs were well tolerated.", "output": {"entities": {}}, "schema": []}
{"input": "Repeated silexan (160 mg/day) administration has no clinically relevant inhibitory or inducing effects on the CYP1A2, 2C9, 2C19, 2D6, and 3A4 enzymes in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Tacticity-induced changes in the micellization and degradation properties of poly (lactic acid)-block-poly (ethylene glycol) copolymers.", "output": {"entities": {"chemical": [{"text": "poly (lactic acid)-block-poly (ethylene glycol)", "start": 77, "end": 124}]}}, "schema": []}
{"input": "Poly (lactic acid)-block-poly (ethylene glycol) copolymers (PLA-b-PEG) featuring varying tacticities (atactic, heterotactic, isotactic) in the PLA block were synthesized and investigated for their micellar stability, degradation, and thermal properties.", "output": {"entities": {"chemical": [{"text": "Poly (lactic acid)-block-poly (ethylene glycol)", "start": 0, "end": 47}, {"text": "PLA-b-PEG", "start": 60, "end": 69}, {"text": "PLA", "start": 143, "end": 146}]}}, "schema": []}
{"input": "Utilizing tin (II) bis (2-ethylhexanoate), aluminum salan, and aluminum salen catalysts, the copolymers were synthesized through the ring-opening polymerization of d-, l-, rac-, or a blend of l-and rac-lactide using monomethoxy-poly (ethylene glycol) as a macroinitiator.", "output": {"entities": {"chemical": [{"text": "tin (II) bis (2-ethylhexanoate)", "start": 10, "end": 41}, {"text": "aluminum salan", "start": 43, "end": 57}, {"text": "aluminum salen", "start": 63, "end": 77}, {"text": "l-and rac-lactide", "start": 192, "end": 209}, {"text": "monomethoxy-poly (ethylene glycol)", "start": 216, "end": 250}]}}, "schema": []}
{"input": "The critical micelle concentration, which reflects the micellar stability, was probed using a fluorescence spectroscopic method with pyrene as the probe.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 133, "end": 139}]}}, "schema": []}
{"input": "The copolymers were degraded in a methanolic solution of 1, 5, 7-triaza-bicyclo [4. 4. 0] dec-5-ene and the degradation was measured by (1) H NMR spectroscopic and gel permeation chromatographic analyses.", "output": {"entities": {"chemical": [{"text": "1, 5, 7-triaza-bicyclo [4. 4. 0] dec-5-ene", "start": 57, "end": 99}, {"text": "(1) H", "start": 136, "end": 141}]}}, "schema": []}
{"input": "Differential scanning calorimetry and thermogravimetric analysis provided information on the thermal properties of the copolymers.", "output": {"entities": {}}, "schema": []}
{"input": "Atactic and heterotactic microstructures in the PLA block resulted in lower micellar stability, as well as faster degradation and shorter erosion time compared to polymers with high isotactic enchainment (Pm).", "output": {"entities": {"chemical": [{"text": "PLA", "start": 48, "end": 51}]}}, "schema": []}
{"input": "By modification of the Pm, micellar stability, degradation, and erosion rates of the copolymers can be tuned to specific biomedical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, while tin (II) bis (2-ethylhexanoate) and aluminum salan-catalyzed PLA-b-PEG copolymers exhibited similar micellization behavior, the aluminum salen-catalyzed PLA-b-PEG exhibited unique behavior at high micelle concentration in the presence of the pyrene probe.", "output": {"entities": {"chemical": [{"text": "tin (II) bis (2-ethylhexanoate)", "start": 21, "end": 52}, {"text": "aluminum salan", "start": 57, "end": 71}, {"text": "PLA-b-PEG", "start": 82, "end": 91}, {"text": "aluminum salen", "start": 149, "end": 163}, {"text": "PLA-b-PEG", "start": 174, "end": 183}, {"text": "pyrene", "start": 263, "end": 269}]}}, "schema": []}
{"input": "This unique behavior can be attributed to the disintegration of the micelles through the interactions of long isotactic stereoblock segments.", "output": {"entities": {}}, "schema": []}
{"input": "Vitamin B12 and homocysteine status during pregnancy in the metformin in gestational diabetes trial: responses to maternal metformin compared with insulin treatment (+)", "output": {"entities": {"chemical": [{"text": "Vitamin B12", "start": 0, "end": 11}, {"text": "homocysteine", "start": 16, "end": 28}, {"text": "metformin", "start": 60, "end": 69}, {"text": "metformin", "start": 123, "end": 132}]}}, "schema": []}
{"input": "AIM: The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus (GDM) on vitamin B12 and homocysteine (Hcy) status.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 55, "end": 64}, {"text": "vitamin B12", "start": 130, "end": 141}, {"text": "homocysteine", "start": 146, "end": 158}, {"text": "Hcy", "start": 160, "end": 163}]}}, "schema": []}
{"input": "METHODS: Women with GDM, who met criteria for insulin treatment, were randomly assigned to metformin (n = 89) or insulin (n = 91) in the Adelaide cohort of the metformin in gestational diabetes (MiG) trial.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 91, "end": 100}, {"text": "metformin", "start": 160, "end": 169}]}}, "schema": []}
{"input": "Fasting serum total vitamin B12 (TB12), holotranscobalamin (HoloTC), a marker of functional B12 status and plasma Hcy concentrations were measured at 20-34 weeks (at randomization) and 36 weeks gestation, then at 6-8 weeks postpartum.", "output": {"entities": {"chemical": [{"text": "vitamin B12", "start": 20, "end": 31}, {"text": "Hcy", "start": 114, "end": 117}]}}, "schema": []}
{"input": "RESULTS: Circulating TB12, HoloTC and Hcy were similar in both treatment groups at each time point.", "output": {"entities": {"chemical": [{"text": "Hcy", "start": 38, "end": 41}]}}, "schema": []}
{"input": "Women who were taking dietary folate supplements at randomization had higher serum TB12 and HoloTC at randomization than those not taking folate.", "output": {"entities": {"chemical": [{"text": "folate", "start": 30, "end": 36}, {"text": "folate", "start": 138, "end": 144}]}}, "schema": []}
{"input": "Overall, serum TB12 fell more between randomization and 36 weeks gestation in the metformin group than in the insulin group (metformin:-19. 7 +/- 4. 7 pmol/l, insulin:-6. 4 +/- 3. 6 pmol/l, p = 0. 004).", "output": {"entities": {"chemical": [{"text": "metformin", "start": 82, "end": 91}, {"text": "metformin", "start": 125, "end": 134}]}}, "schema": []}
{"input": "The decrease in serum TB12 during treatment was greater with increasing treatment duration in metformin-treated (p < 0. 001), but not in insulin-treated women.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 94, "end": 103}]}}, "schema": []}
{"input": "CONCLUSIONS: Total, but not bioavailable, vitamin B12 stores were depleted during pregnancy to a greater extent in metformin-treated than in insulin-treated women with GDM, but neither analyte differed between groups at any stage.", "output": {"entities": {"chemical": [{"text": "vitamin B12", "start": 42, "end": 53}, {"text": "metformin", "start": 115, "end": 124}]}}, "schema": []}
{"input": "This adds further evidence supporting metformin as a safe alternative treatment to insulin in GDM.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 38, "end": 47}]}}, "schema": []}
{"input": "Further investigation is needed to evaluate whether women treated with metformin for longer periods in pregnancy require additional B12 or other supplementation.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 71, "end": 80}]}}, "schema": []}
{"input": "Between superexchange and hopping: an intermediate charge-transfer mechanism in poly (A)-poly (T) DNA hairpins.", "output": {"entities": {}}, "schema": []}
{"input": "We developed a model for hole migration along relatively short DNA hairpins with fewer that seven adenine (A): thymine (T) base pairs.", "output": {"entities": {"chemical": [{"text": "adenine", "start": 98, "end": 105}, {"text": "thymine", "start": 111, "end": 118}]}}, "schema": []}
{"input": "The model was used to simulate hole migration along poly (A)-poly (T) sequences with a particular emphasis on the impact of partial hole localization on the different rate processes.", "output": {"entities": {}}, "schema": []}
{"input": "The simulations, performed within the framework of the stochastic surrogate Hamiltonian approach, give values for the arrival rate in good agreement with experimental data.", "output": {"entities": {}}, "schema": []}
{"input": "Theoretical results obtained for hairpins with fewer than three A: T base pairs suggest that hole transfer along short hairpins occurs via superexchange.", "output": {"entities": {}}, "schema": []}
{"input": "This mechanism is characterized by the exponential distance dependence of the arrival rate on the donor/acceptor distance, k (a) ~ e (-beta R), with beta = 0. 9 A (-1).", "output": {"entities": {}}, "schema": []}
{"input": "For longer systems, up to six A: T pairs, the distance dependence follows a power law k (a) ~ R (-eta) with eta = 2.", "output": {"entities": {}}, "schema": []}
{"input": "Despite this seemingly clear signature of unbiased hopping, our simulations show the complete delocalization of the hole density along the entire hairpin.", "output": {"entities": {}}, "schema": []}
{"input": "According to our analysis, the hole transfer along relatively long sequences may proceed through a mechanism which is distinct from both coherent single-step superexchange and incoherent multistep hopping.", "output": {"entities": {}}, "schema": []}
{"input": "The criterion for the validity of this mechanism intermediate between superexchange and hopping is proposed.", "output": {"entities": {}}, "schema": []}
{"input": "The impact of partial localization on the rate of hole transfer between neighboring A bases was also investigated.", "output": {"entities": {}}, "schema": []}
{"input": "New insight into artifactual phenomena during in vitro toxicity assessment of engineered nanoparticles: study of TNF-alpha adsorption on alumina oxide nanoparticle.", "output": {"entities": {"chemical": [{"text": "alumina oxide", "start": 137, "end": 150}]}}, "schema": []}
{"input": "Biomolecules can be adsorbed on nanoparticles (NPs) and degraded during in vitro toxicity assays.", "output": {"entities": {}}, "schema": []}
{"input": "These artifactual phenomena could lead to misinterpretation of biological activity, such as false-negative results.", "output": {"entities": {}}, "schema": []}
{"input": "To avoid possible underestimation of cytokine release after contact between NP and cells, we propose a methodology to account for these artifactual phenomena and lead to accurate measurements.", "output": {"entities": {}}, "schema": []}
{"input": "We focused on the pro-inflammatory cytokine tumor necrosis factor TNF-alpha.", "output": {"entities": {}}, "schema": []}
{"input": "We studied well-characterized boehmite engineered NP [aluminum oxide hydroxide, AlO (OH)].", "output": {"entities": {"chemical": [{"text": "boehmite", "start": 30, "end": 38}, {"text": "aluminum oxide hydroxide", "start": 54, "end": 78}, {"text": "AlO (OH)", "start": 80, "end": 88}]}}, "schema": []}
{"input": "The rate of TNF-alpha degradation and its adsorption (on boehmite and on the walls of wells) were determined in cell-free conditions by adding a known TNF-alpha concentration (1500 pg/ml) under various experimental conditions.", "output": {"entities": {"chemical": [{"text": "boehmite", "start": 57, "end": 65}]}}, "schema": []}
{"input": "After a 24-h incubation, we quantified that 7 wt.% of the initial TNF-alpha was degraded over time, 6 wt.% adsorbed on the walls of 96-well plates, and 13 wt.% adsorbed on the boehmite surface.", "output": {"entities": {"chemical": [{"text": "boehmite", "start": 176, "end": 184}]}}, "schema": []}
{"input": "Finally, boehmite NP were incubated with murine macrophages (RAW 264. 7 cell line).", "output": {"entities": {"chemical": [{"text": "boehmite", "start": 9, "end": 17}]}}, "schema": []}
{"input": "The release of TNF-alpha was assessed for boehmite NP and the experimental data were corrected considering the artifactual phenomena, which accounted for about 20-30% of the total.", "output": {"entities": {"chemical": [{"text": "boehmite", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Anti-atherosclerotic mechanisms of statin therapy.", "output": {"entities": {}}, "schema": []}
{"input": "HMG-CoA-Reductase inhibitors, also known as statins, are currently the most powerful cholesterol-lowering drugs available on the market.", "output": {"entities": {"chemical": [{"text": "CoA", "start": 4, "end": 7}, {"text": "cholesterol", "start": 85, "end": 96}]}}, "schema": []}
{"input": "Clinical trials and experimental evidence suggest that statins have anti-atherosclerotic effects.", "output": {"entities": {}}, "schema": []}
{"input": "These are in part consequence of lipid lowering but also result from pleiotropic actions of the drugs.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, the anti-atherosclerotic actions of statins will be reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of mitochondrial carnitine/acylcarnitine transporter by H2O2: Molecular mechanism and possible implication in pathophysiology.", "output": {"entities": {"chemical": [{"text": "carnitine", "start": 28, "end": 37}, {"text": "acylcarnitine", "start": 38, "end": 51}, {"text": "H2O2", "start": 67, "end": 71}]}}, "schema": []}
{"input": "H2O2 inhibits the [(3) H] carnitine/carnitine antiport catalysed by the mitochondrial carnitine/acylcarnitine transporter reconstituted in proteoliposomes.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 0, "end": 4}, {"text": "[(3) H] carnitine", "start": 18, "end": 35}, {"text": "carnitine", "start": 36, "end": 45}, {"text": "carnitine", "start": 86, "end": 95}, {"text": "acylcarnitine", "start": 96, "end": 109}]}}, "schema": []}
{"input": "The inhibition was reversed by dithioerythritol, N-acetylcysteine and l-cysteine.", "output": {"entities": {"chemical": [{"text": "dithioerythritol", "start": 31, "end": 47}, {"text": "N-acetylcysteine", "start": 49, "end": 65}, {"text": "l-cysteine", "start": 70, "end": 80}]}}, "schema": []}
{"input": "Inhibition time-dependence revealed a faster and a slower reaction stages with orders of reaction of 1. 0 and 1. 9, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition was tested on mutants in which one or more of the six Cys residues had been substituted with Ser or with Val.", "output": {"entities": {"chemical": [{"text": "Cys", "start": 65, "end": 68}, {"text": "Ser", "start": 104, "end": 107}, {"text": "Val", "start": 116, "end": 119}]}}, "schema": []}
{"input": "The four replacement mutant C23S/C58S/C89S/C283S containing C136 and C155 was inhibited as the wild-type.", "output": {"entities": {}}, "schema": []}
{"input": "Mutants C23V/C58V/C155V/C89S/C283S and C23V/C58V/C136V/C89S/C283S containing only C136 or C155, respectively, were inhibited at a much lower extent respect to the wild-type, while the mutant C136S/C155S in which the two Cys were substituted and the C-less protein were virtually insensitive to inhibition.", "output": {"entities": {"chemical": [{"text": "Cys", "start": 220, "end": 223}]}}, "schema": []}
{"input": "DTE reversed the inhibition of the H2O2 sensitive proteins except that in the case of the mutants containing only C136 or C155 after long time of incubation with H2O2.", "output": {"entities": {"chemical": [{"text": "DTE", "start": 0, "end": 3}, {"text": "H2O2", "start": 35, "end": 39}, {"text": "H2O2", "start": 162, "end": 166}]}}, "schema": []}
{"input": "The IC50 values obtained by dose-response curves of H2O2 inhibition were 0. 17mM for the wild-type, 0. 39mM for the four replacement mutant containing C136 and C155, 2. 23 or 1. 8mM in the five replacement mutants containing the single C136 or C155, respectively.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 52, "end": 56}]}}, "schema": []}
{"input": "Carnitine and acetylcarnitine protected the protein from the inhibition by H2O2.", "output": {"entities": {"chemical": [{"text": "Carnitine", "start": 0, "end": 9}, {"text": "acetylcarnitine", "start": 14, "end": 29}, {"text": "H2O2", "start": 75, "end": 79}]}}, "schema": []}
{"input": "Inhibition kinetics showed a competitive behaviour of H2O2 respect to carnitine.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 54, "end": 58}, {"text": "carnitine", "start": 70, "end": 79}]}}, "schema": []}
{"input": "All the data concur to demonstrate that H2O2 interacts with C136 and C155 and completely inactivates the transporter by inducing the formation of a disulphide.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 40, "end": 44}, {"text": "disulphide", "start": 148, "end": 158}]}}, "schema": []}
{"input": "Hematologic and hepatic responses of the freshwater fish Hoplias malabaricus after saxitoxin exposure.", "output": {"entities": {"chemical": [{"text": "saxitoxin", "start": 83, "end": 92}]}}, "schema": []}
{"input": "The bioaccumulation of saxitoxins (STX) in the trophic chain, mainly in freshwater, are not completely known.", "output": {"entities": {"chemical": [{"text": "saxitoxins", "start": 23, "end": 33}, {"text": "STX", "start": 35, "end": 38}]}}, "schema": []}
{"input": "This work aimed to elucidate the effects of STX on Hoplias malabaricus through trophic bioassay.", "output": {"entities": {"chemical": [{"text": "STX", "start": 44, "end": 47}]}}, "schema": []}
{"input": "The fish were fed once every five days with Astyanax sp. before being subjected to an intraperitoneal inoculation with the lysate of Cylindrospermopsis raciborskii culture containing 97% STX and 3% by neosaxitoxin and gonyautoxin during 20 days.", "output": {"entities": {"chemical": [{"text": "STX", "start": 187, "end": 190}, {"text": "neosaxitoxin", "start": 201, "end": 213}, {"text": "gonyautoxin", "start": 218, "end": 229}]}}, "schema": []}
{"input": "The animal' s liver was assessed using biomarkers as activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx), and concentrations of reduced glutathione (GSH) and lipoperoxidation (LPO) and protein carbonylation (PCO).", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 67, "end": 77}, {"text": "glutathione", "start": 111, "end": 122}, {"text": "glutathione", "start": 148, "end": 159}, {"text": "reduced glutathione", "start": 200, "end": 219}, {"text": "GSH", "start": 221, "end": 224}]}}, "schema": []}
{"input": "In the blood was analyzed the genotoxic and hematological parameters.", "output": {"entities": {}}, "schema": []}
{"input": "The hepatosomatic index and the relative condition factor did not show a significant difference between the exposed and control groups.", "output": {"entities": {}}, "schema": []}
{"input": "The values of mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin increased in the STX group.", "output": {"entities": {"chemical": [{"text": "STX", "start": 105, "end": 108}]}}, "schema": []}
{"input": "The hepatic tissue from both groups exhibited a typical pattern that have been already described for most teleost fish.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggested the generation of reactive oxygen species, with increased activity of GPx and concentrations of LPO and GSH; whereas the specific activity of SOD decreased.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 49, "end": 55}, {"text": "GSH", "start": 126, "end": 129}]}}, "schema": []}
{"input": "However, no changes were observed in the CAT, PCO, and DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Although the STX effects are known as neurotoxic, this cyanotoxin caused liver biochemical alterations that can be considered ecologically relevant.", "output": {"entities": {"chemical": [{"text": "STX", "start": 13, "end": 16}]}}, "schema": []}
{"input": "Elemental composition of dog foods using nitric acid and simulated gastric digestions.", "output": {"entities": {"chemical": [{"text": "nitric acid", "start": 41, "end": 52}]}}, "schema": []}
{"input": "Eighteen dry dog foods obtained commercially in the United States were digested using microwave assisted nitric acid digestion and a simulated gastric digestion.", "output": {"entities": {"chemical": [{"text": "nitric acid", "start": 105, "end": 116}]}}, "schema": []}
{"input": "Digests were analysed for 23 elements using inductively coupled plasma-mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Data, expressed as dry matter concentrations, were compared to published nitric acid digestion results.", "output": {"entities": {"chemical": [{"text": "nitric acid", "start": 73, "end": 84}]}}, "schema": []}
{"input": "Nitric acid data obtained in the present study were not statistically different from published data, with the exception of Mo, Sn, Sb, Tl and Th.", "output": {"entities": {"chemical": [{"text": "Nitric acid", "start": 0, "end": 11}, {"text": "Mo", "start": 123, "end": 125}, {"text": "Sn", "start": 127, "end": 129}, {"text": "Sb", "start": 131, "end": 133}, {"text": "Tl", "start": 135, "end": 137}, {"text": "Th", "start": 142, "end": 144}]}}, "schema": []}
{"input": "However, significant differences in individual intra-sample results were observed between published studies and the present work.", "output": {"entities": {}}, "schema": []}
{"input": "Simulated gastric digestions demonstrated lower extraction efficiencies (< 50% nitric acid digestions) that were statistically significant.", "output": {"entities": {}}, "schema": []}
{"input": "Much lower bioavailability was observed for Al, Ba and Pb.", "output": {"entities": {"chemical": [{"text": "Al", "start": 44, "end": 46}, {"text": "Ba", "start": 48, "end": 50}, {"text": "Pb", "start": 55, "end": 57}]}}, "schema": []}
{"input": "In general, elemental concentrations were determined to be lower than the appropriate Mineral Tolerance Limit or consistent with background concentrations in foodstuffs.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation against Reference Doses (RfDs) showed concentrations for many elements obtained by nitric acid digestion to be above RfD levels.", "output": {"entities": {"chemical": [{"text": "nitric acid", "start": 94, "end": 105}]}}, "schema": []}
{"input": "However, the respective simulated gastric digestion data were below or only moderately elevated above RfDs.", "output": {"entities": {}}, "schema": []}
{"input": "Only arsenic displayed median and maximum concentrations at factors of five and ten above the relevant RfD.", "output": {"entities": {}}, "schema": []}
{"input": "Biological clues to potent DNA-damaging activities in food and flavoring.", "output": {"entities": {}}, "schema": []}
{"input": "Population differences in age-related diseases and cancer could stem from differences in diet.", "output": {"entities": {}}, "schema": []}
{"input": "To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks.", "output": {"entities": {}}, "schema": []}
{"input": "Substances testing positive included reference chemicals: quinacrine (peak response, 51 x) and etoposide (33 x); flavonoids: EGCG (19 x), curcumin (12 x), apigenin (9 x), and quercetin (7 x); beverages: chamomile (11 x), green (21 x), and black tea (26 x) and coffee (3-29 x); and liquid smoke (4-28 x).", "output": {"entities": {"chemical": [{"text": "quinacrine", "start": 58, "end": 68}, {"text": "etoposide", "start": 95, "end": 104}, {"text": "flavonoids", "start": 113, "end": 123}, {"text": "EGCG", "start": 125, "end": 129}, {"text": "curcumin", "start": 138, "end": 146}, {"text": "apigenin", "start": 155, "end": 163}, {"text": "quercetin", "start": 175, "end": 184}]}}, "schema": []}
{"input": "Damage occurred at dietary concentrations: etoposide near 5 mu g/ml produced responses similar to a 1: 1000 dilution of liquid smoke, a 1: 20 dilution of coffee, and a 1: 5 dilution of tea.", "output": {"entities": {"chemical": [{"text": "etoposide", "start": 43, "end": 52}]}}, "schema": []}
{"input": "Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30 x), 3-methoxycatechol (25 x), gallic acid (21 x), and 1, 2, 4-benzenetriol (21 x).", "output": {"entities": {"chemical": [{"text": "Pyrogallol", "start": 0, "end": 10}, {"text": "tannins", "start": 33, "end": 40}, {"text": "pyrogallol", "start": 115, "end": 125}, {"text": "3-methoxycatechol", "start": 134, "end": 151}, {"text": "gallic acid", "start": 160, "end": 171}, {"text": "1, 2, 4-benzenetriol", "start": 184, "end": 204}]}}, "schema": []}
{"input": "From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring.", "output": {"entities": {"chemical": [{"text": "hydroxyls", "start": 92, "end": 101}, {"text": "benzene", "start": 109, "end": 116}]}}, "schema": []}
{"input": "Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation.", "output": {"entities": {}}, "schema": []}
{"input": "Breaks were also directly detected by comet assay.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.", "output": {"entities": {}}, "schema": []}
{"input": "The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Part 2.", "output": {"entities": {}}, "schema": []}
{"input": "Various substituted indazole and benzoxazolone amino acids were investigated as d-tyrosine surrogates in highly potent CGRP receptor antagonists.", "output": {"entities": {"chemical": [{"text": "indazole", "start": 20, "end": 28}, {"text": "benzoxazolone amino acids", "start": 33, "end": 58}, {"text": "d-tyrosine", "start": 80, "end": 90}]}}, "schema": []}
{"input": "Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1.", "output": {"entities": {"chemical": [{"text": "7-methylindazole", "start": 29, "end": 45}, {"text": "indazole", "start": 136, "end": 144}]}}, "schema": []}
{"input": "When dosed at 0. 03mg/kg SC, compound 2 (a racemic mixture of 3 and its (S)-enantiomer) demonstrated robust inhibition of CGRP-induced increases in mamoset facial blood flow up to 105min.", "output": {"entities": {}}, "schema": []}
{"input": "The compound possesses a favorable predictive in vitro toxicology profile, and good aqueous solubility.", "output": {"entities": {}}, "schema": []}
{"input": "When dosed as a nasal spray in rabbits, 3 was rapidly absorbed and showed good intranasal bioavailability (42%).", "output": {"entities": {}}, "schema": []}
{"input": "Production of dosage forms for oral drug delivery by laminar extrusion of wet masses.", "output": {"entities": {}}, "schema": []}
{"input": "Laminar extrusion of wet masses was studied as a novel technology for the production of dosage forms for oral drug delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Extrusion was carried out with a ram extruder.", "output": {"entities": {}}, "schema": []}
{"input": "Formulations contained either microcrystalline cellulose (MCC) or dicalcium phosphate (DCP) as diluent, hydroxypropyl methylcellulose (HPMC), lactose, and water.", "output": {"entities": {"chemical": [{"text": "dicalcium phosphate", "start": 66, "end": 85}, {"text": "DCP", "start": 87, "end": 90}, {"text": "lactose", "start": 142, "end": 149}]}}, "schema": []}
{"input": "Extrudates were characterized for their tensile strength, Young' s modulus of elasticity, water absorption, gel forming capacity, and release of two model drugs, coumarin (COU) and propranolol hydrochloride (PRO).", "output": {"entities": {"chemical": [{"text": "coumarin", "start": 162, "end": 170}, {"text": "COU", "start": 172, "end": 175}, {"text": "propranolol hydrochloride", "start": 181, "end": 206}, {"text": "PRO", "start": 208, "end": 211}]}}, "schema": []}
{"input": "Cohesive extrudates could be produced with both filling materials (MCC and DCP) when HPMC was included as a binder at low amounts (3. 3-4. 5% w/w dry weight).", "output": {"entities": {"chemical": [{"text": "DCP", "start": 75, "end": 78}]}}, "schema": []}
{"input": "Employing more HPMC, the elasticity of the wet masses increased which resulted in distinct surface defects.", "output": {"entities": {}}, "schema": []}
{"input": "For MCC, the maximum HPMC amount that could be included in the formulations (15% w/w dry weight) did not affect the mechanical properties or decrease the drug release significantly.", "output": {"entities": {}}, "schema": []}
{"input": "For DCP extrudates, the maximally effective HPMC amount was 30% (w/w dry weight) with influence on both the mechanical properties and drug release.", "output": {"entities": {"chemical": [{"text": "DCP", "start": 4, "end": 7}]}}, "schema": []}
{"input": "This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Stabilisation of amorphous drugs under high humidity using pharmaceutical thin films.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, the stabilization effects of three polymers on four model drugs (felodipine, fenofibrate, carbamazepine, and celecoxib) under saturated humidity were investigated.", "output": {"entities": {"chemical": [{"text": "felodipine", "start": 80, "end": 90}, {"text": "fenofibrate", "start": 92, "end": 103}, {"text": "carbamazepine", "start": 105, "end": 118}, {"text": "celecoxib", "start": 124, "end": 133}]}}, "schema": []}
{"input": "Three different types of thin films (solid dispersions, drug films with a polymer film coating and drug films laid on top of polymer coated surfaces) were prepared and compared with films containing the drug alone.", "output": {"entities": {}}, "schema": []}
{"input": "ATR-FTIR spectroscopy, polarised light microscopy (PLM), scanning electron microscopy (SEM) and nano-thermal analysis (nano-TA) were performed on the model systems after storage under saturated humidity.", "output": {"entities": {}}, "schema": []}
{"input": "The recrystallisation tendency of the drug in the drug containing thin films was found to be strongly related to the intrinsic crystallization tendency of the drug film alone and the strength of drug-polymer interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, under high humidity, the glass transition temperature of the polymer is no longer an indicator of its drug stabilization capability.", "output": {"entities": {}}, "schema": []}
{"input": "Instead, it is the hygroscobicity of the polymer that appears to be the most important parameter.", "output": {"entities": {}}, "schema": []}
{"input": "Amongst the polymers tested in this study, EUDRAGIT E PO was found to have the greatest inhibitory effect on crystallization, whilst PVP K30 was found to have the least protective effect; presumably because of its hygroscopic nature.", "output": {"entities": {"chemical": [{"text": "EUDRAGIT E PO", "start": 43, "end": 56}, {"text": "PVP K30", "start": 133, "end": 140}]}}, "schema": []}
{"input": "Triethylenetetramine prevents insulin aggregation and fragmentation during copper catalyzed oxidation.", "output": {"entities": {"chemical": [{"text": "Triethylenetetramine", "start": 0, "end": 20}, {"text": "copper", "start": 75, "end": 81}]}}, "schema": []}
{"input": "Metal catalyzed oxidation via the oxidative system Cu (2 +)/ascorbate is known to induce aggregation of therapeutic proteins, resulting in enhanced immunogenicity.", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 51, "end": 59}, {"text": "ascorbate", "start": 60, "end": 69}]}}, "schema": []}
{"input": "Hence, inclusion of antioxidants in protein formulations is of great interest.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, using recombinant human insulin (insulin) as a model, we investigated the ability of several excipients, in particular triethylenetetramine (TETA), reduced glutathione (GSH) and ethylenediamine tetraacetic acid (EDTA), for their ability to prevent protein oxidation, aggregation, and fragmentation.", "output": {"entities": {"chemical": [{"text": "triethylenetetramine", "start": 134, "end": 154}, {"text": "TETA", "start": 156, "end": 160}, {"text": "reduced glutathione", "start": 163, "end": 182}, {"text": "GSH", "start": 184, "end": 187}, {"text": "ethylenediamine tetraacetic acid", "start": 193, "end": 225}, {"text": "EDTA", "start": 227, "end": 231}]}}, "schema": []}
{"input": "Insulin (1mg/ml) was oxidized with 40 mu M Cu (2 +) and 4mM ascorbic acid in absence or presence of excipients.", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 43, "end": 51}, {"text": "ascorbic acid", "start": 60, "end": 73}]}}, "schema": []}
{"input": "Among the excipients studied, 1mM of TETA, EDTA, or GSH prevented insulin aggregation upon metal catalyzed oxidation (MCO) for 3h at room temperature, based on size exclusion chromatography (SEC).", "output": {"entities": {"chemical": [{"text": "TETA", "start": 37, "end": 41}, {"text": "EDTA", "start": 43, "end": 47}, {"text": "GSH", "start": 52, "end": 55}]}}, "schema": []}
{"input": "At lower concentration (100 mu M), for 72h at + 4 degrees C, TETA was the only one to inhibit almost completely oxidation-induced insulin aggregation, fragmentation, and structural changes, as indicated by SEC, nanoparticle tracking analysis, light obscuration particle counting, intrinsic/extrinsic fluorescence, circular dichroism, and chemical derivatization.", "output": {"entities": {"chemical": [{"text": "TETA", "start": 61, "end": 65}]}}, "schema": []}
{"input": "In contrast, GSH had a slight pro-oxidant effect, as demonstrated by the higher percentage of aggregates and a more severe structural damage, whereas EDTA offered substantially less protection.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 13, "end": 16}, {"text": "EDTA", "start": 150, "end": 154}]}}, "schema": []}
{"input": "TETA also protected a monoclonal IgG1 against MCO-induced aggregation, suggesting its general applicability.", "output": {"entities": {"chemical": [{"text": "TETA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "In conclusion, TETA is a potential candidate excipient for inclusion in formulations of oxidation-sensitive proteins.", "output": {"entities": {"chemical": [{"text": "TETA", "start": 15, "end": 19}]}}, "schema": []}
{"input": "Optimized glucocorticoid therapy: Teaching old drugs new tricks.", "output": {"entities": {}}, "schema": []}
{"input": "Glucocorticoids (GCs) are commonly used in the treatment of a wide range of rheumatic and other inflammatory diseases.", "output": {"entities": {}}, "schema": []}
{"input": "They exert their potent anti-inflammatory and immunosuppressive effects primarily via so called genomic mechanisms, mediated by the cytosolic glucocorticoid receptor (cGR).", "output": {"entities": {}}, "schema": []}
{"input": "This mechanism of GC action can be divided into the transactivation and the transrepression processes.", "output": {"entities": {}}, "schema": []}
{"input": "However, also rapid effects of GCs exist which are mediated by specific and unspecific non-genomic mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "A clinical relevance of this mode of GC action is assumed for effects mediated by membrane-bound glucocorticoid receptors, but detailed knowledge on the underlying mechanisms is still missing.", "output": {"entities": {}}, "schema": []}
{"input": "Great efforts have been made in the past to diminish GC-induced adverse effects, thus improving the benefit/risk ratio of the drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Besides approaches to improve the treatment with conventional glucocorticoids currently available to clinicians, new innovative GCs or GC receptor ligands are also being developed.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and Nrf2-inducing activity of the isothiocyanates iberverin, iberin and cheirolin.", "output": {"entities": {"chemical": [{"text": "isothiocyanates iberverin", "start": 44, "end": 69}, {"text": "iberin", "start": 71, "end": 77}, {"text": "cheirolin", "start": 82, "end": 91}]}}, "schema": []}
{"input": "Numerous studies have reported a potent induction of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent gene expression by the isothiocyanate sulforaphane.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 152, "end": 164}]}}, "schema": []}
{"input": "However, little is known regarding the Nrf2-inducing activities of the lower structure-related sulforaphane homologues, such as iberverin, iberin and cheirolin, which exhibit different sulfur oxidation states.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 95, "end": 107}, {"text": "iberverin", "start": 128, "end": 137}, {"text": "iberin", "start": 139, "end": 145}, {"text": "cheirolin", "start": 150, "end": 159}]}}, "schema": []}
{"input": "Therefore, in this study we synthesized the isothiocyanates iberverin, iberin and cheirolin with a high yield and purity and determined their Nrf2-inducing activity in NIH3T3 fibroblasts.", "output": {"entities": {"chemical": [{"text": "isothiocyanates iberverin", "start": 44, "end": 69}, {"text": "iberin", "start": 71, "end": 77}, {"text": "cheirolin", "start": 82, "end": 91}]}}, "schema": []}
{"input": "Iberverin, iberin and cheirolin significantly induced Nrf2 nuclear translocation.", "output": {"entities": {"chemical": [{"text": "Iberverin", "start": 0, "end": 9}, {"text": "iberin", "start": 11, "end": 17}, {"text": "cheirolin", "start": 22, "end": 31}]}}, "schema": []}
{"input": "The increase in nuclear Nrf2 levels was accompanied by a significant increase in heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (gamma GCS) mRNA and protein levels.", "output": {"entities": {"chemical": [{"text": "gamma-glutamylcysteine", "start": 109, "end": 131}]}}, "schema": []}
{"input": "Overall, iberverin, iberin and cheirolin exhibited a similar potency to sulforaphane in inducing Nrf2-dependent gene-expression.", "output": {"entities": {"chemical": [{"text": "iberverin", "start": 9, "end": 18}, {"text": "iberin", "start": 20, "end": 26}, {"text": "cheirolin", "start": 31, "end": 40}, {"text": "sulforaphane", "start": 72, "end": 84}]}}, "schema": []}
{"input": "Furthermore, our data suggest that the induction of Nrf2 by iberverin, iberin and cheirolin may have occurred via an extracellular signal-related kinase (ERK)-dependent signal-transduction pathway.", "output": {"entities": {"chemical": [{"text": "iberverin", "start": 60, "end": 69}, {"text": "iberin", "start": 71, "end": 77}, {"text": "cheirolin", "start": 82, "end": 91}]}}, "schema": []}
{"input": "The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: interest of ex vivo models as an alternative to in vivo experiments.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 21, "end": 35}]}}, "schema": []}
{"input": "Trichothecenes induce changes in the intestinal barrier function through decreased expression of cell junction proteins and apoptosis of enterocytes.", "output": {"entities": {"chemical": [{"text": "Trichothecenes", "start": 0, "end": 14}]}}, "schema": []}
{"input": "The mitogen activated protein kinases (MAPK) play an important role in the signaling pathways of cell turnover and differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Using ex vivo and in vivo approaches, the purpose of this study was to investigate the ability of low doses of DON to induce histological changes in the intestine and to activate the MAPK ERK 1/2, p38 and JNK.", "output": {"entities": {"chemical": [{"text": "DON", "start": 111, "end": 114}]}}, "schema": []}
{"input": "Twelve weaning piglets received during four weeks a control diet or a DON-contaminated diet (2. 3 mg DON/kg feed).", "output": {"entities": {"chemical": [{"text": "DON", "start": 70, "end": 73}, {"text": "DON", "start": 101, "end": 104}]}}, "schema": []}
{"input": "Six weaning piglets were used to prepare jejunal explants (ex vivo model).", "output": {"entities": {}}, "schema": []}
{"input": "Explants were exposed during 4 h to vehicle, 5 or 10 mu M DON.", "output": {"entities": {"chemical": [{"text": "DON", "start": 58, "end": 61}]}}, "schema": []}
{"input": "Intestinal changes were graded using a histological score.", "output": {"entities": {}}, "schema": []}
{"input": "Pigs fed a DON-diet and explants exposed to DON showed a significant decrease in the jejunal score.", "output": {"entities": {"chemical": [{"text": "DON", "start": 11, "end": 14}, {"text": "DON", "start": 44, "end": 47}]}}, "schema": []}
{"input": "In both models, the toxin significantly enhanced phosphorylation of ERK 1/2 and p38, whereas the increased phosphorylation of JNK was non significant.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together these results indicate that in vivo or ex vivo exposure of intestinal tissue to DON lead to similar intestinal lesions and activation of MAPK.", "output": {"entities": {"chemical": [{"text": "DON", "start": 95, "end": 98}]}}, "schema": []}
{"input": "These effects could impair the homeostasis of intestinal tissue in the aspects of barrier function and immune protection.", "output": {"entities": {}}, "schema": []}
{"input": "The similarity of the in vivo and ex vivo results provides also strong evidence that the jejunal explant model is a good alternative for toxicological studies in intestinal tissue.", "output": {"entities": {}}, "schema": []}
{"input": "Antofine-induced connexin43 gap junction disassembly in rat astrocytes involves protein kinase C beta.", "output": {"entities": {"chemical": [{"text": "Antofine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Antofine, a phenanthroindolizidine alkaloid derived from Cryptocaryachinensis and Ficusseptica in the Asclepiadaceae milkweed family, is cytotoxic for various cancer cell lines.", "output": {"entities": {"chemical": [{"text": "Antofine", "start": 0, "end": 8}, {"text": "phenanthroindolizidine alkaloid", "start": 12, "end": 43}]}}, "schema": []}
{"input": "In this study, we demonstrated that treatment of rat primary astrocytes with antofine induced dose-dependent inhibition of gap junction intercellular communication (GJIC), as assessed by scrape-loading 6-carboxyfluorescein dye transfer.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 77, "end": 85}, {"text": "6-carboxyfluorescein", "start": 202, "end": 222}]}}, "schema": []}
{"input": "Levels of Cx43 protein were also decreased in a dose-and time-dependent manner following antofine treatment.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Double-labeling immunofluorescence microscopy showed that antofine (10ng/ml) induced endocytosis of surface gap junctions into the cytoplasm, where Cx43 was co-localized with the early endosome marker EEA1.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 58, "end": 66}]}}, "schema": []}
{"input": "Inhibition of lysosomes or proteasomes by co-treatment with antofine and their respective specific inhibitors, NH4Cl or MG132, partially inhibited the antofine-induced decrease in Cx43 protein levels, but did not inhibit the antofine-induced inhibition of GJIC.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 60, "end": 68}, {"text": "NH4Cl", "start": 111, "end": 116}, {"text": "MG132", "start": 120, "end": 125}]}}, "schema": []}
{"input": "After 30min of treatment, antofine induced a rapid increase in the intracellular Ca (2 +) concentration and activation of protein kinase C (PKC) alpha/beta II, which was maintained for at least 6h.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Co-treatment of astrocytes with antofine and the intracellular Ca (2 +) chelator BAPTA-AM prevented downregulation of Cx43 and inhibition of GJIC.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 32, "end": 40}, {"text": "Ca (2 +)", "start": 63, "end": 71}, {"text": "BAPTA-AM", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Moreover, co-treatment with antofine and a specific PKC beta inhibitor prevented endocytosis of gap junctions, downregulation of Cx43, and inhibition of GJIC.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 28, "end": 36}]}}, "schema": []}
{"input": "Taken together, these findings indicate that antofine induces Cx43 gap junction disassembly by the PKC beta signaling pathway.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Inhibition of GJIC by antofine may undermine the neuroprotective effect of astrocytes in CNS.", "output": {"entities": {"chemical": [{"text": "antofine", "start": 22, "end": 30}]}}, "schema": []}
{"input": "HIV protease inhibitors in pregnancy: pharmacology and clinical use.", "output": {"entities": {}}, "schema": []}
{"input": "The impact of antiretroviral therapy (ART) on the natural history of HIV-1 infection has resulted in dramatic reductions in disease-associated morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, the epidemiology of HIV-1 infection worldwide is changing, as women now represent a substantial proportion of infected adults.", "output": {"entities": {}}, "schema": []}
{"input": "As more highly effective and tolerable antiretroviral regimens become available, and as the prevention of mother-to-child transmission becomes an attainable goal in the management of HIV-infected individuals, more and more HIV-positive women are choosing to become pregnant and have children.", "output": {"entities": {}}, "schema": []}
{"input": "Consequently, it is important to consider the efficacy and safety of antiretroviral agents in pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Protease inhibitors are a common class of medication used in the treatment of HIV-1 infection and are increasingly being used in pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "However, several studies have raised concerns regarding pharmacokinetic alterations in pregnancy, particularly in the third trimester, which results in suboptimal drug concentrations and a theoretically higher risk of virologic failure and perinatal transmission.", "output": {"entities": {}}, "schema": []}
{"input": "Drug level reductions have been observed with each individual protease inhibitor and dose adjustments in pregnancy are suggested for certain agents.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, studies have also raised concerns regarding the safety of protease inhibitors in pregnancy, particularly as they may increase the risk of pre-term birth and metabolic disturbances.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, protease inhibitors are safe and effective for the treatment of HIV-infected pregnant women.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, ritonavir-boosted lopinavir-and atazanavir-based regimens are preferred in pregnancy, while ritonavir-boosted darunavir-and saquinavir-based therapies are reasonable alternatives.", "output": {"entities": {"chemical": [{"text": "ritonavir", "start": 14, "end": 23}, {"text": "lopinavir", "start": 32, "end": 41}, {"text": "atazanavir", "start": 46, "end": 56}, {"text": "ritonavir", "start": 106, "end": 115}, {"text": "darunavir", "start": 124, "end": 133}, {"text": "saquinavir", "start": 138, "end": 148}]}}, "schema": []}
{"input": "This paper reviews the use of protease inhibitors in pregnancy, focusing on pharmacokinetic and safety considerations, and outlines the recommendations for use of this class of medication in the HIV-1-infected pregnant woman.", "output": {"entities": {}}, "schema": []}
{"input": "Predicting Macro-and Microvascular Complications in Type 2 Diabetes: The Japan Diabetes Complications Study/the Japanese Elderly Diabetes Intervention Trial risk engine.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE To develop and validate a risk engine that calculates the risks of macro-and microvascular complications in type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "RESEARCH DESIGN AND METHODS We analyzed pooled data from two clinical trials on 1, 748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7. 2 years.", "output": {"entities": {}}, "schema": []}
{"input": "End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy.", "output": {"entities": {}}, "schema": []}
{"input": "We fit a multistate Cox regression model to derive an algorithm for prediction.", "output": {"entities": {}}, "schema": []}
{"input": "The predictive accuracy of the calculated 5-year risks was cross-validated.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS Sex, age, HbA1c, years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro-and microvascular complications and were incorporated into the risk engine.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 86, "end": 97}, {"text": "creatinine", "start": 110, "end": 120}]}}, "schema": []}
{"input": "The observed-to-predicted (O/P) ratios for each event were between 0. 93 and 1. 08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0. 30 for CHD and 0. 72 for stroke).", "output": {"entities": {}}, "schema": []}
{"input": "C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0. 725, 0. 696, and 0. 767) but moderate for stroke and progression of retinopathy (0. 636 and 0. 614).", "output": {"entities": {}}, "schema": []}
{"input": "By combining macro-and microvascular risks, the classification of low-and high-risk patients was improved by a net reclassification improvement of 5. 7% (P = 0. 02).", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS The risk engine accurately predicts macro-and microvascular complications and would provide helpful information in risk classification and health economic simulations.", "output": {"entities": {}}, "schema": []}
{"input": "MRI morphometric characterisation of the paediatric cervical spine and spinal cord in children with MPS IVA (Morquio-Brailsford syndrome).", "output": {"entities": {}}, "schema": []}
{"input": "Nearly all children with MPS IVA develop skeletal deformities affecting the spine.", "output": {"entities": {}}, "schema": []}
{"input": "At the atlanto-axial spine, odontoid hypoplasia occurs.", "output": {"entities": {}}, "schema": []}
{"input": "GAG deposition around the dens, leads to peri-odontoid infiltration.", "output": {"entities": {}}, "schema": []}
{"input": "Transverse/alar ligament incompetence causes instability.", "output": {"entities": {}}, "schema": []}
{"input": "Atlanto-axial instability is associated with cord compression and myelopathy, leading to major morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Intervention is often required.", "output": {"entities": {}}, "schema": []}
{"input": "Does the presence of widened bullet shaped vertebra in platyspondily encroach on the spinal canal and cause spinal stenosis in MPS IVA?", "output": {"entities": {}}, "schema": []}
{"input": "So far, there have been no standardised morphometric measurements of the paediatric MPS IVA cervical spine to evaluate whether there is pre-existing spinal stenosis predisposing to compressive myelopathy or whether this is purely an acquired process secondary to instability and compression.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides the first radiological quantitative analysis of the cervical spine and spinal cord in a series of affected children.", "output": {"entities": {}}, "schema": []}
{"input": "MRI morphometry indicates that the MPS IVA spine is narrower at C1-2 level giving an inverted funnel shape.", "output": {"entities": {}}, "schema": []}
{"input": "There is no evidence of a reduction in the Torg ratio (canal-body ratio) in the cervical spine.", "output": {"entities": {}}, "schema": []}
{"input": "The spinal canal does not exceed 11 mm at any level, significantly smaller than normal historical cohorts (14 mm).", "output": {"entities": {}}, "schema": []}
{"input": "The sagittal diameter and axial surface area of both spinal canal and cord are reduced.", "output": {"entities": {}}, "schema": []}
{"input": "C1-2 level cord compression was evident in the canal-cord ratio but the Torg ratio was not predictive of cord compression.", "output": {"entities": {}}, "schema": []}
{"input": "In MPS IVA the reduction in the space available for the cord (SAC) is multifactorial rather than due to congenital spinal stenosis.", "output": {"entities": {}}, "schema": []}
{"input": "A pathophysiologic role for epidermal growth factor receptor in pemphigus acantholysis.", "output": {"entities": {}}, "schema": []}
{"input": "The pemphigus family of autoimmune bullous disorders is characterized by autoantibody binding to desmoglein 1 and/or 3 (dsg1/dsg3).", "output": {"entities": {}}, "schema": []}
{"input": "In this study we show that EGF receptor (EGFR) is activated following pemphigus vulgaris (PV) IgG treatment of primary human keratinocytes and that EGFR activation is downstream of p38 mitogen-activated protein kinase (p38).", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of EGFR blocked PV IgG-triggered dsg3 endocytosis, keratin intermediate filament retraction, and loss of cell-cell adhesion in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Significantly, inhibiting EGFR prevented PV IgG-induced blister formation in the passive transfer mouse model of pemphigus.", "output": {"entities": {}}, "schema": []}
{"input": "These data demonstrate cross-talk between dsg3 and EGFR, that this cross-talk is regulated by p38, and that EGFR is a potential therapeutic target for pemphigus.", "output": {"entities": {}}, "schema": []}
{"input": "Small-molecule inhibitors and monoclonal antibodies directed against EGFR are currently used to treat several types of solid tumors.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides the experimental rationale for investigating the use of EGFR inhibitors in pemphigus.", "output": {"entities": {}}, "schema": []}
{"input": "The propeptides of VEGF-D determine heparin binding, receptor heterodimerization, and effects on tumor biology.", "output": {"entities": {}}, "schema": []}
{"input": "VEGF-D is an angiogenic and lymphangiogenic glycoprotein that can be proteolytically processed generating various forms differing in subunit composition due to the presence or absence of N-and C-terminal propeptides.", "output": {"entities": {"chemical": [{"text": "N", "start": 187, "end": 188}, {"text": "C", "start": 193, "end": 194}]}}, "schema": []}
{"input": "These propeptides flank the central VEGF homology domain, that contains the binding sites for VEGF receptors (VEGFRs), but their biological functions were unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of propeptide function will be important to clarify which forms of VEGF-D are biologically active and therefore clinically relevant.", "output": {"entities": {}}, "schema": []}
{"input": "Here we use VEGF-D mutants deficient in either propeptide, and in the capacity to process the remaining propeptide, to monitor the functions of these domains.", "output": {"entities": {}}, "schema": []}
{"input": "We report for the first time that VEGF-D binds heparin, and that the C-terminal propeptide significantly enhances this interaction (removal of this propeptide from full-length VEGF-D completely prevents heparin binding).", "output": {"entities": {"chemical": [{"text": "C", "start": 69, "end": 70}]}}, "schema": []}
{"input": "We also show that removal of either the N-or C-terminal propeptide is required for VEGF-D to drive formation of VEGFR-2/VEGFR-3 heterodimers which have recently been shown to positively regulate angiogenic sprouting.", "output": {"entities": {"chemical": [{"text": "N", "start": 40, "end": 41}, {"text": "C", "start": 45, "end": 46}]}}, "schema": []}
{"input": "The mature form of VEGF-D, lacking both propeptides, can also promote formation of these receptor heterodimers.", "output": {"entities": {}}, "schema": []}
{"input": "In a mouse tumor model, removal of only the C-terminal propeptide from full-length VEGF-D was sufficient to enhance angiogenesis and tumor growth.", "output": {"entities": {"chemical": [{"text": "C", "start": 44, "end": 45}]}}, "schema": []}
{"input": "In contrast, removal of both propeptides is required for high rates of lymph node metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "The findings reported here show that the propeptides profoundly influence molecular interactions of VEGF-D with VEGF receptors, co-receptors, and heparin, and its effects on tumor biology.", "output": {"entities": {}}, "schema": []}
{"input": "Increased immunoreactive 11-ketotestosterone concentrations in sheep feces after acth challenge.", "output": {"entities": {"chemical": [{"text": "11-ketotestosterone", "start": 25, "end": 44}]}}, "schema": []}
{"input": "11-Oxoetiocholanolone and related substances are important metabolites of cortisol and are excreted via feces in ruminants.", "output": {"entities": {"chemical": [{"text": "11-Oxoetiocholanolone", "start": 0, "end": 21}, {"text": "cortisol", "start": 74, "end": 82}]}}, "schema": []}
{"input": "To investigate whether 11-ketotestosterone (11-KT) or its immunoreactive metabolites are formed and excreted in ruminant feces, an enzyme immunoassay (EIA) was developed and validated.", "output": {"entities": {"chemical": [{"text": "11-ketotestosterone", "start": 23, "end": 42}, {"text": "11-KT", "start": 44, "end": 49}]}}, "schema": []}
{"input": "The antibody was raised in rabbits against 11-KT-3-CMO: bovine serum albumin with biotinylated 11-KT as a label.", "output": {"entities": {"chemical": [{"text": "11-KT-3-CMO", "start": 43, "end": 54}, {"text": "biotinylated 11-KT", "start": 82, "end": 100}]}}, "schema": []}
{"input": "The assay showed a sensitivity of 0. 3 pg/well.", "output": {"entities": {}}, "schema": []}
{"input": "To validate the assay biologically, 6 rams were injected with a synthetic analogue of the adrenocorticotropic hormone (Synacthen, 2 micro g/kg body wt).", "output": {"entities": {}}, "schema": []}
{"input": "An aliquot was collected of each fecal portion spontaneously defecated 8 h before Synacthen injection to 24 h after injection and stored at-20 degrees C until analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Samples (0. 5 g) were extracted using 80% methanol and immunoreactive metabolites measured using the 11-KT EIA and an already established 11, 17-dioxoandrostane (11, 17-DOA) EIA.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 42, "end": 50}, {"text": "11-KT", "start": 101, "end": 106}, {"text": "11, 17-dioxoandrostane", "start": 138, "end": 160}, {"text": "11, 17-DOA", "start": 162, "end": 172}]}}, "schema": []}
{"input": "High-performance liquid chromatography separation revealed no peak in the same elution position as authentic 11-KT; therefore, reacting substances were referred to as 11-KT equivalents.", "output": {"entities": {"chemical": [{"text": "11-KT", "start": 109, "end": 114}, {"text": "11-KT", "start": 167, "end": 172}]}}, "schema": []}
{"input": "In the case of 11-KT immunoreactive substances, the values increased from baseline (median, 136 ng/g feces) to a peak concentration (median, 424 ng/g) 10 to 14 h after Synacthen injection and declined afterwards.", "output": {"entities": {"chemical": [{"text": "11-KT", "start": 15, "end": 20}]}}, "schema": []}
{"input": "Concentrations of 11, 17-DOA showed the same pattern, but the values were 2 to 4 times higher.", "output": {"entities": {"chemical": [{"text": "11, 17-DOA", "start": 18, "end": 28}]}}, "schema": []}
{"input": "From this data, the authors conclude that 11-KT-like substances, specifically C19 O3-androgens with a 17 beta-hydroxy group, were present in the feces.", "output": {"entities": {"chemical": [{"text": "11-KT", "start": 42, "end": 47}, {"text": "C19 O3-androgens", "start": 78, "end": 94}, {"text": "17 beta-hydroxy", "start": 102, "end": 117}]}}, "schema": []}
{"input": "These substances originate from the adrenals and are most likely cortisol metabolites.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 65, "end": 73}]}}, "schema": []}
{"input": "Environ Toxicol Chem 2013; 32: 1332-1336.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Fractionation of organosolv lignin from olive tree clippings and its valorization to simple phenolic compounds.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 92, "end": 100}]}}, "schema": []}
{"input": "Lignin valorization practices have attracted a great deal of interest in recent years due to the large excess of lignin produced by the pulp and paper industry, together with second-generation bioethanol plants.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, a new lignin valorization approach is proposed.", "output": {"entities": {}}, "schema": []}
{"input": "It involves ultrafiltration as a fractionation process to separate different molecular weight lignin fractions followed by a hydrogen-free, mild, hydrogenolytic, heterogeneously catalyzed methodology assisted by microwave irradiation to obtain simple phenolic, monomeric products by depolymerization using a nickel-based catalyst.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 125, "end": 133}, {"text": "phenolic", "start": 251, "end": 259}]}}, "schema": []}
{"input": "The main products obtained were desaspidinol, syringaldehyde, and syringol; this proves the efficiency of the depolymerization conditions applied.", "output": {"entities": {"chemical": [{"text": "desaspidinol", "start": 32, "end": 44}, {"text": "syringaldehyde", "start": 46, "end": 60}, {"text": "syringol", "start": 66, "end": 74}]}}, "schema": []}
{"input": "The concentration of these observed compounds increased when the molecular weights of the lignin fractions increased.", "output": {"entities": {}}, "schema": []}
{"input": "The applied depolymerization conditions, which take advantage of the use of formic acid as a hydrogen-donating solvent, did not generate any biochar in the systems.", "output": {"entities": {"chemical": [{"text": "formic acid", "start": 76, "end": 87}, {"text": "hydrogen", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Searching the coding region for microRNA targets.", "output": {"entities": {}}, "schema": []}
{"input": "Finding microRNA targets in the coding region is difficult due to the overwhelming signal encoding the amino acid sequence.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 103, "end": 113}]}}, "schema": []}
{"input": "Here, we introduce an algorithm (called PACCMIT-CDS) that finds potential microRNA targets within coding sequences by searching for conserved motifs that are complementary to the microRNA seed region and also overrepresented in comparison with a background model preserving both codon usage and amino acid sequence.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 295, "end": 305}]}}, "schema": []}
{"input": "Precision and sensitivity of PACCMIT-CDS are evaluated using PAR-CLIP and proteomics data sets.", "output": {"entities": {}}, "schema": []}
{"input": "Thanks to the properly constructed background, the new algorithm achieves a lower rate of false positives and better ranking of predictions than do currently available algorithms, which were designed to find microRNA targets within 3' UTRs.", "output": {"entities": {}}, "schema": []}
{"input": "A nonionic inhibitor with high specificity for the UDP-Gal donor binding site of human blood group B galactosyltransferase: design, synthesis, and characterization.", "output": {"entities": {"chemical": [{"text": "UDP-Gal", "start": 51, "end": 58}]}}, "schema": []}
{"input": "9-(5-O-alpha-D-galactopyranosyl)-D-arabinityl-1, 3, 7-trihydropurine-2, 6, 8-trione (1) was designed and synthesized as a nonionic inhibitor for the donor binding site of human blood group B galactosyltransferase (GTB).", "output": {"entities": {"chemical": [{"text": "9-(5-O-alpha-D-galactopyranosyl)-D-arabinityl-1, 3, 7-trihydropurine-2, 6, 8-trione", "start": 0, "end": 83}]}}, "schema": []}
{"input": "Enzymatic characterization showed 1 to be extremely specific, as the highly homologous human N-acetylgalactosaminyltransferase (GTA) is not inhibited.", "output": {"entities": {"chemical": [{"text": "N", "start": 93, "end": 94}]}}, "schema": []}
{"input": "The binding epitope of 1 demonstrates a high involvement of the arabinityl linker, whereas the galactose residue is only making contact to the protein via its C-2 site, which is very important for the discrimination between galactose and N-acetylgalactosamine, the substrate transferred by GTA.", "output": {"entities": {"chemical": [{"text": "arabinityl", "start": 64, "end": 74}, {"text": "galactose", "start": 95, "end": 104}, {"text": "galactose", "start": 224, "end": 233}, {"text": "N-acetylgalactosamine", "start": 238, "end": 259}]}}, "schema": []}
{"input": "The approach can generate highly specific glycosyltransferase inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Switchable Elastin-Like Polypeptides that Respond to Chemical Inducers of Dimerization.", "output": {"entities": {}}, "schema": []}
{"input": "Elastin-like polypeptides (ELPs) are protein polymers that reversibly phase separate in response to increased temperature, pressure, concentration, ionic strength, and molecular weight.", "output": {"entities": {}}, "schema": []}
{"input": "If it were possible to engineer their phase separation to respond to specific molecular substrates, ELP fusion proteins might be engineered as biosensors, smart biomaterials, diagnostic imaging agents, and targeted therapies.", "output": {"entities": {}}, "schema": []}
{"input": "What has been lacking is a strategy to design ELPs to respond to specific substrates.", "output": {"entities": {}}, "schema": []}
{"input": "To address this deficiency, we report that ELP fusion proteins phase separate in response to chemical inducers of dimerization (CID).", "output": {"entities": {}}, "schema": []}
{"input": "The rationale is that ELP phase separation depends on molecular weight, concentration, and local hydrophobicity; therefore, processes that affect these properties, including noncovalent dimerization, can be tuned to produce isothermal phase separation.", "output": {"entities": {}}, "schema": []}
{"input": "To test this hypothesis, constructs were evaluated consisting of an immunophilin: human FK-506 binding protein 12 (FKBP) attached to an ELP.", "output": {"entities": {"chemical": [{"text": "FK-506", "start": 88, "end": 94}]}}, "schema": []}
{"input": "Under stoichiometric binding of a CID, the fusion protein homodimerizes and triggers phase separation.", "output": {"entities": {}}, "schema": []}
{"input": "This dimerization is reversible upon saturation with excess CID or competitive binding of a small lipophilic macrolide to FKBP.", "output": {"entities": {}}, "schema": []}
{"input": "By modulating the ELP molecular weight, phase separation was tuned for isothermal response to CID at physiological ionic strength and temperature (37 degrees C).", "output": {"entities": {}}, "schema": []}
{"input": "To interpret the relationship between transition temperature and equilibrium binding constants, an empirical mathematical model was employed.", "output": {"entities": {}}, "schema": []}
{"input": "To the best of our knowledge, this report is the first demonstration of reversible ELP switching in response to controlled dimerization.", "output": {"entities": {}}, "schema": []}
{"input": "Due to its simplicity, this strategy may be useful to design ELP fusion proteins that respond to specific dimeric biological entities.", "output": {"entities": {}}, "schema": []}
{"input": "Cause and prevention of moisture-induced degradation of resistance random access memory nanodevices.", "output": {"entities": {}}, "schema": []}
{"input": "Dielectric thin films in nanodevices may absorb moisture, leading to physical changes and property/performance degradation, such as altered data storage and readout in resistance random access memory.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate using a nanometallic memory that such degradation proceeds via nanoporosity, which facilitates water wetting in otherwise nonwetting dielectrics.", "output": {"entities": {}}, "schema": []}
{"input": "Electric degradation only occurs when the device is in the charge-storage state, which provides a nanoscale dielectrophoretic force directing H2O to internal field centers (sites of trapped charge) to enable bond rupture and charged hydroxyl formation.", "output": {"entities": {"chemical": [{"text": "H2O", "start": 142, "end": 145}, {"text": "hydroxyl", "start": 233, "end": 241}]}}, "schema": []}
{"input": "While these processes are dramatically enhanced by an external DC or AC field and electron-donating electrodes, they can be completely prevented by eliminating nanoporosity, depositing a barrier layer, or using an oxidation-resistant electrode.", "output": {"entities": {}}, "schema": []}
{"input": "These findings provide insight for understanding high-performance memory and field-assisted degradation of nanodevices.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of oxidant-antioxidant status in oral toxicity of fish oil methyl esters and diesel fuel in male rats.", "output": {"entities": {"chemical": [{"text": "methyl esters", "start": 70, "end": 83}]}}, "schema": []}
{"input": "This study was conducted to compare the effects of oral toxicity induced by fish oil biodiesel and diesel fuel.", "output": {"entities": {}}, "schema": []}
{"input": "Diesel and fish oil biodiesel were administered by oral gavage to rats.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, 35 rats were divided into five groups.", "output": {"entities": {}}, "schema": []}
{"input": "Sunflower oil of 250 mg kg (-1) was administered to the rats in the control group by oral gavage.", "output": {"entities": {}}, "schema": []}
{"input": "The rats in the D250 and D500 groups were administered by oral gavage 250 mg kg (-1) and 500 mg kg (-1) of diesel fuel dissolved in equal amounts of sunflower oil, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The rats in the F250 and F500 groups were administered by oral gavage 250 mg kg (-1) and 500 mg kg (-1) of fish oil biodiesel dissolved in equal amounts of sunflower oil, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "At the end of the study, malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in the whole blood; catalase (CAT) activity level was measured in erythrocytes; and nitrite (NO (2)) and nitrate (NO (3)) levels were measured in the serum.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 25, "end": 40}, {"text": "MDA", "start": 42, "end": 45}, {"text": "reduced glutathione", "start": 51, "end": 70}, {"text": "GSH", "start": 72, "end": 75}, {"text": "nitrite", "start": 182, "end": 189}, {"text": "NO (2)", "start": 191, "end": 197}, {"text": "nitrate", "start": 203, "end": 210}, {"text": "NO (3)", "start": 212, "end": 218}]}}, "schema": []}
{"input": "It was observed that the whole blood MDA levels of the diesel groups were considerably different from those in the control and fish oil biodiesel groups (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "MDA", "start": 37, "end": 40}]}}, "schema": []}
{"input": "GSH levels in the control group were observed to be considerably different from those in all other groups (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "GSH", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Serum NO (3) concentrations in the diesel groups were found to be considerably different from those in the control and biodiesel groups.", "output": {"entities": {"chemical": [{"text": "NO (3)", "start": 6, "end": 12}]}}, "schema": []}
{"input": "Serum NO (2) concentrations in one of the diesel groups were significantly different from those in the control and biodiesel groups (p < 0. 01 and p < 0. 05, respectively).", "output": {"entities": {"chemical": [{"text": "NO (2)", "start": 6, "end": 12}]}}, "schema": []}
{"input": "The CAT activity of the control group was observed to be different from that in the other groups.", "output": {"entities": {}}, "schema": []}
{"input": "According to these results, both fish oil biodiesel and diesel fuel are thought to cause lipid peroxidation.", "output": {"entities": {}}, "schema": []}
{"input": "It was observed that fish oil biodiesel does not induce as much oxidative damage as does the diesel fuel.", "output": {"entities": {}}, "schema": []}
{"input": "It is suggested that fish oil biodiesel should be preferred as an alternative to the diesel.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of tocopherol on biochemical blood parameters in pleuritis-induced rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin.", "output": {"entities": {"chemical": [{"text": "tocopherol", "start": 10, "end": 20}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 92, "end": 130}]}}, "schema": []}
{"input": "The aim of this study was to evaluate the effect of tocopherol on pleuritis-induced rats exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).", "output": {"entities": {"chemical": [{"text": "tocopherol", "start": 52, "end": 62}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 100, "end": 138}, {"text": "TCDD", "start": 140, "end": 144}]}}, "schema": []}
{"input": "Rats were treated with a single TCDD dose of 5 mu g/kg body weight (b. w.) and then for 3 weeks they were daily supplemented with tocopherol at a dose of 30 mg/kg b. w.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 32, "end": 36}, {"text": "tocopherol", "start": 130, "end": 140}]}}, "schema": []}
{"input": "The inflammation was initiated by intrapleural injection of a single dose of 1% carrageenin solution in a volume of 0. 15 ml.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in biochemical blood parameters were measured three times at the 24th, 72nd and 120th hour of pleuritis and the blood was collected from 20 animals of each group of rats (group with the control inflammation; group treated with TCDD and with control inflammation; group treated with TCDD, supplemented with tocopherol and with the inflammation).", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 235, "end": 239}, {"text": "TCDD", "start": 290, "end": 294}]}}, "schema": []}
{"input": "The following biochemical parameters were measured: tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, IL-4, IL-6, procollagen, telopeptide, fibrinogen, cholesterol, urea, creatinine, aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 159, "end": 170}, {"text": "urea", "start": 172, "end": 176}, {"text": "creatinine", "start": 178, "end": 188}, {"text": "aspartate", "start": 190, "end": 199}, {"text": "alanine", "start": 229, "end": 236}]}}, "schema": []}
{"input": "Daily supplementation of tocopherol caused significant changes in the level of TNF, IL-1, IL-4, IL-6, urea, creatinine, AspAT and AlAT.", "output": {"entities": {"chemical": [{"text": "tocopherol", "start": 25, "end": 35}, {"text": "urea", "start": 102, "end": 106}, {"text": "creatinine", "start": 108, "end": 118}]}}, "schema": []}
{"input": "According to the results of these studies, we suggest that tocopherol supplementation in high doses could act as a protective treatment to improve liver metabolism.", "output": {"entities": {"chemical": [{"text": "tocopherol", "start": 59, "end": 69}]}}, "schema": []}
{"input": "Cytotoxic and phytotoxic actions of Heliotropium strigosum.", "output": {"entities": {}}, "schema": []}
{"input": "This study describes the cytotoxic and phytotoxic activities of the crude extract of Heliotropium strigosum and its resultant fractions.", "output": {"entities": {}}, "schema": []}
{"input": "In brine shrimp toxicology assays, profound cytotoxicity was displayed by ethyl acetate (LD (50) 8. 3 mu g/ml) and chloroform (LD (50) 8. 8 mu g/ml) fractions, followed by relatively weak crude methanolic extract of H. strigosum (LD (50) 909 mu g/ml) and n-hexane fraction (LD (50) 1000 mu g/ml).", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 74, "end": 87}, {"text": "chloroform", "start": 115, "end": 125}, {"text": "n-hexane", "start": 255, "end": 263}]}}, "schema": []}
{"input": "In case of phytotoxicity activity against Lemna acquinoctialis, highest phytotoxic effect was showed by ethyl acetate fraction (LD (50) 91. 0 mu g/ml), while chloroform fraction, plant crude extract and n-hexane, respectively, caused 50%, 30. 76 +/- 1. 1% and 30. 7 +/- 1. 1% inhibitory action at maximum concentration used, that is, 1000 mu g/ml.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 104, "end": 117}, {"text": "chloroform", "start": 158, "end": 168}, {"text": "n-hexane", "start": 203, "end": 211}]}}, "schema": []}
{"input": "These data indicates that H. strigosum exhibits cytotoxic and phytotoxic potential, which explore its use as anticancer and herbicidal medicine.", "output": {"entities": {}}, "schema": []}
{"input": "The ethyl acetate and chloroform fractions were more potent for the evaluated toxicity effects, thus recommended for isolation and identification of the active compounds.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 4, "end": 17}, {"text": "chloroform", "start": 22, "end": 32}]}}, "schema": []}
{"input": "Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor beta (TGF beta) signaling is essential for testicular aging and regulating testis size.", "output": {"entities": {}}, "schema": []}
{"input": "Follistatin-like 3 (FSTL3) is a glycoprotein that binds and inhibits the action of TGF beta ligands such as activin.", "output": {"entities": {}}, "schema": []}
{"input": "The roles played by FSTL3 and activin signaling in organ development and homeostasis are not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "The authors show mice deficient in FSTL3 develop markedly enlarged testes that are also delayed in their age-related regression.", "output": {"entities": {}}, "schema": []}
{"input": "These FSTL3 knockout mice exhibit increased Sertoli cell numbers, allowing for increased spermatogenesis but otherwise showing normal testicular function.", "output": {"entities": {}}, "schema": []}
{"input": "The data show that FSTL3 deletion leads to increased AKT signaling and SIRT1 expression in the testis.", "output": {"entities": {}}, "schema": []}
{"input": "This demonstrates a cross-talk between TGF beta ligand and AKT signaling and leads to a potential mechanism for increased cellular survival and antiaging.", "output": {"entities": {}}, "schema": []}
{"input": "The findings identify crucial roles for FSTL3 in limiting testis organ size and promoting age-related testicular regression.", "output": {"entities": {}}, "schema": []}
{"input": "Ruthenium (II) polypyridyl complexes as G-quadruplex inducing and stabilizing ligands in telomeric DNA.", "output": {"entities": {"chemical": [{"text": "Ruthenium (II) polypyridyl", "start": 0, "end": 26}]}}, "schema": []}
{"input": "Two ruthenium (ii) polypyridyl complexes [Ru (phen) 2 (4idip)] (ClO4) 2 () and [Ru (bpy) 2 (4idip)] (ClO4) 2 () (phen = 1, 10-phenanthroline, bpy = 2, 2'-bipyridine, 4idip = 4-indoleimidazo [4, 5-f] [1, 10] phenanthroline) designed as telomeric G-quadruplex ligands have been synthesized and characterized.", "output": {"entities": {"chemical": [{"text": "ruthenium (ii) polypyridyl", "start": 4, "end": 30}, {"text": "[Ru (phen) 2 (4idip)] (ClO4) 2", "start": 41, "end": 71}, {"text": "[Ru (bpy) 2 (4idip)] (ClO4) 2", "start": 79, "end": 108}, {"text": "phen", "start": 113, "end": 117}, {"text": "1, 10-phenanthroline", "start": 120, "end": 140}, {"text": "bpy", "start": 142, "end": 145}, {"text": "2, 2'-bipyridine", "start": 148, "end": 164}, {"text": "4idip", "start": 166, "end": 171}, {"text": "4-indoleimidazo [4, 5-f] [1, 10] phenanthroline", "start": 174, "end": 221}]}}, "schema": []}
{"input": "The interaction of human telomeric G-quadruplex DNA (HTG21) with the designed ligands was explored by fluorescence analysis, absorption spectroscopy, continuous variation, circular dichroism spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, telomerase repeat amplification protocol (TRAP), and visual studies.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that both complexes could induce and stabilize different G-quadruplex structures by using a 1: 1 [quadruplex]/[complex] binding mode ratio.", "output": {"entities": {}}, "schema": []}
{"input": "Complex exhibited higher interaction ability and better G-quadruplex selectivity than duplex DNA.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, both ruthenium complexes led to the inhibition of the enzyme telomerase, and complex was the significantly better inhibitor.", "output": {"entities": {"chemical": [{"text": "ruthenium", "start": 18, "end": 27}]}}, "schema": []}
{"input": "Characterization of the head-twitch response induced by hallucinogens in mice: Detection of the behavior based on the dynamics of head movement.", "output": {"entities": {}}, "schema": []}
{"input": "RATIONALE: The head-twitch response (HTR) is a rapid side-to-side rotational head movement that occurs in rats and mice after administration of serotonergic hallucinogens and other 5-HT (2A) agonists.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 181, "end": 185}]}}, "schema": []}
{"input": "The HTR is widely used as a behavioral assay for 5-HT (2A) activation and to probe for interactions between the 5-HT (2A) receptor and other transmitter systems.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 49, "end": 53}, {"text": "5-HT", "start": 112, "end": 116}]}}, "schema": []}
{"input": "OBJECTIVE: High-speed video recordings were used to analyze the head movement that occurs during head twitches in C57BL/6J mice.", "output": {"entities": {}}, "schema": []}
{"input": "Experiments were also conducted in C57BL/6J mice to determine whether a head-mounted magnet and a magnetometer coil could be used to detect the HTR induced by serotonergic hallucinations based on the dynamics of the response.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Head movement during the HTR was highly rhythmic and occurred within a specific frequency range (mean head movement frequency of 90. 3 Hz).", "output": {"entities": {}}, "schema": []}
{"input": "Head twitches produced wave-like oscillations of magnetometer coil voltage that matched the frequency of head movement during the response.", "output": {"entities": {}}, "schema": []}
{"input": "The magnetometer coil detected the HTR induced by the serotonergic hallucinogens 2, 5-dimethoxy-4-iodoamphetamine (DOI; 0. 25, 0. 5, and 1. 0 mg/kg, i. p.) and lysergic acid diethylamide (LSD; 0. 05, 0. 1, 0. 2, and 0. 4 mg/kg, i. p.) with extremely high sensitivity and specificity.", "output": {"entities": {"chemical": [{"text": "2, 5-dimethoxy-4-iodoamphetamine", "start": 81, "end": 113}, {"text": "DOI", "start": 115, "end": 118}, {"text": "lysergic acid diethylamide", "start": 160, "end": 186}, {"text": "LSD", "start": 188, "end": 191}]}}, "schema": []}
{"input": "Magnetometer coil recordings demonstrated that the non-hallucinogenic compounds (+)-amphetamine (2. 5 and 5. 0 mg/kg, i. p.) and lisuride (0. 8, 1. 6, and 3. 2 mg/kg, i. p.) did not induce the HTR.", "output": {"entities": {"chemical": [{"text": "(+)-amphetamine", "start": 80, "end": 95}, {"text": "lisuride", "start": 129, "end": 137}]}}, "schema": []}
{"input": "CONCLUSIONS: These studies confirm that a magnetometer coil can be used to detect the HTR induced by hallucinogens.", "output": {"entities": {}}, "schema": []}
{"input": "The use of magnetometer-based HTR detection provides a high-throughput, semi-automated assay for this behavior, and offers several advantages over traditional assessment methods.", "output": {"entities": {}}, "schema": []}
{"input": "Faecal Excretion Dynamic during Subacute Oral Exposure to Different Pb Species in Rattus norvegicus.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 68, "end": 70}]}}, "schema": []}
{"input": "Faecal excretion is a basic means of detoxification upon ingestion of Pb-contaminated feed.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 70, "end": 72}]}}, "schema": []}
{"input": "In order to determine a time course of Pb elimination after oral exposure to two different forms of this heavy metal (lead acetate vs. phyto-bound Pb), a feeding study was carried out in experimental rats using the Pb phyto-hyperaccumulator Pistia stratiotes as a model diet.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 39, "end": 41}, {"text": "lead acetate", "start": 118, "end": 130}, {"text": "Pb", "start": 147, "end": 149}, {"text": "Pb", "start": 215, "end": 217}]}}, "schema": []}
{"input": "The effect of starvation on Pb excretion was further studied in rats that were fed plant material.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 28, "end": 30}]}}, "schema": []}
{"input": "Twelve Pb doses (7 mu g Pb/1 g BW) were administered orally over a 5-week period.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 7, "end": 9}, {"text": "Pb", "start": 24, "end": 26}]}}, "schema": []}
{"input": "Faeces samples were collected 24 and 72 h post-exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Inductively coupled plasma optical emission spectrometry and electrothermal absorption spectrometry methods were used for determination of heavy metal concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "Up to 53% of ingested Pb was rapidly eliminated from the exposed rats via faeces within 24 h after exposure.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 22, "end": 24}]}}, "schema": []}
{"input": "Faecal excretion in exposed rats differed significantly when compared to that of the control group.", "output": {"entities": {}}, "schema": []}
{"input": "Fasting before exposure reduced Pb excretion by up to 50%.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 32, "end": 34}]}}, "schema": []}
{"input": "Faecal excretions of both examined Pb forms exhibited almost identical patterns.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 35, "end": 37}]}}, "schema": []}
{"input": "Considerable differences were revealed concerning total excretion levels; lead acetate was excreted in amount greater extent than those of phytobound Pb.", "output": {"entities": {"chemical": [{"text": "lead acetate", "start": 74, "end": 86}, {"text": "Pb", "start": 150, "end": 152}]}}, "schema": []}
{"input": "Results of our study suggest that Pb forms occurring in the P. stratiotes tissues are absorbed through the gastrointestinal tract to a greater extent than Pb from lead acetate.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 34, "end": 36}, {"text": "Pb", "start": 155, "end": 157}, {"text": "lead acetate", "start": 163, "end": 175}]}}, "schema": []}
{"input": "Therefore, higher portions of ingested Pb can be available for potential accumulation in tissues of exposed subjects.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 39, "end": 41}]}}, "schema": []}
{"input": "Echinacea sanguinea and Echinacea pallida extracts stimulate glucuronidation and basolateral transfer of Bauer alkamides 8 and 10 and ketone 24 and inhibit P-glycoprotein transporter in Caco-2 cells.", "output": {"entities": {"chemical": [{"text": "alkamides", "start": 111, "end": 120}, {"text": "ketone", "start": 134, "end": 140}]}}, "schema": []}
{"input": "The use of Echinacea as a medicinal herb is prominent in the United States, and many studies have assessed the effectiveness of Echinacea as an immunomodulator.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that Bauer alkamides 8, 10, and 11 and ketone 24 were absorbed similarly either as pure compounds or from Echinacea sanguinea and Echinacea pallida ethanol extracts, and that these Echinacea extracts could inhibit the P-glycoprotein transporter in Caco-2 human intestinal epithelial cells.", "output": {"entities": {"chemical": [{"text": "alkamides", "start": 27, "end": 36}, {"text": "ketone", "start": 55, "end": 61}, {"text": "ethanol", "start": 164, "end": 171}]}}, "schema": []}
{"input": "Using HPLC analysis, the permeation rate of Bauer alkamides by passive diffusion across Caco-2 cells corresponded with compound hydrophilicity (alkamide 8 > 10 > 11), independent of the plant extract matrix.", "output": {"entities": {"chemical": [{"text": "alkamides", "start": 50, "end": 59}, {"text": "alkamide", "start": 144, "end": 152}]}}, "schema": []}
{"input": "Both Echinacea ethanol extracts stimulated apparent glucuronidation and basolateral efflux of glucuronides of alkamides 8 and 10 but not alkamide 11.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 15, "end": 22}, {"text": "alkamides", "start": 110, "end": 119}, {"text": "alkamide", "start": 137, "end": 145}]}}, "schema": []}
{"input": "Bauer ketone 24 was totally metabolized to more hydrophilic metabolites when administered as a single compound, but was also glucuronidated when present in Echinacea extracts.", "output": {"entities": {"chemical": [{"text": "ketone", "start": 6, "end": 12}]}}, "schema": []}
{"input": "Bauer alkamides 8, 10, and 11 (175-230 micro M) and ethanol extracts of E. sanguinea (1 mg/mL, containing ~ 90 micro M total alkamides) and E. pallida (5 mg/mL, containing 285 micro M total alkamides) decreased the efflux of the P-glycoprotein transporter probe calcein-AM from Caco-2 cells.", "output": {"entities": {"chemical": [{"text": "alkamides", "start": 6, "end": 15}, {"text": "ethanol", "start": 52, "end": 59}, {"text": "alkamides", "start": 125, "end": 134}]}}, "schema": []}
{"input": "These results suggest that other constituents in these Echinacea extracts facilitated the metabolism and efflux of alkamides and ketones, which might improve therapeutic benefits.", "output": {"entities": {"chemical": [{"text": "alkamides", "start": 115, "end": 124}, {"text": "ketones", "start": 129, "end": 136}]}}, "schema": []}
{"input": "Alkamides and Echinacea extracts might be useful in potentiating some chemotherapeutics, which are substrates for the P-glycoprotein transporter.", "output": {"entities": {"chemical": [{"text": "Alkamides", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Concentrations and trends of halogenated flame retardants in the pooled serum of residents of Laizhou Bay, China.", "output": {"entities": {}}, "schema": []}
{"input": "The south coast of Laizhou Bay, in northeastern China, is a production area for halogenated flame retardants (HFR).", "output": {"entities": {}}, "schema": []}
{"input": "In 2007, the authors measured serum concentrations of polybrominated diphenyl ethers (PBDEs) in Laizhou Bay residents.", "output": {"entities": {"chemical": [{"text": "polybrominated diphenyl ethers", "start": 54, "end": 84}, {"text": "PBDEs", "start": 86, "end": 91}]}}, "schema": []}
{"input": "To assess the PBDE concentration trend, and determine the concentrations of the emerging flame retardants Dechlorane Plus (DP) and bis (2-ethylhexyl)-3, 4, 5, 6-tetrabromophthalate (TBPH), the authors measured the concentrations of 8 PBDE congeners, 2 DP isomers, and TBPH in 10 composite samples, which were pooled from the serum collected from 305 Laizhou Bay residents in October 2011.", "output": {"entities": {"chemical": [{"text": "PBDE", "start": 14, "end": 18}, {"text": "Dechlorane Plus", "start": 106, "end": 121}, {"text": "bis (2-ethylhexyl)-3, 4, 5, 6-tetrabromophthalate", "start": 131, "end": 180}, {"text": "TBPH", "start": 182, "end": 186}, {"text": "PBDE", "start": 234, "end": 238}, {"text": "TBPH", "start": 268, "end": 272}]}}, "schema": []}
{"input": "The average concentration of the total PBDE (sum 8 PBDE) concentration in all serum pools was 240 ng/g lipid weight, and the highest serum pool concentration (in the 30-to 39-yr-old male group) was 780 ng/g lipid weight.", "output": {"entities": {"chemical": [{"text": "PBDE", "start": 39, "end": 43}, {"text": "PBDE", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Brominated diphenyl ether-209 was the dominant congener, accounting for 87% of sum 8 PBDE.", "output": {"entities": {"chemical": [{"text": "Brominated diphenyl ether-209", "start": 0, "end": 29}, {"text": "PBDE", "start": 85, "end": 89}]}}, "schema": []}
{"input": "Compared with a previous study, sum 8 PBDE serum concentrations in the present study showed no change in order of magnitude, but the relative contribution of BDE-209 to sum 8 PBDE was higher.", "output": {"entities": {"chemical": [{"text": "PBDE", "start": 38, "end": 42}, {"text": "BDE-209", "start": 158, "end": 165}, {"text": "PBDE", "start": 175, "end": 179}]}}, "schema": []}
{"input": "The average concentration of sum DP in all serum pools was 3. 6 ng/g lipid weight, ranging from 1. 4 ng/g lipid weight (in the 50-to 59-yr-old male group) to 11 ng/g lipid weight (in the 20-to 29-yr-old male group).", "output": {"entities": {}}, "schema": []}
{"input": "The concentration of DP was lower than in other reported studies.", "output": {"entities": {}}, "schema": []}
{"input": "The study also detected TBPH in the 30-to 39-yr-old female group, suggesting that TBPH, as an emerging HFR, requires further monitoring.", "output": {"entities": {"chemical": [{"text": "TBPH", "start": 24, "end": 28}, {"text": "TBPH", "start": 82, "end": 86}]}}, "schema": []}
{"input": "Environ Toxicol Chem 2013; 32: 1242-1247.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and NMR studies of novel chromone-2-carboxamide derivatives.", "output": {"entities": {"chemical": [{"text": "chromone-2-carboxamide", "start": 35, "end": 57}]}}, "schema": []}
{"input": "Chromones are heterocyclic compounds of natural or synthetic origin that possess relevant pharmacological activities.", "output": {"entities": {"chemical": [{"text": "Chromones", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Versatile functionalization of the chromone nucleus allows attaining of a chemical diversity suitable to perform structure-activity relationships in drug discovery and development programs.", "output": {"entities": {"chemical": [{"text": "chromone", "start": 35, "end": 43}]}}, "schema": []}
{"input": "Accordingly, the synthesis and identification of novel chromone carboxamide derivatives with electron-donating and electron-withdrawing substituents in different positions of the exocyclic ring are reported in this work.", "output": {"entities": {"chemical": [{"text": "chromone carboxamide", "start": 55, "end": 75}]}}, "schema": []}
{"input": "Their complete structural characterization was performed using one-dimensional and two-dimensional resonance techniques.", "output": {"entities": {}}, "schema": []}
{"input": "The data acquired are useful for a prompt analysis of related compounds that encompass our integrated medicinal chemistry sketch.", "output": {"entities": {}}, "schema": []}
{"input": "Correlates of bone microarchitectural parameters and serum sclerostin levels in men-the STRAMBO study.", "output": {"entities": {}}, "schema": []}
{"input": "Sclerostin is predominantly expressed by osteocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Serum sclerostin levels are positively correlated with areal bone mineral density (aBMD) measured by DXA and bone microarchitecture assessed by high resolution peripheral quantitative computed tomography (HR-pQCT) in small studies.", "output": {"entities": {}}, "schema": []}
{"input": "We assessed the relation of serum sclerostin levels with aBMD and microarchitectural parameters based on HR-pQCT in 1134 men aged 20-87 years using multivariable models adjusted for confounders (age, body size, lifestyle, co-morbidities, hormones regulating bone metabolism, muscle mass and strength).", "output": {"entities": {}}, "schema": []}
{"input": "The apparent age-related increase in serum sclerostin levels was faster before the age of 63 than afterwards (0. 43SD vs 0. 20SD per decade).", "output": {"entities": {}}, "schema": []}
{"input": "In 446 men aged <= 63, aBMD (spine, hip, whole body), trabecular volumetric BMD (Tb. vBMD) and trabecular number (Tb. N) at the distal radius and tibia were higher in the highest sclerostin quartile vs the three lower quartiles combined.", "output": {"entities": {}}, "schema": []}
{"input": "After adjustment for aBMD, men in the highest sclerostin quartile had higher Tb. vBMD (mainly in the central compartment) and Tb. N at both skeletal sites (p < 0. 05-0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "In 688 men aged > 63, aBMD was positively associated with serum sclerostin levels at all skeletal sites.", "output": {"entities": {}}, "schema": []}
{"input": "Cortical vBMD (Ct. vBMD) and cortical thickness (Ct. Th) were lower in the first sclerostin quartile vs the three higher quartiles combined.", "output": {"entities": {}}, "schema": []}
{"input": "Tb. vBMD increased across the sclerostin quartiles which was associated with lower Tb. N and more heterogeneous trabecular distribution (higher Tb. Sp. SD) in men in the lowest sclerostin quartile.", "output": {"entities": {}}, "schema": []}
{"input": "After adjustment for aBMD, men in the lowest sclerostin quartile had lower Tb. vBMD and Tb. N, but higher Tb. Sp. SD (p < 0. 05-0. 001) at both the skeletal sites.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, serum sclerostin levels in men are strongly positively associated with better bone microarchitectural parameters, mainly trabecular architecture, regardless of the potential confounders.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "MMP driven endochondral fracture union proceeds independently of osteoclast activity.", "output": {"entities": {}}, "schema": []}
{"input": "As new insights into the complexities of endochondral fracture repair emerge, the temporal role of osteoclast activity remains ambiguous.", "output": {"entities": {}}, "schema": []}
{"input": "With numerous anti-resorptive agents available to treat bone disease, understanding their impact on bone repair is vital.", "output": {"entities": {}}, "schema": []}
{"input": "Further, in light of recent work suggesting osteoclast activity may not be necessary during early endochondral fracture union, we hypothesize instead a pivotal role of MMP secreting cells in driving this process.", "output": {"entities": {}}, "schema": []}
{"input": "While the role of MMPs in fracture healing has been examined, no directly comparative experiments exist.", "output": {"entities": {}}, "schema": []}
{"input": "We examined a number of anti-resorptive treatments to either block osteoclast activity, including the potent bisphosphonates zoledronic acid (ZA) and clodronate (CLOD), which work via differing mechanisms, or antagonize osteoclastogenesis with recombinant OPG (HuOPG-Fc), comparing these directly to an inhibitor of matrix metalloproteinase (MMP) activity (MMI270).", "output": {"entities": {"chemical": [{"text": "bisphosphonates zoledronic acid", "start": 109, "end": 140}, {"text": "clodronate", "start": 150, "end": 160}, {"text": "CLOD", "start": 162, "end": 166}]}}, "schema": []}
{"input": "Endochondral ossification to union occurred normally in all anti-resorptive groups.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, MMP inhibition greatly impaired endochondral union, significantly delaying cartilage callus removal.", "output": {"entities": {}}, "schema": []}
{"input": "MMP inhibition also produced smaller, denser hard calluses.", "output": {"entities": {}}, "schema": []}
{"input": "Hard callus remodeling was, as expected, delayed with ZA, CLOD and OPG treatment at 4 and 6 weeks, resulting in larger more mineralized calluses at 6 weeks.", "output": {"entities": {"chemical": [{"text": "CLOD", "start": 58, "end": 62}]}}, "schema": []}
{"input": "As a result of reduced hard callus turnover, bone formation was reduced with anti-resorptive agents at these time points.", "output": {"entities": {}}, "schema": []}
{"input": "These results confirm that the achievement of endochondral fracture union occurs independently of osteoclast activity.", "output": {"entities": {}}, "schema": []}
{"input": "Alternatively, MMP secretion by invading cells is obligatory to endochondral union.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides new insight into cellular contributions to bone repair and may abate concerns regarding anti-resorptive therapies impeding initial fracture union.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: A systematic review and meta-analysis.", "output": {"entities": {"chemical": [{"text": "Bisphosphonates", "start": 0, "end": 15}]}}, "schema": []}
{"input": "While there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that these medications may be associated with rare atypical femoral fractures (AFF).", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 36, "end": 51}]}}, "schema": []}
{"input": "Recent published studies examining this potential association are conflicting in regards to the existence and strength of this association.", "output": {"entities": {}}, "schema": []}
{"input": "We conducted a systematic review and meta-analysis of published studies examining the association of bisphosphonates with subtrochanteric, femoral shaft, and AFF.", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 101, "end": 116}]}}, "schema": []}
{"input": "The random-effects model was used to calculate the pooled estimates of adjusted risk ratios (RR).", "output": {"entities": {}}, "schema": []}
{"input": "Subgroup analysis was performed by study design, for studies that used validated outcome definitions for AFF, and for studies reporting on duration of bisphosphonate use.", "output": {"entities": {"chemical": [{"text": "bisphosphonate", "start": 151, "end": 165}]}}, "schema": []}
{"input": "Eleven studies were included in the meta-analysis: five case-control and six cohort studies.", "output": {"entities": {}}, "schema": []}
{"input": "Bisphosphonate exposure was associated with an increased risk of subtrochanteric, femoral shaft, and AFF with adjusted RR of 1. 70 (95% CI 1. 22-2. 37).", "output": {"entities": {"chemical": [{"text": "Bisphosphonate", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Subgroup analysis of studies using the ASBMR-criteria to define AFF suggests a higher risk of AFF with bisphosphonate use with RR of 11. 78 (95% CI 0. 39-359. 69) as compared to studies using mainly diagnosis codes (RR 1. 62, 95% CI 1. 18-2. 22), although there is a wide confidence interval and severe heterogeneity (I (2) = 96. 15%) in this subgroup analysis.", "output": {"entities": {"chemical": [{"text": "bisphosphonate", "start": 103, "end": 117}]}}, "schema": []}
{"input": "Subgroup analysis of studies examining at least 5 years of bisphosphonate use showed adjusted RR of 1. 62 (95% CI 1. 29-2. 04).", "output": {"entities": {"chemical": [{"text": "bisphosphonate", "start": 59, "end": 73}]}}, "schema": []}
{"input": "This meta-analysis suggests there is an increased risk of subtrochanteric, femoral shaft, and AFF among bisphosphonate users.", "output": {"entities": {"chemical": [{"text": "bisphosphonate", "start": 104, "end": 118}]}}, "schema": []}
{"input": "Further research examining the risk of AFF with long-term use of bisphosphonates is indicated as there was limited data in this subgroup.", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 65, "end": 80}]}}, "schema": []}
{"input": "The public health implication of this observed increase in AFF risk is not clear.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Novel inhibition of archaeal family-D DNA polymerase by uracil.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 56, "end": 62}]}}, "schema": []}
{"input": "Archaeal family-D DNA polymerase is inhibited by the presence of uracil in DNA template strands.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 65, "end": 71}]}}, "schema": []}
{"input": "When the enzyme encounters uracil, following three parameters change: DNA binding increases roughly 2-fold, the rate of polymerization slows by a factor of ~ 5 and 3'-5' proof-reading exonuclease activity is stimulated by a factor of ~ 2.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 27, "end": 33}]}}, "schema": []}
{"input": "Together these changes result in a significant decrease in polymerization activity and a reduction in net DNA synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Pol D appears to interact with template strand uracil irrespective of its distance ahead of the replication fork.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 47, "end": 53}]}}, "schema": []}
{"input": "Polymerization does not stop at a defined location relative to uracil, rather a general decrease in DNA synthesis is observed.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 63, "end": 69}]}}, "schema": []}
{"input": "' Trans' inhibition, the slowing of Pol D by uracil on a DNA strand not being replicated is also observed.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 45, "end": 51}]}}, "schema": []}
{"input": "It is proposed that Pol D is able to interact with uracil by looping out the single-stranded template, allowing simultaneous contact of both the base and the primer-template junction to give a polymerase-DNA complex with diminished extension ability.", "output": {"entities": {"chemical": [{"text": "uracil", "start": 51, "end": 57}]}}, "schema": []}
{"input": "The renin-angiotensin system: new insight into old therapies.", "output": {"entities": {}}, "schema": []}
{"input": "Although the renin-angiotensin system (RAS) is already an old acquaintance, there are often exciting discoveries that improve our knowledge of it and open new therapeutic possibilities.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, well-established drugs, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or beta-blockers, show that their mechanism of action may be the result of parallel pathways other than the ones initially established.", "output": {"entities": {}}, "schema": []}
{"input": "A detailed analysis of the RAS can be carried out in part through the study of the enzymes, named angiotensinases, involved in its cascade, whose activity is a reflection of the functionality of their peptide substrates.", "output": {"entities": {}}, "schema": []}
{"input": "The study of these enzymes offers the possibility of controlling the effects of angiotensins through various pharmacological manipulations.", "output": {"entities": {}}, "schema": []}
{"input": "For example, angiotensinase inhibitors or activators are being used or have been proposed as antihypertensive agents.", "output": {"entities": {}}, "schema": []}
{"input": "They have also been suggested as analgesic and antidepressant drugs or targets for drug development against different pathologies such as Alzheimer' s disease, epilepsy or ischemia.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, the analysis of brain asymmetry has revealed surprising results about the laterality of central and peripheral components of the RAS.", "output": {"entities": {}}, "schema": []}
{"input": "Such studies indicate that the neurovisceral integration, already proposed by Claude Bernard (1867) should also be analyzed from a bilateral perspective.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, the RAS and the role of various angiotensinases implicated in the cascade are revisited.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutic strategies involving some components of the RAS with an unusual vision resulting from a bilateral perspective added to their study are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Myeloid derived suppressor cells and their role in diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitors that can play a major role in tumour development and chronic inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "The importance of the suppressive function ofMDSCs was first suggested by studies involving cancer patients and cancer-bearing mice.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, recent studies have demonstrated that MDSCs can also be involved in many other pathological conditions.", "output": {"entities": {}}, "schema": []}
{"input": "MDSCs have unique ways of abrogatingan immune response in addition to those utilised by other immune-suppressive cell types, for example via the induction of arginase-1 and consequent upregulation in reactive oxygen species (ROS) production.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 209, "end": 215}]}}, "schema": []}
{"input": "Due to their heterogeneity, they further can express a variety of lineage markers, which overlap with other myeloid cell types such as Gr1, CD11b, MHCIIlo, Ly6C and Ly6G, making it difficult to identify them by surface phenotype alone.", "output": {"entities": {}}, "schema": []}
{"input": "The disparity between mouse and human MDSCs further complicates the identification of these elusive cell populations.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we will summarise the recent updates on the methods for eliciting and studying different MDSC subsets, including newly proposed surface phenotypes, as well as insights into how their function is being characterised in both mice and humans.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, exciting new discoveries suggesting their involvement across a number of different pathological settings, such as sepsis, autoimmunity and Leishmaniasis, will be discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Developing FGFR4 inhibitors as potential anti-cancer agents via in silico design, supported by in vitro and cell-based testing.", "output": {"entities": {}}, "schema": []}
{"input": "Fibroblast growth factor receptor-4 (FGFR4) is a tyrosine kinase with a range of important physiological functions.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 49, "end": 57}]}}, "schema": []}
{"input": "However, it is also frequently mutated in various cancers and is now generating significant interest as a potential therapeutic target.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, biochemical characterization of its role in disease, and further evaluation as a drug target is hampered by lack of a specific inhibitor.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to discover new inhibitors for FGFR4 ab initio using a strategy combining in silico, in vitro and cell-based assays.", "output": {"entities": {}}, "schema": []}
{"input": "We used the homologous FGFR1 to calculate docking scores of a chemically-diverse library of approximately 2000 potential kinase inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Nineteen potential inhibitors and ten randomly-selected negative controls were taken forward for in vitro FGFR4 kinase assays.", "output": {"entities": {}}, "schema": []}
{"input": "All compounds with good docking scores significantly inhibited FGFR4 kinase activity, some with sub-micromolar (most potent being V4-015 with an IC (50) of 0. 04 mu M).", "output": {"entities": {"chemical": [{"text": "V4-015", "start": 130, "end": 136}]}}, "schema": []}
{"input": "Four of these compounds also demonstrated substantial activity in cellular assays using the FGFR4-overexpressing breast carcinoma cell line, MDA-MB453.", "output": {"entities": {}}, "schema": []}
{"input": "Through immunoblot assays, these compounds were shown to block the phosphorylation of the FGFR4 adaptor protein, FGFR substrate protein-2 alpha (FRS2 alpha).", "output": {"entities": {}}, "schema": []}
{"input": "The most potent compound to date, V4-015, suppressed proliferation of MDA-MB453 cells at sub-micromolar concentrations, activated the pro-apoptotic caspases 3/7 and inhibited cellular migration.", "output": {"entities": {"chemical": [{"text": "V4-015", "start": 34, "end": 40}]}}, "schema": []}
{"input": "While achieving complete selectivity of this compound for FGFR4 will require further lead optimization, this study has successfully identified new chemical scaffolds with unprecedented FGFR4 inhibition capacities that will support mechanism of action studies and future anti-cancer drug design.", "output": {"entities": {}}, "schema": []}
{"input": "Long-Acting Beta-Agonists and their Association with Inhaled Corticosteroids in COPD.", "output": {"entities": {}}, "schema": []}
{"input": "Inhaled bronchodilators, including beta2-agonists and antimuscaric receptor antagonists, are the mainstay of pharmacotherapy in chronic obstructive pulmonary disease (COPD).", "output": {"entities": {}}, "schema": []}
{"input": "The short-acting beta2-agonists, including salbutamol, and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand.", "output": {"entities": {"chemical": [{"text": "salbutamol", "start": 43, "end": 53}, {"text": "fenoterol", "start": 59, "end": 68}]}}, "schema": []}
{"input": "The longacting beta2-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a twice-daily dosing regimen for long-term COPD treatment.", "output": {"entities": {"chemical": [{"text": "salmeterol", "start": 49, "end": 59}, {"text": "formoterol", "start": 64, "end": 74}]}}, "schema": []}
{"input": "Unlike salmeterol, formoterol has a rapid onset of action.", "output": {"entities": {"chemical": [{"text": "salmeterol", "start": 7, "end": 17}, {"text": "formoterol", "start": 19, "end": 29}]}}, "schema": []}
{"input": "Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta2-adrenoceptors, rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance.", "output": {"entities": {}}, "schema": []}
{"input": "Indacaterol, which has been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily dosing regimen.", "output": {"entities": {"chemical": [{"text": "Indacaterol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development.", "output": {"entities": {"chemical": [{"text": "olodaterol", "start": 29, "end": 39}, {"text": "vilanterol", "start": 41, "end": 51}, {"text": "milveterol", "start": 53, "end": 63}, {"text": "carmoterol", "start": 65, "end": 75}, {"text": "abediterol", "start": 81, "end": 91}]}}, "schema": []}
{"input": "Combination with ICS (fluticasone/salmeterol, budesonide/formoterol, beclomethasone/formoterol) appears to provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often not clinically significant in all the endpoints assessed.", "output": {"entities": {"chemical": [{"text": "fluticasone", "start": 22, "end": 33}, {"text": "salmeterol", "start": 34, "end": 44}, {"text": "budesonide", "start": 46, "end": 56}, {"text": "formoterol", "start": 57, "end": 67}, {"text": "beclomethasone", "start": 69, "end": 83}, {"text": "formoterol", "start": 84, "end": 94}]}}, "schema": []}
{"input": "In patients with COPD, treatment with ICS is associated with increased risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations.", "output": {"entities": {}}, "schema": []}
{"input": "Subphenotyping of patients with COPD (e. g., frequent exacerbations, sputum eosinophilia, mixed asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Ultra-LABA/long-acting muscarinic receptor antagonist (LAMA) combination treatment is under development and is likely to become a standard pharmacological strategy for COPD.", "output": {"entities": {}}, "schema": []}
{"input": "Dual-pharmacology inhaled muscarinic antagonist-beta2 agonist (MABA) molecules provide a new approach to the treatment of COPD.", "output": {"entities": {}}, "schema": []}
{"input": "The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 57, "end": 67}]}}, "schema": []}
{"input": "G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets.", "output": {"entities": {}}, "schema": []}
{"input": "Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential.", "output": {"entities": {}}, "schema": []}
{"input": "One in particular that has been gaining attention in recent times is that of GPCR ligands that bind to allosteric sites on the receptor distinct from the orthosteric site of the endogenous ligand.", "output": {"entities": {}}, "schema": []}
{"input": "As therapeutics, allosteric ligands possess many theoretical advantages over their orthosteric counterparts, including more complex modes of action, improved safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis.", "output": {"entities": {}}, "schema": []}
{"input": "Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge of identifying allosteric leads and their often flat or confusing SAR.", "output": {"entities": {}}, "schema": []}
{"input": "The present review will consider the advantages and challenges associated with allosteric GPCR ligands, and examine how the particular properties of these ligands may be exploited to uncover the therapeutic potential for free fatty acid sensitive GPCRs.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 226, "end": 236}]}}, "schema": []}
{"input": "Dynamics of site switching in DNA polymerase.", "output": {"entities": {}}, "schema": []}
{"input": "DNA polymerases replicate DNA by catalyzing the template-directed polymerization of deoxynucleoside triphosphate (dNTP) substrates onto the 3' end of a growing DNA primer strand.", "output": {"entities": {"chemical": [{"text": "deoxynucleoside triphosphate", "start": 84, "end": 112}, {"text": "dNTP", "start": 114, "end": 118}]}}, "schema": []}
{"input": "Many DNA polymerases also possess a separate 3'-5' exonuclease activity that is used to remove misincorporated nucleotides from the nascent DNA (proofreading).", "output": {"entities": {"chemical": [{"text": "nucleotides", "start": 111, "end": 122}]}}, "schema": []}
{"input": "The polymerase (pol) and exonuclease (exo) activities are spatially separated in different enzyme domains, indicating that a mechanism must exist to transfer the growing primer terminus from one site to the other.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report a single-molecule F o rster resonance energy transfer (smFRET) system that directly monitors the movement of a DNA substrate between the pol and exo sites of DNA polymerase I Klenow fragment (KF).", "output": {"entities": {}}, "schema": []}
{"input": "FRET trajectories recorded during the encounter between single polymerase and DNA molecules reveal that DNA can channel between the pol and exo sites in both directions while remaining closely associated with the enzyme (intramolecular transfer).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, it is evident from the trajectories that DNA can also dissociate from one site and subsequently rebind at the other (intermolecular transfer).", "output": {"entities": {}}, "schema": []}
{"input": "Rate constants for each pathway have been determined by dwell-time analysis, revealing that intramolecular transfer is the faster of the two pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Unexpectedly, a mispaired primer terminus accesses the exo site more frequently when dNTP substrates are also present in solution, which is expected to enhance proofreading.", "output": {"entities": {"chemical": [{"text": "dNTP", "start": 85, "end": 89}]}}, "schema": []}
{"input": "Together, these results explain how the separate pol and exo activities of KF are physically coordinated to achieve efficient proofreading.", "output": {"entities": {}}, "schema": []}
{"input": "Novel HldE-K Inhibitors Leading to Attenuated Gram Negative Bacterial Virulence.", "output": {"entities": {}}, "schema": []}
{"input": "We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains.", "output": {"entities": {}}, "schema": []}
{"input": "One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pump deleted E. coli strains.", "output": {"entities": {}}, "schema": []}
{"input": "This compound did not interfere with E. coli bacterial growth (MIC > 32 mu g/mL) but sensitized this pathogen to hydrophobic antibiotics like macrolides normally inactive on Gram-negative bacteria.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, 86 could sensitize E. coli to serum complement killing.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate that HldE kinase is a suitable target for drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "They also pave the way toward novel possibilities of treating or preventing bloodstream infections caused by pathogenic Gram negative bacteria by inhibiting specific virulence factors.", "output": {"entities": {}}, "schema": []}
{"input": "Compound and compositions as TGR5 agonists: WO2012082947.", "output": {"entities": {}}, "schema": []}
{"input": "The patent application WO2012082947 claims novel compounds as agonists of a plasma membrane-bound bile acid receptor TGR5.", "output": {"entities": {}}, "schema": []}
{"input": "By activating TGR5, the agonists improve glycemic control and enhance energy expenditure.", "output": {"entities": {}}, "schema": []}
{"input": "The basic generic claim of the patent covers pyrazole derivatives, different permutations on the core pyrazole ring are covered in the subsidiary claims.", "output": {"entities": {"chemical": [{"text": "pyrazole", "start": 45, "end": 53}, {"text": "pyrazole", "start": 102, "end": 110}]}}, "schema": []}
{"input": "The claimed compounds are human TGR5 agonists having potency in the nM range.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and structure-activity relationships of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists.", "output": {"entities": {"chemical": [{"text": "indazole arylsulfonamides", "start": 50, "end": 75}]}}, "schema": []}
{"input": "A series of indazole arylsulfonamides were synthesized and examined as human CCR4 antagonists.", "output": {"entities": {"chemical": [{"text": "indazole arylsulfonamides", "start": 12, "end": 37}]}}, "schema": []}
{"input": "Methoxy-or hydroxyl-containing groups were the more potent indazole C4 substituents.", "output": {"entities": {"chemical": [{"text": "Methoxy", "start": 0, "end": 7}, {"text": "hydroxyl", "start": 11, "end": 19}, {"text": "indazole", "start": 59, "end": 67}]}}, "schema": []}
{"input": "Only small groups were tolerated at C5, C6, or C7, with the C6 analogues being preferred.", "output": {"entities": {}}, "schema": []}
{"input": "The most potent N3-substituent was 5-chlorothiophene-2-sulfonamide.", "output": {"entities": {"chemical": [{"text": "5-chlorothiophene-2-sulfonamide", "start": 35, "end": 66}]}}, "schema": []}
{"input": "N1 meta-substituted benzyl groups possessing an alpha-amino-3-[(methylamino) acyl]-group were the most potent N1-substituents.", "output": {"entities": {"chemical": [{"text": "benzyl", "start": 20, "end": 26}, {"text": "3-[(methylamino) acyl]", "start": 60, "end": 82}]}}, "schema": []}
{"input": "Strongly basic amino groups had low oral absorption in vivo.", "output": {"entities": {"chemical": [{"text": "amino", "start": 15, "end": 20}]}}, "schema": []}
{"input": "Less basic analogues, such as morpholines, had good oral absorption; however, they also had high clearance.", "output": {"entities": {"chemical": [{"text": "morpholines", "start": 30, "end": 41}]}}, "schema": []}
{"input": "The most potent compound with high absorption in two species was analogue 6 (GSK2239633A), which was selected for further development.", "output": {"entities": {"chemical": [{"text": "GSK2239633A", "start": 77, "end": 88}]}}, "schema": []}
{"input": "Aryl sulfonamide antagonists bind to CCR4 at an intracellular allosteric site denoted site II.", "output": {"entities": {"chemical": [{"text": "Aryl sulfonamide", "start": 0, "end": 16}]}}, "schema": []}
{"input": "X-ray diffraction studies on two indazole sulfonamide fragments suggested the presence of an important intramolecular interaction in the active conformation.", "output": {"entities": {"chemical": [{"text": "indazole sulfonamide", "start": 33, "end": 53}]}}, "schema": []}
{"input": "Structure-based discovery of pyrazolobenzothiazine derivatives as inhibitors of hepatitis C virus replication.", "output": {"entities": {"chemical": [{"text": "pyrazolobenzothiazine", "start": 29, "end": 50}]}}, "schema": []}
{"input": "The NS5B RNA-dependent RNA polymerase is an attractive target for the development of novel and selective inhibitors of hepatitis C virus replication.", "output": {"entities": {}}, "schema": []}
{"input": "To identify novel structural hits as anti-HCV agents, we performed structure-based virtual screening of our in-house library followed by rational drug design, organic synthesis, and biological testing.", "output": {"entities": {}}, "schema": []}
{"input": "These studies led to the identification of pyrazolobenzothiazine scaffold as a suitable template for obtaining novel anti-HCV agents targeting the NS5B polymerase.", "output": {"entities": {"chemical": [{"text": "pyrazolobenzothiazine", "start": 43, "end": 64}]}}, "schema": []}
{"input": "The best compound of this series was the meta-fluoro-N-1-phenyl pyrazolobenzothiazine derivative 4a, which exhibited an EC50 = 3. 6 mu M, EC90 = 25. 6 mu M, and CC50 > 180 mu M in the Huh 9-13 replicon system, thus providing a good starting point for further hit evolution.", "output": {"entities": {"chemical": [{"text": "meta-fluoro-N-1-phenyl pyrazolobenzothiazine", "start": 41, "end": 85}]}}, "schema": []}
{"input": "Acute arsenic treatment alters cytochrome P450 expression and arachidonic acid metabolism in lung, liver and kidney of C57Bl/6 mice.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 6, "end": 13}, {"text": "arachidonic acid", "start": 62, "end": 78}]}}, "schema": []}
{"input": "Abstract 1. Arsenic (As (III)) toxicity has received increasing attention as human exposure to arsenic is associated with pulmonary, hepatic and renal toxicities.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 12, "end": 19}, {"text": "As (III)", "start": 21, "end": 29}, {"text": "arsenic", "start": 95, "end": 102}]}}, "schema": []}
{"input": "Therefore, in the present study, we investigated the effect of acute As (III) treatment on pulmonary, hepatic and renal cytochrome (CYP) P450-mediated arachidonic acid metabolism.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 69, "end": 77}, {"text": "arachidonic acid", "start": 151, "end": 167}]}}, "schema": []}
{"input": "2. Our results demonstrated that acute As (III) treatment (12. 5 mg/kg) altered CYP epoxygenases, CYP omega-hydroxylases and EPHX2 mRNA levels that were isozyme and tissue specific.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 39, "end": 47}]}}, "schema": []}
{"input": "3. Furthermore, As (III) increased the formation of epoxyeicosatrienoic acids (EETs) in the kidney without affecting their levels in the lung or liver.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 16, "end": 24}, {"text": "epoxyeicosatrienoic acids", "start": 52, "end": 77}, {"text": "EETs", "start": 79, "end": 83}]}}, "schema": []}
{"input": "In addition, acute As (III) treatment increased dihydroxyeicosatrienoic acid (DHETs) formation in the lung, while it did not affect liver DHETs formation and decreased kidney DHETs formation.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 19, "end": 27}, {"text": "dihydroxyeicosatrienoic acid", "start": 48, "end": 76}, {"text": "DHETs", "start": 78, "end": 83}, {"text": "DHETs", "start": 138, "end": 143}, {"text": "DHETs", "start": 175, "end": 180}]}}, "schema": []}
{"input": "4. As (III) also increased total epoxygenases activity in the lung while it decreased its levels in the kidney and had no effect on the liver.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 3, "end": 11}]}}, "schema": []}
{"input": "Furthermore, As (III) increased 20-hydroxyeicosatetraenoic acid formation in the liver while it decreased its formation in the kidney.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 13, "end": 21}, {"text": "20-hydroxyeicosatetraenoic acid", "start": 32, "end": 63}]}}, "schema": []}
{"input": "5. Lastly, As (III) increased soluble epoxide hydrolase activity in the lung, while it decreased its levels in the kidney and had no effect on the liver.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 11, "end": 19}, {"text": "epoxide", "start": 38, "end": 45}]}}, "schema": []}
{"input": "In conclusion, this is the first demonstration that As (III) alters arachidonic acid metabolism in a tissue specific manner.", "output": {"entities": {"chemical": [{"text": "As (III)", "start": 52, "end": 60}, {"text": "arachidonic acid", "start": 68, "end": 84}]}}, "schema": []}
{"input": "Protein recognition of the S23906-1-DNA adduct by nuclear proteins: direct involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 1.", "output": {"entities": {"chemical": [{"text": "S23906-1", "start": 27, "end": 35}, {"text": "glyceraldehyde-3-phosphate", "start": 90, "end": 116}]}}, "schema": []}
{"input": "In a view to develop new DNA alkylating antitumour drugs, evaluating the precise mechanism of action and the molecular/cellular consequences of the alkylation is a point of major interest.", "output": {"entities": {}}, "schema": []}
{"input": "The benzo-b-acronycine derivative S23906-1 alkylates guanine nucleobases in the minor groove of the DNA helix and presents an original ability to locally open the double helix of DNA, which appears to be associated with its cytotoxic activity.", "output": {"entities": {"chemical": [{"text": "benzo-b-acronycine", "start": 4, "end": 22}, {"text": "S23906-1", "start": 34, "end": 42}, {"text": "guanine nucleobases", "start": 53, "end": 72}]}}, "schema": []}
{"input": "However, the molecular mechanism linking adduct formation to cellular consequences is not precisely known.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of the present study was to identify proteins involved in the recognition and mechanism of action of S23906-DNA adducts.", "output": {"entities": {"chemical": [{"text": "S23906", "start": 115, "end": 121}]}}, "schema": []}
{"input": "We found that GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is a protein that binds to S23906-alkylated single-stranded, double-stranded and telomeric sequences in a drug-dependent and DNA sequence/structure-dependent manner.", "output": {"entities": {"chemical": [{"text": "glyceraldehyde-3-phosphate", "start": 21, "end": 47}, {"text": "S23906", "start": 90, "end": 96}]}}, "schema": []}
{"input": "We used the CASTing (cyclic amplification of sequence targeting) method to identify GAPDH DNA-binding selectivity and then evaluated its binding to such selected S23906-alkylated sequences.", "output": {"entities": {"chemical": [{"text": "S23906", "start": 162, "end": 168}]}}, "schema": []}
{"input": "At the cellular level, alkylation of S23906-1 results in an increase in the binding of GAPDH and its protein partner HMG (high-mobility group) B1 to the chromatin.", "output": {"entities": {"chemical": [{"text": "S23906-1", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Regarding the multiple roles of GAPDH in apoptosis and DNA repair, the cytotoxic and apoptotic activities of GAPDH were evaluated and present opposite effects in two different cellular models.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and cancer stem cell-based activity of substituted 5-morpholino-7H-thieno [3, 2-b] pyran-7-ones designed as next generation PI3K inhibitors.", "output": {"entities": {"chemical": [{"text": "5-morpholino-7H-thieno [3, 2-b] pyran-7-ones", "start": 61, "end": 105}]}}, "schema": []}
{"input": "Dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway in a wide range of tumors has made PI3K a consensus target to inhibit as illustrated by more than 15 inhibitors now in clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only PI3K vascular-targeted PI3K inhibitor prodrug, SF1126, which has now completed Phase I clinical trials.", "output": {"entities": {"chemical": [{"text": "LY294002", "start": 71, "end": 79}, {"text": "SF1126", "start": 149, "end": 155}]}}, "schema": []}
{"input": "This inhibitor has properties that impart more in vivo activity than should be warranted by its enzymatic potency, which in general is much lower than other clinical stage PI3K inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "We embarked on the exploration of scaffolds that retained such properties while simultaneously exhibiting an increased potency toward PI3K.", "output": {"entities": {}}, "schema": []}
{"input": "This work resulted in the discovery of the 5-morpholino-7H-thieno [3, 2-b] pyran-7-one system as the foundation of a new compound class of potential PI3K inhibitors having improved potency toward PI3K.", "output": {"entities": {"chemical": [{"text": "5-morpholino-7H-thieno [3, 2-b] pyran-7-one", "start": 43, "end": 86}]}}, "schema": []}
{"input": "The synthesis and cancer stem cell-based activity of these compounds are reported herein.", "output": {"entities": {}}, "schema": []}
{"input": "Injectable superparamagnets: highly elastic and degradable poly (N-isopropylacrylamide)-superparamagnetic iron oxide nanoparticle (SPION) composite hydrogels.", "output": {"entities": {"chemical": [{"text": "poly (N-isopropylacrylamide)", "start": 59, "end": 87}, {"text": "iron oxide", "start": 106, "end": 116}]}}, "schema": []}
{"input": "Injectable, in situ-gelling magnetic composite materials have been fabricated by using aldehyde-functionalized dextran to cross-link superparamagnetic nanoparticles surface-functionalized with hydrazide-functionalized poly (N-isopropylacrylamide) (pNIPAM).", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 87, "end": 95}, {"text": "hydrazide", "start": 193, "end": 202}, {"text": "poly (N-isopropylacrylamide)", "start": 218, "end": 246}, {"text": "pNIPAM", "start": 248, "end": 254}]}}, "schema": []}
{"input": "The resulting composites exhibit high water contents (82-88 wt.%) while also displaying significantly higher elasticities (G' > 60 kPa) than other injectable hydrogels previously reported.", "output": {"entities": {}}, "schema": []}
{"input": "The composites hydrolytically degrade via slow hydrolysis of the hydrazone cross-link at physiological temperature and pH into degradation products that show no significant cytotoxicity.", "output": {"entities": {"chemical": [{"text": "hydrazone", "start": 65, "end": 74}]}}, "schema": []}
{"input": "Subcutaneous injections indicate only minor chronic inflammation associated with material degradation, with no fibrous capsule formation evident.", "output": {"entities": {}}, "schema": []}
{"input": "Drug release experiments indicate the potential of these materials to facilitate pulsatile, \" on-demand \" changes in drug release upon the application of an external oscillating magnetic field.", "output": {"entities": {}}, "schema": []}
{"input": "The injectable but high-strength and externally triggerable nature of these materials, coupled with their biological degradability and inertness, suggest potential biological applications in tissue engineering and drug delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of Novel Drug Targets in HpB38, HpP12, HpG27, Hpshi470, HpSJM180 Strains of Helicobacter pylori: An In Silico Approach for Therapeutic Intervention.", "output": {"entities": {}}, "schema": []}
{"input": "Helicobacter species colonizes the stomach and are associated with the development of gastritis disease.", "output": {"entities": {}}, "schema": []}
{"input": "Drugs for treatment of Helicobacter infection relieve pain or gastritis symptoms but they are not targeted specifically to Helicobacter pylori.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, there is dire need for discovery of new drug targets and drugs for the treatment of H. pylori.", "output": {"entities": {}}, "schema": []}
{"input": "The main objective of this study is to screen the potential drug targets by in silico analysis for the potent strains of H. pylori which include HpB38, HpP12, HpG27, Hpshi470 and HpSJM180.", "output": {"entities": {}}, "schema": []}
{"input": "Genome and metabolic pathways of pathogen H. pylori and the host Homosapien sapiens are compared and genes which were unique to H. pylori were filtered and catalogued.", "output": {"entities": {}}, "schema": []}
{"input": "These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets.", "output": {"entities": {}}, "schema": []}
{"input": "Among the total number of genes analysed in different strains of H. pylori nearly 558, 569, 539, 569, 567 number of genes in HpB38, HpP12, HpG27, Hpshi470 and HpSJM180 found qualified as unique molecules and among them 17 qualified as potential drug targets.", "output": {"entities": {}}, "schema": []}
{"input": "Membrane fusion protein of hefABC efflux system, 50 S ribosomal protein L33, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X, Apolipoprotein N acyl transferase, DNA methyalse, Histone like binding protein, Peptidoglycan-associated lipoprotein OprL were found to be critical drug targets to H. pylori.", "output": {"entities": {"chemical": [{"text": "N acyl", "start": 178, "end": 184}]}}, "schema": []}
{"input": "Three (hefABC efflux system, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X) of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach.", "output": {"entities": {}}, "schema": []}
{"input": "Profiling the structural determinants of heteroarylnitrile scaffold-based derivatives as falcipain-2 inhibitors by in silico methods.", "output": {"entities": {"chemical": [{"text": "heteroarylnitrile", "start": 41, "end": 58}]}}, "schema": []}
{"input": "Evidence indicates that cysteine protease falcipain-2 plays essential role in malaria parasites; therefore the potent and selective inhibitors of falcipain-2 may be therapeutically useful drugs for treatment of various forms of malaria parasite plasmodium.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 24, "end": 32}]}}, "schema": []}
{"input": "In order to understand the structure-activity correlation of falcipain-2 inhibitors, a set of ligand-and receptor-based 3D-QSAR models were, for the first time, developed in the present work employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) for 240 promising molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the ligand-based alignment, an optimal 3D-QSAR model was obtained with good predictive power of Q (2) = 0. 501, R (2) ncv = 0. 890, SEE = 0. 282, F = 153. 522 and R (2) pred = 0. 768.", "output": {"entities": {}}, "schema": []}
{"input": "And the contour maps intuitively suggest where to modify the molecular structures in order to improve the binding affinity.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, docking analysis and molecular dynamics simulation (MD) study were also carried out on the dataset with purpose of exploring the detailed binding modes of ligand in the falcipain-2 binding pocket.", "output": {"entities": {}}, "schema": []}
{"input": "The combination of docking analysis and MD simulation shows that Gly83, Trp43 and Ala175 which formed several H-bonds are crucial for falcipain-2 inhibitors.", "output": {"entities": {"chemical": [{"text": "Gly83", "start": 65, "end": 70}, {"text": "Trp43", "start": 72, "end": 77}, {"text": "Ala175", "start": 82, "end": 88}, {"text": "H", "start": 110, "end": 111}]}}, "schema": []}
{"input": "The analysis of the best QSAR model reveals the structural features related to the activity, and provides an insight into molecular mechanisms of inhibition and possible modification of the molecules for better activity.", "output": {"entities": {}}, "schema": []}
{"input": "Multitarget drugs of plants origin acting on Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "The etiopathology of Alzheimer' s disease (AD) is extremely complex and heterogeneous, often associated with comorbidities.", "output": {"entities": {}}, "schema": []}
{"input": "As a result it may be unlikely that AD may be mitigated by drug acting on a single specific target.", "output": {"entities": {}}, "schema": []}
{"input": "The current tendency in drug design and discovery in AD is the rational design or \" serendipitous \" discovery of new drug entities challenging multiple targets.", "output": {"entities": {}}, "schema": []}
{"input": "Since two of the presently approved drugs for AD are based on natural products (galantamine and the physostigmine-derivative rivastigmine), many plants are now under investigation as a potential source of new drugs.", "output": {"entities": {"chemical": [{"text": "galantamine", "start": 80, "end": 91}, {"text": "physostigmine", "start": 100, "end": 113}, {"text": "rivastigmine", "start": 125, "end": 137}]}}, "schema": []}
{"input": "Multifunctional drugs often have their origin in natural sources.", "output": {"entities": {}}, "schema": []}
{"input": "This review is limited to plant chemicals having different targets with actual (galantamine) or promising (drugs from Crocus sativus, Ginkgo biloba, Salvia species, and Huperzia serrata) clinical evidence in people with dementia or AD.", "output": {"entities": {"chemical": [{"text": "galantamine", "start": 80, "end": 91}]}}, "schema": []}
{"input": "Hedgehog Signaling in Medullary Thyroid Carcinoma: A Novel Signaling Pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Background: Locally or widely metastatic medullary thyroid carcinoma (MTC) is difficult to treat and therapeutic options are limited.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, kinase inhibitors have shown partial efficacy in this cancer, but there is a continued need for the development of novel therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Within this context, the Hedgehog (Hh) pathway has been implicated in several types of human tumors, and early clinical trials with Hh antagonists have validated Hh as a novel therapeutic target.", "output": {"entities": {}}, "schema": []}
{"input": "For the first time, we evaluated Hh pathway activity in MTC and examined the effect of Hh pathway perturbation in highly characterized MTC cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Methods: We examined immunohistochemical expression of Hh signaling mediators Sonic Hedgehog (Shh) and Glioblastoma (Gli) 2 in paraffin-embedded normal versus histologically characterized human MTC tissue.", "output": {"entities": {}}, "schema": []}
{"input": "We examined pharmacologic disruption of Hh signaling in vitro using two established MTC cell lines (TT and MZ-CRC-1).", "output": {"entities": {}}, "schema": []}
{"input": "Hh signaling was either pharmacologically activated (SAG) or inhibited (GDC-0449) in MTC cell lines; Hh activity was assessed by qRT-PCR, Western blot analysis, and quantification of cellular growth and apoptotic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Results: Our data showed increased expression of Hh signaling factors in human MTC compared to normal tissue.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro, activation of the Hh pathway resulted in increased expression of key Hh signaling components Smoothened (Smo) and Gli2.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, inhibition of the Hh pathway decreased expression of these genes, leading to significantly reduced cellular growth and increased apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: Hedgehog signaling components are markedly upregulated in MTC.", "output": {"entities": {}}, "schema": []}
{"input": "Hh pathway inhibitors have potential as novel therapeutic options in patients with metastatic and/or surgically unresectable MTC.", "output": {"entities": {}}, "schema": []}
{"input": "High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Dynamic epigenetic reprogramming occurs during mammalian germ cell development, although the targets of this process, including DNA demethylation and de novo methylation, remain poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "We performed genome-wide DNA methylation analysis in male and female mouse primordial germ cells at embryonic days 10. 5, 13. 5, and 16. 5 by whole-genome shotgun bisulfite sequencing.", "output": {"entities": {"chemical": [{"text": "bisulfite", "start": 163, "end": 172}]}}, "schema": []}
{"input": "Our high-resolution DNA methylome maps demonstrated gender-specific differences in CpG methylation at genome-wide and gene-specific levels during fetal germline progression.", "output": {"entities": {"chemical": [{"text": "CpG", "start": 83, "end": 86}]}}, "schema": []}
{"input": "There was extensive intra-and intergenic hypomethylation with erasure of methylation marks at imprinted, X-linked, or germline-specific genes during gonadal sex determination and partial methylation at particular retrotransposons.", "output": {"entities": {}}, "schema": []}
{"input": "Following global demethylation and sex determination, CpG sites switched to de novo methylation in males, but the X-linked genes appeared resistant to the wave of de novo methylation.", "output": {"entities": {"chemical": [{"text": "CpG", "start": 54, "end": 57}]}}, "schema": []}
{"input": "Significant differential methylation at a subset of imprinted loci was identified in both genders, and non-CpG methylation occurred only in male gonocytes.", "output": {"entities": {"chemical": [{"text": "CpG", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Our data establish the basis for future studies on the role of epigenetic modifications in germline development and other biological processes.", "output": {"entities": {}}, "schema": []}
{"input": "Aspulvinones from a mangrove rhizosphere soil-derived fungus Aspergillus terreus Gwq-48 with anti-influenza A viral (H1N1) activity.", "output": {"entities": {"chemical": [{"text": "Aspulvinones", "start": 0, "end": 12}]}}, "schema": []}
{"input": "A new butenolide isoaspulvinone E (1), together with two known butenolides aspulvinone E (2) and pulvic acid (3) were isolated from the marine-derived fungus, Aspergillus terreus Gwq-48.", "output": {"entities": {"chemical": [{"text": "butenolide isoaspulvinone E", "start": 6, "end": 33}, {"text": "butenolides aspulvinone E", "start": 63, "end": 88}, {"text": "pulvic acid", "start": 97, "end": 108}]}}, "schema": []}
{"input": "They showed significant anti-influenza A H1N1 virus activities, with IC50 values of 32. 3, 56. 9, and 29. 1 mu g/mL, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, only compound 1 exhibited effective inhibitory activity against H1N1 viral neuraminidase (NA), and docking of two isomers (1-2) into the active sites of NA showed that the E double bond Delta (5 (10)) was essential to achieve activity.", "output": {"entities": {}}, "schema": []}
{"input": "A novel fluorogenic substrate for dinuclear Zn (II)-containing metallo-beta-lactamases.", "output": {"entities": {"chemical": [{"text": "Zn (II)", "start": 44, "end": 51}]}}, "schema": []}
{"input": "In an effort to prepare a fluorogenic substrate to be used in activity assays with metallo-beta-lactamases, (6R, 7R)-8-oxo-7-(2-oxo-2H-chromene-3-carboxamido)-3-((4-(2-oxo-2H-chromene-3-carboxamido)-phenylthio) methyl)-5-thia-1-azabicyclo [4. 2. 0] oct-2-ene-2-carboxylic acid (CA) was synthesized and characterized.", "output": {"entities": {"chemical": [{"text": "(6R, 7R)-8-oxo-7-(2-oxo-2H-chromene-3-carboxamido)-3-((4-(2-oxo-2H-chromene-3-carboxamido)-phenylthio) methyl)-5-thia-1-azabicyclo [4. 2. 0] oct-2-ene-2-carboxylic acid", "start": 108, "end": 276}]}}, "schema": []}
{"input": "CA exhibited a fluorescence quantum yield (phi) of 0. 0059, two fluorescence lifetimes of 3. 63 x 10 (-10) and 5. 38 x 10 (-9) s, and fluorescence intensity that is concentration-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Steady-state kinetic assays revealed that CA is a substrate for metallo-beta-lactamases (M beta Ls) L1 and CcrA, exhibiting Km and kcat values of 18 mu M and 5s (-1) and 11 mu M and 17s (-1), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and physicochemical properties of new tripodal amphiphiles bearing fatty acids as a hydrophobic group.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 77, "end": 88}]}}, "schema": []}
{"input": "Saturated fatty acids (FA) were grafted using tyrosine as a spacer group to the cyclotriphosphazene ring along with equimolar hydrophilic methoxy poly (ethylene glycol) (MPEG) in cis-nongeminal way.", "output": {"entities": {"chemical": [{"text": "Saturated fatty acids", "start": 0, "end": 21}, {"text": "tyrosine", "start": 46, "end": 54}, {"text": "cyclotriphosphazene", "start": 80, "end": 99}, {"text": "methoxy poly (ethylene glycol)", "start": 138, "end": 168}, {"text": "MPEG", "start": 170, "end": 174}]}}, "schema": []}
{"input": "Seven new cyclotriphosphazene amphiphiles were prepared from combinations of hydrophilic MPEGs with different molecular weights of 350, 550, 750 and 1000 and four different fatty acids of different hydrophobicity including lauric, myristic, palmitic and stearic acids.", "output": {"entities": {"chemical": [{"text": "cyclotriphosphazene", "start": 10, "end": 29}, {"text": "MPEGs", "start": 89, "end": 94}, {"text": "fatty acids", "start": 173, "end": 184}, {"text": "lauric, myristic, palmitic and stearic acids", "start": 223, "end": 267}]}}, "schema": []}
{"input": "These steric amphiphiles bearing fatty acids as a hydrophobic group were found to form more stable micelles with very low critical micelle concentrations (CMC) (2. 95-7. 80mg/L) compared with oligopeptide analogues, and their highly hydrophobic core environment is unique and potentially useful for various biomedical applications.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 33, "end": 44}]}}, "schema": []}
{"input": "Electrochemical determination of Sudan I in food samples at graphene modified glassy carbon electrode based on the enhancement effect of sodium dodecyl sulphonate.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 33, "end": 40}, {"text": "graphene", "start": 60, "end": 68}, {"text": "carbon", "start": 85, "end": 91}, {"text": "sodium dodecyl sulphonate", "start": 137, "end": 162}]}}, "schema": []}
{"input": "This paper describes a novel electrochemical method for the determination of Sudan I in food samples based on the electrochemical catalytic activity of graphene modified glassy carbon electrode (GMGCE) and the enhancement effect of an anionic surfactant: sodium dodecyl sulphonate (SDS).", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 77, "end": 84}, {"text": "graphene", "start": 152, "end": 160}, {"text": "carbon", "start": 177, "end": 183}, {"text": "sodium dodecyl sulphonate", "start": 255, "end": 280}, {"text": "SDS", "start": 282, "end": 285}]}}, "schema": []}
{"input": "Using pH 6. 0 phosphate buffer solution (PBS) as supporting electrolyte and in the presence of 1. 5 x 10 (-4) mol L (-1) SDS, Sudan I yielded a well-defined and sensitive oxidation peak at a GMGCE.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 14, "end": 23}, {"text": "SDS", "start": 121, "end": 124}, {"text": "Sudan I", "start": 126, "end": 133}]}}, "schema": []}
{"input": "The oxidation peak current of Sudan I remarkably increased in the presence of SDS.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 30, "end": 37}, {"text": "SDS", "start": 78, "end": 81}]}}, "schema": []}
{"input": "The experimental parameters, such as supporting electrolyte, concentration of SDS, and accumulation time, were optimised for Sudan I determination.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 78, "end": 81}, {"text": "Sudan I", "start": 125, "end": 132}]}}, "schema": []}
{"input": "The oxidation peak current showed a linear relationship with the concentrations of Sudan I in the range of 7. 50 x 10 (-8)-7. 50 x 10 (-6) mol L (-1), with the detection limit of 4. 0 x 10 (-8) mol L (-1).", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 83, "end": 90}]}}, "schema": []}
{"input": "This new voltammetric method was successfully used to determine Sudan I in food products such as ketchup and chili sauce with satisfactory results.", "output": {"entities": {"chemical": [{"text": "Sudan I", "start": 64, "end": 71}]}}, "schema": []}
{"input": "Pterostilbene inhibits dimethylnitrosamine-induced liver fibrosis in rats.", "output": {"entities": {"chemical": [{"text": "Pterostilbene", "start": 0, "end": 13}, {"text": "dimethylnitrosamine", "start": 23, "end": 42}]}}, "schema": []}
{"input": "Pterostilbene, found in grapes and berries, exhibits pleiotropic effects, including anti-inflammatory, antioxidant, and anti-proliferative activities.", "output": {"entities": {"chemical": [{"text": "Pterostilbene", "start": 0, "end": 13}]}}, "schema": []}
{"input": "This study was conducted to investigate the effect of pterostilbene on liver fibrosis and the potential underlying mechanism for such effect.", "output": {"entities": {"chemical": [{"text": "pterostilbene", "start": 54, "end": 67}]}}, "schema": []}
{"input": "Sprague-Dawley rats were intraperitoneally given dimethyl n-nitrosamine (DMN) (10mg/kg) 3 days per week for 4 weeks.", "output": {"entities": {"chemical": [{"text": "dimethyl n-nitrosamine", "start": 49, "end": 71}, {"text": "DMN", "start": 73, "end": 76}]}}, "schema": []}
{"input": "Pterostilbene (10 or 20mg/kg) was administered by oral gavage daily.", "output": {"entities": {"chemical": [{"text": "Pterostilbene", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Liver function, morphology, histochemistry, and fibrotic parameters were examined.", "output": {"entities": {}}, "schema": []}
{"input": "Pterostilbene supplementation alleviated the DMN-induced changes in the serum levels of alanine transaminase and aspartate transaminase (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "Pterostilbene", "start": 0, "end": 13}, {"text": "DMN", "start": 45, "end": 48}]}}, "schema": []}
{"input": "Fibrotic status and the activation of hepatic stellate cells were improved upon pterostilbene supplementation as evidenced by histopathological examination as well as the expression of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta 1 (TGF-beta 1), and matrix metalloproteinase 2 (MMP2).", "output": {"entities": {"chemical": [{"text": "pterostilbene", "start": 80, "end": 93}]}}, "schema": []}
{"input": "These data demonstrated that pterostilbene exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-beta 1/Smad signaling.", "output": {"entities": {"chemical": [{"text": "pterostilbene", "start": 29, "end": 42}]}}, "schema": []}
{"input": "Thermal-induced changes of kale' s antioxidant activity analyzed by HPLC-UV/Vis-online-TEAC detection.", "output": {"entities": {}}, "schema": []}
{"input": "Generally, boiling of vegetables is assumed leading to lower nutritional values because of leaching effects and activity loss of bioactive compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Kale (Brassica oleracea var. sabellica) reveals a great diversity of flavonoids, which have been shown to be good antioxidants.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 69, "end": 79}]}}, "schema": []}
{"input": "As Brassica vegetables are mainly consumed cooked, the influence of boiling on kale' s flavonoids and their antioxidant activity was investigated.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 87, "end": 97}]}}, "schema": []}
{"input": "Therefore, three kale cultivars were cooked at 100 degrees C for 2 and 4h prior to analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The total phenolic content (TPC) and the total antioxidant activity (TEAC assay and EPR spectrometry) of each cultivar were determined and revealed no change, independent of cooking time, although kale samples visually altered.", "output": {"entities": {}}, "schema": []}
{"input": "Using the HPLC-UV/Vis-online-TEAC approach, distinct changes in composition and antioxidant activity of the flavonoids were detectable.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 108, "end": 118}]}}, "schema": []}
{"input": "Thus, it was observable, that the antioxidant activities of the reaction products compensated the \" loss \" of the antioxidant activity of the original compounds of the uncooked material.", "output": {"entities": {}}, "schema": []}
{"input": "Dispersive liquid-liquid microextraction combined with field-amplified sample stacking in capillary electrophoresis for the determination of non-steroidal anti-inflammatory drugs in milk and dairy products.", "output": {"entities": {"chemical": [{"text": "steroidal", "start": 145, "end": 154}]}}, "schema": []}
{"input": "Dispersive liquid-liquid microextraction (DLLME) was coupled with field-amplified sample stacking in capillary electrophoresis (FASS) for the determination of five non-steroidal anti-inflammatory drugs (NSAIDs) in bovine milk and dairy products.", "output": {"entities": {"chemical": [{"text": "steroidal", "start": 168, "end": 177}]}}, "schema": []}
{"input": "After extraction, the enriched analytes were back-extracted into a basic aqueous solution for injection into CE.", "output": {"entities": {}}, "schema": []}
{"input": "Under optimum conditions, enrichment factors were in the range 46-229.", "output": {"entities": {}}, "schema": []}
{"input": "Limits of detection of the analytes ranged from 3. 0 to 13. 1 mu g kg (-1) for all matrices analysed.", "output": {"entities": {}}, "schema": []}
{"input": "Calibration graphs showed good linearity with coefficients of determination (R (2)) >= 0. 9915 and relative standard deviations (RSD%) of the analyses in the range of 0. 6-6. 2% (n = 5).", "output": {"entities": {}}, "schema": []}
{"input": "Recoveries of all NSAIDs from bottled milk, raw milk, yogurt and white cheese samples were in the ranges of 86. 6-109. 3%, 84. 3-100. 5%, 77. 4-107. 3%, and 90. 9-101. 6%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "DLLME-FASS-CE was demonstrated to be a rapid and convenient method for the determination of NSAIDs in milk and dairy products.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activities of the synthesized thiol-contained peptides derived from computer-aided pepsin hydrolysis of yam tuber storage protein, dioscorin.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 42, "end": 47}, {"text": "dioscorin", "start": 143, "end": 152}]}}, "schema": []}
{"input": "Our previous report showed that yam dioscorin and its peptic hydrolysates exhibit radical scavenging activities; however, the functions of these peptic hydrolases are still under investigation.", "output": {"entities": {"chemical": [{"text": "dioscorin", "start": 36, "end": 45}]}}, "schema": []}
{"input": "In this study, the thiol-containing peptides derived from computer-aided simulation of pepsin hydrolysis of dioscorin, namely, KTCGNGME (diotide1), PPCSE (diotide2), CDDRVIRTPLT (diotide3), KTCGY (diotide4), and PPCTE (diotide5) were synthesized to compare their antioxidant activities with GSH and/or carnosine by examining hydroxyl radical scavenging activity by electron spin resonance spectrometry, anti-low-density lipoprotein peroxidation, anti-AAPH-induced hemolysis, and oxygen radical absorbance capacity activity.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 19, "end": 24}, {"text": "dioscorin", "start": 108, "end": 117}, {"text": "GSH", "start": 291, "end": 294}, {"text": "carnosine", "start": 302, "end": 311}, {"text": "hydroxyl", "start": 325, "end": 333}, {"text": "AAPH", "start": 451, "end": 455}, {"text": "oxygen", "start": 479, "end": 485}]}}, "schema": []}
{"input": "We found that while all the synthesized diotides showed antioxidant activity, diotide4 exhibited the highest levels.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, all diotides (100 mu M) showed protective effects against methylglyoxal-induced human umbilical vein endothelial cell death.", "output": {"entities": {"chemical": [{"text": "methylglyoxal", "start": 68, "end": 81}]}}, "schema": []}
{"input": "These results suggest that thiol-containing diotides derived from dioscorin hydrolysis exhibit antioxidant activities and reveal the benefits of yam tuber as an antioxidant-rich food.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 27, "end": 32}, {"text": "dioscorin", "start": 66, "end": 75}]}}, "schema": []}
{"input": "Winter wheat hull (husk) is a valuable source for tricin, a potential selective cytotoxic agent.", "output": {"entities": {"chemical": [{"text": "tricin", "start": 50, "end": 56}]}}, "schema": []}
{"input": "The flavone, tricin (5, 7, 4'-trihydroxy-3', 5'-dimethoxyflavone) has great potential as an anticancer agent, due to its specific chemopreventive activity.", "output": {"entities": {"chemical": [{"text": "flavone", "start": 4, "end": 11}, {"text": "tricin", "start": 13, "end": 19}, {"text": "5, 7, 4'-trihydroxy-3', 5'-dimethoxyflavone", "start": 21, "end": 64}]}}, "schema": []}
{"input": "In spite of these characteristics, its use in preclinical studies is still limited, mainly because of its limited availability and high production cost.", "output": {"entities": {}}, "schema": []}
{"input": "Tricin is found mainly in cereal grains, such as wheat, rice, barley, oat and maize.", "output": {"entities": {"chemical": [{"text": "Tricin", "start": 0, "end": 6}]}}, "schema": []}
{"input": "However, its concentration in these plants is not sufficient for commercial use.", "output": {"entities": {}}, "schema": []}
{"input": "To find a reliable, rich source of tricin, we investigated its distribution in different parts of wheat (Triticum aestivum) and designed an efficient method for its isolation and purification.", "output": {"entities": {"chemical": [{"text": "tricin", "start": 35, "end": 41}]}}, "schema": []}
{"input": "The highest amount (770 +/- 157 mg/kg dry weight) was found in the husks of winter wheat.", "output": {"entities": {}}, "schema": []}
{"input": "This concentration is one of the highest in any plant species and is considered as a cheap source of natural tricin.", "output": {"entities": {"chemical": [{"text": "tricin", "start": 109, "end": 115}]}}, "schema": []}
{"input": "The purified wheat husks tricin was found to be a selective potent inhibitor of two cancer cell lines of liver and pancreas, while having no side effects on normal cells.", "output": {"entities": {"chemical": [{"text": "tricin", "start": 25, "end": 31}]}}, "schema": []}
{"input": "This selective action suggests that tricin could be considered as a potential candidate for pre-clinical trials as a chemopreventive agent.", "output": {"entities": {"chemical": [{"text": "tricin", "start": 36, "end": 42}]}}, "schema": []}
{"input": "In addition, fibre-rich crude wheat husk could be used as a natural chemopreventive agent in food supplement.", "output": {"entities": {}}, "schema": []}
{"input": "Glycosidic aroma precursors of Syrah and Chardonnay grapes after an oak extract application to the grapevines.", "output": {"entities": {}}, "schema": []}
{"input": "Syrah and Chardonnay grapevines were treated with an oak extract in order to determine the effect on glycosidic aroma precursors.", "output": {"entities": {}}, "schema": []}
{"input": "Grapevines were treated at three different timings of the veraison (treatment 1, 2 and 3).", "output": {"entities": {}}, "schema": []}
{"input": "Aglycons were obtained by enzymatic hydrolysis, and these were identified and quantified by means of gas chromatography-mass spectrometry (GC-MS).", "output": {"entities": {}}, "schema": []}
{"input": "Results suggest that after the applications the majority of compounds from the oak extract were assimilated and stored as glycosidic forms in both cultivars.", "output": {"entities": {}}, "schema": []}
{"input": "Also, other compounds not present in the extract were affected, with a different behaviour observed depending on the timing of application and the variety.", "output": {"entities": {}}, "schema": []}
{"input": "In general, C6 compounds, alcohols, terpenes, phenols and C13-norisoprenoids in Syrah showed a decrease and in Chardonnay an increase.", "output": {"entities": {"chemical": [{"text": "C6", "start": 12, "end": 14}, {"text": "alcohols", "start": 26, "end": 34}, {"text": "terpenes", "start": 36, "end": 44}, {"text": "phenols", "start": 46, "end": 53}, {"text": "C13-norisoprenoids", "start": 58, "end": 76}]}}, "schema": []}
{"input": "Thus, this study proved a change in the glycosidic aroma profile in grapes after the oak application, so these treated grapes could produce wines with different aromatic quality.", "output": {"entities": {}}, "schema": []}
{"input": "1H NMR-based metabolic fingerprinting of urine metabolites after consumption of lingonberries (Vaccinium vitis-idaea) with a high-fat meal.", "output": {"entities": {"chemical": [{"text": "1H", "start": 0, "end": 2}]}}, "schema": []}
{"input": "The use of NMR metabolomics in clinical trials is growing; however, reports of postprandial experiments in humans are scarce.", "output": {"entities": {}}, "schema": []}
{"input": "The present study investigated whether consumption of lingonberries as a supplement to an oil-rich meal modifies the postprandial fingerprints of human urine.", "output": {"entities": {}}, "schema": []}
{"input": "Urine samples were analysed by (1) H NMR, and untargeted multivariate analysis was applied to the data for comprehensive fingerprinting.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 31, "end": 36}]}}, "schema": []}
{"input": "A clear separation of postprandial lingonberry meal samples was revealed.", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate statistical differences, a targeted approach was applied for the informative spectral areas.", "output": {"entities": {}}, "schema": []}
{"input": "Significantly (p < 0. 05) increased levels of polyphenol metabolites, hippuric acid and 4-hydroxyhippuric acid, and decreased creatinine and dimethylamine levels were the major explanations for the grouping of the postprandial samples after the different meals.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 46, "end": 56}, {"text": "hippuric acid", "start": 70, "end": 83}, {"text": "4-hydroxyhippuric acid", "start": 88, "end": 110}, {"text": "creatinine", "start": 126, "end": 136}, {"text": "dimethylamine", "start": 141, "end": 154}]}}, "schema": []}
{"input": "Thus, inclusion of polyphenol-rich lingonberry powder in a rapeseed oil-rich meal modifies the metabolic profile of urine which may be used to reveal both consumption of berries and health-promoting changes in the common metabolism.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 19, "end": 29}]}}, "schema": []}
{"input": "Simultaneous determination of Mn2 + and Fe3 + as 4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol) complexes in some foods, vegetable and water samples by artificial neural networks.", "output": {"entities": {"chemical": [{"text": "Mn2 +", "start": 30, "end": 35}, {"text": "Fe3 +", "start": 40, "end": 45}, {"text": "4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol)", "start": 49, "end": 124}]}}, "schema": []}
{"input": "A simple and sensitive spectrophotometric method to the simultaneous determination of Mn (2 +) and Fe (3 +) in foods, vegetable and water sample with the aid of artificial neural networks (ANNs) is described.", "output": {"entities": {"chemical": [{"text": "Mn (2 +)", "start": 86, "end": 94}, {"text": "Fe (3 +)", "start": 99, "end": 107}]}}, "schema": []}
{"input": "It relies on the complexation of analytes with recently synthesised bis pyrazol base ligand as 4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol) (CMBPP).", "output": {"entities": {"chemical": [{"text": "pyrazol", "start": 72, "end": 79}, {"text": "4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol)", "start": 95, "end": 170}, {"text": "CMBPP", "start": 172, "end": 177}]}}, "schema": []}
{"input": "The analytical data show that the ratio of ligand to metal in metal complexes is 1: 1 and 1: 2 for Fe (3 +) and Mn (2 +), respectively.", "output": {"entities": {"chemical": [{"text": "Fe (3 +)", "start": 99, "end": 107}, {"text": "Mn (2 +)", "start": 112, "end": 120}]}}, "schema": []}
{"input": "It was found that the complexation reactions are completed at pH 6. 7 and 5 min after mixing.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that Mn (2 +) and Fe (3 +) could be determined simultaneously in the range of 0. 20-7. 5 and 0. 30-9. 0 mgl (-1), respectively.", "output": {"entities": {"chemical": [{"text": "Mn (2 +)", "start": 24, "end": 32}, {"text": "Fe (3 +)", "start": 37, "end": 45}]}}, "schema": []}
{"input": "The analytical characteristics of the method such as the detection limit and the relative standard error predictions were calculated.", "output": {"entities": {}}, "schema": []}
{"input": "The data obtained from synthetic mixtures of the metal ions were processed by radial basis function networks (RBFNs) and feed forward neural networks (FFNNs).", "output": {"entities": {}}, "schema": []}
{"input": "The optimal conditions of the neural networks were obtained by adjusting various parameters by trial-and-error.", "output": {"entities": {}}, "schema": []}
{"input": "Under the working conditions, the proposed methods were successfully applied to the simultaneous determination of elements in different water, tablet, rice, tea leaves, tomato, cabbage and lettuce samples.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of cation exchange treatment on the final characteristics of red wines.", "output": {"entities": {}}, "schema": []}
{"input": "Ion exchange technology has been applied to adjust the pH of red wine and improve its tartaric and oxidative stability.", "output": {"entities": {}}, "schema": []}
{"input": "Ion exchange appears to be a useful technique to achieve these objectives.", "output": {"entities": {}}, "schema": []}
{"input": "Regarding the effect of ion exchange on organoleptic characteristics and the quality of the obtained wines, a slight decrease in both anthocyanin and tannin contents was observed along with a small drop in the aromatic content.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 134, "end": 145}, {"text": "tannin", "start": 150, "end": 156}]}}, "schema": []}
{"input": "However, the treated wines had lower hue and higher colour intensity and gave better punctuations in the sensory evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "These results confirm that ion exchange is an interesting technique for application in red winemaking.", "output": {"entities": {}}, "schema": []}
{"input": "Multidisciplinary analytical investigation of phospholipids and triglycerides in offshore farmed gilthead sea bream (Sparus aurata) fed commercial diets.", "output": {"entities": {"chemical": [{"text": "triglycerides", "start": 64, "end": 77}]}}, "schema": []}
{"input": "In this work, a quantitative characterisation of lipid (both triglycerides and phospholipids) rearrangements in the muscle of offshore-raised gilthead sea bream was carried out as a function of fish growth between April and September.", "output": {"entities": {"chemical": [{"text": "triglycerides", "start": 61, "end": 74}]}}, "schema": []}
{"input": "Relative percentages of lipid classes and fatty acids/acyls composition of the commercial feeds and fish dorsal muscles were assessed by means of an interdisciplinary analytical approach.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 42, "end": 53}, {"text": "acyls", "start": 54, "end": 59}]}}, "schema": []}
{"input": "A combination of preparative chemistry and experimental results from NMR spectroscopy, GC, 3D-TLC as well as proximate analysis permitted the observed growth parameters in key metabolic events to be linked with fish fattening and lipid turnover.", "output": {"entities": {}}, "schema": []}
{"input": "While defined effects of feed composition on fatty acid profiles of fillets were ascertained, the relative increase of fatty acyls in triglycerides and phospholipids were also estimated enabling detailed evaluation of TAG: PL ratio in adult offshore-farmed gilthead sea bream.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 45, "end": 55}, {"text": "fatty acyls", "start": 119, "end": 130}, {"text": "triglycerides", "start": 134, "end": 147}]}}, "schema": []}
{"input": "NMR was also used to quantify PUFA regiospecific distribution in TAG and PL.", "output": {"entities": {"chemical": [{"text": "PUFA", "start": 30, "end": 34}, {"text": "TAG", "start": 65, "end": 68}]}}, "schema": []}
{"input": "Non-destructive determination of chemical composition in intact and minced pork using near-infrared hyperspectral imaging.", "output": {"entities": {}}, "schema": []}
{"input": "In this study a near-infrared (NIR) hyperspectral imaging technique was investigated for non-destructive determination of chemical composition of intact and minced pork.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperspectral images (900-1700 nm) were acquired for both intact and minced pork samples and the mean spectra were extracted by automatic segmentation.", "output": {"entities": {}}, "schema": []}
{"input": "Protein, moisture and fat contents were determined by traditional methods and then related with the spectral information by partial least-squares (PLS) regression models.", "output": {"entities": {}}, "schema": []}
{"input": "The coefficient of determination obtained by cross-validated PLS models indicated that the NIR spectral range had an excellent ability to predict the content of protein (R (2) (cv) = 0. 88), moisture (R (2) (cv) = 0. 87) and fat (R (2) (cv) = 0. 95) in pork.", "output": {"entities": {}}, "schema": []}
{"input": "Regression models using a few selected feature-related wavelengths showed that chemical composition could be predicted with coefficients of determination of 0. 92, 0. 87 and 0. 95 for protein, moisture and fat, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Prediction of chemical contents in each pixel of the hyperspectral image using these prediction models yielded spatially distributed visualisations of the sample composition.", "output": {"entities": {}}, "schema": []}
{"input": "Simple, fast, and efficient process for producing and purifying trehalulose.", "output": {"entities": {"chemical": [{"text": "trehalulose", "start": 64, "end": 75}]}}, "schema": []}
{"input": "A new property of recombinant trehalose synthase (GTase) from Thermus thermophilus HB-8 (ATCC 27634) was found and described in this study.", "output": {"entities": {"chemical": [{"text": "trehalose", "start": 30, "end": 39}]}}, "schema": []}
{"input": "GTase can act on sucrose and catalyze trehalulose formation without isomaltose, isomaltulose, or isomelezitose, releasing small amounts of glucose and fructose as byproducts.", "output": {"entities": {"chemical": [{"text": "sucrose", "start": 17, "end": 24}, {"text": "trehalulose", "start": 38, "end": 49}, {"text": "isomaltose", "start": 68, "end": 78}, {"text": "isomaltulose", "start": 80, "end": 92}, {"text": "isomelezitose", "start": 97, "end": 110}, {"text": "glucose", "start": 139, "end": 146}, {"text": "fructose", "start": 151, "end": 159}]}}, "schema": []}
{"input": "Maximum trehalulose yield (approximately 81%) was obtained at an optimum temperature of 65 degrees C and was independent of substrate concentration.", "output": {"entities": {"chemical": [{"text": "trehalulose", "start": 8, "end": 19}]}}, "schema": []}
{"input": "A simple, fast, and efficient method of producing and purifying trehalulose is then described.", "output": {"entities": {"chemical": [{"text": "trehalulose", "start": 64, "end": 75}]}}, "schema": []}
{"input": "In the first step, GTase catalyzed trehalulose formation using a 20% sucrose substrate.", "output": {"entities": {"chemical": [{"text": "trehalulose", "start": 35, "end": 46}, {"text": "sucrose", "start": 69, "end": 76}]}}, "schema": []}
{"input": "Miscellaneous sugars were then rapidly removed, while trehalulose was completely preserved by Saccharomyces cerevisiae cells.", "output": {"entities": {"chemical": [{"text": "sugars", "start": 14, "end": 20}, {"text": "trehalulose", "start": 54, "end": 65}]}}, "schema": []}
{"input": "Finally, the cells were separated by centrifugation, and salt ions were removed by an ion-exchange resin, subsequently obtaining a high-purity trehalulose solution.", "output": {"entities": {"chemical": [{"text": "trehalulose", "start": 143, "end": 154}]}}, "schema": []}
{"input": "A trehalulose recovery rate of over 95% was achieved using this process.", "output": {"entities": {"chemical": [{"text": "trehalulose", "start": 2, "end": 13}]}}, "schema": []}
{"input": "This method has a simple process, fast separation efficiency, and low investment in production equipment, so greatly to improve production efficiency and reduce production costs.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of peeling and three cooking methods on the content of selected phytochemicals in potato tubers with various colour of flesh.", "output": {"entities": {}}, "schema": []}
{"input": "The impact of peeling and three cooking treatments (boiling, baking and microwaving) on the content of selected phytochemicals in white-, yellow-, red-and purple-fleshed potatoes was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Ascorbic acid and chlorogenic acid contents were determined by HPLC-DAD, total anthocyanin content by pH-differential spectrophotometry, glycoalkaloid, alpha-chaconine and alpha-solanine contents by HPLC-ESI/MS/MS.", "output": {"entities": {"chemical": [{"text": "Ascorbic acid", "start": 0, "end": 13}, {"text": "chlorogenic acid", "start": 18, "end": 34}, {"text": "anthocyanin", "start": 79, "end": 90}, {"text": "glycoalkaloid", "start": 137, "end": 150}, {"text": "alpha-chaconine", "start": 152, "end": 167}, {"text": "alpha-solanine", "start": 172, "end": 186}]}}, "schema": []}
{"input": "All cooking treatments reduced ascorbic and chlorogenic acid contents, total glycoalkaloids, alpha-chaconine and alpha-solanine with the exception of total anthocyanins.", "output": {"entities": {"chemical": [{"text": "ascorbic and chlorogenic acid", "start": 31, "end": 60}, {"text": "glycoalkaloids", "start": 77, "end": 91}, {"text": "alpha-chaconine", "start": 93, "end": 108}, {"text": "alpha-solanine", "start": 113, "end": 127}, {"text": "anthocyanins", "start": 156, "end": 168}]}}, "schema": []}
{"input": "The losses of ascorbic and chlorogenic acids were minimised with boiling and total anthocyanin levels retained the highest.", "output": {"entities": {"chemical": [{"text": "ascorbic and chlorogenic acids", "start": 14, "end": 44}, {"text": "anthocyanin", "start": 83, "end": 94}]}}, "schema": []}
{"input": "Boiling of peeled tubers decreased contents of total glycoalkaloids (alpha-chaconine and alpha-solanine) and appeared as the most favourable among the three tested methods.", "output": {"entities": {"chemical": [{"text": "glycoalkaloids", "start": 53, "end": 67}, {"text": "alpha-chaconine and alpha-solanine", "start": 69, "end": 103}]}}, "schema": []}
{"input": "Moreover, due to higher initial levels, red-and purple-fleshed cultivars retained higher amounts of antioxidants (ascorbic acid, chlorogenic acid and total anthocyanin) after boiling and may be healthier as compared with white or yellow cultivars.", "output": {"entities": {"chemical": [{"text": "ascorbic acid", "start": 114, "end": 127}, {"text": "chlorogenic acid", "start": 129, "end": 145}, {"text": "anthocyanin", "start": 156, "end": 167}]}}, "schema": []}
{"input": "A multi-residue method for the determination of 124 pesticides in rice by modified QuEChERS extraction and gas chromatography-tandem mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "A modified QuEChERS method for simultaneous determination of 124 pesticide residues in rice was established and validated.", "output": {"entities": {}}, "schema": []}
{"input": "The rice samples were initially extracted with acetonitrile (MeCN), and the targeted pesticides were purified following the dispersive solid phase extraction (d-SPE) cleanup method and detected by gas chromatography-tandem mass spectrometry (GC-MS/MS).", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 47, "end": 59}, {"text": "MeCN", "start": 61, "end": 65}]}}, "schema": []}
{"input": "The efficiency of citrate-buffered and unbuffered method in liquid extraction procedure was compared; the amount of primary secondary amine (PSA) was optimised.", "output": {"entities": {"chemical": [{"text": "citrate", "start": 18, "end": 25}, {"text": "primary secondary amine", "start": 116, "end": 139}, {"text": "PSA", "start": 141, "end": 144}]}}, "schema": []}
{"input": "In the method validation, correlation coefficients (r (2)) were higher than 0. 990 with the linear ranging from 10 to 200 mu g kg (-1).", "output": {"entities": {}}, "schema": []}
{"input": "At the fortification levels of 20-200 mu g kg (-1), average recoveries ranged from 70% to 122. 7% with the RSD < 20%.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activity of phytosteryl phenolates in different model systems.", "output": {"entities": {"chemical": [{"text": "phytosteryl phenolates", "start": 24, "end": 46}]}}, "schema": []}
{"input": "As part of a comprehensive study of the physiochemical and biological properties of phytosteryl phenolates, successfully synthesized chemoenzymatically in our lab, their antioxidant activity was evaluated using three different in vitro model systems, namely bulk oil model system, beta-carotene-linoleate model system and low-density lipoprotein cholesterol (LDL-C) oxidation assay.", "output": {"entities": {"chemical": [{"text": "phytosteryl phenolates", "start": 84, "end": 106}, {"text": "beta-carotene", "start": 281, "end": 294}, {"text": "linoleate", "start": 295, "end": 304}, {"text": "cholesterol", "start": 346, "end": 357}]}}, "schema": []}
{"input": "In the bulk oil system, phytosteryl phenolates showed similar or lower antioxidant activity compared with those of phenolic acids.", "output": {"entities": {"chemical": [{"text": "phytosteryl phenolates", "start": 24, "end": 46}, {"text": "phenolic acids", "start": 115, "end": 129}]}}, "schema": []}
{"input": "However, in beta-carotene-linoleate assay, an emulsion model system, phytosteryl phenolates showed enhanced antioxidant activity except phytosteryl ferulates.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 12, "end": 25}, {"text": "linoleate", "start": 26, "end": 35}, {"text": "phytosteryl phenolates", "start": 69, "end": 91}, {"text": "phytosteryl ferulates", "start": 136, "end": 157}]}}, "schema": []}
{"input": "Moderate inhibitory effect of LDL-C oxidation by phytosteryl phenolates was observed.", "output": {"entities": {"chemical": [{"text": "phytosteryl phenolates", "start": 49, "end": 71}]}}, "schema": []}
{"input": "These findings demonstrate that use of multidimensional antioxidant activity determinations with differing reaction mechanisms is necessary to provide an overall understanding of the mechanisms of antioxidant action of phytosteryl phenolates.", "output": {"entities": {"chemical": [{"text": "phytosteryl phenolates", "start": 219, "end": 241}]}}, "schema": []}
{"input": "A nanosilver-based spectrophotometry method for sensitive determination of tartrazine in food samples.", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 75, "end": 85}]}}, "schema": []}
{"input": "A new method is reported for sensitive determination of tartrazine in the food samples.", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 56, "end": 66}]}}, "schema": []}
{"input": "The method is based on the catalytic effect of silver nanoparticle (AgNPs) on the oxidation reaction of tartrazine by potassium iodate in the acetate buffer medium.", "output": {"entities": {"chemical": [{"text": "silver", "start": 47, "end": 53}, {"text": "tartrazine", "start": 104, "end": 114}, {"text": "potassium iodate", "start": 118, "end": 134}, {"text": "acetate", "start": 142, "end": 149}]}}, "schema": []}
{"input": "The reaction is followed spectrophotometrically by measuring the change in absorbance (Delta A) at 420 nm using a fixed time method (70 s).", "output": {"entities": {}}, "schema": []}
{"input": "The reaction variables were optimised in order to achieve the highest sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "The thirty six criterion detection limit was 0. 3 ng/mL, and the relative standard deviation for ten replicate measurements of 30 ng/mL of tartrazine was 0. 98% (n = 10).", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 139, "end": 149}]}}, "schema": []}
{"input": "The method was successfully applied to the determination of tartrazine in lemon, and papaya-flavoured gelatin, candy, and in fruit syrup.", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 60, "end": 70}]}}, "schema": []}
{"input": "Root tubers of Lactuca tuberosa as a source of antioxidant phenolic compounds and new furofuran lignans.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 59, "end": 67}, {"text": "furofuran lignans", "start": 86, "end": 103}]}}, "schema": []}
{"input": "From the root tubers of Lactuca tuberosa, a wild edible plant species, nine phenolic compounds were isolated, including two new furofuran lignan glucosides, named lactuberin A and lactuberin B.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 76, "end": 84}, {"text": "furofuran lignan glucosides", "start": 128, "end": 155}, {"text": "lactuberin A", "start": 163, "end": 175}, {"text": "lactuberin B", "start": 180, "end": 192}]}}, "schema": []}
{"input": "Their structures were elucidated by spectroscopic methods, especially HRESIMS and 2D NMR techniques.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first time that compounds belonging to the epi series of 2, 6-diaryl-3, 7-dioxabicyclo [3. 3. 0] octane type furofuran lignans have been found in Lactuca species.", "output": {"entities": {"chemical": [{"text": "2, 6-diaryl-3, 7-dioxabicyclo [3. 3. 0] octane", "start": 69, "end": 115}, {"text": "furofuran lignans", "start": 121, "end": 138}]}}, "schema": []}
{"input": "The total phenolic content of the root tuber extract was evaluated and its major phenolic constituents, caffeic acid, chlorogenic acid and 3, 5 dicaffeoylquinic acid, known to possess antioxidant activity, were quantified.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 10, "end": 18}, {"text": "caffeic acid", "start": 104, "end": 116}, {"text": "chlorogenic acid", "start": 118, "end": 134}, {"text": "3, 5 dicaffeoylquinic acid", "start": 139, "end": 165}]}}, "schema": []}
{"input": "Additionally, the root tuber extract showed DPPH radical scavenging activity implying its potential as functional food.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 44, "end": 48}]}}, "schema": []}
{"input": "Compositional characterisation of soluble apple polysaccharides, and their antioxidant and hepatoprotective effects on acute CCl4-caused liver damage in mice.", "output": {"entities": {"chemical": [{"text": "CCl4", "start": 125, "end": 129}]}}, "schema": []}
{"input": "Water-soluble apple peel polysaccharides (APP) and apple flesh polysaccharides (AFP) were isolated from Pink Lady fruits, and their in vitro antioxidant capacities were characterised by DPPH (), HO (), and O (2) (-) systems, and ferric-reducing antioxidant power assay.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 186, "end": 190}, {"text": "HO", "start": 195, "end": 197}, {"text": "O (2) (-)", "start": 206, "end": 215}, {"text": "ferric", "start": 229, "end": 235}]}}, "schema": []}
{"input": "Oral administration of APP at 250 and 500 mg/kg bw in mice was shown to be as effective as AFP in lowering the CCl (4)-caused increases of serum alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase activities, and hepatic malondialdehyde level, and antagonising the decreases in antioxidant superoxide dismutase and glutathione peroxidase activities caused by CCl (4) (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "CCl (4)", "start": 111, "end": 118}, {"text": "alanine", "start": 145, "end": 152}, {"text": "aspartate", "start": 171, "end": 180}, {"text": "malondialdehyde", "start": 247, "end": 262}, {"text": "superoxide", "start": 316, "end": 326}, {"text": "glutathione", "start": 341, "end": 352}, {"text": "CCl (4)", "start": 385, "end": 392}]}}, "schema": []}
{"input": "Histopathological examinations further confirmed that both APP and AFP could protect the liver from CCl (4)-induced histological alteration.", "output": {"entities": {"chemical": [{"text": "CCl (4)", "start": 100, "end": 107}]}}, "schema": []}
{"input": "HPLC analysis also showed similar profiles of monosaccharide composition for APP and AFP with arabinose, galactose and galacturonic acid being main component monosaccharides.", "output": {"entities": {"chemical": [{"text": "arabinose", "start": 94, "end": 103}, {"text": "galactose", "start": 105, "end": 114}, {"text": "galacturonic acid", "start": 119, "end": 136}]}}, "schema": []}
{"input": "All of these findings demonstrate that the extracts of both APP and AFP possess antioxidant and hepatoprotective potential.", "output": {"entities": {}}, "schema": []}
{"input": "Modelling the interactions between free phenols, L-ascorbic acid, apple polyphenoloxidase and oxygen during a thermal treatment.", "output": {"entities": {"chemical": [{"text": "phenols", "start": 40, "end": 47}, {"text": "L-ascorbic acid", "start": 49, "end": 64}, {"text": "oxygen", "start": 94, "end": 100}]}}, "schema": []}
{"input": "The kinetics of degradation of chlorogenic acid (CG), (-) epicatechin (EPI), L-ascorbic acid (AA) and polyphenoloxidase (PPO) activity from Marie-M e nard apple in pH 3. 8 solutions at 20 and 50 degrees C were investigated to provide information on the impact of the presence of CG, EPI and/or AA on PPO thermostability.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 31, "end": 47}, {"text": "(-) epicatechin", "start": 54, "end": 69}, {"text": "EPI", "start": 71, "end": 74}, {"text": "L-ascorbic acid", "start": 77, "end": 92}, {"text": "EPI", "start": 283, "end": 286}]}}, "schema": []}
{"input": "The effect of the heat treatment on their degradation by enzymatic and/or nonenzymatic ways was also studied.", "output": {"entities": {}}, "schema": []}
{"input": "Stoechiokinetic reactions on the basis of experimental data and literature and determination of the kinetic constants (k) at 20 and 50 degrees C were elaborated before modelling the interaction among reactants, by fitting the reaction curves to predictive model.", "output": {"entities": {}}, "schema": []}
{"input": "Apple PPO was thermolabile, denaturing after 10min at 70 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "Losses of PPO activity were favoured by the presence of EPI in model solutions, compared with CG, due to the formation of o-quinones of EPI (QEPI) lowering PPO stability.", "output": {"entities": {"chemical": [{"text": "EPI", "start": 56, "end": 59}, {"text": "o-quinones", "start": 122, "end": 132}, {"text": "EPI", "start": 136, "end": 139}]}}, "schema": []}
{"input": "Temperature quickened both enzymatic phenol oxidations before PPO deteriorated and the whole set of the chemical reactions, including the production of secondary oxidation products and CG or EPI regeneration.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 37, "end": 43}, {"text": "EPI", "start": 191, "end": 194}]}}, "schema": []}
{"input": "Results also confirmed that AA in excess induced a fast regeneration of CG and EPI from the corresponding o-quinones formed enzymatically via redox chemical reactions.", "output": {"entities": {"chemical": [{"text": "EPI", "start": 79, "end": 82}, {"text": "o-quinones", "start": 106, "end": 116}]}}, "schema": []}
{"input": "Evaluation of antioxidant activities and chemical characterisation of staghorn sumac fruit (Rhus hirta L.).", "output": {"entities": {}}, "schema": []}
{"input": "Staghorn sumac (Rhus hirta L.) is a native tree in Eastern Canada whose fruit has been used by aboriginal peoples to treat various illnesses, and has recently been found to be a good source of antioxidants.", "output": {"entities": {}}, "schema": []}
{"input": "However, the phytochemical composition of R. hirta is not known.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we used Four highly accepted assays and confirmed its FRAP, ORAC, beta-CLAMS and PCL values to be 79. 95 mu mol AAE/g DW, 1544 mu mol TE/g DW, RAA 129% and 4513 mu mol TE/g DW, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The antioxidant activities correlated positively to the total polyphenols content, which was higher in the ethanolic extract (81. 6 mg GAE/g DW) compared to the water extract (46. 3mg GAE/g DW), suggesting polyphenols play an important role.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 62, "end": 73}, {"text": "polyphenols", "start": 206, "end": 217}]}}, "schema": []}
{"input": "Quantitative data from UHPLC and qualitative studies using HPLC-DAD-MS showed that in addition to commonly found phenolic acids, flavonoids and anthocyanins, R. hirta fruit contained a novel group of unique anthocyanins with aglycones (anthocyanidins) at 449, 419 and 433 Da.", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 113, "end": 127}, {"text": "flavonoids", "start": 129, "end": 139}, {"text": "anthocyanins", "start": 144, "end": 156}, {"text": "anthocyanins", "start": 207, "end": 219}, {"text": "anthocyanidins", "start": 236, "end": 250}]}}, "schema": []}
{"input": "Further studies on the identification and their health beneficial effects are being conducted.", "output": {"entities": {}}, "schema": []}
{"input": "Relationships between the evolution of the percentage in weight of polar compounds and that of the molar percentage of acyl groups of edible oils submitted to frying temperature.", "output": {"entities": {"chemical": [{"text": "acyl", "start": 119, "end": 123}]}}, "schema": []}
{"input": "The evolution of the molar percentage of several kinds of acyl groups of extra virgin olive, sunflower and virgin linseed oils was monitored throughout heating at frying temperature by means of (1) H nuclear magnetic resonance.", "output": {"entities": {"chemical": [{"text": "acyl", "start": 58, "end": 62}, {"text": "(1) H", "start": 194, "end": 199}]}}, "schema": []}
{"input": "Likewise, the evolution of the percentage in weight of the polar compounds of the same oils under the same heating conditions was also determined.", "output": {"entities": {}}, "schema": []}
{"input": "Relationships between both sets of parameters, in each oil and in the oils as a group, were studied.", "output": {"entities": {}}, "schema": []}
{"input": "An equation which is able to accurately predict the percentage in weight of the polar compounds, throughout the heating at frying temperature, of any one of these three oils, from the molar percentage of triunsaturated, diunsaturated and monounsaturated acyl groups, was obtained.", "output": {"entities": {"chemical": [{"text": "acyl", "start": 254, "end": 258}]}}, "schema": []}
{"input": "In this way both molar percentage of acyl groups and percentage in weight of polar compounds can be obtained in a few minutes that registration of the (1) H NMR spectrum of the oil takes, in addition to the rest of information provided by this technique.", "output": {"entities": {"chemical": [{"text": "acyl", "start": 37, "end": 41}, {"text": "(1) H", "start": 151, "end": 156}]}}, "schema": []}
{"input": "The study reveals the close relationships between percentage in weight of polar compounds and the composition expressed in terms of molar percentages of acyl groups in edible oils heated at frying temperature.", "output": {"entities": {"chemical": [{"text": "acyl", "start": 153, "end": 157}]}}, "schema": []}
{"input": "Evaluation of sea bream (Sparus aurata) shelf life using an optoelectronic nose.", "output": {"entities": {}}, "schema": []}
{"input": "A new optoelectronic nose for the shelf-life assessment of fresh sea bream in cold storage has been developed.", "output": {"entities": {}}, "schema": []}
{"input": "The chromogenic array used eight sensing materials (based on aluminium oxide and silica gel) containing pH indicators, Lewis acids and an oxidation-reduction indicator.", "output": {"entities": {"chemical": [{"text": "aluminium oxide", "start": 61, "end": 76}, {"text": "silica gel", "start": 81, "end": 91}, {"text": "Lewis acids", "start": 119, "end": 130}]}}, "schema": []}
{"input": "The colour changes of the sensor array were characteristic of sea bream spoilage.", "output": {"entities": {}}, "schema": []}
{"input": "Colour modulations were measured on day 0 and for the samples held in cold storage for 2, 4, 7, 9 and 11 days.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of moisture content, pH, total volatile basic nitrogen (TVB-N), drip loss, ATP-related compounds and K (1)-value and microbial (mesophilic bacteria and Enterobacteriaceae) analyses were carried out on the same days.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 60, "end": 68}, {"text": "N", "start": 74, "end": 75}, {"text": "ATP", "start": 89, "end": 92}]}}, "schema": []}
{"input": "The changes in the chromogenic arrays data were processed by statistical analysis (PCA).", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, PLS statistical studies allowed the creation of models to correlate the chromogenic data with concentrations of mesophilic and Enterobacteriaceae.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest the feasibility of this system to help develop optoelectronic noses for fish freshness monitoring.", "output": {"entities": {}}, "schema": []}
{"input": "A water-alcohol extract of Citrus grandis whole fruits has beneficial metabolic effects in the obese Zucker rats fed with high fat/high cholesterol diet.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 8, "end": 15}, {"text": "cholesterol", "start": 136, "end": 147}]}}, "schema": []}
{"input": "Epidemiological studies suggest that citrus fruits and compounds such as flavonoids, limonoids and pectins have health promoting effects.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 73, "end": 83}]}}, "schema": []}
{"input": "Our aim was to study the effects of Citrus grandis (L.) Osbeck var. tomentosa hort. fruit extract on the energy metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "A whole fruit powder from dry water and alcohol extracts of C. grandis containing 19% naringin flavonoid was prepared.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 40, "end": 47}, {"text": "naringin", "start": 86, "end": 94}]}}, "schema": []}
{"input": "The effects of the citrus extract were followed in the obese Zucker rats fed with the HFD.", "output": {"entities": {}}, "schema": []}
{"input": "The circulatory levels of GLP-1 decreased significantly by the extract in comparison to the HFD group, whereas the decreased ghrelin levels were reversed.", "output": {"entities": {}}, "schema": []}
{"input": "The levels of PYY were decreased in all HFD groups.", "output": {"entities": {}}, "schema": []}
{"input": "The leptin amounts decreased but not significantly whereas insulin and amylin were unchanged.", "output": {"entities": {}}, "schema": []}
{"input": "The cholesterol and glucose levels were somewhat but not systematically improved in the HFD fed rats.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 4, "end": 15}, {"text": "glucose", "start": 20, "end": 27}]}}, "schema": []}
{"input": "Further studies are needed to identify the active compounds and their mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of incorporating hydrothermal, kilned and defatted oats on antioxidant and chapatti making properties of wheat flour.", "output": {"entities": {}}, "schema": []}
{"input": "Oats were subjected to treatments like defatting, hydrothermal cooking and kilning, milled into flour and then the control and treated flours were incorporated into wheat flour at 25% and 50% levels and chapatti making behaviour and antioxidant properties were studied.", "output": {"entities": {}}, "schema": []}
{"input": "The treatments significantly affected the antioxidant properties of oats.", "output": {"entities": {}}, "schema": []}
{"input": "Incorporating oat flours to wheat increased total phenolic content but lowered the antioxidant activity however both were decreased significantly upon baking.", "output": {"entities": {}}, "schema": []}
{"input": "The reducing power of the oat blended flour was higher than the wheat flours and ranged from 8. 0 to 15. 5 mu mol AAE/g and was further increased upon baking.", "output": {"entities": {}}, "schema": []}
{"input": "The metal chelating activity of flour blends varied from 62. 0% to 73. 8% and further increased upon baking.", "output": {"entities": {}}, "schema": []}
{"input": "After baking the total flavonoid content was lowered and ranged from 308 to 389 mu g CE/g.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 23, "end": 32}]}}, "schema": []}
{"input": "The non-enzymatic browning index significantly increased up to 27. 6% upon baking.", "output": {"entities": {}}, "schema": []}
{"input": "Piceatannol, a potent bioactive stilbene, as major phenolic component in Rhodomyrtus tomentosa.", "output": {"entities": {"chemical": [{"text": "Piceatannol", "start": 0, "end": 11}, {"text": "stilbene", "start": 32, "end": 40}, {"text": "phenolic", "start": 51, "end": 59}]}}, "schema": []}
{"input": "The sim fruit (Rhodomyrtus tomentosa) has long been used in folk medicine to treat diarrhoea, dysentery, and to boost the immune system.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this work was to determine its phenolic profile and to evaluate the changes of content during maturation, as well as the variations induced by environmental conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Using HPLC-ESI-HR-MS, 19 phenolic compounds (PCs) were tentatively characterised and included stilbenes and ellagitannins as major components, followed by anthocyanins, flavonols, and gallic acid.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 25, "end": 33}, {"text": "stilbenes", "start": 94, "end": 103}, {"text": "anthocyanins", "start": 155, "end": 167}, {"text": "flavonols", "start": 169, "end": 178}, {"text": "gallic acid", "start": 184, "end": 195}]}}, "schema": []}
{"input": "PCs were then further quantified by HPLC-DAD.", "output": {"entities": {}}, "schema": []}
{"input": "Piceatannol, a promising health-promoting stilbene component, was the major PC in the fruit with a concentration of 2. 3mg/g dry weight at full maturity stage.", "output": {"entities": {"chemical": [{"text": "Piceatannol", "start": 0, "end": 11}, {"text": "stilbene", "start": 42, "end": 50}]}}, "schema": []}
{"input": "This concentration is 1000-2000 times higher than that of red grapes, a major source of stilbene in the human diet.", "output": {"entities": {"chemical": [{"text": "stilbene", "start": 88, "end": 96}]}}, "schema": []}
{"input": "During maturation, the contents in piceatannol and other stilbenes, ellagitannins, and flavonols decreased while the anthocyanin content increased.", "output": {"entities": {"chemical": [{"text": "piceatannol", "start": 35, "end": 46}, {"text": "stilbenes", "start": 57, "end": 66}, {"text": "flavonols", "start": 87, "end": 96}, {"text": "anthocyanin", "start": 117, "end": 128}]}}, "schema": []}
{"input": "Shade-grown sim fruits showed significantly higher piceatannol levels than sun-exposed fruits.", "output": {"entities": {"chemical": [{"text": "piceatannol", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Taken together, these findings highlight the potential of sim, an under-utilised plant species from South-East Asia, as a source of health-promoting fruits.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative study on hypocholesterolemic and antioxidant activities of various extracts of fenugreek seeds.", "output": {"entities": {}}, "schema": []}
{"input": "The hypocholesterolemic and antioxidant activities of various extracts (water, methanol, ethyl acetate, hexane, dichloro-methane) of fenugreek seeds were investigated in cholesterol-fed rats.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 79, "end": 87}, {"text": "ethyl acetate", "start": 89, "end": 102}, {"text": "hexane", "start": 104, "end": 110}, {"text": "dichloro-methane", "start": 112, "end": 128}, {"text": "cholesterol", "start": 170, "end": 181}]}}, "schema": []}
{"input": "Only the ethyl acetate extract reduced total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) compared with those of rats fed a cholesterol-rich diet (HCD).", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 9, "end": 22}, {"text": "cholesterol", "start": 45, "end": 56}, {"text": "triglycerides", "start": 58, "end": 71}, {"text": "cholesterol", "start": 101, "end": 112}, {"text": "cholesterol", "start": 160, "end": 171}, {"text": "cholesterol", "start": 214, "end": 225}]}}, "schema": []}
{"input": "Furthermore, the content of thiobarbituric acid-reactive substances (TBARS), and catalase and superoxide dismutase (SOD) in liver, heart and kidney decreased significantly after oral administration of the ethyl acetate extract, compared with those of HCD-fed rats.", "output": {"entities": {"chemical": [{"text": "thiobarbituric acid", "start": 28, "end": 47}, {"text": "superoxide", "start": 94, "end": 104}, {"text": "ethyl acetate", "start": 205, "end": 218}]}}, "schema": []}
{"input": "The phenolic and flavono i d contents were highest in the methanol and the ethyl acetate extracts.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 4, "end": 12}, {"text": "flavono i d", "start": 17, "end": 28}, {"text": "methanol", "start": 58, "end": 66}, {"text": "ethyl acetate", "start": 75, "end": 88}]}}, "schema": []}
{"input": "These results showed that the ethyl acetate extract of the fenugreek seeds had a significant hypocholesterolemic effect and antioxidant activity in cholesterol-fed rats, whether this is partly due to the presence of flavono i ds in the extract needs further study.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 30, "end": 43}, {"text": "flavono i ds", "start": 216, "end": 228}]}}, "schema": []}
{"input": "Structural elucidation and antioxidant activity of a water-soluble polysaccharide from the fruit bodies of Bulgaria inquinans (Fries).", "output": {"entities": {}}, "schema": []}
{"input": "The non-lichenized ascomycete Bulgaria inquinans (Fries), growing in the Changbai Mountain of China, has been used as medicinal diet for many years.", "output": {"entities": {}}, "schema": []}
{"input": "In a previous study, we have reported that a heteropolysaccharide BIWS-4b from the fruit bodies of B. inquinans (Fries) exhibited markedly antimalarial and immunostimulating activities.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, the structural features and antioxidant activity of BIWS-4b were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that BIWS-4b contains an alpha-(1 --> 2), (1 --> 6)-mannan core to which the glucogalactan chains are attached.", "output": {"entities": {}}, "schema": []}
{"input": "The glucogalactan chains were composed of (1 --> 6)-, (1 --> 5)-and (1 --> 5, 6)-linked beta-Galf, (1 --> 4)-linked and non-reducing terminal beta-Glcp units, and might be attached to the mannan core at the O-2 positions of alpha-Manp units.", "output": {"entities": {"chemical": [{"text": "beta-Galf", "start": 88, "end": 97}, {"text": "beta-Glcp", "start": 142, "end": 151}, {"text": "alpha-Manp", "start": 224, "end": 234}]}}, "schema": []}
{"input": "The antioxidant assays showed that BIWS-4b exhibited good activities, including free radicals scavenging effects, ferrous ion-chelating ability and reducing power.", "output": {"entities": {"chemical": [{"text": "ferrous", "start": 114, "end": 121}]}}, "schema": []}
{"input": "Thus, BIWS-4b could be used as a natural antioxidant agent for food and pharmaceutical industries.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of different freezing treatments on the biogenic amine and quality changes of bighead carp (Aristichthys nobilis) heads during ice storage.", "output": {"entities": {"chemical": [{"text": "amine", "start": 57, "end": 62}]}}, "schema": []}
{"input": "The effects of different freezing treatments on the quality changes of bighead carp heads were evaluated in terms of pH value, TBARS, TVB-N, K-value, biogenic amine, total aerobic counts (TACs), drip loss, cooking loss and electrical conductivity (EC) during ice storage.", "output": {"entities": {"chemical": [{"text": "amine", "start": 159, "end": 164}]}}, "schema": []}
{"input": "Fish heads were stored at-40 degrees C (T1),-40 degrees C for 12h and then-18 degrees C (T2),-18 degrees C (T3) for 3months prior to ice storage.", "output": {"entities": {}}, "schema": []}
{"input": "No significant differences were observed among T1, T2 and T3 for drip loss, cooking loss and EC (p > 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "T2 showed lower TACs, pH value, TBARS and TVB-N than T3 did.", "output": {"entities": {}}, "schema": []}
{"input": "Significant lower value of spermine and spermidine were observed in T1, T2 and T3 than those of control group (fresh) from 9th to 18th day (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "spermine", "start": 27, "end": 35}, {"text": "spermidine", "start": 40, "end": 50}]}}, "schema": []}
{"input": "Drip loss was significantly correlated with TBARS, pH value, TVB-N, and TACs in groups T1, T2 and T3 (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Isomerisation of carrot beta-carotene in presence of oil during thermal and combined thermal/high pressure processing.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 24, "end": 37}]}}, "schema": []}
{"input": "The effect of thermal processing (85-130 degrees C) and combined thermal/high pressure processing (100 degrees C combined with 0. 1 to 700 MPa and 700 MPa combined with 85-115 degrees C) on beta-carotene isomerisation in an olive oil/carrot emulsion and pure olive oil phase enriched with carrot beta-carotene was investigated.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 190, "end": 203}, {"text": "beta-carotene", "start": 296, "end": 309}]}}, "schema": []}
{"input": "Thermal processing always resulted in an increase in the contribution of the cis-isomers, with the increase being more pronounced at higher temperatures.", "output": {"entities": {}}, "schema": []}
{"input": "In the oil/carrot emulsion, less beta-carotene isomerisation was observed during combined thermal/high pressure processing compared to thermal processing.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 33, "end": 46}]}}, "schema": []}
{"input": "This effect was attributed to strengthening of the carrot cell walls under high pressure, thereby hindering the transfer of beta-carotene to the oil phase and lowering its susceptibility to isomerisation.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 124, "end": 137}]}}, "schema": []}
{"input": "In an oil phase enriched with beta-carotene, beta-carotene isomerisation was not influenced by the applied pressure at 100 degrees C and became almost temperature insensitive at 700 MPa.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 30, "end": 43}, {"text": "beta-carotene", "start": 45, "end": 58}]}}, "schema": []}
{"input": "Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylase.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 77, "end": 86}]}}, "schema": []}
{"input": "Histidine decarboxylase (HDC) catalyses the formation of histamine, a bioactive amine.", "output": {"entities": {"chemical": [{"text": "Histidine", "start": 0, "end": 9}, {"text": "histamine", "start": 57, "end": 66}, {"text": "amine", "start": 80, "end": 85}]}}, "schema": []}
{"input": "Agents that control HDC activity are beneficial for treating histamine-mediated symptoms, such as allergies and stomach ulceration.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 61, "end": 70}]}}, "schema": []}
{"input": "We searched for inhibitors of HDC from the ethyl acetate extract of the petal of Filipendula ulmaria, also called meadowsweet.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 43, "end": 56}]}}, "schema": []}
{"input": "Rugosin D, rugosin A, rugosin A methyl ester (a novel compound), and tellimagrandin II were the main components; these 4 ellagitannins exhibited a non-competitive type of inhibition, with K (i) values of approximately 0. 35-1 mu M.", "output": {"entities": {"chemical": [{"text": "Rugosin D", "start": 0, "end": 9}, {"text": "rugosin A", "start": 11, "end": 20}, {"text": "rugosin A methyl ester", "start": 22, "end": 44}, {"text": "tellimagrandin II", "start": 69, "end": 86}]}}, "schema": []}
{"input": "These K (i) values are nearly equal to that of histidine methyl ester (K (i) = 0. 46 mu M), an existing substrate analogue inhibitor.", "output": {"entities": {"chemical": [{"text": "histidine methyl ester", "start": 47, "end": 69}]}}, "schema": []}
{"input": "Our results show that food products contain potent HDC inhibitors and that these active food constituents might be useful for designing clinically available HDC inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant properties of different edible mushroom species and increased bioconversion efficiency of Pleurotus eryngii using locally available casing materials.", "output": {"entities": {}}, "schema": []}
{"input": "Total phenolics, radical scavenging activity (RSA) on DPPH, ascorbic acid content and chelating activity on Fe (2 +) of Pleurotus citrinopileatus, Pleurotus djamor, Pleurotus eryngii, Pleurotus flabellatus, Pleurotus florida, Pleurotus ostreatus, Pleurotus sajor-caju and Hypsizygus ulmarius have been evaluated.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 6, "end": 15}, {"text": "DPPH", "start": 54, "end": 58}, {"text": "ascorbic acid", "start": 60, "end": 73}, {"text": "Fe (2 +)", "start": 108, "end": 116}]}}, "schema": []}
{"input": "The assayed mushrooms contained 3. 94-21. 67 mg TAE of phenolics, 13. 63-69. 67% DPPH scavenging activity, 3. 76-6. 76 mg ascorbic acid and 60. 25-82. 7% chelating activity.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 55, "end": 64}, {"text": "DPPH", "start": 81, "end": 85}, {"text": "ascorbic acid", "start": 122, "end": 135}]}}, "schema": []}
{"input": "Principal Component Analysis (PCA) revealed that significantly higher total phenolics, RSA on DPPH and growth/day was present in P. eryngii whereas P. citrinopileatus showed higher ascorbic acid and chelating activity.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 76, "end": 85}, {"text": "DPPH", "start": 94, "end": 98}, {"text": "ascorbic acid", "start": 181, "end": 194}]}}, "schema": []}
{"input": "Agglomerative hierarchical clustering analysis revealed that studied mushroom species fall into two clusters; Cluster I included P. djamor, P. eryngii and P. flabellatus, while Cluster II included H. ulmarius, P. sajor-caju, P. citrinopileatus, P. ostreatus and P. florida.", "output": {"entities": {}}, "schema": []}
{"input": "Enhanced yield of P. eryngii was achieved on spent compost casing material.", "output": {"entities": {}}, "schema": []}
{"input": "Use of casing materials enhanced yield by 21-107% over non-cased substrate.", "output": {"entities": {}}, "schema": []}
{"input": "Interaction between lysozyme and procyanidin: multilevel structural nature and effect of carbohydrates.", "output": {"entities": {"chemical": [{"text": "procyanidin", "start": 33, "end": 44}, {"text": "carbohydrates", "start": 89, "end": 102}]}}, "schema": []}
{"input": "The interaction of procyanidins with proteins has aroused extensive attention due to its important relationship with the bioavailability and astringent property of polyphenols.", "output": {"entities": {"chemical": [{"text": "procyanidins", "start": 19, "end": 31}, {"text": "polyphenols", "start": 164, "end": 175}]}}, "schema": []}
{"input": "In the present work, we have investigated the interactions of lysozyme with procyanidin dimer (B3) using various biophysical approaches, which aims to provide insights into the mechanism of protein/polyphenol aggregation.", "output": {"entities": {"chemical": [{"text": "procyanidin", "start": 76, "end": 87}, {"text": "polyphenol", "start": 198, "end": 208}]}}, "schema": []}
{"input": "Procyanidin B3 spontaneously binds lysozyme, inducing the multilevel structural changes in lysozyme and the formation of insoluble complexes.", "output": {"entities": {"chemical": [{"text": "Procyanidin B3", "start": 0, "end": 14}]}}, "schema": []}
{"input": "The relationship between lysozyme aggregation and the loss of enzymatic activity was monitored using dynamic light scattering and fluorescence quenching.", "output": {"entities": {}}, "schema": []}
{"input": "The influences of two carbohydrates (gum arabic and sucrose) on lysozyme/B3 aggregation were also studied.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 22, "end": 35}, {"text": "sucrose", "start": 52, "end": 59}]}}, "schema": []}
{"input": "Gum arabic effectively inhibited the formation of insoluble aggregates, but was unable to restore the fluorescence and activity of lysozyme.", "output": {"entities": {}}, "schema": []}
{"input": "However, sucrose concomitantly decreased the aggregate size with the recovery of fluorescence and lysozyme activity.", "output": {"entities": {}}, "schema": []}
{"input": "These results proposed two probable mechanisms by which these two carbohydrates inhibit protein/polyphenol aggregation.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 66, "end": 79}, {"text": "polyphenol", "start": 96, "end": 106}]}}, "schema": []}
{"input": "The protein interactions and rheological properties of skim milk heated in the presence of low levels of reducing agent.", "output": {"entities": {}}, "schema": []}
{"input": "Skim milk with low levels of added beta-mercaptoethanol (SM-ME) and untreated skim milk (SM) were heated and then made into acid gels.", "output": {"entities": {"chemical": [{"text": "beta-mercaptoethanol", "start": 35, "end": 55}]}}, "schema": []}
{"input": "Acid gels prepared from heated SM-ME had markedly higher firmness and contained more protein connections than acid gels prepared from heated SM.", "output": {"entities": {}}, "schema": []}
{"input": "Electrophoretic analyses of the milks showed that the levels of beta-lactoglobulin and alpha-lactalbumin associated with the casein micelles increased with increasing beta-ME concentration.", "output": {"entities": {}}, "schema": []}
{"input": "The levels of disulphide-linked whey proteins were higher in SM-ME than in SM.", "output": {"entities": {"chemical": [{"text": "disulphide", "start": 14, "end": 24}]}}, "schema": []}
{"input": "This suggested that there may be higher levels of initiators for thiol-disulphide exchange reactions, resulting in an increase in the rate of the reactions and the formation of greater numbers of small aggregates, in SM-ME than in SM.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 65, "end": 70}, {"text": "disulphide", "start": 71, "end": 81}]}}, "schema": []}
{"input": "Consequently, acid gels made from SM-ME may have more bonds and more particles participating in the network, resulting in firmer gels, than acid gels made from SM.", "output": {"entities": {}}, "schema": []}
{"input": "A novel colloidal gold-based lateral flow immunoassay for rapid simultaneous detection of cyromazine and melamine in foods of animal origin.", "output": {"entities": {"chemical": [{"text": "cyromazine", "start": 90, "end": 100}, {"text": "melamine", "start": 105, "end": 113}]}}, "schema": []}
{"input": "A rapid and sensitive lateral flow immunoassay (LFIA) based on competitive format was developed and validated for simultaneous detection of cyromazine (CA) and melamine (MA) in foods of animal origin.", "output": {"entities": {"chemical": [{"text": "cyromazine", "start": 140, "end": 150}, {"text": "melamine", "start": 160, "end": 168}]}}, "schema": []}
{"input": "With this method, the cut-off value for the two test lines were achieved at 25 ng/g, which was lower than the maximum residue levels (MRLs) established for CA and MA.", "output": {"entities": {}}, "schema": []}
{"input": "At three fortified levels (50, 100, and 150 ng/g), the recoveries for CA and MA ranged from 73. 9% to 104. 2% with the relative standard deviation (RSD) less than 11. 9%, based on within day and interday analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The lower detection limit for CA and MA in matrix sample were 0. 22 ng/ml and 0. 26 ng/ml, respectively, which were lower than those of published literatures.", "output": {"entities": {}}, "schema": []}
{"input": "A parallel analysis of CA and MA in real samples conducted by HPLC showed comparable results to those obtained from LFIA.", "output": {"entities": {}}, "schema": []}
{"input": "The results of LFIA were in good agreement with those of high performance liquid chromatography (HPLC) in the analysis of CA and MA in foods of animal origin, demonstrating the practical applicability of the developed assay in real samples.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, to our knowledge, this is the first report of quantitative or semi-quantitative simultaneous detection for CA and MA by immunochromatographic assay.", "output": {"entities": {}}, "schema": []}
{"input": "Total amino acid profiles of heat-processed fresh Elaeis guineensis and Raphia hookeri wines.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 6, "end": 16}]}}, "schema": []}
{"input": "Total amino acid (AA) profiles of heat-processed fresh Elaeis guineensis and Raphia hookeri wines were studied.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 6, "end": 16}]}}, "schema": []}
{"input": "Heating their fresh wines to 85 degrees C, cooling and diluting to original volumes distilled off ethanol, but did not change their moisture and nitrogen contents.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 98, "end": 105}, {"text": "nitrogen", "start": 145, "end": 153}]}}, "schema": []}
{"input": "R. hookeri wine contained more (p < 0. 05) Phe, Val, Ala, Gly, Pro, Asp, Asn, His and Lys than E. guineensis wine which contained more (p < 0. 05) Met, Cys, Glu, Gln, Ser and Arg.", "output": {"entities": {"chemical": [{"text": "Phe", "start": 43, "end": 46}, {"text": "Val", "start": 48, "end": 51}, {"text": "Ala", "start": 53, "end": 56}, {"text": "Gly", "start": 58, "end": 61}, {"text": "Pro", "start": 63, "end": 66}, {"text": "Asp", "start": 68, "end": 71}, {"text": "Asn", "start": 73, "end": 76}, {"text": "His", "start": 78, "end": 81}, {"text": "Lys", "start": 86, "end": 89}, {"text": "Met", "start": 147, "end": 150}, {"text": "Cys", "start": 152, "end": 155}, {"text": "Glu", "start": 157, "end": 160}, {"text": "Gln", "start": 162, "end": 165}, {"text": "Ser", "start": 167, "end": 170}, {"text": "Arg", "start": 175, "end": 178}]}}, "schema": []}
{"input": "Tyrosine, Leu, Ile and Thr contents did not vary (p > 0. 05).", "output": {"entities": {"chemical": [{"text": "Tyrosine", "start": 0, "end": 8}, {"text": "Leu", "start": 10, "end": 13}, {"text": "Ile", "start": 15, "end": 18}, {"text": "Thr", "start": 23, "end": 26}]}}, "schema": []}
{"input": "Glycine and Pro contents were low suggesting high globular protein concentrations.", "output": {"entities": {"chemical": [{"text": "Glycine", "start": 0, "end": 7}, {"text": "Pro", "start": 12, "end": 15}]}}, "schema": []}
{"input": "sum basic AA/sum acidic AA ratios were > 1 suggesting high basic protein contents.", "output": {"entities": {}}, "schema": []}
{"input": "The E. guineensis and R. hookeri wines contained 58. 25 +/- 0. 56% and 56. 79 +/- 0. 4% essential AAs, respectively.", "output": {"entities": {"chemical": [{"text": "AAs", "start": 98, "end": 101}]}}, "schema": []}
{"input": "Essential AA scores suggested Leu as their limiting AA.", "output": {"entities": {"chemical": [{"text": "Leu", "start": 30, "end": 33}]}}, "schema": []}
{"input": "In conclusion, the wines can adequately meet daily nitrogen and essential AA needs when a 70 kg adult drinks 1425. 45 ml.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 51, "end": 59}]}}, "schema": []}
{"input": "Quality and antioxidant properties of breads enriched with dry onion (Allium cepa L.) skin.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the study was to investigate the effect on the antioxidant properties and sensory value of bread of adding ground onion skin (OS).", "output": {"entities": {}}, "schema": []}
{"input": "For a determination of bioaccessibility and bioavailability in vitro the human gastrointestinal tract model was used.", "output": {"entities": {}}, "schema": []}
{"input": "OS contained mastication-extractable quercetin (4. 6 mg/g).", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 37, "end": 46}]}}, "schema": []}
{"input": "Quercetin from OS was highly bioaccessible during in vitro conditions, but only approximately 4% of quercetin released during simulated digestion was bioavailable in vitro.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "quercetin", "start": 100, "end": 109}]}}, "schema": []}
{"input": "The antioxidant potential of bread with OS was significantly higher than the activity noted in the control.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, OS addition significantly fortificated bread with bioaccessible lipid oxidation preventers and compounds with reducing and chelating abilities.", "output": {"entities": {}}, "schema": []}
{"input": "The 2-3% OS addition caused significant improvement of antioxidant abilities (further increases in the OS supplement did not increase the activity of bread).", "output": {"entities": {}}, "schema": []}
{"input": "Sensory evaluation showed that replacement of wheat flour in bread with up to 3% OS powder gave satisfactory consumer acceptability.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of total iron in food samples after flow injection preconcentration on polyurethane foam functionalized with N, N-bis (salicylidene)-1, 3-propanediamine.", "output": {"entities": {"chemical": [{"text": "iron", "start": 23, "end": 27}, {"text": "polyurethane", "start": 85, "end": 97}, {"text": "N, N-bis (salicylidene)-1, 3-propanediamine", "start": 123, "end": 166}]}}, "schema": []}
{"input": "A highly selective flow injection sorption system was developed for the fast determination of total iron in food samples.", "output": {"entities": {"chemical": [{"text": "iron", "start": 100, "end": 104}]}}, "schema": []}
{"input": "Iron (III) was reduced to iron (II) by ascorbic acid and preconcentrated on a mini-column packed with polyurethane foam (PUF) functionalized with N, N-bis (salicylidene)-1, 3-propanediamine (SPDA).", "output": {"entities": {"chemical": [{"text": "Iron (III)", "start": 0, "end": 10}, {"text": "iron (II)", "start": 26, "end": 35}, {"text": "ascorbic acid", "start": 39, "end": 52}, {"text": "polyurethane", "start": 102, "end": 114}, {"text": "N, N-bis (salicylidene)-1, 3-propanediamine", "start": 146, "end": 189}, {"text": "SPDA", "start": 191, "end": 195}]}}, "schema": []}
{"input": "The retained Fe (II) was eluted with hydrochloric acid and subsequently reacted to 2, 4, 6-tri (2'-pyridyl)-1, 3, 5-triazine (TPTZ) then measured at 593 nm.", "output": {"entities": {"chemical": [{"text": "Fe (II)", "start": 13, "end": 20}, {"text": "hydrochloric acid", "start": 37, "end": 54}, {"text": "2, 4, 6-tri (2'-pyridyl)-1, 3, 5-triazine", "start": 83, "end": 124}, {"text": "TPTZ", "start": 126, "end": 130}]}}, "schema": []}
{"input": "The procedure has resulted preconcentration factor 36, sample frequency 20 h (-1) and detection limit 18 mu g L (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The precision (RSD) was found to be 5. 7% and 3. 1% at concentration levels 0. 1 and 5. 0 mu g mL (-1) iron (II), respectively.", "output": {"entities": {"chemical": [{"text": "iron (II)", "start": 103, "end": 112}]}}, "schema": []}
{"input": "Finally, the method was successfully applied to determination of total iron in reference material and food samples.", "output": {"entities": {"chemical": [{"text": "iron", "start": 71, "end": 75}]}}, "schema": []}
{"input": "Effects of blanching on polyphenol stability of innovative paste-like parsley (Petroselinum crispum (Mill.) Nym ex A. W. Hill) and marjoram (Origanum majorana L.) products.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 24, "end": 34}]}}, "schema": []}
{"input": "Fresh herbs were water-and steam-blanched at 90-100 degrees C and 100 degrees C, respectively, for 1-10 min and 30 s to 7 min for parsley and marjoram, respectively, and subsequently minced to obtain a paste.", "output": {"entities": {}}, "schema": []}
{"input": "For the first time, phenolic compounds of unheated marjoram were characterised by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS).", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 20, "end": 28}]}}, "schema": []}
{"input": "Hereby, 10 phenolics were detected.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 11, "end": 20}]}}, "schema": []}
{"input": "Among them, apigenin-glucuronide, lucenin-2 and lithospermic acid were tentatively identified for the first time.", "output": {"entities": {"chemical": [{"text": "apigenin-glucuronide", "start": 12, "end": 32}, {"text": "lucenin-2", "start": 34, "end": 43}, {"text": "lithospermic acid", "start": 48, "end": 65}]}}, "schema": []}
{"input": "In unheated parsley, apart from the major compound apiin, 10 further phenolics were characterised including several p-coumaric acid derivatives which were newly detected.", "output": {"entities": {"chemical": [{"text": "apiin", "start": 51, "end": 56}, {"text": "phenolics", "start": 69, "end": 78}, {"text": "p-coumaric acid", "start": 116, "end": 131}]}}, "schema": []}
{"input": "Except for apiin, short-time steam-and water-blanching (1 min), respectively, did not cause significant losses of phenolic compounds, and thus proved to be the most suitable measures to ensure polyphenol retention.", "output": {"entities": {"chemical": [{"text": "apiin", "start": 11, "end": 16}, {"text": "phenolic", "start": 114, "end": 122}, {"text": "polyphenol", "start": 193, "end": 203}]}}, "schema": []}
{"input": "Consequently, blanching is a recommendable initial operation in the processing of parsley and marjoram into novel paste-like products.", "output": {"entities": {}}, "schema": []}
{"input": "Phenolic compounds and antioxidant activities of selected species of seaweeds from Danish coast.", "output": {"entities": {"chemical": [{"text": "Phenolic", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Water and ethanolic extracts of 16 species of seaweeds collected along the Danish coasts were screened for antioxidant activities using four in vitro antioxidant assays (2, 2-diphenyl-1-picrylhydrazyl radical scavenging activity, reducing power, ferrous ion-chelating and liposome model system).", "output": {"entities": {"chemical": [{"text": "2, 2-diphenyl-1-picrylhydrazyl", "start": 170, "end": 200}, {"text": "ferrous", "start": 246, "end": 253}]}}, "schema": []}
{"input": "Furthermore their effectiveness in retarding lipid peroxidation in fish oil was evaluated by an accelerated stability test.", "output": {"entities": {}}, "schema": []}
{"input": "Significant differences were observed in total and individual phenolic content and the antioxidant activities of seaweed species evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Ethanol was more efficient for polyphenol extraction than water.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 0, "end": 7}, {"text": "polyphenol", "start": 31, "end": 41}]}}, "schema": []}
{"input": "Polysiphonia fucoides and all the Fucus species tested showed highest radical scavenging activity, reducing power, inhibition of oxidation in liposome model system and in fish oil and were high in phenolic content.", "output": {"entities": {}}, "schema": []}
{"input": "These seaweeds could be potential rich sources of natural antioxidants for protection of foods against oxidation.", "output": {"entities": {}}, "schema": []}
{"input": "In general, the various antioxidative assays correlated well with the total phenolic content, indicating that algal polyphenols are active components in these extracts.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 116, "end": 127}]}}, "schema": []}
{"input": "However, in some of the antioxidative assays some species with low total phenolic content also showed good antioxidative effects indicating that some other co-extracted active compounds such as pigments and tocopherols in ethanolic extracts and sulphated polysaccharides, proteins or peptides in water extracts may also contribute to the overall antioxidant properties and this needs further investigation.", "output": {"entities": {"chemical": [{"text": "tocopherols", "start": 207, "end": 218}]}}, "schema": []}
{"input": "Relationships between harvest time and wine composition in Vitis vinifera L.", "output": {"entities": {}}, "schema": []}
{"input": "cv.", "output": {"entities": {}}, "schema": []}
{"input": "Cabernet Sauvignon 1.", "output": {"entities": {}}, "schema": []}
{"input": "Grape and wine chemistry.", "output": {"entities": {}}, "schema": []}
{"input": "The study aimed to quantify the effects of grape maturity on wine alcohol, phenolics, flavour compounds and polysaccharides in Vitis vinifera L.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 75, "end": 84}]}}, "schema": []}
{"input": "cv Cabernet Sauvignon.", "output": {"entities": {}}, "schema": []}
{"input": "Grapes were harvested at juice soluble solids from 20 to 26 degrees Brix which corresponded to a range of wine ethanol concentrations between 12% and 15. 5%.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 111, "end": 118}]}}, "schema": []}
{"input": "Grape anthocyanin and skin tannin concentration increased as ripening progressed, while seed tannin declined.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 6, "end": 17}, {"text": "tannin", "start": 27, "end": 33}, {"text": "tannin", "start": 93, "end": 99}]}}, "schema": []}
{"input": "In the corresponding wines, monomeric anthocyanin and wine tannin concentration increased with harvest date, consistent with an enhanced extraction of skin-derived phenolics.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 38, "end": 49}, {"text": "tannin", "start": 59, "end": 65}, {"text": "phenolics", "start": 164, "end": 173}]}}, "schema": []}
{"input": "In wines, there was an observed increase in yeast-derived metabolites, including volatile esters, dimethyl sulfide, glycerol and mannoproteins with harvest date.", "output": {"entities": {"chemical": [{"text": "esters", "start": 90, "end": 96}, {"text": "dimethyl sulfide", "start": 98, "end": 114}, {"text": "glycerol", "start": 116, "end": 124}]}}, "schema": []}
{"input": "Wine volatiles which were significantly influenced by harvest date were isobutyl methoxypyrazine, C (6) alcohols and hexyl acetate, all of which decreased as ripening progressed.", "output": {"entities": {"chemical": [{"text": "isobutyl methoxypyrazine", "start": 72, "end": 96}, {"text": "alcohols", "start": 104, "end": 112}, {"text": "hexyl acetate", "start": 117, "end": 130}]}}, "schema": []}
{"input": "The implications of harvest date for wine composition is discussed in terms of both grape composition and yeast metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "D/H exchange in C-H bonds of fatty acids: implication for geographical discrimination of food materials.", "output": {"entities": {"chemical": [{"text": "D", "start": 0, "end": 1}, {"text": "H", "start": 2, "end": 3}, {"text": "C-H", "start": 16, "end": 19}, {"text": "fatty acids", "start": 29, "end": 40}]}}, "schema": []}
{"input": "The stable isotope analysis of non-exchangeable hydrogen in food materials has been believed as a powerful tool for tracing geographical origins and delivery of the materials.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 48, "end": 56}]}}, "schema": []}
{"input": "However, little information is available for the D/H exchanges even in hydrophobic molecules, which leads to potential uncertainty on the observed results.", "output": {"entities": {"chemical": [{"text": "D", "start": 49, "end": 50}, {"text": "H", "start": 51, "end": 52}]}}, "schema": []}
{"input": "To further evaluate the reliability of hydrogen isotopes of organic molecules, we examined the isotope exchangeability in fatty acids within phospholipid bilayers exposed to D (2) O for 12h.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 39, "end": 47}, {"text": "fatty acids", "start": 122, "end": 133}, {"text": "D (2) O", "start": 174, "end": 181}]}}, "schema": []}
{"input": "The results indicate that the isotope ratio is clearly increased during all examines (e. g., 93-328 /1000 in 50% D (2) O), in which its magnitude depends on type of fatty acids and state of bilayers.", "output": {"entities": {"chemical": [{"text": "D (2) O", "start": 113, "end": 120}, {"text": "fatty acids", "start": 165, "end": 176}]}}, "schema": []}
{"input": "However, these results also indicate very clearly that the observed exchange rate is negligible if samples are exposed to natural abundance of deuterium (0. 0156%) in natural and laboratory environments before/during analysis.", "output": {"entities": {"chemical": [{"text": "deuterium", "start": 143, "end": 152}]}}, "schema": []}
{"input": "The potential to intensify sulforaphane formation in cooked broccoli (Brassica oleracea var. italica) using mustard seeds (Sinapis alba).", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 27, "end": 39}]}}, "schema": []}
{"input": "Sulforaphane, a naturally occurring cancer chemopreventive, is the hydrolysis product of glucoraphanin, the main glucosinolate in broccoli.", "output": {"entities": {"chemical": [{"text": "Sulforaphane", "start": 0, "end": 12}, {"text": "glucoraphanin", "start": 89, "end": 102}, {"text": "glucosinolate", "start": 113, "end": 126}]}}, "schema": []}
{"input": "The hydrolysis requires myrosinase isoenzyme to be present in sufficient activity; however, processing leads to its denaturation and hence reduced hydrolysis.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, the effect of adding mustard seeds, which contain a more resilient isoform of myrosinase, to processed broccoli was investigated with a view to intensify the formation of sulforaphane.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 186, "end": 198}]}}, "schema": []}
{"input": "Thermal inactivation of myrosinase from both broccoli and mustard seeds was studied.", "output": {"entities": {}}, "schema": []}
{"input": "Thermal degradation of broccoli glucoraphanin was investigated in addition to the effects of thermal processing on the formation of sulforaphane and sulforaphane nitrile.", "output": {"entities": {"chemical": [{"text": "glucoraphanin", "start": 32, "end": 45}, {"text": "sulforaphane", "start": 132, "end": 144}, {"text": "sulforaphane nitrile", "start": 149, "end": 169}]}}, "schema": []}
{"input": "Limited thermal degradation of glucoraphanin (less than 12%) was observed when broccoli was placed in vacuum sealed bag (sous vide) and cooked in a water bath at 100 degrees C for 8 and 12 min.", "output": {"entities": {"chemical": [{"text": "glucoraphanin", "start": 31, "end": 44}]}}, "schema": []}
{"input": "Boiling broccoli in water prevented the formation of any significant levels of sulforaphane due to inactivated myrosinase.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 79, "end": 91}]}}, "schema": []}
{"input": "However, addition of powdered mustard seeds to the heat processed broccoli significantly increased the formation of sulforaphane.", "output": {"entities": {"chemical": [{"text": "sulforaphane", "start": 116, "end": 128}]}}, "schema": []}
{"input": "Effect of thermal heating on some lignans in flax seeds, sesame seeds and rye.", "output": {"entities": {"chemical": [{"text": "lignans", "start": 34, "end": 41}]}}, "schema": []}
{"input": "Consumption of lignan rich food is presumed to have positive effects on human health.", "output": {"entities": {"chemical": [{"text": "lignan", "start": 15, "end": 21}]}}, "schema": []}
{"input": "As numerous foods are consumed mainly in processed form it is important to investigate the changes of the lignan content during processing.", "output": {"entities": {"chemical": [{"text": "lignan", "start": 106, "end": 112}]}}, "schema": []}
{"input": "To this end, unheated and heated sesame seeds, sesame products, rye grains, rye flour, rye bread and flax seeds were extracted by sonication with ethanol/water (70: 30, v: v) or sodium methoxide.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 146, "end": 153}, {"text": "sodium methoxide", "start": 178, "end": 194}]}}, "schema": []}
{"input": "The extracts were additionally hydrolysed enzymatically (beta-glucuronidase/arylsulphatase, cellulase), the compounds separated on a reversed phase column by gradient elution and detected by UV/ESI-MS in the negative ionisation multiple reaction monitoring mode (MRM).", "output": {"entities": {}}, "schema": []}
{"input": "Secoisolariciresinol, lariciresinol, pinoresinol, 7-hydroxymatairesinol, syringaresinol, isolariciresinol, secoisolariciresinol diglycoside, lariciresinol monoglycoside, pinoresinol mono-, di-and triglycoside, sesaminol, sesaminol triglycoside, sesamolinol and sesamolinol diglycoside were identified.", "output": {"entities": {"chemical": [{"text": "Secoisolariciresinol", "start": 0, "end": 20}, {"text": "lariciresinol", "start": 22, "end": 35}, {"text": "pinoresinol", "start": 37, "end": 48}, {"text": "7-hydroxymatairesinol", "start": 50, "end": 71}, {"text": "syringaresinol", "start": 73, "end": 87}, {"text": "isolariciresinol", "start": 89, "end": 105}, {"text": "secoisolariciresinol diglycoside", "start": 107, "end": 139}, {"text": "lariciresinol monoglycoside", "start": 141, "end": 168}, {"text": "pinoresinol mono-, di-and triglycoside", "start": 170, "end": 208}, {"text": "sesaminol", "start": 210, "end": 219}, {"text": "sesaminol triglycoside", "start": 221, "end": 243}, {"text": "sesamolinol", "start": 245, "end": 256}, {"text": "sesamolinol diglycoside", "start": 261, "end": 284}]}}, "schema": []}
{"input": "Moderate heating at 100 degrees C did not degrade the lignan aglycones and glycosides in dry foods.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, heating was responsible for the better extractability of the lignans.", "output": {"entities": {"chemical": [{"text": "lignans", "start": 74, "end": 81}]}}, "schema": []}
{"input": "If samples with high moisture content were heated, the degradation of the lignans in sesame seeds and rye was observed already at 100 degrees C.", "output": {"entities": {"chemical": [{"text": "lignans", "start": 74, "end": 81}]}}, "schema": []}
{"input": "Higher roasting temperatures caused degradation of aglycones and glycosides.", "output": {"entities": {}}, "schema": []}
{"input": "Especially at 250 degrees C, lignans were degraded rapidly in sesame seeds and rye but not in flax seeds.", "output": {"entities": {}}, "schema": []}
{"input": "Dung-shen (Codonopsis pilosula) attenuated the cardiac-impaired insulin-like growth factor II receptor pathway on myocardial cells.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies from our lab showed that increase in AngII in H9c2 cells causes elevated IGFII and IGFIIR through MEK and JNK, leading to rise in intracellular calcium, calcineurin activation by PLC-beta 3 via G alpha q, insertion into mitochondrial membranes of Bad, and apoptosis via caspases 9 and 3.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 161, "end": 168}]}}, "schema": []}
{"input": "Codonopsis pilosula is traditionally used to lower blood pressure.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of our study is to investigate if C. pilosula attenuates AngII plus Leu (27)-IGFII-induced calcium influx and apoptosis in H9c2 cardiomyoblasts.", "output": {"entities": {"chemical": [{"text": "Leu", "start": 80, "end": 83}, {"text": "calcium", "start": 103, "end": 110}]}}, "schema": []}
{"input": "C. pilosula significantly attenuated AngII induced IGFIIR promoter activity.", "output": {"entities": {}}, "schema": []}
{"input": "Leu (27)-IGFII was applied to enhance the AngII effect.", "output": {"entities": {"chemical": [{"text": "Leu", "start": 0, "end": 3}]}}, "schema": []}
{"input": "C. pilosula also reversed Ca (2 +) influx, MOMP and apoptosis increased by AngII plus Leu (27)-IGFII.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 26, "end": 34}, {"text": "Leu", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Molecular markers in IGFIIR apoptotic pathway (IGFIIR, calcineurin, etc.) and IGFIIR-G alpha q association were downregulated by C. pilosula.", "output": {"entities": {}}, "schema": []}
{"input": "However, p-Bad (Ser136) and Bcl-2 were increased.", "output": {"entities": {"chemical": [{"text": "Ser136", "start": 16, "end": 22}]}}, "schema": []}
{"input": "Therefore, C. pilosula suppresses AngII plus Leu (27)-IGFII-induced IGFII/IGFIIR pathway in myocardial cells.", "output": {"entities": {"chemical": [{"text": "Leu", "start": 45, "end": 48}]}}, "schema": []}
{"input": "Characterization and identification of gamma-irradiated sauces by electron spin resonance spectroscopy using different sample pretreatments.", "output": {"entities": {}}, "schema": []}
{"input": "Tomato ketchup, barbeque sauce, sweet chili sauce, and spaghetti sauce were gamma irradiated at 0, 1, 5, and 10 kGy.", "output": {"entities": {}}, "schema": []}
{"input": "Electron spin resonance (ESR) technique was used to characterize the irradiated sauces, targeting radiation-induced cellulose radicals and using a modified sample pretreatment method.", "output": {"entities": {}}, "schema": []}
{"input": "The samples were first washed with water, and then the residues were extracted with alcohol.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 84, "end": 91}]}}, "schema": []}
{"input": "The non-irradiated sauces exhibited the single central signal, whose intensity showed a significant increase on irradiation.", "output": {"entities": {}}, "schema": []}
{"input": "The ESR spectra from the radiation-induced cellulose radicals, with two side peaks (g = 2. 02012 and g = 1. 98516) equally spaced (+/- 3 mT) from the central signal, were also observed in the irradiated sauces.", "output": {"entities": {}}, "schema": []}
{"input": "The improvements in the central (natural) and radiation-induced (two side peaks corresponding to the cellulose radicals) signal intensities were obvious, when compared with routine freeze-drying and alcoholic-extraction techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Near infrared reflectance spectroscopy for determination of the geographical origin of wheat.", "output": {"entities": {}}, "schema": []}
{"input": "The feasibility of using near infrared reflectance (NIR) spectroscopy combined with chemometrics was investigated to discriminate wheat geographical origins.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 240 wheat samples from two growing years from four major wheat producing regions in China were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "After spectral data pre-treatment to wheat kernel and whole wheat flour, linear discriminant analysis (LDA) based on principal component scores and discriminant partial least squares analysis (DPLS) were applied to classify origins of samples excluding water spectrum.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that there were significant differences among wheat NIR spectra from different regions.", "output": {"entities": {}}, "schema": []}
{"input": "Wheat could be classified based on geographical origins with chemometrics.", "output": {"entities": {}}, "schema": []}
{"input": "DPLS were better than LDA for wheat origin determination.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, NIRS combined with chemometrics is a promising method for identifying wheat according to geographical origin, but the effectiveness should be verified further.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of tartrazine in beverage samples by stopped-flow analysis and three-way multivariate calibration of non-linear kinetic-spectrophotometric data.", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 17, "end": 27}]}}, "schema": []}
{"input": "The performance of MCR-ALS was studied in the modeling of non-linear kinetic-spectrophotometric data acquired by a stopped-flow system for the quantitation of tartrazine in the presence of brilliant blue and sunset yellow FCF as possible interferents.", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 159, "end": 169}, {"text": "brilliant blue and sunset yellow FCF", "start": 189, "end": 225}]}}, "schema": []}
{"input": "In the present work, MCR-ALS and U-PCA/RBL were firstly applied to remove the contribution of unexpected components not included in the calibration set.", "output": {"entities": {}}, "schema": []}
{"input": "Secondly, a polynomial function was used to model the non-linear data obtained by the implementation of the algorithms.", "output": {"entities": {}}, "schema": []}
{"input": "MCR-ALS was the only strategy that allowed the determination of tartrazine in test samples accurately.", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 64, "end": 74}]}}, "schema": []}
{"input": "Therefore, it was applied for the analysis of tartrazine in beverage samples with minimum sample preparation and short analysis time.", "output": {"entities": {"chemical": [{"text": "tartrazine", "start": 46, "end": 56}]}}, "schema": []}
{"input": "The proposed method was validated by comparison with a chromatographic procedure published in the literature.", "output": {"entities": {}}, "schema": []}
{"input": "Mean recovery values between 98% and 100% and relative errors of prediction values between 4% and 9% were indicative of the good performance of the method.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of ferrous sulfate fortification in germinated brown rice on seed iron concentration and bioavailability.", "output": {"entities": {"chemical": [{"text": "ferrous sulfate", "start": 10, "end": 25}, {"text": "iron", "start": 73, "end": 77}]}}, "schema": []}
{"input": "The present study evaluated the effectiveness of germination and iron fortification on iron concentration and bioavailability of brown rice.", "output": {"entities": {"chemical": [{"text": "iron", "start": 65, "end": 69}, {"text": "iron", "start": 87, "end": 91}]}}, "schema": []}
{"input": "Iron fortification during germination process with 0. 05-2 g/L ferrous sulfate increased the iron concentration in germinated brown rice from 1. 1 to 15. 6 times than those in raw brown rice.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "ferrous sulfate", "start": 63, "end": 78}, {"text": "iron", "start": 93, "end": 97}]}}, "schema": []}
{"input": "Based on the recommended dietary allowance of iron, maximum germination rate and gamma-aminobutyric acid, we recommend the brown rice fortified with 0. 25 g/L FeSO (4) as a suitable fortification level to use in germination process.", "output": {"entities": {"chemical": [{"text": "iron", "start": 46, "end": 50}, {"text": "gamma-aminobutyric acid", "start": 81, "end": 104}, {"text": "FeSO (4)", "start": 159, "end": 167}]}}, "schema": []}
{"input": "Iron fortification during the germination process has a positive effect on iron concentration and bioavailability.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "iron", "start": 75, "end": 79}]}}, "schema": []}
{"input": "A significant difference was observed among the cultivars in respect to the capacity for iron accumulation and bioavailability.", "output": {"entities": {"chemical": [{"text": "iron", "start": 89, "end": 93}]}}, "schema": []}
{"input": "Germination alone could improve in vitro iron solubility, but had no effect on iron bioavailability in Caco-2 cell, the additional fortification process should be combined to get high amount of bioavailable iron from the brown rice.", "output": {"entities": {"chemical": [{"text": "iron", "start": 41, "end": 45}, {"text": "iron", "start": 79, "end": 83}, {"text": "iron", "start": 207, "end": 211}]}}, "schema": []}
{"input": "Apoptosis of human breast cancer cells induced by microencapsulated betulinic acid from sour jujube fruits through the mitochondria transduction pathway.", "output": {"entities": {"chemical": [{"text": "betulinic acid", "start": 68, "end": 82}]}}, "schema": []}
{"input": "Betulinic acid (BA), a natural pentacyclic triterpenoid, was isolated from sour jujube fruits for the first time.", "output": {"entities": {"chemical": [{"text": "Betulinic acid", "start": 0, "end": 14}, {"text": "pentacyclic triterpenoid", "start": 31, "end": 55}]}}, "schema": []}
{"input": "An inclusion complex comprising BA and beta-cyclodextrin (beta-CD) was formed to improve the dissolution of BA, but little is known about its anticancer effect.", "output": {"entities": {"chemical": [{"text": "beta-cyclodextrin", "start": 39, "end": 56}, {"text": "beta-CD", "start": 58, "end": 65}]}}, "schema": []}
{"input": "In this study, the anti-proliferative and apoptosis mechanisms of BA-beta-CD on human breast cancer MCF-7 cells were further investigated.", "output": {"entities": {"chemical": [{"text": "BA-beta-CD", "start": 66, "end": 76}]}}, "schema": []}
{"input": "Experimental results confirmed that the complexation model inhibited the growth of MCF-7 cells in a dose-dependent manner, arrested cell cycle in the G2/M phase and induced apoptosis via the mitochondria transduction pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Gene and protein analyses showed that the complexation model significantly inhibited Bcl-2 expression and promoted Bax expression, causing caspase-3 and caspase-9 cascade activation.", "output": {"entities": {}}, "schema": []}
{"input": "These findings corroborated evidence on microencapsulated BA as an apoptosis inducer in MCF-7 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, sour jujube fruits may have potential use as a breast cancer chemotherapeutic agent.", "output": {"entities": {}}, "schema": []}
{"input": "Transglycosylation of stevioside to improve the edulcorant quality by lower substitution using cornstarch hydrolyzate and CGTase.", "output": {"entities": {"chemical": [{"text": "stevioside", "start": 22, "end": 32}]}}, "schema": []}
{"input": "Stevioside is an abundant sweetener extracted from Stevia rebaudiana leaf with a bitter aftertaste.", "output": {"entities": {"chemical": [{"text": "Stevioside", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Enzymatic transglycosylation of stevioside is a solution to improve the edulcorant quality of stevioside, but highly derivatised stevioside coming with high conversion of stevioside is undesired.", "output": {"entities": {"chemical": [{"text": "stevioside", "start": 32, "end": 42}, {"text": "stevioside", "start": 94, "end": 104}, {"text": "stevioside", "start": 129, "end": 139}, {"text": "stevioside", "start": 171, "end": 181}]}}, "schema": []}
{"input": "In this experiment, the transglycosylation of stevioside was investigated by using a commercial cyclodextrin glucanotransferase and cornstarch hydrolyzate.", "output": {"entities": {"chemical": [{"text": "stevioside", "start": 46, "end": 56}]}}, "schema": []}
{"input": "With controlled parameters, the product was mainly composed of mono-and di-glucosylated stevioside while the highest stevioside conversion reached 77. 11%.", "output": {"entities": {"chemical": [{"text": "mono-and di-glucosylated stevioside", "start": 63, "end": 98}, {"text": "stevioside", "start": 117, "end": 127}]}}, "schema": []}
{"input": "Neither kinetic nor thermodynamic factor stimulated the formation of high substituted steviosides.", "output": {"entities": {"chemical": [{"text": "steviosides", "start": 86, "end": 97}]}}, "schema": []}
{"input": "The simultaneous hydrolysis in the reaction might inhibit the yield of highly substituted steviosides.", "output": {"entities": {"chemical": [{"text": "steviosides", "start": 90, "end": 101}]}}, "schema": []}
{"input": "Effects of oil exposure and dispersant use upon environmental adaptation performance and fitness in the European sea bass, Dicentrarchus labrax.", "output": {"entities": {}}, "schema": []}
{"input": "The worldwide increasing recourse to chemical dispersants to deal with oil spills in marine coastal ecosystems is a controversial issue.", "output": {"entities": {}}, "schema": []}
{"input": "Yet, there exists no adequate methodology that can provide reliable predictions of how oil and dispersant-treated oil can affect relevant organism or population-level performance.", "output": {"entities": {}}, "schema": []}
{"input": "The primary objective of the present study was to examine and compare the effects of exposure to untreated oil (weathered Arabian light crude oil), chemically dispersed oil (Finasol, TOTAL-Fluides) or dispersant alone, upon the ability of fish for environmental adaptation.", "output": {"entities": {}}, "schema": []}
{"input": "To reach that goal, we implemented high-throughput, non-lethal challenge tests to estimate individual hypoxia and heat tolerance as surrogate measures of their capacity to face natural contingencies.", "output": {"entities": {}}, "schema": []}
{"input": "Experimental populations were then transferred into semi-natural tidal ponds and correlates of individuals' fitness (growth and survival) were monitored over a period of 6 months.", "output": {"entities": {}}, "schema": []}
{"input": "In accordance with our stated objectives, the contamination conditions tested corresponded to those observed under an oil slick drifting in shallow waters.", "output": {"entities": {}}, "schema": []}
{"input": "Our results revealed that the response of control fish to both challenges was variable among individuals and temporally stable (repeatable) over a 2-month period.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to chemical dispersant did not affect the repeatability of fish performance.", "output": {"entities": {}}, "schema": []}
{"input": "However, exposure to oil or to a mixture of oil plus dispersant affected the repeatability of individuals' responses to the experimental challenge tests.", "output": {"entities": {}}, "schema": []}
{"input": "At population level, no difference between contamination treatments was observed in the distribution of individual responses to the hypoxia and temperature challenge tests.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, no correlation between hypoxia tolerance and heat tolerance was noticed.", "output": {"entities": {}}, "schema": []}
{"input": "During the field experiment, hypoxia tolerance and heat tolerance were found to be determinants of survivorship.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, experimental groups exposed to oil or to dispersant-treated oil displayed significantly lower survival than control or dispersant-exposed groups.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, from the four experimental populations tested, the one exposed to chemically dispersed oil presented the lowest growth rate.", "output": {"entities": {}}, "schema": []}
{"input": "High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 11, "end": 20}]}}, "schema": []}
{"input": "Recent studies suggest an association of vitamin D with obesity, diabetes and cardiovascular diseases.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 41, "end": 50}]}}, "schema": []}
{"input": "We analyzed the association of serum vitamin D level assessed by 25-hydroxyvitamin D (3) {25 (OH) D (3)} with nonalcoholic fatty liver disease (NAFLD) in apparently healthy men.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 37, "end": 46}, {"text": "25-hydroxyvitamin D (3)", "start": 65, "end": 88}, {"text": "25 (OH) D (3)", "start": 90, "end": 103}]}}, "schema": []}
{"input": "We performed a cross-sectional study of 6, 567 Korean men who participated in a health screening program, evaluating the association of serum 25 (OH) D (3) levels with the risk of NAFLD assessed by abdominal ultrasonogram.", "output": {"entities": {"chemical": [{"text": "25 (OH) D (3)", "start": 142, "end": 155}]}}, "schema": []}
{"input": "Of the participants, 43. 6% had NAFLD and 21. 1% had metabolic syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Age, serum calcium, and aspartate aminotransferase levels showed weak but significant positive correlations with 25 (OH) D (3) level; total cholesterol, triglycerides, low-density lipoprotein cholesterol and fasting insulin level showed weak but significant negative correlations with 25 (OH) D (3) level.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 11, "end": 18}, {"text": "aspartate", "start": 24, "end": 33}, {"text": "25 (OH) D (3)", "start": 113, "end": 126}, {"text": "cholesterol", "start": 140, "end": 151}, {"text": "triglycerides", "start": 153, "end": 166}, {"text": "cholesterol", "start": 192, "end": 203}, {"text": "25 (OH) D (3)", "start": 285, "end": 298}]}}, "schema": []}
{"input": "The mean 25 (OH) D (3) level was significantly lower in participants with NAFLD than in those without (38. 7 +/- 9. 0 vs. 39. 7 +/- 9. 7 nmol/L, p < 0. 001).", "output": {"entities": {"chemical": [{"text": "25 (OH) D (3)", "start": 9, "end": 22}]}}, "schema": []}
{"input": "When participants were divided into tertiles based on mean 25 (OH) D (3) level, the proportion with NAFLD significantly increased as mean 25 (OH) D (3) level decreased (40. 0, 45. 0 and 45. 9%, p for linear trend < 0. 001).", "output": {"entities": {"chemical": [{"text": "25 (OH) D (3)", "start": 59, "end": 72}, {"text": "25 (OH) D (3)", "start": 138, "end": 151}]}}, "schema": []}
{"input": "Multiple logistic regression analyses with NAFLD as the dependent variable showed that the tertiles with lower 25 (OH) D (3) levels had a significantly increased risk for NAFLD compared with the highest tertile, even after adjusting for body mass index and metabolic syndrome (OR 1. 247 and 1. 408 vs. the highest tertile, p < 0. 001).", "output": {"entities": {"chemical": [{"text": "25 (OH) D (3)", "start": 111, "end": 124}]}}, "schema": []}
{"input": "Thus, participants with higher serum 25 (OH) D (3) showed a significantly reduced risk for NAFLD compared with the low 25 (OH) D (3) groups, independent of obesity and metabolic syndrome.", "output": {"entities": {"chemical": [{"text": "25 (OH) D (3)", "start": 37, "end": 50}, {"text": "25 (OH) D (3)", "start": 119, "end": 132}]}}, "schema": []}
{"input": "Peer influences on drug self-administration: an econometric analysis in socially housed rats.", "output": {"entities": {}}, "schema": []}
{"input": "Social-learning theories of substance use propose that members of peer groups influence the drug use of other members by selectively modeling, reinforcing, and punishing either abstinence-related or drug-related behaviors.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of the present study was to examine the social influences on cocaine self-administration in isolated and socially housed rats, under conditions where the socially housed rats were tested simultaneously with their partner in the same chamber.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 75, "end": 82}]}}, "schema": []}
{"input": "To this end, male rats were obtained at weaning and housed in isolated or pair-housed conditions for 6 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Rats were then implanted with intravenous catheters and cocaine self-administration was examined in custom-built operant conditioning chambers that allowed two rats to be tested simultaneously.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 56, "end": 63}]}}, "schema": []}
{"input": "For some socially housed subjects, both rats had simultaneous access to cocaine; for others, only one rat of the pair had access to cocaine.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 72, "end": 79}, {"text": "cocaine", "start": 132, "end": 139}]}}, "schema": []}
{"input": "An econometric analysis was applied to the data, and the reinforcing strength of cocaine was measured by examining consumption (i. e. quantity demanded) and elasticity of demand as a function of price, which was manipulated by varying the dose and ratio requirements on a fixed ratio schedule of reinforcement.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 81, "end": 88}]}}, "schema": []}
{"input": "Cocaine consumption decreased as a function of price in all groups.", "output": {"entities": {"chemical": [{"text": "Cocaine", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Elasticity of demand did not vary across groups, but consumption was significantly lower in socially housed rats paired with a rat without access to cocaine.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 149, "end": 156}]}}, "schema": []}
{"input": "These data suggest that the presence of an abstaining peer decreases the reinforcing strength of cocaine, thus supporting the development of social interventions in drug abuse prevention and treatment programs.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Inhibition of G beta gamma-subunit signaling potentiates morphine-induced antinociception but not respiratory depression, constipation, locomotion, and reward.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 57, "end": 65}]}}, "schema": []}
{"input": "Inhibition of G beta gamma-subunit signaling to phospholipase C beta 3 has been shown to potentiate morphine-mediated antinociception while attenuating the development of tolerance and dependence in mice.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 100, "end": 108}]}}, "schema": []}
{"input": "The objective of this study was to determine the effect of G beta gamma-subunit inhibition on antinociception and other pharmacological effects, such as respiratory depression, constipation, and hyperlocomotion, mediated by the mu-opioid receptor.", "output": {"entities": {}}, "schema": []}
{"input": "The G beta gamma-subunit inhibitor, gallein, was administered to C57BL/6J mice by intraperitoneal injection before morphine, and data were compared with mice treated with vehicle, morphine, or gallein alone.", "output": {"entities": {"chemical": [{"text": "gallein", "start": 36, "end": 43}, {"text": "morphine", "start": 115, "end": 123}, {"text": "morphine", "start": 180, "end": 188}, {"text": "gallein", "start": 193, "end": 200}]}}, "schema": []}
{"input": "Morphine-induced antinociception was measured using the 55 degrees C warm-water tail-withdrawal test.", "output": {"entities": {"chemical": [{"text": "Morphine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Pretreatment with gallein produced a dose-dependent potentiation of morphine-mediated antinociception, producing up to a 10-fold leftward shift in the morphine dose-response curve and extending the duration of antinociception induced by a single dose of morphine.", "output": {"entities": {"chemical": [{"text": "gallein", "start": 18, "end": 25}, {"text": "morphine", "start": 68, "end": 76}, {"text": "morphine", "start": 151, "end": 159}, {"text": "morphine", "start": 254, "end": 262}]}}, "schema": []}
{"input": "Gallein pretreatment also prevented acute antinociceptive tolerance induced by morphine.", "output": {"entities": {"chemical": [{"text": "Gallein", "start": 0, "end": 7}, {"text": "morphine", "start": 79, "end": 87}]}}, "schema": []}
{"input": "In contrast, the dose-dependent respiratory depression and hyperlocomotion induced by morphine were not potentiated by gallein pretreatment.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 86, "end": 94}, {"text": "gallein", "start": 119, "end": 126}]}}, "schema": []}
{"input": "Similarly, gallein pretreatment did not potentiate morphine-conditioned place preference responses or morphine-induced constipation, as measured as a reduction in excreta.", "output": {"entities": {"chemical": [{"text": "gallein", "start": 11, "end": 18}, {"text": "morphine", "start": 51, "end": 59}, {"text": "morphine", "start": 102, "end": 110}]}}, "schema": []}
{"input": "These results suggest that selectively inhibiting G beta gamma-mediated signaling may selectively increase mu-opioid receptor-mediated antinociception without matching increases in adverse physiological effects.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclodextrin alleviates neuronal storage of cholesterol in Niemann-Pick C disease without evidence of detectable blood-brain barrier permeability.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 44, "end": 55}]}}, "schema": []}
{"input": "Niemann-Pick type C disease is an inherited autosomal recessive neurodegenerative disorder characterised by the accumulation of unesterified cholesterol and sphingolipids within the endosomal/lysosomal compartments.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 141, "end": 152}, {"text": "sphingolipids", "start": 157, "end": 170}]}}, "schema": []}
{"input": "It has been observed that the administration of hydroxypropyl-beta-cyclodextrin (HPBCD) delays onset of clinical symptoms and reduces accumulation of cholesterol and gangliosides within neuronal cells.", "output": {"entities": {"chemical": [{"text": "hydroxypropyl-beta-cyclodextrin", "start": 48, "end": 79}, {"text": "HPBCD", "start": 81, "end": 86}, {"text": "cholesterol", "start": 150, "end": 161}, {"text": "gangliosides", "start": 166, "end": 178}]}}, "schema": []}
{"input": "It was assumed that HPBCD exerts its action by readily entering the CNS and directly interacting with neurones and other brain cells to facilitate removal of stored cholesterol from the late endosomal/lysosomal compartment.", "output": {"entities": {"chemical": [{"text": "HPBCD", "start": 20, "end": 25}, {"text": "cholesterol", "start": 165, "end": 176}]}}, "schema": []}
{"input": "Here, we present evidence that refutes this hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "We use two well established techniques for accurately measuring brain uptake of solutes from blood and show that there is no significant crossing of HPBCD into the brain.", "output": {"entities": {"chemical": [{"text": "HPBCD", "start": 149, "end": 154}]}}, "schema": []}
{"input": "The two techniques are brain in situ perfusion and intraperitoneal injection followed by multi-time-point regression analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Neither study demonstrates significant, time-dependent uptake of HPBCD in either adult or neonatal mice.", "output": {"entities": {"chemical": [{"text": "HPBCD", "start": 65, "end": 70}]}}, "schema": []}
{"input": "However, the volume of distribution available to HPBCD (0. 113 +/- 0. 010 ml/g) exceeds the accepted values for plasma and vascular volume of the brain.", "output": {"entities": {"chemical": [{"text": "HPBCD", "start": 49, "end": 54}]}}, "schema": []}
{"input": "In fact, it is nearly three times larger than that for sucrose (0. 039 +/- 0. 006 ml/g).", "output": {"entities": {"chemical": [{"text": "sucrose", "start": 55, "end": 62}]}}, "schema": []}
{"input": "We propose that this indicates cell surface binding of HPBCD to the endothelium of the cerebral vasculature and may provide a mechanism for the mobilisation and clearance of cholesterol from the CNS.", "output": {"entities": {"chemical": [{"text": "HPBCD", "start": 55, "end": 60}, {"text": "cholesterol", "start": 174, "end": 185}]}}, "schema": []}
{"input": "Differential gene expression in ER alpha-positive and ER alpha-negative breast cancer cells upon leptin stimulation.", "output": {"entities": {}}, "schema": []}
{"input": "In postmenopausal women, adipositas represents a serious risk factor for cancer development and progression.", "output": {"entities": {}}, "schema": []}
{"input": "White adipose tissue secretes the 16 kDa hormone leptin which plays a key role in the regulation of appetite and metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "An increasing number of reports indicate that leptin also interferes with signal transduction pathways implicated in the development of breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "In our previous study, we identified the estrogen receptor alpha (ER alpha) as a relevant enhancer of leptin-induced signal transduction leading to transactivation of signal transducer and activator of transcription 3 (Stat3).", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 41, "end": 49}]}}, "schema": []}
{"input": "The purpose of this study is the investigation of specific target gene expression in response to leptin-mediated Stat3 signaling.", "output": {"entities": {}}, "schema": []}
{"input": "We performed a comprehensive microarray analysis of ER alpha-positive and ER alpha-negative MDA-MB-231 cells upon leptin treatment and identified 49 genes which showed a significant ER alpha-dependent regulation in leptin-treated MDA-MB-231 cells.", "output": {"entities": {}}, "schema": []}
{"input": "There was no intersection with genes which were merely up-or downregulated by ER alpha expression and only 9 and 11 genes overlapping targets which were regulated by leptin stimulation either in ER alpha-expressing or ER alpha-negative MDA-MB-231 cells, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "To demonstrate the specificity, expression of three target genes was validated by quantitative real-time PCR.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, these data imply that leptin can induce a different set of target genes dependent on ER alpha expression, which might contribute to the development and progression of cancer diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Phosphorus-doped silicon nanocrystals exhibiting mid-infrared localized surface plasmon resonance.", "output": {"entities": {"chemical": [{"text": "Phosphorus", "start": 0, "end": 10}, {"text": "silicon", "start": 17, "end": 24}]}}, "schema": []}
{"input": "Localized surface plasmon resonances (LSPRs) enable tailoring of the optical response of nanomaterials through their free carrier concentration, morphology, and dielectric environment.", "output": {"entities": {}}, "schema": []}
{"input": "Recent efforts to expand the spectral range of usable LSPR frequencies into the infrared successfully demonstrated LSPRs in doped semiconductor nanocrystals.", "output": {"entities": {}}, "schema": []}
{"input": "Despite silicon' s importance for electronic and photonic applications, no LSPRs have been reported for doped silicon nanocrystals.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 8, "end": 15}, {"text": "silicon", "start": 110, "end": 117}]}}, "schema": []}
{"input": "Here we demonstrate doped silicon nanocrystals synthesized via a nonthermal plasma technique that exhibits tunable LSPRs in the energy range of 0. 07-0. 3 eV or mid-infrared wavenumbers of 600-2500 cm (-1).", "output": {"entities": {"chemical": [{"text": "silicon", "start": 26, "end": 33}]}}, "schema": []}
{"input": "Immunosensor based on immobilization of antigenic peptide NS5A-1 from HCV and silk fibroin in nanostructured films.", "output": {"entities": {}}, "schema": []}
{"input": "The peptide NS5A-1 (PPLLESWKDPDYVPPWHG), derived from hepatitis C virus (HCV) NS5A protein, was immobilized into layer-by-layer (LbL) silk fibroin (SF) films.", "output": {"entities": {}}, "schema": []}
{"input": "Deposition was monitored by UV-vis absorption measurements at each bilayer deposited.", "output": {"entities": {}}, "schema": []}
{"input": "The interaction SF/peptide film induced secondary structure in NS5A-1 as indicated by fluorescence and circular dichroism (CD) measurements.", "output": {"entities": {}}, "schema": []}
{"input": "Voltammetric sensor (SF/NS5A-1) properties were observed when the composite film was tested in the presence of anti-HCV.", "output": {"entities": {}}, "schema": []}
{"input": "The peptide-silk fibroin interaction studied here showed new architectures for immunosensors based on antigenic peptides and SF as a suitable immobilization matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Developing the potential ophthalmic applications of pilocarpine entrapped into polyvinylpyrrolidone-poly (acrylic acid) nanogel dispersions prepared by gamma radiation.", "output": {"entities": {"chemical": [{"text": "pilocarpine", "start": 52, "end": 63}, {"text": "polyvinylpyrrolidone", "start": 79, "end": 99}, {"text": "poly (acrylic acid)", "start": 100, "end": 119}]}}, "schema": []}
{"input": "The aim of this study was to improve the stability and bioavailability of pilocarpine in order to maintain an adequate concentration of the pilocarpine at the site of action for prolonged period of time.", "output": {"entities": {"chemical": [{"text": "pilocarpine", "start": 74, "end": 85}, {"text": "pilocarpine", "start": 140, "end": 151}]}}, "schema": []}
{"input": "Thus, pH-sensitive polyvinylpyrrolidone-poly (acrylic acid) (PVP/PAAc) nanogels prepared by gamma radiation-induced polymerization of acrylic acid (AAc) in an aqueous solution of polyvinylpyrrolidone (PVP) as a template polymer were used to encapsulate pilocarpine.", "output": {"entities": {"chemical": [{"text": "polyvinylpyrrolidone", "start": 19, "end": 39}, {"text": "poly (acrylic acid)", "start": 40, "end": 59}, {"text": "PVP", "start": 61, "end": 64}, {"text": "PAAc", "start": 65, "end": 69}, {"text": "acrylic acid", "start": 134, "end": 146}, {"text": "AAc", "start": 148, "end": 151}, {"text": "polyvinylpyrrolidone", "start": 179, "end": 199}, {"text": "PVP", "start": 201, "end": 204}, {"text": "pilocarpine", "start": 253, "end": 264}]}}, "schema": []}
{"input": "Factors affecting size and encapsulation efficiency were optimized to obtain nanogel suitable for entrapping drug efficiently.", "output": {"entities": {}}, "schema": []}
{"input": "The PVP/PAAc nanogel particles were characterized by dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM), and their size can be controlled by the feed composition and concentration as well as the irradiation dose.", "output": {"entities": {"chemical": [{"text": "PVP", "start": 4, "end": 7}, {"text": "PAAc", "start": 8, "end": 12}]}}, "schema": []}
{"input": "Pilocarpine was loaded into the nanogel particles through electrostatic interactions where the AAc-rich nanogels exhibited the highest loading efficiency.", "output": {"entities": {"chemical": [{"text": "Pilocarpine", "start": 0, "end": 11}, {"text": "AAc", "start": 95, "end": 98}]}}, "schema": []}
{"input": "The transmittance, mucoadhesion, and rheological characteristics of the nanogel particles were studied to evaluate their ocular applicability.", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro release study conducted in simulated tear fluid showed a relatively long sustained release of pilocarpine from the prepared PVP/PAAc nanogel particles if compared with pilocarpine in solution.", "output": {"entities": {"chemical": [{"text": "pilocarpine", "start": 107, "end": 118}, {"text": "PVP", "start": 137, "end": 140}, {"text": "PAAc", "start": 141, "end": 145}, {"text": "pilocarpine", "start": 181, "end": 192}]}}, "schema": []}
{"input": "High-Performance Surface Acoustic Wave Immunosensing System on a PEG/Aptamer Hybridized Surface.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 65, "end": 68}]}}, "schema": []}
{"input": "Label-free immunoassay systems have the advantages of procedural simplicity and a low construction cost of surfaces for immunosensing.", "output": {"entities": {}}, "schema": []}
{"input": "When label-free immunoassay systems are considered, the nonspecific adsorption of unwanted materials should be eliminated unless it aids in the detection of error.", "output": {"entities": {}}, "schema": []}
{"input": "PEG is well-known as a blocking agent for the prevention of the adsorption of nonspecific binding materials when coimmobilized with ligands for targets such as antibodies and oligonucleotides.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The construction strategy for PEG/ligand coimmobilized surfaces is an important point in the preparation of a high-performance assays because the physiological condition of the ligand depends strongly on its interaction with the PEG chain.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 30, "end": 33}, {"text": "PEG", "start": 229, "end": 232}]}}, "schema": []}
{"input": "In this report, we investigate the interaction between thrombin and a thrombin-binding aptamer (TBA) on a PEG/TBA coimmobilized surface by using a shear horizontal surface acoustic wave (SAW) sensor.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 106, "end": 109}]}}, "schema": []}
{"input": "The thrombin-TBA binding property shows remarkable differences with changes in the PEG density and the distance from the gold surface to the aptamer.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 83, "end": 86}]}}, "schema": []}
{"input": "Influence of the bifunctional chelator on the pharmacokinetic properties of 99mTc (CO) 3-labeled cyclic alpha-melanocyte stimulating hormone analog.", "output": {"entities": {"chemical": [{"text": "99mTc (CO) 3", "start": 76, "end": 88}, {"text": "cyclic alpha-melanocyte stimulating hormone", "start": 97, "end": 140}]}}, "schema": []}
{"input": "Aiming at the design of specific melanocortin-1 receptor (MC1R) targeted imaging probes, we report on the effect of different azolyl-ring substitution patterns (carboxylate at the 4-position and/or methyl groups at the 3, 5 positions) of pyrazolyl-diamine bifunctional chelators (Pz (2)-Pz (4)) on the pharmacokinetic profile of the (99m) Tc (CO) 3-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone derivative, beta AlaNleCycMSH (hex).", "output": {"entities": {"chemical": [{"text": "azolyl", "start": 126, "end": 132}, {"text": "carboxylate", "start": 161, "end": 172}, {"text": "methyl", "start": 198, "end": 204}, {"text": "pyrazolyl-diamine", "start": 238, "end": 255}, {"text": "(99m) Tc (CO) 3", "start": 333, "end": 348}, {"text": "lactam", "start": 357, "end": 363}, {"text": "cyclized alpha-melanocyte stimulating hormone", "start": 371, "end": 416}, {"text": "beta AlaNleCycMSH (hex)", "start": 429, "end": 452}]}}, "schema": []}
{"input": "Three pyrazolyl-diamine-containing chelators were conjugated to beta AlaNleCycMSHhex, with the resulting peptide conjugates displaying subnanomolar MC1R binding affinity.", "output": {"entities": {"chemical": [{"text": "pyrazolyl-diamine", "start": 6, "end": 23}, {"text": "beta AlaNleCycMSHhex", "start": 64, "end": 84}]}}, "schema": []}
{"input": "Biodistribution studies in B16F1 melanoma-bearing mice show that all radiopeptides present a good melanoma uptake.", "output": {"entities": {}}, "schema": []}
{"input": "The introduction of a carboxylate group in the azolyl-ring leads to a remarkable reduction of the kidney (> 89%) and liver (> 91%) accumulation for (99m) Tc (CO) 3-Pz (3)-beta AlaNleCycMSH (hex) and (99m) Tc (CO) 3-Pz (4)-beta AlaNleCycMSH (hex) when compared to the radiopeptide (99m) Tc (CO) 3-Pz (1)-beta AlaNleCycMSH (hex), where that group is absent.", "output": {"entities": {"chemical": [{"text": "carboxylate", "start": 22, "end": 33}, {"text": "azolyl", "start": 47, "end": 53}, {"text": "(99m) Tc (CO) 3-Pz (3)-beta AlaNleCycMSH (hex)", "start": 148, "end": 194}, {"text": "(99m) Tc (CO) 3-Pz (4)-beta AlaNleCycMSH (hex)", "start": 199, "end": 245}, {"text": "(99m) Tc (CO) 3-Pz (1)-beta AlaNleCycMSH (hex)", "start": 280, "end": 326}]}}, "schema": []}
{"input": "The good tumor uptake and favorable tumor-to-nontarget-organs ratios of (99m) Tc (CO) 3-Pz (3)-beta AlaNleCycMSH (hex) and (99m) Tc (CO) 3-Pz (4)-beta AlaNleCycMSH (hex) highlights the potential of both compounds as melanoma imaging agents.", "output": {"entities": {"chemical": [{"text": "(99m) Tc (CO) 3-Pz (3)-beta AlaNleCycMSH (hex)", "start": 72, "end": 118}, {"text": "(99m) Tc (CO) 3-Pz (4)-beta AlaNleCycMSH (hex)", "start": 123, "end": 169}]}}, "schema": []}
{"input": "Vegfrecine, an Inhibitor of VEGF Receptor Tyrosine Kinases Isolated from the Culture Broth of Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "Vegfrecine", "start": 0, "end": 10}, {"text": "Tyrosine", "start": 42, "end": 50}]}}, "schema": []}
{"input": "A new inhibitor of VEGF receptor tyrosine kinases, vegfrecine (1), was isolated from the culture broth of Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 33, "end": 41}, {"text": "vegfrecine", "start": 51, "end": 61}]}}, "schema": []}
{"input": "MK931-CF8.", "output": {"entities": {}}, "schema": []}
{"input": "The molecular structure of 1 was determined by NMR and MS analysis combined with synthesis.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 1 showed potent inhibitory activity against vascular endothelial growth factor receptor (VEGFR) tyrosine kinases in in vitro enzyme assays, but platelet-derived growth factor receptors (PDGFRs), fibroblast growth factor receptor (FGFR), and epidermal growth factor receptor (EGFR) responded only weakly.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 1 is a promising new selective VEGFR inhibitor for investigating new treatments of cancer and inflammatory diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Reduction of dimethylarsinic acid to the highly toxic dimethylarsinous acid by rats and rat liver cytosol.", "output": {"entities": {"chemical": [{"text": "dimethylarsinic acid", "start": 13, "end": 33}, {"text": "dimethylarsinous acid", "start": 54, "end": 75}]}}, "schema": []}
{"input": "Dimethylarsinic acid (DMAs (V)), the major urinary metabolite of inorganic arsenic, is weakly cytotoxic, whereas its reduced form, dimethylarsinous acid (DMAs (III)), is highly toxic.", "output": {"entities": {"chemical": [{"text": "Dimethylarsinic acid", "start": 0, "end": 20}, {"text": "DMAs (V)", "start": 22, "end": 30}, {"text": "arsenic", "start": 75, "end": 82}, {"text": "dimethylarsinous acid", "start": 131, "end": 152}, {"text": "DMAs (III)", "start": 154, "end": 164}]}}, "schema": []}
{"input": "Although glutathione S-transferase omega 1 (GSTO1) and arsenic methyltransferase have been shown or thought to catalyze DMAs (V) reduction, their role in DMAs (V) reduction in vivo, or in cell extracts is uncertain.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 9, "end": 22}, {"text": "arsenic", "start": 55, "end": 62}, {"text": "DMAs (V)", "start": 120, "end": 128}, {"text": "DMAs (V)", "start": 154, "end": 162}]}}, "schema": []}
{"input": "Therefore, the reduction of DMAs (V) to DMAs (III) in rats and in rat liver cytosol was studied to better understand its mechanism.", "output": {"entities": {"chemical": [{"text": "DMAs (V)", "start": 28, "end": 36}, {"text": "DMAs (III)", "start": 40, "end": 50}]}}, "schema": []}
{"input": "To assess DMAs (V) reduction in rats, a novel procedure was devised based on following the accumulation of red blood cell (RBC)-bound dimethylarsenic (DMAs), which represents DMAs (III), in the blood of DMAs (V)-injected anesthetized rats.", "output": {"entities": {"chemical": [{"text": "DMAs (V)", "start": 10, "end": 18}, {"text": "dimethylarsenic", "start": 134, "end": 149}, {"text": "DMAs", "start": 151, "end": 155}, {"text": "DMAs (III)", "start": 175, "end": 185}, {"text": "DMAs (V)", "start": 203, "end": 211}]}}, "schema": []}
{"input": "These studies indicated that rats reduced DMAs (V) to DMAs (III) to a significant extent, as in 90 min 31% of the injected 50 mu mol/kg DMAs (V) dose was converted to DMAs (III) that was sequestered by the circulating erythrocytes.", "output": {"entities": {"chemical": [{"text": "DMAs (V)", "start": 42, "end": 50}, {"text": "DMAs (III)", "start": 54, "end": 64}, {"text": "DMAs (V)", "start": 136, "end": 144}, {"text": "DMAs (III)", "start": 167, "end": 177}]}}, "schema": []}
{"input": "Pretreatment of rats with glutathione (GSH) depletors (phorone or BSO) delayed the elimination of DMAs (V) and the accumulation of RBC-bound DMAs, whereas the indirect methyltransferase inhibitor periodate-oxidized adenosine was without effect.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 26, "end": 37}, {"text": "GSH", "start": 39, "end": 42}, {"text": "phorone", "start": 55, "end": 62}, {"text": "BSO", "start": 66, "end": 69}, {"text": "DMAs (V)", "start": 98, "end": 106}, {"text": "DMAs", "start": 141, "end": 145}, {"text": "periodate", "start": 196, "end": 205}, {"text": "adenosine", "start": 215, "end": 224}]}}, "schema": []}
{"input": "Assessment of DMAs (V)-reducing activity of rat liver cytosol revealed that reduction of DMAs (V) required cytosolic protein and GSH and was inhibited by thiol reagents, GSSG and dehydroascorbate.", "output": {"entities": {"chemical": [{"text": "DMAs (V)", "start": 14, "end": 22}, {"text": "DMAs (V)", "start": 89, "end": 97}, {"text": "GSH", "start": 129, "end": 132}, {"text": "thiol", "start": 154, "end": 159}, {"text": "GSSG", "start": 170, "end": 174}, {"text": "dehydroascorbate", "start": 179, "end": 195}]}}, "schema": []}
{"input": "Although thioredoxin reductase (TRR) inhibitors (aurothioglucose and Sb (III)) inhibited cytosolic DMAs (V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs (V) reduction.", "output": {"entities": {"chemical": [{"text": "aurothioglucose", "start": 49, "end": 64}, {"text": "Sb (III)", "start": 69, "end": 77}, {"text": "DMAs (V)", "start": 99, "end": 107}, {"text": "NADPH", "start": 144, "end": 149}, {"text": "DMAs (V)", "start": 205, "end": 213}]}}, "schema": []}
{"input": "On ultrafiltration of the cytosol through a 3 kDa filter, the reducing activity in the retentate was lost but was largely restored by NADPH.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 134, "end": 139}]}}, "schema": []}
{"input": "Such experiments also suggested that the reducing enzyme was larger than 100 kDa and was not GSTO1.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, reduction of DMAs (V) to the highly toxic DMAs (III) in rats and rat liver cytosol is a GSH-dependent enzymatic process, yet its mechanism remains uncertain.", "output": {"entities": {"chemical": [{"text": "DMAs (V)", "start": 25, "end": 33}, {"text": "DMAs (III)", "start": 54, "end": 64}, {"text": "GSH", "start": 100, "end": 103}]}}, "schema": []}
{"input": "Embryonic and induced pluripotent stem cells: understanding, creating, and exploiting the nano-niche for regenerative medicine.", "output": {"entities": {}}, "schema": []}
{"input": "Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any specialized cell type of the human body, and therefore, ESC/iPSC-derived cell types offer great potential for regenerative medicine.", "output": {"entities": {}}, "schema": []}
{"input": "However, key to realizing this potential requires a strong understanding of stem cell biology, techniques to maintain stem cells, and strategies to manipulate cells to efficiently direct cell differentiation toward a desired cell type.", "output": {"entities": {}}, "schema": []}
{"input": "As nanoscale science and engineering continues to produce novel nanotechnology platforms, which inform, infiltrate, and impinge on many aspects of everyday life, it is no surprise that stem cell research is turning toward developments in nanotechnology to answer research questions and to overcome obstacles in regenerative medicine.", "output": {"entities": {}}, "schema": []}
{"input": "Here we discuss recent advances in ESC and iPSC manipulation using nanomaterials and highlight future challenges within this area of research.", "output": {"entities": {}}, "schema": []}
{"input": "Large-scale spinning assembly of neat, morphology-defined, graphene-based hollow fibers.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 59, "end": 67}]}}, "schema": []}
{"input": "Large-scale assembly of graphenes in a well-controlled macroscopic fashion is important for practical applications.", "output": {"entities": {"chemical": [{"text": "graphenes", "start": 24, "end": 33}]}}, "schema": []}
{"input": "We have developed a facile and straightforward approach for continuous fabrication of neat, morphology-defined, graphene-based hollow fibers (HFs) via a coaxial two-capillary spinning strategy.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 112, "end": 120}]}}, "schema": []}
{"input": "With a high throughput, HFs and necklace-like HFs of graphene oxide have been well-controlled produced with the ease of functionalization and conversion to graphene HFs via simply thermal or chemical reduction.", "output": {"entities": {"chemical": [{"text": "graphene oxide", "start": 53, "end": 67}, {"text": "graphene", "start": 156, "end": 164}]}}, "schema": []}
{"input": "This work paves the way toward the mass production of graphene-based HFs with desirable functionalities and morphologies for many of important applications in fluidics, catalysis, purification, separation, and sensing.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 54, "end": 62}]}}, "schema": []}
{"input": "Kisspeptin as a link between metabolism and reproduction: Evidences from rodent and primate studies.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in metabolic status gate reproductive activity by still incompletely deciphered mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Many neuropeptides have been shown to be involved in restraining hypothalamic gonadotropin releasing hormone (GnRH) release under conditions of negative energy balance.", "output": {"entities": {}}, "schema": []}
{"input": "Broadly, on the basis of their effect on feeding, these can be grouped as orexigenic and anorexigenic neuropeptides.", "output": {"entities": {}}, "schema": []}
{"input": "Reciprocally correlated, in response to changes in systemic concentrations of metabolic hormones, the secretion of orexigenic neuropeptides increases while that of anorexigenic neuropeptides decreases during conditions of food restriction.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, kisspeptin signaling in hypothalamus has appeared as a pivotal regulator of the GnRH pulse generator.", "output": {"entities": {}}, "schema": []}
{"input": "Kisspeptin apparently does not affect feeding, but in light of accumulating data, it has emerged as one of the major conduits in relaying body metabolic status information to GnRH neurons.", "output": {"entities": {}}, "schema": []}
{"input": "The present review examines such data obtained from rodent and primate models, which suggest kisspeptin-Kiss1r signaling as a possible pathway providing a link between metabolism and reproduction.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of novel 7-membered cyclic amide derivatives that inhibit 11beta-hydroxysteroid dehydrogenase type 1.", "output": {"entities": {"chemical": [{"text": "7-membered cyclic amide", "start": 19, "end": 42}, {"text": "11beta-hydroxysteroid", "start": 68, "end": 89}]}}, "schema": []}
{"input": "A series of novel 5-trans-hydroxyadamantan-2-yl-5, 6, 7, 8-tetrahydropyrazolo [4, 3-c] azepin-4 (1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described.", "output": {"entities": {"chemical": [{"text": "5-trans-hydroxyadamantan-2-yl-5, 6, 7, 8-tetrahydropyrazolo [4, 3-c] azepin-4 (1H)-ones", "start": 18, "end": 105}, {"text": "11beta-hydroxysteroid", "start": 119, "end": 140}]}}, "schema": []}
{"input": "We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included in X-ray co-crystal structures.", "output": {"entities": {"chemical": [{"text": "7-membered cyclic amide", "start": 20, "end": 43}]}}, "schema": []}
{"input": "Further optimization using docking studies led to highly potent inhibitors 15b and 27, which furthermore showed the potent efficacy in in vivo studies.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical tagging of a drug target using 5-sulfonyl tetrazole.", "output": {"entities": {"chemical": [{"text": "5-sulfonyl tetrazole", "start": 40, "end": 60}]}}, "schema": []}
{"input": "Irreversible modification is one of the most promising strategies to identify cellular receptors of bioactive small molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report that receptor proteins can be chemically tagged using a 5-sulfonyl tetrazole probe.", "output": {"entities": {"chemical": [{"text": "5-sulfonyl tetrazole", "start": 71, "end": 91}]}}, "schema": []}
{"input": "5-Sulfonyl tetrazole easily accepted nucleophilic attack of thiol groups, while 5-sulfinyl tetrazole did not.", "output": {"entities": {"chemical": [{"text": "5-Sulfonyl tetrazole", "start": 0, "end": 20}, {"text": "thiol", "start": 60, "end": 65}, {"text": "5-sulfinyl tetrazole", "start": 80, "end": 100}]}}, "schema": []}
{"input": "These functional groups were introduced into probe molecules of a natural product.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclosporine A, an immunosuppressant produced by a microbe, was derivatized to possess 5-sulfonyl tetrazole and a tag group, which enabled chemical tagging of cyclophilin A, the cellular receptor of cyclosporine A.", "output": {"entities": {"chemical": [{"text": "Cyclosporine A", "start": 0, "end": 14}, {"text": "5-sulfonyl tetrazole", "start": 87, "end": 107}, {"text": "cyclosporine A", "start": 199, "end": 213}]}}, "schema": []}
{"input": "Cyclosporine A derivative possessing 5-sulfinyl tetrazole could not tag cyclophilin A.", "output": {"entities": {"chemical": [{"text": "Cyclosporine A", "start": 0, "end": 14}, {"text": "5-sulfinyl tetrazole", "start": 37, "end": 57}]}}, "schema": []}
{"input": "This technique will allow efficient identification of cellular receptors of bioactive small molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Anion inhibition studies of the alpha-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.", "output": {"entities": {}}, "schema": []}
{"input": "An alpha-carbonic anhydrase (CA, EC 4. 2. 1. 1) has been recently cloned and characterized in the human pathogenic bacterium Vibrio cholerae, denominated VchCA (Del Prete et al. J. Med. Chem. 2012, 55, 10742).", "output": {"entities": {}}, "schema": []}
{"input": "This enzyme shows a good catalytic activity for the CO2 hydration reaction, comparable to that of the human (h) isoform hCA I.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 52, "end": 55}]}}, "schema": []}
{"input": "Many inorganic anions and several small molecules were investigated as VchCA inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Inorganic anions such as cyanate, cyanide, hydrogen sulfide, hydrogen sulfite, and trithiocarbonate were effective VchCA inhibitors with inhibition constants in the range of 33-88 mu M.", "output": {"entities": {"chemical": [{"text": "cyanate", "start": 25, "end": 32}, {"text": "cyanide", "start": 34, "end": 41}, {"text": "hydrogen sulfide", "start": 43, "end": 59}, {"text": "hydrogen sulfite", "start": 61, "end": 77}, {"text": "trithiocarbonate", "start": 83, "end": 99}]}}, "schema": []}
{"input": "Other effective inhibitors were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, with KIs of 7-43 mu M.", "output": {"entities": {"chemical": [{"text": "diethyldithiocarbamate", "start": 32, "end": 54}, {"text": "sulfamide", "start": 56, "end": 65}, {"text": "sulfamate", "start": 67, "end": 76}, {"text": "phenylboronic acid", "start": 78, "end": 96}, {"text": "phenylarsonic acid", "start": 101, "end": 119}]}}, "schema": []}
{"input": "Halides (bromide, iodide), bicarbonate and carbonate were much less effective VchCA inhibitors, with KIs in the range of 4. 64-28. 0mM.", "output": {"entities": {"chemical": [{"text": "Halides", "start": 0, "end": 7}, {"text": "bromide", "start": 9, "end": 16}, {"text": "iodide", "start": 18, "end": 24}, {"text": "bicarbonate", "start": 27, "end": 38}, {"text": "carbonate", "start": 43, "end": 52}]}}, "schema": []}
{"input": "The resistance of VchCA to bicarbonate inhibition may represent an evolutionary adaptation of this enzyme to living in an environment rich in this ion, such as the gastrointestinal tract, as bicarbonate is a virulence enhancer of this bacterium.", "output": {"entities": {"chemical": [{"text": "bicarbonate", "start": 27, "end": 38}, {"text": "bicarbonate", "start": 191, "end": 202}]}}, "schema": []}
{"input": "Synthesis of tetrazole analogues of phosphonohydroxamic acids: an attempt to improve the inhibitory activity against the DXR.", "output": {"entities": {"chemical": [{"text": "phosphonohydroxamic acids", "start": 36, "end": 61}]}}, "schema": []}
{"input": "This work is focused on the design of new antimicrobial drugs and on the development of lipophilic inhibitors of the DXR, the second enzyme of the MEP pathway for the biosynthesis of isoprene units in most bacteria, by replacing the phosphonate group of fosmidomycin derivatives by a tetrazoyl moiety capable of multiple hydrogen bonding.", "output": {"entities": {"chemical": [{"text": "isoprene", "start": 183, "end": 191}, {"text": "phosphonate", "start": 233, "end": 244}, {"text": "fosmidomycin", "start": 254, "end": 266}, {"text": "tetrazoyl", "start": 284, "end": 293}, {"text": "hydrogen", "start": 321, "end": 329}]}}, "schema": []}
{"input": "The N-and C-substituted tetrazole analogues of phosphonohydroxamate inhibitors were synthesized and tested on the DXR of Escherichia coli.", "output": {"entities": {"chemical": [{"text": "N", "start": 4, "end": 5}, {"text": "C", "start": 10, "end": 11}, {"text": "tetrazole", "start": 24, "end": 33}, {"text": "phosphonohydroxamate", "start": 47, "end": 67}]}}, "schema": []}
{"input": "This work points out the hypothesis that the phosphonate/phosphate recognition site might be too rigid to accommodate other functional groups.", "output": {"entities": {"chemical": [{"text": "phosphonate", "start": 45, "end": 56}, {"text": "phosphate", "start": 57, "end": 66}]}}, "schema": []}
{"input": "3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (sigma 1) receptor.", "output": {"entities": {"chemical": [{"text": "pentacycloundecylamines", "start": 31, "end": 54}]}}, "schema": []}
{"input": "Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases.", "output": {"entities": {"chemical": [{"text": "Pentacycloundecylamine", "start": 0, "end": 22}, {"text": "PCU", "start": 24, "end": 27}]}}, "schema": []}
{"input": "Here we show for the first time a 3D quantitative structure-activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (sigma 1) receptor.", "output": {"entities": {"chemical": [{"text": "aza-PCU", "start": 108, "end": 115}]}}, "schema": []}
{"input": "A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q (2)) regression value of 0. 6, and a non-cross validated r (2) of 0. 9.", "output": {"entities": {}}, "schema": []}
{"input": "The CoMFA model was effective at predicting the sigma-1 activities of a test set with an r (2) > 0. 7.", "output": {"entities": {}}, "schema": []}
{"input": "We also describe here the docking of the PCU-derived compounds into a homology model of the sigma-1 (sigma 1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor.", "output": {"entities": {"chemical": [{"text": "PCU", "start": 41, "end": 44}]}}, "schema": []}
{"input": "Based on docking studies we evaluated in a [(3) H] pentazocine binding assay an oxa-PCU, NGP1-01 (IC50 = 1. 78 mu M) and its phenethyl derivative (IC50 = 1. 54 mu M).", "output": {"entities": {"chemical": [{"text": "[(3) H] pentazocine", "start": 43, "end": 62}, {"text": "oxa-PCU", "start": 80, "end": 87}, {"text": "NGP1-01", "start": 89, "end": 96}, {"text": "phenethyl", "start": 125, "end": 134}]}}, "schema": []}
{"input": "Results from these studies can be used to develop new compounds with specific affinity for the sigma-1 (sigma 1) receptor.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation of antibacterial mode of action for traditional and amphiphilic aminoglycosides.", "output": {"entities": {"chemical": [{"text": "aminoglycosides", "start": 78, "end": 93}]}}, "schema": []}
{"input": "Aminoglycoside represents a class of versatile and broad spectrum antibacterial agents.", "output": {"entities": {"chemical": [{"text": "Aminoglycoside", "start": 0, "end": 14}]}}, "schema": []}
{"input": "In an effort to revive the antibacterial activity against aminoglycoside resistant bacteria, our laboratory has developed two new classes of aminoglycoside, pyranmycin and amphiphilic neomycin (NEOF004).", "output": {"entities": {"chemical": [{"text": "aminoglycoside", "start": 58, "end": 72}, {"text": "aminoglycoside", "start": 141, "end": 155}, {"text": "pyranmycin", "start": 157, "end": 167}, {"text": "neomycin", "start": 184, "end": 192}, {"text": "NEOF004", "start": 194, "end": 201}]}}, "schema": []}
{"input": "The former resembles the traditional aminoglycoside, neomycin.", "output": {"entities": {"chemical": [{"text": "aminoglycoside", "start": 37, "end": 51}, {"text": "neomycin", "start": 53, "end": 61}]}}, "schema": []}
{"input": "The latter, albeit derived from neomycin, appears to exert antibacterial action via a different mode of action.", "output": {"entities": {"chemical": [{"text": "neomycin", "start": 32, "end": 40}]}}, "schema": []}
{"input": "In order to discern that these aminoglycoside derivatives have distinct antibacterial mode of action, RNA-binding affinity and fluorogenic dye were employed.", "output": {"entities": {"chemical": [{"text": "aminoglycoside", "start": 31, "end": 45}]}}, "schema": []}
{"input": "These studies, together with our previous investigation, confirm that pyranmycin exhibit the traditional antibacterial mode of action of aminoglycosides by binding toward the bacterial rRNA.", "output": {"entities": {"chemical": [{"text": "aminoglycosides", "start": 137, "end": 152}]}}, "schema": []}
{"input": "On the other hand, the amphiphilic neomycin, NEOF004 disrupts the bacterial cell wall.", "output": {"entities": {"chemical": [{"text": "neomycin", "start": 35, "end": 43}, {"text": "NEOF004", "start": 45, "end": 52}]}}, "schema": []}
{"input": "In a broader perspective, it verifies that structurally modified neomycin can exert different antibacterial mode of action leading to the revival of activity against aminoglycoside resistant bacteria.", "output": {"entities": {"chemical": [{"text": "neomycin", "start": 65, "end": 73}, {"text": "aminoglycoside", "start": 166, "end": 180}]}}, "schema": []}
{"input": "Structure-based discovery of cellular-active allosteric inhibitors of FAK.", "output": {"entities": {}}, "schema": []}
{"input": "In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo [4, 3-c] [2, 1] benzothiazines targeted for the FAK allosteric site were carried out.", "output": {"entities": {"chemical": [{"text": "pyrazolo [4, 3-c] [2, 1] benzothiazines", "start": 102, "end": 141}]}}, "schema": []}
{"input": "Based on the X-ray structural analysis of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1, 5-dihydropyrazolo [4, 3-c] [2, 1] benzothiazine 4, 4-dioxide 1 with FAK, we designed and prepared 1, 5-dimethyl-1, 5-dihydropyrazolo [4, 3-c] [2, 1] benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases.", "output": {"entities": {"chemical": [{"text": "8-(4-ethylphenyl)-5-methyl-1, 5-dihydropyrazolo [4, 3-c] [2, 1] benzothiazine 4, 4-dioxide", "start": 79, "end": 169}, {"text": "1, 5-dimethyl-1, 5-dihydropyrazolo [4, 3-c] [2, 1] benzothiazin", "start": 207, "end": 270}]}}, "schema": []}
{"input": "The optimized compound, N-(4-tert-butylbenzyl)-1, 5-dimethyl-1, 5-dihydropyrazolo [4, 3-c] [2, 1] benzothiazin-8-amine 4, 4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC50 = 0. 64 mu M) and in cellular assays (IC50 = 7. 1 mu M).", "output": {"entities": {"chemical": [{"text": "N-(4-tert-butylbenzyl)-1, 5-dimethyl-1, 5-dihydropyrazolo [4, 3-c] [2, 1] benzothiazin-8-amine 4, 4-dioxide", "start": 24, "end": 131}]}}, "schema": []}
{"input": "These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents.", "output": {"entities": {}}, "schema": []}
{"input": "Stability of black cohosh triterpene glycosides and polyphenols: Potential clinical relevance.", "output": {"entities": {"chemical": [{"text": "triterpene glycosides", "start": 26, "end": 47}, {"text": "polyphenols", "start": 52, "end": 63}]}}, "schema": []}
{"input": "Concurrent to a clinical trial of black cohosh for menopausal hot flashes, the long-term stability of the black cohosh, over the duration of the clinical trial, was examined.", "output": {"entities": {}}, "schema": []}
{"input": "Analytical results showed that the major constituents, both triterpene glycosides and polyphenols, were stable over the 3-year period of testing.", "output": {"entities": {"chemical": [{"text": "triterpene glycosides", "start": 60, "end": 81}, {"text": "polyphenols", "start": 86, "end": 97}]}}, "schema": []}
{"input": "These results indicate that a black cohosh product stored for several years in a controlled environment does not undergo significant changes in its major constituents.", "output": {"entities": {}}, "schema": []}
{"input": "These results have implications not only for clinical research in natural products, but for basic science, as well as the dietary supplements industry.", "output": {"entities": {}}, "schema": []}
{"input": "Evidence-based review and assessment of botulinum neurotoxin for the treatment of urologic conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions.", "output": {"entities": {}}, "schema": []}
{"input": "To assess the efficacy and safety of BoNT injections for the treatment of certain urologic conditions, including detrusor sphincter dyssynergia (DSD), lower urinary tract symptoms due to benign prostatic hyperplasia (BPH), and detrusor overactivity (both neurogenic [NDO] and idiopathic [IDO]), an expert panel reviewed evidence from the published literature.", "output": {"entities": {}}, "schema": []}
{"input": "Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials.", "output": {"entities": {}}, "schema": []}
{"input": "Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for autonomic disorders were also reviewed and updated.", "output": {"entities": {}}, "schema": []}
{"input": "The panel evaluated evidence at several levels, supporting BoNT as a class, for the serotypes BoNT-A and BoNT-B, as well as for the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima).", "output": {"entities": {}}, "schema": []}
{"input": "The panel ultimately made recommendations on the use of BoNT for the management of these urologic conditions based upon the strength of clinical evidence and following the AAN classification scale.", "output": {"entities": {}}, "schema": []}
{"input": "For the treatment of DSD, the evidence supported a Level B recommendation for the use of A/Ona; A/Abo, A/Inco, and B/Rima received a Level U recommendation.", "output": {"entities": {}}, "schema": []}
{"input": "For the treatment of NDO, there was sufficient clinical evidence to support a Level A recommendation for BoNT-A as well as for both A/Ona and A/Abo; no published data were identified for either A/Inco or B/Rima (Level U).", "output": {"entities": {}}, "schema": []}
{"input": "For the treatment of IDO, the evidence supported a Level A recommendation for A/Ona; A/Inco, A/Abo, and B/Rima received a Level U recommendation.", "output": {"entities": {}}, "schema": []}
{"input": "For the management of BPH, the evidence supported a Level B recommendation for BoNT and A/Ona; no published studies were identified for A/Abo, A/Inco, or B/Rima, warranting a Level U recommendation for these three formulations.", "output": {"entities": {}}, "schema": []}
{"input": "Further studies are needed to evaluate the efficacy and safety of BoNT for the management of urologic conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism of profenofos to 4-bromo-2-chlorophenol, a specific and sensitive exposure biomarker.", "output": {"entities": {"chemical": [{"text": "profenofos", "start": 14, "end": 24}, {"text": "4-bromo-2-chlorophenol", "start": 28, "end": 50}]}}, "schema": []}
{"input": "Profenofos is a direct acting phosphorothioate organophosphorus (OP) pesticide capable of inhibiting beta-esterases such as acetylcholinesterase, butyrylcholinesterase, and carboxylesterase.", "output": {"entities": {"chemical": [{"text": "Profenofos", "start": 0, "end": 10}, {"text": "phosphorothioate organophosphorus", "start": 30, "end": 63}]}}, "schema": []}
{"input": "Profenofos is known to be detoxified to the biologically inactive metabolite, 4-bromo-2-chlorophenol (BCP); however, limited data are available regarding the use of urinary BCP as an exposure biomarker in humans.", "output": {"entities": {"chemical": [{"text": "Profenofos", "start": 0, "end": 10}, {"text": "4-bromo-2-chlorophenol", "start": 78, "end": 100}, {"text": "BCP", "start": 102, "end": 105}, {"text": "BCP", "start": 173, "end": 176}]}}, "schema": []}
{"input": "A pilot study conducted in Egyptian agriculture workers, demonstrated that urinary BCP levels prior to application (3. 3-30. 0 mu g/g creatinine) were elevated to 34. 5-3566 mu g/g creatinine during the time workers were applying profenofos to cotton fields.", "output": {"entities": {"chemical": [{"text": "BCP", "start": 83, "end": 86}, {"text": "creatinine", "start": 134, "end": 144}, {"text": "creatinine", "start": 181, "end": 191}, {"text": "profenofos", "start": 230, "end": 240}]}}, "schema": []}
{"input": "Subsequently, the in vitro enzymatic formation of BCP was examined using pooled human liver microsomes and recombinant human cytochrome P-450s (CYPs) incubated with profenofos.", "output": {"entities": {"chemical": [{"text": "BCP", "start": 50, "end": 53}, {"text": "profenofos", "start": 165, "end": 175}]}}, "schema": []}
{"input": "Of the nine human CYPs studied, only CYPs 3A4, 2B6, and 2C19 were able to metabolize profenofos to BCP.", "output": {"entities": {"chemical": [{"text": "profenofos", "start": 85, "end": 95}, {"text": "BCP", "start": 99, "end": 102}]}}, "schema": []}
{"input": "Kinetic studies indicated that CYP 2C19 has the lowest Km, 0. 516 mu M followed by 2B6 (Km = 1. 02 mu M) and 3A4 (Km = 18. 9 mu M).", "output": {"entities": {}}, "schema": []}
{"input": "The Vmax for BCP formation was 47. 9, 25. 1, and 19. 2nmol/min/nmol CYP for CYP2B6, 2C19, and 3A4, respectively.", "output": {"entities": {"chemical": [{"text": "BCP", "start": 13, "end": 16}]}}, "schema": []}
{"input": "Intrinsic clearance (Vmax/Km) values of 48. 8, 46. 9, and 1. 02ml/min/nmol CYP 2C19, 2B6, and 3A4, respectively, indicate that CYP2C19 and CYP2B6 are primarily responsible for the detoxification of profenofos.", "output": {"entities": {"chemical": [{"text": "profenofos", "start": 198, "end": 208}]}}, "schema": []}
{"input": "These findings support the use of urinary BCP as a biomarker of exposure to profenofos in humans and suggest polymorphisms in CYP 2C19 and CYP 2B6 as potential biomarkers of susceptibility.", "output": {"entities": {"chemical": [{"text": "BCP", "start": 42, "end": 45}, {"text": "profenofos", "start": 76, "end": 86}]}}, "schema": []}
{"input": "Signaling of an allosteric, nanomolar potent, low molecular weight agonist for the follicle-stimulating hormone receptor.", "output": {"entities": {}}, "schema": []}
{"input": "Follicle-stimulating hormone (FSH) activates FSH receptors (FSHR) in granulosa cells to induce follicle differentiation, growth and estradiol production.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 132, "end": 141}]}}, "schema": []}
{"input": "FSH is used clinically to treat female infertility and is administered by injection.", "output": {"entities": {}}, "schema": []}
{"input": "To increase patient convenience and compliance, compound homogeneity and composition, low molecular weight (LMW), orally bioavailable, FSHR agonists are now being developed to replace FSH.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we present the signaling mechanisms of a newly developed LMW dihydropyridine agonist of the FSHR, Org 214444-0.", "output": {"entities": {"chemical": [{"text": "dihydropyridine", "start": 76, "end": 91}, {"text": "Org 214444-0", "start": 113, "end": 125}]}}, "schema": []}
{"input": "Org 214444-0 is shown to be a stereoselective, nanomolar potent FSHR agonist and selective over the structurally related LHR and TSHR.", "output": {"entities": {"chemical": [{"text": "Org 214444-0", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Org 214444-0 is an allosteric agonist interacting with the transmembrane region of the FSHR.", "output": {"entities": {"chemical": [{"text": "Org 214444-0", "start": 0, "end": 12}]}}, "schema": []}
{"input": "When co-incubated with FSH, Org 214444-0 augments FSH' s potency in binding (6. 5-fold) and adenylyl cyclase/cAMP activation (3. 5-fold) in a concentration-dependent manner.", "output": {"entities": {"chemical": [{"text": "Org 214444-0", "start": 28, "end": 40}, {"text": "cAMP", "start": 109, "end": 113}]}}, "schema": []}
{"input": "Like FSH, Org 214444-0 induces FSHR internalization and is only marginally effective in stimulating phospholipase C.", "output": {"entities": {"chemical": [{"text": "Org 214444-0", "start": 10, "end": 22}]}}, "schema": []}
{"input": "Moreover, Org 214444-0 stimulates cAMP and estradiol production in human granulosa cells in culture and supports the follicular phase in mature female rats.", "output": {"entities": {"chemical": [{"text": "Org 214444-0", "start": 10, "end": 22}, {"text": "cAMP", "start": 34, "end": 38}, {"text": "estradiol", "start": 43, "end": 52}]}}, "schema": []}
{"input": "We conclude that Org 214444-0 is a bonafide FSHR agonist.", "output": {"entities": {"chemical": [{"text": "Org 214444-0", "start": 17, "end": 29}]}}, "schema": []}
{"input": "A high-throughput-compatible, fluorescence anisotropy-based assay for ATP-dependent supercoiled DNA relaxation by human topoisomerase II alpha.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 70, "end": 73}]}}, "schema": []}
{"input": "A novel, high-throughput-compatible assay for the ATP-dependent supercoiled DNA relaxing activity of human topoisomerase II alpha (hTopoII alpha) is described.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 50, "end": 53}]}}, "schema": []}
{"input": "The principle of detection is the preferential binding of the oligodeoxyribonucleotide BODIPY-TMR-5'-TTCTTCTTCT-3' to relaxed double-stranded plasmid containing the triplex forming sequence (TTC) 9 versus the supercoiled plasmid.", "output": {"entities": {"chemical": [{"text": "BODIPY", "start": 87, "end": 93}, {"text": "TMR", "start": 94, "end": 97}]}}, "schema": []}
{"input": "Binding of the oligonucleotide to the plasmid increases the fluorescence anisotropy of the BODIPY-TMR label.", "output": {"entities": {"chemical": [{"text": "BODIPY", "start": 91, "end": 97}, {"text": "TMR", "start": 98, "end": 101}]}}, "schema": []}
{"input": "Optimization of the assay conditions was conducted to maximize the signal and the activity of the topoisomerase.", "output": {"entities": {}}, "schema": []}
{"input": "The multiwell assay plate-based fluorescence anisotropy assay gave the same values for the potencies of several previously reported inhibitors of hTopoII alpha as a gel electrophoresis-based assay of DNA relaxation.", "output": {"entities": {}}, "schema": []}
{"input": "Design and synthesis of bicyclic pyrazinone and pyrimidinone amides as potent TF-FVIIa inhibitors.", "output": {"entities": {"chemical": [{"text": "bicyclic pyrazinone and pyrimidinone amides", "start": 24, "end": 67}]}}, "schema": []}
{"input": "Bicyclic pyrazinone and pyrimidinone amides were designed and synthesized as potent TF-FVIIa inhibitors.", "output": {"entities": {"chemical": [{"text": "Bicyclic pyrazinone and pyrimidinone amides", "start": 0, "end": 43}]}}, "schema": []}
{"input": "SAR demonstrated that the S2 and S3 pockets of FVIIa prefer to bind small, lipophilic groups.", "output": {"entities": {}}, "schema": []}
{"input": "An X-ray crystal structure of optimized compound 9b bound in the active site of FVIIa showed that the bicyclic scaffold provides 5 hydrogen bonding interactions in addition to projecting groups for interactions within the S1, S2 and S3 pockets.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 131, "end": 139}]}}, "schema": []}
{"input": "Compound 9b showed excellent FVIIa potency, good selectivity against FIXa, Xa, XIa and chymotrypsin, and good clotting activity.", "output": {"entities": {}}, "schema": []}
{"input": "Efficient synthesis of anacardic acid analogues and their antibacterial activities.", "output": {"entities": {"chemical": [{"text": "anacardic acid", "start": 23, "end": 37}]}}, "schema": []}
{"input": "Anacardic acid derivatives exhibit a broad range of biological activities.", "output": {"entities": {"chemical": [{"text": "Anacardic acid", "start": 0, "end": 14}]}}, "schema": []}
{"input": "In this report, an efficient method for the synthesis of anacardic acid derivatives was explored, and a small set of salicylic acid variants synthesised retaining a constant hydrophobic element (a naphthyl tail).", "output": {"entities": {"chemical": [{"text": "anacardic acid", "start": 57, "end": 71}, {"text": "salicylic acid", "start": 117, "end": 131}, {"text": "naphthyl", "start": 197, "end": 205}]}}, "schema": []}
{"input": "The naphthyl side chain was introduced via Wittig reaction and the aldehyde installed using directed ortho-metalation reaction of the substituted o-anisic acids.", "output": {"entities": {"chemical": [{"text": "naphthyl", "start": 4, "end": 12}, {"text": "aldehyde", "start": 67, "end": 75}, {"text": "o-anisic acids", "start": 146, "end": 160}]}}, "schema": []}
{"input": "The failure of ortho-metalation using unprotected carboxylic acid group compelled us to use directed ortho-metalation in which a tertiary amide was used as a strong ortho-directing group.", "output": {"entities": {"chemical": [{"text": "carboxylic acid", "start": 50, "end": 65}, {"text": "tertiary amide", "start": 129, "end": 143}]}}, "schema": []}
{"input": "In the initial route, tertiary amide cleavage during final step was challenging, but cleaving the tertiary amide before Wittig reaction was beneficial.", "output": {"entities": {"chemical": [{"text": "tertiary amide", "start": 22, "end": 36}, {"text": "tertiary amide", "start": 98, "end": 112}]}}, "schema": []}
{"input": "The Wittig reaction with protected carboxylic group (methyl ester) resulted in side-products whereas using sodium salt resulted in higher yields.", "output": {"entities": {"chemical": [{"text": "carboxylic", "start": 35, "end": 45}, {"text": "methyl ester", "start": 53, "end": 65}, {"text": "sodium", "start": 107, "end": 113}]}}, "schema": []}
{"input": "The novel compounds were screened for antibacterial activity and cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Although substitution on the salicylic head group enhanced antibacterial activities they also enhanced cytotoxicity.", "output": {"entities": {"chemical": [{"text": "salicylic", "start": 29, "end": 38}]}}, "schema": []}
{"input": "Substituted piperidinyl glycinyl 2-cyano-4, 5-methano pyrrolidines as potent and stable dipeptidyl peptidase IV inhibitors.", "output": {"entities": {"chemical": [{"text": "piperidinyl glycinyl 2-cyano-4, 5-methano pyrrolidines", "start": 12, "end": 66}]}}, "schema": []}
{"input": "Synthesis and structure-activity relationship of a series of substituted piperidinyl glycine 2-cyano-4, 5-methano pyrroline DPP-IV inhibitors are described.", "output": {"entities": {"chemical": [{"text": "piperidinyl glycine 2-cyano-4, 5-methano pyrroline", "start": 73, "end": 123}]}}, "schema": []}
{"input": "Improvement of the inhibitory activity and chemical stability of this series of compounds was respectively achieved by the introduction of bulky groups at the 4-position and 1-position of the piperidinyl glycine, leading to a series of potent and stable DPP-IV inhibitors.", "output": {"entities": {"chemical": [{"text": "piperidinyl glycine", "start": 192, "end": 211}]}}, "schema": []}
{"input": "A multivalent peptide as an activator of hypoxia inducible factor-1 alpha.", "output": {"entities": {}}, "schema": []}
{"input": "Hypoxia inducible factor-1 alpha (HIF-1 alpha) is a transcription factor found in mammalian cells under hypoxia.", "output": {"entities": {}}, "schema": []}
{"input": "While HIF-1 alpha in hypoxia translocates to the nucleus where it transcribes the target genes including vascular endothelial growth factor (VEGF) mRNA, HIF-1 alpha is degraded under normoxia, which involves its proline hydroxylation and subsequent binding to the von Hippel-Lindau protein-Elongin B-Elogin C (VBC) complex.", "output": {"entities": {"chemical": [{"text": "proline", "start": 212, "end": 219}]}}, "schema": []}
{"input": "Previously, peptide inhibitors against this interaction between hydroxylated HIF-1 alpha and VBC have been developed to stabilize the transcriptional activity of HIF-1 alpha by preventing the degradation of the protein even under normoxia.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the specific inhibition by these peptides, their poor inhibition potency needs to be improved for further clinical application.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we have designed and prepared a streptavidin-based multivalent peptide inhibitor against the HIF-1 alpha-VBC complexation.", "output": {"entities": {}}, "schema": []}
{"input": "We have evaluated the potency of the multivalent peptide in terms of stabilization of HIF-1 alpha and the downstream effect.", "output": {"entities": {}}, "schema": []}
{"input": "As the result, we have found that the inhibitor showed about 13-fold lowered IC50 value compared with that of the corresponding monovalent peptide, thereby activating HIF-1 alpha and leading to up-regulation of VEGF protein at the cellular level.", "output": {"entities": {}}, "schema": []}
{"input": "The alpha 3 beta 4 * nicotinic acetylcholine receptor subtype mediates nicotine reward and physical nicotine withdrawal signs independently of the alpha 5 subunit in the mouse.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 31, "end": 44}, {"text": "nicotine", "start": 71, "end": 79}, {"text": "nicotine", "start": 100, "end": 108}]}}, "schema": []}
{"input": "The 15q25 gene cluster contains genes that code for the alpha 5, alpha 3, and beta 4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 95, "end": 108}, {"text": "nicotine", "start": 231, "end": 239}]}}, "schema": []}
{"input": "The limited available animal studies implicate a role for the alpha 5 and beta 4 nAChR subunits in nicotine dependence and withdrawal; however studies focusing on the behavioral role of the alpha 3 beta 4 * nAChR receptor subtype in nicotine dependence are lacking.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 99, "end": 107}, {"text": "nicotine", "start": 233, "end": 241}]}}, "schema": []}
{"input": "Because of the apparent role of the alpha 3 beta 4 * nAChR subtype in nicotine dependence, the goal of the current study was to better evaluate the involvement of this subtype in nicotine mediated behavioral responses.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 70, "end": 78}, {"text": "nicotine", "start": 179, "end": 187}]}}, "schema": []}
{"input": "Using the selective alpha 3 beta 4 * nAChR antagonist, alpha-conotoxin AuIB, we assessed the role of alpha 3 beta 4 * nAChRs in acute nicotine, nicotine reward, and physical and affective nicotine withdrawal.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 134, "end": 142}, {"text": "nicotine", "start": 144, "end": 152}, {"text": "nicotine", "start": 188, "end": 196}]}}, "schema": []}
{"input": "Because alpha 5 has also been implicated in nicotine dependence behaviors in mice and can form functional receptors with alpha 3 beta 4 *, we also evaluated the role of the alpha 3 beta 4 alpha 5 * nAChR subtype in nicotine reward and somatic nicotine withdrawal signs by blocking the alpha 3 beta 4 * nAChR subtype in alpha 5 nAChR knockout mice with AuIB.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 44, "end": 52}, {"text": "nicotine", "start": 215, "end": 223}, {"text": "nicotine", "start": 243, "end": 251}]}}, "schema": []}
{"input": "AuIB had no significant effect on acute nicotine behaviors, but dose-dependently attenuated nicotine reward and physical withdrawal signs, with no significant effect in affective withdrawal measures.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 40, "end": 48}, {"text": "nicotine", "start": 92, "end": 100}]}}, "schema": []}
{"input": "Interestingly, AuIB also attenuated nicotine reward and somatic signs in alpha 5 nAChR knockout mice.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 36, "end": 44}]}}, "schema": []}
{"input": "This study shows that alpha 3 beta 4 * nAChRs mediate nicotine reward and physical nicotine withdrawal, but not acute nicotine behaviors or affective nicotine withdrawal signs in mice.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 54, "end": 62}, {"text": "nicotine", "start": 83, "end": 91}, {"text": "nicotine", "start": 118, "end": 126}, {"text": "nicotine", "start": 150, "end": 158}]}}, "schema": []}
{"input": "The alpha 5 subunit is not required in the receptor assembly to mediate these effects.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest an important role for the alpha 3 beta 4 * nAChR subtype in nicotine reward and physical aspects of the nicotine withdrawal syndrome.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 81, "end": 89}, {"text": "nicotine", "start": 125, "end": 133}]}}, "schema": []}
{"input": "Human serum albumin-based design of a diflunisal prodrug.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 38, "end": 48}]}}, "schema": []}
{"input": "The cyclooxygenase-2 inhibitor, diflunisal, is used in the clinic for its anti-inflammatory activity.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 32, "end": 42}]}}, "schema": []}
{"input": "About 99% of a dose of diflunisal is unavailable for reaction with the target enzyme, because diflunisal strongly binds to human serum albumin (HSA).", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 23, "end": 33}, {"text": "diflunisal", "start": 94, "end": 104}]}}, "schema": []}
{"input": "To reduce the binding affinity of diflunisal to albumin, we designed and synthesized the prodrug acetyldiflunisal.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 34, "end": 44}, {"text": "acetyldiflunisal", "start": 97, "end": 113}]}}, "schema": []}
{"input": "The crystal structure of HSA complexed with fatty acid and acetyldiflunisal revealed that acetyldiflunisal binds to the IIA subdomain and that upon binding, it acetylates lysine 199.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 44, "end": 54}, {"text": "acetyldiflunisal", "start": 59, "end": 75}, {"text": "acetyldiflunisal", "start": 90, "end": 106}, {"text": "lysine", "start": 171, "end": 177}]}}, "schema": []}
{"input": "Mass spectrometry confirmed that acetyldiflunisal acetylates Lys199.", "output": {"entities": {"chemical": [{"text": "acetyldiflunisal", "start": 33, "end": 49}, {"text": "Lys199", "start": 61, "end": 67}]}}, "schema": []}
{"input": "The acetylated albumin had twofold weaker binding affinity for diflunisal as demonstrated by fluorescence quenching.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 63, "end": 73}]}}, "schema": []}
{"input": "Reduced binding affinity means that diflunisal is more easily released from acetylated albumin into the circulation.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 36, "end": 46}]}}, "schema": []}
{"input": "Therefore, lower doses of acetyldiflunisal compared to diflunisal will be required.", "output": {"entities": {"chemical": [{"text": "acetyldiflunisal", "start": 26, "end": 42}, {"text": "diflunisal", "start": 55, "end": 65}]}}, "schema": []}
{"input": "Taken together, our results not only provide a template for design of HSA-based prodrugs, but also pave the way toward more effective use of diflunisal in the clinic.", "output": {"entities": {"chemical": [{"text": "diflunisal", "start": 141, "end": 151}]}}, "schema": []}
{"input": "Antitumor and immunomodulatory activity of a water-soluble low molecular weight polysaccharide from Schisandra chinensis (Turcz.) Baill.", "output": {"entities": {}}, "schema": []}
{"input": "A water-soluble low molecular weight polysaccharide (SCPP11) was extracted and purified using DEAE-cellulose and Sephadex G-100 column from Schisandra chinensis (Turcz.) Baill.", "output": {"entities": {}}, "schema": []}
{"input": "Its in vivo and in vitro antitumor and immunomodulatory activity were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that SCPP11 with a molecular weight of 3. 4 x 10 (3) Da exhibited indirect cyctotoxic activity against tumor cells in vitro, but could significantly inhibit the growth of Heps cells in vivo at dose of 50mg/kg, and its inhibition rate is higher than that in the positive group.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, SCPP11 could ameliorate the hematological and biochemical parameters to almost normal and no significant changes in organ weight, and could increase the body weight.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, SCPP11 (at 50mg/kg) could also increased in thymus indexes as well as IL-2 and TNF-alpha levels in serum in vivo and significantly enhance the phagocytosis activity and the productions of NO of RAW264. 7 in vitro.", "output": {"entities": {"chemical": [{"text": "NO", "start": 201, "end": 203}]}}, "schema": []}
{"input": "The results indicated that antitumor properties of SCPP11 might be achieved by improving immune response.", "output": {"entities": {}}, "schema": []}
{"input": "It could be explored as a potential adjuvant against cancer used in the health food and pharmaceutical therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Narirutin fraction from citrus peels attenuates alcoholic liver disease in mice.", "output": {"entities": {"chemical": [{"text": "Narirutin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "This study aimed to demonstrate protective activities of the narirutin fraction from peels of Citrus unshiu against ethanol-induced hepatic damage through an animal study.", "output": {"entities": {"chemical": [{"text": "narirutin", "start": 61, "end": 70}, {"text": "ethanol", "start": 116, "end": 123}]}}, "schema": []}
{"input": "Citrus narirutin fraction (CNF), contained 75% of narirutin, was obtained by an ultra-sonicated extraction and further purification.", "output": {"entities": {"chemical": [{"text": "narirutin", "start": 7, "end": 16}, {"text": "narirutin", "start": 50, "end": 59}]}}, "schema": []}
{"input": "ICR mice were divided into four groups; normaldiet control, ethanol control (6. 5g ethanol/kg), low-CNF (ethanol + 150mg CNF/kg) and high-CNF (ethanol + 300mg CNF/kg) groups.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 60, "end": 67}, {"text": "ethanol", "start": 83, "end": 90}, {"text": "ethanol", "start": 105, "end": 112}, {"text": "ethanol", "start": 143, "end": 150}]}}, "schema": []}
{"input": "Consumption of alcohol for 8weeks induced severe liver damage with increases in prognostic indicators such as aspartate transaminase, alanine transaminase in serum whereas co-administration of CNF suppressed their increases.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 15, "end": 22}, {"text": "aspartate", "start": 110, "end": 119}]}}, "schema": []}
{"input": "Excessive accumulations in liver TG and TC in ethanol control group were also suppressed by co-administration of CNF.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 46, "end": 53}]}}, "schema": []}
{"input": "Co-administration of CNF maintained SOD activity, GSH and malondialdehyde levels close to those of the normal diet group.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 50, "end": 53}, {"text": "malondialdehyde", "start": 58, "end": 73}]}}, "schema": []}
{"input": "Chronic consumption of alcohol also stimulated abrupt increases in pro-inflammatory cytokines such as nuclear factor (NF)-kappa B, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta in liver otherwise co-administration of CNF effectively suppressed production of these cytokines dose-dependently.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 23, "end": 30}]}}, "schema": []}
{"input": "These results indicate that co-administration of CNF with alcohol can alleviate alcohol induced liver damage through preventing lipid formation, protecting antioxidant system and suppressing productions of pro-inflammatory cytokines.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 58, "end": 65}, {"text": "alcohol", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Linking pesticide exposure and dementia: What is the evidence?", "output": {"entities": {}}, "schema": []}
{"input": "There has been a steep increase in the prevalence of dementia in recent decades, which has roughly followed an increase in pesticide use some decades earlier, a time when it is probable that current dementia patients could have been exposed to pesticides.", "output": {"entities": {}}, "schema": []}
{"input": "This raises the question whether pesticides contribute to dementia pathogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, many studies have found increased prevalence of cognitive, behavioral and psychomotor dysfunction in individuals chronically exposed to pesticides.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, evidence from recent studies shows a possible association between chronic pesticide exposure and an increased prevalence of dementia, including Alzheimer' s disease (AD) dementia.", "output": {"entities": {}}, "schema": []}
{"input": "At the cellular and molecular level, the mechanism of action of many classes of pesticides suggests that these compounds could be, at least partly, accountable for the neurodegeneration accompanying AD and other dementias.", "output": {"entities": {}}, "schema": []}
{"input": "For example, organophosphates, which inhibit acetylcholinesterase as do the drugs used in treating AD symptoms, have also been shown to lead to microtubule derangements and tau hyperphosphorylation, a hallmark of AD.", "output": {"entities": {"chemical": [{"text": "organophosphates", "start": 13, "end": 29}]}}, "schema": []}
{"input": "This emerging association is of considerable public health importance, given the increasing dementia prevalence and pesticide use.", "output": {"entities": {}}, "schema": []}
{"input": "Here we review the epidemiological links between dementia and pesticide exposure and discuss the possible pathophysiological mechanisms and clinical implications of this association.", "output": {"entities": {}}, "schema": []}
{"input": "Mutagenicity of the cysteine S-conjugate sulfoxides of trichloroethylene and tetrachloroethylene in the Ames test.", "output": {"entities": {"chemical": [{"text": "cysteine S", "start": 20, "end": 30}, {"text": "sulfoxides", "start": 41, "end": 51}, {"text": "trichloroethylene", "start": 55, "end": 72}, {"text": "tetrachloroethylene", "start": 77, "end": 96}]}}, "schema": []}
{"input": "The nephrotoxicity and nephrocarcinogenicity of trichloroethylene (TCE) and tetrachloroethylene (PCE) are believed to be mediated primarily through the cysteine S-conjugate beta-lyase-dependent bioactivation of the corresponding cysteine S-conjugate metabolites S-(1, 2-dichlorovinyl)-l-cysteine (DCVC) and S-(1, 2, 2-trichlorovinyl)-l-cysteine (TCVC), respectively.", "output": {"entities": {"chemical": [{"text": "trichloroethylene", "start": 48, "end": 65}, {"text": "TCE", "start": 67, "end": 70}, {"text": "tetrachloroethylene", "start": 76, "end": 95}, {"text": "PCE", "start": 97, "end": 100}, {"text": "cysteine S", "start": 152, "end": 162}, {"text": "cysteine S", "start": 229, "end": 239}, {"text": "S-(1, 2-dichlorovinyl)-l-cysteine", "start": 262, "end": 295}, {"text": "DCVC", "start": 297, "end": 301}, {"text": "S-(1, 2, 2-trichlorovinyl)-l-cysteine", "start": 307, "end": 344}, {"text": "TCVC", "start": 346, "end": 350}]}}, "schema": []}
{"input": "DCVC and TCVC have previously been demonstrated to be mutagenic by the Ames Salmonella mutagenicity assay, and reduction in mutagenicity was observed upon treatment with the beta-lyase inhibitor aminooxyacetic acid (AOAA).", "output": {"entities": {"chemical": [{"text": "DCVC", "start": 0, "end": 4}, {"text": "TCVC", "start": 9, "end": 13}, {"text": "aminooxyacetic acid", "start": 195, "end": 214}, {"text": "AOAA", "start": 216, "end": 220}]}}, "schema": []}
{"input": "Because DCVC and TCVC can also be bioactivated through sulfoxidation to yield the potent nephrotoxicants S-(1, 2-dichlorovinyl)-l-cysteine sulfoxide (DCVCS) and S-(1, 2, 2-trichlorovinyl)-l-cysteine sulfoxide (TCVCS), respectively, the mutagenic potential of these two sulfoxides was investigated using the Ames Salmonella typhimurium TA100 mutagenicity assay.", "output": {"entities": {"chemical": [{"text": "DCVC", "start": 8, "end": 12}, {"text": "TCVC", "start": 17, "end": 21}, {"text": "S-(1, 2-dichlorovinyl)-l-cysteine sulfoxide", "start": 105, "end": 148}, {"text": "DCVCS", "start": 150, "end": 155}, {"text": "S-(1, 2, 2-trichlorovinyl)-l-cysteine sulfoxide", "start": 161, "end": 208}, {"text": "TCVCS", "start": 210, "end": 215}, {"text": "sulfoxides", "start": 269, "end": 279}]}}, "schema": []}
{"input": "The results show both DCVCS and TCVCS were mutagenic, and TCVCS exhibited 3-fold higher mutagenicity than DCVCS.", "output": {"entities": {"chemical": [{"text": "DCVCS", "start": 22, "end": 27}, {"text": "TCVCS", "start": 32, "end": 37}, {"text": "TCVCS", "start": 58, "end": 63}, {"text": "DCVCS", "start": 106, "end": 111}]}}, "schema": []}
{"input": "However, DCVCS and TCVCS mutagenic activity was approximately 700-fold and 30-fold lower than DCVC and TCVC, respectively.", "output": {"entities": {"chemical": [{"text": "DCVCS", "start": 9, "end": 14}, {"text": "TCVCS", "start": 19, "end": 24}, {"text": "DCVC", "start": 94, "end": 98}, {"text": "TCVC", "start": 103, "end": 107}]}}, "schema": []}
{"input": "DCVC and DCVCS appeared to induce toxicity in TA100, as evidenced by increased microcolony formation and decreased mutant frequency above threshold concentrations.", "output": {"entities": {"chemical": [{"text": "DCVC", "start": 0, "end": 4}, {"text": "DCVCS", "start": 9, "end": 14}]}}, "schema": []}
{"input": "TCVC and TCVCS were not toxic in TA100.", "output": {"entities": {"chemical": [{"text": "TCVC", "start": 0, "end": 4}, {"text": "TCVCS", "start": 9, "end": 14}]}}, "schema": []}
{"input": "The toxic effects of DCVC limited the sensitivity of TA100 to DCVC mutagenic effects and rendered it difficult to investigate the effects of AOAA on DCVC mutagenic activity.", "output": {"entities": {"chemical": [{"text": "DCVC", "start": 21, "end": 25}, {"text": "DCVC", "start": 62, "end": 66}, {"text": "AOAA", "start": 141, "end": 145}, {"text": "DCVC", "start": 149, "end": 153}]}}, "schema": []}
{"input": "Collectively, these results suggest that DCVCS and TCVCS exerted a definite but weak mutagenicity in the TA100 strain.", "output": {"entities": {"chemical": [{"text": "DCVCS", "start": 41, "end": 46}, {"text": "TCVCS", "start": 51, "end": 56}]}}, "schema": []}
{"input": "Therefore, despite their potent nephrotoxicity, DCVCS and TCVCS are not likely to play a major role in DCVC or TCVC mutagenicity in this strain.", "output": {"entities": {"chemical": [{"text": "DCVCS", "start": 48, "end": 53}, {"text": "TCVCS", "start": 58, "end": 63}, {"text": "DCVC", "start": 103, "end": 107}, {"text": "TCVC", "start": 111, "end": 115}]}}, "schema": []}
{"input": "First synthesis and biological evaluation of indeno [2, 1-e] pyrazolo [3, 4-b] pyrazin-5-one and related derivatives.", "output": {"entities": {"chemical": [{"text": "indeno [2, 1-e] pyrazolo [3, 4-b] pyrazin-5-one", "start": 45, "end": 92}]}}, "schema": []}
{"input": "The synthesis of indeno [2, 1-e] pyrazolo [3, 4-b] pyrazin-5-one was achieved by intramolecular Friedel-Crafts reaction of the acid chloride 3-methyl-1, 6-diphenyl-1H-pyrazolo [3, 4-b] pyrazine-5-carboxylic acid chloride (4) using AlCl3 in boiling CS2.", "output": {"entities": {"chemical": [{"text": "indeno [2, 1-e] pyrazolo [3, 4-b] pyrazin-5-one", "start": 17, "end": 64}, {"text": "acid chloride 3-methyl-1, 6-diphenyl-1H-pyrazolo [3, 4-b] pyrazine-5-carboxylic acid chloride", "start": 127, "end": 220}, {"text": "AlCl3", "start": 231, "end": 236}, {"text": "CS2", "start": 248, "end": 251}]}}, "schema": []}
{"input": "Compound 4 proved to be a versatile compound for the synthesis of several Indenopyrazolopyrazinone derivatives.", "output": {"entities": {"chemical": [{"text": "Indenopyrazolopyrazinone", "start": 74, "end": 98}]}}, "schema": []}
{"input": "The antibacterial and antifungal activities of selected derivatives were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of nanoparticles of TiO2 on food depletion and life-history responses of Daphnia magna.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 28, "end": 32}]}}, "schema": []}
{"input": "The extent to which different forms of nanoparticles of titanium dioxide (nano-TiO2) aggregated with microalgae, decreased food levels and hence impaired growth, reproduction and fitness of Daphnia magna individuals were studied.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 56, "end": 72}, {"text": "TiO2", "start": 79, "end": 83}]}}, "schema": []}
{"input": "Treatments included three different types of nano-TiO2 differing in their coating or crystalline structure but of similar primary size (20 nm) plus a micron-sized bulk material, two exposure levels (1, 10mg/l) and two food ration levels of the microalgae Chlorella vulgaris that included a non limiting (1. 5 mu gC/ml) and a limiting one (0. 3 mu gC/ml).", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 50, "end": 54}]}}, "schema": []}
{"input": "Effects were assessed using standardized chronic tests and assays that maximized food depletion in the water column under semi-static and re-suspension conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Results indicated that the high ion levels in culture medium lead to the aggregation of nanoparticles followed by particle destabilization.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticle aggregates interacted with the algae cells, forming clusters.", "output": {"entities": {}}, "schema": []}
{"input": "Large TiO2-algae agglomerates settled readily dramatically depleting the concentration of available food for D. magna.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 6, "end": 10}]}}, "schema": []}
{"input": "At limiting food rations food depletion by nanoparticle aggregation had dramatic effects on reproduction and fitness of exposed D. magna at 1mg/l irrespectively of the particle form.", "output": {"entities": {}}, "schema": []}
{"input": "At high food rations effects were only observed for one of the nano-TiO2, P-25, at high exposure levels (10 mg/l) under both semi-static and particle re-suspension conditions, which suggest that P-25 effects were mediated by clogging the gut and hence diminishing food acquisition.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 68, "end": 72}, {"text": "P-25", "start": 74, "end": 78}, {"text": "P-25", "start": 195, "end": 199}]}}, "schema": []}
{"input": "These results indicate that nano-TiO2 may affect the transfer of energy throughout the planktonic aquatic food webs increasing the settlement of edible particles from the water column.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 33, "end": 37}]}}, "schema": []}
{"input": "Reproductive and health assessment of fathead minnows (Pimephales promelas) inhabiting a pond containing oil sands process-affected water.", "output": {"entities": {}}, "schema": []}
{"input": "Previous laboratory based studies have shown that oil sands process-affected waters (OSPWs) containing high concentrations of naphthenic acids (> 25 mg/l) have adverse effects on the reproductive physiology of fish.", "output": {"entities": {"chemical": [{"text": "naphthenic acids", "start": 126, "end": 142}]}}, "schema": []}
{"input": "The purpose of this study was to assess the reproductive development and health of a wild population of fathead minnows (Pimephales promelas) inhabiting an OSPW pond that has moderate concentrations of naphthenic acids (~ 10 mg/l).", "output": {"entities": {"chemical": [{"text": "naphthenic acids", "start": 202, "end": 218}]}}, "schema": []}
{"input": "Fathead minnows were collected at various times during the period of 2006 through 2008 from Demonstration Pond (OSPW) located at Syncrude Canada Ltd., and two reference sites, Beaver Creek reservoir and Poplar Creek reservoir, which are all north of Fort McMurray, AB, Canada.", "output": {"entities": {}}, "schema": []}
{"input": "Condition factor, gill histopathology, gonadosomatic indices, liver somatic indices, male secondary sexual characteristics, and plasma sex steroids were examined.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 139, "end": 147}]}}, "schema": []}
{"input": "Depending on the time of year that fathead minnows were collected, there were differences in the condition factor, gonadosomatic indices, liver somatic indices, and secondary sexual characteristics of fathead minnows (in males) from Demonstration Pond when compared to the fathead minnows from the reference sites.", "output": {"entities": {}}, "schema": []}
{"input": "In comparison to reference fish, lower concentrations of 11-ketotestosterone were measured in the plasma of male fathead minnows collected from Demonstration Pond in June 2006 and July 2007.", "output": {"entities": {"chemical": [{"text": "11-ketotestosterone", "start": 57, "end": 76}]}}, "schema": []}
{"input": "Black spot disease and Ligula intestinalis were prevalent in fathead minnows from the reference sites but were not observed in fathead minnows from Demonstration Pond.", "output": {"entities": {}}, "schema": []}
{"input": "The opercula of fathead minnows from Demonstration Pond also differed from those of reference fish.", "output": {"entities": {}}, "schema": []}
{"input": "An examination of the gills of fathead minnows from Demonstration Pond revealed that were a number of proliferative and degenerative alterations relative to reference fish.", "output": {"entities": {}}, "schema": []}
{"input": "Even though the fathead minnow population has been maintained in this OSPW pond since 1993, the results of this study demonstrate that the OSPW continues to affect the reproductive development and health of the fathead minnows compared to fish collected at reference sites.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular phylogeny of the Indian Ocean Terpsiphone paradise flycatchers: Undetected evolutionary diversity revealed amongst island populations.", "output": {"entities": {}}, "schema": []}
{"input": "We construct a molecular phylogeny of Terpsiphone flycatchers of the Indian Ocean and use this to investigate their evolutionary relationships.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 4. 4kb of mitochondrial (cyt-b, ND3, ND2, control region) and nuclear (G3PDH, MC1R) sequence data were obtained from all species, sub-species and island populations of the region.", "output": {"entities": {}}, "schema": []}
{"input": "Colonisation of the western Indian Ocean has been within the last two million years and greatly postdates the formation of the older islands of the region.", "output": {"entities": {}}, "schema": []}
{"input": "A minimum of two independent continent-island colonisation events must have taken place in order to explain the current distribution and phylogenetic placement of Terpsiphone in this region.", "output": {"entities": {}}, "schema": []}
{"input": "While five well-diverged Indian Ocean clades are detected, the relationship between them is unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Short intermodal branches are indicative of rapid range expansion across the region, masking exact routes and chronology of colonisation.", "output": {"entities": {}}, "schema": []}
{"input": "The Indian Ocean Terpsiphone taxa fall into five well supported clades, two of which (the Seychelles paradise flycatcher and the Mascarene paradise flycatcher) correspond with currently recognised species, whilst a further three (within the Madagascar paradise flycatcher) are not entirely predicted by taxonomy, and are neither consistent with distance-based nor island age-based models of colonisation.", "output": {"entities": {}}, "schema": []}
{"input": "We identify the four non-Mascarene clades as Evolutionarily Significant Units (ESUs), while the Mascarene paradise flycatcher contains two ESUs corresponding to the Mauritius and R e union subspecies.", "output": {"entities": {}}, "schema": []}
{"input": "All six ESUs are sufficiently diverged to be worthy of management as if they were separate species.", "output": {"entities": {}}, "schema": []}
{"input": "This phylogenetic reconstruction highlights the importance of sub-specific molecular phylogenetic reconstructions in complex island archipelago settings in clarifying phylogenetic history and ESUs that may otherwise be overlooked and inadvertently lost.", "output": {"entities": {}}, "schema": []}
{"input": "Our phylogenetic reconstruction has identified hidden pockets of evolutionary distinctiveness, which provide a valuable platform upon which to re-evaluate investment of conservation resources within the Terpsiphone flycatchers of the Indian Ocean.", "output": {"entities": {}}, "schema": []}
{"input": "Improving correlated SERS measurements with scanning electron microscopy: an assessment of the problem arising from the deposition of amorphous carbon.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 144, "end": 150}]}}, "schema": []}
{"input": "For surface-enhanced Raman scattering (SERS) substrates with nonspherical symmetry, it is critical to correlate spectroscopy measurements with imaging by scanning electron microscopy (SEM).", "output": {"entities": {}}, "schema": []}
{"input": "However, the deposition of carbon resulting from e-beam exposure during SEM imaging contaminates the surface of nanoparticles, potentially preventing their further functionalization with Raman probe molecules.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 27, "end": 33}]}}, "schema": []}
{"input": "In addition, the deposited carbon leads to unwanted background SERS signals.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 27, "end": 33}]}}, "schema": []}
{"input": "In this study, we systematically investigated the deposition of carbon during SEM imaging and examined how it affects the functionalization of nanoparticles with probe molecules and impacts the detection of SERS signals.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 64, "end": 70}]}}, "schema": []}
{"input": "Significantly, we found that the carbon could be removed or replaced from the surface of Ag nanoparticles through chemical or physical means, rendering the nanoparticles the capability for correlated SEM/SERS studies.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 33, "end": 39}, {"text": "Ag", "start": 89, "end": 91}]}}, "schema": []}
{"input": "The first report on some toxic effects of green scat, Scatophagus argus an Iranian Persian Gulf venomous fish.", "output": {"entities": {}}, "schema": []}
{"input": "Green scat namely as Scatophagus argus is a venomous aquarium fish belonging to Scatophagidae family.", "output": {"entities": {}}, "schema": []}
{"input": "It can induce painful wounds in injured hand with partial paralysis to whom that touch the spines.", "output": {"entities": {}}, "schema": []}
{"input": "Dorsal and ventral rough spines contain cells that produce venom with toxic activities.", "output": {"entities": {}}, "schema": []}
{"input": "According to unpublished data collected from local hospitals in southern coastal region of Iran, S. argus is reported as a venomous fish.", "output": {"entities": {}}, "schema": []}
{"input": "Envenomation induces clinical symptoms such as local pain, partial paralysis, erythema and itching.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study green scat (spotted scat) was collected from Persian Gulf coastal waters.", "output": {"entities": {}}, "schema": []}
{"input": "SDS-PAGE indicated 12 distinct bands in the venom ranged between 7 and 250 kDa.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The crude venom had hemolytic activity on human erythrocytes (1%) with an LC100 (Lytic Concentration) of about 1. 7 mu g.", "output": {"entities": {}}, "schema": []}
{"input": "The crude venom can release 813 mu g protein from 0. 5% casein.", "output": {"entities": {}}, "schema": []}
{"input": "Phospholipase C activity was recorded at 3. 125 mu g of total venom.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings showed that the edematic activity remained over 24 h after injection.", "output": {"entities": {}}, "schema": []}
{"input": "The results demonstrated that crude venom extracted from Iranian coastal border has different toxic and enzymatic activities.", "output": {"entities": {}}, "schema": []}
{"input": "This study is pending to further investigation on animal model regarding protein purification and in vivo studies.", "output": {"entities": {}}, "schema": []}
{"input": "An evaluation of the serotonin system and perseverative, compulsive, stereotypical, and hyperactive behaviors in dopamine transporter (DAT) knockout mice.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 21, "end": 30}, {"text": "dopamine", "start": 113, "end": 121}]}}, "schema": []}
{"input": "RATIONALE: Mice lacking the dopamine transporter (DAT) display major behavioral alterations that include hyperactivity, perseverative locomotor patterns, and reduced prepulse inhibition of the acoustic startle reflex.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 28, "end": 36}]}}, "schema": []}
{"input": "OBJECTIVES: The objectives of this study were to investigate perseverative, compulsive, stereotypical, and hyperactive behaviors, as well as serotonin and its involvement with these behaviors, in DAT gene-altered mice.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 141, "end": 150}]}}, "schema": []}
{"input": "RESULTS: In the open field, mean turn angle and meandering were decreased in DAT knockout (DAT-KO) mice.", "output": {"entities": {}}, "schema": []}
{"input": "DAT-KO mice displayed increased hyperactivity, increased velocity, less time immobile, and a failure to habituate over time in the open field unlike their DAT wildtype (DAT-WT) and heterozygous (DAT-HET) littermates.", "output": {"entities": {}}, "schema": []}
{"input": "DAT-KO mice buried fewer marbles than DAT-WT and-HET mice in an assessment of compulsive-like behaviors, likely due to extreme hyperactivity and related inattention.", "output": {"entities": {}}, "schema": []}
{"input": "Stereotypical head weaving was increased in untreated DAT-KO mice.", "output": {"entities": {}}, "schema": []}
{"input": "Following administration of the 5-HT (1A/7) agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), stereotypical head weaving and forepaw treading were increased more in DAT-KO mice than in DAT-WT or-HET mice.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 32, "end": 36}, {"text": "8-hydroxy-2-(di-n-propylamino) tetralin", "start": 52, "end": 91}, {"text": "8-OH-DPAT", "start": 93, "end": 102}]}}, "schema": []}
{"input": "By contrast, head twitches induced by treatment with the 5-HT (2A/2C) agonist (+/-)-2, 5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) were similar in mice of all three DAT genotypes.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 57, "end": 61}, {"text": "(+/-)-2, 5-dimethoxy-4-iodophenyl-2-aminopropane", "start": 78, "end": 126}, {"text": "DOI", "start": 128, "end": 131}]}}, "schema": []}
{"input": "5-HT (1A) autoreceptor function was intact in DAT-KO mice.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Compared to DAT-WT mice, serotonin levels were increased in DAT-HET and-KO mice in frontal cortex and hippocampus, respectively, and serotonin turnover rates were increased ~ 30% in the striatum of DAT-KO mice.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 25, "end": 34}]}}, "schema": []}
{"input": "CONCLUSIONS: These findings extend and confirm prior behavioral and biochemical characterization of DAT-KO mice.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperactivity, stereotypy, and perseverative behaviors are increased in these mice, with brain-area specific increases in serotonin levels and serotonin turnover, and marked increases in postsynaptic 5-HT (1A) receptor-mediated stereotypic responses.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 122, "end": 131}, {"text": "serotonin", "start": 143, "end": 152}, {"text": "5-HT", "start": 200, "end": 204}]}}, "schema": []}
{"input": "Quantum dots exhibit less bioaccumulation than free cadmium and selenium in the earthworm Eisenia andrei.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 52, "end": 59}, {"text": "selenium", "start": 64, "end": 72}]}}, "schema": []}
{"input": "The present study addresses the bioaccumulation behavior of cadmium selenide quantum dots by Eisenia andrei earthworms in a terrestrial environment.", "output": {"entities": {"chemical": [{"text": "cadmium selenide", "start": 60, "end": 76}]}}, "schema": []}
{"input": "Earthworms were exposed to quantum dot-treated soil for up to 4 wk and analyzed for cadmium and selenium concentration using inductively coupled plasma mass spectrometry.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 84, "end": 91}, {"text": "selenium", "start": 96, "end": 104}]}}, "schema": []}
{"input": "Results were compared with those from earthworms exposed to cadmium nitrate and selenious acid, as positive controls, and those exposed in untreated soil (negative control).", "output": {"entities": {"chemical": [{"text": "cadmium nitrate", "start": 60, "end": 75}, {"text": "selenious acid", "start": 80, "end": 94}]}}, "schema": []}
{"input": "Earthworms exposed to quantum dots showed significant bioaccumulation of cadmium and selenium (5. 3-and 1. 5-fold higher concentration over negative controls, respectively) after 4 wk.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 73, "end": 80}, {"text": "selenium", "start": 85, "end": 93}]}}, "schema": []}
{"input": "Over the same 4 wk, positive control earthworms accumulated 9. 2-and 2. 2-fold higher cadmium and selenium, respectively, than negative controls for a much more substantial final body burden of the 2 elements.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 86, "end": 93}, {"text": "selenium", "start": 98, "end": 106}]}}, "schema": []}
{"input": "The concentrations also increased with exposure time; cadmium concentrations increased from 3600 +/- 310 ng/g to 8080 +/- 660 ng/g, from 1 to 4 wk, suggesting that further bioaccumulation may take place with even longer exposure time.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 54, "end": 61}]}}, "schema": []}
{"input": "The molar ratio of cadmium to selenium in the quantum dot-exposed worms (6. 2) is closer to the ratios seen in positive control worms (7. 2) than to the pure quantum dots (1. 8), which implies that quantum dots are taken up predominantly in the degraded form.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 19, "end": 26}, {"text": "selenium", "start": 30, "end": 38}]}}, "schema": []}
{"input": "The results suggest that chemical modification of quantum dots to protect them from environmental degradation could potentially reduce bioaccumulation of the nanoparticles by earthworms.", "output": {"entities": {}}, "schema": []}
{"input": "Environ Toxicol Chem 2013; 32: 1288-1294.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Polymers for the cell-specific immobilisation of megakaryocytic cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Primary human megakaryocytes, the precursor cells of platelets, are difficult to collect and cultivate.", "output": {"entities": {}}, "schema": []}
{"input": "Polymers that enrich these cells without affecting their regulation or function are of interest for basic research as well as for cord blood transplantation purposes since co-transplantation of enriched megakaryocyte concentrates increase the success of stem cell therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, polymer microarrays were used for the discovery of substrates for MEG-01 cells, with five polymers identified which selectively bound cells of the megakaryocytic lineage.", "output": {"entities": {}}, "schema": []}
{"input": "Flow cytometry and miRNA profiling revealed that immobilisation had only a minor effect on the cellular maturation status, making the identified substrates potential candidates for concentrating megakaryocytes from patients prior to transplantation.", "output": {"entities": {}}, "schema": []}
{"input": "Plasmonic-enhanced organic photovoltaics: breaking the 10% efficiency barrier.", "output": {"entities": {}}, "schema": []}
{"input": "Recent advances in molecular organic photovoltaics (OPVs) have shown 10% power conversion efficiency (PCE) for single-junction cells, which put them in direct competition with PVs based on amorphous silicon.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 199, "end": 206}]}}, "schema": []}
{"input": "Incorporation of plasmonic nanostructures for light trapping in these thin-film devices offers an attractive solution to realize higher-efficiency OPVs with PCE >> 10%.", "output": {"entities": {}}, "schema": []}
{"input": "This article reviews recent progress on plasmonic-enhanced OPV devices using metallic nanoparticles, and one-dimensional (1D) and two-dimensional (2D) patterned periodic nanostructures.", "output": {"entities": {}}, "schema": []}
{"input": "We discuss the benefits of using various plasmonic nanostructures for broad-band, polarization-insensitive and angle-independent absorption enhancement, and their integration with one or two electrode (s) of an OPV device.", "output": {"entities": {}}, "schema": []}
{"input": "Tuning the Stability of Graphene Layers by Phthalocyanine-Based oPPV Oligomers Towards Photo-and Redoxactive Materials.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 24, "end": 32}, {"text": "Phthalocyanine", "start": 43, "end": 57}]}}, "schema": []}
{"input": "In contrast to pristine zinc phthalocyanine (1), zinc phthalocyanine based oPPV-oligomers (2-4) of different chain lengths interact tightly and reversibly with graphite, affording stable and finely dispersed suspensions of mono-to few-layer graphene-nanographene (NG)-that are photoactive.", "output": {"entities": {"chemical": [{"text": "zinc phthalocyanine", "start": 24, "end": 43}, {"text": "zinc phthalocyanine", "start": 49, "end": 68}, {"text": "oPPV", "start": 75, "end": 79}, {"text": "graphite", "start": 160, "end": 168}, {"text": "graphene", "start": 241, "end": 249}]}}, "schema": []}
{"input": "The p-type character of the oPPV backbones and the increasing length of the oPPV backbones facilitate the overall pi-pi interactions with the graphene layers.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 142, "end": 150}]}}, "schema": []}
{"input": "In NG/2, NG/3, and NG/4 hybrids, strong electronic coupling between the individual components gives rise to charge transfer from the photoexcited zinc phthalocyanines to NG to form hundreds of picoseconds lived charge transfer states.", "output": {"entities": {"chemical": [{"text": "zinc phthalocyanines", "start": 146, "end": 166}]}}, "schema": []}
{"input": "The resulting features, namely photo-and redoxactivity, serve as incentives to construct and to test novel solar cells.", "output": {"entities": {}}, "schema": []}
{"input": "Solar cells made out of NG/4 feature stable and repeatable photocurrent generation during several' on-off' cycles of illumination with monochromatic IPCE values of around 1%.", "output": {"entities": {}}, "schema": []}
{"input": "Superhydrophobic and Superoleophilic PVDF Membranes for Effective Separation of Water-in-Oil Emulsions with High Flux.", "output": {"entities": {"chemical": [{"text": "PVDF", "start": 37, "end": 41}]}}, "schema": []}
{"input": "A superhydrophobic-superoleophilic PVDF membrane is fabricated via an inert solvent-induced phase inversion for effective separation of both micrometer and nanometer-sized surfactant-free and surfactant-stabilized water-in-oil emulsions solely driven by gravity, with high separation efficiency (oil purity in filtrate after separation > 99. 95 wt%) and high flux, which is several times higher than those of commercial filtration membranes and reported materials with similar permeation properties.", "output": {"entities": {}}, "schema": []}
{"input": "Ultralight and highly compressible graphene aerogels.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 35, "end": 43}]}}, "schema": []}
{"input": "Chemically converted graphene aerogels with ultralight density and high compressibility are prepared by diamine-mediated functionalization and assembly, followed by microwave irradiation.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 21, "end": 29}, {"text": "diamine", "start": 104, "end": 111}]}}, "schema": []}
{"input": "The resulting graphene aerogels with density as low as 3 mg cm (-3) show excellent resilience and can completely recover after more than 90% compression.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 14, "end": 22}]}}, "schema": []}
{"input": "The ultralight graphene aerogels possessing high elasticity are promising as compliant and energy-absorbing materials.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 15, "end": 23}]}}, "schema": []}
{"input": "A Biochemical and Cellular Approach to Explore the Antiproliferative and Prodifferentiative Activity of Aloe Arborescens Leaf Extract.", "output": {"entities": {}}, "schema": []}
{"input": "Aloe arborescens Miller, belonging to the Aloe genus (Liliaceae family), is one of the main varieties of Aloe used worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Although less characterized than the commonest Aloe vera, Aloe arborescens is known to be richer in beneficial phytotherapeutic, anticancer, and radio-protective properties.", "output": {"entities": {}}, "schema": []}
{"input": "It is commonly used as a pharmaceutical ingredient for its effect in burn treatment and ability to increase skin wound healing properties.", "output": {"entities": {}}, "schema": []}
{"input": "However, very few studies have addressed the biological effects of Aloe at molecular level.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the research is to provide evidences for the antiproliferative properties of Aloe arborescens crude leaf extract using an integrated proteomic and cellular biological approach.", "output": {"entities": {}}, "schema": []}
{"input": "We analysed the composition of an Aloe arborescens leaf extract by gas chromatography-mass spectrometry analysis.", "output": {"entities": {}}, "schema": []}
{"input": "We found it rich in Aloe-emodin, a hydroxylanthraquinone with known antitumoral activity and in several compounds with anti-oxidant properties.", "output": {"entities": {"chemical": [{"text": "emodin", "start": 25, "end": 31}, {"text": "hydroxylanthraquinone", "start": 35, "end": 56}]}}, "schema": []}
{"input": "Accordingly, we show that the Aloe extract has antiproliferative effects on several human transformed cell lines and exhibits prodifferentiative effects on both primary and immortalized human keratinocyte.", "output": {"entities": {}}, "schema": []}
{"input": "Proteomic analysis of whole cell extracts revealed the presence of proteins with a strong antiproliferative and antimicrobial activity specifically induced in human keratinocytes by Aloe treatment supporting its application as a therapeutical agent.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.", "output": {"entities": {"chemical": [{"text": "steviol", "start": 47, "end": 54}, {"text": "isosteviol", "start": 59, "end": 69}]}}, "schema": []}
{"input": "Seventeen steviol derivatives, i. e., 2-18, and 19 isosteviol derivatives, i. e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1).", "output": {"entities": {"chemical": [{"text": "steviol", "start": 10, "end": 17}, {"text": "isosteviol", "start": 51, "end": 61}, {"text": "diterpenoid glycoside", "start": 110, "end": 131}, {"text": "stevioside", "start": 133, "end": 143}]}}, "schema": []}
{"input": "Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i. e., 5-9 and 11-14, and five isosteviol derivatives, i. e., 28-32, exhibited activities with single-digit micromolar IC (50) values against one or more cell lines.", "output": {"entities": {"chemical": [{"text": "steviol", "start": 163, "end": 170}, {"text": "isosteviol", "start": 215, "end": 225}]}}, "schema": []}
{"input": "All of these active compounds possess C (19)-O-acyl group, and among which, ent-kaur-16-ene-13, 19-diol 19-O-4', 4', 4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC (50) values in the range of 1. 2-4. 1 mu M.", "output": {"entities": {"chemical": [{"text": "O-acyl", "start": 45, "end": 51}, {"text": "ent-kaur-16-ene-13, 19-diol 19-O-4', 4', 4'-trifluorocrotonate", "start": 76, "end": 138}]}}, "schema": []}
{"input": "Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggested that acylation of the 19-OH group of kaurane-and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity.", "output": {"entities": {"chemical": [{"text": "OH", "start": 49, "end": 51}, {"text": "kaurane", "start": 61, "end": 68}, {"text": "beyerane", "start": 73, "end": 81}, {"text": "diterpenoids", "start": 87, "end": 99}]}}, "schema": []}
{"input": "Chemical composition and antimicrobial and allelopathic activity of Tunisian Conyza sumatrensis (Retz.) E. WALKER essential oils.", "output": {"entities": {}}, "schema": []}
{"input": "Conyza sumatrensis (Retz.) E. WALKER (Asteraceae) is a spontaneous annual herb, fairly widespread throughout Tunisia, which has rarely been studied or valued in any sector.", "output": {"entities": {}}, "schema": []}
{"input": "Essential oils were obtained by hydrodistillation of different parts (flower heads, leaves, stems, and roots) of C. sumatrensis plants, which were collected in autumn (November 2007) at the flowering stage in the area of Monastir, Tunisia.", "output": {"entities": {}}, "schema": []}
{"input": "In total, 98 compounds, representing 88. 1-99. 3% of the oil composition, were identified by GC-FID and GC/MS analyses.", "output": {"entities": {}}, "schema": []}
{"input": "The root essential oil was distinguished by its high content in acetylenes (matricaria ester, 4; 74. 3%), while those from flower heads and leaves were dominated by oxygenated sesquiterpenes (61. 1 and 50. 3%, resp.).", "output": {"entities": {"chemical": [{"text": "acetylenes", "start": 64, "end": 74}, {"text": "matricaria ester", "start": 76, "end": 92}, {"text": "sesquiterpenes", "start": 176, "end": 190}]}}, "schema": []}
{"input": "The oils of C. sumatrensis from Tunisia belonged to a matricaria ester/caryophyllene oxide chemotype.", "output": {"entities": {"chemical": [{"text": "matricaria ester", "start": 54, "end": 70}, {"text": "caryophyllene oxide", "start": 71, "end": 90}]}}, "schema": []}
{"input": "All the oils were evaluated for antibacterial, antifungal, and allelopathic activities.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that the leaf oil exhibited significant in vitro antibacterial activity against Enterococcus faecalis, Staphylococcus aureus, and Proteus mirabilis and that the C. sumatrensis oils isolated from the aerial parts presented high mycelia-growth inhibition of Candida albicans and the filamentous fungi tested.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the essential oils of the different plant parts inhibited the shoot and root growth of Raphanus sativus (radish) seedlings.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, the inhibition of the hypocotyl growth varied from 28. 6 to 90. 1% and that of the radicle from 42. 3 to 96. 2%.", "output": {"entities": {}}, "schema": []}
{"input": "Nicotinamide N-oxidation by CYP2E1 in human liver microsomes.", "output": {"entities": {"chemical": [{"text": "Nicotinamide N", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Excess nicotinamide, a form of vitamin B (3), is metabolized through two enzymatic systems and eventually excreted from the body.", "output": {"entities": {"chemical": [{"text": "nicotinamide", "start": 7, "end": 19}, {"text": "vitamin B (3)", "start": 31, "end": 44}]}}, "schema": []}
{"input": "The first system starts with the methylation of nicotinamide by nicotinamide N-methyltransferase, which can subsequently be oxidized by aldehyde oxidase.", "output": {"entities": {"chemical": [{"text": "nicotinamide", "start": 48, "end": 60}, {"text": "nicotinamide N", "start": 64, "end": 78}, {"text": "aldehyde", "start": 136, "end": 144}]}}, "schema": []}
{"input": "The second enzymatic system oxidizes nicotinamide to nicotinamide N-oxide.", "output": {"entities": {"chemical": [{"text": "nicotinamide", "start": 37, "end": 49}, {"text": "nicotinamide N-oxide", "start": 53, "end": 73}]}}, "schema": []}
{"input": "It is located in the endoplasmic reticulum of hepatocytes but the precise enzyme is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "We have used human liver microsomes in combination with selective cytochrome P450 inhibitors, specific substrates, and antibodies to identify CYP2E1 as the main activity producing nicotinamide N-oxide.", "output": {"entities": {"chemical": [{"text": "nicotinamide N-oxide", "start": 180, "end": 200}]}}, "schema": []}
{"input": "Our results suggest the potential use of nicotinamide N-oxide as a biomarker of CYP2E1 activity from urine or blood samples.", "output": {"entities": {"chemical": [{"text": "nicotinamide N-oxide", "start": 41, "end": 61}]}}, "schema": []}
{"input": "Optical response of individual Au-Ag @SiO 2 heterodimers.", "output": {"entities": {"chemical": [{"text": "Au-Ag", "start": 31, "end": 36}, {"text": "SiO 2", "start": 38, "end": 43}]}}, "schema": []}
{"input": "The optical extinction response of individual Au-Ag @SiO2 heterodimers whose individual morphologies are determined by transmission electron microscopy (TEM) is investigated using spatial modulation spectroscopy.", "output": {"entities": {"chemical": [{"text": "Au-Ag", "start": 46, "end": 51}, {"text": "SiO2", "start": 53, "end": 57}]}}, "schema": []}
{"input": "The extinction spectra show two resonances spectrally close to the surface plasmon resonances of the constituting Au and Ag @SiO2 core-shell particles.", "output": {"entities": {"chemical": [{"text": "Au", "start": 114, "end": 116}, {"text": "Ag", "start": 121, "end": 123}, {"text": "SiO2", "start": 125, "end": 129}]}}, "schema": []}
{"input": "The interparticle electromagnetic coupling is demonstrated to induce a large increase of the optical extinction of the dimer around its Au-like surface plasmon resonance for light polarized along its axis, as compared to that for perpendicular polarization and to that of an isolated Au nanoparticle.", "output": {"entities": {"chemical": [{"text": "Au", "start": 136, "end": 138}, {"text": "Au", "start": 284, "end": 286}]}}, "schema": []}
{"input": "For spherical particles, this interaction also leads to comparable shifts with light polarization of the two dimer resonances, an effect masked or even reversed for particles significantly deviating from sphericity.", "output": {"entities": {}}, "schema": []}
{"input": "Both amplitude and spectral effects are found to be in excellent quantitative agreement with numerical simulations when using the TEM-measured dimer morphology (i. e., size, shape, and orientation of the individual dimers), stressing the importance of individual morphology characterization for interpreting heterodimer optical response.", "output": {"entities": {}}, "schema": []}
{"input": "A polar copper-boron one-electron sigma-bond.", "output": {"entities": {"chemical": [{"text": "copper", "start": 8, "end": 14}, {"text": "boron", "start": 15, "end": 20}]}}, "schema": []}
{"input": "Virtually all chemical bonds consist of one or several pairs of electrons shared by two atoms.", "output": {"entities": {}}, "schema": []}
{"input": "Examples of sigma-bonds made of a single electron delocalized over two neighboring atoms were until recently found only in gas-phase cations such as H2 (+) and Li2 (+) and in highly unstable species generated in solid matrices.", "output": {"entities": {"chemical": [{"text": "H2 (+)", "start": 149, "end": 155}, {"text": "Li2 (+)", "start": 160, "end": 167}]}}, "schema": []}
{"input": "Only in the past decade was bona fide one-electron bonding observed for molecules in fluid solution.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report the isolation and structural characterization of a thermally stable compound featuring a Cu-B one-electron bond, as well as its oxidized (nonbonded) and reduced (two-electrons-bonded) congeners.", "output": {"entities": {"chemical": [{"text": "Cu-B", "start": 104, "end": 108}]}}, "schema": []}
{"input": "This triad provides an excellent opportunity to study the degree of sigma-bonding in a metalloboratrane as a function of electron count.", "output": {"entities": {"chemical": [{"text": "metalloboratrane", "start": 87, "end": 103}]}}, "schema": []}
{"input": "Beyond H (2) S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO).", "output": {"entities": {"chemical": [{"text": "H (2) S", "start": 7, "end": 14}, {"text": "NO", "start": 19, "end": 21}, {"text": "Hydrogen Sulfide", "start": 33, "end": 49}, {"text": "Nitroprusside", "start": 54, "end": 67}, {"text": "Nitroxyl", "start": 91, "end": 99}, {"text": "HNO", "start": 101, "end": 104}]}}, "schema": []}
{"input": "A New Pharmacological Source of HNO.", "output": {"entities": {"chemical": [{"text": "HNO", "start": 32, "end": 35}]}}, "schema": []}
{"input": "Hydrogen sulfide (H (2) S) has been increasingly recognized as an important signaling molecule that regulates both blood pressure and neuronal activity.", "output": {"entities": {"chemical": [{"text": "Hydrogen sulfide", "start": 0, "end": 16}, {"text": "H (2) S", "start": 18, "end": 25}]}}, "schema": []}
{"input": "Attention has been drawn to its interactions with another gasotransmitter, nitric oxide (NO).", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 75, "end": 87}, {"text": "NO", "start": 89, "end": 91}]}}, "schema": []}
{"input": "Here, we provide evidence that the physiological effects observed upon the application of sodium nitroprusside (SNP) and H (2) S can be ascribed to the generation of nitroxyl (HNO), which is a direct product of the reaction between SNP and H (2) S, not a consequence of released NO subsequently reacting with H (2) S.", "output": {"entities": {"chemical": [{"text": "sodium nitroprusside", "start": 90, "end": 110}, {"text": "SNP", "start": 112, "end": 115}, {"text": "H (2) S", "start": 121, "end": 128}, {"text": "nitroxyl", "start": 166, "end": 174}, {"text": "HNO", "start": 176, "end": 179}, {"text": "SNP", "start": 232, "end": 235}, {"text": "H (2) S", "start": 240, "end": 247}, {"text": "NO", "start": 279, "end": 281}, {"text": "H (2) S", "start": 309, "end": 316}]}}, "schema": []}
{"input": "Intracellular HNO formation has been confirmed, and the subsequent release of calcitonin gene-related peptide from a mouse heart has been demonstrated.", "output": {"entities": {"chemical": [{"text": "HNO", "start": 14, "end": 17}]}}, "schema": []}
{"input": "Unlike with other thiols, SNP reacts with H (2) S in the same way as rhodanese, i. e., the cyanide transforms into a thiocyanate.", "output": {"entities": {"chemical": [{"text": "thiols", "start": 18, "end": 24}, {"text": "SNP", "start": 26, "end": 29}, {"text": "H (2) S", "start": 42, "end": 49}, {"text": "cyanide", "start": 91, "end": 98}, {"text": "thiocyanate", "start": 117, "end": 128}]}}, "schema": []}
{"input": "These findings shed new light on how H (2) S is understood to interact with nitroprusside.", "output": {"entities": {"chemical": [{"text": "H (2) S", "start": 37, "end": 44}, {"text": "nitroprusside", "start": 76, "end": 89}]}}, "schema": []}
{"input": "Additionally, they offer a new and convenient pharmacological source of HNO for therapeutic purposes.", "output": {"entities": {"chemical": [{"text": "HNO", "start": 72, "end": 75}]}}, "schema": []}
{"input": "Two new compounds from Scolopendra multidens Newport.", "output": {"entities": {}}, "schema": []}
{"input": "Two new compounds, 5 beta-pregnane-2 alpha, 6 alpha, 20 (S)-triol (1) and 8-hydroxyl-3-methoxyl-2 (1H)-quinolone (2), were isolated from Scolopendra multidens Newport.", "output": {"entities": {"chemical": [{"text": "5 beta-pregnane-2 alpha, 6 alpha, 20 (S)-triol", "start": 19, "end": 65}, {"text": "8-hydroxyl-3-methoxyl-2 (1H)-quinolone", "start": 74, "end": 112}]}}, "schema": []}
{"input": "Their structures were elucidated on the basis of spectroscopic methods including 1D and 2D NMR and HR-TOF-MS.", "output": {"entities": {}}, "schema": []}
{"input": "Soluble conjugated one-dimensional nanowires prepared by topochemical polymerization of a butadiynes-containing star-shaped molecule in the xerogel state.", "output": {"entities": {"chemical": [{"text": "butadiynes", "start": 90, "end": 100}]}}, "schema": []}
{"input": "A star-shaped molecule with three butadiyne moieties attached to a central phenyl core was self-assembled via organogel formation in different solvents and subjected to UV irradiation in its xerogels form to give a soluble conjugated 1D nanowire made of three connected polydiacetylene (PDA) chains.", "output": {"entities": {"chemical": [{"text": "butadiyne", "start": 34, "end": 43}, {"text": "phenyl", "start": 75, "end": 81}, {"text": "polydiacetylene", "start": 270, "end": 285}, {"text": "PDA", "start": 287, "end": 290}]}}, "schema": []}
{"input": "The resulting polymer has a slightly lower optical band gap than its linear counterpart and presents no chromism property, indicative of the rigid nature of the polymer thus obtained.", "output": {"entities": {}}, "schema": []}
{"input": "Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally.", "output": {"entities": {}}, "schema": []}
{"input": "IL-2/anti-IL-2 mAb immunocomplexes were described to have dramatically higher activity than free IL-2 in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "We designed protein chimera consisting of IL-2 linked to light chain of anti-IL-2 mAb S4B6 through flexible oligopeptide spacer (Gly4Ser) 3.", "output": {"entities": {}}, "schema": []}
{"input": "This protein chimera mimics the structure of IL-2/S4B6 mAb immunocomplexes but eliminates general disadvantages of immunocomplexes like possible excess of either IL-2 or anti-IL-2 mAb and their dissociation to antibody and IL-2 at low concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "This novel kind of protein chimera is characterized by an intramolecular interaction between IL-2 and binding site of S4B6 mAb similarly as in IL-2/S4B6 mAb immunocomplexes.", "output": {"entities": {}}, "schema": []}
{"input": "Our protein chimera has biological activity comparable to IL-2/S4B6 mAb immunocomplexes in vitro, as shown by stimulation of proliferation of purified and activated OT-I CD8 (+) T cells.", "output": {"entities": {}}, "schema": []}
{"input": "The protein chimera exerts higher stimulatory activity to drive expansion of purified CFSE-labeled OT-I CD8 (+) T cells activated by an injection of a low dose of SIINFEKL peptide than IL-2/S4B6 mAb immunocomplexes in vivo.", "output": {"entities": {"chemical": [{"text": "CFSE", "start": 86, "end": 90}]}}, "schema": []}
{"input": "The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study we show that a number of cancer cell lines from different tissues display dramatically increased expression of the Cockayne Syndrome group B (CSB) protein, a DNA repair factor, that has recently been shown to be involved in cell robustness.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we demonstrated that ablation of this protein by antisense technology causes devastating effects on tumor cells through a drastic reduction of cell proliferation and massive induction of apoptosis, while non-transformed cells remain unaffected.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, suppression of CSB in cancer cells makes these cells hypersensitive to a variety of commonly used cancer chemotherapeutic agents.", "output": {"entities": {}}, "schema": []}
{"input": "Based on these results, we conclude that cancer cells overexpress CSB protein in order to enhance their anti-apoptotic capacity.", "output": {"entities": {}}, "schema": []}
{"input": "The fact that CSB suppression specifically affects only cancerous cells, without harming healthy cells, suggests that CSB may be a very attractive target for the development of new anticancer therapies.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of cocoa supplementation, caloric restriction, and regular exercise, on oxidative stress markers of brain and memory in the rat model.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of treadmill running (8weeks, 5 times/week, 1h/day at 27m/min), caloric restriction, and cocoa supplementation on brain function and oxidative stress markers were tested.", "output": {"entities": {}}, "schema": []}
{"input": "The Morris maze test was used to appraise rat memory.", "output": {"entities": {}}, "schema": []}
{"input": "Regular exercise significantly improved spatial learning performance.", "output": {"entities": {}}, "schema": []}
{"input": "The level of oxidative stress was measured by the concentration of carbonylated proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The free radical concentration increased in brain of the training groups but not the controls.", "output": {"entities": {}}, "schema": []}
{"input": "The content of reactive carbonyl derivates did not change with exercise, suggesting that the increased production of reactive oxygen species (ROS) were well tolerated in this experimental model.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 24, "end": 32}, {"text": "oxygen", "start": 126, "end": 132}]}}, "schema": []}
{"input": "Caloric restriction (CR) decreased the accumulation of free radicals in the frontal lobe.", "output": {"entities": {}}, "schema": []}
{"input": "The protein content of brain-derived neutrophic factors (BDNFs) was evaluated and changes did not occur either with exercise or cocoa supplementation treatments.", "output": {"entities": {}}, "schema": []}
{"input": "These data did not show significant effects of the administration of cocoa (2% w/w) on the concentration of ROS, BDNF or on spatial memory.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, exercise and CR can play a role in ROS generation and brain function.", "output": {"entities": {}}, "schema": []}
{"input": "The neurobehavioral impact of manganese: Results and challenges obtained by a meta-analysis of individual participant data.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 30, "end": 39}]}}, "schema": []}
{"input": "Results from a meta-analysis of aggregated data provoked a new analysis using individual data on the neuropsychological performance of occupationally exposed workers.", "output": {"entities": {}}, "schema": []}
{"input": "Data from eight studies examining 579 exposed and 433 reference participants were included, 28 performance variables analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "The performance scores were adjusted for well-known individual-level covariates; the influence of possible, but unknown study-level covariates was attenuated by means of a z-normalization.", "output": {"entities": {}}, "schema": []}
{"input": "Associations between performance and exposure were estimated by ANOVAs and ANCOVAs, the latter representing multi-level models.", "output": {"entities": {}}, "schema": []}
{"input": "Four cognitive and motor performance variables each indicated significantly lower performances of exposed individuals when confounding was considered; slowed motor performances and deficits in attention and short-term memory were found.", "output": {"entities": {}}, "schema": []}
{"input": "Performance on a single test was significantly related to the biomarker manganese in blood.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 72, "end": 81}]}}, "schema": []}
{"input": "The outcomes on susceptibility were weak.", "output": {"entities": {}}, "schema": []}
{"input": "The slowing of responses was the most distinct feature of performances of exposed workers.", "output": {"entities": {}}, "schema": []}
{"input": "It remains unclear, whether this result is related to the employed tests or provides important information about early stages of the neurotoxic impairment.", "output": {"entities": {}}, "schema": []}
{"input": "More specific cognitive tests need to be employed to answer this question.", "output": {"entities": {}}, "schema": []}
{"input": "The lack of dose-response relationships was related to features of the biomarker: it does not reflect the Mn in brain responsible for changes in performances.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 106, "end": 108}]}}, "schema": []}
{"input": "Proposed pathogenesis for atypical femoral fractures: Lessons from material research.", "output": {"entities": {}}, "schema": []}
{"input": "Atypical femoral fractures (AFFs) have been well defined clinically and epidemiologically.", "output": {"entities": {}}, "schema": []}
{"input": "Less clear are the underlying mechanisms responsible.", "output": {"entities": {}}, "schema": []}
{"input": "This commentary points out the likely sources of decreased resistance to fracture using lessons from bone material studies and biomechanics.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesize that the key element in the cascade of events leading to failure of the largest and strongest bone in the human body is long-term suppression of normal bone turnover caused by exposure to potent anti-remodeling agents, most notably the bisphosphonates (BPs).", "output": {"entities": {"chemical": [{"text": "bisphosphonates", "start": 251, "end": 266}, {"text": "BPs", "start": 268, "end": 271}]}}, "schema": []}
{"input": "Suppressed bone turnover produces changes in bone that alter its material quality and these changes could lead to adverse effects on its mechanical function.", "output": {"entities": {}}, "schema": []}
{"input": "At the submicroscopic [< 1 mu m] level of collagen fibrils, suppression of bone turnover allows continued addition of non-enzymatic cross links that can reduce collagen' s plasticity and this in turn contributes to reduced bone toughness.", "output": {"entities": {}}, "schema": []}
{"input": "Further, adverse changes in hydroxyapatite crystalline structure and composition can occur, perhaps increasing collagen' s brittleness.", "output": {"entities": {}}, "schema": []}
{"input": "At the microscopic level [~ 1-500 mu m] of the bone-matrix structure, suppressed bone turnover allows full mineralization of cortical bone osteons and results in a microstructure of bone that is more homogeneous.", "output": {"entities": {}}, "schema": []}
{"input": "Both brittleness and loss of heterogeneity allow greater progression of microscopic cracks that can occur with usual physical activity; in crack mechanical terms, normal mechanisms that dissipate crack tip growth energy are greatly reduced and crack progression is less impeded.", "output": {"entities": {}}, "schema": []}
{"input": "Further, the targeted repair of cracks by newly activated BMUs appears to be preferentially suppressed by BPs.", "output": {"entities": {"chemical": [{"text": "BPs", "start": 106, "end": 109}]}}, "schema": []}
{"input": "We further hypothesize that it is not necessary to have accumulation of many cracks to produce an AFF, just one that progresses-one that is not stopped by bone' s several protective mechanisms and is allowed to penetrate through a homogeneous environment.", "output": {"entities": {}}, "schema": []}
{"input": "The remarkable straight transverse fracture line is an indicator of the slow progression of a \" mother crack \" and the failure of usual mechanisms to bridge or deflect the crack.", "output": {"entities": {}}, "schema": []}
{"input": "Research in AFF mechanisms has been focused at the organ level, describing the clinical presentation and radiologic appearance.", "output": {"entities": {}}, "schema": []}
{"input": "Although today we have not yet connected all the dots in the pathophysiology of BP-induced AFF, recent advances in measuring bone mechanical qualities at the submicroscopic and tissue levels allow us to explain how spontaneous catastrophic failure of the femur can occur.", "output": {"entities": {}}, "schema": []}
{"input": "Infected nail plate model made of human hair keratin for evaluating the efficacy of different topical antifungal formulations against Trichophyton rubrum in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "A novel model of infected nail plate for testing the efficacy of topical antifungal formulations has been developed.", "output": {"entities": {}}, "schema": []}
{"input": "This model utilized keratin film made of human hair keratin as a nail plate model.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequent to infection by Trichophyton rubrum, the common causative agent of onychomycosis, keratin films as infected nail plate models were treated with selected topical formulations, that is cream, gel, and nail lacquer.", "output": {"entities": {}}, "schema": []}
{"input": "Bovine hoof was compared to keratin film.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to the common antifungal susceptibility test, the antifungal drugs tested were applied as ready-to-use formulations because the vehicle may modify and control the drug action both in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Extrapolating the potency of an antifungal drug from an in vitro susceptibility test only would not be representative of the in vivo situation since these drugs are applied as ready-to-use formulations, for example as a nail lacquer.", "output": {"entities": {}}, "schema": []}
{"input": "Although terbinafine has been acknowledged to be the most effective antifungal agent against T. rubrum, its antifungal efficacy was improved by its incorporation into an optimal formulation.", "output": {"entities": {"chemical": [{"text": "terbinafine", "start": 9, "end": 20}]}}, "schema": []}
{"input": "Different gels proved superior to cream.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, this study is able to discriminate between efficacies of different topical antifungal formulations based on their activities against T. rubrum.", "output": {"entities": {}}, "schema": []}
{"input": "Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: Influence of mass flow and rotation speed variations.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to develop a quantitative Near-Infrared (NIR) method which monitors the homogeneity of a pharmaceutical formulation coming out of a continuous blender.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, a NIR diode array spectrometer with fast data acquisition was selected.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, the dynamic aspects of a continuous blending process were studied; the results showed a well-defined cluster for the steady state, and the paths for the start-up and emptying stages were clearly identified.", "output": {"entities": {}}, "schema": []}
{"input": "The end point of the start-up phase was detected by moving block of standard deviation, relative standard deviation, and principal component analysis.", "output": {"entities": {}}, "schema": []}
{"input": "A partial least square (PLS) model was generated for the quantification of the drug, with a standard error of prediction of 0. 2% m/m.", "output": {"entities": {}}, "schema": []}
{"input": "The PLS model was successfully applied for monitoring the drug level at the outlet of the continuous blender.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the PLS model was tested under different flow and stirring rates.", "output": {"entities": {}}, "schema": []}
{"input": "Flow and stirring rate variations caused different powder flow dynamics, which were reflected on the NIR measurements.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the PLS model was sensitive to changes in mass flow and rotation speeds.", "output": {"entities": {}}, "schema": []}
{"input": "Charge affects the oral toxicity of poly (amidoamine) dendrimers.", "output": {"entities": {"chemical": [{"text": "poly (amidoamine)", "start": 36, "end": 53}]}}, "schema": []}
{"input": "Poly (amidoamine) (PAMAM) dendrimers have been evaluated for the influence of surface functionality and size on the epithelial barrier of the gut with the goal of identifying safe carriers that can be used for oral drug delivery.", "output": {"entities": {"chemical": [{"text": "Poly (amidoamine)", "start": 0, "end": 17}, {"text": "PAMAM", "start": 19, "end": 24}]}}, "schema": []}
{"input": "Limited studies are conducted to date, however, to assess the toxicity of PAMAM dendrimers in vivo when administered by the oral route.", "output": {"entities": {"chemical": [{"text": "PAMAM", "start": 74, "end": 79}]}}, "schema": []}
{"input": "The goal of this research was to conduct an oral acute toxicity study of PAMAM dendrimers as a function of size and charge in immune competent CD-1 mice.", "output": {"entities": {"chemical": [{"text": "PAMAM", "start": 73, "end": 78}]}}, "schema": []}
{"input": "Maximum tolerated doses (MTD) of PAMAM dendrimers as a function of size and surface functionality were established and clinical signs of toxicity monitored.", "output": {"entities": {"chemical": [{"text": "PAMAM", "start": 33, "end": 38}]}}, "schema": []}
{"input": "Results demonstrate that positively charged dendrimers caused more toxicity, whereas their anionic counterparts were tolerated at ten times higher doses.", "output": {"entities": {}}, "schema": []}
{"input": "Severe signs of toxicity observed for large (G7) cationic amine-or hydroxyl-terminated dendrimers include hemobilia and spleenomegaly.", "output": {"entities": {"chemical": [{"text": "amine", "start": 58, "end": 63}, {"text": "hydroxyl", "start": 67, "end": 75}]}}, "schema": []}
{"input": "The MTD for these dendrimers ranged from 30mg/kg to 200mg/kg.", "output": {"entities": {}}, "schema": []}
{"input": "Anionic G6. 5 or smaller molecular weight carboxyl-, amine-, or hydroxyl-terminated dendrimers (G3. 5-COOH, G4-NH2, G4-OH) on the other hand were tolerated at doses of up to 500mg/kg (300mg/kg in some cases) with minimal or no signs of toxicity.", "output": {"entities": {"chemical": [{"text": "carboxyl", "start": 42, "end": 50}, {"text": "amine", "start": 53, "end": 58}, {"text": "hydroxyl", "start": 64, "end": 72}, {"text": "COOH", "start": 102, "end": 106}, {"text": "NH2", "start": 111, "end": 114}, {"text": "OH", "start": 119, "end": 121}]}}, "schema": []}
{"input": "Establishing the MTD of orally delivered PAMAM dendrimers and the influence of surface functionality and size on toxicity aids in the rational design of PAMAM-drug conjugates for oral drug delivery applications.", "output": {"entities": {"chemical": [{"text": "PAMAM", "start": 41, "end": 46}, {"text": "PAMAM", "start": 153, "end": 158}]}}, "schema": []}
{"input": "Modulation of mitochondrial glutathione status and cellular energetics in primary cultures of proximal tubular cells from remnant kidney of uninephrectomized rats.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 28, "end": 39}]}}, "schema": []}
{"input": "Compensatory renal hypertrophy following reduction in renal mass leads to a hypermetabolic state and increases in basal mitochondrial oxidative stress and susceptibility to several nephrotoxicants.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies provide conflicting data on whether renal mitochondria after reduction in renal mass undergo proliferation or hypertrophy or both.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, our goal was to determine whether mitochondria of hypertrophied kidney undergo hypertrophy or proliferation after uninephrectomy using the uninephrectomized (NPX) rat model.", "output": {"entities": {}}, "schema": []}
{"input": "Renal proximal tubular (PT) cells from NPX rats exhibited increased mitochondrial density, membrane potential and protein but no significant difference in mitochondrial DNA, as compared to PT cells from control rats.", "output": {"entities": {}}, "schema": []}
{"input": "Our previous studies showed that overexpression of two mitochondrial anion transporters, the dicarboxylate (DIC, Slc25a10) and oxoglutarate (OGC, Slc25a11) carriers, in NRK-52E cells resulted in increased mitochondrial uptake of glutathione (GSH) and protection from chemically induced apoptosis.", "output": {"entities": {"chemical": [{"text": "dicarboxylate", "start": 93, "end": 106}, {"text": "DIC", "start": 108, "end": 111}, {"text": "oxoglutarate", "start": 127, "end": 139}, {"text": "OGC", "start": 141, "end": 144}, {"text": "glutathione", "start": 229, "end": 240}, {"text": "GSH", "start": 242, "end": 245}]}}, "schema": []}
{"input": "In the present study, we overexpressed DIC-and OGC-cDNA plasmids to assess their function in renal PT cells after compensatory renal hypertrophy.", "output": {"entities": {"chemical": [{"text": "DIC", "start": 39, "end": 42}, {"text": "OGC", "start": 47, "end": 50}]}}, "schema": []}
{"input": "PT cells from NPX rats that were first preincubated with GSH were protected from cytotoxicity due to the mitochondrial inhibitor antimycin A by overexpression of either of the two mitochondrial GSH transporters.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 57, "end": 60}, {"text": "antimycin A", "start": 129, "end": 140}, {"text": "GSH", "start": 194, "end": 197}]}}, "schema": []}
{"input": "Our present results provide further evidence that compensatory renal hypertrophy is associated primarily with mitochondrial hypertrophy and hyperpolarization and that manipulation of mitochondrial GSH transporters in PT cells of hypertrophied kidney can alter susceptibility to chemically induced injury under appropriate conditions and may be a suitable therapeutic approach.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 197, "end": 200}]}}, "schema": []}
{"input": "Screening of transition and post-transition metals to incorporate into copper oxide and copper bismuth oxide for photoelectrochemical hydrogen evolution.", "output": {"entities": {"chemical": [{"text": "copper oxide", "start": 71, "end": 83}, {"text": "copper bismuth oxide", "start": 88, "end": 108}, {"text": "hydrogen", "start": 134, "end": 142}]}}, "schema": []}
{"input": "A new dispenser and scanner system is used to create and screen Bi-M-Cu oxide arrays for cathodic photoactivity, where M represents 1 of 22 different transition and post-transition metals.", "output": {"entities": {"chemical": [{"text": "Bi", "start": 64, "end": 66}, {"text": "Cu oxide", "start": 69, "end": 77}]}}, "schema": []}
{"input": "Over 3000 unique Bi: M: Cu atomic ratios are screened.", "output": {"entities": {"chemical": [{"text": "Bi", "start": 17, "end": 19}, {"text": "Cu", "start": 24, "end": 26}]}}, "schema": []}
{"input": "Of the 22 metals tested, 10 show a M-Cu oxide with higher photoactivity than CuO and 10 show a Bi-M-Cu oxide with higher photoactivity than CuBi2O4.", "output": {"entities": {"chemical": [{"text": "Cu oxide", "start": 37, "end": 45}, {"text": "CuO", "start": 77, "end": 80}, {"text": "Bi", "start": 95, "end": 97}, {"text": "Cu oxide", "start": 100, "end": 108}, {"text": "CuBi2O4", "start": 140, "end": 147}]}}, "schema": []}
{"input": "Cd, Zn, Sn, and Co produce the most photoactive M-Cu oxides, all showing a 200-300% improvement in photocurrent over CuO.", "output": {"entities": {"chemical": [{"text": "Cd", "start": 0, "end": 2}, {"text": "Zn", "start": 4, "end": 6}, {"text": "Sn", "start": 8, "end": 10}, {"text": "Co", "start": 16, "end": 18}, {"text": "Cu oxides", "start": 50, "end": 59}, {"text": "CuO", "start": 117, "end": 120}]}}, "schema": []}
{"input": "Ag, Cd, and Zn produce the highest photoactivity Bi-M-Cu oxides with a 200-400% improvement over CuBi2O4.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 0, "end": 2}, {"text": "Cd", "start": 4, "end": 6}, {"text": "Zn", "start": 12, "end": 14}, {"text": "Bi", "start": 49, "end": 51}, {"text": "Cu oxides", "start": 54, "end": 63}, {"text": "CuBi2O4", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Most notable is a Bi-Ag-Cu oxide (Bi: Ag: Cu atomic ratio of 22: 3: 11) which shows 4 times higher photocurrent than CuBi2O4.", "output": {"entities": {"chemical": [{"text": "Bi-Ag-Cu oxide", "start": 18, "end": 32}, {"text": "Bi", "start": 34, "end": 36}, {"text": "Ag", "start": 38, "end": 40}, {"text": "Cu", "start": 42, "end": 44}, {"text": "CuBi2O4", "start": 117, "end": 124}]}}, "schema": []}
{"input": "This material is capable of evolving hydrogen under illumination in neutral electrolyte solutions at 0. 6 V vs. RHE when Pt is added to the surface as an electrocatalyst.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 37, "end": 45}, {"text": "Pt", "start": 121, "end": 123}]}}, "schema": []}
{"input": "A structural mapping of mutations causing succinyl-CoA: 3-ketoacid CoA transferase (SCOT) deficiency.", "output": {"entities": {"chemical": [{"text": "succinyl-CoA", "start": 42, "end": 54}]}}, "schema": []}
{"input": "Succinyl-CoA: 3-ketoacid CoA transferase (SCOT) deficiency is a rare inherited metabolic disorder of ketone metabolism, characterized by ketoacidotic episodes and often permanent ketosis.", "output": {"entities": {"chemical": [{"text": "Succinyl-CoA", "start": 0, "end": 12}, {"text": "ketone", "start": 101, "end": 107}]}}, "schema": []}
{"input": "To date there are ~ 20 disease-associated alleles on the OXCT1 gene that encodes the mitochondrial enzyme SCOT.", "output": {"entities": {}}, "schema": []}
{"input": "SCOT catalyzes the first, rate-limiting step of ketone body utilization in peripheral tissues, by transferring a CoA moiety from succinyl-CoA to form acetoacetyl-CoA, for entry into the tricarboxylic acid cycle for energy production.", "output": {"entities": {"chemical": [{"text": "ketone", "start": 48, "end": 54}, {"text": "CoA", "start": 113, "end": 116}, {"text": "succinyl-CoA", "start": 129, "end": 141}, {"text": "acetoacetyl-CoA", "start": 150, "end": 165}, {"text": "tricarboxylic acid", "start": 186, "end": 204}]}}, "schema": []}
{"input": "We have determined the crystal structure of human SCOT, providing a molecular understanding of the reported mutations based on their potential structural effects.", "output": {"entities": {}}, "schema": []}
{"input": "An interactive version of this manuscript (which may contain additional mutations appended after acceptance of this manuscript) may be found on the web address: http://www. thesgc. org/jimd/SCOT.", "output": {"entities": {}}, "schema": []}
{"input": "Gelatin-Methacrylamide Hydrogels as Potential Biomaterials for Fabrication of Tissue-Engineered Cartilage Constructs.", "output": {"entities": {"chemical": [{"text": "Methacrylamide", "start": 8, "end": 22}]}}, "schema": []}
{"input": "Gelatin-methacrylamide (gelMA) hydrogels are shown to support chondrocyte viability and differentiation and give wide ranging mechanical properties depending on several cross-linking parameters.", "output": {"entities": {"chemical": [{"text": "methacrylamide", "start": 8, "end": 22}]}}, "schema": []}
{"input": "Polymer concentration, UV exposure time, and thermal gelation prior to UV exposure allow for control over hydrogel stiffness and swelling properties.", "output": {"entities": {}}, "schema": []}
{"input": "GelMA solutions have a low viscosity at 37 degrees C, which is incompatible with most biofabrication approaches.", "output": {"entities": {}}, "schema": []}
{"input": "However, incorporation of hyaluronic acid (HA) and/or co-deposition with thermoplastics allows gelMA to be used in biofabrication processes.", "output": {"entities": {}}, "schema": []}
{"input": "These attributes may allow engineered constructs to match the natural functional variations in cartilage mechanical and geometrical properties.", "output": {"entities": {}}, "schema": []}
{"input": "Glyconanosomes: disk-shaped nanomaterials for the water solubilization and delivery of hydrophobic molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we describe the first report on a new class of disk-shaped and quite monodisperse water-soluble nanomaterials that we named glyconanosomes (GNS).", "output": {"entities": {}}, "schema": []}
{"input": "GNSs were obtained by sliding out the cylindrical structures formed upon self-organization and photopolymerization of glycolipid 1 on single-walled carbon nanotube (SWCNT) sidewalls.", "output": {"entities": {}}, "schema": []}
{"input": "GNSs present a sheltered hydrophobic inner cavity formed by the carbonated tails, surrounded by PEG and lactose moieties.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 96, "end": 99}]}}, "schema": []}
{"input": "The amphiphilic character of GNSs allows the water solubility of insoluble hydrophobic cargos such as a perylene-bisimide derivative, [60] fullerene, or the anti-carcinogenic drug camptothecin (CPT).", "output": {"entities": {"chemical": [{"text": "perylene-bisimide", "start": 104, "end": 121}, {"text": "[60] fullerene", "start": 134, "end": 148}, {"text": "camptothecin", "start": 180, "end": 192}, {"text": "CPT", "start": 194, "end": 197}]}}, "schema": []}
{"input": "GNS/C60 inclusion complexes are able to establish specific interactions between peanut agglutinin (PNA) lectin and the lactose moiety surrounding the complexes, while CPT solubilized by GNS shows higher cytotoxicity toward MCF7-type breast cancer cells than CPT alone.", "output": {"entities": {"chemical": [{"text": "C60", "start": 4, "end": 7}, {"text": "CPT", "start": 167, "end": 170}, {"text": "CPT", "start": 258, "end": 261}]}}, "schema": []}
{"input": "Thus, GNS represents an attractive extension of nanoparticle-based drug delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Three new lanostanoid triterpenes from the fruiting bodies of Ganoderma tropicum.", "output": {"entities": {"chemical": [{"text": "lanostanoid triterpenes", "start": 10, "end": 33}]}}, "schema": []}
{"input": "Three new lanostanoid triterpenes, 3 beta, 7 beta, 15 beta-trihydroxy-11, 23-dioxo-lanost-8, 16-dien-26-oic acid (1), 3 beta, 7 beta, 15 beta-trihydroxy-11, 23-dioxo-lanost-8, 16-dien-26-oic acid methyl ester (2), and 3 beta, 15 beta-dihydroxy-7, 11, 23-trioxo-lanost-8, 16-dien-26-oic acid methyl ester (3) were isolated from the EtOAc extract of the fruiting bodies of Ganoderma tropicum.", "output": {"entities": {"chemical": [{"text": "lanostanoid triterpenes", "start": 10, "end": 33}, {"text": "3 beta, 7 beta, 15 beta-trihydroxy-11, 23-dioxo-lanost-8, 16-dien-26-oic acid", "start": 35, "end": 112}, {"text": "3 beta, 7 beta, 15 beta-trihydroxy-11, 23-dioxo-lanost-8, 16-dien-26-oic acid methyl ester", "start": 118, "end": 208}, {"text": "3 beta, 15 beta-dihydroxy-7, 11, 23-trioxo-lanost-8, 16-dien-26-oic acid methyl ester", "start": 218, "end": 303}, {"text": "EtOAc", "start": 331, "end": 336}]}}, "schema": []}
{"input": "Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy as well as MS.", "output": {"entities": {}}, "schema": []}
{"input": "The bioassay of inhibitory activity against acetylcholinesterase (AChE) of these isolates was evaluated and compound 2 exhibited definite inhibitory activity against AChE.", "output": {"entities": {}}, "schema": []}
{"input": "Strategies to control morphology in hybrid group III-V/group IV heterostructure nanowires.", "output": {"entities": {}}, "schema": []}
{"input": "By combining in situ and ex situ transmission electron microscopy measurements, we examine the factors that control the morphology of \" hybrid \" nanowires that include group III-V and group IV materials.", "output": {"entities": {}}, "schema": []}
{"input": "We focus on one materials pair, GaP/Si, for which we use a wide range of growth parameters.", "output": {"entities": {"chemical": [{"text": "GaP", "start": 32, "end": 35}, {"text": "Si", "start": 36, "end": 38}]}}, "schema": []}
{"input": "We show through video imaging that nanowire morphology depends on growth conditions, but that a general pattern emerges where either single kinks or inclined defects form some distance after the heterointerface.", "output": {"entities": {}}, "schema": []}
{"input": "We show that pure Si nanowires can be made to exhibit the same kinks and defects by changing their droplet volume.", "output": {"entities": {"chemical": [{"text": "Si", "start": 18, "end": 20}]}}, "schema": []}
{"input": "From this we derive a model where droplet geometry drives growth morphology and discuss optimization strategies.", "output": {"entities": {}}, "schema": []}
{"input": "We finally discuss morphology control for material pairs where the second material kinks immediately at the heterointerface and show that an interlayer between segments can enable the growth of unkinked hybrid nanowires.", "output": {"entities": {}}, "schema": []}
{"input": "Reversal effect of rosmarinic acid on multidrug resistance in SGC7901/Adr cell.", "output": {"entities": {"chemical": [{"text": "rosmarinic acid", "start": 19, "end": 34}, {"text": "Adr", "start": 70, "end": 73}]}}, "schema": []}
{"input": "Multidrug resistance (MDR) has been a major problem in cancer chemotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, the aim was to explore the reversal effect and its potential mechanism of rosmarinic acid (RA) on SGC7901/Adr cells.", "output": {"entities": {"chemical": [{"text": "rosmarinic acid", "start": 89, "end": 104}]}}, "schema": []}
{"input": "3-(4, 5-Dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay was used to investigate the reversal index of RA in SGC7901/Adr cell line.", "output": {"entities": {"chemical": [{"text": "3-(4, 5-Dimethylthiazol)-2, 5-diphenyl tetrazolium bromide", "start": 0, "end": 58}, {"text": "MTT", "start": 60, "end": 63}, {"text": "Adr", "start": 131, "end": 134}]}}, "schema": []}
{"input": "The intracellular accumulation of adriamycin, rhodamine123 (Rh123), and the expression of P-glycoprotein (P-gp) were assayed by flow cytometry.", "output": {"entities": {"chemical": [{"text": "adriamycin", "start": 34, "end": 44}, {"text": "rhodamine123", "start": 46, "end": 58}, {"text": "Rh123", "start": 60, "end": 65}]}}, "schema": []}
{"input": "The influence of RA on the transcription of MDR1 gene was determined by reverse transcription-polymerase chain reaction.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that RA could reverse the MDR of SGC7901/Adr cells, increase the intracellular accumulation of Adr and Rh123, and decrease the transcription of MDR1 gene and the expression of P-gp in SGC7901/Adr cells.", "output": {"entities": {"chemical": [{"text": "Adr", "start": 60, "end": 63}, {"text": "Adr", "start": 114, "end": 117}, {"text": "Rh123", "start": 122, "end": 127}]}}, "schema": []}
{"input": "These results indicated that RA was a potential multidrug resistance-reversing agent and warranted further investigations.", "output": {"entities": {}}, "schema": []}
{"input": "Two new piperidine alkaloids from Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "piperidine alkaloids", "start": 8, "end": 28}]}}, "schema": []}
{"input": "NEAU-Z4.", "output": {"entities": {}}, "schema": []}
{"input": "Two new piperidine alkaloids, streptazones E (1) and F (2), were isolated from Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "piperidine alkaloids", "start": 8, "end": 28}, {"text": "streptazones", "start": 30, "end": 42}]}}, "schema": []}
{"input": "NEAU-Z4.", "output": {"entities": {}}, "schema": []}
{"input": "Their structures were elucidated on the basis of MS and NMR analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, cytotoxicity and in vitro antileishmanial activity of naphthothiazoles.", "output": {"entities": {"chemical": [{"text": "naphthothiazoles", "start": 65, "end": 81}]}}, "schema": []}
{"input": "The leishmaniasis is a spectral disease caused by the protozoan Leishmania spp, which threatens millions of people worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Current treatments exhibit high toxicity and there is no vaccine available.", "output": {"entities": {}}, "schema": []}
{"input": "The need for new lead compounds with leishmanicidal activity is urgent.", "output": {"entities": {}}, "schema": []}
{"input": "Considering that many lead leishmanicidal compounds contain a quinoidal scaffold and the thiazole heterocyclic ring is found in a number of antimicrobial drugs, we proposed a hybridization approach to generate a diverse set of semi-synthetic heterocycles with antileishmanial activity.", "output": {"entities": {"chemical": [{"text": "quinoidal", "start": 62, "end": 71}, {"text": "thiazole", "start": 89, "end": 97}]}}, "schema": []}
{"input": "We found that almost all synthesized compounds demonstrated potent activity against promastigotes of Leishmania (Viannia) braziliensis and reduced the survival index of Leishmania amastigotes in mammalian macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the compounds were not cytotoxic to macrophages at 5-fold higher concentrations than the EC (50) for promastigotes.", "output": {"entities": {}}, "schema": []}
{"input": "All molecules fulfilled Lipinski' s Rule of Five, which predicts efficient orally absorption and permeation through biological membranes, the in silico pharmacokinetic profile confirmed these characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "The potent and selective activity of semi-synthetic naphthothiazoles against promastigotes and amastigotes reveals that the 2-amino-naphthothiazole ring may represent a scaffold for the design of compounds with leishmanicidal properties and encourage the development of drug formulation and new compounds for further studies in vivo.", "output": {"entities": {"chemical": [{"text": "naphthothiazoles", "start": 52, "end": 68}, {"text": "2-amino-naphthothiazole", "start": 124, "end": 147}]}}, "schema": []}
{"input": "(c) 2013 John Wiley & Sons A/S.", "output": {"entities": {}}, "schema": []}
{"input": "Two new sesquiterpenes from cultures of the basidiomycete Agaricus arvensis.", "output": {"entities": {"chemical": [{"text": "sesquiterpenes", "start": 8, "end": 22}]}}, "schema": []}
{"input": "Two new drimane sesquiterpenoids, 11, 12-dihydroxy-15-drimeneoic acid (1) and 3 alpha, 11, 15-trihydroxydrimene (2), were isolated from cultures of the basidiomycete Agaricus arvensis, together with one known compound 3 beta, 11, 12-trihydroxydrimene (3).", "output": {"entities": {"chemical": [{"text": "drimane sesquiterpenoids", "start": 8, "end": 32}, {"text": "11, 12-dihydroxy-15-drimeneoic acid", "start": 34, "end": 69}, {"text": "3 alpha, 11, 15-trihydroxydrimene", "start": 78, "end": 111}, {"text": "3 beta, 11, 12-trihydroxydrimene", "start": 218, "end": 250}]}}, "schema": []}
{"input": "Their structures were established by means of spectroscopic analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Calmodulin as a potential target by which berberine induce cell cycle arrest in human hepatoma Bel7402 cells.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 42, "end": 51}]}}, "schema": []}
{"input": "Berberine is an isoquinoline alkaloid that has drawn extensive attention since it possesses various biological activities.", "output": {"entities": {"chemical": [{"text": "Berberine", "start": 0, "end": 9}, {"text": "isoquinoline alkaloid", "start": 16, "end": 37}]}}, "schema": []}
{"input": "Several mechanisms have been proposed to interpret the anticancer activity of berberine.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 78, "end": 87}]}}, "schema": []}
{"input": "However, these explanations are mostly based on its downstream-regulated genes or proteins, information on the direct target proteins that mediate the antiproliferative action of berberine remain unclear.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 179, "end": 188}]}}, "schema": []}
{"input": "In the present study, a computational pipeline based on a ligand-protein inverse docking program and mining of the \" Connectivity MAP \" data was adopted to explore the potential target proteins for berberine.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 198, "end": 207}]}}, "schema": []}
{"input": "The results showed that four proteins, i. e., calmodulin, cytochrome P450 3A4, sex hormone-binding globulin and carbonic anhydrase II, were suggested to be the potential targets of berberine.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 181, "end": 190}]}}, "schema": []}
{"input": "The anti-calmodulin property of berberine was demonstrated with an in vitro phosphodiesterase activity assay.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 32, "end": 41}]}}, "schema": []}
{"input": "Flow cytometric analysis found that G1 cell cycle arrest induced by berberine in Bel7402 cells was enhanced by cotreatment with calmodulin inhibitors.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 68, "end": 77}]}}, "schema": []}
{"input": "Western blotting results indicated that berberine treatment decreased phosphorylation of calmodulin kinase II and blocked subsequent MEK1 activation as well as p27 protein degradation.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 40, "end": 49}]}}, "schema": []}
{"input": "These results suggested that calmodulin might play crucial roles in berberine-induced cell cycle arrest in cancer cells.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 68, "end": 77}]}}, "schema": []}
{"input": "(c) 2013 John Wiley & Sons A/S.", "output": {"entities": {}}, "schema": []}
{"input": "Two new sesquiterpenoids from the fungus Ceriporia alachuana.", "output": {"entities": {"chemical": [{"text": "sesquiterpenoids", "start": 8, "end": 24}]}}, "schema": []}
{"input": "Two new sesquiterpenoids, tremulenolide D (1) and muurolane-10 beta, 15-diol (2), together with four known sesquiterpenoids, tremulenediol A (3), 2 beta-hydroxy-alpha-candinol (4), epicubenol (5), and 3 beta-hydroxy-delta-candinol (6), were isolated from cultures of the fungus Ceriporia alachuana.", "output": {"entities": {"chemical": [{"text": "sesquiterpenoids", "start": 8, "end": 24}, {"text": "tremulenolide D", "start": 26, "end": 41}, {"text": "muurolane-10 beta, 15-diol", "start": 50, "end": 76}, {"text": "sesquiterpenoids", "start": 107, "end": 123}, {"text": "tremulenediol A", "start": 125, "end": 140}, {"text": "2 beta-hydroxy-alpha-candinol", "start": 146, "end": 175}, {"text": "epicubenol", "start": 181, "end": 191}, {"text": "3 beta-hydroxy-delta-candinol", "start": 201, "end": 230}]}}, "schema": []}
{"input": "The structures of new compounds were determined by extensive spectroscopic analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Structurally, compounds 1 and 3 are tremulane-type sesquiterpenoids with an unusual perhydroazulene carbon skeleton.", "output": {"entities": {"chemical": [{"text": "tremulane", "start": 36, "end": 45}, {"text": "sesquiterpenoids", "start": 51, "end": 67}, {"text": "perhydroazulene carbon", "start": 84, "end": 106}]}}, "schema": []}
{"input": "Adsorption, organization, and rheology of catanionic layers at the air/water interface.", "output": {"entities": {}}, "schema": []}
{"input": "We have investigated the adsorption and organization at the air/water interface of catanionic molecules released from a dispersion of solid-like catanionic vesicles composed of myristic acid and cetyl trimethylammonium chloride at the 2: 1 ratio.", "output": {"entities": {"chemical": [{"text": "myristic acid", "start": 177, "end": 190}, {"text": "cetyl trimethylammonium chloride", "start": 195, "end": 227}]}}, "schema": []}
{"input": "These vesicles were shown recently to be promising foam stabilizers.", "output": {"entities": {}}, "schema": []}
{"input": "Using Brewster angle microscopy, we observed the formation of a catanionic monolayer at the air/water interface composed of liquid-condensed domains in a liquid-expanded matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Further adsorption of catanionic molecules forced them to pack, thereby forming a very dense monolayer that prevented further vesicle rupture by avoiding contact of the vesicles with air.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, confocal fluorescence microscopy revealed the presence of layers of intact vesicles that were progressively creaming toward this catanionic monolayer; the surface tension of the vesicle dispersion remained constant upon creaming.", "output": {"entities": {}}, "schema": []}
{"input": "The catanionic monolayer behaved as a soft glassy material, an amorphous solid with time-and temperature-dependent properties.", "output": {"entities": {}}, "schema": []}
{"input": "Using interfacial oscillatory rheology, we found that the monolayer relaxed mechanical stresses in seconds and melted at a temperature very close to the melting transition temperature of the vesicle bilayers.", "output": {"entities": {}}, "schema": []}
{"input": "These results have potential application in the design of smart foams that have temperature-tunable stability.", "output": {"entities": {}}, "schema": []}
{"input": "Three new phenyl-ethanediols from the fruiting bodies of the mushroom Fomes fomentarius.", "output": {"entities": {"chemical": [{"text": "phenyl-ethanediols", "start": 10, "end": 28}]}}, "schema": []}
{"input": "Three new phenyl-ethanediols, (1R)-(3-ethenylphenyl)-1, 2-ethanediol (1), (1R)-(3-formylphenyl)-1, 2-ethanediol (2), and (1R)-(3-acetophenyl)-1, 2-ethanediol (3), were isolated from the fruiting bodies of the mushroom Fomes fomentarius, together with two related known compounds, (3-ethylphenyl)-1, 2-ethanediol (4) and (4-acetophenyl)-1, 2-ethanediol (5).", "output": {"entities": {"chemical": [{"text": "phenyl-ethanediols", "start": 10, "end": 28}, {"text": "(1R)-(3-ethenylphenyl)-1, 2-ethanediol", "start": 30, "end": 68}, {"text": "(1R)-(3-formylphenyl)-1, 2-ethanediol", "start": 74, "end": 111}, {"text": "(1R)-(3-acetophenyl)-1, 2-ethanediol", "start": 121, "end": 157}, {"text": "(3-ethylphenyl)-1, 2-ethanediol", "start": 280, "end": 311}, {"text": "(4-acetophenyl)-1, 2-ethanediol", "start": 320, "end": 351}]}}, "schema": []}
{"input": "Their structures were elucidated by spectroscopic methods including extensive 2D NMR techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1-3 showed weak antimicrobial activity.", "output": {"entities": {}}, "schema": []}
{"input": "p53-mediated autophagy adjustment is involved in the protection of silibinin against murine dermal inflammation and epidermal apoptosis induced by UVB irradiation.", "output": {"entities": {"chemical": [{"text": "silibinin", "start": 67, "end": 76}]}}, "schema": []}
{"input": "Apoptosis in murine dermal cells is retarded by ultraviolet B (UVB) irradiation-induced autophagic intervention while simultaneously epidermal cells commit apoptosis, during which inflammatory cytokines released from the lost epidermal cells promote immune responses of dermal inflammatory cells, forming morphological symptoms of acute cutaneous diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Autophagy is involved in prevention or provocation of apoptosis of dermal or epidermal cells of UVB-irradiated mice via modulation of intracellular metabolism, intervening the balance between cell death and survival in dermis and epidermis.", "output": {"entities": {}}, "schema": []}
{"input": "p53 expressed in immune system affects autophagy function through activating or inactivating genes encoding apoptotic factors and inflammatory cytokines.", "output": {"entities": {}}, "schema": []}
{"input": "Silibinin protects dermal and epidermal cells of UVB irradiated skin against abnormally autophagy-mediated apoptosis adjustments.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In this study, how UVB irradiation intervenes autophagy in dermal and epidermal cells as well as how silibinin protects UVB irradiated skin through physiological recovering of autophagy function in dermis and epidermis are focused and elucidated preliminarily.", "output": {"entities": {"chemical": [{"text": "silibinin", "start": 101, "end": 110}]}}, "schema": []}
{"input": "Silibinin treatment (50 mg/kg/day for 4 days) reversed dermal and epidermal autophagy levels from UVB irradiation-induced improper autophagy intervention, repaired the balance between cell survival and death in dermis and epidermis, and protected skin against damage through mediation of p53 activation in dermal and epidermal cells.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Two new coumarin glycosides from Chimonanthus nitens.", "output": {"entities": {"chemical": [{"text": "coumarin glycosides", "start": 8, "end": 27}]}}, "schema": []}
{"input": "Two new coumarin glycosides, namely nitensosides A-B (1-2), together with six known compounds, scopolin (3), 5, 6, 7-trimethoxycoumarin (4), d-calycanthine (5), calycanthoside (6), xeroboside (7), and scopoletin (8), were isolated from Chimonanthus nitens.", "output": {"entities": {"chemical": [{"text": "coumarin glycosides", "start": 8, "end": 27}, {"text": "nitensosides A-B", "start": 36, "end": 52}, {"text": "scopolin", "start": 95, "end": 103}, {"text": "5, 6, 7-trimethoxycoumarin", "start": 109, "end": 135}, {"text": "d-calycanthine", "start": 141, "end": 155}, {"text": "calycanthoside", "start": 161, "end": 175}, {"text": "xeroboside", "start": 181, "end": 191}, {"text": "scopoletin", "start": 201, "end": 211}]}}, "schema": []}
{"input": "The structures of the new compounds were elucidated by comprehensive analysis of IR, MS, and NMR spectroscopic data.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 3, 4, 7, and 8 showed moderate inhibitory activity against Micrococcus luteus.", "output": {"entities": {}}, "schema": []}
{"input": "Electronic Spectroscopy and Electronic Structure of Copper Acetylide, CuCCH.", "output": {"entities": {"chemical": [{"text": "Copper Acetylide", "start": 52, "end": 68}, {"text": "CuCCH", "start": 70, "end": 75}]}}, "schema": []}
{"input": "The optical spectrum of the linear CuCCH molecule has been investigated for the first time, using resonant two-photon ionization spectroscopy employing ArF (193 nm) or F2 (157 nm) excimer radiation for photoionization.", "output": {"entities": {"chemical": [{"text": "CuCCH", "start": 35, "end": 40}, {"text": "ArF", "start": 152, "end": 155}, {"text": "F2", "start": 168, "end": 170}]}}, "schema": []}
{"input": "Scans over the range 19 400-25 200 cm (-1) were conducted, leading to the observation of three electronic band systems.", "output": {"entities": {}}, "schema": []}
{"input": "These are identified as the [20. 2] a 1 <-- X (1) Sigma (+), the [23. 1] A (1) Sigma (+) <-- X (1) Sigma (+), and the [24. 7] B (1) Pi <-- X (1) Sigma (+) systems, although only the first two have been rotationally resolved.", "output": {"entities": {}}, "schema": []}
{"input": "The a 1 state is tentatively assigned as having (3) Pi 1 symmetry, becoming optically accessible through spin-orbit interaction with the B (1) Pi state.", "output": {"entities": {}}, "schema": []}
{"input": "Vibrational assignments have provided the frequency of the Cu-C stretching mode, nu 3, in the ground and all three excited states, along with both bending modes, nu 4 and nu 5, in the A (1) Sigma (+) and B (1) Pi states, and the Cu-C = C bending mode, nu 5, in the ground state.", "output": {"entities": {"chemical": [{"text": "Cu-C", "start": 59, "end": 63}, {"text": "Cu-C = C", "start": 229, "end": 237}]}}, "schema": []}
{"input": "Comparisons are made to the known electronic states of CuF, CuCl, CuBr, and CuI, and it is argued that like these molecules, the CuCCH molecule is essentially ionic in both the ground and excited states, with the ground state correlating diabatically to Cu (+) (3d (10), (1) S) + CCH (-) (X (1) Sigma (+)) and the excited states correlating diabatically to Cu (+) (3d (9) 4s (1), (1, 3) D) + CCH (-) (X (1) Sigma (+)).", "output": {"entities": {"chemical": [{"text": "CuF", "start": 55, "end": 58}, {"text": "CuCl", "start": 60, "end": 64}, {"text": "CuBr", "start": 66, "end": 70}, {"text": "CuI", "start": 76, "end": 79}, {"text": "CuCCH", "start": 129, "end": 134}, {"text": "Cu (+)", "start": 254, "end": 260}, {"text": "CCH (-)", "start": 280, "end": 287}, {"text": "Cu (+)", "start": 357, "end": 363}, {"text": "CCH (-)", "start": 392, "end": 399}]}}, "schema": []}
{"input": "Human fibrinogen monolayers on latex particles: role of ionic strength.", "output": {"entities": {}}, "schema": []}
{"input": "The adsorption of human serum fibrinogen on polystyrene latex particles was studied using the microelectrophoretic and concentration depletion methods.", "output": {"entities": {}}, "schema": []}
{"input": "Measurements were carried out for pH 3. 5 and an ionic strength range of 10 (-3) to 0. 15 M NaCl.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 92, "end": 96}]}}, "schema": []}
{"input": "The electrophoretic mobility of latex was determined as a function of the amount of adsorbed fibrinogen (surface concentration).", "output": {"entities": {}}, "schema": []}
{"input": "A monotonic increase in the electrophoretic mobility (zeta potential) of the latex was observed, indicating a significant adsorption of fibrinogen on latex for all ionic strengths.", "output": {"entities": {}}, "schema": []}
{"input": "No changes in the latex mobility were observed for prolonged time periods, suggesting the irreversibility of fibrinogen adsorption.", "output": {"entities": {}}, "schema": []}
{"input": "The maximum coverage of fibrinogen on latex particles was precisely determined using the depletion method.", "output": {"entities": {}}, "schema": []}
{"input": "The residual protein concentration after making contact with latex particles was determined by electrokinetic measurements and AFM imaging where the surface coverage of fibrinogen on mica was quantitatively determined.", "output": {"entities": {"chemical": [{"text": "mica", "start": 183, "end": 187}]}}, "schema": []}
{"input": "The maximum fibrinogen coverage increased monotonically with ionic strength from 1. 8 mg m (-2) for 10 (-3) M NaCl to 3. 6 mg m (-2) for 0. 15 M NaCl.", "output": {"entities": {}}, "schema": []}
{"input": "The increase in the maximum coverage was interpreted in terms of the reduced electrostatic repulsion among adsorbed fibrinogen molecules.", "output": {"entities": {}}, "schema": []}
{"input": "The experimental data agree with theoretical simulations made by assuming a 3D unoriented adsorption of fibrinogen.", "output": {"entities": {}}, "schema": []}
{"input": "The stability of fibrinogen monolayers on latex was also determined in ionic strength cycling experiments.", "output": {"entities": {}}, "schema": []}
{"input": "It was revealed that cyclic variations in NaCl concentration between 10 (-3) and 0. 15 M induced no changes in the latex electrophoretic mobility, suggesting that there were no irreversible molecule orientation changes in the monolayers.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 42, "end": 46}]}}, "schema": []}
{"input": "On the basis of these experimental data, a robust procedure of preparing fibrinogen monolayers on latex particles of well-controlled coverage was proposed.", "output": {"entities": {}}, "schema": []}
{"input": "A new type of protective surface layer for high-capacity Ni-based cathode materials: nanoscaled surface pillaring layer.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 57, "end": 59}]}}, "schema": []}
{"input": "A solid solution series of lithium nickel metal oxides, Li [Ni (1-x) M (x)] O2 (with M = Co, Mn, and Al) have been investigated intensively to enhance the inherent structural instability of LiNiO2.", "output": {"entities": {"chemical": [{"text": "lithium nickel metal oxides", "start": 27, "end": 54}, {"text": "Li [Ni (1-x) M (x)] O2", "start": 56, "end": 78}, {"text": "Co", "start": 89, "end": 91}, {"text": "Mn", "start": 93, "end": 95}, {"text": "Al", "start": 101, "end": 103}, {"text": "LiNiO2", "start": 190, "end": 196}]}}, "schema": []}
{"input": "However, when a voltage range of Ni-based cathode materials was increased up to > 4. 5 V, phase transitions occurring above 4. 3 V resulted in accelerated formation of the trigonal phase (P3m1) and NiO phases, leading to and pulverization of the cathode during cycling at 60 degrees C.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 33, "end": 35}, {"text": "NiO", "start": 198, "end": 201}]}}, "schema": []}
{"input": "In an attempt to overcome these problems, LiNi0. 62Co0. 14Mn0. 24O2 cathode material with pillar layers in which Ni (2 +) ions were resided in Li slabs near the surface having a thickness of ~ 10 nm was prepared using a polyvinylpyrrolidone (PVP) functionalized Mn precursor coating on Ni0. 7Co0. 15Mn0. 15 (OH) 2.", "output": {"entities": {"chemical": [{"text": "LiNi0. 62Co0. 14Mn0. 24O2", "start": 42, "end": 67}, {"text": "Ni (2 +)", "start": 113, "end": 121}, {"text": "Li", "start": 143, "end": 145}, {"text": "polyvinylpyrrolidone", "start": 220, "end": 240}, {"text": "PVP", "start": 242, "end": 245}, {"text": "Mn", "start": 262, "end": 264}, {"text": "Ni0. 7Co0. 15Mn0. 15 (OH) 2", "start": 286, "end": 313}]}}, "schema": []}
{"input": "We confirmed the formation of a pillar layer via various analysis methods (XPS, HRTEM, and STEM).", "output": {"entities": {}}, "schema": []}
{"input": "This material showed excellent structural stability due to a pillar layer, corresponding to 85% capacity retention between 3. 0 and 4. 5 V at 60 degrees C after 100 cycles.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the amount of heat generation was decreased by 40%, compared to LiNi0. 70Co0. 15Mn0. 15O2.", "output": {"entities": {"chemical": [{"text": "LiNi0. 70Co0. 15Mn0. 15O2", "start": 77, "end": 102}]}}, "schema": []}
{"input": "Bioactive phenolics from Seriphidium stenocephalum.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 10, "end": 19}]}}, "schema": []}
{"input": "Chromatographic separation of the ethyl acetate soluble part of the methanolic extract from Seriphidium stenocephalum yielded three new compounds: stenocepflavone (1), stenocepflavan (2), and stenocephol (3), together with cirsimaritin (4), 5, 7, 5'-trihydroxy-3', 4', 6-trimethoxyflavone (5), 5, 6, 7, 5'-tetrahydroxy-4'-methoxyflavone (6), and axillaroside (7).", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 34, "end": 47}, {"text": "stenocepflavone", "start": 147, "end": 162}, {"text": "stenocepflavan", "start": 168, "end": 182}, {"text": "stenocephol", "start": 192, "end": 203}, {"text": "cirsimaritin", "start": 223, "end": 235}, {"text": "5, 7, 5'-trihydroxy-3', 4', 6-trimethoxyflavone", "start": 241, "end": 288}, {"text": "5, 6, 7, 5'-tetrahydroxy-4'-methoxyflavone", "start": 294, "end": 336}, {"text": "axillaroside", "start": 346, "end": 358}]}}, "schema": []}
{"input": "All isolates were characterized with the help of spectroscopic data including 1D, 2D NMR, and high resolution mass spectrometry and/or in comparison with the related compounds in literature.", "output": {"entities": {}}, "schema": []}
{"input": "All compounds were tested for in vitro enzyme inhibitory activities against acetylcholinesterase, butyrylcholinesterase, and lipoxygenase.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1 and 4-7 exhibited significant activity against all the tested enzymes, whereas compounds 2 and 3 were found inactive.", "output": {"entities": {}}, "schema": []}
{"input": "Applications of flow cytometry to toxicological mycotoxin effects in cultured mammalian cells: A review.", "output": {"entities": {}}, "schema": []}
{"input": "This review gives an overview of flow cytometry applications to toxicological studies of several physiological target sites of mycotoxins on different mammalian cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Mycotoxins are secondary metabolites of fungi that may be present in food, feed, air and water.", "output": {"entities": {}}, "schema": []}
{"input": "The increasing presence of mycotoxins in crops, their wide distribution in the food chain, and their potential for toxicity demonstrate the need for further knowledge.", "output": {"entities": {}}, "schema": []}
{"input": "Flow cytometry has become a valuable tool in mycotoxin studies in recent years for the rapid analysis of single cells in a mixture.", "output": {"entities": {}}, "schema": []}
{"input": "In toxicology, the power of these methods lies in the possibility of determining a wide range of cell parameters, providing valuable information to elucidate cell growth and viability, metabolic activity, mitochondrial membrane potential and membrane integrity mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "There are studies using flow cytometry technique on Alternaria, Aspergillus, Fusarium and Penicillium mycotoxins including information about cell type, assay conditions and functional parameters.", "output": {"entities": {}}, "schema": []}
{"input": "Most of the studies collected in the literature are on deoxynivalenol and zearalenone mycotoxins.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 55, "end": 69}, {"text": "zearalenone", "start": 74, "end": 85}]}}, "schema": []}
{"input": "Cell cycle analysis and apoptosis are the processes more widely investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Proteomic and metabolomic approaches to the study of polycystic ovary syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Polycystic ovary syndrome (PCOS) is considered a complex multifactorial disorder resulting from the interaction of genetic, environmental, and lifestyle influences.", "output": {"entities": {}}, "schema": []}
{"input": "Nontargeted proteomics and metabolomics have been used in the past years with the aim of identifying molecules potentially involved in the pathophysiology of this frequent disorder.", "output": {"entities": {}}, "schema": []}
{"input": "The biomolecules identified so far participate in many metabolic pathways, including energy metabolism (glucose and lipid metabolism), protein metabolic processes and protein folding, cytoskeleton structure, immune response, inflammation and iron metabolism, fibrinolysis and thrombosis, oxidative stress and intracellular calcium metabolism.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 104, "end": 111}, {"text": "calcium", "start": 323, "end": 330}]}}, "schema": []}
{"input": "These molecules provide key information about molecular functions altered in PCOS and raise questions concerning their precise role in the pathogenesis of this syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "The biomolecules identified by nontargeted proteomic and metabolomic approaches should be considered as candidates in future studies aiming to define specific molecular phenotypes of PCOS.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidative polyphenols from Nigerian mistletoe Loranthus micranthus (Linn.) parasitizing on Hevea brasiliensis.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 14, "end": 25}]}}, "schema": []}
{"input": "Two new phenolic glycosides, linamarin gallate (1) and walsuraside B (2), together with nine known compounds, catechin (3), epicatechin (4), epicatechin 3-O-gallate (5), epicatechin 3-O-(3-O-methyl) gallate (6), epicatechin 3-O-(3, 5-O-dimethyl) gallate (7), epicatechin 3-O-(3, 4, 5-O-trimethyl) gallate (8), quercetin 3-O-beta-d-glucopyranoside (9), rutin (10), and peltatoside (11), were isolated from the leafy twigs of Nigerian mistletoe Loranthus micranthus (Linn.) parasitic on Hevea brasiliensis.", "output": {"entities": {"chemical": [{"text": "phenolic glycosides", "start": 8, "end": 27}, {"text": "linamarin gallate", "start": 29, "end": 46}, {"text": "walsuraside B", "start": 55, "end": 68}, {"text": "catechin", "start": 110, "end": 118}, {"text": "epicatechin", "start": 124, "end": 135}, {"text": "epicatechin 3-O-gallate", "start": 141, "end": 164}, {"text": "epicatechin 3-O-(3-O-methyl) gallate", "start": 170, "end": 206}, {"text": "epicatechin 3-O-(3, 5-O-dimethyl) gallate", "start": 212, "end": 253}, {"text": "epicatechin 3-O-(3, 4, 5-O-trimethyl) gallate", "start": 259, "end": 304}, {"text": "quercetin 3-O-beta-d-glucopyranoside", "start": 310, "end": 346}, {"text": "rutin", "start": 352, "end": 357}, {"text": "peltatoside", "start": 368, "end": 379}]}}, "schema": []}
{"input": "Compound 1 was characterized as an unusual cyanogenic glycoside, while compound 8 was isolated for the first time from a natural source.", "output": {"entities": {"chemical": [{"text": "cyanogenic glycoside", "start": 43, "end": 63}]}}, "schema": []}
{"input": "This is the first report of a cyanogenic glycoside from mistletoes.", "output": {"entities": {"chemical": [{"text": "cyanogenic glycoside", "start": 30, "end": 50}]}}, "schema": []}
{"input": "The structures of the new compounds were unambiguously elucidated by 1D ((1) H, (13) C), 2D NMR (COSY, HSQC, and HMBC) and by mass spectroscopy.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 73, "end": 78}, {"text": "(13) C", "start": 80, "end": 86}]}}, "schema": []}
{"input": "The antioxidant activities of the isolated compounds (1-11) were evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay.", "output": {"entities": {"chemical": [{"text": "2, 2-diphenyl-1-picrylhydrazyl", "start": 85, "end": 115}, {"text": "DPPH", "start": 117, "end": 121}]}}, "schema": []}
{"input": "The neuroprotector kynurenic acid increases neuronal cell survival through neprilysin induction.", "output": {"entities": {"chemical": [{"text": "kynurenic acid", "start": 19, "end": 33}]}}, "schema": []}
{"input": "Kynurenic acid (KYNA), one of the main product of the kynurenine pathway originating from tryptophan, is considered to be neuroprotective.", "output": {"entities": {"chemical": [{"text": "Kynurenic acid", "start": 0, "end": 14}, {"text": "KYNA", "start": 16, "end": 20}, {"text": "kynurenine", "start": 54, "end": 64}, {"text": "tryptophan", "start": 90, "end": 100}]}}, "schema": []}
{"input": "Dysregulation of KYNA activity is thought to be involved in neurodegenerative diseases, the physiopathology of which evokes excitotoxicity, oxidative stress and/or protein aggregation.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 17, "end": 21}]}}, "schema": []}
{"input": "The neuroprotective effect of KYNA is generally attributed to its antagonistic action on NMDA receptors.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 30, "end": 34}, {"text": "NMDA", "start": 89, "end": 93}]}}, "schema": []}
{"input": "However, this single target action appears insufficient to support KYNA beneficial effects against complex neurodegenerative processes including neuroinflammation, beta-amyloid peptide (A beta) toxicity and apoptosis.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 67, "end": 71}]}}, "schema": []}
{"input": "Novel insights are therefore required to elucidate KYNA neuroprotective mechanisms.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Here, we combined cellular, biochemical, molecular and pharmacological approaches to demonstrate that low micromolar concentrations of KYNA strongly induce neprilysin (NEP) gene expression, protein level and enzymatic activity increase in human neuroblastoma SH-SY5Y cells.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 135, "end": 139}]}}, "schema": []}
{"input": "Furthermore, our studies revealed that KYNA exerts a protective effect on SH-SY5Y cells by increasing their viability through a mechanism independent from NMDA receptors.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 39, "end": 43}, {"text": "NMDA", "start": 155, "end": 159}]}}, "schema": []}
{"input": "Interestingly, KYNA also induced NEP activity and neuroprotection in mouse cortical neuron cultures the viability of which was more promoted than SH-SY5Y cell survival under KYNA treatment.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 15, "end": 19}, {"text": "KYNA", "start": 174, "end": 178}]}}, "schema": []}
{"input": "KYNA-evoked neuroprotection disappeared in the presence of thiorphan, an inhibitor of NEP activity.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 0, "end": 4}, {"text": "thiorphan", "start": 59, "end": 68}]}}, "schema": []}
{"input": "NEP is a well characterized metallopeptidase whose deregulation leads to cerebral A beta accumulation and neuronal death in Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, our results suggest that a part of the neuroprotective role of KYNA may depend on its ability to induce the expression and/or activity of the amyloid-degrading enzyme NEP in nerve cells.", "output": {"entities": {"chemical": [{"text": "KYNA", "start": 74, "end": 78}]}}, "schema": []}
{"input": "Molecular tweezers modulate 14-3-3 protein-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule).", "output": {"entities": {}}, "schema": []}
{"input": "We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins.", "output": {"entities": {"chemical": [{"text": "lysine", "start": 17, "end": 23}]}}, "schema": []}
{"input": "The tweezers inhibit binding between the 14-3-3 protein and two partner proteins--a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)--in a concentration-dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins.", "output": {"entities": {"chemical": [{"text": "lysine", "start": 115, "end": 121}, {"text": "Lys214", "start": 123, "end": 129}]}}, "schema": []}
{"input": "A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: Implications for vascular aging.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 15, "end": 20}]}}, "schema": []}
{"input": "Vascular aging is characterized by up-regulation of NADPH oxidase, oxidative stress and endothelial dysfunction.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 52, "end": 57}]}}, "schema": []}
{"input": "Previous studies demonstrate that the activity of the evolutionarily conserved NAD (+)-dependent deacetylase SIRT1 declines with age and that pharmacological activators of SIRT1 confer significant anti-aging cardiovascular effects.", "output": {"entities": {"chemical": [{"text": "NAD (+)", "start": 79, "end": 86}]}}, "schema": []}
{"input": "To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of SIRT1 (nicotinamide, sirtinol, EX527) in aorta segments isolated from young Wistar rats.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 53, "end": 58}, {"text": "oxygen", "start": 100, "end": 106}, {"text": "nicotinamide", "start": 231, "end": 243}, {"text": "sirtinol", "start": 245, "end": 253}, {"text": "EX527", "start": 255, "end": 260}]}}, "schema": []}
{"input": "Inhibition of SIRT1 induced endothelial dysfunction, as shown by the significantly reduced relaxation to the endothelium-dependent vasodilators acetylcholine and the calcium ionophore A23187.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 144, "end": 157}, {"text": "calcium", "start": 166, "end": 173}, {"text": "A23187", "start": 184, "end": 190}]}}, "schema": []}
{"input": "Endothelial dysfunction induced by SIRT1 inhibition was prevented by treatment of the vessels with the NADPH oxidase inhibitor apocynin or superoxide dismutase.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 103, "end": 108}, {"text": "apocynin", "start": 127, "end": 135}, {"text": "superoxide", "start": 139, "end": 149}]}}, "schema": []}
{"input": "Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22 (phox) and NOX4, which were prevented by resveratrol.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 53, "end": 63}, {"text": "NADPH", "start": 85, "end": 90}, {"text": "resveratrol", "start": 190, "end": 201}]}}, "schema": []}
{"input": "Peroxisome proliferator-activated receptor-alpha (PPAR alpha) activation mimicked the effects of resveratrol while PPAR alpha inhibition prevented the effects of this SIRT1 activator.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 97, "end": 108}]}}, "schema": []}
{"input": "SIRT1 co-precipitated with PPAR alpha and nicotinamide increased the acetylation of the PPAR alpha coactivator PGC-1 alpha, which was suppressed by resveratrol.", "output": {"entities": {"chemical": [{"text": "nicotinamide", "start": 42, "end": 54}, {"text": "resveratrol", "start": 148, "end": 159}]}}, "schema": []}
{"input": "In conclusion, impaired activity of SIRT1 induces endothelial dysfunction and up-regulates NADPH oxidase-derived ROS production in the vascular wall, mimicking the vascular aging phenotype.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 91, "end": 96}]}}, "schema": []}
{"input": "Moreover, a new mechanism for controlling endothelial function after SIRT1 activation involves a decreased PGC-1 alpha acetylation and the subsequent PPAR alpha activation, resulting in both decreased NADPH oxidase-driven ROS production and NO inactivation.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 201, "end": 206}, {"text": "NO", "start": 241, "end": 243}]}}, "schema": []}
{"input": "Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and cynomolgus monkeys.", "output": {"entities": {}}, "schema": []}
{"input": "A block/homo-mixed polyplex micelle, comprising of cationic homo polymer: poly {N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} P [Asp (DET)] and block copolymer: polyethylene glycol (PEG)-b-P [Asp (DET)], has been reported to exhibit the efficient transgene expression in vivo by intratracheal and systemic administration.", "output": {"entities": {"chemical": [{"text": "poly {N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} P [Asp (DET)]", "start": 74, "end": 141}, {"text": "polyethylene glycol (PEG)-b-P [Asp (DET)]", "start": 163, "end": 204}]}}, "schema": []}
{"input": "In the present study, we investigated the potential of immunogene therapy by intraperitoneal (i. p.) administration of block/homo polyplex micelles for peritoneal dissemination.", "output": {"entities": {}}, "schema": []}
{"input": "For evaluation of transgene expression in vivo, block/homo polyplex micelles showed 12-fold higher level in luciferase expression evaluated by bioluminescence imaging system at 24h after the i. p. administration compared with block polyplex micelles composed with only PEG-b-P [Asp (DET)] in nude mice bearing peritoneal dissemination.", "output": {"entities": {"chemical": [{"text": "PEG-b-P [Asp (DET)]", "start": 269, "end": 288}]}}, "schema": []}
{"input": "The distribution of block/homo polyplex micelles and intracellular uptake of pDNA was observed in tumor nodules.", "output": {"entities": {}}, "schema": []}
{"input": "The tumor growth and the prolonged survival rate for the mice harboring disseminated pancreatic cancer more significantly compared with the mock.", "output": {"entities": {}}, "schema": []}
{"input": "The antitumor effect of GM-CSF gene therapy was mediated via the activation of natural killer cells.", "output": {"entities": {}}, "schema": []}
{"input": "For safety evaluation, block/homo polyplex micelles indicated almost no adverse events for patho-physical findings and blood examinations in mice and cynomolgus monkeys, although slight increases in serum fibrinogen were observed in the monkey model.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, block/homo polyplex micelle-based immunogene therapy via i. p. administration may be a safe and effective approach for suppressing intractable peritoneal dissemination.", "output": {"entities": {}}, "schema": []}
{"input": "High-glucose environment enhanced oxidative stress and increased interleukin-8 secretion from keratinocytes: New insights on impaired diabetic wound healing.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 5, "end": 12}]}}, "schema": []}
{"input": "Impaired wound healing frequently occurs in patients with diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Interluekin-8 (IL-8) production by keratinocyte is responsible for recruiting neutrophils during healing.", "output": {"entities": {}}, "schema": []}
{"input": "Intense inflammation is associated with diabetic wounds while reduction of neutrophil infiltration is associated with enhanced healing.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that increased neutrophil recruitment by keratinocytes may contribute to the delayed healing of diabetic wound.", "output": {"entities": {}}, "schema": []}
{"input": "Using cultured human keratinocytes and diabetic rat model, the current study showed that high-glucose environment enhanced IL-8 production via epidermal growth factor receptor (EGFR)-extracelluar signal-regulated kinase (ERK) pathway in a reactive oxygen species (ROS)-dependent manner in keratinocytes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 94, "end": 101}, {"text": "oxygen", "start": 248, "end": 254}]}}, "schema": []}
{"input": "In addition, diabetic rat skin showed enhanced EGFR, ERK and IL-8 expression as compared to control rats.", "output": {"entities": {}}, "schema": []}
{"input": "The dermal neutrophil infiltration of the wound, as represented by expression of myeloperoxidase level, was also significantly higher in diabetic rats.", "output": {"entities": {}}, "schema": []}
{"input": "Treating diabetic rats with dapsone, an agent known to inhibit neutrophil function, was associated with improved healing.", "output": {"entities": {"chemical": [{"text": "dapsone", "start": 28, "end": 35}]}}, "schema": []}
{"input": "In conclusion, IL-8 production and neutrophil infiltration are increased in high-glucose environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 81, "end": 88}]}}, "schema": []}
{"input": "Targeting these dysfunctions may present novel therapeutic approaches.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative stress in the lung of mice exposed to cigarette smoke either early in life or in adulthood.", "output": {"entities": {}}, "schema": []}
{"input": "Birth and early life stages are critical periods characterized by severe alterations of the redox balance and by \" physiological \" genomic changes in lung cells, which may be responsible for cancer and other diseases in adulthood.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative stress is a major mechanism accounting for the carcinogenicity of cigarette smoke (CS), which becomes more potently carcinogenic in mice when exposure starts at birth and continues early in life.", "output": {"entities": {}}, "schema": []}
{"input": "We compared herewith a variety of end-points related to oxidative stress, mitochondrial alterations, and cell turnover in the lung of Swiss H mice, either sham-exposed or CS-exposed for 4 weeks, starting either at birth or at 4 months of age.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that the physiological levels of certain end-points are affected by age.", "output": {"entities": {}}, "schema": []}
{"input": "In fact, the baseline proportion of hypodiploid cells and the mitochondrial potential and mass were higher in adults, whereas 8-hydroxy-2'-deoxyguanosine (8-oxo-dGuo) levels, the proportion of necrotic cells, and the extent of autophagy were higher early in life.", "output": {"entities": {"chemical": [{"text": "8-hydroxy-2'-deoxyguanosine", "start": 126, "end": 153}, {"text": "8-oxo-dGuo", "start": 155, "end": 165}]}}, "schema": []}
{"input": "Adult mice were more responsive to CS by increasing the proportion of necrotic cells and of cells in S/G2 phase, whereas young mice maintained a high extent of autophagy, exhibited a greater increase of lipid peroxidation products and 8-oxo-dGuo levels, and had a higher frequency of micronucleated cells.", "output": {"entities": {"chemical": [{"text": "8-oxo-dGuo", "start": 235, "end": 245}]}}, "schema": []}
{"input": "In addition, exposure to CS affected the mitochondrial potential/mass, especially in young mice.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, these data provide evidence that oxidative stress and the resulting DNA damage provide a major contribution to the high susceptibility of mice to CS early in life.", "output": {"entities": {}}, "schema": []}
{"input": "Nuclear Flux Densities during a Model Pericyclic Reaction with Energies Well Above and Below the Potential Barrier.", "output": {"entities": {}}, "schema": []}
{"input": "Pericyclic reactions with energies E well above the potential energy barrier B (case E > B) proceed with quantum nuclear flux densities < j > which are essentially proportional to the nuclear densities rho in the femtosecond time domain.", "output": {"entities": {}}, "schema": []}
{"input": "This corresponds to the definition of classical (cl) mechanics, jcl = upsilon cl rho cl, with almost constant velocity vcl.", "output": {"entities": {}}, "schema": []}
{"input": "For the other case E < B, however, that is, in the domain of coherent tunneling, we discover the opposite trend, that is, < j > has maximum value close to the barrier where rho is a minimum (in fact where rho is close to zero).", "output": {"entities": {}}, "schema": []}
{"input": "The general conclusion is that quantum mechanical nuclear flux densities may be at variance from traditional expectations based on classical trajectories.", "output": {"entities": {}}, "schema": []}
{"input": "This prediction calls for experimental demonstration.", "output": {"entities": {}}, "schema": []}
{"input": "The counter-intuitive proof-of-principle is demonstrated for a simple, one-dimensional model of the Cope rearrangement of semibullvalene.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of salinity on acute nickel toxicity to the two euryhaline fish species, Fundulus heteroclitus and Kryptolebias marmoratus.", "output": {"entities": {"chemical": [{"text": "nickel", "start": 35, "end": 41}]}}, "schema": []}
{"input": "Nickel (Ni) is a common pollutant found in aquatic environments and may be harmful at elevated concentrations.", "output": {"entities": {"chemical": [{"text": "Nickel", "start": 0, "end": 6}, {"text": "Ni", "start": 8, "end": 10}]}}, "schema": []}
{"input": "Increasing salinity has been shown to decrease the bioavailability and toxicity of other metals to aquatic organisms.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, acute Ni toxicity experiments (96-h) were conducted at various salinities (0-36 ppt) to determine the effects of salinity on Ni toxicity to 2 euryhaline fish species, Kryptolebias marmoratus and Fundulus heteroclitus.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 28, "end": 30}, {"text": "Ni", "start": 147, "end": 149}]}}, "schema": []}
{"input": "Nickel concentrations causing lethality to 50% of the fish ranged from 2 mg/L in moderately hard freshwater to 66. 6 mg/L in 36 ppt saltwater.", "output": {"entities": {"chemical": [{"text": "Nickel", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Nickel toxicity to F. heteroclitus decreased linearly with increasing salinity; however, Ni toxicity to K. marmoratus was only lowered by salinities above 6 ppt, demonstrating potential physiological differences between the 2 species when they are functioning as freshwater fish.", "output": {"entities": {"chemical": [{"text": "Nickel", "start": 0, "end": 6}, {"text": "Ni", "start": 89, "end": 91}]}}, "schema": []}
{"input": "Furthermore, the authors investigated the influence of Mg (2 +), Ca (2 +), Na (+), and Cl (-) on Ni toxicity to F. heteroclitus.", "output": {"entities": {"chemical": [{"text": "Mg (2 +)", "start": 55, "end": 63}, {"text": "Ca (2 +)", "start": 65, "end": 73}, {"text": "Na (+)", "start": 75, "end": 81}, {"text": "Cl (-)", "start": 87, "end": 93}, {"text": "Ni", "start": 97, "end": 99}]}}, "schema": []}
{"input": "Freshwater with up to 120 mg/L Ca (2 +) as CaSO4, 250 mg/L Mg (2 +) as MgSO4, or 250 mg/L Na (+) as NaHCO3 did not provide protection against Ni toxicity.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 31, "end": 39}, {"text": "CaSO4", "start": 43, "end": 48}, {"text": "Mg (2 +)", "start": 59, "end": 67}, {"text": "MgSO4", "start": 71, "end": 76}, {"text": "Na (+)", "start": 90, "end": 96}, {"text": "NaHCO3", "start": 100, "end": 106}, {"text": "Ni", "start": 142, "end": 144}]}}, "schema": []}
{"input": "Alternatively, 250 mg/L Na (+), as NaCl, was protective against Ni toxicity; and the extent of protection was similar to that demonstrated from salt water with the same Cl (-) concentration.", "output": {"entities": {"chemical": [{"text": "Na (+)", "start": 24, "end": 30}, {"text": "NaCl", "start": 35, "end": 39}, {"text": "Ni", "start": 64, "end": 66}, {"text": "Cl (-)", "start": 169, "end": 175}]}}, "schema": []}
{"input": "These results suggest that Cl (-) is the predominant ion responsible for reducing Ni toxicity to K. marmoratus and F. heteroclitus in higher salinity waters.", "output": {"entities": {"chemical": [{"text": "Cl (-)", "start": 27, "end": 33}, {"text": "Ni", "start": 82, "end": 84}]}}, "schema": []}
{"input": "Environ Toxicol Chem 2013; 32: 1354-1359.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of phytotoxicity and genotoxicity of nitrobenzene with A battery of Vicia Faba assay system.", "output": {"entities": {"chemical": [{"text": "nitrobenzene", "start": 48, "end": 60}]}}, "schema": []}
{"input": "Nitrobenzene (NB) is an important organic compound intermediate that is used widely in industry.", "output": {"entities": {"chemical": [{"text": "Nitrobenzene", "start": 0, "end": 12}]}}, "schema": []}
{"input": "In the present study, to evaluate the phytotoxicity and genotoxicity of NB on plants, Vicia faba was exposed to increasing concentrations of NB (5 mg L (-1), 10 mg L (-1), 25 mg L (-1), 50 mg L (-1), and 100 mg L (-1)).", "output": {"entities": {}}, "schema": []}
{"input": "The data revealed that germination rate and radicle length of V. faba seedlings were promoted by low NB concentrations and short exposure periods, whereas these parameters were inhibited at greater NB concentrations and longer exposures.", "output": {"entities": {}}, "schema": []}
{"input": "When assessed by mitotic index, micronucleus, and chromosomal aberration assays, NB showed dose-dependent genotoxicity at 0 mg L (-1) to 50 mg L (-1).", "output": {"entities": {}}, "schema": []}
{"input": "Environ Toxicol Chem 2013; 32: 1426-1432.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of the mutagenic potential and acute oral toxicity of standardized extract of Ocimum sanctum (OciBest (TM)).", "output": {"entities": {}}, "schema": []}
{"input": "Ocimum sanctum L.", "output": {"entities": {}}, "schema": []}
{"input": "(Lamiaceae) is found throughout India and in many parts of world.", "output": {"entities": {}}, "schema": []}
{"input": "O. sanctum is used for the treatment of various health indications.", "output": {"entities": {}}, "schema": []}
{"input": "In this lieu, it is of prime importance to investigate the safety aspects of the plant.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, the present study was conducted to investigate the possible genotoxic potential and acute oral toxicity of the extract of O. sanctum (OciBest (TM)).", "output": {"entities": {}}, "schema": []}
{"input": "The standard battery of in vitro genotoxicity tests, namely bacterial reverse mutation, chromosome aberration and micronucleus (MN) tests were employed to assess the possible mutagenic activity.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that OciBest (TM) (7. 9-2500. 0 micro g/mL) did not increase the number of histidine revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with and without exogenous metabolic activation (S9).", "output": {"entities": {"chemical": [{"text": "histidine", "start": 94, "end": 103}]}}, "schema": []}
{"input": "OciBest (TM) (10. 0-100. 0 micro g/mL) did not show structural chromosomal aberrations or increase in MN induction, with and without S9, at the tested dose range in both 4-h and 18-h exposure cell cultures.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, OciBest (TM) is not genotoxic in bacterial reverse mutation, chromosomal aberration and MN tests.", "output": {"entities": {}}, "schema": []}
{"input": "In an acute oral toxicity test, rats were treated with 5 g/kg of OciBest (TM) and observed for signs of toxicity for 14 days and the results did not show any treatment-related toxic effects to Wistar rats.", "output": {"entities": {}}, "schema": []}
{"input": "N-Acetylcysteine prevents doxorubucine-induced cardiotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "N-Acetylcysteine", "start": 0, "end": 16}, {"text": "doxorubucine", "start": 26, "end": 38}]}}, "schema": []}
{"input": "This study is designed to observe the effects of N-acetylcysteine (NAC) on doxorubucine-induced cardiac toxicity in rats both histologically and biochemically.", "output": {"entities": {"chemical": [{"text": "N-acetylcysteine", "start": 49, "end": 65}, {"text": "NAC", "start": 67, "end": 70}, {"text": "doxorubucine", "start": 75, "end": 87}]}}, "schema": []}
{"input": "Totally 32 rats divided equally into four groups were studied.", "output": {"entities": {}}, "schema": []}
{"input": "The first group received only 200 mg/kg NAC intraperitoneal (i. p.) once every 24 h for 5 days (group 1); the second group received 20 mg/kg doxorubucine (DOX) i. p. single dose plus NAC 200 mg/kg i. p. once every 24 h for 5 days (group 2); the third group received DOX 20 mg/kg DOX i. p. single dose (group 3) and the fourth group, which is also the control group, received saline (group 4).", "output": {"entities": {"chemical": [{"text": "NAC", "start": 40, "end": 43}, {"text": "doxorubucine", "start": 141, "end": 153}, {"text": "DOX", "start": 155, "end": 158}, {"text": "NAC", "start": 183, "end": 186}, {"text": "DOX", "start": 266, "end": 269}, {"text": "DOX", "start": 279, "end": 282}]}}, "schema": []}
{"input": "Following 24 h of the final dose, blood samples were drawn from a portal vein and heart tissue were obtained.", "output": {"entities": {}}, "schema": []}
{"input": "Tissue thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) levels were highest in the DOX group.", "output": {"entities": {"chemical": [{"text": "thiobarbituric acid", "start": 7, "end": 26}, {"text": "nitric oxide", "start": 58, "end": 70}, {"text": "NO", "start": 72, "end": 74}, {"text": "DOX", "start": 103, "end": 106}]}}, "schema": []}
{"input": "In the DOX-treated rats, serum TBARS, NO, aspartate transaminase, lactate dehydrogenase and creatine kinase levels were highest when compared with other groups.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 7, "end": 10}, {"text": "NO", "start": 38, "end": 40}, {"text": "aspartate", "start": 42, "end": 51}, {"text": "lactate", "start": 66, "end": 73}, {"text": "creatine", "start": 92, "end": 100}]}}, "schema": []}
{"input": "Except for serum superoxide dismutase levels, all other parameters differed significantly between the DOX plus NAC group and the DOX group.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 17, "end": 27}, {"text": "DOX", "start": 102, "end": 105}, {"text": "NAC", "start": 111, "end": 114}, {"text": "DOX", "start": 129, "end": 132}]}}, "schema": []}
{"input": "In the DOX plus NAC group, general architecture was preserved better than the DOX group and myofibril loss was minimal compared with the DOX group.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 7, "end": 10}, {"text": "NAC", "start": 16, "end": 19}, {"text": "DOX", "start": 78, "end": 81}, {"text": "DOX", "start": 137, "end": 140}]}}, "schema": []}
{"input": "NAC demonstrated, both biochemically and histologically, to be effective in the prevention of DOX-induced cardiotoxicity in rat models.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 0, "end": 3}, {"text": "DOX", "start": 94, "end": 97}]}}, "schema": []}
{"input": "Evaluation of NAC' s effect on DOX toxicity warrants further clinical trials on cancer patients.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 14, "end": 17}, {"text": "DOX", "start": 31, "end": 34}]}}, "schema": []}
{"input": "Synergistic GABA-Enhancing Therapy against Seizures in a Mouse Model of Dravet Syndrome.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 12, "end": 16}]}}, "schema": []}
{"input": "Seizures remain uncontrolled in 30% of patients with epilepsy, even with concurrent use of multiple drugs, and uncontrolled seizures result in increased morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "An extreme example is Dravet syndrome (DS), an infantile-onset severe epilepsy caused by heterozygous loss of function mutations in SCN1A, the gene encoding the brain type-I voltage-gated sodium channel NaV1. 1.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 188, "end": 194}]}}, "schema": []}
{"input": "Studies in Scn1a heterozygous knockout mice demonstrate reduced excitability of GABAergic interneurons, suggesting that enhancement of GABA signaling may improve seizure control and comorbidities.", "output": {"entities": {"chemical": [{"text": "GABAergic", "start": 80, "end": 89}]}}, "schema": []}
{"input": "We studied the efficacy of two GABA-enhancing drugs, clonazepam and tiagabine, alone and in combination, against thermally evoked myoclonic and generalized tonic-clonic seizures.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 31, "end": 35}, {"text": "clonazepam", "start": 53, "end": 63}, {"text": "tiagabine", "start": 68, "end": 77}]}}, "schema": []}
{"input": "Clonazepam, a positive allosteric modulator of GABA-A receptors, protected against myoclonic and generalized tonic-clonic seizures.", "output": {"entities": {"chemical": [{"text": "Clonazepam", "start": 0, "end": 10}, {"text": "GABA", "start": 47, "end": 51}]}}, "schema": []}
{"input": "Tiagabine, a presynaptic GABA reuptake inhibitor, was protective against generalized tonic-clonic seizures but only minimally protective against myoclonic seizures and enhanced myoclonic seizure susceptibility at high doses.", "output": {"entities": {"chemical": [{"text": "Tiagabine", "start": 0, "end": 9}, {"text": "GABA", "start": 25, "end": 29}]}}, "schema": []}
{"input": "Combined therapy with clonazepam and tiagabine was synergistic against generalized tonic-clonic seizures but was additive against myoclonic seizures.", "output": {"entities": {"chemical": [{"text": "clonazepam", "start": 22, "end": 32}, {"text": "tiagabine", "start": 37, "end": 46}]}}, "schema": []}
{"input": "Toxicity determined by rotorod testing was additive for combination therapy.", "output": {"entities": {}}, "schema": []}
{"input": "The synergistic actions of clonazepam and tiagabine gave enhanced seizure protection and reduced toxicity, suggesting that combination therapy may be well tolerated and effective for seizures in DS.", "output": {"entities": {"chemical": [{"text": "clonazepam", "start": 27, "end": 37}, {"text": "tiagabine", "start": 42, "end": 51}]}}, "schema": []}
{"input": "Binding of glyco-acridine derivatives to lysozyme leads to inhibition of amyloid fibrillization.", "output": {"entities": {"chemical": [{"text": "acridine", "start": 17, "end": 25}]}}, "schema": []}
{"input": "While amyloid-related diseases are at the center of intense research efforts, no feasible cure is currently available for these diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The experimental and computational techniques were used to study the ability of glyco-acridines to prevent lysozyme amyloid fibrillization in vitro.", "output": {"entities": {"chemical": [{"text": "acridines", "start": 86, "end": 95}]}}, "schema": []}
{"input": "Fluorescence spectroscopy and atomic force microscopy have shown that glyco-acridines inhibit amyloid aggregation of lysozyme; the inhibition efficiency characterized by the half-maximal inhibition concentration IC50 was affected by the structure and concentration of the derivative.", "output": {"entities": {"chemical": [{"text": "acridines", "start": 76, "end": 85}]}}, "schema": []}
{"input": "We next investigated relationship between the binding affinity and the inhibitory activity of the compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The semiempirical quantum PM6-DH + method provided a good correlation pointing to the importance of quantum effects on the binding of glyco-acridine derivatives to lysozyme.", "output": {"entities": {"chemical": [{"text": "acridine", "start": 140, "end": 148}]}}, "schema": []}
{"input": "The contribution of linkers may be explained by the valence bond theory.", "output": {"entities": {}}, "schema": []}
{"input": "Our data provide a basis for the development of new small molecule inhibitors effective in therapy of amyloid-related diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Small-molecule inhibitors/modulators of amyloid-beta peptide aggregation and toxicity for the treatment of Alzheimer' s disease: a patent review (2010-2012).", "output": {"entities": {}}, "schema": []}
{"input": "Introduction: Genetic, physiological, and biochemical data indicate that agglomerates of the 42-amino acid form of the amyloid-beta (A beta 42) peptide are strongly linked to Alzheimer' s disease (AD) etiology and thus represent a particularly attractive target for the development of an effective disease-modifying approach for AD treatment.", "output": {"entities": {}}, "schema": []}
{"input": "A plethora of chemical entities able to modulate A beta 42 self-assembly have been developed in recent years, among them, several are in clinical or preclinical development.", "output": {"entities": {}}, "schema": []}
{"input": "Areas covered: This review accounts for small-molecule inhibitors of A beta peptide polymerization and toxicity, reported in the patent literature during the 2010-2012 period, and their potential use as disease-modifying therapeutics for AD cure.", "output": {"entities": {}}, "schema": []}
{"input": "Expert opinion: The earliest pathogenic event is the formation of soluble A beta oligomers that disrupt synaptic communication.", "output": {"entities": {}}, "schema": []}
{"input": "Drug design strategies targeting these primary toxic agents could hold considerable promises for obtaining effective anti-AD drugs candidate.", "output": {"entities": {}}, "schema": []}
{"input": "The heterogeneous aggregation of A beta and the resulting difficulty to structurally characterize the peptide represent important drawbacks.", "output": {"entities": {}}, "schema": []}
{"input": "Essential oil composition and antibacterial activity of the different parts of Thymus maroccanus Ball: an endemic species in Morocco (+).", "output": {"entities": {}}, "schema": []}
{"input": "Three essential oils from three samples: stems, leaves and inflorescences of Thymus maroccanus Ball, obtained by hydrodistillation, were analysed by gas chromatography and gas chromatography coupled to mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The oils of stems, leaves and inflorescences afforded 68, 49 and 51 constituents, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative and qualitative differences have been found between the analysed parts.", "output": {"entities": {}}, "schema": []}
{"input": "The most abundant components in the stems oil included carvacrol (60. 8%), alpha-terpineol (4. 7%) and p-cymene (2. 4%), while carvacrol (33%), p-cymene (25. 3%) and alpha-pinene (11. 6%) were the main components in the leaves.", "output": {"entities": {"chemical": [{"text": "carvacrol", "start": 55, "end": 64}, {"text": "alpha-terpineol", "start": 75, "end": 90}, {"text": "p-cymene", "start": 103, "end": 111}, {"text": "carvacrol", "start": 127, "end": 136}, {"text": "p-cymene", "start": 144, "end": 152}, {"text": "alpha-pinene", "start": 166, "end": 178}]}}, "schema": []}
{"input": "In the inflorescences, carvacrol (84. 9%) is the major component.", "output": {"entities": {"chemical": [{"text": "carvacrol", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Antibacterial activity of the T. maroccanus Ball leaves oil was tested against eight Gram-positive and Gram-negative bacteria by the disc diffusion method.", "output": {"entities": {}}, "schema": []}
{"input": "The values of inhibition zones for bacterial strains, which were sensitive to the essential oil of T. maroccanus leaves, were in the range of 11-43 mm.", "output": {"entities": {}}, "schema": []}
{"input": "Quantum mechanics/molecular mechanics modeling of fatty acid amide hydrolase reactivation distinguishes substrate from irreversible covalent inhibitors.", "output": {"entities": {"chemical": [{"text": "fatty acid amide", "start": 50, "end": 66}]}}, "schema": []}
{"input": "Carbamate and urea derivatives are important classes of fatty acid amide hydrolase (FAAH) inhibitors that carbamoylate the active-site nucleophile Ser241.", "output": {"entities": {"chemical": [{"text": "Carbamate", "start": 0, "end": 9}, {"text": "urea", "start": 14, "end": 18}, {"text": "fatty acid amide", "start": 56, "end": 72}, {"text": "carbamoylate", "start": 106, "end": 118}, {"text": "Ser241", "start": 147, "end": 153}]}}, "schema": []}
{"input": "In the present work, the reactivation mechanism of carbamoylated FAAH is investigated by means of a quantum mechanics/molecular mechanics (QM/MM) approach.", "output": {"entities": {}}, "schema": []}
{"input": "The potential energy surfaces for decarbamoylation of FAAH covalent adducts, derived from the O-aryl carbamate URB597 and from the N-piperazinylurea JNJ1661610, were calculated and compared to that for deacylation of FAAH acylated by the substrate oleamide.", "output": {"entities": {"chemical": [{"text": "O", "start": 94, "end": 95}, {"text": "URB597", "start": 111, "end": 117}, {"text": "N", "start": 131, "end": 132}, {"text": "JNJ1661610", "start": 149, "end": 159}, {"text": "oleamide", "start": 248, "end": 256}]}}, "schema": []}
{"input": "Calculations show that a carbamic group bound to Ser241 prevents efficient stabilization of transition states of hydrolysis, leading to large increments in the activation barrier.", "output": {"entities": {"chemical": [{"text": "carbamic", "start": 25, "end": 33}, {"text": "Ser241", "start": 49, "end": 55}]}}, "schema": []}
{"input": "Moreover, the energy barrier for the piperazine carboxylate was significantly lower than that for the cyclohexyl carbamate derived from URB597.", "output": {"entities": {"chemical": [{"text": "piperazine carboxylate", "start": 37, "end": 59}, {"text": "cyclohexyl carbamate", "start": 102, "end": 122}, {"text": "URB597", "start": 136, "end": 142}]}}, "schema": []}
{"input": "This is consistent with experimental data showing slowly reversible FAAH inhibition for the N-piperazinylurea inhibitor and irreversible inhibition for URB597.", "output": {"entities": {"chemical": [{"text": "N-piperazinylurea", "start": 92, "end": 109}, {"text": "URB597", "start": 152, "end": 158}]}}, "schema": []}
{"input": "Conference Report: Bioanalysis-related topics presented at the International Conference and Exhibition on Biowaivers and Biosimilars.", "output": {"entities": {}}, "schema": []}
{"input": "This conference of approximately 30 professionals attracted a diverse group of attendees, whose expertise spanned the broad topics of development, production, testing and regulation of biosimilars.", "output": {"entities": {}}, "schema": []}
{"input": "The topics covered during this meeting were varied in scope due to the breadth of knowledge of the attendees.", "output": {"entities": {}}, "schema": []}
{"input": "Topics of discussion included: biowaivers for small molecules; patent law and interpretation of the Biologics Price Competition and Innovation Act; analytical tools for the characterization of a biosimilar; novel production methods; bioanalytical methods; immunogenicity considerations; formulation techniques; and the characterization of the glycosylation of biosimilars.", "output": {"entities": {}}, "schema": []}
{"input": "Gel electrophoretic methods for the analysis of biosimilar pharmaceuticals using the example of recombinant erythropoietin.", "output": {"entities": {}}, "schema": []}
{"input": "Due to their versatility and cost-effectiveness, gel electrophoretic methods provide an important set of tools for the analysis of therapeutic proteins.", "output": {"entities": {}}, "schema": []}
{"input": "As an increasing number of biosimilar pharmaceuticals are entering the market, techniques are required that allow reliable demonstration of comparability of these products with the reference products.", "output": {"entities": {}}, "schema": []}
{"input": "Isoelectric focusing, SDS-PAGE, native PAGE and 2D electrophoresis (2D-PAGE) have been frequently applied for this purpose.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 22, "end": 25}]}}, "schema": []}
{"input": "Supplementary techniques are fluorophore-assisted carbohydrate electrophoresis and sarcosyl-PAGE.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 50, "end": 62}, {"text": "sarcosyl", "start": 83, "end": 91}]}}, "schema": []}
{"input": "Of additional importance is the comparison of recombinant with endogenously synthesized glycoproteins.", "output": {"entities": {}}, "schema": []}
{"input": "Reagent array analysis combined with SDS-PAGE and western blotting proved especially useful for this purpose.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 37, "end": 40}]}}, "schema": []}
{"input": "As an example for the application of these methods, the analysis of recombinant originator erythropoietins and some of their biosimilar counterparts is described.", "output": {"entities": {}}, "schema": []}
{"input": "Silver-zwitterion organic-inorganic nanocomposite with antimicrobial and antiadhesive capabilities.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In this work, we demonstrate a convenient, efficient, and environmentally benign strategy to achieving antimicrobial and antiadhesive purposes using a silver-zwitterion nanocomposite.", "output": {"entities": {"chemical": [{"text": "silver", "start": 151, "end": 157}]}}, "schema": []}
{"input": "The synthesis of the nanocomposite relies on loading zwitterionic polymer brushes with Ag (+) precursor ions, followed by their in situ reduction to Ag nanoparticle by ultraviolet (UV) irradiation.", "output": {"entities": {"chemical": [{"text": "Ag (+)", "start": 87, "end": 93}, {"text": "Ag", "start": 149, "end": 151}]}}, "schema": []}
{"input": "Both poly (sulfobetaine methacrylate) (pSBMA) and poly (carboxybetaine methacrylate) (pCBMA) have been studied as matrices for the embedding of silver.", "output": {"entities": {"chemical": [{"text": "poly (sulfobetaine methacrylate)", "start": 5, "end": 37}, {"text": "pSBMA", "start": 39, "end": 44}, {"text": "poly (carboxybetaine methacrylate)", "start": 50, "end": 84}, {"text": "pCBMA", "start": 86, "end": 91}, {"text": "silver", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Well-dispersed silver nanoparticles are embedded into pCBMA matrices.", "output": {"entities": {"chemical": [{"text": "silver", "start": 15, "end": 21}, {"text": "pCBMA", "start": 54, "end": 59}]}}, "schema": []}
{"input": "The obtained pCBMA-silver hybrid (CB-Ag) is capable of killing bacteria upon contact and releasing dead bacteria under wet conditions.", "output": {"entities": {"chemical": [{"text": "pCBMA", "start": 13, "end": 18}, {"text": "silver", "start": 19, "end": 25}, {"text": "Ag", "start": 37, "end": 39}]}}, "schema": []}
{"input": "Results suggest the feasibility of using this nanocomposite system as a robust and reliable antimicrobial and antiadhesive platform for the prevention of microbial colonization.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, in vitro antiplatelet activity and molecular modelling studies of 10-substituted 2-(1-piperazinyl) pyrimido [1, 2-a] benzimidazol-4 (10H)-ones.", "output": {"entities": {"chemical": [{"text": "10-substituted 2-(1-piperazinyl) pyrimido [1, 2-a] benzimidazol-4 (10H)-ones", "start": 77, "end": 153}]}}, "schema": []}
{"input": "The multistep preparation of the new 10-substituted 2-(1-piperazinyl) pyrimido [1, 2-a] benzimidazol-4 (10H)-ones 6a-o, and of the two isomers 10-ethyl-2-(diethylamino) pyrimido [1, 2-a] benzimidazol-4 (10H)-one 6p and 10-ethyl-4-(diethylamino) pyrimido [1, 2-a] benzimidazol-2 (10H)-one 13, as well as the in vitro evaluation of their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen or the Ca (2 +) ionophore A23187 were here described.", "output": {"entities": {"chemical": [{"text": "10-substituted 2-(1-piperazinyl) pyrimido [1, 2-a] benzimidazol-4 (10H)-ones", "start": 37, "end": 113}, {"text": "10-ethyl-2-(diethylamino) pyrimido [1, 2-a] benzimidazol-4 (10H)-one", "start": 143, "end": 211}, {"text": "10-ethyl-4-(diethylamino) pyrimido [1, 2-a] benzimidazol-2 (10H)-one", "start": 219, "end": 287}, {"text": "ADP", "start": 421, "end": 424}, {"text": "Ca (2 +)", "start": 442, "end": 450}, {"text": "A23187", "start": 461, "end": 467}]}}, "schema": []}
{"input": "Nine out of fifteen 2-(1-piperazinyl) derivatives (6g-o) showed good inhibitory properties towards all the platelet aggregation agonists used.", "output": {"entities": {"chemical": [{"text": "2-(1-piperazinyl)", "start": 20, "end": 37}]}}, "schema": []}
{"input": "Moreover, a molecular modelling study has been performed on two of the best compounds of this series (6i and 6o) to confirm in silico their interactions with the catalytic site of human platelet PDE3, using the X-ray data of the PDE3B isoform in complex with an inhibitor.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological evaluation of novel pyranochalcone derivatives as a new class of microtubule stabilizing agents.", "output": {"entities": {"chemical": [{"text": "pyranochalcone", "start": 45, "end": 59}]}}, "schema": []}
{"input": "Twenty-five novel pyranochalcone derivatives were synthesized and evaluated for their in vitro and in vivo antiproliferative activities.", "output": {"entities": {"chemical": [{"text": "pyranochalcone", "start": 18, "end": 32}]}}, "schema": []}
{"input": "Among them, compound 10i exhibited superior potent activity against 21 tumor cell lines including multidrug resistant phenotype with the IC50 values ranged from 0. 09 to 1. 30 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, 10i significantly induced cell cycle arrest in G2/M phase, promoted tubulin polymerization into microtubules and caused microtubule stabilization.", "output": {"entities": {}}, "schema": []}
{"input": "Further studies confirmed that 10i significantly suppressed the growth of tumor volume in HepG2 xenograft tumor model.", "output": {"entities": {}}, "schema": []}
{"input": "Our study demonstrated that 10i could have beneficial antitumor activity as a novel microtubule stabilizing agent.", "output": {"entities": {}}, "schema": []}
{"input": "Improved excitation uniformity in multiple-quantum NMR experiments of mixtures.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple-quantum (1) H NMR spectroscopy has been finding a renewed interest for its possible applications in the analysis of mixtures of small molecules, due to its simplification properties.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 17, "end": 22}]}}, "schema": []}
{"input": "A crucial aspect of this application of multiple-quantum NMR is the sensitivity of the spectrum intensity to the molecular structure and to the parameterization of the experiment, which could result in the missing of some components.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that a general scheme to overcome this drawback consists in varying the experiment parameterizations over a small number of values, selected according the values of the couplings and the relaxation rates.", "output": {"entities": {}}, "schema": []}
{"input": "Experimental models of disseminated scedosporiosis with cerebral involvement.", "output": {"entities": {}}, "schema": []}
{"input": "Scedosporium apiospermum is a soil fungus which can cause severe and often fatal cerebral infections in both immunocompetent patients in the event of near drowning and immunosuppressed patients such as lung transplant recipients.", "output": {"entities": {}}, "schema": []}
{"input": "Because of the low susceptibility of this fungus to antifungal drugs, and the low permeability of the blood-brain barrier (BBB), therapeutic drug monitoring is necessary to reach an effective tissue concentration with limited side effects.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, diffusion of the drug in the brain is dependent on several parameters, such as the integrity of the BBB and the activity of efflux pumps.", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate drug diffusion, two experimental models were developed in immunocompetent and immunosuppressed rats.", "output": {"entities": {}}, "schema": []}
{"input": "Inocula were administered via the penile vein and a clinical scale (0-9) was established, based on weight and clinical and neurologic signs evaluated by the tail suspension test.", "output": {"entities": {}}, "schema": []}
{"input": "Cerebral involvement was confirmed by magnetic resonance imaging and histologic examination of brain sections after hematoxylin-eosin-safran or silver staining.", "output": {"entities": {"chemical": [{"text": "hematoxylin", "start": 116, "end": 127}, {"text": "eosin", "start": 128, "end": 133}, {"text": "silver", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Voriconazole or posaconazole was given to the rats at doses ranging from 10 to 75 mg/kg/day via i. v. or oral routes, respectively.", "output": {"entities": {"chemical": [{"text": "Voriconazole", "start": 0, "end": 12}, {"text": "posaconazole", "start": 16, "end": 28}]}}, "schema": []}
{"input": "Whatever the immune status, the effective doses (defined by a doubling of the survival time and the absence of neurologic sequelae) were 30 mg/kg/day for voriconazole and 50 mg/kg/day for posaconazole.", "output": {"entities": {"chemical": [{"text": "voriconazole", "start": 154, "end": 166}, {"text": "posaconazole", "start": 188, "end": 200}]}}, "schema": []}
{"input": "Overall, the results demonstrated that these models may constitute valuable tools for the performance of pharmacokinetic and pharmacodynamic studies for pharmacokinetic-pharmacodynamic modeling.", "output": {"entities": {}}, "schema": []}
{"input": "Modeling toxic stress by atrazine in a marine consumer-resource system.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 25, "end": 33}]}}, "schema": []}
{"input": "The present study combines short-term experiments with food chain modeling to explore the long-term effects of the herbicide atrazine on consumer-resource dynamics in a marine intertidal ecosystem.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 125, "end": 133}]}}, "schema": []}
{"input": "Short-term (28 d) lab experiments indicated that the intrinsic rate of increase (r) and carrying capacity (K) of the marine diatom Seminavis robusta decreased with increasing atrazine exposure.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 175, "end": 183}]}}, "schema": []}
{"input": "This decrease did not show the concave shape expected from the lifetime productivity for nonexposed diatoms and from single-species toxicity data in the literature but instead was described best by a linear model.", "output": {"entities": {}}, "schema": []}
{"input": "These experimentally observed atrazine-induced decreases of r and K were used to parameterize a Rosenzweig-MacArthur model representing a simple food chain including the tested diatom and its grazer, the harpacticoid copepod Delavalia palustris var. palustris.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 30, "end": 38}]}}, "schema": []}
{"input": "Stable oscillation zoo-phytobenthos systems were produced at diatom exposures of 0, 100, and 150 micro g/L atrazine.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 107, "end": 115}]}}, "schema": []}
{"input": "An atrazine concentration of 150 micro g/L contributed to a 15% increase of the oscillation periods of both diatoms and copepods as well as a 52% reduction of oscillation amplitudes compared with the control situation.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 3, "end": 11}]}}, "schema": []}
{"input": "Although the amplitudes of copepods increased only 7% at 150 micro g/L atrazine, the maximum and minimum copepod densities at that concentration were reduced 61 and 63%, respectively.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 71, "end": 79}]}}, "schema": []}
{"input": "The effects of atrazine on periodicity and amplitudes were robust to 20% changes in the food-chain model parameters that represented allometric relationships.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 15, "end": 23}]}}, "schema": []}
{"input": "The simulations in the present study suggest food chain-mediated indirect effects on zoobenthos populations, indicating a reduced diatom and copepod availability throughout the year.", "output": {"entities": {}}, "schema": []}
{"input": "Environ.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicol.", "output": {"entities": {}}, "schema": []}
{"input": "Chem.", "output": {"entities": {}}, "schema": []}
{"input": "2013; 32: 1088-1095.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "KBP-cytoskeleton interactions underlie developmental anomalies in Goldberg-Shprintzen syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Goldberg-Shprintzen syndrome (GOSHS, MIM #609460) is an autosomal recessive disorder of intellectual disability, specific facial gestalt and Hirschsprung' s disease (HSCR).", "output": {"entities": {}}, "schema": []}
{"input": "In 2005, homozygosity mapping in a large consanguineous family identified KIAA1279 as the disease-causing gene.", "output": {"entities": {}}, "schema": []}
{"input": "KIAA1279 encodes KIF-binding protein (KBP), whose function is incompletely understood.", "output": {"entities": {}}, "schema": []}
{"input": "Studies have identified either the mitochondria or the cytoskeleton as the site of KBP localization and interactions.", "output": {"entities": {}}, "schema": []}
{"input": "To better delineate the KIAA1279-related clinical spectrum and the molecular mechanisms involved in GOSHS, we studied five new patients from three different families.", "output": {"entities": {}}, "schema": []}
{"input": "The homozygous KIAA1279 mutations in these patients (p. Arg90X, p. Ser200X or p. Arg202IlefsX2) led to nonsense-mediated mRNA decay and loss of KBP function.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the absence of functional KBP, respiratory chain complex activity in patient fibroblasts was normal.", "output": {"entities": {}}, "schema": []}
{"input": "KBP did not co-localize with mitochondria in control human fibroblasts, but interacted with the actin and tubulin cytoskeleton.", "output": {"entities": {}}, "schema": []}
{"input": "KBP expression directly affected neurite growth in a neuron-like cell line (human neuroblastoma SH-SY5Y), in keeping with the central (polymicrogyria) and enteric (HSCR) neuronal developmental defects seen in GOSHS patients.", "output": {"entities": {}}, "schema": []}
{"input": "The KBP interactions with actin filaments and microtubules (MTs) demonstrated in our study constitute the first evidence that an actin MT cross-link protein is involved in neuronal development in humans.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of the phosphodiesterase type 5 inhibitor vardenafil on cognitive performance in healthy adults: a behavioral-electroencephalography study.", "output": {"entities": {"chemical": [{"text": "vardenafil", "start": 54, "end": 64}]}}, "schema": []}
{"input": "Phosphodiesterase type 5 inhibitors (PDE5-Is) improve cognitive performance of rodents, but the few human studies investigating their effects did not systematically investigate cognitive effects and the results have been quite contradictory.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we examined whether the PDE5-I vardenafil improves memory and executive functioning and affect electroencephalography (EEG) in healthy young adults.", "output": {"entities": {"chemical": [{"text": "vardenafil", "start": 42, "end": 52}]}}, "schema": []}
{"input": "Participants were selected out of a group of volunteers, based on their performance on a memory screening and they were orally treated with vardenafil (10-20 mg or placebo).", "output": {"entities": {"chemical": [{"text": "vardenafil", "start": 140, "end": 150}]}}, "schema": []}
{"input": "Memory and executive functioning were tested while EEG activity was recorded.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, a simple reaction time task and questionnaires addressing various complaints were presented.", "output": {"entities": {}}, "schema": []}
{"input": "No prominent effects of vardenafil on cognition were found: participants only made more mistakes on a reaction time task after 20 mg vardenafil.", "output": {"entities": {"chemical": [{"text": "vardenafil", "start": 24, "end": 34}, {"text": "vardenafil", "start": 133, "end": 143}]}}, "schema": []}
{"input": "During encoding of words, the P300 was generally smaller after vardenafil treatment.", "output": {"entities": {"chemical": [{"text": "vardenafil", "start": 63, "end": 73}]}}, "schema": []}
{"input": "Furthermore, the N400 was larger after vardenafil 10 mg than placebo treatment in a spatial memory task at Fz.", "output": {"entities": {"chemical": [{"text": "vardenafil", "start": 39, "end": 49}]}}, "schema": []}
{"input": "Finally, headache and feeling weak were reported more after vardenafil treatment.", "output": {"entities": {"chemical": [{"text": "vardenafil", "start": 60, "end": 70}]}}, "schema": []}
{"input": "Vardenafil did not affect cognitive performance of healthy adults and showed only some incidental effects on ERPs.", "output": {"entities": {"chemical": [{"text": "Vardenafil", "start": 0, "end": 10}]}}, "schema": []}
{"input": "These findings in humans do not corroborate the cognition-enhancing effects of PDE5-Is in healthy animals.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of the anti-dopamine D2 and anti-serotonin 5-HT2A activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 23, "end": 31}, {"text": "serotonin", "start": 44, "end": 53}, {"text": "chlorpromazine", "start": 75, "end": 89}, {"text": "bromperidol", "start": 91, "end": 102}, {"text": "haloperidol", "start": 104, "end": 115}]}}, "schema": []}
{"input": "Second-generation antipsychotics, which have become the standard drug therapies for schizophrenia, are known to have a serotonin 5-HT2A receptor blocking effect in addition to a dopamine D2 receptor blocking effect.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 119, "end": 128}, {"text": "dopamine", "start": 178, "end": 186}]}}, "schema": []}
{"input": "However, although chlorpromazine (CPZ) has a 5-HT2A receptor blocking effect and has the profile of a second-generation antipsychotic in vitro, it loses this pharmacological profile in vivo.", "output": {"entities": {"chemical": [{"text": "chlorpromazine", "start": 18, "end": 32}, {"text": "CPZ", "start": 34, "end": 37}]}}, "schema": []}
{"input": "In order to elucidate the differences between the in vivo and in vitro pharmacological characteristics of CPZ, we used a radioreceptor assay to measure the anti-D2 activity and the anti-5-HT2A activity of CPZ and five major metabolites of CPZ, and compared the results to the anti-D2 activity and anti-5-HT2A activity of risperidone, zotepine, perospirone, the major metabolites of each of these drugs, and olanzapine, bromperidol, and haloperidol.", "output": {"entities": {"chemical": [{"text": "CPZ", "start": 106, "end": 109}, {"text": "CPZ", "start": 205, "end": 208}, {"text": "CPZ", "start": 239, "end": 242}, {"text": "risperidone", "start": 321, "end": 332}, {"text": "zotepine", "start": 334, "end": 342}, {"text": "perospirone", "start": 344, "end": 355}, {"text": "olanzapine", "start": 407, "end": 417}, {"text": "bromperidol", "start": 419, "end": 430}, {"text": "haloperidol", "start": 436, "end": 447}]}}, "schema": []}
{"input": "The subjects were 182 patients who had received diagnoses of schizophrenia based on the DSM-IV criteria.", "output": {"entities": {}}, "schema": []}
{"input": "The results revealed that CPZ exhibited little anti-5-HT2A activity, regardless of the anti-D2 activity level, and that none of the metabolites possessed anti-5-HT2A activity.", "output": {"entities": {"chemical": [{"text": "CPZ", "start": 26, "end": 29}]}}, "schema": []}
{"input": "However, both the parent compounds and the metabolites of each of the second-generation antipsychotics possessed both anti-D2 activity and anti-5-HT2A activity.", "output": {"entities": {}}, "schema": []}
{"input": "This clarified that, unlike second-generation antipsychotics, the reason CPZ loses its second-generation antipsychotic profiles in vivo is because it does not have any metabolites that possess anti-5-HT2A activity.", "output": {"entities": {"chemical": [{"text": "CPZ", "start": 73, "end": 76}]}}, "schema": []}
{"input": "Vapor-solid growth of high optical quality MoS 2 monolayers with near-unity valley polarization.", "output": {"entities": {"chemical": [{"text": "MoS 2", "start": 43, "end": 48}]}}, "schema": []}
{"input": "Monolayers of transition metal dichalcogenides (TMDCs) are atomically thin direct-gap semiconductors with potential applications in nanoelectronics, optoelectronics, and electrochemical sensing.", "output": {"entities": {"chemical": [{"text": "transition metal dichalcogenides", "start": 14, "end": 46}, {"text": "TMDCs", "start": 48, "end": 53}]}}, "schema": []}
{"input": "Recent theoretical and experimental efforts suggest that they are ideal systems for exploiting the valley degrees of freedom of Bloch electrons.", "output": {"entities": {}}, "schema": []}
{"input": "For example, Dirac valley polarization has been demonstrated in mechanically exfoliated monolayer MoS2 samples by polarization-resolved photoluminescence, although polarization has rarely been seen at room temperature.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 98, "end": 102}]}}, "schema": []}
{"input": "Here we report a new method for synthesizing high optical quality monolayer MoS2 single crystals up to 25 mu m in size on a variety of standard insulating substrates (SiO2, sapphire, and glass) using a catalyst-free vapor-solid growth mechanism.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 76, "end": 80}, {"text": "SiO2", "start": 167, "end": 171}, {"text": "sapphire", "start": 173, "end": 181}]}}, "schema": []}
{"input": "The technique is simple and reliable, and the optical quality of the crystals is extremely high, as demonstrated by the fact that the valley polarization approaches unity at 30 K and persists at 35% even at room temperature, suggesting a virtual absence of defects.", "output": {"entities": {}}, "schema": []}
{"input": "This will allow greatly improved optoelectronic TMDC monolayer devices to be fabricated and studied routinely.", "output": {"entities": {"chemical": [{"text": "TMDC", "start": 48, "end": 52}]}}, "schema": []}
{"input": "2-Arylpyrazolo [4, 3-d] pyrimidin-7-amino derivatives as new potent and selective human A3 Adenosine receptor antagonists.", "output": {"entities": {"chemical": [{"text": "2-Arylpyrazolo [4, 3-d] pyrimidin-7-amino", "start": 0, "end": 41}, {"text": "Adenosine", "start": 91, "end": 100}]}}, "schema": []}
{"input": "Molecular modeling studies and pharmacological evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of our previously reported 2-arylpyrazolo [4, 3-d] pyrimidin-7-ones, a set of 2-arylpyrazolo [4, 3-d] pyrimidin-7-amines were designed as new human (h) A3 adenosine receptor (AR) antagonists.", "output": {"entities": {"chemical": [{"text": "2-arylpyrazolo [4, 3-d] pyrimidin-7-ones", "start": 40, "end": 80}, {"text": "2-arylpyrazolo [4, 3-d] pyrimidin-7-amines", "start": 91, "end": 133}, {"text": "adenosine", "start": 168, "end": 177}]}}, "schema": []}
{"input": "Lipophilic groups with different steric bulk were introduced at the 5-position of the bicyclic scaffold (R5 = Me, Ph, CH2Ph), and different acyl and carbamoyl moieties (R7) were appended on the 7-amino group, as well as a para-methoxy group inserted on the 2-phenyl ring.", "output": {"entities": {"chemical": [{"text": "Me", "start": 110, "end": 112}, {"text": "Ph", "start": 114, "end": 116}, {"text": "CH2Ph", "start": 118, "end": 123}, {"text": "acyl", "start": 140, "end": 144}, {"text": "carbamoyl", "start": 149, "end": 158}, {"text": "7-amino", "start": 194, "end": 201}, {"text": "para-methoxy", "start": 222, "end": 234}, {"text": "2-phenyl", "start": 257, "end": 265}]}}, "schema": []}
{"input": "The presence of acyl groups turned out to be of paramount importance for an efficient and selective binding at the hA3 AR.", "output": {"entities": {"chemical": [{"text": "acyl", "start": 16, "end": 20}]}}, "schema": []}
{"input": "In fact, most of the 7-acylamino derivatives showed low nanomolar affinity (Ki = 2. 5-45 nM) and high selectivity toward this receptor.", "output": {"entities": {"chemical": [{"text": "7-acylamino", "start": 21, "end": 32}]}}, "schema": []}
{"input": "A few selected pyrazolo [4, 3-d] pyrimidin-7-amides were effective in counteracting oxaliplatin-induced apoptosis in rat astrocyte cell cultures, an in vitro model of neurotoxicity.", "output": {"entities": {"chemical": [{"text": "pyrazolo [4, 3-d] pyrimidin-7-amides", "start": 15, "end": 51}, {"text": "oxaliplatin", "start": 84, "end": 95}]}}, "schema": []}
{"input": "Through an in silico receptor-driven approach the obtained binding data were rationalized and the molecular bases of the observed hA3 AR affinity and hA3 versus hA2A AR selectivity were explained.", "output": {"entities": {}}, "schema": []}
{"input": "Absolute Configurations of Fungal and Plant Metabolites by Chiroptical Methods.", "output": {"entities": {}}, "schema": []}
{"input": "ORD, ECD, and VCD Studies on Phyllostin, Scytolide, and Oxysporone.", "output": {"entities": {"chemical": [{"text": "Phyllostin", "start": 29, "end": 39}, {"text": "Scytolide", "start": 41, "end": 50}, {"text": "Oxysporone", "start": 56, "end": 66}]}}, "schema": []}
{"input": "The absolute configuration (AC) of the bioactive metabolites phyllostin (1) and scytolide (2), two hexahydro-1, 4-benzodioxines produced by Phyllosticta cirsii, and oxysporone (3), a dihydrofuropyranone recently isolated from a strain of Diplodia africana, has been assigned by computational analysis of their optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) spectra.", "output": {"entities": {"chemical": [{"text": "phyllostin", "start": 61, "end": 71}, {"text": "scytolide", "start": 80, "end": 89}, {"text": "hexahydro-1, 4-benzodioxines", "start": 99, "end": 127}, {"text": "oxysporone", "start": 165, "end": 175}, {"text": "dihydrofuropyranone", "start": 183, "end": 202}]}}, "schema": []}
{"input": "Computational prediction of ORD, ECD, and VCD allowed us to assign (3S, 4aR, 8S, 8aR) AC to naturally occurring (-)-1, while (4aR, 8S, 8aR) AC was assigned to (-)-2 employing only ECD and VCD, because in this case ORD analysis turned out to be unsuitable for AC assignment.", "output": {"entities": {}}, "schema": []}
{"input": "Theoretical prediction of both ORD and ECD spectra of 3 led to assignment of (4S, 5R, 6R) AC to (+)-3.", "output": {"entities": {}}, "schema": []}
{"input": "In this case a satisfactory agreement between experimental and calculated VCD spectra was obtained only after taking into account solvent effects.", "output": {"entities": {}}, "schema": []}
{"input": "This study shows that in the case of flexible and complex natural products only a concerted application of more than a single chiroptical technique permits unambiguous assignment of absolute configuration.", "output": {"entities": {}}, "schema": []}
{"input": "Generalized indirect Fourier transformation as a valuable tool for the structural characterization of aqueous nanocrystalline cellulose suspensions by small angle X-ray scattering.", "output": {"entities": {}}, "schema": []}
{"input": "Small angle X-ray scattering (SAXS) is employed to characterize the inner structure and shape of aqueous nanocrystalline cellulose suspensions using the generalized indirect Fourier transformation (GIFT).", "output": {"entities": {}}, "schema": []}
{"input": "The use of the GIFT approach provides a single fitting procedure for the determination of intra-and interparticle interactions due to a simultaneous treatment of the form factor P (q) and the structure factor S (q).", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, GIFT allows for the determination of particle charges and polydispersity indices.", "output": {"entities": {}}, "schema": []}
{"input": "As test material, aqueous nanocrystalline cellulose suspensions (aNCS) prepared by the H2SO4 route have been investigated and characterized (SAXS, dynamic light scattering, zeta potential).", "output": {"entities": {"chemical": [{"text": "H2SO4", "start": 87, "end": 92}]}}, "schema": []}
{"input": "Evaluation of difluoromethyl ketones as agonists of the gamma-aminobutyric acid type B (GABAB) receptor.", "output": {"entities": {"chemical": [{"text": "difluoromethyl ketones", "start": 14, "end": 36}, {"text": "gamma-aminobutyric acid", "start": 56, "end": 79}]}}, "schema": []}
{"input": "The design, synthesis, biological evaluation, and in vivo studies of difluoromethyl ketones as GABAB agonists that are not structurally analogous to known GABAB agonists, such as baclofen or 3-aminopropyl phosphinic acid, are presented.", "output": {"entities": {"chemical": [{"text": "difluoromethyl ketones", "start": 69, "end": 91}, {"text": "baclofen", "start": 179, "end": 187}, {"text": "3-aminopropyl phosphinic acid", "start": 191, "end": 220}]}}, "schema": []}
{"input": "The difluoromethyl ketones were assembled in three synthetic steps using a trifluoroacetate-release aldol reaction.", "output": {"entities": {"chemical": [{"text": "difluoromethyl ketones", "start": 4, "end": 26}, {"text": "trifluoroacetate", "start": 75, "end": 91}]}}, "schema": []}
{"input": "Following evaluation at clinically relevant GABA receptors, we have identified a difluoromethyl ketone that is a potent GABAB agonist, obtained its X-ray structure, and presented preliminary in vivo data in alcohol-preferring mice.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 44, "end": 48}, {"text": "difluoromethyl ketone", "start": 81, "end": 102}, {"text": "alcohol", "start": 207, "end": 214}]}}, "schema": []}
{"input": "The behavioral studies in mice demonstrated that this compound tended to reduce the acoustic startle response, which is consistent with an anxiolytic profile.", "output": {"entities": {}}, "schema": []}
{"input": "Structure-activity investigations determined that replacing the fluorines of the difluoromethyl ketone with hydrogens resulted in an inactive analogue.", "output": {"entities": {"chemical": [{"text": "fluorines", "start": 64, "end": 73}, {"text": "difluoromethyl ketone", "start": 81, "end": 102}, {"text": "hydrogens", "start": 108, "end": 117}]}}, "schema": []}
{"input": "Resolution of the individual enantiomers of the difluoromethyl ketone provided a compound with full biological activity at concentrations less than an order of magnitude greater than the pharmaceutical, baclofen.", "output": {"entities": {"chemical": [{"text": "difluoromethyl ketone", "start": 48, "end": 69}, {"text": "baclofen", "start": 203, "end": 211}]}}, "schema": []}
{"input": "Platinum-modulated cobalt nanocatalysts for low-temperature aqueous-phase Fischer-Tropsch synthesis.", "output": {"entities": {"chemical": [{"text": "Platinum", "start": 0, "end": 8}, {"text": "cobalt", "start": 19, "end": 25}]}}, "schema": []}
{"input": "Fischer-Tropsch synthesis (FTS) is an important catalytic process for liquid fuel generation, which converts coal/shale gas/biomass-derived syngas (a mixture of CO and H2) to oil.", "output": {"entities": {"chemical": [{"text": "CO", "start": 161, "end": 163}, {"text": "H2", "start": 168, "end": 170}]}}, "schema": []}
{"input": "While FTS is thermodynamically favored at low temperature, it is desirable to develop a new catalytic system that could allow working at a relatively low reaction temperature.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we present a one-step hydrogenation-reduction route for the synthesis of Pt-Co nanoparticles (NPs) which were found to be excellent catalysts for aqueous-phase FTS at 433 K.", "output": {"entities": {"chemical": [{"text": "Pt-Co", "start": 90, "end": 95}]}}, "schema": []}
{"input": "Coupling with atomic-resolution scanning transmission electron microscopy (STEM) and theoretical calculations, the outstanding activity is rationalized by the formation of Co overlayer structures on Pt NPs or Pt-Co alloy NPs.", "output": {"entities": {"chemical": [{"text": "Coupling", "start": 0, "end": 8}, {"text": "Pt", "start": 199, "end": 201}, {"text": "Pt-Co", "start": 209, "end": 214}]}}, "schema": []}
{"input": "The improved energetics and kinetics from the change of the transition states imposed by the lattice mismatch between the two metals are concluded to be the key factors responsible for the dramatically improved FTS performance.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.", "output": {"entities": {}}, "schema": []}
{"input": "This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 mu g/100 g body weight (BW), i. p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 mu g/100 g BW, oral) and were found to improve in the Bzf co-treated condition.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 88, "end": 98}, {"text": "triiodothyronine", "start": 145, "end": 161}, {"text": "bezafibrate", "start": 297, "end": 308}, {"text": "Bzf", "start": 310, "end": 313}, {"text": "Bzf", "start": 372, "end": 375}]}}, "schema": []}
{"input": "Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration.", "output": {"entities": {"chemical": [{"text": "Bzf", "start": 91, "end": 94}]}}, "schema": []}
{"input": "Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 101, "end": 104}, {"text": "Bzf", "start": 154, "end": 157}]}}, "schema": []}
{"input": "Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment.", "output": {"entities": {"chemical": [{"text": "Bzf", "start": 187, "end": 190}]}}, "schema": []}
{"input": "In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclopia maculata and Cyclopia subternata (honeybush tea) inhibits adipogenesis in 3T3-L1 pre-adipocytes.", "output": {"entities": {}}, "schema": []}
{"input": "The stems, leaves and flowers of Cyclopia have been consumed as a herbal tea' honeybush tea' to treat various medical ailments since the 19th century.", "output": {"entities": {}}, "schema": []}
{"input": "Plant polyphenols are reported to inhibit adipogenesis in cell and animal models of obesity.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 6, "end": 17}]}}, "schema": []}
{"input": "The aim of this study was to assess the effect of hot water extracts of two Cyclopia species, C. maculata and C. subternata on obesity in an in vitro model.", "output": {"entities": {}}, "schema": []}
{"input": "The total polyphenol content of unfermented C. subternata, unfermented C. maculata and fermented C. maculata extracts was 25. 6, 22. 4 and 10. 8g GAE/100g, respectively.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 10, "end": 20}]}}, "schema": []}
{"input": "The major compounds present in the extracts were: the flavonoid, phloretin-3', 5'-di-C-glucoside in C. subternata, the xanthone, mangiferin in unfermented C. maculata and the flavanone, hesperidin in fermented C. maculata.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 54, "end": 63}, {"text": "phloretin-3', 5'-di-C-glucoside", "start": 65, "end": 96}, {"text": "xanthone", "start": 119, "end": 127}, {"text": "mangiferin", "start": 129, "end": 139}, {"text": "flavanone", "start": 175, "end": 184}]}}, "schema": []}
{"input": "All of the plant extracts inhibited intracellular triglyceride and fat accumulation, and decreased PPAR gamma 2 expression.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 50, "end": 62}]}}, "schema": []}
{"input": "The higher concentrations of unfermented C. maculata (800 and 1600 mu g/ml) and C. subternata (1600 mu g/ml) were cytotoxic in terms of decreased mitochondrial dehydrogenase activity.", "output": {"entities": {}}, "schema": []}
{"input": "Both fermented and unfermented C. maculata, at concentrations greater than 100 mu g/ml, decreased cellular ATP content.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Cyclopia maculata and C. subternata inhibit adipogenesis in vitro, suggesting their potential as anti-obesity agents.", "output": {"entities": {}}, "schema": []}
{"input": "Unraveling the mode of action of an obesogen: Mechanistic analysis of the model obesogen tributyltin in the 3T3-L1 cell line.", "output": {"entities": {"chemical": [{"text": "tributyltin", "start": 89, "end": 100}]}}, "schema": []}
{"input": "Obesogenic compounds are chemicals that have an influence on obesity development.", "output": {"entities": {}}, "schema": []}
{"input": "This study was designed to unravel the molecular mechanisms of the model obesogen TBT, using microarray analysis in the 3T3-L1 in vitro system, and to evaluate the use of toxicogenomics for obesogen screening.", "output": {"entities": {"chemical": [{"text": "TBT", "start": 82, "end": 85}]}}, "schema": []}
{"input": "The microarray results revealed enrichment of Gene Ontology terms involved in energy and fat metabolism after 10days of TBT exposure.", "output": {"entities": {"chemical": [{"text": "TBT", "start": 120, "end": 123}]}}, "schema": []}
{"input": "Pathway analysis unveiled PPAR signalling pathway as the sole pathway significantly enriched after 1day and the most significantly enriched pathway after 10days of exposure.", "output": {"entities": {}}, "schema": []}
{"input": "To our knowledge, this is the first study delivering an in depth mechanistic outline of the mode of action of TBT as an obesogen, combining effects on both cell physiological and gene expression level.", "output": {"entities": {"chemical": [{"text": "TBT", "start": 110, "end": 113}]}}, "schema": []}
{"input": "Furthermore, our results show that combining transcriptomics with 3T3-L1 cells is a promising tool for screening of potential obesogenic compounds.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.", "output": {"entities": {"chemical": [{"text": "cannabidiol", "start": 15, "end": 26}]}}, "schema": []}
{"input": "(-)-Delta (9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases.", "output": {"entities": {"chemical": [{"text": "(-)-Delta (9)-Tetrahydrocannabinol", "start": 0, "end": 34}]}}, "schema": []}
{"input": "In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "(-)-cannabidiol", "start": 57, "end": 72}]}}, "schema": []}
{"input": "Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol.", "output": {"entities": {"chemical": [{"text": "(-)-cannabidiol", "start": 148, "end": 163}]}}, "schema": []}
{"input": "Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs.", "output": {"entities": {"chemical": [{"text": "(-)-cannabidiol", "start": 27, "end": 42}]}}, "schema": []}
{"input": "(-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A.", "output": {"entities": {"chemical": [{"text": "(-)-Cannabidiol", "start": 0, "end": 15}, {"text": "carbachol", "start": 85, "end": 94}, {"text": "histamine", "start": 96, "end": 105}]}}, "schema": []}
{"input": "In contrast, (-)-cannabidiol inhibited anandamide-and virodhamine-induced responses of isolated bronchi.", "output": {"entities": {"chemical": [{"text": "(-)-cannabidiol", "start": 13, "end": 28}, {"text": "anandamide", "start": 39, "end": 49}, {"text": "virodhamine", "start": 54, "end": 65}]}}, "schema": []}
{"input": "A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions.", "output": {"entities": {"chemical": [{"text": "fatty acid amide", "start": 2, "end": 18}, {"text": "phenylmethanesulfonyl fluoride", "start": 40, "end": 70}, {"text": "(-)-cannabidiol", "start": 105, "end": 120}, {"text": "anandamide", "start": 124, "end": 134}]}}, "schema": []}
{"input": "In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin.", "output": {"entities": {"chemical": [{"text": "(-)-cannabidiol", "start": 13, "end": 28}]}}, "schema": []}
{"input": "In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction.", "output": {"entities": {"chemical": [{"text": "(-)-cannabidiol", "start": 9, "end": 24}]}}, "schema": []}
{"input": "In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders.", "output": {"entities": {"chemical": [{"text": "cannabidiol", "start": 40, "end": 51}]}}, "schema": []}
{"input": "Serial infusions of low-dose ketamine for major depression.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Background: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 32, "end": 40}]}}, "schema": []}
{"input": "Side effects during the infusions have been common.", "output": {"entities": {}}, "schema": []}
{"input": "It is not known whether serial infusions or lower infusion rates result in greater efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "Methods: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0. 5 mg/kg administered over 100 min until either remission was achieved or four infusions were given.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 63, "end": 71}, {"text": "ketamine", "start": 85, "end": 93}]}}, "schema": []}
{"input": "Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).", "output": {"entities": {}}, "schema": []}
{"input": "Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions.", "output": {"entities": {}}, "schema": []}
{"input": "Results: Five of 10 patients achieved remission status.", "output": {"entities": {}}, "schema": []}
{"input": "There were no significant increases on the BPRS or YMRS.", "output": {"entities": {}}, "schema": []}
{"input": "Two of the remitting patients sustained their improvement throughout the four week follow-up period.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care.", "output": {"entities": {"chemical": [{"text": "Ketamine", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Serial ketamine infusions appear to be more effective than a single infusion.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 7, "end": 15}]}}, "schema": []}
{"input": "Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 73, "end": 81}]}}, "schema": []}
{"input": "Nephroprotective effect of calcium channel blockers against toxicity of lead exposure in mice.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 27, "end": 34}]}}, "schema": []}
{"input": "Exposure to lead (Pb) can induce kidney damage, which is related to induction of oxidative damage and disturbance of intracellular calcium homeostasis.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 18, "end": 20}, {"text": "calcium", "start": 131, "end": 138}]}}, "schema": []}
{"input": "Pb can readily permeate through dihydropyridine-sensitive L-type calcium channels and accumulate within cells.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 0, "end": 2}, {"text": "calcium", "start": 65, "end": 72}]}}, "schema": []}
{"input": "The objective of this study was to investigate protective effects of calcium channel blockers (CCBs) verapamil and nimodipine on nephrotoxicity induced by Pb acetate in mice.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 69, "end": 76}, {"text": "verapamil", "start": 101, "end": 110}, {"text": "nimodipine", "start": 115, "end": 125}, {"text": "Pb acetate", "start": 155, "end": 165}]}}, "schema": []}
{"input": "One hundred and twenty male mice were randomly divided into 6 groups: control, Pb, low-dose verapamil, high-dose verapamil, low-dose nimodipine and high-dose nimodipine (n = 20 per group).", "output": {"entities": {"chemical": [{"text": "Pb", "start": 79, "end": 81}, {"text": "verapamil", "start": 92, "end": 101}, {"text": "verapamil", "start": 113, "end": 122}, {"text": "nimodipine", "start": 133, "end": 143}, {"text": "nimodipine", "start": 158, "end": 168}]}}, "schema": []}
{"input": "Pb acetate was injected intraperitoneally (i. p.) at 40 mg/kg body weight/day for 10 days to establish the Pb toxicity model.", "output": {"entities": {"chemical": [{"text": "Pb acetate", "start": 0, "end": 10}, {"text": "Pb", "start": 107, "end": 109}]}}, "schema": []}
{"input": "While control mice received saline, mice of the treated groups simultaneously received i. p. injections of verapamil or nimodipine daily for 10 days.", "output": {"entities": {"chemical": [{"text": "verapamil", "start": 107, "end": 116}, {"text": "nimodipine", "start": 120, "end": 130}]}}, "schema": []}
{"input": "Both verapamil and nimodipine showed protection against Pb-induced kidney injury, including alleviation of renal pathological damage and decreasing the level of Pb in kidney homogenate and extent of apoptosis in nephrocytes.", "output": {"entities": {"chemical": [{"text": "verapamil", "start": 5, "end": 14}, {"text": "nimodipine", "start": 19, "end": 29}, {"text": "Pb", "start": 56, "end": 58}, {"text": "Pb", "start": 161, "end": 163}]}}, "schema": []}
{"input": "Moreover, verapamil and nimodipine significantly down-regulated levels of blood urea nitrogen and creatinine in the serum.", "output": {"entities": {"chemical": [{"text": "verapamil", "start": 10, "end": 19}, {"text": "nimodipine", "start": 24, "end": 34}, {"text": "urea nitrogen", "start": 80, "end": 93}, {"text": "creatinine", "start": 98, "end": 108}]}}, "schema": []}
{"input": "In addition, verapamil and nimodipine administration decreased malondialdehyde content and increased activities of super oxide dismutase activity and glutathione peroxidase in the kidney homogenate.", "output": {"entities": {"chemical": [{"text": "verapamil", "start": 13, "end": 22}, {"text": "nimodipine", "start": 27, "end": 37}, {"text": "malondialdehyde", "start": 63, "end": 78}, {"text": "super oxide", "start": 115, "end": 126}, {"text": "glutathione", "start": 150, "end": 161}]}}, "schema": []}
{"input": "The findings in the present study implicate the therapeutic potential of CCBs for Pb-induced nephrotoxicity, which were at least partly due to the decrease of Pb uptake and inhibition of lipid peroxidation.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 82, "end": 84}, {"text": "Pb", "start": 159, "end": 161}]}}, "schema": []}
{"input": "What is Comet assay not telling us: AFLP reveals wider aspects of genotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "DNA damage detected by genotoxicity biomarkers such as the Comet assay is not always a reliable indicator of the consequences that genotoxic agents can have on the genome integrity of the exposed organisms.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, to reveal the existence of more permanent alterations of DNA structure after genotoxic stress, the RTG-2 rainbow trout cell line was exposed for 3days to benzo [a] pyrene (B [a] P, 0. 1-10 mu M) and ethyl methanesulfonate (EMS, 0. 1-1mM) followed by 3days of recovery period.", "output": {"entities": {"chemical": [{"text": "benzo [a] pyrene", "start": 165, "end": 181}, {"text": "B [a] P", "start": 183, "end": 190}, {"text": "ethyl methanesulfonate", "start": 210, "end": 232}, {"text": "EMS", "start": 234, "end": 237}]}}, "schema": []}
{"input": "Primary DNA damage was evaluated by the Comet assay and DNA alterations were assessed using AFLP (amplified fragment length polymorphism).", "output": {"entities": {}}, "schema": []}
{"input": "Qualitative and quantitative modifications in AFLP profiles were analyzed in order to detect genetic alterations arising from mutation events and/or DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Significant induction in DNA damage measured by the Comet assay was noticed after B [a] P treatment at all concentrations but values returned to the control level after recovery.", "output": {"entities": {"chemical": [{"text": "B [a] P", "start": 82, "end": 89}]}}, "schema": []}
{"input": "Exposure to EMS induced significant DNA damage only at the highest concentration and damage persisted after the recovery period.", "output": {"entities": {}}, "schema": []}
{"input": "AFLP profiles detected DNA alterations even when Comet assay indicated complete DNA repair, revealing more persistent damage.", "output": {"entities": {}}, "schema": []}
{"input": "Since such DNA damage can impair its structure and function, Comet assay results should preferably be supplemented with other methods in order to predict the consequences of genotoxic insult more accurately.", "output": {"entities": {}}, "schema": []}
{"input": "The sensitivity of the KeratinoSens ((TM)) assay to evaluate plant extracts: A pilot study.", "output": {"entities": {}}, "schema": []}
{"input": "Several tests to assess skin sensitization hazard are in peer-review for pre-validation.", "output": {"entities": {}}, "schema": []}
{"input": "These tests, as well as the animal tests they aim to replace, were developed (and validated) for the testing of pure substances.", "output": {"entities": {}}, "schema": []}
{"input": "However, in the cosmetic field, active ingredients are often mixtures from natural sources.", "output": {"entities": {}}, "schema": []}
{"input": "It is therefore important to understand which tests could be used to evaluate their safety.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe a proof-of-concept study to test whether the KeratinoSens ((TM)) assay is able to detect sensitizing constituents within botanical mixtures.", "output": {"entities": {}}, "schema": []}
{"input": "Four extracts were spiked with different doses of the sensitizers citral, cinnamic aldehyde and isoeugenol.", "output": {"entities": {"chemical": [{"text": "citral", "start": 66, "end": 72}, {"text": "cinnamic aldehyde", "start": 74, "end": 91}, {"text": "isoeugenol", "start": 96, "end": 106}]}}, "schema": []}
{"input": "The tested extracts were negative in the test whereas they became positive in most cases when spiked with the sensitizers.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of the results from the samples spiked with different doses allowed the determination of the minimal level of sensitizers being detectable.", "output": {"entities": {}}, "schema": []}
{"input": "The contribution to sensitization potential of doses of 2% and above of the spiked sensitizers were reliably detected.", "output": {"entities": {}}, "schema": []}
{"input": "There were limitations for an extract with high cytotoxicity, in which case detection of the artificially spiked sensitizers proved difficult.", "output": {"entities": {}}, "schema": []}
{"input": "This study gives a proof of principle for testing of mixtures in the KeratinoSens ((TM)) assay and indicates how sensitive the assay is to detect minor components with sensitizing potential.", "output": {"entities": {}}, "schema": []}
{"input": "Reversible effect of developmental exposure to chlorpyrifos on late-stage neurogenesis in the hippocampal dentate gyrus in mouse offspring.", "output": {"entities": {"chemical": [{"text": "chlorpyrifos", "start": 47, "end": 59}]}}, "schema": []}
{"input": "The effect of developmental exposure to chlorpyrifos (CPF) on hippocampal neurogenesis was examined in male mice after maternal dietary exposure to CPF at 0, 4, 20, or 100ppm from gestation day 10 to postnatal day (PND) 21.", "output": {"entities": {"chemical": [{"text": "chlorpyrifos", "start": 40, "end": 52}, {"text": "CPF", "start": 54, "end": 57}, {"text": "CPF", "start": 148, "end": 151}]}}, "schema": []}
{"input": "Cholinesterase activity was dose-dependently decreased in red blood cells at >= 4ppm and in the brain at 100ppm both in dams and offspring on PND 21.", "output": {"entities": {}}, "schema": []}
{"input": "Immunohistochemically, doublecortin (+) cells were decreased at >= 20ppm in the subgranular zone (SGZ) of the dentate gyrus, and NeuN (+)-expressing mature neurons were decreased at 100ppm in the hilus on PND 21.", "output": {"entities": {}}, "schema": []}
{"input": "There were no differences in the numbers of progenitor populations expressing Tbr2 or M1 muscarinic acetylcholine receptors.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 100, "end": 113}]}}, "schema": []}
{"input": "Transcript levels of Dcx also decreased at >= 20ppm, and those of Pcna, Casp3, Bax, Bcl2, Pax6 and Tbr2 were unchanged in the dentate gyrus by real-time RT-PCR.", "output": {"entities": {}}, "schema": []}
{"input": "At PND 77, hippocampal neurogenesis was unchanged.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that developmental CPF exposure directly but transiently suppresses maturation of late-stage granule cell lineages in the SGZ and affects interneuron populations in the hilus.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 41, "end": 44}]}}, "schema": []}
{"input": "The role of lipid domains in bacterial cell processes.", "output": {"entities": {}}, "schema": []}
{"input": "Membranes are vital structures for cellular life forms.", "output": {"entities": {}}, "schema": []}
{"input": "As thin, hydrophobic films, they provide a physical barrier separating the aqueous cytoplasm from the outside world or from the interiors of other cellular compartments.", "output": {"entities": {}}, "schema": []}
{"input": "They maintain a selective permeability for the import and export of water-soluble compounds, enabling the living cell to maintain a stable chemical environment for biological processes.", "output": {"entities": {}}, "schema": []}
{"input": "Cell membranes are primarily composed of two crucial substances, lipids and proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterial membranes can sense environmental changes or communication signals from other cells and they support different cell processes, including cell division, differentiation, protein secretion and supplementary protein functions.", "output": {"entities": {}}, "schema": []}
{"input": "The original fluid mosaic model of membrane structure has been recently revised because it has become apparent that domains of different lipid composition are present in both eukaryotic and prokaryotic cell membranes.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we summarize different aspects of phospholipid domain formation in bacterial membranes, mainly in Gram-negative Escherichia coli and Gram-positive Bacillus subtilis.", "output": {"entities": {}}, "schema": []}
{"input": "We describe the role of these lipid domains in membrane dynamics and the localization of specific proteins and protein complexes in relation to the regulation of cellular function.", "output": {"entities": {}}, "schema": []}
{"input": "Intracellular localization of the BCL-2 family member BOK and functional implications.", "output": {"entities": {}}, "schema": []}
{"input": "The pro-apoptotic BCL-2 family member BOK is widely expressed and resembles the multi-BH domain proteins BAX and BAK based on its amino acid sequence.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 130, "end": 140}]}}, "schema": []}
{"input": "The genomic region encoding BOK was reported to be frequently deleted in human cancer and it has therefore been hypothesized that BOK functions as a tumor suppressor.", "output": {"entities": {}}, "schema": []}
{"input": "However, little is known about the molecular functions of BOK.", "output": {"entities": {}}, "schema": []}
{"input": "We show that enforced expression of BOK activates the intrinsic (mitochondrial) apoptotic pathway in BAX/BAK-proficient cells but fails to kill cells lacking both BAX and BAK or sensitize them to cytotoxic insults.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, major portions of endogenous BOK are localized to and partially inserted into the membranes of the Golgi apparatus as well as the endoplasmic reticulum (ER) and associated membranes.", "output": {"entities": {}}, "schema": []}
{"input": "The C-terminal transmembrane domain of BOK thereby constitutes a' tail-anchor' specific for targeting to the Golgi and ER.", "output": {"entities": {"chemical": [{"text": "C", "start": 4, "end": 5}]}}, "schema": []}
{"input": "Overexpression of full-length BOK causes early fragmentation of ER and Golgi compartments.", "output": {"entities": {}}, "schema": []}
{"input": "A role for BOK on the Golgi apparatus and the ER is supported by an abnormal response of Bok-deficient cells to the Golgi/ER stressor brefeldin A.", "output": {"entities": {"chemical": [{"text": "brefeldin A", "start": 134, "end": 145}]}}, "schema": []}
{"input": "Based on these results, we propose that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclic stretch induces inducible nitric oxide synthase and soluble guanylate cyclase in pulmonary artery smooth muscle cells.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 33, "end": 45}, {"text": "guanylate", "start": 67, "end": 76}]}}, "schema": []}
{"input": "In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation.", "output": {"entities": {"chemical": [{"text": "Nitric oxide", "start": 0, "end": 12}, {"text": "guanylate", "start": 46, "end": 55}, {"text": "cGMP", "start": 84, "end": 88}]}}, "schema": []}
{"input": "Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 64, "end": 76}]}}, "schema": []}
{"input": "In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclic stretch significantly increased cytosolic oxidative stress as compared to static cells (62. 9 +/- 5. 9% vs. 33. 3 +/- 5. 7% maximal oxidation), as measured by the intracellular redox sensor roGFP.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclic stretch also increased sGC beta protein expression (2. 5 +/- 0. 9-fold), sGC activity (1. 5 +/- 0. 2-fold) and cGMP levels (1. 8 +/- 0. 2-fold), as well as iNOS mRNA and protein expression (3. 0 +/- 0. 9 and 2. 6 +/- 0. 7-fold, respectively) relative to control cells.", "output": {"entities": {"chemical": [{"text": "cGMP", "start": 118, "end": 122}]}}, "schema": []}
{"input": "An antioxidant, recombinant human superoxide dismutase (rhSOD), significantly decreased stretch-induced cytosolic oxidative stress, but did not block stretch-induced sGC activity.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 34, "end": 44}]}}, "schema": []}
{"input": "Inhibition of iNOS with 1400 W or an iNOS-specific siRNA inhibited stretch-induced sGC activity by 30% and 68% respectively vs. static controls.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, cyclic stretch increases sGC expression and activity in an iNOS-dependent manner in PASMC from fetal lambs.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism that produces iNOS and sGC upregulation is not yet known, but we speculate these effects represent an early compensatory mechanism to counteract the effects of stretch-induced oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "A better understanding of the interplay between these two distinct pathways could provide key insights into future avenues to treat infants with pulmonary hypertension.", "output": {"entities": {}}, "schema": []}
{"input": "A simple, rapid, low-cost diagnostic test for sickle cell disease.", "output": {"entities": {}}, "schema": []}
{"input": "This communication describes a very simple, rapid and inexpensive point-of-care diagnostic test for sickle cell disease (SCD) that can conclusively differentiate between blood samples from normal healthy individuals, sickle cell trait carriers and SCD patients using the characteristic blood stain patterns produced by each sample on paper.", "output": {"entities": {}}, "schema": []}
{"input": "Microfluidic oscillators with widely tunable periods.", "output": {"entities": {}}, "schema": []}
{"input": "We present experiments and theory of a constant flow-driven microfluidic oscillator with widely tunable oscillation periods.", "output": {"entities": {}}, "schema": []}
{"input": "This oscillator converts two constant input-flows from a syringe pump into an alternating, periodic output-flow with oscillation periods that can be adjusted to between 0. 3 s to 4. 1 h by tuning an external membrane capacitor.", "output": {"entities": {}}, "schema": []}
{"input": "This capacitor allows multiple adjustable periods at a given input flow-rate, thus providing great flexibility in device operation.", "output": {"entities": {}}, "schema": []}
{"input": "Also, we show that a sufficiently large external capacitance, relative to the internal capacitance of the microfluidic valve itself, is a critical requirement for oscillation.", "output": {"entities": {}}, "schema": []}
{"input": "These widely tunable microfluidic oscillators are envisioned to be broadly useful for the study of biological rhythms, as on-chip timing sources for microfluidic logic circuits, and other applications that require variation in timed flow switching.", "output": {"entities": {}}, "schema": []}
{"input": "The interfacial-organized monolayer water film (MWF) induced \" two-step \" aggregation of nanographene: both in stacking and sliding assembly pathways.", "output": {"entities": {"chemical": [{"text": "nanographene", "start": 89, "end": 101}]}}, "schema": []}
{"input": "A computational investigation was carried out to understand the aggregation of nanoscale graphene with two typical pathways of stacking assembly and sliding assembly in water.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 89, "end": 97}]}}, "schema": []}
{"input": "The interfacial-organized monolayer water film (MWF) induced \" two-step \" aggregation of nanographene in both stacking and sliding assembly pathways was reported for the first time.", "output": {"entities": {"chemical": [{"text": "nanographene", "start": 89, "end": 101}]}}, "schema": []}
{"input": "By means of potential mean forces (PMFs) calculation, no energy barrier was observed during the sliding assembly of two graphene nanosheets, while the PMF profiles could be impacted by the contact forms of nanographene and the MWF within the interplate of two graphene nanosheets.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 120, "end": 128}, {"text": "nanographene", "start": 206, "end": 218}, {"text": "graphene", "start": 260, "end": 268}]}}, "schema": []}
{"input": "To explore the potential physical basis of the \" hindering role \" of self-organized interfacial water, the dynamical and structural properties as well as the status of hydrogen bonds (H-bonds) for interfacial water were investigated.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 168, "end": 176}, {"text": "H", "start": 184, "end": 185}]}}, "schema": []}
{"input": "We found that the compact, ordered structure and abundant H-bonds of the MWF could be taken as the fundamental aspects of the \" hindering role \" of interfacial water for the hydrophobic assembly of nanographene.", "output": {"entities": {"chemical": [{"text": "H", "start": 58, "end": 59}, {"text": "nanographene", "start": 198, "end": 210}]}}, "schema": []}
{"input": "These findings are displaying a potential to further understand the hydrophobic assembly which mostly dominate the behaviors of nanomaterials, proteins etc. in aqueous solutions.", "output": {"entities": {}}, "schema": []}
{"input": "TCDD inhibition of canonical wnt signaling disrupts prostatic bud formation in mouse urogenital sinus.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}]}}, "schema": []}
{"input": "In mice, in utero exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) reduces the number of dorsolateral prostatic buds resulting in a smaller dorsolateral prostate and prevents formation of ventral buds culminating in ventral prostate agenesis.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 30, "end": 68}, {"text": "TCDD", "start": 70, "end": 74}]}}, "schema": []}
{"input": "The genes and signaling pathways affected by TCDD that are responsible for disrupting prostate development are largely unknown.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 45, "end": 49}]}}, "schema": []}
{"input": "Here we show that treatment of urogenital sinus (UGS) organ cultures with known inhibitors of canonical Wnt signaling also inhibits prostatic bud formation.", "output": {"entities": {}}, "schema": []}
{"input": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 34, "end": 38}, {"text": "TCDD", "start": 108, "end": 112}, {"text": "TCDD", "start": 241, "end": 245}, {"text": "TCDD", "start": 655, "end": 659}]}}, "schema": []}
{"input": "Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 10, "end": 14}]}}, "schema": []}
{"input": "This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of TCDD on canonical Wnt signaling and prostatic bud formation.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 55, "end": 59}, {"text": "TCDD", "start": 160, "end": 164}]}}, "schema": []}
{"input": "We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 71, "end": 75}]}}, "schema": []}
{"input": "Hypoxaemia affects male reproduction: a case study of how to differentiate between primary and secondary hypoxic testicular toxicity due to chemical exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Classification for fertility is based on two conditions, namely on evidence of an adverse effect on sexual function and fertility and that the effect is not secondary to other toxic effects.", "output": {"entities": {}}, "schema": []}
{"input": "To decide on an adverse effect is a relatively simple day-to-day decision in toxicology but whether this effect is secondary often leads to serious controversy.", "output": {"entities": {}}, "schema": []}
{"input": "As the seminiferous epithelium operates on the verge of hypoxia, oxygen deficit can lead to secondary impairment of testicular function.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 65, "end": 71}]}}, "schema": []}
{"input": "This is well known from healthy mountaineers exposing themselves to high altitude.", "output": {"entities": {}}, "schema": []}
{"input": "They have reduced blood oxygen content that goes in parallel with impairment of testicular function and this effect remains for some time in spite of a compensatory polycythaemia.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 24, "end": 30}]}}, "schema": []}
{"input": "Similar findings are described for experimental animals exposed to hypobaric oxygen/high altitude.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 77, "end": 83}]}}, "schema": []}
{"input": "In addition, testicular function is affected in severe diseases in humans associated with systemic oxygen deficit like chronic obstructive pulmonary disease, sickle cell disease or beta-thalassaemia as well as in transgenic animals simulating haemolytic anaemia or sickle cell disease.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 99, "end": 105}]}}, "schema": []}
{"input": "The problem of insufficient oxygen supply as the underlying cause for testicular impairment has received relatively little attention in toxicology, mainly because blood oxygen content is generally not measured in these animal experiments.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 28, "end": 34}, {"text": "oxygen", "start": 169, "end": 175}]}}, "schema": []}
{"input": "The difficulties associated with the decision whether testicular toxicity is primary or secondary to hypoxia are exemplified by the results of inhalation studies with nickel subsulphide and gallium arsenide (GaAs).", "output": {"entities": {"chemical": [{"text": "nickel subsulphide", "start": 167, "end": 185}, {"text": "gallium arsenide", "start": 190, "end": 206}, {"text": "GaAs", "start": 208, "end": 212}]}}, "schema": []}
{"input": "Both of these particulate substances lead to severe lung toxicity that might impair oxygen uptake, but testicular toxicity is only observed with GaAs.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 84, "end": 90}, {"text": "GaAs", "start": 145, "end": 149}]}}, "schema": []}
{"input": "This may first be explained by different effects on the blood: nickel subsulphide inhalation leads to a compensatory erythropoiesis that may mitigate pulmonary lack of oxygen uptake.", "output": {"entities": {"chemical": [{"text": "nickel subsulphide", "start": 63, "end": 81}, {"text": "oxygen", "start": 168, "end": 174}]}}, "schema": []}
{"input": "In contrast, GaAs exposure is associated with microcytic haemolytic anaemia thereby aggravating any possible oxygen undersupply.", "output": {"entities": {"chemical": [{"text": "GaAs", "start": 13, "end": 17}, {"text": "oxygen", "start": 109, "end": 115}]}}, "schema": []}
{"input": "Furthermore, the predominant pulmonary effect caused by GaAs (but not by nickel subsulphide) is alveolar proteinosis.", "output": {"entities": {"chemical": [{"text": "GaAs", "start": 56, "end": 60}, {"text": "nickel subsulphide", "start": 73, "end": 91}]}}, "schema": []}
{"input": "Pulmonary alveolar proteinosis is also known as a severe disease in humans associated with hypoxaemia.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we conclude that the testicular effects observed after GaAs are secondary to hypoxaemia caused by the combination of pulmonary proteinosis and haemolytic anaemia.", "output": {"entities": {"chemical": [{"text": "GaAs", "start": 66, "end": 70}]}}, "schema": []}
{"input": "This publication tries to raise awareness to the severe consequences of hypoxaemia on testicular function that may already be caused by reduced oxygen pressure at high altitude without any chemical exposure.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Exogenous sodium nitroprusside alleviates arsenic-induced oxidative stress in wheat (Triticum aestivum L.) seedlings by enhancing antioxidant defense and glyoxalase system.", "output": {"entities": {"chemical": [{"text": "sodium nitroprusside", "start": 10, "end": 30}, {"text": "arsenic", "start": 42, "end": 49}]}}, "schema": []}
{"input": "The present study investigates the possible regulatory role of exogenous nitric oxide (NO) in mitigating oxidative stress in wheat seedlings exposed to arsenic (As).", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 73, "end": 85}, {"text": "NO", "start": 87, "end": 89}, {"text": "arsenic", "start": 152, "end": 159}, {"text": "As", "start": 161, "end": 163}]}}, "schema": []}
{"input": "Seedlings were treated with NO donor (0. 25 mM sodium nitroprusside, SNP) and As (0. 25 and 0. 5 mM Na2HAsO4. 7H2O) separately and/or in combination and grown for 72 h.", "output": {"entities": {"chemical": [{"text": "NO", "start": 28, "end": 30}, {"text": "sodium nitroprusside", "start": 47, "end": 67}, {"text": "SNP", "start": 69, "end": 72}, {"text": "As", "start": 78, "end": 80}, {"text": "Na2HAsO4. 7H2O", "start": 100, "end": 114}]}}, "schema": []}
{"input": "Relative water content (RWC) and chlorophyll (chl) content were decreased by As treatment but proline (Pro) content was increased.", "output": {"entities": {"chemical": [{"text": "chlorophyll", "start": 33, "end": 44}, {"text": "chl", "start": 46, "end": 49}, {"text": "As", "start": 77, "end": 79}, {"text": "proline", "start": 94, "end": 101}, {"text": "Pro", "start": 103, "end": 106}]}}, "schema": []}
{"input": "The ascorbate (AsA) content was decreased significantly with increased As concentration.", "output": {"entities": {"chemical": [{"text": "ascorbate", "start": 4, "end": 13}, {"text": "AsA", "start": 15, "end": 18}, {"text": "As", "start": 71, "end": 73}]}}, "schema": []}
{"input": "The imposition of As caused marked increase in the MDA and H2O2 content.", "output": {"entities": {"chemical": [{"text": "As", "start": 18, "end": 20}, {"text": "MDA", "start": 51, "end": 54}, {"text": "H2O2", "start": 59, "end": 63}]}}, "schema": []}
{"input": "The amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) significantly increased with an increase in the level of As (both 0. 25 and 0. 5 mM), while the GSH/GSSG ratio decreased at higher concentration (0. 5 mM).", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 22, "end": 33}, {"text": "GSH", "start": 35, "end": 38}, {"text": "glutathione disulfide", "start": 44, "end": 65}, {"text": "GSSG", "start": 67, "end": 71}, {"text": "As", "start": 130, "end": 132}, {"text": "GSH", "start": 169, "end": 172}, {"text": "GSSG", "start": 173, "end": 177}]}}, "schema": []}
{"input": "The ascorbate peroxidase and glutathione S-transferase activities consistently increased with an increase in the As concentration, while glutathione reductase (GR) activities increased only at 0. 25 mM.", "output": {"entities": {"chemical": [{"text": "ascorbate", "start": 4, "end": 13}, {"text": "glutathione S", "start": 29, "end": 42}, {"text": "As", "start": 113, "end": 115}, {"text": "glutathione", "start": 137, "end": 148}]}}, "schema": []}
{"input": "The monodehydroascorbate reductase (MDHAR) and catalase (CAT) activities were not changed upon exposure to As.", "output": {"entities": {"chemical": [{"text": "monodehydroascorbate", "start": 4, "end": 24}, {"text": "As", "start": 107, "end": 109}]}}, "schema": []}
{"input": "The activities of dehydroascorbate reductase (DHAR) and glyoxalase I (Gly I) decreased at any levels of As, while glutathione peroxidase (GPX) and glyoxalase II (Gly II) activities decreased only upon 0. 5 mM As.", "output": {"entities": {"chemical": [{"text": "dehydroascorbate", "start": 18, "end": 34}, {"text": "As", "start": 104, "end": 106}, {"text": "glutathione", "start": 114, "end": 125}, {"text": "As", "start": 209, "end": 211}]}}, "schema": []}
{"input": "Exogenous NO alone had little influence on the non-enzymatic and enzymatic components compared to the control seedlings.", "output": {"entities": {"chemical": [{"text": "NO", "start": 10, "end": 12}]}}, "schema": []}
{"input": "These inhibitory effects of As were markedly recovered by supplementation with SNP; that is, the treatment with SNP increased the RWC, chl and Pro contents; AsA and GSH contents and the GSH/GSSG ratio as well as the activities of MDHAR, DHAR, GR, GPX, CAT, Gly I and Gly II in the seedlings subjected to As stress.", "output": {"entities": {"chemical": [{"text": "As", "start": 28, "end": 30}, {"text": "SNP", "start": 79, "end": 82}, {"text": "SNP", "start": 112, "end": 115}, {"text": "chl", "start": 135, "end": 138}, {"text": "Pro", "start": 143, "end": 146}, {"text": "AsA", "start": 157, "end": 160}, {"text": "GSH", "start": 165, "end": 168}, {"text": "GSH", "start": 186, "end": 189}, {"text": "GSSG", "start": 190, "end": 194}, {"text": "As", "start": 304, "end": 306}]}}, "schema": []}
{"input": "These results suggest that the exogenous application of NO rendered the plants more tolerant to As-induced oxidative damage by enhancing their antioxidant defense and glyoxalase system.", "output": {"entities": {"chemical": [{"text": "NO", "start": 56, "end": 58}, {"text": "As", "start": 96, "end": 98}]}}, "schema": []}
{"input": "Design of an Escherichia coli Expressed HIV-1 gp120 Fragment Immunogen That Binds to b12 and Induces Broad and Potent Neutralizing Antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "b12, one of the few broadly neutralizing antibodies against HIV-1, binds to the CD4 binding site (CD4bs) on the gp120 subunit of HIV-1 Env.", "output": {"entities": {}}, "schema": []}
{"input": "Two small fragments of HIV-1 gp120, b121a and b122a, which display about 70% of the b12 epitope and include solubility-enhancing mutations, were designed.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterially expressed b121a/b122a were partially folded and could bind b12 but not the CD4bs-directed non-neutralizing antibody b6.", "output": {"entities": {}}, "schema": []}
{"input": "Sera from rabbits primed with b121a or b122a protein fragments and boosted with full-length gp120 showed broad neutralizing activity in a TZM-bl assay against a 16-virus panel that included nine Tier 2 and 3 viruses as well as in a five-virus panel previously designed to screen for broad neutralization.", "output": {"entities": {}}, "schema": []}
{"input": "Using a mean IC50 cut-off of 50, sera from control rabbits immunized with gp120 alone neutralized only one virus of the 14 non-Tier 1 viruses tested (7%), whereas sera from b121a-and b122a-immunized rabbits neutralized seven (50%) and twelve (86%) viruses, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Serum depletion studies confirmed that neutralization was gp120-directed and that sera from animals immunized with gp120 contained lower amounts of CD4bs-directed antibodies than corresponding sera from animals immunized with b121a/b122a.", "output": {"entities": {}}, "schema": []}
{"input": "Competition binding assays with b12 also showed that b121a/2a sera contained significantly higher amounts of antibodies directed toward the CD4 binding site than the gp120 sera.", "output": {"entities": {}}, "schema": []}
{"input": "The data demonstrate that it is possible to elicit broadly neutralizing sera against HIV-1 in small animals.", "output": {"entities": {}}, "schema": []}
{"input": "Human Antigen R-mediated mRNA Stabilization Is Required for Ultraviolet B-induced Autoinduction of Amphiregulin in Keratinocytes.", "output": {"entities": {}}, "schema": []}
{"input": "All members of the EGF family are produced as transmembrane precursors that are proteolytically processed into soluble forms by disintegrin and metalloproteinases (ADAMs) for autocrine/paracrine pathways.", "output": {"entities": {}}, "schema": []}
{"input": "In turn, the ligand-activated EGF receptor (EGFR) induces the expression of EGF family members, so-called \" autoinduction. \" However, it is not well understood how this autoinduction occurs.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated the molecular mechanism of the autoinduction of amphiregulin (AREG), a member of the EGF family.", "output": {"entities": {}}, "schema": []}
{"input": "We found that ultraviolet B (UVB) exposure increased the AREG mRNA level by stabilization of its mRNA in a human immortalized keratinocyte cell line, HaCaT.", "output": {"entities": {}}, "schema": []}
{"input": "The 3' UTR of AREG mRNA was responsible for binding to an mRNA-binding protein, human antigen R (HuR), and the interaction between AREG mRNA and HuR was enhanced by UVB.", "output": {"entities": {}}, "schema": []}
{"input": "Inducible knockdown of HuR expression significantly decreased AREG mRNA stability.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, treatment of HaCaT cells with an EGFR inhibitor, an EGFR neutralizing antibody, or an ADAM inhibitor destabilized AREG mRNA.", "output": {"entities": {}}, "schema": []}
{"input": "In the case of ADAM inhibition, administration of soluble AREG restored the mRNA level, indicating that the stabilization occurs in a shedding-dependent manner of EGFR ligands.", "output": {"entities": {}}, "schema": []}
{"input": "The HuR dependence of AREG mRNA and protein expression was also confirmed in human primary keratinocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, we propose a novel mechanism by which HuR regulates the stability of AREG mRNA in keratinocytes after UVB exposure and suggest that targeting of HuR functions might be crucial for understanding skin cancers caused by aberrant EGF family member-EGFR signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterial infection probes and imaging strategies in clinical nuclear medicine and preclinical molecular imaging.", "output": {"entities": {}}, "schema": []}
{"input": "At present, a limited number of strategies exist for diagnostic imaging of patients with bacterial infection.", "output": {"entities": {}}, "schema": []}
{"input": "While radiolabeled probes and white blood cells provide robust solutions to detect bacteria in humans, they also give false positives in cases of sterile inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "With the onset of bacterial drug resistance, and a clinical trend toward reducing the prescription of antibiotics, the need for highly specific infection detection protocols has been renewed.", "output": {"entities": {}}, "schema": []}
{"input": "The preclinical research community has recently utilized new optical imaging strategies, alongside traditional radioimaging research, to develop novel infection probes with translational potential.", "output": {"entities": {}}, "schema": []}
{"input": "Here we review the current clinical methods for imaging bacteria in humans, and discuss the efforts within the preclinical community to validate new strategies.", "output": {"entities": {}}, "schema": []}
{"input": "The review of preclinical infection imaging probes is limited to those probes that could be feasibly adapted for use in humans with currently available clinical modalities.", "output": {"entities": {}}, "schema": []}
{"input": "Transient Receptor Potential (TRP) Channels and Cardiac Fibrosis.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiac fibrosis is associated with most cardiac diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Fibrosis is an accumulation of excessive extracellular matrix proteins (ECM) synthesized by cardiac fibroblasts and myofibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Fibroblasts are the most prevalent cell type in the heart, comprising 75% of cardiac cells.", "output": {"entities": {}}, "schema": []}
{"input": "Myofibroblasts are hardly present in healthy normal heart tissue, but appear abundantly in diseased hearts.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiac fibroblasts are activated by a variety of pathological stimuli, such as myocardial injury, oxidative stress, mechanical stretch, and elevated autocrine-paracrine mediators, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins.", "output": {"entities": {}}, "schema": []}
{"input": "A number of signaling pathways and bioactive molecules are involved and work in concert to activate fibroblasts and myofibroblasts in the fibrogenesis cascade.", "output": {"entities": {}}, "schema": []}
{"input": "Fibroblasts and myofibroblasts are not only principal ECM producers, but also play a central role in fibrogenesis and myocardial remodeling in fibrotic heart disease.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, understanding the biological processes of cardiac fibroblasts will provide novel insights into the underlying mechanisms of fibrosis and provide potential targets for developing antifibrotic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies demonstrate that Ca2 + signal is essential for fibroblast proliferation, differentiation, and ECM-protein production.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 32, "end": 37}]}}, "schema": []}
{"input": "This review focuses on the recent advances in understanding molecular mechanisms of Ca2 + signaling in cardiac fibrogenesis, and potential role of Ca2 +-permeable channels, in particular, the transient potential (TRP) channels in fibrotic heart disease.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 84, "end": 89}, {"text": "Ca2 +", "start": 147, "end": 152}]}}, "schema": []}
{"input": "TRP channels are highly expressed in cardiac fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "TRPM7 has been shown to be essential in TGF beta 1 mediated fibrogenesis, and TRPC3 has been demonstrated to play an essential role in regulating fibroblast function.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the Ca2 +-permeable TRP channels may serve as potential novel targets for developing anti-fibrotic drugs.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 10, "end": 15}]}}, "schema": []}
{"input": "TRP Channels in Vascular Disorders.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years, research on the roles of TRP channels in vascular function and disease has undergone a rapid expansion from tens of reports published in the early 2000s to several hundreds of papers published to date.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple TRP subtypes are expressed in vascular smooth muscle cells and endothelial cells, where they form diverse non-selective cation channels permeable to Ca2 +.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 158, "end": 163}]}}, "schema": []}
{"input": "These channels mediate Ca2 + entry following receptor stimulation, Ca2 + store depletion and mechanical stimulation of vascular myocytes and endothelial cells.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 23, "end": 28}, {"text": "Ca2 +", "start": 67, "end": 72}]}}, "schema": []}
{"input": "The complex molecular composition and signalling pathways leading to the activation of various vascular TRP channels and the growing evidence for their involvement in various vascular disorders, including dysregulation of vascular tone and hypertension, impaired endothelium-dependent vasodilatation, increased endothelial permeability, occlusive vascular disease, vascular injury and oxidative stress, are summarised and discussed in this review.", "output": {"entities": {}}, "schema": []}
{"input": "Oncogenic and anti-oncogenic effects of transient receptor potential channels.", "output": {"entities": {}}, "schema": []}
{"input": "Transient Receptor Potential (TRP) channels affect several inflammatory and neoplastic conditions.", "output": {"entities": {}}, "schema": []}
{"input": "About thirty TRPs have been identified to date and divided into seven families: TRPC (Canonical), TRPV (Vanilloid), TRPM (Melastatin), TRPML (Mucolipin), TRPP (Polycystin), and TRPA (Ankyrin transmembrane protein) and TRPN (NomPClike).", "output": {"entities": {"chemical": [{"text": "Vanilloid", "start": 104, "end": 113}]}}, "schema": []}
{"input": "Among these, the TRPC, TRPM, and TRPV families have been mainly correlated with malignant growth and progression.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this review is to summarize data reported so far on the expression and functional role of TRP channels in different types of cancers.", "output": {"entities": {}}, "schema": []}
{"input": "TRP channels have been recently implicated in the triggering of enhanced proliferation, aberrant differentiation, and resistance to apoptotic cell death, leading to uncontrolled tumor growth and progression.", "output": {"entities": {}}, "schema": []}
{"input": "Depending on cancer stage, up and down-regulation of TRP mRNAs and protein expression have been reported.", "output": {"entities": {}}, "schema": []}
{"input": "These changes have been shown to exhibit cancer promoting (oncogenic) or inhibiting/delaying (tumor suppressor) effects.", "output": {"entities": {}}, "schema": []}
{"input": "We are only at the beginning, and more detailed study on the physiopathologic role of TRP channels is required to understand how the deregulation of TRP channel expression and function contributes to tumor development and progression.", "output": {"entities": {}}, "schema": []}
{"input": "It is hoped that greater knowledge about TRP biology will enable future development of new chemotherapeutic agents for specific TRP targets, and the use of TRP channels as evaluable markers in diagnostic and/or prognostic analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple Roles of Transient Receptor Potential (TRP) Channels in Inflammatory Conditions and Current Status of Drug Development.", "output": {"entities": {}}, "schema": []}
{"input": "During inflammation, several Transient Receptor Potential (TRP) channels are directly or indirectly activated by inflammatory signaling molecules and microenvironmental changes including heat, oxidative conditions or low pH.", "output": {"entities": {}}, "schema": []}
{"input": "In either case, specific TRP isoforms participate in chains of pro-or anti-inflammatory signaling cascades often including activation of transcription factors, protein kinases and phospholipases, which result in signal integration or amplification.", "output": {"entities": {}}, "schema": []}
{"input": "In a few cases, their potentials as therapeutic targets for inflammatory conditions like pruritis, cystitis, dermatitis, asthma among other conditions are investigated pre-clinically or clinically by pioneering academic groups and industries.", "output": {"entities": {}}, "schema": []}
{"input": "Significant efforts are still devoted to the understanding of the detailed physiological roles played by TRP channels during inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "This review intends to summarize key biological findings and reports of drug discovery activities when available, in an overview of the current status and recent developments in the field.", "output": {"entities": {}}, "schema": []}
{"input": "Correlation between structural, spectroscopic, and reactivity properties within a series of structurally analogous metastable manganese (III)-alkylperoxo complexes.", "output": {"entities": {"chemical": [{"text": "manganese (III)-alkylperoxo complexes", "start": 126, "end": 163}]}}, "schema": []}
{"input": "Manganese-peroxos are proposed as key intermediates in a number of important biochemical and synthetic transformations.", "output": {"entities": {"chemical": [{"text": "Manganese-peroxos", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Our understanding of the structural, spectroscopic, and reactivity properties of these metastable species is limited, however, and correlations between these properties have yet to be established experimentally.", "output": {"entities": {}}, "schema": []}
{"input": "Herein we report the crystallographic structures of a series of structurally related metastable Mn (III)-OOR compounds, and examine their spectroscopic and reactivity properties.", "output": {"entities": {"chemical": [{"text": "Mn (III)-OOR", "start": 96, "end": 108}]}}, "schema": []}
{"input": "The four reported Mn (III)-OOR compounds extend the number of known end-on Mn (III)-(eta (1)-peroxos) to six.", "output": {"entities": {"chemical": [{"text": "Mn (III)-OOR", "start": 18, "end": 30}, {"text": "Mn (III)-(eta (1)-peroxos)", "start": 75, "end": 101}]}}, "schema": []}
{"input": "The ligand backbone is shown to alter the metal-ligand distances and modulate the electronic properties key to bonding and activation of the peroxo.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism of thermal decay of these metastable species is examined via variable-temperature kinetics.", "output": {"entities": {}}, "schema": []}
{"input": "Strong correlations between structural (O-O and Mn... N (py, quin) distances), spectroscopic (E (pi v * (O-O) --> Mn CT band), nu (O-O)), and kinetic (Delta H (++) and Delta S (++)) parameters for these complexes provide compelling evidence for rate-limiting O-O bond cleavage.", "output": {"entities": {"chemical": [{"text": "O-O", "start": 40, "end": 43}, {"text": "Mn", "start": 48, "end": 50}, {"text": "N (py, quin)", "start": 54, "end": 66}, {"text": "O-O", "start": 105, "end": 108}, {"text": "Mn", "start": 114, "end": 116}, {"text": "O-O", "start": 131, "end": 134}, {"text": "O-O", "start": 259, "end": 262}]}}, "schema": []}
{"input": "Products identified in the final reaction mixtures of Mn (III)-OOR decay are consistent with homolytic O-O bond scission.", "output": {"entities": {"chemical": [{"text": "Mn (III)-OOR", "start": 54, "end": 66}, {"text": "O-O", "start": 103, "end": 106}]}}, "schema": []}
{"input": "The N-heterocyclic amines and ligand backbone (Et vs Pr) are found to modulate structural and reactivity properties, and O-O bond activation is shown, both experimentally and theoretically, to track with metal ion Lewis acidity.", "output": {"entities": {"chemical": [{"text": "N-heterocyclic amines", "start": 4, "end": 25}, {"text": "O-O", "start": 121, "end": 124}]}}, "schema": []}
{"input": "The peroxo O-O bond is shown to gradually become more activated as the N-heterocyclic amines move closer to the metal ion causing a decrease in pi-donation from the peroxo pi v * (O-O) orbital.", "output": {"entities": {"chemical": [{"text": "peroxo O-O", "start": 4, "end": 14}, {"text": "N-heterocyclic amines", "start": 71, "end": 92}, {"text": "O-O", "start": 180, "end": 183}]}}, "schema": []}
{"input": "The reported work represents one of very few examples of experimentally verified relationships between structure and function.", "output": {"entities": {}}, "schema": []}
{"input": "Phase discrimination through oxidant selection in low-temperature atomic layer deposition of crystalline iron oxides.", "output": {"entities": {"chemical": [{"text": "iron oxides", "start": 105, "end": 116}]}}, "schema": []}
{"input": "Control over the oxidation state and crystalline phase of thin-film iron oxides was achieved by low-temperature atomic layer deposition (ALD), utilizing a novel iron precursor, bis (2, 4-methylpentadienyl) iron.", "output": {"entities": {"chemical": [{"text": "iron oxides", "start": 68, "end": 79}, {"text": "iron", "start": 161, "end": 165}, {"text": "bis (2, 4-methylpentadienyl) iron", "start": 177, "end": 210}]}}, "schema": []}
{"input": "This low-temperature (T = 120 degrees C) route to conformal deposition of crystalline Fe3O4 or alpha-Fe2O3 thin films is determined by the choice of oxygen source selected for the second surface half-reaction.", "output": {"entities": {"chemical": [{"text": "Fe3O4", "start": 86, "end": 91}, {"text": "alpha-Fe2O3", "start": 95, "end": 106}, {"text": "oxygen", "start": 149, "end": 155}]}}, "schema": []}
{"input": "The approach employs ozone to produce fully oxidized alpha-Fe2O3 or a milder oxidant, H2O2, to generate the Fe (2 +)/Fe (3 +) spinel, Fe3O4.", "output": {"entities": {"chemical": [{"text": "alpha-Fe2O3", "start": 53, "end": 64}, {"text": "H2O2", "start": 86, "end": 90}, {"text": "Fe (2 +)", "start": 108, "end": 116}, {"text": "Fe (3 +)", "start": 117, "end": 125}, {"text": "Fe3O4", "start": 134, "end": 139}]}}, "schema": []}
{"input": "Both processes show self-limiting surface reactions and deposition rates of at least 0. 6 A/cycle, a significantly high growth rate at such mild conditions.", "output": {"entities": {}}, "schema": []}
{"input": "We utilized this process to prepare conformal iron oxide thin films on a porous framework, for which alpha-Fe2O3 is active for photocatalytic water splitting.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 46, "end": 56}, {"text": "alpha-Fe2O3", "start": 101, "end": 112}]}}, "schema": []}
{"input": "Studies on an (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid (AMPA) receptor antagonist IKM-159: asymmetric synthesis, neuroactivity, and structural characterization.", "output": {"entities": {"chemical": [{"text": "(S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid", "start": 14, "end": 76}, {"text": "AMPA", "start": 78, "end": 82}, {"text": "IKM-159", "start": 104, "end": 111}]}}, "schema": []}
{"input": "IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as AMPA receptor-selective antagonists.", "output": {"entities": {"chemical": [{"text": "IKM-159", "start": 0, "end": 7}, {"text": "glutamate", "start": 83, "end": 92}, {"text": "AMPA", "start": 115, "end": 119}]}}, "schema": []}
{"input": "However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities.", "output": {"entities": {"chemical": [{"text": "IKM-159", "start": 46, "end": 53}]}}, "schema": []}
{"input": "Here, we report in vivo and in vitro neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis.", "output": {"entities": {"chemical": [{"text": "IKM-159", "start": 80, "end": 87}]}}, "schema": []}
{"input": "By employment of (R)-2-amino-2-(4-methoxyphenyl) ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0. 70% and 1. 5% yields, respectively, over a total of 18 steps.", "output": {"entities": {"chemical": [{"text": "(R)-2-amino-2-(4-methoxyphenyl) ethanol", "start": 17, "end": 56}, {"text": "(2R)-IKM-159", "start": 80, "end": 92}]}}, "schema": []}
{"input": "Both behavioral and electrophysiological assays showed that the biological activity observed for the racemic mixture was reproduced only with (2R)-IKM-159, whereas the (2S)-counterpart was inactive in both assays.", "output": {"entities": {"chemical": [{"text": "(2R)-IKM-159", "start": 142, "end": 154}]}}, "schema": []}
{"input": "Racemic IKM-159 was crystallized with the ligand-binding domain of GluA2, and the structure revealed a complex containing (2R)-IKM-159 at the glutamate binding site.", "output": {"entities": {"chemical": [{"text": "Racemic IKM-159", "start": 0, "end": 15}, {"text": "(2R)-IKM-159", "start": 122, "end": 134}]}}, "schema": []}
{"input": "(2R)-IKM-159 locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors.", "output": {"entities": {"chemical": [{"text": "(2R)-IKM-159", "start": 0, "end": 12}]}}, "schema": []}
{"input": "A new guaianolide from Artemisia roxburghiana.", "output": {"entities": {"chemical": [{"text": "guaianolide", "start": 6, "end": 17}]}}, "schema": []}
{"input": "A new member of 5 alpha H, 6 beta H, 7 alpha H, 11 alpha H-guaian-12, 6 alpha-olides, 11-epi-8 alpha-hydroxyarborescin, together with a mixture of (24R)-and (24S)-cycloart-25-en-3b, 24-diols, palmitic acid and 1-octacosanol were isolated from the leaves of Artemisia roxburghiana Bess.", "output": {"entities": {"chemical": [{"text": "5 alpha H, 6 beta H, 7 alpha H, 11 alpha H-guaian-12, 6 alpha-olides", "start": 16, "end": 84}, {"text": "11-epi-8 alpha-hydroxyarborescin", "start": 86, "end": 118}, {"text": "(24R)-and (24S)-cycloart-25-en-3b, 24-diols", "start": 147, "end": 190}, {"text": "palmitic acid", "start": 192, "end": 205}, {"text": "1-octacosanol", "start": 210, "end": 223}]}}, "schema": []}
{"input": "(Asteraceae) of Vietnam.", "output": {"entities": {}}, "schema": []}
{"input": "Their structures were determined on the basis of spectroscopic methods.", "output": {"entities": {}}, "schema": []}
{"input": "Challenges in exploring the cytochrome P450 system as a source of variation in canine drug pharmacokinetics.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract The cytochrome P450 (CYP) superfamily constitutes a collection of enzymes responsible for the metabolism of a wide array of endo-and xenobiotic compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Much of the knowledge on substrate specificity and genetic identification of the various CYP isoforms is derived from research in rodents and humans and only limited information has been captured in the dog.", "output": {"entities": {}}, "schema": []}
{"input": "Currently, there exist many gaps in our knowledge of canine CYP diversity as a result of the paucity of studies focusing on canine CYPs, canine CYP polymorphisms, and the therapeutic consequences of these genetic variants.", "output": {"entities": {}}, "schema": []}
{"input": "Challenges engendered by this lack of information is further amplified by inter-and intraspecies differences in the specificity and affinity of substrates and inhibitors, prohibiting a simple extrapolation of probe substances used in human CYP research.", "output": {"entities": {}}, "schema": []}
{"input": "This creates a need to develop and validate canine-specific CYP probes.", "output": {"entities": {}}, "schema": []}
{"input": "Failure to understand this potential metabolic and pharmacogenomic diversity can also influence the interpretation of data generated in dogs to support human drug development.", "output": {"entities": {}}, "schema": []}
{"input": "It is with these objectives in mind that we provide an overview of what is currently known about canine CYPs with the hope that it will encourage further exploration into this important area of research.", "output": {"entities": {}}, "schema": []}
{"input": "Nanobiocomposite adhesion: role of graft length and temperature in a hybrid biomimetic approach.", "output": {"entities": {}}, "schema": []}
{"input": "Cellulose microspheres bearing poly (epsilon-caprolactone) grafts of different molecular weights were investigated to evaluate the effect of graft length on the interfacial properties.", "output": {"entities": {"chemical": [{"text": "poly (epsilon-caprolactone)", "start": 31, "end": 58}]}}, "schema": []}
{"input": "Surface force and friction measurements were performed using an atomic force microscope in colloidal probe mode.", "output": {"entities": {}}, "schema": []}
{"input": "The maximum interaction distance and adhesion is dependent on the temperature and the time in contact via a diffusion controlled mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "The effects are highest for the longer grafts, and molecular weight thresholds were found to lie between 21 and 34 kDa at 25 degrees C and between 9 and 21 kDa at 40 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "The interpenetration of the graft into a matrix leads to \" hidden length \" contributions to adhesion, analogous to those in natural biocomposites.", "output": {"entities": {}}, "schema": []}
{"input": "The nanotribology results display Amontonian behavior, and the friction force at zero applied load is higher at the graft-graft interface than for a bare cellulose sphere interacting with the graft.", "output": {"entities": {}}, "schema": []}
{"input": "These results clearly demonstrate the benefits of the grafted polymer layer on the adhesion, toughness, and resistance to shear in the design of cellulosic nanobiocomposites.", "output": {"entities": {}}, "schema": []}
{"input": "SNAIL Induces Epithelial-to-Mesenchymal Transition and Cancer Stem Cell-like Properties in Aldehyde Dehydroghenase-Negative Thyroid Cancer Cells.", "output": {"entities": {"chemical": [{"text": "Aldehyde", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Background: Epithelial-to-mesenchymal transition (EMT) has been thought to play a critical role in invasion and metastasis of cancer and to be associated with cancer stem cell (CSC) properties.", "output": {"entities": {}}, "schema": []}
{"input": "It is not clear if there is a link between EMT and CSCs in thyroid cancers.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore investigated CSC properties of thyroid cancers that underwent EMT.", "output": {"entities": {}}, "schema": []}
{"input": "Method: To induce EMT (spindle-like cell morphology, loss and acquisition of expression of an epithelial marker E-cadherin and a mesenchymal marker vimentin, respectively) in an epithelial type thyroid cancer cell line ACT-1, we used transforming growth factor-beta (TGF-beta), BRAFV600E and/or Snail homolog 1 (SNAI1, also known as SNAIL).", "output": {"entities": {}}, "schema": []}
{"input": "CSC properties were analyzed with assays for cell proliferation, chemosensitivity, in vitro and in vivo tumor formation ability, cell surface antigens and intracellular aldehyde dehydrogenase (ALDH; a known CSC marker) activities.", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 169, "end": 177}]}}, "schema": []}
{"input": "Results: EMT was induced most efficiently by SNAIL (ACT-SNAIL cells), whereas TGF-beta and BRAFV600E were less efficient.", "output": {"entities": {}}, "schema": []}
{"input": "ACT-SNAIL cells showed slightly but significantly enhanced tumor formation ability in in vitro sphere assay (~ 3 fold) but not in vivo subcutaneous tumor growth assay, and showed comparable chemosensitivity, as compared to the parental ACT-1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "However, of interest, although in vitro sphere formation ability of ALDH + cells was almost unchanged after SNAIL induction, SNAIL overexpression induced much higher (~ 14 fold) spheres in ALDH-cells.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, ALDH was no longer a CSC marker in ACT-SNAIL cells.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: All these data indicate that EMT confers CSC properties in ALDH-cells and appears to influence the ability of ALDH to enrich CSCs.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolic Activation of Polycyclic Aromatic Hydrocarbons and Aryl and Heterocyclic Amines by Human Cytochromes P450 2A13 and 2A6.", "output": {"entities": {"chemical": [{"text": "Polycyclic Aromatic Hydrocarbons", "start": 24, "end": 56}, {"text": "Aryl and Heterocyclic Amines", "start": 61, "end": 89}]}}, "schema": []}
{"input": "Human cytochrome P450 (P450) 2A13 was found to interact with several polycyclic aromatic hydrocarbons (PAHs) to produce Type I binding spectra, including acenaphthene, acenaphthylene, benzo [c] phenanthrene, fluoranthene, fluoranthene-2, 3-diol, and 1-nitropyrene.", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbons", "start": 69, "end": 101}, {"text": "PAHs", "start": 103, "end": 107}, {"text": "acenaphthene", "start": 154, "end": 166}, {"text": "acenaphthylene", "start": 168, "end": 182}, {"text": "benzo [c] phenanthrene", "start": 184, "end": 206}, {"text": "fluoranthene", "start": 208, "end": 220}, {"text": "fluoranthene-2, 3-diol", "start": 222, "end": 244}, {"text": "1-nitropyrene", "start": 250, "end": 263}]}}, "schema": []}
{"input": "P450 2A6 also interacted with acenaphthene and acenaphthylene, but not with fluoranthene, fluoranthene-2, 3-diol, or 1-nitropyrene.", "output": {"entities": {"chemical": [{"text": "acenaphthene", "start": 30, "end": 42}, {"text": "acenaphthylene", "start": 47, "end": 61}, {"text": "fluoranthene", "start": 76, "end": 88}, {"text": "fluoranthene-2, 3-diol", "start": 90, "end": 112}, {"text": "1-nitropyrene", "start": 117, "end": 130}]}}, "schema": []}
{"input": "P450 1B1 is well-known to oxidize many carcinogenic PAHs, and we found that several PAHs (i. e., 7, 12-dimethylbenz [a] anthracene, 7, 12-dimethylbenz [a] anthracene-5, 6-diol, benzo [c] phenanthrene, fluoranthene, fluoranthene-2, 3-diol, 5-methylchrysene, benz [a] pyrene-4, 5-diol, benzo [a] pyrene-7, 8-diol, 1-nitropyrene, 2-aminoanthracene, 2-aminofluorene, and 2-acetylaminofluorene) interacted with P450 1B1, producing Reverse Type I binding spectra.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 52, "end": 56}, {"text": "PAHs", "start": 84, "end": 88}, {"text": "7, 12-dimethylbenz [a] anthracene", "start": 97, "end": 130}, {"text": "7, 12-dimethylbenz [a] anthracene-5, 6-diol", "start": 132, "end": 175}, {"text": "benzo [c] phenanthrene", "start": 177, "end": 199}, {"text": "fluoranthene", "start": 201, "end": 213}, {"text": "fluoranthene-2, 3-diol", "start": 215, "end": 237}, {"text": "5-methylchrysene", "start": 239, "end": 255}, {"text": "benz [a] pyrene-4, 5-diol", "start": 257, "end": 282}, {"text": "benzo [a] pyrene-7, 8-diol", "start": 284, "end": 310}, {"text": "1-nitropyrene", "start": 312, "end": 325}, {"text": "2-aminoanthracene", "start": 327, "end": 344}, {"text": "2-aminofluorene", "start": 346, "end": 361}, {"text": "2-acetylaminofluorene", "start": 367, "end": 388}]}}, "schema": []}
{"input": "Metabolic activation of PAHs and aryl-and heterocyclic amines to genotoxic products was examined in Salmonella typhimurium NM2009, and we found that P450 2A13 and 2A6 (as well as P450 1B1) were able to activate several of these procarcinogens.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 24, "end": 28}, {"text": "aryl-and heterocyclic amines", "start": 33, "end": 61}]}}, "schema": []}
{"input": "The former two enzymes were particularly active in catalyzing 2-aminofluorene and 2-aminoanthracene activation, and molecular docking simulations supported the results with these procarcinogens, in terms of binding in the active sites of P450 2A13 and 2A6.", "output": {"entities": {"chemical": [{"text": "2-aminofluorene", "start": 62, "end": 77}, {"text": "2-aminoanthracene", "start": 82, "end": 99}]}}, "schema": []}
{"input": "These results suggest that P450 2A enzymes, as well as P450 Family 1 enzymes including P450 1B1, are major enzymes involved in activating PAHs and aryl-and heterocyclic amines, as well as tobacco-related nitrosamines.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 138, "end": 142}, {"text": "aryl-and heterocyclic amines", "start": 147, "end": 175}, {"text": "nitrosamines", "start": 204, "end": 216}]}}, "schema": []}
{"input": "Immunomodulatory properties of farnesoids: the new steroids?", "output": {"entities": {"chemical": [{"text": "farnesoids", "start": 31, "end": 41}, {"text": "steroids", "start": 51, "end": 59}]}}, "schema": []}
{"input": "Farnesylthiosalisylic acid (FTS) is a potent non-toxic anticancer drug that targets oncogenic and pathologically activated Ras.", "output": {"entities": {"chemical": [{"text": "Farnesylthiosalisylic acid", "start": 0, "end": 26}, {"text": "FTS", "start": 28, "end": 31}]}}, "schema": []}
{"input": "The mechanism of action of FTS is well understood.", "output": {"entities": {"chemical": [{"text": "FTS", "start": 27, "end": 30}]}}, "schema": []}
{"input": "It interferes with the binding of activated Ras proteins to their escort chaperons and with Ras tethering to the plasma membrane.", "output": {"entities": {}}, "schema": []}
{"input": "This agent has been evaluated successfully in phase II clinical trials of pancreatic and lung cancer patients.", "output": {"entities": {}}, "schema": []}
{"input": "It is generally agreed that Ras proteins play an important role in cancer, but they also drive activation of the immune system.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore we hypothesized that inhibiting Ras might be beneficial in autoimmune and inflammatory conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Over the past decade we have extensively studied the effects of FTS in multiple animal models of such diseases.", "output": {"entities": {"chemical": [{"text": "FTS", "start": 64, "end": 67}]}}, "schema": []}
{"input": "We were able to show potent anti-inflammatory properties of FTS in autoimmune disease models such as systemic lupus erythematous, antiphospholipd syndrome, Guillain-Barr e syndrome, multiple sclerosis, and inflammatory bowel diseases.", "output": {"entities": {"chemical": [{"text": "FTS", "start": 60, "end": 63}]}}, "schema": []}
{"input": "Its potential was also shown in type I and type II diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Animal models of contact dermatitis, allergic inflammation, and proliferative nephritis were studied as well.", "output": {"entities": {}}, "schema": []}
{"input": "We have also investigated the molecular mechanisms, signaling pathways, and inflammatory mediators underlying these conditions.", "output": {"entities": {}}, "schema": []}
{"input": "In this review we summarize our (and others) published data, and conclude that FTS has great potential as a safe anti-inflammatory drug.", "output": {"entities": {"chemical": [{"text": "FTS", "start": 79, "end": 82}]}}, "schema": []}
{"input": "Recent advances in carbon nanotubes as delivery systems for anticancer drugs.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 19, "end": 25}]}}, "schema": []}
{"input": "Problems associated with the administration of anticancer drugs, such as limited solubility, poor biodistribution, lack of selectivity, and healthy tissue damage, can be overcome by the implementation of drug delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "A wide range of materials, including liposomes, microspheres, polymers and recently, carbon nanotubes (CNTs), have been investigated for delivering anticancer drugs on the purpose of reducing the number of necessary administrations, providing more localized and better use of the active agents, and increasing patient compliance.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 85, "end": 91}]}}, "schema": []}
{"input": "Carbon nanotubes (CNTs) have attracted particular attention as carriers of biologically relevant molecules due to their unique physical, chemical and physiological properties.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}]}}, "schema": []}
{"input": "The exact relationship between the physical-chemical properties of carbon nanotubes, their cell to-cell interactions, reactivity, and biological/systemic consequences are relevant issues and it is important to know suchinter-relationships beforehand to employ the benefits of these nanomaterials without the hazardous consequences.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 67, "end": 73}]}}, "schema": []}
{"input": "The purpose of this review is to present highlight of recent developments in the application of carbon nanotubes as cargoes for anti cancer drugs and in the diagnosis of cancer diseases.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 96, "end": 102}]}}, "schema": []}
{"input": "Camptothecin Resistance in Cancer: Insights into the Molecular Mechanisms of a DNA-Damaging Drug.", "output": {"entities": {"chemical": [{"text": "Camptothecin", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Poisoning of DNA topoisomerase I is the mechanism by which camptothecins interfere with tumor growth.", "output": {"entities": {"chemical": [{"text": "camptothecins", "start": 59, "end": 72}]}}, "schema": []}
{"input": "Although the clinical use of camptothecins has had a significant impact on cancer therapy, de novo or acquired clinical resistance to these drugs is common.", "output": {"entities": {"chemical": [{"text": "camptothecins", "start": 29, "end": 42}]}}, "schema": []}
{"input": "Clinical resistance to camptothecins is still a poorly understood phenomenon, likely involving pharmacological and tumor-related factors.", "output": {"entities": {"chemical": [{"text": "camptothecins", "start": 23, "end": 36}]}}, "schema": []}
{"input": "Experimental models including yeast and mammalian cell cultures suggest three general mechanisms of camptothecin resistance: i) reduced cellular accumulation of drugs, ii) alteration in the structure/expression of topoisomerase I, and iii) alterations in the cellular response to camptothecin-DNA-ternary complex formation.", "output": {"entities": {"chemical": [{"text": "camptothecin", "start": 100, "end": 112}, {"text": "camptothecin", "start": 280, "end": 292}]}}, "schema": []}
{"input": "Some lines of evidence have also suggested links between cellular camptothecin resistance, the existence of a subset of tumor-initiating cells and miRNA deregulation.", "output": {"entities": {"chemical": [{"text": "camptothecin", "start": 66, "end": 78}]}}, "schema": []}
{"input": "In this regard, a better definition of the molecular events clarifying the regulation of tumorigenesis and gene expression might contribute to gain insight into the molecular mechanisms on the basis of camptothecin resistance of tumors and to identify new molecular tools for targeting cancer cells.", "output": {"entities": {"chemical": [{"text": "camptothecin", "start": 202, "end": 214}]}}, "schema": []}
{"input": "The relevance of these mechanisms to clinical drug resistance has not yet been completely defined, but their evaluation in clinical specimens should help to define personalized treatments including camptothecins as single agents or in combination with other cytotoxic and target-specific anticancer agents.", "output": {"entities": {"chemical": [{"text": "camptothecins", "start": 198, "end": 211}]}}, "schema": []}
{"input": "The present review focuses on the cellular/molecular aspects involved in resistance of tumor cells to camptothecins, including the potential role of cancer stem cells and deregulated miRNAs, and on the approaches proposed for overcoming resistance.", "output": {"entities": {"chemical": [{"text": "camptothecins", "start": 102, "end": 115}]}}, "schema": []}
{"input": "Discovery of a Novel Selective PPAR gamma Ligand with Partial Agonist Binding Properties by Integrated in Silico/in Vitro Work Flow.", "output": {"entities": {}}, "schema": []}
{"input": "Full agonists to the peroxisome proliferator-activated receptor (PPAR) gamma, such as Rosiglitazone, have been associated with a series of undesired side effects, such as weight gain, fluid retention, cardiac hypertrophy, and hepatotoxicity.", "output": {"entities": {"chemical": [{"text": "Rosiglitazone", "start": 86, "end": 99}]}}, "schema": []}
{"input": "Nevertheless, PPAR gamma is involved in the expression of genes that control glucose and lipid metabolism and is an important target for drugs against type 2 diabetes, dyslipidemia, atherosclerosis, and cardiovascular disease.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 77, "end": 84}]}}, "schema": []}
{"input": "In an effort to identify novel PPAR gamma ligands with an improved pharmacological profile, emphasis has shifted to selective ligands with partial agonist binding properties.", "output": {"entities": {}}, "schema": []}
{"input": "Toward this end we applied an integrated in silico/in vitro workflow, based on pharmacophore-and structure-based virtual screening of the ZINC library, coupled with competitive binding and transactivation assays, and adipocyte differentiation and gene expression studies.", "output": {"entities": {}}, "schema": []}
{"input": "Hit compound 9 was identified as the most potent ligand (IC50 = 0. 3 mu M) and a relatively poor inducer of adipocyte differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "The binding mode of compound 9 was confirmed by molecular dynamics simulation, and the calculated free energy of binding was-8. 4 kcal/mol.", "output": {"entities": {}}, "schema": []}
{"input": "A novel functional group, the carbonitrile group, was identified to be a key substituent in the ligand-protein interactions.", "output": {"entities": {"chemical": [{"text": "carbonitrile", "start": 30, "end": 42}]}}, "schema": []}
{"input": "Further studies on the transcriptional regulation properties of compound 9 revealed a gene regulatory profile that was to a large extent unique, however functionally closer to that of a partial agonist.", "output": {"entities": {}}, "schema": []}
{"input": "Comprehensive insights into the structural and chemical changes in mixed-anion FeOF electrodes by using operando PDF and NMR spectroscopy.", "output": {"entities": {"chemical": [{"text": "FeOF", "start": 79, "end": 83}]}}, "schema": []}
{"input": "In-depth analysis of operando X-ray pair distribution function (PDF) data is combined with Li NMR spectroscopy to gain comprehensive insights into the electrochemical reaction mechanism of high-performance iron oxyfluoride electrodes.", "output": {"entities": {"chemical": [{"text": "Li", "start": 91, "end": 93}, {"text": "iron oxyfluoride", "start": 206, "end": 222}]}}, "schema": []}
{"input": "While the full discharge capacity could be recovered upon charge, implying reversibility of the electrochemical reaction, the atomic structure of the electrode formed after cycling (discharge-charge) differs from the pristine uncycled electrode material.", "output": {"entities": {}}, "schema": []}
{"input": "Instead, the \" active \" electrode that forms upon cycling is a nanocomposite of an amorphous rutile phase and a nanoscale rock salt phase.", "output": {"entities": {}}, "schema": []}
{"input": "Bond valence sum analysis, based on the precise structural parameters (bond lengths and coordination number) extracted from the in situ PDF data, suggests that anion partitioning occurs during the electrochemical reaction, with the rutile phase being F-rich and the rock salt phase being O-rich.", "output": {"entities": {"chemical": [{"text": "O", "start": 288, "end": 289}]}}, "schema": []}
{"input": "The F-and O-rich phases react sequentially; Fe in a F-rich environment reacts preferentially during both discharge and charge.", "output": {"entities": {"chemical": [{"text": "F", "start": 4, "end": 5}, {"text": "O", "start": 10, "end": 11}, {"text": "Fe", "start": 44, "end": 46}, {"text": "F", "start": 52, "end": 53}]}}, "schema": []}
{"input": "Design, synthesis and SAR of novel glucokinase activators.", "output": {"entities": {}}, "schema": []}
{"input": "Guided by co-crystal structures of compounds 15, 22 and 30, an SBDD approach led to the discovery of the 6-methyl pyridone series as a novel class of GKAs that potently activate GK in enzyme and cell assays.", "output": {"entities": {"chemical": [{"text": "6-methyl pyridone", "start": 105, "end": 122}]}}, "schema": []}
{"input": "Anti-diabetic OGTT efficacy was demonstrated with 54 in a mouse model of type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "The role of omega-3 derived resolvins in arthritis.", "output": {"entities": {"chemical": [{"text": "resolvins", "start": 28, "end": 37}]}}, "schema": []}
{"input": "Omega-3 polyunsaturated fatty acids (PUFAs) are known to alleviate joint stiffness and pain in rheumatoid arthritis patients.", "output": {"entities": {"chemical": [{"text": "Omega-3 polyunsaturated fatty acids", "start": 0, "end": 35}, {"text": "PUFAs", "start": 37, "end": 42}]}}, "schema": []}
{"input": "However, the mechanisms by which omega-3s exert their beneficial effects has not been fully explored.", "output": {"entities": {}}, "schema": []}
{"input": "Herein we discuss a novel class of bioactive lipid mediators, which are enzymatically biosynthesized in vivo from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), termed resolvins.", "output": {"entities": {"chemical": [{"text": "omega-3 eicosapentaenoic acid", "start": 114, "end": 143}, {"text": "EPA", "start": 145, "end": 148}, {"text": "docosahexaenoic acid", "start": 154, "end": 174}, {"text": "DHA", "start": 176, "end": 179}, {"text": "resolvins", "start": 189, "end": 198}]}}, "schema": []}
{"input": "These lipid mediators exert anti-inflammatory and pro-resolving properties and are log-orders more potent than their precursors.", "output": {"entities": {}}, "schema": []}
{"input": "We also highlight that formation of pro-resolving mediators can be enhanced by widely used anti-inflammatory and cardioprotective drugs (aspirin and statins) via the modification of cyclooxygenase-2 enzymatic activity.", "output": {"entities": {"chemical": [{"text": "aspirin", "start": 137, "end": 144}]}}, "schema": []}
{"input": "These bioactive pro-resolving lipid mediators provide further rationale for the beneficial effects of dietary supplementation with fish oils, and offer new avenues for developing therapeutics for inflammatory conditions such as rheumatoid arthritis.", "output": {"entities": {}}, "schema": []}
{"input": "A one-pot domino synthesis and discovery of highly functionalized dihydrobenzo [b] thiophenes as AChE inhibitors.", "output": {"entities": {"chemical": [{"text": "dihydrobenzo [b] thiophenes", "start": 66, "end": 93}]}}, "schema": []}
{"input": "A library of novel 5-amino-2, 7-diaryl-2, 3-dihydrobenzo [b] thiophene-4, 6-dicarbonitriles have been synthesized regioselectively in good yields through the one-pot domino reactions of 5-aryldihydro-3 (2H)-thiophenones, malononitrile and aromatic aldehydes in the presence of morpholine.", "output": {"entities": {"chemical": [{"text": "5-amino-2, 7-diaryl-2, 3-dihydrobenzo [b] thiophene-4, 6-dicarbonitriles", "start": 19, "end": 91}, {"text": "5-aryldihydro-3 (2H)-thiophenones", "start": 186, "end": 219}, {"text": "malononitrile", "start": 221, "end": 234}, {"text": "aromatic aldehydes", "start": 239, "end": 257}, {"text": "morpholine", "start": 277, "end": 287}]}}, "schema": []}
{"input": "This transformation presumably involves Knoevenagel condensation-Michael addition-intramolecular Thorpe-Ziegler cyclization-Tautomerization-Elimination sequence of reactions.", "output": {"entities": {}}, "schema": []}
{"input": "These compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity and 5-amino-2, 7-bis (4-methoxyphenyl)-2, 3-dihydrobenzo [b] thiophene-4, 6-dicarbonitrile was found to be the most potent against AChE with IC50 4. 16 mu mol/L.", "output": {"entities": {"chemical": [{"text": "5-amino-2, 7-bis (4-methoxyphenyl)-2, 3-dihydrobenzo [b] thiophene-4, 6-dicarbonitrile", "start": 93, "end": 179}]}}, "schema": []}
{"input": "Pyridine to aniline: an exceptional biologically driven rearrangement.", "output": {"entities": {"chemical": [{"text": "Pyridine", "start": 0, "end": 8}, {"text": "aniline", "start": 12, "end": 19}]}}, "schema": []}
{"input": "During the course of our study on the innovative ligand for nicotinic acetylcholinergic receptors, LNAChR, and in order to assess activity and toxicity profiles of the drug' s metabolites, synthesis of the main metabolites was undertaken.", "output": {"entities": {}}, "schema": []}
{"input": "This synthesis work was done in parallel by organic chemistry and by biotransformation of LNAChR.", "output": {"entities": {}}, "schema": []}
{"input": "Filamentous fungus Aspergillus alliaceus (NRRL 315) neatly afforded three of the main metabolites, one of which arose from a very unexpected and very uncommon rearrangement.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and cytotoxicity evaluation of oleanolic acid derivatives.", "output": {"entities": {"chemical": [{"text": "oleanolic acid", "start": 41, "end": 55}]}}, "schema": []}
{"input": "Twelve derivatives of oleanolic acid (1) have been synthesized and evaluated for their inhibitory activities against the growth of prostate PC3, breast MCF-7, lung A549, and gastric BGC-823 cancer cells by MTT assays.", "output": {"entities": {"chemical": [{"text": "oleanolic acid", "start": 22, "end": 36}, {"text": "MTT", "start": 206, "end": 209}]}}, "schema": []}
{"input": "Within these series of derivatives, compound 17 exhibited the most potent cytotoxicity against PC3 cell line (IC50 = 0. 39 mu M) and compound 28 displayed the best activity against A549 cell line (IC50 = 0. 22 mu M).", "output": {"entities": {}}, "schema": []}
{"input": "SAR analysis indicates that H-donor substitution at C-3 position of oleanolic acid may be advantageous for improvement of cytotoxicity against PC3, A549 and MCF-7 cell lines.", "output": {"entities": {"chemical": [{"text": "H", "start": 28, "end": 29}, {"text": "oleanolic acid", "start": 68, "end": 82}]}}, "schema": []}
{"input": "The MRN-CtIP pathway is required for metaphase chromosome alignment.", "output": {"entities": {}}, "schema": []}
{"input": "Faithful duplication of the genome in S phase followed by its accurate segregation in mitosis is essential to maintain genomic integrity.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies have suggested that proteins involved in DNA transactions are also required for whole-chromosome stability.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that the MRN (Mre11, Rad50, and Nbs1) complex and CtIP are required for accurate chromosome segregation.", "output": {"entities": {}}, "schema": []}
{"input": "Depletion of Mre11 or CtIP, antibody-mediated inhibition of Mre11, or small-molecule inhibition of MRN using mirin results in metaphase chromosome alignment defects in Xenopus egg extracts.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, loss of MRN function adversely affects spindle assembly around DNA-coated beads in egg extracts.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of MRN function in mammalian cells triggers a metaphase delay and disrupts the RCC1-dependent RanGTP gradient.", "output": {"entities": {}}, "schema": []}
{"input": "Addition of the Mre11 inhibitor mirin to egg extracts and mammalian cells reduces RCC1 association with mitotic chromosomes.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the MRN-CtIP pathway contributes to Ran-dependent mitotic spindle assembly by modulating RCC1 chromosome association.", "output": {"entities": {}}, "schema": []}
{"input": "2-(Benzothiazol-2-yl)-phenyl-beta-d-galactopyranoside derivatives as fluorescent pigment dyeing substrates and their application for the assay of beta-d-galactosidase activities.", "output": {"entities": {"chemical": [{"text": "2-(Benzothiazol-2-yl)-phenyl-beta-d-galactopyranoside", "start": 0, "end": 53}]}}, "schema": []}
{"input": "2-(Benzothiazol-2-yl)-phenyl-beta-d-galactopyranoside derivatives were synthesized as novel artificial fluorescent pigment dyeing substrates for beta-d-galactosidase.", "output": {"entities": {"chemical": [{"text": "2-(Benzothiazol-2-yl)-phenyl-beta-d-galactopyranoside", "start": 0, "end": 53}]}}, "schema": []}
{"input": "The substrates, which exhibited non-fluorescence or weak fluorescence in solution phase, were smoothly hydrolyzed by beta-d-galactosidase from Aspergillus oryzae and yielded a water-insoluble strong fluorescent pigment.", "output": {"entities": {}}, "schema": []}
{"input": "The difference of fluorescent intensity exhibited a linear relationship with the amount of enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Coenzyme Q10 protects Pc12 cells from cisplatin-induced DNA damage and neurotoxicity.", "output": {"entities": {"chemical": [{"text": "Coenzyme Q10", "start": 0, "end": 12}, {"text": "cisplatin", "start": 38, "end": 47}]}}, "schema": []}
{"input": "The purpose of this study was to investigate the neuroprotective effect of a water-soluble formulation of coenzyme Q10 (WS-CoQ10) in PC12 cells exposed to cisplatin, a chemotherapeutic agent with a dose-limiting factor due to neurotoxicity.", "output": {"entities": {"chemical": [{"text": "coenzyme Q10", "start": 106, "end": 118}, {"text": "CoQ10", "start": 123, "end": 128}, {"text": "cisplatin", "start": 155, "end": 164}]}}, "schema": []}
{"input": "In the cytokinesis-block micronucleus cytome assay (CBMN Cyt), WS-CoQ10 (at concentrations of 0. 1, 0. 5 and 1. 0 mu gmL (-1)) protected PC12 cells from cisplatin-induced DNA damage (0. 1 mu gmL (-1)), reducing the frequency of micronuclei (MNi) and nuclear buds (NBUDs).", "output": {"entities": {"chemical": [{"text": "CoQ10", "start": 66, "end": 71}, {"text": "cisplatin", "start": 153, "end": 162}]}}, "schema": []}
{"input": "WS-CoQ10 did not alter the mRNA expression levels of Tp53 (at a concentration of 1. 0 mu gmL (-1)) and exhibited neuroprotective activity by stimulating cisplatin-inhibited neurite outgrowth in nerve growth factor (NGF)-differentiated PC12 cells (at a concentration of 0. 1 mu gmL (-1)).", "output": {"entities": {"chemical": [{"text": "CoQ10", "start": 3, "end": 8}, {"text": "cisplatin", "start": 153, "end": 162}]}}, "schema": []}
{"input": "In conclusion, WS-CoQ10 protected the PC12 cells from cisplatin-induced DNA damage and neurotoxicity.", "output": {"entities": {"chemical": [{"text": "CoQ10", "start": 18, "end": 23}, {"text": "cisplatin", "start": 54, "end": 63}]}}, "schema": []}
{"input": "Moreover, the neuroprotective effects of WS-CoQ10 suggest a possible application in chemotherapeutic protocols.", "output": {"entities": {"chemical": [{"text": "CoQ10", "start": 44, "end": 49}]}}, "schema": []}
{"input": "Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application.", "output": {"entities": {"chemical": [{"text": "Timosaponin AIII", "start": 37, "end": 53}]}}, "schema": []}
{"input": "A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS).", "output": {"entities": {"chemical": [{"text": "timosaponin AIII", "start": 132, "end": 148}, {"text": "TA-III", "start": 150, "end": 156}, {"text": "ginsenoside Re", "start": 179, "end": 193}]}}, "schema": []}
{"input": "TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer.", "output": {"entities": {"chemical": [{"text": "TA-III", "start": 0, "end": 6}]}}, "schema": []}
{"input": "The calibration curves were linear over the concentration ranges from 11. 14 to 1114 ng/mL and the lower limit of quantification (LLOQ) was 11. 14 ng/mL.", "output": {"entities": {}}, "schema": []}
{"input": "Intra-day and inter-day precisions (RSD) were within 10%, and accuracy ranged from 6. 4% to 9. 1%.", "output": {"entities": {}}, "schema": []}
{"input": "The extraction recovery at three concentrations ranged from 92. 3% to 95. 5%.", "output": {"entities": {}}, "schema": []}
{"input": "The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration.", "output": {"entities": {"chemical": [{"text": "TA-III", "start": 79, "end": 85}]}}, "schema": []}
{"input": "The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III.", "output": {"entities": {"chemical": [{"text": "TA-III", "start": 172, "end": 178}]}}, "schema": []}
{"input": "International journal of molecular science best paper award 2013.", "output": {"entities": {}}, "schema": []}
{"input": "Since 2012, International Journal of Molecular Science has instituted an annual award to recognize outstanding papers in the area of chemistry, molecular physics and molecular biology that meet the aims, scope and high standards of this journal [1].", "output": {"entities": {}}, "schema": []}
{"input": "We are pleased to announce the second \" International Journal of Molecular Science Best Paper Award \" for 2013.", "output": {"entities": {}}, "schema": []}
{"input": "Nominations were made by the Section Editor-in-Chiefs of International Journal of Molecular Science, with all papers published in 2009 eligible for consideration.", "output": {"entities": {}}, "schema": []}
{"input": "The awards are issued for reviews and articles separately.", "output": {"entities": {}}, "schema": []}
{"input": "Upregulation of drug transporter expression by osteopontin in prostate cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Multidrug resistance is a major cause of chemotherapy failure.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies indicate that drug resistance can be rapidly induced by some soluble factors, such as cytokines, chemokines, growth factors, and cell adhesion factors in the tumor microenvironment.", "output": {"entities": {}}, "schema": []}
{"input": "Osteopontin (OPN), an extracellular matrix protein, has a functional arginine-glycine-aspartic acid (RGD) domain for binding to integrin.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 69, "end": 77}, {"text": "glycine", "start": 78, "end": 85}, {"text": "aspartic acid", "start": 86, "end": 99}]}}, "schema": []}
{"input": "Here we found OPN expression to be upregulated by hypoxic condition in PC-3 prostate tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "OPN increased the mRNA and protein expression of p-glycoprotein (P-gp), a subfamily of ATP-binding cassette transporter in a concentration-and time-dependent manner.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 87, "end": 90}]}}, "schema": []}
{"input": "The increase in P-gp transporter by OPN was mediated by binding to alpha v beta 3 integrin.", "output": {"entities": {}}, "schema": []}
{"input": "Daunomycin (DUN), a chemotherapeutic agent with autofluorescence, was used to evaluate the pump activity, and OPN increased the drug pumping-out activity.", "output": {"entities": {"chemical": [{"text": "Daunomycin", "start": 0, "end": 10}, {"text": "DUN", "start": 12, "end": 15}]}}, "schema": []}
{"input": "OPN inhibited DUN-induced cell death, which was antagonized by alpha v beta 3 monoclonal antibody.", "output": {"entities": {"chemical": [{"text": "DUN", "start": 14, "end": 17}]}}, "schema": []}
{"input": "Long-term treatment with DUN further enhanced the expression of OPN.", "output": {"entities": {"chemical": [{"text": "DUN", "start": 25, "end": 28}]}}, "schema": []}
{"input": "Knockdown of endogenous OPN potentiated the DUN-induced apoptosis of PC-3 cells.", "output": {"entities": {"chemical": [{"text": "DUN", "start": 44, "end": 47}]}}, "schema": []}
{"input": "Furthermore, knockdown of OPN enhanced cell death caused by other drugs, including paclitaxel, doxorubicin, actinomycin-D, and rapamycin, which are also P-gp substrates.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 83, "end": 93}, {"text": "doxorubicin", "start": 95, "end": 106}, {"text": "actinomycin-D", "start": 108, "end": 121}, {"text": "rapamycin", "start": 127, "end": 136}]}}, "schema": []}
{"input": "The animal studies also showed that OPN knockdown enhanced the cytotoxic action of DUN.", "output": {"entities": {"chemical": [{"text": "DUN", "start": 83, "end": 86}]}}, "schema": []}
{"input": "These results indicate that OPN is a potential therapeutic target for cancer therapy to reduce drug resistance in sensitive tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Asperolide A, a marine-derived tetranorditerpenoid, induces G2/M arrest in human NCI-H460 lung carcinoma cells, is mediated by p53-p21 stabilization and modulated by Ras/Raf/MEK/ERK signaling pathway.", "output": {"entities": {"chemical": [{"text": "Asperolide A", "start": 0, "end": 12}, {"text": "tetranorditerpenoid", "start": 31, "end": 50}]}}, "schema": []}
{"input": "Here we first demonstrate that asperolide A, a very recently reported marine-derived tetranorditerpenoid, leads to the inhibition of NCI-H460 lung carcinoma cell proliferation by G2/M arrest with the activation of the Ras/Raf/MEK/ERK signaling and p53-dependent p21 pathway.", "output": {"entities": {"chemical": [{"text": "asperolide A", "start": 31, "end": 43}, {"text": "tetranorditerpenoid", "start": 85, "end": 104}]}}, "schema": []}
{"input": "Treatment with 35 mu M asperolide A (2 x IC (50)) resulted in a significant increase in the proportion of G2/M phase cells, about a 2. 9-fold increase during 48 h.", "output": {"entities": {"chemical": [{"text": "asperolide A", "start": 23, "end": 35}]}}, "schema": []}
{"input": "Immunoblot assays demonstrated time-dependent inhibition of G2/M regulatory proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, asperolide A significantly activated MAP kinases (ERK1/2, JNK and p38 MAP kinase) by phosphorylation, and only the inhibition of ERK activation by PD98059 reversed downregulation of G2/M regulatory proteins CDC2, and suppressed upregulation of p21 and p-p53 levels.", "output": {"entities": {"chemical": [{"text": "asperolide A", "start": 10, "end": 22}, {"text": "PD98059", "start": 157, "end": 164}]}}, "schema": []}
{"input": "Transfection of cells with dominant-negative Ras (RasN17) mutant genes up-regulated asperolide A-induced the decrease of cyclin B1 and CDC2, suppressed Raf, ERK activity and p53-p21 expression, and at last, abolished G2/M arrest.", "output": {"entities": {"chemical": [{"text": "asperolide A", "start": 84, "end": 96}]}}, "schema": []}
{"input": "This study indicates that asperolide A-induced G2/M arrest in human NCI-H460 lung carcinoma cells relys on the participation of the Ras/Raf/MEK/ERK signaling pathway in p53-p21 stabilization.", "output": {"entities": {"chemical": [{"text": "asperolide A", "start": 26, "end": 38}]}}, "schema": []}
{"input": "An in vivo study with asperolide A illustrated a marked inhibition of tumor growth, and little toxcity compared to Cisplatin therapy.", "output": {"entities": {"chemical": [{"text": "asperolide A", "start": 22, "end": 34}, {"text": "Cisplatin", "start": 115, "end": 124}]}}, "schema": []}
{"input": "Overall, these findings provide potential effectiveness and a theoretical basis for the therapeutic use of asperolide A in the treatment of malignancies.", "output": {"entities": {"chemical": [{"text": "asperolide A", "start": 107, "end": 119}]}}, "schema": []}
{"input": "Construction of monophosphoryl lipid A producing Escherichia coli mutants and comparison of immuno-stimulatory activities of their lipopolysaccharides.", "output": {"entities": {"chemical": [{"text": "monophosphoryl lipid A", "start": 16, "end": 38}]}}, "schema": []}
{"input": "The lipid A moiety of Escherichia coli lipopolysaccharide is a hexaacylated disaccharide of glucosamine phosphorylated at the 1-and 4'-positions.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 4, "end": 11}, {"text": "hexaacylated disaccharide", "start": 63, "end": 88}, {"text": "glucosamine", "start": 92, "end": 103}]}}, "schema": []}
{"input": "It can be recognized by the TLR4/MD-2 complex of mammalian immune cells, leading to release of proinflammatory cytokines.", "output": {"entities": {}}, "schema": []}
{"input": "The toxicity of lipid A depends on its structure.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 16, "end": 23}]}}, "schema": []}
{"input": "In this study, two E. coli mutants, HW001 and HW002, were constructed by deleting or integrating key genes related to lipid A biosynthesis in the chromosome of E. coli W3110.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 118, "end": 125}]}}, "schema": []}
{"input": "HW001 was constructed by deleting lacI and replacing lacZ with the Francisella novicida lpxE gene in the chromosome and only synthesizes monophosphoryl lipid A.", "output": {"entities": {"chemical": [{"text": "monophosphoryl lipid A", "start": 137, "end": 159}]}}, "schema": []}
{"input": "HW002 was constructed by deleting lpxM in HW001 and synthesizes only the pentaacylated monophosphoryl lipid A.", "output": {"entities": {"chemical": [{"text": "pentaacylated monophosphoryl lipid A", "start": 73, "end": 109}]}}, "schema": []}
{"input": "The structures of lipid A made in HW001 and HW002 were confirmed by thin layer chromatography and electrospray ionization mass spectrometry.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 18, "end": 25}]}}, "schema": []}
{"input": "HW001 and HW002 grew as well as the wild-type W3110.", "output": {"entities": {}}, "schema": []}
{"input": "LPS purified from HW001 or HW002 was used to stimulate murine macrophage RAW264. 7 cells, and less TNF-alpha were released.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides a feasible way to produce interesting lipid A species in E. coli.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 58, "end": 65}]}}, "schema": []}
{"input": "All-Cause and Cardiovascular Mortality in Middle-Aged People With Type 2 Diabetes Compared With People Without Diabetes in a Large U. K.", "output": {"entities": {}}, "schema": []}
{"input": "Primary Care Database.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEMiddle-aged people with diabetes have been reported to have significantly higher risks of cardiovascular events than people without diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "However, recent falls in cardiovascular disease rates and more active management of risk factors may have abolished the increased risk.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to provide an up-to-date assessment of the relative risks associated with type 2 diabetes of all-cause and cardiovascular mortality in middle-aged people in the U. K. RESEARCH DESIGN AND METHODSUsing data from the General Practice Research Database, from 2004 to 2010, we conducted a cohort study of 87, 098 people, 40-65 years of age at baseline, comparing 21, 798 with type 2 diabetes and 65, 300 without diabetes, matched on age, sex, and general practice.", "output": {"entities": {}}, "schema": []}
{"input": "We produced hazard ratios (HRs) for mortality and compared rates of blood pressure testing, cholesterol monitoring, and use of aspirin, statins, and antihypertensive drugs. RESULTSPeople with type 2 diabetes, compared with people without diabetes, had a twofold increased risk of all-cause mortality (HR 2. 07 [95% CI 1. 95-2. 20], adjusted for smoking) and a threefold increased risk of cardiovascular mortality (3. 25 [2. 87-3. 68], adjusted for smoking).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 92, "end": 103}, {"text": "aspirin", "start": 127, "end": 134}]}}, "schema": []}
{"input": "Women had a higher relative risk than men, and people < 55 years of age had a higher relative risk than those > 55 years of age.", "output": {"entities": {}}, "schema": []}
{"input": "Monitoring and medication rates were higher in those with diabetes (all P < 0. 001). CONCLUSIONSDespite efforts to manage risk factors, administer effective treatments, and develop new therapies, middle-aged people with type 2 diabetes remain at significantly increased risk of death.", "output": {"entities": {}}, "schema": []}
{"input": "Reduced Heart Rate Variability Is Associated With Increased Arterial Stiffness in Youth With Type 1 Diabetes: The SEARCH Cardiovascular Disease Study.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEReduced heart rate variability (HRV) and increased arterial stiffness (AS) are both present in youth with type 1 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "However, it is unclear whether they are associated and whether their association is independent of cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODSThe SEARCH Cardiovascular Disease Study explored the cross-sectional relationships between HRV and several measures of AS in youth with (n = 344) and without (n = 171) type 1 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "The SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure HRV using SD of normal R-R interval (SDNN), as well as AS, using pulse wave velocity in the carotid to femoral segment (PWV-trunk) and augmentation index adjusted to a heart rate of 75 bpm (AIx75).", "output": {"entities": {}}, "schema": []}
{"input": "Brachial distensibility (BrachD), another index of AS, was measured with a DynaPulse instrument (Pulse Metric, San Diego, CA).", "output": {"entities": {}}, "schema": []}
{"input": "Multiple linear regression analyses explored the associations between HRV and each of the three AS measures, after adjusting for demographic characteristics and traditional CVD risk factors (blood pressure, lipids, obesity, microalbuminuria, and smoking) separately, for youth with and without type 1 diabetes. RESULTSAmong youth with type 1 diabetes, lower SDNN was associated with peripheral AS (lower BrachD, P = 0. 01; r (2) = 0. 30) and central AS (higher PVW-trunk, P < 0. 0001; r (2) = 0. 37; and higher AIx75, P = 0. 007; r (2) = 0. 08).", "output": {"entities": {}}, "schema": []}
{"input": "These associations were attenuated with adjustment for CVD risk factors, but remained statistically significant for BrachD and PWV-trunk.", "output": {"entities": {}}, "schema": []}
{"input": "While a similar association between HRV and BrachD was present in control youth, lower HRV was not associated with increased central AS or with AIx75. CONCLUSIONSLongitudinal studies are needed to understand the pathways responsible for these associations.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in A1C Levels Are Significantly Associated With Changes in Levels of the Cardiovascular Risk Biomarker hs-CRP: Results from SteP Study.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEThe effect of therapeutic strategies on cardiovascular (CV) disease can be evaluated by monitoring changes in CV risk biomarkers.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigated the effect of a structured self-monitoring of blood glucose (SMBG) protocol and the resulting improvements in glycemic control on changes in high-sensitivity C-reactive protein (hs-CRP) in insulin-na i ve patients with type 2 diabetes. RESEARCH DESIGN AND METHODSThe Structured Testing Program (STeP) study was a prospective, cluster-randomized, multicenter trial in which 483 poorly controlled, insulin-na i ve patients with type 2 diabetes were randomized to active control (ACG) or structured testing (STG) that included quarterly structured SMBG.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 76, "end": 83}]}}, "schema": []}
{"input": "Changes in A1C, hs-CRP, and glycemic variability (STG subjects only) were measured at baseline and quarterly. RESULTSReductions in geometric mean hs-CRP values were significantly greater in the STG group at months 3 (P = 0. 005), 6 (P = 0. 0003), and 12 (P = 0. 04) than in the ACG group.", "output": {"entities": {}}, "schema": []}
{"input": "STG patients at high CV risk (> 3 mg/L) showed significantly greater reductions in hs-CRP levels than ACG patients at high CV risk:-3. 64 mg/dL (95% CI-4. 21 to-3. 06) versus-2. 18 mg/dL (-2. 93 to-1. 43), respectively (P = 0. 002).", "output": {"entities": {}}, "schema": []}
{"input": "There was a strong correlation between reductions in hs-CRP and A1C in both groups: standardized coefficient (beta) was 0. 25 for the entire cohort (P < 0. 0001), 0. 31 for STG (P < 0. 0001), and 0. 16 for ACG (P = 0. 02). CONCLUSIONSReductions in hs-CRP level are associated with reductions in A1C but not reductions in lipids or glycemic variability.", "output": {"entities": {}}, "schema": []}
{"input": "Comprehensive structured SMBG-based interventions that lower A1C may translate into improvements in CV risk, as evidenced by levels of the biomarker hs-CRP.", "output": {"entities": {}}, "schema": []}
{"input": "Rational development of novel leads from animal secretion based on coagulation and cell targets: 1.", "output": {"entities": {}}, "schema": []}
{"input": "In silico analysis to explore a peptide derivative as lipocalins' signature.", "output": {"entities": {}}, "schema": []}
{"input": "Animal venoms and secretions have been screened, in our research group, to discover, identify and isolate peptide molecules active in the mammalian haemostatic system.", "output": {"entities": {}}, "schema": []}
{"input": "As result, this kind of research has provided a portfolio of promising drug candidates.", "output": {"entities": {}}, "schema": []}
{"input": "These novel recombinant proteins have turned out to be multifunctional molecules, and are currently under different development phases.", "output": {"entities": {}}, "schema": []}
{"input": "Lopap from bristles of the Lonomia obliqua moth caterpillar, for instance, is a prothrombin activator which belongs to the lipocalin family.", "output": {"entities": {}}, "schema": []}
{"input": "It displays serine protease-like activity with procoagulant effect, and also induces cytokine secretion and antiapoptotic pathways in human cultured endothelial cells.", "output": {"entities": {"chemical": [{"text": "serine", "start": 12, "end": 18}]}}, "schema": []}
{"input": "Furthermore, a Lopap-derived peptide has showed to induce collagen synthesis in fibroblast culture and in animal dermis.", "output": {"entities": {}}, "schema": []}
{"input": "Here, the molecular properties (steric, electronic, hydrophobic, geometric), which are strongly dependent on chemical structure, were investigated by applying chemometric and computational chemistry methods.", "output": {"entities": {}}, "schema": []}
{"input": "It was considered different patterns of amino acid substitution related to the lipocalins' motif 2, which was recently shown to modulate cell survival.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 40, "end": 50}]}}, "schema": []}
{"input": "The calculated molecular properties were generally maintained in all investigated peptides extracted from three-dimensional structures of Protein Data Bank (1t0v, 1bbp, 1kxo, 2hzr, 1iiu, 1jyj, 1gka, 1s44, 3ebw) when compared to Lopap-derived peptide, specially the molecular shape and electronic density distribution, validating the lipocalin sequence signature previously reported.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, those two properties are quite important for the molecular recognition process.", "output": {"entities": {}}, "schema": []}
{"input": "Pro-inflammatory and pathogenic properties of Annexin-A1: The whole is greater than the sum of its parts.", "output": {"entities": {}}, "schema": []}
{"input": "According to Aristotle, \" The whole is greater than the sum of its parts \" and yet, although a long time has passed still, we seem to struggle to accept this universal concept.", "output": {"entities": {}}, "schema": []}
{"input": "Searching in the literature for the biological function of Annexin-A1, one would find a wealth of information on its homeostatic and protective anti-inflammatory effects.", "output": {"entities": {}}, "schema": []}
{"input": "However, very little has been said on its emerging role in a wide variety of pathological conditions ranging from cancer to autoimmunity.", "output": {"entities": {}}, "schema": []}
{"input": "In this commentary, we will focus our attention on this novel pro-inflammatory and pathogenic \" dark side \" of Annexin-A1.", "output": {"entities": {}}, "schema": []}
{"input": "We will summarize our current understanding of the signaling pathways regulated by this protein and link it to clinical and experimental evidences.", "output": {"entities": {}}, "schema": []}
{"input": "Finally we will discuss assets and limitations of Annexin-A1 therapeutic strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Most importantly, we hope that this commentary will provide scientific support to \" controversial \" findings one might encounter while studying this fascinating protein.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in morphometry and association between whole-body fatty acids and steroid hormone profiles in relation to bioaccumulation patterns in salmon larvae exposed to perfluorooctane sulfonic or perfluorooctane carboxylic acids.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 58, "end": 69}, {"text": "steroid", "start": 74, "end": 81}, {"text": "perfluorooctane sulfonic or perfluorooctane carboxylic acids", "start": 167, "end": 227}]}}, "schema": []}
{"input": "In the present study, we have used salmon embryos whose continuous exposure to waterborne PFOA or PFOS at 100 mu g/L started as freshly fertilized eggs, and lasted for a total of 52 days.", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 90, "end": 94}, {"text": "PFOS", "start": 98, "end": 102}]}}, "schema": []}
{"input": "PFOS and PFOA were dissolved in methanol (carrier vehicle) whose concentration never exceeded 0. 01% of total tank volume.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 0, "end": 4}, {"text": "PFOA", "start": 9, "end": 13}, {"text": "methanol", "start": 32, "end": 40}]}}, "schema": []}
{"input": "Samples were collected at day 21, 28, 35, 52, 49 and 56 after the start of the exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Note that days 49 and 56 represent end of exposure and 1 week after a recovery period, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Tissue bioaccumulations were determined by HPLC/MS/MS, steroid hormones, fatty acids (FAs) and lipids were determined by GC-MS, while mRNA expression levels of genes were determined by qPCR in whole body homogenate.", "output": {"entities": {"chemical": [{"text": "steroid", "start": 55, "end": 62}, {"text": "fatty acids", "start": 73, "end": 84}, {"text": "FAs", "start": 86, "end": 89}]}}, "schema": []}
{"input": "We observed that PFOS and PFOA showed a steady increase in whole body burden during the exposure period, with a slight decrease after the recovery period.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 17, "end": 21}, {"text": "PFOA", "start": 26, "end": 30}]}}, "schema": []}
{"input": "Calculated somatic indexes showed that PFOA produced increases in heart-, thymus-, liver-and kidney somatic indexes (HSI, TSI, LSI and KSI).", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 39, "end": 43}]}}, "schema": []}
{"input": "PFOA and PFOS exposure produced significant decreases in whole body dehydroepiandrosterone (DHEA), estrone and testosterone at sampling day 21 and a strong increase of cortisol and cholesterol at the end of recovery period (day 56).", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 0, "end": 4}, {"text": "PFOS", "start": 9, "end": 13}, {"text": "dehydroepiandrosterone", "start": 68, "end": 90}, {"text": "DHEA", "start": 92, "end": 96}, {"text": "testosterone", "start": 111, "end": 123}, {"text": "cortisol", "start": 168, "end": 176}, {"text": "cholesterol", "start": 181, "end": 192}]}}, "schema": []}
{"input": "PFOA and PFOS effects differed with DHEA and estrone.", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 0, "end": 4}, {"text": "PFOS", "start": 9, "end": 13}, {"text": "DHEA", "start": 36, "end": 40}, {"text": "estrone", "start": 45, "end": 52}]}}, "schema": []}
{"input": "While PFOS decreased DHEA levels, PFOA produced an increase at day 49, and while PFOS decreased estrone, PFOA produced a slight increase at day 56.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 6, "end": 10}, {"text": "DHEA", "start": 21, "end": 25}, {"text": "PFOA", "start": 34, "end": 38}, {"text": "PFOS", "start": 81, "end": 85}, {"text": "estrone", "start": 96, "end": 103}, {"text": "PFOA", "start": 105, "end": 109}]}}, "schema": []}
{"input": "We observed changes in FA composition that predominantly involved increases in FA methyl esters (FAMEs), mono-and poly-unsaturated FA (MUFA and PUFA) and a decrease in n-3/n-6 PUFA ratio by both PFOA and PFOS.", "output": {"entities": {"chemical": [{"text": "FA methyl esters", "start": 79, "end": 95}, {"text": "FAMEs", "start": 97, "end": 102}, {"text": "mono-and poly-unsaturated FA", "start": 105, "end": 133}, {"text": "MUFA", "start": 135, "end": 139}, {"text": "PUFA", "start": 144, "end": 148}, {"text": "PUFA", "start": 176, "end": 180}, {"text": "PFOA", "start": 195, "end": 199}, {"text": "PFOS", "start": 204, "end": 208}]}}, "schema": []}
{"input": "Particularly, an increase in-pentadecenoic MUFA (15: 1), two n-3 PUFAs alpha-linolenic acid [ALA: 18: 3 n3] and eicosapentaenoic acid [EPA: 20: 5 n-3] and n-6 PUFA: arachidonic acid [ARA: 20: 4 n6], docosapentaenoic acid (DPA) by PFOA and PFOS were observed.", "output": {"entities": {"chemical": [{"text": "pentadecenoic MUFA", "start": 29, "end": 47}, {"text": "PUFAs alpha-linolenic acid", "start": 65, "end": 91}, {"text": "ALA", "start": 93, "end": 96}, {"text": "eicosapentaenoic acid", "start": 112, "end": 133}, {"text": "EPA", "start": 135, "end": 138}, {"text": "PUFA", "start": 159, "end": 163}, {"text": "arachidonic acid", "start": 165, "end": 181}, {"text": "ARA", "start": 183, "end": 186}, {"text": "docosapentaenoic acid", "start": 199, "end": 220}, {"text": "DPA", "start": 222, "end": 225}, {"text": "PFOA", "start": 230, "end": 234}, {"text": "PFOS", "start": 239, "end": 243}]}}, "schema": []}
{"input": "These effects were associated with changes in mRNA expression of FA elongase (FAE), Delta 5-desaturase (FAD5) and Delta 6-desaturase (FAD6) genes.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, the changes in hormonal and FA profiles may represent cellular and/or physiological adaptation to continuous PFOS and PFOA exposure by increasing membrane fluidity, and/or overt developmental effects.", "output": {"entities": {"chemical": [{"text": "PFOS", "start": 121, "end": 125}, {"text": "PFOA", "start": 130, "end": 134}]}}, "schema": []}
{"input": "The present findings provide some potential insights and basis for a better understanding on the possible mechanisms of PFCs toxicity in fish.", "output": {"entities": {}}, "schema": []}
{"input": "Transcriptional regulation of human ferredoxin 1 in ovarian granulosa cells.", "output": {"entities": {}}, "schema": []}
{"input": "Ferredoxin 1 (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including steroid hormone synthesis in mammalian tissues.", "output": {"entities": {"chemical": [{"text": "iron", "start": 39, "end": 43}, {"text": "sulfur", "start": 44, "end": 50}, {"text": "steroid hormone", "start": 118, "end": 133}]}}, "schema": []}
{"input": "We investigated the transcriptional regulation of FDX1 in ovarian granulosa cells.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, we reported that the NR5A family, including steroidogenic factor-1 (SF-1) and liver receptor homolog-1 could induce differentiation of human mesenchymal stem cells (hMSCs) into steroidogenic cells.", "output": {"entities": {}}, "schema": []}
{"input": "A ChIP assay showed that SF-1 could bind to the FDX1 promoter in differentiated hMSCs.", "output": {"entities": {}}, "schema": []}
{"input": "Luciferase reporter assays showed that transcription of FDX1 was synergistically activated by the NR5A family and 8Br-cAMP treatment through two SF-1 binding sites and a CRE-like sequence in a human ovarian granulosa cell line, KGN.", "output": {"entities": {"chemical": [{"text": "8Br-cAMP", "start": 114, "end": 122}]}}, "schema": []}
{"input": "Knockdown of FDX1 attenuated progesterone production in KGN cells.", "output": {"entities": {"chemical": [{"text": "progesterone", "start": 29, "end": 41}]}}, "schema": []}
{"input": "These results indicate transcription of FDX1 is regulated by the NR5A family and cAMP signaling, and participates in steroid hormone production in ovarian granulosa cells.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 81, "end": 85}, {"text": "steroid hormone", "start": 117, "end": 132}]}}, "schema": []}
{"input": "Attenuation by statins of membrane raft-redox signaling in coronary arterial endothelium.", "output": {"entities": {"chemical": [{"text": "statins", "start": 15, "end": 22}]}}, "schema": []}
{"input": "Membrane raft (MR)-redox signaling platforms associated with NADPH oxidase are involved in coronary endothelial dysfunction.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 61, "end": 66}]}}, "schema": []}
{"input": "Here, we studied whether statins interfere with the formation of MR-redox signaling platforms to protect the coronary arterial endothelium from oxidized low-density lipoprotein (OxLDL)-induced injury and from acute hypercholesterolemia.", "output": {"entities": {"chemical": [{"text": "statins", "start": 25, "end": 32}]}}, "schema": []}
{"input": "In cultured human coronary arterial endothelial cells, confocal microscopy detected the formation of an MRs clustering when they were exposed to OxLDL, and such MR platform formation was inhibited markedly by statins, including pravastatin and simvastatin.", "output": {"entities": {"chemical": [{"text": "statins", "start": 209, "end": 216}, {"text": "pravastatin", "start": 228, "end": 239}, {"text": "simvastatin", "start": 244, "end": 255}]}}, "schema": []}
{"input": "In these MR clusters, NADPH oxidase subunits gp91 (phox) and p47 (phox) were aggregated and were markedly blocked by both statins.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 22, "end": 27}, {"text": "statins", "start": 122, "end": 129}]}}, "schema": []}
{"input": "In addition, colocalization of acid sphingomyelinase (ASM) and ceramide was induced by OxLDL, which was blocked by statins.", "output": {"entities": {"chemical": [{"text": "ceramide", "start": 63, "end": 71}, {"text": "statins", "start": 115, "end": 122}]}}, "schema": []}
{"input": "Electron spin resonance spectrometry showed that OxLDL-induced superoxide (O2 (.-)) production in the MR fractions was substantially reduced by statins.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 63, "end": 73}, {"text": "O2 (.-)", "start": 75, "end": 82}, {"text": "statins", "start": 144, "end": 151}]}}, "schema": []}
{"input": "In coronary artery intima of mice with acute hypercholesterolemia, confocal microscopy revealed a colocalization of gp91 (phox), p47 (phox), ASM, or ceramide in MR clusters.", "output": {"entities": {"chemical": [{"text": "ceramide", "start": 149, "end": 157}]}}, "schema": []}
{"input": "Such colocalization was rarely observed in the arteries of normal mice or significantly reduced by pretreatment of hypercholesterolemic mice with statins.", "output": {"entities": {"chemical": [{"text": "statins", "start": 146, "end": 153}]}}, "schema": []}
{"input": "Furthermore, O2 (.-) production in situ was 3-fold higher in the coronary arteries from hypercholesterolemic mice than in those from normal mice, and such increase was inhibited by statins.", "output": {"entities": {"chemical": [{"text": "O2 (.-)", "start": 13, "end": 20}, {"text": "statins", "start": 181, "end": 188}]}}, "schema": []}
{"input": "Our results indicate that blockade of MR-redox signaling platform formation in endothelial cell membrane may be another important therapeutic mechanism of statins in preventing endothelial injury and atherosclerosis and may be associated with their direct action on membrane cholesterol structure and function.", "output": {"entities": {"chemical": [{"text": "statins", "start": 155, "end": 162}, {"text": "cholesterol", "start": 275, "end": 286}]}}, "schema": []}
{"input": "Pharmacogenomics of acetylsalicylic acid and other nonsteroidal anti-inflammatory agents: clinical implications.", "output": {"entities": {"chemical": [{"text": "acetylsalicylic acid", "start": 20, "end": 40}]}}, "schema": []}
{"input": "PURPOSE: Pharmacogenomics investigates interindividual genetic variability in the DNA sequence of drug targets, drug-metabolizing enzymes or disease genes, RNA expression, or protein translation of genes affecting drug response and drug safety.", "output": {"entities": {}}, "schema": []}
{"input": "Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications with well-documented variation in patient response in terms of efficacy and safety.", "output": {"entities": {"chemical": [{"text": "Aspirin", "start": 0, "end": 7}]}}, "schema": []}
{"input": "This variation may in part be explained by pharmacogenomics.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: In this paper I review data on the pharmacogenomics of aspirin and other NSAIDs focusing on clinical implications.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Existing scientific evidence supports the pharmacogenomic basis of interindividual variation in treatment response to aspirin and NSAIDs, with clinical implications for antiplatelet action, cancer chemoprevention, and drug safety.", "output": {"entities": {}}, "schema": []}
{"input": "However, further research efforts are needed before knowledge on the pharmacogenomics of aspirin and NSAIDs can be implemented in clinical practice.", "output": {"entities": {"chemical": [{"text": "aspirin", "start": 89, "end": 96}]}}, "schema": []}
{"input": "CONCLUSION: The outcome of these research efforts would be anticipated to have added value for both science and society, contributing to the enhanced efficacy and safety of these agents through patient selection.", "output": {"entities": {}}, "schema": []}
{"input": "Surface-enhanced Raman scattering spectra of adsorbates on Cu 2 O nanospheres: charge-transfer and electromagnetic enhancement.", "output": {"entities": {"chemical": [{"text": "Cu 2 O", "start": 59, "end": 65}]}}, "schema": []}
{"input": "Surface-enhanced Raman scattering (SERS) spectra of 4-mercaptobenzoic acid (4-MBA) have been investigated on the surface of Cu2O nanospheres.", "output": {"entities": {"chemical": [{"text": "4-mercaptobenzoic acid", "start": 52, "end": 74}, {"text": "4-MBA", "start": 76, "end": 81}, {"text": "Cu2O", "start": 124, "end": 128}]}}, "schema": []}
{"input": "The SERS signals were believed to originate from the static chemical enhancement, resonant chemical enhancement and electromagnetic enhancement.", "output": {"entities": {}}, "schema": []}
{"input": "The coupling between the adsorbates and the semiconductor, evidenced by the shift in absorption spectrum of modified Cu2O and the enhancement of non-totally symmetric modes of the 4-MBA and 4-mercaptopyridine (4-MPY) molecules, were invoked to explain the experimental results.", "output": {"entities": {"chemical": [{"text": "Cu2O", "start": 117, "end": 121}, {"text": "4-MBA", "start": 180, "end": 185}, {"text": "4-mercaptopyridine", "start": 190, "end": 208}, {"text": "4-MPY", "start": 210, "end": 215}]}}, "schema": []}
{"input": "Furthermore, simulations were employed to investigate the nature of the enhancement mechanisms operative between the molecules and the semiconductor.", "output": {"entities": {}}, "schema": []}
{"input": "Density functional theory (DFT) calculations suggested a charge transfer (CT) transition process between the molecules and the Cu2O nanospheres.", "output": {"entities": {"chemical": [{"text": "Cu2O", "start": 127, "end": 131}]}}, "schema": []}
{"input": "Three-dimensional finite-difference time domain (3D-FDTD) simulations were conducted to map out the electromagnetic field around the Cu2O nanospheres.", "output": {"entities": {"chemical": [{"text": "Cu2O", "start": 133, "end": 137}]}}, "schema": []}
{"input": "The experimental and simulation results have revealed the promise of the Cu2O nanospheres as a good SERS substrate and the prospect of using the SERS substrate as a valuable tool for in situ investigation and assay of the adsorption behavior on semiconductor surfaces.", "output": {"entities": {"chemical": [{"text": "Cu2O", "start": 73, "end": 77}]}}, "schema": []}
{"input": "The characteristics of genistin-induced inhibitory effects on intestinal motility.", "output": {"entities": {"chemical": [{"text": "genistin", "start": 23, "end": 31}]}}, "schema": []}
{"input": "Genistin belongs to isoflavones.", "output": {"entities": {"chemical": [{"text": "Genistin", "start": 0, "end": 8}, {"text": "isoflavones", "start": 20, "end": 31}]}}, "schema": []}
{"input": "Based on the facts that genistin exerts inhibitory effects on the contractility of vascular smooth muscle, the present study was designed to characterize the effects of genistin on intestinal contractility and evaluate its potential clinical implication.", "output": {"entities": {"chemical": [{"text": "genistin", "start": 24, "end": 32}, {"text": "genistin", "start": 169, "end": 177}]}}, "schema": []}
{"input": "Ex vivo [isolated jejunal segment (IJS) of rat], in vitro, and in vivo assays were used in the study.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicated that genistin (5-80 mu mol/L) inhibited the contraction of IJS in a dose-dependent manner and inhibited the increased-contractility of IJS induced by acetylcholine (ACh), histamine, high Ca (2 +), and erythromycin, respectively.", "output": {"entities": {"chemical": [{"text": "genistin", "start": 27, "end": 35}, {"text": "acetylcholine", "start": 172, "end": 185}, {"text": "ACh", "start": 187, "end": 190}, {"text": "histamine", "start": 193, "end": 202}, {"text": "Ca (2 +)", "start": 209, "end": 217}, {"text": "erythromycin", "start": 223, "end": 235}]}}, "schema": []}
{"input": "The inhibitory effects of genistin were correlated with the stimulation of alpha adrenergic and beta adrenergic receptors since these inhibitory effects were significantly blocked in the presence of phentolamine and propranolol respectively.", "output": {"entities": {"chemical": [{"text": "genistin", "start": 26, "end": 34}, {"text": "phentolamine", "start": 199, "end": 211}, {"text": "propranolol", "start": 216, "end": 227}]}}, "schema": []}
{"input": "No further inhibitory effects of genistin were observed in the presence of verapamil or in Ca (2 +)-free condition, indicating genistin-induced inhibitory effects are Ca (2 +)-dependent.", "output": {"entities": {"chemical": [{"text": "genistin", "start": 33, "end": 41}, {"text": "verapamil", "start": 75, "end": 84}, {"text": "Ca (2 +)", "start": 91, "end": 99}, {"text": "genistin", "start": 127, "end": 135}, {"text": "Ca (2 +)", "start": 167, "end": 175}]}}, "schema": []}
{"input": "Genistin decreased myosin light chain kinase (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg (2 +)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects.", "output": {"entities": {"chemical": [{"text": "Genistin", "start": 0, "end": 8}, {"text": "Mg (2 +)", "start": 141, "end": 149}, {"text": "genistin", "start": 285, "end": 293}]}}, "schema": []}
{"input": "The study suggests the potential clinical implications of genistin in relieving intestinal hypercontractility.", "output": {"entities": {"chemical": [{"text": "genistin", "start": 58, "end": 66}]}}, "schema": []}
{"input": "The pharmacokinetics and pharmacodynamics of zaleplon delivered as a thermally generated aerosol in a single breath to volunteers.", "output": {"entities": {"chemical": [{"text": "zaleplon", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Pharmacokinetics, pharmacodynamics, safety, and tolerability of inhaled zaleplon were assessed in healthy volunteers.", "output": {"entities": {"chemical": [{"text": "zaleplon", "start": 72, "end": 80}]}}, "schema": []}
{"input": "Forty participants received 0. 5, 1, 2, or 4 mg zaleplon or placebo as a thermally generated aerosol in a randomized, double-blind, parallel-group, dose escalation study.", "output": {"entities": {"chemical": [{"text": "zaleplon", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Blood was collected up to 24 hours after dosing, and sedation was assessed up to 8 hours.", "output": {"entities": {}}, "schema": []}
{"input": "Following inhalation, the observed median time to maximum plasma concentrations (25%, 75%) was 1. 89 (1. 45, 3. 08) minutes and the mean (SD) elimination half-life was 1. 24 (0. 24) hours.", "output": {"entities": {}}, "schema": []}
{"input": "The equilibration half-life for sedation (t (1/2) k (e0)) was 1. 16 (0. 62, 2. 17) minutes.", "output": {"entities": {}}, "schema": []}
{"input": "The zaleplon AUC was dose proportional across doses, with a slope (90% confidence interval) of log-AUC versus log-dose of 0. 92 (0. 82, 1. 02).", "output": {"entities": {"chemical": [{"text": "zaleplon", "start": 4, "end": 12}]}}, "schema": []}
{"input": "No clinically significant changes were noted in laboratory values, vital signs, or spirometry.", "output": {"entities": {}}, "schema": []}
{"input": "The most common adverse events were dizziness, somnolence, euphoria, headache, and visual disturbance.", "output": {"entities": {}}, "schema": []}
{"input": "Zaleplon inhalation represents a safe, well-tolerated means of rapidly achieving effective plasma concentrations.", "output": {"entities": {"chemical": [{"text": "Zaleplon", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The combination of exposure-response and case-control analyses in regulatory decision making.", "output": {"entities": {}}, "schema": []}
{"input": "To reduce the bias introduced by confounding risk factors, a case-control comparison was incorporated in the exposure-response (ER) analysis to evaluate the recommended dosing regimen for trastuzumab in a pivotal trial.", "output": {"entities": {}}, "schema": []}
{"input": "Results of Kaplan-Meier survival analysis suggest that patients with metastatic gastric cancer (mGC) in the lowest quartile trough concentrations of trastuzumab in cycle 1 (C (min 1)) had shorter overall survival (OS) than did those in other quartiles.", "output": {"entities": {}}, "schema": []}
{"input": "The result of the case-matched control comparison suggests that adjusting for these risk factors, patients with the lowest quartile of trastuzumab exposure did not benefit from addition of trastuzumab treatment to chemotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "The identified subgroup without survival benefit and the ER relationship support the recommendation on conducting clinical trials to identify a treatment regimen with greater exposure and acceptable safety profiles and to prospectively evaluate whether this treatment regimen will result in survival benefit for the identified subgroup.", "output": {"entities": {}}, "schema": []}
{"input": "Drug-induced liver injury: the role of drug metabolism and transport.", "output": {"entities": {}}, "schema": []}
{"input": "Many studies have pinpointed the significant contribution of liver-mediated drug metabolism and transport to the complexity of drug-induced liver injury (DILI).", "output": {"entities": {}}, "schema": []}
{"input": "Phase I cytochrome P450 (CYP450) enzymes can lead to altered drug metabolism and formation of toxic metabolites, whilst Phase II enzymes are also associated with DILI.", "output": {"entities": {}}, "schema": []}
{"input": "The emerging role of hepatic transporters in regulating the movement of endogenous and exogenous chemicals (e. g., bile acids and drugs) across cellular and tissue membranes is critical in determining the pathophysiology of liver disease as well as drug toxicity and efficacy.", "output": {"entities": {"chemical": [{"text": "bile acids", "start": 115, "end": 125}]}}, "schema": []}
{"input": "Genetic and environmental factors can have a significant impact on drug metabolism and transporter proteins, consequently increasing the risk of DILI in susceptible individuals.", "output": {"entities": {}}, "schema": []}
{"input": "The assessment of these factors therefore represents an important approach for predicting and preventing DILI, by better understanding the pharmacological profile of a specific drug.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on the mechanisms of DILI associated with drug metabolism and hepatic transport, and how they can be influenced by underlying factors.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of excipients on acetaminophen metabolism and its implications for prevention of liver injury.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 24, "end": 37}]}}, "schema": []}
{"input": "Acetaminophen poisoning is the most frequent cause of acute hepatic failure in the US.", "output": {"entities": {"chemical": [{"text": "Acetaminophen", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Toxicity requires reductive metabolism of acetaminophen, primarily via CYP2E1.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 42, "end": 55}]}}, "schema": []}
{"input": "Liquid acetaminophen preparations contain propylene glycol, a common excipient that has been shown to reduce hepatocellular injury in vitro and in rodents.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 7, "end": 20}, {"text": "propylene glycol", "start": 42, "end": 58}]}}, "schema": []}
{"input": "Children are less susceptible to acetaminophen toxicity for unclear reasons.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 33, "end": 46}]}}, "schema": []}
{"input": "We conducted a pharmacokinetic single-blinded crossover study of 15 healthy adult volunteers comparing the CYP2E1 and conjugative metabolism of a 15 mg/kg dose of liquid versus solid preparations of acetaminophen.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 199, "end": 212}]}}, "schema": []}
{"input": "Measured AUC' s for the CYP2E1 metabolites were 16-17% lower and extrapolated AUC' s were 25-28% lower in the liquid formulation arm while there was no difference in conjugative metabolite production.", "output": {"entities": {}}, "schema": []}
{"input": "The formation rate constants for reductive metabolites were equivalent between solid and liquid formulations indicating that enzyme inhibition was competitive.", "output": {"entities": {}}, "schema": []}
{"input": "Propylene glycol, an established CYP2E1 competitive antagonist, was detected in the liquid formulation but not solid formulation arm.", "output": {"entities": {"chemical": [{"text": "Propylene glycol", "start": 0, "end": 16}]}}, "schema": []}
{"input": "Since children tend to ingest liquid preparations, the protective effect of this excipient could explain their decreased susceptibility to acetaminophen toxicity.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 139, "end": 152}]}}, "schema": []}
{"input": "A less hepatotoxic formulation of acetaminophen could potentially be developed if co-formulated with a CYP2E1 inhibitor.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 34, "end": 47}]}}, "schema": []}
{"input": "Addition of cilostazol to conventional dual antiplatelet therapy reduces the risk of cardiac events and restenosis after drug-eluting stent implantation: a meta-analysis.", "output": {"entities": {"chemical": [{"text": "cilostazol", "start": 12, "end": 22}]}}, "schema": []}
{"input": "This meta-analysis was performed to compare the risk of cardiac events and restenosis between triple antiplatelet therapy (TAT, addition of cilostazol to aspirin and clopidogrel) and conventional dual antiplatelet therapy (DAT, aspirin and clopidogrel) in drug-eluting stents (DES) implantation patients.", "output": {"entities": {"chemical": [{"text": "cilostazol", "start": 140, "end": 150}, {"text": "aspirin", "start": 154, "end": 161}, {"text": "clopidogrel", "start": 166, "end": 177}, {"text": "aspirin", "start": 228, "end": 235}, {"text": "clopidogrel", "start": 240, "end": 251}]}}, "schema": []}
{"input": "We performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation.", "output": {"entities": {}}, "schema": []}
{"input": "Five clinical trials were involved in the study.", "output": {"entities": {}}, "schema": []}
{"input": "TAT was associated with a 36% reduction in major adverse cardiac events (MACE; odds ratio (OR) = 0. 64; 95% confidence interval (CI) = 0. 51-0. 81, P <. 01), a 40% reduction (OR = 0. 60, 95% CI = 0. 44-0. 80; P <. 01) in target vessel revascularization (TVR), a 44% reduction (OR = 0. 56, 95% CI = 0. 34-0. 91; P =. 02) in target lesion revascularization (TLR) and a 47%/44% reduction in in-segment/in-stent restenosis (P <. 01) and lower in-segment/in-stent late loss (P <. 01).", "output": {"entities": {}}, "schema": []}
{"input": "As regards to the safety assessment, there was no significant difference about the risk of stent thrombosis and bleeding between TAT and DAT group, while the risk of gastrointestinal trouble was significantly higher in TAT group (OR = 2. 46, 95% CI = 1. 25-4. 86; P <. 01).", "output": {"entities": {}}, "schema": []}
{"input": "Addition of cilostazol to DAT reduced the incidence of MACE, TVR, and TLR after DES implantation.", "output": {"entities": {"chemical": [{"text": "cilostazol", "start": 12, "end": 22}]}}, "schema": []}
{"input": "TAT also reduced the risk of restenosis and late loss in patients after DES implantation.", "output": {"entities": {}}, "schema": []}
{"input": "Blood Pressure Lowering Effect of Nigella sativa L.", "output": {"entities": {}}, "schema": []}
{"input": "Seed Oil in Healthy Volunteers: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.", "output": {"entities": {}}, "schema": []}
{"input": "Nigella sativa L. seeds (N. sativa) have been used as a traditional remedy for a wide range of diseases including hypertension.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was performed to explore the effects of N. sativa oil on blood pressure (BP) in healthy volunteers.", "output": {"entities": {}}, "schema": []}
{"input": "In a double-blind, randomized study, 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were randomly allocated to receive 2. 5 mL N. sativa oil or placebo two times a day for 8 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "The systolic and diastolic BPs, body mass index and blood levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, creatinine and blood urea nitrogen were determined at baseline and endpoint.", "output": {"entities": {"chemical": [{"text": "aspartate", "start": 68, "end": 77}, {"text": "alanine", "start": 92, "end": 99}, {"text": "creatinine", "start": 136, "end": 146}, {"text": "urea nitrogen", "start": 157, "end": 170}]}}, "schema": []}
{"input": "Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint.", "output": {"entities": {}}, "schema": []}
{"input": "Other parameters did not significantly change in both groups at the endpoint.", "output": {"entities": {}}, "schema": []}
{"input": "No adverse effects were reported.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Readily accessible fluorescent probes for sensitive biological imaging of hydrogen peroxide.", "output": {"entities": {"chemical": [{"text": "hydrogen peroxide", "start": 74, "end": 91}]}}, "schema": []}
{"input": "Hydrogen peroxide is a major component of oxygen metabolism in biological systems that, when present in high concentrations, can lead to oxidative stress in cells.", "output": {"entities": {"chemical": [{"text": "Hydrogen peroxide", "start": 0, "end": 17}, {"text": "oxygen", "start": 42, "end": 48}]}}, "schema": []}
{"input": "Noninvasive molecular imaging of H (2) O (2) using fluorogenic systems represents an effective way to detect and measure the accumulation of this metabolite.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 33, "end": 44}]}}, "schema": []}
{"input": "Herein, we detail the development of robust H (2) O (2)-sensitive fluorescent probes using a boronic ester trigger appended to the fluorophore through a benzyl ether linkage.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 44, "end": 55}, {"text": "boronic ester", "start": 93, "end": 106}, {"text": "benzyl ether", "start": 153, "end": 165}]}}, "schema": []}
{"input": "A major advantage of the probes presented here is their synthetic accessibility, with only one step needed to generate the probes on the gram scale.", "output": {"entities": {}}, "schema": []}
{"input": "The sensitivity of the probes was evaluated in simulated physiological conditions, showing micromolar sensitivity to H (2) O (2).", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 117, "end": 128}]}}, "schema": []}
{"input": "The probes were tested in biological model systems, demonstrating effective imaging of unstimulated, endogenous H (2) O (2) levels in RAW 264. 7 cells and murine brain tissue.", "output": {"entities": {"chemical": [{"text": "H (2) O (2)", "start": 112, "end": 123}]}}, "schema": []}
{"input": "Mifepristone for management of Cushing' s syndrome.", "output": {"entities": {"chemical": [{"text": "Mifepristone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Cushing' s syndrome is a debilitating endocrine disorder caused by elevated circulating glucocorticoid levels.", "output": {"entities": {}}, "schema": []}
{"input": "Although uncommon, Cushing' s syndrome is associated with significant morbidity necessitating rapid reversal of hypercortisolemia.", "output": {"entities": {}}, "schema": []}
{"input": "Primary therapy for most patients with Cushing' s syndrome is surgical, but many patients will require additional treatments with radiation or drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Although several options for drug therapy exist, few are readily available and all have dose-limiting adverse effects.", "output": {"entities": {}}, "schema": []}
{"input": "Mifepristone (RU 486), a first-in-class glucocorticoid receptor antagonist, was approved by the United States Food and Drug Administration in 2012 for use in Cushing' s syndrome to control hyperglycemia in patients who are not surgical candidates or have not achieved remission from surgery.", "output": {"entities": {"chemical": [{"text": "Mifepristone", "start": 0, "end": 12}, {"text": "RU 486", "start": 14, "end": 20}]}}, "schema": []}
{"input": "The drug is approved for oral once-daily administration.", "output": {"entities": {}}, "schema": []}
{"input": "In its pivotal trial, 60% of patients responded to mifepristone with significant improvements in glycemic control and 38% had a reduction in diastolic blood pressure.", "output": {"entities": {"chemical": [{"text": "mifepristone", "start": 51, "end": 63}]}}, "schema": []}
{"input": "The most common adverse events were nausea, fatigue, headache, endometrial hyperplasia, and hypokalemia.", "output": {"entities": {}}, "schema": []}
{"input": "Adrenal insufficiency occurred in fewer than 5% of patients.", "output": {"entities": {}}, "schema": []}
{"input": "The recommended starting dosage of mifepristone is 300 mg/day.", "output": {"entities": {"chemical": [{"text": "mifepristone", "start": 35, "end": 47}]}}, "schema": []}
{"input": "The dosage may be increased every 2-4 weeks up to a maximum of 1200 mg/day, although it should not exceed 20 mg/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "Significant drug-drug interactions exist due to mifepristone' s effects on a number of cytochrome P450 enzymes.", "output": {"entities": {"chemical": [{"text": "mifepristone", "start": 48, "end": 60}]}}, "schema": []}
{"input": "Despite its limitations, mifepristone is a welcome addition and an appropriate alternative to the available drug therapy for Cushing' s syndrome.", "output": {"entities": {"chemical": [{"text": "mifepristone", "start": 25, "end": 37}]}}, "schema": []}
{"input": "UV/Vis spectra of subporphyrazines and subphthalocyanines with aluminum and gallium: a time-dependent DFT study.", "output": {"entities": {"chemical": [{"text": "subporphyrazines", "start": 18, "end": 34}, {"text": "subphthalocyanines", "start": 39, "end": 57}, {"text": "aluminum", "start": 63, "end": 71}, {"text": "gallium", "start": 76, "end": 83}]}}, "schema": []}
{"input": "The UV/Vis spectra of selected substituted subporphyrazines (SubPz) and subphthalocyanines (SubPc) with aluminum and gallium as central atoms are analyzed through time-dependent DFT calculations in chloroform.", "output": {"entities": {"chemical": [{"text": "subporphyrazines", "start": 43, "end": 59}, {"text": "SubPz", "start": 61, "end": 66}, {"text": "subphthalocyanines", "start": 72, "end": 90}, {"text": "SubPc", "start": 92, "end": 97}, {"text": "aluminum", "start": 104, "end": 112}, {"text": "gallium", "start": 117, "end": 124}, {"text": "chloroform", "start": 198, "end": 208}]}}, "schema": []}
{"input": "The results are compared with previous results with boron as the central atom to analyze the photochemical properties of these two families of compounds on varying the metal along the same group.", "output": {"entities": {"chemical": [{"text": "boron", "start": 52, "end": 57}]}}, "schema": []}
{"input": "The absorptions of SubPz (Al, Ga) are redshifted or blueshifted with respect to SubPz (B) depending on the nature of the R substituents of the molecule, whereas the absorptions of SubPc (Al, Ga) structures are redshifted and with smaller energy gaps with respect to SubPc (B) for all kinds of R substituents.", "output": {"entities": {"chemical": [{"text": "SubPz", "start": 19, "end": 24}, {"text": "Al", "start": 26, "end": 28}, {"text": "Ga", "start": 30, "end": 32}, {"text": "SubPz", "start": 80, "end": 85}, {"text": "SubPc", "start": 180, "end": 185}, {"text": "Al", "start": 187, "end": 189}, {"text": "Ga", "start": 191, "end": 193}, {"text": "SubPc", "start": 266, "end": 271}]}}, "schema": []}
{"input": "Looking at their absorption spectra, these systems with aluminum and gallium may also have, as in the case of boron, promising photochemical properties.", "output": {"entities": {"chemical": [{"text": "aluminum", "start": 56, "end": 64}, {"text": "gallium", "start": 69, "end": 76}, {"text": "boron", "start": 110, "end": 115}]}}, "schema": []}
{"input": "Pu-erh tea hot-water extract activates Akt and induces insulin-independent glucose transport in rat skeletal muscle.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 75, "end": 82}]}}, "schema": []}
{"input": "Skeletal muscle is a major organ that is important for whole-body glucose metabolism.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 66, "end": 73}]}}, "schema": []}
{"input": "We found that when isolated rat epitrochlearis muscle was incubated with a Pu-erh tea hot-water extract (PTE) for 30 min, the rate of 3-O-methyl-D-glucose (3MG) transport increased in the absence of insulin.", "output": {"entities": {"chemical": [{"text": "3-O-methyl-D-glucose", "start": 134, "end": 154}, {"text": "3MG", "start": 156, "end": 159}]}}, "schema": []}
{"input": "This activation was associated with an increase in Ser (473) phosphorylation of Akt, a signaling intermediary leading to insulin-dependent glucose transport, but not Tyr (458) phosphorylation of phosphoinositide 3-kinase p85, an upstream molecule of Akt.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 51, "end": 54}, {"text": "glucose", "start": 139, "end": 146}, {"text": "Tyr", "start": 166, "end": 169}]}}, "schema": []}
{"input": "PTE-stimulated 3MG transport was also not accompanied by Thr (172) phosphorylation of the catalytic alpha-subunit of 5'-AMP-activated protein kinase (AMPK).", "output": {"entities": {"chemical": [{"text": "Thr", "start": 57, "end": 60}, {"text": "AMP", "start": 120, "end": 123}]}}, "schema": []}
{"input": "Gallic acid, a water-soluble ingredient in Pu-erh tea, stimulated Akt phosphorylation, but not AMPK phosphorylation.", "output": {"entities": {"chemical": [{"text": "Gallic acid", "start": 0, "end": 11}]}}, "schema": []}
{"input": "These results suggest that Pu-erh tea potentially promotes skeletal muscle glucose transport at least in part by activating Akt.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 75, "end": 82}]}}, "schema": []}
{"input": "Discovery, biological evaluation, and structure-activity and-selectivity relationships of 6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-methylacetamides, a novel class of potent and selective monoamine oxidase inhibitors.", "output": {"entities": {"chemical": [{"text": "6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-methylacetamides", "start": 90, "end": 157}, {"text": "monoamine", "start": 197, "end": 206}]}}, "schema": []}
{"input": "The use of selective inhibitors of monoamine oxidase A (MAO-A) and B (MAO-B) holds a therapeutic relevance in the treatment of depressive disorders and Parkinson' s disease (PD), respectively.", "output": {"entities": {"chemical": [{"text": "monoamine", "start": 35, "end": 44}]}}, "schema": []}
{"input": "Here, the discovery of a new class of compounds acting as monoamine oxidase inhibitors (MAO-Is) and bearing a 6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-alkylacetamide skeleton is reported.", "output": {"entities": {"chemical": [{"text": "monoamine", "start": 58, "end": 67}, {"text": "6'-substituted (E)-2-(benzofuran-3 (2H)-ylidene)-N-alkylacetamide", "start": 110, "end": 175}]}}, "schema": []}
{"input": "6'-Sulfonyloxy derivatives exhibited outstanding affinities to MAO-A (7. 0 nM < IC50 < 49 nM, much higher than moclobemide) and a pronounced MAO-A/B selectivity.", "output": {"entities": {"chemical": [{"text": "6'-Sulfonyloxy", "start": 0, "end": 14}, {"text": "moclobemide", "start": 111, "end": 122}]}}, "schema": []}
{"input": "The corresponding 6'-benzyloxy derivatives showed potent MAO-B inhibition and inverted selectivity profile.", "output": {"entities": {"chemical": [{"text": "6'-benzyloxy", "start": 18, "end": 30}]}}, "schema": []}
{"input": "The rigid E-geometry of the exocyclic double bond allowed a more efficient binding conformation compared to more flexible and less active 2-(1-benzofuran-3-yl)-N-methylacetamide isomers and 4-N-methylcarboxamidomethylcoumarin analogues.", "output": {"entities": {"chemical": [{"text": "2-(1-benzofuran-3-yl)-N-methylacetamide", "start": 138, "end": 177}, {"text": "4-N-methylcarboxamidomethylcoumarin", "start": 190, "end": 225}]}}, "schema": []}
{"input": "Focused structural modifications and docking simulations enabled the identification of key molecular determinants for high affinity toward both MAO isoforms.", "output": {"entities": {}}, "schema": []}
{"input": "These novel MAO-Is may represent promising hits for the development of safer therapeutic agents with a potential against depression, PD, and other age-related neurodegenerative pathologies.", "output": {"entities": {}}, "schema": []}
{"input": "From rings to crescents: a novel fabrication technique uncovers the transition details.", "output": {"entities": {}}, "schema": []}
{"input": "A novel fabrication route is reported for the generation of substrate-supported symmetric and asymmetric metal nanostructures.", "output": {"entities": {}}, "schema": []}
{"input": "We combine a colloidal template and angled evaporation to deposit in situ mask materials for subsequent lithographic pattern transfer.", "output": {"entities": {}}, "schema": []}
{"input": "The technique is demonstrated for the fabrication of concentric and nonconcentric gold rings and crescents.", "output": {"entities": {}}, "schema": []}
{"input": "Optical properties of localized plasmon resonances in such structures are studied by UV-vis-NIR spectroscopy and finite-difference time domain simulations during the transition from rings to crescents revealing the development of strong quadrupolar modes.", "output": {"entities": {}}, "schema": []}
{"input": "Counterion Density Profile around Charged Cylinders: The Strong-Coupling Needle Limit.", "output": {"entities": {}}, "schema": []}
{"input": "Charged rod-like polymers are not able to bind all their neutralizing counterions: a fraction of them evaporates, while the others are said to be condensed.", "output": {"entities": {}}, "schema": []}
{"input": "We study here counterion condensation and its ramifications, both numerically by means of Monte Carlo simulations employing a previously introduced powerful logarithmic sampling of radial coordinates and analytically, with special emphasis on the strong-coupling regime.", "output": {"entities": {}}, "schema": []}
{"input": "We focus on the thin rod or needle limit that is naturally reached under strong Coulombic couplings, where the typical intercounterion spacing a' along the rod is much larger than its radius R.", "output": {"entities": {}}, "schema": []}
{"input": "This regime is complementary and opposite to the simpler thick rod case where a' << R.", "output": {"entities": {}}, "schema": []}
{"input": "We show that due account of counterion evaporation, a universal phenomenon in the sense that it occurs in the same clothing for both weakly and strongly coupled systems, allows one to obtain excellent agreement between the numerical simulations and the strong-coupling calculations.", "output": {"entities": {}}, "schema": []}
{"input": "pH-controlled nanoaggregation in amphiphilic polymer co-networks.", "output": {"entities": {}}, "schema": []}
{"input": "Domain formation and control in pH-responsive amphiphilic polymer co-networks are studied theoretically.", "output": {"entities": {}}, "schema": []}
{"input": "Two different molecular architectures of the polymer network are considered, depending on whether the pH-sensitive motif is borne by the hydrophobic or the hydrophilic monomer.", "output": {"entities": {}}, "schema": []}
{"input": "When the hydrophobic polymer contains acidic groups, such chains form nanometric aggregates at acidic conditions, but they are found in a swollen state at alkaline pH.", "output": {"entities": {}}, "schema": []}
{"input": "At intermediate pH, the nanoaggregation behavior of the hydrophobic polymer depends critically on the environment salt concentration.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, our results indicate the presence of microphase separation into domains of swollen and aggregated hydrophobic chains.", "output": {"entities": {}}, "schema": []}
{"input": "If the hydrophilic polymer is the ionizable component of the network, the nanoaggregation of hydrophobic monomers is weakly dependent on the pH and salt concentration, and except at very low volume fraction, the aggregate is the most probable conformation of the network in the entire range of pH and salt concentration studied.", "output": {"entities": {}}, "schema": []}
{"input": "The two different hydrogels display quantitatively similar swelling transition and apparent pKa, but at the nanoscale, their behavior is qualitatively different.", "output": {"entities": {}}, "schema": []}
{"input": "The spatial distribution of electric charge on the network as well as the local density of the different chemical species within the hydrogel can be controlled, as a function of pH and salt concentration, by the molecular architecture of the polymer network.", "output": {"entities": {}}, "schema": []}
{"input": "These findings have relevance for applications in biomaterials and nanotechnology, in particular, in the design of oral delivery devices for the administration of hydrophobic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Isolation, characterization, cloning and expression of an alpha-neurotoxin from the venom of the Mexican coral snake Micrurus laticollaris (Squamata: Elapidae).", "output": {"entities": {}}, "schema": []}
{"input": "A new member of short chain alpha-neurotoxic protein family from venom of the Mexican coral snake, Micrurus laticollaris, was characterized.", "output": {"entities": {}}, "schema": []}
{"input": "This protein, named MlatA1, possesses 61 amino acids with 8 conserved cysteine residues, sharing 30-91% sequence identity with other fully sequenced Micrurus toxins.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 41, "end": 52}, {"text": "cysteine", "start": 70, "end": 78}]}}, "schema": []}
{"input": "MlatA1 (LD50i. v. = 0. 064 mg/kg) antagonizes with both fetal and adult nicotinic acetylcholine receptor (nAChR) as well as alpha-7 neuronal nAChR in a dose-dependent way.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 82, "end": 95}]}}, "schema": []}
{"input": "Specific rabbit anti-Mlat serum (titer higher than 18, 000) does not show any protective ability against this toxin, nevertheless it was able to recognize protein bands in six out of twelve Micrurus venoms showing the existence of two distinct antigenic groups for alpha-neurotoxins in North American coral snakes species.", "output": {"entities": {}}, "schema": []}
{"input": "The MlatA1 gene was cloned and used to produce recombinant toxin (rMlatA1) that was recognized by rabbit anti-native toxin but was depleted of toxic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Rare-variant genome-wide association studies: a new frontier in genetic analysis of complex traits.", "output": {"entities": {}}, "schema": []}
{"input": "Genome-wide association studies have, in the last few years, identified thousands of common genetic variants associated with common complex traits and diseases, implicating many genes not previously known to be involved in the biology of those traits.", "output": {"entities": {}}, "schema": []}
{"input": "However, these variants have so far explained little of the population variance in trait values or disease susceptibility.", "output": {"entities": {}}, "schema": []}
{"input": "As large-scale genome sequencing efforts have revealed the extent of genetic variation at the low end of the frequency range in human populations, the effects of rare variants have been proposed as an explanation of the' missing genetic variance.' Improved technologies for genotyping rare variants, including inexpensive whole-genome and whole-exome sequencing and rare-variant genotyping chips, coupled with novel analytical methods, are making genome-wide scans for the effects of rare variants possible, and seem likely to usher in a new era in the genetic analysis of complex traits.", "output": {"entities": {}}, "schema": []}
{"input": "Does Microsecond Sugar Ring Flexing Encode 3D-Shape and Bioactivity in the Heparanome?", "output": {"entities": {"chemical": [{"text": "Sugar", "start": 17, "end": 22}]}}, "schema": []}
{"input": "The biological information encoded in carbohydrate sequences dwarfs that of proteins and nucleic acids.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 38, "end": 50}]}}, "schema": []}
{"input": "Deciphering structure-function relationships in heparin and heparan sulfate (the heparanome) is further compounded by extreme sequence diversity, experimental difficulties, and the computational cost of rigorous modeling.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 68, "end": 75}]}}, "schema": []}
{"input": "Here we perform unbiased microsecond dynamics simulations of 11 heparanome oligosaccharides (55 microseconds total) to investigate the effect of sequence on 3D-structure and to underpin a coarse-grained model that is consistent with long-time scale experimentally validated atomic motions in water.", "output": {"entities": {}}, "schema": []}
{"input": "Pyranose ring flexing (puckering) in 2-O-sulfo-alpha-l-iduronic acid, which underlies heparin-mediated anticoagulation, was modulated by polymerization (chain position and adjacent residues), which is supported by previous experiments.", "output": {"entities": {"chemical": [{"text": "Pyranose", "start": 0, "end": 8}, {"text": "2-O-sulfo-alpha-l-iduronic acid", "start": 37, "end": 68}]}}, "schema": []}
{"input": "Furthermore, in coarse-grained simulations, inclusion of puckering was essential to predict macroscopic hydrodynamic properties of heparan sulfate chains containing hundreds of monosaccharaides.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 139, "end": 146}, {"text": "monosaccharaides", "start": 177, "end": 193}]}}, "schema": []}
{"input": "Our structural findings and model enable rational molecular design, and we propose that, in the heparanome, puckering, polymer 3D-shape, and bioactivity are inextricably linked.", "output": {"entities": {}}, "schema": []}
{"input": "Definition of formulation design space, in vitro bioactivity and in vivo biodistribution for hydrophilic drug loaded PLGA/PEO-PPO-PEO nanoparticles using OFAT experiments.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 117, "end": 121}, {"text": "PEO-PPO-PEO", "start": 122, "end": 133}]}}, "schema": []}
{"input": "Modified nanoprecipitation method was used for improved incorporation of hydrophilic drug (irinotecan hydrochloride) into the PLGA/PEO-PPO-PEO blended and blended/adsorbed nanoparticles.", "output": {"entities": {"chemical": [{"text": "irinotecan hydrochloride", "start": 91, "end": 115}, {"text": "PLGA", "start": 126, "end": 130}, {"text": "PEO-PPO-PEO", "start": 131, "end": 142}]}}, "schema": []}
{"input": "One factor at a time (OFAT) variation experiments were conducted in order to determine key formulation factors (concentration and volume of drug solution, evaporation rate and PLGA/PEO-PPO-PEO ratio) influencing nanoparticle properties (particle size and size distribution, encapsulation efficiency, drug content, zeta potential, drug dissolution rate, as well as protein binding capacity).", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 176, "end": 180}, {"text": "PEO-PPO-PEO", "start": 181, "end": 192}]}}, "schema": []}
{"input": "The insight into in vivo behavior of prepared nanoparticles and their potential for effective anticancer treatment was gained by performing biodistribution and cell culture studies as part of OFAT experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The mean particle size, mainly dependent upon PLGA/PEO-PPO-PEO ratio, was in the range of 112-125nm, with narrow unimodal distribution (PDI ~ 0. 1).", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 46, "end": 50}, {"text": "PEO-PPO-PEO", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Encapsulation efficiency (32-63%) was impacted by evaporation rate and PLGA/PEO-PPO-PEO ratio.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 71, "end": 75}, {"text": "PEO-PPO-PEO", "start": 76, "end": 87}]}}, "schema": []}
{"input": "Drug content (0. 2-1. 51%) and controlled release properties were related to the influence of all tested formulation factors.", "output": {"entities": {}}, "schema": []}
{"input": "Structural information for the studied nanoparticles was obtained using DSC and FT-IR spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Zeta potential values indicated that presence of PEO-PPO-PEO in the formulations shielded the high surface negative charge of PLGA.", "output": {"entities": {"chemical": [{"text": "PEO-PPO-PEO", "start": 49, "end": 60}, {"text": "PLGA", "start": 126, "end": 130}]}}, "schema": []}
{"input": "PEO-PPO-PEO surface coverage of PLGA/PEO-PPO-PEO blended as well as blended/adsorbed nanoparticles depended upon amount of used PEO-PPO-PEO during preparation procedure and was related to the protein resistant characteristics of nanoparticles.", "output": {"entities": {"chemical": [{"text": "PEO-PPO-PEO", "start": 0, "end": 11}, {"text": "PLGA", "start": 32, "end": 36}, {"text": "PEO-PPO-PEO", "start": 37, "end": 48}, {"text": "PEO-PPO-PEO", "start": 128, "end": 139}]}}, "schema": []}
{"input": "Results from in vivo studies evidenced prolonged blood circulation time of the prepared nanoparticles, while cell culture studies indicated higher in vitro bioefficacy compared to free drug.", "output": {"entities": {}}, "schema": []}
{"input": "Performed experiments defined possible design space and justified further optimization of formulation using experimental design studies.", "output": {"entities": {}}, "schema": []}
{"input": "Potential for preventive effects of cocoa and cocoa polyphenols in cancer.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 52, "end": 63}]}}, "schema": []}
{"input": "Prevention of cancer through the diet is receiving increasing interest, and cocoa because of its polyphenolic compounds has become an important potential chemopreventive and therapeutic natural agent.", "output": {"entities": {"chemical": [{"text": "polyphenolic", "start": 97, "end": 109}]}}, "schema": []}
{"input": "Cocoa and its main polyphenols have been reported to interfere at the initiation, promotion and progression of cancer.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 19, "end": 30}]}}, "schema": []}
{"input": "Cocoa flavonoids have been demonstrated to influence several important biological functions in vitro and in vivo by their free radical scavenging ability or through the regulation of signal transduction pathways to stimulate apoptosis and to inhibit inflammation, cellular proliferation, apoptosis, angiogenesis and metastasis.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 6, "end": 16}]}}, "schema": []}
{"input": "Nevertheless, these molecular mechanisms of action are not completely characterized and many features remain to be elucidated.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this review is to provide insights into the molecular basis of the potential chemopreventive activity of cocoa and its polyphenolic components by summarizing cell culture and animal models studies, as well as interventional and epidemiological studies on humans.", "output": {"entities": {"chemical": [{"text": "polyphenolic", "start": 130, "end": 142}]}}, "schema": []}
{"input": "Biosafety and antioxidant effects of a beverage containing silymarin and arginine.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 73, "end": 81}]}}, "schema": []}
{"input": "A pilot, human intervention cross-over trial.", "output": {"entities": {}}, "schema": []}
{"input": "The study objective was to investigate the potential of a beverage containing silymarin and l-arginine to alter basic physiological and urodynamic parameters in 22 normal healthy men aged 38-59years.", "output": {"entities": {"chemical": [{"text": "l-arginine", "start": 92, "end": 102}]}}, "schema": []}
{"input": "The volunteers drank 500ml/day beverage without silymarin and l-arginine for 10days followed, after a 7-day washout period, by the beverage with 400mg silymarin and 295mg l-arginine for 10days.", "output": {"entities": {"chemical": [{"text": "l-arginine", "start": 62, "end": 72}, {"text": "l-arginine", "start": 171, "end": 181}]}}, "schema": []}
{"input": "Blood and urine samples were collected on days 0, 10 and 27.", "output": {"entities": {}}, "schema": []}
{"input": "The beverages were well-tolerated with no adverse effects.", "output": {"entities": {}}, "schema": []}
{"input": "Most of the biochemical, hematological and urodynamic parameters remained unchanged.", "output": {"entities": {}}, "schema": []}
{"input": "Total antioxidant capacity, total level of antioxidants, lipoperoxidation products (malondialdehyde), advanced oxidation products of proteins in plasma and glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase levels in erythrocytes were not influenced.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 84, "end": 99}, {"text": "glutathione", "start": 156, "end": 167}, {"text": "glutathione", "start": 169, "end": 180}, {"text": "glutathione", "start": 193, "end": 204}, {"text": "superoxide", "start": 216, "end": 226}]}}, "schema": []}
{"input": "Serum gamma-glutamyl transferase, malondialdehyde level and activity of glutathione S-transferase in erythrocytes were lowered at day 27 and the concentration of total plasma SH-groups was higher on day 10.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 34, "end": 49}, {"text": "glutathione S", "start": 72, "end": 85}, {"text": "SH", "start": 175, "end": 177}]}}, "schema": []}
{"input": "Using an ex vivo system, we found that silymarin/silybin at 10-100 mu M is able to adsorb onto human erythrocytes and the complexes displayed antioxidant properties as studied using ex situ square-wave voltammetry.", "output": {"entities": {"chemical": [{"text": "silybin", "start": 49, "end": 56}]}}, "schema": []}
{"input": "The trial showed that silymarin in vivo may protect erythrocytes against oxidative damage.", "output": {"entities": {}}, "schema": []}
{"input": "Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa.", "output": {"entities": {"chemical": [{"text": "sodium metabisulfite", "start": 17, "end": 37}]}}, "schema": []}
{"input": "This study aimed to investigate the effect of ghrelin administration on sulfite induced oxidative and apoptotic changes in rat gastric mucosa.", "output": {"entities": {"chemical": [{"text": "sulfite", "start": 72, "end": 79}]}}, "schema": []}
{"input": "Forty male albino Wistar rats were randomized into control (C), sodium metabisulfite (Na2S2O5) treated (S), ghrelin treated (G) and, Na2S2O5 + ghrelin treated (SG) groups.", "output": {"entities": {"chemical": [{"text": "sodium metabisulfite", "start": 64, "end": 84}, {"text": "Na2S2O5", "start": 86, "end": 93}, {"text": "Na2S2O5", "start": 133, "end": 140}]}}, "schema": []}
{"input": "Sodium metabisulfite (100mg/kg/day) was given by gastric gavage and, ghrelin (20 mu g/kg/day) was given intraperitoneally for 5weeks.", "output": {"entities": {"chemical": [{"text": "Sodium metabisulfite", "start": 0, "end": 20}]}}, "schema": []}
{"input": "Plasma-S-sulfonate level was increased in S and SG groups.", "output": {"entities": {"chemical": [{"text": "S", "start": 7, "end": 8}, {"text": "sulfonate", "start": 9, "end": 18}]}}, "schema": []}
{"input": "Na2S2O5 administration significantly elevated total oxidant status (TOS) levels while depleting total antioxidant status (TAS) levels in gastric mucosa.", "output": {"entities": {"chemical": [{"text": "Na2S2O5", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Ghrelin significantly decreased gastric TOS levels in the SG group compared with the S group.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, TAS levels were found to be higher in SG group in reference to S group.", "output": {"entities": {}}, "schema": []}
{"input": "Na2S2O5 administration also markedly increased the number of apoptotic cells, cleaved caspase-3 and PAR expression (PARP activity indicator) and, decreased Ki67 expression (cell proliferation index) in gastric mucosal cells.", "output": {"entities": {"chemical": [{"text": "Na2S2O5", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Ghrelin treatment decreased the number apoptotic cells, cytochrome C release, PAR and, caspase-3 expressions while increasing Ki67 expression in gastric mucosa exposed to Na2S2O5.", "output": {"entities": {"chemical": [{"text": "Na2S2O5", "start": 171, "end": 178}]}}, "schema": []}
{"input": "In conclusion, we suggest that ghrelin treatment might ameliorate ingested-Na2S2O5 induced gastric mucosal injury stemming from apoptosis and oxidative stress in rats.", "output": {"entities": {"chemical": [{"text": "Na2S2O5", "start": 75, "end": 82}]}}, "schema": []}
{"input": "The development of synthetic antitumour vaccines from mucin glycopeptide antigens.", "output": {"entities": {}}, "schema": []}
{"input": "Based on important cell-biological and biochemical results concerning the structural difference between membrane glycoproteins of normal epithelial cells and epithelial tumour cells, tumour-associated glycopeptide antigens have been chemically synthesised and structurally confirmed.", "output": {"entities": {}}, "schema": []}
{"input": "Glycopeptide structures of the tandem repeat sequence of mucin MUC1 of epithelial tumour cells constitute the most promising tumour-associated antigens.", "output": {"entities": {}}, "schema": []}
{"input": "In order to generate a sufficient immunogenicity of these endogenous structures, usually tolerated by the immune system, these synthetic glycopeptide antigens were conjugated to immune stimulating components: in fully synthetic two-component vaccines either with T-cell peptide epitopes or with Toll-like receptor2 lipopeptide ligands or in three-component vaccines with both these stimulants.", "output": {"entities": {}}, "schema": []}
{"input": "Alternatively, the synthetic glycopeptide antigens were coupled to immune stimulating carrier proteins.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, MUC1 glycopeptide conjugates with Tetanus toxoid proved to be efficient vaccines inducing very strong immune responses in mice.", "output": {"entities": {}}, "schema": []}
{"input": "The antibodies elicited with the fully synthetic vaccines showed selective recognition of the tumour-associated glycopeptides as was shown by neutralisation and micro-array binding experiments.", "output": {"entities": {}}, "schema": []}
{"input": "After booster immunisations, most of the immune responses showed the installation of an immunological memory.", "output": {"entities": {}}, "schema": []}
{"input": "Immunisation with fully synthetic three-component vaccines induced immune reactions with therapeutic effects in terms of reduction of the tumour burden in mice or in killing of tumour cells in culture, while MUC1 glycopeptide-Tetanus toxoid vaccines elicited antibodies in mice which recognised tumour cells in human tumour tissues.", "output": {"entities": {}}, "schema": []}
{"input": "The results achieved so far are considered to be promising for the development of an active immunisation against tumours.", "output": {"entities": {}}, "schema": []}
{"input": "Lab-on-DVD: standard DVD drives as a novel laser scanning microscope for image based point of care diagnostics.", "output": {"entities": {}}, "schema": []}
{"input": "We present a novel \" Lab-on-DVD \" system and demonstrate its capability for rapid and low-cost HIV diagnostics by counting CD4 + cells isolated from whole blood.", "output": {"entities": {}}, "schema": []}
{"input": "We show that a commercial DVD drive can, with certain modifications, be turned into an improved DVD-based laser scanning microscope (DVD-LSM).", "output": {"entities": {}}, "schema": []}
{"input": "The system consists of a multi-layered disposable polymer disc and a modified commercial DVD reader with rotational control for sample handling, temperature control for optimized bioassay, a photodiode array for detection, and software for signal processing and user interface-all the necessary components required for a truly integrated lab-on-a-chip system, with the capability to deliver high-resolution images down to 1 mu m in size.", "output": {"entities": {}}, "schema": []}
{"input": "Using discs modified with antibodies, we specifically captured CD4 + cells from whole blood, demonstrating single cell resolution imaging.", "output": {"entities": {}}, "schema": []}
{"input": "The novel integrated DVD platform with sub-micron image resolution brings, for the first time, affordable cellular diagnostic testing to the point-of-care and should be readily applicable at resource-limited settings.", "output": {"entities": {}}, "schema": []}
{"input": "Vitamin A and retinoid signaling: genomic and non-genomic effects.", "output": {"entities": {"chemical": [{"text": "Vitamin A", "start": 0, "end": 9}, {"text": "retinoid", "start": 14, "end": 22}]}}, "schema": []}
{"input": "Vitamin A or retinol is arguably the most multifunctional vitamin in the human body as it is essential from embryogenesis to adulthood.", "output": {"entities": {"chemical": [{"text": "Vitamin A", "start": 0, "end": 9}, {"text": "retinol", "start": 13, "end": 20}, {"text": "vitamin", "start": 58, "end": 65}]}}, "schema": []}
{"input": "The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs and PPAR beta/delta), polymorphic retinoic acid (RA) response elements and multiple coregulators.", "output": {"entities": {"chemical": [{"text": "vitamin A", "start": 27, "end": 36}, {"text": "all-trans retinoic acid", "start": 82, "end": 105}, {"text": "atRA", "start": 107, "end": 111}, {"text": "retinoic acid", "start": 266, "end": 279}]}}, "schema": []}
{"input": "It also involves extra nuclear and non-transcriptional effects such as the activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of several actors of RA signaling.", "output": {"entities": {}}, "schema": []}
{"input": "However, vitamin A itself proved recently to be active and RARs to be present in the cytosol to regulate translation and cell plasticity.", "output": {"entities": {"chemical": [{"text": "vitamin A", "start": 9, "end": 18}]}}, "schema": []}
{"input": "All these new concepts expand the scope of the biologic functions of vitamin A and RA.", "output": {"entities": {"chemical": [{"text": "vitamin A", "start": 69, "end": 78}]}}, "schema": []}
{"input": "Synthesis and antiproliferative activity evaluation of imidazole-based indeno [1, 2-b] quinoline-9, 11-dione derivatives.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 55, "end": 64}, {"text": "indeno [1, 2-b] quinoline-9, 11-dione", "start": 71, "end": 108}]}}, "schema": []}
{"input": "A series of new imidazole substituted indeno [1, 2-b] quinoline-9, 11-dione derivatives were synthesized and evaluated for their antiproliferative effects on HeLa, LS180, MCF-7 and Jurkat human cancer cell lines.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 16, "end": 25}, {"text": "indeno [1, 2-b] quinoline-9, 11-dione", "start": 38, "end": 75}]}}, "schema": []}
{"input": "Antiproliferative effects were evaluated using MTT assay.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 47, "end": 50}]}}, "schema": []}
{"input": "Prepared compounds exhibited weak to good antiproliferative activity in evaluated cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Prepared compounds were more potent in Jurkat cell line when compared to LS180, HeLa and MCF-7 cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 29 (IC16 = 0. 7 mu M) and 31 (IC16 = 1. 7 mu M) and 33 (IC16 = 1. 7 mu M) were found to be the most potent molecules on Jurkat cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover; it was found that some of the tested compounds bearing imidazole-2-yl moiety on the C11-position of dihydropyridine ring exhibited superior antiproliferative activity in comparison to cis-platin especially in Jurkat cell line (compounds 29, 31, and 33).", "output": {"entities": {"chemical": [{"text": "imidazole-2-yl", "start": 65, "end": 79}, {"text": "dihydropyridine", "start": 110, "end": 125}, {"text": "cis-platin", "start": 194, "end": 204}]}}, "schema": []}
{"input": "It seemed that the introduction of electron-withdrawing groups on the imidazole ring enhanced the antiproliferative potential of these compounds (compounds 27, 29 and 31).", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 70, "end": 79}]}}, "schema": []}
{"input": "The results of this study proposed that some of the imidazole substituted indeno [1, 2-b] quinoline-9, 11-dione compounds may act as efficient anticancer agents in vitro, emphasizing their potential role as a source for rational design of potent antiproliferative agents.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 52, "end": 61}, {"text": "indeno [1, 2-b] quinoline-9, 11-dione", "start": 74, "end": 111}]}}, "schema": []}
{"input": "Epigenetic regulation of hypoxia inducible factor in diseases and therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Hypoxia-inducible factors (HIFs) are master regulators of angiogenesis and cellular adaptation in hypoxic microenvironments.", "output": {"entities": {}}, "schema": []}
{"input": "Accumulating evidence indicates that HIFs also regulate cell survival, glucose metabolism, microenvironmental remodeling, cancer metastasis, and tumor progression, and thus, HIFs are viewed as therapeutic targets in many diseases.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 71, "end": 78}]}}, "schema": []}
{"input": "Epigenetic changes are involved in the switching' on' and' off' of many genes, and it has been suggested that the DNA hypermethylation of specific gene promoters, histone modifications (acetylation, phosphorylation, and methylation) and small interfering or micro RNAs be regarded epigenetic gene targets for the regulation of disease-associated cellular changes.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the hypoxic microenvironment is one of the most important cellular stress stimuli in terms of the regulation of cellular epigenetic status via histone modification.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, drug development and therapeutic approaches to ischemic diseases or cancer for targeting HIFs by modulation of epigenetic status become an attractive area.", "output": {"entities": {}}, "schema": []}
{"input": "Here, the authors provide a review of the literature regarding the targeting of HIF, a key modulator of hypoxic-cell response under various disease conditions, by modulating histone or DNA using endogenous small RNAs or exogenous chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Unraveling a municipal effluent' s toxicity to Tripneustes gratilla sperm fertilization.", "output": {"entities": {}}, "schema": []}
{"input": "A tiered investigative approach was employed to characterize and identify substances responsible for the persistent toxicity of a primary-treated municipal effluent to gametes of the Hawaiian sea urchin, Tripneustes gratilla.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicity identification evaluation (TIE) procedures from the US Environmental Protection Agency were modified to account for the tolerance of T. gratilla gametes to various sample manipulations.", "output": {"entities": {}}, "schema": []}
{"input": "Microtox rapid toxicity screening was applied in some aspects of the study after verifying a correlation between the pattern of toxic responses of T. gratilla gametes and that of the bioluminescent bacteria Vibrio fischeri.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicity identification evaluation phase I manipulations revealed a toxicity profile implicating surfactants as possible toxicants, and TIE phase II toxicity assessment of isolated fractions coupled with colorimetric surfactant analyses confirmed the possible role of surfactants in effluent toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The toxic effects of standard reference surfactants on T. gratilla fertilization indicated a concordance with the effects of the more nonpolar effluent fractions.", "output": {"entities": {}}, "schema": []}
{"input": "Treatability studies showed that biodegradation by activated sludge eliminated effluent toxicity to urchin gametes.", "output": {"entities": {}}, "schema": []}
{"input": "Environ Toxicol Chem 2013; 32: 1382-1387.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Phase stability and elastic properties of chromium borides with various stoichiometries.", "output": {"entities": {"chemical": [{"text": "chromium borides", "start": 42, "end": 58}]}}, "schema": []}
{"input": "Phase stability is important to the application of materials.", "output": {"entities": {}}, "schema": []}
{"input": "By first-principles calculations, we establish the phase stability of chromium borides with various stoichiometries.", "output": {"entities": {"chemical": [{"text": "chromium borides", "start": 70, "end": 86}]}}, "schema": []}
{"input": "Moreover, the phases of CrB3 and CrB4 have been predicted by using a newly developed particle swarm optimization (PSO) algorithm.", "output": {"entities": {"chemical": [{"text": "CrB3", "start": 24, "end": 28}, {"text": "CrB4", "start": 33, "end": 37}]}}, "schema": []}
{"input": "Formation enthalpy-pressure diagrams reveal that the MoB-type structure is more energetically favorable than the TiI-type structure for CrB.", "output": {"entities": {"chemical": [{"text": "MoB", "start": 53, "end": 56}, {"text": "TiI", "start": 113, "end": 116}, {"text": "CrB", "start": 136, "end": 139}]}}, "schema": []}
{"input": "For CrB2, the WB2-type structure is preferred at zero pressure.", "output": {"entities": {"chemical": [{"text": "CrB2", "start": 4, "end": 8}, {"text": "WB2", "start": 14, "end": 17}]}}, "schema": []}
{"input": "The predicted new phase of CrB3 belongs to the hexagonal P-6m2 space group and it transforms into an orthorhombic phase as the pressure exceeds 93 GPa.", "output": {"entities": {"chemical": [{"text": "CrB3", "start": 27, "end": 31}]}}, "schema": []}
{"input": "The predicted CrB4 (space group: Pnnm) phase is more energetically favorable than the previously proposed Immm structure.", "output": {"entities": {"chemical": [{"text": "CrB4", "start": 14, "end": 18}]}}, "schema": []}
{"input": "The mechanical and thermodynamic stabilities of predicted CrB3 and CrB4 are verified by the calculated elastic constants and formation enthalpies.", "output": {"entities": {"chemical": [{"text": "CrB3", "start": 58, "end": 62}, {"text": "CrB4", "start": 67, "end": 71}]}}, "schema": []}
{"input": "The full phonon dispersion calculations confirm the dynamic stability of WB2-type CrB2 and predicted CrB3.", "output": {"entities": {"chemical": [{"text": "WB2", "start": 73, "end": 76}, {"text": "CrB2", "start": 82, "end": 86}, {"text": "CrB3", "start": 101, "end": 105}]}}, "schema": []}
{"input": "The large shear moduli, large Young' s moduli, low Poisson ratios, and low bulk and shear modulus ratios of CrB4 <F8FF> PSC and CrB4 <F8FF> PSD indicate that they are potential hard materials.", "output": {"entities": {"chemical": [{"text": "CrB4", "start": 108, "end": 112}, {"text": "CrB4", "start": 128, "end": 132}]}}, "schema": []}
{"input": "Analyses of Debye temperature, electronic localization function, and electronic structure provide further understanding of the chemical and physical properties of these borides.", "output": {"entities": {}}, "schema": []}
{"input": "Mussel-inspired histidine-based transient network metal coordination hydrogels.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 16, "end": 25}]}}, "schema": []}
{"input": "Transient network hydrogels cross-linked through histidine-divalent cation coordination bonds were studied by conventional rheologic methods using histidine-modified star poly (ethylene glycol) (PEG) polymers.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 49, "end": 58}, {"text": "histidine", "start": 147, "end": 156}, {"text": "poly (ethylene glycol)", "start": 171, "end": 193}, {"text": "PEG", "start": 195, "end": 198}]}}, "schema": []}
{"input": "These materials were inspired by the mussel, which is thought to use histidine-metal coordination bonds to impart self-healing properties in the mussel byssal thread.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 69, "end": 78}]}}, "schema": []}
{"input": "Hydrogel viscoelastic mechanical properties were studied as a function of metal, pH, concentration, and ionic strength.", "output": {"entities": {}}, "schema": []}
{"input": "The equilibrium metal-binding constants were determined by dilute solution potentiometric titration of monofunctional histidine-modified methoxy-PEG and were found to be consistent with binding constants of small molecule analogs previously studied.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 118, "end": 127}, {"text": "methoxy-PEG", "start": 137, "end": 148}]}}, "schema": []}
{"input": "pH-dependent speciation curves were then calculated using the equilibrium constants determined by potentiometric titration, providing insight into the pH dependence of histidine-metal ion coordination and guiding the design of metal coordination hydrogels.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 168, "end": 177}]}}, "schema": []}
{"input": "Gel relaxation dynamics were found to be uncorrelated with the equilibrium constants measured, but were correlated to the expected coordination bond dissociation rate constants.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative Study of Chromatographic Medium-Associated Mass and Potential Antitumor Activity Loss with Bioactive Extracts.", "output": {"entities": {}}, "schema": []}
{"input": "Natural product drug discovery programs often rely on the use of silica (Si) gel, reversed-phase media, or size-exclusion resins (e. g., RP-C (18), Sephadex LH-20) for compound purification.", "output": {"entities": {"chemical": [{"text": "silica", "start": 65, "end": 71}, {"text": "Si", "start": 73, "end": 75}]}}, "schema": []}
{"input": "The synthetic polymer-based sorbent Diaion HP20SS (cross-linked polystyrene matrix) is used as an alternative to prepare purified natural product libraries.", "output": {"entities": {"chemical": [{"text": "Diaion HP20SS", "start": 36, "end": 49}, {"text": "polystyrene", "start": 64, "end": 75}]}}, "schema": []}
{"input": "To evaluate the impact of chromatographic media on the isolation of biologically active, yet chromatographically unstable natural products, Diaion HP20SS was evaluated side-by-side with normal-phase sorbents for irreversible binding of extract constituents and their effects on bioactivity.", "output": {"entities": {"chemical": [{"text": "Diaion HP20SS", "start": 140, "end": 153}]}}, "schema": []}
{"input": "An array of chemically diverse natural product-rich extracts was selected as a test panel, and a cell-based reporter assay for hypoxia-inducible factor-1 (HIF-1) was employed to monitor potential change (s) in bioactivity.", "output": {"entities": {}}, "schema": []}
{"input": "Silica gel caused significant irreversible binding of three out of 10 extracts.", "output": {"entities": {}}, "schema": []}
{"input": "Curcuma longa, Saururus cernuus, and Citrus reticulata extracts showed decreased HIF-1 inhibitory activity after elution through Si gel.", "output": {"entities": {"chemical": [{"text": "Si", "start": 129, "end": 131}]}}, "schema": []}
{"input": "An additional nonpolar column wash of HP20SS with EtOAc retained considerable bioactivities of active extracts.", "output": {"entities": {"chemical": [{"text": "HP20SS", "start": 38, "end": 44}, {"text": "EtOAc", "start": 50, "end": 55}]}}, "schema": []}
{"input": "In general, Si gel produced the greatest loss of bioactivity.", "output": {"entities": {"chemical": [{"text": "Si", "start": 12, "end": 14}]}}, "schema": []}
{"input": "However, HP20SS elution reduced significantly HIF-1 inhibitory activity of certain extracts (e. g., Asimina triloba).", "output": {"entities": {"chemical": [{"text": "HP20SS", "start": 9, "end": 15}]}}, "schema": []}
{"input": "A new pentacyclic phenol and other constituents from the root bark of Bauhinia racemosa Lamk.", "output": {"entities": {"chemical": [{"text": "pentacyclic phenol", "start": 6, "end": 24}]}}, "schema": []}
{"input": "This work reported the isolation of one unknown (1) and 10 known compounds (2-11) from the root bark of Bauhinia racemosa Lamk.", "output": {"entities": {}}, "schema": []}
{"input": "(family: Caesalpiniaceae).", "output": {"entities": {}}, "schema": []}
{"input": "Racemosolone (1) was characterised as a pentacyclic phenolic compound possessing an unusual skeleton with a cycloheptane ring and a rare furopyran moiety.", "output": {"entities": {"chemical": [{"text": "Racemosolone", "start": 0, "end": 12}, {"text": "pentacyclic phenolic", "start": 40, "end": 60}, {"text": "cycloheptane", "start": 108, "end": 120}, {"text": "furopyran", "start": 137, "end": 146}]}}, "schema": []}
{"input": "The structure elucidation was carried out on the basis of UV, infrared (IR), HR-ESI-MS, 1D and 2D NMR spectra and finally confirmed by the single crystal X-ray analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The known compounds were characterised as n-tetracosane, beta-sitosteryl stearate, eicosanoic acid, stigmasterol, beta-sitosterol, racemosol, octacosyl ferulate, de-O-methyl racemosol, lupeol and 1, 7, 8, 12b-tetrahydro-2, 2, 4-trimethyl-2H-benzo [6, 7] cyclohepta [1, 2, 3-de] [1] benzopyran-5, 10, 11 triol on the basis of spectroscopic data comparison with the literature value.", "output": {"entities": {"chemical": [{"text": "n-tetracosane", "start": 42, "end": 55}, {"text": "beta-sitosteryl stearate", "start": 57, "end": 81}, {"text": "eicosanoic acid", "start": 83, "end": 98}, {"text": "stigmasterol", "start": 100, "end": 112}, {"text": "beta-sitosterol", "start": 114, "end": 129}, {"text": "racemosol", "start": 131, "end": 140}, {"text": "octacosyl ferulate", "start": 142, "end": 160}, {"text": "de-O-methyl racemosol", "start": 162, "end": 183}, {"text": "lupeol", "start": 185, "end": 191}, {"text": "1, 7, 8, 12b-tetrahydro-2, 2, 4-trimethyl-2H-benzo [6, 7] cyclohepta [1, 2, 3-de] [1] benzopyran-5, 10, 11 triol", "start": 196, "end": 308}]}}, "schema": []}
{"input": "Compounds with skeleton similar to 1 have never been reported from any natural or other source.", "output": {"entities": {}}, "schema": []}
{"input": "Spur reactions observed by picosecond pulse radiolysis in highly concentrated bromide aqueous solutions.", "output": {"entities": {"chemical": [{"text": "bromide", "start": 78, "end": 85}]}}, "schema": []}
{"input": "The formation of the well-known product Br3 (-), observed in the steady-state radiolysis of highly concentrated Br (-) aqueous solutions, has now been directly observed at ultrashort times corresponding to the relaxation of the spur.", "output": {"entities": {"chemical": [{"text": "Br3 (-)", "start": 40, "end": 47}, {"text": "Br (-)", "start": 112, "end": 118}]}}, "schema": []}
{"input": "The transient absorption induced by picosecond pulse radiolysis of 6 M Br (-) aqueous solution was probed simultaneously at 260 nm with the third harmonic laser wave and from 350 to 750 nm with a supercontinuum generated by the fundamental laser wave.", "output": {"entities": {"chemical": [{"text": "Br (-)", "start": 71, "end": 77}]}}, "schema": []}
{"input": "This approach allows several transient radiolytic species to be followed in parallel, particularly the solvated electron, BrOH (-*), Br2 (-*), and Br3 (-).", "output": {"entities": {"chemical": [{"text": "BrOH (-*)", "start": 122, "end": 131}, {"text": "Br2 (-*)", "start": 133, "end": 141}, {"text": "Br3 (-)", "start": 147, "end": 154}]}}, "schema": []}
{"input": "The kinetics measured within 4 ns at 260 and 370 nm clearly exhibit that the decay of Br2 (*-) is correlated with the formation of Br3 (-).", "output": {"entities": {"chemical": [{"text": "Br2 (*-)", "start": 86, "end": 94}, {"text": "Br3 (-)", "start": 131, "end": 138}]}}, "schema": []}
{"input": "In highly concentrated Br (-) solutions, the OH (*) radical is fully replaced by Br2 (*-), and the spur kinetics of OH (*) radical in pure water is comparable with that of Br2 (-*).", "output": {"entities": {"chemical": [{"text": "Br (-)", "start": 23, "end": 29}, {"text": "OH (*)", "start": 45, "end": 51}, {"text": "Br2 (*-)", "start": 81, "end": 89}, {"text": "OH (*)", "start": 116, "end": 122}, {"text": "Br2 (-*)", "start": 172, "end": 180}]}}, "schema": []}
{"input": "Model calculations indicate that the main OH (*) radical combination product H2O2 in pure water has formation kinetics similar to that of Br3 (-) in 6 M Br (-) solutions.", "output": {"entities": {"chemical": [{"text": "OH (*)", "start": 42, "end": 48}, {"text": "H2O2", "start": 77, "end": 81}, {"text": "Br3 (-)", "start": 138, "end": 145}, {"text": "Br (-)", "start": 153, "end": 159}]}}, "schema": []}
{"input": "Moreover, they point out that oxidation of Br (-) occurs within the electron pulse both by direct energy absorption and by scavenging of the water radical cation, H2O (* +).", "output": {"entities": {"chemical": [{"text": "Br (-)", "start": 43, "end": 49}, {"text": "H2O (* +)", "start": 163, "end": 172}]}}, "schema": []}
{"input": "Nanomechanical properties of proteins and membranes depend on loading rate and electrostatic interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Knowing the dynamic mechanical response of tissue, cells, membranes, proteins, nucleic acids, and carbohydrates to external perturbations is important to understand various biological and biotechnological problems.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 98, "end": 111}]}}, "schema": []}
{"input": "Atomic force microscopy (AFM)-based approaches are the most frequently used nanotechnologies to determine the mechanical properties of biological samples that range in size from microscopic to (sub) nanoscopic.", "output": {"entities": {}}, "schema": []}
{"input": "However, the dynamic nature of biomechanical properties has barely been addressed by AFM imaging.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we characterizethe viscoelastic properties of the native light-driven proton pump bacteriorhodopsin of the purple membrane of Halobacterium salinarum.", "output": {"entities": {}}, "schema": []}
{"input": "Using force-distance curve (F-D)-based AFM we imaged purple membranes while force probing their mechanical response over a wide range of loading rates (from ~ 0. 5 to 100 mu N/s).", "output": {"entities": {}}, "schema": []}
{"input": "Our results show that the mechanical stiffness of protein and membrane increases with the loading rate up to a factor of 10 (from ~ 0. 3 to 3. 2 N/m).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the electrostatic repulsion between AFM tip and sample can alter the mechanical stiffness measured by AFM up to ~ 60% (from ~ 0. 8 to 1. 3 N/m). These findings indicate that the mechanical response of membranes and proteins and probably of other biomolecular systems should be determined at different loading rates to fully understand their properties.", "output": {"entities": {}}, "schema": []}
{"input": "Through the looking glass: adventures in kinase inhibitor design and optimization.", "output": {"entities": {}}, "schema": []}
{"input": "Developing a viable new drug candidate is difficult.", "output": {"entities": {}}, "schema": []}
{"input": "Developing one that is a small molecule kinase inhibitor that binds competitively with respect to ATP with superb selectivity is even more difficult, which makes the design and optimization work described by Jimenez et al.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 98, "end": 101}]}}, "schema": []}
{"input": "(J. Med. Chem., DOI: 10. 1021/jm301465a) particularly remarkable.", "output": {"entities": {}}, "schema": []}
{"input": "They took a lead from a high-throughput screen against protein kinase C theta (PKC theta) through a series of optimization steps, culminating in the demonstration of in vivo activity in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Having identified and improved the hinge-binding \" warhead \" at one end of their lead molecule, they proceeded to use structure-based design tools to guide modification of the other end to enhance selectivity over a closely related isoform of the kinase.", "output": {"entities": {}}, "schema": []}
{"input": "With that accomplished, they used a series of protection and deprotection maneuvers to modify the central portion of the series scaffold to further enhance potency against the target while also improving pharmacokinetic properties.", "output": {"entities": {}}, "schema": []}
{"input": "The project was a success at the preclinical level: oral administration of the ultimate analogue obtained was effective at suppressing interleukin-2 induction in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of Palytoxin Binding to HaCaT Cells Using a Monoclonal Anti-Palytoxin Antibody.", "output": {"entities": {"chemical": [{"text": "Palytoxin", "start": 20, "end": 29}, {"text": "Palytoxin", "start": 77, "end": 86}]}}, "schema": []}
{"input": "Palytoxin (PLTX) is the reference compound for a group of potent marine biotoxins, for which the molecular target is Na +/K +-ATPase.", "output": {"entities": {"chemical": [{"text": "Palytoxin", "start": 0, "end": 9}, {"text": "PLTX", "start": 11, "end": 15}, {"text": "Na +", "start": 117, "end": 121}, {"text": "K +", "start": 122, "end": 125}]}}, "schema": []}
{"input": "Indeed, ouabain (OUA), a potent blocker of the pump, is used to inhibit some PLTX effects in vitro.", "output": {"entities": {"chemical": [{"text": "ouabain", "start": 8, "end": 15}, {"text": "OUA", "start": 17, "end": 20}, {"text": "PLTX", "start": 77, "end": 81}]}}, "schema": []}
{"input": "However, in an effort to explain incomplete inhibition of PLTX cytotoxicity, some studies suggest the possibility of two different binding sites on Na +/K +-ATPase.", "output": {"entities": {"chemical": [{"text": "PLTX", "start": 58, "end": 62}, {"text": "Na +", "start": 148, "end": 152}, {"text": "K +", "start": 153, "end": 156}]}}, "schema": []}
{"input": "Hence, this study was performed to characterize PLTX binding to intact HaCaT keratinocytes and to investigate the ability of OUA to compete for this binding.", "output": {"entities": {"chemical": [{"text": "PLTX", "start": 48, "end": 52}, {"text": "OUA", "start": 125, "end": 128}]}}, "schema": []}
{"input": "PLTX binding to HaCaT cells was demonstrated by immunocytochemical analysis after 10 min exposure.", "output": {"entities": {"chemical": [{"text": "PLTX", "start": 0, "end": 4}]}}, "schema": []}
{"input": "An anti-PLTX monoclonal antibody-based ELISA showed that the binding was saturable and reversible, with a K (d) of 3 x 10-10 M.", "output": {"entities": {"chemical": [{"text": "PLTX", "start": 8, "end": 12}]}}, "schema": []}
{"input": "However, kinetic experiments revealed that PLTX binding dissociation was incomplete, suggesting an additional, OUA-insensitive, PLTX binding site.", "output": {"entities": {"chemical": [{"text": "PLTX", "start": 43, "end": 47}, {"text": "OUA", "start": 111, "end": 114}, {"text": "PLTX", "start": 128, "end": 132}]}}, "schema": []}
{"input": "Competitive experiments suggested that OUA acts as a negative allosteric modulator against high PLTX concentrations (0. 3-1. 0 x 10-7 M) and possibly as a non-competitive antagonist against low PLTX concentrations (0. 1-3. 0 x 10-9 M).", "output": {"entities": {"chemical": [{"text": "OUA", "start": 39, "end": 42}, {"text": "PLTX", "start": 96, "end": 100}, {"text": "PLTX", "start": 194, "end": 198}]}}, "schema": []}
{"input": "Antagonism was supported by PLTX cytotoxicity inhibition at OUA concentrations that displaced PLTX binding (1 x 10-5 M).", "output": {"entities": {"chemical": [{"text": "PLTX", "start": 28, "end": 32}, {"text": "OUA", "start": 60, "end": 63}, {"text": "PLTX", "start": 94, "end": 98}]}}, "schema": []}
{"input": "However, this inhibition was incomplete, supporting the existence of both OUA-sensitive and-insensitive PLTX binding sites.", "output": {"entities": {"chemical": [{"text": "OUA", "start": 74, "end": 77}, {"text": "PLTX", "start": 104, "end": 108}]}}, "schema": []}
{"input": "Correlation of photobleaching, oxidation and metal induced fluorescence quenching of DNA-templated silver nanoclusters.", "output": {"entities": {"chemical": [{"text": "silver", "start": 99, "end": 105}]}}, "schema": []}
{"input": "Few-atom noble metal nanoclusters have attracted a lot of interest due to their potential applications in biosensor development, imaging and catalysis.", "output": {"entities": {}}, "schema": []}
{"input": "DNA-templated silver nanoclusters (AgNCs) are of particular interest as different emission colors can be obtained by changing the DNA sequence.", "output": {"entities": {"chemical": [{"text": "silver", "start": 14, "end": 20}]}}, "schema": []}
{"input": "A popular analytical application is fluorescence quenching by Hg (2 +), where d (10)-d (10) metallophilic interaction has often been proposed for associating Hg (2 +) with nanoclusters.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 62, "end": 70}, {"text": "Hg (2 +)", "start": 158, "end": 166}]}}, "schema": []}
{"input": "However, it cannot explain the lack of response to other d (10) ions such as Zn (2 +) and Cd (2 +).", "output": {"entities": {"chemical": [{"text": "Zn (2 +)", "start": 77, "end": 85}, {"text": "Cd (2 +)", "start": 90, "end": 98}]}}, "schema": []}
{"input": "In our effort to elucidate the quenching mechanism, we studied a total of eight AgNCs prepared by different hairpin DNA sequences; they showed different sensitivity to Hg (2 +), and DNA with a larger cytosine loop size produced more sensitive AgNCs.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 168, "end": 176}, {"text": "cytosine", "start": 200, "end": 208}]}}, "schema": []}
{"input": "In all the cases, samples strongly quenched by Hg (2 +) were also more easily photobleached.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 47, "end": 55}]}}, "schema": []}
{"input": "Light of shorter wavelengths bleached AgNCs more potently, and photobleached samples can be recovered by NaBH4.", "output": {"entities": {"chemical": [{"text": "NaBH4", "start": 105, "end": 110}]}}, "schema": []}
{"input": "Strong fluorescence quenching was also observed with high redox potential metal ions such as Ag (+), Au (3 +), Cu (2 +) and Hg (2 +), but not with low redox potential ions.", "output": {"entities": {"chemical": [{"text": "Ag (+)", "start": 93, "end": 99}, {"text": "Au (3 +)", "start": 101, "end": 109}, {"text": "Cu (2 +)", "start": 111, "end": 119}, {"text": "Hg (2 +)", "start": 124, "end": 132}]}}, "schema": []}
{"input": "Such metal induced quenching cannot be recovered by NaBH4.", "output": {"entities": {"chemical": [{"text": "NaBH4", "start": 52, "end": 57}]}}, "schema": []}
{"input": "Electronic absorption and mass spectrometry studies offered further insights into the oxidation reaction.", "output": {"entities": {}}, "schema": []}
{"input": "Our results correlate many important experimental observations and will fuel the further growth of this field.", "output": {"entities": {}}, "schema": []}
{"input": "Computational drug repositioning: from data to therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Traditionally, most drugs have been discovered using phenotypic or target-based screens.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, their indications are often expanded on the basis of clinical observations, providing additional benefit to patients.", "output": {"entities": {}}, "schema": []}
{"input": "This review highlights computational techniques for systematic analysis of transcriptomics (Connectivity Map, CMap), side effects, and genetics (genome-wide association study, GWAS) data to generate new hypotheses for additional indications.", "output": {"entities": {}}, "schema": []}
{"input": "We also discuss data domains such as electronic health records (EHRs) and phenotypic screening that we consider promising for novel computational repositioning methods.", "output": {"entities": {}}, "schema": []}
{"input": "On the accuracy of explicitly correlated methods to generate potential energy surfaces for scattering calculations and clustering: application to the HCl-He complex.", "output": {"entities": {"chemical": [{"text": "HCl", "start": 150, "end": 153}, {"text": "He", "start": 154, "end": 156}]}}, "schema": []}
{"input": "We closely compare the accuracy of multidimensional potential energy surfaces (PESs) generated by the recently developed explicitly correlated coupled cluster (CCSD (T)-F12) methods in connection with the cc-pVXZ-F12 (X = D, T) and aug-cc-pVTZ basis sets and those deduced using the well-established orbital-based coupled cluster techniques employing correlation consistent atomic basis sets (aug-cc-pVXZ, X = T, Q, 5) and extrapolated to the complete basis set (CBS) limit.", "output": {"entities": {}}, "schema": []}
{"input": "This work is performed on the benchmark rare gas-hydrogen halide interaction (HCl-He) system.", "output": {"entities": {"chemical": [{"text": "hydrogen halide", "start": 49, "end": 64}, {"text": "HCl", "start": 78, "end": 81}, {"text": "He", "start": 82, "end": 84}]}}, "schema": []}
{"input": "These PESs are then incorporated into quantum close-coupling scattering dynamical calculations in order to check the impact of the accuracy of the PES on the scattering calculations.", "output": {"entities": {}}, "schema": []}
{"input": "For this system, we deduced inelastic collisional data including (de-) excitation collisional and pressure broadening cross sections.", "output": {"entities": {}}, "schema": []}
{"input": "Our work shows that the CCSD (T)-F12/aug-cc-pVTZ PES describes correctly the repulsive wall, the van der Waals minimum and long range internuclear distances whereas cc-pVXZ-F12 (X = D, T) basis sets are not diffuse enough for that purposes.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, the collision cross sections deduced from the CCSD (T)-F12/aug-cc-pVTZ PES are in excellent agreement with those obtained with CCSD (T)/CBS methodology.", "output": {"entities": {}}, "schema": []}
{"input": "The position of the resonances and the general shape of these cross sections almost coincide.", "output": {"entities": {}}, "schema": []}
{"input": "Since the cost of the electronic structure computations is reduced by several orders of magnitude when using CCSD (T)-F12/aug-cc-pVTZ compared to CCSD (T)/CBS methodology, this approach can be recommended as an alternative for generation of PESs of molecular clusters and for the interpretation of accurate scattering experiments as well as for a wide production of collisional data to be included in astrophysical and atmospherical models.", "output": {"entities": {}}, "schema": []}
{"input": "Eugenol alters the integrity of cell membrane and acts against the nosocomial pathogen Proteus mirabilis.", "output": {"entities": {"chemical": [{"text": "Eugenol", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Eugenol, a member of the phenylpropanoids class of chemical compounds, is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, and bay leaf.", "output": {"entities": {"chemical": [{"text": "Eugenol", "start": 0, "end": 7}]}}, "schema": []}
{"input": "The antibacterial activity of eugenol and its mechanism of bactericidal action against Proteus mirabilis were evaluated.", "output": {"entities": {"chemical": [{"text": "eugenol", "start": 30, "end": 37}]}}, "schema": []}
{"input": "Treatment with eugenol at their minimum inhibitory concentration [0. 125% (v/v)] and minimum bactericidal concentration [0. 25% (v/v)] reduced the viability and resulted in complete inhibition of P. mirabilis.", "output": {"entities": {"chemical": [{"text": "eugenol", "start": 15, "end": 22}]}}, "schema": []}
{"input": "A strong bactericidal effect on P. mirabilis was also evident, as eugenol inactivated the bacterial population within 30 min exposure.", "output": {"entities": {"chemical": [{"text": "eugenol", "start": 66, "end": 73}]}}, "schema": []}
{"input": "Chemo-attractant property and the observance of highest antibacterial activity at alkaline pH suggest that eugenol can work more effectively when given in vivo.", "output": {"entities": {"chemical": [{"text": "eugenol", "start": 107, "end": 114}]}}, "schema": []}
{"input": "Eugenol inhibits the virulence factors produced by P. mirabilis as observed by swimming motility, swarming behavior and urease activity.", "output": {"entities": {"chemical": [{"text": "Eugenol", "start": 0, "end": 7}]}}, "schema": []}
{"input": "It interacts with cellular membrane of P. mirabilis and makes it highly permeable, forming nonspecific pores on plasma membrane, which in turn directs the release of 260 nm absorbing materials and uptake of more crystal violet from the medium into the cells.", "output": {"entities": {"chemical": [{"text": "crystal violet", "start": 212, "end": 226}]}}, "schema": []}
{"input": "SDS-polyacrylamide gel, scanning electron microscopy and Fourier transform infrared analysis further proves the disruptive action of eugenol on the plasma membrane of P. mirabilis.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 0, "end": 3}, {"text": "polyacrylamide", "start": 4, "end": 18}, {"text": "eugenol", "start": 133, "end": 140}]}}, "schema": []}
{"input": "The findings reveal that eugenol shows an excellent bactericidal activity against P. mirabilis by altering the integrity of cell membrane.", "output": {"entities": {"chemical": [{"text": "eugenol", "start": 25, "end": 32}]}}, "schema": []}
{"input": "miR-7641 modulates the expression of CXCL1 during endothelial differentiation derived from human embryonic stem cells.", "output": {"entities": {}}, "schema": []}
{"input": "MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulate gene expression through binding to 3' untranslated region.", "output": {"entities": {}}, "schema": []}
{"input": "We identified and characterized the novel miRNA, miR-7641, in human mesenchymal stem cells.", "output": {"entities": {}}, "schema": []}
{"input": "The expression of miR-7641 was downregulated during differentiation from human embryonic stem cells to endothelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "The CXCL1, a member of the CXC chemokine family, is known as promoting neovascularization by binding G-protein coupled receptors and is related to endothelial cells biogenesis such as angiogenesis, and it was predicted as target gene of miR-7641 by computerized analysis and the luciferase reporter assay.", "output": {"entities": {}}, "schema": []}
{"input": "The miR-7641 significantly suppressed CXCL1 of transcriptional and post-translational levels.", "output": {"entities": {}}, "schema": []}
{"input": "These data suggest that miR-7641 might be related with differentiation of human endothelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "Phenolic constituents from Parakmeria yunnanensis and their anti-HIV-1 activity.", "output": {"entities": {"chemical": [{"text": "Phenolic", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Three new phenolic compounds, yunnanensins A-C (1-3), together with fourteen known ones (4-17), were isolated from the leaves and stems of Parakmeria yunnanensis.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 10, "end": 18}, {"text": "yunnanensins A-C", "start": 30, "end": 46}]}}, "schema": []}
{"input": "The structures of new compounds were established on the basis of extensive spectroscopic analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Several compounds showed weak anti-HIV-1 activity.", "output": {"entities": {}}, "schema": []}
{"input": "Selective inhibition of an apicoplastic aminoacyl-tRNA synthetase from Plasmodium falciparum.", "output": {"entities": {"chemical": [{"text": "aminoacyl", "start": 40, "end": 49}]}}, "schema": []}
{"input": "The resistance of malaria parasites to available drugs continues to grow, and this makes the need for new antimalarial therapies pressing.", "output": {"entities": {}}, "schema": []}
{"input": "Aminoacyl-tRNA synthetases (ARSs) are essential enzymes and well-established antibacterial targets and so constitute a promising set of targets for the development of new antimalarials.", "output": {"entities": {"chemical": [{"text": "Aminoacyl", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Despite their potential as drug targets, apicoplastic ARSs remain unexplored.", "output": {"entities": {}}, "schema": []}
{"input": "We have characterized the lysylation system of Plasmodium falciparum, and designed, synthesized, and tested a set of inhibitors based on the structure of the natural substrate intermediate: lysyl-adenylate.", "output": {"entities": {"chemical": [{"text": "lysyl-adenylate", "start": 190, "end": 205}]}}, "schema": []}
{"input": "Here we demonstrate that selective inhibition of apicoplastic ARSs is feasible and describe new compounds that that specifically inhibit Plasmodium apicoplastic lysyl-tRNA synthetase and show antimalarial activities in the micromolar range.", "output": {"entities": {"chemical": [{"text": "lysyl", "start": 161, "end": 166}]}}, "schema": []}
{"input": "Pseudo-complementary PNA actuators as reversible switches in dynamic DNA nanotechnology.", "output": {"entities": {}}, "schema": []}
{"input": "The structural reorganization of nanoscale DNA architectures is a fundamental aspect in dynamic DNA nanotechnology.", "output": {"entities": {}}, "schema": []}
{"input": "Commonly, DNA nanoarchitectures are reorganized by means of toehold-expanded DNA sequences in a strand exchange process.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe an unprecedented, toehold-free switching process that relies on pseudo-complementary peptide nucleic acid (pcPNA) by using a mechanism that involves double-strand invasion.", "output": {"entities": {}}, "schema": []}
{"input": "The usefulness of this approach is demonstrated by application of these peptide nucleic acids (PNAs) as switches in a DNA rotaxane architecture.", "output": {"entities": {}}, "schema": []}
{"input": "The monomers required for generating the pcPNA were obtained by an improved synthesis strategy and were incorporated into a PNA actuator sequence as well as into a short DNA strand that subsequently was integrated into the rotaxane architecture.", "output": {"entities": {}}, "schema": []}
{"input": "Alternate addition of a DNA and PNA actuator sequence allowed the multiple reversible switching between a mobile rotaxane macrocycle and a stationary pseudorotaxane state.", "output": {"entities": {}}, "schema": []}
{"input": "The switching occurs in an isothermal process at room temperature and is nearly quantitative in each switching step.", "output": {"entities": {}}, "schema": []}
{"input": "pcPNAs can potentially be combined with light-and toehold-based switches, thus broadening the toolbox of orthogonal switching approaches for DNA architectures that open up new avenues in dynamic DNA nanotechnology.", "output": {"entities": {}}, "schema": []}
{"input": "The neonicotinoid imidacloprid shows high chronic toxicity to mayfly nymphs.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 18, "end": 30}]}}, "schema": []}
{"input": "The present study evaluated the acute and chronic toxicity of imidacloprid to a range of freshwater arthropods.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 62, "end": 74}]}}, "schema": []}
{"input": "Mayfly and caddisfly species were most sensitive to short-term imidacloprid exposures (10 tests), whereas the mayflies showed by far the most sensitive response to long-term exposure of all seven arthropod species tested (28-d EC10 values of approximately 0. 03 micro g/L).", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 63, "end": 75}]}}, "schema": []}
{"input": "The results indicated a high aquatic risk of chronic exposure of imidacloprid to mayflies.", "output": {"entities": {"chemical": [{"text": "imidacloprid", "start": 65, "end": 77}]}}, "schema": []}
{"input": "Environ.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicol.", "output": {"entities": {}}, "schema": []}
{"input": "Chem.", "output": {"entities": {}}, "schema": []}
{"input": "2013; 32: 1096-1100.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 SETAC.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetics of modified-release prednisone tablets in healthy subjects and patients with rheumatoid arthritis.", "output": {"entities": {"chemical": [{"text": "prednisone", "start": 37, "end": 47}]}}, "schema": []}
{"input": "In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain.", "output": {"entities": {}}, "schema": []}
{"input": "Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients.", "output": {"entities": {}}, "schema": []}
{"input": "Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night.", "output": {"entities": {"chemical": [{"text": "prednisone", "start": 17, "end": 27}]}}, "schema": []}
{"input": "Single-center crossover studies were conducted, each in <= 24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability.", "output": {"entities": {"chemical": [{"text": "prednisone", "start": 159, "end": 169}, {"text": "prednisone", "start": 187, "end": 197}]}}, "schema": []}
{"input": "There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C (max) 97%, AUC (0-infinity) 101%, 90% confidence intervals within the requisite range for bioequivalence).", "output": {"entities": {}}, "schema": []}
{"input": "Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22: 00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.", "output": {"entities": {"chemical": [{"text": "prednisone", "start": 81, "end": 91}]}}, "schema": []}
{"input": "Modification of the Catalytic Function of Human Hydroxysteroid Sulfotransferase hSULT2A1 by Formation of Disulfide Bonds.", "output": {"entities": {"chemical": [{"text": "Hydroxysteroid", "start": 48, "end": 62}, {"text": "Disulfide", "start": 105, "end": 114}]}}, "schema": []}
{"input": "The human cytosolic sulfotransferase hSULT2A1 catalyzes the sulfation of a broad range of xenobiotics, as well as endogenous hydroxysteroids and bile acids.", "output": {"entities": {"chemical": [{"text": "hydroxysteroids", "start": 125, "end": 140}, {"text": "bile acids", "start": 145, "end": 155}]}}, "schema": []}
{"input": "Reversible modulation of the catalytic activity of this enzyme could play important roles in its physiologic functions.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas other mammalian sulfotransferases are known to be reversibly altered by changes in their redox environment, this has not been previously shown for hSULT2A1.", "output": {"entities": {}}, "schema": []}
{"input": "We have examined the hypothesis that the formation of disulfide bonds in hSULT2A1 can reversibly regulate the catalytic function of the enzyme.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 54, "end": 63}]}}, "schema": []}
{"input": "Three thiol oxidants were used as model compounds to investigate their effects on homogeneous preparations of hSULT2A1: glutathione disulfide, 5, 5'-dithiobis (2-nitrobenzoic acid), and 1, 1'-azobis (N, N-dimethylformamide) (diamide).", "output": {"entities": {"chemical": [{"text": "thiol", "start": 6, "end": 11}, {"text": "glutathione disulfide", "start": 120, "end": 141}, {"text": "5, 5'-dithiobis (2-nitrobenzoic acid)", "start": 143, "end": 180}, {"text": "1, 1'-azobis (N, N-dimethylformamide", "start": 186, "end": 222}, {"text": "diamide", "start": 225, "end": 232}]}}, "schema": []}
{"input": "Examination of the effects of disulfide bond formation with these agents indicated that the activity of the enzyme is reversibly altered.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 30, "end": 39}]}}, "schema": []}
{"input": "Studies on the kinetics of the hSULT2A1-catalyzed sulfation of dehydroepiandrosterone (DHEA) showed the effects of disulfide bond formation on the substrate inhibition characteristics of the enzyme.", "output": {"entities": {"chemical": [{"text": "dehydroepiandrosterone", "start": 63, "end": 85}, {"text": "DHEA", "start": 87, "end": 91}, {"text": "disulfide", "start": 115, "end": 124}]}}, "schema": []}
{"input": "The effects of these agents on the binding of substrates and products, liquid chromatography-mass spectrometry identification of the disulfides formed, and structural modeling of the modified enzyme were examined.", "output": {"entities": {"chemical": [{"text": "disulfides", "start": 133, "end": 143}]}}, "schema": []}
{"input": "Our results indicate that conformational changes at cysteines near the nucleotide binding site affect the binding of both the nucleotide and DHEA to the enzyme, with the specific effects dependent on the structure of the resulting disulfide.", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 52, "end": 61}, {"text": "nucleotide", "start": 71, "end": 81}, {"text": "nucleotide", "start": 126, "end": 136}, {"text": "DHEA", "start": 141, "end": 145}, {"text": "disulfide", "start": 231, "end": 240}]}}, "schema": []}
{"input": "Thus, the formation of disulfide bonds in hSULT2A1 is a potentially important reversible mechanism for alterations in the rates of sulfation of both endogenous and xenobiotic substrates.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Prokaryotic multicellularity: a nanopore array for bacterial cell communication.", "output": {"entities": {}}, "schema": []}
{"input": "The transition from unicellular to multicellular life, which occurred several times during evolution, requires tight interaction and communication of neighboring cells.", "output": {"entities": {}}, "schema": []}
{"input": "The multicellular cyanobacterium Nostoc punctiforme ATCC 29133 forms filaments of hundreds of interacting cells exchanging metabolites and signal molecules and is able to differentiate specialized cells in response to environmental stimuli.", "output": {"entities": {}}, "schema": []}
{"input": "Mutation of cell wall amidase AmiC2 leads to a severe phenotype with formation of aberrant septa in the distorted filaments, which completely lack cell communication and potential for cell differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate the function of the amidase AmiC2 in formation of cell-joining structures.", "output": {"entities": {}}, "schema": []}
{"input": "The AmiC2 protein localizes to the young septum between cells and shows bona fide amidase activity in vivo and in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Vancomycin staining identified the overall septum morphology in living cells.", "output": {"entities": {"chemical": [{"text": "Vancomycin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "By electron microscopy of isolated peptidoglycan sacculi, the submicroscopic structure of the cell junctions could be visualized, revealing a novel function for a cell wall amidase: AmiC2 drills holes into the cross-walls, forming an array of ~ 155 nanopores with a diameter of ~ 20 nm each.", "output": {"entities": {}}, "schema": []}
{"input": "These nanopores seem to constitute a framework for cell-joining proteins, penetrating the cell wall.", "output": {"entities": {}}, "schema": []}
{"input": "The entire array of junctional nanopores appears as a novel bacterial organelle, establishing multicellularity in a filamentous prokaryote.-Lehner, J., Berendt, S., D o rsam, B., P e rez, R., Forchhammer, K., Maldener, I.", "output": {"entities": {}}, "schema": []}
{"input": "Prokaryotic multicellularity: a nanopore array for bacterial cell communication.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization, pharmacokinetics, tissue distribution and antitumor activity of honokiol submicron lipid emulsions in tumor-burdened mice.", "output": {"entities": {"chemical": [{"text": "honokiol", "start": 82, "end": 90}]}}, "schema": []}
{"input": "Honokiol, isolated from the Chinese traditional herb magnolia, is a poorly water-soluble component and has been found to have anti-tumor properties.", "output": {"entities": {"chemical": [{"text": "Honokiol", "start": 0, "end": 8}]}}, "schema": []}
{"input": "In the current study, honokiol submicron lipid emulsions (HK-SLEs) were prepared by high pressure homogenization technology.", "output": {"entities": {"chemical": [{"text": "honokiol", "start": 22, "end": 30}]}}, "schema": []}
{"input": "After HK-SLEs were physically characterized, their pharmacokinetics, tissue distribution and antitumor activity after intravenous (i. v.) administration to tumor-burdened mice were examined, using honokiol solution (HK-SOL) as the control.", "output": {"entities": {"chemical": [{"text": "honokiol", "start": 197, "end": 205}]}}, "schema": []}
{"input": "The results showed that the mean particle size, zeta potential, pH value, osmolality, drug loading (DL)% and entrapment efficiency (EE)% of HK-SLEs were 186. 6 +/-1. 7 nm,-35. 65 +/-0. 67 mV, 7. 22 +/-0. 26, 298 +/-2. 3 mOsm/L, 7. 1 +/-0. 2% and 95. 5 +/-0. 2%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "HK-SLEs were stable for at least 12 months when stored at 4 +/-2 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacokinetic results showed that the drug concentration-time curves of HK-SLEs and HK-SOL could both be described by an open two-compartment model.", "output": {"entities": {}}, "schema": []}
{"input": "The half-life of HK-SLEs (t1/2 (alpha) = 8. 014 min, t1/2 (beta) = 35. 784 min) was remarkably prolonged compared to that of HK-SOL (t1/2 (alpha) = 4. 318 min, t1/2 (beta) = 15. 522 min).", "output": {"entities": {}}, "schema": []}
{"input": "HK-SLEs exhibited a greater AUC and reduced plasma clearance.", "output": {"entities": {}}, "schema": []}
{"input": "The tissue distribution results indicated that HK-SLEs have better targeting properties to lung and tumor tissues compared with those of HK-SOL.", "output": {"entities": {}}, "schema": []}
{"input": "Both HK-SLEs and HK-SOL tended to accumulate in brain tissue.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo study showed that HK-SLEs treatment caused significant inhibition of mouse sarcoma S180 tumor growth compared to HK-SOL.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that HK-SLEs might be an effective parenteral carrier for honokiol delivery in cancer treatment.", "output": {"entities": {"chemical": [{"text": "honokiol", "start": 80, "end": 88}]}}, "schema": []}
{"input": "Membrane Topology of Yeast Alkaline Ceramidase YPC1.", "output": {"entities": {}}, "schema": []}
{"input": "Ypc1p and Ydc1p are alkaline ceramide hydrolases, which reside in the ER.", "output": {"entities": {}}, "schema": []}
{"input": "Ypc1p can catalyze the reverse reaction, i. e. the condensation of free fatty acids with phytosphingosine or dihydrosphingosine and overexpression of YPC1 or YDC1 can provide enough ceramide synthesis as to rescue the viability of cells lacking the normal acyl-CoA-dependent ceramide synthases.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 72, "end": 83}, {"text": "phytosphingosine", "start": 89, "end": 105}, {"text": "dihydrosphingosine", "start": 109, "end": 127}, {"text": "ceramide", "start": 182, "end": 190}, {"text": "acyl-CoA", "start": 256, "end": 264}]}}, "schema": []}
{"input": "To better understand the coexistence of acyl-CoA dependent ceramide synthases and ceramidases in the ER we investigated the membrane topology of Ypc1p by probing cysteine accessibility of natural and substituted cysteines with membrane non-permeating mass-tagged probes.", "output": {"entities": {"chemical": [{"text": "acyl-CoA", "start": 40, "end": 48}, {"text": "ceramide", "start": 59, "end": 67}, {"text": "ceramidases", "start": 82, "end": 93}, {"text": "cysteine", "start": 162, "end": 170}, {"text": "cysteines", "start": 212, "end": 221}]}}, "schema": []}
{"input": "The N-and C-terminal ends of Ypc1p are oriented towards the lumen and cytosol, respectively.", "output": {"entities": {"chemical": [{"text": "N", "start": 4, "end": 5}, {"text": "C", "start": 10, "end": 11}]}}, "schema": []}
{"input": "Two of the 5 natural cysteines, Cys27 and Cys219, are essential for enzymatic activity and form a disulfide bridge.", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 21, "end": 30}, {"text": "disulfide", "start": 98, "end": 107}]}}, "schema": []}
{"input": "The data allow inferring that all amino acids of Ypc1p that are conserved in the pfam PF05875 ceramidase motif and the CREST superfamily are located in or near the ER lumen.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 34, "end": 45}]}}, "schema": []}
{"input": "Microsomal assays using a lysine-specific reagent show that the reverse ceramidase activity can only be blocked when the reagent has access to Ypc1p from the lumenal side.", "output": {"entities": {"chemical": [{"text": "lysine", "start": 26, "end": 32}]}}, "schema": []}
{"input": "Overall the data suggest that the active site of Ypc1p resides at the lumenal side of the ER membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Optoelectronic Functional Materials Based on Alkylated-pi Molecules: Self-Assembled Architectures and Nonassembled Liquids.", "output": {"entities": {}}, "schema": []}
{"input": "The engineering of single molecules into higher-order hierarchical assemblies is a current research focus in molecular materials chemistry.", "output": {"entities": {}}, "schema": []}
{"input": "Molecules containing pi-conjugated units are an important class of building blocks because their self-assembly is not only of fundamental interest, but also the key to fabricating functional systems for organic electronic and photovoltaic applications.", "output": {"entities": {}}, "schema": []}
{"input": "Functionalizing the pi-cores with \" alkyl chains \" is a common strategy in the molecular design that can give the system desirable properties, such as good solubility in organic solvents for solution processing.", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 36, "end": 41}]}}, "schema": []}
{"input": "Moreover, the alkylated-pi system can regulate the self-assembly behavior by fine-tuning the intermolecular forces.", "output": {"entities": {}}, "schema": []}
{"input": "The optimally assembled structures can then exhibit advanced functions.", "output": {"entities": {}}, "schema": []}
{"input": "However, while some general rules have been revealed, a comprehensive understanding of the function played by the attached alkyl chains is still lacking, and current methodology is system-specific in many cases.", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 123, "end": 128}]}}, "schema": []}
{"input": "Better clarification of this issue requires contributions from carefully designed libraries of alkylated-pi molecular systems in both self-assembly and nonassembly materialization strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Here, based on recent efforts toward this goal, we show the power of the alkyl chains in controlling the self-assembly of soft molecular materials and their resulting optoelectronic properties.", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 73, "end": 78}]}}, "schema": []}
{"input": "The design of alkylated-C60 is selected from our recent research achievements, as the most attractive example of such alkylated-pi systems.", "output": {"entities": {"chemical": [{"text": "alkylated-C60", "start": 14, "end": 27}]}}, "schema": []}
{"input": "Some other closely related systems composed of alkyl chains and pi-units are also reviewed to indicate the universality of the methodology.", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 47, "end": 52}]}}, "schema": []}
{"input": "Finally, as a contrast to the self-assembled molecular materials, nonassembled, solvent-free, novel functional liquid materials are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "In doing so, a new journey toward the ultimate organic \" soft \" materials is introduced, based on alkylated-pi molecular design.", "output": {"entities": {}}, "schema": []}
{"input": "Rapid method for the separation and recovery of endocrine-disrupting compound bisphenol AP from wastewater.", "output": {"entities": {"chemical": [{"text": "bisphenol AP", "start": 78, "end": 90}]}}, "schema": []}
{"input": "The removal of bisphenol AP (BPAP) by a multiwalled carbon nanotube (MWCNT) was investigated.", "output": {"entities": {"chemical": [{"text": "bisphenol AP", "start": 15, "end": 27}, {"text": "BPAP", "start": 29, "end": 33}, {"text": "carbon", "start": 52, "end": 58}]}}, "schema": []}
{"input": "BPAP, representing typical scenarios for the BPAP-MWCNT interactions, was employed as a probe molecule.", "output": {"entities": {"chemical": [{"text": "BPAP", "start": 0, "end": 4}, {"text": "BPAP", "start": 45, "end": 49}]}}, "schema": []}
{"input": "It was found that BPAP exhibited great adsorptive affinity to MWCNT, and the adsorption kinetics equilibrium was arrived within 4. 0 min following the pseudo-second-order model.", "output": {"entities": {"chemical": [{"text": "BPAP", "start": 18, "end": 22}]}}, "schema": []}
{"input": "The overall rate process was mainly controlled by the external mass transfer.", "output": {"entities": {}}, "schema": []}
{"input": "The hydrogen bond, hydrophobic, and pi-pi stacking interactions were dominant factors for the strong adsorption of BPAP, instead of the pH ionic strength and other ionic species in contaminated water.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 4, "end": 12}, {"text": "BPAP", "start": 115, "end": 119}]}}, "schema": []}
{"input": "The MWCNT has higher stability within 8 removal-regeneration recycles, and up to 95% of recovery could be obtained by eluting the adsorbed BPAP on MWCNT adsorbent using ethanol/sodium hydrate solution.", "output": {"entities": {"chemical": [{"text": "BPAP", "start": 139, "end": 143}, {"text": "ethanol", "start": 169, "end": 176}, {"text": "sodium hydrate", "start": 177, "end": 191}]}}, "schema": []}
{"input": "The results of the experiment on real samples verified the effectiveness for the recovery and removal of BPAP from wastewater samples.", "output": {"entities": {"chemical": [{"text": "BPAP", "start": 105, "end": 109}]}}, "schema": []}
{"input": "Signaling between Transforming Growth Factor beta (TGF-beta) and Transcription Factor SNAI2 Represses Expression of MicroRNA miR-203 to Promote Epithelial-Mesenchymal Transition and Tumor Metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "TGF-beta promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT).", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the molecular and epigenetic mechanisms by which TGF-beta induces EMT may facilitate the development of new therapeutic strategies for metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report that TGF-beta induced SNAI2 to promote EMT by repressing miR-203.", "output": {"entities": {}}, "schema": []}
{"input": "Although miR-203 targeted SNAI2, SNAI2 induced by TGF-beta could directly bind to the miR-203 promoter to inhibit its transcription.", "output": {"entities": {}}, "schema": []}
{"input": "SNAI2 and miR-203 formed a double negative feedback loop to inhibit each other' s expression, thereby controlling EMT.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, we found that miR-203 was significantly down-regulated in highly metastatic breast cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "The restoration of miR-203 in highly metastatic breast cancer cells inhibited tumor cell invasion in vitro and lung metastatic colonization in vivo by repressing SNAI2.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our results suggest that the SNAI2 and miR-203 regulatory loop plays important roles in EMT and tumor metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "Newer insulin analogs: advances in basal insulin replacement.", "output": {"entities": {}}, "schema": []}
{"input": "Basal insulin analog therapy is the most common method of introducing insulin replacement therapy for the majority of patients with type 2 diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Long-acting insulin analogs provide relatively peakless and more physiologic insulin replacement therapy than neutral protaminated Hagedorn insulin.", "output": {"entities": {}}, "schema": []}
{"input": "Recently 2 new basal insulin analogs have been developed with superior pharmacokinetic and pharmacodynamics properties; insulin degludec and a pegylated insulin lispro.", "output": {"entities": {}}, "schema": []}
{"input": "These agents are generally well tolerated and have been evaluated in both type 1 and type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "In this article we review the results of clinical trials assessing the efficacy, safety and tolerability of these newer longer-acting insulin analogs.", "output": {"entities": {}}, "schema": []}
{"input": "In general rates of hypoglycaemia in these trials were low, glucose control was comparable to currently available basal insulin analogs, and rates of nocturnal hypoglycaemia were significantly and substantially lower.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 60, "end": 67}]}}, "schema": []}
{"input": "While further study will be required, advances in basal insulin replacement may offer important advantages over existing options for starting insulin strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Direct observation of a bent carbonyl ligand in a 19-electron transition metal complex.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 29, "end": 37}, {"text": "transition metal", "start": 62, "end": 78}]}}, "schema": []}
{"input": "The photochemistry of [CpRu (CO) 2] 2 in P (OMe) 3/CH2Cl2 solution has been studied using picosecond time-resolved infrared (TRIR) spectroscopy.", "output": {"entities": {"chemical": [{"text": "[CpRu (CO) 2] 2", "start": 22, "end": 37}, {"text": "P (OMe) 3", "start": 41, "end": 50}, {"text": "CH2Cl2", "start": 51, "end": 57}]}}, "schema": []}
{"input": "Photolysis at 400 nm leads to the formation of 17-electron CpRu (CO) 2 (*) radicals, which react on the picosecond time scale to form 19-electron CpRu (CO) 2P (OMe) 3 (*) adducts.", "output": {"entities": {"chemical": [{"text": "CpRu (CO) 2 (*)", "start": 59, "end": 74}, {"text": "CpRu (CO) 2P (OMe) 3 (*)", "start": 146, "end": 170}]}}, "schema": []}
{"input": "The TRIR spectra of this adduct display an unusually low CO stretching frequency for the antisymmetric CO stretching mode, suggesting that one carbonyl ligand adopts a bent configuration to avoid a 19-electron count at the metal center.", "output": {"entities": {"chemical": [{"text": "CO", "start": 57, "end": 59}, {"text": "CO", "start": 103, "end": 105}, {"text": "carbonyl", "start": 143, "end": 151}]}}, "schema": []}
{"input": "This spectral assignment is supported by analogous experiments on [CpFe (CO) 2] 2 in the same solvent, combined with DFT studies on the structures of the 19-electron adducts.", "output": {"entities": {"chemical": [{"text": "[CpFe (CO) 2] 2", "start": 66, "end": 81}]}}, "schema": []}
{"input": "The DFT results predict a bent CO ligand in CpRu (CO) 2P (OMe) 3 (*), whereas approximately linear Fe-C-O bond angles are predicted for CpFe (CO) 2P (OMe) 3 (*).", "output": {"entities": {"chemical": [{"text": "CO", "start": 31, "end": 33}, {"text": "CpRu (CO) 2P (OMe) 3 (*)", "start": 44, "end": 68}, {"text": "Fe-C-O", "start": 99, "end": 105}, {"text": "CpFe (CO) 2P (OMe) 3 (*)", "start": 136, "end": 160}]}}, "schema": []}
{"input": "The observation of a bent CO ligand in the 19-electron ruthenium adduct is a surprising result, and it provides new insight into the solution-phase behavior of 19-electron complexes.", "output": {"entities": {"chemical": [{"text": "CO", "start": 26, "end": 28}, {"text": "ruthenium", "start": 55, "end": 64}]}}, "schema": []}
{"input": "TRIR spectra were also collected for [CpRu (CO) 2] 2 in neat CH2Cl2, and it is interesting to note that no singly bridged [CpRu (CO)] 2 (mu-CO) photoproduct was observed to form following 400-or 267-nm excitation, despite previous observations of this species on longer time scales.", "output": {"entities": {"chemical": [{"text": "[CpRu (CO) 2] 2", "start": 37, "end": 52}, {"text": "CH2Cl2", "start": 61, "end": 67}, {"text": "[CpRu (CO)] 2 (mu-CO)", "start": 122, "end": 143}]}}, "schema": []}
{"input": "Enzyme responsive hyaluronic Acid nanocapsules containing polyhexanide and their exposure to bacteria to prevent infection.", "output": {"entities": {"chemical": [{"text": "polyhexanide", "start": 58, "end": 70}]}}, "schema": []}
{"input": "Antibacterial nanodevices could bring coatings of plastic materials and wound dressings a big step forward if the release of the antibacterial agents could be triggered by the presence of the bacteria themselves.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that novel hyaluronic acid (HA)-based nanocapsules containing the antimicrobial agent polyhexanide are specifically cleaved in the presence of hyaluronidase, a factor of pathogenicity and invasion for bacteria like Staphylococcus aureus and Escherichia coli.", "output": {"entities": {"chemical": [{"text": "polyhexanide", "start": 100, "end": 112}]}}, "schema": []}
{"input": "This resulted in an efficient killing of the pathogenic bacteria by the antimicrobial agent.", "output": {"entities": {}}, "schema": []}
{"input": "The formation of different polymeric nanocapsules was achieved through a polyaddition reaction in inverse miniemulsion.", "output": {"entities": {}}, "schema": []}
{"input": "After the synthesis, the nanocapsules were transferred to an aqueous medium and investigated in terms of size, size distribution, functionality, and morphology using dynamic light scattering, zeta potential measurements and scanning electron microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "The enzyme triggered release of a model dye and the antimicrobial polyhexanide was monitored using fluorescence and UV spectroscopy.", "output": {"entities": {"chemical": [{"text": "polyhexanide", "start": 66, "end": 78}]}}, "schema": []}
{"input": "The stability of the nanocapsules in several biological media was tested and the interaction of nanocapsules with human serum protein was studied using isothermal titration calorimetry.", "output": {"entities": {}}, "schema": []}
{"input": "The antibacterial effectiveness is demonstrated by determination of the antibacterial activity and determination of the minimal bactericidal concentration (MBC).", "output": {"entities": {}}, "schema": []}
{"input": "Formulation, optimization, in vivo pharmacokinetic, behavioral and biochemical estimations of minocycline loaded chitosan nanoparticles for enhanced brain uptake.", "output": {"entities": {"chemical": [{"text": "minocycline", "start": 94, "end": 105}]}}, "schema": []}
{"input": "The minocycline hydrochloride (MH), at higher doses, is useful in the treatment of neurodegenerative disorders and owing to its antioxidant potential, it may have nootropic effects.", "output": {"entities": {"chemical": [{"text": "minocycline hydrochloride", "start": 4, "end": 29}]}}, "schema": []}
{"input": "MH loaded nanoparticles (MHNP) were coated with tween 80 (cMHNP) to improve its brain uptake followed by their optimization employing two factor-three level (3 (2)) central composite design (CCD) in order to minimize particle size and maximize drug entrapment efficiency (DEE) and validated.", "output": {"entities": {"chemical": [{"text": "tween 80", "start": 48, "end": 56}]}}, "schema": []}
{"input": "The optimized formulations were further subjected to in vitro drug release study; in vivo biodistribution studies in male wistar rats.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacodynamic study was carried out using elevated plus maze (EPM) and Morris water maze (MWM) behavioral models for nootropic activity in swiss albino mice; and biochemical estimations (acetylcholine esterase, reduced glutathione, malondialdehyde and brain nitrite level).", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 193, "end": 206}, {"text": "reduced glutathione", "start": 217, "end": 236}, {"text": "malondialdehyde", "start": 238, "end": 253}, {"text": "nitrite", "start": 264, "end": 271}]}}, "schema": []}
{"input": "After intravenous (i. v.) administration, the concentration of MH in brain of cMHNP (6. 21 +/- 0. 64 micro g/mL) treated rats was significantly higher with MH solution treated (0. 70 +/- 0. 06 micro g/mL) as well as MHNP (1. 03 +/- 0. 12 micro g/mL) treated animals.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacodynamic studies revealed a significant improvement in memory of MH, MHNP and cMHNP treated swiss albino mice than saline treated control group.", "output": {"entities": {}}, "schema": []}
{"input": "However, cMHNP revealed maximum decrease in transfer latency (TL) in EPM and maximum increase in time spent in target quadrant (TSTQ) in MWM.", "output": {"entities": {}}, "schema": []}
{"input": "Although cMHNP did not produce significant change in brain acetylcholinesterase, but, significantly increased reduced glutathione, malondialdehyde and reduced brain nitrite level as compared to saline, MH solution and MHNP treated groups.", "output": {"entities": {"chemical": [{"text": "reduced glutathione", "start": 110, "end": 129}, {"text": "malondialdehyde", "start": 131, "end": 146}, {"text": "nitrite", "start": 165, "end": 172}]}}, "schema": []}
{"input": "The results suggest that cMHNP is a promising candidate for improved brain uptake of MH with better nootropic effect.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of 7-methoxy-6-[4-(4-methyl-1, 3-thiazol-2-yl)-1H-imidazol-5-yl]-1, 3-benzothiazole (TASP0382088): a potent and selective transforming growth factor-beta type I receptor inhibitor as a topical drug for alopecia.", "output": {"entities": {"chemical": [{"text": "7-methoxy-6-[4-(4-methyl-1, 3-thiazol-2-yl)-1H-imidazol-5-yl]-1, 3-benzothiazole", "start": 13, "end": 93}, {"text": "TASP0382088", "start": 95, "end": 106}]}}, "schema": []}
{"input": "7-Methoxy-6-[4-(4-methyl-1, 3-thiazol-2-yl)-1H-imidazol-5-yl]-1, 3-benzothiazole 11 (TASP0382088) was synthesized and evaluated as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitor.", "output": {"entities": {"chemical": [{"text": "7-Methoxy-6-[4-(4-methyl-1, 3-thiazol-2-yl)-1H-imidazol-5-yl]-1, 3-benzothiazole", "start": 0, "end": 80}, {"text": "TASP0382088", "start": 85, "end": 96}]}}, "schema": []}
{"input": "Compound 11, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50 = 4. 8 nM) as well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a cellular level (IC50 = 17 nM).", "output": {"entities": {}}, "schema": []}
{"input": "The introduction of a methoxy group to the benzothiazole ring in 1 and the break up of the planarity between the imidazole ring and the thiazole ring improved the solubility in the lotion base of 11.", "output": {"entities": {"chemical": [{"text": "methoxy", "start": 22, "end": 29}, {"text": "benzothiazole", "start": 43, "end": 56}, {"text": "imidazole", "start": 113, "end": 122}, {"text": "thiazole", "start": 136, "end": 144}]}}, "schema": []}
{"input": "Furthermore, the topical application of 3% 11 lotion significantly inhibited Smad2 phosphorylation in mouse skin at 8 h after application (71% inhibition, compared with vehicle-treated animals).", "output": {"entities": {}}, "schema": []}
{"input": "Self-organizing map analysis using multivariate data from theophylline tablets predicted by a thin-plate spline interpolation.", "output": {"entities": {"chemical": [{"text": "theophylline", "start": 58, "end": 70}]}}, "schema": []}
{"input": "The \" quality by design \" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and a design space.", "output": {"entities": {}}, "schema": []}
{"input": "We integrated thin-plate spline (TPS) interpolation and Kohonen' s self-organizing map (SOM) to visualize the latent structure underlying causal factors and pharmaceutical responses.", "output": {"entities": {}}, "schema": []}
{"input": "As a model pharmaceutical product, theophylline tablets were prepared based on a standard formulation.", "output": {"entities": {"chemical": [{"text": "theophylline", "start": 35, "end": 47}]}}, "schema": []}
{"input": "The tensile strength, disintegration time, and stability of these variables were measured as response variables.", "output": {"entities": {}}, "schema": []}
{"input": "These responses were predicted quantitatively based on nonlinear TPS.", "output": {"entities": {}}, "schema": []}
{"input": "A large amount of data on these tablets was generated and classified into several clusters using an SOM.", "output": {"entities": {}}, "schema": []}
{"input": "The experimental values of the responses were predicted with high accuracy, and the data generated for the tablets were classified into several distinct clusters.", "output": {"entities": {}}, "schema": []}
{"input": "The SOM feature map allowed us to analyze the global and local correlations between causal factors and tablet characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study suggest that increasing the proportion of microcrystalline cellulose (MCC) improved the tensile strength and the stability of tensile strength of these theophylline tablets.", "output": {"entities": {"chemical": [{"text": "theophylline", "start": 178, "end": 190}]}}, "schema": []}
{"input": "In addition, the proportion of MCC has an optimum value for disintegration time and stability of disintegration.", "output": {"entities": {}}, "schema": []}
{"input": "Increasing the proportion of magnesium stearate extended disintegration time.", "output": {"entities": {"chemical": [{"text": "magnesium stearate", "start": 29, "end": 47}]}}, "schema": []}
{"input": "Increasing the compression force improved tensile strength, but degraded the stability of disintegration.", "output": {"entities": {}}, "schema": []}
{"input": "This technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulations.", "output": {"entities": {"chemical": [{"text": "theophylline", "start": 123, "end": 135}]}}, "schema": []}
{"input": "Discovery of aromatic components with excellent fragrance properties and biological activities: beta-ionols with antimelanogenetic effects and their asymmetric syntheses.", "output": {"entities": {"chemical": [{"text": "beta-ionols", "start": 96, "end": 107}]}}, "schema": []}
{"input": "Both enantiomers of dihydro-beta-ionol and beta-ionol, contained in the aromatic components of Osmanthus flower and of Hakuto peach, were obtained with high optical purity by lipase-catalyzed kinetic resolution of the racemates.", "output": {"entities": {"chemical": [{"text": "dihydro-beta-ionol", "start": 20, "end": 38}, {"text": "beta-ionol", "start": 43, "end": 53}]}}, "schema": []}
{"input": "It was found that all these enantiomers had different characteristic favorable scents and high antimelanogenetic effects.", "output": {"entities": {}}, "schema": []}
{"input": "The absolute configuration and the enantiomer ratios of dihydro-beta-ionol in the aromatic components of Osmanthus flower and of Hakuto peach were determined.", "output": {"entities": {"chemical": [{"text": "dihydro-beta-ionol", "start": 56, "end": 74}]}}, "schema": []}
{"input": "The asymmetric synthesis of (R)-dihydro-beta-ionol, one of the most valuable raw materials for fragrance and flavor, was performed from inexpensive beta-ionone via lipase-catalyzed dynamic kinetic resolution followed by reduction.", "output": {"entities": {"chemical": [{"text": "(R)-dihydro-beta-ionol", "start": 28, "end": 50}, {"text": "beta-ionone", "start": 148, "end": 159}]}}, "schema": []}
{"input": "Three new orcinol-conjugated hydrolysable tannins from the leaves of Cleyera japonica.", "output": {"entities": {"chemical": [{"text": "orcinol", "start": 10, "end": 17}, {"text": "tannins", "start": 42, "end": 49}]}}, "schema": []}
{"input": "Three new orcinol (3-hydroxy-5-methylphenol)-conjugated hydrolysable tannins, together with two known compounds were isolated from the leaves of Cleyera japonica (CJ), and have been tentatively named cleyeratannin A (1), cleyeratannin B (2) and cleyeratannin C (3).", "output": {"entities": {"chemical": [{"text": "orcinol", "start": 10, "end": 17}, {"text": "3-hydroxy-5-methylphenol", "start": 19, "end": 43}, {"text": "tannins", "start": 69, "end": 76}, {"text": "cleyeratannin A", "start": 200, "end": 215}, {"text": "cleyeratannin B", "start": 221, "end": 236}, {"text": "cleyeratannin C", "start": 245, "end": 260}]}}, "schema": []}
{"input": "The chemical structures of these compounds were elucidated using 1 dimensional (1D)/2D NMR and high resolution FAB-MS, and the absolute configuration was confirmed by circular dichroism (CD).", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate their anti-oxidative activities, 1, 1-diphenyl-2-picrylhydrazyl (DPPH)/free radical scavenging activity and nitroblue tetrazolium (NBT)/superoxide anion scavenging activity were determined.", "output": {"entities": {"chemical": [{"text": "1, 1-diphenyl-2-picrylhydrazyl", "start": 45, "end": 75}, {"text": "DPPH", "start": 77, "end": 81}, {"text": "nitroblue tetrazolium", "start": 120, "end": 141}, {"text": "NBT", "start": 143, "end": 146}, {"text": "superoxide", "start": 148, "end": 158}]}}, "schema": []}
{"input": "ARF represses androgen receptor transactivation in prostate cancer.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 14, "end": 22}]}}, "schema": []}
{"input": "Androgen receptor (AR) signaling is essential for prostate cancer (PCa) development in humans.", "output": {"entities": {"chemical": [{"text": "Androgen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The initiation of prostate malignancy and progression to a castration-resistant stage are largely contributed by the modulation of AR activity through its coregulatory proteins.", "output": {"entities": {}}, "schema": []}
{"input": "We and others previously reported that p14 alternative reading frame (ARF) expression is positively correlated with the disease progression and severity of PCa.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we provide evidence that p14ARF physically interacts with AR and functions as an AR corespressor in both an androgen-dependent and androgen-independent manner.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 114, "end": 122}, {"text": "androgen", "start": 137, "end": 145}]}}, "schema": []}
{"input": "Endogenous ARF (p14ARF in human and p19ARF in mouse) and AR colocalize in both human PCa cells in vitro and PCa tissues of mouse and human in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Overexpression of p14ARF in PCa cells significantly attenuates the activities of androgen response region (ARR2)-probasin and prostate-specific antigen (PSA) promoters.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 81, "end": 89}]}}, "schema": []}
{"input": "The forced expression of p14ARF in cells resulted in a suppression of PSA and NK transcription factor locus 1 (NKX3. 1) expression.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, knockdown of endogenous p14ARF in human PCa cells with short hairpin RNA enhanced AR transactivation activities in a dose-dependent and p53-independent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we demonstrated that p14ARF binds to both the N-terminal domain and the ligand-binding domain of AR, and the human double minute 2 (HDM2)-binding motif of p14ARF is required for the interaction of p14ARF and AR proteins.", "output": {"entities": {"chemical": [{"text": "N", "start": 59, "end": 60}]}}, "schema": []}
{"input": "p14ARF perturbs the androgen-induced interaction between the N terminus and C terminus of AR.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 20, "end": 28}, {"text": "N", "start": 61, "end": 62}, {"text": "C", "start": 76, "end": 77}]}}, "schema": []}
{"input": "Most importantly, we observed that the expression of PSA is reversely correlated with p14ARF in human prostate tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our results reveal a novel function of ARF in modulation of AR transactivation in PCa.", "output": {"entities": {}}, "schema": []}
{"input": "Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen.", "output": {"entities": {"chemical": [{"text": "Ceramide phosphoethanolamine", "start": 0, "end": 28}, {"text": "ethanolamine", "start": 80, "end": 92}]}}, "schema": []}
{"input": "Sphingomyelin (SM) is a vital component of mammalian membranes, providing mechanical stability and a structural framework for plasma membrane organization.", "output": {"entities": {"chemical": [{"text": "Sphingomyelin", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase in the Golgi lumen.", "output": {"entities": {"chemical": [{"text": "phosphocholine", "start": 40, "end": 54}, {"text": "phosphatidylcholine", "start": 60, "end": 79}, {"text": "ceramide", "start": 85, "end": 93}]}}, "schema": []}
{"input": "Drosophila lacks SM and instead synthesizes the SM analogue ceramide phosphoethanolamine (CPE) as the principal membrane sphingolipid.", "output": {"entities": {"chemical": [{"text": "ceramide phosphoethanolamine", "start": 60, "end": 88}, {"text": "CPE", "start": 90, "end": 93}, {"text": "sphingolipid", "start": 121, "end": 133}]}}, "schema": []}
{"input": "The corresponding CPE synthase shares mechanistic features with enzymes mediating phospholipid biosynthesis via the Kennedy pathway.", "output": {"entities": {"chemical": [{"text": "CPE", "start": 18, "end": 21}]}}, "schema": []}
{"input": "Using a functional cloning strategy, we here identified a CDP-ethanolamine: ceramide ethanolamine phosphotransferase as the enzyme responsible for CPE production in Drosophila.", "output": {"entities": {"chemical": [{"text": "CDP", "start": 58, "end": 61}, {"text": "ethanolamine", "start": 62, "end": 74}, {"text": "ceramide ethanolamine", "start": 76, "end": 97}, {"text": "CPE", "start": 147, "end": 150}]}}, "schema": []}
{"input": "CPE synthase constitutes a new branch within the CDP-alcohol phosphotransferase superfamily with homologues in Arthropoda (insects, spiders, mites, scorpions), Cnidaria (Hydra, sea anemones), and Mollusca (oysters) but not in most other animal phyla.", "output": {"entities": {"chemical": [{"text": "CPE", "start": 0, "end": 3}, {"text": "CDP", "start": 49, "end": 52}, {"text": "alcohol", "start": 53, "end": 60}]}}, "schema": []}
{"input": "The enzyme resides in the Golgi complex with its active site facing the lumen, contrary to the membrane topology of other CDP-alcohol phosphotransferases.", "output": {"entities": {"chemical": [{"text": "CDP", "start": 122, "end": 125}, {"text": "alcohol", "start": 126, "end": 133}]}}, "schema": []}
{"input": "Our findings open up an important new avenue to address the biological role of CPE, an enigmatic membrane constituent of a wide variety of invertebrate and marine organisms.", "output": {"entities": {"chemical": [{"text": "CPE", "start": 79, "end": 82}]}}, "schema": []}
{"input": "The gas-phase reaction of methane sulfonic acid with the hydroxyl radical without and with water vapor.", "output": {"entities": {"chemical": [{"text": "methane sulfonic acid", "start": 26, "end": 47}, {"text": "hydroxyl", "start": 57, "end": 65}]}}, "schema": []}
{"input": "The gas phase reaction between methane sulfonic acid (CH3SO3H; MSA) and the hydroxyl radical (HO), without and with a water molecule, was investigated with DFT-B3LYP and CCSD (T)-F12 methods.", "output": {"entities": {"chemical": [{"text": "methane sulfonic acid", "start": 31, "end": 52}, {"text": "CH3SO3H", "start": 54, "end": 61}, {"text": "MSA", "start": 63, "end": 66}, {"text": "hydroxyl", "start": 76, "end": 84}, {"text": "HO", "start": 94, "end": 96}]}}, "schema": []}
{"input": "For the bare reaction we have found two reaction mechanisms, involving proton coupled electron transfer and hydrogen atom transfer processes that produce CH3SO3 and H2O.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 108, "end": 116}, {"text": "CH3SO3", "start": 154, "end": 160}, {"text": "H2O", "start": 165, "end": 168}]}}, "schema": []}
{"input": "We also found a third reaction mechanism involving the double proton transfer process, where the products and reactants are identical.", "output": {"entities": {}}, "schema": []}
{"input": "The computed rate constant for the oxidation process is 8. 3 x 10 (-15) cm (3) s (-1) molecule (-1).", "output": {"entities": {}}, "schema": []}
{"input": "CH3SO3H forms two very stable complexes with water with computed binding energies of about 10 kcal mol (-1).", "output": {"entities": {"chemical": [{"text": "CH3SO3H", "start": 0, "end": 7}]}}, "schema": []}
{"input": "The presence of a single water molecule makes the reaction between CH3SO3H and HO much more complex, introducing a new reaction that consists in the interchange of H2O between HO and CH3SO3H.", "output": {"entities": {"chemical": [{"text": "CH3SO3H", "start": 67, "end": 74}, {"text": "HO", "start": 79, "end": 81}, {"text": "H2O", "start": 164, "end": 167}, {"text": "HO", "start": 176, "end": 178}, {"text": "CH3SO3H", "start": 183, "end": 190}]}}, "schema": []}
{"input": "Our kinetic calculations show that 99. 5% of the reaction involves this interchange of the water molecule and, consequently, water vapor does not play any role in the oxidation reaction of methane sulfonic acid by the hydroxyl radical.", "output": {"entities": {"chemical": [{"text": "methane sulfonic acid", "start": 189, "end": 210}, {"text": "hydroxyl", "start": 218, "end": 226}]}}, "schema": []}
{"input": "Principles of electron capture and transfer dissociation mass spectrometry applied to peptide and protein structure analysis.", "output": {"entities": {}}, "schema": []}
{"input": "This tutorial review describes the principles and practices of electron capture and transfer dissociation (ECD/ETD or ExD) mass spectrometry (MS) employed for peptide and protein structure analysis.", "output": {"entities": {}}, "schema": []}
{"input": "ExD MS relies on interactions between gas phase peptide or protein ions carrying multiple positive charges with either free low-energy (~ 1 eV) electrons (ECD), or with reagent radical anions possessing an electron available for transfer (ETD).", "output": {"entities": {}}, "schema": []}
{"input": "As a result of recent implementation on sensitive, high resolution, high mass accuracy, and liquid chromatography timescale-compatible mass spectrometers, ExD, more specifically, ETD MS has received particular interest in life science research.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to describing the fundamental aspects of ExD radical ion chemistry, this tutorial provides practical guidelines for peptide de novo sequencing with ExD MS, as well as reviews some of the current capabilities and limitations of these techniques.", "output": {"entities": {}}, "schema": []}
{"input": "The merits of ExD MS are discussed primarily within the context of life science research.", "output": {"entities": {}}, "schema": []}
{"input": "New directions in thermoresponsive polymers.", "output": {"entities": {}}, "schema": []}
{"input": "Interest in thermoresponsive polymers has steadily grown over many decades, and a great deal of work has been dedicated to developing temperature sensitive macromolecules that can be crafted into new smart materials.", "output": {"entities": {}}, "schema": []}
{"input": "However, the overwhelming majority of previously reported temperature-responsive polymers are based on poly (N-isopropylacrylamide) (PNIPAM), despite the fact that a wide range of other thermoresponsive polymers have demonstrated similar promise for the preparation of adaptive materials.", "output": {"entities": {"chemical": [{"text": "poly (N-isopropylacrylamide)", "start": 103, "end": 131}, {"text": "PNIPAM", "start": 133, "end": 139}]}}, "schema": []}
{"input": "Herein, we aim to highlight recent results that involve thermoresponsive systems that have not yet been as fully considered.", "output": {"entities": {}}, "schema": []}
{"input": "Many of these (co) polymers represent clear opportunities for advancements in emerging biomedical and materials fields due to their increased biocompatibility and tuneable response.", "output": {"entities": {}}, "schema": []}
{"input": "By highlighting recent examples of newly developed thermoresponsive polymer systems, we hope to promote the development of new generations of smart materials.", "output": {"entities": {}}, "schema": []}
{"input": "Droplet-based lipid bilayer system integrated with microfluidic channels for solution exchange.", "output": {"entities": {}}, "schema": []}
{"input": "This paper proposes a solution exchange of a droplet-based lipid bilayer system, in which the inner solution of a droplet is replaced for the purpose of efficient ion channel analyses.", "output": {"entities": {}}, "schema": []}
{"input": "In our previous report, we successfully recorded the channel conductance of alpha-hemolysin in a bilayer lipid membrane using a droplet contact method that can create a spontaneous lipid bilayer at the interface of contacting droplets; this method is widely used as highly efficient method for preparing planar lipid membranes.", "output": {"entities": {}}, "schema": []}
{"input": "When only pipetting droplets of the solution, this method is highly efficient for preparing lipid membranes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the drawback of droplet-based systems is their inability to exchange the solution within the droplets.", "output": {"entities": {}}, "schema": []}
{"input": "To study the effect of inhibitors and promoters of ion channels in drug discovery, it would be beneficial to conduct a solution exchange of droplets to introduce membrane proteins and to apply or wash-out the chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we propose a droplet contact method that allows for the solution exchange of droplets via microfluidic channels.", "output": {"entities": {}}, "schema": []}
{"input": "We experimentally and numerically investigated the bilayer stability with respect to exchanging flow rates, and then demonstrated a binding assay of an alpha-hemolysin using one of its blockers.", "output": {"entities": {}}, "schema": []}
{"input": "The solution exchange in this system was conducted in less than 20 s without rupturing the membrane.", "output": {"entities": {}}, "schema": []}
{"input": "We believe that the proposed system will enhance the efficiency of ion channel analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Bacteriopheophytin a in the active branch of the reaction center of rhodobacter sphaeroides is not disturbed by the protein matrix as shown by 13C photo-CIDNP MAS NMR.", "output": {"entities": {"chemical": [{"text": "Bacteriopheophytin a", "start": 0, "end": 20}, {"text": "13C", "start": 143, "end": 146}]}}, "schema": []}
{"input": "The electronic structure of bacteriopheophytin a (BPhe a), the primary electron acceptor (Phi A) in photosynthetic reaction centers (RCs) of the purple bacterium Rhodobacter sphaeroides, is investigated by photochemically induced dynamic nuclear polarization (photo-CIDNP) magic-angle spinning (MAS) NMR spectroscopy at atomic resolution.", "output": {"entities": {"chemical": [{"text": "bacteriopheophytin a", "start": 28, "end": 48}, {"text": "BPhe a", "start": 50, "end": 56}]}}, "schema": []}
{"input": "By using various isotope labeling systems, introduced by adding different (13) C selectively labeled delta-aminolevulinic acid precursors in the growing medium of R. sphaeroides wild type (WT), we were able to extract light-induced (13) C NMR signals originating from the primary electron acceptor.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 74, "end": 80}, {"text": "delta-aminolevulinic acid", "start": 101, "end": 126}, {"text": "(13) C", "start": 232, "end": 238}]}}, "schema": []}
{"input": "The assignments are backed by theoretical calculations.", "output": {"entities": {}}, "schema": []}
{"input": "By comparison of these chemical shifts to those obtained from monomeric BPhe a in solution, it is demonstrated that Phi A in the active branch appears to be electronically close to free bacteriopheophytin.", "output": {"entities": {"chemical": [{"text": "BPhe a", "start": 72, "end": 78}, {"text": "bacteriopheophytin", "start": 186, "end": 204}]}}, "schema": []}
{"input": "Hence, there is little effect of the protein surrounding on the cofactor functionally which contributes with its standard redox potential to the electron transfer process that is asymmetric.", "output": {"entities": {}}, "schema": []}
{"input": "Interplay between BDF1 and BDF2 and their roles in regulating the yeast salt stress response.", "output": {"entities": {}}, "schema": []}
{"input": "The homologous genes BDF1 and BDF2 in Saccharomyces cerevisiae encode bromodomain-containing transcription factors.", "output": {"entities": {}}, "schema": []}
{"input": "Although double deletion of BDF1 and BDF2 is lethal, single deletion does not affect cell viability.", "output": {"entities": {}}, "schema": []}
{"input": "The bdf2 increment cells showed normal growth upon salt stress.", "output": {"entities": {}}, "schema": []}
{"input": "However, the absence of Bdf1p resulted in a salt-sensitive phenotype, and the salt sensitivity was suppressed by overexpression of BDF2.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we further demonstrated that BDF2 shows dosage compensation in suppressing the salt sensitivity of bdf1 increment.", "output": {"entities": {}}, "schema": []}
{"input": "None of the tested domains replaced the function of intact Bdf1p.", "output": {"entities": {}}, "schema": []}
{"input": "The 494-626 region in Bdf1p was more important than the other domains for salt resistance.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, Bdf1p negatively regulated the expression of BDF2 by binding its promoter at loci-387 to-48.", "output": {"entities": {}}, "schema": []}
{"input": "However, Bdf2p did not affect the expression of BDF1.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, Bdf1p and its defective functional domain mutants could combine with Bdf2p.", "output": {"entities": {}}, "schema": []}
{"input": "This physical interaction increased the salt tolerance of bdf1 increment.", "output": {"entities": {}}, "schema": []}
{"input": "The mitochondrial dysfunctions caused by BDF1 deletion were restored by overexpression of BDF2 under salt stress conditions.", "output": {"entities": {}}, "schema": []}
{"input": "STRUCTURED DIGITAL ABSTRACT: BDF2 physically interacts with BDF1 by anti tag coimmunoprecipitation (View interaction) BDF2 physically interacts with BDF1 by pull down (View interaction).", "output": {"entities": {}}, "schema": []}
{"input": "Highly enantioselective rhodium-catalyzed [2 + 2 + 2] cycloaddition of diynes to sulfonimines.", "output": {"entities": {"chemical": [{"text": "rhodium", "start": 24, "end": 31}, {"text": "diynes", "start": 71, "end": 77}, {"text": "sulfonimines", "start": 81, "end": 93}]}}, "schema": []}
{"input": "A new asymmetric [2 + 2 + 2] cycloaddition of diynes to sulfonimines under rhodium catalysis that provides the corresponding enantioenriched 1, 2-dihydropyridines in good yields is described.", "output": {"entities": {"chemical": [{"text": "diynes", "start": 46, "end": 52}, {"text": "sulfonimines", "start": 56, "end": 68}, {"text": "rhodium", "start": 75, "end": 82}, {"text": "1, 2-dihydropyridines", "start": 141, "end": 162}]}}, "schema": []}
{"input": "1, 3, 4-thiadiazole and its derivatives: a review on recent progress in biological activities.", "output": {"entities": {"chemical": [{"text": "1, 3, 4-thiadiazole", "start": 0, "end": 19}]}}, "schema": []}
{"input": "The 1, 3, 4-thiadiazole nucleus is one of the most important and well-known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents.", "output": {"entities": {"chemical": [{"text": "1, 3, 4-thiadiazole", "start": 4, "end": 23}]}}, "schema": []}
{"input": "Thiadiazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular agents.", "output": {"entities": {"chemical": [{"text": "Thiadiazole", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds.", "output": {"entities": {"chemical": [{"text": "thiadiazole", "start": 33, "end": 44}]}}, "schema": []}
{"input": "In this study, an attempt has been made with recent research findings on this nucleus, to review the structural modifications on different thiadiazole derivatives for various pharmacological activities.", "output": {"entities": {"chemical": [{"text": "thiadiazole", "start": 139, "end": 150}]}}, "schema": []}
{"input": "mGluR2 positive allosteric modulators: a patent review (2009-present).", "output": {"entities": {}}, "schema": []}
{"input": "Introduction: The mGlu2 receptor, which belongs to the group II subfamily of metabotropic glutamate receptors (mGlu) along with the mGlu3 receptor, has proven to be of particular importance in neuropharmacology.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 90, "end": 99}]}}, "schema": []}
{"input": "Preferentially expressed on presynaptic nerve terminals, the mGlu2 receptor negatively modulates glutamate and GABA release and is widely distributed in the brain.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 97, "end": 106}, {"text": "GABA", "start": 111, "end": 115}]}}, "schema": []}
{"input": "High levels of mGlu2 receptors are seen in brain areas such as prefrontal cortex, hippocampus and amygdala where glutamate hyperfunction may be implicated in disorders and diseases such as anxiety and schizophrenia.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 113, "end": 122}]}}, "schema": []}
{"input": "Given the promise offered by mGlu2/3 receptor activation, there is increased interest in identifying small molecules which activate the receptor.", "output": {"entities": {}}, "schema": []}
{"input": "A preferred approach is via positive allosteric modulators (PAMs) which bind at an alternative site to agonists.", "output": {"entities": {}}, "schema": []}
{"input": "Areas covered: This review covers the patent applications which were published between April 2009 and December 2012 on PAMs of the mGlu2, and it is a continuation of an earlier review published in this journal.", "output": {"entities": {}}, "schema": []}
{"input": "Expert opinion: Advances in medicinal chemistry and pharmacology have set the stage in the field of mGlu2 receptor PAMs.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds currently advancing in clinical trials will soon establish the therapeutic potential of this allosteric approach.", "output": {"entities": {}}, "schema": []}
{"input": "Extensive paternal mtDNA leakage in natural populations of Drosophila melanogaster.", "output": {"entities": {}}, "schema": []}
{"input": "Strict maternal inheritance is considered a hallmark of animal mtDNA.", "output": {"entities": {}}, "schema": []}
{"input": "Although recent reports suggest that paternal leakage occurs in a broad range of species, it is still considered an exceptionally rare event.", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate the impact of paternal leakage on the evolution of mtDNA, it is essential to reliably estimate the frequency of paternal leakage in natural populations.", "output": {"entities": {}}, "schema": []}
{"input": "Using allele-specific real-time quantitative PCR (RT-qPCR), we show that heteroplasmy is common in natural populations with at least 14% of the individuals carrying multiple mitochondrial haplotypes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the average frequency of the minor mtDNA haplotype is low (0. 8%), which suggests that this pervasive heteroplasmy has not been noticed before due to a lack of power in sequencing surveys.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the distribution of mtDNA haplotypes in the offspring of heteroplasmic mothers, we found no evidence for strong selection against one of the haplotypes.", "output": {"entities": {}}, "schema": []}
{"input": "We estimated that the rate of paternal leakage is 6% and that at least 100 generations are required for complete sorting of mtDNA haplotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the high proportion of heteroplasmic individuals in natural populations, we found no evidence for recombination between mtDNA molecules, suggesting that either recombination is rare or recombinant haplotypes are counter-selected.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that evolutionary studies using mtDNA as a marker might be biased by paternal leakage in this species.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of a pre-export enzyme-chaperone complex on the twin-arginine transport pathway.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 70, "end": 78}]}}, "schema": []}
{"input": "The Tat (twin-arginine translocation) system is a protein targeting pathway utilized by prokaryotes and chloroplasts.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 14, "end": 22}]}}, "schema": []}
{"input": "Tat substrates are produced with distinctive N-terminal signal peptides and are translocated as fully folded proteins.", "output": {"entities": {"chemical": [{"text": "N", "start": 45, "end": 46}]}}, "schema": []}
{"input": "In Escherichia coli, Tat-dependent proteins often contain redox cofactors that must be loaded before translocation.", "output": {"entities": {}}, "schema": []}
{"input": "Trimethylamine N-oxide reductase (TorA) is a model bacterial Tat substrate and is a molybdenum cofactor-dependent enzyme.", "output": {"entities": {"chemical": [{"text": "Trimethylamine N-oxide", "start": 0, "end": 22}, {"text": "molybdenum", "start": 84, "end": 94}]}}, "schema": []}
{"input": "Co-ordination of cofactor loading and translocation of TorA is directed by the TorD protein, which is a cytoplasmic chaperone known to interact physically with the TorA signal peptide.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, a pre-export TorAD complex has been characterized using biochemical and biophysical techniques, including SAXS (small-angle X-ray scattering).", "output": {"entities": {}}, "schema": []}
{"input": "A stable, cofactor-free TorAD complex was isolated, which revealed a 1: 1 binding stoichiometry.", "output": {"entities": {}}, "schema": []}
{"input": "Surprisingly, a TorAD complex with similar architecture can be isolated in the complete absence of the 39-residue TorA signal peptide.", "output": {"entities": {}}, "schema": []}
{"input": "The present study demonstrates that two high-affinity binding sites for TorD are present on TorA, and that a single TorD protein binds both of those simultaneously.", "output": {"entities": {}}, "schema": []}
{"input": "Further characterization suggested that the C-terminal' Domain IV' of TorA remained solvent-exposed in the cofactor-free pre-export TorAD complex.", "output": {"entities": {"chemical": [{"text": "C", "start": 44, "end": 45}]}}, "schema": []}
{"input": "It is possible that correct folding of Domain IV upon cofactor loading is the trigger for TorD release and subsequent export of TorA.", "output": {"entities": {}}, "schema": []}
{"input": "beta-Sheet Nanocrystalline Domains Formed from Phosphorylated Serine-Rich Motifs in Caddisfly Larval Silk: A Solid State NMR and XRD Study.", "output": {"entities": {"chemical": [{"text": "Phosphorylated Serine", "start": 47, "end": 68}]}}, "schema": []}
{"input": "Adhesive silks spun by aquatic caddisfly (order Trichoptera) larvae are used to build both intricate protective shelters and food harvesting nets underwater.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we use (13) C and (31) P solid-state NMR and wide angle X-ray diffraction (WAXD) as tools to elucidate molecular protein structure of caddisfly larval silk from the species Hesperophylax consimilis.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 22, "end": 28}, {"text": "(31) P", "start": 33, "end": 39}]}}, "schema": []}
{"input": "Caddisfly larval silk is a fibroin protein based biopolymer containing mostly repetitive amino acid motifs.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 89, "end": 99}]}}, "schema": []}
{"input": "NMR and X-ray results provide strong supporting evidence for a structural model in which phosphorylated serine repeats (pSX) 4 complex with divalent cations Ca (2 +) and Mg (2 +) to form rigid nanocrystalline beta-sheet structures in caddisfly silk.", "output": {"entities": {"chemical": [{"text": "phosphorylated serine", "start": 89, "end": 110}, {"text": "Ca (2 +)", "start": 157, "end": 165}, {"text": "Mg (2 +)", "start": 170, "end": 178}]}}, "schema": []}
{"input": "(13) C NMR data suggests that both phosphorylated serine and neighboring valine residues exist in a beta-sheet conformation while glycine and leucine residues common in GGX repeats likely reside in random coil conformations.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 0, "end": 6}, {"text": "phosphorylated serine", "start": 35, "end": 56}, {"text": "valine", "start": 73, "end": 79}, {"text": "glycine", "start": 130, "end": 137}, {"text": "leucine", "start": 142, "end": 149}]}}, "schema": []}
{"input": "Additionally, (31) P chemical shift anisotropy (CSA) analysis indicates that the phosphates on phosphoserine residues are doubly ionized, and are charge-stabilized by divalent cations.", "output": {"entities": {"chemical": [{"text": "(31) P", "start": 14, "end": 20}, {"text": "phosphates", "start": 81, "end": 91}, {"text": "phosphoserine", "start": 95, "end": 108}]}}, "schema": []}
{"input": "Positively charged arginine side chains also likely play a role in charge stabilization.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 19, "end": 27}]}}, "schema": []}
{"input": "Finally, WAXD results finds that the silk is at least 7-8% crystalline, with beta-sheet interplane spacings of 3. 7 and 4. 5 A.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.", "output": {"entities": {"chemical": [{"text": "Hydrocarbons", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease.", "output": {"entities": {}}, "schema": []}
{"input": "The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease.", "output": {"entities": {"chemical": [{"text": "hydrocarbon", "start": 49, "end": 60}]}}, "schema": []}
{"input": "Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period.", "output": {"entities": {}}, "schema": []}
{"input": "The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females.", "output": {"entities": {}}, "schema": []}
{"input": "The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations.", "output": {"entities": {}}, "schema": []}
{"input": "Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures.", "output": {"entities": {"chemical": [{"text": "hydrocarbons", "start": 25, "end": 37}]}}, "schema": []}
{"input": "Synthesis and evaluation of nicotinamide derivative as anti-angiogenic agents.", "output": {"entities": {"chemical": [{"text": "nicotinamide", "start": 28, "end": 40}]}}, "schema": []}
{"input": "Previously, we have found that BRN-103, a nicotinamide derivative, inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis signaling in human endothelial cells.", "output": {"entities": {"chemical": [{"text": "BRN-103", "start": 31, "end": 38}, {"text": "nicotinamide", "start": 42, "end": 54}]}}, "schema": []}
{"input": "During our continuous efforts to identify more potent anti-angiogenic agents, we synthesized various nicotinamide derivatives and evaluated their anti-angiogenic effects.", "output": {"entities": {"chemical": [{"text": "nicotinamide", "start": 101, "end": 113}]}}, "schema": []}
{"input": "We found that 2-{1-[1-(6-chloro-5-fluoropyrimidin-4-yl) ethyl] piperidin-4-ylamino}-N-(3-chlorophenyl) pyridine-3-carboxamide (BRN-250) significantly inhibited human umbilical vascular endothelial cells (HUVECs) proliferation, migration, tube formation, and microvessel growth in a concentration range of 10-100 nM.", "output": {"entities": {"chemical": [{"text": "2-{1-[1-(6-chloro-5-fluoropyrimidin-4-yl) ethyl] piperidin-4-ylamino}-N-(3-chlorophenyl) pyridine-3-carboxamide", "start": 14, "end": 125}, {"text": "BRN-250", "start": 127, "end": 134}]}}, "schema": []}
{"input": "Furthermore, BRN-250 inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway.", "output": {"entities": {"chemical": [{"text": "BRN-250", "start": 13, "end": 20}, {"text": "tyrosine", "start": 82, "end": 90}]}}, "schema": []}
{"input": "Taken together, these findings suggest that BRN-250 be considered a potential lead compound for cancer therapy.", "output": {"entities": {"chemical": [{"text": "BRN-250", "start": 44, "end": 51}]}}, "schema": []}
{"input": "Small molecule modulators of Wnt/beta-catenin signaling.", "output": {"entities": {}}, "schema": []}
{"input": "The Wnt signal transduction pathway is dysregulated in many highly prevalent diseases, including cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, drug discovery efforts have been hampered by the paucity of targets and drug-like lead molecules amenable to drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, we reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/beta-catenin signaling by a unique mechanism, though the target responsible remains unknown.", "output": {"entities": {"chemical": [{"text": "Niclosamide", "start": 57, "end": 68}]}}, "schema": []}
{"input": "We interrogated the mechanism and structure-activity relationships to understand drivers of potency and to assist target identification efforts.", "output": {"entities": {}}, "schema": []}
{"input": "We found inhibition of Wnt signaling by Niclosamide appears unique among the structurally-related anthelmintic agents tested and found the potency and functional response was dependent on small changes in the chemical structure of Niclosamide.", "output": {"entities": {"chemical": [{"text": "Niclosamide", "start": 40, "end": 51}, {"text": "Niclosamide", "start": 231, "end": 242}]}}, "schema": []}
{"input": "Overall, these findings support efforts to identify the target of Niclosamide inhibition of Wnt/beta-catenin signaling and the discovery of potent and selective modulators to treat human disease.", "output": {"entities": {"chemical": [{"text": "Niclosamide", "start": 66, "end": 77}]}}, "schema": []}
{"input": "Jacaric acid and its octadecatrienoic acid geoisomers induce apoptosis selectively in cancerous human prostate cells: a mechanistic and 3-D structure-activity study.", "output": {"entities": {"chemical": [{"text": "Jacaric acid", "start": 0, "end": 12}, {"text": "octadecatrienoic acid", "start": 21, "end": 42}]}}, "schema": []}
{"input": "Plant-derived non-essential fatty acids are important dietary nutrients, and some are purported to have chemopreventive properties against various cancers, including that of the prostate.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 28, "end": 39}]}}, "schema": []}
{"input": "In this study, we determined the ability of seven dietary C-18 fatty acids to cause cytotoxicity and induce apoptosis in various types of human prostate cancer cells.", "output": {"entities": {"chemical": [{"text": "C-18 fatty acids", "start": 58, "end": 74}]}}, "schema": []}
{"input": "These fatty acids included jacaric and punicic acid found in jacaranda and pomegranate seed oil, respectively, three octadecatrienoic geometric isomers (alpha-and beta-calendic and catalpic acid) and two mono-unsaturated C-18 fatty acids (trans-and cis-vaccenic acid).", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 6, "end": 17}, {"text": "jacaric and punicic acid", "start": 27, "end": 51}, {"text": "alpha-and beta-calendic and catalpic acid", "start": 153, "end": 194}, {"text": "mono-unsaturated C-18 fatty acids", "start": 204, "end": 237}, {"text": "trans-and cis-vaccenic acid", "start": 239, "end": 266}]}}, "schema": []}
{"input": "Jacaric acid and four of its octadecatrienoic geoisomers selectively induced apoptosis in hormone-dependent (LNCaP) and-independent (PC-3) human prostate cancer cells, whilst not affecting the viability of normal human prostate epithelial cells (RWPE-1).", "output": {"entities": {"chemical": [{"text": "Jacaric acid", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Jacaric acid induced concentration-and time-depedent LNCaP cell death through activation of intrinsic and extrinsic apoptotic pathways resulting in cleavage of PARP-1, modulation of pro-and antiapoptotic Bcl-2 family of proteins and increased cleavage of caspase-3,-8 and-9.", "output": {"entities": {"chemical": [{"text": "Jacaric acid", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Moreover, activation of a cell death-inducing signalling cascade involving death receptor 5 was observed.", "output": {"entities": {}}, "schema": []}
{"input": "Jacaric acid induced apoptosis in PC-3 cells by activation of the intrinsic pathway only.", "output": {"entities": {"chemical": [{"text": "Jacaric acid", "start": 0, "end": 12}]}}, "schema": []}
{"input": "The spatial conformation cis, trans, cis of jacaric and punicic acid was shown to play a key role in the increased potency and efficacy of these two fatty acids in comparison to the five other C-18 fatty acids tested.", "output": {"entities": {"chemical": [{"text": "jacaric and punicic acid", "start": 44, "end": 68}, {"text": "fatty acids", "start": 149, "end": 160}, {"text": "C-18 fatty acids", "start": 193, "end": 209}]}}, "schema": []}
{"input": "Three-dimensional conformational analysis using the PubChem Database (http://pubchem. ncbi. nlm. nih. gov) showed that the cytotoxic potency of the C-18 fatty acids was related to their degree of conformational similarity to our cytotoxic reference compound, punicic acid, based on optimized shape (ST) and feature (CT) similarity scores, with jacaric acid being most' biosimilar' (ST (ST-opt) = 0. 81; CT (CT-opt) = 0. 45).", "output": {"entities": {"chemical": [{"text": "C-18 fatty acids", "start": 148, "end": 164}, {"text": "punicic acid", "start": 259, "end": 271}, {"text": "jacaric acid", "start": 344, "end": 356}]}}, "schema": []}
{"input": "This 3-D analysis of structural similarity enabled us to rank geoisomeric fatty acids according to cytotoxic potency, whereas a 2-D positional assessment of cis/trans structure did not.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 74, "end": 85}]}}, "schema": []}
{"input": "Our findings provide mechanistic evidence that nutrition-derived non-essential fatty acids have chemopreventive biological activities and Exhibit 3-D structure-activity relationships that could be exploited to develop new strategies for the prevention or treatment of prostate cancer regardless of hormone dependency.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 79, "end": 90}]}}, "schema": []}
{"input": "The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation.", "output": {"entities": {}}, "schema": []}
{"input": "Past studies have documented a crosstalk between H2B ubiquitylation (H2Bub) and H3K4 methylation, but little (if any) direct evidence exists explaining the mechanism underlying H2Bub-dependent H3K4 methylation on chromatin templates.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we took advantage of an in vitro histone methyltransferase assay employing a reconstituted yeast Set1 complex (ySet1C) and a recombinant chromatin template containing fully ubiquitylated H2B to gain valuable insights.", "output": {"entities": {}}, "schema": []}
{"input": "Combined with genetic analyses, we demonstrate that the n-SET domain within Set1, but not Swd2, is essential for H2Bub-dependent H3K4 methylation.", "output": {"entities": {}}, "schema": []}
{"input": "Spp1, a homolog of human CFP1, is conditionally involved in this crosstalk.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings extend to the human Set1 complex, underscoring the conserved nature of this disease-relevant crosstalk pathway.", "output": {"entities": {}}, "schema": []}
{"input": "As not all members of the H3K4 methyltransferase family contain n-SET domains, our studies draw attention to the n-SET domain as a predictor of an H2B ubiquitylation-sensing mechanism that leads to downstream H3K4 methylation.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and anti-acetylcholinesterase properties of novel beta-and gamma-substituted alkoxy organophosphonates.", "output": {"entities": {"chemical": [{"text": "beta-and gamma-substituted alkoxy organophosphonates", "start": 60, "end": 112}]}}, "schema": []}
{"input": "Activated organophosphate (OP) insecticides and chemical agents inhibit acetylcholinesterase (AChE) to form OP-AChE adducts.", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 10, "end": 25}]}}, "schema": []}
{"input": "Whereas the structure of the OP correlates with the rate of inhibition, the structure of the OP-AChE adduct influences the rate at which post-inhibitory reactivation or aging phenomena occurs.", "output": {"entities": {}}, "schema": []}
{"input": "In this report, we prepared a panel of beta-substituted ethoxy and gamma-substituted propoxy phosphonoesters of the type p-NO (2) PhO-P (X) (R) [(O (CH (2)) (n) Z] (R = Me, Et; X = O, S; n = 2, 3; Z = halogen, OTs) and examined the inhibition of three AChEs by select structures in the panel.", "output": {"entities": {"chemical": [{"text": "beta-substituted ethoxy and gamma-substituted propoxy phosphonoesters", "start": 39, "end": 108}, {"text": "p-NO (2) PhO-P (X) (R) [(O (CH (2)) (n) Z]", "start": 121, "end": 163}, {"text": "R = Me, Et; X = O, S; n = 2, 3; Z = halogen, OTs", "start": 165, "end": 213}]}}, "schema": []}
{"input": "The beta-fluoroethoxy methylphosphonate analog (R = Me, Z = F, n = 2) was the most potent anti-AChE compound comparable (ki ~ 6 x 10 (6) M (-1) min (-1)) to paraoxon against EEAChE.", "output": {"entities": {"chemical": [{"text": "beta-fluoroethoxy methylphosphonate", "start": 4, "end": 39}, {"text": "R = Me, Z = F, n = 2", "start": 48, "end": 68}, {"text": "paraoxon", "start": 157, "end": 165}]}}, "schema": []}
{"input": "Analogs with Z = Br, I, or OTs were weak inhibitors of the AChEs, and methyl phosphonates (R = Me) were more potent than the corresponding ethyl phosphonates (R = Et).", "output": {"entities": {"chemical": [{"text": "Z = Br, I, or OTs", "start": 13, "end": 30}, {"text": "methyl phosphonates", "start": 70, "end": 89}, {"text": "R = Me", "start": 91, "end": 97}, {"text": "ethyl phosphonates", "start": 139, "end": 157}, {"text": "R = Et", "start": 159, "end": 165}]}}, "schema": []}
{"input": "As expected, analogs with a thionate linkage (PS) were poor inhibitors of the AChEs.", "output": {"entities": {"chemical": [{"text": "thionate", "start": 28, "end": 36}]}}, "schema": []}
{"input": "N-Alkyldeoxynojirimycin derivatives with novel terminal tertiary amide substitution for treatment of bovine viral diarrhea virus (BVDV), Dengue, and Tacaribe virus infections.", "output": {"entities": {"chemical": [{"text": "N-Alkyldeoxynojirimycin", "start": 0, "end": 23}, {"text": "tertiary amide", "start": 56, "end": 70}]}}, "schema": []}
{"input": "Novel N-alkyldeoxynojirimycins (NADNJs) with two hydrophobic groups attached to a nitrogen linker on the alkyl chain were designed.", "output": {"entities": {"chemical": [{"text": "N-alkyldeoxynojirimycins", "start": 6, "end": 30}, {"text": "NADNJs", "start": 32, "end": 38}, {"text": "alkyl", "start": 105, "end": 110}]}}, "schema": []}
{"input": "A novel NADNJ containing a terminal tertiary carboxamide moiety was discovered that was a potent inhibitor against BVDV.", "output": {"entities": {"chemical": [{"text": "NADNJ", "start": 8, "end": 13}, {"text": "tertiary carboxamide", "start": 36, "end": 56}]}}, "schema": []}
{"input": "Further optimization resulted in a structurally more stable lead compound 24 with a submicromolar EC50 against BVDV, Dengue, and Tacaribe; and low cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors.", "output": {"entities": {"chemical": [{"text": "2-Substituted-2-amino-6-boronohexanoic acids", "start": 0, "end": 44}]}}, "schema": []}
{"input": "Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II.", "output": {"entities": {"chemical": [{"text": "2-amino-6-boronohexanoic acid", "start": 71, "end": 100}, {"text": "ABH", "start": 102, "end": 105}]}}, "schema": []}
{"input": "In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms.", "output": {"entities": {"chemical": [{"text": "tertiary amine", "start": 35, "end": 49}, {"text": "carbon", "start": 67, "end": 73}]}}, "schema": []}
{"input": "This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I).", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 126, "end": 134}, {"text": "carboxylic acid", "start": 143, "end": 158}, {"text": "Asp200", "start": 173, "end": 179}, {"text": "Asp181", "start": 254, "end": 260}]}}, "schema": []}
{"input": "We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases.", "output": {"entities": {"chemical": [{"text": "ABH", "start": 121, "end": 124}]}}, "schema": []}
{"input": "Memantine-sulfur containing antioxidant conjugates as potential prodrugs to improve the treatment of Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "Memantine", "start": 0, "end": 9}, {"text": "sulfur", "start": 10, "end": 16}]}}, "schema": []}
{"input": "The approved treatments for Alzheimer' s disease (AD) exploit mainly a symptomatic approach based on the use of cholinesterase inhibitors or N-methyl-d-aspartate (NMDA) receptor antagonists.", "output": {"entities": {"chemical": [{"text": "N-methyl-d-aspartate", "start": 141, "end": 161}, {"text": "NMDA", "start": 163, "end": 167}]}}, "schema": []}
{"input": "Natural antioxidant compounds, able to pass through the blood-brain barrier (BBB), have been extensively studied as useful neuroprotective agents.", "output": {"entities": {}}, "schema": []}
{"input": "A novel approach towards excitotoxicity protection and oxidative stress associated with excess beta amyloid (A beta) preservation in AD is represented by selective glutamatergic antagonists that possess as well antioxidant capabilities.", "output": {"entities": {}}, "schema": []}
{"input": "In the present work, GSH (1) or (R)-alpha-lipoic acid (LA) (2) have been covalently linked with the NMDA receptor antagonists memantine (MEM).", "output": {"entities": {"chemical": [{"text": "GSH", "start": 21, "end": 24}, {"text": "(R)-alpha-lipoic acid", "start": 32, "end": 53}, {"text": "NMDA", "start": 100, "end": 104}, {"text": "memantine", "start": 126, "end": 135}, {"text": "MEM", "start": 137, "end": 140}]}}, "schema": []}
{"input": "The new conjugates, proposed as potential antialzheimer drugs, should act both as glutamate receptor antagonists and radical scavenging agents.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 82, "end": 91}]}}, "schema": []}
{"input": "The physico-chemical properties and \" in vitro \" membrane permeability, the enzymatic and chemical stability, the demonstrated \" in vitro \" antioxidant activity associated to the capacity to inhibit A beta (1-42) aggregation makes at least compound 2 a promising candidate for treatment of AD patients.", "output": {"entities": {}}, "schema": []}
{"input": "Return flight to the Canary Islands-The key role of peripheral populations of Afrocanarian blue tits (Aves: Cyanistes teneriffae) in multi-gene reconstructions of colonization pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Afrocanarian blue tits (Cyanistes teneriffae) have a scattered distribution on the Canary Islands and on the North African continent.", "output": {"entities": {}}, "schema": []}
{"input": "To date, the Canary Islands have been considered the species' main Pleistocene evolutionary center, but their colonization pathways remain uncertain.", "output": {"entities": {}}, "schema": []}
{"input": "We set out to reconstruct a dated multi-gene phylogeny and ancestral ranges for Cyanistes tit species including the currently unstudied, peripheral Libyan population of C.", "output": {"entities": {}}, "schema": []}
{"input": "t. cyrenaicae.", "output": {"entities": {}}, "schema": []}
{"input": "In all reconstructions the most easterly and westerly peripheral populations (in Libya and on La Palma) represented basal offshoots of C. teneriffae.", "output": {"entities": {}}, "schema": []}
{"input": "These two peripheral populations shared all four major indels and differed in this respect from all other members of the Afrocanarian core group.", "output": {"entities": {}}, "schema": []}
{"input": "The basal split of Afrocanarian blue tits from their European relatives was dated to the early Pliocene.", "output": {"entities": {}}, "schema": []}
{"input": "The two ancestral area reconstructions were contradictory and suggested either a Canarian or a North African origin of C. teneriffae-but unambiguously ruled out a continental European ancestral range.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that the peripheral populations of C. teneriffae represent relic lineages of a first faunal interchange, presumably downstream colonization from North Africa to the Canary Islands.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequent eastward stepping-stone colonization within the Canarian Archipelago culminated in a very recent late (possibly even post-) Pleistocene back-colonization from the Canary Islands to North Africa.", "output": {"entities": {}}, "schema": []}
{"input": "Tumor delivery of Photofrin (R) by PLL-g-PEG for photodynamic therapy.", "output": {"entities": {"chemical": [{"text": "Photofrin", "start": 18, "end": 27}, {"text": "PLL-g-PEG", "start": 35, "end": 44}]}}, "schema": []}
{"input": "Photofrin (R) (porfimer sodium) is a photosensitive reagent used for photodynamic therapy (PDT) of tumors and dysplasias.", "output": {"entities": {"chemical": [{"text": "Photofrin", "start": 0, "end": 9}, {"text": "porfimer sodium", "start": 15, "end": 30}]}}, "schema": []}
{"input": "Because only photo-irradiated sites are damaged, PDT is less invasive than systemic treatments.", "output": {"entities": {}}, "schema": []}
{"input": "However, a photosensitive reaction is a major side effect of systemically delivered Photofrin.", "output": {"entities": {"chemical": [{"text": "Photofrin", "start": 84, "end": 93}]}}, "schema": []}
{"input": "To enhance localization of Photofrin to tumors, we have formulated Photofrin with the tumor-localizing graft copolymer poly (ethylene glycol)-grafted poly (l-lysine), PLL-g-PEG.", "output": {"entities": {"chemical": [{"text": "Photofrin", "start": 27, "end": 36}, {"text": "Photofrin", "start": 67, "end": 76}, {"text": "poly (ethylene glycol)-grafted poly (l-lysine)", "start": 119, "end": 165}, {"text": "PLL-g-PEG", "start": 167, "end": 176}]}}, "schema": []}
{"input": "We demonstrate that Photofrin preferentially interacts with PLL-g-PEG through both ionic and hydrophobic interactions.", "output": {"entities": {"chemical": [{"text": "Photofrin", "start": 20, "end": 29}, {"text": "PLL-g-PEG", "start": 60, "end": 69}]}}, "schema": []}
{"input": "The serum competitive study showed that the highly PEG-grafted PLL is better for preventing serum binding to the Photofrin/PLL-g-PEG complex.", "output": {"entities": {"chemical": [{"text": "PEG-grafted PLL", "start": 51, "end": 66}, {"text": "Photofrin", "start": 113, "end": 122}, {"text": "PLL-g-PEG", "start": 123, "end": 132}]}}, "schema": []}
{"input": "In tumor-bearing mice, formulation of Photofrin with PLL-g-PEG enhanced tumor localization of Photofrin as twice as Photofrin alone and concomitantly suppressed the photosensitivity reaction drastically.", "output": {"entities": {"chemical": [{"text": "Photofrin", "start": 38, "end": 47}, {"text": "PLL-g-PEG", "start": 53, "end": 62}, {"text": "Photofrin", "start": 94, "end": 103}, {"text": "Photofrin", "start": 116, "end": 125}]}}, "schema": []}
{"input": "Examination of the effect of increasing the number of intra-disulfide amino functional groups on the performance of small molecule cyclic polyamine disulfide vectors.", "output": {"entities": {"chemical": [{"text": "disulfide amino", "start": 60, "end": 75}, {"text": "polyamine disulfide", "start": 138, "end": 157}]}}, "schema": []}
{"input": "Establishing structure-activity relationships is vital if the efficacy of non-viral vectors is to match that of their viral counter-parts.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, we reported on the ability of a series of small molecule, cyclic polyamine disulfides to condense and cage plasmid DNA (pDNA) by a process of thermodynamically controlled template polymerization, leading to a series of corresponding pDNA-polyplex nanoparticles able to mediate high levels of transfection with no associated cytotoxicities.", "output": {"entities": {"chemical": [{"text": "cyclic polyamine disulfides", "start": 68, "end": 95}]}}, "schema": []}
{"input": "The leading cyclic polyamine disulfide was shown to be the spermine tetra-amine disulfide (TetraN-3, 4, 3).", "output": {"entities": {"chemical": [{"text": "cyclic polyamine disulfide", "start": 12, "end": 38}, {"text": "spermine tetra-amine disulfide", "start": 59, "end": 89}, {"text": "TetraN-3, 4, 3", "start": 91, "end": 105}]}}, "schema": []}
{"input": "Herein we report on the significantly more challenging syntheses of cyclic disulfides with longer polyamine motifs.", "output": {"entities": {"chemical": [{"text": "cyclic disulfides", "start": 68, "end": 85}]}}, "schema": []}
{"input": "Two new cyclic polyamine disulfides, based on hexa-and octa-amine inserts, were prepared and their transfection efficacies and cytotoxicities compared with our previously reported cyclic tri-and tetra-amine disulfides.", "output": {"entities": {"chemical": [{"text": "cyclic polyamine disulfides", "start": 8, "end": 35}, {"text": "hexa-and octa-amine", "start": 46, "end": 65}, {"text": "cyclic tri-and tetra-amine disulfides", "start": 180, "end": 217}]}}, "schema": []}
{"input": "The new cyclic hexa-and octa-amine disulfides prove more effective at transfection in vitro, especially of lung epithelial A549 cell line.", "output": {"entities": {"chemical": [{"text": "cyclic hexa-and octa-amine disulfides", "start": 8, "end": 45}]}}, "schema": []}
{"input": "By contrast, our original cyclic tetra-amine disulfide remains the most efficient agent for the transfection of lung epithelial cells in vivo following intra-nasal administration.", "output": {"entities": {"chemical": [{"text": "cyclic tetra-amine disulfide", "start": 26, "end": 54}]}}, "schema": []}
{"input": "Hypothetical mechanistic reasons are presented to explain this outcome.", "output": {"entities": {}}, "schema": []}
{"input": "Our data in toto support the concept of shorter cyclic polyamine disulfides as preferred agents for polycation-mediated controlled condensation and functional delivery of pDNA to lung epithelial cells in vivo.", "output": {"entities": {"chemical": [{"text": "cyclic polyamine disulfides", "start": 48, "end": 75}]}}, "schema": []}
{"input": "DNA delivery via cationic solid lipid nanoparticles (SLNs).", "output": {"entities": {}}, "schema": []}
{"input": "In recent years the use of solid lipid nanoparticles (SLNs) as transport systems for the delivery of drugs and biomolecules has become particularly important.", "output": {"entities": {}}, "schema": []}
{"input": "The use of cationic SLNs developed by the technique of microemulsion, which are complexed with DNA in order to study their application as non-viral vectors in gene therapy, is reported.", "output": {"entities": {}}, "schema": []}
{"input": "The nanoparticles are characterized by scanning electron microscopy and transmission electron microscopy (SEM and TEM), atomic force microscopy (AFM) and differential scanning calorimetry (DSC).", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the process of lyophilization of the samples and their stability was studied.", "output": {"entities": {}}, "schema": []}
{"input": "The nanoparticles obtained presented a particle size of 340nm with a positive surface charge of 44mV and the capability of forming lipoplexes with DNA plasmids was stated.", "output": {"entities": {}}, "schema": []}
{"input": "Nitrosylation: An adverse factor in Uremic Hemolytic Syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Antitoxin effect of Ziziphus mistol Griseb.", "output": {"entities": {}}, "schema": []}
{"input": "Toxins of Escherichia coli (STEC) causing Uremic Hemolytic Syndrome (UHS) generate oxidative stress in human blood with more production of nitric oxide (NO) than reactive oxygen species (ROS).", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 139, "end": 151}, {"text": "NO", "start": 153, "end": 155}, {"text": "oxygen", "start": 171, "end": 177}]}}, "schema": []}
{"input": "Shiga toxin (Stx) together with the hemolysin (Hly) increased lipid oxidation, as evaluated by malondialdehyde MDA and oxidation of proteins.", "output": {"entities": {"chemical": [{"text": "malondialdehyde MDA", "start": 95, "end": 114}]}}, "schema": []}
{"input": "The addition of Ziziphus mistol Griseb extracts decreased NO, ROS, MDA and simultaneously caused an increase in the degradation of oxidized proteins to advanced oxidation protein products (AOPPs) in controls and samples with toxins.", "output": {"entities": {"chemical": [{"text": "NO", "start": 58, "end": 60}, {"text": "MDA", "start": 67, "end": 70}]}}, "schema": []}
{"input": "Furthermore, the nitrosylated proteins/AOPP ratio was reduced, due to the increase of AOPP.", "output": {"entities": {}}, "schema": []}
{"input": "Z. mistol Griseb extracts exhibited a high proportion of polyphenols and flavonoids, with evident correlation with ferrous reduction antioxidant potential (FRAP).", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 57, "end": 68}, {"text": "flavonoids", "start": 73, "end": 83}, {"text": "ferrous", "start": 115, "end": 122}]}}, "schema": []}
{"input": "The plasma of eight children with UHS showed oxidative stress and NO stimulus, comparable to the effect of toxins during the assays in vitro.", "output": {"entities": {"chemical": [{"text": "NO", "start": 66, "end": 68}]}}, "schema": []}
{"input": "UHS children presented high levels of nitrosylated proteins respect to control children of similar age.", "output": {"entities": {}}, "schema": []}
{"input": "Although the degradation of oxidized proteins to AOPP rose in UHS children, the nitrosylated proteins/AOPP rate increased as a consequence of the elevated nitrosative stress observed in these patients.", "output": {"entities": {}}, "schema": []}
{"input": "PK/PD assessment in CNS drug discovery: Prediction of CSF concentration in rodents for P-glycoprotein substrates and application to in vivo potency estimation.", "output": {"entities": {}}, "schema": []}
{"input": "The unbound drug concentration in brain parenchyma is considered to be the relevant driver for interaction with central nervous system (CNS) biological targets.", "output": {"entities": {}}, "schema": []}
{"input": "Drug levels in cerebrospinal fluid (C _ CSF) are frequently used surrogates for the unbound concentrations in brain.", "output": {"entities": {}}, "schema": []}
{"input": "For drugs actively transported across the blood-brain barrier (BBB), C _ CSF differs from unbound plasma concentration (Cu _ p) to an extent that is commonly unknown.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, the relationship between CSF-to-unbound plasma drug partitioning in rats and the mouse Pgp (Mdr1a) efflux ratio (ER) obtained from in vitro transcellular studies has been investigated for a set of 61 CNS compounds exhibiting substantial diversity in chemical structure and physico-chemical properties.", "output": {"entities": {}}, "schema": []}
{"input": "In order to understand the in vitro-in vivo extrapolation of Pgp efflux, a mechanistic model was derived relating in vivo CNS distribution kinetics to in vitro active transport.", "output": {"entities": {}}, "schema": []}
{"input": "The model was applied to predict C _ CSF from Cu _ p and ER data for 19 proprietary Roche CNS drug candidates.", "output": {"entities": {}}, "schema": []}
{"input": "The calculated CSF concentrations were correlated with CNS pharmacodynamic responses observed in rodent models.", "output": {"entities": {}}, "schema": []}
{"input": "The correlation between in vitro and in vivo potency for different pharmacological endpoints indicated that the predicted C _ CSF is a valuable surrogate of the concentration at the target site.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, C _ CSF proved superior description of PK/PD data than unbound plasma or total brain concentration for Mdr1a substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Predicted C _ CSF can be used as a default approach to understand the PK/PD relationships in CNS efficacy models and can support the extrapolation of efficacious brain exposure for new drug candidates from rodent to man.", "output": {"entities": {}}, "schema": []}
{"input": "Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in SD rats.", "output": {"entities": {"chemical": [{"text": "rotigotine", "start": 55, "end": 65}]}}, "schema": []}
{"input": "Continuous dopaminergic stimulation (CDS) has been an important strategy of drug development for the treatment of Parkinson' s disease (PD).", "output": {"entities": {}}, "schema": []}
{"input": "Rotigotine is a non-ergoline D3/D2/D1 dopamine agonist for treating PD.", "output": {"entities": {"chemical": [{"text": "Rotigotine", "start": 0, "end": 10}, {"text": "ergoline", "start": 20, "end": 28}, {"text": "dopamine", "start": 38, "end": 46}]}}, "schema": []}
{"input": "As a new treatment option for CDS, rotigotine-loaded microspheres (RoMS), a long-acting sustained-release microspheres for injection with poly (lactide-co-glycolide) as drug carrier, are now being evaluated in clinical trial.", "output": {"entities": {"chemical": [{"text": "rotigotine", "start": 35, "end": 45}, {"text": "poly (lactide-co-glycolide)", "start": 138, "end": 165}]}}, "schema": []}
{"input": "In this study, subchronic toxicity of RoMS in SD rats has been characterized via intramuscular administration with RoMS (0-240mg/kg/week) on a consecutive weekly dosing schedule for 3months followed by 1-month recovery period.", "output": {"entities": {}}, "schema": []}
{"input": "The No Observed Adverse Effect Level (NOAEL) was 45mg/kg/week.", "output": {"entities": {}}, "schema": []}
{"input": "One male at 240mg/kg died from an extensive pulmonary embolism.", "output": {"entities": {}}, "schema": []}
{"input": "The major toxicological effects were associated with the dopamine agonist-related pharmacodynamic properties of rotigotine (e. g. hyperactivity and stereotype, enlarged ovary, sporadic gastric mucous membrane lesions, decreased body weight, food consumption and prolactin, and increased mononuclear cell, neutrophil granulocyte, aspartate aminotransferase and alanine aminotransferase) and foreign body removal reaction induced by poly (lactide-co-glycolide) and carboxymethycellulose sodium.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 57, "end": 65}, {"text": "rotigotine", "start": 112, "end": 122}, {"text": "aspartate", "start": 329, "end": 338}, {"text": "alanine", "start": 360, "end": 367}, {"text": "poly (lactide-co-glycolide)", "start": 431, "end": 458}, {"text": "sodium", "start": 485, "end": 491}]}}, "schema": []}
{"input": "At the end of recovery period, all findings had recovered to a normal level or to a certain degree except foreign body reaction at injection sites.", "output": {"entities": {}}, "schema": []}
{"input": "RoMS has exhibited high safety on SD rats.", "output": {"entities": {}}, "schema": []}
{"input": "A cell-penetrating peptide suppresses the hypoxia inducible factor-1 function by binding to the helix-loop-helix domain of the aryl hydrocarbon receptor nuclear translocator.", "output": {"entities": {"chemical": [{"text": "aryl hydrocarbon", "start": 127, "end": 143}]}}, "schema": []}
{"input": "The heterodimeric hypoxia inducible factor-1 (HIF-1) complex is composed of the hypoxia inducible factor-1 alpha (HIF-1 alpha) and the aryl hydrocarbon receptor nuclear translocator (ARNT).", "output": {"entities": {"chemical": [{"text": "aryl hydrocarbon", "start": 135, "end": 151}]}}, "schema": []}
{"input": "Activation of the HIF-1 function is essential for tumor growth and metastasis.", "output": {"entities": {}}, "schema": []}
{"input": "We previously showed that transfection of a plasmid containing an ARNT-interacting peptide (Ainp1) cDNA suppresses the HIF-1 signaling in Hep3B cells.", "output": {"entities": {}}, "schema": []}
{"input": "Here we generated TAT fusion of the Ainp1 peptide (6His-TAT-Ainp1) to determine whether and how the Ainp1 peptide suppresses the HIF-1 function.", "output": {"entities": {"chemical": [{"text": "6His", "start": 51, "end": 55}]}}, "schema": []}
{"input": "The bacterially expressed 6His-TAT-Ainp1 was purified under denatured condition and then refolded by limited dialysis.", "output": {"entities": {"chemical": [{"text": "6His", "start": 26, "end": 30}]}}, "schema": []}
{"input": "The refolded 6His-TAT-Ainp1 interacts with the helix-loop-helix (HLH) domain of ARNT in a similar fashion as the native 6His-Ainp1.", "output": {"entities": {"chemical": [{"text": "6His", "start": 13, "end": 17}, {"text": "6His", "start": 120, "end": 124}]}}, "schema": []}
{"input": "6His-TAT-Ainp1 colocalizes with ARNT in the nucleus of HeLa and Hep3B cells after protein transduction.", "output": {"entities": {"chemical": [{"text": "6His", "start": 0, "end": 4}]}}, "schema": []}
{"input": "The transduced protein reaches the maximum intracellular levels within 2h while remains detectable up to 96h in HeLa cells.", "output": {"entities": {}}, "schema": []}
{"input": "At 2 mu M concentration, 6His-TAT-Ainp1 is not cytotoxic in HeLa cells but suppresses the cobalt chloride-activated, hypoxia responsive enhancer-driven luciferase expression in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "6His", "start": 25, "end": 29}, {"text": "cobalt chloride", "start": 90, "end": 105}]}}, "schema": []}
{"input": "In addition, it decreases the cobalt chloride-dependent induction of the HIF-1 target genes at both the message (vascular endothelial growth factor and aldolase C) and protein (carbonic anhydrase IX and glucose transporter 1) levels.", "output": {"entities": {"chemical": [{"text": "cobalt chloride", "start": 30, "end": 45}, {"text": "glucose", "start": 203, "end": 210}]}}, "schema": []}
{"input": "The protein levels of HIF-1 alpha and ARNT are not altered in the presence of 6His-TAT-Ainp1.", "output": {"entities": {"chemical": [{"text": "6His", "start": 78, "end": 82}]}}, "schema": []}
{"input": "In summary, we provided evidence to support that the Ainp1 peptide directly suppresses the HIF-1 function by interacting with the ARNT HLH domain, and in turn interfering with the heterodimerization of HIF-1 alpha and ARNT.", "output": {"entities": {}}, "schema": []}
{"input": "Genotoxicity assessment of vaccine adjuvant squalene.", "output": {"entities": {"chemical": [{"text": "squalene", "start": 44, "end": 52}]}}, "schema": []}
{"input": "The genotoxic potential of the vaccine adjuvant Squalene was assessed by the chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronucleus (MNs) tests in human lymphocytes and comet assay in both human and rat lymphocytes.", "output": {"entities": {"chemical": [{"text": "Squalene", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Five different concentrations of squalene (1250-20, 000 mu g/ml for human lymphocytes and 0. 07-1. 12mg/kg for rat lymphocytes) were studied.", "output": {"entities": {"chemical": [{"text": "squalene", "start": 33, "end": 41}]}}, "schema": []}
{"input": "Squalene did not affect the CAs and MN frequency, in all treatments in vitro.", "output": {"entities": {"chemical": [{"text": "Squalene", "start": 0, "end": 8}]}}, "schema": []}
{"input": "A significant increase in SCEs was observed in almost all concentrations at 24h treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Squalene did not affect significantly the comet tail length (CTL) (except 2500 mu g/ml) and comet tail intensity (CTI) at all treatments in vitro.", "output": {"entities": {"chemical": [{"text": "Squalene", "start": 0, "end": 8}]}}, "schema": []}
{"input": "In rats, squalene significantly increased and decreased CTL and CTI in some doses.", "output": {"entities": {"chemical": [{"text": "squalene", "start": 9, "end": 17}]}}, "schema": []}
{"input": "Although there are increasing and reduction in the effect, squalene cannot be regarded as genotoxic in human lymphocytes.", "output": {"entities": {"chemical": [{"text": "squalene", "start": 59, "end": 67}]}}, "schema": []}
{"input": "However, further in vivo studies are required to be sure on the effect.", "output": {"entities": {}}, "schema": []}
{"input": "Phenotypic analysis of ovine antigen presenting cells loaded with nanoparticles migrating from the site of vaccination.", "output": {"entities": {}}, "schema": []}
{"input": "Virus-sized particulate adjuvants such as ISCOMs, polystyrene nanoparticles and virus-like particles have been shown to target dendritic cells, resulting in the activation of T and B cells in vivo.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 50, "end": 61}]}}, "schema": []}
{"input": "Using an ovine pseudo-afferent lymph cannulation model to capture APC that traffic from the site of injection to the local lymph node, we show that 40-50nm nanoparticles are taken up at the site of injection by dendritic cells (DCs) migrating to the draining lymph node.", "output": {"entities": {}}, "schema": []}
{"input": "These DCs can express CD11c, CD1b, CD5, MHC class II and CD8.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticles transported by DCs migrating from the site of injection to the local lymph node therefore needs to be considered as a new mechanism underlying the immunogenicity of virus-sized vaccine delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Toxic and genotoxic effects of Roundup on tadpoles of the Indian skittering frog (Euflictis cyanophlyctis) in the presence and absence of predator stress.", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 31, "end": 38}]}}, "schema": []}
{"input": "Glyphosate, a post emergent herbicide, has become the backbone of no-till agriculture and is considered safe for animals.", "output": {"entities": {"chemical": [{"text": "Glyphosate", "start": 0, "end": 10}]}}, "schema": []}
{"input": "However, the impact of glyphosate on non-target organisms, especially on amphibians, is the subject of major concern and debate in recent times.", "output": {"entities": {"chemical": [{"text": "glyphosate", "start": 23, "end": 33}]}}, "schema": []}
{"input": "We examined the toxic and genotoxic effects of Roundup, a commercial formulation of glyphosate, in the tadpoles of the Indian skittering frog (Euflictis cyanophlyctis).", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 47, "end": 54}, {"text": "glyphosate", "start": 84, "end": 94}]}}, "schema": []}
{"input": "Roundup at different concentrations (0, 1, 2, 3, 4 and 8mg acid equivalent (ae)/L), tested in a 2 x 6 factorial design in the presence and absence of predator stress, induced concentration-dependent lethality in tadpoles.", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 0, "end": 7}]}}, "schema": []}
{"input": "The 96-h LC50 for Roundup in the absence and presence of predator stress were 3. 76mgae/L and 3. 39mgae/L, respectively.", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 18, "end": 25}]}}, "schema": []}
{"input": "The 10-day LC50 value for Roundup was significantly lower, 2. 12mgae/L and 1. 91mgae/L in the absence and presence of predator stress, respectively.", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 26, "end": 33}]}}, "schema": []}
{"input": "Lower concentrations of Roundup (1, 2 and 3mgae/L) induced the formation of micronuclei (MN) in the erythrocytes of tadpoles at 24-h (F3, 56 = 10. 286, p < 0. 001), 48-h (F3, 56 = 48. 255, p < 0. 001), 72-h (F3, 56 = 118. 933, p < 0. 001) and 96-h (F3, 56 = 85. 414, p < 0. 001) in a concentration-dependent manner.", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 24, "end": 31}]}}, "schema": []}
{"input": "Presence of predator stress apparently increased the toxicity and genotoxicity of Roundup; but these effects were not statistically significant.", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 82, "end": 89}]}}, "schema": []}
{"input": "These findings suggest that Roundup at environmentally relevant concentrations has lethal and genotoxic impact on E. cyanophlyctis; which may have long-term fitness consequence to the species.", "output": {"entities": {"chemical": [{"text": "Roundup", "start": 28, "end": 35}]}}, "schema": []}
{"input": "Synthesis and biochemical activities of antiproliferative amino acid and phosphate derivatives of microtubule-disrupting beta-lactam combretastatins.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 58, "end": 68}, {"text": "phosphate", "start": 73, "end": 82}, {"text": "beta-lactam combretastatins", "start": 121, "end": 148}]}}, "schema": []}
{"input": "The synthesis and biochemical activities of novel water-soluble beta-lactam analogues of combretastatin A-4 are described.", "output": {"entities": {"chemical": [{"text": "beta-lactam", "start": 64, "end": 75}, {"text": "combretastatin A-4", "start": 89, "end": 107}]}}, "schema": []}
{"input": "The first series of compounds investigated, beta-lactam phosphate esters 7a, 8a and 9a, exhibited potent antiproliferative activity and caused microtubule disruption in human breast carcinoma-derived MCF-7 cells.", "output": {"entities": {"chemical": [{"text": "beta-lactam phosphate esters", "start": 44, "end": 72}]}}, "schema": []}
{"input": "They did not inhibit tubulin polymerisation in vitro, indicating that biotransformation was necessary for their antiproliferative and tubulin binding effects in MCF-7 cells.", "output": {"entities": {}}, "schema": []}
{"input": "The second series of compounds, beta-lactam amino acid amides (including 10k and 11l) displayed potent antiproliferative activity in MCF-7 cells, disrupted microtubules in MCF-7 cells and also inhibited the polymerisation of tubulin in vitro.", "output": {"entities": {"chemical": [{"text": "beta-lactam amino acid amides", "start": 32, "end": 61}]}}, "schema": []}
{"input": "This indicates that the beta-lactam amides did not require metabolic activation to have antiproliferative effects, in contrast to the phosphate series.", "output": {"entities": {"chemical": [{"text": "beta-lactam amides", "start": 24, "end": 42}, {"text": "phosphate", "start": 134, "end": 143}]}}, "schema": []}
{"input": "Both series of compounds caused mitotic catastrophe and apoptosis in MCF-7 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular modelling studies indicated potential binding conformations for the beta-lactam amino acid amides 10k and 11l in the colchicine-binding site of tubulin.", "output": {"entities": {"chemical": [{"text": "beta-lactam amino acid amides", "start": 78, "end": 107}, {"text": "colchicine", "start": 127, "end": 137}]}}, "schema": []}
{"input": "Due to their aqueous solubility and potent biochemical effects, these compounds are promising candidates for further development as microtubule-disrupting agents.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, evaluation and absolute configuration assignment of novel dihydropyrimidin-2-ones as picomolar sodium iodide symporter inhibitors.", "output": {"entities": {"chemical": [{"text": "dihydropyrimidin-2-ones", "start": 69, "end": 92}, {"text": "sodium iodide", "start": 106, "end": 119}]}}, "schema": []}
{"input": "A small library of dihydropyrimidin-2-ones (DHPMs) was synthesized and evaluated for their potency to block iodide entrapment in rat thyroid cells.", "output": {"entities": {"chemical": [{"text": "dihydropyrimidin-2-ones", "start": 19, "end": 42}, {"text": "DHPMs", "start": 44, "end": 49}, {"text": "iodide", "start": 108, "end": 114}]}}, "schema": []}
{"input": "Synthesis was achieved using the multicomponent Biginelli reaction.", "output": {"entities": {}}, "schema": []}
{"input": "Twelve compounds were tested for the inhibition of sodium iodide symporter (NIS) in a cell-based assay.", "output": {"entities": {"chemical": [{"text": "sodium iodide", "start": 51, "end": 64}]}}, "schema": []}
{"input": "One newly synthesized derivative exhibited a remarkably strong activity, with a half-maximum inhibitory concentration value (IC50) of 65 pM.", "output": {"entities": {}}, "schema": []}
{"input": "Three DHPMs were further resolved from racemates using chiral HPLC and absolute configurations were assigned using circular dichroism spectroscopy.", "output": {"entities": {"chemical": [{"text": "DHPMs", "start": 6, "end": 11}]}}, "schema": []}
{"input": "Biological evaluation showed that most of the activity against NIS resides in one enantiomer.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides new insights for the development of anti-thyroid drugs, as well as for the synthesis of novel pharmacological tools designed to investigate iodide transport mechanisms at cellular and molecular levels.", "output": {"entities": {"chemical": [{"text": "iodide", "start": 160, "end": 166}]}}, "schema": []}
{"input": "Effect of chronic heroin and cocaine administration on global DNA methylation in brain and liver.", "output": {"entities": {"chemical": [{"text": "heroin", "start": 18, "end": 24}, {"text": "cocaine", "start": 29, "end": 36}]}}, "schema": []}
{"input": "Drug abuse is associated with epigenetic changes, such as histone modifications and DNA methylation.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of the present study was to examine the effect of chronic cocaine and heroin administration on global DNA methylation in brain and liver.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 70, "end": 77}, {"text": "heroin", "start": 82, "end": 88}]}}, "schema": []}
{"input": "Male, 8 week old, C57BL/6J mice received heroin in a chronic' intermittent' escalating dose paradigm, or cocaine in a chronic escalating dose' binge' paradigm, which mimic the human pattern of opioid or cocaine abuse respectively.", "output": {"entities": {"chemical": [{"text": "heroin", "start": 41, "end": 47}, {"text": "cocaine", "start": 105, "end": 112}, {"text": "cocaine", "start": 203, "end": 210}]}}, "schema": []}
{"input": "Following sacrifice, livers and brains were removed and DNA was extracted from them.", "output": {"entities": {}}, "schema": []}
{"input": "The extracted DNA was hydrolyzed and 2'-deoxycytidine and 5-methyl-2'-deoxycytidine were determined by HPLC-UV.", "output": {"entities": {"chemical": [{"text": "2'-deoxycytidine", "start": 37, "end": 53}, {"text": "5-methyl-2'-deoxycytidine", "start": 58, "end": 83}]}}, "schema": []}
{"input": "The% 5-methyl-2'-deoxycytidine content of DNA was significantly higher in the brain compared to the liver.", "output": {"entities": {"chemical": [{"text": "5-methyl-2'-deoxycytidine", "start": 5, "end": 30}]}}, "schema": []}
{"input": "There were no differences between the control animals and the cocaine or heroin treated animals in neither of the tissues examined, which is surprising since cocaine administration induced gross morphological changes in the liver.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 62, "end": 69}, {"text": "heroin", "start": 73, "end": 79}, {"text": "cocaine", "start": 158, "end": 165}]}}, "schema": []}
{"input": "Moreover, there was no difference in the% 5-methyl-2'-deoxycytidine content of DNA between the cocaine and the heroin treated animals.", "output": {"entities": {"chemical": [{"text": "5-methyl-2'-deoxycytidine", "start": 42, "end": 67}, {"text": "cocaine", "start": 95, "end": 102}, {"text": "heroin", "start": 111, "end": 117}]}}, "schema": []}
{"input": "The global DNA methylation status in the brain and liver of mice chronically treated with cocaine or heroin remains unaffected, but this finding cannot exclude the existence of anatomical region or gene-specific methylation differences.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 90, "end": 97}, {"text": "heroin", "start": 101, "end": 107}]}}, "schema": []}
{"input": "This is the first time that global DNA methylation in the liver and whole brain has been studied following chronic cocaine or heroin treatment.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 115, "end": 122}, {"text": "heroin", "start": 126, "end": 132}]}}, "schema": []}
{"input": "Rational design, synthesis and QSAR study of vasorelaxant active 3-pyridinecarbonitriles incorporating 1H-benzimidazol-2-yl function.", "output": {"entities": {"chemical": [{"text": "3-pyridinecarbonitriles", "start": 65, "end": 88}, {"text": "1H-benzimidazol-2-yl", "start": 103, "end": 123}]}}, "schema": []}
{"input": "A variety of 2-alkoxy-4-aryl-6-(1H-benzimidazol-2-yl)-3-pyridinecarbonitriles 4a-r were prepared via either regioselective reaction of 3-aryl-1-(1H-benzimidazol-2-yl)-2-propen-1-ones 3 with malononitrile or ylidenemalononitriles 6 with 2-acetyl-1H-benzimidazoles 1 in the presence of sodium alkoxide in the corresponding alcohol.", "output": {"entities": {"chemical": [{"text": "2-alkoxy-4-aryl-6-(1H-benzimidazol-2-yl)-3-pyridinecarbonitriles", "start": 13, "end": 77}, {"text": "3-aryl-1-(1H-benzimidazol-2-yl)-2-propen-1-ones", "start": 135, "end": 182}, {"text": "malononitrile", "start": 190, "end": 203}, {"text": "ylidenemalononitriles", "start": 207, "end": 228}, {"text": "2-acetyl-1H-benzimidazoles", "start": 236, "end": 262}, {"text": "sodium alkoxide", "start": 284, "end": 299}, {"text": "alcohol", "start": 321, "end": 328}]}}, "schema": []}
{"input": "All the synthesized compounds showed significant vasodilation properties using isolated thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride standard technique.", "output": {"entities": {"chemical": [{"text": "norepinephrine hydrochloride", "start": 138, "end": 166}]}}, "schema": []}
{"input": "Compounds 4d, 4p, 4l, and 4f exhibited remarkable activity compared with prazosin hydrochloride, which was used as a reference standard in the present study.", "output": {"entities": {"chemical": [{"text": "prazosin hydrochloride", "start": 73, "end": 95}]}}, "schema": []}
{"input": "QSAR studies revealed a good predictive and statistically significant 3 descriptor model (r (2) = 0. 913, radjusted (2) = 0. 8808, rprediction (2) = 0. 7911).", "output": {"entities": {}}, "schema": []}
{"input": "Nonclassical antifolates, part 3: Synthesis, biological evaluation and molecular modeling study of some new 2-heteroarylthio-quinazolin-4-ones.", "output": {"entities": {"chemical": [{"text": "2-heteroarylthio-quinazolin-4-ones", "start": 108, "end": 142}]}}, "schema": []}
{"input": "A new series of 2-heteroarylthio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities.", "output": {"entities": {"chemical": [{"text": "2-heteroarylthio-6-substituted-quinazolin-4-one", "start": 16, "end": 63}]}}, "schema": []}
{"input": "Compounds 21, 25, and 39 proved to be active DHFR inhibitors with IC50 range of 0. 3-0. 8 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 25, 28, 33, 35 and 36 showed broad spectrum antimicrobial activity comparable to the known antibiotic gentamicin.", "output": {"entities": {"chemical": [{"text": "gentamicin", "start": 112, "end": 122}]}}, "schema": []}
{"input": "Compound 29 showed broad spectrum antitumor activity toward several tumor cell lines with GI values range of 25. 8-41. 2%.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular modeling studies concluded that recognition with key amino acid Arg38 and Lys31 are essential for binding and biological activities.", "output": {"entities": {"chemical": [{"text": "amino acid Arg38", "start": 63, "end": 79}, {"text": "Lys31", "start": 84, "end": 89}]}}, "schema": []}
{"input": "Flexible alignment; electrostatic and hydrophobic mappings revealed that the obtained model could be useful for the development of new DHFR inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Human exposure to mycotoxins and their masked forms through cereal-based foods in Belgium.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, a quantitative dietary exposure assessment of mycotoxins and their masked forms was conducted on a national representative sample of the Belgian population using the contamination data of cereal-based foods.", "output": {"entities": {}}, "schema": []}
{"input": "Cereal-based food products (n = 174) were analysed for the occurrence of deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, zearalenone, alpha-zearalenol, beta-zearalenol, T-2-toxin, HT-2-toxin, and their respective masked forms, including, deoxynivalenol-3-glucoside, zearalenone-4-glucoside, alpha-zearalenol-4-glucoside, beta-zearalenol-4-glucoside and zearalenone-4-sulfate.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 73, "end": 87}, {"text": "3-acetyldeoxynivalenol", "start": 89, "end": 111}, {"text": "15-acetyldeoxynivalenol", "start": 113, "end": 136}, {"text": "zearalenone", "start": 138, "end": 149}, {"text": "alpha-zearalenol", "start": 151, "end": 167}, {"text": "beta-zearalenol", "start": 169, "end": 184}, {"text": "T-2-toxin", "start": 186, "end": 195}, {"text": "HT-2-toxin", "start": 197, "end": 207}, {"text": "deoxynivalenol-3-glucoside", "start": 255, "end": 281}, {"text": "zearalenone-4-glucoside", "start": 283, "end": 306}, {"text": "alpha-zearalenol-4-glucoside", "start": 308, "end": 336}, {"text": "beta-zearalenol-4-glucoside", "start": 338, "end": 365}, {"text": "zearalenone-4-sulfate", "start": 370, "end": 391}]}}, "schema": []}
{"input": "Fibre-enriched bread, bran-enriched bread, breakfast cereals, popcorn and oatmeal were collected in Belgian supermarkets according to a structured sampling plan and analysed during the period from April 2010 to October 2011.", "output": {"entities": {}}, "schema": []}
{"input": "The habitual intake of these food groups was estimated from a national representative food intake survey.", "output": {"entities": {}}, "schema": []}
{"input": "According to a probabilistic exposure analysis, the mean (and P95) mycotoxin intake for the sum of the deoxynivalenol-equivalents, zearalenone-equivalents, and the sum of HT-2-and T-2-toxin for all cereal-based foods was 0. 1162 (0. 4047, P95), 0. 0447 (0. 1568, P95) and 0. 0258 (0. 0924, P95) mu g kg (-1) body weight day (-1), respectively.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 103, "end": 117}, {"text": "zearalenone", "start": 131, "end": 142}, {"text": "HT-2-and T-2-toxin", "start": 171, "end": 189}]}}, "schema": []}
{"input": "These values were below the tolerable daily intake (TDI) levels for deoxynivalenol, zearalenone and the sum of T-2 and HT-2 toxin (1. 0, 0. 25 and 0. 1 mu g kg (-1) body weight day (-1), respectively).", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 68, "end": 82}, {"text": "zearalenone", "start": 84, "end": 95}, {"text": "T-2 and HT-2 toxin", "start": 111, "end": 129}]}}, "schema": []}
{"input": "The absolute level exceeding the TDI for all cereal-based foods was calculated, and recorded 0. 85%, 2. 75% and 4. 11% of the Belgian population, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of microelectrode array data using Bayesian modeling as an approach to screening and prioritization for neurotoxicity testing.", "output": {"entities": {}}, "schema": []}
{"input": "The need to assess large numbers of chemicals for their potential toxicities has resulted in increased emphasis on medium-and high-throughput in vitro screening approaches.", "output": {"entities": {}}, "schema": []}
{"input": "For such approaches to be useful, efficient and reliable data analysis and hit detection methods are also required.", "output": {"entities": {}}, "schema": []}
{"input": "Assessment of chemical effects on neuronal network activity using microelectrode arrays (MEAs) has been proposed as a screening tool for neurotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The current study examined a Bayesian data analysis approach for assessing effects of a 30 chemical training set on activity of primary cortical neurons grown in multi-well MEA plates.", "output": {"entities": {}}, "schema": []}
{"input": "Each well of the MEA plate contained 64 microelectrodes and the data set contains the number of electrical spikes registered by each electrode over the course of each experiment.", "output": {"entities": {}}, "schema": []}
{"input": "A Bayesian data analysis approach was developed and then applied to several different parsings of the data set to produce probability determinations for hit selection and ranking.", "output": {"entities": {}}, "schema": []}
{"input": "This methodology results in an approach that is approximately 74% sensitive in detecting chemicals in the training set known to alter neuronal function (23 expected positives) while being 100% specific in detecting chemicals expected to have no effect (7 expected negatives).", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, this manuscript demonstrates that the Bayesian approach may be combined with a previously published weighted mean firing rate approach in order to produce a more robust hit detection method.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, when combined with the weighted mean firing rate approach, the joint analysis produces a sensitivity of approximately 96% and a specificity of 100%.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate the utility of a novel approach to analysis of MEA data and support the use of neuronal networks grown on MEAs as a for neurotoxicity screening approach.", "output": {"entities": {}}, "schema": []}
{"input": "Lipophilic components from Fructus Viticis Negundo and their anti-tumor activities.", "output": {"entities": {}}, "schema": []}
{"input": "Two new triterpenoids, (24R/S)-24-hydroxy-3 alpha 10 alpha-epoxy-9-eip-cucurbita-25-ene (1a, b), as well as six known compounds (3-8), were isolated from the extraction of Fructus Viticis Negundo.", "output": {"entities": {"chemical": [{"text": "triterpenoids", "start": 8, "end": 21}, {"text": "(24R/S)-24-hydroxy-3 alpha 10 alpha-epoxy-9-eip-cucurbita-25-ene", "start": 23, "end": 87}]}}, "schema": []}
{"input": "Their structures were established on the basis of spectral analysis.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, all the compounds were tested for inhibitory effect against K-562 and A-549 cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular determinants of drug-receptor binding kinetics.", "output": {"entities": {}}, "schema": []}
{"input": "It is increasingly appreciated that the rates at which drugs associate with and dissociate from receptors-the binding kinetics-directly impact drug efficacy and safety.", "output": {"entities": {}}, "schema": []}
{"input": "The molecular determinants of drug-receptor binding kinetics remain poorly understood, however, especially when compared with the well-known factors that affect binding affinity.", "output": {"entities": {}}, "schema": []}
{"input": "The rational modulation of kinetics during lead optimization thus remains challenging.", "output": {"entities": {}}, "schema": []}
{"input": "We review some of the key factors thought to control drug-receptor binding kinetics at the molecular level-molecular size, conformational fluctuations, electrostatic interactions and hydrophobic effects-and discuss several possible approaches for the rational design of drugs with desired binding kinetics.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro nanotoxicity of single-walled carbon nanotube-dendrimer nanocomplexes against murine myoblast cells.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 39, "end": 45}]}}, "schema": []}
{"input": "Single-wall carbon nanotubes (SWCNTs) and polyamidoamine dendrimers (PAMAM) have been proposed for a variety of biomedical applications.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 12, "end": 18}, {"text": "polyamidoamine", "start": 42, "end": 56}]}}, "schema": []}
{"input": "The combination of both molecules makes this new composite nanomaterial highly functionalizable and versatile to theranostic and drug-delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "However, recent toxicological studies have shown that nanomaterials such as SWCNTs and PAMAM may have high toxicity in biological environments.", "output": {"entities": {}}, "schema": []}
{"input": "Aiming to elucidate such behavior, in vitro studies with different cultured cells have been conducted in the past few years.", "output": {"entities": {}}, "schema": []}
{"input": "This study focuses on the effects of SWCNT-PAMAM nanomaterials and their individual components on the C2C12 murine cell line, which is a mixed population of stem and progenitor cells.", "output": {"entities": {}}, "schema": []}
{"input": "The interactions between the cells and the nanomaterials were studied with different techniques usually employed in toxicological analyses.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that SWCNT-PAMAM and PAMAM inhibited the proliferation and caused DNA damage of C2C12 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Data from flow cytometry revealed a less toxicity in C2C12 cells exposed to SWCNT compared to the other nanomaterials.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicated that the toxicity of SWCNT, SWCNT-PAMAM and PAMAM in C2C12 cells can be strongly correlated with the charge of the nanomaterials.", "output": {"entities": {}}, "schema": []}
{"input": "The suppression of hematopoiesis function in Balb/c mice induced by prolonged exposure of microcystin-LR.", "output": {"entities": {"chemical": [{"text": "microcystin-LR", "start": 90, "end": 104}]}}, "schema": []}
{"input": "Microcystins (MCs) cause normocytic anemia in patients in a hemodialysis unit in Caruaru, Brazil in 1996, but the underlying mechanisms are still unclear.", "output": {"entities": {"chemical": [{"text": "Microcystins", "start": 0, "end": 12}]}}, "schema": []}
{"input": "In the present study, Balb/c mice were intraperitoneally injected with microcystin-LR (MC-LR) at the doses of 0. 5, 2 and 8 mu g/kg body weight (bw) every 48h for 30d.", "output": {"entities": {"chemical": [{"text": "microcystin-LR", "start": 71, "end": 85}, {"text": "MC-LR", "start": 87, "end": 92}]}}, "schema": []}
{"input": "After the prolonged exposure of MC-LR, significant decreases of red blood cell count (RBC), hemoglobin (Hb) and hematocrit (Ht) were observed in 2 and 8 mu g/kg bw groups, but erythrocyte mean corpuscular volume (MCV) showed no significant changes.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 32, "end": 37}]}}, "schema": []}
{"input": "Significantly elevated micronucleus frequency was observed in bone marrow cells (BMCs) in all MC-LR treatments.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 94, "end": 99}]}}, "schema": []}
{"input": "The proliferation of BMCs significantly declined in both 2 and 8 mu g/kg bw groups.", "output": {"entities": {}}, "schema": []}
{"input": "Serum levels of some hematopoietic growth factors significantly changed in 8 mu g/kg bw group, mainly including granulocyte-macrophage (GM-CSF), erythropoietin (EPO), interleukin-3 (IL-3) and TNF-alpha.", "output": {"entities": {}}, "schema": []}
{"input": "The transcriptional levels of these 4 genes in BMCs were also significantly changed in 8 mu g/kg bw group.", "output": {"entities": {}}, "schema": []}
{"input": "MC-LR exposure significantly increased the apoptosis rates in all MC-LR treatments.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 0, "end": 5}, {"text": "MC-LR", "start": 66, "end": 71}]}}, "schema": []}
{"input": "The present study indicates prolonged exposure of MC-LR induces normocytic anemia, and the disturbed hematopoietic growth factors and BMCs apoptosis are responsible for this normocytic anemia.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 50, "end": 55}]}}, "schema": []}
{"input": "Evaluation of the adjuvant effect of silver nanoparticles both in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "silver", "start": 37, "end": 43}]}}, "schema": []}
{"input": "The immunological adjuvant effect of silver nanoparticles (AgNPs) was investigated both in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "silver", "start": 37, "end": 43}]}}, "schema": []}
{"input": "The in vivo adjuvant effect of AgNPs was evaluated with model antigen ovalbumin (OVA) and bovine serum albumin (BSA) in mice by intraperitoneal and subcutaneous immunization.", "output": {"entities": {}}, "schema": []}
{"input": "Serum antigen-specific IgG level significantly increased in AgNPs-treated mice comparing to the control group.", "output": {"entities": {}}, "schema": []}
{"input": "AgNPs induced the increase of IgG1/IgG2a ratio and antigen-specific IgE, indicating that AgNPs elicited Th2-biased immune responses.", "output": {"entities": {}}, "schema": []}
{"input": "By in vitro assay, the mechanism of adjuvant effect was explored.", "output": {"entities": {}}, "schema": []}
{"input": "After 48h treatment with AgNPs, both the number of leukocytes and levels of cytokines TNF-alpha and IFN-gamma in abdominal lavage fluid of mice increased.", "output": {"entities": {}}, "schema": []}
{"input": "The expression of the major histocompatibility complex class II molecule on the surface of peritoneal macrophages significantly increased.", "output": {"entities": {}}, "schema": []}
{"input": "AgNPs can be easily phagocytosed by peritoneal macrophages, while do not affect antigen uptake by the cell.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore conclude that AgNPs have significant adjuvant effect and the mechanism of this effect is mainly ascribed to the recruitment and activation of local leukocytes and especially macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "For the first time we found the remarkable adjuvant effect of AgNPs, and the result is beneficial for the future applications, especially in biomedicine.", "output": {"entities": {}}, "schema": []}
{"input": "Platinum (II) complexes with mono-aminophosphonate ester targeting group that induce apoptosis through G1 cell-cycle arrest: Synthesis, crystal structure and antitumour activity.", "output": {"entities": {"chemical": [{"text": "Platinum (II)", "start": 0, "end": 13}, {"text": "mono-aminophosphonate ester", "start": 29, "end": 56}]}}, "schema": []}
{"input": "Six new platinum (II) complexes with mono-aminophosphonate ester were synthesized and characterized by elemental analysis, (1) H NMR, ESI-MS as well as single crystal X-ray diffraction analysis.", "output": {"entities": {"chemical": [{"text": "platinum (II)", "start": 8, "end": 21}, {"text": "mono-aminophosphonate ester", "start": 37, "end": 64}, {"text": "(1) H", "start": 123, "end": 128}]}}, "schema": []}
{"input": "They are mononuclear structures.", "output": {"entities": {}}, "schema": []}
{"input": "In all the crystal structures of complexes 1-6, the platinum centre adopts an approximately square-planar geometry, which were found to possess excellent solubility in both organic solvents and water and exhibit considerable cytotoxicity against MG-63, SK-OV-3 and HepG2 cell lines, but low cytotoxicity towards normal human liver cell HL-7702.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 52, "end": 60}]}}, "schema": []}
{"input": "In contrast to cisplatin, their antitumour activities are achieved through the induction of cell apoptosis by G1 cell-cycle arrest.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 15, "end": 24}]}}, "schema": []}
{"input": "Activation of Both Protein Kinase A (PKA) Type I and PKA Type II Isozymes Is Required for Retinoid-Induced Maturation of Acute Promyelocytic Leukemia Cells.", "output": {"entities": {"chemical": [{"text": "Retinoid", "start": 90, "end": 98}]}}, "schema": []}
{"input": "Acute promyelocytic leukemia (APL) is characterized by granulopoietic differentiation arrest at the promyelocytic stage.", "output": {"entities": {}}, "schema": []}
{"input": "In most cases, this defect can be overcome by treatment with all-trans-retinoic acid (ATRA), leading to complete clinical remission.", "output": {"entities": {"chemical": [{"text": "all-trans-retinoic acid", "start": 61, "end": 84}, {"text": "ATRA", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Cyclic AMP signaling has a key role in retinoid treatment efficacy: it enhances ATRA-induced maturation in ATRA-sensitive APL cells (including NB4 cells) and restores it in some ATRA-resistant cells (including NB4-LR1 cells).", "output": {"entities": {"chemical": [{"text": "Cyclic AMP", "start": 0, "end": 10}, {"text": "retinoid", "start": 39, "end": 47}, {"text": "ATRA", "start": 80, "end": 84}, {"text": "ATRA", "start": 107, "end": 111}, {"text": "ATRA", "start": 178, "end": 182}]}}, "schema": []}
{"input": "We show that the two cell types express identical levels of the C alpha catalytic subunit and comparable global cAMP-dependent protein kinase A (PKA) enzyme activity.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 112, "end": 116}]}}, "schema": []}
{"input": "However, the maturation-resistant NB4-LR1 cells have a PKA isozyme switch: compared with the NB4 cells, they have decreased content of the juxtanuclearly located PKA regulatory subunit II alpha and PKA regulatory subunit II beta, and a compensatory increase of the generally cytoplasmically distributed PKA-RI alpha.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the PKA regulatory subunit II exists mainly in the less cAMP-responsive nonautophosphorylated state in the NB4-LR1 cells.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 69, "end": 73}]}}, "schema": []}
{"input": "By the use of isozyme-specific cAMP analog pairs, we show that both PKA-I and PKA-II must be activated to achieve maturation in NB4-LR1 as well as NB4 cells.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 31, "end": 35}]}}, "schema": []}
{"input": "Therefore, special attention should be paid to activating not only PKA-I but also PKA-II in attempts to enhance ATRA-induced APL maturation in a clinical setting.", "output": {"entities": {"chemical": [{"text": "ATRA", "start": 112, "end": 116}]}}, "schema": []}
{"input": "Insula' s functional connectivity with ventromedial prefrontal cortex mediates the impact of trait alexithymia on state tobacco craving.", "output": {"entities": {}}, "schema": []}
{"input": "RATIONALE: Alexithymia is a personality trait characterized by difficulty indentifying and describing subjective emotional experiences.", "output": {"entities": {}}, "schema": []}
{"input": "Decreased aptitude in the perception, evaluation, and communication of affectively laden mental states has been associated with reduced emotion regulation, more severe drug craving in addicts, and structural/functional alterations in insula and anterior cingulate cortex (ACC).", "output": {"entities": {}}, "schema": []}
{"input": "The insula and ACC represent sites of convergence between the putative neural substrates of alexithymia and those perpetuating cigarette smoking.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVES: We examined the interrelations between alexithymia, tobacco craving, and insula/ACC neurocircuitry using resting-state functional connectivity (rsFC).", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Overnight-deprived smokers (n = 24) and nonsmokers (n = 20) completed six neuroimaging assessments on different days both in the absence of, and following, varenicline and/or nicotine administration.", "output": {"entities": {"chemical": [{"text": "varenicline", "start": 165, "end": 176}, {"text": "nicotine", "start": 184, "end": 192}]}}, "schema": []}
{"input": "In this secondary analysis of data from a larger study, we assessed trait alexithymia and state tobacco craving using self-reports and examined the rsFC of bilateral insular subregions (anterior, middle, posterior) and dorsal ACC.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Higher alexithymia in smokers predicted reduced rsFC strength between the right anterior insula (aI) and ventromedial prefrontal cortex (vmPFC).", "output": {"entities": {}}, "schema": []}
{"input": "Higher alexithymia also predicted more severe tobacco craving during nicotine withdrawal.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 69, "end": 77}]}}, "schema": []}
{"input": "Critically, the identified aI-vmPFC circuit fully mediated this alexithymia-craving relation.", "output": {"entities": {}}, "schema": []}
{"input": "That is, elevated alexithymia predicted decreased aI-vmPFC rsFC and, in turn, decreased aI-vmPFC rsFC predicted increased craving during withdrawal.", "output": {"entities": {}}, "schema": []}
{"input": "A moderated mediation analysis indicated that this aI-vmPFC mediational effect was not observed following drug administration.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: These results suggest that a weakened right aI-vmPFC functional circuit confers increased liability for tobacco craving during smoking abstinence.", "output": {"entities": {}}, "schema": []}
{"input": "Individual differences in alexithymia and/or aI-vmPFC functional coupling may be relevant factors for smoking cessation success.", "output": {"entities": {}}, "schema": []}
{"input": "Acute behavioural effects of bupropion and naltrexone, alone and in combination, in non-deprived male rats presented with palatable mash.", "output": {"entities": {"chemical": [{"text": "bupropion", "start": 29, "end": 38}, {"text": "naltrexone", "start": 43, "end": 53}]}}, "schema": []}
{"input": "RATIONALE: In appetite research, drugs frequently progress to clinical trials on the basis of outcome (reduced food intake/body weight gain) with insufficient attention to process (behavioural analysis).", "output": {"entities": {}}, "schema": []}
{"input": "Although bupropion and naltrexone (alone and in combination) reduce food consumption in rodents and humans, their effects on behaviour during feeding tests have not been thoroughly investigated.", "output": {"entities": {"chemical": [{"text": "bupropion", "start": 9, "end": 18}, {"text": "naltrexone", "start": 23, "end": 33}]}}, "schema": []}
{"input": "OBJECTIVES: This study aimed to assess the behavioural specificity of anorectic responses to bupropion, naltrexone and their combination.", "output": {"entities": {"chemical": [{"text": "bupropion", "start": 93, "end": 102}, {"text": "naltrexone", "start": 104, "end": 114}]}}, "schema": []}
{"input": "METHODS: Video analysis was employed to characterise the behavioural effects of acute systemic treatment with bupropion (10. 0-40. 0 mg/kg), naltrexone (0. 1-3. 0 mg/kg) and combined bupropion (20 mg/kg) plus naltrexone (0. 1-1. 0 mg/kg) in non-deprived male rats exposed for 1 h to palatable mash.", "output": {"entities": {"chemical": [{"text": "bupropion", "start": 110, "end": 119}, {"text": "naltrexone", "start": 141, "end": 151}, {"text": "bupropion", "start": 183, "end": 192}, {"text": "naltrexone", "start": 209, "end": 219}]}}, "schema": []}
{"input": "Particular attention was paid to the behavioural satiety sequence (BSS).", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: In experiment 1, the anorectic response to 40 mg/kg bupropion was associated with significant psychomotor stimulation and a complete disruption of the BSS.", "output": {"entities": {"chemical": [{"text": "bupropion", "start": 61, "end": 70}]}}, "schema": []}
{"input": "In experiment 2, the anorectic response to 3 mg/kg naltrexone was associated with an accelerated but otherwise normal BSS.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 51, "end": 61}]}}, "schema": []}
{"input": "In experiment 3, the co-administration of 20 mg/kg bupropion and naltrexone (0. 1 and 1. 0 mg/kg) not only produced an additive anorectic profile (including a reduced rate of eating), but the addition of the opioid receptor antagonist also concurrently attenuated the psychomotor stimulant response to the atypical antidepressant.", "output": {"entities": {"chemical": [{"text": "bupropion", "start": 51, "end": 60}, {"text": "naltrexone", "start": 65, "end": 75}]}}, "schema": []}
{"input": "CONCLUSIONS: Low-dose co-treatment with naltrexone and bupropion produces a stronger suppression of appetite than that seen with either agent alone and has the additional advantage of reducing some of the unwanted effects of bupropion.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 40, "end": 50}, {"text": "bupropion", "start": 55, "end": 64}, {"text": "bupropion", "start": 225, "end": 234}]}}, "schema": []}
{"input": "Effects of vegetative-periodic-induced rhizosphere variation on the uptake and translocation of metals in Phragmites australis (Cav.) Trin ex.", "output": {"entities": {}}, "schema": []}
{"input": "Steudel growing in the Sun Island Wetland.", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate the vegetative periodic effect of rhizosphere on the patterns of metal bioaccumulation, the concentrations of Mg, K, Ca, Mn, Zn, Fe, Cu, Cr, Ni, Cd and Pb in the corresponding rhizosphere soil and tissues of Phragmites australis growing in the Sun Island wetland (Harbin, China) were compared.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 122, "end": 124}, {"text": "K", "start": 126, "end": 127}, {"text": "Ca", "start": 129, "end": 131}, {"text": "Mn", "start": 133, "end": 135}, {"text": "Zn", "start": 137, "end": 139}, {"text": "Fe", "start": 141, "end": 143}, {"text": "Cu", "start": 145, "end": 147}, {"text": "Cr", "start": 149, "end": 151}, {"text": "Ni", "start": 153, "end": 155}, {"text": "Cd", "start": 157, "end": 159}, {"text": "Pb", "start": 164, "end": 166}]}}, "schema": []}
{"input": "The concentrations of Zn, Fe, Cu, Cr, Ni, Cd and Pb in roots were higher than in shoots, suggesting that roots are the primary accumulation organs for these metals and there exists an exclusion strategy for metal tolerance.", "output": {"entities": {"chemical": [{"text": "Zn", "start": 22, "end": 24}, {"text": "Fe", "start": 26, "end": 28}, {"text": "Cu", "start": 30, "end": 32}, {"text": "Cr", "start": 34, "end": 36}, {"text": "Ni", "start": 38, "end": 40}, {"text": "Cd", "start": 42, "end": 44}, {"text": "Pb", "start": 49, "end": 51}]}}, "schema": []}
{"input": "In contrast, the rest of the metals showed an opposite trend, suggesting that they were not restricted in roots.", "output": {"entities": {}}, "schema": []}
{"input": "Harvesting would particularly be an effective method to remove Mn from the environment.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 63, "end": 65}]}}, "schema": []}
{"input": "The concentrations of metals in shoots were generally higher in autumn than in summer, suggesting that Ph. australis possesses an efficient root-to-shoot translocation system, which is activated at the end of the growing season and allows more metals into the senescent tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, metal bioaccumulation of Ph. australis was affected by vegetative periodic variation through the changing of physicochemical and microbial conditions.", "output": {"entities": {}}, "schema": []}
{"input": "The rhizospheric microbial characteristics were significantly related to the concentrations of Mg, K, Zn, Fe and Cu, suggesting that microbial influence on metal accumulation is specific and selective, not eurytopic.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 95, "end": 97}, {"text": "K", "start": 99, "end": 100}, {"text": "Zn", "start": 102, "end": 104}, {"text": "Fe", "start": 106, "end": 108}, {"text": "Cu", "start": 113, "end": 115}]}}, "schema": []}
{"input": "Hypoxia-inducible factor and vascular endothelial growth factor are targets of dietary soy during acute stroke in female rats.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary soy and soy isoflavones are neuroprotective in experimental cerebral ischemia.", "output": {"entities": {"chemical": [{"text": "isoflavones", "start": 20, "end": 31}]}}, "schema": []}
{"input": "Because these isoflavones have estrogenic properties, we hypothesized that, like estrogens, they would inhibit acute vascular injury and the detrimental acute increase in hypoxia-induced vascular endothelial growth factor (VEGF) that leads to cerebral edema after stroke.", "output": {"entities": {"chemical": [{"text": "isoflavones", "start": 14, "end": 25}, {"text": "estrogens", "start": 81, "end": 90}]}}, "schema": []}
{"input": "Mature ovariectomized female Sprague Dawley rats were fed soy-free or soy-containing diets for 4 weeks followed by 90 minutes of transient middle cerebral artery occlusion.", "output": {"entities": {}}, "schema": []}
{"input": "Similar to estrogens, dietary soy significantly reduced cerebral edema and vascular apoptosis 24 hours after stroke.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 11, "end": 20}]}}, "schema": []}
{"input": "Soy also inhibited the ischemia-induced increase in cortical VEGF and VEGF receptor (VEGFR)-2 protein expression observed 4 and 24 hours after stroke, although mRNA levels increased.", "output": {"entities": {}}, "schema": []}
{"input": "The reduction in VEGF/VEGFR-2 was associated both with decreases in receptor phosphorylation and signaling to AKT and endothelial nitric oxide synthase.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore degradation of the VEGFR-2 was increased with dietary soy.", "output": {"entities": {}}, "schema": []}
{"input": "The primary ischemic stimulus for VEGF, hypoxia-inducible factor 1 alpha (HIF1 alpha), was similarly reduced by dietary soy 4 hours after transient middle cerebral artery occlusion in both the cortex and striatum.", "output": {"entities": {}}, "schema": []}
{"input": "The inhibition of HIF1 alpha activity was further confirmed by a significant decrease in the HIF1 alpha-activated apoptotic mediator BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Nip3-like protein X).", "output": {"entities": {}}, "schema": []}
{"input": "These data suggest that soy isoflavones target events early in the ischemic cascade as part of their neuroprotective actions and counterbalance some of the detrimental effects of the endogenous response to cerebral injury.", "output": {"entities": {"chemical": [{"text": "isoflavones", "start": 28, "end": 39}]}}, "schema": []}
{"input": "Genotoxic, antigenotoxic and antioxidant properties of methanol extracts obtained from Peltigera horizontalis and Peltigera praetextata.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 55, "end": 63}]}}, "schema": []}
{"input": "Now-a-days, there is a big need to reduce genotoxic effects of mutagenic and carcinogenic agents in environment, which are increased by the technological development.", "output": {"entities": {}}, "schema": []}
{"input": "Lichens produce a wide variety of unique metabolites due to being in various extreme areas and being symbiotic organisms of fungi and algae.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, this study was planned to search new sources having antimutagenic activity by researching two different lichen species and to determine whether their usage is safe.", "output": {"entities": {}}, "schema": []}
{"input": "With this respect, the mutagenic and antimutagenic properties of methanol extracts of the lichens were determined by the bacterial reverse mutation and sister chromatid exchange assays.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 65, "end": 73}]}}, "schema": []}
{"input": "Furthermore, the malondialdehyde level, superoxide dismutase, glutathione and glutathione peroxidase activities against aflatoxin B1 were determined for understanding the ways in which the lichens showed their genotoxic properties.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 17, "end": 32}, {"text": "superoxide", "start": 40, "end": 50}, {"text": "glutathione", "start": 62, "end": 73}, {"text": "glutathione", "start": 78, "end": 89}, {"text": "aflatoxin B1", "start": 120, "end": 132}]}}, "schema": []}
{"input": "Rapid cortical bone loss in patients with chronic kidney disease.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described.", "output": {"entities": {}}, "schema": []}
{"input": "In this longitudinal study of 53 patients with CKD Stages 2-5D, we used dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT) and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton.", "output": {"entities": {}}, "schema": []}
{"input": "Median follow-up was 1. 5 years (Range 0. 9 to 4. 3 years); bone changes were annualized and compared to baseline.", "output": {"entities": {}}, "schema": []}
{"input": "By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius:-1. 3% (95% CI:-2. 1 to-0. 6) and-2. 4% (95% CI:-4. 0 to-0. 9), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "By HRpQCT at the distal radius, there were significant declines in cortical area, density and thickness, and increases in porosity:-2. 9% (95% CI-3. 7 to-2. 2),-1. 3% (95% CI-1. 6 to-0. 6),-2. 8% (95% CI-3. 6 to-1. 9), and + 4. 2% (95% CI 2. 0 to 6. 4) respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Radius trabecular area increased significantly: + 0. 4% (95% CI 0. 2 to 0. 6), without significant changes in trabecular density or microarchitecture.", "output": {"entities": {}}, "schema": []}
{"input": "Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration.", "output": {"entities": {}}, "schema": []}
{"input": "Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity.", "output": {"entities": {"chemical": [{"text": "25-hydroxyvitamin D", "start": 23, "end": 42}]}}, "schema": []}
{"input": "These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover.", "output": {"entities": {}}, "schema": []}
{"input": "Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "New flavonol and diterpenoids from the endophytic fungus Aspergillus sp.", "output": {"entities": {"chemical": [{"text": "flavonol", "start": 4, "end": 12}, {"text": "diterpenoids", "start": 17, "end": 29}]}}, "schema": []}
{"input": "YXf3.", "output": {"entities": {}}, "schema": []}
{"input": "One new flavonol, chlorflavonin A (1), four new diterpenoids, aspergiloids E-H (3, 5-7), together with eight known compounds (2, 4, 8-13) were isolated from solid fermentation of Aspergillus sp.", "output": {"entities": {"chemical": [{"text": "flavonol", "start": 8, "end": 16}, {"text": "chlorflavonin A", "start": 18, "end": 33}, {"text": "diterpenoids", "start": 48, "end": 60}, {"text": "aspergiloids E-H", "start": 62, "end": 78}]}}, "schema": []}
{"input": "(strain no. YXf3), an endophytic fungus from Ginkgo biloba.", "output": {"entities": {}}, "schema": []}
{"input": "Their structures were determined through detailed spectroscopic analysis combined with comparison of NMR spectra data with reported ones.", "output": {"entities": {}}, "schema": []}
{"input": "All of them were screened on cytotoxicity against KB, SGC-7901, SW1116, and A549 cell lines; compounds 4, 9-11 exhibited moderate activities with IC50 values ranging from 6. 74 to 46. 64 micro M.", "output": {"entities": {}}, "schema": []}
{"input": "Unique role of self-assembled monolayers in carbon nanomaterial-based field-effect transistors.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 44, "end": 50}]}}, "schema": []}
{"input": "Molecular self-assembly is a promising technology for creating reliable functional films in optoelectronic devices with full control of thickness and even spatial resolution.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, rationally designed self-assembled monolayers (SAMs) play an important role in modifying the electrode/semiconductor and semiconductor/dielectric interfaces in field-effect transistors.", "output": {"entities": {}}, "schema": []}
{"input": "Carbon nanomaterials, especially single-walled carbon nanotubes and graphene, have attracted intense interest in recent years due to their remarkable physicochemical properties.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}, {"text": "carbon", "start": 47, "end": 53}, {"text": "graphene", "start": 68, "end": 76}]}}, "schema": []}
{"input": "The combination of the advantages of both SAMs and carbon nanomaterials has been opening up a thriving research field.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 51, "end": 57}]}}, "schema": []}
{"input": "In this Review article, the unique role of SAMs acting as either active or auxiliary layers in carbon nanomaterials-based field-effect transistors is highlighted for tuning the substrate effect, controlling the carrier type and density in the conducting channel, and even installing new functionalities.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 95, "end": 101}]}}, "schema": []}
{"input": "The combination of molecular self-assembly and molecular engineering with materials fabrication could incorporate diverse molecular functionalities into electrical nanocircuits, thus speeding the development of nanometer/molecular electronics in the future.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of Isoidide through Epimerization of Isosorbide using Ruthenium on Carbon.", "output": {"entities": {"chemical": [{"text": "Isoidide", "start": 13, "end": 21}, {"text": "Isosorbide", "start": 47, "end": 57}, {"text": "Ruthenium", "start": 64, "end": 73}, {"text": "Carbon", "start": 77, "end": 83}]}}, "schema": []}
{"input": "A highly efficient procedure for obtaining resin-grade isoidide through catalytic epimerization of isosorbide using a ruthenium-on-carbon (Ru/C) catalyst is reported.", "output": {"entities": {"chemical": [{"text": "isoidide", "start": 55, "end": 63}, {"text": "isosorbide", "start": 99, "end": 109}, {"text": "ruthenium", "start": 118, "end": 127}, {"text": "carbon", "start": 131, "end": 137}, {"text": "Ru", "start": 139, "end": 141}, {"text": "C", "start": 142, "end": 143}]}}, "schema": []}
{"input": "A comprehensive reaction-parameter variation study involving substrate concentration, catalyst (type of metal, support, and loading), initial pH value, hydrogen pressure, solvent, and reaction temperature demonstrates that superior performance and high selectivity can be achieved.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 152, "end": 160}]}}, "schema": []}
{"input": "Epimerization of isosorbide in water (pH 8) at 220 degrees C, under 40 bar of hydrogen, and using a Ru/C catalyst (5% Ru) for 2 h results in a thermodynamic equilibrium mixture containing 55% isoidide, 40% isosorbide, and 5% isomannide.", "output": {"entities": {"chemical": [{"text": "isosorbide", "start": 17, "end": 27}, {"text": "hydrogen", "start": 78, "end": 86}, {"text": "Ru", "start": 100, "end": 102}, {"text": "C", "start": 103, "end": 104}, {"text": "Ru", "start": 118, "end": 120}, {"text": "isoidide", "start": 192, "end": 200}, {"text": "isosorbide", "start": 206, "end": 216}, {"text": "isomannide", "start": 225, "end": 235}]}}, "schema": []}
{"input": "In comparison with previously reported nickel-based catalysts, the Ru/C catalyst is advantageous because it is highly active (as low as 360 ppm Ru) and recyclable.", "output": {"entities": {"chemical": [{"text": "nickel", "start": 39, "end": 45}, {"text": "Ru", "start": 67, "end": 69}, {"text": "C", "start": 70, "end": 71}, {"text": "Ru", "start": 144, "end": 146}]}}, "schema": []}
{"input": "High purity isoidide is obtained by high-vacuum distillation of an equilibrium mixture on a 200 g scale.", "output": {"entities": {"chemical": [{"text": "isoidide", "start": 12, "end": 20}]}}, "schema": []}
{"input": "The high substrate loading (50 wt% in water), high selectivity, and the possibility for substrate reuse makes this procedure highly atom efficient and therefore, highly attractive for industrial use.", "output": {"entities": {}}, "schema": []}
{"input": "Delay and impairment in brain development and function in rat offspring after maternal exposure to methylmercury.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 99, "end": 112}]}}, "schema": []}
{"input": "Maternal exposure to the neurotoxin methylmercury (MeHg) has been shown to have adverse effects on neural development of the offspring in man.", "output": {"entities": {"chemical": [{"text": "methylmercury", "start": 36, "end": 49}, {"text": "MeHg", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Little is known about the underlying mechanisms by which MeHg affects the developing brain.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 57, "end": 61}]}}, "schema": []}
{"input": "To explore the neurodevelopmental defects and the underlying mechanism associated with MeHg exposure, the cerebellum and cerebrum of Wistar rat pups were analyzed by [(18) F] FDG PET functional imaging, field potential analysis, and microarray gene expression profiling.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 87, "end": 91}, {"text": "[(18) F] FDG", "start": 166, "end": 178}]}}, "schema": []}
{"input": "Female rat pups were exposed to MeHg via maternal diet during intrauterinal and lactational period (from gestational day 6 to postnatal day (PND) 10), and their brain tissues were sampled for the analysis at weaning (PND18-21) and adulthood (PND61-70).", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 32, "end": 36}]}}, "schema": []}
{"input": "The [(18) F] FDG PET imaging and field potential analysis suggested a delay in brain activity and impaired neural function by MeHg.", "output": {"entities": {"chemical": [{"text": "[(18) F] FDG", "start": 4, "end": 16}, {"text": "MeHg", "start": 126, "end": 130}]}}, "schema": []}
{"input": "Genome-wide transcriptome analysis substantiated these findings by showing (1) a delay in the onset of gene expression related to neural development, and (2) alterations in pathways related to both structural and functional aspects of nervous system development.", "output": {"entities": {}}, "schema": []}
{"input": "The latter included changes in gene expression of developmental regulators, developmental phase-associated genes, small GTPase signaling molecules, and representatives of all processes required for synaptic transmission.", "output": {"entities": {}}, "schema": []}
{"input": "These findings were observed at dose levels at which only marginal changes in conventional developmental toxicity endpoints were detected.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the approaches applied in this study are promising in terms of yielding increased sensitivity compared with classical developmental toxicity tests.", "output": {"entities": {}}, "schema": []}
{"input": "Thioflavin T and its photoirradiative derivatives: exploring their spectroscopic properties in the absence and presence of amyloid fibrils.", "output": {"entities": {"chemical": [{"text": "Thioflavin T", "start": 0, "end": 12}]}}, "schema": []}
{"input": "In this work, we found that, during storage or after UV irradiation, ThT is demethylated or oxidized, forming three derivatives.", "output": {"entities": {"chemical": [{"text": "ThT", "start": 69, "end": 72}]}}, "schema": []}
{"input": "These three derivatives were purified by high performance liquid chromatography and characterized by mass and nuclear magnetic resonance spectroscopy and the spectroscopic properties of pure ThT and the derivatives carefully compared.", "output": {"entities": {"chemical": [{"text": "ThT", "start": 191, "end": 194}]}}, "schema": []}
{"input": "Our results show that the emission peak at 450 nm results from oxidized ThT and not from the monomeric form of ThT, as previously proposed.", "output": {"entities": {"chemical": [{"text": "ThT", "start": 72, "end": 75}, {"text": "ThT", "start": 111, "end": 114}]}}, "schema": []}
{"input": "The partial conversion of ThT into oxidized and demethylated derivatives has an effect on amyloid detection using ThT assay.", "output": {"entities": {"chemical": [{"text": "ThT", "start": 26, "end": 29}, {"text": "ThT", "start": 114, "end": 117}]}}, "schema": []}
{"input": "Irradiated ThT has the same lag time as pure ThT in the amyloidogenesis of insulin, but the intensity of the emitted fluorescence is significantly decreased.", "output": {"entities": {"chemical": [{"text": "ThT", "start": 11, "end": 14}, {"text": "ThT", "start": 45, "end": 48}]}}, "schema": []}
{"input": "pH-Dependent Aggregation and Disaggregation of Native beta-Lactoglobulin in Low Salt.", "output": {"entities": {}}, "schema": []}
{"input": "The aggregation of beta-lactoglobulin (BLG) near its isoelectric point was studied as a function of ionic strength and pH.", "output": {"entities": {}}, "schema": []}
{"input": "We compared the behavior of native BLG with those of its two isoforms, BLG-A and BLG-B, and with that of a protein with a very similar pI, bovine serum albumin (BSA).", "output": {"entities": {}}, "schema": []}
{"input": "Rates of aggregation were obtained through a highly precise and convenient pH/turbidimetric titration that measures transmittance to +/- 0. 05% T.", "output": {"entities": {}}, "schema": []}
{"input": "A comparison of BLG and BSA suggests that the difference between pHmax (the pH of the maximum aggregation rate) and pI is systematically related to the nature of protein charge asymmetry, as further supported by the effect of localized charge density on the dramatically different aggregation rates of the two BLG isoforms.", "output": {"entities": {}}, "schema": []}
{"input": "Kinetic measurements including very short time periods show well-differentiated first and second steps.", "output": {"entities": {}}, "schema": []}
{"input": "BLG was analyzed by light scattering under conditions corresponding to maxima in the first and second steps.", "output": {"entities": {}}, "schema": []}
{"input": "Dynamic light scattering (DLS) was used to monitor the kinetics, and static light scattering (SLS) was used to evaluate the aggregate structure fractal dimensions at different quench points.", "output": {"entities": {}}, "schema": []}
{"input": "The rate of the first step is relatively symmetrical around pHmax and is attributed to the local charges within the negative domain of the free protein.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the remarkably linear pH dependence of the second step is related to the uniform reduction in global protein charge with increasing pH below pI, accompanied by an attractive force due to surface charge fluctuations.", "output": {"entities": {}}, "schema": []}
{"input": "TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies.", "output": {"entities": {}}, "schema": []}
{"input": "Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a pro-apoptotic ligand that has shown the exquisite ability to trigger extrinsic apoptosis in various types of cancer cells without significant toxicity toward normal cells, when compared to other pro-apoptotic ligands such as tumor necrosis factor (TNF) alpha or Fas ligand.", "output": {"entities": {}}, "schema": []}
{"input": "Consequently, TRAIL-based therapies aim to trigger apoptosis in cancer cells by providing the soluble TRAIL or monoclonal antibodies targeting the death receptors TRAIL-R1 or TRAIL-R2.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we start by highlighting the relevance of the tumor microenvironment in tumor development and elimination.", "output": {"entities": {}}, "schema": []}
{"input": "We then address conventional and targeted therapeutic approaches for cancer treatment, highlighting the mechanisms involved or targeted.", "output": {"entities": {}}, "schema": []}
{"input": "We describe the extrinsic and intrinsic pro-apoptotic pathways of TRAIL, together with the evidences for its pro-survival signaling, and with the relevance of these pathways in therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Possible mechanisms of resistance to TRAIL-induced apoptosis are highlighted (i. e. c-FLIP, Bcl-2, IAPs, p53, NF-kappa B) and the rationale for the combined administration of TRAIL with drugs targeting these mechanisms is provided.", "output": {"entities": {}}, "schema": []}
{"input": "Preclinical data are reported and show encouraging evidences for TRAIL consideration in pediatric malignancies (i. e., leukemia, lymphomas, neuroblastoma, osteosarcoma, medulloblastoma).", "output": {"entities": {}}, "schema": []}
{"input": "Clinical trials of TRAIL-based therapies on the overall population are in phase I or II, and we put particular focus on the pediatric population, on which only few trials have been conducted or are ongoing.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we consider emerging cellular therapies based on TRAIL, such as TRAIL-engineered mesenchymal stem cells or' inflammatory' dendritic cells.", "output": {"entities": {}}, "schema": []}
{"input": "Potential Advantages of Using Synchrotron X-ray Based Techniques in Pediatric Research.", "output": {"entities": {}}, "schema": []}
{"input": "Synchrotron radiation (SR), which combines extremely high intensity, high collimation, tunability, and continuous energy spectrum, allows the development of advanced X-ray based techniques that are becoming a uniquely useful tool in life science research, along providing exciting opportunities in biomedical imaging and radiotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "This review summarize emerging techniques and their potential to greatly enhance the exploration of dynamical biological process occurring across various spatial and temporal regimes, from whole body physiology, down to the location of individual chemical species within single cells.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years pediatric research and clinic practice have started to profit from these new opportunities, particularly by extending the diagnostic and therapeutic capabilities of these X-ray based techniques.", "output": {"entities": {}}, "schema": []}
{"input": "In diagnosis, technical advances in DEI and KES imaging modalities have been demonstrated as particularly valuable for children and women since SR allows dose minimization, with significant reductions compared to conventional approaches.", "output": {"entities": {}}, "schema": []}
{"input": "However, the greatest expectations are in the field of SR based radiotherapy, increasingly studies are demonstrating SR radiotherapy provides improved chances of recovery; this is especially the case for pediatric patients.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we report on the applicability of advanced X-ray microscopy techniques that offer exceptional spatial and quantitative resolution in elemental detection.", "output": {"entities": {}}, "schema": []}
{"input": "These techniques, which are useful for in vitro studies, will be particularly advantageous where investigators seek deeper understanding of diseases where mismetabolism of metals, either physiological important (i. e. Cu, Zn) or outright toxic (i. e. Pb), underlies pathogenesis.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 218, "end": 220}, {"text": "Zn", "start": 222, "end": 224}, {"text": "Pb", "start": 251, "end": 253}]}}, "schema": []}
{"input": "Pharmacogenomic approaches for tailored anti-leukemic therapy in children.", "output": {"entities": {}}, "schema": []}
{"input": "Several lympholytic and cytotoxic agents are used in acute lymphoblastic leukemia (ALL) polychemotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "Genetic variants for cellular components involved in the pharmacokinetics and pharmacodynamics of these drugs can influence the pharmacological response, and molecular characterization of these genetic variants could be helpful for the comprehension of the mechanisms of resistance or increased sensitivity.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this review is to carry out an update of recent publications on genes that might influence ALL treatment in terms of outcome and/or toxicity and to underlie the role of genetic variants, particularly single nucleotide polymorphisms (SNP), in predicting clinical response, with particular reference to the current protocol for ALL therapy used in Italy, AIEOP-BFM ALL 2009.", "output": {"entities": {}}, "schema": []}
{"input": "Potential use of polymeric nanoparticles for drug delivery across the blood-brain barrier.", "output": {"entities": {}}, "schema": []}
{"input": "Nanomedicine is certainly one of the scientific and technological challenges of the coming years.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, biodegradable nanoparticles formulated from poly (D, L-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted delivery of different agents, including recombinant proteins, plasmid DNA, and low molecular weight compounds.", "output": {"entities": {"chemical": [{"text": "poly (D, L-lactide-co-glycolide)", "start": 59, "end": 91}, {"text": "PLGA", "start": 93, "end": 97}]}}, "schema": []}
{"input": "PLGA NPs present some very attractive properties such as biodegradability and biocompatibility, protection of drug from degradation, possibility of sustained release, and the possibility to modify surface properties to target nanoparticles to specific organs or cells.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Moreover, PLGA NPs have received the FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, thus reducing the time for human clinical applications.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 10, "end": 14}]}}, "schema": []}
{"input": "This review in particular deals on surface modification of PLGA NPs and their possibility of clinical applications, including treatment for brain pathologies such as brain tumors and Lysosomal Storage Disorders with neurological involvement.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 59, "end": 63}]}}, "schema": []}
{"input": "Since a great number of pharmacologically active molecules are not able to cross the Blood-Brain Barrier (BBB) and reach the Central Nervous System (CNS), new brain targeted polymeric PLGA NPs modified with glycopeptides (g7-NPs) have been recently produced.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 184, "end": 188}]}}, "schema": []}
{"input": "In this review several in vivo biodistribution studies and pharmacological proof-of evidence of brain delivery of model drugs are reported, demonstrating the ability of g7-NPs to create BBB interaction and trigger an efficacious BBB crossing.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, another relevant development of NPs surface engineering was achieved by conjugating to the surface of g7-NPs, some specific and selective antibodies to drive NPs directly to a specific cell type once inside the CNS parenchyma.", "output": {"entities": {}}, "schema": []}
{"input": "Crotonaldehyde-exposed macrophages induce IL-8 release from airway epithelial cells through NF-kappa B and AP-1 pathways.", "output": {"entities": {"chemical": [{"text": "Crotonaldehyde", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Crotonaldehyde, a highly toxic alpha, beta-unsaturated aldehyde, is a major component of cigarette smoke and a ubiquitous environmental pollutant.", "output": {"entities": {"chemical": [{"text": "Crotonaldehyde", "start": 0, "end": 14}, {"text": "alpha, beta-unsaturated aldehyde", "start": 31, "end": 63}]}}, "schema": []}
{"input": "Crotonaldehyde exposure is known to have adverse effects on respiratory health, but the underlying mechanisms remain obscure.", "output": {"entities": {"chemical": [{"text": "Crotonaldehyde", "start": 0, "end": 14}]}}, "schema": []}
{"input": "To examine the interaction between macrophages and airway epithelial cells after exposure to crotonaldehyde, BEAS-2B and A549 cells were treated with conditioned media from a human monocytic leukemia cell line (THP-1) cells stimulated with crotonaldehyde.", "output": {"entities": {"chemical": [{"text": "crotonaldehyde", "start": 93, "end": 107}, {"text": "crotonaldehyde", "start": 240, "end": 254}]}}, "schema": []}
{"input": "We demonstrate that conditioned media from THP-1 cells stimulated with crotonaldehyde increased interleukin (IL)-8 production, enhanced nuclear factor (NF)-kappa B and AP-1 DNA-binding activity in BEAS-2B and A549 cells.", "output": {"entities": {"chemical": [{"text": "crotonaldehyde", "start": 71, "end": 85}]}}, "schema": []}
{"input": "Analysis of these conditioned media revealed marked increases in tumor necrosis factor (TNF)-alpha, IL-1 beta and IL-8 levels.", "output": {"entities": {}}, "schema": []}
{"input": "Preincubation of conditioned media with either TNF-alpha-or IL-1 beta-neutralizing antibodies reduced IL-8 production.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, BEAS-2B and A549 cells directly treated with crotonaldehyde induced increase in IL-8 production.", "output": {"entities": {"chemical": [{"text": "crotonaldehyde", "start": 58, "end": 72}]}}, "schema": []}
{"input": "These data suggest that crotonaldehyde is capable of directly stimulating the production of IL-8 in both macrophages and airway epithelial cells.", "output": {"entities": {"chemical": [{"text": "crotonaldehyde", "start": 24, "end": 38}]}}, "schema": []}
{"input": "Crotonaldehyde-stimulated macrophages also amplify the inflammatory response by enhancing IL-8 release from airway epithelial cells mediated by NF-kappa B and AP-1 pathways through a mechanism involving TNF-alpha and IL-1 beta.", "output": {"entities": {"chemical": [{"text": "Crotonaldehyde", "start": 0, "end": 14}]}}, "schema": []}
{"input": "These findings indicate that crotonaldehyde can cause lung inflammatory response via multiple mechanisms, and may contribute to chronic airway inflammation in smokers.", "output": {"entities": {"chemical": [{"text": "crotonaldehyde", "start": 29, "end": 43}]}}, "schema": []}
{"input": "Sub-acute, moderate-dose, but not short-term, low-dose dietary pre-exposure of mice to perfluorooctanoate aggravates concanavalin A-induced hepatitis.", "output": {"entities": {"chemical": [{"text": "perfluorooctanoate", "start": 87, "end": 105}]}}, "schema": []}
{"input": "Exposure of mice to perfluorooctanoate (PFOA) evokes pronounced hepatomegaly along with significant alterations in both the histological structure and immune status of the liver.", "output": {"entities": {"chemical": [{"text": "perfluorooctanoate", "start": 20, "end": 38}, {"text": "PFOA", "start": 40, "end": 44}]}}, "schema": []}
{"input": "The present study was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage.", "output": {"entities": {}}, "schema": []}
{"input": "In this connection, the influence of both sub-acute (10 days), moderate-dose (0. 002% w/w = 3 +/- 0. 7mg/kg body weight/day) and short-term (28 days), low-dose (0. 00005% w/w = 70 +/- 2 mu g/kg body weight/day) dietary pretreatment with PFOA on the development of concanavalin A (Con A)-induced liver damage in mice was examined.", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 237, "end": 241}]}}, "schema": []}
{"input": "With sub-acute, moderate, but not short-term, low-dose exposure, PFOA aggravated the acute liver damage caused by Con A, i. e., elevated serum levels of transaminases and led to more pronounced damage of hepatic tissue.", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 65, "end": 69}]}}, "schema": []}
{"input": "This aggravation was associated with significantly enhanced hepatic level of interleukin-6 (IL-6), but unaltered hepatic levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4).", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, hepatic DNA fragmentation was not changed by sub-acute exposure to the moderate-dose.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings imply that exposure to PFOA may sensitize hepatic parenchymal cells to other toxicants that activate the hepatic immune system and thereby aggravate liver injury during acute inflammation.", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 36, "end": 40}]}}, "schema": []}
{"input": "Antioxidant and Anti-inflammatory Meroterpenoids from the Brown Alga Cystoseira usneoides.", "output": {"entities": {"chemical": [{"text": "Meroterpenoids", "start": 34, "end": 48}]}}, "schema": []}
{"input": "A chemical study of the alga Cystoseira usneoides has led to the isolation of six new meroterpenoids, cystodiones A-F (1-6), together with six known related compounds (7-12).", "output": {"entities": {"chemical": [{"text": "meroterpenoids", "start": 86, "end": 100}, {"text": "cystodiones A-F", "start": 102, "end": 117}]}}, "schema": []}
{"input": "The structures of the new metabolites have been established by spectroscopic techniques.", "output": {"entities": {}}, "schema": []}
{"input": "In antioxidant assays all of the tested meroterpenes, and in particular cystodiones A (1) and B (2), 6-cis-amentadione-1'-methyl ether (7), and amentadione-1'-methyl ether (8), exhibited strong radical-scavenging activity.", "output": {"entities": {"chemical": [{"text": "meroterpenes", "start": 40, "end": 52}, {"text": "cystodiones A (1) and B", "start": 72, "end": 95}, {"text": "6-cis-amentadione-1'-methyl ether", "start": 101, "end": 134}, {"text": "amentadione-1'-methyl ether", "start": 144, "end": 171}]}}, "schema": []}
{"input": "In anti-inflammatory assays, usneoidone Z (11) and its corresponding 6E isomer (12) showed significant activity as inhibitors of the production of the proinflammatory cytokine TNF-alpha in LPS-stimulated THP-1 human macrophages.", "output": {"entities": {"chemical": [{"text": "usneoidone Z", "start": 29, "end": 41}]}}, "schema": []}
{"input": "Zinc oxide nanoparticle induced autophagic cell death and mitochondrial damage via reactive oxygen species generation.", "output": {"entities": {"chemical": [{"text": "Zinc oxide", "start": 0, "end": 10}, {"text": "oxygen", "start": 92, "end": 98}]}}, "schema": []}
{"input": "Zinc oxide nanoparticles (ZnO-np) are used in an increasing number of industrial products such as paint, coating and cosmetics, and in other biological applications.", "output": {"entities": {"chemical": [{"text": "Zinc oxide", "start": 0, "end": 10}, {"text": "ZnO", "start": 26, "end": 29}]}}, "schema": []}
{"input": "There have been many suggestions of a ZnO-np toxicity paradigm but the underlying molecular mechanisms about the toxicity of ZnO-np remain unclear.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 38, "end": 41}, {"text": "ZnO", "start": 125, "end": 128}]}}, "schema": []}
{"input": "This study was done to determine the potential toxicity of ZnO-np and to assess the toxicity mechanism in normal skin cells.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 59, "end": 62}]}}, "schema": []}
{"input": "Synthesized ZnO-np generated reactive oxygen species (ROS), as determined by electron spin resonance.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 12, "end": 15}, {"text": "oxygen", "start": 38, "end": 44}]}}, "schema": []}
{"input": "After uptake into cells, ZnO-np induced ROS in a concentration-and time-dependent manner.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 25, "end": 28}]}}, "schema": []}
{"input": "To demonstrate ZnO-np toxicity mechanism related to ROS, we detected abnormal autophagic vacuoles accumulation and mitochondria dysfunction after ZnO-np treatment.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 15, "end": 18}, {"text": "ZnO", "start": 146, "end": 149}]}}, "schema": []}
{"input": "Furthermore mitochondria membrane potential and adenosine-5'-triphosphate (ATP) production are decreased for culture with ZnO-np.", "output": {"entities": {"chemical": [{"text": "adenosine-5'-triphosphate", "start": 48, "end": 73}, {"text": "ATP", "start": 75, "end": 78}, {"text": "ZnO", "start": 122, "end": 125}]}}, "schema": []}
{"input": "We conclude that ZnO-np leads to cell death through autophagic vacuole accumulation and mitochondria damage in normal skin cells via ROS induction.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 17, "end": 20}]}}, "schema": []}
{"input": "Accordingly, ZnO-np may cause toxicity and the results highlight and need for careful regulation of ZnO-np production and use.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 13, "end": 16}, {"text": "ZnO", "start": 100, "end": 103}]}}, "schema": []}
{"input": "In vitro and in vivo evaluation of superparamagnetic iron oxide nanoparticles coated by bisphosphonates: The effects of electrical charge and molecule length.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 53, "end": 63}, {"text": "bisphosphonates", "start": 88, "end": 103}]}}, "schema": []}
{"input": "Physicochemical coating properties are often considered to be determining factors for in vivo characteristics of superparamagnetic iron oxide nanoparticles, used as contrast agent in Magnetic Resonance Imaging (MRI).", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 131, "end": 141}]}}, "schema": []}
{"input": "To investigate the electrical charge (modified by zero, one or two ammonium groups) and the molecule length (3, 5 or 7 methylene chains) effects of bisphosphonate-type coatings, we assessed the complement activation, in vivo plasma and tissue relaxation time alterations of intravenously injected small iron oxide nanoparticles (< 25nm) on male healthy Wistar rats.", "output": {"entities": {"chemical": [{"text": "ammonium", "start": 67, "end": 75}, {"text": "methylene", "start": 119, "end": 128}, {"text": "bisphosphonate", "start": 148, "end": 162}, {"text": "iron oxide", "start": 303, "end": 313}]}}, "schema": []}
{"input": "The presence of ammonium groups induces a weak activation of the complement whatever the size and the concentration of particles, whereas hydroxyethylenebisphosphonate (HEBP)-coated particles are poor complement activators only at the lowest concentration.", "output": {"entities": {"chemical": [{"text": "ammonium", "start": 16, "end": 24}, {"text": "hydroxyethylenebisphosphonate", "start": 138, "end": 167}, {"text": "HEBP", "start": 169, "end": 173}]}}, "schema": []}
{"input": "In vivo, HEBP-coated nanoparticles have the greatest prolonged relaxation time effects, despite their higher negative electrical charge, contrary to two ammonium bearing coatings.", "output": {"entities": {"chemical": [{"text": "HEBP", "start": 9, "end": 13}, {"text": "ammonium", "start": 153, "end": 161}]}}, "schema": []}
{"input": "No significant differences were observed between mono-ammonium molecular coatings.", "output": {"entities": {"chemical": [{"text": "mono-ammonium", "start": 49, "end": 62}]}}, "schema": []}
{"input": "Electrospinning covalently cross-linking biocompatible hydrogelators.", "output": {"entities": {}}, "schema": []}
{"input": "Many hydrogel materials of interest are homogeneous on the micrometer scale.", "output": {"entities": {}}, "schema": []}
{"input": "Electrospinning, the formation of sub-micrometer to micrometer diameter fibers by a jet of fluid formed under an electric field, is one process being explored to create rich microstructures.", "output": {"entities": {}}, "schema": []}
{"input": "However, electrospinning a hydrogel system as it reacts requires an understanding of the gelation kinetics and corresponding rheology near the liquid-solid transition.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we correlate the structure of electrospun fibers of a covalently cross-linked hydrogelator with the corresponding gelation transition and kinetics.", "output": {"entities": {}}, "schema": []}
{"input": "Polyethylene oxide (PEO) is used as a carrier polymer in a chemically cross-linking poly (ethylene glycol)-high molecular weight heparin (PEG-HMWH) hydrogel.", "output": {"entities": {"chemical": [{"text": "Polyethylene oxide", "start": 0, "end": 18}, {"text": "PEO", "start": 20, "end": 23}, {"text": "poly (ethylene glycol)", "start": 84, "end": 106}, {"text": "PEG", "start": 138, "end": 141}]}}, "schema": []}
{"input": "Using measurements of gelation kinetics from multiple particle tracking microrheology (MPT), we correlate the material rheology with the the formation of stable fibers.", "output": {"entities": {}}, "schema": []}
{"input": "An equilibrated, cross-linked hydrogel is then spun and the PEO is dissolved.", "output": {"entities": {"chemical": [{"text": "PEO", "start": 60, "end": 63}]}}, "schema": []}
{"input": "In both cases, microstructural features of the electrospun fibers are retained, confirming the covalent nature of the network.", "output": {"entities": {}}, "schema": []}
{"input": "The ability to spin fibers of a cross-linking hydrogel system ultimately enables the engineering of materials and microstructural length scales suitable for biological applications.", "output": {"entities": {}}, "schema": []}
{"input": "Exploring the genetic basis of chronic periodontitis: a genome-wide association study.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age-62 years, moderate CP-43% and severe CP-17%).", "output": {"entities": {}}, "schema": []}
{"input": "We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 x 10 (-6)) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP.", "output": {"entities": {}}, "schema": []}
{"input": "Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study.", "output": {"entities": {}}, "schema": []}
{"input": "Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)-NPY, rs2521634 [G]: odds ratio [OR = 1. 49 (95% confidence interval (CI = 1. 28-1. 73, P = 3. 5 x 10 (-7)))]; moderate CP (n = 2293)-NCR2, rs7762544 [G]: OR = 1. 40 (95% CI = 1. 24-1. 59, P = 7. 5 x 10 (-8)), EMR1, rs3826782 [A]: OR = 2. 01 (95% CI = 1. 52-2. 65, P = 8. 2 x 10 (-7)).", "output": {"entities": {}}, "schema": []}
{"input": "Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "A significant interaction of NUAK1 (rs11112872, interaction P = 2. 9 x 10 (-9)) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking.", "output": {"entities": {}}, "schema": []}
{"input": "These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo binding of the dopamine-1 receptor PET tracers [(11) C] NNC112 and [(11) C] SCH23390: a comparison study in individuals with schizophrenia.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 23, "end": 31}, {"text": "[(11) C] NNC112", "start": 55, "end": 70}, {"text": "[(11) C] SCH23390", "start": 75, "end": 92}]}}, "schema": []}
{"input": "RATIONALE: A deficit in dopamine-1 (D1) receptor function in the prefrontal cortex is suggested to play a role in the cognitive dysfunction observed in patients with schizophrenia.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 24, "end": 32}]}}, "schema": []}
{"input": "However, the results from positron emission tomography imaging studies of D1 receptor levels in individuals with schizophrenia are mixed.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVES: The aim of this investigation was to determine whether the in vivo characteristics of the different D1 receptor tracers used in previous reports, [(11) C] SCH23390 and [(11) C] NNC112, may have contributed to these discrepancies reported in the literature.", "output": {"entities": {"chemical": [{"text": "[(11) C] SCH23390", "start": 158, "end": 175}, {"text": "[(11) C] NNC112", "start": 180, "end": 195}]}}, "schema": []}
{"input": "METHODS: Eight patients with schizophrenia and 12 healthy control subjects were scanned with both [(11) C] SCH23390 and [(11) C] NNC112.", "output": {"entities": {"chemical": [{"text": "[(11) C] SCH23390", "start": 98, "end": 115}, {"text": "[(11) C] NNC112", "start": 120, "end": 135}]}}, "schema": []}
{"input": "RESULTS: [(11) C] SCH23390 and [(11) C] NNC112 binding potentials in both patients and control subjects were compared and no tracer by diagnosis interactions were observed.", "output": {"entities": {"chemical": [{"text": "[(11) C] SCH23390", "start": 9, "end": 26}, {"text": "[(11) C] NNC112", "start": 31, "end": 46}]}}, "schema": []}
{"input": "CONCLUSIONS: The results of this study suggest that differences in the binding of [(11) C] SCH23390 and [(11) C] NNC112 observed in previous studies are not due to differences in the in vivo behavior of these tracers.", "output": {"entities": {"chemical": [{"text": "[(11) C] SCH23390", "start": 82, "end": 99}, {"text": "[(11) C] NNC112", "start": 104, "end": 119}]}}, "schema": []}
{"input": "Replication of genetic effects of MC4R polymorphisms on body mass index in a Korean population.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity is associated with a variety of adverse health risks.", "output": {"entities": {}}, "schema": []}
{"input": "Several genome-wide association studies of obesity have identified candidate genes, including the fat mass and obesity-associated gene (FTO) and the melanocortin-4 receptor (MC4R) gene.", "output": {"entities": {}}, "schema": []}
{"input": "We carried out a replication study of MC4R and FTO variants in a Korean cohort.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 2, 281 subjects in the Bundang-gu region were analyzed using selected markers.", "output": {"entities": {}}, "schema": []}
{"input": "Another 8, 826 subjects in the Ansung/Ansan city were used for a meta-analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Two single nucleotide polymorphisms (SNPs) in FTO and one SNP in the MC4R gene were genotyped.", "output": {"entities": {}}, "schema": []}
{"input": "Multivariate linear regression models were employed to test for genotypic effects on obesity traits while adjusting for age and sex using an additive model.", "output": {"entities": {}}, "schema": []}
{"input": "The SNP rs17782313 near the MC4R gene was associated with mean body mass index in the Bundang-gu cohort (effect per allele 0. 288 kg/m (2), p = 0. 0023).", "output": {"entities": {}}, "schema": []}
{"input": "The p value for meta-analysis of rs17782313 in all 11, 107 individuals in the Bundang-gu and Ansung/Ansan cohorts was 2. 82 x 10 (-6) (effect per allele 0. 22 kg/m (2)).", "output": {"entities": {}}, "schema": []}
{"input": "Two SNPs in FTO were significantly associated with weight (effect per allele 0. 969 kg, p = 0. 011 for rs9939609; 0. 943, p = 0. 014 for rs8050136) but not with body mass index.", "output": {"entities": {}}, "schema": []}
{"input": "This study demonstrates that genetic variants in MC4R influence obesity traits in Korean adults.", "output": {"entities": {}}, "schema": []}
{"input": "Decorin Potentiates Interferon-gamma Activity in a Model of Allergic Inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "The proteoglycan decorin modulates leukocyte recruitment during delayed-type hypersensitivity responses.", "output": {"entities": {}}, "schema": []}
{"input": "Decorin-deficient (Dcn (-/-)) mice show reduced edema formation during the first 24 h with a concurrent attenuated recruitment of CD8 (+) leukocytes in the inflamed Dcn (-/-) ears.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to elucidate the molecular pathways affected by the loss of decorin.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo, reduced numbers of CD8 (+) cells in Dcn (-/-) ears correlated with a reduced interferon-gamma (Ifn-gamma) and CXCL-10 expression.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro, Dcn (-/-) lymphocytes displayed an increased adhesion to brain microvascular (bEnd. 3) endothelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "Decorin treatment of bEnd. 3 increased Icam1 and down-regulated Vcam1 expression after TNF-alpha stimulation.", "output": {"entities": {}}, "schema": []}
{"input": "However, Dcn (-/-) and wild-type lymphocytes produced IFN-gamma after activation with CD3 epsilon.", "output": {"entities": {}}, "schema": []}
{"input": "Upon incubation with decorin, endothelial cells and fibroblasts responded differently to IFN-gamma and TNF-alpha; CCL2 in bEnd. 3 cells was more prominently up-regulated by TNF-alpha compared with IFN-gamma.", "output": {"entities": {}}, "schema": []}
{"input": "Notably, both factors were more potent in the presence of decorin.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with TNF-alpha, IFN-gamma treatment induced significantly more CXCL-10, and both factors increased synthesis of CXCL-10 in the presence of decorin.", "output": {"entities": {}}, "schema": []}
{"input": "The response to IFN-gamma was similar in Dcn (-/-) and wild-type fibroblasts, an additional source of CXCL-10.", "output": {"entities": {}}, "schema": []}
{"input": "However, addition of decorin yielded significantly more CXCL-10.", "output": {"entities": {}}, "schema": []}
{"input": "Notably, decorin increased the stability of IFN-gamma in vitro and potentiated IFN-gamma-induced activation of STAT-1.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, only dermatan sulfate influenced IFN-gamma signaling by significantly increasing CXCL-10 expression in contrast to decorin protein core alone.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 27, "end": 34}]}}, "schema": []}
{"input": "Our data demonstrate that decorin modulates delayed-type hypersensitivity responses by augmenting the induction of downstream effector cytokines of IFN-gamma and TNF-alpha, thereby influencing the recruitment of CD8 (+) lymphocytes into the inflamed tissue.", "output": {"entities": {}}, "schema": []}
{"input": "(+)-Laburnamine, a Natural Selective Ligand and Partial Agonist for the alpha 4 beta 2 Nicotinic Receptor Subtype.", "output": {"entities": {"chemical": [{"text": "(+)-Laburnamine", "start": 0, "end": 15}]}}, "schema": []}
{"input": "(+)-Laburnamine (1), a rare alkaloid extracted from Laburnum anagyroides seeds (~ 4 mg from 1 kg), was shown to bind with high affinity (Ki, 293 nM) to the alpha 4 beta 2 nicotinic receptor subtype, which is, respectively, 126 and 136 times higher than to the alpha 3 beta 4 (Ki 37 mu M) and alpha 7 subtypes (Ki 40 mu M).", "output": {"entities": {"chemical": [{"text": "(+)-Laburnamine", "start": 0, "end": 15}]}}, "schema": []}
{"input": "When its ability to release [(3) H]-dopamine from striatal slices was tested in a functional assay, compound 1 behaved as a partial agonist with an EC50 of 5. 8 mu M and an Emax that was 43% that of nicotine.", "output": {"entities": {"chemical": [{"text": "[(3) H]-dopamine", "start": 28, "end": 44}, {"text": "nicotine", "start": 199, "end": 207}]}}, "schema": []}
{"input": "When incubated with nicotine in the same assay, 1 prevented a maximal effect from being reached.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 20, "end": 28}]}}, "schema": []}
{"input": "Grazing-incidence neutron-induced fluorescence probes density profiles of labeled molecules at solid/liquid interfaces.", "output": {"entities": {}}, "schema": []}
{"input": "We report on the use of characteristic prompt gamma-fluorescence after neutron capture induced by an evanescent neutron wave to probe densities and depth profiles of labeled molecules at solid/liquid interfaces.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to classical scattering techniques and X-ray fluorescence, this method of \" grazing-incidence neutron-induced fluorescence \" combines direct chemical specificity, provided by the label, with sensitivity to the interface, inherent to the evanescent wave.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that the formation of a supported lipid membrane can be quantitatively monitored from the characteristic fluorescence of (157) Gd (3 +) ions bound to the headgroup of chelator lipids.", "output": {"entities": {"chemical": [{"text": "(157) Gd (3 +)", "start": 136, "end": 150}]}}, "schema": []}
{"input": "Moreover, we were able to localize the (157) Gd (3 +) ions along the surface normal with nanometer precision.", "output": {"entities": {"chemical": [{"text": "(157) Gd (3 +)", "start": 39, "end": 53}]}}, "schema": []}
{"input": "This first proof of principle with a well-defined model system suggests that the method has a great potential for biology and soft matter studies where spatial resolution and chemical sensitivity are required.", "output": {"entities": {}}, "schema": []}
{"input": "Power spectral density of free-standing viscoelastic films by adiabatic approximation.", "output": {"entities": {}}, "schema": []}
{"input": "In a previous study, we calculated the surface dynamics of noisy viscoelastic supported films by using an adiabatic approximation.", "output": {"entities": {}}, "schema": []}
{"input": "An expression was derived for the time-dependent power spectral density (PSD), which was found to produce good agreement with experiment.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we extend the treatment to viscoelastic free-standing films.", "output": {"entities": {}}, "schema": []}
{"input": "Two sets of surface capillary normal modes, namely, the squeezing and bending modes, were found.", "output": {"entities": {}}, "schema": []}
{"input": "The frequency dispersion relation of the former resembles that of supported films.", "output": {"entities": {}}, "schema": []}
{"input": "The latter is distinctively different and diverges at long wavelengths.", "output": {"entities": {}}, "schema": []}
{"input": "By incorporating the experimental conditions, we obtained satisfactory agreement between theory and experiment.", "output": {"entities": {}}, "schema": []}
{"input": "Microneedle/nanoencapsulation-mediated transdermal delivery: Mechanistic insights.", "output": {"entities": {}}, "schema": []}
{"input": "A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored.", "output": {"entities": {}}, "schema": []}
{"input": "Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium-size molecules, respectively, were encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and delivered through full thickness porcine skin pretreated with MN array.", "output": {"entities": {"chemical": [{"text": "Rhodamine B", "start": 0, "end": 11}, {"text": "Rh B", "start": 13, "end": 17}, {"text": "fluorescein isothiocyanate", "start": 23, "end": 49}, {"text": "FITC", "start": 51, "end": 55}, {"text": "poly lactic-co-glycolic acid", "start": 158, "end": 186}, {"text": "PLGA", "start": 188, "end": 192}]}}, "schema": []}
{"input": "Permeation through MN-treated skin was affected by physicochemical characteristics of NPs and the encapsulated dyes.", "output": {"entities": {}}, "schema": []}
{"input": "Dye flux was enhanced by smaller particle size, hydrophilicity, and negative zeta potential of NPs.", "output": {"entities": {}}, "schema": []}
{"input": "Regarding encapsulated dyes, solubility at physiological pH and potential interaction with skin proteins proved to outweigh molecular weight as determinants of skin permeation.", "output": {"entities": {}}, "schema": []}
{"input": "Data were verified using confocal laser scanning microscopy imaging.", "output": {"entities": {}}, "schema": []}
{"input": "Findings coupled with the literature data are supportive of a mechanism involving influx of NPs, particularly of smaller size, deep into MN-created channels, generating depot dye-rich reservoirs.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular diffusion of the released dye across viable skin layers proceeds at a rate determined by its molecular characteristics.", "output": {"entities": {}}, "schema": []}
{"input": "Data obtained provide mechanistic information of importance to the development of formulation strategies for more effective intradermal and transdermal MN-mediated delivery of nanoencapsulated therapeutic agents.", "output": {"entities": {}}, "schema": []}
{"input": "Correlation between aflatoxin M1 content of breast milk, dietary exposure to aflatoxin B1 and socioeconomic status of lactating mothers in Ogun State, Nigeria.", "output": {"entities": {"chemical": [{"text": "aflatoxin M1", "start": 20, "end": 32}, {"text": "aflatoxin B1", "start": 77, "end": 89}]}}, "schema": []}
{"input": "Aflatoxin M1 (AF M1), a hydroxylated metabolite of AF B1, is an important toxin that can contaminate the milk of lactating mothers.", "output": {"entities": {"chemical": [{"text": "Aflatoxin M1", "start": 0, "end": 12}, {"text": "AF M1", "start": 14, "end": 19}, {"text": "AF B1", "start": 51, "end": 56}]}}, "schema": []}
{"input": "A correlation study was conducted to determine the relationship between AF M1 content of breast milk, dietary exposure to AF B1 and socioeconomic status of lactating mothers in the three Senatorial districts of Ogun State, Nigeria.", "output": {"entities": {"chemical": [{"text": "AF M1", "start": 72, "end": 77}, {"text": "AF B1", "start": 122, "end": 127}]}}, "schema": []}
{"input": "Equal amounts of breast milk (20ml) and food rations (40kg) obtained from 50 volunteer lactating mothers and eighty-two frequently consumed food commodities in the preceding month were used for the study.", "output": {"entities": {}}, "schema": []}
{"input": "The level of contamination of the foods by AF B1 was low (0. 16-0. 33 mu g/kg) and differed significantly (p < 0. 05) across the state but did not exceed the EU limit of 2 mu g/kg.", "output": {"entities": {"chemical": [{"text": "AF B1", "start": 43, "end": 48}]}}, "schema": []}
{"input": "The occurrence level of AF B1 was however high (93. 75-94. 45%) and was more pronounced in Ogun East Senatorial district (94. 45%).", "output": {"entities": {"chemical": [{"text": "AF B1", "start": 24, "end": 29}]}}, "schema": []}
{"input": "Eighty-two percent of the breast milk was contaminated with AF M1 (3. 49-35ng/l) and 16% exceeded the EU limit of 25ng/l while a 100% occurrence risk was recorded in Ogun Central Senatorial district.", "output": {"entities": {"chemical": [{"text": "AF M1", "start": 60, "end": 65}]}}, "schema": []}
{"input": "The socioeconomic status of the mothers also significantly influenced their dietary exposure and exposure risk of the sucklings to AF M1.", "output": {"entities": {"chemical": [{"text": "AF M1", "start": 131, "end": 136}]}}, "schema": []}
{"input": "Preclinical Assessment of Ketamine.", "output": {"entities": {"chemical": [{"text": "Ketamine", "start": 26, "end": 34}]}}, "schema": []}
{"input": "BACKGROUND: Ketamine is used as a general anesthetic, and recent data suggest that anesthetics can cause neurodegeneration and/or neuroprotection.", "output": {"entities": {"chemical": [{"text": "Ketamine", "start": 12, "end": 20}]}}, "schema": []}
{"input": "The precise mechanisms are not completely understood.", "output": {"entities": {}}, "schema": []}
{"input": "AIMS: This review is to examine the work on ketamine and to address how developmental biology may be utilized when combined with biochemical, pathological, and pharmacokinetic assessments to produce a bridging model that may decrease the uncertainty in extrapolating preclinical data to human conditions.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 44, "end": 52}]}}, "schema": []}
{"input": "RESULTS: Advantages of using preclinical models to study critical issues related to ketamine anesthesia have been described.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 84, "end": 92}]}}, "schema": []}
{"input": "These include the relationships between ketamine-induced neurotoxicity/protection and the preclinical models/approaches in elucidating mechanisms associated with ketamine exposure.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 40, "end": 48}, {"text": "ketamine", "start": 162, "end": 170}]}}, "schema": []}
{"input": "CONCLUSIONS: The discussions focus on the following: (1) the doses and time-course over which ketamine is associated with damage to, or protection of, neural cells, (2) how ketamine directs or signals neural cells to undergo apoptosis or necrosis, (3) how such exposures can trigger mitochondrial dysfunction, (4) how antioxidants and knockdowns of specific transcription modulators or receptors affect neurotoxicity induced by ketamine, and (5) whether the potential neural damage can be monitored after ketamine exposure in living animals using positron emission tomography.", "output": {"entities": {"chemical": [{"text": "ketamine", "start": 94, "end": 102}, {"text": "ketamine", "start": 173, "end": 181}, {"text": "ketamine", "start": 428, "end": 436}, {"text": "ketamine", "start": 505, "end": 513}]}}, "schema": []}
{"input": "Cell cycle arrest, extracellular matrix changes and intrinsic apoptosis in human melanoma cells are induced by Boron Neutron Capture Therapy.", "output": {"entities": {"chemical": [{"text": "Boron", "start": 111, "end": 116}]}}, "schema": []}
{"input": "Boron Neutron Capture Therapy (BNCT) involves the selective accumulation of boron carriers in tumor tissue followed by irradiation with a thermal or epithermal neutron beam.", "output": {"entities": {"chemical": [{"text": "Boron", "start": 0, "end": 5}]}}, "schema": []}
{"input": "This therapy is therefore a cellular irradiation suited to treat tumors that have infiltrated into healthy tissues.", "output": {"entities": {}}, "schema": []}
{"input": "BNCT has been used clinically to treat patients with cutaneous melanomas which have a high mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Human normal melanocytes and melanoma cells were treated with BNCT at different boronophenylalanine concentrations for signaling pathways analysis.", "output": {"entities": {"chemical": [{"text": "boronophenylalanine", "start": 80, "end": 99}]}}, "schema": []}
{"input": "BNCT induced few morphological alterations in normal melanocytes, with a negligible increase in free radical production.", "output": {"entities": {}}, "schema": []}
{"input": "Melanoma cells treated with BNCT showed significant extracellular matrix (ECM) changes and a significant cyclin D1 decrease, suggesting cell death by necrosis and apoptosis and cell cycle arrest, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "BNCT also induced a significant increase in cleaved caspase-3 and a decrease in the mitochondrial electrical potential with selectivity for melanoma cells.", "output": {"entities": {}}, "schema": []}
{"input": "Normal melanocytes had no significant differences due to BNCT treatment, confirming the data from the literature regarding the selectivity of BNCT.", "output": {"entities": {}}, "schema": []}
{"input": "The results from this study suggest that some signaling pathways are involved in human melanoma treatment by BNCT, such as cell cycle arrest, ECM changes and intrinsic apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Placental transfer of (125) Iodinated humanized immunoglobulin G2 Delta a in the Sprague Dawley rat.", "output": {"entities": {}}, "schema": []}
{"input": "Antibody-like biopharmaceuticals cross the placenta by utilizing transport pathways available for transfer of maternal antibodies to the conceptus.", "output": {"entities": {}}, "schema": []}
{"input": "To characterize the timing and magnitude of this transfer in the rat, embryo/fetal biodistribution of maternally administered radiolabeled humanized IgG2 was quantified over the course of gestation using gamma counting and whole body autoradiography.", "output": {"entities": {}}, "schema": []}
{"input": "The result was humanized IgG2 found in rat embryo/fetal tissues as early as gestation day 11 with a > 1000-fold increase in the amount of total IgG2 by day 21.", "output": {"entities": {}}, "schema": []}
{"input": "The concentration of IgG2 in rat embryo/fetal tissues generally remained unchanged from gestation day 11 to 17 with a slight increase from day 17 to 21.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, fetal-maternal tissue concentration ratios remained stable during organogenesis with a slight increase from gestation day 17 to 21.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the empirical amount of antibody present in the embryo/fetus during specific developmental windows, direct antibody binding to biological targets could potentially result in adverse developmental outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Carrier free rapamycin loaded drug eluting stent: In vitro and in vivo evaluation.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 13, "end": 22}]}}, "schema": []}
{"input": "In the search for improving the performance of drug eluting stent (DES) various developments are in progress worldwide including use of carrier free DES, use of biodegradable polymers, biodegradable stents etc.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, carrier free-rapamycin (RM) coated DES has been prepared, and evaluated by in vitro and in vivo procedures necessary for clinical development.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 27, "end": 36}]}}, "schema": []}
{"input": "In vitro drug release from the developed stents was carried in different release media, normal saline-isopropanol (NS-IP), phosphate buffer (PB), phosphate buffer saline (PBS) and in human plasma.", "output": {"entities": {"chemical": [{"text": "isopropanol", "start": 102, "end": 113}, {"text": "phosphate", "start": 123, "end": 132}, {"text": "phosphate", "start": 146, "end": 155}]}}, "schema": []}
{"input": "Simultaneously, drug released at site of implantation and biocompatibility of developed stents was determined after subcutaneous implantation in the SD rats.", "output": {"entities": {}}, "schema": []}
{"input": "Developed stent coating method enables fabrication of controllable and homogeneous crystalline RM coatings on stent scaffolds.", "output": {"entities": {}}, "schema": []}
{"input": "Continuous release of RM was observed in different release conditions with different release rate, maximum in NS-IP and least in PB.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, after subcutaneous implantation of these stents, RM was found in surrounding tissues and in implanted stent up to 28days.", "output": {"entities": {}}, "schema": []}
{"input": "Biocompatibility studies showed no evidence for presence of necrosis, foreign body giant cell reaction or any type of increased severity of inflammatory reaction, proving potential of developed stents for further clinical development.", "output": {"entities": {}}, "schema": []}
{"input": "Polyalkylcyanoacrylates as in situ formed diffusion barriers in multimaterial drug carriers.", "output": {"entities": {"chemical": [{"text": "Polyalkylcyanoacrylates", "start": 0, "end": 23}]}}, "schema": []}
{"input": "Polymeric hydrogels typically release their drug payload rapidly due to their high water content and the diffusivity for drug molecules.", "output": {"entities": {}}, "schema": []}
{"input": "This study proposes a multimaterial system to sustain the release by covering the hydrogel with a poly (alkyl-2-cyanoacrylate) [PACA]-based film, which should be formed by an in situ polymerization on the hydrogel surface initiated upon contact with water.", "output": {"entities": {"chemical": [{"text": "poly (alkyl-2-cyanoacrylate)", "start": 98, "end": 126}, {"text": "PACA", "start": 128, "end": 132}]}}, "schema": []}
{"input": "A series of PACA-hydrogel hybrid systems with increasing PACA side chain hydrophobicity was prepared using physically crosslinked alginate films and hydrophilic diclofenac sodium as model hydrogel/drug system.", "output": {"entities": {"chemical": [{"text": "PACA", "start": 12, "end": 16}, {"text": "PACA", "start": 57, "end": 61}, {"text": "diclofenac sodium", "start": 161, "end": 178}]}}, "schema": []}
{"input": "Successful synthesis of PACA at the hydrogel surface was confirmed and the PACA layer was identified to be most homogeneous for poly (n-butyl-2-cyanoacrylate) on both the micro-and nanolevel.", "output": {"entities": {"chemical": [{"text": "PACA", "start": 24, "end": 28}, {"text": "PACA", "start": 75, "end": 79}, {"text": "poly (n-butyl-2-cyanoacrylate)", "start": 128, "end": 158}]}}, "schema": []}
{"input": "At the same time, the diclofenac release from the hybrid systems was substantially sustained from ~ 1day for unmodified hydrogels up to > 14days depending on the type of PACA employed as diffusion barrier.", "output": {"entities": {"chemical": [{"text": "diclofenac", "start": 22, "end": 32}, {"text": "PACA", "start": 170, "end": 174}]}}, "schema": []}
{"input": "Overall, in situ polymerized PACA films on hydrogels may be widely applicable to various hydrogel matrices, different matrix sizes as well as more complex shaped hydrogel carriers.", "output": {"entities": {"chemical": [{"text": "PACA", "start": 29, "end": 33}]}}, "schema": []}
{"input": "Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice.", "output": {"entities": {}}, "schema": []}
{"input": "AIMS/HYPOTHESIS: Cholecystokinin (CCK) and leptin are important hormones with effects on energy balance.", "output": {"entities": {}}, "schema": []}
{"input": "The present study assessed the biological effects of (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3, smaller isoforms of CCK and leptin, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: The actions and overall therapeutic use of (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3, alone and in combination, were evaluated in normal and high-fat-fed mice.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: (pGlu-Gln)-CCK-8 had prominent (p < 0. 01 to p < 0. 001), acute feeding-suppressive effects, which were significantly augmented (p < 0. 05 to p < 0. 01) by [D-Leu-4]-OB3.", "output": {"entities": {}}, "schema": []}
{"input": "In agreement, the acute dose-dependent glucose-lowering and insulinotropic actions of (pGlu-Gln)-CCK-8 were significantly enhanced by concurrent administration of [D-Leu-4]-OB3.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 39, "end": 46}]}}, "schema": []}
{"input": "Twice daily injection of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in high-fat-fed mice for 18 days decreased body weight (p < 0. 05 to p < 0. 001), energy intake (p < 0. 01), circulating triacylglycerol (p < 0. 01), non-fasting glucose (p < 0. 05 to p < 0. 001) and triacylglycerol deposition in liver and adipose tissue (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "triacylglycerol", "start": 207, "end": 222}, {"text": "triacylglycerol", "start": 286, "end": 301}]}}, "schema": []}
{"input": "All treatment regimens improved glucose tolerance (p < 0. 05 to p < 0. 001) and insulin sensitivity (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 32, "end": 39}]}}, "schema": []}
{"input": "Combined treatment with (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3 resulted in significantly lowered plasma insulin levels, normalisation of circulating LDL-cholesterol and decreased triacylglycerol deposition in muscle.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 149, "end": 160}, {"text": "triacylglycerol", "start": 175, "end": 190}]}}, "schema": []}
{"input": "These effects were superior to either treatment regimen alone.", "output": {"entities": {}}, "schema": []}
{"input": "There were no changes in overall locomotor activity or respiratory exchange ratio, but treatment with (pGlu-Gln)-CCK-8 significantly reduced (p < 0. 001) energy expenditure.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS/INTERPRETATION: These studies highlight the potential of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in the treatment of obesity and diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of surface morphology on friction of graphene on various substrates.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 44, "end": 52}]}}, "schema": []}
{"input": "The friction of graphene on various substrates, such as SiO2, h-BN, bulk-like graphene, and mica, was investigated to characterize the adhesion level between graphene and the underlying surface.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 16, "end": 24}, {"text": "SiO2", "start": 56, "end": 60}, {"text": "graphene", "start": 78, "end": 86}, {"text": "mica", "start": 92, "end": 96}, {"text": "graphene", "start": 158, "end": 166}]}}, "schema": []}
{"input": "The friction of graphene on SiO2 decreased with increasing thickness and converged around the penta-layers due to incomplete contact between the two surfaces.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 16, "end": 24}, {"text": "SiO2", "start": 28, "end": 32}]}}, "schema": []}
{"input": "However, the friction of graphene on an atomically flat substrate, such as h-BN or bulk-like graphene, was low and comparable to that of bulk-like graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 25, "end": 33}, {"text": "graphene", "start": 93, "end": 101}, {"text": "graphene", "start": 147, "end": 155}]}}, "schema": []}
{"input": "In contrast, the friction of graphene folded onto bulk-like graphene was indistinguishable from that of mono-layer graphene on SiO2 despite the ultra-smoothness of bulk-like graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 29, "end": 37}, {"text": "graphene", "start": 60, "end": 68}, {"text": "graphene", "start": 115, "end": 123}, {"text": "SiO2", "start": 127, "end": 131}, {"text": "graphene", "start": 174, "end": 182}]}}, "schema": []}
{"input": "The characterization of the graphene' s roughness before and after folding showed that the corrugation of graphene induced by SiO2 morphology was preserved even after it was folded onto an atomically flat substrate.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 28, "end": 36}, {"text": "graphene", "start": 106, "end": 114}, {"text": "SiO2", "start": 126, "end": 130}]}}, "schema": []}
{"input": "In addition, graphene deposited on mica, when folded, preserved the same corrugation level as before the folding event.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 13, "end": 21}, {"text": "mica", "start": 35, "end": 39}]}}, "schema": []}
{"input": "Our friction measurements revealed that graphene, once exfoliated from the bulk crystal, tends to maintain its corrugation level even after it is folded onto an atomically flat substrate and that ultra-flatness in both graphene and the substrate is required to achieve the intimate contact necessary for strong adhesion.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 40, "end": 48}, {"text": "graphene", "start": 219, "end": 227}]}}, "schema": []}
{"input": "Protein fibrillation and nanoparticle interactions: opportunities and challenges.", "output": {"entities": {}}, "schema": []}
{"input": "Due to their ultra-small size, nanoparticles (NPs) have distinct properties compared with the bulk form of the same materials.", "output": {"entities": {}}, "schema": []}
{"input": "These properties are rapidly revolutionizing many areas of medicine and technology.", "output": {"entities": {}}, "schema": []}
{"input": "NPs are recognized as promising and powerful tools to fight against the human brain diseases such as multiple sclerosis or Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, after an introductory part on the nature of protein fibrillation and the existing approaches for its investigations, the effects of NPs on the fibrillation process have been considered.", "output": {"entities": {}}, "schema": []}
{"input": "More specifically, the role of biophysicochemical properties of NPs, which define their affinity for protein monomers, unfolded monomers, oligomers, critical nuclei, and other prefibrillar states, together with their influence on protein fibrillation kinetics has been described in detail.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, current and possible-future strategies for controlling the desired effect of NPs and their corresponding effects on the conformational changes of the proteins, which have significant roles in the fibrillation process, have been presented.", "output": {"entities": {}}, "schema": []}
{"input": "Developmental Changes in the Expression and Function of Cytochrome P450 3A Isoforms: Evidence from In Vitro and In Vivo Investigations.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this review is to discuss our current understanding of the developmental changes of the drug-metabolizing enzyme cytochrome P450 (CYP) 3A and its impact on drug therapy.", "output": {"entities": {}}, "schema": []}
{"input": "In the last 10 years, several methods have been used to study the ontogeny of specific CYP3A isoforms in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Although most studies confirm previous findings that CYP3A4/5 activity is low at birth and reaches adult values in the first years of life, there are still important gaps in our knowledge of the exact developmental patterns of individual CYP3A isoforms, especially in this age range.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, most in vivo clinical studies have also failed to cover the whole pediatric age range.", "output": {"entities": {}}, "schema": []}
{"input": "To date, this information gap still hampers the design of age-specific dosing guidelines of CYP3A substrate drugs, especially in neonates and infants.", "output": {"entities": {}}, "schema": []}
{"input": "Innovative study methods, including opportunistic sampling and sensitive analytical assays used in combination with physiologically based pharmacokinetics, and population pharmacokinetic model concepts may help to improve our understanding of the ontogeny of CYP3A and aid the application of this knowledge in clinical practice.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticle Accumulation in Angiogenic Tissues: Towards Predictable Pharmacokinetics.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration.", "output": {"entities": {}}, "schema": []}
{"input": "Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined.", "output": {"entities": {}}, "schema": []}
{"input": "It is shown that deposition is dependent on surface charge.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry.", "output": {"entities": {}}, "schema": []}
{"input": "These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.", "output": {"entities": {}}, "schema": []}
{"input": "Tubulin: an example of targeted chemotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "Anticancer drugs directed against the microtubule, including taxanes and vinca alkaloids, have been the backbone of many chemotherapy regimes for decades.", "output": {"entities": {"chemical": [{"text": "taxanes", "start": 61, "end": 68}, {"text": "vinca alkaloids", "start": 73, "end": 88}]}}, "schema": []}
{"input": "These drugs have, however, significant limitations, which have prompted the development of novel microtubule targeting agents (MTAs).", "output": {"entities": {}}, "schema": []}
{"input": "This article will discuss MTAs for anticancer therapies and recent debates regarding their mechanisms of action.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the limitations of taxanes, including hypersensitivity reactions, neurotoxicity, drug resistance and lack of validated biomarkers to guide therapy will be discussed, all of which have driven the development of novel agents.", "output": {"entities": {"chemical": [{"text": "taxanes", "start": 32, "end": 39}]}}, "schema": []}
{"input": "The mechanisms of action and drug development of new generations of MTAs will also be outlined.", "output": {"entities": {}}, "schema": []}
{"input": "Agents demonstrating utility in Phase III clinical trials, including eribulin, ixabepilone, cabazitaxel and trastuzumab-DM1 will be highlighted, as well as novel agents currently in development and future directions for MTAs.", "output": {"entities": {"chemical": [{"text": "eribulin", "start": 69, "end": 77}, {"text": "ixabepilone", "start": 79, "end": 90}, {"text": "cabazitaxel", "start": 92, "end": 103}, {"text": "DM1", "start": 120, "end": 123}]}}, "schema": []}
{"input": "Hierarchical or not?", "output": {"entities": {}}, "schema": []}
{"input": "Effect of the length scale and hierarchy of the surface roughness on omniphobicity of lubricant-infused substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Lubricant-infused textured solid substrates are gaining remarkable interest as a new class of omni-repellent nonfouling materials and surface coatings.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the effect of the length scale and hierarchy of the surface topography of the underlying substrates on their ability to retain the lubricant under high shear conditions, which is important for maintaining nonwetting properties under application-relevant conditions.", "output": {"entities": {}}, "schema": []}
{"input": "By comparing the lubricant loss, contact angle hysteresis, and sliding angles for water and ethanol droplets on flat, microscale, nanoscale, and hierarchically textured surfaces subjected to various spinning rates (from 100 to 10 000 rpm), we show that lubricant-infused textured surfaces with uniform nanofeatures provide the most shear-tolerant liquid-repellent behavior, unlike lotus leaf-inspired superhydrophobic surfaces, which generally favor hierarchical structures for improved pressure stability and low contact angle hysteresis.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 92, "end": 99}]}}, "schema": []}
{"input": "On the basis of these findings, we present generalized, low-cost, and scalable methods to manufacture uniform or regionally patterned nanotextured coatings on arbitrary materials and complex shapes.", "output": {"entities": {}}, "schema": []}
{"input": "After functionalization and lubrication, these coatings show robust, shear-tolerant omniphobic behavior, transparency, and nonfouling properties against highly contaminating media.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of stachydrine on endoplasmic reticulum stress-induced apoptosis in rat kidney after unilateral ureteral obstruction.", "output": {"entities": {"chemical": [{"text": "stachydrine", "start": 10, "end": 21}]}}, "schema": []}
{"input": "Our study aimed at determining the effect of stachydrine on the PERK, CHOP, and caspase-3 in rat kidney with RIF.", "output": {"entities": {"chemical": [{"text": "stachydrine", "start": 45, "end": 56}]}}, "schema": []}
{"input": "Rats were randomly divided into control group, model group, enalapril group, high stachydrine group, medium stachydrine group, and low stachydrine group.", "output": {"entities": {"chemical": [{"text": "enalapril", "start": 60, "end": 69}, {"text": "stachydrine", "start": 82, "end": 93}, {"text": "stachydrine", "start": 108, "end": 119}, {"text": "stachydrine", "start": 135, "end": 146}]}}, "schema": []}
{"input": "RIF models of five groups were developed by unilateral ureteral obstruction except the control group.", "output": {"entities": {}}, "schema": []}
{"input": "The rats were sacrificed 12 days after surgery and blood samples were collected.", "output": {"entities": {}}, "schema": []}
{"input": "Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were detected.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 6, "end": 16}, {"text": "nitrogen", "start": 38, "end": 46}]}}, "schema": []}
{"input": "Renal tubular damage index was determined by HE staining.", "output": {"entities": {}}, "schema": []}
{"input": "The area percentage of RIF was determined by the Masson method.", "output": {"entities": {}}, "schema": []}
{"input": "Expressions of PERK, CHOP, and caspase-3 in kidney were determined by immunohistochemistry.", "output": {"entities": {}}, "schema": []}
{"input": "Tubulointerstitial injury index, RIF, serum Scr, BUN level, and expressions of PERK, CHOP, and caspase-3 were different between the model and treatment groups (P < 0. 05; P < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "The expressions of PERK, CHOP, and caspase-3 in nephridial tissue were reduced (P < 0. 05), tubulointerstitial injury and RIF were reduced (P < 0. 05), and Scr and BUN were lower (P < 0. 05) in the high stachydrine group than those in the enalapril group.", "output": {"entities": {"chemical": [{"text": "stachydrine", "start": 203, "end": 214}, {"text": "enalapril", "start": 239, "end": 248}]}}, "schema": []}
{"input": "The expressions of PERK, CHOP, and caspase-3 were reduced in the endoplasmic reticulum stress-related apoptosis pathway after stachydrine treatment.", "output": {"entities": {"chemical": [{"text": "stachydrine", "start": 126, "end": 137}]}}, "schema": []}
{"input": "Consequently, apoptosis was prevented, and RIF was inhibited.", "output": {"entities": {}}, "schema": []}
{"input": "Uncinataflavone, a new flavonoid with a methyl benzoate substituent from Selaginella uncinata.", "output": {"entities": {"chemical": [{"text": "Uncinataflavone", "start": 0, "end": 15}, {"text": "flavonoid", "start": 23, "end": 32}, {"text": "methyl benzoate", "start": 40, "end": 55}]}}, "schema": []}
{"input": "Uncinataflavone (1), a new flavonoid, together with four known compounds (2-5), was isolated from Selaginella uncinata (Desv.) Spring.", "output": {"entities": {"chemical": [{"text": "Uncinataflavone", "start": 0, "end": 15}, {"text": "flavonoid", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Compounds 2 and 3 were isolated from the genus selaginella for the first time.", "output": {"entities": {}}, "schema": []}
{"input": "The structure of the new compound was determined as methyl 3-(5, 7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-6-yl)-4-methoxybenzoate by means of spectroscopic evidence, including UV, IR, 1D and 2D NMR analyses as well as HR-ESI-MS.", "output": {"entities": {"chemical": [{"text": "methyl 3-(5, 7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-6-yl)-4-methoxybenzoate", "start": 52, "end": 137}]}}, "schema": []}
{"input": "These compounds (1-5) were evaluated for the antioxidant activity in 1, 1-diphenyl-2-picrylhydrazyl assay system.", "output": {"entities": {"chemical": [{"text": "1, 1-diphenyl-2-picrylhydrazyl", "start": 69, "end": 99}]}}, "schema": []}
{"input": "The antiviral effect of 7-hydroxyisoflavone against Enterovirus 71 in vitro.", "output": {"entities": {"chemical": [{"text": "7-hydroxyisoflavone", "start": 24, "end": 43}]}}, "schema": []}
{"input": "Enterovirus 71 (EV71) is the major causative agent of hand foot and mouth disease.", "output": {"entities": {}}, "schema": []}
{"input": "And EV71 causes epidemics worldwide, particularly in the Asia-Pacific region.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, currently there is no approved vaccine or antiviral drug for EV71-induced disease prevention and therapy.", "output": {"entities": {}}, "schema": []}
{"input": "In screening for anti-EV71 candidates, we found that 7-hydroxyisoflavone was active against EV71.", "output": {"entities": {"chemical": [{"text": "7-hydroxyisoflavone", "start": 53, "end": 72}]}}, "schema": []}
{"input": "7-Hydroxyisoflavone exhibited strong antiviral activity against three different EV71 strains.", "output": {"entities": {"chemical": [{"text": "7-Hydroxyisoflavone", "start": 0, "end": 19}]}}, "schema": []}
{"input": "The 50% inhibitory concentration range was between 3. 25 and 4. 92 mu M by cytopathic effect assay.", "output": {"entities": {}}, "schema": []}
{"input": "7-Hydroxyisoflavone could reduce EV71 viral RNA and protein synthesis in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "7-Hydroxyisoflavone", "start": 0, "end": 19}]}}, "schema": []}
{"input": "Time course study showed that treatment of Vero cells with 7-hydroxyisoflavone at indicated times after EV71 inoculation (0-6 h) resulted in significant antiviral activity.", "output": {"entities": {"chemical": [{"text": "7-hydroxyisoflavone", "start": 59, "end": 78}]}}, "schema": []}
{"input": "Results showed that 7-hydroxyisoflavone acted at an early step of EV71 replication.", "output": {"entities": {"chemical": [{"text": "7-hydroxyisoflavone", "start": 20, "end": 39}]}}, "schema": []}
{"input": "7-Hydroxyisoflavone also exhibited strong antiviral activity against coxsackievirus B2, B3, and B6.", "output": {"entities": {"chemical": [{"text": "7-Hydroxyisoflavone", "start": 0, "end": 19}]}}, "schema": []}
{"input": "In short, 7-hydroxyisoflavone may be used as a lead compound for anti-EV71 drug development.", "output": {"entities": {"chemical": [{"text": "7-hydroxyisoflavone", "start": 10, "end": 29}]}}, "schema": []}
{"input": "Two new tri-nor-eudesmanolides from Inula racemosa.", "output": {"entities": {"chemical": [{"text": "tri-nor-eudesmanolides", "start": 8, "end": 30}]}}, "schema": []}
{"input": "Two new tri-nor-eudesmane-type sesquiterpenoids were isolated from the roots of Inula racemosa, and their structures were elucidated as 8-oxo-tri-nor-eudesm-6-en-5 alpha-ol (1) and tri-nor-eudesm-5-en-7 beta, 8 beta-diol (2).", "output": {"entities": {"chemical": [{"text": "tri-nor-eudesmane", "start": 8, "end": 25}, {"text": "sesquiterpenoids", "start": 31, "end": 47}, {"text": "8-oxo-tri-nor-eudesm-6-en-5 alpha-ol", "start": 136, "end": 172}, {"text": "tri-nor-eudesm-5-en-7 beta, 8 beta-diol", "start": 181, "end": 220}]}}, "schema": []}
{"input": "The cytotoxic activity of compound 1 against five human cancer cell lines had been tested, but exhibited no cytotoxic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Spectral Phonon Scattering from Sub-10 nm Surface Roughness Wavelengths in Metal-Assisted Chemically Etched Si Nanowires.", "output": {"entities": {"chemical": [{"text": "Si", "start": 108, "end": 110}]}}, "schema": []}
{"input": "Frequency dependence in phonon surface scattering is a debated topic in fundamental phonon physics.", "output": {"entities": {}}, "schema": []}
{"input": "Recent experiments and theory suggest such a phenomenon, but an independent agreement between the two remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "We report low-temperature dependence of thermal conductivity in silicon nanowires fabricated using a two-step, metal-assisted chemical etch.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 64, "end": 71}]}}, "schema": []}
{"input": "By reducing etch rates down to 0. 5 nm/s from the typical > 100 nm/s, we report controllable roughening of nanowire surfaces and selectively focus on moderate roughness scales rather than the extreme scales investigated previously.", "output": {"entities": {}}, "schema": []}
{"input": "This critically enables direct comparison with perturbation-based spectral scattering theory.", "output": {"entities": {}}, "schema": []}
{"input": "Using experimentally characterized surface roughness, we show that a multiple scattering theory provides excellent agreement and explanation of the observed low-temperature dependence of rough surface nanowires.", "output": {"entities": {}}, "schema": []}
{"input": "The theory does not employ any fitting parameters.", "output": {"entities": {}}, "schema": []}
{"input": "A 5-10 nm roughness correlation length is typical in metal-assisted chemical etching and resonantly scatters dominant phonons in silicon, leading to the observed ~ T (1. 6-2. 4) behavior.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 129, "end": 136}]}}, "schema": []}
{"input": "Our work provides fundamental and quantitative insight into spectral phonon scattering from rough surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "This advances applications of nanowires in thermoelectric energy conversion.", "output": {"entities": {}}, "schema": []}
{"input": "A new flavanol from Cynomorium songaricum.", "output": {"entities": {"chemical": [{"text": "flavanol", "start": 6, "end": 14}]}}, "schema": []}
{"input": "A new flavanol, named songarin A (1), was isolated from Cynomorium songaricum Rupr.", "output": {"entities": {"chemical": [{"text": "flavanol", "start": 6, "end": 14}, {"text": "songarin A", "start": 22, "end": 32}]}}, "schema": []}
{"input": "The structure was established on the basis of spectroscopic methods including 2D NMR techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 1 displayed the protective effect against d-galactosamine-induced HepG2 damage and reduced the damage from 58. 64% to 22. 26%.", "output": {"entities": {"chemical": [{"text": "d-galactosamine", "start": 51, "end": 66}]}}, "schema": []}
{"input": "Progress, challenges, and opportunities in two-dimensional materials beyond graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 76, "end": 84}]}}, "schema": []}
{"input": "Graphene' s success has shown that it is possible to create stable, single and few-atom-thick layers of van der Waals materials, and also that these materials can exhibit fascinating and technologically useful properties.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Here we review the state-of-the-art of 2D materials beyond graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 59, "end": 67}]}}, "schema": []}
{"input": "Initially, we will outline the different chemical classes of 2D materials and discuss the various strategies to prepare single-layer, few-layer, and multilayer assembly materials in solution, on substrates, and on the wafer scale.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, we present an experimental guide for identifying and characterizing single-layer-thick materials, as well as outlining emerging techniques that yield both local and global information.", "output": {"entities": {}}, "schema": []}
{"input": "We describe the differences that occur in the electronic structure between the bulk and the single layer and discuss various methods of tuning their electronic properties by manipulating the surface.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we highlight the properties and advantages of single-, few-, and many-layer 2D materials in field-effect transistors, spin-and valley-tronics, thermoelectrics, and topological insulators, among many other applications.", "output": {"entities": {}}, "schema": []}
{"input": "Protein Targets of Thioacetamide Metabolites in Rat Hepatocytes.", "output": {"entities": {"chemical": [{"text": "Thioacetamide", "start": 19, "end": 32}]}}, "schema": []}
{"input": "Thioacetamide (TA) has long been known as a hepatotoxicant whose bioactivation requires S-oxidation to thioacetamide S-oxide (TASO) and then to the very reactive S, S-dioxide (TASO2).", "output": {"entities": {"chemical": [{"text": "Thioacetamide", "start": 0, "end": 13}, {"text": "S", "start": 88, "end": 89}, {"text": "thioacetamide S-oxide", "start": 103, "end": 124}, {"text": "TASO", "start": 126, "end": 130}, {"text": "S, S-dioxide", "start": 162, "end": 174}, {"text": "TASO2", "start": 176, "end": 181}]}}, "schema": []}
{"input": "The latter can tautomerize to form acylating species capable of covalently modifying cellular nucleophiles including phosphatidylethanolamine (PE) lipids and protein lysine side chains.", "output": {"entities": {"chemical": [{"text": "phosphatidylethanolamine", "start": 117, "end": 141}, {"text": "lysine", "start": 166, "end": 172}]}}, "schema": []}
{"input": "Isolated hepatocytes efficiently oxidize TA to TASO but experience little covalent binding or cytotoxicity because TA is a very potent inhibitor of the oxidation of TASO to TASO2.", "output": {"entities": {"chemical": [{"text": "TASO", "start": 47, "end": 51}, {"text": "TASO", "start": 165, "end": 169}, {"text": "TASO2", "start": 173, "end": 178}]}}, "schema": []}
{"input": "However, hepatocytes treated with TASO show extensive covalent binding to both lipids and proteins accompanied by extensive cytotoxicity.", "output": {"entities": {"chemical": [{"text": "TASO", "start": 34, "end": 38}]}}, "schema": []}
{"input": "In this work, we treated rat hepatocytes with [(14) C]-TASO and submitted the mitochondrial, microsomal, and cytosolic fractions to 2DGE, which revealed a total of 321 radioactive protein spots.", "output": {"entities": {"chemical": [{"text": "[(14) C]-TASO", "start": 46, "end": 59}]}}, "schema": []}
{"input": "To facilitate the identification of target proteins and adducted peptides, we also treated cells with a mixture of TASO/[(13) C2D3]-TASO.", "output": {"entities": {"chemical": [{"text": "TASO", "start": 115, "end": 119}, {"text": "[(13) C2D3]-TASO", "start": 120, "end": 136}]}}, "schema": []}
{"input": "Using a combination of 1DGE-and 2DGE-based proteomic approaches, we identified 187 modified peptides (174 acetylated, 50 acetimidoylated, and 37 in both forms) from a total of 88 nonredundant target proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Among the latter, 57 are also known targets of at least one other hepatotoxin.", "output": {"entities": {}}, "schema": []}
{"input": "The formation of both amide-and amidine-type adducts to protein lysine side chains is in contrast to the exclusive formation of amidine-type adducts with PE phospholipids.", "output": {"entities": {"chemical": [{"text": "amide", "start": 22, "end": 27}, {"text": "amidine", "start": 32, "end": 39}, {"text": "lysine", "start": 64, "end": 70}, {"text": "amidine", "start": 128, "end": 135}]}}, "schema": []}
{"input": "Thiobenzamide (TB) undergoes the same two-step oxidative bioactivation as TA, and it also gives rise to both amide and amidine adducts on protein lysine side chains but only amidine adducts to PE lipids.", "output": {"entities": {"chemical": [{"text": "Thiobenzamide", "start": 0, "end": 13}, {"text": "amide", "start": 109, "end": 114}, {"text": "amidine", "start": 119, "end": 126}, {"text": "lysine", "start": 146, "end": 152}, {"text": "amidine", "start": 174, "end": 181}]}}, "schema": []}
{"input": "Despite their similarity in functional group chemical reactivity, only 38 of 62 known TB target proteins are found among the 88 known targets of TASO.", "output": {"entities": {"chemical": [{"text": "TASO", "start": 145, "end": 149}]}}, "schema": []}
{"input": "The potential roles of protein modification by TASO in triggering cytotoxicity are discussed in terms of enzyme inhibition, protein folding, and chaperone function, and the emerging role of protein acetylation in intracellular signaling and the regulation of biochemical pathways.", "output": {"entities": {"chemical": [{"text": "TASO", "start": 47, "end": 51}]}}, "schema": []}
{"input": "PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency.", "output": {"entities": {"chemical": [{"text": "PF-04859989", "start": 0, "end": 11}, {"text": "pyrazole", "start": 81, "end": 89}]}}, "schema": []}
{"input": "The structure-based design, synthesis, and biological evaluation of a new pyrazole series of irreversible KAT II inhibitors are described herein.", "output": {"entities": {"chemical": [{"text": "pyrazole", "start": 74, "end": 82}]}}, "schema": []}
{"input": "The modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core to a tetrahydropyrazolopyridinone core led to discovery of a new series of potent KAT II inhibitors with excellent physicochemical properties.", "output": {"entities": {"chemical": [{"text": "dihydroquinolinone", "start": 61, "end": 79}, {"text": "tetrahydropyrazolopyridinone", "start": 90, "end": 118}]}}, "schema": []}
{"input": "Compound 20 is the most potent and lipophilically efficient of these new pyrazole analogs, with a k (inact)/K (i) value of 112, 000 M (-1) s (-1) and lipophilic efficiency (LipE) of 8. 53.", "output": {"entities": {"chemical": [{"text": "pyrazole", "start": 73, "end": 81}]}}, "schema": []}
{"input": "The X-ray crystal structure of 20 with KAT II demonstrates key features that contribute to this remarkable potency and binding efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate.", "output": {"entities": {"chemical": [{"text": "dabigatran", "start": 57, "end": 67}, {"text": "methyl ferulate", "start": 88, "end": 103}]}}, "schema": []}
{"input": "A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl) propenoate (methyl ferulate) were synthesized.", "output": {"entities": {"chemical": [{"text": "dabigatran", "start": 38, "end": 48}, {"text": "methyl (E)-3-(4-hydroxy-2-methoxyphenyl) propenoate", "start": 53, "end": 104}, {"text": "methyl ferulate", "start": 106, "end": 121}]}}, "schema": []}
{"input": "All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50 = 3. 7 +/- 1. 0 mu mol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50 = 7. 8 +/- 1. 5 mu mol/kg).", "output": {"entities": {"chemical": [{"text": "dabigatran etexilate", "start": 188, "end": 208}]}}, "schema": []}
{"input": "A new series of N2-substituted-5-(p-toluenesulfonylamino) phthalimide analogues as alpha-glucosidase inhibitors.", "output": {"entities": {"chemical": [{"text": "N2-substituted-5-(p-toluenesulfonylamino) phthalimide", "start": 16, "end": 69}]}}, "schema": []}
{"input": "Several members of a new family of non-sugar-type alpha-glycosidase inhibitors, bearing a 5-(p-toluenesulfonylamino) phthalimide moiety and various substituent at the N2 position, were synthesized and their activities were investigated.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 39, "end": 44}, {"text": "5-(p-toluenesulfonylamino) phthalimide", "start": 90, "end": 128}]}}, "schema": []}
{"input": "The newly synthesized compounds displayed different inhibition profile towards yeast alpha-glycosidase and rat intestinal alpha-glycosidase.", "output": {"entities": {}}, "schema": []}
{"input": "Almost all the compounds had strong inhibitory activities against yeast alpha-glycosidase.", "output": {"entities": {}}, "schema": []}
{"input": "Regarding rat intestinal alpha-glycosidase, only analogs with N2-aromatic substituents displayed varying degrees of inhibitory activities on rat intestinal maltase and lactase and nearly all compounds showed no inhibition against rat intestinal alpha-amylase.", "output": {"entities": {}}, "schema": []}
{"input": "Structure-activity relationship studies indicated that 5-(p-toluenesulfonylamino) phthalimide moiety is a favorable scaffold to exert the alpha-glucosidase inhibitory activity and substituents at the N2 position have considerable influence on the efficacy of the inhibition activities.", "output": {"entities": {"chemical": [{"text": "5-(p-toluenesulfonylamino) phthalimide", "start": 55, "end": 93}]}}, "schema": []}
{"input": "Efficient synthesis and antimicrobial activity of some novel S-beta-d-glucosides of 5-aryl-1, 2, 4-triazole-3-thiones derivatives.", "output": {"entities": {"chemical": [{"text": "S-beta-d-glucosides", "start": 61, "end": 80}, {"text": "5-aryl-1, 2, 4-triazole-3-thiones", "start": 84, "end": 117}]}}, "schema": []}
{"input": "A series of 3-S-beta-d-glucosides-4-arylideneamino-5-aryl-1, 2, 4-triazoles were rationally designed and synthesized according to the principle of superposition of bioactive substructures by the combination of 1, 2, 4-triazole, Schiff base and glucosides.", "output": {"entities": {"chemical": [{"text": "3-S-beta-d-glucosides-4-arylideneamino-5-aryl-1, 2, 4-triazoles", "start": 12, "end": 75}, {"text": "1, 2, 4-triazole", "start": 210, "end": 226}, {"text": "Schiff base", "start": 228, "end": 239}, {"text": "glucosides", "start": 244, "end": 254}]}}, "schema": []}
{"input": "The structures of the target compounds have been characterized by (1) H NMR, (13) C NMR, IR, MS and HRMS.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 66, "end": 71}, {"text": "(13) C", "start": 77, "end": 83}]}}, "schema": []}
{"input": "All the newly synthesized compounds have been evaluated for their antimicrobial activities in vitro against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8099) as well as Monilia albican (ATCC 10231).", "output": {"entities": {}}, "schema": []}
{"input": "The bioactive assay showed that most of the tested compounds displayed variable inhibitory effects on the growth of the Gram-positive bacterial strain (Staphylococcus aureus), Gram-negative bacterial strains (Escherichia coli) and fungal strains (Monilia albican).", "output": {"entities": {}}, "schema": []}
{"input": "All the target compounds exhibited better antifungal activity than antibacterial activity.", "output": {"entities": {}}, "schema": []}
{"input": "Especially, compounds 6b, 6c, 6f, 6j, 6k and 6l showed excellent activity against fungus Monilia albican with MIC values of 16 mu g/mL.", "output": {"entities": {}}, "schema": []}
{"input": "Noradrenergic control of the bed nucleus of the stria terminalis in stress and reward.", "output": {"entities": {}}, "schema": []}
{"input": "The bed nucleus of the stria terminalis (BNST) is a group of inter-connected subnuclei that play critical roles in stress-reward interactions.", "output": {"entities": {}}, "schema": []}
{"input": "An interesting feature of this brain region is the massive noradrenergic input that it receives.", "output": {"entities": {}}, "schema": []}
{"input": "Important roles for norepinephrine in this region have been documented in a number of stress and reward related behaviors.", "output": {"entities": {"chemical": [{"text": "norepinephrine", "start": 20, "end": 34}]}}, "schema": []}
{"input": "This work has been paralleled over the last several years by efforts to understand the actions of norepinephrine on neuronal function in the region.", "output": {"entities": {"chemical": [{"text": "norepinephrine", "start": 98, "end": 112}]}}, "schema": []}
{"input": "In this review, we will summarize the current state of these research areas.", "output": {"entities": {}}, "schema": []}
{"input": "The two faces of the pharmacological interaction of mGlu2 and 5-HT2A-Relevance of receptor heterocomplexes and interaction through functional brain pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Important functional interactions between the metabotropic glutamate 2 (mGlu2) and 5-hydroxytryptamine2A (5-HT2A) neurotransmitter receptors have been established based on electrophysiological, biochemical and behavioral evidence.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 59, "end": 68}]}}, "schema": []}
{"input": "Over the last several years, dimerization between 5-HT2A and mGlu2 receptors has been proposed to account for the functional cross-talk between these two receptors in the prefrontal cortex.", "output": {"entities": {}}, "schema": []}
{"input": "The pros and cons for the existence of a heteromeric complex between 5-HT2A and mGlu2 receptors will be reviewed here.", "output": {"entities": {}}, "schema": []}
{"input": "First, the fundamental criteria needing to establish evidence for heteromeric complexes will be reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "Then, the in vitro evidence for and against heteromeric complexes between 5-HT2A and mGlu2 receptors will be discussed in regard to physical and functional interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, the data with native in situ mGlu2 and 5-HT2A receptors will be discussed with respect to whether heteromeric complexes or a simple functional interaction between two distinct GPCRs based on brain network activity is the more simple explanation for a range of in vivo data.", "output": {"entities": {}}, "schema": []}
{"input": "Reversal of P-glycoprotein-mediated multidrug resistance is induced by mollugin in MCF-7/adriamycin cells.", "output": {"entities": {"chemical": [{"text": "mollugin", "start": 71, "end": 79}]}}, "schema": []}
{"input": "P-glycoprotein (P-gp), an important efflux transporter, is encoded by the MDR1 class of genes and is a central element of the multidrug resistance (MDR) phenomenon in cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we investigated whether mollugin, purified from roots of Rubica cordifolia L., down-regulated MDR1 expression in MCF-7/adriamycin (MCF-7/adr) cells, a human breast multidrug-resistant cancer cell line.", "output": {"entities": {"chemical": [{"text": "mollugin", "start": 46, "end": 54}, {"text": "adriamycin", "start": 141, "end": 151}]}}, "schema": []}
{"input": "Mollugin treatment significantly inhibited MDR1 expression by blocking MDR1 transcription.", "output": {"entities": {"chemical": [{"text": "Mollugin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Mollugin treatment also significantly increased intracellular accumulation of the fluorescently-tagged P-gp substrate, rhodamine-123.", "output": {"entities": {"chemical": [{"text": "Mollugin", "start": 0, "end": 8}, {"text": "rhodamine-123", "start": 119, "end": 132}]}}, "schema": []}
{"input": "The suppression of MDR1 promoter activity and protein expression was mediated through mollugin-induced activation of AMP-activated protein kinase (AMPK).", "output": {"entities": {"chemical": [{"text": "mollugin", "start": 86, "end": 94}, {"text": "AMP", "start": 117, "end": 120}]}}, "schema": []}
{"input": "Furthermore, mollugin inhibited MDR1 expression through the suppression of NF-kappa B and CREB activation.", "output": {"entities": {"chemical": [{"text": "mollugin", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Interestingly, mollugin also inhibited COX-2 expression.", "output": {"entities": {"chemical": [{"text": "mollugin", "start": 15, "end": 23}]}}, "schema": []}
{"input": "These results suggest that mollugin treatment enhanced suppression of P-gp expression by inhibiting the NF-kappa B signaling pathway and COX-2 expression, as well as attenuating CRE transcriptional activity through AMPK activation.", "output": {"entities": {"chemical": [{"text": "mollugin", "start": 27, "end": 35}]}}, "schema": []}
{"input": "Membranar effects exerted in vitro by polyphenols-quercetin, epigallocatechin gallate and curcumin-on HUVEC and Jurkat cells, relevant for diabetes mellitus.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 38, "end": 49}, {"text": "quercetin", "start": 50, "end": 59}, {"text": "epigallocatechin gallate", "start": 61, "end": 85}, {"text": "curcumin", "start": 90, "end": 98}]}}, "schema": []}
{"input": "Polyphenols are largely studied for their beneficial action in various pathologies, but the correlation with their effects on cell membranes is still elusive.", "output": {"entities": {"chemical": [{"text": "Polyphenols", "start": 0, "end": 11}]}}, "schema": []}
{"input": "In the present study we assessed the effects exerted in vitro by quercetin, epigallocatechin gallate and curcumin on membrane fluidity and transmembrane potential of human umbilical vein endothelial cells and Jurkat T lymphoblasts, in experimental conditions mimicking diabetes mellitus, i. e. high glucose conditions or increased concentration of advanced glycation end products.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 65, "end": 74}, {"text": "epigallocatechin gallate", "start": 76, "end": 100}, {"text": "curcumin", "start": 105, "end": 113}, {"text": "glucose", "start": 299, "end": 306}]}}, "schema": []}
{"input": "Results showed that the investigated polyphenols had beneficial effects on cell membranes altered in diabetic conditions, by restoring transmembrane potential and by membrane \" stiffening \".", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 37, "end": 48}]}}, "schema": []}
{"input": "Moreover, they limited the release of pro-inflammatory factors, like monocyte chemotactic protein-1.", "output": {"entities": {}}, "schema": []}
{"input": "These effects were more obvious for cells exposed to advanced glycation end products specific for the late stages of diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Apparently, the inhibitory action of polyphenols on lipid peroxidation was associated with a decrease of membrane fluidity.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 37, "end": 48}]}}, "schema": []}
{"input": "Concluding, our in vitro study highlighted the potential beneficial action of polyphenols mainly in the late stages of diabetes, exerted at the level of membrane fluidity and transmembrane potential, accompanied by an anti-inflammatory effect on endothelial and immune cells.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 78, "end": 89}]}}, "schema": []}
{"input": "miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 15, "end": 24}]}}, "schema": []}
{"input": "Resistance to chemotherapy is a major obstacle for the effective treatment of cancers.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism of chemo-resistance is still poorly understood, however, mounting evidence supports a role for microRNAs (miRNAs) in modulating key cellular pathways mediating response to chemotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "microRNA-21 (miR-21) has been implicated in many cancers and contributed to chemo-resistance, but its role in gastric cancer drug resistance still remains unexplored.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to investigate whether miR-21 mediated resistance of the gastric cancer cell line SGC7901 to the chemotherapeutic agent cisplatin (DDP).", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 146, "end": 155}, {"text": "DDP", "start": 157, "end": 160}]}}, "schema": []}
{"input": "Our study found that the expression of miR-21 upregulated in the cisplatin resistant cell line SGC7901/DDP compared to its parental line SGC7901.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 65, "end": 74}, {"text": "DDP", "start": 103, "end": 106}]}}, "schema": []}
{"input": "Moreover, over-expression of miR-21 significantly decreased antiproliferative effects and apoptosis induced by cisplatin, while knockdown of miR-21 dramatically increased antiproliferative effects and apoptosis induction by cisplatin.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 111, "end": 120}, {"text": "cisplatin", "start": 224, "end": 233}]}}, "schema": []}
{"input": "In addition, miR-21 induced cell survival and cisplatin resistance through downregulating the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN) and activation of Akt pathway.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 46, "end": 55}]}}, "schema": []}
{"input": "Inhibition of Akt using PI3K inhibitor LY 294002 could abrogate miR-21 induced cell survival.", "output": {"entities": {"chemical": [{"text": "LY 294002", "start": 39, "end": 48}]}}, "schema": []}
{"input": "These results suggest that miR-21 may provide a novel mechanism for understanding cisplatin resistance in gastric cancer by modulating PTEN/PI3K/Akt pathway.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 82, "end": 91}]}}, "schema": []}
{"input": "p-Cresol induces disruption of cardiomyocyte adherens junctions.", "output": {"entities": {"chemical": [{"text": "p-Cresol", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Higher serum levels of p-cresol in chronic kidney disease populations have been associated with increased cardiovascular mortality.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 23, "end": 31}]}}, "schema": []}
{"input": "However, studies on how p-cresol affects intercellular junctions between cardiomyocytes were limited.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 24, "end": 32}]}}, "schema": []}
{"input": "This study investigated the effect of p-cresol on adherens junction (AJ) of neonatal cultured cardiomyocytes and its underlying mechanism.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 38, "end": 46}]}}, "schema": []}
{"input": "A loss of N-cadherin and p120-catenin (p120ctn) immunostaining from cell-cell contact sites was noted by p-cresol treatment.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 105, "end": 113}]}}, "schema": []}
{"input": "In addition, p-cresol disrupted AJs by inducing formation of intercellular gaps.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Our previous study has revealed that p-cresol increased intracellular calcium levels and activated protein kinase C alpha (PKC alpha) by phosphorylation.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 37, "end": 45}, {"text": "calcium", "start": 70, "end": 77}]}}, "schema": []}
{"input": "The PKC alpha activation was involved in the p-cresol-mediated AJ disassembly, since pharmacological inhibition of PKC alpha abolished the above-mentioned p-cresol effect.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 45, "end": 53}, {"text": "p-cresol", "start": 155, "end": 163}]}}, "schema": []}
{"input": "This PKC alpha activation also led to the serine dephosphorylation of p120ctn and caused the dissociation of p120ctn from N-cadherin.", "output": {"entities": {"chemical": [{"text": "serine", "start": 42, "end": 48}]}}, "schema": []}
{"input": "This hypothesis was further confirmed in H9c2 cells by siRNA approach.", "output": {"entities": {}}, "schema": []}
{"input": "SiRNA knockdown of PKC alpha prevented p-cresol-induced serine dephosphorylation of p120ctn and splitting of AJ.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 39, "end": 47}]}}, "schema": []}
{"input": "In conclusion, p-cresol caused PKC alpha-dependent AJ disassembly of cardiomyocytes, which might be related to asychronized contraction.", "output": {"entities": {"chemical": [{"text": "p-cresol", "start": 15, "end": 23}]}}, "schema": []}
{"input": "ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.", "output": {"entities": {"chemical": [{"text": "zinc", "start": 5, "end": 9}]}}, "schema": []}
{"input": "Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR).", "output": {"entities": {}}, "schema": []}
{"input": "MWS is caused by de novo heterozygous mutations in the ZEB2 gene.", "output": {"entities": {}}, "schema": []}
{"input": "The majority of mutations lead to haplo-insufficiency through premature stop codons or large gene deletions.", "output": {"entities": {}}, "schema": []}
{"input": "Only three missense mutations have been reported so far; none of which resides in a known functional domain of ZEB2.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we report and analyze the functional consequences of three novel missense mutations, p. Tyr1055Cys, p. Ser1071Pro and p. His1045Arg, identified in the highly conserved C-zinc-finger (C-ZF) domain of ZEB2.", "output": {"entities": {"chemical": [{"text": "zinc", "start": 185, "end": 189}]}}, "schema": []}
{"input": "Patients' phenotype included the facial gestalt of MWS and moderate ID, but no microcephaly, heart defects or HSCR.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro studies showed that all the three mutations prevented binding and repression of the E-cadherin promoter, a characterized ZEB2 target gene.", "output": {"entities": {}}, "schema": []}
{"input": "Taking advantage of the zebrafish morphant technology, we performed rescue experiments using wild-type (WT) and mutant human ZEB2 mRNAs.", "output": {"entities": {}}, "schema": []}
{"input": "Variable, mutation-dependent, embryo rescue, correlating with the severity of patients' phenotype, was observed.", "output": {"entities": {}}, "schema": []}
{"input": "Our data provide evidence that these missense mutations cause a partial loss of function of ZEB2, suggesting that its role is not restricted to repression of E-cadherin.", "output": {"entities": {}}, "schema": []}
{"input": "Functional domains other than C-ZF may play a role in early embryonic development.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, these findings broaden the clinical spectrum of ZEB2 mutations, indicating that MWS ought to be considered in patients with lesser degrees of ID and a suggestive facial gestalt, even in the absence of congenital malformation.", "output": {"entities": {}}, "schema": []}
{"input": "Potent vasorelaxant analogs from chemical modification and biotransformation of isosteviol.", "output": {"entities": {"chemical": [{"text": "isosteviol", "start": 80, "end": 90}]}}, "schema": []}
{"input": "Isosteviol (1) has been reported to exhibit moderate vasorelaxant activity.", "output": {"entities": {"chemical": [{"text": "Isosteviol", "start": 0, "end": 10}]}}, "schema": []}
{"input": "In order to enhance the bioactivity of this compound, chemical modification of 1 to the dihydro analog, ent-16 beta-hydroxybeyeran-19-oic acid (2), was undertaken.", "output": {"entities": {"chemical": [{"text": "ent-16 beta-hydroxybeyeran-19-oic acid", "start": 104, "end": 142}]}}, "schema": []}
{"input": "Compound 2 was then converted to the corresponding acetate derivative, ent-16 beta-acetoxybeyeran-19-oic acid (3).", "output": {"entities": {"chemical": [{"text": "acetate", "start": 51, "end": 58}, {"text": "ent-16 beta-acetoxybeyeran-19-oic acid", "start": 71, "end": 109}]}}, "schema": []}
{"input": "Biotransformation of compounds 1-3 by the fungus Cunninghamella echinulata NRRL 1386 was investigated and the metabolites 4-9 were obtained.", "output": {"entities": {}}, "schema": []}
{"input": "The substrates and their metabolites were subjected to in vitro rat aorta relaxant activity evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "The metabolite 4, ent-7 alpha-hydroxy-16-ketobeyeran-19-oic acid, exhibited the most highly potent activity, with EC50 of 3. 46 nM, whereas the parent compound 1 showed relatively low activity (EC50 57. 41 nM).", "output": {"entities": {"chemical": [{"text": "ent-7 alpha-hydroxy-16-ketobeyeran-19-oic acid", "start": 18, "end": 64}]}}, "schema": []}
{"input": "A 17-fold increase in vasorelaxant activity of the analog 4 relative to compound 1 is of particular significant.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 4 exerted vasorelaxant activity at particularly low concentration and the vasorelaxant profile reached maximum at relatively low concentration, especially when compared with acetylcholine, the positive control.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 183, "end": 196}]}}, "schema": []}
{"input": "A novel insulin mimetic vanadium-flavonol complex: Synthesis, characterization and in vivo evaluation in STZ-induced rats.", "output": {"entities": {"chemical": [{"text": "vanadium-flavonol", "start": 24, "end": 41}, {"text": "STZ", "start": 105, "end": 108}]}}, "schema": []}
{"input": "Since 1985, when Heyliger et al., first demonstrated a serendipitous discovery that oral administration of 0. 8 mg/ml of sodium orthovanadate in drinking water to streptozotocin-induced diabetic rats resulted in normoglycemia, numerous extensive studies have been pursued on the anti-diabetic and insulinomimetic actions of vanadium.", "output": {"entities": {"chemical": [{"text": "sodium orthovanadate", "start": 121, "end": 141}, {"text": "streptozotocin", "start": 163, "end": 177}, {"text": "vanadium", "start": 324, "end": 332}]}}, "schema": []}
{"input": "The acceptance of vanadium compounds as promising therapeutic antidiabetic agents has been slowed due to the concern for chronic toxicity associated with vanadium accumulation.", "output": {"entities": {"chemical": [{"text": "vanadium", "start": 18, "end": 26}, {"text": "vanadium", "start": 154, "end": 162}]}}, "schema": []}
{"input": "In order to circumvent the toxic effects of vanadium, we have taken up a combinational approach wherein a novel vanadium-flavonol complex was synthesized, characterized and its toxic as well as insulin mimetic potential was evaluated in STZ-induced experimental diabetes in rats.", "output": {"entities": {"chemical": [{"text": "vanadium", "start": 44, "end": 52}, {"text": "vanadium-flavonol", "start": 112, "end": 129}, {"text": "STZ", "start": 237, "end": 240}]}}, "schema": []}
{"input": "The results indicate that the complex is non-toxic and possess anti-diabetic activity.", "output": {"entities": {}}, "schema": []}
{"input": "GPER: A novel target for non-genomic estrogen action in the cardiovascular system.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 37, "end": 45}]}}, "schema": []}
{"input": "A key to harnessing the enormous therapeutic potential of estrogens is understanding the diversity of estrogen receptors and their signaling mechanisms.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 58, "end": 67}, {"text": "estrogen", "start": 102, "end": 110}]}}, "schema": []}
{"input": "In addition to the classic nuclear estrogen receptors (i. e., ER alpha and ER beta), over the past decade a novel G-protein-coupled estrogen receptor (GPER) has been discovered in cancer and other cell types.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 35, "end": 43}, {"text": "estrogen", "start": 132, "end": 140}]}}, "schema": []}
{"input": "More recently, this non-genomic signaling mechanism has been found in blood vessels, and mediates vasodilatory responses to estrogen and estrogen-like agents; however, downstream signaling events involved acute estrogen action remain unclear.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 124, "end": 132}, {"text": "estrogen", "start": 137, "end": 145}, {"text": "estrogen", "start": 211, "end": 219}]}}, "schema": []}
{"input": "The purpose of this review is to discuss the latest knowledge concerning GPER modulation of cardiovascular function, with a particular emphasis upon how activation of this receptor could mediate acute estrogen effects in the heart and blood vessels (i. e., vascular tone, cell growth and differentiation, apoptosis, endothelial function, myocardial protection).", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 201, "end": 209}]}}, "schema": []}
{"input": "Understanding the role of GPER in estrogen signaling may help resolve some of the controversies associated with estrogen and cardiovascular function.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 34, "end": 42}, {"text": "estrogen", "start": 112, "end": 120}]}}, "schema": []}
{"input": "Moreover, a more thorough understanding of GPER function could also open significant opportunities for the development of new pharmacological strategies that would provide the cardiovascular benefits of estrogen while limiting the potentially dangerous side effects.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 203, "end": 211}]}}, "schema": []}
{"input": "Monitoring abacavir bioactivation in humans: Screening for an aldehyde metabolite.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 11, "end": 19}, {"text": "aldehyde", "start": 62, "end": 70}]}}, "schema": []}
{"input": "The anti-HIV drug abacavir is associated with idiosyncratic hypersensitivity reactions and cardiotoxicity.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 18, "end": 26}]}}, "schema": []}
{"input": "Although the mechanism underlying abacavir-toxicity is not fully understood, drug bioactivation to reactive metabolites may be involved.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 34, "end": 42}]}}, "schema": []}
{"input": "This work was aimed at identifying abacavir-protein adducts in the hemoglobin of HIV patients as biomarkers of abacavir bioactivation and protein modification.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 35, "end": 43}, {"text": "abacavir", "start": 111, "end": 119}]}}, "schema": []}
{"input": "The protocol received prior approval from the Hospital Ethics Committee, patients gave their written informed consent and adherence was controlled through a questionnaire.", "output": {"entities": {}}, "schema": []}
{"input": "Abacavir-derived Edman adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method.", "output": {"entities": {"chemical": [{"text": "Abacavir", "start": 0, "end": 8}, {"text": "N", "start": 40, "end": 41}, {"text": "valine", "start": 51, "end": 57}]}}, "schema": []}
{"input": "Abacavir-valine adducts were detected in three out of ten patients.", "output": {"entities": {"chemical": [{"text": "Abacavir", "start": 0, "end": 8}, {"text": "valine", "start": 9, "end": 15}]}}, "schema": []}
{"input": "This work represents the first evidence of abacavir-protein adduct formation in humans.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 43, "end": 51}]}}, "schema": []}
{"input": "The data confirm the ability of abacavir to modify self-proteins and suggest that the molecular mechanism (s) of some abacavir-induced adverse reactions may require bioactivation.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 32, "end": 40}, {"text": "abacavir", "start": 118, "end": 126}]}}, "schema": []}
{"input": "Refinement of the ECETOC approach to identify endocrine disrupting properties of chemicals in ecotoxicology.", "output": {"entities": {}}, "schema": []}
{"input": "To use and implement an assessment scheme for the evaluation of endocrine disrupting properties of chemicals in ecotoxicology, the types of effect need to be agreed.", "output": {"entities": {}}, "schema": []}
{"input": "Effects that merit further consideration in this context should fulfil the following three criteria: caused by an endocrine mode of action, be adverse, and be relevant at the population level to reflect the protection goal of ecotoxicological assessments.", "output": {"entities": {}}, "schema": []}
{"input": "Thereafter, a comparison of effect values, regardless of the causative mechanisms, should be made, firstly to determine if endocrine toxicity generates the lowest endpoint within a taxon, and secondly if it is the lowest endpoint compared to that of other taxa living in the same compartment.", "output": {"entities": {}}, "schema": []}
{"input": "These comparisons inform on two levels of specificity and determine if endocrine-mediated side-effects determine the ecotoxicological profile of a chemical.", "output": {"entities": {}}, "schema": []}
{"input": "Various quantitative measures for the assessment of potency are also presented, which could assist in determining how to handle substances in the risk assessment when a regulatory concern is identified.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, derogation criteria should be defined for compounds that were designed as endocrine disruptors for non-vertebrates and those for which there is' negligible exposure'.", "output": {"entities": {}}, "schema": []}
{"input": "This paper discusses and provides proposals on how to apply these concepts for assessment of substances.", "output": {"entities": {}}, "schema": []}
{"input": "Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.", "output": {"entities": {"chemical": [{"text": "alcoholism", "start": 18, "end": 28}]}}, "schema": []}
{"input": "RATIONALE: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA).", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 54, "end": 61}]}}, "schema": []}
{"input": "One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 182, "end": 189}]}}, "schema": []}
{"input": "METHODS: Twenty-two family history-positive (FHP; age = 22. 7 years, SD = 1. 9) and 18 family history-negative (FHN; age = 23. 7, SD = 1. 8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 238, "end": 245}, {"text": "alcohol", "start": 280, "end": 287}]}}, "schema": []}
{"input": "An independent reference group (n = 13, age = 23. 7, SD = 1. 8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to \" Go \" trials that carried no need for inhibition [Inh > Go].", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 29, "end": 36}, {"text": "alcohol", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55: 149-158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35: 1759-1770, 2011), with FHP being less sensitive to alcohol' s effects.", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 96, "end": 103}, {"text": "Alcohol", "start": 141, "end": 148}, {"text": "alcohol", "start": 217, "end": 224}]}}, "schema": []}
{"input": "3-Hydroxyazetidine carboxylic acids: non-proteinogenic amino acids for medicinal chemists.", "output": {"entities": {"chemical": [{"text": "3-Hydroxyazetidine carboxylic acids", "start": 0, "end": 35}, {"text": "amino acids", "start": 55, "end": 66}]}}, "schema": []}
{"input": "The formation from D-glucose of both enantiomers of 2, 4-dideoxy-2, 4-iminoribonic acid is the first chemical synthesis of unprotected 3-hydroxyazetidine carboxylic acids.", "output": {"entities": {"chemical": [{"text": "D-glucose", "start": 19, "end": 28}, {"text": "2, 4-dideoxy-2, 4-iminoribonic acid", "start": 52, "end": 87}, {"text": "3-hydroxyazetidine carboxylic acids", "start": 135, "end": 170}]}}, "schema": []}
{"input": "The long-term stability of 3-hydroxyazetidine amides is established at acidic and neutral pH and implies their value as non-proteinogenic amino acid components of peptides, providing medicinal chemists with a new class of peptide isosteres.", "output": {"entities": {"chemical": [{"text": "3-hydroxyazetidine amides", "start": 27, "end": 52}, {"text": "amino acid", "start": 138, "end": 148}]}}, "schema": []}
{"input": "The structure of N, 3-O-dibenzyl-2, 4-dideoxy-2, 4-imino-D-ribonic acid was established by X-ray crystallographic analysis.", "output": {"entities": {"chemical": [{"text": "N, 3-O-dibenzyl-2, 4-dideoxy-2, 4-imino-D-ribonic acid", "start": 17, "end": 71}]}}, "schema": []}
{"input": "An N-methylazetidine amide derivative is a specific inhibitor of beta-hexosaminidases at the micromolar level, and is only the second example of potent inhibition of any glycosidase by an amide of a sugar amino acid related to an iminosugar.", "output": {"entities": {"chemical": [{"text": "N-methylazetidine amide", "start": 3, "end": 26}, {"text": "amide", "start": 188, "end": 193}, {"text": "sugar amino acid", "start": 199, "end": 215}, {"text": "iminosugar", "start": 230, "end": 240}]}}, "schema": []}
{"input": "The Role of Surface Chemistry on the Toxicity of Ag Nanoparticles.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 49, "end": 51}]}}, "schema": []}
{"input": "The role of surface chemistry on the toxicity of Ag nanoparticles is investigated using Saccharomyces cerevisiae yeast as a platform for evaluation.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 49, "end": 51}]}}, "schema": []}
{"input": "Combining the shape-controlled synthesis of Ag nanoparticles with a comprehensive characterization of their physicochemical properties, an understanding is formed of the correlation between the physicochemical parameters of nanoparticles and the inhibition growth of yeast cells upon the introduction of nanoparticles into the cell culture system.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 44, "end": 46}]}}, "schema": []}
{"input": "Capping agents, surface facets, and sample stability-the three experimental parameters that are inherent from the wet-chemical synthesis of Ag nanoparticles-have a strong impact on toxicity evaluation.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 140, "end": 142}]}}, "schema": []}
{"input": "Hence, it is important to characterize surface properties of Ag nanoparticles in the nature of biological media and to understand the role that surface chemistry may interplay to correlate the physicochemical properties of nanoparticles with their biological response upon exposure.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 61, "end": 63}]}}, "schema": []}
{"input": "This work demonstrates the great importance of surface chemistry in designing experiments for reliable toxicity evaluation and in mitigating the toxicity of Ag nanoparticles for their safe use in future commercialization.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 157, "end": 159}]}}, "schema": []}
{"input": "Hybridization of Phenylthiolate-and Methylthiolate-Adatom Species at Low Coverage on the Au (111) Surface.", "output": {"entities": {"chemical": [{"text": "Phenylthiolate", "start": 17, "end": 31}, {"text": "Methylthiolate", "start": 36, "end": 50}, {"text": "Au (111)", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Using scanning tunneling microscopy we observed reaction products of two chemisorbed thiolate species, methylthiolate and phenylthiolate, on the Au (111) surface.", "output": {"entities": {"chemical": [{"text": "thiolate", "start": 85, "end": 93}, {"text": "methylthiolate", "start": 103, "end": 117}, {"text": "phenylthiolate", "start": 122, "end": 136}, {"text": "Au (111)", "start": 145, "end": 153}]}}, "schema": []}
{"input": "Despite the apparent stability, organometallic complexes of methylthiolate and phenylthiolate with the gold-adatom (RS-Au-SR, with R-the hydrocarbon group) undergo a stoichiometric exchange reaction, forming hybridized CH3S-Au-SPh complexes.", "output": {"entities": {"chemical": [{"text": "organometallic", "start": 32, "end": 46}, {"text": "methylthiolate", "start": 60, "end": 74}, {"text": "phenylthiolate", "start": 79, "end": 93}, {"text": "RS-Au-SR", "start": 116, "end": 124}, {"text": "hydrocarbon", "start": 137, "end": 148}, {"text": "CH3S-Au-SPh", "start": 219, "end": 230}]}}, "schema": []}
{"input": "Complementary density functional theory calculations suggest that the reaction is most likely mediated by a monothiolate RS-Au complex bonded to the gold surface, which forms a trithiolate RS-Au-(SR)-Au-SR complex as a key intermediate.", "output": {"entities": {"chemical": [{"text": "RS-Au", "start": 121, "end": 126}, {"text": "trithiolate RS-Au-(SR)-Au-SR", "start": 177, "end": 205}]}}, "schema": []}
{"input": "This work therefore reveals the novel chemical reactivity of the low-coverage \" striped \" phase of alkanethiols on gold and strongly points to the involvement of monoadatom thiolate intermediates in this reaction.", "output": {"entities": {"chemical": [{"text": "alkanethiols", "start": 99, "end": 111}, {"text": "thiolate", "start": 173, "end": 181}]}}, "schema": []}
{"input": "By extension, such intermediates may be involved in the self-assembly process itself, shedding new light on this long-standing problem.", "output": {"entities": {}}, "schema": []}
{"input": "Targeted d4 dopamine receptors: implications for drug discovery and therapeutic development.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 12, "end": 20}]}}, "schema": []}
{"input": "A wealth of preclinical and clinical literature has established functional associations of CNS dopamine (DA) and its multiple G protein-coupled receptor (GPCR) types in the integration of key neurological processes linked to complex behavioral activities.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 95, "end": 103}]}}, "schema": []}
{"input": "Conversely, an equivalent vast literature supports the role of aberrant CNS DA expression and DA receptor signaling in the etiology and persistence of major psychiatric illnesses and has established selective targeting of DA-ergic systems as a cornerstone of pharmacotherapeutic intervention and current neuroleptic drug development.", "output": {"entities": {}}, "schema": []}
{"input": "The present short review focuses on potential functional/behavioral alterations linked to polymorphisms in the primary DNA sequence of the DA receptor type 4 (DRD4) gene in reference to major psychiatric illnesses.", "output": {"entities": {}}, "schema": []}
{"input": "The potential clinical relevance of major polymorphisms of the DRD4 gene are discussed within the context of practical aspects of typical and atypical neuroleptic drug usage within afflicted populations of psychiatric patients.", "output": {"entities": {}}, "schema": []}
{"input": "It is anticipated that additional complementary molecular, biochemical, and behavioral studies of DRD4 gene polymorphisms will provide essential information for selective targeting of heterogeneous populations of CNS D4 receptors and advance drug discovery and therapeutic development efforts for highly efficacious treatment of psychiatric illnesses.", "output": {"entities": {}}, "schema": []}
{"input": "Polyclonal Antibody to Soman-Tyrosine.", "output": {"entities": {"chemical": [{"text": "Soman", "start": 23, "end": 28}, {"text": "Tyrosine", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Soman forms a stable, covalent bond with tyrosine 411 of human albumin, with tyrosines 257 and 593 in human transferrin, and with tyrosine in many other proteins.", "output": {"entities": {"chemical": [{"text": "Soman", "start": 0, "end": 5}, {"text": "tyrosine", "start": 41, "end": 49}, {"text": "tyrosines", "start": 77, "end": 86}, {"text": "tyrosine", "start": 130, "end": 138}]}}, "schema": []}
{"input": "The pinacolyl group of soman is retained, suggesting that pinacolyl methylphosphonate bound to tyrosine could generate specific antibodies.", "output": {"entities": {"chemical": [{"text": "pinacolyl", "start": 4, "end": 13}, {"text": "soman", "start": 23, "end": 28}, {"text": "pinacolyl methylphosphonate", "start": 58, "end": 85}, {"text": "tyrosine", "start": 95, "end": 103}]}}, "schema": []}
{"input": "Tyrosine in the pentapeptide RYGRK was covalently modified with soman simply by adding soman to the peptide.", "output": {"entities": {"chemical": [{"text": "Tyrosine", "start": 0, "end": 8}, {"text": "pentapeptide", "start": 16, "end": 28}, {"text": "soman", "start": 64, "end": 69}, {"text": "soman", "start": 87, "end": 92}]}}, "schema": []}
{"input": "The phosphonylated-peptide was linked to keyhole limpet hemocyanin, and the conjugate was injected into rabbits.", "output": {"entities": {}}, "schema": []}
{"input": "The polyclonal antiserum recognized soman-labeled human albumin, soman-mouse albumin, and soman human transferrin but not nonphosphonylated control proteins.", "output": {"entities": {"chemical": [{"text": "soman", "start": 36, "end": 41}, {"text": "soman", "start": 65, "end": 70}, {"text": "soman", "start": 90, "end": 95}]}}, "schema": []}
{"input": "The soman-labeled tyrosines in these proteins are surrounded by different amino acid sequences, suggesting that the polyclonal recognizes soman-tyrosine independent of the amino acid sequence.", "output": {"entities": {"chemical": [{"text": "soman", "start": 4, "end": 9}, {"text": "tyrosines", "start": 18, "end": 27}, {"text": "amino acid", "start": 74, "end": 84}, {"text": "soman", "start": 138, "end": 143}, {"text": "tyrosine", "start": 144, "end": 152}, {"text": "amino acid", "start": 172, "end": 182}]}}, "schema": []}
{"input": "Antiserum obtained after 4 antigen injections over a period of 18 weeks was tested in a competition ELISA where it had an IC50 of 10 (-11) M.", "output": {"entities": {}}, "schema": []}
{"input": "The limit of detection on Western blots was 0. 01 mu g (15 picomoles) of soman-labeled albumin.", "output": {"entities": {"chemical": [{"text": "soman", "start": 73, "end": 78}]}}, "schema": []}
{"input": "In conclusion, a high-affinity, polyclonal antibody that specifically recognizes soman adducts on tyrosine in a variety of proteins has been produced.", "output": {"entities": {"chemical": [{"text": "soman", "start": 81, "end": 86}, {"text": "tyrosine", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Such an antibody could be useful for identifying secondary targets of soman toxicity.", "output": {"entities": {"chemical": [{"text": "soman", "start": 70, "end": 75}]}}, "schema": []}
{"input": "NTproBNP: An Important Biomarker in Cardiac Diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Natriuretic neuropeptides (ANP, BNP, CNP) are produced primarily in the cardiac atria under normal conditions.", "output": {"entities": {}}, "schema": []}
{"input": "The main stimulus for ANP and BNP peptide synthesis and secretion is cardiac wall stress.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiac ventricular myocytes constitute the major source of BNP-related peptides.", "output": {"entities": {}}, "schema": []}
{"input": "Ventricular NT-proBNP production is upregulated in cardiac failure and locally in the area surrounding a myocardial infarct.", "output": {"entities": {}}, "schema": []}
{"input": "NT-proBNP is cleared passively by organs with high rate of blood flow (muscle, liver, kidney).", "output": {"entities": {}}, "schema": []}
{"input": "It has a longer half life than BNP and higher plasma concentration.", "output": {"entities": {}}, "schema": []}
{"input": "BNP and NTproBNP tend to be higher in women and lower in obese individuals.", "output": {"entities": {}}, "schema": []}
{"input": "They are also higher in elderly, in left ventricular tachycardia, right ventricular overload, myocardial ischemia, hypoxaemia, renal dysfunction, liver cirrhosis, sepsis and infection.", "output": {"entities": {}}, "schema": []}
{"input": "NT-proBNP is useful both in the diagnosis and prognosis of heart failure and is considered to be a gold standard biomarker in heart failure similar to BNP.", "output": {"entities": {}}, "schema": []}
{"input": "A cut-off point 300 pg/ml has 99% sensitivity, 60% specificity and NPV 98% for exclusion of acute heart failure.", "output": {"entities": {}}, "schema": []}
{"input": "NT proBNP has also a strong prognostic value of death in acute and chronic heart failure and also predicts short and long term mortality in patient with suspected or confirmed unstable CVD.", "output": {"entities": {}}, "schema": []}
{"input": "Natriuretic peptides are also prognostic markers for the RV (Right Ventricular) Dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Their release is due to myocardial stretch from right ventricular pressure overload. Finally, there are data supporting that NT-proBNP might be useful to put a time frame on atrial fibrillation of unknown onset.", "output": {"entities": {}}, "schema": []}
{"input": "Biocompatible, functional spheres based on oxidative coupling assembly of green tea polyphenols.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 84, "end": 95}]}}, "schema": []}
{"input": "Green luminescent, monodisperse, smooth, porous and hollow spheres were simply prepared by Cu (2 +) and temperature mediated oxidative coupling assembly of green tea polyphenols in water.", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 91, "end": 99}, {"text": "polyphenols", "start": 166, "end": 177}]}}, "schema": []}
{"input": "These polymeric tea polyphenol spheres are GSH responsive, acid resistant but alkali-responsive, ideally used as platform for controlled delivery of functional guests.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 20, "end": 30}, {"text": "GSH", "start": 43, "end": 46}]}}, "schema": []}
{"input": "Crystalline growth of rubrene film enhanced by vertical ordering in cadmium arachidate multilayer substrate.", "output": {"entities": {"chemical": [{"text": "rubrene", "start": 22, "end": 29}, {"text": "cadmium arachidate", "start": 68, "end": 86}]}}, "schema": []}
{"input": "The growth of highly crystalline rubrene thin films for organic field effect transistor (OFET) application remains a challenge.", "output": {"entities": {"chemical": [{"text": "rubrene", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Here, we report on the vapor-deposited growth of rubrene films on the substrates made of cadmium arachidate (CdA) multilayers deposited onto SiO2/Si (100) via the Langmuir-Blodgett technique.", "output": {"entities": {"chemical": [{"text": "rubrene", "start": 49, "end": 56}, {"text": "cadmium arachidate", "start": 89, "end": 107}, {"text": "CdA", "start": 109, "end": 112}, {"text": "SiO2", "start": 141, "end": 145}, {"text": "Si", "start": 146, "end": 148}]}}, "schema": []}
{"input": "The CdA films, containing 2n + 1 layers, with integer n ranging from 0 to 4, are surface-terminated identically by the methyl group but exhibit the thickness-dependent morphology.", "output": {"entities": {"chemical": [{"text": "CdA", "start": 4, "end": 7}, {"text": "methyl", "start": 119, "end": 125}]}}, "schema": []}
{"input": "The morphology and structure of both CdA and rubrene films are characterized by X-ray reflectivity (XRR), X-ray diffraction (XRD), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, and atomic force microscopy (AFM).", "output": {"entities": {"chemical": [{"text": "CdA", "start": 37, "end": 40}, {"text": "rubrene", "start": 45, "end": 52}]}}, "schema": []}
{"input": "Crystalline rubrene films, evidenced by XRD and marked by platelet features in AFM images, become observable when grown onto the CdA layer thicker than 5L.", "output": {"entities": {"chemical": [{"text": "rubrene", "start": 12, "end": 19}, {"text": "CdA", "start": 129, "end": 132}]}}, "schema": []}
{"input": "XRD data show that vertical ordering, that is, ordering along surface normal, of CdA multilayer substrates exerts a strong influence in promoting the crystalline growth of rubrene films.", "output": {"entities": {"chemical": [{"text": "CdA", "start": 81, "end": 84}, {"text": "rubrene", "start": 172, "end": 179}]}}, "schema": []}
{"input": "This promoted growth is not due to the surface energy of CdA layer but derived from the additional interaction localized between rubrene and CdA island sidewall and presumably strengthened by a close dimensional match between the a-axis of rubrene lattice and the layer spacing of CdA multilayer.", "output": {"entities": {"chemical": [{"text": "CdA", "start": 57, "end": 60}, {"text": "rubrene", "start": 129, "end": 136}, {"text": "CdA", "start": 141, "end": 144}, {"text": "rubrene", "start": 240, "end": 247}, {"text": "CdA", "start": 281, "end": 284}]}}, "schema": []}
{"input": "The best OFET mobility is recorded for 9L CdA substrate and reaches 6. 7 x 10 (-2) cm (2) V (-1) s (-1), presumably limited by the roughness of the interface between CdA and rubrene films.", "output": {"entities": {"chemical": [{"text": "CdA", "start": 42, "end": 45}, {"text": "CdA", "start": 166, "end": 169}, {"text": "rubrene", "start": 174, "end": 181}]}}, "schema": []}
{"input": "Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 40, "end": 47}]}}, "schema": []}
{"input": "Toxoplasma gondii is sensitive to bulky pyrazolo [3, 4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1).", "output": {"entities": {"chemical": [{"text": "pyrazolo [3, 4-d] pyrimidine", "start": 40, "end": 68}, {"text": "Gly", "start": 110, "end": 113}, {"text": "calcium", "start": 142, "end": 149}]}}, "schema": []}
{"input": "Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1).", "output": {"entities": {"chemical": [{"text": "3-methyl-benzyl-PP", "start": 51, "end": 69}, {"text": "3-MB-PP", "start": 71, "end": 78}]}}, "schema": []}
{"input": "The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity.", "output": {"entities": {}}, "schema": []}
{"input": "Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.", "output": {"entities": {}}, "schema": []}
{"input": "A newly synthesized sinapic Acid derivative inhibits endothelial activation in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "sinapic Acid", "start": 20, "end": 32}]}}, "schema": []}
{"input": "Inhibition of oxidative stress and inflammation in vascular endothelial cells (ECs) may represent a new therapeutic strategy against endothelial activation.", "output": {"entities": {}}, "schema": []}
{"input": "Sinapic acid (SA), a phenylpropanoid compound, is found in natural herbs and high-bran cereals and has moderate antioxidant activity.", "output": {"entities": {"chemical": [{"text": "Sinapic acid", "start": 0, "end": 12}, {"text": "phenylpropanoid", "start": 21, "end": 36}]}}, "schema": []}
{"input": "We aimed to develop new SA agents with the properties of antioxidation and blocking EC activation for possible therapy of cardiovascular disease.", "output": {"entities": {}}, "schema": []}
{"input": "We designed and synthesized 10 SA derivatives according to their chemical structures.", "output": {"entities": {}}, "schema": []}
{"input": "Preliminary screening of the compounds involved scavenging hydroxyl radicals and 2, 2-diphenyl-1-picrylhydrazyl (DPPH (.)), croton oil-induced ear edema in mice, and analysis of the mRNA expression of adhesion molecules in ECs.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 59, "end": 67}, {"text": "2, 2-diphenyl-1-picrylhydrazyl", "start": 81, "end": 111}, {"text": "DPPH (.)", "start": 113, "end": 121}]}}, "schema": []}
{"input": "1-Acetyl-sinapic acyl-4-(3'-chlorine-) benzylpiperazine (SA9) had the strongest antioxidant and anti-inflammatory activities both in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "1-Acetyl-sinapic acyl-4-(3'-chlorine-) benzylpiperazine", "start": 0, "end": 55}, {"text": "SA9", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Thus, the effect of SA9 was further studied.", "output": {"entities": {"chemical": [{"text": "SA9", "start": 20, "end": 23}]}}, "schema": []}
{"input": "SA9 inhibited tumor necrosis factor alpha-induced upregulation of adhesion molecules in ECs at both mRNA and protein levels, as well as the consequent monocyte adhesion to ECs.", "output": {"entities": {"chemical": [{"text": "SA9", "start": 0, "end": 3}]}}, "schema": []}
{"input": "In vivo, result of face-to-face immunostaining showed that SA9 reduced lipopolysaccharide-induced expression of intercellular adhesion molecule-1 in mouse aortic intima.", "output": {"entities": {}}, "schema": []}
{"input": "To study the molecular mechanism, results from luciferase assay, nuclear translocation of NF-kappa B, and Western blot indicated that the mechanism of the anti-inflammatory effects of SA9 might be suppression of intracellular generation of ROS and inhibition of NF-kappa B activation in ECs.", "output": {"entities": {"chemical": [{"text": "SA9", "start": 184, "end": 187}]}}, "schema": []}
{"input": "SA9 is a prototype of a novel class of antioxidant with anti-inflammatory effects in ECs.", "output": {"entities": {"chemical": [{"text": "SA9", "start": 0, "end": 3}]}}, "schema": []}
{"input": "It may represent a new therapeutic approach for preventing endothelial activation in cardiovascular disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Measurement of Transport Activities of 3 beta-Hydroxy-Delta (5)-bile Acids in Bile Salt Export Pump and Multidrug Resistance-Associated Proteins Using LC-MS/MS.", "output": {"entities": {"chemical": [{"text": "3 beta-Hydroxy-Delta (5)-bile Acids", "start": 39, "end": 74}, {"text": "Bile Salt", "start": 78, "end": 87}]}}, "schema": []}
{"input": "A method has been developed for the measurement of transport activities in membrane vesicles obtained from Sf9 cells for 3 beta-hydroxy-Delta (5)-bile acids by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.", "output": {"entities": {"chemical": [{"text": "3 beta-hydroxy-Delta (5)-bile acids", "start": 121, "end": 156}]}}, "schema": []}
{"input": "Calibration curves for the bile acids were linear over the range of 10 to 2000 pmol/mL, and the detection limit was less than 1 pmol/mL for 3 beta-hydroxy-Delta (5)-bile acids using selected reaction monitoring analysis.", "output": {"entities": {"chemical": [{"text": "bile acids", "start": 27, "end": 37}, {"text": "3 beta-hydroxy-Delta (5)-bile acids", "start": 140, "end": 175}]}}, "schema": []}
{"input": "The analytical method was applied to measurements of transport activities in membrane vesicles obtained from human multidrug resistance-associated protein 2-, 3-, and human bile salt export pump-expressing Sf9 cells for conjugated 3 beta-hydroxy-Delta (5)-bile acids.", "output": {"entities": {"chemical": [{"text": "bile salt", "start": 173, "end": 182}, {"text": "3 beta-hydroxy-Delta (5)-bile acids", "start": 231, "end": 266}]}}, "schema": []}
{"input": "The present study demonstrated that human multidrug resistance-associated protein 3 vesicles accepted conjugated 3 beta-hydroxy-Delta (5)-bile acids along with common bile acids such as glycocholic acid and taurolithocholic acid 3-sulfate.", "output": {"entities": {"chemical": [{"text": "3 beta-hydroxy-Delta (5)-bile acids", "start": 113, "end": 148}, {"text": "bile acids", "start": 167, "end": 177}, {"text": "glycocholic acid", "start": 186, "end": 202}, {"text": "taurolithocholic acid 3-sulfate", "start": 207, "end": 238}]}}, "schema": []}
{"input": "Investigation of the effects of chest physiotherapy in different positions on the heart and the respiratory system after coronary artery bypass surgery.", "output": {"entities": {}}, "schema": []}
{"input": "This trial was conducted to investigate the effect of chest physiotherapy in different positions on the heart and the respiratory system after coronary artery bypass surgery.", "output": {"entities": {}}, "schema": []}
{"input": "Patients are divided into two groups of 30 patients each in the study.", "output": {"entities": {}}, "schema": []}
{"input": "To the patients in the first group (30 patients), percussion-vibration was performed in the 45 degrees supine position, while slightly laterally lying and endotracheal aspiration was performed in the supine position.", "output": {"entities": {}}, "schema": []}
{"input": "To the patients in the second group (30 patients), percussion-vibration was performed in the 0 degrees supine position, while slightly laterally lying and endotracheal aspiration was performed in the supine position.", "output": {"entities": {}}, "schema": []}
{"input": "The procedures are repeated two times for all patients and their means were taken.", "output": {"entities": {}}, "schema": []}
{"input": "The pre-and postapplication values of patients were measured from central venous and arterial catheters and the values of patient monitors were recorded.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of the two groups in terms of respiratory values did not reveal a significant difference, but chest physiotherapy with the head of the bed at 0 degrees was determined to improve cardiac functions.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of the groups in terms of pre-and postphysiotherapy applications showed a significant increase in mixed venous oxygen saturation in both groups.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 122, "end": 128}]}}, "schema": []}
{"input": "Chest physiotherapy with the head of the bed elevated to 45 degrees may be recommended in patients who carry a risk of pulmonary complications and who are candidates for chest physiotherapy at an early stage.", "output": {"entities": {}}, "schema": []}
{"input": "A new anti-inflammatory triterpene saponin isolated from Anabasis setifera.", "output": {"entities": {"chemical": [{"text": "triterpene saponin", "start": 24, "end": 42}]}}, "schema": []}
{"input": "A bio-guided fractionation of Anabasis setifera Moq.", "output": {"entities": {}}, "schema": []}
{"input": "(Chenopodiaceae) for anti-inflammatory activity was carried out using carrageenin rat paw edema model in rats.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of percent edema inhibition after 3 h of carrageenin injection, n-butanol fraction showed promising activity through a significant (p < 0. 05) decrease in paw volume by 85. 6% from control using indomethacin as reference standard.", "output": {"entities": {"chemical": [{"text": "n-butanol", "start": 77, "end": 86}, {"text": "indomethacin", "start": 208, "end": 220}]}}, "schema": []}
{"input": "Moreover, the n-butanol fraction significantly (p < 0. 05) decreased PGE2 and TNF-alpha in the exudates of rat paw edema.", "output": {"entities": {"chemical": [{"text": "n-butanol", "start": 14, "end": 23}, {"text": "PGE2", "start": 69, "end": 73}]}}, "schema": []}
{"input": "Chemical investigation of n-butanol fraction afforded alpha-amyrin 3-O-glucopyranoside (1), patuletin 7-O-glucopyranoside (2), myricitrin (3) and a new oleanane triterpene saponin derivative (4), sophradiol 3-O-alpha-L-(1) C4-rhamnopyranosyl-(1''' --> 4'')-O-beta-D-(4) C1-galactopyranosyl (1'' --> 6')-O-beta-D-(4) C1-glucopyranoside.", "output": {"entities": {"chemical": [{"text": "n-butanol", "start": 26, "end": 35}, {"text": "alpha-amyrin 3-O-glucopyranoside", "start": 54, "end": 86}, {"text": "patuletin 7-O-glucopyranoside", "start": 92, "end": 121}, {"text": "myricitrin", "start": 127, "end": 137}, {"text": "oleanane triterpene saponin", "start": 152, "end": 179}, {"text": "sophradiol 3-O-alpha-L-(1) C4-rhamnopyranosyl-(1''' --> 4'')-O-beta-D-(4) C1-galactopyranosyl (1'' --> 6')-O-beta-D-(4) C1-glucopyranoside", "start": 196, "end": 334}]}}, "schema": []}
{"input": "The structure of the new compound was determined by comprehensive analyses of their 1D and 2D NMR, mass spectral data and comparison with previously known analogs.", "output": {"entities": {}}, "schema": []}
{"input": "Only compound 4 revealed a significant (p < 0. 05) inhibition of cyclooxygenase 1 and 2 (COX) activities.", "output": {"entities": {}}, "schema": []}
{"input": "Bladder Polypoid Cystitis-Derived A20 Associates with Tumorigenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Bladder chronic inflammation is associated with the pathogenesis of bladder cancer; the underlying mechanism is unclear.", "output": {"entities": {}}, "schema": []}
{"input": "The PT53 gene is an important anticancer gene in the body, which is suppressed in cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The ubiquitin E3 ligase A20 (A20) plays a role in regulating the activities of epithelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "This study was designed to investigate the correlation between A20 and the pathogenesis of bladder cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The biopsy tissues of human bladder cancer, bladder polypoid cystitis, and chronic inflammation were collected; the levels of A20 and p53 were analyzed by quantitative real-time RT-PCR, Western blotting, and immune precipitation.", "output": {"entities": {}}, "schema": []}
{"input": "HEK293 cells were employed to test the role of overexpression of A20 in the suppression of the p53 gene in the cells.", "output": {"entities": {}}, "schema": []}
{"input": "Fifty-six patients with bladder cancer, 48 patients with bladder polypoid cystitis, and 16 patients with bladder chronic inflammation were recruited into this study.", "output": {"entities": {}}, "schema": []}
{"input": "Human bladder cancer tissue and the polypoid tissue showed high levels of A20, which had a positive correlation with the tumorigenesis in the bladder; 12 out of 46 (26. 1%) patients with bladder polypoid cystitis were diagnosed as bladder cancer.", "output": {"entities": {}}, "schema": []}
{"input": "A20 bound to p53 to form complexes in bladder cancer tissue and bladder polypoid tissue.", "output": {"entities": {}}, "schema": []}
{"input": "The overexpression of A20 suppresses p53 protein levels in HEK293 cells.", "output": {"entities": {}}, "schema": []}
{"input": "A20 has a positive correlation in the tumorigenesis of bladder polypoid disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Acute Myocardial Infarction During Regadenoson Myocardial Perfusion Imaging.", "output": {"entities": {"chemical": [{"text": "Regadenoson", "start": 35, "end": 46}]}}, "schema": []}
{"input": "Pharmacologic stress testing uses vasodilators to provide objective evidence of myocardial ischemia.", "output": {"entities": {}}, "schema": []}
{"input": "Adenosine and dipyridamole are nonselective adenosine receptor agonists that have been associated with myocardial infarction (MI) during intravenous infusion.", "output": {"entities": {"chemical": [{"text": "Adenosine", "start": 0, "end": 9}, {"text": "dipyridamole", "start": 14, "end": 26}, {"text": "adenosine", "start": 44, "end": 53}]}}, "schema": []}
{"input": "Mechanisms postulated for this effect include coronary steal, transmural steal, global hypotension, and direct vasoconstriction.", "output": {"entities": {}}, "schema": []}
{"input": "Regadenoson, a direct A2A agonist, was approved for use in stress testing in 2008.", "output": {"entities": {"chemical": [{"text": "Regadenoson", "start": 0, "end": 11}]}}, "schema": []}
{"input": "We describe a 68-year-old man who presented to our institution with typical angina, relieved by nitroglycerin.", "output": {"entities": {"chemical": [{"text": "nitroglycerin", "start": 96, "end": 109}]}}, "schema": []}
{"input": "He did not have electrocardiogram (ECG) changes suggestive of myocardial pathology, and laboratory testing did not reveal a significant rise in troponin-I levels.", "output": {"entities": {}}, "schema": []}
{"input": "To further assess the etiology of his symptoms, he underwent a pharmacologic stress test with regadenoson followed by technetium 99 m sestamibi.", "output": {"entities": {"chemical": [{"text": "regadenoson", "start": 94, "end": 105}, {"text": "technetium 99 m sestamibi", "start": 118, "end": 143}]}}, "schema": []}
{"input": "Six minutes after regadenoson infusion, the patient developed severe retrosternal chest pain accompanied by ST elevations on ECG.", "output": {"entities": {"chemical": [{"text": "regadenoson", "start": 18, "end": 29}]}}, "schema": []}
{"input": "Sublingual nitroglycerin was administered that resolved both the pain and ECG changes.", "output": {"entities": {"chemical": [{"text": "nitroglycerin", "start": 11, "end": 24}]}}, "schema": []}
{"input": "The patient subsequently underwent urgent coronary angiography and was found to have a 95% critical stenosis involving the left anterior descending artery.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude this case represents a MI secondary to coronary steal phenomenon induced by regadenoson infusion.", "output": {"entities": {"chemical": [{"text": "regadenoson", "start": 88, "end": 99}]}}, "schema": []}
{"input": "Clinicians should be aware this adverse effect can occur despite the improved side-effect profile of regadenoson.", "output": {"entities": {"chemical": [{"text": "regadenoson", "start": 101, "end": 112}]}}, "schema": []}
{"input": "Continuous monitoring of vital signs and the ECG with regular assessment of symptoms is imperative to identify this rare but potentially devastating adverse event.", "output": {"entities": {}}, "schema": []}
{"input": "The Efficiency of the Metal Catalysts in the Nucleophilic Substitution of Alcohols is Dependent on the Nucleophile and Not on the Electrophile.", "output": {"entities": {"chemical": [{"text": "Alcohols", "start": 74, "end": 82}]}}, "schema": []}
{"input": "In this study, we investigate the effect of the electrophiles and the nucleophiles for eight catalysts in the catalytic SN 1 type substitution of alcohols with different degree of activation by sulfur-, carbon-, oxygen-, and nitrogen-centered nucleophiles.", "output": {"entities": {"chemical": [{"text": "alcohols", "start": 146, "end": 154}, {"text": "sulfur", "start": 194, "end": 200}, {"text": "carbon", "start": 203, "end": 209}, {"text": "oxygen", "start": 212, "end": 218}, {"text": "nitrogen", "start": 225, "end": 233}]}}, "schema": []}
{"input": "The catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols and follow the trend of alcohol reactivity.", "output": {"entities": {"chemical": [{"text": "alcohols", "start": 96, "end": 104}, {"text": "alcohol", "start": 129, "end": 136}]}}, "schema": []}
{"input": "However, when it comes to the nucleophile, the eight catalysts show general and specific variances in the efficiency and selectivity to perform the desired substitution.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, the selectivity of the alcohols to produce the desired substitution products was found to be independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation.", "output": {"entities": {"chemical": [{"text": "alcohols", "start": 38, "end": 46}]}}, "schema": []}
{"input": "Catalysts based on iron (III), bismuth (III), and gold (III) show higher conversions for S-, C-, and N-centered nucleophiles, and Bi (III) was the most efficient catalyst in all combinations.", "output": {"entities": {"chemical": [{"text": "iron (III)", "start": 19, "end": 29}, {"text": "bismuth (III)", "start": 31, "end": 44}, {"text": "gold (III)", "start": 50, "end": 60}, {"text": "S", "start": 89, "end": 90}, {"text": "C", "start": 93, "end": 94}, {"text": "N", "start": 101, "end": 102}, {"text": "Bi (III)", "start": 130, "end": 138}]}}, "schema": []}
{"input": "Catalysts based on rhenium (I) or rhenium (VII), palladium (II), and lanthanum (III) were the most efficient in performing the nucleophilic substitution on the various alcohols with the O-centered nucleophiles.", "output": {"entities": {"chemical": [{"text": "rhenium (I)", "start": 19, "end": 30}, {"text": "rhenium (VII)", "start": 34, "end": 47}, {"text": "palladium (II)", "start": 49, "end": 63}, {"text": "lanthanum (III)", "start": 69, "end": 84}, {"text": "alcohols", "start": 168, "end": 176}, {"text": "O", "start": 186, "end": 187}]}}, "schema": []}
{"input": "These catalysts generate the symmetrical ether as a by-product from the reactions of S-, C-, and N-centered nucleophiles as well, resulting in lower chemoselectivity.", "output": {"entities": {"chemical": [{"text": "S", "start": 85, "end": 86}, {"text": "C", "start": 89, "end": 90}, {"text": "N", "start": 97, "end": 98}]}}, "schema": []}
{"input": "Energies and Spin States of FeS (0/-), FeS2 (0/-), Fe2 S2 (0/-), Fe3 S4 (0/-), and Fe4 S4 (0/-) Clusters.", "output": {"entities": {"chemical": [{"text": "FeS", "start": 28, "end": 31}, {"text": "FeS2", "start": 39, "end": 43}, {"text": "Fe2 S2", "start": 51, "end": 57}, {"text": "Fe3 S4", "start": 65, "end": 71}, {"text": "Fe4 S4", "start": 83, "end": 89}]}}, "schema": []}
{"input": "The structures and energies of the electronic ground states of the FeS (0/-), FeS2 (0/-), Fe2 S2 (0/-), Fe3 S4 (0/-), and Fe4 S4 (0/-) neutral and anionic clusters have been computed systematically with nine computational methods in combination with seven basis sets.", "output": {"entities": {"chemical": [{"text": "FeS", "start": 67, "end": 70}, {"text": "FeS2", "start": 78, "end": 82}, {"text": "Fe2 S2", "start": 90, "end": 96}, {"text": "Fe3 S4", "start": 104, "end": 110}, {"text": "Fe4 S4", "start": 122, "end": 128}]}}, "schema": []}
{"input": "The computed adiabatic electronic affinities (AEA) have been compared with available experimental data.", "output": {"entities": {}}, "schema": []}
{"input": "Most reasonable agreements between theory and experiment have been found for both hybrid B3LYP and B3PW91 functionals in conjugation with 6-311 + G * and QZVP basis sets.", "output": {"entities": {}}, "schema": []}
{"input": "Detailed comparisons between the available experimental and computed AEA data at the B3LYP/6-311 + G * level identified the electronic ground state of (5) Delta for FeS, (4) Delta for FeS (-), (5) B2 for FeS2, (6) A1 for FeS2 (-), (1) A1 for Fe2 S2, (8) A' for Fe2 S2 (-), (5) A'' for Fe3 S4, (6) A'' for Fe3 S4 (-), (1) A1 for Fe4 S4, and (1) A2 for Fe4 S4 (-).", "output": {"entities": {"chemical": [{"text": "FeS", "start": 165, "end": 168}, {"text": "FeS (-)", "start": 184, "end": 191}, {"text": "FeS2", "start": 204, "end": 208}, {"text": "FeS2 (-)", "start": 221, "end": 229}, {"text": "Fe2 S2", "start": 242, "end": 248}, {"text": "Fe2 S2 (-)", "start": 261, "end": 271}, {"text": "Fe3 S4", "start": 285, "end": 291}, {"text": "Fe3 S4 (-)", "start": 305, "end": 315}, {"text": "Fe4 S4", "start": 328, "end": 334}, {"text": "Fe4 S4 (-)", "start": 351, "end": 361}]}}, "schema": []}
{"input": "In addition, Fe2 S2, Fe3 S4, Fe3 S4 (-), Fe4 S4, and Fe4 S4 (-) are antiferromagnetic at the B3LYP/6-311 + G * level.", "output": {"entities": {"chemical": [{"text": "Fe2 S2", "start": 13, "end": 19}, {"text": "Fe3 S4", "start": 21, "end": 27}, {"text": "Fe3 S4 (-)", "start": 29, "end": 39}, {"text": "Fe4 S4", "start": 41, "end": 47}, {"text": "Fe4 S4 (-)", "start": 53, "end": 63}]}}, "schema": []}
{"input": "The magnetic properties are discussed on the basis of natural bond orbital analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Ras/cAMP-dependent Protein Kinase (PKA) Regulates Multiple Aspects of Cellular Events by Phosphorylating the Whi3 Cell Cycle Regulator in Budding Yeast.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 4, "end": 8}]}}, "schema": []}
{"input": "The Start/G1 phase in the cell cycle is an important period during which cells determine their developmental fate, onset of mitotic progression, or the switch to developmental stages in response to both external and internal signals.", "output": {"entities": {}}, "schema": []}
{"input": "In the budding yeast Saccharomyces cerevisiae, Whi3, a negative regulator of the G1 cyclins, has been identified as a positive regulator of cell size control and is involved in the regulation of Start.", "output": {"entities": {}}, "schema": []}
{"input": "However, the regulatory pathway of Whi3 governing the response to multiple signals remains largely unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that Whi3 is phosphorylated by the Ras/cAMP-dependent protein kinase (PKA) and that phosphorylation of Ser-568 in Whi3 by PKA plays an inhibitory role in Whi3 function.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 53, "end": 57}, {"text": "Ser", "start": 117, "end": 120}]}}, "schema": []}
{"input": "Phosphorylation of Whi3 by PKA led to its decreased interaction with CLN3 G1 cyclin mRNA and was required for the promotion of G1/S progression.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we demonstrate that the phosphomimetic S568D mutation of Whi3 prevented the developmental fate switch to sporulation or invasive growth.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticles Adsorbed at the Water/Oil Interface: Coverage and Composition Effects on Structure and Diffusion.", "output": {"entities": {}}, "schema": []}
{"input": "Dissipative particle dynamics simulations are performed to study the structural and dynamical properties of various systems of nanoparticles accumulated at the water/oil interface.", "output": {"entities": {}}, "schema": []}
{"input": "Homogeneous and Janus nanoparticles with different surface compositions are studied.", "output": {"entities": {}}, "schema": []}
{"input": "For all nanoparticles, as the surface density increases, a transition from a liquidlike to a solidlike state is observed, as expected.", "output": {"entities": {}}, "schema": []}
{"input": "At a high density of nanoparticles, hexagonal structures emerge and the nanoparticles' self-diffusion coefficient decreases because of caging effects.", "output": {"entities": {}}, "schema": []}
{"input": "Similar results are observed for nanoparticles with different surface chemistry.", "output": {"entities": {}}, "schema": []}
{"input": "Because different nanoparticles have different contact angles at the water/oil interface, the results obtained for systems containing mixed nanoparticles are more interesting.", "output": {"entities": {}}, "schema": []}
{"input": "For example, our results show that the self-diffusion coefficient is not a monotonic function of the system composition, caused by the complex relation between hydrodynamic interactions and effective nanoparticle-nanoparticle interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Presence of hydrophobic groups may modify the specific ion effect in aqueous polyelectrolyte solutions.", "output": {"entities": {}}, "schema": []}
{"input": "Enthalpies of dilution of aqueous solutions of aliphatic 6, 12-and 12, 12-ionene bromides and fluorides and enthalpies of mixing with low molecular-weight salts, such as sodium fluoride and bromide, are determined.", "output": {"entities": {"chemical": [{"text": "aliphatic 6, 12-and 12, 12-ionene bromides and fluorides", "start": 47, "end": 103}, {"text": "sodium fluoride and bromide", "start": 170, "end": 197}]}}, "schema": []}
{"input": "In the second part of the study, the various x, y-ionenes (x, y are numbers of methylene groups between the adjacent charges) with fluoride, bromide, and iodide counterions are mixed with aqueous sodium sulfate solution.", "output": {"entities": {"chemical": [{"text": "methylene", "start": 79, "end": 88}, {"text": "fluoride", "start": 131, "end": 139}, {"text": "bromide", "start": 141, "end": 148}, {"text": "iodide", "start": 154, "end": 160}, {"text": "sodium sulfate", "start": 196, "end": 210}]}}, "schema": []}
{"input": "The polyelectrolytes examined in this part of the work are 3, 3-, 6, 9-, 6, 12-, and 12, 12-ionenes.", "output": {"entities": {"chemical": [{"text": "3, 3-, 6, 9-, 6, 12-, and 12, 12-ionenes", "start": 59, "end": 99}]}}, "schema": []}
{"input": "A comparison with theoretical results, based on the Poisson-Boltzmann cell model, is presented.", "output": {"entities": {}}, "schema": []}
{"input": "The theory predicts for the enthalpy of dilution to be exothermic and the enthalpy of mixing endothermic, while experiments show that signs of the heat effects depend on the nature of the counterion of the added salt, as also on the hydrophobicity (numbers x, y of methylene groups) of the ionene.", "output": {"entities": {"chemical": [{"text": "methylene", "start": 265, "end": 274}]}}, "schema": []}
{"input": "We show that the salts when ordered by heat effects produced by mixing of NaF and NaBr with 3, 3-, 6, 9-, or 6, 12-ionene fluorides and bromides follow the opposite ordering than in the case when the same alkali halide salts are mixed with more hydrophobic 12, 12-ionene salts.", "output": {"entities": {"chemical": [{"text": "NaF", "start": 74, "end": 77}, {"text": "NaBr", "start": 82, "end": 86}, {"text": "3, 3-, 6, 9-, or 6, 12-ionene fluorides and bromides", "start": 92, "end": 144}, {"text": "alkali halide", "start": 205, "end": 218}, {"text": "12, 12-ionene", "start": 257, "end": 270}]}}, "schema": []}
{"input": "The results for the enthalpy of mixing of ionenes under study with Na2SO4 follow the same order as obtained for monovalent salts.", "output": {"entities": {"chemical": [{"text": "Na2SO4", "start": 67, "end": 73}]}}, "schema": []}
{"input": "Do the physical properties of water in mixed reverse micelles follow a synergistic effect: a spectroscopic investigation.", "output": {"entities": {}}, "schema": []}
{"input": "In this contribution we have tried to investigate whether the mechanical properties of the reverse micellar (RM) interface dictate the physical properties of entrapped water molecules in the RM waterpool.", "output": {"entities": {}}, "schema": []}
{"input": "We choose AOT/Igepal-520/cyclohexane (Cy) mixed RM as a model system which exhibits synergistic water solubilization behavior as a function of interfacial stoichiometry.", "output": {"entities": {"chemical": [{"text": "AOT", "start": 10, "end": 13}, {"text": "Igepal-520", "start": 14, "end": 24}, {"text": "cyclohexane", "start": 25, "end": 36}]}}, "schema": []}
{"input": "Such a phenomenon associates systematic modification of the interface curvature.", "output": {"entities": {}}, "schema": []}
{"input": "Dynamic light scattering (DLS) studies reveal linear increase in the droplet size and aggregation number of the RMs with increasing XIgepal (mole fraction of Igepal in the surfactant mixture).", "output": {"entities": {}}, "schema": []}
{"input": "FTIR study in the 3000-3800 cm (-1) region identifies that the relative population of the surface-bound water molecules is higher in AOT RM compared to that in Igepal RM, and in mixed systems it also follows a linear trend with XIgepal.", "output": {"entities": {"chemical": [{"text": "AOT", "start": 133, "end": 136}, {"text": "Igepal", "start": 160, "end": 166}]}}, "schema": []}
{"input": "Water relaxation dynamics as probed by time-resolved fluorescence spectroscopy using Coumarin-500 also reveals an overall linear trend with no characteristic feature around the solubilization inflation point.", "output": {"entities": {"chemical": [{"text": "Coumarin-500", "start": 85, "end": 97}]}}, "schema": []}
{"input": "Our study clearly identifies that the physical properties of water in RM are mostly governed by the interfacial stoichiometry and water content, and merely bares any dependence on the mechanical properties of the interface.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid and congeners as highly potent inhibitors of human arginases I and II for treatment of myocardial reperfusion injury.", "output": {"entities": {"chemical": [{"text": "(R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid", "start": 13, "end": 76}]}}, "schema": []}
{"input": "Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent alpha, alpha-disubstituted amino acid-based arginase inhibitors.", "output": {"entities": {"chemical": [{"text": "alpha, alpha-disubstituted amino acid", "start": 147, "end": 184}]}}, "schema": []}
{"input": "The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid, compound 9, inhibits human arginases I and II with IC50s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells).", "output": {"entities": {"chemical": [{"text": "(R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid", "start": 20, "end": 83}]}}, "schema": []}
{"input": "It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we report the design, synthesis, and structure-activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.", "output": {"entities": {}}, "schema": []}
{"input": "Xenobiotics and the human gut microbiome: metatranscriptomics reveal the active players.", "output": {"entities": {}}, "schema": []}
{"input": "The human gut microbiome plays an important role in the metabolism of xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "In a recent issue of Cell, Maurice et al.", "output": {"entities": {}}, "schema": []}
{"input": "(2013) identify the active members of the gut microbiome and show how gene-expression profiles change within the gut microbial community in response to antibiotics and host-targeted xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "Design, Synthesis, and Biological Evaluation of a Series of Benzo [de] [1, 7] naphthyridin-7 (8H)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors.", "output": {"entities": {"chemical": [{"text": "Benzo [de] [1, 7] naphthyridin-7 (8H)-ones", "start": 60, "end": 102}]}}, "schema": []}
{"input": "A series of benzo [de] [1, 7] naphthyridin-7 (8H)-ones possessing a functionalized long-chain appendage have been designed and evaluated as novel PARP1 inhibitors.", "output": {"entities": {"chemical": [{"text": "benzo [de] [1, 7] naphthyridin-7 (8H)-ones", "start": 12, "end": 54}]}}, "schema": []}
{"input": "The initial effort led to the first-generation PARP1 inhibitor 26 bearing a terminal phthalazin-1 (2H)-one framework and showing remarkably high PARP1 inhibitory activity (0. 31 nM) but only moderate potency in the cell.", "output": {"entities": {"chemical": [{"text": "phthalazin-1 (2H)-one", "start": 85, "end": 106}]}}, "schema": []}
{"input": "Further effort generated the second-generation lead 41, showing high potency against both the PARP1 enzyme and BRCA-deficient cells, especially for the BRCA1-deficient MDA-MB-436 cells (CC50 < 0. 26 nM).", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistic studies revealed that the new PARP1 inhibitors significantly inhibited H2O2-triggered PARylation in SKOV3 cells, induced cellular accumulation of DNA double-strand breaks, and impaired cell-cycle progression in BRCA2-deficient cells.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 83, "end": 87}]}}, "schema": []}
{"input": "Significant potentiation on the cytotoxicity of Temozolomide was also observed.", "output": {"entities": {"chemical": [{"text": "Temozolomide", "start": 48, "end": 60}]}}, "schema": []}
{"input": "The unique structural character and exceptionally high potency of 41 made it stand out as a promising drug candidate worthy for further evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "Engineered Magnetic Shape Anisotropy in BiFeO3-CoFe2O4 Self-Assembled Thin Films.", "output": {"entities": {"chemical": [{"text": "BiFeO3", "start": 40, "end": 46}, {"text": "CoFe2O4", "start": 47, "end": 54}]}}, "schema": []}
{"input": "We report growth of various phase architectures of self-assembled BiFeO3-CoFe2O4 (BFO-CFO) thin films on differently oriented SrTiO3 (STO) substrates.", "output": {"entities": {"chemical": [{"text": "BiFeO3", "start": 66, "end": 72}, {"text": "CoFe2O4", "start": 73, "end": 80}, {"text": "BFO", "start": 82, "end": 85}, {"text": "CFO", "start": 86, "end": 89}, {"text": "SrTiO3", "start": 126, "end": 132}, {"text": "STO", "start": 134, "end": 137}]}}, "schema": []}
{"input": "CFO forms segregated square, stripe, and triangular nanopillars embedded in a coherent BFO matrix on (001)-, (110)-, and (111)-oriented STO substrates, respectively.", "output": {"entities": {"chemical": [{"text": "CFO", "start": 0, "end": 3}, {"text": "BFO", "start": 87, "end": 90}, {"text": "STO", "start": 136, "end": 139}]}}, "schema": []}
{"input": "Nanostructures with an aspect ratio of up to 5: 1 with a prominent magnetic anisotropy were obtained on both (001) and (110) STO along out-of-plane and in-plane directions.", "output": {"entities": {"chemical": [{"text": "STO", "start": 125, "end": 128}]}}, "schema": []}
{"input": "Magnetic easy axis rotation from in-plane to out-of-plane directions was realized through aspect ratio control.", "output": {"entities": {}}, "schema": []}
{"input": "An intractable in-plane anisotropy was fixed in CFO on (111) STO due to the triangular shape of the ferromagnetic phase nanopillars.", "output": {"entities": {"chemical": [{"text": "CFO", "start": 48, "end": 51}, {"text": "STO", "start": 61, "end": 64}]}}, "schema": []}
{"input": "These studies established a detailed relationship of magnetic anisotropy with specific shape and dimensions of ordered magnetic arrays.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest a way to effectively control the magnetic anisotropy in patterned ferromagnetic oxide arrays with tunable shape, aspect ratio, and elastic strain conditions of the nanostructures.", "output": {"entities": {"chemical": [{"text": "oxide", "start": 100, "end": 105}]}}, "schema": []}
{"input": "Biodistribution of different sized nanoparticles assessed by positron emission tomography: a general strategy for direct activation of metal oxide particles.", "output": {"entities": {"chemical": [{"text": "metal oxide", "start": 135, "end": 146}]}}, "schema": []}
{"input": "The extraordinary small size of NPs makes them difficult to detect and quantify once distributed in a material or biological system.", "output": {"entities": {}}, "schema": []}
{"input": "We present a simple and straightforward method for the direct proton beam activation of synthetic or commercially available aluminum oxide NPs (Al2O3 NPs) via the (16) O (p, alpha) (13) N nuclear reaction in order to assess their biological fate using positron emission tomography (PET).", "output": {"entities": {"chemical": [{"text": "aluminum oxide", "start": 124, "end": 138}, {"text": "Al2O3", "start": 144, "end": 149}, {"text": "(16) O", "start": 163, "end": 169}, {"text": "(13) N", "start": 181, "end": 187}]}}, "schema": []}
{"input": "The radiolabeling of the NPs does not alter their surface or structural properties as demonstrated by TEM, DLS, and zeta-potential measurements.", "output": {"entities": {}}, "schema": []}
{"input": "The incorporation of radioactive (13) N atoms in the Al2O3 NPs allowed the study of the biodistribution of the metal oxide NPs in rats after intravenous administration via PET.", "output": {"entities": {"chemical": [{"text": "(13) N", "start": 33, "end": 39}, {"text": "Al2O3", "start": 53, "end": 58}, {"text": "metal oxide", "start": 111, "end": 122}]}}, "schema": []}
{"input": "Despite the short half-life of (13) N (9. 97 min), the accumulation of NPs in different organs could be measured during the first 68 min after administration.", "output": {"entities": {"chemical": [{"text": "(13) N", "start": 31, "end": 37}]}}, "schema": []}
{"input": "The percentage amount of radioactivity per organ was calculated to evaluate the relative amount of NPs per organ.", "output": {"entities": {}}, "schema": []}
{"input": "This simple and robust activation strategy can be applied to any synthetic or commercially available metal oxide particle.", "output": {"entities": {"chemical": [{"text": "metal oxide", "start": 101, "end": 112}]}}, "schema": []}
{"input": "Sonochemical synthesis and characterization of nano-sized lead (II) 3D coordination polymer: Precursor for the synthesis of lead (II) oxybromide nanoparticles.", "output": {"entities": {"chemical": [{"text": "lead (II)", "start": 58, "end": 67}, {"text": "lead (II) oxybromide", "start": 124, "end": 144}]}}, "schema": []}
{"input": "Nanoparticles of a three-dimensional coordination polymer, [Pb (L) (mu 2-Br) (H2O)] n (1), (L (-) = 1H-1, 2, 4-triazole-3-carboxylate), have been synthesized by an ultrasonic method and characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and elemental analyses.", "output": {"entities": {"chemical": [{"text": "[Pb (L) (mu 2-Br) (H2O)] n", "start": 59, "end": 85}, {"text": "1H-1, 2, 4-triazole-3-carboxylate", "start": 100, "end": 133}]}}, "schema": []}
{"input": "The thermal stability of compound 1 both its bulk and nano-size has been studied by thermal gravimetric (TG) and differential thermal (DTA) analyses and compared each other.", "output": {"entities": {}}, "schema": []}
{"input": "Concentration of initial reagents effects and the role of power ultrasound irradiation on size and morphology of nano-structured compound 1, have been studied.", "output": {"entities": {}}, "schema": []}
{"input": "Calcination of the compound 1 at 500 degrees C under air atmosphere yields Pb3O2Br2 nanoparticles.", "output": {"entities": {"chemical": [{"text": "Pb3O2Br2", "start": 75, "end": 83}]}}, "schema": []}
{"input": "Co-ordination of base excision repair and genome stability.", "output": {"entities": {}}, "schema": []}
{"input": "Base excision repair (BER) is a major DNA repair pathway employed in mammalian cells that is required to maintain genome stability, thus preventing several human diseases, such as ageing, neurodegenerative diseases and cancer.", "output": {"entities": {}}, "schema": []}
{"input": "This is achieved through the repair of damaged DNA bases, sites of base loss and single strand breaks of varying complexity that are continuously induced endogenously or via exogenous mutagens.", "output": {"entities": {}}, "schema": []}
{"input": "Whilst the enzymes involved in BER are now well known and characterised, the role of the co-ordination of BER enzymatic activities in the cellular response to DNA damage and the mechanisms regulating this process are only now being revealed.", "output": {"entities": {}}, "schema": []}
{"input": "Post-translational modifications of BER proteins, including ubiquitylation and phosphorylation, are increasingly being identified as key processes that regulate BER.", "output": {"entities": {}}, "schema": []}
{"input": "In this review we will summarise recent evidence discovering novel mechanisms that are involved in maintaining genome stability by regulation of the key BER proteins in response to DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Melanoma targeting property of a Lu-177-labeled lactam bridge-cyclized alpha-MSH peptide.", "output": {"entities": {"chemical": [{"text": "Lu-177", "start": 33, "end": 39}, {"text": "lactam", "start": 48, "end": 54}]}}, "schema": []}
{"input": "The purpose of this study was to determine the melanoma targeting property of (177) Lu-DOTA-GGNle-CycMSHhex in B16/F1 melanoma-bearing C57 mice.", "output": {"entities": {"chemical": [{"text": "(177) Lu-DOTA-GGNle-CycMSHhex", "start": 78, "end": 107}]}}, "schema": []}
{"input": "(177) Lu-DOTA-GGNle-CycMSHhex exhibited high receptor-mediated melanoma uptake and fast urinary clearance.", "output": {"entities": {"chemical": [{"text": "(177) Lu-DOTA-GGNle-CycMSHhex", "start": 0, "end": 29}]}}, "schema": []}
{"input": "The tumor uptake of (177) Lu-DOTA-GGNle-CycMSHhex was 20. 25 +/- 4. 59 and 21. 63 +/- 6. 27% ID/g at 0. 5 and 2h post-injection, respectively.", "output": {"entities": {"chemical": [{"text": "(177) Lu-DOTA-GGNle-CycMSHhex", "start": 20, "end": 49}]}}, "schema": []}
{"input": "Approximately 83% of injected dose cleared out the body via urinary system at 2h post-injection.", "output": {"entities": {}}, "schema": []}
{"input": "(177) Lu-DOTA-GGNle-CycMSHhex showed high tumor to normal organ uptake ratios except for the kidneys.", "output": {"entities": {"chemical": [{"text": "(177) Lu-DOTA-GGNle-CycMSHhex", "start": 0, "end": 29}]}}, "schema": []}
{"input": "The tumor/kidney uptake ratios of (177) Lu-DOTA-GGNle-CycMSHhex were 2. 76 and 1. 74 at 2 and 24h post-injection.", "output": {"entities": {"chemical": [{"text": "(177) Lu-DOTA-GGNle-CycMSHhex", "start": 34, "end": 63}]}}, "schema": []}
{"input": "The melanoma lesions were clearly visualized by SPECT/CT using (177) Lu-DOTA-GGNle-CycMSHhex as an imaging probe at 2h post-injection.", "output": {"entities": {"chemical": [{"text": "(177) Lu-DOTA-GGNle-CycMSHhex", "start": 63, "end": 92}]}}, "schema": []}
{"input": "Overall, high melanoma uptake coupled with fast urinary clearance of (177) Lu-DOTA-GGNle-CycMSHhex underscored its potential for melanoma treatment in the future.", "output": {"entities": {"chemical": [{"text": "(177) Lu-DOTA-GGNle-CycMSHhex", "start": 69, "end": 98}]}}, "schema": []}
{"input": "BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 8, "end": 16}, {"text": "phenylaminopyrimidine", "start": 79, "end": 100}, {"text": "PAP", "start": 108, "end": 111}]}}, "schema": []}
{"input": "To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec).", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 56, "end": 64}, {"text": "phenylaminopyrimidine", "start": 134, "end": 155}, {"text": "PAP", "start": 163, "end": 166}, {"text": "imatinib", "start": 191, "end": 199}]}}, "schema": []}
{"input": "A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine).", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 70, "end": 78}]}}, "schema": []}
{"input": "The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0. 886 and a survival score of 4. 97 for training set molecules.", "output": {"entities": {}}, "schema": []}
{"input": "The model showed excellent predictive power, with a correlation coefficient of Q (2) = 0. 768 for an external test set of ten molecules.", "output": {"entities": {}}, "schema": []}
{"input": "The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.", "output": {"entities": {}}, "schema": []}
{"input": "Time-dependent effects of corticosterone on reward-based decision-making in a rodent model of the Iowa Gambling Task.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 26, "end": 40}]}}, "schema": []}
{"input": "Corticosteroid hormones, released after stress, are known to change neuronal activity in two time-domains: within minutes via non-genomic pathways and with a delay of > 1 h through pathways involving transcriptional regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Recent evidence in rodents and humans indicates that these two modes of corticosteroid action differently affect cognitive tasks.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we investigated whether reward-based decision-making, in a rat model of the Iowa Gambling Task (rIGT), is also differently altered by rapid versus delayed actions of corticosterone.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 172, "end": 186}]}}, "schema": []}
{"input": "We targeted the rapid and delayed time domain by injecting corticosterone (CORT, 1 mg/kg, s. c.) at 30 min (rapid) or 180 min (delayed) respectively prior to behavioural testing, during the final 3 days of the behavioural paradigm.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 59, "end": 73}, {"text": "CORT", "start": 75, "end": 79}]}}, "schema": []}
{"input": "In saline treated rats, the number of visits to the disadvantageous arm decreased over trial blocks, whilst this was attenuated when CORT was administered 30 min before testing.", "output": {"entities": {"chemical": [{"text": "CORT", "start": 133, "end": 137}]}}, "schema": []}
{"input": "This attenuation was associated with a significantly increased c-Fos expression in the lateral orbitofrontal cortex and insular cortex, and a trend for an increase in the infralimbic cortex.", "output": {"entities": {}}, "schema": []}
{"input": "The rapid corticosteroid effect contrasted with treatment 180 min before testing, where the number of visits to the disadvantageous arm as well as c-Fos labelling was not affected.", "output": {"entities": {}}, "schema": []}
{"input": "These findings indicate that rapid corticosteroid actions impair reward-based decision-making.", "output": {"entities": {}}, "schema": []}
{"input": "Bioinspired peptides as versatile nucleic acid delivery platforms.", "output": {"entities": {}}, "schema": []}
{"input": "Non-viral gene therapy approaches have strongly established the utility of peptides as integral constituents of delivery platforms devised for efficient transfer of therapeutic molecules into cells.", "output": {"entities": {}}, "schema": []}
{"input": "Among these, cell-penetrating peptides (CPPs), encompassing a family of short peptide sequences and their chimeric derivatives, have gained versatility through the addition of de novo peptide ligands primarily to facilitate cell-specific nucleic acid delivery in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "The review illustrates the structural requirements of a noteworthy peptide TAT-PTD and other derivatives chiefly to exemplify their implication in gene therapy.", "output": {"entities": {}}, "schema": []}
{"input": "An overview of the emerging concept and recent explorations will be presented through unique examples which form a facet in nanotechnology-based cancer therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Finally the basis for the utility of CPPs in plants will be discussed in view of its biotechnological potential.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of the Antibiotic Phosacetamycin via a New Mass Spectrometry-Based Method for Phosphonic Acid Detection.", "output": {"entities": {"chemical": [{"text": "Phosacetamycin", "start": 28, "end": 42}, {"text": "Phosphonic Acid", "start": 88, "end": 103}]}}, "schema": []}
{"input": "Naturally occurring phosphonates such as phosphinothricin (Glufosinate, a commercially used herbicide) and fosfomycin (Monurol, a clinically used antibiotic) have proved to be potent and useful biocides.", "output": {"entities": {"chemical": [{"text": "phosphonates", "start": 20, "end": 32}, {"text": "phosphinothricin", "start": 41, "end": 57}, {"text": "Glufosinate", "start": 59, "end": 70}, {"text": "fosfomycin", "start": 107, "end": 117}, {"text": "Monurol", "start": 119, "end": 126}]}}, "schema": []}
{"input": "Yet this class of natural products is still an under explored family of secondary metabolites.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of the biosynthetic pathways responsible for the production of these compounds has been simplified by using gene based screening approaches, but detection and identification of the natural products the genes produce have been hampered by a lack of high-throughput methods for screening potential producers under various culture conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present an efficient mass-spectrometric method for the selective detection of natural products containing phosphonate and phosphinate functional groups.", "output": {"entities": {"chemical": [{"text": "phosphonate", "start": 115, "end": 126}, {"text": "phosphinate", "start": 131, "end": 142}]}}, "schema": []}
{"input": "We have used this method to identify a new phosphonate metabolite, phosacetamycin, whose structure, biological activity, and biosynthetic gene cluster are reported.", "output": {"entities": {"chemical": [{"text": "phosphonate", "start": 43, "end": 54}, {"text": "phosacetamycin", "start": 67, "end": 81}]}}, "schema": []}
{"input": "Anti-tuberculosis neolignans from Piper regnellii.", "output": {"entities": {}}, "schema": []}
{"input": "The present study determined the anti-Mycobacterium tuberculosis activities of supercritical CO2 extracts, neolignans eupomatenoid-5 (1), conocarpan (4) and eupomatenoid-3 (7) and their derivatives (2, 3, 5, 6, and 8) from Piper regnellii, as well as their cytotoxicities.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 93, "end": 96}, {"text": "neolignans eupomatenoid-5", "start": 107, "end": 132}, {"text": "conocarpan", "start": 138, "end": 148}, {"text": "eupomatenoid-3", "start": 157, "end": 171}]}}, "schema": []}
{"input": "The supercritical CO2 extract from leaves was purified by chromatographic methods, yielding compounds (1), (4) and (7), which were identified by (1) H NMR and comparison with literature data.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 18, "end": 21}, {"text": "(1) H", "start": 145, "end": 150}]}}, "schema": []}
{"input": "Anti-M. tuberculosis activity (H37Rv and clinical isolates) was evaluated using a resazurin microtiter assay plate (REMA) to determine the MIC.", "output": {"entities": {}}, "schema": []}
{"input": "The cytotoxicity assay was carried out in macrophages J774G. 8 by sulforhodamine B colorimetric assay.", "output": {"entities": {"chemical": [{"text": "sulforhodamine B", "start": 66, "end": 82}]}}, "schema": []}
{"input": "The supercritical CO2 extracts from leaves and stems, and compound (4) showed activity against M. tuberculosis (MIC 15. 6 mu g/ml).", "output": {"entities": {"chemical": [{"text": "CO2", "start": 18, "end": 21}]}}, "schema": []}
{"input": "Compound (1) showed the best activity (MIC 1. 9 mu g/ml), with good SI.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds (7) and (8) showed low activity against M. tuberculosis H37Rv.", "output": {"entities": {}}, "schema": []}
{"input": "The derivative compounds did not show increased anti-M. tuberculosis activity.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first report, to our knowledge, to describe neolignans from P. regnellii with activity against M. tuberculosis, and compound (1) is a potential candidate for future antituberculosis drugs.", "output": {"entities": {"chemical": [{"text": "neolignans", "start": 56, "end": 66}]}}, "schema": []}
{"input": "The crucial role of the MyD88 adaptor protein in the inflammatory response induced by Bothrops atrox venom.", "output": {"entities": {}}, "schema": []}
{"input": "Most snake accidents in North Brazil are attributed to Bothrops atrox, a snake species of the Viperidae family whose venom simultaneously induces local and systemic effects in the victims.", "output": {"entities": {}}, "schema": []}
{"input": "The former are clinically more important than the latter, as they cause severe tissue lesions associated with strong inflammatory responses.", "output": {"entities": {}}, "schema": []}
{"input": "Although several studies have shown that inflammatory mediators are produced in response to B. atrox venom (BaV), there is little information concerning the molecular pathways involved in innate immune system signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Myeloid differentiation factor 88 (MyD88) is an adaptor molecule responsible for transmitting intracellular signals from most toll-like receptors (TLRs) after they interact with pathogen-associated molecular patterns (PAMPs) or other stimuli such as endogenous damage-associated molecular patterns (DAMPs).", "output": {"entities": {}}, "schema": []}
{"input": "The MyD88-dependent pathway leads to activation of transcription factors, which in turn induce synthesis of inflammatory mediators such as eicosanoids, cytokines and chemokines.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to investigate the involvement of MyD88 on the acute inflammatory response induced by BaV.", "output": {"entities": {}}, "schema": []}
{"input": "Wild-type (WT) C57BL/6 mice and MyD88 knockout (MyD88 (-/-)) mice were intraperitoneally injected with BaV.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to WT mice, MyD88 (-/-) animals showed an impaired inflammatory response to BaV, with lower influx of polymorphonuclear and mononuclear cells to the peritoneal cavity.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, peritoneal leukocytes from BaV-injected MyD88 (-/-) mice did not induce COX-2 or LTB4 protein expression and released low concentrations of PGE2.", "output": {"entities": {}}, "schema": []}
{"input": "These mice also failed to produce Th1 and Th17 cytokines and CCL-2, but IL-10 levels were similar to those of BaV-injected WT mice.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that MyD88 signaling is required for activation of the inflammatory response elicited by BaV, raising the possibility of developing new therapeutic targets to treat Bothrops sp. poisoning.", "output": {"entities": {}}, "schema": []}
{"input": "Prilling of fatty acids as a continuous process for the development of controlled release multiparticulate dosage forms.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 12, "end": 23}]}}, "schema": []}
{"input": "In this study, prilling was evaluated as a technique for the development of multiparticulate dosage forms using the fatty acids, stearic acid, and behenic acid as potential matrix formers to control the release of metoprolol tartrate (MPT), a highly water soluble drug.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 116, "end": 127}, {"text": "stearic acid", "start": 129, "end": 141}, {"text": "behenic acid", "start": 147, "end": 159}, {"text": "metoprolol tartrate", "start": 214, "end": 233}, {"text": "MPT", "start": 235, "end": 238}]}}, "schema": []}
{"input": "The in vitro drug release was dependent on the drug load, type of fatty acid, and pH of the dissolution medium.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 66, "end": 76}]}}, "schema": []}
{"input": "Higher drug loads resulted in faster release with behenic acid releasing drug over longer periods relative to stearic acid.", "output": {"entities": {"chemical": [{"text": "behenic acid", "start": 50, "end": 62}, {"text": "stearic acid", "start": 110, "end": 122}]}}, "schema": []}
{"input": "The in vitro drug release was pH-dependent at low drug load with the release being slower at lower pH.", "output": {"entities": {}}, "schema": []}
{"input": "Due to ionization of the fatty acid at pH 7. 4, drug release was susceptible to the ionic strength at this pH value.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 25, "end": 35}]}}, "schema": []}
{"input": "Solid state characterization indicated that the crystalline state of the fatty acids was not affected by thermal processing via prilling, while the crystallinity of MPT was decreased.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 73, "end": 84}, {"text": "MPT", "start": 165, "end": 168}]}}, "schema": []}
{"input": "During storage, the amorphous MPT fraction recrystallized in the entire matrix.", "output": {"entities": {"chemical": [{"text": "MPT", "start": 30, "end": 33}]}}, "schema": []}
{"input": "Drug release from behenic acid matrices was increased during storage at 40 degrees C; however, no polymorphism of behenic acid was detected.", "output": {"entities": {"chemical": [{"text": "behenic acid", "start": 18, "end": 30}, {"text": "behenic acid", "start": 114, "end": 126}]}}, "schema": []}
{"input": "The bioavailability of MPT, after oral administration to dogs as prills containing 30% and 40% MPT using behenic acid as matrix former, was not significantly different from a commercial sustained release reference formulation, although the 40% MPT prills showed a burst release.", "output": {"entities": {"chemical": [{"text": "MPT", "start": 23, "end": 26}, {"text": "MPT", "start": 95, "end": 98}, {"text": "behenic acid", "start": 105, "end": 117}, {"text": "MPT", "start": 244, "end": 247}]}}, "schema": []}
{"input": "Synthesis and evaluation of 3-(benzylthio)-5-(1H-indol-3-yl)-1, 2, 4-triazol-4-amines as Bcl-2 inhibitory anticancer agents.", "output": {"entities": {"chemical": [{"text": "3-(benzylthio)-5-(1H-indol-3-yl)-1, 2, 4-triazol-4-amines", "start": 28, "end": 85}]}}, "schema": []}
{"input": "A series of substituted 3-(benzylthio)-5-(1H-indol-3-yl)-4H-1, 2, 4-triazol-4-amines has been synthesised and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents.", "output": {"entities": {"chemical": [{"text": "3-(benzylthio)-5-(1H-indol-3-yl)-4H-1, 2, 4-triazol-4-amines", "start": 24, "end": 84}]}}, "schema": []}
{"input": "Synthesis of the target compounds was readily accomplished in good yields through a cyclisation reaction between indole-3-carboxylic acid hydrazide and carbon disulfide under basic conditions, followed by S-benzylation.", "output": {"entities": {"chemical": [{"text": "indole-3-carboxylic acid hydrazide", "start": 113, "end": 147}, {"text": "carbon disulfide", "start": 152, "end": 168}, {"text": "S", "start": 205, "end": 206}]}}, "schema": []}
{"input": "Active compounds, such as the nitrobenzyl analogue 6c, were found to exhibit sub-micromolar IC50 values in Bcl-2 expressing human cancer cell lines.", "output": {"entities": {"chemical": [{"text": "nitrobenzyl", "start": 30, "end": 41}]}}, "schema": []}
{"input": "Molecular modelling and ELISA studies further implicated anti-apoptotic Bcl-2 as a candidate molecular target underpinning anticancer activity.", "output": {"entities": {}}, "schema": []}
{"input": "Sulfur-nitrogen co-doped three-dimensional carbon foams with hierarchical pore structures as efficient metal-free electrocatalysts for oxygen reduction reactions.", "output": {"entities": {"chemical": [{"text": "Sulfur", "start": 0, "end": 6}, {"text": "nitrogen", "start": 7, "end": 15}, {"text": "carbon", "start": 43, "end": 49}, {"text": "oxygen", "start": 135, "end": 141}]}}, "schema": []}
{"input": "Despite the good progress in developing doped carbon catalysts for oxygen-reduction reaction (ORR), the current metal-free carbon catalysts are still far from satisfactory for large-scale applications of fuel cell.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 67, "end": 73}, {"text": "carbon", "start": 123, "end": 129}]}}, "schema": []}
{"input": "Developing new metal free doped carbon materials with abundance active sites as well as excellent electron transfer and reactant transport rate towards ORR may be a potential solution.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 32, "end": 38}]}}, "schema": []}
{"input": "Herein, we develop a novel three-dimensional (3D) sulfur-nitrogen co-doped carbon foams (S-N-CF) with hierarchical pore structures, using a convenient, economical, and scalable method.", "output": {"entities": {"chemical": [{"text": "sulfur-nitrogen co-doped carbon", "start": 50, "end": 81}, {"text": "S", "start": 89, "end": 90}, {"text": "N", "start": 91, "end": 92}]}}, "schema": []}
{"input": "The experimental results have demonstrated that the obtained 3D S-N-CF exhibited better catalytic activity, longer-term stability and higher methanol tolerance than a commercial Pt/C catalyst.", "output": {"entities": {"chemical": [{"text": "S", "start": 64, "end": 65}, {"text": "N", "start": 66, "end": 67}, {"text": "methanol", "start": 141, "end": 149}, {"text": "Pt", "start": 178, "end": 180}, {"text": "C", "start": 181, "end": 182}]}}, "schema": []}
{"input": "Such excellent performances may be attributed to the synergistic effect, which includes high catalytic sites for ORR provided by high S-N heteroatom loading, excellent reactant transport caused by hierarchical pore structures and high electron transfer rate provided by 3D continuous networks.", "output": {"entities": {"chemical": [{"text": "Such", "start": 0, "end": 4}, {"text": "N", "start": 136, "end": 137}]}}, "schema": []}
{"input": "Our results not only develop a new type of catalysts with excellent electrocatalytic performance by a commercially valid route, but also provide useful information for further clarification of the relationship between the microstructures of metal-free carbon materials and catalyst properties for ORR.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 252, "end": 258}]}}, "schema": []}
{"input": "More importantly, the idea to design hierarchical pore structures could be applied to other catalytic materials and serve as a general strategy for improving the activity of various ORR catalysts.", "output": {"entities": {}}, "schema": []}
{"input": "Aortic Distensibility in Type 1 Diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVESTo evaluate the relationship between long-term glycemia, traditional cardiovascular disease (CVD) risk factors, and ascending aortic stiffness in type 1 diabetes. RESEARCH DESIGN AND METHODSEight hundred seventy-nine subjects in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "The stiffness/distensibility of the ascending thoracic aorta (AA) was measured with magnetic resonance imaging.", "output": {"entities": {}}, "schema": []}
{"input": "Associations of AA distensibility and CVD risk factors, mean HbA1c, and cardiovascular complications including macroalbuminuria were assessed using multivariate linear regression models. RESULTSThe mean age of the subjects was 50 +/- 7 years (47% women, mean diabetes duration of 28 years).", "output": {"entities": {}}, "schema": []}
{"input": "Over 22 years of follow-up, 27% of participants had cardiovascular complications.", "output": {"entities": {}}, "schema": []}
{"input": "After adjusting for gender and cohort, AA distensibility was lower with increasing age, mean systolic blood pressure, LDL, and HbA1c measured over an average of 22 years (-26. 3% per 10 years,-11. 0% per 10 mmHg SBP,-1. 8% per 10 mg/dL of LDL, and-9. 3% per unit mean HbA1c [%], respectively).", "output": {"entities": {}}, "schema": []}
{"input": "Patients with macroalbuminuria had 25% lower AA distensibility compared with those without (P < 0. 0001).", "output": {"entities": {}}, "schema": []}
{"input": "Lower AA distensibility also was associated with greater ratio of left ventricular mass to volume (-3. 4% per 0. 1 g/mL; P < 0. 0001). CONCLUSIONSOur findings indicate strong adverse effects of hypertension, chronic hyperglycemia and macroalbuminuria on AA stiffness in type 1 diabetes in the DCCT/EDIC cohort.", "output": {"entities": {}}, "schema": []}
{"input": "Biotransformation of Two beta-Secretase Inhibitors Including Ring Opening and Contraction of a Pyrimidine Ring.", "output": {"entities": {"chemical": [{"text": "Pyrimidine", "start": 95, "end": 105}]}}, "schema": []}
{"input": "Recently, the discovery of the aminoisoindoles as potent and selective inhibitors of beta-secretase was reported, including the close structural analogs compound (S)-1-pyridin-4-yl-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine [(S)-25] and (S)-1-(2-(difluoromethyl) pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine hemifumarate (AZD3839), the latter being recently progressed to the clinic.", "output": {"entities": {"chemical": [{"text": "aminoisoindoles", "start": 31, "end": 46}, {"text": "(S)-1-pyridin-4-yl-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine", "start": 162, "end": 239}, {"text": "(S)-1-(2-(difluoromethyl) pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine hemifumarate", "start": 253, "end": 364}, {"text": "AZD3839", "start": 366, "end": 373}]}}, "schema": []}
{"input": "The biotransformation of (S)-25 was investigated in vitro and in vivo in rat, rabbit, and human and compared with AZD3839 to further understand the metabolic fate of these compounds.", "output": {"entities": {"chemical": [{"text": "AZD3839", "start": 114, "end": 121}]}}, "schema": []}
{"input": "In vitro, CYP3A4 was the major responsible enzyme and metabolized both compounds to a large extent in the commonly shared pyridine and pyrimidine rings.", "output": {"entities": {"chemical": [{"text": "pyridine", "start": 122, "end": 130}, {"text": "pyrimidine", "start": 135, "end": 145}]}}, "schema": []}
{"input": "The main proposed metabolic pathways in various in vitro systems were N-oxidation of the pyridine and/or pyrimidine ring and conversion to 4-pyrimidone and pyrimidine-2, 4-dione.", "output": {"entities": {"chemical": [{"text": "N", "start": 70, "end": 71}, {"text": "pyridine", "start": 89, "end": 97}, {"text": "pyrimidine", "start": 105, "end": 115}, {"text": "4-pyrimidone", "start": 139, "end": 151}, {"text": "pyrimidine-2, 4-dione", "start": 156, "end": 177}]}}, "schema": []}
{"input": "Both compounds were extensively metabolized, and more than 90% was excreted in feces after intravenous administration of radiolabeled compound to the rat.", "output": {"entities": {}}, "schema": []}
{"input": "Here, the main pathways were N-oxidation of the pyridine and/or pyrimidine ring and a ring contraction of the pyrimidine ring into an imidazole ring.", "output": {"entities": {"chemical": [{"text": "N", "start": 29, "end": 30}, {"text": "pyridine", "start": 48, "end": 56}, {"text": "pyrimidine", "start": 64, "end": 74}, {"text": "pyrimidine", "start": 110, "end": 120}, {"text": "imidazole", "start": 134, "end": 143}]}}, "schema": []}
{"input": "Ring-contracted metabolites accounted for 25% of the total metabolism in the rat for (S)-25, whereas the contribution was much smaller for AZD3839.", "output": {"entities": {"chemical": [{"text": "AZD3839", "start": 139, "end": 146}]}}, "schema": []}
{"input": "This metabolic pathway was not foreseen on the basis of the obtained in vitro data.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, we discovered an unusual metabolic pathway of aryl-pyrimidine-containing compounds by a ring-opening reaction followed by elimination of a carbon atom and a ring closure to form an imidazole ring.", "output": {"entities": {"chemical": [{"text": "aryl-pyrimidine", "start": 61, "end": 76}, {"text": "carbon", "start": 154, "end": 160}, {"text": "imidazole", "start": 196, "end": 205}]}}, "schema": []}
{"input": "Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers.", "output": {"entities": {}}, "schema": []}
{"input": "Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair.", "output": {"entities": {}}, "schema": []}
{"input": "As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel.", "output": {"entities": {}}, "schema": []}
{"input": "Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms. Oncogene advance online publication, 11 March 2013; doi: 10. 1038/onc. 2013. 48.", "output": {"entities": {}}, "schema": []}
{"input": "Impact of the virus purification protocol on aggregation and electrokinetics of MS2 phages and corresponding virus-like particles.", "output": {"entities": {}}, "schema": []}
{"input": "Previous experimental and theoretical studies have established that electrokinetic and aggregation properties of soft MS2 phages are not only governed by the physico-chemical features of their proteinaceous outer surface but are also significantly impacted by those of their inner RNA component (Dika et al. Appl. Environ. Microbiol., 2011, 14, 4939-4948).", "output": {"entities": {}}, "schema": []}
{"input": "These conclusions contradict the recent findings of Nguyen et al.", "output": {"entities": {}}, "schema": []}
{"input": "(Soft Matter, 2011, 7, 10449-10456) who reported identical electrokinetic and aggregation characteristics for MS2 and corresponding virus like particles (VLPs) that lack the internal RNA component.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate here that this contradiction originates from the different purification methods adopted prior to measurements.", "output": {"entities": {}}, "schema": []}
{"input": "More generally, we show that stability and electrohydrodynamics of viruses differ according to purification by (i) dialysis, (ii) isopycnic centrifugation in the cesium chloride gradient, and (iii) precipitation using polyethylene glycol (PEG).", "output": {"entities": {"chemical": [{"text": "cesium chloride", "start": 162, "end": 177}, {"text": "polyethylene glycol", "start": 218, "end": 237}, {"text": "PEG", "start": 239, "end": 242}]}}, "schema": []}
{"input": "Methods (i) and (iii) lead to aggregation of MS2 phages at pH <= 4 and pH <= 6 in 1-100 mM NaNO3 solutions, respectively, while under such conditions aggregation is not observed for MS2 and VLP suspensions prepared according to (ii).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, VLPs prepared following methods (i) and (iii) aggregate only at the isoelectric point (pH ~ 3-4) in 1 mM NaNO3 solution.", "output": {"entities": {"chemical": [{"text": "NaNO3", "start": 118, "end": 123}]}}, "schema": []}
{"input": "Electrophoretic mobility data of stable MS2 and VLP particles were further examined using a recent formalism for electrokinetics of soft multilayered colloids.", "output": {"entities": {}}, "schema": []}
{"input": "The analysis qualitatively shows how the purification protocol may affect either the outer particle surface properties and/or the inner particle content.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, the non-DLVO aggregation behavior of MS2 and VLPs purified via the above protocols is discussed in terms of the possible change in corresponding interparticular interactions.", "output": {"entities": {}}, "schema": []}
{"input": "The antipsychotic-like effects of the mGlu group III orthosteric agonist, LSP1-2111, involves 5-HT1A signalling.", "output": {"entities": {"chemical": [{"text": "LSP1-2111", "start": 74, "end": 83}]}}, "schema": []}
{"input": "RATIONALE: Several studies have suggested that modulation of the glutamatergic system via metabotropic glutamate receptors (mGlu) could be a new way to achieve antipsychotic-like activity.", "output": {"entities": {"chemical": [{"text": "glutamatergic", "start": 65, "end": 78}]}}, "schema": []}
{"input": "LSP1-2111, the group III mGlu receptor orthosteric agonist, with a high affinity towards mGlu4 receptors, was previously shown to exhibit antipsychotic-like action in animal models displaying positive symptoms of schizophrenia.", "output": {"entities": {"chemical": [{"text": "LSP1-2111", "start": 0, "end": 9}]}}, "schema": []}
{"input": "OBJECTIVES: Here, we decided to investigate the possible role of LSP1-2111 in models of negative (social interaction) and cognitive (NOR) symptoms of psychosis.", "output": {"entities": {"chemical": [{"text": "LSP1-2111", "start": 65, "end": 74}]}}, "schema": []}
{"input": "We also investigated the involvement of 5-HT1A receptors in the LSP1-2111-induced antipsychotic effects.", "output": {"entities": {"chemical": [{"text": "LSP1-2111", "start": 64, "end": 73}]}}, "schema": []}
{"input": "Apart from the above-mentioned models of negative and cognitive symptoms, MK-801 and amphetamine-induced hyperactivity tests, plus the DOI-induced head twitches in mice as models for positive symptoms of psychosis, were used in this part of the investigations.", "output": {"entities": {"chemical": [{"text": "MK-801", "start": 74, "end": 80}, {"text": "amphetamine", "start": 85, "end": 96}, {"text": "DOI", "start": 135, "end": 138}]}}, "schema": []}
{"input": "RESULTS: LSP1-2111 (0. 5, 2, and 5 mg/kg) dose-dependently inhibited MK-801-induced deficits in social interaction and NOR tests.", "output": {"entities": {"chemical": [{"text": "LSP1-2111", "start": 9, "end": 18}, {"text": "MK-801", "start": 69, "end": 75}]}}, "schema": []}
{"input": "The effects of the drug were antagonized by 5-HT1A antagonist, WAY100635 (0. 1 mg/kg).", "output": {"entities": {"chemical": [{"text": "WAY100635", "start": 63, "end": 72}]}}, "schema": []}
{"input": "A similar inhibition of LSP1-2111-induced effects was observed in models of positive symptoms of schizophrenia.", "output": {"entities": {"chemical": [{"text": "LSP1-2111", "start": 24, "end": 33}]}}, "schema": []}
{"input": "Moreover, the concomitant administration of subeffective doses of LSP1-2111 (0. 3-0. 5 mg/kg) with a subeffective dose of 5-HT1A agonist, (R)-(+)-8-Hydroxy-DPAT (0. 01 mg/kg), induced a clear antipsychotic-like effect in all of the procedures used.", "output": {"entities": {"chemical": [{"text": "LSP1-2111", "start": 66, "end": 75}, {"text": "(R)-(+)-8-Hydroxy-DPAT", "start": 138, "end": 160}]}}, "schema": []}
{"input": "CONCLUSIONS: Altogether, we propose that the activation of group III mGlu receptors may be a promising target for the development of novel antipsychotic drugs, towards not only positive but also negative and cognitive symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "The action of the compound is 5-HT1A-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound.", "output": {"entities": {"chemical": [{"text": "chromene", "start": 25, "end": 33}, {"text": "retinoic acid", "start": 54, "end": 67}]}}, "schema": []}
{"input": "Retinoic acid receptor alpha (RAR alpha) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer.", "output": {"entities": {"chemical": [{"text": "Retinoic acid", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Herein we report a modified synthesis of a known RAR alpha antagonist, 2-fluoro-4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid.", "output": {"entities": {"chemical": [{"text": "2-fluoro-4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid", "start": 71, "end": 169}, {"text": "4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid", "start": 220, "end": 309}]}}, "schema": []}
{"input": "The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step.", "output": {"entities": {}}, "schema": []}
{"input": "Structure-activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RAR alpha for both compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular modeling within the RAR alpha binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of decacationic [60] fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation.", "output": {"entities": {"chemical": [{"text": "decacationic [60] fullerene decaiodides", "start": 13, "end": 52}, {"text": "superoxide", "start": 87, "end": 97}]}}, "schema": []}
{"input": "We report a novel class of highly water-soluble decacationic methano [60] fullerene decaiodides C60 [> M (C3N6 (+) C3) 2]-(I (-)) 10 [1-(I (-)) 10] capable of co-producing singlet oxygen (Type-II) and highly reactive hydroxyl radicals, formed from superoxide radicals in Type-I photosensitizing reactions, upon illumination at both UVA and white light wavelengths.", "output": {"entities": {"chemical": [{"text": "decacationic methano [60] fullerene decaiodides C60 [> M (C3N6 (+) C3) 2]-(I (-)) 10", "start": 48, "end": 132}, {"text": "(I (-)) 10", "start": 136, "end": 146}, {"text": "oxygen", "start": 180, "end": 186}, {"text": "hydroxyl", "start": 217, "end": 225}, {"text": "superoxide", "start": 248, "end": 258}]}}, "schema": []}
{"input": "The O2 (-).-production efficiency of 1-(I (-)) 10 was confirmed by using an O2 (-).-reactive bis (2, 4-dinitrobenzenesulfonyl) tetrafluorofluorescein probe and correlated to the photoinduced electron-transfer event going from iodide anions to (3) C60 * [> M (C3N6 (+) C3) 2] leading to C60 (-). [> M (C3N6 (+) C3) 2].", "output": {"entities": {"chemical": [{"text": "O2 (-).", "start": 4, "end": 11}, {"text": "(I (-)) 10", "start": 39, "end": 49}, {"text": "O2 (-).", "start": 76, "end": 83}, {"text": "bis (2, 4-dinitrobenzenesulfonyl) tetrafluorofluorescein", "start": 93, "end": 149}, {"text": "iodide", "start": 226, "end": 232}, {"text": "(3) C60 * [> M (C3N6 (+) C3) 2]", "start": 243, "end": 274}, {"text": "C60 (-). [> M (C3N6 (+) C3) 2]", "start": 286, "end": 316}]}}, "schema": []}
{"input": "Incorporation of a defined number (ten) of quaternary ammonium cationic charges per C60 in 1 was aimed to enhance its ability to target pathogenic Gram-positive and Gram-negative bacterial cells.", "output": {"entities": {"chemical": [{"text": "quaternary ammonium", "start": 43, "end": 62}, {"text": "C60", "start": 84, "end": 87}]}}, "schema": []}
{"input": "We used the well-characterized malonato [60] fullerene diester monoadduct C60 [> M (t-Bu) 2] as the starting fullerene derivative to provide a better synthetic route to C60 [> M (C3N6 (+) C3) 2] via transesterification reaction under trifluoroacetic acid catalyzed conditions.", "output": {"entities": {"chemical": [{"text": "malonato [60] fullerene diester", "start": 31, "end": 62}, {"text": "C60 [> M (t-Bu) 2]", "start": 74, "end": 92}, {"text": "fullerene", "start": 109, "end": 118}, {"text": "C60 [> M (C3N6 (+) C3) 2]", "start": 169, "end": 194}, {"text": "trifluoroacetic acid", "start": 234, "end": 254}]}}, "schema": []}
{"input": "These compounds may be used as effective photosensitizers and nano-PDT drugs for photoinactivation of pathogens.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of fused [1, 3, 4] thiadiazoles.", "output": {"entities": {"chemical": [{"text": "[1, 3, 4] thiadiazoles", "start": 104, "end": 126}]}}, "schema": []}
{"input": "New series of [1, 3, 4] thiadiazolo [3, 2-a] pyrimidines, benzo [h] [1, 3, 4] thiadiazolo [2, 3-b] quinazolines, benzothiadiazolotriazocine, and imidazo [2, 1-b] [1, 3, 4] thiadiazoles have been synthesized and characterized by analytical and spectrometrical methods (IR, MS, (1) H and (13) C NMR).", "output": {"entities": {"chemical": [{"text": "[1, 3, 4] thiadiazolo [3, 2-a] pyrimidines", "start": 14, "end": 56}, {"text": "benzo [h] [1, 3, 4] thiadiazolo [2, 3-b] quinazolines", "start": 58, "end": 111}, {"text": "benzothiadiazolotriazocine", "start": 113, "end": 139}, {"text": "imidazo [2, 1-b] [1, 3, 4] thiadiazoles", "start": 145, "end": 184}, {"text": "(1) H", "start": 276, "end": 281}, {"text": "(13) C", "start": 286, "end": 292}]}}, "schema": []}
{"input": "Twenty of the synthesized compounds were screened for antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus.", "output": {"entities": {}}, "schema": []}
{"input": "They were found to be either moderately active, slightly active or inactive against the tested microorganisms.", "output": {"entities": {}}, "schema": []}
{"input": "The antifungal activity of these compounds were also tested against Candida albicans, Aspergillus fumigatus 293 and Aspergillus flavus 3375.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 3g, h showed potent antifungal activity against C. albicans.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the same compounds were tested for antiquorum-sensing activity against Chromobacterium violacium ATCC 12472, where compounds 3b, c, 3f-h, 6b-d, 9, 10 and 12 demonstrated acceptable activity.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 3d, 9 and 10 were screened for antitumor activity at National Cancer Institute, USA.", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro cytotoxic activity of eighteen of the synthesized compounds was studied by brine shrimp lethality bioassay, and results indicated that compounds 6c, 13, 3h, 6d and 3d have the highest cytotoxic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis using microwave irradiation and antibacterial evaluation of new N, O-acetals and N, S-acetals derived from 2-amino-1, 4-naphthoquinones.", "output": {"entities": {"chemical": [{"text": "N, O-acetals", "start": 74, "end": 86}, {"text": "N, S-acetals", "start": 91, "end": 103}, {"text": "2-amino-1, 4-naphthoquinones", "start": 117, "end": 145}]}}, "schema": []}
{"input": "This paper describes a novel series of N, O-acetals and N, S-acetals (7a-o) derived from 2-amino-1, 4-naphthoquinones that were synthesized and evaluated as potential antimicrobial agents.", "output": {"entities": {"chemical": [{"text": "N, O-acetals", "start": 39, "end": 51}, {"text": "N, S-acetals", "start": 56, "end": 68}, {"text": "2-amino-1, 4-naphthoquinones", "start": 89, "end": 117}]}}, "schema": []}
{"input": "These compounds were obtained in good yields using microwave irradiation, and several of them showed promising antibacterial profiles.", "output": {"entities": {}}, "schema": []}
{"input": "Three of our biologically active 2-amino-1, 4-naphthoquinone N, O-acetals and N, S-acetals tested against hospital bacterial strains were identified as potential lead compounds.", "output": {"entities": {"chemical": [{"text": "2-amino-1, 4-naphthoquinone N, O-acetals", "start": 33, "end": 73}, {"text": "N, S-acetals", "start": 78, "end": 90}]}}, "schema": []}
{"input": "Characterization of all compounds was performed using one-dimensional NMR techniques ((1) H, (13) C-APT), IR spectra, elemental analyses and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS).", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 86, "end": 91}, {"text": "(13) C", "start": 93, "end": 99}]}}, "schema": []}
{"input": "Exact time-dependent density functional theory for impurity models.", "output": {"entities": {}}, "schema": []}
{"input": "We employ the density matrix renormalization group to construct the exact time-dependent exchange-correlation potential for an impurity model with an applied transport voltage.", "output": {"entities": {}}, "schema": []}
{"input": "Even for short-ranged interaction we find an infinitely long-ranged exchange-correlation potential which is built up instantly after switching on the voltage.", "output": {"entities": {}}, "schema": []}
{"input": "Our result demonstrates the fundamental difficulties of transport calculations based on time-dependent density functional theory.", "output": {"entities": {}}, "schema": []}
{"input": "While formally the approach works, important information can be missing in the ground-state functionals and may be hidden in the usually unknown non-equilibrium functionals.", "output": {"entities": {}}, "schema": []}
{"input": "Isoflavone supplementation influenced levels of triglyceride and luteunizing hormone in Korean postmenopausal women.", "output": {"entities": {"chemical": [{"text": "Isoflavone", "start": 0, "end": 10}, {"text": "triglyceride", "start": 48, "end": 60}]}}, "schema": []}
{"input": "We conducted a double-blind, randomized, placebo-controlled trial to evaluate the effects of soy-derived isoflavone on blood glucose, lipid profiles, and sex hormones related to cardiovascular disease in Korean postmenopausal women.", "output": {"entities": {"chemical": [{"text": "isoflavone", "start": 105, "end": 115}, {"text": "glucose", "start": 125, "end": 132}]}}, "schema": []}
{"input": "One hundred thirteen postmenopausal women were recruited from the Seoul metropolitan area.", "output": {"entities": {}}, "schema": []}
{"input": "To confirm postmenopausal and gynecologic status, the subjects were clinically examined by a gynecologist using ultra sound and X-ray.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, 85 postmenopausal women whose follicle-stimulating hormone (FSH) levels were higher than 40 IU/ml were enrolled.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects received either 70 mg isoflavone or placebo capsules daily for 12 weeks.", "output": {"entities": {"chemical": [{"text": "isoflavone", "start": 31, "end": 41}]}}, "schema": []}
{"input": "As a result, the values of fasting glucose, insulin and HOMA-IR, as well as those of TC, LDL-C, HDL-C and FFA, were not different between the groups after supplementation.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 35, "end": 42}]}}, "schema": []}
{"input": "However, triglyceride (TG) levels in the treatment group decreased significantly compared with those of the placebo group (p = 0. 0215).", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 9, "end": 21}]}}, "schema": []}
{"input": "The levels of luteinizing hormone (LH) significantly decreased in the treatment group (p = 0. 027); however, the levels of FSH, estrone and estradiol were not changed after intervention.", "output": {"entities": {"chemical": [{"text": "estrone", "start": 128, "end": 135}, {"text": "estradiol", "start": 140, "end": 149}]}}, "schema": []}
{"input": "In conclusion, isoflavone supplement of 70 mg/day for 12 weeks decreased blood levels of TG and LH in Korean postmenopausal women.", "output": {"entities": {"chemical": [{"text": "isoflavone", "start": 15, "end": 25}]}}, "schema": []}
{"input": "Arsenic speciation and spatial and interspecies differences of metal concentrations in mollusks and crustaceans from a South China estuary.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Arsenic speciation and concentrations were determined in mollusks and crustaceans in the intertidal zone from twelve locations in Zhanjiang estuary, South China.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Metal concentrations (Ag, As, Cd, Cu, Hg, Ni, Pb, and Zn) were also concurrently determined in these species.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 22, "end": 24}, {"text": "As", "start": 26, "end": 28}, {"text": "Cd", "start": 30, "end": 32}, {"text": "Cu", "start": 34, "end": 36}, {"text": "Hg", "start": 38, "end": 40}, {"text": "Ni", "start": 42, "end": 44}, {"text": "Pb", "start": 46, "end": 48}, {"text": "Zn", "start": 54, "end": 56}]}}, "schema": []}
{"input": "Arsenic speciation analysis showed that the less-toxic arsenobetaine (AsB) constituted 80. 6-98. 8% of all As compounds, and dimethylarsinic acid (DMA) constituted 0. 47-3. 44%.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}, {"text": "arsenobetaine", "start": 55, "end": 68}, {"text": "AsB", "start": 70, "end": 73}, {"text": "dimethylarsinic acid", "start": 125, "end": 145}, {"text": "DMA", "start": 147, "end": 150}]}}, "schema": []}
{"input": "Monomethylarsonic acid (MMA) and As (V) were only detected in the whelk Drupa fiscella and the crab Heteropilumnus ciliatus, respectively.", "output": {"entities": {"chemical": [{"text": "Monomethylarsonic acid", "start": 0, "end": 22}, {"text": "MMA", "start": 24, "end": 27}, {"text": "As (V)", "start": 33, "end": 39}]}}, "schema": []}
{"input": "Arsenite [As (III)] was not detected in any of the sampled specimens, but there were also unidentified other As species.", "output": {"entities": {"chemical": [{"text": "Arsenite", "start": 0, "end": 8}, {"text": "As (III)", "start": 10, "end": 18}, {"text": "As", "start": 109, "end": 111}]}}, "schema": []}
{"input": "A strong spatial variation of metals in the oyster Saccostrea cucullata was found in the estuary, confirming that oysters can be used as a good biomonitor of metal contamination in the studied area.", "output": {"entities": {}}, "schema": []}
{"input": "The concentrations of eight metals in the studied mollusks and crustaceans clearly revealed that these invertebrates accumulated different metals to different degrees.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, As, Cd, Cu, Hg, and Pb contents in mollusks and crustacean samples were below the Food and Agricultural Organization (FAO) safe concentrations, thus there was no obvious health risk from the intake of the metals through marine mollusks and crustaceans consumption.", "output": {"entities": {"chemical": [{"text": "As", "start": 13, "end": 15}, {"text": "Cd", "start": 17, "end": 19}, {"text": "Cu", "start": 21, "end": 23}, {"text": "Hg", "start": 25, "end": 27}, {"text": "Pb", "start": 33, "end": 35}]}}, "schema": []}
{"input": "Pharmacological inhibition of Eph receptors enhances glucose-stimulated insulin secretion from mouse and human pancreatic islets.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 53, "end": 60}]}}, "schema": []}
{"input": "AIMS/HYPOTHESIS: Type 2 diabetes is characterised by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 62, "end": 69}]}}, "schema": []}
{"input": "Since erythropoietin-producing hepatoma (Eph)-ephrin bidirectional signalling fine-tunes GSIS from pancreatic beta cells, we investigated Eph receptor tyrosine kinases (RTK) as potential drug targets for selectively increasing GSIS.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 151, "end": 159}]}}, "schema": []}
{"input": "METHODS: Insulin secretion assays were carried out using mouse and human pancreatic islets as well as mouse insulinoma (MIN6) cells in the presence or absence of two Eph RTK inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the most potent inhibitor was injected into mice to evaluate its effects on glucose tolerance and plasma insulin levels.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 89, "end": 96}]}}, "schema": []}
{"input": "RESULTS: We showed that the Eph RTK inhibitors selectively increased GSIS from MIN6 cells as well as mouse and human islets.", "output": {"entities": {}}, "schema": []}
{"input": "Our results also showed that the insulin secretory effects of these compounds required Eph-ephrin signalling.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, pharmacological inhibition of Eph receptor signalling improved glucose tolerance in mice.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 72, "end": 79}]}}, "schema": []}
{"input": "CONCLUSIONS/INTERPRETATION: We showed for the first time that Eph RTKs represent targets for small molecules to selectively increase GSIS and improve glucose tolerance.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 150, "end": 157}]}}, "schema": []}
{"input": "Effects of Strontium on Collagen Content and Expression of Related Genes in Rat Chondrocytes Cultured In Vitro.", "output": {"entities": {"chemical": [{"text": "Strontium", "start": 11, "end": 20}]}}, "schema": []}
{"input": "Strontium stimulates cartilage matrix formation in vitro.", "output": {"entities": {"chemical": [{"text": "Strontium", "start": 0, "end": 9}]}}, "schema": []}
{"input": "However, the mechanisms governing these effects have not yet been extensively reported.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, chondrocytes were isolated from rat articular cartilage by enzymatic digestion and cultured for 24-72 h with 1-5 mM strontium.", "output": {"entities": {"chemical": [{"text": "strontium", "start": 131, "end": 140}]}}, "schema": []}
{"input": "We investigated the effects of different concentrations of strontium on collagen content, type II collagen, insulin-like growth factor (IGF-1) and matrix metalloproteinase (MMP)-13 expression in rat cultured articular chondrocytes in vitro.", "output": {"entities": {"chemical": [{"text": "strontium", "start": 59, "end": 68}]}}, "schema": []}
{"input": "The collagen content of the chondrocytes, determined as hydroxyproline, was measured by a colorimetry method.", "output": {"entities": {"chemical": [{"text": "hydroxyproline", "start": 56, "end": 70}]}}, "schema": []}
{"input": "Type II collagen, IGF-1, and MMP-13 mRNA abundance and protein expression levels were determined by real-time polymerase chain reaction (real-time PCR) and western blot, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that collagen content from the chondrocytes extracellular matrix increased with increasing strontium concentration.", "output": {"entities": {"chemical": [{"text": "strontium", "start": 110, "end": 119}]}}, "schema": []}
{"input": "Moreover, 3 and 5 mM strontium strongly stimulated protein expression and mRNA levels of type II collagen and IGF-1.", "output": {"entities": {"chemical": [{"text": "strontium", "start": 21, "end": 30}]}}, "schema": []}
{"input": "Conversely, MMP-13 expression in chondrocytes decreased dose-dependently with increasing strontium concentration.", "output": {"entities": {"chemical": [{"text": "strontium", "start": 89, "end": 98}]}}, "schema": []}
{"input": "These results should provide insight into the ability of strontium to promote chondrocyte extracellular matrix synthesis.", "output": {"entities": {"chemical": [{"text": "strontium", "start": 57, "end": 66}]}}, "schema": []}
{"input": "Strontium could promote collagen synthesis and suppress collagen degradation via the repression of MMP-13 expression.", "output": {"entities": {"chemical": [{"text": "Strontium", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Effect of nicotine pretreatment on arsenic-induced oxidative stress in male Wistar rats.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 10, "end": 18}, {"text": "arsenic", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Humans are commonly exposed to nicotine, one of the most important lifestyle chemicals.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 31, "end": 39}]}}, "schema": []}
{"input": "The occurrence of high levels of arsenic in the groundwater of the southeast region of Asia has received much attention in the past decade and has become a global health concern.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Predominant occurrence of both these chemicals and ease of their human exposure led us to investigate the effect of nicotine, a major tobacco alkaloid, on arsenic toxicity.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 116, "end": 124}, {"text": "arsenic", "start": 155, "end": 162}]}}, "schema": []}
{"input": "Adult male rats were pre-exposed to two different doses of nicotine (0. 75 and 3 mg/kg, intraperitoneally) for 7 days followed by 30 days of arsenic exposure (50 ppm sodium arsenite in drinking water).", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 59, "end": 67}, {"text": "arsenic", "start": 141, "end": 148}, {"text": "sodium arsenite", "start": 166, "end": 181}]}}, "schema": []}
{"input": "Nicotine pre-exposure resulted in an increased brain arsenic accumulation and a decreased liver arsenic concentration.", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}, {"text": "arsenic", "start": 53, "end": 60}, {"text": "arsenic", "start": 96, "end": 103}]}}, "schema": []}
{"input": "Arsenic also caused a significant oxidative stress in the blood, brain and liver of the exposed rats.", "output": {"entities": {"chemical": [{"text": "Arsenic", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Glutathione-S-transferase, a phase II enzyme, was inhibited by both arsenic and nicotine but no such inhibition was noted in arsenic-treated animals pre-exposed to nicotine.", "output": {"entities": {"chemical": [{"text": "Glutathione", "start": 0, "end": 11}, {"text": "S", "start": 12, "end": 13}, {"text": "arsenic", "start": 68, "end": 75}, {"text": "nicotine", "start": 80, "end": 88}, {"text": "arsenic", "start": 125, "end": 132}, {"text": "nicotine", "start": 164, "end": 172}]}}, "schema": []}
{"input": "Upon nicotine pre-exposure, brain acetylcholinesterase increased, while monoamine oxidase (MAO) decreased.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 5, "end": 13}]}}, "schema": []}
{"input": "The toxic effects of MAO significantly attenuated with nicotine pre-exposure.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 55, "end": 63}]}}, "schema": []}
{"input": "The present study suggests that nicotine may not be the major contributing factor for the previously reported synergistic toxic interaction between tobacco and arsenic.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 32, "end": 40}, {"text": "arsenic", "start": 160, "end": 167}]}}, "schema": []}
{"input": "Nicotine pre-exposure in arsenic-exposed animals revealed interesting toxicokinetics and oxidative stress modulating interactions in the brain and liver of rats, which requires further exploration.", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}, {"text": "arsenic", "start": 25, "end": 32}]}}, "schema": []}
{"input": "Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: II.", "output": {"entities": {}}, "schema": []}
{"input": "Computational Modeling.", "output": {"entities": {}}, "schema": []}
{"input": "Endocrine-disrupting chemicals can affect reproduction and development in humans and wildlife.", "output": {"entities": {}}, "schema": []}
{"input": "We developed a computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC) behaviors for endocrine effects of the aromatase inhibitor, fadrozole (FAD).", "output": {"entities": {"chemical": [{"text": "fadrozole", "start": 218, "end": 227}, {"text": "FAD", "start": 229, "end": 232}]}}, "schema": []}
{"input": "The model describes adaptive responses to endocrine stress involving regulated secretion of a generic gonadotropin (LH/FSH) from the hypothalamic-pituitary complex.", "output": {"entities": {}}, "schema": []}
{"input": "For model development, we used plasma 17 beta-estradiol (E2) concentrations and ovarian cytochrome P450 (CYP) 19A aromatase mRNA data from two time-course experiments, each of which included both an exposure and a depuration phase, and plasma E2 data from a third 4-day study.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 38, "end": 55}]}}, "schema": []}
{"input": "Model parameters were estimated using E2 concentrations for 0, 0. 5, and 3 micro g/l FAD exposure concentrations, and good fits to these data were obtained.", "output": {"entities": {"chemical": [{"text": "FAD", "start": 85, "end": 88}]}}, "schema": []}
{"input": "The model accurately predicted CYP19A mRNA fold changes for controls and three FAD doses (0, 0. 5, and 3 micro g/l) and plasma E2 dose response from the 4-day study.", "output": {"entities": {"chemical": [{"text": "FAD", "start": 79, "end": 82}]}}, "schema": []}
{"input": "Comparing the model-predicted DRTC with experimental data provided insight into how the feedback control mechanisms in the HPG axis mediate these changes: specifically, adaptive changes in plasma E2 levels occurring during exposure and \" overshoot \" occurring postexposure.", "output": {"entities": {}}, "schema": []}
{"input": "This study demonstrates the value of mechanistic modeling to examine and predict dynamic behaviors in perturbed systems.", "output": {"entities": {}}, "schema": []}
{"input": "As this work progresses, we will obtain a refined understanding of how adaptive responses within the vertebrate HPG axis affect DRTC behaviors for aromatase inhibitors and other types of endocrine-active chemicals and apply that knowledge in support of risk assessments.", "output": {"entities": {}}, "schema": []}
{"input": "A novel nontoxic inhibitor of the activation of NADPH oxidase reduces reactive oxygen species production in mouse lung.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 48, "end": 53}, {"text": "oxygen", "start": 79, "end": 85}]}}, "schema": []}
{"input": "1-Hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33) is a fluorinated phospholipid analog that inhibits the phospholipase A2 (PLA2) activity of peroxiredoxin 6 (Prdx6).", "output": {"entities": {"chemical": [{"text": "1-Hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol", "start": 0, "end": 56}, {"text": "MJ33", "start": 58, "end": 62}]}}, "schema": []}
{"input": "Prdx6 PLA2 activity is required for activation of NADPH oxidase 2 and subsequent generation of reactive oxygen species (ROS).", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 50, "end": 55}, {"text": "oxygen", "start": 104, "end": 110}]}}, "schema": []}
{"input": "In vitro, MJ33 inhibited agonist-stimulated production of ROS by the isolated perfused mouse lung, lung microvascular endothelial cells, and polymorphonuclear leukocytes.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 10, "end": 14}]}}, "schema": []}
{"input": "MJ33 (0. 02-0. 5 micro mol MJ33/kg body weight) in mixed unilamellar liposomes was administered to C57BL/6 mice by either intratracheal (i. t.) or i. v. routes.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 0, "end": 4}, {"text": "MJ33", "start": 27, "end": 31}]}}, "schema": []}
{"input": "Lung MJ33 content, measured by liquid chromatography/mass spectroscopy, showed uptake of 67-87% of the injected dose for i. t. and 23-42% for i. v. administration at 4 hours postinjection.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 5, "end": 9}]}}, "schema": []}
{"input": "PLA2 activity of lung homogenates was markedly inhibited (> 85%) at 4 hours postadministration.", "output": {"entities": {}}, "schema": []}
{"input": "Both MJ33 content and PLA2 activity gradually returned to near control levels over the subsequent 24-72 hours.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 5, "end": 9}]}}, "schema": []}
{"input": "Mice treated with MJ33 at 12. 5-25 micro mol/kg did not show changes (compared with control) in clinical symptomatology, body weight, hematocrit, and histology of lung, liver, and kidney during a 30-to 50-day observation period.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 18, "end": 22}]}}, "schema": []}
{"input": "Thus, the toxic dose of MJ33 was > 25 micro mol/kg, whereas the PLA2 inhibitory dose was approximately 0. 02 micro mol/kg, indicating a high margin of safety.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 24, "end": 28}]}}, "schema": []}
{"input": "MJ33 administered to mice prior to lung isolation markedly reduced ROS production and tissue lipid and protein oxidation during ischemia followed by reperfusion.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Thus, MJ33 could be useful as a therapeutic agent to prevent ROS-mediated tissue injury associated with lung inflammation or in harvested lungs prior to transplantation.", "output": {"entities": {"chemical": [{"text": "MJ33", "start": 6, "end": 10}]}}, "schema": []}
{"input": "When bugs reveal biodiversity.", "output": {"entities": {}}, "schema": []}
{"input": "One of the fundamental challenges of conservation biology is gathering data on species distribution and abundance.", "output": {"entities": {}}, "schema": []}
{"input": "And unless conservationists know where a species is found and in which numbers, it is very difficult to apply effective conservation efforts.", "output": {"entities": {}}, "schema": []}
{"input": "In today' s age of increasingly powerful monitoring tools, instant communication and online databases, one might be forgiven for thinking that such knowledge is easy to come by.", "output": {"entities": {}}, "schema": []}
{"input": "However, of the approximately 5, 400 terrestrial mammals on the IUCN Red List, no fewer than 789 (ca. 14%) are listed as' Data Deficient' (IUCN 2012)-IUCN' s term for' haven' t got a clue'.", "output": {"entities": {}}, "schema": []}
{"input": "Until recently, the only way to gather information of numbers and distribution of terrestrial mammals (and many other vertebrates) was through observational-based approaches such as visual records, the presence of tracks or spoor or even identification from bushmeat or hunters' trophies pinned to the walls in local villages.", "output": {"entities": {}}, "schema": []}
{"input": "While recent technological developments have considerably improved the efficacy of such approaches, for example, using remote-sensing devices such as audio-or camera-traps or even remote drones (Koh & Wich 2012), there has been a growing realization of the power of molecular methods that identify mammals based on trace evidence.", "output": {"entities": {}}, "schema": []}
{"input": "Suitable substrates include the obvious, such as faecal and hair samples (e. g. Vigilant et al. 2009), to the less obvious, including environmental DNA extracted from sediments, soil or water samples (e. g. Taberlet et al. 2012), and as recently demonstrated, the dietary content of blood-sucking invertebrates (Gariepy et al. 2012; Schnell et al. 2012).", "output": {"entities": {}}, "schema": []}
{"input": "In this issue of Molecular Ecology, Calvignac-Spencer et al.", "output": {"entities": {}}, "schema": []}
{"input": "(2013) present a potentially powerful development in this regard; diet analysis of carrion flies.", "output": {"entities": {}}, "schema": []}
{"input": "With their near global distribution, and as most field biologists know, irritatingly high frequency in most terrestrial areas of conservation concern (which directly translates into ease of sampling them), the authors present extremely encouraging results that indicate how carnivorous flies may soon represent a strong weapon in the conservation arsenal.", "output": {"entities": {}}, "schema": []}
{"input": "Modeling ring/chain equilibrium in nanoconfined sulfur.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 48, "end": 54}]}}, "schema": []}
{"input": "The effect of nanoconfinement on the thermodynamics of free radical polymerization of sulfur is examined.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 86, "end": 92}]}}, "schema": []}
{"input": "We extend Tobolsky and Eisenberg' s model of bulk sulfur polymerization to nanopores accounting for the confinement entropy of the chains and ring using scaling reported in literature.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 50, "end": 56}]}}, "schema": []}
{"input": "The model quantitatively captures literature data from Yannopoulos and co-workers for the extent of polymerization versus temperature for bulk sulfur polymerization and for polymerization in 20, 7. 5, and 2. 5 nm diameter Gelsil nanopores, assuming that the change of entropy of nanoconfined chains scales with molecular size to the second power and with nanopore diameter to either the-3. 0 or-3. 8 power, the former of which fits slightly better.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 143, "end": 149}, {"text": "Gelsil", "start": 222, "end": 228}]}}, "schema": []}
{"input": "The scaling, which is valid for strong confinement in spherical pores, predicts that the propagation equilibrium constant will depend on both nanopore size and chain length, such that the average chain length decreases significantly upon confinement.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanisms of vesicle spreading on surfaces: coarse-grained simulations.", "output": {"entities": {}}, "schema": []}
{"input": "Exposition of unilamellar vesicles to attractive surfaces is a frequently used way to create supported lipid bilayers.", "output": {"entities": {}}, "schema": []}
{"input": "Although this approach is known to produce continuous supported bilayer coatings, the mechanism of their formation and its dependence on factors like surface interaction and roughness or membrane tension as well as the interplay between neighboring vesicles or the involvement of preadsorbed bilayer patches are not well understood.", "output": {"entities": {}}, "schema": []}
{"input": "Using dissipative particle dynamics simulations, we assess different mechanisms of vesicle spreading on attractive surfaces, placing special emphasis on the orientation of the resulting bilayer.", "output": {"entities": {}}, "schema": []}
{"input": "Making use of the universality of collective phenomena in lipid membranes, we employed a solvent-free coarse-grained model, enabling us to cover the relatively large system sizes and time scales required.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that one can control the mechanism of vesicle spreading by tuning the strength and range of the interactions with the substrate as well as the surface' s roughness, resulting in a switch from a predominant inside-up to an outside-up orientation of the created supported bilayer.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary Metabolites of Capsicum Species and Their Importance in the Human Diet.", "output": {"entities": {}}, "schema": []}
{"input": "The genus Capsicum (pepper) comprises a large number of wild and cultivated species.", "output": {"entities": {}}, "schema": []}
{"input": "The plants are grown all over the world, primarily in tropical and subtropical countries.", "output": {"entities": {}}, "schema": []}
{"input": "The fruits are an excellent source of health-related compounds, such as ascorbic acid (vitamin C), carotenoids (provitamin A), tocopherols (vitamin E), flavonoids, and capsaicinoids.", "output": {"entities": {"chemical": [{"text": "ascorbic acid", "start": 72, "end": 85}, {"text": "vitamin C", "start": 87, "end": 96}, {"text": "tocopherols", "start": 127, "end": 138}, {"text": "vitamin E", "start": 140, "end": 149}, {"text": "flavonoids", "start": 152, "end": 162}, {"text": "capsaicinoids", "start": 168, "end": 181}]}}, "schema": []}
{"input": "Pepper fruits have been used for fresh and cooked consumption, as well as for medicinal purposes, such as treatment of asthma, coughs, sore throats, and toothache.", "output": {"entities": {}}, "schema": []}
{"input": "Depending on its uses, there are several main characters important for product quality; pungency, bright attractive colors, highly concentrated extracts, and a small number of seeds are the main characters on which quality is based and priced.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, a general overview of biochemical composition, medical properties of these compounds, and characteristics of quality attributes of pepper fruits is presented.", "output": {"entities": {}}, "schema": []}
{"input": "Thermorheological complexity and fragility in plasticized lignocellulose.", "output": {"entities": {}}, "schema": []}
{"input": "It is demonstrated that plasticized lignocellulose fails to satisfy classic criteria normally required to validate time/temperature superposition (TTS) in dynamic mechanical analysis (DMA).", "output": {"entities": {}}, "schema": []}
{"input": "However, insightful relaxation behavior is available and dismissing it would be a mistake.", "output": {"entities": {}}, "schema": []}
{"input": "TTS was applied to Liriodendron tulipifera wood using parallel plate compressive-torsion DMA with specimens immersed in different organic liquids, ranging from weak to strong swelling power.", "output": {"entities": {}}, "schema": []}
{"input": "While all storage moduli shifted smoothly, thermorheological complexity was detected in loss modulus shift failures, which themselves must reflect unknown structural features.", "output": {"entities": {}}, "schema": []}
{"input": "Storage modulus shift factors clearly distinguished solvent specific relaxation behavior and interpretations through the WLF model or through fragility (cooperativity) analysis are useful.", "output": {"entities": {}}, "schema": []}
{"input": "However, it is demonstrated that fragility analysis is preferred and solvents of different swelling power are compared.", "output": {"entities": {}}, "schema": []}
{"input": "Coupled with other methods, TTS and fragility analysis warrant further development as a means to improve the understanding of structure/property relationships in plasticized lignocellulose.", "output": {"entities": {}}, "schema": []}
{"input": "DNA Adducts in Aldehyde Dehydrogenase-Positive Lung Stem Cells of A/J Mice Treated with the Tobacco Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).", "output": {"entities": {"chemical": [{"text": "Aldehyde", "start": 15, "end": 23}, {"text": "4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone", "start": 125, "end": 171}, {"text": "NNK", "start": 173, "end": 176}]}}, "schema": []}
{"input": "Lung cancer is the leading cause of cancer death in the world.", "output": {"entities": {}}, "schema": []}
{"input": "Evidence suggests that lung cancer could originate from mutations accumulating in a subpopulation of self-renewing cells, lung stem cells.", "output": {"entities": {}}, "schema": []}
{"input": "Aldehyde dehydrogenase (ALDH) is a marker of stem cells.", "output": {"entities": {"chemical": [{"text": "Aldehyde", "start": 0, "end": 8}]}}, "schema": []}
{"input": "To investigate the presence of DNA modifications in these cells, we isolated ALDH-positive lung cells from A/J mice exposed to the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.", "output": {"entities": {"chemical": [{"text": "4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone", "start": 147, "end": 193}]}}, "schema": []}
{"input": "Using LC-NSI-HRMS/MS-PRM, O (6)-methyl-G, 7-POB-G, and O (2)-POB-dT were positively identified in ALDH-positive cell DNA.", "output": {"entities": {"chemical": [{"text": "O (6)-methyl-G", "start": 26, "end": 40}, {"text": "7-POB-G", "start": 42, "end": 49}, {"text": "O (2)-POB-dT", "start": 55, "end": 67}]}}, "schema": []}
{"input": "This is the first example of detection of carcinogen-DNA adducts in lung stem cells, supporting the hypothesis of their role in lung carcinogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.", "output": {"entities": {"chemical": [{"text": "polycalcium", "start": 23, "end": 34}]}}, "schema": []}
{"input": "Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1: 9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies.", "output": {"entities": {"chemical": [{"text": "Polycalcium", "start": 0, "end": 11}, {"text": "calcium lactate-gluconate", "start": 40, "end": 65}]}}, "schema": []}
{"input": "These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety.", "output": {"entities": {"chemical": [{"text": "Polycalcium", "start": 93, "end": 104}]}}, "schema": []}
{"input": "In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks.", "output": {"entities": {"chemical": [{"text": "Polycalcium", "start": 75, "end": 86}]}}, "schema": []}
{"input": "The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium.", "output": {"entities": {"chemical": [{"text": "deoxypyridinoline", "start": 43, "end": 60}, {"text": "DPYR", "start": 62, "end": 66}, {"text": "N", "start": 230, "end": 231}, {"text": "calcium", "start": 270, "end": 277}, {"text": "Ca", "start": 279, "end": 281}, {"text": "phosphorus", "start": 288, "end": 298}, {"text": "P", "start": 300, "end": 301}, {"text": "Polycalcium", "start": 382, "end": 393}]}}, "schema": []}
{"input": "After 4 weeks of Polycalcium administration, 27 subjects completed the test plan.", "output": {"entities": {"chemical": [{"text": "Polycalcium", "start": 17, "end": 28}]}}, "schema": []}
{"input": "Three subjects withdrew their consent to participate.", "output": {"entities": {}}, "schema": []}
{"input": "The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by-28. 44%, 14. 37%, 6. 11%, and 1. 42%, respectively.", "output": {"entities": {"chemical": [{"text": "Ca", "start": 37, "end": 39}, {"text": "P", "start": 51, "end": 52}]}}, "schema": []}
{"input": "Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by-13. 40%, 6. 67%,-5. 13%,-22. 43%, and-3. 04%, respectively.", "output": {"entities": {"chemical": [{"text": "DPYR", "start": 39, "end": 43}, {"text": "Ca", "start": 75, "end": 77}, {"text": "P", "start": 91, "end": 92}]}}, "schema": []}
{"input": "Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe.", "output": {"entities": {"chemical": [{"text": "Polycalcium", "start": 155, "end": 166}]}}, "schema": []}
{"input": "Polycalcium was apparently safe and efficacious.", "output": {"entities": {"chemical": [{"text": "Polycalcium", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor.", "output": {"entities": {"chemical": [{"text": "BMS-593214", "start": 38, "end": 48}]}}, "schema": []}
{"input": "A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design.", "output": {"entities": {"chemical": [{"text": "6-amidinotetrahydroquinoline", "start": 2, "end": 30}]}}, "schema": []}
{"input": "An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation.", "output": {"entities": {"chemical": [{"text": "BMS-593214", "start": 59, "end": 69}]}}, "schema": []}
{"input": "Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model.", "output": {"entities": {"chemical": [{"text": "BMS-593214", "start": 13, "end": 23}]}}, "schema": []}
{"input": "A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket.", "output": {"entities": {"chemical": [{"text": "BMS-593214", "start": 23, "end": 33}, {"text": "Asp", "start": 78, "end": 81}, {"text": "Lys", "start": 87, "end": 90}]}}, "schema": []}
{"input": "Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4.", "output": {"entities": {"chemical": [{"text": "amino-acid", "start": 85, "end": 95}]}}, "schema": []}
{"input": "Autophagy is an evolutionarily conserved catabolic mechanism that targets intracellular molecules and damaged organelles to lysosomes.", "output": {"entities": {}}, "schema": []}
{"input": "Autophagy is achieved by a series of membrane trafficking events, but their regulatory mechanisms are poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report small GTPase Rab12 as a new type of autophagic regulator that controls the degradation of an amino-acid transporter.", "output": {"entities": {"chemical": [{"text": "amino-acid", "start": 109, "end": 119}]}}, "schema": []}
{"input": "Knockdown of Rab12 results in inhibition of autophagy and in increased activity of mTORC1 (mammalian/mechanistic target of rapamycin complex 1), an upstream regulator of autophagy.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 123, "end": 132}]}}, "schema": []}
{"input": "We also found that Rab12 promotes constitutive degradation of PAT4 (proton-coupled amino-acid transporter 4), whose accumulation in Rab12-knockdown cells modulates mTORC1 activity and autophagy.", "output": {"entities": {"chemical": [{"text": "amino-acid", "start": 83, "end": 93}]}}, "schema": []}
{"input": "Our findings reveal a new mechanism of regulation of mTORC1 signalling and autophagy, that is, quality control of PAT4 by Rab12.", "output": {"entities": {}}, "schema": []}
{"input": "Chondroitin sulfate, hyaluronic Acid and chitin/chitosan production using marine waste sources: characteristics, applications and eco-friendly processes: a review.", "output": {"entities": {}}, "schema": []}
{"input": "In the last decade, an increasing number of glycosaminoglycans (GAGs), chitin and chitosan applications have been reported.", "output": {"entities": {}}, "schema": []}
{"input": "Their commercial demands have been extended to different markets, such as cosmetics, medicine, biotechnology, food and textiles.", "output": {"entities": {}}, "schema": []}
{"input": "Marine wastes from fisheries and aquaculture are susceptible sources for polymers but optimized processes for their recovery and production must be developed to satisfy such necessities.", "output": {"entities": {}}, "schema": []}
{"input": "In the present work, we have reviewed different alternatives reported in the literature to produce and purify chondroitin sulfate (CS), hyaluronic acid (HA) and chitin/chitosan (CH/CHs) with the aim of proposing environmentally friendly processes by combination of various microbial, chemical, enzymatic and membranes strategies and technologies.", "output": {"entities": {}}, "schema": []}
{"input": "Benzoquinone Reveals a Cysteine-Dependent Desensitization Mechanism of TRPA1.", "output": {"entities": {"chemical": [{"text": "Benzoquinone", "start": 0, "end": 12}, {"text": "Cysteine", "start": 23, "end": 31}]}}, "schema": []}
{"input": "The transient receptor potential ankyrin 1 (TRPA1) nonselective cation channel has a conserved function as a noxious chemical sensor throughout much of Metazoa.", "output": {"entities": {}}, "schema": []}
{"input": "Electrophilic chemicals activate both insect and vertebrate TRPA1 via covalent modification of cysteine residues in the amino-terminal region.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 95, "end": 103}, {"text": "amino", "start": 120, "end": 125}]}}, "schema": []}
{"input": "Although naturally occurring electrophilic plant compounds, such as mustard oil and cinnamaldehyde, are TRPA1 agonists, it is unknown whether arthropod-produced electrophiles activate mammalian TRPA1.", "output": {"entities": {"chemical": [{"text": "cinnamaldehyde", "start": 84, "end": 98}]}}, "schema": []}
{"input": "We characterized the effects of the electrophilic arthropod defensive compound para-benzoquinone (pBQN) on the human TRPA1 channel.", "output": {"entities": {"chemical": [{"text": "para-benzoquinone", "start": 79, "end": 96}, {"text": "pBQN", "start": 98, "end": 102}]}}, "schema": []}
{"input": "We used whole-cell recordings of human embryonic kidney cells heterologously expressing either wild-type TRPA1 or TRPA1 with three serine-substituted cysteines crucial for electrophile activation (C621S, C641S, C665S).", "output": {"entities": {"chemical": [{"text": "serine", "start": 131, "end": 137}, {"text": "cysteines", "start": 150, "end": 159}]}}, "schema": []}
{"input": "We found that pBQN activates TRPA1 starting at 10 nM and peaking at 300 nM; higher concentrations caused rapid activation followed by a fast decline.", "output": {"entities": {"chemical": [{"text": "pBQN", "start": 14, "end": 18}]}}, "schema": []}
{"input": "Activation by pBQN required reactivity with cysteine residues, but ones that are distinct from those previously reported to be the key targets of electrophiles.", "output": {"entities": {"chemical": [{"text": "pBQN", "start": 14, "end": 18}, {"text": "cysteine", "start": 44, "end": 52}]}}, "schema": []}
{"input": "The current reduction we found at higher pBQN concentrations was a cysteine-dependent desensitization of TRPA1, and did not require prior activation.", "output": {"entities": {"chemical": [{"text": "pBQN", "start": 41, "end": 45}]}}, "schema": []}
{"input": "The cysteines required for desensitization are not accessible to all electrophiles as iodoacetamide and internally applied 2-(trimethylammonium) ethyl methanesulfonate failed to cause desensitization (despite large activation).", "output": {"entities": {"chemical": [{"text": "cysteines", "start": 4, "end": 13}, {"text": "iodoacetamide", "start": 86, "end": 99}, {"text": "2-(trimethylammonium) ethyl methanesulfonate", "start": 123, "end": 167}]}}, "schema": []}
{"input": "Interestingly, following pBQN desensitization, wild-type TRPA1 had dramatically reduced response to the nonelectrophile agonist carvacrol, whereas the triple cysteine mutant TRPA1 retained its full response.", "output": {"entities": {"chemical": [{"text": "pBQN", "start": 25, "end": 29}, {"text": "carvacrol", "start": 128, "end": 137}, {"text": "cysteine", "start": 158, "end": 166}]}}, "schema": []}
{"input": "Our results suggest that modification of multiple cysteine residues by electrophilic compounds can generate both activation and desensitization of the TRPA1 channel.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 50, "end": 58}]}}, "schema": []}
{"input": "Multiplex analysis of enzyme kinetics and inhibition by droplet microfluidics using picoinjectors.", "output": {"entities": {}}, "schema": []}
{"input": "Enzyme kinetics and inhibition is important for a wide range of disciplines including pharmacology, medicine and industrial bioprocess technology.", "output": {"entities": {}}, "schema": []}
{"input": "We present a novel microdroplet-based device for extensive characterization of the reaction kinetics of enzyme substrate inhibitor systems in a single experiment utilizing an integrated droplet picoinjector for bioanalysis.", "output": {"entities": {}}, "schema": []}
{"input": "This device enables the scanning of multiple fluorescently-barcoded inhibitor concentrations and substrate conditions in a single, highly time-resolved experiment yielding the Michaelis constant (Km), the turnover number (kcat) and the enzyme inhibitor dissociation constants (ki, ki').", "output": {"entities": {}}, "schema": []}
{"input": "Using this device we determine Km and kcat for beta-galactosidase and the fluorogenic substrate Resorufin beta-d-galactopyranoside (RBG) to be 442 mu M and 1070 s (-1), respectively.", "output": {"entities": {"chemical": [{"text": "Resorufin beta-d-galactopyranoside", "start": 96, "end": 130}, {"text": "RBG", "start": 132, "end": 135}]}}, "schema": []}
{"input": "Furthermore, we examine the inhibitory effects of isopropyl-beta-d-thiogalactopyranoside (IPTG) on beta-galactosidase.", "output": {"entities": {"chemical": [{"text": "isopropyl-beta-d-thiogalactopyranoside", "start": 50, "end": 88}, {"text": "IPTG", "start": 90, "end": 94}]}}, "schema": []}
{"input": "This system has a number of potential applications, for example it could be used to screen inhibitors to pharmaceutically relevant enzymes and to characterize engineered enzyme variants for biofuels production, in both cases acquiring detailed information about the enzyme catalysis and enzyme inhibitor interaction at high throughput and low cost.", "output": {"entities": {}}, "schema": []}
{"input": "A study of parabens and bisphenol A in surface water and fish brain tissue from the Greater Pittsburgh Area.", "output": {"entities": {"chemical": [{"text": "parabens", "start": 11, "end": 19}, {"text": "bisphenol A", "start": 24, "end": 35}]}}, "schema": []}
{"input": "Pollution from xenoestrogens has been discovered in the aquatic environment of the Greater Pittsburgh Area and is suspected to be caused by the failing sewer system.", "output": {"entities": {"chemical": [{"text": "xenoestrogens", "start": 15, "end": 28}]}}, "schema": []}
{"input": "Personal care products and plasticizers have the potential to enter the water supply though treated and untreated sewage.", "output": {"entities": {}}, "schema": []}
{"input": "Many of these compounds are suspected xenoestrogens.", "output": {"entities": {"chemical": [{"text": "xenoestrogens", "start": 38, "end": 51}]}}, "schema": []}
{"input": "Paraben detection in surface waters was as follows: methyl paraben ranged between 2. 2 to 17. 3 ppt; ethyl paraben was not detectable; propyl paraben was detected at 9. 2 and 12. 0 ppt; butyl paraben was detected at 0. 2 ppt.", "output": {"entities": {"chemical": [{"text": "Paraben", "start": 0, "end": 7}, {"text": "methyl paraben", "start": 52, "end": 66}, {"text": "ethyl paraben", "start": 101, "end": 114}, {"text": "propyl paraben", "start": 135, "end": 149}, {"text": "butyl paraben", "start": 186, "end": 199}]}}, "schema": []}
{"input": "BPA was detected between 0. 6 and 15. 4 ppt.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Estrogenic potential of extracts from fish brain tissue was tested via Bromodeoxyuridine MCF-7 analysis and paired with HPLC-MS to investigate the presence of xenoestrogens.", "output": {"entities": {"chemical": [{"text": "Bromodeoxyuridine", "start": 71, "end": 88}, {"text": "xenoestrogens", "start": 159, "end": 172}]}}, "schema": []}
{"input": "All samples were non-detectable for parabens.", "output": {"entities": {}}, "schema": []}
{"input": "BPA was detected in 44 of the 58 samples, with a range from non-detectable to 120 pg/g.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "BCFs were calculated.", "output": {"entities": {}}, "schema": []}
{"input": "Results were statistically significant for location of capture (p < 0. 05) and correlation existed between estrogenicity and BPA.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 125, "end": 128}]}}, "schema": []}
{"input": "Sulfide induces apoptosis and Rho kinase-dependent cell blebbing in Jurkat cells.", "output": {"entities": {"chemical": [{"text": "Sulfide", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Hydrogen sulfide (H2S) is a toxic gaseous substance, and accidental exposure to high concentrations of H2S has been reported to be lethal to humans.", "output": {"entities": {"chemical": [{"text": "Hydrogen sulfide", "start": 0, "end": 16}, {"text": "H2S", "start": 18, "end": 21}, {"text": "H2S", "start": 103, "end": 106}]}}, "schema": []}
{"input": "Inhaled and absorbed H2S is partially dissolved within the circulation and causes toxic effects on lymphocytes.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 21, "end": 24}]}}, "schema": []}
{"input": "However, the mechanisms involved in H2S toxicity have not been well documented.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 36, "end": 39}]}}, "schema": []}
{"input": "In this study, we examined the cellular uptake and injury of sulfide-exposed human T lymphocytes (Jurkat).", "output": {"entities": {"chemical": [{"text": "sulfide", "start": 61, "end": 68}]}}, "schema": []}
{"input": "Cells were exposed to a H2S donor, sodium hydroxysulfide (NaHS), at pH 6. 0, 7. 0, or 8. 0 for 1 h at 37 degrees C in a sealed conical tube to avoid the loss of dissolved H2S gas.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 24, "end": 27}, {"text": "sodium hydroxysulfide", "start": 35, "end": 56}, {"text": "NaHS", "start": 58, "end": 62}, {"text": "H2S", "start": 171, "end": 174}]}}, "schema": []}
{"input": "Cytotoxicity and cellular sulfide concentrations increased dramatically as the pH of the NaHS solution decreased.", "output": {"entities": {"chemical": [{"text": "sulfide", "start": 26, "end": 33}, {"text": "NaHS", "start": 89, "end": 93}]}}, "schema": []}
{"input": "Sulfide enhanced the cleavage of caspase-3 and poly (ADP-ribose) polymerase and induced early cellular apoptosis.", "output": {"entities": {"chemical": [{"text": "Sulfide", "start": 0, "end": 7}, {"text": "poly (ADP-ribose)", "start": 47, "end": 64}]}}, "schema": []}
{"input": "A pan-caspase inhibitor reduced sulfide-induced apoptosis.", "output": {"entities": {"chemical": [{"text": "sulfide", "start": 32, "end": 39}]}}, "schema": []}
{"input": "These results indicate that sulfide induces pH-dependent and caspase-dependent apoptosis.", "output": {"entities": {"chemical": [{"text": "sulfide", "start": 28, "end": 35}]}}, "schema": []}
{"input": "We also found that blebbing of the plasma membrane occurred in sulfide-exposed cells.", "output": {"entities": {"chemical": [{"text": "sulfide", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Both ROCK-1 and ROCK-2 (Rho kinases) were activated by sulfide, and sulfide-induced cell blebbing was suppressed by a ROCK inhibitor, suggesting that a Rho pathway is involved in sulfide-induced blebbing in lymphocytes.", "output": {"entities": {"chemical": [{"text": "sulfide", "start": 55, "end": 62}, {"text": "sulfide", "start": 68, "end": 75}, {"text": "sulfide", "start": 179, "end": 186}]}}, "schema": []}
{"input": "Association Between Lipids, Lipoproteins Composition of HDL Particles and Triglyceride-Rich Lipoproteins, and LCAT and CETP Activity in Post-renal Transplant Patients.", "output": {"entities": {"chemical": [{"text": "Triglyceride", "start": 74, "end": 86}]}}, "schema": []}
{"input": "High-density lipoprotein (HDL) remodeling within the plasma compartment and the association between lecithin-cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, and lipid, lipoprotein concentrations and composition were investigated.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 109, "end": 120}, {"text": "cholesterol ester", "start": 148, "end": 165}]}}, "schema": []}
{"input": "The aim was to examine the high sensitivity of C-reactive protein (hsCRP), lipid, apolipoprotein B (apoB), apoAI, total apoAII, apoAIInonB, apoB-containing apoAII (apoB: AII), total apoCIII, apoCIIInonB, apoB-containing apoCIII (apoB: CIII) concentration and LCAT and CETP activity to gain an insight into the association between them and LCAT and CETP, 57 post-renal transplant (Tx) patients with and without statin therapy and in 15 healthy subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Tx patients had moderate hypertriglyceridemia, hypercholesterolemia, and dyslipoproteinemia, disturbed triglyceride-rich lipoproteins (TRLs) and HDL composition, decreased LCAT, and slightly increased hsCRP but no CETP activity.", "output": {"entities": {}}, "schema": []}
{"input": "Spearman' s correlation test showed the association between lipids and lipoproteins and LCAT or CETP, and multiple ridge stepwise forward regression showed that immunosuppressive therapy in Tx patients can disturb HDL and TRLs composition.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest that inhibition or activation of LCAT is due, in part, to HDL-associated lipoprotein.", "output": {"entities": {}}, "schema": []}
{"input": "Lipoprotein composition of apoAI, apoAIInonB, and apoCIIInonB in HDL particle and apoB: AII TRLs can contribute to decrease LCAT mass in Tx patients.", "output": {"entities": {}}, "schema": []}
{"input": "Tx patients without statin and with lower triglycerides but higher HDL cholesterol concentration and disturbed lipoprotein composition of ApoAI and apoAII in HDL particle can decrease LCAT, increase LDL cholesterol, aggravate renal graft, and accelerate atherosclerosis and chronic heart diseases.", "output": {"entities": {"chemical": [{"text": "statin", "start": 20, "end": 26}, {"text": "triglycerides", "start": 42, "end": 55}, {"text": "cholesterol", "start": 71, "end": 82}, {"text": "cholesterol", "start": 203, "end": 214}]}}, "schema": []}
{"input": "Quercetin mitochondriotropic derivatives antagonize nitrate tolerance and endothelial dysfunction of isolated rat aorta rings.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "nitrate", "start": 52, "end": 59}]}}, "schema": []}
{"input": "Chronic use of glyceryl trinitrate is limited by serious side effects, inter alia tolerance and endothelial dysfunction of coronary and resistance arteries.", "output": {"entities": {"chemical": [{"text": "glyceryl trinitrate", "start": 15, "end": 34}]}}, "schema": []}
{"input": "The natural flavonoid quercetin has been shown to counteract the development of glyceryl trinitrate tolerance in vitro.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 22, "end": 31}, {"text": "glyceryl trinitrate", "start": 80, "end": 99}]}}, "schema": []}
{"input": "Two mitochondriotropic, 4-O-triphenylphosphoniumbutyl derivatives of quercetin (QTA-3BTPI and Q-3BTPI) were compared to quercetin for protection against glyceryl trinitrate-induced tolerance and endothelial dysfunction of isolated rat aorta rings.", "output": {"entities": {"chemical": [{"text": "4-O-triphenylphosphoniumbutyl", "start": 24, "end": 53}, {"text": "quercetin", "start": 69, "end": 78}, {"text": "QTA-3BTPI", "start": 80, "end": 89}, {"text": "Q-3BTPI", "start": 94, "end": 101}, {"text": "quercetin", "start": 120, "end": 129}, {"text": "glyceryl trinitrate", "start": 153, "end": 172}]}}, "schema": []}
{"input": "Both QTA-3BTPI and Q-3BTPI significantly counteracted the reduced vascular responsiveness to both glyceryl trinitrate and acetylcholine caused by prolonged exposure of the vessel to glyceryl trinitrate itself, their potency being much greater than that of quercetin.", "output": {"entities": {"chemical": [{"text": "QTA-3BTPI", "start": 5, "end": 14}, {"text": "Q-3BTPI", "start": 19, "end": 26}, {"text": "glyceryl trinitrate", "start": 98, "end": 117}, {"text": "acetylcholine", "start": 122, "end": 135}, {"text": "glyceryl trinitrate", "start": 182, "end": 201}, {"text": "quercetin", "start": 256, "end": 265}]}}, "schema": []}
{"input": "QTA-3BTPI, however, turned out to cause endothelial dysfunction per se.", "output": {"entities": {"chemical": [{"text": "QTA-3BTPI", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Since Q-3BTPI antagonized in vitro nitrate tolerance and endothelial dysfunction of vessels, this encourages assessing whether this effect is displayed also in vivo during long-term glyceryl trinitrate treatment.", "output": {"entities": {"chemical": [{"text": "Q-3BTPI", "start": 6, "end": 13}, {"text": "nitrate", "start": 35, "end": 42}, {"text": "glyceryl trinitrate", "start": 182, "end": 201}]}}, "schema": []}
{"input": "Cytotoxic pentacyclic triterpenoids from Prinsepia utilis.", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenoids", "start": 10, "end": 35}]}}, "schema": []}
{"input": "Phytochemical investigation of the aerial parts of Prinsepia utilis Royle resulted in the isolation and identification of ten pentacyclic triterpenoids, including two new triterpenoids, 2 alpha-O-trans-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid (1) and 2 alpha-O-cis-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid (2), along with eight known pentacyclic triterpenoids (3-10).", "output": {"entities": {"chemical": [{"text": "pentacyclic triterpenoids", "start": 126, "end": 151}, {"text": "triterpenoids", "start": 171, "end": 184}, {"text": "2 alpha-O-trans-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid", "start": 186, "end": 262}, {"text": "2 alpha-O-cis-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid", "start": 271, "end": 345}, {"text": "pentacyclic triterpenoids", "start": 374, "end": 399}]}}, "schema": []}
{"input": "The structures were elucidated by extensive spectroscopic methods and by comparison to previously reported spectroscopic data.", "output": {"entities": {}}, "schema": []}
{"input": "Most of these compounds showed significant cytotoxic activities against four human cancer cell lines (A549, HCT116, MDA-MB-231, and CCRF-CEM), and the structure-activity relationships are also discussed.", "output": {"entities": {}}, "schema": []}
{"input": "New Concepts, Experimental Approaches, and Dereplication Strategies for the Discovery of Novel Phytoestrogens from Natural Sources.", "output": {"entities": {}}, "schema": []}
{"input": "Phytoestrogens constitute an attractive research topic due to their estrogenic profile and their biological involvement in woman' s health.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, numerous studies are currently performed in natural products chemistry area aiming at the discovery of novel phytoestrogens.", "output": {"entities": {}}, "schema": []}
{"input": "The main classes of phytoestrogens are flavonoids (flavonols, flavanones), isoflavonoids (isoflavones, coumestans), lignans, stilbenoids as well as miscellaneous chemical groups abundant in several edible and/or medicinal plants, belonging mostly to the Leguminosae family.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 39, "end": 49}, {"text": "flavonols", "start": 51, "end": 60}, {"text": "flavanones", "start": 62, "end": 72}, {"text": "isoflavonoids", "start": 75, "end": 88}, {"text": "isoflavones", "start": 90, "end": 101}, {"text": "coumestans", "start": 103, "end": 113}, {"text": "lignans", "start": 116, "end": 123}, {"text": "stilbenoids", "start": 125, "end": 136}]}}, "schema": []}
{"input": "As for other bioactives, the detection of new structures and more potent plant-derived phytoestrogens typically follows the general approaches currently available in the natural product discovery process.", "output": {"entities": {}}, "schema": []}
{"input": "Plant-based approaches selected from traditional medicine knowledge and bioguided concepts are routinely employed.", "output": {"entities": {}}, "schema": []}
{"input": "However, these approaches are associated with serious disadvantages such as time-consuming, repeated, and labor intensive processes as well as lack of specificity and reproducibility.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years, the natural products chemistry became more technology-driven, and several different strategies have been developed.", "output": {"entities": {}}, "schema": []}
{"input": "Structure-oriented procedures and miniaturized approaches employing advanced hyphenated analytical platforms have recently emerged.", "output": {"entities": {}}, "schema": []}
{"input": "They facilitate significantly not only the discovery of novel phytoestrogens but also the dereplication procedure leading to the anticipation of major drawbacks in natural products discovery.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, apart from the traditional concepts followed in phytochemistry for the discovery of novel biologically active compounds, recent applications in the field of extraction, analysis, fractionation, and identification of phytoestrogens will be discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, specific methodologies combining identification of actives and biological evaluation in parallel, such as liquid chromatography-biochemical detection, frontal affinity chromatography-mass spectrometry and pulsed ultrafiltration-MS will also be presented.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, miniaturized methods (microchip and biosensor) will be also discussed. With the current review, we attempt to give a wide and holistic overview of the different approaches which could be employed in the discovery of new phytoestrogens.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, we anticipate to attract more scientists to the area of phytoestrogens and to indicate the need of multidisciplinary concepts.", "output": {"entities": {}}, "schema": []}
{"input": "Structural Units Important for Activity of a Novel-type Phosphoserine Phosphatase from Hydrogenobacter thermophilus TK-6 Revealed by Crystal Structure Analysis.", "output": {"entities": {"chemical": [{"text": "Phosphoserine", "start": 56, "end": 69}]}}, "schema": []}
{"input": "Novel-type serine-synthesizing enzymes, termed metal-independent phosphoserine phosphatases (iPSPs), were recently identified and characterized from Hydrogenobacter thermophilus, a chemolithoautotrophic bacterium belonging to the order Aquificales.", "output": {"entities": {"chemical": [{"text": "serine", "start": 11, "end": 17}, {"text": "phosphoserine", "start": 65, "end": 78}]}}, "schema": []}
{"input": "iPSPs are cofactor-dependent phosphoglycerate mutase (dPGM)-like phosphatases that have significant amino acid sequence similarity to dPGMs but lack phosphoglycerate mutase activity.", "output": {"entities": {"chemical": [{"text": "phosphoglycerate", "start": 29, "end": 45}, {"text": "amino acid", "start": 100, "end": 110}, {"text": "phosphoglycerate", "start": 149, "end": 165}]}}, "schema": []}
{"input": "Genes coding dPGM-like phosphatases have been identified in a broad range of organisms; however, predicting the function of the corresponding proteins based on sequence information alone is difficult due to their diverse substrate preferences.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we determined the crystal structure of iPSP1 from H. thermophilus in the apo-form and in complex with its substrate l-phosphoserine to find structural units important for its phosphatase activity toward l-phosphoserine.", "output": {"entities": {"chemical": [{"text": "l-phosphoserine", "start": 122, "end": 137}, {"text": "l-phosphoserine", "start": 209, "end": 224}]}}, "schema": []}
{"input": "Structural and biochemical characterization of iPSP1 revealed that the side chains of His (85) and C-terminal region characteristic of iPSP1 are responsible for the PSP activity.", "output": {"entities": {"chemical": [{"text": "His", "start": 86, "end": 89}, {"text": "C", "start": 99, "end": 100}]}}, "schema": []}
{"input": "The importance of these structural units for PSP activity was confirmed by high PSP activity observed in two novel dPGM-like proteins from Cyanobacteria and Chloroflexus in which the two structural units were conserved.", "output": {"entities": {}}, "schema": []}
{"input": "We anticipate that our present findings will facilitate understanding of the serine biosynthesis pathways of organisms that lack gene (s) encoding conventional PSPs, as the structural information revealed here will help to identify iPSP from sequence databases.", "output": {"entities": {"chemical": [{"text": "serine", "start": 77, "end": 83}]}}, "schema": []}
{"input": "N-[9-(ortho-Fluorobenzyl)-2-Phenyl-8-Azapurin-6-yl]-Amides as Potent and Selective Ligands for A1 Adenosine Receptors.", "output": {"entities": {"chemical": [{"text": "N-[9-(ortho-Fluorobenzyl)-2-Phenyl-8-Azapurin-6-yl]-Amides", "start": 0, "end": 58}, {"text": "Adenosine", "start": 98, "end": 107}]}}, "schema": []}
{"input": "A series of N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides were synthesised and tested for their affinity toward A1, A2A and A3 adenosine receptor subtypes.", "output": {"entities": {"chemical": [{"text": "N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides", "start": 12, "end": 70}, {"text": "adenosine", "start": 140, "end": 149}]}}, "schema": []}
{"input": "Biological results demonstrated that the introduction of a fluorine atom at the ortho position of the 9-benzyl group generally enhanced affinity toward A1 subtype and did not significantly affect A2A and A3 affinity.", "output": {"entities": {"chemical": [{"text": "fluorine", "start": 59, "end": 67}, {"text": "9-benzyl", "start": 102, "end": 110}]}}, "schema": []}
{"input": "Very interesting is the compound bearing a meta-fluorophenyl substituent on the carbonyl carbon of the amide group, which shows significantly high A1/A2A-A3 selectivity.", "output": {"entities": {"chemical": [{"text": "meta-fluorophenyl", "start": 43, "end": 60}, {"text": "carbonyl carbon", "start": 80, "end": 95}, {"text": "amide", "start": 103, "end": 108}]}}, "schema": []}
{"input": "Compounds of this new series, together with the previously published analogs without the fluorine atom on the 9-benzyl group, constituted the starting dataset for the development of QSAR models.", "output": {"entities": {"chemical": [{"text": "fluorine", "start": 89, "end": 97}, {"text": "9-benzyl", "start": 110, "end": 118}]}}, "schema": []}
{"input": "The models obtained were able to rationally describe the affinity trends resulting from biological testing, and to enable investigation of the role of different substituents on the 8-azapurine scaffold, as well as the influence of the newly introduced fluorine atom on the benzyl moiety.", "output": {"entities": {"chemical": [{"text": "8-azapurine", "start": 181, "end": 192}, {"text": "fluorine", "start": 252, "end": 260}, {"text": "benzyl", "start": 273, "end": 279}]}}, "schema": []}
{"input": "The said QSAR models can also assist in the design of new compounds selectively active on A1 adenosine receptors.", "output": {"entities": {"chemical": [{"text": "adenosine", "start": 93, "end": 102}]}}, "schema": []}
{"input": "Furthermore, a molecular docking study was carried out in order to assess hypothetical binding mode of N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides to A1 adenosine receptors.", "output": {"entities": {"chemical": [{"text": "N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides", "start": 103, "end": 161}, {"text": "adenosine", "start": 168, "end": 177}]}}, "schema": []}
{"input": "(c) 2013 John Wiley & Sons A/S.", "output": {"entities": {}}, "schema": []}
{"input": "Physicochemical Properties and Supernucleophilicity of Oxime-Functionalized Surfactants: Hydrolytic Catalysts toward Dephosphorylation of Di-and Triphosphate Esters.", "output": {"entities": {"chemical": [{"text": "Oxime", "start": 55, "end": 60}, {"text": "Di-and Triphosphate Esters", "start": 138, "end": 164}]}}, "schema": []}
{"input": "Aggregation and kinetic studies have been performed to understand the hydrolytic potencies of the series of oxime-functionalized surfactants, viz., 3-hydroxyiminomethyl-1-alkylpyridinium bromide (alkyl = CnH2n + 1, n = 10, 12, 14, 16, 18) in the cleavage of phosphate esters, p-nitrophenyl diphenyl phosphate (PNPDPP) and bis (2, 4-dinitrophenyl) phosphate (BNDPP), in mixed micelles with cetylpyridinium bromide (CPB).", "output": {"entities": {"chemical": [{"text": "oxime", "start": 108, "end": 113}, {"text": "3-hydroxyiminomethyl-1-alkylpyridinium bromide", "start": 148, "end": 194}, {"text": "alkyl", "start": 196, "end": 201}, {"text": "CnH2n + 1", "start": 204, "end": 213}, {"text": "phosphate esters", "start": 258, "end": 274}, {"text": "p-nitrophenyl diphenyl phosphate", "start": 276, "end": 308}, {"text": "PNPDPP", "start": 310, "end": 316}, {"text": "bis (2, 4-dinitrophenyl) phosphate", "start": 322, "end": 356}, {"text": "BNDPP", "start": 358, "end": 363}, {"text": "cetylpyridinium bromide", "start": 389, "end": 412}, {"text": "CPB", "start": 414, "end": 417}]}}, "schema": []}
{"input": "Micellization and surface properties of mixed micelles functional surfactants with CPB were studied by conductivity and surface tension measurements.", "output": {"entities": {"chemical": [{"text": "CPB", "start": 83, "end": 86}]}}, "schema": []}
{"input": "Acid dissociation constants (pKa) were determined, the effect of functional surfactant alkyl chain length and pH on the observed rate constant (kobs) for phosphate ester cleavage has been discussed, and the effect of substrate on the supernucleophilicities of the studied oximes was monitored.", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 87, "end": 92}, {"text": "phosphate ester", "start": 154, "end": 169}, {"text": "oximes", "start": 272, "end": 278}]}}, "schema": []}
{"input": "Functionalized oxime-based surfactants were proved to be supernucleophiles to attack on the P = O center of tri-and diphosphate esters.", "output": {"entities": {"chemical": [{"text": "oxime", "start": 15, "end": 20}, {"text": "P = O", "start": 92, "end": 97}, {"text": "tri-and diphosphate esters", "start": 108, "end": 134}]}}, "schema": []}
{"input": "Oximes with hexadecyl alkyl chain length (3-C16) showed maximum micellar effect on the rate constants toward PNPDPP.", "output": {"entities": {"chemical": [{"text": "Oximes", "start": 0, "end": 6}, {"text": "hexadecyl alkyl", "start": 12, "end": 27}, {"text": "3-C16", "start": 42, "end": 47}, {"text": "PNPDPP", "start": 109, "end": 115}]}}, "schema": []}
{"input": "Micellar effects were analyzed in terms of the pseudophase model.", "output": {"entities": {}}, "schema": []}
{"input": "A concise total synthesis of the natural carbazole clauraila A.", "output": {"entities": {"chemical": [{"text": "carbazole", "start": 41, "end": 50}]}}, "schema": []}
{"input": "A short and efficient total synthesis of naturally occurring carbazole clauraila A (1) is described.", "output": {"entities": {"chemical": [{"text": "carbazole clauraila A", "start": 61, "end": 82}]}}, "schema": []}
{"input": "The approach is designed on the basis of the key regioselective Diels-Alder reaction of the properly substituted exo-2-oxazolidinone diene 3 with acrolein (4) to give the corresponding adduct 2.", "output": {"entities": {"chemical": [{"text": "exo-2-oxazolidinone diene", "start": 113, "end": 138}, {"text": "acrolein", "start": 146, "end": 154}]}}, "schema": []}
{"input": "The latter is converted to functionalised diarylamine 8, which is cyclised to the desired carbazole 1 through a Pd-promoted or-catalysed double C-H bond activation process in a fairly good overall yield.", "output": {"entities": {"chemical": [{"text": "diarylamine", "start": 42, "end": 53}, {"text": "carbazole", "start": 90, "end": 99}, {"text": "Pd", "start": 112, "end": 114}, {"text": "C-H", "start": 144, "end": 147}]}}, "schema": []}
{"input": "Free fatty acid binding protein-4 and retinol binding protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 5, "end": 15}, {"text": "retinol", "start": 38, "end": 45}, {"text": "simvastatin", "start": 106, "end": 117}, {"text": "metformin", "start": 122, "end": 131}]}}, "schema": []}
{"input": "Abstract Free fatty acid binding protein-4 (FABP4) and retinol binding protein-4 (RBP4) contribute to metabolic syndrome.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 14, "end": 24}, {"text": "retinol", "start": 55, "end": 62}]}}, "schema": []}
{"input": "We investigated serum FABP4 and RBP4 responses to insulin sensitizing and lipid lowering therapies in polycystic ovary syndrome (PCOS).", "output": {"entities": {}}, "schema": []}
{"input": "Sixty-two healthy, untreated women with PCOS (age 25. 1 +/- 3. 6 years, BMI: 24. 0 +/- 4. 7 kg/m (2)) were randomized to metformin (n = 24), simvastatin (n = 20) or metformin plus simvastatin (n = 18) for 3 months.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 121, "end": 130}, {"text": "simvastatin", "start": 141, "end": 152}, {"text": "metformin", "start": 165, "end": 174}, {"text": "simvastatin", "start": 180, "end": 191}]}}, "schema": []}
{"input": "Anthropometric measures, fasting blood tests and oral glucose tolerance tests (OGTT) were obtained at the baseline and the end.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 54, "end": 61}]}}, "schema": []}
{"input": "At the baseline serum FABP4 correlated with obesity (BMI: r = 0. 63, p < 0. 001), insulin resistance (fasting insulin: r = 0. 44, p = 0. 0002; QUICKI: r =-0. 30, p = 0. 02; OGTT-insulin sensitivity index: r =-0. 27, p = 0. 04), dyslipidemia (HDL: r =-0. 26, p = 0. 03) and hyperandrogenemia (free-testosterone: r = 0. 23, p = 0. 03; SHBG: r =-0. 28, p = 0. 03); while RBP4 correlated with total-cholesterol (r = 0. 33, p = 0. 009).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 395, "end": 406}]}}, "schema": []}
{"input": "Multiple regression analysis indicated that t best predictors of serum FABP4 and RBP4 were BMI (beta = 1. 02, p = 0. 0003) and total cholesterol (beta = 2326, p = 0. 01), respectively.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 133, "end": 144}]}}, "schema": []}
{"input": "Simvastatin, alone or with metformin did not affect serum FABP4 or RBP4.", "output": {"entities": {"chemical": [{"text": "Simvastatin", "start": 0, "end": 11}, {"text": "metformin", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Serum FABP4 related to the obesity, insulin resistance and inflammation while RBP4 related to lipids.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin sensitizing and lipid lowering therapies did not affect FABP4 or RBP4 levels in PCOS.", "output": {"entities": {}}, "schema": []}
{"input": "Temperature-Dependent Conformations of a Membrane Supported Zinc Porphyrin Tweezer by 2D Fluorescence Spectroscopy.", "output": {"entities": {"chemical": [{"text": "Zinc Porphyrin", "start": 60, "end": 74}]}}, "schema": []}
{"input": "We studied the equilibrium conformations of a zinc porphyrin tweezer composed of two carboxylphenyl-functionalized zinc tetraphenyl porphyrin subunits connected by a 1, 4-butyndiol spacer, which was suspended inside the amphiphilic regions of 1, 2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposomes.", "output": {"entities": {"chemical": [{"text": "zinc porphyrin", "start": 46, "end": 60}, {"text": "carboxylphenyl", "start": 85, "end": 99}, {"text": "zinc tetraphenyl porphyrin", "start": 115, "end": 141}, {"text": "1, 4-butyndiol", "start": 166, "end": 180}, {"text": "1, 2-distearoyl-sn-glycero-3-phosphocholine", "start": 243, "end": 286}, {"text": "DSPC", "start": 288, "end": 292}]}}, "schema": []}
{"input": "By combining phase-modulation two-dimensional fluorescence spectroscopy (2D FS) with linear absorbance and fluorimetry, we determined that the zinc porphyrin tweezer adopts a mixture of folded and extended conformations in the membrane.", "output": {"entities": {"chemical": [{"text": "zinc porphyrin", "start": 143, "end": 157}]}}, "schema": []}
{"input": "By fitting an exciton-coupling model to a series of data sets recorded over a range of temperatures (17-85 degrees C) and at different laser center wavelengths, we determined that the folded form of the tweezer is stabilized by a favorable change in the entropy of the local membrane environment.", "output": {"entities": {}}, "schema": []}
{"input": "Our results provide insights toward understanding the balance of thermodynamic factors that govern molecular assembly in membranes.", "output": {"entities": {}}, "schema": []}
{"input": "Efficient MRI labeling of endothelial progenitor cells: Design of thiolated surface stabilized superparamagnetic iron oxide nanoparticles.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 113, "end": 123}]}}, "schema": []}
{"input": "The aim of this study was to design thiolated surface stabilized superparamagnetic iron oxide nanoparticles (TSS-SPIONs) for efficient internalization with high MRI sensitivity.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 83, "end": 93}]}}, "schema": []}
{"input": "TSS-SPIONs were developed by chelation between thiolated chitosan-thioglycolic acid (chitosan-TGA) hydrogel and iron ions (Fe (2 +)/Fe (3 +)).", "output": {"entities": {"chemical": [{"text": "thioglycolic acid", "start": 66, "end": 83}, {"text": "TGA", "start": 94, "end": 97}, {"text": "iron", "start": 112, "end": 116}, {"text": "Fe (2 +)", "start": 123, "end": 131}, {"text": "Fe (3 +)", "start": 132, "end": 140}]}}, "schema": []}
{"input": "Likely, unmodified chitosan hydrogel SPIONs (UC-SPIONs) and uncoated SPIONs were used as control.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, TSS-SPIONs were investigated regarding to their iron core size, hydrodynamic diameter, zeta potential, iron contents, molar relaxivities (r1 and r2), and cellular internalization.", "output": {"entities": {"chemical": [{"text": "iron", "start": 58, "end": 62}, {"text": "iron", "start": 113, "end": 117}]}}, "schema": []}
{"input": "TSS-SPIONs demonstrated an iron oxide core diameter (crystallite size by XRD) of 3. 1 +/- 0. 02nm, a hydrodynamic diameter of 94 +/- 20nm, a zeta potential of + 21 +/- 5mV, and an iron content of 3. 6 +/- 0. 9mg/mL.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 27, "end": 37}, {"text": "iron", "start": 180, "end": 184}]}}, "schema": []}
{"input": "In addition, internalization of TSS-SPIONs into human endothelial progenitor cells (EPC) from umbilical cord blood was more than threefold and 17-fold higher in contrast to UC-SPIONs and SPIONs, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "With twofold lower incubation iron concentration of TSS-SPIONs, more than threefold higher internalization was achieved as compared to Resovist (R).", "output": {"entities": {"chemical": [{"text": "iron", "start": 30, "end": 34}]}}, "schema": []}
{"input": "Also, cell viability of more than 90% was observed in the presence of TSS-SPIONs after 24h.", "output": {"entities": {}}, "schema": []}
{"input": "The molar MR relaxivities (r2) value at 1. 5T was threefold higher than that of Resovist (R) and demonstrated that TSS-SPIONs have the potential as very effective T2 contrast-enhancement agent.", "output": {"entities": {}}, "schema": []}
{"input": "According to these findings, TSS-SPIONs with efficient internalization, lower cytotoxicity, and high MRI sensitivity seem to be promising for cell tracking.", "output": {"entities": {}}, "schema": []}
{"input": "Rules for the recognition of dilysine retrieval motifs by coatomer.", "output": {"entities": {"chemical": [{"text": "dilysine", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Cytoplasmic dilysine motifs on transmembrane proteins are captured by coatomer alpha-COP and beta'-COP subunits and packaged into COPI-coated vesicles for Golgi-to-ER retrieval.", "output": {"entities": {"chemical": [{"text": "dilysine", "start": 12, "end": 20}]}}, "schema": []}
{"input": "Numerous ER/Golgi proteins contain K (x) Kxx motifs, but the rules for their recognition are unclear.", "output": {"entities": {}}, "schema": []}
{"input": "We present crystal structures of alpha-COP and beta'-COP bound to a series of naturally occurring retrieval motifs-encompassing KKxx, KxKxx and non-canonical RKxx and viral KxHxx sequences.", "output": {"entities": {}}, "schema": []}
{"input": "Binding experiments show that alpha-COP and beta'-COP have generally the same specificity for KKxx and KxKxx, but only beta'-COP recognizes the RKxx signal.", "output": {"entities": {}}, "schema": []}
{"input": "Dilysine motif recognition involves lysine side-chain interactions with two acidic patches.", "output": {"entities": {"chemical": [{"text": "Dilysine", "start": 0, "end": 8}, {"text": "lysine", "start": 36, "end": 42}]}}, "schema": []}
{"input": "Surprisingly, however, KKxx and KxKxx motifs bind differently, with their lysine residues transposed at the binding patches.", "output": {"entities": {"chemical": [{"text": "lysine", "start": 74, "end": 80}]}}, "schema": []}
{"input": "We derive rules for retrieval motif recognition from key structural features: the reversed binding modes, the recognition of the C-terminal carboxylate group which enforces lysine positional context, and the tolerance of the acidic patches for non-lysine residues.", "output": {"entities": {"chemical": [{"text": "C", "start": 129, "end": 130}, {"text": "carboxylate", "start": 140, "end": 151}, {"text": "lysine", "start": 173, "end": 179}, {"text": "lysine", "start": 248, "end": 254}]}}, "schema": []}
{"input": "First report on predictive chemometric modeling, 3D-toxicophore mapping and in silico screening of in vitro basal cytotoxicity of diverse organic chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "Classification and regression based quantitative structure-toxicity relationship (QSTR) as well as toxicophore models were developed for the first time on basal cytotoxicity data (in vitro 3T3 neutral red uptake data) of a diverse series of chemicals (including drugs and environmental pollutants) collected from the ACuteTox database (http://www. acutetox. eu/).", "output": {"entities": {}}, "schema": []}
{"input": "Statistically significant QSTR models were obtained using linear discriminant analysis (classification) and partial least squares (regression) methodologies.", "output": {"entities": {}}, "schema": []}
{"input": "Generated toxicophore models showed four important features responsible for basal cytotoxicity: (i) two hydrophobic aliphatic groups (HYD Aliphatic), (ii) ring aromatic group (RA) and (iii) hydrogen bond donor (HBD).", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 190, "end": 198}]}}, "schema": []}
{"input": "The most predictive hypothesis (Hypo 1) had a correlation coefficient of 0. 932 for the training set, a low rms deviation of 1. 105, and an acceptable cost difference of 62. 8 bits, which represents a true correlation and a good predictivity.", "output": {"entities": {}}, "schema": []}
{"input": "QSTR and toxicophore models were rigorously validated internally as well as externally along with the randomization test to nullify the possibilities of chance correlation.", "output": {"entities": {}}, "schema": []}
{"input": "Our in silico models enable to identify the essential structural attributes and quantify the prime molecular pre-requisites which were chiefly responsible for in vitro basal cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The developed models were also implemented to screen basal cytotoxicity for huge number DrugBank database (http://www. drugbank. ca/) compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Testosterone modulates spatial recognition memory in male rats.", "output": {"entities": {"chemical": [{"text": "Testosterone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "A growing body of research indicates that testosterone influences spatial cognition in male rats; however, the overwhelming majority of studies have been conducted on tasks motivated by either food deprivation or water escape.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 42, "end": 54}]}}, "schema": []}
{"input": "The hippocampus-dependent version of the Y-maze task, which characterizes spatial recognition memory, capitalizes on the propensity of rats to gravitate toward novel spatial environments and is not contingent upon either appetite or the stress associated with water escape, two factors also affected by testosterone.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 303, "end": 315}]}}, "schema": []}
{"input": "Accordingly, the aim of the current study was to examine the effects of orchidectomy and subsequent testosterone treatment on spatial recognition memory.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 100, "end": 112}]}}, "schema": []}
{"input": "Orchidectomy did not impact spatial recognition memory when the delay between the information and retention trials of the Y-maze task was 24h.", "output": {"entities": {}}, "schema": []}
{"input": "Alternatively, on the second Y-maze task, which featured a 48-h delay between trials, orchidectomy reduced, and treatments that produced higher levels of testosterone restored, preference for the arm associated with the novel spatial environment.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 154, "end": 166}]}}, "schema": []}
{"input": "Importantly, there were no differences in activity levels as a function of orchidectomy or testosterone treatment on either of the two tasks.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 91, "end": 103}]}}, "schema": []}
{"input": "Consistent with previous findings, orchidectomy attenuated, and testosterone treatment restored, both body weight gain and the relative weight of the androgen-sensitive ischiocavernosus muscle, which confirmed the efficacy of orchidectomy and testosterone treatments on physiological outcomes.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 64, "end": 76}, {"text": "androgen", "start": 150, "end": 158}, {"text": "testosterone", "start": 243, "end": 255}]}}, "schema": []}
{"input": "Therefore, testosterone influenced spatial cognition on a task that minimized the influence of non-mnemonic factors and took advantage of the innate preference of rodents to seek out novel spatial environments.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 11, "end": 23}]}}, "schema": []}
{"input": "Identification of mRNAs bound and regulated by human LIN28 proteins and molecular requirements for RNA recognition.", "output": {"entities": {}}, "schema": []}
{"input": "Human LIN28A and LIN28B are RNA-binding proteins (RBPs) conserved in animals with important roles during development and stem cell reprogramming.", "output": {"entities": {}}, "schema": []}
{"input": "We used Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) in HEK293 cells and identified a largely overlapping set of ~ 3000 mRNAs at ~ 9500 sites located in the 3' UTR and CDS.", "output": {"entities": {"chemical": [{"text": "Ribonucleoside", "start": 25, "end": 39}]}}, "schema": []}
{"input": "In vitro and in vivo, LIN28 preferentially bound single-stranded RNA containing a uridine-rich element and one or more flanking guanosines and appeared to be able to disrupt base-pairing to access these elements when embedded in predicted secondary structure.", "output": {"entities": {"chemical": [{"text": "uridine", "start": 82, "end": 89}, {"text": "guanosines", "start": 128, "end": 138}]}}, "schema": []}
{"input": "In HEK293 cells, LIN28 protein binding mildly stabilized target mRNAs and increased protein abundance.", "output": {"entities": {}}, "schema": []}
{"input": "The top targets were its own mRNAs and those of other RBPs and cell cycle regulators.", "output": {"entities": {}}, "schema": []}
{"input": "Alteration of LIN28 protein levels also negatively regulated the abundance of some but not all let-7 miRNA family members, indicating sequence-specific binding of let-7 precursors to LIN28 proteins and competition with cytoplasmic miRNA biogenesis factors.", "output": {"entities": {}}, "schema": []}
{"input": "Novel tacrine-related drugs as potential candidates for the treatment of Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "tacrine", "start": 6, "end": 13}]}}, "schema": []}
{"input": "A summary of the recently published efforts on tacrine derivatives as a renewed potential therapeutic approach for the treatment of Alzheimer' s disease is presented.", "output": {"entities": {"chemical": [{"text": "tacrine", "start": 47, "end": 54}]}}, "schema": []}
{"input": "The mammalian clock and chronopharmacology.", "output": {"entities": {}}, "schema": []}
{"input": "Increases in our understanding of the molecular control of circadian rhythms and subsequent signaling pathways has allowed for new therapeutic drug targets to be identified as well as for a better understanding of how to more efficaciously and safely utilize current drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review recent advances in targeting components of the molecular clock in mammals for the development of novel therapeutics as well as describe the impact of the circadian rhythm on drug efficacy and toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, receptor binding and activity of iso and azakainoids.", "output": {"entities": {"chemical": [{"text": "iso and azakainoids", "start": 44, "end": 63}]}}, "schema": []}
{"input": "Two syntheses for the production of an unsubstituted azakainoid are described.", "output": {"entities": {"chemical": [{"text": "azakainoid", "start": 53, "end": 63}]}}, "schema": []}
{"input": "The 1, 3-dipolar cycloaddition of diazomethane with trans-dibenzyl glutaconate yields a 1-pyrazoline, which may be reduced directly to the pyrazolidine.", "output": {"entities": {"chemical": [{"text": "diazomethane", "start": 34, "end": 46}, {"text": "trans-dibenzyl glutaconate", "start": 52, "end": 78}, {"text": "1-pyrazoline", "start": 88, "end": 100}, {"text": "pyrazolidine", "start": 139, "end": 151}]}}, "schema": []}
{"input": "An unexpected trans-cis isomerization is observed during Hg/Al reduction of the 1-pyrazoline NN bond.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 57, "end": 59}, {"text": "Al", "start": 60, "end": 62}, {"text": "1-pyrazoline NN", "start": 80, "end": 95}]}}, "schema": []}
{"input": "Alternatively, when TMS diazomethane is used as the dipole, the resulting 2-pyrazoline obtained after desilylation may be reduced with NaCNBH3 to provide the trans azakainate analog exclusively.", "output": {"entities": {"chemical": [{"text": "TMS diazomethane", "start": 20, "end": 36}, {"text": "2-pyrazoline", "start": 74, "end": 86}, {"text": "NaCNBH3", "start": 135, "end": 142}, {"text": "trans azakainate", "start": 158, "end": 174}]}}, "schema": []}
{"input": "The synthesis of an unsubstituted isokainoid via Michael addition is also described.", "output": {"entities": {"chemical": [{"text": "isokainoid", "start": 34, "end": 44}]}}, "schema": []}
{"input": "Glutamate receptor binding assays revealed that the azakaniod has a moderate affinity for unspecified glutamate receptors.", "output": {"entities": {"chemical": [{"text": "Glutamate", "start": 0, "end": 9}, {"text": "azakaniod", "start": 52, "end": 61}, {"text": "glutamate", "start": 102, "end": 111}]}}, "schema": []}
{"input": "Membrane depolarization of Aplysia neurons upon application of the azakainoid demonstrates that it is an ionotropic glutamate receptor agonist.", "output": {"entities": {"chemical": [{"text": "azakainoid", "start": 67, "end": 77}, {"text": "glutamate", "start": 116, "end": 125}]}}, "schema": []}
{"input": "Demonstration of a sucrose-derived contrast agent for magnetic resonance imaging of the GI tract.", "output": {"entities": {"chemical": [{"text": "sucrose", "start": 19, "end": 26}]}}, "schema": []}
{"input": "A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd-DOTA complex were attached via copper (I)-catalyzed azide-alkyne cycloaddition.", "output": {"entities": {"chemical": [{"text": "alkyne", "start": 34, "end": 40}, {"text": "sucrose", "start": 69, "end": 76}, {"text": "azide", "start": 95, "end": 100}, {"text": "Gd-DOTA", "start": 112, "end": 119}, {"text": "copper (I)", "start": 146, "end": 156}, {"text": "azide-alkyne", "start": 167, "end": 179}]}}, "schema": []}
{"input": "The resulting contrast agent (CA) was administered by gavage to C3H mice.", "output": {"entities": {}}, "schema": []}
{"input": "Passage of the CA through the gastrointestinal (GI) tract was followed by T1-weighted magnetic resonance imaging (MRI) over a period of 47h, by which time the CA had exited the GI tract.", "output": {"entities": {}}, "schema": []}
{"input": "No evidence for leakage of the CA from the GI tract was observed.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxic and Anti-Inflammatory Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi.", "output": {"entities": {"chemical": [{"text": "Eunicellin", "start": 32, "end": 42}, {"text": "Diterpenoids", "start": 49, "end": 61}]}}, "schema": []}
{"input": "Five new eunicellin-based diterpenoids, krempfielins E-I (1-5) and seven known compounds (6-12) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi.", "output": {"entities": {"chemical": [{"text": "eunicellin", "start": 9, "end": 19}, {"text": "diterpenoids", "start": 26, "end": 38}, {"text": "krempfielins E-I", "start": 40, "end": 56}]}}, "schema": []}
{"input": "The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolites 5, 6, 10 and 12 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, compounds 6 and 10 could potently inhibit the accumulation of the pro-inflammatory iNOS protein, and 6 and 12 could significantly reduce the expression of COX-2 protein in LPS-stimulated RAW264. 7 macrophage cells.", "output": {"entities": {}}, "schema": []}
{"input": "New Azalomycin F Analogs from Mangrove Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "Azalomycin F", "start": 4, "end": 16}]}}, "schema": []}
{"input": "211726 with Activity against Microbes and Cancer Cells.", "output": {"entities": {}}, "schema": []}
{"input": "Seven new azalomycin F analogs (1-7) were isolated from the broth of mangrove Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "azalomycin F", "start": 10, "end": 22}]}}, "schema": []}
{"input": "211726, and respectively identified as 25-malonyl demalonylazalomycin F5a monoester (1), 23-valine demalonylazalomycin F5a ester (2), 23-(6-methyl) heptanoic acid demalonylazalomycins F3a ester (3), F4a ester (4) and F5a ester (5), 23-(9-methyl) decanoic acid demalonylazalomycin F4a ester (6) and 23-(10-methyl) undecanoic acid demalony lazalomycin F4a ester (7).", "output": {"entities": {"chemical": [{"text": "25-malonyl demalonylazalomycin F5a monoester", "start": 39, "end": 83}, {"text": "23-valine demalonylazalomycin F5a ester", "start": 89, "end": 128}, {"text": "23-(6-methyl) heptanoic acid demalonylazalomycins F3a ester", "start": 134, "end": 193}, {"text": "F4a ester", "start": 199, "end": 208}, {"text": "F5a ester", "start": 217, "end": 226}, {"text": "23-(9-methyl) decanoic acid demalonylazalomycin F4a ester", "start": 232, "end": 289}, {"text": "23-(10-methyl) undecanoic acid demalony lazalomycin F4a ester", "start": 298, "end": 359}]}}, "schema": []}
{"input": "Their structures were established by their spectroscopic data and by comparing with those of azalomycins F3a, F4a and F5a.", "output": {"entities": {"chemical": [{"text": "azalomycins F3a, F4a and F5a", "start": 93, "end": 121}]}}, "schema": []}
{"input": "Biological assays exhibited that 1-7 showed broad-spectrum antimicrobial and anti HCT-116 activities.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative annotation of functional regions in the human genome using epigenomic data.", "output": {"entities": {}}, "schema": []}
{"input": "Epigenetic regulation is dynamic and cell-type dependent.", "output": {"entities": {}}, "schema": []}
{"input": "The recently available epigenomic data in multiple cell types provide an unprecedented opportunity for a comparative study of epigenetic landscape.", "output": {"entities": {}}, "schema": []}
{"input": "We developed a machine-learning method called ChroModule to annotate the epigenetic states in eight ENCyclopedia Of DNA Elements cell types.", "output": {"entities": {}}, "schema": []}
{"input": "The trained model successfully captured the characteristic histone-modification patterns associated with regulatory elements, such as promoters and enhancers, and showed superior performance on identifying enhancers compared with the state-of-art methods.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, given the fixed number of epigenetic states in the model, ChroModule allows straightforward illustration of epigenetic variability in multiple cell types.", "output": {"entities": {}}, "schema": []}
{"input": "Using this feature, we found that invariable and variable epigenetic states across cell types correspond to housekeeping functions and stimulus response, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Especially, we observed that enhancers, but not the other regulatory elements, dictate cell specificity, as similar cell types share common enhancers, and cell-type-specific enhancers are often bound by transcription factors playing critical roles in that cell type.", "output": {"entities": {}}, "schema": []}
{"input": "More interestingly, we found some genomic regions are dormant in cell type but primed to become active in other cell types.", "output": {"entities": {}}, "schema": []}
{"input": "These observations highlight the usefulness of ChroModule in comparative analysis and interpretation of multiple epigenomes.", "output": {"entities": {}}, "schema": []}
{"input": "Sorafenib Hepatobiliary Disposition: Mechanisms of Hepatic Uptake and Disposition of Generated Metabolites.", "output": {"entities": {"chemical": [{"text": "Sorafenib", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Sorafenib is an orally active tyrosine kinase inhibitor used in the treatment of renal and hepatocellular carcinoma.", "output": {"entities": {"chemical": [{"text": "Sorafenib", "start": 0, "end": 9}, {"text": "tyrosine", "start": 30, "end": 38}]}}, "schema": []}
{"input": "This study was designed to establish whether transport proteins are involved in the hepatic uptake of sorafenib, and to determine the extent of biliary excretion of sorafenib/metabolites in human hepatocytes.", "output": {"entities": {"chemical": [{"text": "sorafenib", "start": 102, "end": 111}, {"text": "sorafenib", "start": 165, "end": 174}]}}, "schema": []}
{"input": "Initial uptake was assessed in freshly isolated, suspended human hepatocytes in the presence of inhibitors and modulators.", "output": {"entities": {}}, "schema": []}
{"input": "[(14) C] Sorafenib (1 mu M) uptake at 4 degrees C was ~ 61-63% of the uptake at 37 degrees C, suggesting a high degree of passive diffusion.", "output": {"entities": {"chemical": [{"text": "[(14) C] Sorafenib", "start": 0, "end": 18}]}}, "schema": []}
{"input": "Hepatocyte uptake of [(14) C] sorafenib was not Na (+)-dependent or influenced by the organic anion transporter 2 (OAT2) inhibitor ketoprofen.", "output": {"entities": {"chemical": [{"text": "[(14) C] sorafenib", "start": 21, "end": 39}, {"text": "Na (+)", "start": 48, "end": 54}, {"text": "ketoprofen", "start": 131, "end": 141}]}}, "schema": []}
{"input": "However, initial [(14) C] sorafenib hepatocyte uptake was reduced by 46 and 30% compared to control values in the presence of the organic anion transporting polypeptide (OATP) inhibitor rifamycin SV, and the organic cation transporter (OCT) inhibitor decynium 22, respectively.", "output": {"entities": {"chemical": [{"text": "[(14) C] sorafenib", "start": 17, "end": 35}, {"text": "rifamycin SV", "start": 186, "end": 198}, {"text": "decynium 22", "start": 251, "end": 262}]}}, "schema": []}
{"input": "[(14) C] Sorafenib (0. 5 to 5 mu M) uptake was significantly higher in hOCT1-transfected CHO cells compared to mock cells, and inhibited by the general OCT inhibitor, MPP (+).", "output": {"entities": {"chemical": [{"text": "[(14) C] Sorafenib", "start": 0, "end": 18}, {"text": "MPP (+)", "start": 167, "end": 174}]}}, "schema": []}
{"input": "OCT1-mediated uptake was saturable with a Km of 3. 80 +/- 2. 53 mu M and Vmax of 116 +/- 42 pmol/mg/min.", "output": {"entities": {}}, "schema": []}
{"input": "The biliary excretion index (BEI) and in vitro biliary clearance (Clbiliary) of sorafenib (1 mu M) in sandwich-cultured human hepatocytes were low (~ 11% and 11 ml/min/kg, respectively).", "output": {"entities": {"chemical": [{"text": "sorafenib", "start": 80, "end": 89}]}}, "schema": []}
{"input": "Results suggest that sorafenib uptake in human hepatocytes occurs via passive diffusion, and by OCT1 and a rifamycin-sensitive transporter.", "output": {"entities": {"chemical": [{"text": "sorafenib", "start": 21, "end": 30}, {"text": "rifamycin", "start": 107, "end": 116}]}}, "schema": []}
{"input": "Sorafenib undergoes modest biliary excretion, predominantly as glucuronide conjugate (s).", "output": {"entities": {"chemical": [{"text": "Sorafenib", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Enhanced photovoltaic performance of a dye-sensitized solar cell using graphene-TiO2 photoanode prepared by a novel in situ simultaneous reduction-hydrolysis technique.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 71, "end": 79}, {"text": "TiO2", "start": 80, "end": 84}]}}, "schema": []}
{"input": "Enhanced photovoltaic performance of a DSSC using graphene-TiO2 photoelectrodes prepared by our recent in situ simultaneous reduction-hydrolysis technique (Adv. Funct. Mater., 2012, DOI: 10. 1002/adfm. 201202349, in press) was achieved.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 50, "end": 58}, {"text": "TiO2", "start": 59, "end": 63}]}}, "schema": []}
{"input": "The DSSCs based on the G-TiO2 nanocomposites improved their overall energy conversion efficiency to 7. 1%.", "output": {"entities": {"chemical": [{"text": "G-TiO2", "start": 23, "end": 29}]}}, "schema": []}
{"input": "The results prove that the promoting effect of graphene is strongly dependent on its content; namely, the efficiency of DSSCs increases and then decreases with increasing graphene content in TiO2-graphene composites.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 47, "end": 55}, {"text": "graphene", "start": 171, "end": 179}, {"text": "TiO2", "start": 191, "end": 195}, {"text": "graphene", "start": 196, "end": 204}]}}, "schema": []}
{"input": "Excessive graphene in the nanocomposite leads to a decrease of the light harvest of dye molecules and thus a negative effect on the power conversion efficiency of DSSCs.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 10, "end": 18}]}}, "schema": []}
{"input": "Effects of treatment with a carbon monoxide-releasing molecule and a heme oxygenase 1 inducer in the antinociceptive effects of morphine in different models of acute and chronic pain in mice.", "output": {"entities": {"chemical": [{"text": "carbon monoxide", "start": 28, "end": 43}, {"text": "morphine", "start": 128, "end": 136}]}}, "schema": []}
{"input": "RATIONALE: Treatment with a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium (II) dimer, CORM-2) or a classical heme oxygenase 1 inducer (cobalt protoporphyrin IX, CoPP) has potent anti-inflammatory effects, but the role played by these treatments in the antinociceptive effects of morphine during acute and chronic pain was not evaluated.", "output": {"entities": {"chemical": [{"text": "carbon monoxide", "start": 28, "end": 43}, {"text": "tricarbonyldichlororuthenium (II)", "start": 64, "end": 97}, {"text": "CORM-2", "start": 105, "end": 111}, {"text": "cobalt protoporphyrin IX", "start": 154, "end": 178}, {"text": "CoPP", "start": 180, "end": 184}, {"text": "morphine", "start": 298, "end": 306}]}}, "schema": []}
{"input": "OBJECTIVES: In wild type (WT), neuronal (NOS1-KO), or inducible (NOS2-KO) nitric oxide synthases knockout mice, we evaluated the effects of CORM-2 and CoPP treatments in the antinociceptive actions of morphine and their interaction with nitric oxide during acute, visceral, and chronic inflammatory or neuropathic pain.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 74, "end": 86}, {"text": "CORM-2", "start": 140, "end": 146}, {"text": "CoPP", "start": 151, "end": 155}, {"text": "morphine", "start": 201, "end": 209}, {"text": "nitric oxide", "start": 237, "end": 249}]}}, "schema": []}
{"input": "METHODS: Acute and visceral pain was assessed through formalin and acid acetic writhing tests.", "output": {"entities": {"chemical": [{"text": "formalin", "start": 54, "end": 62}, {"text": "acid acetic", "start": 67, "end": 78}]}}, "schema": []}
{"input": "Chronic inflammatory pain induced by the intra-articular administration of complete Freund' s adjuvant and neuropathic pain by partial ligation of sciatic nerve were evaluated by measuring allodynia and hyperalgesia using the von Frey filaments, plantar, or cold plate tests.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: While nitric oxide, synthetized by NOS1 and/or NOS2, increased the local antinociceptive effects of morphine during acute and chronic pain, it decreased the inhibitory effects of morphine after visceral pain.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 15, "end": 27}, {"text": "morphine", "start": 109, "end": 117}, {"text": "morphine", "start": 188, "end": 196}]}}, "schema": []}
{"input": "Moreover, while CORM-2 or CoPP treatments did not alter or reduced the antinociceptive effects of morphine during acute and visceral pain, both treatments improved the local antiallodynic and antihyperalgesic effects of morphine after chronic inflammatory or neuropathic pain in WT, but not in KO mice.", "output": {"entities": {"chemical": [{"text": "CORM-2", "start": 16, "end": 22}, {"text": "CoPP", "start": 26, "end": 30}, {"text": "morphine", "start": 98, "end": 106}, {"text": "morphine", "start": 220, "end": 228}]}}, "schema": []}
{"input": "CONCLUSIONS: CORM-2 and CoPP treatments improved the local antinociceptive effects of morphine during chronic inflammatory and neuropathic pain by interaction with nitric oxide synthetized by NOS1 and NOS2 isoforms.", "output": {"entities": {"chemical": [{"text": "CORM-2", "start": 13, "end": 19}, {"text": "CoPP", "start": 24, "end": 28}, {"text": "morphine", "start": 86, "end": 94}, {"text": "nitric oxide", "start": 164, "end": 176}]}}, "schema": []}
{"input": "Liquid-Crystalline Blue Phase Laser with Widely Tunable Wavelength.", "output": {"entities": {}}, "schema": []}
{"input": "A lasing peak shift of more than 100 nm is realized due to the large shift of a photonic bandgap of a liquid-crystalline blue phase.", "output": {"entities": {}}, "schema": []}
{"input": "Protein-protein nanoimprinting of silk fibroin films.", "output": {"entities": {}}, "schema": []}
{"input": "Protein-protein imprinting of silk fibroin is introduced as a rapid, high-throughput method for the fabrication of nanoscale structures in silk films, through the application of heat and pressure.", "output": {"entities": {}}, "schema": []}
{"input": "Imprinting on conformal surfaces is demonstrated with minor adjustments to the system, at resolutions comparable to other currently available nonplanar nanoimprint lithography techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Paclitaxel is an inhibitor and its boron dipyrromethene derivative is a fluorescent recognition agent for botulinum neurotoxin subtype a.", "output": {"entities": {"chemical": [{"text": "Paclitaxel", "start": 0, "end": 10}, {"text": "boron dipyrromethene", "start": 35, "end": 55}]}}, "schema": []}
{"input": "We have successfully identified one new inhibitor and one new fluorescent recognition agent for the botulinum neurotoxin subtype A (BoNT/A) using the virtual screening protocol \" protein scanning with virtual ligand screening \" (PSVLS).", "output": {"entities": {}}, "schema": []}
{"input": "Hit selection used an in-house developed holistic binding scoring method.", "output": {"entities": {}}, "schema": []}
{"input": "Selected hits were tested experimentally for inhibitory activity using fluorescence resonance energy transfer (FRET) assays against the light chain (catalytic domain) of BoNT/A.", "output": {"entities": {}}, "schema": []}
{"input": "Ligand binding was determined against the light and heavy chain BoNT/A complex through either radiolabeled ligand binding assays (nonfluorescent ligands) or fluorescence intensity assays (fluorescent ligands).", "output": {"entities": {}}, "schema": []}
{"input": "These experimental assays have confirmed one compound (paclitaxel) to inhibit BoNT/A' s proteolytic activity experimentally with an IC50 of 5. 2 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "A fluorescent derivative was also confirmed to bind to the toxin and therefore is a suitable candidate for the rational design of new detection agents and for the development of fluorescence-based multiprobe detection assays.", "output": {"entities": {}}, "schema": []}
{"input": "Embellicines A and B: Absolute Configuration and NF-kappa B Transcriptional Inhibitory Activity.", "output": {"entities": {"chemical": [{"text": "Embellicines A and B", "start": 0, "end": 20}]}}, "schema": []}
{"input": "Two new metabolites, embellicines A and B (1 and 2), were isolated from the EtOAc extract of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae).", "output": {"entities": {"chemical": [{"text": "embellicines A and B", "start": 21, "end": 41}, {"text": "EtOAc", "start": 76, "end": 81}]}}, "schema": []}
{"input": "The structures of these new compounds were determined on the basis of extensive one-and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The absolute configuration of embellicine A (1) was determined by TDDFT ECD calculations of solution conformers, whereas that of embellicine B (2) was deduced based on ROESY correlations and on biogenetic considerations in comparison to 1.", "output": {"entities": {"chemical": [{"text": "embellicine A", "start": 30, "end": 43}, {"text": "embellicine B", "start": 129, "end": 142}]}}, "schema": []}
{"input": "Both embellicines (1 and 2) are cytostatic, cytotoxic, and inhibit NF-kappa B transcriptional activity, indicating that inhibition of NF-kappa B may be a possible mechanism of action of these compounds.", "output": {"entities": {"chemical": [{"text": "embellicines", "start": 5, "end": 17}]}}, "schema": []}
{"input": "Embellicine B (2) was the most active compound encountered in this study and acts at nanomolar concentrations without affecting tumor microenvironment.", "output": {"entities": {"chemical": [{"text": "Embellicine B", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Tin-coated viral nanoforests as sodium-ion battery anodes.", "output": {"entities": {"chemical": [{"text": "Tin", "start": 0, "end": 3}, {"text": "sodium", "start": 32, "end": 38}]}}, "schema": []}
{"input": "Designed as a high-capacity alloy host for Na-ion chemistry, a forest of Sn nanorods with a unique core-shell structure was synthesized on viral scaffolds, which were genetically engineered to ensure a nearly vertical alignment upon self-assembly onto a metal substrate.", "output": {"entities": {"chemical": [{"text": "Na", "start": 43, "end": 45}, {"text": "Sn", "start": 73, "end": 75}]}}, "schema": []}
{"input": "The interdigital spaces thus formed between individual rods effectively accommodated the volume expansion and contraction of the alloy upon sodiation/desodiation, while additional carbon-coating engineered over these nanorods further suppressed Sn aggregation during extended electrochemical cycling.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 180, "end": 186}, {"text": "Sn", "start": 245, "end": 247}]}}, "schema": []}
{"input": "Due to the unique nanohierarchy of multiple functional layers, the resultant 3D nanoforest of C/Sn/Ni/TMV1cys, binder-free composite electrode already and evenly assembled on a stainless steel current collector, exhibited supreme capacity utilization and cycling stability toward Na-ion storage and release.", "output": {"entities": {"chemical": [{"text": "C", "start": 94, "end": 95}, {"text": "Sn", "start": 96, "end": 98}, {"text": "Ni", "start": 99, "end": 101}, {"text": "steel", "start": 187, "end": 192}, {"text": "Na", "start": 280, "end": 282}]}}, "schema": []}
{"input": "An initial capacity of 722 mA. h (g Sn) (-1) along with 405 mA. h (g Sn) (-1) retained after 150 deep cycles demonstrates the longest-cycling nano-Sn anode material for Na-ion batteries reported in the literature to date and marks a significant performance improvement for neat Sn material as alloy host for Na-ion chemistry.", "output": {"entities": {"chemical": [{"text": "Sn", "start": 36, "end": 38}, {"text": "Sn", "start": 69, "end": 71}, {"text": "Sn", "start": 147, "end": 149}, {"text": "Na", "start": 169, "end": 171}, {"text": "Sn", "start": 278, "end": 280}, {"text": "Na", "start": 308, "end": 310}]}}, "schema": []}
{"input": "Direct modulation of microtubule stability contributes to anthracene general anesthesia.", "output": {"entities": {"chemical": [{"text": "anthracene", "start": 58, "end": 68}]}}, "schema": []}
{"input": "Recently, we identified 1-aminoanthracene as a fluorescent general anesthetic.", "output": {"entities": {"chemical": [{"text": "1-aminoanthracene", "start": 24, "end": 41}]}}, "schema": []}
{"input": "To investigate the mechanism of action, a photoactive analogue, 1-azidoanthracene, was synthesized.", "output": {"entities": {"chemical": [{"text": "1-azidoanthracene", "start": 64, "end": 81}]}}, "schema": []}
{"input": "Administration of 1-azidoanthracene to albino stage 40-47 tadpoles was found to immobilize animals upon near-UV irradiation of the forebrain region.", "output": {"entities": {"chemical": [{"text": "1-azidoanthracene", "start": 18, "end": 35}]}}, "schema": []}
{"input": "The immobilization was often reversible, but it was characterized by a longer duration consistent with covalent attachment of the ligand to functionally important targets.", "output": {"entities": {}}, "schema": []}
{"input": "IEF/SDS-PAGE examination of irradiated tadpole brain homogenate revealed labeled protein, identified by mass spectrometry as beta-tubulin.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro assays with aminoanthracene-cross-linked tubulin indicated inhibition of microtubule polymerization, similar to colchicine.", "output": {"entities": {"chemical": [{"text": "aminoanthracene", "start": 21, "end": 36}, {"text": "colchicine", "start": 121, "end": 131}]}}, "schema": []}
{"input": "Tandem mass spectrometry confirmed anthracene binding near the colchicine site.", "output": {"entities": {"chemical": [{"text": "anthracene", "start": 35, "end": 45}, {"text": "colchicine", "start": 63, "end": 73}]}}, "schema": []}
{"input": "Stage 40-47 tadpoles were also incubated 1 h with microtubule stabilizing agents, epothilone D or discodermolide, followed by dosing with 1-aminoanthracene.", "output": {"entities": {"chemical": [{"text": "epothilone D", "start": 82, "end": 94}, {"text": "discodermolide", "start": 98, "end": 112}, {"text": "1-aminoanthracene", "start": 138, "end": 155}]}}, "schema": []}
{"input": "The effective concentration of 1-aminoanthracene required to immobilize the tadpoles was significantly increased in the presence of either microtubule stabilizing agent.", "output": {"entities": {"chemical": [{"text": "1-aminoanthracene", "start": 31, "end": 48}]}}, "schema": []}
{"input": "Epothilone D similarly mitigated the effects of a clinical neurosteroid general anesthetic, allopregnanolone, believed to occupy the colchicine site in tubulin.", "output": {"entities": {"chemical": [{"text": "Epothilone D", "start": 0, "end": 12}, {"text": "allopregnanolone", "start": 92, "end": 108}, {"text": "colchicine", "start": 133, "end": 143}]}}, "schema": []}
{"input": "We conclude that neuronal microtubules are \" on-pathway \" targets for anthracene general anesthetics and may also represent functional targets for some neurosteroid general anesthetics.", "output": {"entities": {"chemical": [{"text": "anthracene", "start": 70, "end": 80}]}}, "schema": []}
{"input": "Unraveling the Role of the Protein Environment for [FeFe]-Hydrogenase: A New Application of Coarse-Graining.", "output": {"entities": {"chemical": [{"text": "[FeFe]", "start": 51, "end": 57}]}}, "schema": []}
{"input": "Hydrogenase enzymes are natural biocatalysts that might be harnessed to reduce the cost of hydrogen gas production.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 91, "end": 99}]}}, "schema": []}
{"input": "[FeFe]-hydrogenases are the most effective of three such enzymes at catalyzing H (+) reduction.", "output": {"entities": {"chemical": [{"text": "[FeFe]", "start": 0, "end": 6}, {"text": "H (+)", "start": 79, "end": 84}]}}, "schema": []}
{"input": "In this study, we develop and apply a novel combination of all-atom molecular dynamics and coarse-grained (CG) analysis to characterize two important steps of the catalytic cycle of [FeFe]-hydrogenase.", "output": {"entities": {"chemical": [{"text": "[FeFe]", "start": 182, "end": 188}]}}, "schema": []}
{"input": "The first is the electron transport through FeS clusters to the active site.", "output": {"entities": {"chemical": [{"text": "FeS", "start": 44, "end": 47}]}}, "schema": []}
{"input": "We use a Marcus formulation to compute the free energy and the reorganization energy of three electron transport steps and decompose these values into contributions from the CG protein sites and the solvent.", "output": {"entities": {}}, "schema": []}
{"input": "The three-step transport process is found to be downhill with relative free energies of-11. 7 for the first step,-14. 8 for the second step, and-17. 1 kcal/mol for the third step.", "output": {"entities": {}}, "schema": []}
{"input": "The electron-transport process is also found to activate a water channel suggesting a coupled mechanism for proton and electron transport to the active site.", "output": {"entities": {}}, "schema": []}
{"input": "The channel opening is orchestrated by three CG sites located in the active-site domain of the protein with one of the sites also contributing a strong attractive electrostatic potential (ESP) to help shuttle protons to the active site.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, our CG analysis points to a concerted mechanism of electron and proton delivery to the active site in these proteins thus providing important insight for the development of biomimetic devices.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutic effectiveness of botulinum neurotoxin A: Potent blockade of autonomic transmission by targeted cleavage of only the pertinent SNAP-25.", "output": {"entities": {}}, "schema": []}
{"input": "In search of a basis for the impressive potency of an endoprotease that cleaves SNAP-25, botulinum neurotoxin type A (BoNT/A), in treating numerous diseases due to hyper-active autonomic nerves, truncation of its target and inhibition of neurotransmission were studied in rat sympathetic neurons.", "output": {"entities": {}}, "schema": []}
{"input": "Tetrodotoxin-sensitive spontaneous cholinergic neurotransmission was blocked > 80% by 1 pM BoNT/A despite cleaving < 20% of the SNAP-25.", "output": {"entities": {"chemical": [{"text": "Tetrodotoxin", "start": 0, "end": 12}]}}, "schema": []}
{"input": "A maximum cleavage of ~ 60% SNAP-25 could be achieved with > 1 nM BoNT/A, despite an absence of non-cleavable SNAP-25 in the detergent-solubilised neurons.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, BoNT/E (100 nM) truncated nearly all the SNAP-25 in the intact cells, but was unable to block neurotransmission at low concentrations like BoNT/A.", "output": {"entities": {}}, "schema": []}
{"input": "Chimeras created by inserting the acceptor-binding HC domain of BoNT/A into BoNT/E still cleaved all the SNAP-25, indicating ubiquitous expression of BoNT/A acceptors.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, SV2 and SNAP-25 were found to be co-expressed and broadly co-localised in neurons, but absent from non-neuronal cells.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, partial cleavage by the BoNT/A protease persisted upon replacing its HC with counterparts from BoNT/E or BoNT/B.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, limited cleavage of SNAP-25 was conferred onto the protease from BoNT/E when fused to the N-terminus of BoNT/A.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the BoNT/A protease is uniquely well-adapted for selectively inactivating the SNAP-25 directly involved in neurotransmission; this together with the toxin' s acceptor and its target being localised on the peri-somatic boutons likely contribute to its exceptional therapeutic utility in the clinic.", "output": {"entities": {}}, "schema": []}
{"input": "Structural modifications of polymethacrylates: Impact on thermal behavior and release characteristics of glassy solid solutions.", "output": {"entities": {"chemical": [{"text": "polymethacrylates", "start": 28, "end": 45}]}}, "schema": []}
{"input": "Polymethacrylates such as Eudragit (R) polymers are well established as drug delivery matrix.", "output": {"entities": {"chemical": [{"text": "Polymethacrylates", "start": 0, "end": 17}, {"text": "Eudragit", "start": 26, "end": 34}]}}, "schema": []}
{"input": "Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization.", "output": {"entities": {"chemical": [{"text": "Eudragit E PO", "start": 28, "end": 41}, {"text": "n-butyl", "start": 43, "end": 50}, {"text": "dimethylaminoethyl", "start": 53, "end": 71}, {"text": "methyl-methacrylate", "start": 74, "end": 93}, {"text": "terpolymer", "start": 94, "end": 104}]}}, "schema": []}
{"input": "These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets.", "output": {"entities": {}}, "schema": []}
{"input": "Three chemical modifications increased the glass transition temperature of the polymer: (a) substitution of n-butyl by t-butyl groups, (b) reduction of the dimethylaminoethyl methacrylate (DMAEMA) content, and (c) incorporation of a bulky isobornyl repeating unit.", "output": {"entities": {"chemical": [{"text": "n-butyl", "start": 108, "end": 115}, {"text": "t-butyl", "start": 119, "end": 126}, {"text": "dimethylaminoethyl methacrylate", "start": 156, "end": 187}, {"text": "DMAEMA", "start": 189, "end": 195}, {"text": "isobornyl", "start": 239, "end": 248}]}}, "schema": []}
{"input": "These structural modifications revealed the possibility to increase the mechanical stability of the tablets via altering the polymer Tg without influencing the drug release characteristics and glassy solid solution forming properties.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of DMAEMA units proved to be crucial with respect to API/polymer interaction (essential in creating glassy solid solutions) and drug release characteristics.", "output": {"entities": {"chemical": [{"text": "DMAEMA", "start": 16, "end": 22}]}}, "schema": []}
{"input": "Moreover, these chemical modifications accentuate the need for a more rational design of (methacrylate) polymer matrix excipients for drug formulation via hot melt extrusion and injection molding.", "output": {"entities": {"chemical": [{"text": "methacrylate", "start": 90, "end": 102}]}}, "schema": []}
{"input": "Mercury in fishes from Augusta Bay (southern Italy): Risk assessment and health implication.", "output": {"entities": {"chemical": [{"text": "Mercury", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Our study reports on the total mercury (HgT) concentrations measured in the muscles and livers of several benthic, demersal and pelagic fish species caught inside and outside of Augusta Bay (southern Italy), a semi-enclosed marine area, highly contaminated by the uncontrolled (since the 1950s to 1978s) discharge of the largest European petrochemical plant.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 31, "end": 38}]}}, "schema": []}
{"input": "Mercury levels in fish tissues are discussed with regard to specific habitat, size and/or age of the specimens and HgT distribution in the bottom sediments.", "output": {"entities": {"chemical": [{"text": "Mercury", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Results suggest a still active Hg release mechanism from the polluted sediments to the marine environment.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 31, "end": 33}]}}, "schema": []}
{"input": "Also, the high HgT concentrations measured in fishes caught in the external area of the bay imply a potential role of Augusta Bay as a pollutant source for the Mediterranean ecosystem.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, values of hazard target quotient (THQ) and estimated weekly intake (EWI) demonstrate that consumption of fishes caught inside the bay represents a serious risk for human health.", "output": {"entities": {}}, "schema": []}
{"input": "Also, data indicate that intake of fishes caught from the external area of the bay, especially for that concern demersal and benthic species, could be represent a significant component of risk for the local population.", "output": {"entities": {}}, "schema": []}
{"input": "1-Methylimidazolium hydrogen sulfate catalyzed convenient synthesis of 2, 5-dimethyl-N-substituted pyrroles under ultrasonic irradiation.", "output": {"entities": {"chemical": [{"text": "1-Methylimidazolium hydrogen sulfate", "start": 0, "end": 36}, {"text": "2, 5-dimethyl-N-substituted pyrroles", "start": 71, "end": 107}]}}, "schema": []}
{"input": "Ionic liquid [HMIM] HSO4 was found to be an efficient catalyst for the synthesis of N-substituted pyrroles through the reaction of 2, 5-hexanedione with amines under ultrasonic irradiation at room temperature.", "output": {"entities": {"chemical": [{"text": "[HMIM] HSO4", "start": 13, "end": 24}, {"text": "N-substituted pyrroles", "start": 84, "end": 106}, {"text": "2, 5-hexanedione", "start": 131, "end": 147}, {"text": "amines", "start": 153, "end": 159}]}}, "schema": []}
{"input": "These reactions proceed with good yields under short reaction time.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the green catalytic system can be recycled specific times with no decreases in yields and reaction rates.", "output": {"entities": {}}, "schema": []}
{"input": "Platycodi Radix attenuates dimethylnitrosamine-induced liver fibrosis in rats by inducing Nrf2-mediated antioxidant enzymes.", "output": {"entities": {"chemical": [{"text": "dimethylnitrosamine", "start": 27, "end": 46}]}}, "schema": []}
{"input": "The purpose of this study was to investigate the anti-fibrotic effects of the aqueous extract of the Platycodi Radix root (Changkil: CK) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats.", "output": {"entities": {"chemical": [{"text": "dimethylnitrosamine", "start": 140, "end": 159}, {"text": "DMN", "start": 161, "end": 164}]}}, "schema": []}
{"input": "DMN treatment for 4weeks led to marked liver fibrosis as assessed by serum biochemistry, histopathological examination, and hepatic lipid peroxidation and collagen content.", "output": {"entities": {"chemical": [{"text": "DMN", "start": 0, "end": 3}]}}, "schema": []}
{"input": "CK significantly inhibited DMN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content.", "output": {"entities": {"chemical": [{"text": "DMN", "start": 27, "end": 30}, {"text": "alanine", "start": 58, "end": 65}, {"text": "aspartate", "start": 93, "end": 102}, {"text": "malondialdehyde", "start": 166, "end": 181}]}}, "schema": []}
{"input": "CK also inhibited DMN-induced reductions in rat body and liver weights.", "output": {"entities": {"chemical": [{"text": "DMN", "start": 18, "end": 21}]}}, "schema": []}
{"input": "Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited DMN-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-alpha) mRNA, and collagen type I and alpha-smooth muscle actin protein.", "output": {"entities": {"chemical": [{"text": "DMN", "start": 110, "end": 113}]}}, "schema": []}
{"input": "DMN-induced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-kappa B) activation was reduced by CK treatment.", "output": {"entities": {"chemical": [{"text": "DMN", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Furthermore, CK induced activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant enzymes such as gamma-glutamylcysteine synthetase (gamma-GCS), heme oxygenase-1 (HO-1), NAD (P) H quinone oxidoreductase 1 (NQO1), and glutathione-S-transferase (GST) in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "gamma-glutamylcysteine", "start": 119, "end": 141}, {"text": "heme", "start": 166, "end": 170}, {"text": "NAD (P) H quinone", "start": 191, "end": 208}, {"text": "glutathione", "start": 238, "end": 249}, {"text": "S", "start": 250, "end": 251}]}}, "schema": []}
{"input": "These results demonstrated that CK attenuates DMN-induced liver fibrosis through the activation of Nrf2-mediated antioxidant enzymes.", "output": {"entities": {"chemical": [{"text": "DMN", "start": 46, "end": 49}]}}, "schema": []}
{"input": "Subchronic and reproductive toxicity of whole dried Hoodia parviflora aerial parts in the rat.", "output": {"entities": {}}, "schema": []}
{"input": "Hoodia parviflora is being developed commercially for use in weight loss food and dietary supplement products.", "output": {"entities": {}}, "schema": []}
{"input": "As part of the safety assessment process for H. parviflora, a freeze dried powder preparation was tested in a 90-day oral toxicity study with reproductive/recovery component in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Groups of 10 male and female Sprague-Dawley rats were administered H. parviflora dried powder at doses of 0, 100, 250, and 350mg/kg body weight/day by gavage for an 11-week pre-mating period and a 14-day co-habitation period, and for females, through lactation day 4.", "output": {"entities": {}}, "schema": []}
{"input": "An additional 5 rats/sex/group received 0 or 350mg/kg bw/day for 90days and were sacrificed 28days after cessation of treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Statistically significant, non-adverse reductions in body weight, body weight gain, food consumption and food efficiency were observed at 250 and 350mg/kg/day in females.", "output": {"entities": {}}, "schema": []}
{"input": "Food consumption was reduced in high-dose males.", "output": {"entities": {}}, "schema": []}
{"input": "There were no adverse effects on hematological, blood biochemical, coagulation or urinalysis parameters or on the results of the functional observational battery and histopathological examinations.", "output": {"entities": {}}, "schema": []}
{"input": "No evidence of any effect was noted on reproductive or developmental parameters.", "output": {"entities": {}}, "schema": []}
{"input": "The NOAEL for dried H. parviflora powder was 350mg/kg bw/day, the highest permissible dose tested, for both male and female rats.", "output": {"entities": {}}, "schema": []}
{"input": "Migrants determination and bioaccessibility study of ethyl lauroyl arginate (LAE) from a LAE based antimicrobial food packaging material.", "output": {"entities": {"chemical": [{"text": "ethyl lauroyl arginate", "start": 53, "end": 75}, {"text": "LAE", "start": 77, "end": 80}, {"text": "LAE", "start": 89, "end": 92}]}}, "schema": []}
{"input": "Ethyl lauroyl arginate (LAE, ethyl-N-dodecanoyl-L-arginate hydrochloride) is a strong antimicrobial agent that was included as an active compound in an antimicrobial food packaging material.", "output": {"entities": {"chemical": [{"text": "Ethyl lauroyl arginate", "start": 0, "end": 22}, {"text": "LAE", "start": 24, "end": 27}, {"text": "ethyl-N-dodecanoyl-L-arginate hydrochloride", "start": 29, "end": 72}]}}, "schema": []}
{"input": "The potential existence of non-intentionally added substances (NIASs) such as impurities must therefore be checked before launching any food contact material onto the market.", "output": {"entities": {}}, "schema": []}
{"input": "For this reason, an untargeted analysis of the migration was performed in both food simulants and fresh chicken breast fillets wrapped with the active material.", "output": {"entities": {}}, "schema": []}
{"input": "The analysis was performed by liquid chromatography coupled to mass spectrometry detection with a quadrupole-time-of-flight analyzer, LC-MS (QTOF), for the identification of nonvolatile substances.", "output": {"entities": {}}, "schema": []}
{"input": "The migration values found for LAE were 0. 94 +/- 0. 14 and 1. 62 +/- 0. 70 mu g/g in ethanol 10% v/v (simulant A) and in ethanol 95% v/v (simulant D), respectively, and 0. 93 +/- 0. 17 mu g/g in chicken.", "output": {"entities": {"chemical": [{"text": "LAE", "start": 31, "end": 34}, {"text": "ethanol", "start": 86, "end": 93}, {"text": "ethanol", "start": 122, "end": 129}]}}, "schema": []}
{"input": "Other migrants such as dipropylene glycol methyl ether or tributyl-o-acetylcitrate, both coming from the coating were also found, but none of them have potential adverse effects.", "output": {"entities": {"chemical": [{"text": "dipropylene glycol methyl ether", "start": 23, "end": 54}, {"text": "tributyl-o-acetylcitrate", "start": 58, "end": 82}]}}, "schema": []}
{"input": "Bioaccessibility studies showed that after a simulated gastrointestinal digestion, LAE was not available anymore for subsequent intestinal absorption and new toxic compounds were not formed.", "output": {"entities": {"chemical": [{"text": "LAE", "start": 83, "end": 86}]}}, "schema": []}
{"input": "Cadmium telluride quantum dots cause oxidative stress leading to extrinsic and intrinsic apoptosis in hepatocellular carcinoma HepG2 cells.", "output": {"entities": {"chemical": [{"text": "Cadmium telluride", "start": 0, "end": 17}]}}, "schema": []}
{"input": "The mechanisms of toxicity related to human hepatocellular carcinoma HepG2 cell exposures to cadmium telluride quantum dots (CdTe-QDs) were investigated.", "output": {"entities": {"chemical": [{"text": "cadmium telluride", "start": 93, "end": 110}, {"text": "CdTe", "start": 125, "end": 129}]}}, "schema": []}
{"input": "CdTe-QDs caused cytotoxicity in HepG2 cells in a dose-and time-dependent manner.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Treated cells showed an increase in reactive oxygen species (ROS).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 45, "end": 51}]}}, "schema": []}
{"input": "Altered antioxidant levels were demonstrated by depletion of reduced glutathione (GSH), a decreased ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and an increased NF-E2-related Factor 2 (Nrf2) activation.", "output": {"entities": {"chemical": [{"text": "reduced glutathione", "start": 61, "end": 80}, {"text": "GSH", "start": 82, "end": 85}, {"text": "glutathione", "start": 117, "end": 128}, {"text": "oxidized glutathione", "start": 132, "end": 152}, {"text": "GSH", "start": 154, "end": 157}, {"text": "GSSG", "start": 158, "end": 162}]}}, "schema": []}
{"input": "Enzyme assays showed that superoxide dismutase (SOD) activity was elevated whereas catalase (CAT) and glutathione-S-transferase (GST) activities were depressed.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 26, "end": 36}, {"text": "glutathione", "start": 102, "end": 113}, {"text": "S", "start": 114, "end": 115}]}}, "schema": []}
{"input": "Further analyses revealed that CdTe-QD exposure resulted in apoptosis, indicated by changes in levels of caspase-3 activity, poly ADP-ribose polymerase (PARP) cleavage and phosphatidylserine externalization.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 31, "end": 35}, {"text": "poly ADP-ribose", "start": 125, "end": 140}, {"text": "phosphatidylserine", "start": 172, "end": 190}]}}, "schema": []}
{"input": "Extrinsic apoptotic pathway markers such as Fas levels and caspase-8 activity increased as a result of CdTe-QD exposure.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 103, "end": 107}]}}, "schema": []}
{"input": "Involvement of the intrinsic/mitochondrial apoptotic pathway was indicated by decreased levels of B-cell lymphoma 2 (Bcl2) protein and mitochondrial cytochrome c, and by increased levels of mitochondrial Bcl-2-associated X protein (Bax) and cytosolic cytochrome c.", "output": {"entities": {}}, "schema": []}
{"input": "Further, mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (Erk1/2), and p38 were all activated.", "output": {"entities": {"chemical": [{"text": "N", "start": 65, "end": 66}]}}, "schema": []}
{"input": "Our findings reveal that CdTe-QDs cause oxidative stress, interfere with antioxidant defenses and activate protein kinases, leading to apoptosis via both extrinsic and intrinsic pathways.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 25, "end": 29}]}}, "schema": []}
{"input": "Since the effects of CdTe-QDs on selected biomarkers were similar or greater compared to those of CdCl2 at equivalent concentrations of cadmium, the study suggests that the toxicity of CdTe-QDs arises from a combination of the effects of cadmium and ROS generated from the NPs.", "output": {"entities": {"chemical": [{"text": "CdTe", "start": 21, "end": 25}, {"text": "CdCl2", "start": 98, "end": 103}, {"text": "cadmium", "start": 136, "end": 143}, {"text": "CdTe", "start": 185, "end": 189}]}}, "schema": []}
{"input": "Stimulation of rat liver branched-chain alpha-keto acid dehydrogenase activity by low doses of bezafibrate.", "output": {"entities": {"chemical": [{"text": "alpha-keto acid", "start": 40, "end": 55}, {"text": "bezafibrate", "start": 95, "end": 106}]}}, "schema": []}
{"input": "Multienzyme branched-chain alpha-ketoacid dehydrogenase complex (BCKDH) catalyzes the regulatory step of oxidative catabolism of indispensable branched-chain amino acids (BCAA).", "output": {"entities": {"chemical": [{"text": "alpha-ketoacid", "start": 27, "end": 41}, {"text": "amino acids", "start": 158, "end": 169}]}}, "schema": []}
{"input": "The activity of the BCKDH complex is regulated by a reversible phosphorylation, end-product inhibition and by changes in the gene expression of BCKDH component enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "It has been shown previously that a high dose of bezafibrate (an agent added to rat chow at final concentration of 0. 5%) changes mRNA levels of BCKDH-related enzymes and increases dephosphorylation of the complex leading to stimulation of liver BCKDH activity and the enhanced BCAA catabolism.", "output": {"entities": {"chemical": [{"text": "bezafibrate", "start": 49, "end": 60}]}}, "schema": []}
{"input": "The aim of the present study was to determine an in vivo effect of low, clinically relevant doses of bezafibrate on BCKDH activity in rat liver.", "output": {"entities": {"chemical": [{"text": "bezafibrate", "start": 101, "end": 112}]}}, "schema": []}
{"input": "Bezafibrate was administrated for 14 days by gastric gavage to Wistar male rats (fed low-protein chow; 8% protein) at one of the following daily doses of 5, 10 and 20mg/kgb. wt.", "output": {"entities": {"chemical": [{"text": "Bezafibrate", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The control group was given the vehicle (0. 3% methylcellulose) only.", "output": {"entities": {}}, "schema": []}
{"input": "The actual BCKDH and total BCKDH activities were assayed spectrophotometrically before and after incubation with a broad-specificity phosphatase, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The mRNA levels of the selected genes (BCKDH catalytic subunits and regulatory enzymes) were quantified by means of semi-quantitative RT-PCR.", "output": {"entities": {}}, "schema": []}
{"input": "Current catalytic activity of BCKDH (described as BCKDH activity state-the proportion of the BCKDH complex in its active dephosphorylated form) increased by 2. 1 +/- 0. 2, 2. 3 +/- 0. 2 and 2. 7 +/- 0. 2 fold (p < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "Changes in BCKDH activity did not correspond with changes in mRNA levels of the complex catalytic subunits.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, mRNA levels of regulatory enzymes remained unaltered.", "output": {"entities": {}}, "schema": []}
{"input": "Initially bezafibrate caused a transient insignificant reduction in body weight, but it had no effect on the final body weight.", "output": {"entities": {"chemical": [{"text": "bezafibrate", "start": 10, "end": 21}]}}, "schema": []}
{"input": "The highest dose of bezafibrate induced hepatomegaly.", "output": {"entities": {"chemical": [{"text": "bezafibrate", "start": 20, "end": 31}]}}, "schema": []}
{"input": "In conclusion, these data indicate that under conditions of dietary protein restriction low, clinically relevant doses of bezafibrate have a similar adverse effect on rat liver BCKDH activity and BCAA degradation rate as the high experimental dose.", "output": {"entities": {"chemical": [{"text": "bezafibrate", "start": 122, "end": 133}]}}, "schema": []}
{"input": "Up-regulation of liver BCKDH activity by low doses of bezafibrate appears to result mainly from changes in phosphorylation status of the complex (increased dephosphorylation) and is not associated with elevations in mRNA levels of BCKDH enzymatic components.", "output": {"entities": {"chemical": [{"text": "bezafibrate", "start": 54, "end": 65}]}}, "schema": []}
{"input": "Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants.", "output": {"entities": {}}, "schema": []}
{"input": "Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites.", "output": {"entities": {"chemical": [{"text": "Amitriptyline", "start": 0, "end": 13}, {"text": "clomipramine", "start": 15, "end": 27}, {"text": "doxepin", "start": 29, "end": 36}, {"text": "imipramine", "start": 38, "end": 48}, {"text": "trimipramine", "start": 54, "end": 66}]}}, "schema": []}
{"input": "These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites.", "output": {"entities": {"chemical": [{"text": "desipramine", "start": 46, "end": 57}, {"text": "nortriptyline", "start": 62, "end": 75}]}}, "schema": []}
{"input": "Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype-directed dosing of tricyclic antidepressants.", "output": {"entities": {}}, "schema": []}
{"input": "Structural Explanation for Allolactose (lac Operon Inducer) Synthesis by lacZ beta-Galactosidase and the Evolutionary Relationship between Allolactose Synthesis and the lac Repressor.", "output": {"entities": {"chemical": [{"text": "Allolactose", "start": 27, "end": 38}, {"text": "Allolactose", "start": 139, "end": 150}]}}, "schema": []}
{"input": "beta-Galactosidase (lacZ) has bifunctional activity.", "output": {"entities": {}}, "schema": []}
{"input": "It hydrolyzes lactose to galactose and glucose and catalyzes the intramolecular isomerization of lactose to allolactose, the lac operon inducer.", "output": {"entities": {"chemical": [{"text": "lactose", "start": 14, "end": 21}, {"text": "galactose", "start": 25, "end": 34}, {"text": "glucose", "start": 39, "end": 46}, {"text": "lactose", "start": 97, "end": 104}, {"text": "allolactose", "start": 108, "end": 119}]}}, "schema": []}
{"input": "beta-Galactosidase promotes the isomerization by means of an acceptor site that binds glucose after its cleavage from lactose and thus delays its exit from the site.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 86, "end": 93}, {"text": "lactose", "start": 118, "end": 125}]}}, "schema": []}
{"input": "However, because of its relatively low affinity for glucose, details of this site have remained elusive.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 52, "end": 59}]}}, "schema": []}
{"input": "We present structural data mapping the glucose site based on a substituted enzyme (G794A-beta-galactosidase) that traps allolactose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 39, "end": 46}, {"text": "allolactose", "start": 120, "end": 131}]}}, "schema": []}
{"input": "Various lines of evidence indicate that the glucose of the trapped allolactose is in the acceptor position.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 44, "end": 51}, {"text": "allolactose", "start": 67, "end": 78}]}}, "schema": []}
{"input": "The evidence includes structures with Bis-Tris (2, 2-bis (hydroxymethyl)-2, 2', 2''-nitrilotriethanol) and l-ribose in the site and kinetic binding studies with substituted beta-galactosidases.", "output": {"entities": {"chemical": [{"text": "Bis-Tris (2, 2-bis (hydroxymethyl)-2, 2', 2''-nitrilotriethanol)", "start": 38, "end": 102}, {"text": "l-ribose", "start": 107, "end": 115}]}}, "schema": []}
{"input": "The site is composed of Asn-102, His-418, Lys-517, Ser-796, Glu-797, and Trp-999.", "output": {"entities": {"chemical": [{"text": "Asn", "start": 24, "end": 27}, {"text": "His", "start": 33, "end": 36}, {"text": "Lys", "start": 42, "end": 45}, {"text": "Ser", "start": 51, "end": 54}, {"text": "Glu", "start": 60, "end": 63}, {"text": "Trp", "start": 73, "end": 76}]}}, "schema": []}
{"input": "Ser-796 and Glu-797 are part of a loop (residues 795-803) that closes over the active site.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 0, "end": 3}, {"text": "Glu", "start": 12, "end": 15}]}}, "schema": []}
{"input": "This loop appears essential for the bifunctional nature of the enzyme because it helps form the glucose binding site.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 96, "end": 103}]}}, "schema": []}
{"input": "In addition, because the loop is mobile, glucose binding is transient, allowing the release of some glucose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 41, "end": 48}, {"text": "glucose", "start": 100, "end": 107}]}}, "schema": []}
{"input": "Bioinformatics studies showed that the residues important for interacting with glucose are only conserved in a subset of related enzymes.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 79, "end": 86}]}}, "schema": []}
{"input": "Thus, intramolecular isomerization is not a universal feature of beta-galactosidases.", "output": {"entities": {}}, "schema": []}
{"input": "Genomic analyses indicated that lac repressors were co-selected only within the conserved subset.", "output": {"entities": {}}, "schema": []}
{"input": "This shows that the glucose binding site of beta-galactosidase played an important role in lac operon evolution.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 20, "end": 27}]}}, "schema": []}
{"input": "Intragenic deletions of the IGF1 receptor gene in five individuals with psychiatric phenotypes and developmental delay.", "output": {"entities": {}}, "schema": []}
{"input": "Haploinsufficiency of the gene encoding the insulin-like growth factor 1 receptor (IGF1R), either caused by telomeric 15q26 deletions, or by heterozygous point mutations in IGF1R, segregate with short stature and various other phenotypes, including microcephaly and dysmorphic facial features.", "output": {"entities": {}}, "schema": []}
{"input": "Psychomotor retardation and behavioral anomalies have been seen in some cases.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report small, intragenic deletions of IGF1R, identified by chromosome microarray analysis in two unrelated families affected primarily with neuropsychiatric phenotypes including developmental delay, intellectual disability and aggressive/autoaggressive behaviors.", "output": {"entities": {}}, "schema": []}
{"input": "The deletions are in frame, and both wild-type and mutant mRNAs are expressed as measured by quantitative real-time PCR.", "output": {"entities": {}}, "schema": []}
{"input": "While short stature is considered a phenotypic hallmark of IGF1R haploinsufficiency, the present report suggests that in frame exon deletions of IGF1R present predominantly with cognitive and neuropsychiatric phenotypes. European Journal of Human Genetics advance online publication, 13 March 2013; doi: 10. 1038/ejhg. 2013. 42.", "output": {"entities": {}}, "schema": []}
{"input": "A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "Angiotensin II type 1 receptor antagonists (ARBs) have become an important drug class in the treatment of hypertension and heart failure and the protection from diabetic nephropathy.", "output": {"entities": {}}, "schema": []}
{"input": "Eight ARBs are clinically available [azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan].", "output": {"entities": {"chemical": [{"text": "azilsartan", "start": 37, "end": 47}, {"text": "candesartan", "start": 49, "end": 60}, {"text": "eprosartan", "start": 62, "end": 72}, {"text": "irbesartan", "start": 74, "end": 84}, {"text": "losartan", "start": 86, "end": 94}, {"text": "olmesartan", "start": 96, "end": 106}, {"text": "telmisartan", "start": 108, "end": 119}, {"text": "valsartan", "start": 121, "end": 130}]}}, "schema": []}
{"input": "Azilsartan (in some countries), candesartan, and olmesartan are orally administered as prodrugs, whereas the blocking action of some is mediated through active metabolites.", "output": {"entities": {"chemical": [{"text": "Azilsartan", "start": 0, "end": 10}, {"text": "candesartan", "start": 32, "end": 43}, {"text": "olmesartan", "start": 49, "end": 59}]}}, "schema": []}
{"input": "On the basis of their chemical structures, ARBs use different binding pockets in the receptor, which are associated with differences in dissociation times and, in most cases, apparently insurmountable antagonism.", "output": {"entities": {}}, "schema": []}
{"input": "The physicochemical differences between ARBs also manifest in different tissue penetration, including passage through the blood-brain barrier.", "output": {"entities": {}}, "schema": []}
{"input": "Differences in binding mode and tissue penetration are also associated with differences in pharmacokinetic profile, particularly duration of action.", "output": {"entities": {}}, "schema": []}
{"input": "Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly telmisartan, are partial agonists at peroxisome proliferator-activated receptor-gamma.", "output": {"entities": {"chemical": [{"text": "telmisartan", "start": 96, "end": 107}]}}, "schema": []}
{"input": "All of these properties are comprehensively reviewed in this article.", "output": {"entities": {}}, "schema": []}
{"input": "Although there is general consensus that a continuous receptor blockade over a 24-hour period is desirable, the clinical relevance of other pharmacological differences between individual ARBs remains to be assessed.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding multi-quantum NMR through secular approximation.", "output": {"entities": {}}, "schema": []}
{"input": "With the development of technology and improved understanding of nuclear spin-spin interactions and their behavior in static/oscillating magnetic fields, NMR spectroscopy has emerged as a powerful tool for characterizing molecular structure in a wide range of systems of chemical, physical and biological relevance.", "output": {"entities": {}}, "schema": []}
{"input": "Here in this article, we revisit the important connection between \" Secular-Approximation \" (a well-known fundamental concept) and NMR spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Employing recent experimental results as the background, an alternate interpretation of the secular approximation is presented for describing and understanding the nuances of Multi-Quantum (MQ) NMR spectroscopy of quadrupolar nuclei.", "output": {"entities": {}}, "schema": []}
{"input": "Since MQ NMR spectroscopy of quadrupolar nuclei forms the basis of the structural characterization of inorganic solids and clusters, we believe that the analytic theory presented herein would be beneficial both in the understanding and design of MQ NMR experiments.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, the analytic results are corroborated with rigorous numerical simulations and could be employed in the quantitative interpretation of experimental results.", "output": {"entities": {}}, "schema": []}
{"input": "Heterogeneous OH oxidation of biomass burning organic aerosol surrogate compounds: assessment of volatilisation products and the role of OH concentration on the reactive uptake kinetics.", "output": {"entities": {"chemical": [{"text": "OH", "start": 14, "end": 16}, {"text": "OH", "start": 137, "end": 139}]}}, "schema": []}
{"input": "The reactive uptake coefficients (gamma) of OH by levoglucosan, abietic acid, and nitroguaiacol serving as surrogate compounds for biomass burning aerosol have been determined employing a chemical ionisation mass spectrometer coupled to a rotating-wall flow-tube reactor over a wide range of [OH] ~ 10 (7)-10 (11) molecule cm (-3).", "output": {"entities": {"chemical": [{"text": "OH", "start": 44, "end": 46}, {"text": "levoglucosan", "start": 50, "end": 62}, {"text": "abietic acid", "start": 64, "end": 76}, {"text": "nitroguaiacol", "start": 82, "end": 95}, {"text": "OH", "start": 293, "end": 295}]}}, "schema": []}
{"input": "Volatilisation products of these organic substrates due to heterogeneous oxidation by OH have been determined at 1 atm using a high resolution proton transfer reaction time-of-flight mass spectrometer (HR-PTR-ToF-MS).", "output": {"entities": {"chemical": [{"text": "OH", "start": 86, "end": 88}]}}, "schema": []}
{"input": "gamma range within 0. 05-1 for [OH] = 2. 6 x 10 (7)-3 x 10 (9) molecule cm (-3) for all investigated organic compounds, but decrease to 0. 008-0. 034 for [OH] = 4. 1 x 10 (10)-6. 7 x 10 (10) molecule cm (-3).", "output": {"entities": {"chemical": [{"text": "OH", "start": 32, "end": 34}, {"text": "OH", "start": 155, "end": 157}]}}, "schema": []}
{"input": "gamma as a function of [OH] can be described by a Langmuir-Hinshelwood model, neglecting bulk processes, suggesting that despite its strong reactivity, OH is mobile on surfaces prior to reaction.", "output": {"entities": {"chemical": [{"text": "OH", "start": 24, "end": 26}, {"text": "OH", "start": 152, "end": 154}]}}, "schema": []}
{"input": "The best fit Langmuir-Hinshelwood parameters on average are K (OH) = 3. 81 x 10 (-10) cm (3) molecule (-1) and k (s) = 9. 71 x 10 (-17) cm (2) molecule (-1) s (-1) for all of the investigated organic compounds.", "output": {"entities": {"chemical": [{"text": "OH", "start": 63, "end": 65}]}}, "schema": []}
{"input": "Volatilised products have been identified indicating enhancements over background of 50% up to a factor of 15.", "output": {"entities": {}}, "schema": []}
{"input": "Amongst the common volatile organic compounds (VOCs) identified between levoglucosan, abietic acid, and nitroguaiacol were methanol, acetaldehyde, formic acid, and acetic acid.", "output": {"entities": {"chemical": [{"text": "levoglucosan", "start": 72, "end": 84}, {"text": "abietic acid", "start": 86, "end": 98}, {"text": "nitroguaiacol", "start": 104, "end": 117}, {"text": "methanol", "start": 123, "end": 131}, {"text": "acetaldehyde", "start": 133, "end": 145}, {"text": "formic acid", "start": 147, "end": 158}, {"text": "acetic acid", "start": 164, "end": 175}]}}, "schema": []}
{"input": "VOCs having the greatest enhancement over background were glucic acid from levoglucosan, glycolic acid from abietic acid, and methanol and nitric acid from nitroguaiacol.", "output": {"entities": {"chemical": [{"text": "glucic acid", "start": 58, "end": 69}, {"text": "levoglucosan", "start": 75, "end": 87}, {"text": "glycolic acid", "start": 89, "end": 102}, {"text": "abietic acid", "start": 108, "end": 120}, {"text": "methanol", "start": 126, "end": 134}, {"text": "nitric acid", "start": 139, "end": 150}, {"text": "nitroguaiacol", "start": 156, "end": 169}]}}, "schema": []}
{"input": "Reaction mechanisms leading to the formation of glucic acid, glycolic acid, methanol, and nitric acid are proposed.", "output": {"entities": {"chemical": [{"text": "glucic acid", "start": 48, "end": 59}, {"text": "glycolic acid", "start": 61, "end": 74}, {"text": "methanol", "start": 76, "end": 84}, {"text": "nitric acid", "start": 90, "end": 101}]}}, "schema": []}
{"input": "Estimated lower limits of atmospheric lifetimes of biomass burning aerosol particles, 200 nm in diameter, by heterogeneous OH oxidation under fresh biomass burning plume conditions are ~ 2 days and up to ~ 2 weeks for atmospheric background conditions.", "output": {"entities": {"chemical": [{"text": "OH", "start": 123, "end": 125}]}}, "schema": []}
{"input": "However, estimated lifetimes depend crucially on [OH] and corresponding gamma, emphasising the need to determine gamma under relevant conditions.", "output": {"entities": {"chemical": [{"text": "OH", "start": 50, "end": 52}]}}, "schema": []}
{"input": "Baseline HbA1c predicts attainment of 7. 0% HbA1c target with structured titration of insulin glargine in type 2 diabetes: a patient-level analysis of 12 studies.", "output": {"entities": {}}, "schema": []}
{"input": "AIMS: To determine whether baseline characteristics, especially haemoglobin A1c (HbA1c), predict the likelihood of reaching HbA1c <= 7. 0% or the risk of experiencing hypoglycaemia after the addition of insulin glargine to oral therapy in type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Pooled patient-level data from 12 prospective, randomized, controlled studies that used insulin glargine in a treat-to-target titration regimen seeking fasting glucose levels <= 5. 5 mmol/l (100 mg/dl) were analysed.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 169, "end": 176}]}}, "schema": []}
{"input": "Baseline characteristics were evaluated by logistic regression models as predictors of reaching a target HbA1c <= 7. 0% or experiencing confirmed hypoglycaemia.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of prior glycaemic control was further explored by analysis of categorical ranges of baseline HbA1c.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Of 2312 participants, 95% completed 24 weeks of treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Lower HbA1c at baseline was independently associated with reaching HbA1c target [adjusted odds ratio (OR) for 1% difference: 0. 538, p < 0. 0001] and also with likelihood of experiencing confirmed hypoglycaemic events (adjusted OR: 0. 835, p < 0. 0001) at week 24.", "output": {"entities": {}}, "schema": []}
{"input": "In an unadjusted analysis by baseline HbA1c range, the strong association between baseline control and attaining target HbA1c was confirmed (75% with baseline HbA1c < 8. 0%, 60% with baseline HbA1c >= 8. 0 and < 9. 0% and 38% with baseline HbA1c >= 9. 0% attained HbA1c <= 7. 0%).", "output": {"entities": {}}, "schema": []}
{"input": "The incidence of hypoglycaemia confirmed < 3. 9 mmol/l (70 mg/dl) was higher in the lower baseline HbA1c ranges but severe hypoglycaemia was infrequent at all baseline HbA1c levels.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: Systematically titrated insulin glargine, added to oral agents, was effective over a wide range of baseline HbA1c.", "output": {"entities": {}}, "schema": []}
{"input": "Lower baseline HbA1c was the best clinical predictor of achieving HbA1c <= 7. 0% and also associated with higher risk of glucose-confirmed hypoglycaemia.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 121, "end": 128}]}}, "schema": []}
{"input": "Severe hypoglycaemia was infrequent using this treatment approach.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, crystal structure and biological evaluation of a main group seven-coordinated bismuth (III) complex with 2-acetylpyridine N4-phenylthiosemicarbazone.", "output": {"entities": {"chemical": [{"text": "bismuth (III)", "start": 89, "end": 102}, {"text": "2-acetylpyridine N4-phenylthiosemicarbazone", "start": 116, "end": 159}]}}, "schema": []}
{"input": "Up to now, bismuth (III) complexes with thiosemicarbazones have been comparatively rare.", "output": {"entities": {"chemical": [{"text": "bismuth (III)", "start": 11, "end": 24}, {"text": "thiosemicarbazones", "start": 40, "end": 58}]}}, "schema": []}
{"input": "Here, a main group seven-coordinated bismuth (III) complex [Bi (L) (NO3) 2 (CH3CH2OH)] (1) (HL = 2-acetylpyridine N (4)-phenylthiosemicarbazone) has been synthesized and characterized by elemental analysis, IR, (1) H NMR and single-crystal X-ray diffraction studies.", "output": {"entities": {"chemical": [{"text": "bismuth (III)", "start": 37, "end": 50}, {"text": "Bi (L) (NO3) 2 (CH3CH2OH)", "start": 60, "end": 85}, {"text": "2-acetylpyridine N (4)-phenylthiosemicarbazone", "start": 97, "end": 143}, {"text": "(1) H", "start": 211, "end": 216}]}}, "schema": []}
{"input": "The cytotoxicity data suggest that 1 exhibits higher in vitro antiproliferative activity in four human cancer cells tested.", "output": {"entities": {}}, "schema": []}
{"input": "Its possible apoptotic mechanism has been evaluated in HepG2 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 1 promotes a dose-dependent apoptosis in HepG2 cells and the apoptosis is associated with an increase in intracellular reactive oxygen species (ROS) production and reduction of mitochondrial membrane potential (MMP).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 137, "end": 143}]}}, "schema": []}
{"input": "Identification and synthesis of N-(thiophen-2-yl) benzamide derivatives as BRAF (V600E) inhibitors.", "output": {"entities": {"chemical": [{"text": "N-(thiophen-2-yl) benzamide", "start": 32, "end": 59}]}}, "schema": []}
{"input": "The V600E BRAF kinase mutation, which activates the downstream MAPK signaling pathway, commonly occurs in about 8% of all human malignancies and about 50% of all melanomas.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we employed virtual screening and chemical synthesis to identify a series of N-(thiophen-2-yl) benzamide derivatives as potent BRAF (V600E) inhibitors.", "output": {"entities": {"chemical": [{"text": "N-(thiophen-2-yl) benzamide", "start": 92, "end": 119}]}}, "schema": []}
{"input": "Structure-activity relationship studies of these derivatives revealed that compounds b40 and b47 are the two most potent BRAF (V600E) inhibitors in this series.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetes and Cardiovascular Disease Outcomes in the Metabolically Healthy Obese Phenotype: A cohort study.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVESTo determine the correlates of the \" metabolically healthy obese \" (MHO) phenotype and the longitudinal risks of diabetes and cardiovascular disease (CVD)/stroke associated with this phenotype. RESEARCH DESIGN AND METHODSThe North West Adelaide Health Study is a prospective cohort study of 4, 056 randomly selected adults aged >= 18 years.", "output": {"entities": {}}, "schema": []}
{"input": "Participants free of CVD/stroke and not underweight (n = 3, 743) were stratified by BMI categories and metabolic risk, defined as having two or more International Diabetes Federation metabolic syndrome criteria, excluding waist circumference. RESULTSCorrelates of the MHO (n = 454 [12. 1%]) included smoking, socioeconomic disadvantage, and physical inactivity.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with metabolically healthy normal-weight subjects (n = 1, 172 [31. 3%]), the MHO were more likely to develop metabolic risk (15. 5 vs. 33. 1%, P < 0. 001) and incident diabetes (odds ratio 2. 09 [95% CI 0. 87-5. 03]) but not CVD/stroke (1. 16 [0. 58-2. 29]) during 5. 5-10. 3 years of follow-up.", "output": {"entities": {}}, "schema": []}
{"input": "These risks were not seen in MHO subjects maintaining metabolic health (n = 188 [67%]).", "output": {"entities": {}}, "schema": []}
{"input": "Sustained metabolic health in obese participants was associated with age <= 40 years and lower waist circumference.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with the metabolically at-risk obese, MHO women demonstrated a significantly higher (mean [SE]) percentage of leg fat (49. 9 [0. 5] vs. 53. 2 [0. 7]) and lower waist circumference (104 [0. 6] vs. 101 cm [0. 8]), despite no significant differences in overall adiposity. CONCLUSIONS \" Healthy \" obesity was a transient state for one-third of subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Persistence of a MHO phenotype, which was associated with favorable outcomes, was related to younger age and a more peripheral fat distribution.", "output": {"entities": {}}, "schema": []}
{"input": "The MHO phenotype may be sustained by promoting lower waist circumferences.", "output": {"entities": {}}, "schema": []}
{"input": "Blocking IL-1 beta Induces a Healing-associated Wound Macrophage Phenotype and Improves Healing in Type-2 Diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetes is associated with persistent inflammation and defective tissue repair responses.", "output": {"entities": {}}, "schema": []}
{"input": "The hypothesis of this study was that IL-1 beta is part of a pro-inflammatory positive feedback loop that sustains a persistent pro-inflammatory wound macrophage phenotype which contributes to impaired healing in diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Macrophages isolated from wounds in diabetic humans and mice exhibited a pro-inflammatory phenotype, including expression and secretion of IL-1 beta.", "output": {"entities": {}}, "schema": []}
{"input": "The diabetic wound environment appears to be sufficient to induce these inflammatory phenomena as in vitro studies demonstrated that conditioned medium of both mouse and human wounds upregulates expression of pro-inflammatory genes and downregulates expression of pro-healing factors in cultured macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, inhibiting the IL-1 beta pathway using a neutralizing antibody and macrophages from IL1 receptor knockout mice blocked the conditioned medium-induced upregulation of pro-inflammatory genes and downregulation of pro-healing factors.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, inhibiting the IL-1 beta pathway in wounds of diabetic mice using a neutralizing antibody induced a switch from pro-inflammatory to healing-associated macrophage phenotypes, increased levels of wound growth factors and improved healing of these wounds.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings indicate that targeting the IL-1 beta pathway represents a new therapeutic approach for improving the healing of diabetic wounds.", "output": {"entities": {}}, "schema": []}
{"input": "Atmospheric chemistry of CF3O2: a theoretical study on mechanisms and pathways of the CF3O2 + IO reaction.", "output": {"entities": {"chemical": [{"text": "CF3O2", "start": 25, "end": 30}, {"text": "CF3O2", "start": 86, "end": 91}, {"text": "IO", "start": 94, "end": 96}]}}, "schema": []}
{"input": "The mechanisms and reaction pathways for the CF3O2 + IO reaction have been investigated by quantum chemistry methods.", "output": {"entities": {"chemical": [{"text": "CF3O2", "start": 45, "end": 50}, {"text": "IO", "start": 53, "end": 55}]}}, "schema": []}
{"input": "It has been found that the title reaction takes place on both the singlet and triplet potential energy surfaces (PES).", "output": {"entities": {}}, "schema": []}
{"input": "On the singlet PES, the most important products include CF3OOOI, CF3OOIO, CF3OIO2, and CF2O + FIO2, while other products such as CF2O + FOIO, CF2O + FOOI, CF3OOI + O ((3) P), CF3OI + O2 ((1) Delta and (3) Sigma), and CF3O + OIO are negligible due to high barriers or unstable formations.", "output": {"entities": {"chemical": [{"text": "CF3OOOI", "start": 56, "end": 63}, {"text": "CF3OOIO", "start": 65, "end": 72}, {"text": "CF3OIO2", "start": 74, "end": 81}, {"text": "CF2O", "start": 87, "end": 91}, {"text": "FIO2", "start": 94, "end": 98}, {"text": "CF2O", "start": 129, "end": 133}, {"text": "FOIO", "start": 136, "end": 140}, {"text": "CF2O", "start": 142, "end": 146}, {"text": "FOOI", "start": 149, "end": 153}, {"text": "CF3OOI", "start": 155, "end": 161}, {"text": "O", "start": 164, "end": 165}, {"text": "CF3OI", "start": 175, "end": 180}, {"text": "O2", "start": 183, "end": 185}, {"text": "CF3O", "start": 217, "end": 221}, {"text": "OIO", "start": 224, "end": 227}]}}, "schema": []}
{"input": "On the triplet PES, CF3O + OIO is the dominant product with a lower barrier.", "output": {"entities": {"chemical": [{"text": "CF3O", "start": 20, "end": 24}, {"text": "OIO", "start": 27, "end": 30}]}}, "schema": []}
{"input": "As for FIO2 and it isomers, the most stable one is FIO2.", "output": {"entities": {"chemical": [{"text": "FIO2", "start": 7, "end": 11}, {"text": "FIO2", "start": 51, "end": 55}]}}, "schema": []}
{"input": "TDDFT (Time Dependent Density Functional Theory) calculation indicates that CF3OOOI, CF3OOIO and CF3OIO2 undergo photolysis easily under sunlight.", "output": {"entities": {"chemical": [{"text": "CF3OOOI", "start": 76, "end": 83}, {"text": "CF3OOIO", "start": 85, "end": 92}, {"text": "CF3OIO2", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Moreover, a minor contribution relative to hydrogen is found in the CX3O2 + IO (X = H and F) reactions.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 43, "end": 51}, {"text": "CX3O2", "start": 68, "end": 73}, {"text": "IO", "start": 76, "end": 78}, {"text": "H", "start": 84, "end": 85}, {"text": "F", "start": 90, "end": 91}]}}, "schema": []}
{"input": "Optically healable polymers.", "output": {"entities": {}}, "schema": []}
{"input": "Polymers that can easily be repaired after being damaged are attractive as this characteristic can improve the reliability, functionality, and lifetime of many products.", "output": {"entities": {}}, "schema": []}
{"input": "In the last decade, researchers have thus developed new approaches to create stimuli-responsive polymer systems, which have the ability to autonomously heal or can be repaired upon exposure to an external stimulus.", "output": {"entities": {}}, "schema": []}
{"input": "This review summarizes the current knowledge of optically healable or photo-healable polymers.", "output": {"entities": {}}, "schema": []}
{"input": "The use of light as a stimulus for healing offers several attractive features, including the ability to deliver the stimulus locally, which opens up the possibility of healing the material under load, as well as the ability to tailor the wavelength of light to selectively address a specific component of the material, e. g. only the damaged parts.", "output": {"entities": {}}, "schema": []}
{"input": "So far, two main classes of optically healable polymers have been explored, which are structurally dynamic polymers and mechanically activated reactive systems.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 9, "end": 17}]}}, "schema": []}
{"input": "RATIONALE: Receptor mechanisms underlying the behavioral effects of clinically used nicotinic acetylcholine receptor agonists have not been fully established.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 94, "end": 107}]}}, "schema": []}
{"input": "OBJECTIVE: Drug discrimination was used to compare receptor mechanisms underlying the effects of smoking cessation aids.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Separate groups of male C57BL/6J mice discriminated 0. 56, 1, or 1. 78 mg/kg of nicotine base.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Nicotine, varenicline, and cytisine were administered alone, in combination with each other, and in combination with mecamylamine and dihydro-beta-erythroidine (DH beta E).", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}, {"text": "varenicline", "start": 10, "end": 21}, {"text": "cytisine", "start": 27, "end": 35}, {"text": "mecamylamine", "start": 117, "end": 129}, {"text": "dihydro-beta-erythroidine", "start": 134, "end": 159}, {"text": "DH beta E", "start": 161, "end": 170}]}}, "schema": []}
{"input": "Midazolam and morphine were tested to examine sensitivity to non-nicotinics.", "output": {"entities": {"chemical": [{"text": "Midazolam", "start": 0, "end": 9}, {"text": "morphine", "start": 14, "end": 22}]}}, "schema": []}
{"input": "RESULTS: The ED50 value of nicotine to produce discriminative stimulus effects systematically increased as training dose increased.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 27, "end": 35}]}}, "schema": []}
{"input": "Varenicline and cytisine did not fully substitute for nicotine and, as compared with nicotine, their ED50 values varied less systematically as a function of nicotine training dose.", "output": {"entities": {"chemical": [{"text": "Varenicline", "start": 0, "end": 11}, {"text": "cytisine", "start": 16, "end": 24}, {"text": "nicotine", "start": 54, "end": 62}, {"text": "nicotine", "start": 85, "end": 93}, {"text": "nicotine", "start": 157, "end": 165}]}}, "schema": []}
{"input": "Morphine did not substitute for nicotine, whereas midazolam substituted for the low and not the higher training doses of nicotine.", "output": {"entities": {"chemical": [{"text": "Morphine", "start": 0, "end": 8}, {"text": "nicotine", "start": 32, "end": 40}, {"text": "midazolam", "start": 50, "end": 59}, {"text": "nicotine", "start": 121, "end": 129}]}}, "schema": []}
{"input": "As training dose increased, the dose of mecamylamine needed to produce a significant rightward shift in the nicotine dose-effect function also increased.", "output": {"entities": {"chemical": [{"text": "mecamylamine", "start": 40, "end": 52}]}}, "schema": []}
{"input": "DH beta E antagonized nicotine in animals discriminating the smallest dose of nicotine.", "output": {"entities": {"chemical": [{"text": "DH beta E", "start": 0, "end": 9}, {"text": "nicotine", "start": 22, "end": 30}, {"text": "nicotine", "start": 78, "end": 86}]}}, "schema": []}
{"input": "Varenicline did not antagonize the effects of nicotine, whereas cytisine produced a modest though significant antagonism of nicotine.", "output": {"entities": {"chemical": [{"text": "Varenicline", "start": 0, "end": 11}, {"text": "nicotine", "start": 46, "end": 54}, {"text": "cytisine", "start": 64, "end": 72}, {"text": "nicotine", "start": 124, "end": 132}]}}, "schema": []}
{"input": "CONCLUSIONS: These results suggest that differences in pharmacologic mechanism between nicotine, varenicline, and cytisine include not only differences in efficacy at a common subtype of nicotinic acetylcholine receptor, but also differential affinity and/or efficacy at multiple receptor subtypes.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 87, "end": 95}, {"text": "varenicline", "start": 97, "end": 108}, {"text": "cytisine", "start": 114, "end": 122}, {"text": "acetylcholine", "start": 197, "end": 210}]}}, "schema": []}
{"input": "Reinforcement enhancing effects of nicotine via smoking.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 35, "end": 43}]}}, "schema": []}
{"input": "RATIONALE: In animals, nicotine enhances reinforcement from stimuli unrelated to nicotine intake.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 23, "end": 31}, {"text": "nicotine", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Human research is suggestive but has not clearly shown a similar influence of nicotine.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 78, "end": 86}]}}, "schema": []}
{"input": "OBJECTIVES: We assessed acute effects of nicotine via smoking on enhancement of positive (money, music) or negative (termination of noise) reinforcers, or no \" reward \" (control).", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 41, "end": 49}]}}, "schema": []}
{"input": "These different rewards determined the generalizability of nicotine effects.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 59, "end": 67}]}}, "schema": []}
{"input": "MATERIALS AND METHODS: Dependent (n = 25) and nondependent (n = 27) smokers participated in three sessions, each after overnight abstinence.", "output": {"entities": {}}, "schema": []}
{"input": "Using a within-subjects design, sessions involved no smoking or smoking denicotinized (0. 05 mg) or nicotine (0. 6 mg) Quest (R) brand cigarettes.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 100, "end": 108}]}}, "schema": []}
{"input": "For comparison, a fourth session involved no abstinence prior to smoking one' s own brand to gauge responses under typical nicotine satiation.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 123, "end": 131}]}}, "schema": []}
{"input": "Reinforcement was assessed by responses on a simple operant computer task for the rewards, each available singly on a progressive ratio schedule during separate trials.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The reinforcing effect of music, but not other rewards, was greater due to the nicotine cigarette, compared to the denicotinized cigarette or no smoking.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 88, "end": 96}]}}, "schema": []}
{"input": "Reinforcement enhancing effects of nicotine did not differ between dependent and nondependent groups, indicating no influence of withdrawal relief.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 35, "end": 43}]}}, "schema": []}
{"input": "Responding due to acute nicotine after abstinence was very similar to responding to one' s own brand after no abstinence.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 24, "end": 32}]}}, "schema": []}
{"input": "CONCLUSIONS: Acute nicotine intake per se from smoking after abstinence enhances the reinforcing value of rewards unassociated with smoking, perhaps in a manner comparable to ad lib smoking after no abstinence.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 19, "end": 27}]}}, "schema": []}
{"input": "Nicotine' s reinforcement enhancing effects may be specific to certain rewards, perhaps those sensory in nature.", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Evaporation-Induced Coating of Hydrous Ruthenium Oxide on Mesoporous Silica Nanoparticles to Develop High-Performance Supercapacitors.", "output": {"entities": {"chemical": [{"text": "Hydrous Ruthenium Oxide", "start": 31, "end": 54}, {"text": "Silica", "start": 69, "end": 75}]}}, "schema": []}
{"input": "An efficient evaporation-induced coating method combining microwave-assisted hydrothermal transformation and annealing is developed to fabricate an ideal electrode material from composites with a layer of hydrous RuO2 on mesoporous silica nanoparticles (MSNs), for a high-performance supercapacitor.", "output": {"entities": {"chemical": [{"text": "hydrous RuO2", "start": 205, "end": 217}, {"text": "silica", "start": 232, "end": 238}]}}, "schema": []}
{"input": "Total and RuO2-based specific capacitances are as high as 1125 and 2000 F g (-1), respectively.", "output": {"entities": {"chemical": [{"text": "RuO2", "start": 10, "end": 14}]}}, "schema": []}
{"input": "Anti-biofilm Effects of Honey Against Wound Pathogens Proteus mirabilis and Enterobacter cloacae.", "output": {"entities": {}}, "schema": []}
{"input": "Biofilm growth and its persistence within wounds have recently been suggested as contributing factors to impaired healing.", "output": {"entities": {}}, "schema": []}
{"input": "The goal of this study was to investigate the anti-biofilm effects of several honey samples of different botanical origin, including manuka honey against Proteus mirabilis and Enterobacter cloacae wound isolates.", "output": {"entities": {}}, "schema": []}
{"input": "Quantification of biofilm formation was carried out using a microtiter plate assay.", "output": {"entities": {}}, "schema": []}
{"input": "All honeys at a sub-inhibitory concentration of 10% (w/v) significantly reduced the biofilm development of both isolates.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, at a concentration of 50% (w/v), each of the honeys caused significant partial detachment of Pr. mirabilis biofilm after 24 h.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, no honey was able to significantly detach Ent. cloacae biofilm.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, treatment of Ent. cloacae and Pr. mirabilis biofilms with all honeys resulted in a significant decrease in colony-forming units per well values in a range of 0. 35-1. 16 and 1. 2-7. 5 log units, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Of the tested honeys, manuka honey possessed the most potent anti-biofilm properties.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, methylglyoxal, an antibacterial compound of manuka honey, was shown to be responsible for killing biofilm-embedded wound bacteria.", "output": {"entities": {"chemical": [{"text": "methylglyoxal", "start": 13, "end": 26}]}}, "schema": []}
{"input": "These findings suggest that manuka honey could be used as a potential therapy for the treatment of wounds containing Pr. mirabilis or Ent. cloacae.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Solution-processible highly conducting fullerenes.", "output": {"entities": {"chemical": [{"text": "fullerenes", "start": 39, "end": 49}]}}, "schema": []}
{"input": "n-Doping of solution-processible organic semiconductors: highly conductive fullerenes are demonstrated through solution-processed fulleropyrrolidinium iodide (FPI) and FPI-doped PCBM to reach a high conductivity (3. 2 S/m).", "output": {"entities": {"chemical": [{"text": "fullerenes", "start": 75, "end": 85}, {"text": "fulleropyrrolidinium iodide", "start": 130, "end": 157}, {"text": "FPI", "start": 159, "end": 162}, {"text": "FPI", "start": 168, "end": 171}, {"text": "PCBM", "start": 178, "end": 182}]}}, "schema": []}
{"input": "The n-doping proceeds via anion-induced electron transfer between the iodide on FPI and the fullerene in the solid state.", "output": {"entities": {"chemical": [{"text": "iodide", "start": 70, "end": 76}, {"text": "FPI", "start": 80, "end": 83}, {"text": "fullerene", "start": 92, "end": 101}]}}, "schema": []}
{"input": "Influence of the Green Tea Leaf Extract on Neurotoxicity of Aluminium Chloride in Rats.", "output": {"entities": {"chemical": [{"text": "Aluminium Chloride", "start": 60, "end": 78}]}}, "schema": []}
{"input": "Aluminium may have an important role in the aetiology/pathogenesis/precipitation of Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "Aluminium", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Because green tea (Camellia sinensis L.) reportedly has health-promoting effects in the central nervous system, we evaluated the effects of green tea leaf extract (GTLE) on aluminium chloride (AlCl3) neurotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "aluminium chloride", "start": 173, "end": 191}, {"text": "AlCl3", "start": 193, "end": 198}]}}, "schema": []}
{"input": "All solutions were injected into the cornu ammonis region 1 hippocampal region.", "output": {"entities": {}}, "schema": []}
{"input": "We measured the performance of active avoidance (AA) tasks, various enzyme activities and total glutathione content (TGC) in the forebrain cortex (FbC), striatum, basal forebrain (BFb), hippocampus, brain stem and cerebellum.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 96, "end": 107}]}}, "schema": []}
{"input": "AlCl3 markedly reduced AA performance and activities of cytochrome c oxidase (COX) and acetylcholinesterase (AChE) in all regions.", "output": {"entities": {"chemical": [{"text": "AlCl3", "start": 0, "end": 5}]}}, "schema": []}
{"input": "It decreased TGC in the FbC, striatum, BFb, hippocampus, brain stem and cerebellum, and increased superoxide dismutase activity in the FbC, cerebellum and BFb.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 98, "end": 108}]}}, "schema": []}
{"input": "GTLE pretreatment completely reversed the damaging effects of AlCl3 on AA and superoxide dismutase activity, markedly corrected COX and AChE activities, and moderately improved TGC.", "output": {"entities": {"chemical": [{"text": "AlCl3", "start": 62, "end": 67}, {"text": "superoxide", "start": 78, "end": 88}]}}, "schema": []}
{"input": "GTLE alone increased COX and AChE activities in almost all regions.", "output": {"entities": {}}, "schema": []}
{"input": "GTLE reduces AlCl3 neurotoxicity probably via antioxidative effects and improves mitochondrial and cholinergic synaptic functions through the actions of (-)-epigallocatechin gallate and (-)-epicatechin, compounds most abundantly found in GTLE.", "output": {"entities": {"chemical": [{"text": "AlCl3", "start": 13, "end": 18}, {"text": "(-)-epigallocatechin gallate", "start": 153, "end": 181}, {"text": "(-)-epicatechin", "start": 186, "end": 201}]}}, "schema": []}
{"input": "Our results suggest that green tea might be beneficial in Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Towards squalamine mimics: synthesis and antibacterial activities of head-to-tail dimeric sterol-polyamine conjugates.", "output": {"entities": {"chemical": [{"text": "sterol", "start": 90, "end": 96}, {"text": "polyamine", "start": 97, "end": 106}]}}, "schema": []}
{"input": "Four dimeric sterol-polyamine conjugates have been synthesized from the homo-and hetero-connection of monomeric sterol-polyamine analogs in a head-to-tail manner.", "output": {"entities": {"chemical": [{"text": "sterol", "start": 13, "end": 19}, {"text": "polyamine", "start": 20, "end": 29}, {"text": "sterol", "start": 112, "end": 118}, {"text": "polyamine", "start": 119, "end": 128}]}}, "schema": []}
{"input": "These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria, whereas their corresponding activities against Gram-negative bacteria are relatively moderate.", "output": {"entities": {}}, "schema": []}
{"input": "Though no significant difference was observed in the activities of these conjugates, cholic acid-containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid-derived analogs.", "output": {"entities": {"chemical": [{"text": "cholic acid", "start": 85, "end": 96}, {"text": "deoxycholic acid", "start": 186, "end": 202}]}}, "schema": []}
{"input": "This is in contrast to the finding that a monomeric deoxycholic acid-spermine conjugate was more active than the corresponding cholic acid-derived analog.", "output": {"entities": {"chemical": [{"text": "deoxycholic acid", "start": 52, "end": 68}, {"text": "spermine", "start": 69, "end": 77}, {"text": "cholic acid", "start": 127, "end": 138}]}}, "schema": []}
{"input": "Synthesis and Structure-Activity Relationship Studies of Derivatives of the Dual Aromatase-Sulfatase Inhibitor 4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate.", "output": {"entities": {"chemical": [{"text": "4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate", "start": 111, "end": 188}]}}, "schema": []}
{"input": "4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and sulfatase inhibitors (DASIs).", "output": {"entities": {"chemical": [{"text": "4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate", "start": 0, "end": 77}, {"text": "F", "start": 105, "end": 106}, {"text": "Cl", "start": 108, "end": 110}, {"text": "Br", "start": 112, "end": 114}]}}, "schema": []}
{"input": "Structure-activity relationship studies were performed on these compounds, and various modifications were made to their structures involving relocation of the halogen atom, introduction of more halogen atoms, replacement of the halogen with another group, replacement of the methylene linker with a difluoromethylene linker, replacement of the para-cyanophenyl ring with other ring structures, and replacement of the triazolyl group with an imidazolyl group.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 159, "end": 166}, {"text": "halogen", "start": 194, "end": 201}, {"text": "halogen", "start": 228, "end": 235}, {"text": "methylene", "start": 275, "end": 284}, {"text": "difluoromethylene", "start": 299, "end": 316}, {"text": "para-cyanophenyl", "start": 344, "end": 360}, {"text": "triazolyl", "start": 417, "end": 426}, {"text": "imidazolyl", "start": 441, "end": 451}]}}, "schema": []}
{"input": "The most potent in vitro DASI discovered is an imidazole derivative with IC50 values against aromatase and steroid sulfatase in a JEG-3 cell preparation of 0. 2 and 2. 5 nM, respectively.", "output": {"entities": {"chemical": [{"text": "imidazole", "start": 47, "end": 56}, {"text": "steroid", "start": 107, "end": 114}]}}, "schema": []}
{"input": "The parent phenol of this compound inhibits aromatase with an IC50 value of 0. 028 nM in the same assay.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 11, "end": 17}]}}, "schema": []}
{"input": "P2X and P2Y nucleotide receptors as targets in cardiovascular disease.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 12, "end": 22}]}}, "schema": []}
{"input": "Endogenous nucleotides have widespread actions in the cardiovascular system, but it is only recently that the P2X and P2Y receptor subtypes, at which they act, have been identified and subtype-selective agonists and antagonists developed.", "output": {"entities": {"chemical": [{"text": "nucleotides", "start": 11, "end": 22}]}}, "schema": []}
{"input": "These advances have greatly increased our understanding of the physiological and pathophysiological functions of P2X and P2Y receptors, but investigation of the clinical usefulness of selective ligands is at an early stage.", "output": {"entities": {}}, "schema": []}
{"input": "Nonetheless, the evidence considered in this review demonstrates clearly that various cardiovascular disorders, including vasospasm, hypertension, congestive heart failure and cardiac damage during ischemic episodes, may be viable targets.", "output": {"entities": {}}, "schema": []}
{"input": "With further development of novel, selective agonists and antagonists, our understanding will continue to improve and further therapeutic applications are likely to be discovered.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutic applications of PI3K inhibitors in cardiovascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "PI3Ks are signaling enzymes engaged by different types of membrane receptors and activated in cardiovascular diseases such as hypertension, atherosclerosis, thrombosis and heart failure.", "output": {"entities": {}}, "schema": []}
{"input": "Studies performed on genetically modified animals have provided proof-of-concept that general or isoform-specific blockade of these enzymes can modify disease development and progression.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, therapeutic inhibition of PI3Ks with novel pharmacological compounds constitutes a promising area of drug development.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, inhibitors of PI3Ks have the potential to reduce blood pressure, restrain the development of atherosclerosis and/or stabilize atherosclerotic plaques, blunt platelet aggregation, prevent left ventricular remodeling and preserve myocardial contractility in heart failure.", "output": {"entities": {}}, "schema": []}
{"input": "This review summarizes the rationale of PI3K inhibition in the most prevalent cardiovascular diseases, and the available data on the therapeutic effects of PI3K inhibitors in their preclinical models.", "output": {"entities": {}}, "schema": []}
{"input": "Implications for future drug development and human therapy are also discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Design of UCST Polymers for Chilling Capture of Proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Ureido-derivatized polymers, such as poly (allylurea) (PU) and poly (L-citrulline) derivatives, exhibited upper critical solution temperature (UCST) behavior under physiological buffer conditions as we previously reported.", "output": {"entities": {"chemical": [{"text": "poly (allylurea)", "start": 37, "end": 53}, {"text": "poly (L-citrulline)", "start": 63, "end": 82}]}}, "schema": []}
{"input": "The PU derivatives having amino groups (PU-Am) also showed UCST behavior.", "output": {"entities": {"chemical": [{"text": "amino", "start": 26, "end": 31}, {"text": "PU-Am", "start": 40, "end": 45}]}}, "schema": []}
{"input": "In this study, we modified the amino groups of the polymer with succinyl anhydride (PU-Su) or acetyl anhydride (PU-Ac) to determine the effects of these ionic groups on the UCST behavior and to control interactions between the PU derivatives and biocomponents such as proteins and cells.", "output": {"entities": {"chemical": [{"text": "amino", "start": 31, "end": 36}, {"text": "succinyl anhydride", "start": 64, "end": 82}, {"text": "PU-Su", "start": 84, "end": 89}, {"text": "acetyl anhydride", "start": 94, "end": 110}, {"text": "PU-Ac", "start": 112, "end": 117}]}}, "schema": []}
{"input": "Succinylation of PU-Am resulted in a significant decrease in phase separation temperature (Tp), whereas acetylation of PU-Am resulted in an increase in Tp.", "output": {"entities": {"chemical": [{"text": "PU-Am", "start": 17, "end": 22}, {"text": "PU-Am", "start": 119, "end": 124}]}}, "schema": []}
{"input": "As expected, the Tp of PU-Am and PU-Su changed when the pH of the solution was changed.", "output": {"entities": {"chemical": [{"text": "PU-Am", "start": 23, "end": 28}, {"text": "PU-Su", "start": 33, "end": 38}]}}, "schema": []}
{"input": "The Tp of PU-Am increased at higher pH, whereas that of PU-Su increased at lower pH, indicating that ionic charge decreases Tp of PU derivatives by increasing osmotic pressure and by increasing hydrophilicity of the polymer chains.", "output": {"entities": {"chemical": [{"text": "PU-Am", "start": 10, "end": 15}, {"text": "PU-Su", "start": 56, "end": 61}]}}, "schema": []}
{"input": "Interestingly, these groups did not significantly change UCST when these groups were nonionic.", "output": {"entities": {}}, "schema": []}
{"input": "We then examined capture and separation of particular proteins from a protein mixture by cooling-induced phase separation.", "output": {"entities": {}}, "schema": []}
{"input": "Selective and rapid capture of particular proteins from protein mixture by PU derivatives was shown, indicating that the ureido-derivatized polymers are potential media for bioseparation under biofriendly conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembly of elastin-mimetic double hydrophobic polypeptides.", "output": {"entities": {}}, "schema": []}
{"input": "We have constructed a novel class of \" double-hydrophobic \" block polypeptides based on the hydrophobic domains found in native elastin, an extracellular matrix protein responsible for the elasticity and resilience of tissues.", "output": {"entities": {}}, "schema": []}
{"input": "The block polypeptides comprise proline-rich poly (VPGXG) and glycine-rich poly (VGGVG), both of which dehydrate at higher temperature but form distinct secondary structures, beta-turn and beta-sheet respectively.", "output": {"entities": {"chemical": [{"text": "proline", "start": 32, "end": 39}, {"text": "glycine", "start": 62, "end": 69}]}}, "schema": []}
{"input": "In water at 45 degrees C, the block polypeptides initially assemble into nanoparticles rich in beta-turn structures, which further connect into long (> 10 mu m), beaded nanofibers along with the increase in the beta-sheet content.", "output": {"entities": {}}, "schema": []}
{"input": "The nanofibers obtained are well-dispersed in water, and show thermoresponsive properties.", "output": {"entities": {}}, "schema": []}
{"input": "Polypeptides comprising each block component assemble into different morphologies, showing that the conjugation of poly (VPGXG) and poly (VGGVG) plays a role for beaded fiber formation.", "output": {"entities": {}}, "schema": []}
{"input": "These results may provide innovative ideas for designing peptide-based materials but also opportunities for developing novel materials useful for tissue engineering and drug delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Extraction of the volatile oil from Carum carvi of Tunisia and Lithuania by supercritical carbon dioxide: chemical composition and antiulcerogenic activity.", "output": {"entities": {"chemical": [{"text": "carbon dioxide", "start": 90, "end": 104}]}}, "schema": []}
{"input": "This study investigates whether the essential oil prepared from Carum carvi seeds exhibits antiulcerogenic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Its volatile oil was obtained by supercritical fluid extraction (SFE) and by hydrodistillation.", "output": {"entities": {}}, "schema": []}
{"input": "The essential oils were analysed by GC-MS to monitor their composition.", "output": {"entities": {}}, "schema": []}
{"input": "The chemical analysis revealed that the essential oils extracted under SFE conditions had high carvone and limonene contents.", "output": {"entities": {"chemical": [{"text": "carvone", "start": 95, "end": 102}, {"text": "limonene", "start": 107, "end": 115}]}}, "schema": []}
{"input": "The antiulcerogenic activity was evaluated by the HCl/ethanol method, which causes injury to the gastric mucosa.", "output": {"entities": {"chemical": [{"text": "HCl", "start": 50, "end": 53}, {"text": "ethanol", "start": 54, "end": 61}]}}, "schema": []}
{"input": "Three treated groups received the essential oil (100-300 mg/kg).", "output": {"entities": {}}, "schema": []}
{"input": "The reference group received omeprazole (30 mg/kg) and the control group received NaCl.", "output": {"entities": {"chemical": [{"text": "omeprazole", "start": 29, "end": 39}, {"text": "NaCl", "start": 82, "end": 86}]}}, "schema": []}
{"input": "After 30 min, all groups were treated with HCl/EtOH for gastric ulcer induction.", "output": {"entities": {"chemical": [{"text": "HCl", "start": 43, "end": 46}, {"text": "EtOH", "start": 47, "end": 51}]}}, "schema": []}
{"input": "The results show C. carvi essential oil enhanced a significant inhibition of 47%, 81% and 88%, respectively, for three doses of essential oil used, which was similar to that induced by omeprazole (95%) (p < 0. 005).", "output": {"entities": {"chemical": [{"text": "omeprazole", "start": 185, "end": 195}]}}, "schema": []}
{"input": "Creating \" Living \" Polymer Surfaces to Pattern Biomolecules and Cells on Common Plastics.", "output": {"entities": {}}, "schema": []}
{"input": "Creating patterns of biomolecules and cells has been applied widely in many fields associated with the life sciences, including diagnostics.", "output": {"entities": {}}, "schema": []}
{"input": "In these applications it has become increasingly apparent that the spatiotemporal arrangement of biological molecules in vitro is important for the investigation of the cellular functions found in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "However, the cell patterning techniques often used are limited to creating 2D functional surfaces on glass and silicon.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 111, "end": 118}]}}, "schema": []}
{"input": "In addition, in general, these procedures are not easy to implement in conventional biological laboratories.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show the formation of a living poly (ethylene glycol) (PEG) layer that can be patterned with visible light on plastic surfaces.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol)", "start": 40, "end": 62}, {"text": "PEG", "start": 64, "end": 67}]}}, "schema": []}
{"input": "This new and simple method can be expanded to pattern multiple types of biomolecule on either a previously formed PEG layer or a plastic substrate.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 114, "end": 117}]}}, "schema": []}
{"input": "Using common plastic wares (i. e., polyethylene films and polystyrene cell culture Petri-dishes), we demonstrate that these PEG-modified surfaces have a high resistance to protein adsorption and cell adhesion, while at the same time, being capable of undergoing further molecular grafting with bioactive motifs.", "output": {"entities": {"chemical": [{"text": "polyethylene", "start": 35, "end": 47}, {"text": "polystyrene", "start": 58, "end": 69}, {"text": "PEG", "start": 124, "end": 127}]}}, "schema": []}
{"input": "With a photomask and a fluid delivery system, we illustrate a flexible way to immobilize biological functions with a high degree of 2D and 3D spatial control.", "output": {"entities": {}}, "schema": []}
{"input": "We anticipate that our method can be easily implemented in a typical life science laboratory (without the need for specialized lithography equipment) offering the prospect of imparting desirable properties to plastic products, for example, the creation of functional microenvironments in biological studies or reducing biological adhesion to surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Structural Rearrangement in the Formation of Jet-Cooled Complexes of Chiral (S)-1, 2, 3, 4-Tetrahydro-3-isoquinolinemethanol with Methyl Lactate: Chirality Effect in Conformer Selection.", "output": {"entities": {"chemical": [{"text": "(S)-1, 2, 3, 4-Tetrahydro-3-isoquinolinemethanol", "start": 76, "end": 124}, {"text": "Methyl Lactate", "start": 130, "end": 144}]}}, "schema": []}
{"input": "The jet-cooled complexes between the two enantiomers of methyl lactate (ML) and (S)-1, 2, 3, 4-tetrahydro-3-isoquinolinemethanol (THIQM) are studied by double resonance spectroscopy combined with ab initio calculations.", "output": {"entities": {"chemical": [{"text": "methyl lactate", "start": 56, "end": 70}, {"text": "(S)-1, 2, 3, 4-tetrahydro-3-isoquinolinemethanol", "start": 80, "end": 128}, {"text": "THIQM", "start": 130, "end": 135}]}}, "schema": []}
{"input": "Both diastereomer complexes exist in different isomers, involving either direct addition of THIQM on ML with no structural rearrangement of the subunits or formation of very stable structures involving multiple intermolecular hydrogen bonds and extensive deformation of the subunits.", "output": {"entities": {"chemical": [{"text": "THIQM", "start": 92, "end": 97}, {"text": "hydrogen", "start": 226, "end": 234}]}}, "schema": []}
{"input": "Competition between these two processes and its dependence upon chirality are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "It is shown that the most stable form of the chromophore (THIQMI with an OH... N hydrogen bond) prefers to directly stick to ML to form the addition complex whereas the second conformer (THIQMII with NH... O hydrogen bond) rearranges to form a strongly bound structure.", "output": {"entities": {"chemical": [{"text": "THIQMI", "start": 58, "end": 64}, {"text": "OH", "start": 73, "end": 75}, {"text": "N hydrogen", "start": 79, "end": 89}, {"text": "THIQMII", "start": 187, "end": 194}, {"text": "NH", "start": 200, "end": 202}, {"text": "O hydrogen", "start": 206, "end": 216}]}}, "schema": []}
{"input": "The two structures are formed for the homochiral as well the heterochiral complex, however with different relative abundance.", "output": {"entities": {}}, "schema": []}
{"input": "This shows an enantioselective binding preference of ML for one of the conformers of the chromophore.", "output": {"entities": {}}, "schema": []}
{"input": "Why fluorination of the polar heads reverses the positive sign of the dipole potential of langmuir monolayers: a vibrational sum frequency spectroscopic study.", "output": {"entities": {}}, "schema": []}
{"input": "Natural nonionic amphiphiles forming monolayers, bilayers, micelles, or biomembranes create a positive dipole potential at the boundary with water.", "output": {"entities": {}}, "schema": []}
{"input": "In a series of papers we have reported on Langmuir monolayers with CF3 terminals of the polar heads, which show a negative surface dipole potential Delta V (Petrov, J. G.; Andreeva, T. D.; Kurt, D. K.; M o hwald, H. J. Phys. Chem. B 2005, 109, 14102).", "output": {"entities": {"chemical": [{"text": "CF3", "start": 67, "end": 70}]}}, "schema": []}
{"input": "Here we use vibrational sum frequency spectroscopy (SF) to study the origin of the opposite Delta V signs of Langmuir films of CH3 (CH2) 20COCH2CH3 (ethyl ether, EE) and CH3 (CH2) 20COCH2CF3 (fluorinated ethyl ether, FEE).", "output": {"entities": {"chemical": [{"text": "CH3 (CH2) 20COCH2CH3", "start": 127, "end": 147}, {"text": "ethyl ether", "start": 149, "end": 160}, {"text": "CH3 (CH2) 20COCH2CF3", "start": 170, "end": 190}, {"text": "fluorinated ethyl ether", "start": 192, "end": 215}, {"text": "FEE", "start": 217, "end": 220}]}}, "schema": []}
{"input": "The vibrational sum frequency spectra are recorded at the same film density of the S-phase of the EE and FEE monolayers and analyzed in the spectral regions of OH, COC, CH3, and CF3 stretching vibrations because these functional groups could be responsible for the different dipole potentials.", "output": {"entities": {"chemical": [{"text": "FEE", "start": 105, "end": 108}, {"text": "OH", "start": 160, "end": 162}, {"text": "COC", "start": 164, "end": 167}, {"text": "CH3", "start": 169, "end": 172}, {"text": "CF3", "start": 178, "end": 181}]}}, "schema": []}
{"input": "We compare the rearrangement of the pure water surface by EE and FEE monolayers and the conformations of EE and FEE polar heads.", "output": {"entities": {"chemical": [{"text": "FEE", "start": 65, "end": 68}, {"text": "FEE", "start": 112, "end": 115}]}}, "schema": []}
{"input": "The analysis is performed according to the three-capacitor model of the dipole potential of Langmuir monolayers (Demchak, R. T.; Fort, T., Jr. J. Colloid Interface Sci. 1974, 46, 191).", "output": {"entities": {}}, "schema": []}
{"input": "The results show that reversal of the Delta V sign caused by fluorination of the polar heads originates from the upward-oriented CF3 terminals of the FEE heads, whose negative normal dipole moment component determines the negative dipole potential of the FEE monolayer.", "output": {"entities": {"chemical": [{"text": "CF3", "start": 129, "end": 132}, {"text": "FEE", "start": 150, "end": 153}, {"text": "FEE", "start": 255, "end": 258}]}}, "schema": []}
{"input": "Performances of CN-columns for the analysis of gamma-oryzanol and its p-coumarate and caffeate derivatives by normal phase HPLC and a validated method of quantitation.", "output": {"entities": {"chemical": [{"text": "gamma-oryzanol", "start": 47, "end": 61}, {"text": "p-coumarate", "start": 70, "end": 81}, {"text": "caffeate", "start": 86, "end": 94}]}}, "schema": []}
{"input": "gamma-Oryzanol is an important phytochemical used in pharmaceutical, alimentary and cosmetic preparations.", "output": {"entities": {"chemical": [{"text": "gamma-Oryzanol", "start": 0, "end": 14}]}}, "schema": []}
{"input": "The present article, for the first time, discloses the performances of NP-HPLC in separating gamma-oryzanol components and develops a validated method for its routine quantification.", "output": {"entities": {"chemical": [{"text": "gamma-oryzanol", "start": 93, "end": 107}]}}, "schema": []}
{"input": "The analysis is performed on a cyanopropyl bonded column using the hexane/MTBE gradient elution and UV detection at 325 nm.", "output": {"entities": {"chemical": [{"text": "cyanopropyl", "start": 31, "end": 42}, {"text": "hexane", "start": 67, "end": 73}, {"text": "MTBE", "start": 74, "end": 78}]}}, "schema": []}
{"input": "The method allows: the separation of steryl ferulate, p-coumarate and caffeate esters, the separation of cis-from trans-ferulate isomers, the splitting of steroid moieties into saturated and unsaturated at the side chain.", "output": {"entities": {"chemical": [{"text": "steryl ferulate", "start": 37, "end": 52}, {"text": "p-coumarate", "start": 54, "end": 65}, {"text": "caffeate esters", "start": 70, "end": 85}, {"text": "trans-ferulate", "start": 114, "end": 128}, {"text": "steroid", "start": 155, "end": 162}]}}, "schema": []}
{"input": "The optimised method provides excellent linear response (R (2) = 0. 99997), high precision (RSD < 1. 0%) and satisfactory accuracy (R (*) = 70-86%).", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the established method presents the details of the procedure and the experimental conditions in order to achieve the required precision and instrumental accuracy.", "output": {"entities": {}}, "schema": []}
{"input": "The method is fast and sensitive and it could be a suitable tool for quality assurance and determination of origin.", "output": {"entities": {}}, "schema": []}
{"input": "Lipid components and water soluble metabolites in salted and dried tuna (Thunnus thynnus L.) roes.", "output": {"entities": {}}, "schema": []}
{"input": "The salted and dried product of tuna roe (bottarga) is a seafood characteristic of the Mediterranean area and exported all over the world.", "output": {"entities": {}}, "schema": []}
{"input": "Samples of bottarga from bluefin tunas (Thunnus thynnus, L.) caught in the southwest Mediterranean sea were analysed.", "output": {"entities": {}}, "schema": []}
{"input": "The samples were characterised by high content of marine wax esters (55-67 mol% of lipid classes), of docosahexaenoic (22: 6 n-3, 25 w%) and oleic (18: 1 n-9, 19 w%) fatty acids.", "output": {"entities": {"chemical": [{"text": "esters", "start": 61, "end": 67}, {"text": "docosahexaenoic", "start": 102, "end": 117}, {"text": "oleic", "start": 141, "end": 146}, {"text": "fatty acids", "start": 166, "end": 177}]}}, "schema": []}
{"input": "Cholesterol was detected as 7-9 w% of lipids.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Free fatty acids, index of lipid hydrolysis, represented 32-39 mol% over total fatty acids.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 5, "end": 16}, {"text": "fatty acids", "start": 79, "end": 90}]}}, "schema": []}
{"input": "Among metabolites, nutrients as taurine, nicotinamide and beta-alanine, were found.", "output": {"entities": {"chemical": [{"text": "taurine", "start": 32, "end": 39}, {"text": "nicotinamide", "start": 41, "end": 53}, {"text": "beta-alanine", "start": 58, "end": 70}]}}, "schema": []}
{"input": "The microflora comprised staphylococci, enterococci (2. 2 log (10) CFU/g) and lactic acid bacteria (3 log (10) CFU/g).", "output": {"entities": {"chemical": [{"text": "lactic acid", "start": 78, "end": 89}]}}, "schema": []}
{"input": "The food-borne pathogens Staphylococcus aureus, Listeria monocytogenes and Salmonella spp. were not detected.", "output": {"entities": {}}, "schema": []}
{"input": "These findings indicate tuna bottarga as valuable source of nutrients.", "output": {"entities": {}}, "schema": []}
{"input": "Theaflavins, dimeric catechins, inhibit peptide transport across Caco-2 cell monolayers via down-regulation of AMP-activated protein kinase-mediated peptide transporter PEPT1.", "output": {"entities": {"chemical": [{"text": "Theaflavins", "start": 0, "end": 11}, {"text": "dimeric catechins", "start": 13, "end": 30}, {"text": "AMP", "start": 111, "end": 114}]}}, "schema": []}
{"input": "In the small intestine, peptide transporter 1 (PEPT1) plays a role in the transport of di-and tripeptides.", "output": {"entities": {"chemical": [{"text": "di-and tripeptides", "start": 87, "end": 105}]}}, "schema": []}
{"input": "In this study, we investigated whether theaflavins (TFs) affect the absorption of small peptides in human intestinal Caco-2 cells, since TFs do not penetrate through the cells and might be involved in intestinal transport systems.", "output": {"entities": {"chemical": [{"text": "theaflavins", "start": 39, "end": 50}, {"text": "TFs", "start": 52, "end": 55}, {"text": "TFs", "start": 137, "end": 140}]}}, "schema": []}
{"input": "In transport experiments, the transport of glycyl-sarcosine (Gly-Sar, a model molecule for PEPT1 transport) and other dipeptides (Val-Tyr and Ile-Phe) were significantly reduced (P < 0. 05) in TFs-pretreated cells.", "output": {"entities": {"chemical": [{"text": "glycyl-sarcosine", "start": 43, "end": 59}, {"text": "Gly-Sar", "start": 61, "end": 68}, {"text": "dipeptides", "start": 118, "end": 128}, {"text": "Val-Tyr", "start": 130, "end": 137}, {"text": "Ile-Phe", "start": 142, "end": 149}, {"text": "TFs", "start": 193, "end": 196}]}}, "schema": []}
{"input": "In TF 3'-O-gallate-pretreated cells, Western blot analysis revealed attenuated expression of PEPT1 transporter and Gly-Sar transport was completely ameliorated by 10 mu M Compound C, an AMP-activated protein kinase (AMPK) inhibitor.", "output": {"entities": {"chemical": [{"text": "TF 3'-O-gallate", "start": 3, "end": 18}, {"text": "Gly-Sar", "start": 115, "end": 122}, {"text": "Compound C", "start": 171, "end": 181}, {"text": "AMP", "start": 186, "end": 189}]}}, "schema": []}
{"input": "In conclusion, the present study demonstrated that TFs inhibit peptide transport across Caco-2 cell monolayers, probably through suppression of AMPK-mediated PEPT1 expression, which should be considered a new bioactivity of TFs in black tea.", "output": {"entities": {"chemical": [{"text": "TFs", "start": 51, "end": 54}, {"text": "TFs", "start": 224, "end": 227}]}}, "schema": []}
{"input": "Aqueous enzymatic process assisted by microwave extraction of oil from yellow horn (Xanthoceras sorbifolia Bunge.) seed kernels and its quality evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, aqueous enzymatic process (AEP) assisted by microwave extraction (ME) of oil from yellow horn (Xanthoceras sorbifolia Bunge.) seed kernel was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Central composite design (CCD) and response surface methodology (RSM) were used to optimise an enzyme cocktail (cellulase, hemicellulase, pectinase) for AEP.", "output": {"entities": {}}, "schema": []}
{"input": "The main factors of ME were also studied.", "output": {"entities": {}}, "schema": []}
{"input": "A maximal oil extraction yield of 55. 8% was achieved under optimal conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, scanning electron microscope (SEM) was applied to characterise the extraction process.", "output": {"entities": {}}, "schema": []}
{"input": "Analysing chemical composition of the extracted oil by GC-MS showed that the content of unsaturated fatty acids by this emerging method (91. 18%) was similar to that by conventional organic solvent extraction (88. 76%).", "output": {"entities": {"chemical": [{"text": "unsaturated fatty acids", "start": 88, "end": 111}]}}, "schema": []}
{"input": "In addition, the main physicochemical properties and antioxidant activities of yellow horn oil were measured to evaluate its quality.", "output": {"entities": {}}, "schema": []}
{"input": "The present research supported necessary data for the green extraction method of edible oil in food industry.", "output": {"entities": {}}, "schema": []}
{"input": "Monitoring the effect of high pressure and transglutaminase treatment of milk on the evolution of flavour compounds during lactic acid fermentation using PTR-ToF-MS.", "output": {"entities": {"chemical": [{"text": "lactic acid", "start": 123, "end": 134}]}}, "schema": []}
{"input": "In this study, the effects of thermal or high hydrostatic pressure (HHP) treatment of a milk base in the absence or presence of a transglutaminase (TGase) protein cross-linking step on the flavour development of yoghurt were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of several tentatively identified volatile flavour compounds (VOCs), both during the enzymatic treatment and the lactic acid fermentation of the milk base, were monitored using a proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS).", "output": {"entities": {"chemical": [{"text": "lactic acid", "start": 126, "end": 137}]}}, "schema": []}
{"input": "The formation of the major flavour compounds (acetaldehyde, diacetyl, acetoin, and 2-butanone) followed a sigmoidal trend described by the modified Gompertz model.", "output": {"entities": {"chemical": [{"text": "acetaldehyde", "start": 46, "end": 58}, {"text": "diacetyl", "start": 60, "end": 68}, {"text": "acetoin", "start": 70, "end": 77}, {"text": "2-butanone", "start": 83, "end": 93}]}}, "schema": []}
{"input": "The HHP treatment of milk increased significantly the volatile compound formation rate whereas it did not affect the duration of the lag phase of formation, with the exception of acetaldehyde and diacetyl formation.", "output": {"entities": {"chemical": [{"text": "acetaldehyde", "start": 179, "end": 191}, {"text": "diacetyl", "start": 196, "end": 204}]}}, "schema": []}
{"input": "On the contrary, the TGase cross-linking of milk did not significantly modify the formation rate of the volatile compounds but shortened the duration of the lag phase of their formation.", "output": {"entities": {}}, "schema": []}
{"input": "Purification and characterisation of two enzymes related to endogenous formaldehyde in Lentinula edodes.", "output": {"entities": {"chemical": [{"text": "formaldehyde", "start": 71, "end": 83}]}}, "schema": []}
{"input": "In this study, gamma-glutamyl transpeptidase (GGT) and l-cysteine sulphoxide lyase (C-S lyase) were purified from the fruiting body of Lentinula edodes in three steps and then characterised.", "output": {"entities": {"chemical": [{"text": "gamma-glutamyl", "start": 15, "end": 29}, {"text": "l-cysteine sulphoxide", "start": 55, "end": 76}]}}, "schema": []}
{"input": "We found that GGT together with C-S lyase caused the generation of endogenous formaldehyde in L. edodes.", "output": {"entities": {"chemical": [{"text": "formaldehyde", "start": 78, "end": 90}]}}, "schema": []}
{"input": "GGT was composed of a large subunit of 41 kDa and a small subunit of 25 kDa, and C-S lyase was composed of two identical subunits of 46 kDa, as determined by SDS-PAGE.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 158, "end": 161}]}}, "schema": []}
{"input": "GGT was stable at pH 8. 0-10. 0 with an optimum pH of 8. 8, and was stable at 20-50 degrees C with an optimum activity at 37 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "C-S lyase was stable at pH 8. 0-9. 0 with an optimum pH of 8. 5, and was stable at 20-60 degrees C with an optimum activity at 40 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "The present work supports the study of the mechanism of endogenous formaldehyde in L. edodes.", "output": {"entities": {"chemical": [{"text": "formaldehyde", "start": 67, "end": 79}]}}, "schema": []}
{"input": "PSP activates monocytes in resting human peripheral blood mononuclear cells: immunomodulatory implications for cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Polysaccharopeptide (PSP), from Coriolus versicolor, has been used as an adjuvant to chemotherapy, and has demonstrated anti-tumor and immunomodulating effects.", "output": {"entities": {}}, "schema": []}
{"input": "However its mechanism remains unknown.", "output": {"entities": {}}, "schema": []}
{"input": "To elucidate how PSP affects immune populations, we compared PSP treatments both with and without prior incubation in phytohaemagglutinin (PHA)-a process commonly used in immune population experimentation.", "output": {"entities": {}}, "schema": []}
{"input": "We first standardised a capillary electrophoresis fingerprinting technique for PSP identification and characterisation.", "output": {"entities": {}}, "schema": []}
{"input": "We then established the proliferative capability of PSP on various immune populations in peripheral blood mononuclear cells, using flow cytometry, without prior PHA treatment.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that PSP significantly increased the number of monocytes (CD14 (+)/CD16 (-)) compared to controls without PHA.", "output": {"entities": {}}, "schema": []}
{"input": "This increase in monocytes was confirmed using another antibody panel of CD14 and MHCII.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, proliferations of T-cells, NK, and B-cells were not significantly changed by PSP.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, stimulating monocyte/macrophage function with PSP could be an effective therapeutic intervention in targeting tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Optimisation of synthesis of oligosaccharides derived from lactulose (fructosyl-galacto-oligosaccharides) with beta-galactosidases of different origin.", "output": {"entities": {"chemical": [{"text": "lactulose", "start": 59, "end": 68}, {"text": "fructosyl-galacto-oligosaccharides", "start": 70, "end": 104}]}}, "schema": []}
{"input": "Batch synthesis of fructosyl-galacto-oligosaccharides from lactulose was performed with commercial beta-galactosidase preparations from Aspergillus oryzae, Kluyveromyces lactis and Bacillus circulans.", "output": {"entities": {"chemical": [{"text": "fructosyl-galacto-oligosaccharides", "start": 19, "end": 53}, {"text": "lactulose", "start": 59, "end": 68}]}}, "schema": []}
{"input": "The enzyme from A. oryzae produced the highest yield and specific productivity of synthesis, being selected for further studies.", "output": {"entities": {}}, "schema": []}
{"input": "Optimization of fructosyl-galacto-oligosaccharides synthesis was carried out using response surface methodology, considering temperature and initial sugar concentration as variables and yield and specific productivity as response parameters.", "output": {"entities": {"chemical": [{"text": "fructosyl-galacto-oligosaccharides", "start": 16, "end": 50}, {"text": "sugar", "start": 149, "end": 154}]}}, "schema": []}
{"input": "Maximum yield of 0. 41 g g (-1) fructosyl-galacto-oligosaccharides was obtained at 70 degrees C and 60% w/w lactulose concentration, while maximum specific productivity of 1. 2 g h (-1) mg (-1) was obtained at 70 degrees C and 40% w/w lactulose concentration.", "output": {"entities": {"chemical": [{"text": "fructosyl-galacto-oligosaccharides", "start": 32, "end": 66}, {"text": "lactulose", "start": 108, "end": 117}, {"text": "lactulose", "start": 235, "end": 244}]}}, "schema": []}
{"input": "Identification of novel dietary phytochemicals inhibiting the efflux transporter breast cancer resistance protein (BCRP/ABCG2).", "output": {"entities": {}}, "schema": []}
{"input": "Breast cancer resistance protein (BCRP/ABCG2) plays an important role in determining the absorption and disposition of consumed xenobiotics including various drugs and dietary phytochemicals and is also one of the prominent efflux transporters involved in multidrug resistance (MDR).", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we have investigated the interactions between ABCG2 and 56 naturally-occurring phytochemicals including phenolic acids, flavonoids, triterpenes and other common dietary phytochemicals, as well as two non plant-based compounds (hippuric acid and propyl gallate) using cell-and membrane-based transport inhibition assays.", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 119, "end": 133}, {"text": "flavonoids", "start": 135, "end": 145}, {"text": "triterpenes", "start": 147, "end": 158}, {"text": "hippuric acid", "start": 242, "end": 255}, {"text": "propyl gallate", "start": 260, "end": 274}]}}, "schema": []}
{"input": "Of the non-flavonoid phytochemicals tested, berberine, celastrol, ellagic acid, limonin, oleanolic acid, propyl gallate, sinapic acid and ursolic acid demonstrated significant inhibition of ABCG2-mediated transport.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 11, "end": 20}, {"text": "berberine", "start": 44, "end": 53}, {"text": "celastrol", "start": 55, "end": 64}, {"text": "ellagic acid", "start": 66, "end": 78}, {"text": "limonin", "start": 80, "end": 87}, {"text": "oleanolic acid", "start": 89, "end": 103}, {"text": "propyl gallate", "start": 105, "end": 119}, {"text": "sinapic acid", "start": 121, "end": 133}, {"text": "ursolic acid", "start": 138, "end": 150}]}}, "schema": []}
{"input": "Chrysoeriol, laricitrin, myricetin 3', 4', 5'-trimethylether, pinocembrin, quercitrin, tamarixetin, tricetin and tricetin 3', 4', 5'-trimethylether were also identified as novel flavonoid ABCG2 inhibitors.", "output": {"entities": {"chemical": [{"text": "Chrysoeriol", "start": 0, "end": 11}, {"text": "laricitrin", "start": 13, "end": 23}, {"text": "myricetin 3', 4', 5'-trimethylether", "start": 25, "end": 60}, {"text": "pinocembrin", "start": 62, "end": 73}, {"text": "quercitrin", "start": 75, "end": 85}, {"text": "tamarixetin", "start": 87, "end": 98}, {"text": "tricetin", "start": 100, "end": 108}, {"text": "tricetin 3', 4', 5'-trimethylether", "start": 113, "end": 147}, {"text": "flavonoid", "start": 178, "end": 187}]}}, "schema": []}
{"input": "The identified inhibitory activity of dietary phytochemicals on ABCG2 provides a framework for further investigation of ABCG2-modulated phytochemical bioavailability, MDR, and possible food-drug interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Roasting-induced changes in arabinotriose, a model of coffee arabinogalactan side chains.", "output": {"entities": {"chemical": [{"text": "arabinotriose", "start": 28, "end": 41}]}}, "schema": []}
{"input": "Thermal processing can promote reactions that change the structure of food constituents, often by unknown mechanisms, such as those occurring in arabinose residues of coffee arabinogalactan side chains.", "output": {"entities": {"chemical": [{"text": "arabinose", "start": 145, "end": 154}]}}, "schema": []}
{"input": "Aiming to know more about these modifications, the structurally related alpha-(1 --> 5)-l-arabinotriose was roasted at 200 degrees C and the products obtained were identified by ESI-MS and MALDI-MS and characterised by ESI-MS (n).", "output": {"entities": {"chemical": [{"text": "alpha-(1 --> 5)-l-arabinotriose", "start": 72, "end": 103}]}}, "schema": []}
{"input": "Depolymerised and polymerised oligosaccharides with up to 16 residues and new types of linkages were formed.", "output": {"entities": {}}, "schema": []}
{"input": "Also, products resulting from dehydration, oxidation, and cleavage of a carbon-carbon bond at the reducing end of the corresponding non-modified oligosaccharide were formed, probably promoting the release of formaldehyde, formic acid, glycolaldehyde, glyoxal, acetic acid, glycolic acid, glyceraldehyde, 2-hydroxypropanedialdehyde and lactic acid.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 72, "end": 78}, {"text": "carbon", "start": 79, "end": 85}, {"text": "formaldehyde", "start": 208, "end": 220}, {"text": "formic acid", "start": 222, "end": 233}, {"text": "glycolaldehyde", "start": 235, "end": 249}, {"text": "glyoxal", "start": 251, "end": 258}, {"text": "acetic acid", "start": 260, "end": 271}, {"text": "glycolic acid", "start": 273, "end": 286}, {"text": "glyceraldehyde", "start": 288, "end": 302}, {"text": "2-hydroxypropanedialdehyde", "start": 304, "end": 330}]}}, "schema": []}
{"input": "As many of these compounds have been reported to occur in roasted coffee beans and/or brews, it can be suggested that the degradation of coffee arabinogalactan side chains can contribute to their formation upon roasting.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of pH on phosphorylation of potato protein isolate.", "output": {"entities": {}}, "schema": []}
{"input": "Potato protein isolate (PPI) was phosphorylated with sodium trimetaphosphate (STMP) at ambient temperature and various reaction pH (5. 2, 6. 2, 8. 0 and 10. 5) to improve the functional properties without impairing the nutritional availability.", "output": {"entities": {"chemical": [{"text": "sodium trimetaphosphate", "start": 53, "end": 76}, {"text": "STMP", "start": 78, "end": 82}]}}, "schema": []}
{"input": "Changes in chemical composition (total and coagulable protein content, ash and minerals content and amino acid composition), functional properties (protein solubility index, emulsifying activity and foaming capacity, water and oil absorption capacity) and phosphorus were determined.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 100, "end": 110}, {"text": "phosphorus", "start": 256, "end": 266}]}}, "schema": []}
{"input": "The chemical composition and functional properties of phosphorylated potato protein isolate (PP-PPI) were significantly different (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "The PP-PPI at pH 5. 2 was characterised by the highest content of all amino acids, whereas, PP-PPI under alkaline conditions (pH 10. 5) caused decrease in these compounds.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 70, "end": 81}]}}, "schema": []}
{"input": "PP-PPI at pH 8. 0 had the highest oil absorption capacity, emulsion activity and foam capacity, whereas, PP-PPI at pH 10. 5 had the highest WAC.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of the odour-active cyclic diketone cis-2, 6-dimethyl-1, 4-cyclohexanedione in roasted Arabica coffee brew.", "output": {"entities": {"chemical": [{"text": "cis-2, 6-dimethyl-1, 4-cyclohexanedione", "start": 51, "end": 90}]}}, "schema": []}
{"input": "We investigated odour-active trace compounds in roasted Brazilian Arabica coffee.", "output": {"entities": {}}, "schema": []}
{"input": "Aroma dilution extract analysis (AEDA) applied to the volatile oil extracted from roasted coffee brew revealed 34 odour-active compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Among these, a pungent-smelling unknown odour-active compound was determined.", "output": {"entities": {}}, "schema": []}
{"input": "The volatile oil was fractioned by silica gel column chromatography.", "output": {"entities": {"chemical": [{"text": "silica gel", "start": 35, "end": 45}]}}, "schema": []}
{"input": "Gas chromatography-olfactometry (GC-O) and multidimensional gas chromatography-mass spectrometry (MDGC-MS) of the fraction which contained a significant amount of the target unknown compound revealed the cyclic 1, 4-diketone, cis-2, 6-dimethyl-1, 4-cyclohexanedione, which had a pungent odour, and was thus first identified in roasted coffee.", "output": {"entities": {"chemical": [{"text": "cis-2, 6-dimethyl-1, 4-cyclohexanedione", "start": 226, "end": 265}]}}, "schema": []}
{"input": "Model experiments revealed that cis-2, 6-dimethyl-1, 4-cyclohexanedione was formed via thermal degradation of sugars, especially monosaccharides, under alkaline conditions.", "output": {"entities": {"chemical": [{"text": "cis-2, 6-dimethyl-1, 4-cyclohexanedione", "start": 32, "end": 71}, {"text": "sugars", "start": 110, "end": 116}, {"text": "monosaccharides", "start": 129, "end": 144}]}}, "schema": []}
{"input": "Further, we demonstrated that 2-hydroxy-3-pentanone and 1-hydroxy-2-propanone, thermal degradation products of monosaccharides, were closely related to the formation of cis-2, 6-dimethyl-1, 4-cyclohexanedione.", "output": {"entities": {"chemical": [{"text": "2-hydroxy-3-pentanone", "start": 30, "end": 51}, {"text": "1-hydroxy-2-propanone", "start": 56, "end": 77}, {"text": "monosaccharides", "start": 111, "end": 126}, {"text": "cis-2, 6-dimethyl-1, 4-cyclohexanedione", "start": 169, "end": 208}]}}, "schema": []}
{"input": "Determination of major phlorotannins in Eisenia bicyclis using hydrophilic interaction chromatography: seasonal variation and extraction characteristics.", "output": {"entities": {"chemical": [{"text": "phlorotannins", "start": 23, "end": 36}]}}, "schema": []}
{"input": "In this study, a hydrophilic interaction chromatography (HILIC) condition was developed for the simultaneous determination of five major phlorotannins from an extract of Eisenia bicyclis (Kjellman) Setchell with good linearity (r (2) > 0. 999).", "output": {"entities": {"chemical": [{"text": "phlorotannins", "start": 137, "end": 150}]}}, "schema": []}
{"input": "Based on this method, the seasonal variations and extraction characteristics, in terms of total extraction yield and the content of the phlorotannins, were investigated under various extraction conditions.", "output": {"entities": {"chemical": [{"text": "phlorotannins", "start": 136, "end": 149}]}}, "schema": []}
{"input": "In results, the yields and phlorotannins were increased two-to-four times in summer (June-October) and then, were decreased to normal levels in winter (November-March).", "output": {"entities": {"chemical": [{"text": "phlorotannins", "start": 27, "end": 40}]}}, "schema": []}
{"input": "In the extraction of E. bicyclis, ethanol percentage in water, extraction time and washing time significantly affected the yield of the extract and the phlorotannins, whereas the temperature and the sample/solvent ratio impacted the extraction to a lesser degree.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 34, "end": 41}, {"text": "phlorotannins", "start": 152, "end": 165}]}}, "schema": []}
{"input": "These results will be useful information in the application of this macroalga in the commercial areas related to nutraceuticals, pharmaceuticals, and cosmeceuticals.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of dietary carnosic acid on the fatty acid profile and flavour stability of meat from fattening lambs.", "output": {"entities": {"chemical": [{"text": "carnosic acid", "start": 18, "end": 31}, {"text": "fatty acid", "start": 39, "end": 49}]}}, "schema": []}
{"input": "Thirty-two lambs were fed with barley straw supplemented by a concentrate alone, or a concentrate enriched with either vitamin E (VITE006: 0. 6 g kg (-1) feed concentrate) or carnosic acid (CARN006: 0. 6 g kg (-1) feed concentrate; or CARN012: 1. 2 g kg (-1) feed concentrate).", "output": {"entities": {"chemical": [{"text": "vitamin E", "start": 119, "end": 128}, {"text": "VITE006", "start": 130, "end": 137}, {"text": "carnosic acid", "start": 175, "end": 188}, {"text": "CARN006", "start": 190, "end": 197}, {"text": "CARN012", "start": 235, "end": 242}]}}, "schema": []}
{"input": "In order to elucidate the influence of the dietary supplementation of carnosic compared with a reference diet antioxidant (vitamin E), the animals were slaughtered and the longissimus thoracis were lyophilised to determine the FAs profile and the phenolic compounds.", "output": {"entities": {"chemical": [{"text": "vitamin E", "start": 123, "end": 132}, {"text": "FAs", "start": 227, "end": 230}, {"text": "phenolic", "start": 247, "end": 255}]}}, "schema": []}
{"input": "In addition, longissimus lumborum slices were stored in a modified atmosphere package for 3 days and then grilled to determine volatile compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary carnosic acid did not modify the FAs profile, but had a clear effect on the production of volatile compounds, in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "carnosic acid", "start": 8, "end": 21}, {"text": "FAs", "start": 41, "end": 44}]}}, "schema": []}
{"input": "These results have implications for the food industry, since dietary carnosic acid seems to extend the shelf life of lamb meat.", "output": {"entities": {"chemical": [{"text": "carnosic acid", "start": 69, "end": 82}]}}, "schema": []}
{"input": "Innovative microwave-assisted hydrolysis of ellagitannins and quantification as ellagic acid equivalents.", "output": {"entities": {"chemical": [{"text": "ellagic acid", "start": 80, "end": 92}]}}, "schema": []}
{"input": "The health-promoting effects of ellagic acid and its intestinal degradation products are well-known.", "output": {"entities": {"chemical": [{"text": "ellagic acid", "start": 32, "end": 44}]}}, "schema": []}
{"input": "In plants, ellagic acid mainly appears in the form of its precursors, the so-called ellagitannins.", "output": {"entities": {"chemical": [{"text": "ellagic acid", "start": 11, "end": 23}]}}, "schema": []}
{"input": "Therefore, determination of total ellagic acid content has been accomplished by cleaving ellagitannins with high temperatures and strong acids.", "output": {"entities": {"chemical": [{"text": "ellagic acid", "start": 34, "end": 46}]}}, "schema": []}
{"input": "Microwave-assisted extraction (MAE) has been shown to be a very effective and quick extraction technique.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to establish an MAE-based method for a rapid hydrolysis of ellagitannins and to compare this method with a conventional acid hydrolysis.", "output": {"entities": {}}, "schema": []}
{"input": "For this purpose, strawberries (Fragaria x ananassa), which have been identified as a major source of ellagitannins in human diet, were used as a model.", "output": {"entities": {}}, "schema": []}
{"input": "The newly developed MAE method was quicker, less chemical-consuming and more effective in hydrolysing ellagitannins.", "output": {"entities": {}}, "schema": []}
{"input": "Thermal degradation kinetics of xanthophylls from blood orange in model and real food systems.", "output": {"entities": {}}, "schema": []}
{"input": "Thermal degradation kinetics of the major blood orange xanthophylls (cis-violaxanthin, lutein, beta-cryptoxanthin, zeaxanthin and cis-antheraxanthin) were investigated at 45, 60, 75, and 90 degrees C in real juice and three model systems formulated to evaluate the impact of xanthophyll form (esterified or free) and pH (acid or neutral).", "output": {"entities": {"chemical": [{"text": "cis-violaxanthin", "start": 69, "end": 85}, {"text": "lutein", "start": 87, "end": 93}, {"text": "beta-cryptoxanthin", "start": 95, "end": 113}, {"text": "zeaxanthin", "start": 115, "end": 125}, {"text": "cis-antheraxanthin", "start": 130, "end": 148}]}}, "schema": []}
{"input": "Xanthophylls were monitored by HPLC-DAD and kinetic parameters were identified by non-linear regression.", "output": {"entities": {}}, "schema": []}
{"input": "A second order model best fitted the degradation curves of xanthophylls.", "output": {"entities": {}}, "schema": []}
{"input": "All degradation rates were the lowest in real juice.", "output": {"entities": {}}, "schema": []}
{"input": "Esterified forms were more stable than were the free forms.", "output": {"entities": {}}, "schema": []}
{"input": "In all acidic media, beta-cryptoxanthin exhibited the lowest degradation rates followed by lutein and zeaxanthin.", "output": {"entities": {"chemical": [{"text": "beta-cryptoxanthin", "start": 21, "end": 39}, {"text": "lutein", "start": 91, "end": 97}, {"text": "zeaxanthin", "start": 102, "end": 112}]}}, "schema": []}
{"input": "In comparison, the epoxy carotenoids cis-violaxanthin and cis-antheraxanthin degraded around 3-fold faster in their esterified form.", "output": {"entities": {"chemical": [{"text": "epoxy", "start": 19, "end": 24}, {"text": "cis-violaxanthin", "start": 37, "end": 53}, {"text": "cis-antheraxanthin", "start": 58, "end": 76}]}}, "schema": []}
{"input": "In their free form, cis-antheraxanthin degraded 30-fold faster while cis-violaxanthin instantaneously disappeared because of the isomerisation of its 5, 6-epoxy groups into 5, 8-epoxy.", "output": {"entities": {"chemical": [{"text": "cis-antheraxanthin", "start": 20, "end": 38}, {"text": "cis-violaxanthin", "start": 69, "end": 85}, {"text": "5, 6-epoxy", "start": 150, "end": 160}, {"text": "5, 8-epoxy", "start": 173, "end": 183}]}}, "schema": []}
{"input": "By contrast, in neutral medium, free epoxy-xanthophylls were about 2-fold more stable than were the free hydroxy xanthophylls lutein, zeaxanthin and beta-cryptoxanthin.", "output": {"entities": {"chemical": [{"text": "epoxy", "start": 37, "end": 42}, {"text": "hydroxy", "start": 105, "end": 112}, {"text": "lutein", "start": 126, "end": 132}, {"text": "zeaxanthin", "start": 134, "end": 144}, {"text": "beta-cryptoxanthin", "start": 149, "end": 167}]}}, "schema": []}
{"input": "Kinetic behaviours of xanthophylls were closely dependent on their chemical structures.", "output": {"entities": {}}, "schema": []}
{"input": "Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 105, "end": 112}]}}, "schema": []}
{"input": "OBJECTIVE: To examine the effects of different coffee amounts on blood glucose and insulin concentrations of healthy volunteers, and to assess potential effect modification by sex and body mass index category.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 71, "end": 78}]}}, "schema": []}
{"input": "MATERIALS/METHODS: Thirty-three volunteers [16 female/17 male, 16 normal-weight and 17 overweight/obese, 27. 3 +/- 7. 2 (19-44) y] took part in this randomized, crossover study.", "output": {"entities": {}}, "schema": []}
{"input": "Iota n the morning of each experimental day volunteers received a standardized meal along with 200mL of water or instant coffee containing either 3 or 6mg of caffeine/kg body weight.", "output": {"entities": {"chemical": [{"text": "caffeine", "start": 158, "end": 166}]}}, "schema": []}
{"input": "Blood samples were obtained and analyzed for glucose and insulin concentrations in the fasting state, immediately after meal/drink consumption and at standard time points for the next 3h thereafter.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 45, "end": 52}]}}, "schema": []}
{"input": "RESULTS: Coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Glucose incremental area under the curve (IAUC) was significantly different between interventions (P =. 009) with both coffee amounts inducing a greater area compared to water.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (PIAUC =. 05) and overweight/obese participants (PIAUC =. 03).", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, coffee, mainly the 6mg dose, could be lowering insulin concentrations the first 30min after its consumption compared to water in men and overweight/obese participants.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: Coffee exerts an acute effect on postprandial glucose and insulin concentrations.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 59, "end": 66}]}}, "schema": []}
{"input": "This effect may be modified by sex and overweight/obese status.", "output": {"entities": {}}, "schema": []}
{"input": "Future research is necessary to elucidate underlying mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, preliminary structure-activity relationships, and in vitro biological evaluation of 6-aryl-3-amino-thieno [2, 3-b] pyridine derivatives as potential anti-inflammatory agents.", "output": {"entities": {"chemical": [{"text": "6-aryl-3-amino-thieno [2, 3-b] pyridine", "start": 95, "end": 134}]}}, "schema": []}
{"input": "In our previous study, a series of 6-aryl-3-amino-thieno [2, 3-b] pyridine derivatives exhibited potent antiproliferative activities and an unique hepatocellular carcinoma (HCC)-specific anticancer activity was also observed.", "output": {"entities": {"chemical": [{"text": "6-aryl-3-amino-thieno [2, 3-b] pyridine", "start": 35, "end": 74}]}}, "schema": []}
{"input": "In further anti-inflammatory research, thienopyridine derivative 1a showed potent inhibition of nitric oxide (NO) production.", "output": {"entities": {"chemical": [{"text": "thienopyridine", "start": 39, "end": 53}, {"text": "nitric oxide", "start": 96, "end": 108}, {"text": "NO", "start": 110, "end": 112}]}}, "schema": []}
{"input": "So a series of thienopyridine analogues of 1a were synthesized and evaluated for anti-inflammatory activities.", "output": {"entities": {"chemical": [{"text": "thienopyridine", "start": 15, "end": 29}]}}, "schema": []}
{"input": "The structure-activity relationships (SARs) revealed that the most potent analogues 1f and 1o were identified as potent inhibitors of NO production with IC50 values of 3. 30 and 3. 24 mu M, respectively.", "output": {"entities": {"chemical": [{"text": "NO", "start": 134, "end": 136}]}}, "schema": []}
{"input": "These results suggest that these 6-aryl-3-amino-thieno [2, 3-b] pyridine derivatives might potentially constitute a novel class of anti-inflammatory agents, which require further studies.", "output": {"entities": {"chemical": [{"text": "6-aryl-3-amino-thieno [2, 3-b] pyridine", "start": 33, "end": 72}]}}, "schema": []}
{"input": "Involvement of mu-opioid receptors in antinociceptive action of botulinum toxin type A.", "output": {"entities": {}}, "schema": []}
{"input": "Botulinum toxin A (BTX-A) is approved for treatment of chronic migraine and has been investigated in various other painful conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Recent evidence demonstrated retrograde axonal transport and suggested the involvement of CNS in antinociceptive effect of BTX-A.", "output": {"entities": {}}, "schema": []}
{"input": "However, the mechanism of BTX-A central antinociceptive action is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we investigated the potential role of opioid receptors in BTX-A' s antinociceptive activity.", "output": {"entities": {}}, "schema": []}
{"input": "In formalin-induced inflammatory pain we assessed the effect of opioid antagonists on antinociceptive activity of BTX-A.", "output": {"entities": {"chemical": [{"text": "formalin", "start": 3, "end": 11}]}}, "schema": []}
{"input": "Naltrexone was injected subcutaneously (0. 02-2 mg/kg) or intrathecally (0. 07 mu g/10 mu l-350 mu g/10 mu l), while selective mu-antagonist naloxonazine was administered intraperitoneally (5 mg/kg) prior to nociceptive testing.", "output": {"entities": {"chemical": [{"text": "Naltrexone", "start": 0, "end": 10}, {"text": "naloxonazine", "start": 141, "end": 153}]}}, "schema": []}
{"input": "The influence of naltrexone (2 mg/kg s. c.) on BTX-A antinociceptive activity was examined additionally in an experimental neuropathy induced by partial sciatic nerve transection.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 17, "end": 27}]}}, "schema": []}
{"input": "To investigate the effects of naltrexone and BTX-A on neuronal activation in spinal cord, c-Fos expression was immunohistochemically examined in a model of formalin-induced pain.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 30, "end": 40}, {"text": "formalin", "start": 156, "end": 164}]}}, "schema": []}
{"input": "Antinociceptive effects of BTX-A in formalin and sciatic nerve transection-induced pain were prevented by non-selective opioid antagonist naltrexone.", "output": {"entities": {"chemical": [{"text": "formalin", "start": 36, "end": 44}, {"text": "naltrexone", "start": 138, "end": 148}]}}, "schema": []}
{"input": "Similarly, BTX-A-induced pain reduction was abolished by low dose of intrathecal naltrexone and by selective mu-antagonist naloxonazine.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 81, "end": 91}, {"text": "naloxonazine", "start": 123, "end": 135}]}}, "schema": []}
{"input": "BTX-A-induced decrease in dorsal horn c-Fos expression was prevented by naltrexone.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 72, "end": 82}]}}, "schema": []}
{"input": "Prevention of BTX-A effects on pain and c-Fos expression by opioid antagonists suggest that the central antinociceptive action of BTX-A might be associated with the activity of endogenous opioid system (involving mu-opioid receptor).", "output": {"entities": {}}, "schema": []}
{"input": "These results provide first insights into the mechanism of BTX-A' s central antinociceptive activity.", "output": {"entities": {}}, "schema": []}
{"input": "Gap junction channels and hemichannels in the CNS: Regulation by signaling molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Coordinated interaction among cells is critical to develop the extremely complex and dynamic tasks performed by the central nervous system (CNS).", "output": {"entities": {}}, "schema": []}
{"input": "Cell synchronization is in part mediated by connexins and pannexins; two different protein families that form gap junction channels and hemichannels.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activities, hemichannels communicate intra-and extra-cellular compartments and serve as diffusional pathways for ions and small molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Cells in the CNS depend on paracrine/autocrine communication via several extracellular signaling molecules, such as, cytokines, growth factors, transmitters and free radical species to sense changes in microenvironment as well as to adapt to them.", "output": {"entities": {}}, "schema": []}
{"input": "These signaling molecules modulate crucial processes of the CNS, including, cellular migration and differentiation, synaptic transmission and plasticity, glial activation, cell viability and microvascular blood flow.", "output": {"entities": {}}, "schema": []}
{"input": "Gap junction channels and hemichannels are affected by different signaling transduction pathways triggered by these paracrine/autocrine signaling molecules.", "output": {"entities": {}}, "schema": []}
{"input": "Most of the modulatory effects induced by these signaling molecules are specific to the cell type and the connexin and pannexin subtype expressed in different brain areas.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we summarized and discussed most of the relevant and recently published information on the effects of signaling molecules on connexin or pannexin based channels and their possible relevance in CNS physiology and pathology.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Connexin based channels'.", "output": {"entities": {}}, "schema": []}
{"input": "How do in-vitro release profiles of nanosuspensions from Alzet (R) pumps correspond to the in-vivo situation?", "output": {"entities": {}}, "schema": []}
{"input": "A case study on radiolabeled fenofibrate.", "output": {"entities": {"chemical": [{"text": "radiolabeled fenofibrate", "start": 16, "end": 40}]}}, "schema": []}
{"input": "In research and development sufficiently high and constant plasma levels of drug candidates are often requested, but simple solutions of hydrophobic drugs delivered from the commonly used micro-osmotic pumps cannot meet these demands.", "output": {"entities": {}}, "schema": []}
{"input": "Nanosuspensions released from implanted osmotic devices can be a strategy to overcome this challenge but little is known about their pharmacokinetic behavior after subcutaneous application.", "output": {"entities": {}}, "schema": []}
{"input": "In the current study, four different nanosuspension formulations containing iodinated fenofibrate were prepared, physicochemically characterized and investigated concerning their in-vitro release kinetics from osmotic pumps.", "output": {"entities": {"chemical": [{"text": "iodinated fenofibrate", "start": 76, "end": 97}]}}, "schema": []}
{"input": "One nanosuspension of lower viscosity exhibited thereby an unexpectedly first order release kinetics, whereas the higher viscous counterpart was released in the expected zero-order manner.", "output": {"entities": {}}, "schema": []}
{"input": "To assess the relation of the in-vitro release kinetics to the in-vivo fate of nanosuspensions, various [(131) I] iodinated fenofibrate formulations were subcutaneously applied to mice.", "output": {"entities": {"chemical": [{"text": "[(131) I] iodinated fenofibrate", "start": 104, "end": 135}]}}, "schema": []}
{"input": "The biodistribution was followed by means of gamma-scintigraphy and gamma-scintillation.", "output": {"entities": {}}, "schema": []}
{"input": "Two different nanosuspensions released from osmotic pumps were compared to bolus injections of a nanosuspension and an organic drug solution.", "output": {"entities": {}}, "schema": []}
{"input": "The distribution and elimination of the bolus injected drug solution were almost completed within 48h.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, a long lasting (> 1week) depot at the injection site was formed by the bolus injected nanosuspension.", "output": {"entities": {}}, "schema": []}
{"input": "Ex vivo examination of the organs showed a sustained, but exponential decrease of the radiolabel concentration.", "output": {"entities": {}}, "schema": []}
{"input": "More constant drug levels in the organs were achieved within the nanosuspensions released from osmotic pumps.", "output": {"entities": {}}, "schema": []}
{"input": "The organ levels of [(131) I] labeled fenofibrate were found to be more constant in case of the pump with the higher viscous nanosuspension in contrast to the lower viscous counterpart.", "output": {"entities": {"chemical": [{"text": "[(131) I] labeled fenofibrate", "start": 20, "end": 49}]}}, "schema": []}
{"input": "However, the very different release profiles of the lower and higher viscous nanosuspension observed in-vitro were not observed in-vivo, as both pumps showed zero order release.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, nanosuspensions of poorly soluble compounds released from subcutaneously implanted osmotic pumps can be a suitable approach in pharmacokinetic studies.", "output": {"entities": {}}, "schema": []}
{"input": "Although the in-vivo release of nanosuspensions differed in the expected release profile from the in-vitro test results, these in-vitro release tests present a valuable tool for the pre-selection of suitable nanosuspension candidates.", "output": {"entities": {}}, "schema": []}
{"input": "Construction of block copolymers for the coordinated delivery of doxorubicin and magnetite nanocubes.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 65, "end": 76}, {"text": "magnetite", "start": 81, "end": 90}]}}, "schema": []}
{"input": "Multifunctional nanoparticles combine drug and imaging agent together to assign both therapeutic and diagnostic functions.", "output": {"entities": {}}, "schema": []}
{"input": "However, particle aggregation/dissociation and/or major differences in the bio-distribution and targeting capability of drugs and imaging probes are main obstacles for the efficient, coordinated delivery of multiple agents, unless the different agents can be tightly bound and well-protected during their circulation in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, we report the coordinated in vivo delivery of anti-cancer drugs and imaging agents by chemically loading doxorubicin and magnetite nanocubes (MNs) in the core of polymeric nanoparticles.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 120, "end": 131}, {"text": "magnetite", "start": 136, "end": 145}]}}, "schema": []}
{"input": "Living polymerization, nitroxide-mediated radical polymerization (NMP), was applied to construct the optimal polymers to co-deliver doxorubicin and MNs.", "output": {"entities": {"chemical": [{"text": "nitroxide", "start": 23, "end": 32}, {"text": "doxorubicin", "start": 132, "end": 143}]}}, "schema": []}
{"input": "The resulting diblock polymers consisted of one block with triethylene glycol brushes and another block with carboxylic acid groups to bind doxorubicin and Fe3O4 MNs.", "output": {"entities": {"chemical": [{"text": "triethylene glycol", "start": 59, "end": 77}, {"text": "carboxylic acid", "start": 109, "end": 124}, {"text": "doxorubicin", "start": 140, "end": 151}, {"text": "Fe3O4", "start": 156, "end": 161}]}}, "schema": []}
{"input": "The optimal polymer has narrow polydispersity (PDI = 1. 2) and high doxorubicin/MN loading (30wt.%/28wt.%).", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 68, "end": 79}]}}, "schema": []}
{"input": "Core-shell particles were obtained with good stability and a suitable particle size of ~ 100nm.", "output": {"entities": {}}, "schema": []}
{"input": "The doxorubicin and MNs loaded in this polymeric system showed highly coordinated bio-distribution in the balb/C mice model.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 4, "end": 15}]}}, "schema": []}
{"input": "This system may have important impact on the design of effective and stable dual-agent co-delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "PEGylation of interferon alpha 2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases.", "output": {"entities": {}}, "schema": []}
{"input": "The efficacy of protein-based therapeutics with indications in the treatment of lymphatic diseases is expected to be improved by enhancing lymphatic disposition.", "output": {"entities": {}}, "schema": []}
{"input": "This study was therefore aimed at examining whether PEGylation can usefully be applied to improve the lymphatic uptake of interferon alpha 2 and whether this ultimately translates into improved therapeutic efficacy against lymph-resident cancer.", "output": {"entities": {}}, "schema": []}
{"input": "The lymphatic pharmacokinetics of interferon alpha 2b (IFN, 19kDa) and PEGylated interferon alpha 2b (IFN-PEG12, 31kDa) or alpha 2a (IFN-PEG40, 60kDa) was examined in thoracic lymph duct cannulated rats.", "output": {"entities": {"chemical": [{"text": "PEG12", "start": 106, "end": 111}, {"text": "PEG40", "start": 137, "end": 142}]}}, "schema": []}
{"input": "IFN was poorly absorbed from the SC injection site (Fabs 36%) and showed little uptake into lymph after SC or IV administration (<= 1%).", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, IFN-PEG12 was efficiently absorbed from the SC injection site (Fabs 82%) and approximately 20% and 8% of the injected dose was recovered in thoracic lymph over 30h after SC or IV administration respectively.", "output": {"entities": {"chemical": [{"text": "PEG12", "start": 17, "end": 22}]}}, "schema": []}
{"input": "IFN-PEG40, however, was incompletely absorbed from the SC injection site (Fabs 23%) and showed similar lymphatic access after SC administration to IFN-PEG12 (21%).", "output": {"entities": {"chemical": [{"text": "PEG40", "start": 4, "end": 9}, {"text": "PEG12", "start": 151, "end": 156}]}}, "schema": []}
{"input": "The recovery of IFN-PEG40 in thoracic lymph after IV administration, however, was significantly greater (29%) when compared to IV IFN-PEG12.", "output": {"entities": {"chemical": [{"text": "PEG12", "start": 134, "end": 139}]}}, "schema": []}
{"input": "The anti-tumour efficacy of interferon against axillary metastases of a highly lymph-metastatic variant of human breast MDA-MB-231 carcinoma was significantly increased by SC administration of lymph-targeted IFN-PEG12 when compared to the administration of IFN on the ipsilateral side to the axillary metastasis.", "output": {"entities": {"chemical": [{"text": "PEG12", "start": 212, "end": 217}]}}, "schema": []}
{"input": "Optimal PEGylation may therefore represent a viable approach to improving the lymphatic disposition and efficacy of therapeutic proteins against lymphatic diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative stress responses in zebrafish Danio rerio after subchronic exposure to atrazine.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Atrazine is one of the most used pesticides all over the world and it is frequently detected in surface water.", "output": {"entities": {"chemical": [{"text": "Atrazine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The aim of this study was to investigate if zebrafish exposure to atrazine could induce oxidative stress and changes in detoxifying system.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Juvenile fish were exposed to sublethal concentrations of 0. 3, 3, 30, or 90 mu gL (-1) for 28days.", "output": {"entities": {}}, "schema": []}
{"input": "The level of oxidized lipids increased in experimental groups exposed to atrazine at 30 and 90 mu gL (-1) compared to control.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 73, "end": 81}]}}, "schema": []}
{"input": "Activity of glutathione S-transferase decreased in group with the highest concentration compared to control.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 12, "end": 25}]}}, "schema": []}
{"input": "A significant decline was observed in catalase activity in all experimental groups compared to control.", "output": {"entities": {}}, "schema": []}
{"input": "Activity of superoxide dismutase increased only in experimental group exposed to atrazine at 30 mu gL (-1) compared to control.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 12, "end": 22}, {"text": "atrazine", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Activity of glutathione peroxidase and reductase (GR) increased in experimental groups exposed to atrazine at 0. 3 (only for GR activity) and 90 mu gL (-1) compared to control.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 12, "end": 23}, {"text": "atrazine", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Our results showed that atrazine exposure had profound influence on the oxidative stress markers and detoxifying enzyme of the exposed zebrafish.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 24, "end": 32}]}}, "schema": []}
{"input": "The changes in antioxidant enzyme activities could be an adaptive response to protect the fish from the atrazine-induced toxicity.", "output": {"entities": {"chemical": [{"text": "atrazine", "start": 104, "end": 112}]}}, "schema": []}
{"input": "The animal' s dignity in Swiss Animal Welfare Legislation-Challenges and opportunities.", "output": {"entities": {}}, "schema": []}
{"input": "The introduction of the animal' s dignity as a concern in animal welfare legislation in Switzerland is unique worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Naturally, this measure has raised hopes and fears in those concerned with animal welfare and animal use.", "output": {"entities": {}}, "schema": []}
{"input": "For the past several years, a lively debate has focused on the question of whether the addition is merely a declaration of intent or an explicit demand with, possibly, a profound impact on everyday practice.", "output": {"entities": {}}, "schema": []}
{"input": "What the implications may be in the latter case is not clear.", "output": {"entities": {}}, "schema": []}
{"input": "In the area of research, it has yet to be seen how this concept may be incorporated feasibly, for example, into the harm-benefit analysis, which is the prerequisite for the approval of an animal experiment.", "output": {"entities": {}}, "schema": []}
{"input": "It is foreseeable, therefore, that this addition might have direct implications on research.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, in the legislative text, there are some inconsistencies in wording, at least in the German version, that complicate interpretation.", "output": {"entities": {}}, "schema": []}
{"input": "This article provides a short overview of some aspects of the controversy, which is far from settled at this time.", "output": {"entities": {}}, "schema": []}
{"input": "The commentary will be restricted to the situation of experimental animals in Switzerland.", "output": {"entities": {}}, "schema": []}
{"input": "Quantum dots induced monocyte chemotactic protein-1 expression via MyD88-dependent Toll-like receptor signaling pathways in macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "Quantum dots (QDs) are nano-sized semiconductors.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, intratracheal instillation of QD705s induces persistent inflammation in mouse lungs.", "output": {"entities": {}}, "schema": []}
{"input": "In our present study, QD705-COOH and QD705-PEG activated NF-kappa B and increased monocyte chemotactic protein-1 (MCP-1) expression in macrophages RAW264. 7 via MyD88 dependent Toll-like receptor (TLR) signaling pathways.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 43, "end": 46}]}}, "schema": []}
{"input": "MyD88 is an adapter protein for most TLRs to activate NF-kappa B.", "output": {"entities": {}}, "schema": []}
{"input": "Silencing expression of MyD88 or p65 with siRNA or co-treatment with a NF-kappa B inhibitor tremendously abolished QD705s-induced NF-kappa B activity and MCP-1 expression.", "output": {"entities": {}}, "schema": []}
{"input": "The involved TLRs might locate either on the cell surface or inside of cells.", "output": {"entities": {}}, "schema": []}
{"input": "Co-treatment with a TLR4 inhibitor completely prevented MCP-1 induction by QD705-PEG.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 81, "end": 84}]}}, "schema": []}
{"input": "Nevertheless, QD705-COOH readily entered cells, and co-treatment with either inhibitors of endocytosis or intracellular TLRs prevented MCP-1 induction.", "output": {"entities": {"chemical": [{"text": "COOH", "start": 20, "end": 24}]}}, "schema": []}
{"input": "These findings indicate that, depending on their surface modification, OD705s activate MyD88 dependent-TLRs at the surface or inside of the cells, which is an important mechanism for nanoparticles-induced inflammatory responses.", "output": {"entities": {}}, "schema": []}
{"input": "But other MyD88-independent pathways may also involve in these responses.", "output": {"entities": {}}, "schema": []}
{"input": "Toxicity of thienopyridines on human neutrophil granulocytes and lymphocytes.", "output": {"entities": {"chemical": [{"text": "thienopyridines", "start": 12, "end": 27}]}}, "schema": []}
{"input": "Thienopyridines can cause neutropenia and agranulocytosis.", "output": {"entities": {"chemical": [{"text": "Thienopyridines", "start": 0, "end": 15}]}}, "schema": []}
{"input": "The aim of the current investigations was to compare cytotoxicity of ticlopidine, clopidogrel, clopidogrel carboxylate and prasugrel for human neutrophil granulocytes with the toxicity for lymphocytes and to investigate underlying mechanisms.", "output": {"entities": {"chemical": [{"text": "ticlopidine", "start": 69, "end": 80}, {"text": "clopidogrel", "start": 82, "end": 93}, {"text": "clopidogrel carboxylate", "start": 95, "end": 118}, {"text": "prasugrel", "start": 123, "end": 132}]}}, "schema": []}
{"input": "For granulocytes, clopidogrel, ticlopidine, clopidogrel carboxylate and prasugrel were concentration-dependently toxic starting at 10 mu M.", "output": {"entities": {"chemical": [{"text": "clopidogrel", "start": 18, "end": 29}, {"text": "ticlopidine", "start": 31, "end": 42}, {"text": "clopidogrel carboxylate", "start": 44, "end": 67}, {"text": "prasugrel", "start": 72, "end": 81}]}}, "schema": []}
{"input": "Cytotoxicity could be prevented by the myeloperoxidase inhibitor rutin, but not by the cytochrome P450 inhibitor ketoconazole.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 65, "end": 70}, {"text": "ketoconazole", "start": 113, "end": 125}]}}, "schema": []}
{"input": "All compounds were also toxic for lymphocytes, but cytotoxicity started at 100 mu M and could not be prevented by rutin or ketoconazole.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 114, "end": 119}, {"text": "ketoconazole", "start": 123, "end": 135}]}}, "schema": []}
{"input": "Granulocytes metabolized ticlopidine, clopidogrel, clopidogrel carboxylate and prasugrel, and metabolization was inhibited by rutin, but not by ketoconazole.", "output": {"entities": {"chemical": [{"text": "ticlopidine", "start": 25, "end": 36}, {"text": "clopidogrel", "start": 38, "end": 49}, {"text": "clopidogrel carboxylate", "start": 51, "end": 74}, {"text": "prasugrel", "start": 79, "end": 88}, {"text": "rutin", "start": 126, "end": 131}, {"text": "ketoconazole", "start": 144, "end": 156}]}}, "schema": []}
{"input": "Metabolism of these compounds by lymphocytes was much slower and could not be inhibited by ketoconazole or rutin.", "output": {"entities": {"chemical": [{"text": "ketoconazole", "start": 91, "end": 103}, {"text": "rutin", "start": 107, "end": 112}]}}, "schema": []}
{"input": "In neutrophils, all compounds investigated decreased the electrical potential across the inner mitochondrial membrane, were associated with cellular accumulation of ROS, mitochondrial loss of cytochrome c and induction of apoptosis starting at 10 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "All of these effects could be inhibited by rutin, but not by ketoconazole.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 43, "end": 48}, {"text": "ketoconazole", "start": 61, "end": 73}]}}, "schema": []}
{"input": "Similar findings were obtained in lymphocytes; but compared to neutrophils, the effects were detectable only at higher concentrations and were not inhibited by rutin.", "output": {"entities": {"chemical": [{"text": "rutin", "start": 160, "end": 165}]}}, "schema": []}
{"input": "In conclusion, ticlopidine, clopidogrel, clopidogrel carboxylate and prasugrel are toxic for both granulocytes and lymphocytes.", "output": {"entities": {"chemical": [{"text": "ticlopidine", "start": 15, "end": 26}, {"text": "clopidogrel", "start": 28, "end": 39}, {"text": "clopidogrel carboxylate", "start": 41, "end": 64}, {"text": "prasugrel", "start": 69, "end": 78}]}}, "schema": []}
{"input": "In granulocytes, cytotoxicity is more accentuated than in lymphocytes and depends on metabolization by myeloperoxidase.", "output": {"entities": {}}, "schema": []}
{"input": "These findings suggest a mitochondrial mechanism for cytotoxicity for both myeloperoxidase-associated metabolites and, at higher concentrations, also for the parent compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Recombinant proteins that trigger production of antibodies recognizing botulinum neurotoxin while not possessing sequences of this toxin.", "output": {"entities": {}}, "schema": []}
{"input": "Sequences mimicking epitopes of pathogens can be used as effective tools for fast development and characterization of pathogen-specific antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "To demonstrate this, we used phage displays and isolated a number of short peptides mimicking epitopes of botulinum neurotoxin serotype A (BoNT/A).", "output": {"entities": {}}, "schema": []}
{"input": "Presented data suggest that some of these peptides mimic linear epitopes while others mimic structural epitopes of BoNT/A.", "output": {"entities": {}}, "schema": []}
{"input": "All tested peptides retained their ability to be recognized by BoNT/A-specific antibodies even when transferred into new carrier proteins.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrated how such new hybrids can be used for fast conversion of pathogen-specific serums into panels of mono-epitope specific antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "We also demonstrated that hybrid proteins carrying multiple isolated peptides can be used as a substitute for BoNT/A in immunization studies and triggers production of BoNT/A-specific antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and antifungal activity of C-21 steroids with an aromatic D ring.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Six analogues of salpichrolides with a simplified side chain (6-11) were synthesized using a new methodology to obtain steroids with an aromatic D-ring.", "output": {"entities": {"chemical": [{"text": "salpichrolides", "start": 17, "end": 31}, {"text": "steroids", "start": 119, "end": 127}]}}, "schema": []}
{"input": "The key step was the elimination of HBr in a vicinal dibromo D-homosteroid by treatment with 1, 4-diazabicyclo [2. 2. 2] octane (DABCO).", "output": {"entities": {"chemical": [{"text": "HBr", "start": 36, "end": 39}, {"text": "vicinal dibromo D-homosteroid", "start": 45, "end": 74}, {"text": "1, 4-diazabicyclo [2. 2. 2] octane", "start": 93, "end": 127}, {"text": "DABCO", "start": 129, "end": 134}]}}, "schema": []}
{"input": "All new compounds were completely characterized by 2D NMR techniques and tested on two fungal pathogenic species, Fusarium virguliforme and Fusarium solani.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and G o ttingen minipigs.", "output": {"entities": {"chemical": [{"text": "metoprolol", "start": 66, "end": 76}]}}, "schema": []}
{"input": "This work studied the buccal absorption of metoprolol in vitro, ex vivo and in vivo as a function of buffered pH at 7. 4, 8. 5, 9. 0 and 9. 5.", "output": {"entities": {"chemical": [{"text": "metoprolol", "start": 43, "end": 53}]}}, "schema": []}
{"input": "Permeability studies showed a correlation (r (2) = 0. 92) between in vitro TR146 cell culture and ex vivo porcine buccal mucosa in a modified Ussing chamber.", "output": {"entities": {}}, "schema": []}
{"input": "A higher apparent permeability was observed at higher pH values, i. e. the more compound that was unionised the higher the permeability.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo studies were conducted in anaesthetised G o ttingen mini-pigs.", "output": {"entities": {}}, "schema": []}
{"input": "A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Macroscopically, no local toxic effects were observed by visual inspection of mini-pig cheeks.", "output": {"entities": {}}, "schema": []}
{"input": "A very clear level C in vitro in vivo correlation (r (2) = 0. 98) was obtained between the observed in vitro permeabilities and the bioavailability observed in vivo, suggesting that the two in vitro models have good predictive power for drug delivery, which could be a useful tool for future formulation developments intended for buccal delivery.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of rolling friction on the shear behaviour of non-cohesive pharmaceutical granules-An experimental and numerical investigation.", "output": {"entities": {}}, "schema": []}
{"input": "Granule shear behaviour was investigated experimentally and numerically to evaluate the reliability of the numerical model.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, parameters affecting the ensuing flow regimes-elastic quasi-static and inertial non-collisional-were highlighted.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the influence of using the Lees-Edwards periodic boundary conditions or the standard boundary conditions was studied.", "output": {"entities": {}}, "schema": []}
{"input": "Experiments were performed with microcrystalline cellulose granules of three size distributions using the FT4 powder rheometer.", "output": {"entities": {}}, "schema": []}
{"input": "The numerical parameters, particle size, effective density, and particle stiffness were selected to match the experimental conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Experimentally, an unexpected particle size effect was evident where the resistance to shear increased with particle size.", "output": {"entities": {}}, "schema": []}
{"input": "Numerically, combining rolling friction and increased shear rate enabled a transition from the inertial non-collisional to the elastic quasi-static regime at a reduced sliding friction coefficient.", "output": {"entities": {}}, "schema": []}
{"input": "Presumably, this is an effect of increased particle overlap creating stronger contacts and facilitating force chain formation.", "output": {"entities": {}}, "schema": []}
{"input": "Both boundary conditions provided comparable results provided a correction of system size was made, where larger systems were required for the standard boundary conditions.", "output": {"entities": {}}, "schema": []}
{"input": "A satisfactory qualitative agreement between the experimentally and numerically determined yield loci emphasised the predictive capacity of the DEM.", "output": {"entities": {}}, "schema": []}
{"input": "Rolling friction was in addition concluded to be an essential model parameter for obtaining an improved quantitative agreement.", "output": {"entities": {}}, "schema": []}
{"input": "Gene silencing of TNF-alpha in a murine model of acute colitis using a modified cyclodextrin delivery system.", "output": {"entities": {}}, "schema": []}
{"input": "Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the gastrointestinal tract.", "output": {"entities": {}}, "schema": []}
{"input": "The cytokine TNF-alpha (TNF-alpha) plays a pivotal role in mediating this inflammatory response.", "output": {"entities": {}}, "schema": []}
{"input": "RNA interference (RNAi) holds great promise for the specific and selective silencing of aberrantly expressed genes, such as TNF-alpha in IBD.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to investigate the efficacy of an amphiphilic cationic cyclodextrin (CD) vector for effective TNF-alpha siRNA delivery to macrophage cells and to mice with induced acute-colitis.", "output": {"entities": {}}, "schema": []}
{"input": "The stability of CD. siRNA was examined by gel electrophoresis in biorelevant media reflecting colonic fluids.", "output": {"entities": {}}, "schema": []}
{"input": "RAW264. 7 cells were transfected with CD. TNF-alpha siRNA, stimulated with lipopolysaccharide (LPS) and TNF-alpha and IL-6 responses were measured by PCR and ELISA.", "output": {"entities": {}}, "schema": []}
{"input": "Female C57BL/6 mice were exposed to dextran sodium sulphate (DSS) and treated by intrarectal administration with either CD. siRNA TNF-alpha or a control solution.", "output": {"entities": {"chemical": [{"text": "sodium sulphate", "start": 44, "end": 59}]}}, "schema": []}
{"input": "In vitro, siRNA in CD nanocomplexes remained intact and stable in both fed and fasted simulated colonic fluids.", "output": {"entities": {}}, "schema": []}
{"input": "RAW264. 7 cells transfected with CD. TNF-alpha siRNA and stimulated with LPS displayed a significant reduction in both gene and protein levels of TNF-alpha and IL-6.", "output": {"entities": {}}, "schema": []}
{"input": "CD. TNF-alpha siRNA-treated mice revealed a mild amelioration in clinical signs of colitis, but significant reductions in total colon weight and colonic mRNA expression of TNF-alpha and IL-6 compared to DSS-control mice were detected.", "output": {"entities": {}}, "schema": []}
{"input": "This data indicates the clinical potential of a local CD-based TNF-alpha siRNA delivery system for the treatment of IBD.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo sustained dermal delivery and pharmacokinetics of interferon alpha in biphasic vesicles after topical application.", "output": {"entities": {}}, "schema": []}
{"input": "Biphasic vesicles, a novel nanostructured lipid-based delivery system show potential for topical application of interferon alpha (IFN alpha) for the treatment of human papillomavirus (HPV) infections (anogenital warts).", "output": {"entities": {}}, "schema": []}
{"input": "Dermal delivery of IFN alpha encapsulated in biphasic vesicles (BPV-IFN alpha), applied topically to the skin, was characterized in a guinea pig model.", "output": {"entities": {}}, "schema": []}
{"input": "BPV-IFN alpha (1g, 2MIU/g) was topically applied either as a single or multiple treatments on the skin of guinea pigs.", "output": {"entities": {}}, "schema": []}
{"input": "As a comparison with currently used regimens, IFN alpha solution was administered intravenously or intradermally.", "output": {"entities": {}}, "schema": []}
{"input": "Skin and serum samples were collected over 96h, IFN alpha levels were determined by an antiviral assay, and half-life (t1/2) and elimination (k) rates were calculated.", "output": {"entities": {}}, "schema": []}
{"input": "Topical BPV-IFN alpha treatment resulted in maximum skin levels (about 100, 000U/100cm (2)) of IFN alpha within 6h and maintained for 72-96h.", "output": {"entities": {}}, "schema": []}
{"input": "Clearance from the skin after intradermal injections was initially fast (t1/2 0. 62h, k 1. 1179h (-1)), followed by a slower steady decrease after 6h.", "output": {"entities": {}}, "schema": []}
{"input": "After intravenous and intradermal administration, IFN alpha was rapidly cleared from the serum, t1/2 0. 75h, k 0. 9271h (-1) and t1/2 1. 28h, k 0. 5421h (-1), respectively, whereas after topical application, IFN alpha levels remained below 100U/mL.", "output": {"entities": {}}, "schema": []}
{"input": "Topical application of BPV-IFN alpha resulted in sustained delivery of biologically active IFN alpha locally into skin with minimal systemic exposure.", "output": {"entities": {}}, "schema": []}
{"input": "DNA barcoding in plants: Evolution and applications of in silico approaches and resources.", "output": {"entities": {}}, "schema": []}
{"input": "Bioinformatics has played an important role in the analysis of DNA barcoding data.", "output": {"entities": {}}, "schema": []}
{"input": "The process of DNA barcoding initially involves the available data collection from the existing databases.", "output": {"entities": {}}, "schema": []}
{"input": "Many databases have been developed in recent years, e. g. MMDBD [Medicinal Materials DNA Barcode Database], BioBarcode, etc.", "output": {"entities": {}}, "schema": []}
{"input": "In case of non-availability of sequences, sequencing has to be done in vitro for which a recently developed software ecoPrimers can be helpful.", "output": {"entities": {}}, "schema": []}
{"input": "This is followed by multiple sequence alignment.", "output": {"entities": {}}, "schema": []}
{"input": "Further, basic sequence statistics computation and phylogenetic analysis can be performed by MEGA and PHYLIP/PAUP tools respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Some of the recent tools for in silico and statistical analysis specifically designed for barcoding viz.", "output": {"entities": {}}, "schema": []}
{"input": "CAOS (Character Based DNA Barcoding), BRONX (DNA Barcode Sequence Identification Incorporating Taxonomic Hierarchy and within Taxon Variability), Spider (Analysis of species identity and evolution, particularly DNA barcoding), jMOTU and Taxonerator (Turning DNA Barcode Sequences into Annotated OTUs), OTUbase (Analysis of OTU data and taxonomic data), SAP (Statistical Assignment Package), etc. have been discussed and analysed in this review.", "output": {"entities": {}}, "schema": []}
{"input": "The paper presents a comprehensive overview of the various in silico methods, tools, softwares and databases used for DNA barcoding of plants.", "output": {"entities": {}}, "schema": []}
{"input": "Structural Basis for the ATP-Induced Isomerization of Kinesin.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 25, "end": 28}]}}, "schema": []}
{"input": "Kinesin superfamily proteins (KIFs) are microtubule-based molecular motors driven by the energy derived from the hydrolysis of ATP.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 127, "end": 130}]}}, "schema": []}
{"input": "Previous studies have revealed that the ATP binding step is crucial both for the power stroke to produce motility and for the inter-domain regulation of ATPase activity to guarantee the processive movement of dimeric KIFs.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 40, "end": 43}]}}, "schema": []}
{"input": "Here, we report the first crystal structure of KIF4 complexed with the non-hydrolyzable ATP analog, AMPPNP (adenylyl imidodiphosphate), at 1. 7 A resolution.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 88, "end": 91}, {"text": "AMPPNP", "start": 100, "end": 106}, {"text": "adenylyl imidodiphosphate", "start": 108, "end": 133}]}}, "schema": []}
{"input": "By combining our structure with previously solved KIF1A structures complexed with two ATP analogs, molecular snapshots during ATP binding reveal that the closure of the nucleotide-binding pocket during ATP binding is achieved by closure of the backdoor.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 86, "end": 89}, {"text": "ATP", "start": 126, "end": 129}, {"text": "nucleotide", "start": 169, "end": 179}, {"text": "ATP", "start": 202, "end": 205}]}}, "schema": []}
{"input": "Closure of the backdoor stabilizes two mobile regions, switch I and switch II, to generate the phosphate tube from which hydrolyzed phosphate is released.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 95, "end": 104}, {"text": "phosphate", "start": 132, "end": 141}]}}, "schema": []}
{"input": "Through the stabilization of switch II, the local conformational change at the catalytic center is further relayed to the neck-linker element that fully docks to the catalytic core to produce the power stroke.", "output": {"entities": {}}, "schema": []}
{"input": "Because the neck linker is a sole element that connects the partner heads in dimeric KIFs, this tight structural coordination between the catalytic center and neck linker enables inter-domain communication between the partner heads.", "output": {"entities": {}}, "schema": []}
{"input": "This study also revealed the putative microtubule-binding site of KIF4, thus providing structural insights that describe the specific binding of KIF4 to the microtubule.", "output": {"entities": {}}, "schema": []}
{"input": "A Two-State Cooperative Expansion Converts the Procapsid Shell of Bacteriophage T5 into a Highly Stable Capsid Isomorphous to the Final Virion Head.", "output": {"entities": {}}, "schema": []}
{"input": "Capsids of double-stranded DNA (dsDNA) bacteriophages initially assemble into compact procapsids, which undergo expansion upon the genome packaging.", "output": {"entities": {}}, "schema": []}
{"input": "This shell remodeling results from a structural rearrangement of head protein subunits.", "output": {"entities": {}}, "schema": []}
{"input": "It is a critical step in the capsid maturation pathway that yields final particles capable to withstand the huge internal pressure generated by the packed DNA.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report on the expansion process of the large capsid (T = 13) of bacteriophage T5.", "output": {"entities": {}}, "schema": []}
{"input": "We purified the intermediate prohead II form, which is competent for packaging the 121-kbp dsDNA genome, and we investigated its morphology and dimensions using cryo-electron microscopy and small-angle X-ray scattering.", "output": {"entities": {}}, "schema": []}
{"input": "Decreasing the pH or the ionic strength triggers expansion of prohead II, converting them into thinner and more faceted capsids isomorphous to the mature virion particles.", "output": {"entities": {}}, "schema": []}
{"input": "At low pH, prohead II expansion is a highly cooperative process lacking any detectable intermediate.", "output": {"entities": {}}, "schema": []}
{"input": "This two-state reorganization of the capsid lattice per se leads to a remarkable stabilization of the particle.", "output": {"entities": {}}, "schema": []}
{"input": "The melting temperature of expanded T5 capsid is virtually identical with that of more complex shells that are reinforced by inter-subunit cross-linking (HK97) or by additional cementing proteins (T4).", "output": {"entities": {}}, "schema": []}
{"input": "The T5 capsid with its \" simple \" two-state conversion thus appears to be a very attractive model for investigating the mechanism of the large-scale allosteric transition that takes place upon the genome packaging of dsDNA bacteriophages.", "output": {"entities": {}}, "schema": []}
{"input": "Achieving automated scorpion venom mass fingerprinting (VMF) in the nanogram range.", "output": {"entities": {}}, "schema": []}
{"input": "During the past decade mass spectrometry (MS) has become one of the major suitable techniques for peptide and protein analysis from animal venoms, not only to identify new toxins within these complex mixtures, but also for toxin structural studies.", "output": {"entities": {}}, "schema": []}
{"input": "The goal of the experiments presented here was to test the ultimate limit for producing scorpion venom mass fingerprinting (VMF; i. e. a comprehensive list of all masses in presence).", "output": {"entities": {}}, "schema": []}
{"input": "Thanks to recent developments in nano ultra high performance liquid chromatography (UHPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), we sought the experimental conditions for setting up an automated data acquisition workflow.", "output": {"entities": {}}, "schema": []}
{"input": "As the main result, we demonstrate the possibility to easily achieve VMF having in hand only tens of nanogram of venom.", "output": {"entities": {}}, "schema": []}
{"input": "ELISA on-line was also beneficial to monitor in the picogram range for toxin families using specific antisera raised against major toxins.", "output": {"entities": {}}, "schema": []}
{"input": "Oxysterols in cancer cell proliferation and death.", "output": {"entities": {"chemical": [{"text": "Oxysterols", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Oxysterols have been shown to interfere with proliferation and cause the death of many cancer cell types, such as leukaemia, glioblastoma, colon, breast and prostate cancer cells, while they have little or no effect on senescent cells.", "output": {"entities": {"chemical": [{"text": "Oxysterols", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The mechanisms by which oxysterols may influence proliferation are manifold: they control the transcription and the turnover of the key enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase, by binding to Insig-1, Insig-2 and liver X receptors.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 24, "end": 34}, {"text": "cholesterol", "start": 146, "end": 157}, {"text": "3-hydroxy-3-methylglutaryl CoA", "start": 169, "end": 199}]}}, "schema": []}
{"input": "Oxysterols are thought to be generated in proportion to the rate of cholesterol synthesis.", "output": {"entities": {"chemical": [{"text": "Oxysterols", "start": 0, "end": 10}, {"text": "cholesterol", "start": 68, "end": 79}]}}, "schema": []}
{"input": "Although there is no consensus about the mechanism by which these oxysterols are generated in vivo, it clearly has to be ubiquitous.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 66, "end": 76}]}}, "schema": []}
{"input": "The 25-and the 27-cholesterol hydroxylases, present in almost all tissues, are possible candidates.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 18, "end": 29}]}}, "schema": []}
{"input": "Cholesterol uptake from lipoproteins, intracellular vesicle transport and lipid transfer are also modified by oxysterols.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 0, "end": 11}, {"text": "oxysterols", "start": 110, "end": 120}]}}, "schema": []}
{"input": "Oxysterols interfere with ERK, hedgehog and wnt pathways of proliferation and differentiation.", "output": {"entities": {"chemical": [{"text": "Oxysterols", "start": 0, "end": 10}]}}, "schema": []}
{"input": "When administered in vitro to cancer cell lines, oxysterols invariably both slow down proliferation and provoke cell death.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 49, "end": 59}]}}, "schema": []}
{"input": "Perhaps is it sufficient to stop proliferation of a cancer to provoke its eradication.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the two facets of oxysterol action that seem important for cancer treatment, cytostaticity and cytotoxicity, will be discussed.", "output": {"entities": {"chemical": [{"text": "oxysterol", "start": 29, "end": 38}]}}, "schema": []}
{"input": "Angiotensin II upregulates KCa3. 1 channels and stimulates cell proliferation in rat cardiac fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "The proliferation of cardiac fibroblasts is implicated in the pathogenesis of myocardial remodeling and fibrosis.", "output": {"entities": {}}, "schema": []}
{"input": "Intermediate-conductance calcium-activated K (+) channels (KCa3. 1 channels) have important roles in cell proliferation.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 25, "end": 32}, {"text": "K (+)", "start": 43, "end": 48}]}}, "schema": []}
{"input": "However, it is unknown whether angiotensin II (Ang II), a potent profibrotic molecule, would regulate KCa3. 1 channels in cardiac fibroblasts and participate in cell proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we investigated whether KCa3. 1 channels were regulated by Ang II, and how the channel activity mediated cell proliferation in cultured adult rat cardiac fibroblasts using electrophysiology and biochemical approaches.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that mRNA, protein, and current density of KCa3. 1 channels were greatly enhanced in cultured cardiac fibroblasts treated with 1 mu M Ang II, and the effects were countered by the angiotensin type 1 receptor (AT1R) blocker losartan, the p38-MAPK inhibitor SB203580, the ERK1/2 inhibitor PD98059, and the PI3K/Akt inhibitor LY294002.", "output": {"entities": {"chemical": [{"text": "SB203580", "start": 269, "end": 277}, {"text": "PD98059", "start": 300, "end": 307}, {"text": "LY294002", "start": 336, "end": 344}]}}, "schema": []}
{"input": "Ang II stimulated cell proliferation and the effect was antagonized by the KCa3. 1 blocker TRAM-34 and siRNA targeting KCa3. 1.", "output": {"entities": {"chemical": [{"text": "TRAM-34", "start": 91, "end": 98}]}}, "schema": []}
{"input": "In addition, Ang II-induced increase of KCa3. 1 expression was attenuated by transfection of activator protein-1 (AP-1) decoy oligodeoxynucleotides.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate for the first time that Ang II stimulates cell proliferation mediated by upregulating KCa3. 1 channels via interacting with the AT1R and activating AP-1 complex through ERK1/2, p38-MAPK and PI3K/Akt signaling pathways in cultured adult rat cardiac fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Androgen and estrogen play an important role in the pathogenesis of benign prostatic hyperplasia (BPH).", "output": {"entities": {"chemical": [{"text": "Androgen", "start": 0, "end": 8}, {"text": "estrogen", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Estrogen exerts its action through two distinct estrogen receptors (ERs) either ER-alpha or ER-beta.", "output": {"entities": {"chemical": [{"text": "Estrogen", "start": 0, "end": 8}, {"text": "estrogen", "start": 48, "end": 56}]}}, "schema": []}
{"input": "The phytoestrogenic property of silymarin (SIL) has been previously characterized.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, this study examined the protective effect of SIL against testosterone-induced BPH in rats.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 63, "end": 75}]}}, "schema": []}
{"input": "In an initial dose-response study, SIL in a dose of 50mg/kg was the most effective in preventing the rise in prostate weight, prostate weight/body weight ratio and histopathologic changes induced by testosterone.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 199, "end": 211}]}}, "schema": []}
{"input": "Testosterone significantly decreased ER-beta and increased ER-alpha and AR expressions as compared to the control group and these effects were significantly ameliorated by SIL.", "output": {"entities": {"chemical": [{"text": "Testosterone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "Furthermore, SIL significantly protected against testosterone-provoked decline in mRNA expression of P21 (WAF1/Cip1) and Bax/Bcl-xl ratio as well as caspase-3 activity.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 49, "end": 61}]}}, "schema": []}
{"input": "SIL minimized the number of proliferating cell nuclear antigen (PCNA) positive cells as compared to testosterone-treated group.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 100, "end": 112}]}}, "schema": []}
{"input": "Moreover, SIL significantly blunted the inducible NF-kappa B expression and restored the oxidative status to within normal values in the prostatic tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively these findings elucidate the effectiveness of SIL in preventing testosterone-induced BPH in rats.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 77, "end": 89}]}}, "schema": []}
{"input": "This could be attributed, at least partly, to its phytoestrogenic, pro-apoptotic and anti-oxidative properties.", "output": {"entities": {}}, "schema": []}
{"input": "Vanadium exposure-induced neurobehavioral alterations among Chinese workers.", "output": {"entities": {"chemical": [{"text": "Vanadium", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Vanadium-containing products are manufactured and widely used in the modern industry.", "output": {"entities": {"chemical": [{"text": "Vanadium", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Yet the neurobehavioral toxicity due to occupational exposure to vanadium remained elusive.", "output": {"entities": {"chemical": [{"text": "vanadium", "start": 65, "end": 73}]}}, "schema": []}
{"input": "This cross-sectional study was designed to examine the neurotoxic effects of occupational vanadium exposure.", "output": {"entities": {"chemical": [{"text": "vanadium", "start": 90, "end": 98}]}}, "schema": []}
{"input": "A total of 463 vanadium-exposed workers (exposed group) and 251 non-exposed workers (control group) were recruited from a Steel and Iron Group in Sichuan, China.", "output": {"entities": {"chemical": [{"text": "vanadium", "start": 15, "end": 23}, {"text": "Iron", "start": 132, "end": 136}]}}, "schema": []}
{"input": "A WHO-recommended neurobehavioral core test battery (NCTB) and event-related auditory evoked potentials test (P300) were used to assess the neurobehavioral functions of all study subjects.", "output": {"entities": {}}, "schema": []}
{"input": "A general linear model was used to compare outcome scores between the two groups while controlling for possible confounders.", "output": {"entities": {}}, "schema": []}
{"input": "The exposed group showed a statistically significant neurobehavioral alteration more than the control group in the NCTB tests.", "output": {"entities": {}}, "schema": []}
{"input": "The exposed workers also exhibited an increased anger-hostility, depression-dejection and fatigue-inertia on the profile of mood states (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Performances in the simple reaction time, digit span, benton visual retention and pursuit aiming were also poorer among exposed workers as compared to unexposed control workers (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Some of these poor performances in tests were also significantly related to workers' exposure duration.", "output": {"entities": {}}, "schema": []}
{"input": "P300 latencies were longer in the exposed group than in the control (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Longer mean reaction times and more counting errors were also found in the exposed workers (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Given the findings of our study and the limitations of neurobehavioral workplace testing, we found evidence of altered neurobehavioral outcomes by occupational exposure to vanadium.", "output": {"entities": {"chemical": [{"text": "vanadium", "start": 172, "end": 180}]}}, "schema": []}
{"input": "Health-related lipids components of sardine muscle as affected by photooxidation.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to evaluate the oxidative stability of sardine muscle lipids as related to the storage conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Whole sardines were stored at 4 degrees C for 4h under light exposure and at dark.", "output": {"entities": {}}, "schema": []}
{"input": "The lowest levels of peroxide value (PV), thiobarbituric acid reactive substances (TBARs), cholesterol oxidation products (COPs) and the highest level of polyunsaturated fatty acids (PUFAs) content, especially PUFA n-3, were found in the untreated sardines (time zero).", "output": {"entities": {"chemical": [{"text": "peroxide", "start": 21, "end": 29}, {"text": "thiobarbituric acid", "start": 42, "end": 61}, {"text": "cholesterol", "start": 91, "end": 102}, {"text": "polyunsaturated fatty acids", "start": 154, "end": 181}, {"text": "PUFAs", "start": 183, "end": 188}, {"text": "PUFA n-3", "start": 210, "end": 218}]}}, "schema": []}
{"input": "After light exposure, PUFA dramatically dropped (up to a 19% decrease) and a marked increase of PV (11. 8meq O2/kg fat), TBARs (3. 7mg MDA/kg meat) and COPs (3. 7 mu g/g muscle) was observed; under darkness, the values of the oxidation parameters were similar to those found in untreated sardines.", "output": {"entities": {"chemical": [{"text": "PUFA", "start": 22, "end": 26}, {"text": "O2", "start": 109, "end": 111}]}}, "schema": []}
{"input": "Although cholesterol oxidation rate did not exceed 0. 9%, further research is required about toxicity levels of the single COPs, to better understand if the COPs levels found in untreated and photoxidized muscle (0. 62-3. 72 mu g/g of muscle) do not represent a risk for human health.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 9, "end": 20}]}}, "schema": []}
{"input": "Safety of purified decolorized (low anthraquinone) whole leaf Aloe vera (L) Burm.", "output": {"entities": {"chemical": [{"text": "anthraquinone", "start": 36, "end": 49}]}}, "schema": []}
{"input": "f. juice in a 3-month drinking water toxicity study in F344 rats.", "output": {"entities": {}}, "schema": []}
{"input": "Decolorized (purified, low anthraquinone) whole leaf Aloe vera (L.) Burm.", "output": {"entities": {}}, "schema": []}
{"input": "f. juice was administered at concentrations of 0%, 0. 5%, 1% and 2% in the drinking water of F344Du (R) rats for 3months without any adverse effect.", "output": {"entities": {}}, "schema": []}
{"input": "The no-observed-adverse-effect level (NOAEL) in this study was considered to be > 2% w/v (> 1845mg/kg bodyweight/day for males and > 2920mg/kg bodyweight for females).", "output": {"entities": {}}, "schema": []}
{"input": "The test material contained total anthraquinones at < 0. 1parts per million.", "output": {"entities": {"chemical": [{"text": "anthraquinones", "start": 34, "end": 48}]}}, "schema": []}
{"input": "In the present study there was a complete absence of any histological alteration in samples from the cecum, colon (proximal, mid and distal regions).", "output": {"entities": {}}, "schema": []}
{"input": "Similar concentrations of non-decolorized (unpurified, high anthraquinone) Aloe vera extracts tested in other studies have resulted in an increased incidence and severity of diarrhea and colon adenomas and carcinomas.", "output": {"entities": {"chemical": [{"text": "anthraquinone", "start": 60, "end": 73}]}}, "schema": []}
{"input": "The results of this study supports the assertion that the high levels of anthraquinone present in orally administered, non-purified whole leaf Aloe vera extract may be responsible for the adverse effects observed on the colon.", "output": {"entities": {"chemical": [{"text": "anthraquinone", "start": 73, "end": 86}]}}, "schema": []}
{"input": "EROD activity induction in peripheral blood lymphocytes, liver and brain tissues of rats orally exposed to polycyclic aromatic hydrocarbons.", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbons", "start": 107, "end": 139}]}}, "schema": []}
{"input": "Little is known in terms of multi-matrix cytochrome P450 activity induction under repeated oral exposure to planar halogenated and polycyclic aromatic hydrocarbons (PHH, PAH).", "output": {"entities": {"chemical": [{"text": "halogenated and polycyclic aromatic hydrocarbons", "start": 115, "end": 163}, {"text": "PAH", "start": 170, "end": 173}]}}, "schema": []}
{"input": "In the present study, 60 rats were daily exposed, during 28days, to oral ingestion of a mixture consisting of phenanthrene, pyrene and benzo (a) pyrene at 0, 6 or 600 mu g/day.", "output": {"entities": {"chemical": [{"text": "phenanthrene", "start": 110, "end": 122}, {"text": "pyrene", "start": 124, "end": 130}, {"text": "benzo (a) pyrene", "start": 135, "end": 151}]}}, "schema": []}
{"input": "EROD activity, reflecting almost exclusively CYP1A1 and CYP1B1 activities, was measured in brain and liver microsomes as well as in peripheral blood lymphocytes (PBLs).", "output": {"entities": {"chemical": [{"text": "EROD", "start": 0, "end": 4}]}}, "schema": []}
{"input": "All induction kinetics could be appropriately fitted using logistic-like models.", "output": {"entities": {}}, "schema": []}
{"input": "After 28days of exposure to a 6 mu g/day dose, EROD activity was found to be 91, 152 and 94-fold increased in lymphocytes, liver and brain, respectively, compared to day 0.", "output": {"entities": {"chemical": [{"text": "EROD", "start": 47, "end": 51}]}}, "schema": []}
{"input": "Plateau activities could be appropriately fitted versus ingested doses using Hill or Michaelis-Menten models.", "output": {"entities": {}}, "schema": []}
{"input": "Correlations between matrices made it possible to conclude that EROD activity in PBL should be considered as a sensitive, convenient and non-destructive approach for (i) evaluating EROD activity in liver, which was found to represent 98% of the observed EROD activities in the three tested matrices and (ii) evaluating oral exposure of homogeneous groups of farm animals (race, diet) to CYP inducing PAH and PHH.", "output": {"entities": {"chemical": [{"text": "EROD", "start": 64, "end": 68}, {"text": "EROD", "start": 181, "end": 185}, {"text": "EROD", "start": 254, "end": 258}, {"text": "PHH", "start": 408, "end": 411}]}}, "schema": []}
{"input": "The Procrustean bed of EU food safety notifications via the Rapid Alert System for Food and Feed: Does one size fit all?", "output": {"entities": {}}, "schema": []}
{"input": "Previous reports demonstrated wide variations in contributions by EU Member States (MS) to the Rapid Alert System for Food and Feed (RASFF) especially for border notifications, emphasising that MS with major entry points play a vital role in ensuring that EU food imports meet EU standards.", "output": {"entities": {}}, "schema": []}
{"input": "To further explore the variation this paper aimed to examine notification practices among MS by comparing the levels of detection as a function of the total food imported and population.", "output": {"entities": {}}, "schema": []}
{"input": "RASFF notifications issued between 2003 and 2007 were analysed using descriptive statistics and network analysis for differences in notification practice between MS.", "output": {"entities": {}}, "schema": []}
{"input": "Major variations in contributions to the RASFF database were observed, which did not correlate with MS size or population.", "output": {"entities": {}}, "schema": []}
{"input": "For the key contrast of ratio:' border: non-border notifications', variations between 7%: 89% were observed for the average monthly contributions and, import tonnage per border notification revealed up to 129-fold differences between MS.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, wide variations in food safety practice exist between MS, including both number and type of contributions to the RASFF database, with some MS being relatively highly active in the key class of border notifications.", "output": {"entities": {}}, "schema": []}
{"input": "These findings should inform EU food safety enforcement policies and practices; and central resource allocations.", "output": {"entities": {}}, "schema": []}
{"input": "Novel chiral ferrocenylpyrazolo [1, 5-a] [1, 4] diazepin-4-one derivatives-Synthesis, characterization and inhibition against lung cancer cells.", "output": {"entities": {"chemical": [{"text": "ferrocenylpyrazolo [1, 5-a] [1, 4] diazepin-4-one", "start": 13, "end": 62}]}}, "schema": []}
{"input": "A series of novel 2-ferrocenyl-7-hydroxy-5-phenethyl-5, 6, 7, 8-tetrahydro-4H-pyrazolo [1, 5-a] [1, 4] diazepin-4-one derivatives with optical activity (2) was synthesized in the microwave-assisted condition and characterized by means of IR, (1) H NMR and mass spectroscopy, and furthermore confirmed by X-ray analysis of a representative compound (R)-2a.", "output": {"entities": {"chemical": [{"text": "2-ferrocenyl-7-hydroxy-5-phenethyl-5, 6, 7, 8-tetrahydro-4H-pyrazolo [1, 5-a] [1, 4] diazepin-4-one", "start": 18, "end": 117}, {"text": "(1) H", "start": 242, "end": 247}]}}, "schema": []}
{"input": "Preliminary biological evaluation showed that some compounds could suppress the growth of A549, H322 and H1299 lung cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Among the tested compounds, 2b-d were more effective and might perform their action through cell cycle arrest for A549 cell.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas these compounds inhibited growth of H1299 and H322 cells by inducing apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "The anti-tumor activities of these compounds were related to the nature of substituents in benzene moiety.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the results indicated also that compounds 2b-d possessed notable cytotoxicity and selectivity for A549 vs H1299 and H322 lung cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and evaluation of 7, 8-dehydrorutaecarpine derivatives as potential multifunctional agents for the treatment of Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "7, 8-dehydrorutaecarpine", "start": 28, "end": 52}]}}, "schema": []}
{"input": "A series of 7, 8-dehydrorutaecarpine derivatives were synthesized and characterized as potential multifunctional agents for treatment of Alzheimer' s disease (AD).", "output": {"entities": {"chemical": [{"text": "7, 8-dehydrorutaecarpine", "start": 12, "end": 36}]}}, "schema": []}
{"input": "All of these synthetic compounds showed high acetylcholinesterase (AChE) inhibitory activity with IC50 values ranged from 0. 60 to 196. 7 nM, and good selectivity for AChE over butyrylcholinesterase (BuChE) (125-to 3225-fold).", "output": {"entities": {}}, "schema": []}
{"input": "A Lineweaver-Burk plot and molecular modeling study indicated these compounds could bind to both catalytic active site and the peripheral anionic site of AChE.", "output": {"entities": {}}, "schema": []}
{"input": "Besides, compounds showed higher activity of inhibiting AChE-induced amyloid-beta (A beta) aggregation than curcumin, higher anti-oxidative activity than Trolox, and could also be good metal chelators.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 108, "end": 116}, {"text": "Trolox", "start": 154, "end": 160}]}}, "schema": []}
{"input": "Considering their low cytotoxicity, our results indicated that these derivatives provide good templates for developing new multifunctional agents for AD treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Inflammatory findings on species extrapolations: humans are definitely no 70-kg mice.", "output": {"entities": {}}, "schema": []}
{"input": "Modern toxicology has embraced in vitro methods, and major hopes are based on the Omics technologies and systems biology approaches they bring along (Hartung and McBride in ALTEX 28 (2): 83-93, 2011; Hartung et al. in ALTEX 29 (2): 119-28, 2012).", "output": {"entities": {}}, "schema": []}
{"input": "A culture of stringent validation has been developed for such approaches (Leist et al. in ALTEX 27 (4): 309-317, 2010; ALTEX 29 (4): 373-88, 2012a; Toxicol Res 1: 8-22, 2012b), while the quality and usefulness of animal experiments have been little scrutinized.", "output": {"entities": {}}, "schema": []}
{"input": "A new study (Seok et al. 2013) now shows the low predictivity of animal responses in the field of inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "These findings corroborate earlier findings from comparisons in the fields of neurodegeneration, stroke and sepsis.", "output": {"entities": {}}, "schema": []}
{"input": "The low predictivity of animal experiments in research areas allowing direct comparisons of mouse versus human data puts strong doubt on the usefulness of animal data as key technology to predict human safety.", "output": {"entities": {}}, "schema": []}
{"input": "mu-Opioid receptors in the stimulation of mesolimbic dopamine activity by ethanol and morphine in Long-Evans rats: a delayed effect of ethanol.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 53, "end": 61}, {"text": "ethanol", "start": 74, "end": 81}, {"text": "morphine", "start": 86, "end": 94}, {"text": "ethanol", "start": 135, "end": 142}]}}, "schema": []}
{"input": "RATIONALE: Naltrexone, a non-selective opioid antagonist, decreases the euphoria and positive subjective responses to alcohol in heavy drinkers.", "output": {"entities": {"chemical": [{"text": "Naltrexone", "start": 11, "end": 21}, {"text": "alcohol", "start": 118, "end": 125}]}}, "schema": []}
{"input": "It has been proposed that the mu-opioid receptor plays a role in ethanol reinforcement through modulation of ethanol-stimulated mesolimbic dopamine release.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 65, "end": 72}, {"text": "ethanol", "start": 109, "end": 116}, {"text": "dopamine", "start": 139, "end": 147}]}}, "schema": []}
{"input": "OBJECTIVES: To investigate the ability of naltrexone and beta-funaltrexamine, an irreversible mu-opioid specific antagonist, to inhibit ethanol-stimulated and morphine-stimulated mesolimbic dopamine release, and to determine whether opioid receptors on mesolimbic neurons contribute to these mechanisms.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 42, "end": 52}, {"text": "beta-funaltrexamine", "start": 57, "end": 76}, {"text": "ethanol", "start": 136, "end": 143}, {"text": "morphine", "start": 159, "end": 167}, {"text": "dopamine", "start": 190, "end": 198}]}}, "schema": []}
{"input": "METHODS: Ethanol-na i ve male Long Evans rats were given opioid receptor antagonists either intravenously, subcutaneously, or intracranially into the ventral tegmental area (VTA), followed by intravenous administration of ethanol or morphine.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 9, "end": 16}, {"text": "ethanol", "start": 222, "end": 229}, {"text": "morphine", "start": 233, "end": 241}]}}, "schema": []}
{"input": "We measured extracellular dopamine in vivo using microdialysis probes inserted into the nucleus accumbens shell (n = 114).", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 26, "end": 34}]}}, "schema": []}
{"input": "RESULTS: Administration of naltrexone (intravenously) and beta-funaltrexamine (subcutaneously), as well as intracranial injection of naltrexone into the VTA did not prevent the initiation of dopamine release by intravenous ethanol administration, but prevented it from being as prolonged.", "output": {"entities": {"chemical": [{"text": "naltrexone", "start": 27, "end": 37}, {"text": "beta-funaltrexamine", "start": 58, "end": 77}, {"text": "naltrexone", "start": 133, "end": 143}, {"text": "dopamine", "start": 191, "end": 199}, {"text": "ethanol", "start": 223, "end": 230}]}}, "schema": []}
{"input": "In contrast, morphine-stimulated mesolimbic dopamine release was effectively suppressed.", "output": {"entities": {"chemical": [{"text": "morphine", "start": 13, "end": 21}, {"text": "dopamine", "start": 44, "end": 52}]}}, "schema": []}
{"input": "CONCLUSIONS: Our results provide novel evidence that there are two distinct mechanisms that mediate ethanol-stimulated mesolimbic dopamine release (an initial phase and a delayed phase), and that opioid receptor activation is required to maintain the delayed-phase dopamine release.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 100, "end": 107}, {"text": "dopamine", "start": 130, "end": 138}, {"text": "dopamine", "start": 265, "end": 273}]}}, "schema": []}
{"input": "Moreover, mu-opioid receptors account for this delayed-phase dopamine response, and the VTA is potentially the site of action of this mechanism.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 61, "end": 69}]}}, "schema": []}
{"input": "We conclude that mu-opioid receptors play different roles in the mechanisms of stimulation of mesolimbic dopamine activity by ethanol and morphine.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 105, "end": 113}, {"text": "ethanol", "start": 126, "end": 133}, {"text": "morphine", "start": 138, "end": 146}]}}, "schema": []}
{"input": "Differential antidepressant-like response to lithium treatment between mouse strains: effects of sex, maternal care, and mixed genetic background.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 45, "end": 52}]}}, "schema": []}
{"input": "BACKGROUND: Lithium is a mood stabilizer with both antidepressant and antimanic properties, however its mechanism of action is unclear.", "output": {"entities": {"chemical": [{"text": "Lithium", "start": 12, "end": 19}]}}, "schema": []}
{"input": "Identifying the genetic factors that influence lithium' s therapeutic actions will be an important step to assist in identifying such mechanisms.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 47, "end": 54}]}}, "schema": []}
{"input": "We previously reported that lithium treatment of male mice has antidepressant-like effects in the C57BL/6J strain but that such effects were absent in the BALB/cJ strain.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 28, "end": 35}]}}, "schema": []}
{"input": "OBJECTIVES: This study aimed to assess the roles of both genetic and non-genetic factors such as sex and non-shared environmental conditions that may mediate differential behavioral responses to lithium.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 195, "end": 202}]}}, "schema": []}
{"input": "METHODS: Mice were treated with lithium for 10 days and then tested in the forced swim test followed by lithium discontinuation and retesting to assess effects of lithium withdrawal.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 32, "end": 39}, {"text": "lithium", "start": 104, "end": 111}, {"text": "lithium", "start": 163, "end": 170}]}}, "schema": []}
{"input": "We also assessed effects of sex and cross-fostering on lithium response between the C57BL/6J and BALB/cJ strains, and antidepressant-like effects of lithium in the hybrid CB6F1/J strain that is derived from C57BL/6J and BALB/cJ parental strains.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 55, "end": 62}, {"text": "lithium", "start": 149, "end": 156}]}}, "schema": []}
{"input": "RESULTS: Neither sex nor maternal care significantly influenced the differential antidepressant-like response to lithium.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 113, "end": 120}]}}, "schema": []}
{"input": "Withdrawal from lithium treatment reversed antidepressant-like effects in the C57BL/6J strain but had no effects in BALB/cJ mice.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 16, "end": 23}]}}, "schema": []}
{"input": "Lithium treatment did not result in antidepressant-like effects in the CB6F1/J strain.", "output": {"entities": {"chemical": [{"text": "Lithium", "start": 0, "end": 7}]}}, "schema": []}
{"input": "CONCLUSIONS: Genetic factors are likely primarily responsible for differential antidepressant-like effects of lithium in the C57BL/6J and BALB/cJ strains.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 110, "end": 117}]}}, "schema": []}
{"input": "Future studies identifying such genetic factors may help to elucidate the neurobiological mechanisms of lithium' s therapeutic actions.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 104, "end": 111}]}}, "schema": []}
{"input": "Alcohol dependent patients have weak negative rather than strong positive implicit alcohol associations.", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 0, "end": 7}, {"text": "alcohol", "start": 83, "end": 90}]}}, "schema": []}
{"input": "RATIONALE: Alcohol dependence is characterised by motivational conflict (or ambivalence) in controlled cognitive processes, but it is unclear if ambivalence also exists within automatic cognitive processes, and if ambivalence operates between controlled and automatic processes.", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 11, "end": 18}]}}, "schema": []}
{"input": "OBJECTIVE: To investigate ambivalence operating within and between controlled and automatic processes in alcohol dependence.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 105, "end": 112}]}}, "schema": []}
{"input": "METHOD: Alcohol-dependent patients who had recently completed inpatient alcohol detoxification (N = 47) and social drinking controls (N = 40) completed unipolar implicit association tests and self-report measures of alcohol approach and avoidance motivation and alcohol outcome expectancies.", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 8, "end": 15}, {"text": "alcohol", "start": 72, "end": 79}, {"text": "alcohol", "start": 216, "end": 223}, {"text": "alcohol", "start": 262, "end": 269}]}}, "schema": []}
{"input": "RESULTS: As predicted, both positive and negative alcohol outcome expectancies were stronger in alcohol-dependent patients compared to controls, indicative of ambivalence.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 50, "end": 57}, {"text": "alcohol", "start": 96, "end": 103}]}}, "schema": []}
{"input": "Groups did not differ on implicit alcohol-positive associations, but alcohol-dependent participants had significantly weaker alcohol-negative associations than controls.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 34, "end": 41}, {"text": "alcohol", "start": 69, "end": 76}, {"text": "alcohol", "start": 125, "end": 132}]}}, "schema": []}
{"input": "Regression analyses revealed that implicit negative associations accounted for unique variance in group membership after controlling for alcohol outcome expectancies.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 137, "end": 144}]}}, "schema": []}
{"input": "CONCLUSIONS: Our findings demonstrate that alcohol dependent patients possess weak automatic alcohol-negative associations but not strong automatic alcohol-positive associations, and they suggest the presence of conflict between controlled and automatic processes with regard to negative alcohol cognitions.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 43, "end": 50}, {"text": "alcohol", "start": 93, "end": 100}, {"text": "alcohol", "start": 148, "end": 155}, {"text": "alcohol", "start": 288, "end": 295}]}}, "schema": []}
{"input": "Simultaneous effects of two fungicides (copper and dimethomorph) on their phytoremediation using Lemna minor.", "output": {"entities": {"chemical": [{"text": "copper", "start": 40, "end": 46}, {"text": "dimethomorph", "start": 51, "end": 63}]}}, "schema": []}
{"input": "Effects of two fungicides, copper and dimethomorph ((E, Z) 4-[3-(4-chlorophenyl)-3-(3-4dimethoxyphenyl) acryloyl] morpholine) on Lemna minor growth and phytoremediation were evaluated.", "output": {"entities": {"chemical": [{"text": "copper", "start": 27, "end": 33}, {"text": "dimethomorph", "start": 38, "end": 50}, {"text": "(E, Z) 4-[3-(4-chlorophenyl)-3-(3-4dimethoxyphenyl) acryloyl] morpholine", "start": 52, "end": 124}]}}, "schema": []}
{"input": "The toxicity of copper and dimethomorph alone and in combination, was assessed by growth inhibition of L. minor cultures after 96 and 168 h.", "output": {"entities": {"chemical": [{"text": "copper", "start": 16, "end": 22}, {"text": "dimethomorph", "start": 27, "end": 39}]}}, "schema": []}
{"input": "Copper had a severe impact on growth (max. inhibition: 90% at 1, 000 mu g L (-1)) while dimethomorph (as pure ingredient or formulated as Forum) did not (inhibition < 45% at 1, 000 mu g L (-1)) after 168 h of treatment.", "output": {"entities": {"chemical": [{"text": "Copper", "start": 0, "end": 6}, {"text": "dimethomorph", "start": 88, "end": 100}, {"text": "Forum", "start": 138, "end": 143}]}}, "schema": []}
{"input": "When both chemicals were combined, synergism was observed after 96 h of exposure to copper and Forum.", "output": {"entities": {"chemical": [{"text": "copper", "start": 84, "end": 90}, {"text": "Forum", "start": 95, "end": 100}]}}, "schema": []}
{"input": "However, this interaction was a simple additivity after 168 h.", "output": {"entities": {}}, "schema": []}
{"input": "Additivity was also observed when the pure active ingredient (dimethomorph) replaced Forum in the mixture of copper and dimethomorph at 96 and 168 h.", "output": {"entities": {"chemical": [{"text": "dimethomorph", "start": 62, "end": 74}, {"text": "Forum", "start": 85, "end": 90}, {"text": "copper", "start": 109, "end": 115}, {"text": "dimethomorph", "start": 120, "end": 132}]}}, "schema": []}
{"input": "L. minor showed an excellent performance in removing copper from the medium since after 96 h, 36, 60, and 76% removal were reached for 10, 20, and 30 mu g L (-1) of Cu respectively.", "output": {"entities": {"chemical": [{"text": "copper", "start": 53, "end": 59}, {"text": "Cu", "start": 165, "end": 167}]}}, "schema": []}
{"input": "Copper accumulated in the plants.", "output": {"entities": {"chemical": [{"text": "Copper", "start": 0, "end": 6}]}}, "schema": []}
{"input": "The removal of copper increased with Forum concentration.", "output": {"entities": {"chemical": [{"text": "copper", "start": 15, "end": 21}, {"text": "Forum", "start": 37, "end": 42}]}}, "schema": []}
{"input": "After 96 h copper (10 mu g L (-1) initial concentration) elimination increased from 36. 39 +/- 5. 86-60. 70 +/- 6. 06% when Forum concentration increased from 0 to 500 mu g L (-1).", "output": {"entities": {"chemical": [{"text": "copper", "start": 11, "end": 17}, {"text": "Forum", "start": 124, "end": 129}]}}, "schema": []}
{"input": "Accumulation of copper in plants was also increased by Forum but not by the active ingredient alone.", "output": {"entities": {"chemical": [{"text": "copper", "start": 16, "end": 22}, {"text": "Forum", "start": 55, "end": 60}]}}, "schema": []}
{"input": "Depuration of Forum by L. minor varied between 10 and 40% after 96 h and it was generally more efficient than that of the pure ingredient.", "output": {"entities": {}}, "schema": []}
{"input": "This depuration decreased in the presence of copper possibly due to the metal toxicity.", "output": {"entities": {"chemical": [{"text": "copper", "start": 45, "end": 51}]}}, "schema": []}
{"input": "Sorting out Semiconducting Single-Walled Carbon Nanotube Arrays by Washing off Metallic Tubes Using SDS Aqueous Solution.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 41, "end": 47}, {"text": "SDS", "start": 100, "end": 103}]}}, "schema": []}
{"input": "Semiconducting single-walled carbon nanotube (s-SWNT) arrays are produced via a procedure analogous to a surfactant-assisted decontamination process.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 29, "end": 35}]}}, "schema": []}
{"input": "Aligned individual SWNT arrays grow on a quartz surface as a mixture of metallic SWNTs (m-SWNTs) and s-SWNTs.", "output": {"entities": {"chemical": [{"text": "quartz", "start": 41, "end": 47}]}}, "schema": []}
{"input": "They are immersed in a sodium dodecyl sulfate (SDS) solution, and the SDS molecules selectively adsorb onto m-SWNTs.", "output": {"entities": {"chemical": [{"text": "sodium dodecyl sulfate", "start": 23, "end": 45}, {"text": "SDS", "start": 47, "end": 50}, {"text": "SDS", "start": 70, "end": 73}]}}, "schema": []}
{"input": "This SDS coating minimizes the interaction between m-SWNTs and the substrate, thus the m-SWNTs are easily washed off during ultrasonication while the s-SWNT arrays remain on the substrate.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 5, "end": 8}]}}, "schema": []}
{"input": "The percentage of s-SWNTs in the arrays can be higher than 90%.", "output": {"entities": {}}, "schema": []}
{"input": "Electrochemical Oxygen Reduction Behavior of Selectively Deposited Platinum Atoms on Gold Nanoparticles.", "output": {"entities": {"chemical": [{"text": "Oxygen", "start": 16, "end": 22}, {"text": "Platinum", "start": 67, "end": 75}]}}, "schema": []}
{"input": "Carbon-supported Pt @Au \" core-shell \" nanoparticles with varying surface concentration of platinum atoms have been synthesized using a novel redox-mediated synthesis approach.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}, {"text": "Pt", "start": 17, "end": 19}, {"text": "Au", "start": 21, "end": 23}, {"text": "platinum", "start": 91, "end": 99}]}}, "schema": []}
{"input": "The synthesis technique allows for a selective deposition of platinum atoms on the surface of prefabricated gold nanoparticles.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 61, "end": 69}]}}, "schema": []}
{"input": "Energy dispersive spectroscopic analyses in a scanning electron microscope reveal that the platinum to gold atomic ratios are close to the nominal values, validating the synthesis scheme.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 91, "end": 99}]}}, "schema": []}
{"input": "X-ray diffraction data indicate an un-alloyed structure.", "output": {"entities": {}}, "schema": []}
{"input": "The platinum to gold surface atomic ratio determined from cyclic voltammetry and copper under-potential deposition experiments reveal good agreement with the calculated values at low platinum concentration.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 4, "end": 12}, {"text": "copper", "start": 81, "end": 87}, {"text": "platinum", "start": 183, "end": 191}]}}, "schema": []}
{"input": "However, there is an increase in non-uniformity in the deposition process upon increasing the platinum concentration.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 94, "end": 102}]}}, "schema": []}
{"input": "Koutecky-Levich analysis of the samples indicates a transition of the total number of electrons transferred (n) in the electrochemical oxygen reduction reaction from two to four electrons upon increasing the surface concentration of platinum atoms.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 135, "end": 141}, {"text": "platinum", "start": 233, "end": 241}]}}, "schema": []}
{"input": "Furthermore, the data indicate that isolated platinum atoms can reduce molecular oxygen but via a two-electron route.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 45, "end": 53}, {"text": "oxygen", "start": 81, "end": 87}]}}, "schema": []}
{"input": "Moreover, successful four-electron reduction of molecular oxygen requires clusters of platinum atoms.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 58, "end": 64}, {"text": "platinum", "start": 86, "end": 94}]}}, "schema": []}
{"input": "Synthesis of phenyleneethynylene-doped poly (pphenylenebutadiynylene) s for live cell imaging.", "output": {"entities": {"chemical": [{"text": "phenyleneethynylene", "start": 13, "end": 32}, {"text": "poly (pphenylenebutadiynylene) s", "start": 39, "end": 71}]}}, "schema": []}
{"input": "We developed a new synthetic approach to high molecular weight poly (p-phenylenebutadiynylene) s (PPBs) by increasing backbone flexibility.", "output": {"entities": {"chemical": [{"text": "poly (p-phenylenebutadiynylene) s", "start": 63, "end": 96}, {"text": "PPBs", "start": 98, "end": 102}]}}, "schema": []}
{"input": "The introduction of a small amount of flexible units along the backbone improved both the physical and photophysical properties of the polymers.", "output": {"entities": {}}, "schema": []}
{"input": "These materials were successfully fabricated into conjugated polymer nanoparticles (CPNs) and used for fluorescent live cell imaging for the first time.", "output": {"entities": {}}, "schema": []}
{"input": "Resilin-Like Polypeptide Hydrogels Engineered for Versatile Biological Functions.", "output": {"entities": {}}, "schema": []}
{"input": "Natural resilin, the rubber-like protein that exists in specialized compartments of most arthropods, possesses excellent mechanical properties such as low stiffness, high resilience and effective energy storage.", "output": {"entities": {}}, "schema": []}
{"input": "Recombinantly-engineered resilin-like polypeptides (RLPs) that possess the favorable attributes of native resilin would be attractive candidates for the modular design of biomaterials for engineering mechanically active tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Based on our previous success in creating a novel RLP-based hydrogel and demonstrating useful mechanical and cell-adhesive properties, we have produced a suite of new RLP-based constructs, each equipped with 12 repeats of the putative resilin consensus sequence and a single, distinct biologically active domain.", "output": {"entities": {}}, "schema": []}
{"input": "This approach allows independent control over the concentrations of cell-binding, MMP-sensitive, and polysaccharide-sequestration domains in hydrogels comprising mixtures of the various RLPs.", "output": {"entities": {}}, "schema": []}
{"input": "The high purity, molecular weight and correct compositions of each new polypeptide have been confirmed via high performance liquid chromatography (HPLC), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), and amino acid analysis.", "output": {"entities": {"chemical": [{"text": "sodium dodecyl sulfate polyacrylamide gel", "start": 154, "end": 195}, {"text": "SDS", "start": 213, "end": 216}, {"text": "amino acid", "start": 302, "end": 312}]}}, "schema": []}
{"input": "These RLP-based polypeptides exhibit largely random-coil conformation, both in solution and in the cross-linked hydrogels, as indicated by circular dichroic and infrared spectroscopic analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrogels of various compositions, with a range of elastic moduli (1kPa to 25kPa) can be produced from these polypeptides, and the activity of the cell-binding and matrix metalloproteinase (MMP) sensitive domains was confirmed.", "output": {"entities": {}}, "schema": []}
{"input": "Tris (hydroxymethyl phosphine) cross-linked RLP hydrogels were able to maintain their mechanical integrity as well as the viability of encapsulated primary human mesenchymal stem cells (MSCs).", "output": {"entities": {"chemical": [{"text": "Tris (hydroxymethyl phosphine)", "start": 0, "end": 30}]}}, "schema": []}
{"input": "These results validate the promising properties of these RLP-based elastomeric biomaterials.", "output": {"entities": {}}, "schema": []}
{"input": "Structural Basis for Enzyme I Inhibition by alpha-Ketoglutarate.", "output": {"entities": {"chemical": [{"text": "alpha-Ketoglutarate", "start": 44, "end": 63}]}}, "schema": []}
{"input": "Creating new bacterial strains in which carbon and nitrogen metabolism are uncoupled is potentially very useful for optimizing yields of microbial produced chemicals from renewable carbon sources.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 40, "end": 46}, {"text": "nitrogen", "start": 51, "end": 59}, {"text": "carbon", "start": 181, "end": 187}]}}, "schema": []}
{"input": "However, the mechanisms that balance carbon and nitrogen consumption in bacteria are poorly understood.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 37, "end": 43}, {"text": "nitrogen", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Recently, alpha-ketoglutarate (alpha KG), the carbon substrate for ammonia assimilation, has been observed to inhibit Escherichia coli enzyme I (EI), the first component of the bacterial phosphotransferase system (PTS), thereby providing a direct biochemical link between central carbon and nitrogen metabolism.", "output": {"entities": {"chemical": [{"text": "alpha-ketoglutarate", "start": 10, "end": 29}, {"text": "alpha KG", "start": 31, "end": 39}, {"text": "carbon", "start": 46, "end": 52}, {"text": "ammonia", "start": 67, "end": 74}, {"text": "carbon", "start": 280, "end": 286}, {"text": "nitrogen", "start": 291, "end": 299}]}}, "schema": []}
{"input": "Here we investigate the EI-alpha KG interaction by NMR and enzymatic assays.", "output": {"entities": {"chemical": [{"text": "alpha KG", "start": 27, "end": 35}]}}, "schema": []}
{"input": "We show that alpha KG binds with a KD of ~ 2. 2 mM at the active site of EI, acting as a competitive inhibitor.", "output": {"entities": {"chemical": [{"text": "alpha KG", "start": 13, "end": 21}]}}, "schema": []}
{"input": "In addition, we use molecular docking simulations to derive a structural model of the enzyme-inhibitor complex that is fully consistent with NMR and analytical ultracentrifugation data.", "output": {"entities": {}}, "schema": []}
{"input": "We expect that the EI-alpha KG structure presented here will provide a starting point for structure-based design of EI mutants resistant to alpha KG.", "output": {"entities": {"chemical": [{"text": "alpha KG", "start": 22, "end": 30}, {"text": "alpha KG", "start": 140, "end": 148}]}}, "schema": []}
{"input": "Contact angle hysteresis on randomly rough surfaces: a computational study.", "output": {"entities": {}}, "schema": []}
{"input": "Wetting is important in many applications, and the solid surfaces being wet invariably feature some amount of surface roughness.", "output": {"entities": {}}, "schema": []}
{"input": "A free energy-based computational simulation is used to study the effect of roughness on wetting and especially contact angle hysteresis.", "output": {"entities": {}}, "schema": []}
{"input": "On randomly rough, self-affine surfaces, it is found that hysteresis depends primarily on the value of the Wenzel roughness parameter r, increasing in proportion with r-1.", "output": {"entities": {}}, "schema": []}
{"input": "Micrometer-level roughness causes hysteresis of a few degrees.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical constituents comparison of Codonopsis tangshen, Codonopsis pilosula var. modesta and Codonopsis pilosula.", "output": {"entities": {}}, "schema": []}
{"input": "Dang-shen, radix Codonopsis is one of the best-known traditional Chinese medicines and is used mainly as a tonic agent.", "output": {"entities": {}}, "schema": []}
{"input": "Nine commercial products belong to three species of Codonopsis genus, Codonopsis tangshen, Codonopsis pilosula var. modesta and a cultivated species of Codonopsis pilosula, which were purchased from drug stores in Taipei and Taichung, Taiwan.", "output": {"entities": {}}, "schema": []}
{"input": "To determine the chemical differences between samples of Dang-shen, a method combining solvent partition and HPLC-UV was used.", "output": {"entities": {}}, "schema": []}
{"input": "An enriched fraction of n-butanol was obtained, after partition.", "output": {"entities": {"chemical": [{"text": "n-butanol", "start": 24, "end": 33}]}}, "schema": []}
{"input": "Then, the chemical profile was determined using a C18 reversed column chromatography in a gradient solvent system with 10-40% acetonitrile in 0. 1% formic acid, for 60 min.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 126, "end": 138}, {"text": "formic acid", "start": 148, "end": 159}]}}, "schema": []}
{"input": "A comparison of the constituents in the nine commercial products of Dang-shen showed that compounds codonopyrrolidum A, B and codonoside A only exist in C. tangshen, but not in C. pilosula var. modesta and C. pilosula.", "output": {"entities": {"chemical": [{"text": "codonopyrrolidum A, B", "start": 100, "end": 121}, {"text": "codonoside A", "start": 126, "end": 138}]}}, "schema": []}
{"input": "A predominate compound, codonopyrrolidum A, can be used to distinguish the herbs, C. tangshen from C. pilosula var. modesta and C. pilosula.", "output": {"entities": {"chemical": [{"text": "codonopyrrolidum A", "start": 24, "end": 42}]}}, "schema": []}
{"input": "Low secondary metabolite content was found in the cultivated species of C. pilosula.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanics of interaction and atomic-scale wear of amplitude modulation atomic force microscopy probes.", "output": {"entities": {}}, "schema": []}
{"input": "Wear is one of the main factors that hinders the performance of probes for atomic force microscopy (AFM), including for the widely used amplitude modulation (AM-AFM) mode.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, a comprehensive scientific understanding of nanoscale wear is lacking.", "output": {"entities": {}}, "schema": []}
{"input": "We have developed a protocol for conducting consistent and quantitative AM-AFM wear experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The protocol involves controlling the tip-sample interaction regime during AM-AFM scanning, determining the tip-sample contact geometry, calculating the peak repulsive force and normal stress over the course of the wear test, and quantifying the wear volume using high-resolution transmission electron microscopy imaging.", "output": {"entities": {}}, "schema": []}
{"input": "The peak repulsive tip-sample interaction force is estimated from a closed-form equation accompanied by an effective tip radius measurement procedure, which combines transmission electron microscopy and blind tip reconstruction.", "output": {"entities": {}}, "schema": []}
{"input": "The contact stress is estimated by applying Derjaguin-M u ller-Toporov contact mechanics model and also numerically solving a general contact mechanics model recently developed for the adhesive contact of arbitrary axisymmetric punch shapes.", "output": {"entities": {}}, "schema": []}
{"input": "We discuss the important role that the assumed tip shape geometry plays in calculating both the interaction forces and the contact stresses.", "output": {"entities": {}}, "schema": []}
{"input": "Contact stresses are significantly affected by the tip geometry while the peak repulsive force is mainly determined by experimentally controlled parameters, specifically, the free oscillation amplitude and amplitude ratio.", "output": {"entities": {}}, "schema": []}
{"input": "The applicability of this protocol is demonstrated experimentally by assessing the performance of diamond-like carbon-coated and silicon-nitride-coated silicon probes scanned over ultrananocrystalline diamond substrates in repulsive mode AM-AFM.", "output": {"entities": {"chemical": [{"text": "diamond", "start": 98, "end": 105}, {"text": "carbon", "start": 111, "end": 117}, {"text": "silicon-nitride", "start": 129, "end": 144}, {"text": "silicon", "start": 152, "end": 159}, {"text": "diamond", "start": 201, "end": 208}]}}, "schema": []}
{"input": "There is no sign of fracture or plastic deformation in the case of diamond-like carbon; wear could be characterized as a gradual atom-by-atom process.", "output": {"entities": {"chemical": [{"text": "diamond", "start": 67, "end": 74}, {"text": "carbon", "start": 80, "end": 86}]}}, "schema": []}
{"input": "In contrast, silicon nitride wears through removal of the cluster of atoms and plastic deformation.", "output": {"entities": {"chemical": [{"text": "silicon nitride", "start": 13, "end": 28}]}}, "schema": []}
{"input": "Transition to Reinforced State by Percolating Domains of Intercalated Brush-Modified Cellulose Nanocrystals and Poly (butadiene) in Cross-Linked Composites Based on Thiol-ene Click Chemistry.", "output": {"entities": {"chemical": [{"text": "Poly (butadiene)", "start": 112, "end": 128}, {"text": "Thiol-ene", "start": 165, "end": 174}]}}, "schema": []}
{"input": "The classic nanocomposite approach aims at percolation of low fraction of exfoliated individual reinforcing nanoscale elements within a polymeric matrix.", "output": {"entities": {}}, "schema": []}
{"input": "By contrast, many of the mechanically excellent biological nanocomposites involve self-assembled and space-filled structures of hard reinforcing and soft toughening domains, with high weight fraction of reinforcements.", "output": {"entities": {}}, "schema": []}
{"input": "Here we inspect a new concept toward mimicking such structures by studying whether percolation of intercalated domains consisting of alternating rigid and reinforcing, and soft rubbery domains could allow a transition to a reinforced state.", "output": {"entities": {}}, "schema": []}
{"input": "Toward that, we present the functionalization of rigid native cellulose nanocrystals (CNCs) by esterification with a dense hydrocarbon chain brush containing cross-linkable double bonds.", "output": {"entities": {"chemical": [{"text": "hydrocarbon", "start": 123, "end": 134}]}}, "schema": []}
{"input": "Composite films with 0-80 wt% of such modified CNCs (mCNCs) within a poly (butadiene) (PBD) rubber matrix were prepared via cross-linking by UV-light initiated thiol-ene click reaction.", "output": {"entities": {"chemical": [{"text": "poly (butadiene)", "start": 69, "end": 85}, {"text": "PBD", "start": 87, "end": 90}, {"text": "thiol-ene", "start": 160, "end": 169}]}}, "schema": []}
{"input": "Transmission electron microscopy showed structures at two length scales, where the mCNCs and PBD form domains having internal aligned self-assemblies of alternating hard mCNCs and soft PBD with periodicity of ca.", "output": {"entities": {"chemical": [{"text": "PBD", "start": 93, "end": 96}, {"text": "PBD", "start": 185, "end": 188}]}}, "schema": []}
{"input": "40 nm, and where additional PBD connects such domains.", "output": {"entities": {"chemical": [{"text": "PBD", "start": 28, "end": 31}]}}, "schema": []}
{"input": "Increasing the weight fraction of mCNCs causes an uncommon abrupt transition from PBD-dominated soft materials to significantly reinforced mCNC-dominated mechanical properties, suggesting that the intercalated self-assembled mCNC/PBD domains percolate in PBD upon passing 30-35 wt% of mCNCs.", "output": {"entities": {"chemical": [{"text": "PBD", "start": 82, "end": 85}, {"text": "PBD", "start": 230, "end": 233}, {"text": "PBD", "start": 255, "end": 258}]}}, "schema": []}
{"input": "Maximum stress of 16 MPa at mCNC fraction of 80 wt% was obtained.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanical properties of the composites show exceptional insensitivity to air humidity.", "output": {"entities": {}}, "schema": []}
{"input": "The shown simple concept of percolative intercalated nanocomposites suggests searching for more general biomimetic compositions involving several deformation mechanisms for improved mechanical properties.", "output": {"entities": {}}, "schema": []}
{"input": "Paths to selection on life history loci in different natural environments across the native range of Arabidopsis thaliana.", "output": {"entities": {}}, "schema": []}
{"input": "Selection on quantitative trait loci (QTL) may vary among natural environments due to differences in the genetic architecture of traits, environment-specific allelic effects or changes in the direction and magnitude of selection on specific traits.", "output": {"entities": {}}, "schema": []}
{"input": "To dissect the environmental differences in selection on life history QTL across climatic regions, we grew a panel of interconnected recombinant inbred lines (RILs) of Arabidopsis thaliana in four field sites across its native European range.", "output": {"entities": {}}, "schema": []}
{"input": "For each environment, we mapped QTL for growth, reproductive timing and development.", "output": {"entities": {}}, "schema": []}
{"input": "Several QTL were pleiotropic across environments, three colocalizing with known functional polymorphisms in flowering time genes (CRY2, FRI and MAF2-5), but major QTL differed across field sites, showing conditional neutrality.", "output": {"entities": {}}, "schema": []}
{"input": "We used structural equation models to trace selection paths from QTL to lifetime fitness in each environment.", "output": {"entities": {}}, "schema": []}
{"input": "Only three QTL directly affected fruit number, measuring fitness.", "output": {"entities": {}}, "schema": []}
{"input": "Most QTL had an indirect effect on fitness through their effect on bolting time or leaf length.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of life history traits on fitness differed dramatically across sites, resulting in different patterns of selection on reproductive timing and underlying QTL.", "output": {"entities": {}}, "schema": []}
{"input": "In two oceanic field sites with high prereproductive mortality, QTL alleles contributing to early reproduction resulted in greater fruit production, conferring selective advantage, whereas alleles contributing to later reproduction resulted in larger size and higher fitness in a continental site.", "output": {"entities": {}}, "schema": []}
{"input": "This demonstrates how environmental variation leads to change in both QTL effect sizes and direction of selection on traits, justifying the persistence of allelic polymorphism at life history QTL across the species range.", "output": {"entities": {}}, "schema": []}
{"input": "Binding Specificity and Thermodynamics of Cellulose-Binding Modules from Trichoderma reesei Cel7A and Cel6A.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, Family 1 cellulose binding modules CBMCel7A and CBMCel6A were heterologously expressed and purified from Escherichia coli, and the binding properties between these CBMs and cellulose substrates were studied.", "output": {"entities": {}}, "schema": []}
{"input": "Cellulose nanowhiskers (CNWs, the crystalline portion of cellulose), microcrystalline cellulose Avicel PH101 (partially crystalline cellulose), and phosphoric acid swollen cellulose (PASC, amorphous cellulose) were used as representative models for cellulose to better understand the binding interactions between the CBMs and different regions of native cellulose.", "output": {"entities": {"chemical": [{"text": "phosphoric acid", "start": 148, "end": 163}]}}, "schema": []}
{"input": "Isothermal titration calorimetry (ITC) was combined with adsorption-isotherm experiment to analyze the thermodynamics of CBM binding to various cellulose substrates.", "output": {"entities": {}}, "schema": []}
{"input": "N2 adsorption and static light scattering (SLS) data were used to estimate the accessible surface area of cellulose which was then used for ITC data analysis.", "output": {"entities": {"chemical": [{"text": "N2", "start": 0, "end": 2}]}}, "schema": []}
{"input": "A new method of determining the cellulose molarity based on the available surface area for CBM binding was developed, which allows different cellulose substrates to be compared for binding experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The ITC results showed that the binding constant (Ka) to crystalline CNWs was ~ 10 (5) M (-1) for CBMCel7A, while ~ 10 (6) M (-1) for CBMCel6A, suggesting a higher binding affinity of CBMCel6A to CNWs.", "output": {"entities": {}}, "schema": []}
{"input": "For Avicel, lower binding constants for both CBMs were observed, and weak bindings to PASC were characterized, suggesting that the binding between CBMCel7A, Cel6A and cellulose to some extent relates to the crystallinity of cellulose.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, the binding reactions were driven by a favorable enthalpy change, offset partially by an unfavorable entropy change.", "output": {"entities": {}}, "schema": []}
{"input": "It is suggested that CBMCel6A preferentially binds to the reducing end of cellulose chain, while CBMCel7A does not show such end binding specificities.", "output": {"entities": {}}, "schema": []}
{"input": "Cello-oligosaccharides less than two glucose units did not bind with CBMs, and improved binding affinities were observed for cello-oligosaccharides with longer glucose units.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 37, "end": 44}, {"text": "glucose", "start": 160, "end": 167}]}}, "schema": []}
{"input": "PCNA trimer instability inhibits translesion synthesis by DNA polymerase eta and by DNA polymerase delta.", "output": {"entities": {}}, "schema": []}
{"input": "Translesion synthesis (TLS), the process by which DNA polymerases replicate through DNA lesions, is the source of most DNA damage-induced mutations.", "output": {"entities": {}}, "schema": []}
{"input": "Sometimes TLS is carried out by replicative polymerases that have evolved to synthesize DNA on non-damaged templates.", "output": {"entities": {}}, "schema": []}
{"input": "Most of the time, however, TLS is carried out by specialized translesion polymerases that have evolved to synthesize DNA on damaged templates.", "output": {"entities": {}}, "schema": []}
{"input": "TLS requires the mono-ubiquitylation of the replication accessory factor proliferating cell nuclear antigen (PCNA).", "output": {"entities": {}}, "schema": []}
{"input": "PCNA and ubiquitin-modified PCNA (UbPCNA) stimulate TLS by replicative and translesion polymerases.", "output": {"entities": {}}, "schema": []}
{"input": "Two mutant forms of PCNA, one with an E113G substitution and one with a G178S substitution, support normal cell growth but inhibit TLS thereby reducing mutagenesis in yeast.", "output": {"entities": {}}, "schema": []}
{"input": "A re-examination of the structures of both mutant PCNA proteins revealed substantial disruptions of the subunit interface that forms the PCNA trimer.", "output": {"entities": {}}, "schema": []}
{"input": "Both mutant proteins have reduced trimer stability with the G178S substitution causing a more severe defect.", "output": {"entities": {}}, "schema": []}
{"input": "The mutant forms of PCNA and UbPCNA do not stimulate TLS of an abasic site by either replicative Pol delta or translesion Pol eta.", "output": {"entities": {}}, "schema": []}
{"input": "Normal replication by Pol eta was also impacted, but normal replication by Pol delta was much less affected.", "output": {"entities": {}}, "schema": []}
{"input": "These findings support a model in which reduced trimer stability causes these mutant PCNA proteins to occasionally undergo conformational changes that compromise their ability to stimulate TLS by both replicative and translesion polymerases.", "output": {"entities": {}}, "schema": []}
{"input": "Biomarkers of prolonged exposure to microcystin-LR in mice.", "output": {"entities": {"chemical": [{"text": "microcystin-LR", "start": 36, "end": 50}]}}, "schema": []}
{"input": "The effects of prolonged exposure to microcystins (MCs) on health are not yet sufficiently understood and this type of poisoning is often undiagnosed.", "output": {"entities": {}}, "schema": []}
{"input": "Even though chronic exposure has been linked with liver cancer and alterations have been described in liver damage marker enzymes in exposed populations, there are not profile parameters that indicate prolonged exposure to microcystins.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this work is to determine, based on an animal model of prolonged exposure to successive i. p. doses of 25 mu g MC-LR/kg body weight, several plasma parameters which could be useful as exposure biomarkers.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 122, "end": 127}]}}, "schema": []}
{"input": "Hemoglobin (Hb) and methemoglobin (MetHb) levels were determined on blood samples.", "output": {"entities": {}}, "schema": []}
{"input": "We also studied plasma levels of hydroperoxides (ROOHs), alpha-tocopherol, glutathione and lipid profile as well as superoxide dismutase (SOD) and catalase (CAT) erythrocyte activities.", "output": {"entities": {"chemical": [{"text": "hydroperoxides", "start": 33, "end": 47}, {"text": "ROOHs", "start": 49, "end": 54}, {"text": "alpha-tocopherol", "start": 57, "end": 73}, {"text": "glutathione", "start": 75, "end": 86}, {"text": "superoxide", "start": 116, "end": 126}]}}, "schema": []}
{"input": "In addition, the determination of MC-LR levels in liver, kidney, plasma, urine and feces of treated mice was carried out.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 34, "end": 39}]}}, "schema": []}
{"input": "We found that alteration in MetHb, ROOHs, glutathione, alpha-tocopherol levels, SOD activity and plasma lipid profile, correlates with those expected if the alteration derived from hepatic damage.", "output": {"entities": {"chemical": [{"text": "ROOHs", "start": 35, "end": 40}, {"text": "glutathione", "start": 42, "end": 53}, {"text": "alpha-tocopherol", "start": 55, "end": 71}]}}, "schema": []}
{"input": "The alterated plasma paramenters together with MC-LR determination could be used as biomarkers, helpful tools in screening and epidemiological studies.", "output": {"entities": {"chemical": [{"text": "MC-LR", "start": 47, "end": 52}]}}, "schema": []}
{"input": "LC-MS/MS Determination of Isoprostanes in Plasma Samples Collected from Mice Exposed to Doxorubicin or Tert-Butyl Hydroperoxide.", "output": {"entities": {"chemical": [{"text": "Isoprostanes", "start": 26, "end": 38}, {"text": "Doxorubicin", "start": 88, "end": 99}, {"text": "Tert-Butyl Hydroperoxide", "start": 103, "end": 127}]}}, "schema": []}
{"input": "Isoprostanes are stable products of arachidonic acid peroxidation and are regarded as the most reliable markers of oxidative stress in vivo.", "output": {"entities": {"chemical": [{"text": "Isoprostanes", "start": 0, "end": 12}, {"text": "arachidonic acid", "start": 36, "end": 52}]}}, "schema": []}
{"input": "Here we describe the LC-MS/MS procedure enabling simultaneous determination of four regioisomers (8-iso prostaglandin F2 alpha, 8-iso-15 (R)-prostaglandin F2 alpha, 11 beta-prostaglandin F2 alpha, 15 (R)-prostaglandin F2 alpha) in plasma samples collected from mice.", "output": {"entities": {"chemical": [{"text": "8-iso prostaglandin F2 alpha", "start": 98, "end": 126}, {"text": "8-iso-15 (R)-prostaglandin F2 alpha", "start": 128, "end": 163}, {"text": "11 beta-prostaglandin F2 alpha", "start": 165, "end": 195}, {"text": "15 (R)-prostaglandin F2 alpha", "start": 197, "end": 226}]}}, "schema": []}
{"input": "The four plasma isoprostanes are determined by LC-ESI-MS/MS with deuterated 8-iso-PGF2 alpha-d4 as an internal standard (I. S.).", "output": {"entities": {"chemical": [{"text": "isoprostanes", "start": 16, "end": 28}, {"text": "8-iso-PGF2 alpha-d4", "start": 76, "end": 95}]}}, "schema": []}
{"input": "For plasma samples spiked with the isoprostanes at a level of 200 pg/mL each, the method imprecision has been below 7. 1% and mean inaccuracy equaled 8. 7%.", "output": {"entities": {"chemical": [{"text": "isoprostanes", "start": 35, "end": 47}]}}, "schema": []}
{"input": "The applicability of the proposed approach has been verified by the assessment of changes in isoprostane levels in plasma samples derived from mice exposed to tert-butyl hydroperoxide (TBHP), a model inducer of oxidative stress, or to antitumor drug doxorubicin (DOX) known for potent stimulation of redox cycling.", "output": {"entities": {"chemical": [{"text": "isoprostane", "start": 93, "end": 104}, {"text": "tert-butyl hydroperoxide", "start": 159, "end": 183}, {"text": "TBHP", "start": 185, "end": 189}, {"text": "doxorubicin", "start": 250, "end": 261}, {"text": "DOX", "start": 263, "end": 266}]}}, "schema": []}
{"input": "Compared to the control group of mice, both oxidative stress inducers tested increased the levels of three out of four isoprostanes in exposed animals; 11 beta-prostaglandin F2 alpha being the exception.", "output": {"entities": {"chemical": [{"text": "11 beta-prostaglandin F2 alpha", "start": 152, "end": 182}]}}, "schema": []}
{"input": "The greatest rise was observed in the case of 15 (R)-prostaglandin F2 alpha, by about 50% and 70% in plasma samples derived from mice exposed to DOX and TBHP, respectively.", "output": {"entities": {"chemical": [{"text": "15 (R)-prostaglandin F2 alpha", "start": 46, "end": 75}, {"text": "DOX", "start": 145, "end": 148}, {"text": "TBHP", "start": 153, "end": 157}]}}, "schema": []}
{"input": "Droplet-based microfluidic platform for heterogeneous enzymatic assays.", "output": {"entities": {}}, "schema": []}
{"input": "Heterogeneous enzymatic reactions are used in many industrial processes including pulp and paper, food, and biofuel production.", "output": {"entities": {}}, "schema": []}
{"input": "Industrially-relevant optimization of the enzymes used in these processes requires assaying them with insoluble substrates.", "output": {"entities": {}}, "schema": []}
{"input": "However, platforms for high throughput heterogeneous assays do not exist thereby severely increasing the cost and time of enzyme optimization, or leading to the use of assays with soluble substrates for convenient, but non-ideal, optimization.", "output": {"entities": {}}, "schema": []}
{"input": "We present an innovative approach to perform heterogeneous reactions in a high throughput fashion using droplet microfluidics.", "output": {"entities": {}}, "schema": []}
{"input": "Droplets provide a facile platform for heterogeneous reactions as internal recirculation allows rapid mixing of insoluble substrates with soluble enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, it is easy to generate hundreds or thousands of picoliter droplets in a small footprint chip allowing many parallel reactions.", "output": {"entities": {}}, "schema": []}
{"input": "We validate our approach by screening combinations of cellulases with real-world insoluble substrates, and demonstrate that the chip-based screening is in excellent agreement with the conventional screening methods, while offering advantages of throughput, speed and lower reagent consumption.", "output": {"entities": {}}, "schema": []}
{"input": "We believe that our approach, while demonstrated for a biofuel application, provides a generic platform for high throughput monitoring of heterogeneous reactions.", "output": {"entities": {}}, "schema": []}
{"input": "Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice.", "output": {"entities": {"chemical": [{"text": "Lysophosphatidic acid", "start": 0, "end": 21}, {"text": "glucose", "start": 30, "end": 37}]}}, "schema": []}
{"input": "AIMS/HYPOTHESIS: Lysophosphatidic acid (LPA) is a lipid mediator produced by adipocytes that acts via specific G-protein-coupled receptors; its synthesis is modulated in obesity.", "output": {"entities": {"chemical": [{"text": "Lysophosphatidic acid", "start": 17, "end": 38}, {"text": "LPA", "start": 40, "end": 43}]}}, "schema": []}
{"input": "We previously reported that reducing adipocyte LPA production in high-fat diet (HFD)-fed obese mice is associated with improved glucose tolerance, suggesting a negative impact of LPA on glucose homeostasis.", "output": {"entities": {"chemical": [{"text": "LPA", "start": 47, "end": 50}, {"text": "glucose", "start": 128, "end": 135}, {"text": "LPA", "start": 179, "end": 182}, {"text": "glucose", "start": 186, "end": 193}]}}, "schema": []}
{"input": "Here, our aim was to test this hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: First, glucose tolerance and plasma insulin were assessed after acute (30 min) injection of LPA (50 mg/kg) or of the LPA1/LPA3 receptor antagonist Ki16425 (5 mg kg (-1) day (-1), i. p.) in non-obese mice fed a normal diet (ND) and in obese/prediabetic (defined as glucose-intolerant) HFD mice.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 16, "end": 23}, {"text": "LPA", "start": 101, "end": 104}, {"text": "glucose", "start": 273, "end": 280}]}}, "schema": []}
{"input": "Glucose and insulin tolerance, pancreas morphology, glycogen storage, glucose oxidation and glucose transport were then studied after chronic treatment (3 weeks) of HFD mice with Ki16425.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}, {"text": "glucose", "start": 70, "end": 77}, {"text": "glucose", "start": 92, "end": 99}]}}, "schema": []}
{"input": "RESULTS: In ND and HFD mice, LPA acutely impaired glucose tolerance by inhibiting glucose-induced insulin secretion.", "output": {"entities": {"chemical": [{"text": "LPA", "start": 29, "end": 32}, {"text": "glucose", "start": 50, "end": 57}, {"text": "glucose", "start": 82, "end": 89}]}}, "schema": []}
{"input": "These effects were blocked by pre-injection of Ki16425 (5 mg/kg, i. p.).", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of glucose-induced insulin secretion by LPA also occurred in isolated mouse islets.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 14, "end": 21}, {"text": "LPA", "start": 51, "end": 54}]}}, "schema": []}
{"input": "Plasma LPA was higher in HFD mice than in ND mice and Ki16425 transiently improved glucose tolerance.", "output": {"entities": {"chemical": [{"text": "LPA", "start": 7, "end": 10}, {"text": "glucose", "start": 83, "end": 90}]}}, "schema": []}
{"input": "The beneficial effect of Ki16425 became permanent after chronic treatment and was associated with increased pancreatic islet mass and higher fasting insulinaemia.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic treatment with Ki16425 also improved insulin tolerance and increased liver glycogen storage and basal glucose use in skeletal muscle.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 110, "end": 117}]}}, "schema": []}
{"input": "CONCLUSIONS/INTERPRETATION: Exogenous and endogenous LPA exerts a deleterious effect on glucose disposal through a reduction of plasma insulin; pharmacological blockade of LPA receptors improves glucose homeostasis in obese/prediabetic mice.", "output": {"entities": {"chemical": [{"text": "LPA", "start": 53, "end": 56}, {"text": "glucose", "start": 88, "end": 95}, {"text": "LPA", "start": 172, "end": 175}, {"text": "glucose", "start": 195, "end": 202}]}}, "schema": []}
{"input": "Higher levels of trait impulsiveness and a less effective response inhibition are linked to more intense cue-elicited craving for alcohol in alcohol-dependent patients.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 130, "end": 137}, {"text": "alcohol", "start": 141, "end": 148}]}}, "schema": []}
{"input": "RATIONALE: Cue-elicited craving is a well-researched phenomenon in alcohol literature.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 67, "end": 74}]}}, "schema": []}
{"input": "However, not all alcohol-dependent people display the same reactivity to alcohol cues.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 17, "end": 24}, {"text": "alcohol", "start": 73, "end": 80}]}}, "schema": []}
{"input": "Personality factors such as multiple impulsivity traits may be responsible for individual differences in cue reactivity by modulating its intensity.", "output": {"entities": {}}, "schema": []}
{"input": "Nevertheless, there has been a scarcity of empirical studies testing this assumption in alcohol literature.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 88, "end": 95}]}}, "schema": []}
{"input": "OBJECTIVES: The aim of the present study was to investigate the effects of response inhibition and trait impulsiveness on cue-elicited craving for alcohol in alcohol-dependent drinkers.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 147, "end": 154}, {"text": "alcohol", "start": 158, "end": 165}]}}, "schema": []}
{"input": "METHODS: Participants (n = 41) were inpatients of the private clinic U-Center, Netherlands.", "output": {"entities": {}}, "schema": []}
{"input": "Alcohol exposure took place in a real bar-restaurant close to the premises of the clinic, and participants were exposed to real alcohol cues.", "output": {"entities": {"chemical": [{"text": "Alcohol", "start": 0, "end": 7}, {"text": "alcohol", "start": 128, "end": 135}]}}, "schema": []}
{"input": "Response inhibition was assessed with the stop-signal task and trait impulsiveness with the Barratt impulsivity scale version 11.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The cue exposure was successful as alcohol-dependent patients experienced higher craving for alcohol when exposed to alcohol rather than to neutral cues.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 44, "end": 51}, {"text": "alcohol", "start": 102, "end": 109}, {"text": "alcohol", "start": 126, "end": 133}]}}, "schema": []}
{"input": "Additionally, both response inhibition and trait impulsiveness predicted cue-elicited craving for alcohol.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 98, "end": 105}]}}, "schema": []}
{"input": "Trait impulsiveness predicted both the absolute craving in the bar-restaurant and the increase in cue-elicited craving during the whole alcohol cue exposure, while response inhibition predicted only the former.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 136, "end": 143}]}}, "schema": []}
{"input": "CONCLUSIONS: The results clearly implicate both trait impulsiveness and response inhibition in the modulation of cue-elicited craving in alcohol dependence.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 137, "end": 144}]}}, "schema": []}
{"input": "Theoretical and methodological issues in the findings and their clinical implications in alcohol treatment and relapse are discussed.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 89, "end": 96}]}}, "schema": []}
{"input": "Molecular Basis for Sialic Acid-dependent Receptor Recognition by the Plasmodium falciparum Invasion Protein Erythrocyte-binding Antigen-140/BAEBL.", "output": {"entities": {"chemical": [{"text": "Sialic Acid", "start": 20, "end": 31}]}}, "schema": []}
{"input": "Plasmodium falciparum erythrocyte invasion is dependent on high affinity recognition of sialic acid on cell surface receptors.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 88, "end": 99}]}}, "schema": []}
{"input": "The erythrocyte binding-like (EBL) family of invasion ligands mediates recognition of sialic acid on erythrocyte glycoproteins.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 86, "end": 97}]}}, "schema": []}
{"input": "Erythrocyte-binding antigen-140 (PfEBA-140/BAEBL) is a critical EBL ligand that binds sialic acid on its receptor glycophorin C.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 86, "end": 97}]}}, "schema": []}
{"input": "We present here the crystal structure of the two-domain receptor-binding region of PfEBA-140 in complex with a glycan containing sialic acid.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 129, "end": 140}]}}, "schema": []}
{"input": "The structure identifies two glycan-binding pockets unique to PfEBA-140 and not shared by other EBL ligands.", "output": {"entities": {}}, "schema": []}
{"input": "Specific molecular interactions that enable receptor engagement are identified and reveal that the glycan binding mode is distinct from that of apicomplexan and viral cell surface recognition ligands as well as host immune factors that bind sialic acid.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 241, "end": 252}]}}, "schema": []}
{"input": "Erythrocyte binding experiments elucidated essential glycan contact residues and identified divergent functional roles for each receptor-binding site.", "output": {"entities": {}}, "schema": []}
{"input": "One of four polymorphisms proposed to affect receptor binding was localized to a glycan-binding site, providing a structural basis for altered erythrocyte engagement.", "output": {"entities": {}}, "schema": []}
{"input": "The studies described here provide the first full description of sialic acid-dependent molecular interactions at the P. falciparum erythrocyte invasion interface and define a framework for development of PfEBA-140-based therapeutics, vaccines, and diagnostics assessing vaccine efficacy and natural immunity to infection.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 65, "end": 76}]}}, "schema": []}
{"input": "De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.", "output": {"entities": {}}, "schema": []}
{"input": "The use of fragments with low binding affinity for their targets as starting points has received much attention recently.", "output": {"entities": {}}, "schema": []}
{"input": "Screening of fragment libraries has been the most common method to find attractive starting points.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we describe a unique, alternative approach to generating fragment leads.", "output": {"entities": {}}, "schema": []}
{"input": "A binding model was developed and a set of guidelines were then selected to use this model to design fragments, enabling our discovery of a novel fragment with high LE.", "output": {"entities": {}}, "schema": []}
{"input": "Surface Thermodynamic and Adhesion Force Evaluation of the Role of Chitin-Binding Protein in the Physical Interaction between Pseudomonas aeruginosa and Candida albicans.", "output": {"entities": {}}, "schema": []}
{"input": "Candida albicans and Pseudomonas aeruginosa are able to form pathogenic polymicrobial communities.", "output": {"entities": {}}, "schema": []}
{"input": "P. aeruginosa colonizes and kills hyphae but is unable to attach to yeast.", "output": {"entities": {}}, "schema": []}
{"input": "It is unknown why the interaction of P. aeruginosa is different with yeast than with hyphae.", "output": {"entities": {}}, "schema": []}
{"input": "Here we aim to evaluate the role of P. aeruginosa chitin-binding protein (CbpD) in its physical interaction with C. albicans hyphae or yeast, based on surface thermodynamic and atomic force microscopic analyses.", "output": {"entities": {}}, "schema": []}
{"input": "A P. aeruginosa mutant lacking CbpD was unable to express strong adhesion forces with hyphae (-2. 9 nN) as compared with the parent strain P. aeruginosa PAO1 (-4. 8 nN) and showed less adhesion to hyphae.", "output": {"entities": {}}, "schema": []}
{"input": "Also blocking of CbpD using N-acetyl-glucosamine yielded a lower adhesion force (-4. 3 nN) with hyphae.", "output": {"entities": {"chemical": [{"text": "N-acetyl-glucosamine", "start": 28, "end": 48}]}}, "schema": []}
{"input": "Strong adhesion forces were restored after complementing the expression of CbpD in P. aeruginosa PAO1 Delta cbpD yielding an adhesion force of-5. 1 nN.", "output": {"entities": {}}, "schema": []}
{"input": "These observations were confirmed with microscopic evaluation of adhesion tests.", "output": {"entities": {}}, "schema": []}
{"input": "Regardless of the absence or presence of CbpD on the bacterial cell surfaces, or their blocking, P. aeruginosa experienced favorable thermodynamic conditions for adhesion with hyphae, which were absent with yeast.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, adhesion forces with yeast were less than 0. 5 nN in all cases.", "output": {"entities": {}}, "schema": []}
{"input": "Concluding, CbpD in P. aeruginosa is responsible for strong physical interactions with C. albicans hyphae.", "output": {"entities": {}}, "schema": []}
{"input": "The development of this interaction requires time due to the fact that CbpDs have to invade the outermost mannoprotein layer on the hyphal cell surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "In order to do this, thermodynamic conditions at the outermost cell surfaces have to be favorable.", "output": {"entities": {}}, "schema": []}
{"input": "Degradable Cationic Shell Cross-Linked Knedel-like Nanoparticles: Synthesis, Degradation, Nucleic Acid Binding, and in Vitro Evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, degradable cationic shell cross-linked knedel-like (deg-cSCK) nanoparticles were developed as an alternative platform to replace similar nondegradable cSCK nanoparticles that have been utilized for nucleic acids delivery.", "output": {"entities": {}}, "schema": []}
{"input": "An amphiphilic diblock copolymer poly (acrylamidoethylamine) 90-block-poly (dl-lactide) 40 (PAEA90-b-PDLLA40) was synthesized, self-assembled in aqueous solution, and shell cross-linked using a hydrolyzable cross-linker to afford deg-cSCKs with an average core diameter of 45 +/- 7 nm.", "output": {"entities": {"chemical": [{"text": "poly (acrylamidoethylamine) 90-block-poly (dl-lactide) 40", "start": 33, "end": 90}, {"text": "PAEA90-b-PDLLA40", "start": 92, "end": 108}]}}, "schema": []}
{"input": "These nanoparticles were fluorescently labeled for in vitro tracking.", "output": {"entities": {}}, "schema": []}
{"input": "The enzymatic-and hydrolytic-degradability, siRNA binding affinity, cell uptake and cytotoxicity of the deg-cSCKs were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Esterase-catalyzed hydrolysis of the nanoparticles resulted in the degradation of ca.", "output": {"entities": {}}, "schema": []}
{"input": "24% of the PDLLA core into lactic acid within 5 d, as opposed to only ca.", "output": {"entities": {"chemical": [{"text": "PDLLA", "start": 11, "end": 16}, {"text": "lactic acid", "start": 27, "end": 38}]}}, "schema": []}
{"input": "9% degradation from aqueous solutions of the deg-cSCK nanoparticles in the absence of enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular uptake of deg-cSCKs was efficient, while exhibiting low cytotoxicity with LD50 values of ca.", "output": {"entities": {}}, "schema": []}
{"input": "90 and 30 mu g/mL in RAW 264. 7 mouse macrophages and MLE 12 cell lines, respectively, ca.", "output": {"entities": {}}, "schema": []}
{"input": "5-to 6-fold lower than the cytotoxicity observed for nondegradable cSCK analogs.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, deg-cSCKs were able to complex siRNA at an N/P ratio as low as 2, and were efficiently able to facilitate cellular uptake of the complexed nucleic acids.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutic Nanocarriers with Hydrogen Peroxide-Triggered Drug Release for Cancer Treatment.", "output": {"entities": {"chemical": [{"text": "Hydrogen Peroxide", "start": 30, "end": 47}]}}, "schema": []}
{"input": "Chemotherapy is an important modality in cancer treatment.", "output": {"entities": {}}, "schema": []}
{"input": "The major challenge of recent works in this research field is to develop new types of smart nanocarriers that can respond selectively to cancer cell-specific conditions and realize rapid drug release in target cells.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, a reactive oxygen species-responsive nanocarrier has been successfully self-assembled from an amphiphilic hyperbranched polymer consisting of alternative hydrophobic selenide groups and hydrophilic phosphate segments in the dendritic backbone.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 33, "end": 39}, {"text": "selenide", "start": 188, "end": 196}, {"text": "phosphate", "start": 220, "end": 229}]}}, "schema": []}
{"input": "Because the hydrophobic selenide groups transformed into the hydrophilic selenone groups after oxidation under the exclusive oxidative microenvironment within cancer cells, the amphiphilic hyperbranched precursors become hydrophilic ones.", "output": {"entities": {"chemical": [{"text": "selenide", "start": 24, "end": 32}, {"text": "selenone", "start": 73, "end": 81}]}}, "schema": []}
{"input": "As a result, the nanocarriers were rapidly disassembled in target cells, resulting in fast intracellular drug release.", "output": {"entities": {}}, "schema": []}
{"input": "The hydrophilic products of oxidation can be degraded into harmless small molecular species via the enzymatic digestion of the phosphate segments and then eliminated by renal excretion.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 127, "end": 136}]}}, "schema": []}
{"input": "Meanwhile, the reactive selenium-containing nanocarrier possesses a potent intrinsic anticancer effect since selenium compounds can produce antitumor metabolites which induce apoptosis of cancer cells efficiently.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 24, "end": 32}, {"text": "selenium", "start": 109, "end": 117}]}}, "schema": []}
{"input": "Therefore, this type of therapeutic nanocarriers with a unique drug release mechanism based on an amphiphilic-to-hydrophilic transition provides a new platform for targeted drug delivery and combined therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Modeling Adsorption of Cationic Surfactants at Air/Water Interface without Using the Gibbs Equation.", "output": {"entities": {}}, "schema": []}
{"input": "The Gibbs adsorption equation has been indispensable in predicting the surfactant adsorption at the interfaces, with many applications in industrial and natural processes.", "output": {"entities": {}}, "schema": []}
{"input": "This study uses a new theoretical framework to model surfactant adsorption at the air/water interface without the Gibbs equation.", "output": {"entities": {}}, "schema": []}
{"input": "The model was applied to two surfactants, C14TAB and C16TAB, to determine the maximum surface excesses.", "output": {"entities": {}}, "schema": []}
{"input": "The obtained values demonstrated a fundamental change, which was verified by simulations, in the molecular arrangement at the interface.", "output": {"entities": {}}, "schema": []}
{"input": "The new insights, in combination with recent discoveries in the field, expose the limitations of applying the Gibbs adsorption equation to cationic surfactants at the air/water interface.", "output": {"entities": {}}, "schema": []}
{"input": "Carbonic anhydrase inhibitors: Inhibition of the beta-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides.", "output": {"entities": {"chemical": [{"text": "sulfonamides", "start": 115, "end": 127}, {"text": "sulfamates", "start": 129, "end": 139}, {"text": "sulfamides", "start": 144, "end": 154}]}}, "schema": []}
{"input": "The fungal pathogen Candida glabrata encodes for a beta-carbonic anhydrase (CA, EC 4. 2. 1. 1), CgNce103, recently discovered.", "output": {"entities": {}}, "schema": []}
{"input": "Only anions have been investigated as CgNce103 inhibitors up until now.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report the first sulfonamides inhibition study of this enzyme.", "output": {"entities": {"chemical": [{"text": "sulfonamides", "start": 25, "end": 37}]}}, "schema": []}
{"input": "Simple sulfonamides showed weak or moderate CgNce103 inhibitory properties, whereas acetazolamide, and a series of 4-substituted ureido-benzene-sulfonamides, sulfamates and sulfamides showed effective CgNce103 inhibitory properties, with KIs in the range of 4. 1-115nM, being also ineffective as human CA II inhibitors.", "output": {"entities": {"chemical": [{"text": "sulfonamides", "start": 7, "end": 19}, {"text": "acetazolamide", "start": 84, "end": 97}, {"text": "4-substituted ureido-benzene-sulfonamides", "start": 115, "end": 156}, {"text": "sulfamates", "start": 158, "end": 168}, {"text": "sulfamides", "start": 173, "end": 183}]}}, "schema": []}
{"input": "As there is significant resistance of C. glabrata clinical isolates to many classical antifungal agents, inhibition of the beta-CA from this organism may allow an interesting means of controlling the pathogen growth, eventually leading to antifungals with a novel mechanism of action.", "output": {"entities": {}}, "schema": []}
{"input": "Optoacoustic tweezers: a programmable, localized cell concentrator based on opto-thermally generated, acoustically activated, surface bubbles.", "output": {"entities": {}}, "schema": []}
{"input": "We present a programmable, biocompatible technique for dynamically concentrating and patterning particles and cells in a microfluidic device.", "output": {"entities": {}}, "schema": []}
{"input": "Since our technique utilizes opto-thermally generated, acoustically activated, surface bubbles, we name it \" optoacoustic tweezers \".", "output": {"entities": {}}, "schema": []}
{"input": "The optoacoustic tweezers are capable of concentrating particles/cells at any prescribed locations in a microfluidic chamber without the use of permanent structures, rendering it particularly useful for the formation of flexible, complex cell patterns.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, this technique has demonstrated excellent biocompatibility and can be conveniently integrated with other microfluidic units.", "output": {"entities": {}}, "schema": []}
{"input": "In our experiments, micro-bubbles were generated by focusing a 405 nm diode laser onto a gold-coated glass chamber.", "output": {"entities": {}}, "schema": []}
{"input": "By properly tuning the laser, we demonstrate precise control over the position and size of the generated bubbles.", "output": {"entities": {}}, "schema": []}
{"input": "Acoustic waves were then applied to activate the surface bubbles, causing them to oscillate at an optimized frequency.", "output": {"entities": {}}, "schema": []}
{"input": "The resulting acoustic radiation force allowed us to locally trap particles/cells, including 15 mu m polystyrene beads and HeLa cells, around each bubble.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 101, "end": 112}]}}, "schema": []}
{"input": "Cell-adhesion tests were also conducted after cell concentrating to confirm the biocompatibility of this technique.", "output": {"entities": {}}, "schema": []}
{"input": "Population pharmacokinetics of intramuscular artesunate in african children with severe malaria: implications for a practical dosing regimen.", "output": {"entities": {"chemical": [{"text": "artesunate", "start": 45, "end": 55}]}}, "schema": []}
{"input": "Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria.", "output": {"entities": {"chemical": [{"text": "artesunate", "start": 11, "end": 21}, {"text": "ARS", "start": 23, "end": 26}]}}, "schema": []}
{"input": "Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria.", "output": {"entities": {"chemical": [{"text": "ARS", "start": 39, "end": 42}]}}, "schema": []}
{"input": "A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years.", "output": {"entities": {"chemical": [{"text": "ARS", "start": 38, "end": 41}, {"text": "dihydroartemisinin", "start": 46, "end": 64}, {"text": "DHA", "start": 66, "end": 69}]}}, "schema": []}
{"input": "All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2. 4 mg/kg at 0, 12, and 24 h).", "output": {"entities": {"chemical": [{"text": "ARS", "start": 102, "end": 105}]}}, "schema": []}
{"input": "Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM).", "output": {"entities": {}}, "schema": []}
{"input": "A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA.", "output": {"entities": {"chemical": [{"text": "ARS", "start": 99, "end": 102}, {"text": "DHA", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Body weight significantly affected clearance and apparent volume of distribution (P < 0. 001), resulting in lower ARS and DHA exposure levels in smaller children.", "output": {"entities": {"chemical": [{"text": "ARS", "start": 114, "end": 117}, {"text": "DHA", "start": 122, "end": 125}]}}, "schema": []}
{"input": "An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model.", "output": {"entities": {}}, "schema": []}
{"input": "If you don' t know where you are going, you can' t tell if you have arrived: defining goals for drug safety announcements.", "output": {"entities": {}}, "schema": []}
{"input": "One of the responses available to drug regulators facing a potential drug safety issue is to release a \" Dear Doctor \" letter describing the problem.", "output": {"entities": {}}, "schema": []}
{"input": "Although numerous such safety alerts are issued every year, we know almost nothing about their effectiveness in improving patient outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "The article by Reber et al. in this issue is important because it is one of the few studies to examine the effect of such safety alerts on physician behavior.", "output": {"entities": {}}, "schema": []}
{"input": "A copper hyperaccumulation phenotype correlates with pathogenesis in Cryptococcus neoformans.", "output": {"entities": {"chemical": [{"text": "copper", "start": 2, "end": 8}]}}, "schema": []}
{"input": "Cryptococcus neoformans is a major human pathogen and a cause of meningoencephalitis in immunocompromised patients.", "output": {"entities": {}}, "schema": []}
{"input": "Many factors contribute to the extraordinary survivability and pathogenicity of this fungus in humans, including copper homeostasis pathways.", "output": {"entities": {"chemical": [{"text": "copper", "start": 113, "end": 119}]}}, "schema": []}
{"input": "Previous work has shown that deletion of the copper-dependent regulator Cuf1 results in decreased virulence and dissemination in brain infection, suggesting that copper acquisition is important to the persistence of this pathogen.", "output": {"entities": {"chemical": [{"text": "copper", "start": 45, "end": 51}, {"text": "copper", "start": 162, "end": 168}]}}, "schema": []}
{"input": "Here, we show that the minimal copper quota of C. neoformans is maintained at a high level even when grown under conditions of stringent copper limitation.", "output": {"entities": {"chemical": [{"text": "copper", "start": 31, "end": 37}, {"text": "copper", "start": 137, "end": 143}]}}, "schema": []}
{"input": "Intriguingly, when this fungal pathogen is grown in standard and copper-enriched media, it sequesters even higher levels of this essential metal, achieving levels that are far higher than non-pathogenic S. cerevisiae.", "output": {"entities": {"chemical": [{"text": "copper", "start": 65, "end": 71}]}}, "schema": []}
{"input": "The hypothesis that copper acquisition plays an essential role in virulence is further corroborated by the findings that a hypovirulent CUF1-deletant strain of C. neoformans retrieved from infected mice contains almost a 6-fold lower concentration of intracellular copper than the pathogenic wild-type strain.", "output": {"entities": {"chemical": [{"text": "copper", "start": 20, "end": 26}, {"text": "copper", "start": 265, "end": 271}]}}, "schema": []}
{"input": "The concentration difference arises in part from larger-sized cuf1 Delta cell.", "output": {"entities": {}}, "schema": []}
{"input": "Under in vitro growth conditions, the size of the cuf1 Delta cells is normal and the hypertrophy phenotype is readily induced in vitro under conditions of copper starvation.", "output": {"entities": {"chemical": [{"text": "copper", "start": 155, "end": 161}]}}, "schema": []}
{"input": "Taken together, these data suggest that acquisition of extraordinary levels of copper is an important factor in the survivability of the pathogen in the copper-deplete environment of infection, and effective copper concentration may play an important role in the pathogenesis of C. neoformans.", "output": {"entities": {"chemical": [{"text": "copper", "start": 79, "end": 85}, {"text": "copper", "start": 153, "end": 159}, {"text": "copper", "start": 208, "end": 214}]}}, "schema": []}
{"input": "Effect of voltage polarity and amplitude on electroforming of TiO2 based memristive devices.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 62, "end": 66}]}}, "schema": []}
{"input": "Pt/TiO2/Pt/Ti memristive devices were electrically formed to either the ON or OFF state using voltages of the same polarity but with different amplitudes.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 0, "end": 2}, {"text": "TiO2", "start": 3, "end": 7}, {"text": "Pt", "start": 8, "end": 10}, {"text": "Ti", "start": 11, "end": 13}]}}, "schema": []}
{"input": "The forming step dictated the subsequent switching behaviour.", "output": {"entities": {}}, "schema": []}
{"input": "A qualitative model based on the creation and migration of oxygen vacancies was proposed to explain the experimental results.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 59, "end": 65}]}}, "schema": []}
{"input": "Is Artemisinin the Only Antiplasmodial Compound in the Artemisia annua Tea Infusion?", "output": {"entities": {"chemical": [{"text": "Artemisinin", "start": 3, "end": 14}]}}, "schema": []}
{"input": "An in Vitro Study.", "output": {"entities": {}}, "schema": []}
{"input": "In our ongoing investigation into Artemisia annua for the treatment of malaria, we decided to study the possibility that synergism might enhance the efficacy of artemisinin.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 161, "end": 172}]}}, "schema": []}
{"input": "Our main objective was to test tea infusions and nonpolar extracts prepared from different A. annua varieties against Plasmodium falciparum in vitro in order to determine if synergism will increase the effectiveness of artemisinin in the samples as compared to pure artemisinin.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 219, "end": 230}, {"text": "artemisinin", "start": 266, "end": 277}]}}, "schema": []}
{"input": "We found that the IC50 of artemisinin in the tea and nonpolar extracts was not significantly different to the IC50 of pure artemisinin.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 26, "end": 37}, {"text": "artemisinin", "start": 123, "end": 134}]}}, "schema": []}
{"input": "We could show that the year and country of harvest or storage conditions did not have any influence on the activity and that it narrowly followed the concentration of artemisinin in all the extracts.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 167, "end": 178}]}}, "schema": []}
{"input": "In conclusion, based on these in vitro results, artemisinin seems to be the only active antiplasmodial compound in A. annua.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 48, "end": 59}]}}, "schema": []}
{"input": "Hop Extracts and Hop Substances in Treatment of Menopausal Complaints.", "output": {"entities": {}}, "schema": []}
{"input": "Hop extract is a long used medicinal product and, regarding hormonal activities, in 1999 a number of prenylflavanones have been identified as its major constituents with 8-prenylnaringenin (8-PN) being the main active estrogenic compound.", "output": {"entities": {"chemical": [{"text": "prenylflavanones", "start": 101, "end": 117}, {"text": "8-prenylnaringenin", "start": 170, "end": 188}, {"text": "8-PN", "start": 190, "end": 194}]}}, "schema": []}
{"input": "There have been several in vivo studies performed that demonstrate the potential of hop extract and the single compound 8-PN to alleviate climacteric symptoms like osteoporosis, vasomotoric complaints, and sexual motivation.", "output": {"entities": {"chemical": [{"text": "8-PN", "start": 120, "end": 124}]}}, "schema": []}
{"input": "On the other hand, only a few clinical studies have been performed so far, and these mainly focused on menopausal discomforts, especially hot flushes, yielding rather inconclusive results.", "output": {"entities": {}}, "schema": []}
{"input": "Despite preferentially activating estrogen receptor alpha, 8-PN is only slightly uterotrophic, but it also elucidates estrogenic effects on the mammary gland.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 34, "end": 42}, {"text": "8-PN", "start": 59, "end": 63}]}}, "schema": []}
{"input": "In conclusion, although hop extract and especially 8-PN are promising candidates as a relief for climacteric symptoms, data on the safety and efficacy is still scarce.", "output": {"entities": {"chemical": [{"text": "8-PN", "start": 51, "end": 55}]}}, "schema": []}
{"input": "Cardamonin Ameliorates Insulin Resistance Induced by High Insulin and High Glucose through the mTOR and Signal Pathway.", "output": {"entities": {"chemical": [{"text": "Cardamonin", "start": 0, "end": 10}, {"text": "Glucose", "start": 75, "end": 82}]}}, "schema": []}
{"input": "The mammalian target of rapamycin is crucial in the regulation of cell growth and metabolism.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 24, "end": 33}]}}, "schema": []}
{"input": "Recent studies suggest that the mammalian target of rapamycin and its downstream 70-kDa ribosomal S6 kinase 1 negatively modulate the insulin-signaling pathway, which is considered the main cause of insulin resistance.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 52, "end": 61}]}}, "schema": []}
{"input": "The aim of this study is to investigate the effects of cardamonin, a potential inhibitor of the mammalian target of the rapamycin, on insulin-resistant vascular smooth muscle cells and the molecular mechanisms involved.", "output": {"entities": {"chemical": [{"text": "cardamonin", "start": 55, "end": 65}, {"text": "rapamycin", "start": 120, "end": 129}]}}, "schema": []}
{"input": "Vascular smooth muscle cells were cultured with high glucose and high insulin to induce insulin resistance.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 53, "end": 60}]}}, "schema": []}
{"input": "The mammalian target of rapamycin was overstimulated in cells that were incubated with high glucose and high insulin, as reflected by the excessive activation of S6 kinase 1.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 24, "end": 33}, {"text": "glucose", "start": 92, "end": 99}]}}, "schema": []}
{"input": "Insulin-resistant vascular smooth muscle cells displayed hyperphosphorylation of insulin receptor substrate-1 at Ser residues 636/639, which decreased the activity of insulin receptor substrate-1.", "output": {"entities": {"chemical": [{"text": "Ser", "start": 113, "end": 116}]}}, "schema": []}
{"input": "Also, the activation of protein kinase B and phosphorylation of glycogen synthesis kinase-3 beta were inhibited.", "output": {"entities": {}}, "schema": []}
{"input": "Cardamonin increased the 2-deoxyglucose uptake and glycogen concentration, which was reduced by insulin resistance.", "output": {"entities": {"chemical": [{"text": "Cardamonin", "start": 0, "end": 10}, {"text": "2-deoxyglucose", "start": 25, "end": 39}]}}, "schema": []}
{"input": "As with rapamycin, cardamonin inhibited the activity of the mammalian target of rapamycin and S6 kinase 1, decreased the Ser 636/639 phosphorylation of insulin receptor substrate-1 and increased the activation of protein kinase B.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 8, "end": 17}, {"text": "cardamonin", "start": 19, "end": 29}, {"text": "rapamycin", "start": 80, "end": 89}, {"text": "Ser", "start": 121, "end": 124}]}}, "schema": []}
{"input": "Both of them increased the Ser9 phosphorylation of glycogen synthesis kinase-3 beta and decreased the expression of glycogen synthesis kinase-3 beta.", "output": {"entities": {"chemical": [{"text": "Ser9", "start": 27, "end": 31}]}}, "schema": []}
{"input": "However, neither cardamonin nor rapamycin increased the expression of glucose transport 4 which decreased in insulin-resistant vascular smooth muscle cells.", "output": {"entities": {"chemical": [{"text": "cardamonin", "start": 17, "end": 27}, {"text": "rapamycin", "start": 32, "end": 41}, {"text": "glucose", "start": 70, "end": 77}]}}, "schema": []}
{"input": "This study suggests that cardamonin inhibited the activity of the mammalian target of rapamycin and eliminated the negative feedback of the mammalian target of rapamycin and S6 kinase 1 on the insulin-signaling pathway.", "output": {"entities": {"chemical": [{"text": "cardamonin", "start": 25, "end": 35}, {"text": "rapamycin", "start": 86, "end": 95}, {"text": "rapamycin", "start": 160, "end": 169}]}}, "schema": []}
{"input": "NAD (P) H: Quinone Oxidoreductase 1 Inducer Activity of Some Saudi Arabian Medicinal Plants.", "output": {"entities": {"chemical": [{"text": "NAD (P) H", "start": 0, "end": 9}, {"text": "Quinone", "start": 11, "end": 18}]}}, "schema": []}
{"input": "Medicinal plants are a rich source of biologically-active phytochemicals and have been used in traditional medicine for centuries.", "output": {"entities": {}}, "schema": []}
{"input": "Specific phytochemicals and extracts of their plant sources have the ability to reduce the risk for chronic degenerative diseases by induction of enzymes involved in xenobiotic metabolism, many of which also have antioxidant and anti-inflammatory functions.", "output": {"entities": {}}, "schema": []}
{"input": "One such multifunctional cytoprotective enzyme is NAD (P) H: quinone oxidoreductase.", "output": {"entities": {"chemical": [{"text": "NAD (P) H", "start": 50, "end": 59}, {"text": "quinone", "start": 61, "end": 68}]}}, "schema": []}
{"input": "In this study, we prepared extracts of 27 Saudi Arabian medicinal plants which belong to 18 different plant families and tested their ability to induce NAD (P) H: quinone oxidoreductase in murine hepatoma cells grown in microtiter plate wells.", "output": {"entities": {"chemical": [{"text": "NAD (P) H", "start": 152, "end": 161}, {"text": "quinone", "start": 163, "end": 170}]}}, "schema": []}
{"input": "In addition to the Brassicaceae, a known source of NAD (P) H: quinone oxidoreductase inducer activity, we found substantial inducer activity in extracts from the Apiaceae, Apocynaceae, and the Asteraceae families.", "output": {"entities": {"chemical": [{"text": "NAD (P) H", "start": 51, "end": 60}, {"text": "quinone", "start": 62, "end": 69}]}}, "schema": []}
{"input": "Five out of a total of eight active extracts are from plants which belong to the Asteraceae family.", "output": {"entities": {}}, "schema": []}
{"input": "We further show that artemisinin, an agent which is used clinically for the treatment of malaria, contributes but does not fully account for the inducer activity of the extract of Artemisia monosperma.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 21, "end": 32}]}}, "schema": []}
{"input": "In contrast to artemisinin, deoxyartemisinin is inactive in this assay, demonstrating the critical role of the endoperoxide moiety of artemisinin for inducer activity.", "output": {"entities": {"chemical": [{"text": "artemisinin", "start": 15, "end": 26}, {"text": "deoxyartemisinin", "start": 28, "end": 44}, {"text": "artemisinin", "start": 134, "end": 145}]}}, "schema": []}
{"input": "Thus, the NAD (P) H: quinone oxidoreductase inducer activity of extracts of some Saudi Arabian medicinal plants indicates the presence of specific phytochemicals which have the potential to protect against chronic degenerative diseases.", "output": {"entities": {"chemical": [{"text": "NAD (P) H", "start": 10, "end": 19}, {"text": "quinone", "start": 21, "end": 28}]}}, "schema": []}
{"input": "The protective effects of omega-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "omega-3 fatty acids", "start": 26, "end": 45}, {"text": "doxorubicin", "start": 49, "end": 60}]}}, "schema": []}
{"input": "This study aims to evaluate the protective effects of omega-3 fatty acids (FAs) on doxorubicin (DOX)-induced hepatotoxicity and nephrotoxicity in rats.", "output": {"entities": {"chemical": [{"text": "omega-3 fatty acids", "start": 54, "end": 73}, {"text": "FAs", "start": 75, "end": 78}, {"text": "doxorubicin", "start": 83, "end": 94}, {"text": "DOX", "start": 96, "end": 99}]}}, "schema": []}
{"input": "A total of 24 adult male Sprague Dawley rats were divided into three groups.", "output": {"entities": {}}, "schema": []}
{"input": "Control group was given only saline by intragastric gavage.", "output": {"entities": {}}, "schema": []}
{"input": "DOX group received DOX at the dose of 30 mg/kg intraperitoneally on day 28.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 0, "end": 3}, {"text": "DOX", "start": 19, "end": 22}]}}, "schema": []}
{"input": "DOX-omega-3 FA group was given as omega-3 FAs at the dose of 400 mg/kg daily by intragastric gavage for 30 days and received DOX at the dose of 30 mg/kg intraperitoneally on day 28.", "output": {"entities": {"chemical": [{"text": "DOX-omega-3 FA", "start": 0, "end": 14}, {"text": "omega-3 FAs", "start": 34, "end": 45}, {"text": "DOX", "start": 125, "end": 128}]}}, "schema": []}
{"input": "At the end of the 30-day experimental period, the serum, liver and kidney tissue specimens were taken from the animals by giving a general anesthesia.", "output": {"entities": {}}, "schema": []}
{"input": "Glutathione (GSH) and malondialdehyde (MDA) levels in serum and GSH and MDA levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and kidney tissues were measured spectrophotometrically.", "output": {"entities": {"chemical": [{"text": "Glutathione", "start": 0, "end": 11}, {"text": "GSH", "start": 13, "end": 16}, {"text": "malondialdehyde", "start": 22, "end": 37}, {"text": "MDA", "start": 39, "end": 42}, {"text": "GSH", "start": 64, "end": 67}, {"text": "MDA", "start": 72, "end": 75}, {"text": "superoxide", "start": 87, "end": 97}, {"text": "glutathione", "start": 118, "end": 129}, {"text": "GSH", "start": 142, "end": 145}]}}, "schema": []}
{"input": "In our study, a significant increase in MDA levels was observed in rats when given a dose of DOX and a significant decrease in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues was determined when compared with control group.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 40, "end": 43}, {"text": "DOX", "start": 93, "end": 96}, {"text": "GSH", "start": 141, "end": 144}, {"text": "GSH", "start": 154, "end": 157}]}}, "schema": []}
{"input": "In addition, a significant decrease in MDA levels was observed in rats when a dose of omega-3 FAs was given with DOX and a significant increase was determined in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues, when compared with DOX group.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 39, "end": 42}, {"text": "omega-3 FAs", "start": 86, "end": 97}, {"text": "DOX", "start": 113, "end": 116}, {"text": "GSH", "start": 176, "end": 179}, {"text": "GSH", "start": 189, "end": 192}, {"text": "DOX", "start": 262, "end": 265}]}}, "schema": []}
{"input": "We concluded that omega-3 FA had favorable effects in rat liver and kidney tissues by preventing oxidative damage.", "output": {"entities": {"chemical": [{"text": "omega-3 FA", "start": 18, "end": 28}]}}, "schema": []}
{"input": "Metabolism of Beclomethasone Dipropionate by Cytochrome P450 3A Enzymes.", "output": {"entities": {"chemical": [{"text": "Beclomethasone Dipropionate", "start": 14, "end": 41}]}}, "schema": []}
{"input": "Inhaled glucocorticoids, such as beclomethasone dipropionate (BDP), are the mainstay treatment of asthma.", "output": {"entities": {"chemical": [{"text": "beclomethasone dipropionate", "start": 33, "end": 60}, {"text": "BDP", "start": 62, "end": 65}]}}, "schema": []}
{"input": "However, ~ 30% of patients exhibit little to no benefit from treatment.", "output": {"entities": {}}, "schema": []}
{"input": "It has been postulated that glucocorticoid resistance, or insensitivity, is attributable to individual differences in glucocorticoid receptor-mediated processes.", "output": {"entities": {}}, "schema": []}
{"input": "It is possible that variations in cytochrome P450 3A enzyme-mediated metabolism of BDP may contribute to this phenomenon.", "output": {"entities": {"chemical": [{"text": "BDP", "start": 83, "end": 86}]}}, "schema": []}
{"input": "This hypothesis was explored by evaluating the contributions of CYP3A4, 3A5, 3A7, and esterase enzymes in the metabolism of BDP in vitro and relating metabolism to changes in CYP3A enzyme mRNA expression via the glucocorticoid receptor in lung and liver cells.", "output": {"entities": {"chemical": [{"text": "BDP", "start": 124, "end": 127}]}}, "schema": []}
{"input": "CYP3A4 and CYP3A5 metabolized BDP via hydroxylation ([M4] and [M6]) and dehydrogenation ([M5]) at similar rates; CYP3A7 did not metabolize BDP.", "output": {"entities": {"chemical": [{"text": "BDP", "start": 30, "end": 33}, {"text": "BDP", "start": 139, "end": 142}]}}, "schema": []}
{"input": "A new metabolite [M6], formed by the combined action of esterases and CYP3A4 hydroxylation, was also characterized.", "output": {"entities": {}}, "schema": []}
{"input": "To validate the results observed using microsomes and recombinant enzymes, studies were also conducted using A549 lung and DPX2 liver cells.", "output": {"entities": {}}, "schema": []}
{"input": "Both liver and lung cells produced esterase-dependent metabolites [M1-M3], with [M1] correlating with CYP3A5 mRNA induction in A549 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Liver cells produced both hydroxylated and dehydrogenated metabolites [M4, M5, and M6], but lung cells produced only the dehydrogenated metabolite [M5].", "output": {"entities": {}}, "schema": []}
{"input": "These studies show that CYP3A4 and CYP3A5 metabolize BDP to inactive metabolites and suggest that differences in the expression or function of these enzymes in the lung and/or liver could influence BDP disposition in humans.", "output": {"entities": {"chemical": [{"text": "BDP", "start": 53, "end": 56}, {"text": "BDP", "start": 198, "end": 201}]}}, "schema": []}
{"input": "The Tumor Suppressor Kruppel-Like Factor 6 is a Novel Aryl Hydrocarbon Receptor DNA Binding Partner.", "output": {"entities": {"chemical": [{"text": "Aryl Hydrocarbon", "start": 54, "end": 70}]}}, "schema": []}
{"input": "The Aryl Hydrocarbon Receptor (AhR) is a ligand mediated basic helix-loop-helix transcription factor of Per/Arnt/Sim family that regulates adaptive and toxic responses to variety of chemical pollutants including polycyclic aromatic hydrocarbons (PAH) and halogenated aromatic hydrocarbons, most notably 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).", "output": {"entities": {"chemical": [{"text": "Aryl Hydrocarbon", "start": 4, "end": 20}, {"text": "polycyclic aromatic hydrocarbons", "start": 212, "end": 244}, {"text": "PAH", "start": 246, "end": 249}, {"text": "halogenated aromatic hydrocarbons", "start": 255, "end": 288}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 303, "end": 341}, {"text": "TCDD", "start": 343, "end": 347}]}}, "schema": []}
{"input": "Ligand activation leads to AhR nuclear translocation and binding to a xenobiotic response element (XRE) in association with the aryl receptor nuclear translocator (Arnt) to regulate gene expression.", "output": {"entities": {}}, "schema": []}
{"input": "Several recent genome-wide transcriptional studies identified numerous AhR target genes that lack the canonical XRE recognition site in the promoter regions.", "output": {"entities": {}}, "schema": []}
{"input": "Characterization of one such target gene, the Plasminogen Activator Inhibitor 1 (PAI-1) identified a novel non-consensus XRE (NC-XRE) that confers TCDD responsiveness independently of the Arnt protein.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 147, "end": 151}]}}, "schema": []}
{"input": "Studies reported here show that the NC-XRE is a recognition site for the AhR and a new binding partner, the Kruppel-like Factor (KLF) family member KLF6.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo chromatin immunoprecipitations and in vitro DNA binding studies demonstrate that the AhR and KLF6 proteins form an obligatory heterodimer necessary for NC-XRE binding.", "output": {"entities": {}}, "schema": []}
{"input": "Mutational analyzes show that the protein-protein interactions involve the AhR C-terminus and KLF6 N-terminus, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, NC-XRE binding depends on the 5' basic region in KLF6 rather than the previously characterized zinc finger DNA binding domain.", "output": {"entities": {"chemical": [{"text": "zinc", "start": 105, "end": 109}]}}, "schema": []}
{"input": "Collectively, the results unmask a novel AhR signaling mechanism distinct from the canonical XRE-driven process that will enrich our future understanding of AhR biology.", "output": {"entities": {}}, "schema": []}
{"input": "Epigallocatechin-3-Gallate Inhibits Collagen Production of Nasal Polyp-Derived Fibroblasts.", "output": {"entities": {"chemical": [{"text": "Epigallocatechin-3-Gallate", "start": 0, "end": 26}]}}, "schema": []}
{"input": "Nasal polyps are chronic inflammatory conditions characterized by myofibroblast differentiation and extracelluar matrix accumulation.", "output": {"entities": {}}, "schema": []}
{"input": "The major catechin from green tea is (-)-epigallocatechin-3-gallate (EGCG), which has garnered attention for its potential to prevent oxidative stress-related diseases.", "output": {"entities": {"chemical": [{"text": "catechin", "start": 10, "end": 18}, {"text": "(-)-epigallocatechin-3-gallate", "start": 37, "end": 67}, {"text": "EGCG", "start": 69, "end": 73}]}}, "schema": []}
{"input": "The purpose of this study was twofold: (i) to determine the effect of EGCG on fibroblast differentiation into myofibroblasts and extracellular matrix accumulation in transforming growth factor (TGF)-beta 1-induced nasal polyp-derived fibroblasts (NPDFs) and (ii) to determine if the antioxidative effect of EGCG on reactive oxygen species (ROS) production in TGF-beta 1-induced NPDFs is involved in the aforementioned processes.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 70, "end": 74}, {"text": "EGCG", "start": 307, "end": 311}, {"text": "oxygen", "start": 324, "end": 330}]}}, "schema": []}
{"input": "TGF-beta 1-induced NPDFs were treated with or without EGCG.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 54, "end": 58}]}}, "schema": []}
{"input": "alpha-smooth muscle actin (alpha-SMA) and collagen type I mRNA were analyzed by reverse transcription-polymerase chain reaction.", "output": {"entities": {}}, "schema": []}
{"input": "alpha-SMA protein was also detected using immunofluorescent staining.", "output": {"entities": {}}, "schema": []}
{"input": "The amount of total soluble collagen was analyzed by Sircol collagen assay.", "output": {"entities": {"chemical": [{"text": "Sircol", "start": 53, "end": 59}]}}, "schema": []}
{"input": "ROS activity was measured by the nitroblue tetrazolium reduction assay and visualized by fluorescent microscopy.", "output": {"entities": {"chemical": [{"text": "nitroblue tetrazolium", "start": 33, "end": 54}]}}, "schema": []}
{"input": "EGCG significantly inhibited expressions of alpha-SMA and collagen type I mRNA and reduced alpha-SMA and collagen protein levels at concentrations of 10-20 micro g/mL.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 0, "end": 4}]}}, "schema": []}
{"input": "EGCG also inhibited TGF-beta 1-induced ROS production at the same concentrations.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 0, "end": 4}]}}, "schema": []}
{"input": "These results suggest the possibility that EGCG may be effective at inhibiting the development of nasal polyps through an anti-oxidant effect.", "output": {"entities": {"chemical": [{"text": "EGCG", "start": 43, "end": 47}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Neuroprotective Effects of Puerarin on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine induced Parkinson' s Disease Model in Mice.", "output": {"entities": {"chemical": [{"text": "Puerarin", "start": 27, "end": 35}, {"text": "1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine", "start": 39, "end": 86}]}}, "schema": []}
{"input": "Puerarin, an active component of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep is well-known for its anti-oxidative and neuroprotective activities.", "output": {"entities": {"chemical": [{"text": "Puerarin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Although anti-Parkinson' s disease activity of puerarin was reported in both of in vivo and in vitro model, detailed mechanisms are not clarified.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 47, "end": 55}]}}, "schema": []}
{"input": "In this study, we addressed that puerarin attenuated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced behavioral deficits, dopaminergic neuronal degeneration and dopamine depletion.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 33, "end": 41}, {"text": "1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine", "start": 53, "end": 100}, {"text": "MPTP", "start": 102, "end": 106}, {"text": "dopaminergic", "start": 137, "end": 149}]}}, "schema": []}
{"input": "Puerarin administration enhanced glutathione (GSH) activity, glial cell line-derived neurotrophic factor (GDNF) expression and PI3K/Akt pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice.", "output": {"entities": {"chemical": [{"text": "Puerarin", "start": 0, "end": 8}, {"text": "glutathione", "start": 33, "end": 44}, {"text": "GSH", "start": 46, "end": 49}, {"text": "MPTP", "start": 179, "end": 183}, {"text": "oxygen", "start": 236, "end": 242}]}}, "schema": []}
{"input": "In addition to the effect on ROS, puerarin ameliorated MPTP-reduced lysosome-associated membrane protein type 2A (Lamp 2A) expression.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 34, "end": 42}, {"text": "MPTP", "start": 55, "end": 59}]}}, "schema": []}
{"input": "Taken together, our data demonstrate that puerarin attenuates MPTP-induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate MPTP-induced ROS formation and decrease of Lamp 2A expression.", "output": {"entities": {"chemical": [{"text": "puerarin", "start": 42, "end": 50}, {"text": "MPTP", "start": 62, "end": 66}, {"text": "GSH", "start": 163, "end": 166}, {"text": "MPTP", "start": 209, "end": 213}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "The Minimum Activation Peptide from ilvH Can Activate the Catalytic Subunit of AHAS from Different Species.", "output": {"entities": {}}, "schema": []}
{"input": "Acetohydroxyacid synthases (AHASs), which catalyze the first step in the biosynthesis of branched-chain amino acids, are composed of a catalytic subunit (CSU) and a regulatory subunit (RSU).", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 104, "end": 115}]}}, "schema": []}
{"input": "The CSU harbors the catalytic site, and the RSU is responsible for the activation and feedback regulation of the CSU.", "output": {"entities": {}}, "schema": []}
{"input": "Previous results from Chipman and co-workers and our lab have shown that heterologous activation can be achieved among isozymes of Escherichia coli AHAS.", "output": {"entities": {}}, "schema": []}
{"input": "It would be interesting to find the minimum peptide of ilvH (the RSU of E. coli AHAS III) that could activate other E. coli CSUs, or even those of ##species.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, C-terminal, N-terminal, and C-and N-terminal truncation mutants of ilvH were constructed.", "output": {"entities": {"chemical": [{"text": "C", "start": 15, "end": 16}, {"text": "N", "start": 27, "end": 28}, {"text": "C", "start": 43, "end": 44}, {"text": "N", "start": 49, "end": 50}]}}, "schema": []}
{"input": "The minimum peptide to activate ilvI (the CSU of E. coli AHAS III) was found to be Delta N 14-Delta C 89.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, this peptide could not only activate its homologous ilvI and heterologous ilvB (CSU of E. coli AHAS I), but also heterologously activate the CSUs of AHAS from Saccharomyces cerevisiae, Arabidopsis thaliana, and Nicotiana plumbaginifolia.", "output": {"entities": {}}, "schema": []}
{"input": "However, this peptide totally lost its ability for feedback regulation by valine, thus suggesting different elements for enzymatic activation and feedback regulation.", "output": {"entities": {"chemical": [{"text": "valine", "start": 74, "end": 80}]}}, "schema": []}
{"input": "Additionally, the apparent dissociation constant (Kd) of Delta N 14-Delta C 89 when binding CSUs of different species was found to be 9. 3-66. 5 mu M by using microscale thermophoresis.", "output": {"entities": {}}, "schema": []}
{"input": "The ability of this peptide to activate different CSUs does not correlate well with its binding ability (Kd) to these CSUs, thus implying that key interactions by specific residues is more important than binding ability in promoting enzymatic reactions.", "output": {"entities": {}}, "schema": []}
{"input": "The high sequence similarity of the peptide Delta N 14-Delta C 89 to RSUs across species hints that this peptide represents the minimum activation motif in RSU and that it regulates all AHASs.", "output": {"entities": {}}, "schema": []}
{"input": "Cognitive impairment and dietary habits among elders: the velestino study.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract To investigate the association of dietary habits with cognitive function among elders (> 65 years).", "output": {"entities": {}}, "schema": []}
{"input": "Complete sociodemographic, dietary information, serum measurements, and Mini-Mental State Examination (MMSE) assessments were available for 237 elderly men and 320 women residing in Velestino, Greece (a rural Greek town).", "output": {"entities": {}}, "schema": []}
{"input": "All models were adjusted for age, education, social activity, smoking, depression symptomatology (using the Geriatric Depression Scale), MedDietScore (range 0-55), and metabolic syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "About 49. 8% men and 66. 6% women had MMSE scores < 24, with a mean MMSE score of 22. 7 +/- 4. 43 and 21. 1 +/- 4. 73, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Adherence to the Mediterranean diet was moderate (mean MedDietScore of 34. 1 +/- 3. 25 in men and 35. 1 +/- 2. 48 in women).", "output": {"entities": {}}, "schema": []}
{"input": "Indicative cognitive impairment (MMSE score < 24) was positively associated with age and low education in women and with depressive symptoms, low education status, and low social activity in men.", "output": {"entities": {}}, "schema": []}
{"input": "Adherence to the Mediterranean diet was positively associated with MMSE score in men (P =. 02), but inversely associated in women (P =. 04).", "output": {"entities": {}}, "schema": []}
{"input": "Concerning the food groups studied, intake of pulses, nuts, and seeds was associated with lower likelihood of having MMSE score < 24 in men (P =. 04).", "output": {"entities": {}}, "schema": []}
{"input": "Only the Mediterranean dietary pattern showed a significant association with MMSE score positive for cognitive impairment (i. e., protective in men, but not in women), while individual food groups or nutrients did not achieve significance.", "output": {"entities": {}}, "schema": []}
{"input": "The latter findings support the role of whole diet in the prevention of mental disorders, and state a research hypothesis for a sex-diet interaction on cognitive function among elders.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative and Photoxidative Polymerization of Humic Suprastructures by Heterogeneous Biomimetic Catalysis.", "output": {"entities": {}}, "schema": []}
{"input": "The meso-tetra (2, 6-dichloro-3-sulfonatophenyl) porphyrinate of manganese (III) chloride [Mn-(TDCPPS) Cl] biomimetic catalyst immobilized on spacer-functionalized kaolinite clay mineral was employed in the oxidative coupling reaction of a dissolved humic acid (HA) suprastructure with either chemical (H2O2) or UV-light oxidation.", "output": {"entities": {"chemical": [{"text": "meso-tetra (2, 6-dichloro-3-sulfonatophenyl) porphyrinate", "start": 4, "end": 61}, {"text": "manganese (III) chloride [Mn-(TDCPPS) Cl]", "start": 65, "end": 106}, {"text": "kaolinite", "start": 164, "end": 173}, {"text": "H2O2", "start": 303, "end": 307}]}}, "schema": []}
{"input": "The changes in molecular size of humic matter subjected to catalyzed oxidative reaction were followed by high-performance size exclusion chromatography (HPSEC) with UV-vis and refractive index (RI) detectors in series, and by thermogravimetric (TGA) analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Both the enhanced molecular size shown by differences between HPSEC chromatograms of humic reaction mixtures at either pH 6 or 3. 5 and the increase of thermogravimetric stability suggest that the heterogeneous biomimetic catalysis promoted the stabilization of humic conformations by new intermolecular covalent bonds during oxidative coupling.", "output": {"entities": {}}, "schema": []}
{"input": "The similarity between chemical and light-induced oxidation results suggests potential multiple applications of the kaolinite-supported heterogeneous catalyst in controlling the reactivity of natural organic matter within biogeochemical cycles and environmental reactions.", "output": {"entities": {"chemical": [{"text": "kaolinite", "start": 116, "end": 125}]}}, "schema": []}
{"input": "Stereoselective Potencies and Relative Toxicities of gamma-Coniceine and N-Methylconiine Enantiomers.", "output": {"entities": {"chemical": [{"text": "gamma-Coniceine", "start": 53, "end": 68}, {"text": "N-Methylconiine", "start": 73, "end": 88}]}}, "schema": []}
{"input": "gamma-Coniceine, coniine, and N-methylconiine are toxic alkaloids present in poison hemlock (Conium maculatum).", "output": {"entities": {"chemical": [{"text": "gamma-Coniceine", "start": 0, "end": 15}, {"text": "coniine", "start": 17, "end": 24}, {"text": "N-methylconiine", "start": 30, "end": 45}]}}, "schema": []}
{"input": "We previously reported the comparison of the relative potencies of (+)-and (-)-coniine enantiomers.", "output": {"entities": {"chemical": [{"text": "(+)-and (-)-coniine", "start": 67, "end": 86}]}}, "schema": []}
{"input": "In this study, we synthesized gamma-coniceine and the enantiomers of N-methylconiine and determined the biological activity of gamma-coniceine and each of the N-methylconiine enantiomers in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "gamma-coniceine", "start": 30, "end": 45}, {"text": "N-methylconiine", "start": 69, "end": 84}, {"text": "gamma-coniceine", "start": 127, "end": 142}, {"text": "N-methylconiine", "start": 159, "end": 174}]}}, "schema": []}
{"input": "The relative potencies of these piperidine alkaloids on cells expressing human fetal muscle-type nicotinic acetylcholine receptors had the rank order of gamma-coniceine > (-)-N-methylconiine > (+/-)-N-methylconiine > (+)-N-methylconiine.", "output": {"entities": {"chemical": [{"text": "piperidine alkaloids", "start": 32, "end": 52}, {"text": "acetylcholine", "start": 107, "end": 120}, {"text": "gamma-coniceine", "start": 153, "end": 168}, {"text": "(-)-N-methylconiine", "start": 171, "end": 190}, {"text": "(+/-)-N-methylconiine", "start": 193, "end": 214}, {"text": "(+)-N-methylconiine", "start": 217, "end": 236}]}}, "schema": []}
{"input": "The relative lethalities of gamma-coniceine and (-)-, (+/-)-, and (+)-N-methylconiine in vivo using a mouse bioassay were 4. 4, 16. 1, 17. 8, and 19. 2 mg/kg, respectively.", "output": {"entities": {"chemical": [{"text": "gamma-coniceine", "start": 28, "end": 43}, {"text": "(-)-, (+/-)-, and (+)-N-methylconiine", "start": 48, "end": 85}]}}, "schema": []}
{"input": "The results from this study suggest gamma-coniceine is a more potent agonist than the enantiomers of N-methylconiine and that there is a stereoselective difference in the in vitro potencies of the enantiomers of N-methylconiine that correlates with the relative toxicities of the enantiomers in vivo.", "output": {"entities": {"chemical": [{"text": "gamma-coniceine", "start": 36, "end": 51}, {"text": "N-methylconiine", "start": 101, "end": 116}, {"text": "N-methylconiine", "start": 212, "end": 227}]}}, "schema": []}
{"input": "Defect Chemistry of Oxide Nanomaterials with High Surface Area: Ordered Mesoporous Thin Films of the Oxygen Storage Catalyst CeO2-ZrO2.", "output": {"entities": {"chemical": [{"text": "Oxide", "start": 20, "end": 25}, {"text": "Oxygen", "start": 101, "end": 107}]}}, "schema": []}
{"input": "Herein we report the electrical transport properties of a series of ordered mesoporous ceria-zirconia (CexZr1-xO2, referred to as mp-CZO) thin films with both a cubic structure of (17 +/- 2) nm diameter pores and nanocrystalline walls.", "output": {"entities": {"chemical": [{"text": "ceria-zirconia", "start": 87, "end": 101}, {"text": "CexZr1-xO2", "start": 103, "end": 113}, {"text": "CZO", "start": 133, "end": 136}]}}, "schema": []}
{"input": "Samples over the whole range of composition, including bare CeO2 and ZrO2, were fabricated by templating strategies using the large diblock copolymer KLE as the structure-directing agent.", "output": {"entities": {"chemical": [{"text": "CeO2", "start": 60, "end": 64}, {"text": "ZrO2", "start": 69, "end": 73}, {"text": "KLE", "start": 150, "end": 153}]}}, "schema": []}
{"input": "Both the nanoscale structure and the chemical composition of the mesoporous materials were analyzed by a combination of scanning and transmission electron microscopy, grazing incidence small-angle X-ray scattering, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The total conductivity as a function of the film composition, temperature, and oxygen partial pressure was measured using impedance spectroscopy.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 79, "end": 85}]}}, "schema": []}
{"input": "The mesoporous solid solutions of CeO2-ZrO2 prepared in this work showed a higher stability against thermal ripening than both binary oxides, making them ideal model systems to study both the charge transport properties and the oxygen storage at elevated temperatures.", "output": {"entities": {"chemical": [{"text": "CeO2", "start": 34, "end": 38}, {"text": "ZrO2", "start": 39, "end": 43}]}}, "schema": []}
{"input": "We find that the redox properties of nanocrystalline mp-CZO thin films differ significantly from those of bulk CZO materials reported in the literature and, therefore, propose a defect chemical model of surface regions.", "output": {"entities": {"chemical": [{"text": "CZO", "start": 56, "end": 59}, {"text": "CZO", "start": 111, "end": 114}]}}, "schema": []}
{"input": "Colocalization of the Ganglioside GM1 and Cholesterol Detected by Secondary Ion Mass Spectrometry.", "output": {"entities": {"chemical": [{"text": "Ganglioside GM1", "start": 22, "end": 37}, {"text": "Cholesterol", "start": 42, "end": 53}]}}, "schema": []}
{"input": "The characterization of the lateral organization of components in biological membranes and the evolution of this arrangement in response to external triggers remain a major challenge.", "output": {"entities": {}}, "schema": []}
{"input": "The concept of lipid rafts is widely invoked; however, direct evidence of the existence of these ephemeral entities remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "We report here the use of secondary ion mass spectrometry (SIMS) to image the cholesterol-dependent cohesive phase separation of the ganglioside GM1 into nano-and microscale assemblies in a canonical lipid raft composition of lipids.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 78, "end": 89}, {"text": "ganglioside GM1", "start": 133, "end": 148}]}}, "schema": []}
{"input": "This assembly of domains was interrogated in a model membrane system composed of palmitoyl sphingomyelin (PSM), cholesterol, and an unsaturated lipid (dioleoylphosphatidylcholine, DOPC).", "output": {"entities": {"chemical": [{"text": "palmitoyl sphingomyelin", "start": 81, "end": 104}, {"text": "PSM", "start": 106, "end": 109}, {"text": "cholesterol", "start": 112, "end": 123}, {"text": "dioleoylphosphatidylcholine", "start": 151, "end": 178}, {"text": "DOPC", "start": 180, "end": 184}]}}, "schema": []}
{"input": "Orthogonal isotopic labeling of every lipid bilayer component and monofluorination of GM1 allowed generation of molecule specific images using a NanoSIMS.", "output": {"entities": {"chemical": [{"text": "GM1", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Simultaneous detection of six different ion species in SIMS, including secondary electrons, was used to generate ion ratio images whose signal intensity values could be correlated to composition through the use of calibration curves from standard samples.", "output": {"entities": {}}, "schema": []}
{"input": "Images of this system provide the first direct, molecule specific, visual evidence for the colocalization of cholesterol and GM1 in supported lipid bilayers and further indicate the presence of three compositionally distinct phases: (1) the interdomain region; (2) micrometer-scale domains (d > 3 mu m); (3) nanometer-scale domains (d = 100 nm to 1 mu m) localized within the micrometer-scale domains and the interdomain region.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 109, "end": 120}, {"text": "GM1", "start": 125, "end": 128}]}}, "schema": []}
{"input": "PSM-rich, nanometer-scale domains prefer to partition within the more ordered, cholesterol-rich/DOPC-poor/GM1-rich micrometer-scale phase, while GM1-rich, nanometer-scale domains prefer to partition within the surrounding, disordered, cholesterol-poor/PSM-rich/DOPC-rich interdomain phase.", "output": {"entities": {"chemical": [{"text": "PSM", "start": 0, "end": 3}, {"text": "cholesterol", "start": 79, "end": 90}, {"text": "DOPC", "start": 96, "end": 100}, {"text": "GM1", "start": 106, "end": 109}, {"text": "GM1", "start": 145, "end": 148}, {"text": "cholesterol", "start": 235, "end": 246}, {"text": "PSM", "start": 252, "end": 255}, {"text": "DOPC", "start": 261, "end": 265}]}}, "schema": []}
{"input": "Structure and Absolute Configuration of Methyl (3R)-Malonyl-(13S)-hydroxycheilanth-17-en-19-oate, a Sesterterpene Derivative from the Roots of Aletris farinosa.", "output": {"entities": {"chemical": [{"text": "Methyl (3R)-Malonyl-(13S)-hydroxycheilanth-17-en-19-oate", "start": 40, "end": 96}, {"text": "Sesterterpene", "start": 100, "end": 113}]}}, "schema": []}
{"input": "We report the isolation and structure elucidation of a new cheilanthane sesterterpene from the roots of Aletris farinosa that possesses an unusual malonate half-ester functional group.", "output": {"entities": {"chemical": [{"text": "cheilanthane sesterterpene", "start": 59, "end": 85}, {"text": "malonate half-ester", "start": 147, "end": 166}]}}, "schema": []}
{"input": "The structure of 1 was determined via mass spectrometry and 1D and 2D NMR spectroscopy, while its absolute configuration was determined via X-ray crystallographic analysis performed on its methyl ester derivative 2.", "output": {"entities": {"chemical": [{"text": "methyl ester", "start": 189, "end": 201}]}}, "schema": []}
{"input": "Baseline Markers of Inflammation Are Associated With Progression to Macroalbuminuria in Type 1 Diabetic Subjects.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEThe current study aimed to determine in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort whether or not abnormal levels of markers of inflammation and endothelial dysfunction measured in samples collected at DCCT baseline were able to predict the development of macroalbuminuria. RESEARCH DESIGN AND METHODSLevels of inflammation and endothelial cell dysfunction biomarkers were measured in 1, 237 of 1, 441 patients enrolled in the DCCT study who were both free of albuminuria and cardiovascular disease at baseline.", "output": {"entities": {}}, "schema": []}
{"input": "To test the association of log-transformed biomarkers with albuminuria, generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria.", "output": {"entities": {}}, "schema": []}
{"input": "Normal, micro-, and macroalbuminuria were the outcomes of interest. RESULTSIn the logistic regression models adjusted by DCCT treatment assignment, baseline albumin excretion rate, and use of ACE/angiotensin receptor blocker drugs, one unit increase in the standardized levels of soluble E-selectin (sE-selectin) was associated with an 87% increase in the odds to develop macroalbuminuria and one unit increase in the levels of interleukin-6 (IL-6), plasminogen activator inhibitor 1 (PAI-1; total and active), and soluble tumor necrosis factor receptors (TNFR)-1 and-2 lead to a 30-50% increase in the odds to develop macroalbuminuria.", "output": {"entities": {}}, "schema": []}
{"input": "Following adjustment for DCCT baseline retinopathy status, age, sex, HbA1c, and duration of diabetes, significant associations remained for sE-selectin and TNFR-1 and-2 but not for IL-6 or PAI-1. CONCLUSIONSOur study indicates that high levels of inflammatory markers, mainly E-selectin and sTNRF-1 and-2, are important predictors of macroalbuminuria in patients with type 1 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Biological activity of Pd (II) complexes with mono-and disubstituted pyridines-Experimental and theoretical studies.", "output": {"entities": {"chemical": [{"text": "Pd (II)", "start": 23, "end": 30}, {"text": "mono-and disubstituted pyridines", "start": 46, "end": 78}]}}, "schema": []}
{"input": "Due to the similarity between Pd and Pt, the complexes of palladium (II) can be considered as potential anticancer agents.", "output": {"entities": {"chemical": [{"text": "Pd", "start": 30, "end": 32}, {"text": "Pt", "start": 37, "end": 39}, {"text": "palladium (II)", "start": 58, "end": 72}]}}, "schema": []}
{"input": "Activity of six PdCl2 (X2Py) 2 complexes (Py = pyridine, and X = CH3 or Cl) was measured by MTT test using MCF7, CCRF-SB, PC3 and human B-lymphoblastoid cell lines.", "output": {"entities": {"chemical": [{"text": "PdCl2 (X2Py) 2", "start": 16, "end": 30}, {"text": "Py", "start": 42, "end": 44}, {"text": "pyridine", "start": 47, "end": 55}, {"text": "CH3", "start": 65, "end": 68}, {"text": "Cl", "start": 72, "end": 74}, {"text": "MTT", "start": 92, "end": 95}]}}, "schema": []}
{"input": "We found that the effect of PdCl2 (XnPy) 2 was cell-specific and time-dependent.", "output": {"entities": {"chemical": [{"text": "PdCl2 (XnPy) 2", "start": 28, "end": 42}]}}, "schema": []}
{"input": "Obtained results were discussed and compared with the activation parameters calculated for the hydrolysis of PdCl2 (XnPy) 2, indicating a correlation between viability of MCF7 and CCRF-SB cells and rates of hydrolysis of the Pd (II) complexes.", "output": {"entities": {"chemical": [{"text": "PdCl2 (XnPy) 2", "start": 109, "end": 123}, {"text": "Pd (II)", "start": 225, "end": 232}]}}, "schema": []}
{"input": "The Androgen Metabolite, 5 alpha-Androstane-3 beta, 17 beta-Diol (3 beta-Diol), Activates the Oxytocin Promoter Through an Estrogen Receptor-beta Pathway.", "output": {"entities": {"chemical": [{"text": "Androgen", "start": 4, "end": 12}, {"text": "5 alpha-Androstane-3 beta, 17 beta-Diol", "start": 25, "end": 64}, {"text": "3 beta-Diol", "start": 66, "end": 77}, {"text": "Oxytocin", "start": 94, "end": 102}, {"text": "Estrogen", "start": 123, "end": 131}]}}, "schema": []}
{"input": "Testosterone has been shown to suppress the acute stress-induced activation of the hypothalamic-pituitary-adrenal axis; however, the mechanisms underlying this response remain unclear.", "output": {"entities": {"chemical": [{"text": "Testosterone", "start": 0, "end": 12}]}}, "schema": []}
{"input": "The hypothalamic-pituitary-adrenal axis is regulated by a neuroendocrine subpopulation of medial parvocellular neurons in the paraventricular nucleus of the hypothalamus (PVN).", "output": {"entities": {}}, "schema": []}
{"input": "These neurons are devoid of androgen receptors (ARs).", "output": {"entities": {"chemical": [{"text": "androgen", "start": 28, "end": 36}]}}, "schema": []}
{"input": "Therefore, a possibility is that the PVN target neurons respond to a metabolite in the testosterone catabolic pathway via an AR-independent mechanism.", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 87, "end": 99}]}}, "schema": []}
{"input": "The dihydrotestosterone metabolite, 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol), binds and activates estrogen receptor-beta (ER-beta), the predominant ER in the PVN.", "output": {"entities": {"chemical": [{"text": "dihydrotestosterone", "start": 4, "end": 23}, {"text": "5 alpha-androstane-3 beta, 17 beta-diol", "start": 36, "end": 75}, {"text": "3 beta-diol", "start": 77, "end": 88}, {"text": "estrogen", "start": 111, "end": 119}]}}, "schema": []}
{"input": "In the PVN, ER-beta is coexpressed with oxytocin (OT).", "output": {"entities": {"chemical": [{"text": "oxytocin", "start": 40, "end": 48}]}}, "schema": []}
{"input": "Therefore, we tested the hypothesis that 3 beta-diol regulates OT expression through ER-beta activation.", "output": {"entities": {"chemical": [{"text": "3 beta-diol", "start": 41, "end": 52}]}}, "schema": []}
{"input": "Treatment of ovariectomized rats with estradiol benzoate or 3 beta-diol for 4 days increased OT mRNA selectively in the midcaudal, but not rostral PVN compared with vehicle-treated controls.", "output": {"entities": {"chemical": [{"text": "estradiol benzoate", "start": 38, "end": 56}, {"text": "3 beta-diol", "start": 60, "end": 71}]}}, "schema": []}
{"input": "3 beta-Diol treatment also increased OT mRNA in the hypothalamic N38 cell line in vitro.", "output": {"entities": {"chemical": [{"text": "3 beta-Diol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The functional interactions between 3 beta-diol and ER-beta with the human OT promoter were examined using an OT promoter-luciferase reporter construct (OT-luc).", "output": {"entities": {"chemical": [{"text": "3 beta-diol", "start": 36, "end": 47}]}}, "schema": []}
{"input": "In a dose-dependent manner, 3 beta-diol treatment increased OT-luc activity when cells were cotransfected with ER-beta, but not ER-alpha.", "output": {"entities": {"chemical": [{"text": "3 beta-diol", "start": 28, "end": 39}]}}, "schema": []}
{"input": "The 3 beta-diol-induced OT-luc activity was reduced by deletion of the promoter region containing the composite hormone response element (cHRE).", "output": {"entities": {"chemical": [{"text": "3 beta-diol", "start": 4, "end": 15}]}}, "schema": []}
{"input": "Point mutations of the cHRE also prevented OT-luc activation by 3 beta-diol.", "output": {"entities": {"chemical": [{"text": "3 beta-diol", "start": 64, "end": 75}]}}, "schema": []}
{"input": "These results indicate that 3 beta-diol induces OT promoter activity via ER-beta-cHRE interactions.", "output": {"entities": {"chemical": [{"text": "3 beta-diol", "start": 28, "end": 39}]}}, "schema": []}
{"input": "Pathogenesis of preeclampsia: Implications of apoptotic markers and oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to investigate the implication of some apoptotic and lipid peroxidation markers in preeclampsia (PE).", "output": {"entities": {}}, "schema": []}
{"input": "A total of 25 women with PE and 25 age-and parity-matched normal pregnant women were enrolled in this study.", "output": {"entities": {}}, "schema": []}
{"input": "The malondialdehyde (MDA) level, caspase-9 activity and the percentage of DNA fragmentation were significantly higher in placental tissue of PE than in control women.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 4, "end": 19}, {"text": "MDA", "start": 21, "end": 24}]}}, "schema": []}
{"input": "The serum level of MDA was significantly elevated in women with PE having delivery by cesarean section (CS) than in women with PE having vaginal delivery.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 19, "end": 22}]}}, "schema": []}
{"input": "In vitro study demonstrated that the addition of 0. 5 mM Fe (2 +) and 0. 1 mM ascorbate caused increase in the production of MDA level in placental tissue with PE than normal placentas, and vitamin E (100 micro M) caused lower inhibition of in vitro lipid peroxidation in placental tissue with PE when compared with normal tissue.", "output": {"entities": {"chemical": [{"text": "Fe (2 +)", "start": 57, "end": 65}, {"text": "ascorbate", "start": 78, "end": 87}, {"text": "MDA", "start": 125, "end": 128}, {"text": "vitamin E", "start": 190, "end": 199}]}}, "schema": []}
{"input": "The activity of caspase-9 and percentage of DNA fragmentation were associated with the severity of the PE and both could differentiate between PE and control women with 88% and 100% sensitivity and 96% and 100% specificity, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The activities of caspase-8 and/or-9 were positively correlated with the maternal age but only caspase-8 was negatively correlated with neonatal birth weight and placental weight.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the elevations of MDA, caspase-9 activity and the percentage of DNA fragmentation in the placentas of women with PE implicate the involvement of lipid peroxidation and apoptosis in PE.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 33, "end": 36}]}}, "schema": []}
{"input": "The placenta represents a considerable source of the elevated circulating MDA in PE.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 74, "end": 77}]}}, "schema": []}
{"input": "Ca (2 +)-dependent suicidal erythrocyte death following zearalenone exposure.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 0, "end": 8}, {"text": "zearalenone", "start": 56, "end": 67}]}}, "schema": []}
{"input": "Zearalenone, a cereal mycotoxin with mycoestrogen activity and effect on fertility, is known to trigger apoptosis of a variety of nucleated cell types including hematopoietic progenitor cells.", "output": {"entities": {"chemical": [{"text": "Zearalenone", "start": 0, "end": 11}]}}, "schema": []}
{"input": "In analogy to apoptosis of nucleated cells, eryptosis, the suicidal death of erythrocytes, leads to cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface.", "output": {"entities": {}}, "schema": []}
{"input": "The most important stimulator of eryptosis is an increase in cytosolic Ca (2 +) activity ([Ca (2 +)] i).", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 71, "end": 79}, {"text": "Ca (2 +)", "start": 91, "end": 99}]}}, "schema": []}
{"input": "The present study explored whether zearalenone triggers eryptosis.", "output": {"entities": {"chemical": [{"text": "zearalenone", "start": 35, "end": 46}]}}, "schema": []}
{"input": "Erythrocyte volume was estimated from forward scatter, phosphatidylserine exposure at the erythrocyte surface from annexin-V binding, hemolysis from hemoglobin release, and [Ca (2 +)] i from Fluo3 fluorescence.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 174, "end": 182}, {"text": "Fluo3", "start": 191, "end": 196}]}}, "schema": []}
{"input": "A 48-h exposure to zearalenone (>= 25 mu M) was followed by a significant increase in [Ca (2 +)] i and annexin-V binding, and a significant decrease in forward scatter.", "output": {"entities": {"chemical": [{"text": "zearalenone", "start": 19, "end": 30}, {"text": "Ca (2 +)", "start": 87, "end": 95}]}}, "schema": []}
{"input": "The effect on annexin-V binding was significantly blunted in the nominal absence of extracellular Ca (2 +).", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Zearalenone stimulates the suicidal erythrocyte death, an effect at least partially due to stimulation of Ca (2 +) entry.", "output": {"entities": {"chemical": [{"text": "Zearalenone", "start": 0, "end": 11}, {"text": "Ca (2 +)", "start": 106, "end": 114}]}}, "schema": []}
{"input": "Oxidative DNA damage is involved in ochratoxin A-induced G2 arrest through ataxia telangiectasia-mutated (ATM) pathways in human gastric epithelium GES-1 cells in vitro.", "output": {"entities": {"chemical": [{"text": "ochratoxin A", "start": 36, "end": 48}]}}, "schema": []}
{"input": "Ochratoxin A (OTA), one of the most abundant mycotoxin food contaminants, is classified as \" possibly carcinogenic to humans. \" Our previous study showed that OTA could induce a G2 arrest in immortalized human gastric epithelium cells (GES-1).", "output": {"entities": {"chemical": [{"text": "Ochratoxin A", "start": 0, "end": 12}, {"text": "OTA", "start": 14, "end": 17}, {"text": "OTA", "start": 159, "end": 162}]}}, "schema": []}
{"input": "To explore the putative roles of oxidative DNA damage and the ataxia telangiectasia-mutated (ATM) pathways on the OTA-induced G2 arrest, the current study systematically evaluated the roles of reactive oxygen species (ROS) production, DNA damage, and ATM-dependent pathway activation on the OTA-induced G2 phase arrest in GES-1 cells.", "output": {"entities": {"chemical": [{"text": "OTA", "start": 114, "end": 117}, {"text": "oxygen", "start": 202, "end": 208}, {"text": "OTA", "start": 291, "end": 294}]}}, "schema": []}
{"input": "The results showed that OTA exposure elevated intracellular ROS production, which directly induced DNA damage and increased the levels of 8-OHdG and DNA double-strand breaks (DSBs).", "output": {"entities": {"chemical": [{"text": "OTA", "start": 24, "end": 27}, {"text": "8-OHdG", "start": 138, "end": 144}]}}, "schema": []}
{"input": "In addition, it was found that OTA treatment induced the phosphorylation of the ATM protein, as well as its downstream molecules Chk2 and p53, in response to DNA DSBs.", "output": {"entities": {"chemical": [{"text": "OTA", "start": 31, "end": 34}]}}, "schema": []}
{"input": "Inhibition of ATM by the pharmacological inhibitor caffeine or siRNA effectively prevented the activation of ATM-dependent pathways and rescued the G2 arrest elicited by OTA.", "output": {"entities": {"chemical": [{"text": "OTA", "start": 170, "end": 173}]}}, "schema": []}
{"input": "Finally, pretreatment with the antioxidant N-acetyl-L-cysteine (NAC) reduced the OTA-induced DNA DSBs, ATM phosphorylation, and G2 arrest.", "output": {"entities": {"chemical": [{"text": "N-acetyl-L-cysteine", "start": 43, "end": 62}, {"text": "NAC", "start": 64, "end": 67}, {"text": "OTA", "start": 81, "end": 84}]}}, "schema": []}
{"input": "In conclusion, the results of this study suggested that OTA-induced oxidative DNA damage triggered the ATM-dependent pathways, which ultimately elicited a G2 arrest in GES-1 cells.", "output": {"entities": {"chemical": [{"text": "OTA", "start": 56, "end": 59}]}}, "schema": []}
{"input": "Mitochondrial disease in childhood: nuclear encoded.", "output": {"entities": {}}, "schema": []}
{"input": "Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration (s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain' s ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure.", "output": {"entities": {"chemical": [{"text": "adenosine triphosphophate", "start": 267, "end": 292}]}}, "schema": []}
{"input": "These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults.", "output": {"entities": {}}, "schema": []}
{"input": "Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders.", "output": {"entities": {}}, "schema": []}
{"input": "The childhood presentation of primary mitochondrial disease is mainly due to nuclear DNA mutations, with mitochondrial DNA mutations being less frequent in childhood and more prominent in adulthood disease.", "output": {"entities": {}}, "schema": []}
{"input": "The clinician should be aware of the pediatric presentation of mitochondrial disease and have an understanding of the myriad of nuclear genes responsible for these disorders.", "output": {"entities": {}}, "schema": []}
{"input": "The nuclear genes can be best understood by utilizing a classification system of location and function within the mitochondria.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of Gentamicin on the Proteomes of Aerobic and Oxygen-Limited Escherichia coli.", "output": {"entities": {"chemical": [{"text": "Gentamicin", "start": 11, "end": 21}, {"text": "Oxygen", "start": 54, "end": 60}]}}, "schema": []}
{"input": "The key role of the bacterial ribosome makes it an important target for antibacterial agents.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, a large number of clinically useful antibiotics target this complex translational ribonucleoprotein machinery.", "output": {"entities": {}}, "schema": []}
{"input": "Unfortunately, the development of resistant bacterial strains has compromised the effectiveness of most classes of antibacterial agent, including the classes that target the ribosome.", "output": {"entities": {}}, "schema": []}
{"input": "Combinations of two or more drugs can be used to help overcome resistance, and in certain circumstances their action may be synergistic.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we have used proteomic techniques to establish the effects of gentamicin on the proteomes of aerobic and oxygen-limited Escherichia coli.", "output": {"entities": {"chemical": [{"text": "gentamicin", "start": 76, "end": 86}, {"text": "oxygen", "start": 119, "end": 125}]}}, "schema": []}
{"input": "Ribosomal proteins L1, L9, L10, and S2 were found to be up-regulated in both conditions, and we postulate that these are candidate drug targets for the development of synergistic combinations with gentamicin.", "output": {"entities": {"chemical": [{"text": "gentamicin", "start": 197, "end": 207}]}}, "schema": []}
{"input": "Decreased expression of hepatic low-density lipoprotein related protein 1 in hypothyroidism: a novel mechanism of atherogenic dyslipidemia in hypothyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "Background: The atherogenic effects of hypothyroidism on lipid metabolism could result, in part, from the reduced clearance of remnant lipoproteins.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated the expression of hepatic low-density lipoprotein receptor-related protein 1 (LRP1), a receptor for remnant lipoproteins, in hypothyroidism and the effect of triiodothyronine (T3) treatment on hepatic LRP1 expression.", "output": {"entities": {"chemical": [{"text": "triiodothyronine", "start": 189, "end": 205}]}}, "schema": []}
{"input": "Methods: C57BL/6 mice were fed a normal diet (control group) or a low iodine diet supplemented with 0. 15% propylthiouracil (PTU/LI group) for 4 weeks.", "output": {"entities": {"chemical": [{"text": "iodine", "start": 70, "end": 76}, {"text": "propylthiouracil", "start": 107, "end": 123}, {"text": "PTU", "start": 125, "end": 128}]}}, "schema": []}
{"input": "Mice in PTU/LI group were injected intraperitoneally with T3 (0, 30, and 150 mu g/kg of body weight) for 7 days.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 8, "end": 11}]}}, "schema": []}
{"input": "HepG2 cells were incubated in fetal bovine serum (FBS) or charcoal-stripped FBS (CSS) with various concentrations of T3.", "output": {"entities": {}}, "schema": []}
{"input": "The expression and function of LRP1 in liver samples and cells were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "Results: Hypothyroidism was successfully induced in PTU/LI group mice.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 52, "end": 55}]}}, "schema": []}
{"input": "Hepatic LRP1 protein expression was lower in the PTU/LI group than the control group.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 49, "end": 52}]}}, "schema": []}
{"input": "T3 treatment up-regulated hepatic LRP1 protein expression in PTU/LI group mice.", "output": {"entities": {"chemical": [{"text": "PTU", "start": 61, "end": 64}]}}, "schema": []}
{"input": "LRP1 expression in HepG2 cells was reduced after incubation in media containing CSS, which mimics hypothyroidism in vitro, and was recovered by T3 treatment.", "output": {"entities": {}}, "schema": []}
{"input": "The protein expression of LRP1 in HepG2 cells was increased by T3 treatment in a dose-dependent manner up to 2. 0 nM T3.", "output": {"entities": {}}, "schema": []}
{"input": "However, LRP1 mRNA transcription was not affected by hypothyroidism conditions or T3 treatment, either in liver samples or HepG2 cells.", "output": {"entities": {}}, "schema": []}
{"input": "T3 treatment on HepG2 cells increased cellular uptake of lipid-conjugated apolipoprotein E through LRP1.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: Our data demonstrate that hepatic LRP1 expression and function decrease in hypothyroidism and are regulated by thyroid hormone.", "output": {"entities": {"chemical": [{"text": "thyroid hormone", "start": 124, "end": 139}]}}, "schema": []}
{"input": "These results suggest that in hypothyroidism, decreased expression of hepatic LRP1 may be associated with reduced clearance of circulating remnant lipoproteins.", "output": {"entities": {}}, "schema": []}
{"input": "Outcome of patients with differentiated thyroid cancer risk stratified according to the American Thyroid Association and Latin American Thyroid Society risk of recurrence classification systems.", "output": {"entities": {}}, "schema": []}
{"input": "Objective: To validate the proposed Latin-American Thyroid Society (LATS) risk of recurrence stratification system and to compare the findings with those of the American Thyroid Association (ATA) risk of recurrence stratification system.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects and Methods: Retrospective review of papillary thyroid cancer patients treated with total thyroidectomy and RAI at a single experienced thyroid cancer center and followed according to the LATS management guidelines.", "output": {"entities": {}}, "schema": []}
{"input": "Each patient was risk stratified using both the LATS and ATA staging systems.", "output": {"entities": {}}, "schema": []}
{"input": "The primary endpoints were (1) the best response to initial therapy defined as either remission (stimulated Tg < 1 ng/mL, negative US), or persistent disease (biochemical and/or structural) and (2) clinical status at final follow-up defined as either no evidence of disease (suppressed Tg < 1 ng/mL, negative US), biochemical persistent disease (suppressed Tg > 1 ng/mL in the absence of structural disease), structural persistent disease (loco-regional or distant metastases) or recurrence (biochemical or structural disease identified after a period of no evidence of disease, NED).", "output": {"entities": {}}, "schema": []}
{"input": "Results: One hundred and seventy one papillary thyroid cancer patients were included (mean age 45 +/- 16 yrs, followed for a median of 4 yrs after initial treatment).", "output": {"entities": {}}, "schema": []}
{"input": "Both the ATA and LATS risk stratification systems provided clinically meaningful graded estimates with regard to the (1) likelihood of achieving remission in response to initial therapy, (2) the likelihood of having persistent structural disease in response to initial therapy and at final follow-up, (3) the likely locations of the persistent structural disease (loco-regional vs. distant metastases), (4) the likelihood of recurrence and (5) the likelihood of being NED at final follow-up.", "output": {"entities": {}}, "schema": []}
{"input": "The likelihood of having persistent biochemical evidence of disease was not significantly different across the staging categories.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: Both the ATA and LATS risk of recurrence systems effectively risk stratify patients with regard to multiple important clinical outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "When used in conjunction with a staging system that predicts disease specific mortality, either of these systems can be used to guide risk adapted individualized initial management recommendations.", "output": {"entities": {}}, "schema": []}
{"input": "Disordered Nanowrinkle Substrates for Inducing Crystallization over a Wide Range of Concentration of Protein and Precipitant.", "output": {"entities": {}}, "schema": []}
{"input": "There are large number of proteins, the existence of which are known but not their crystal structure, because of difficulty in finding the exact condition for their crystallization.", "output": {"entities": {}}, "schema": []}
{"input": "Heterogeneous nucleation on disordered porous substrates with small yet large distribution of pores is considered a panacea for this problem, but a universal nucleant suitable for crystallizing large variety of proteins does not really exist.", "output": {"entities": {}}, "schema": []}
{"input": "To this end, we report here a nanowrinkled substrate which displays remarkable ability and control over protein crystallization.", "output": {"entities": {}}, "schema": []}
{"input": "Experiments with different proteins show that on these substrates crystals nucleate even at very low protein concentration in buffer.", "output": {"entities": {}}, "schema": []}
{"input": "A small number of very large crystals appear for precipitant concentrations varied over orders of magnitude, ~ 0. 003-0. 3 M; for some proteins, crystals appear even without addition of any precipitant, not seen with any other heterogeneous substrates.", "output": {"entities": {}}, "schema": []}
{"input": "In essence, these substrates significantly diminish the influence of the above two parameters, thought to be key factors for crystallization, signifying that this advantage can be exploited for finding out crystallization condition for other yet-to-be-crystallized proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Collapse of a hydrophobic polymer in a mixture of denaturants.", "output": {"entities": {}}, "schema": []}
{"input": "The solvent quality of an aqueous mixture of two good solvents, urea and guanidinium chloride (GdmCl), for a hydrophobic polymer was investigated using atomistic molecular dynamics simulations.", "output": {"entities": {"chemical": [{"text": "urea", "start": 64, "end": 68}, {"text": "guanidinium chloride", "start": 73, "end": 93}, {"text": "GdmCl", "start": 95, "end": 100}]}}, "schema": []}
{"input": "A counterintuitive collapse of the polymer was found, suggesting that mixing the two denaturants reduces the solvent quality.", "output": {"entities": {}}, "schema": []}
{"input": "This cononsolvency of the polymer in the urea + GdmCl mixture is found to be caused by the preferential adsorption of urea on the polymer.", "output": {"entities": {"chemical": [{"text": "urea", "start": 41, "end": 45}, {"text": "GdmCl", "start": 48, "end": 53}, {"text": "urea", "start": 118, "end": 122}]}}, "schema": []}
{"input": "The polymer collapses as a result of indirect long-range interactions between monomers resulting from the presence of urea clouds surrounding them.", "output": {"entities": {"chemical": [{"text": "urea", "start": 118, "end": 122}]}}, "schema": []}
{"input": "Surprisingly, urea behaves as the better solvent in the mixture not because there exists a stronger affinity of the polymer for urea.", "output": {"entities": {"chemical": [{"text": "urea", "start": 14, "end": 18}, {"text": "urea", "start": 128, "end": 132}]}}, "schema": []}
{"input": "Instead, attractive interactions between two unlike denaturant molecules combined with the direct dispersion interactions of the polymer with both denaturants determine the solvent quality of the mixture.", "output": {"entities": {}}, "schema": []}
{"input": "Tailoring the Dependency between Rigidity and Water Uptake of a Microfabricated Hydrogel with the Conformational Rigidity of a Polymer Cross-Linker.", "output": {"entities": {}}, "schema": []}
{"input": "Many diverse applications utilize hydrogels as carriers, sensors, and actuators, and these applications rely on the refined control of physical properties of the hydrogel, such as elastic modulus and degree of swelling.", "output": {"entities": {}}, "schema": []}
{"input": "Often, hydrogel properties are interdependent; for example, when elastic modulus is increased, degree of swelling is decreased.", "output": {"entities": {}}, "schema": []}
{"input": "Controlling these inverse dependencies remains a major barrier for broader hydrogel applications.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that polymer cross-linkers with varied chain flexibility would allow us to tune the inverse dependency between the elastic modulus and the degree of swelling of the hydrogels.", "output": {"entities": {}}, "schema": []}
{"input": "We examined this hypothesis by using alginate and poly (acrylic acid) (PAA) modified with a controlled number of methacrylic groups as model inflexible and flexible cross-linkers, respectively.", "output": {"entities": {"chemical": [{"text": "poly (acrylic acid)", "start": 50, "end": 69}, {"text": "PAA", "start": 71, "end": 74}, {"text": "methacrylic", "start": 113, "end": 124}]}}, "schema": []}
{"input": "Interestingly, the polyacrylamide hydrogel cross-linked by the inflexible alginate methacrylates exhibited less dependency between the degree of swelling and the elastic modulus than the hydrogel cross-linked by flexible PAA methacrylates.", "output": {"entities": {"chemical": [{"text": "polyacrylamide", "start": 19, "end": 33}, {"text": "PAA methacrylates", "start": 221, "end": 238}]}}, "schema": []}
{"input": "This critical role of the cross-linker' s inflexibility was related to the difference of the degree of hydrophobic association between polymer cross-linkers, as confirmed with pyrene probes added in pregel solutions.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 176, "end": 182}]}}, "schema": []}
{"input": "Furthermore, hydrogels cross-linked with alginate methacrylates could tune the projection area of adhered cells by solely altering elastic moduli.", "output": {"entities": {"chemical": [{"text": "methacrylates", "start": 50, "end": 63}]}}, "schema": []}
{"input": "In contrast, gels cross-linked with PAA methacrylates failed to modulate the cellular adhesion morphology due to a lower, and smaller, elastic modulus range to be controlled.", "output": {"entities": {"chemical": [{"text": "PAA methacrylates", "start": 36, "end": 53}]}}, "schema": []}
{"input": "Overall, the results of this study will significantly advance the controllability of hydrogel properties and greatly enhance the performance of hydrogels in various biological applications.", "output": {"entities": {}}, "schema": []}
{"input": "Orally Active Opioid Compounds from a Non-Poppy Source.", "output": {"entities": {}}, "schema": []}
{"input": "The basic science and clinical use of morphine and other \" opioid \" drugs are based almost exclusively on the extracts or analogues of compounds isolated from a single source, the opium poppy (Papaver somniferum).", "output": {"entities": {"chemical": [{"text": "morphine", "start": 38, "end": 46}]}}, "schema": []}
{"input": "However, it now appears that biological diversity has evolved an alternative source.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, at least two alkaloids isolated from the plant Mitragyna speciosa, mitragynine ((E)-2-[(2S, 3S)-3-ethyl-8-methoxy-1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo [3, 2-h] quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester; 9-methoxy coryantheidine; MG) and 7-hydroxymitragynine (7-OH-MG), and several synthetic analogues of these natural products display centrally mediated (supraspinal and spinal) antinociceptive (analgesic) activity in various pain models.", "output": {"entities": {"chemical": [{"text": "mitragynine", "start": 81, "end": 92}, {"text": "(E)-2-[(2S, 3S)-3-ethyl-8-methoxy-1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo [3, 2-h] quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester", "start": 94, "end": 235}, {"text": "9-methoxy coryantheidine", "start": 237, "end": 261}, {"text": "7-hydroxymitragynine", "start": 271, "end": 291}, {"text": "7-OH-MG", "start": 293, "end": 300}]}}, "schema": []}
{"input": "Several characteristics of these compounds suggest a classic \" opioid \" mechanism of action: nanomolar affinity for opioid receptors, competitive interaction with the opioid receptor antagonist naloxone, and two-way analgesic cross-tolerance with morphine.", "output": {"entities": {"chemical": [{"text": "naloxone", "start": 194, "end": 202}, {"text": "morphine", "start": 247, "end": 255}]}}, "schema": []}
{"input": "However, other characteristics of the compounds suggest novelty, particularly chemical structure and possible greater separation from side effects.", "output": {"entities": {}}, "schema": []}
{"input": "We review the chemical and pharmacological properties of these compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Intestinal and hepatic first-pass extraction of the 11 beta-HSD1 inhibitor AMG 221 in rats with chronic vascular catheters.", "output": {"entities": {"chemical": [{"text": "AMG 221", "start": 75, "end": 82}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "A catheterized rat model was used to define the intestinal and hepatic components of oral bioavailability for an 11 beta-HSD1 inhibitor, AMG 221.", "output": {"entities": {"chemical": [{"text": "AMG 221", "start": 137, "end": 144}]}}, "schema": []}
{"input": "These data were integrated with standard in vivo metabolism studies to elucidate the components contributing to the oral disposition of a novel drug candidate.", "output": {"entities": {}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "Intestinal and hepatic extraction ratios of AMG 221 obtained using a five-catheter rat model were 0. 56 and 0. 32, respectively.", "output": {"entities": {"chemical": [{"text": "AMG 221", "start": 44, "end": 51}]}}, "schema": []}
{"input": "Therefore, both intestinal and hepatic extraction contributed to the first-pass component of oral bioavailability.", "output": {"entities": {}}, "schema": []}
{"input": "There was no evidence for significant gut extraction of systemically administered drug.", "output": {"entities": {}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "Mass balance data and in vivo metabolite characterization obtained after administration of [(14) C] AMG 221 to rat showed that AMG 221 was completely absorbed from the gut lumen following an oral dose, primarily excreted in urine and was almost completely metabolized prior to excretion.", "output": {"entities": {"chemical": [{"text": "[(14) C] AMG 221", "start": 91, "end": 107}, {"text": "AMG 221", "start": 127, "end": 134}]}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "Hepatic bioavailability (FH), measured in two animals at various time points after oral dose administration was somewhat variable but generally characterized by an initial reduction during the absorption phase followed by an increase during the elimination phase, consistent with hepatic distribution of AMG 221.", "output": {"entities": {"chemical": [{"text": "AMG 221", "start": 304, "end": 311}]}}, "schema": []}
{"input": "5.", "output": {"entities": {}}, "schema": []}
{"input": "The five-catheter rat model afforded estimates of hepatic and intestinal contribution to oral bioavailability that were used with other data to define the preclinical ADME characteristics of a drug candidate.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological activities of some novel aminomethyl derivatives of 4-substituted-5-(2-thienyl)-2, 4-dihydro-3H-1, 2, 4-triazole-3-thiones.", "output": {"entities": {"chemical": [{"text": "aminomethyl", "start": 50, "end": 61}, {"text": "4-substituted-5-(2-thienyl)-2, 4-dihydro-3H-1, 2, 4-triazole-3-thiones", "start": 77, "end": 147}]}}, "schema": []}
{"input": "A novel series of compounds were synthesized by cyclic condensation reaction of substituted isothiocyanate (2a-c) with 2-thiophenecarboxylic acid hydrazide (1) in the presence of ethyl alcohol, to obtain intermediate thiosemicarbazides (3a-c), which were further treated with sodium hydroxide in the presence of ethanol to obtain triazole derivatives (4a-c).", "output": {"entities": {"chemical": [{"text": "isothiocyanate", "start": 92, "end": 106}, {"text": "2-thiophenecarboxylic acid hydrazide", "start": 119, "end": 155}, {"text": "ethyl alcohol", "start": 179, "end": 192}, {"text": "thiosemicarbazides", "start": 217, "end": 235}, {"text": "sodium hydroxide", "start": 276, "end": 292}, {"text": "ethanol", "start": 312, "end": 319}, {"text": "triazole", "start": 330, "end": 338}]}}, "schema": []}
{"input": "The latter were refluxed with substituted secondary amines and formaldehyde for 6-10 h to afford Mannich bases (5a-k).", "output": {"entities": {"chemical": [{"text": "secondary amines", "start": 42, "end": 58}, {"text": "formaldehyde", "start": 63, "end": 75}, {"text": "Mannich bases", "start": 97, "end": 110}]}}, "schema": []}
{"input": "The synthesized compounds were characterized on the basis of their spectral (IR, (13) C and (1) H NMR) data and evaluated for biological activities.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 81, "end": 87}, {"text": "(1) H", "start": 92, "end": 97}]}}, "schema": []}
{"input": "Some of the compounds were found to exhibit significant antimicrobial and antioxidant activity.", "output": {"entities": {}}, "schema": []}
{"input": "Design, modeling, synthesis and biological activity evaluation of camptothecin-linked platinum anticancer agents.", "output": {"entities": {"chemical": [{"text": "camptothecin", "start": 66, "end": 78}, {"text": "platinum", "start": 86, "end": 94}]}}, "schema": []}
{"input": "The design, modeling, synthesis and biological activity evaluation of two hybrid agents formed by 7-oxyiminomethylcamptothecin derivatives and diaminedichloro-platinum (II) complex are reported.", "output": {"entities": {"chemical": [{"text": "7-oxyiminomethylcamptothecin", "start": 98, "end": 126}, {"text": "diaminedichloro-platinum (II)", "start": 143, "end": 172}]}}, "schema": []}
{"input": "The compounds showed growth inhibitory activity against a panel of human tumor cell lines, including sublines resistant to topotecan and platinum compounds.", "output": {"entities": {"chemical": [{"text": "topotecan", "start": 123, "end": 132}, {"text": "platinum", "start": 137, "end": 145}]}}, "schema": []}
{"input": "The derivatives were active in all the tested cell lines, and compound 1b, the most active one, was able to overcome cisplatin resistance in the osteosarcoma U2OS/Pt cell line.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 117, "end": 126}]}}, "schema": []}
{"input": "Platinum-containing camptothecins produced platinum-DNA adducts and topoisomerase I-mediated DNA damage with cleavage pattern and persistence similar to SN38, the active principle of irinotecan.", "output": {"entities": {"chemical": [{"text": "Platinum", "start": 0, "end": 8}, {"text": "camptothecins", "start": 20, "end": 33}, {"text": "platinum", "start": 43, "end": 51}, {"text": "SN38", "start": 153, "end": 157}, {"text": "irinotecan", "start": 183, "end": 193}]}}, "schema": []}
{"input": "Compound 1b exhibited an appreciable antitumor activity in vivo against human H460 tumor xenograft, comparable to that of irinotecan at lower well-tolerated dose levels and superior to cisplatin.", "output": {"entities": {"chemical": [{"text": "irinotecan", "start": 122, "end": 132}, {"text": "cisplatin", "start": 185, "end": 194}]}}, "schema": []}
{"input": "The results support the interpretation that the diaminedichloro-platinum (II) complex conjugated via an oxyiminomethyl linker at the 7-position of the camptothecin resulted in a new class of effective antitumor compounds.", "output": {"entities": {"chemical": [{"text": "diaminedichloro-platinum (II)", "start": 48, "end": 77}, {"text": "oxyiminomethyl", "start": 104, "end": 118}, {"text": "camptothecin", "start": 151, "end": 163}]}}, "schema": []}
{"input": "Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord.", "output": {"entities": {"chemical": [{"text": "silica", "start": 11, "end": 17}]}}, "schema": []}
{"input": "Amorphous mesoporous silica nanoparticles (' protocells') that support surface lipid bilayers recently characterized in vitro as carrier constructs for small drug and DNA delivery are reported here as highly biocompatible both in vitro and in vivo, involving the brain and spinal cord following spinal delivery into the lumbosacral subarachnoid space (intrathecal; i. t.).", "output": {"entities": {"chemical": [{"text": "silica", "start": 21, "end": 27}]}}, "schema": []}
{"input": "Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP)-cholesterol (DOTAP: Chol) liposome-formulated protocells revealed stable in vitro cargo release kinetics and cellular interleukin-10 (IL-10) transgene transfection.", "output": {"entities": {"chemical": [{"text": "1, 2-Dioleoyl-3-Trimethylammonium-Propane", "start": 34, "end": 75}, {"text": "DOTAP", "start": 77, "end": 82}, {"text": "cholesterol", "start": 84, "end": 95}, {"text": "DOTAP", "start": 97, "end": 102}, {"text": "Chol", "start": 104, "end": 108}]}}, "schema": []}
{"input": "Recent approaches using synthetic non-viral vector platforms to deliver the pain-suppressive therapeutic transgene, IL-10, to the spinal subarachnoid space have yielded promising results in animal models of peripheral neuropathy, a condition involving aberrant neuronal communication within sensory pathways in the nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "Non-viral drug and gene delivery protocell platforms offer potential flexibility because cargo release-rates can be pH-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "We report here that i. t. delivery of protocells, with modified chemistry supporting a surface coating of DOTAP: Chol liposomes and containing the IL-10 transgene, results in functional suppression of pain-related behavior in rats for extended periods.", "output": {"entities": {"chemical": [{"text": "DOTAP", "start": 106, "end": 111}, {"text": "Chol", "start": 113, "end": 117}]}}, "schema": []}
{"input": "This study is the first demonstration that protocell vectors offer amenable and enduring in vivo biological characteristics that can be applied to spinal gene delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical characterization of domestic oral tobacco products: Total nicotine, pH, unprotonated nicotine and tobacco-specific N-nitrosamines.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 67, "end": 75}, {"text": "nicotine", "start": 94, "end": 102}, {"text": "N-nitrosamines", "start": 124, "end": 138}]}}, "schema": []}
{"input": "In the United States, moist snuff has been studied more widely than other distinct categories of oral tobacco.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we measured pH, moisture, nicotine (total and unprotonated), and tobacco-specific N-nitrosamines (TSNAs) for other established (twist, loose leaf, plug, and dry snuff without pouch) and emerging oral tobacco products (dry snuff pouch, US-made snus, and dissolvable tobacco).", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 41, "end": 49}, {"text": "N-nitrosamines", "start": 97, "end": 111}]}}, "schema": []}
{"input": "Among the seven product categories, product pH ranged from 4. 7 to 7. 9, and total nicotine concentration spanned from 3. 9 to 40. 1mg/g.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 83, "end": 91}]}}, "schema": []}
{"input": "The most readily absorbable form of nicotine (unprotonated nicotine) varied more than 350-fold, ranging from 0. 01 to 3. 7mg/g.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 36, "end": 44}, {"text": "nicotine", "start": 59, "end": 67}]}}, "schema": []}
{"input": "While the highest total nicotine concentrations were observed in twist products, snus and dissolvable tobacco had the highest unprotonated nicotine levels.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 24, "end": 32}, {"text": "nicotine", "start": 139, "end": 147}]}}, "schema": []}
{"input": "Among all products, total TSNA concentrations ranged from 313 to 76, 500ng/g with dry snuff having the highest total TSNA concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "This study demonstrates the diversity among oral tobacco products and highlights the potential of these products to deliver a wide range of nicotine and carcinogenic TSNAs.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 140, "end": 148}]}}, "schema": []}
{"input": "Characterizing the chemical content of these products may be helpful in further understanding the risk of marketing these products to oral tobacco users and smokers as an alternative and discrete form of tobacco.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis and structure-activity relationships of 3, 5-diaryl-1H-pyrazoles as inhibitors of arylamine N-acetyltransferase.", "output": {"entities": {"chemical": [{"text": "3, 5-diaryl-1H-pyrazoles", "start": 58, "end": 82}, {"text": "arylamine N", "start": 100, "end": 111}]}}, "schema": []}
{"input": "The synthesis and inhibitory potencies of a novel series of 3, 5-diaryl-1H-pyrazoles as specific inhibitors of prokaryotic arylamine N-acetyltransferase enzymes is described.", "output": {"entities": {"chemical": [{"text": "3, 5-diaryl-1H-pyrazoles", "start": 60, "end": 84}, {"text": "arylamine N", "start": 123, "end": 134}]}}, "schema": []}
{"input": "The series is based on hit compound 1 3, 5-diaryl-1H-pyrazole identified from a high-throughout screen that has been carried out previously and found to inhibit the growth of Mycobacterium tuberculosis.", "output": {"entities": {"chemical": [{"text": "1 3, 5-diaryl-1H-pyrazole", "start": 36, "end": 61}]}}, "schema": []}
{"input": "SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities.", "output": {"entities": {}}, "schema": []}
{"input": "Smc5-6 is a highly conserved protein complex related to cohesin and condensin involved in the structural maintenance of chromosomes.", "output": {"entities": {}}, "schema": []}
{"input": "In yeasts the Smc5-6 complex is essential for proliferation and is involved in DNA repair and homologous recombination.", "output": {"entities": {}}, "schema": []}
{"input": "siRNA depletion of genes involved in the Smc5-6 complex in cultured mammalian cells results in sensitivity to some DNA damaging agents.", "output": {"entities": {}}, "schema": []}
{"input": "In order to gain further insight into its role in mammals we have generated mice mutated in the Smc6 gene.", "output": {"entities": {}}, "schema": []}
{"input": "A complete knockout resulted in early embryonic lethality, demonstrating that this gene is essential in mammals.", "output": {"entities": {}}, "schema": []}
{"input": "However, mutation of the highly conserved serine-994 to alanine in the ATP hydrolysis motif in the SMC6 C-terminal domain, resulted in mice with a surprisingly mild phenotype.", "output": {"entities": {"chemical": [{"text": "serine", "start": 42, "end": 48}, {"text": "alanine", "start": 56, "end": 63}, {"text": "ATP", "start": 71, "end": 74}]}}, "schema": []}
{"input": "With the neo gene selection marker in the intron following the mutation, resulting in reduced expression of the SMC6 gene, the mice were reduced in size, but fertile and had normal lifespans.", "output": {"entities": {}}, "schema": []}
{"input": "When the neo gene was removed, the mice had normal size, but detailed phenotypic analysis revealed minor abnormalities in glucose tolerance, haematopoiesis, nociception and global gene expression patterns.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 122, "end": 129}]}}, "schema": []}
{"input": "Embryonic fibroblasts derived from the ser994 mutant mice were not sensitive to killing by a range of DNA damaging agents, but they were sensitive to the induction of sister chromatid exchanges induced by ultraviolet light or mitomycin C.", "output": {"entities": {"chemical": [{"text": "ser994", "start": 39, "end": 45}, {"text": "mitomycin C", "start": 226, "end": 237}]}}, "schema": []}
{"input": "They also accumulated more oxidative damage than wild-type cells.", "output": {"entities": {}}, "schema": []}
{"input": "Experimental evidence for surface freezing in supercooled n-alkane nanodroplets.", "output": {"entities": {"chemical": [{"text": "n-alkane", "start": 58, "end": 66}]}}, "schema": []}
{"input": "Intermediate chain length (16 <= i <= 50) n-alkanes are known to surface freeze at temperatures that are up to three degrees higher than the equilibrium melting point [B. M. Ocko et al., Phys. Rev. E, 1997, 55, 3164-3182].", "output": {"entities": {"chemical": [{"text": "n-alkanes", "start": 42, "end": 51}]}}, "schema": []}
{"input": "Our recent experimental results suggest that highly supercooled nanodroplets of n-octane and n-nonane also surface freeze, and subsequently bulk crystallization occurs.", "output": {"entities": {"chemical": [{"text": "n-octane", "start": 80, "end": 88}, {"text": "n-nonane", "start": 93, "end": 101}]}}, "schema": []}
{"input": "The data yield surface and bulk nucleation rates on the order of ~ 10 (15) cm (-2) s (-1) and ~ 10 (22) cm (-3) s (-1), respectively, at temperatures between 180 K and 200 K.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular dynamics simulations at the united atom level were used to follow the freezing of a supercooled n-octane drop and show that an ordered monolayer develops on the surface of the droplet almost immediately, and the rest of the droplet then freezes in a layer-by-layer manner.", "output": {"entities": {"chemical": [{"text": "n-octane", "start": 106, "end": 114}]}}, "schema": []}
{"input": "UPR Signal Activation by Luminal Sensor Domains.", "output": {"entities": {}}, "schema": []}
{"input": "The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK, and ATF6, which then propagate the signal to the cytosol.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we discuss the various mechanisms of action that have been proposed on how the sensor domains detect the presence of unfolded protein to activate downstream UPR signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Compositional-asymmetry influenced non-linear optical processes of plasmonic nanoparticle dimers.", "output": {"entities": {}}, "schema": []}
{"input": "The influences of compositional asymmetry on the two-photon photoluminescence and the second harmonic generation processes in weakly coupled plasmonic dimers were addressed.", "output": {"entities": {}}, "schema": []}
{"input": "Au-Au homodimer and Au-Ag heterodimer arrays produced using electron-beam lithography were investigated using confocal nonlinear optical imaging and spectroscopy.", "output": {"entities": {"chemical": [{"text": "Au-Au", "start": 0, "end": 5}, {"text": "Au-Ag", "start": 20, "end": 25}]}}, "schema": []}
{"input": "Compared to the Au-Au homodimers, the Au-Ag dimers showed slightly broadened two-photon photoluminescence near the X symmetry point at the first Brillouin zone of Au, whilst that from the L symmetry point stayed the same.", "output": {"entities": {"chemical": [{"text": "Au-Au", "start": 16, "end": 21}, {"text": "Au-Ag", "start": 38, "end": 43}, {"text": "Au", "start": 163, "end": 165}]}}, "schema": []}
{"input": "Additionally, weakly coupled Au-Ag heterodimers generated strong second harmonic signals which were invisible in the Au-Au homodimers.", "output": {"entities": {"chemical": [{"text": "Au-Ag", "start": 29, "end": 34}, {"text": "Au-Au", "start": 117, "end": 122}]}}, "schema": []}
{"input": "The observations highlighted the importance of compositional asymmetry in the non-linear optical studies of plasmonic dimers.", "output": {"entities": {}}, "schema": []}
{"input": "Pregnane X Receptor Mediates Dyslipidemia Induced by the HIV Protease Inhibitor Amprenavir in Mice.", "output": {"entities": {"chemical": [{"text": "Pregnane", "start": 0, "end": 8}, {"text": "Amprenavir", "start": 80, "end": 90}]}}, "schema": []}
{"input": "HIV protease inhibitors (PIs) have been used successfully in extending the lifespan of people infected with HIV.", "output": {"entities": {}}, "schema": []}
{"input": "The use of PIs has also been associated with dyslipidemia and an increased risk of cardiovascular disease but the underlying mechanisms remain elusive.", "output": {"entities": {}}, "schema": []}
{"input": "Several PIs have been implicated to activate the nuclear receptor pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism in the liver and intestine.", "output": {"entities": {"chemical": [{"text": "pregnane", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Recent studies indicate that PXR may also play an important role in the regulation of lipid homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we identified amprenavir, a widely used HIV PI, as a potent PXR-selective agonist.", "output": {"entities": {"chemical": [{"text": "amprenavir", "start": 36, "end": 46}]}}, "schema": []}
{"input": "Computational docking studies combined with site-direct mutagenesis identified several key residues within the ligand binding pocket of PXR that constitute points of interaction with amprenavir.", "output": {"entities": {"chemical": [{"text": "amprenavir", "start": 183, "end": 193}]}}, "schema": []}
{"input": "Amprenavir efficiently activated PXR and induced PXR target gene expression in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "Amprenavir", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Short-term exposure to amprenavir significantly increased plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice.", "output": {"entities": {"chemical": [{"text": "amprenavir", "start": 23, "end": 33}, {"text": "cholesterol", "start": 71, "end": 82}, {"text": "cholesterol", "start": 123, "end": 134}]}}, "schema": []}
{"input": "Amprenavir-mediated PXR activation stimulated the expression of several key intestinal genes involved in lipid homeostasis.", "output": {"entities": {"chemical": [{"text": "Amprenavir", "start": 0, "end": 10}]}}, "schema": []}
{"input": "These findings provide critical mechanistic insight for understanding the impact of PIs on cardiovascular disease and demonstrate a potential role of PXR in mediating adverse effects of HIV PIs in humans.", "output": {"entities": {}}, "schema": []}
{"input": "Chd4 and associated proteins function as corepressors of Sox9 expression during BMP-2-induced chondrogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Mouse embryonic fibroblasts (MEFs) differentiate into fully functional chondrocytes in response to bone morphogenetic protein-2 (BMP-2).", "output": {"entities": {}}, "schema": []}
{"input": "However, the comprehensive proteomic aspect of BMP-2-induced chondrogenesis remains unknown.", "output": {"entities": {}}, "schema": []}
{"input": "We took advantage of quantitative proteomic analysis based on isobaric tag for relative and absolute quantitation (iTRAQ) and on-line 2D nano-liquid chromatography/tandem mass spectrometry (LC/MS/MS) to identify proteins differentially expressed during BMP-2-induced chondrogenic differentiation of MEFs.", "output": {"entities": {}}, "schema": []}
{"input": "We found 85 downregulated proteins, and Ingenuity Pathways Analysis (IPA) revealed a protein-protein network with chromodomain-helicase-DNA-binding protein 4 (Chd4) in the center.", "output": {"entities": {}}, "schema": []}
{"input": "Chromatin immunoprecipitation (ChIP) and nuclease hypersensitivity assays showed that Chd4, interacting with Hdac1/2, cooperates with its related proteins Kap1 and Cbx1 to bind at-207/-148 of the Sox9 promoter.", "output": {"entities": {}}, "schema": []}
{"input": "We also provided evidence that let-7a targets the 3' UTR of Chd4 to promote chondrogenesis of MEFs.", "output": {"entities": {}}, "schema": []}
{"input": "Together, our findings indicate that BMP-2 induced the upregulation of let-7a, targeting Chd4 and positively controlling the chondrogenic differentiation of MEFs.", "output": {"entities": {}}, "schema": []}
{"input": "These findings illustrate epigenetic regulation of the chondrogenic differentiation process and also expand the understanding of the involved intracellular mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Positive Regulation of Insulin Signaling by Neuraminidase 1.", "output": {"entities": {}}, "schema": []}
{"input": "Neuraminidases (sialidases) catalyze the removal of sialic acid residues from sialylated glycoconjugates.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 52, "end": 63}]}}, "schema": []}
{"input": "We now report that mammalian neuraminidase 1 (Neu1), in addition to its catabolic function in lysosomes, is transported to the cell surface where it is involved in regulation of insulin signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin binding to its receptor rapidly induces interaction of the receptor with Neu1, which hydrolyzes sialic acid residues in the glycan chains of the receptor and, consequently, induces its activation.", "output": {"entities": {"chemical": [{"text": "sialic acid", "start": 104, "end": 115}]}}, "schema": []}
{"input": "Cells from sialidosis patients with a genetic deficiency of Neu1 show impairment of insulin-induced phosphorylation of downstream protein kinase AKT, while treatment of these cells with purified Neu1 restores signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Genetically-modified mice with ~ 10% of the normal Neu1 activity exposed to a high-fat diet develop hyperglycemia and insulin resistance twice as fast as their wild type counterparts.", "output": {"entities": {}}, "schema": []}
{"input": "Together, these studies identify Neu1 as a novel component of the signaling pathways of energy metabolism and glucose uptake.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 110, "end": 117}]}}, "schema": []}
{"input": "Specific Transport of Target Molecules by Motor Proteins in Microfluidic Channels.", "output": {"entities": {}}, "schema": []}
{"input": "Direct transport powered by motor proteins can alleviate the challenges presented by miniaturization of microfluidic systems.", "output": {"entities": {}}, "schema": []}
{"input": "There have been several recent attempts to build motor-protein-driven transport systems based on simple capturing or transport mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "However, to achieve a multifunctional device for practical applications, a more complex sorting/transport system should be realized.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, the proof of concept of a sorting device employing selective capture of distinct target molecules and transport of the sorted molecules to different predefined directions is presented.", "output": {"entities": {}}, "schema": []}
{"input": "By combining the bottom-up functionality of biological systems with the top-down handling capabilities of micro-electromechanical systems technology, highly selective molecular recognition and motor-protein-based transport is integrated in a microfluidic channel network.", "output": {"entities": {}}, "schema": []}
{"input": "Peak forces in high-resolution imaging of soft matter in liquid.", "output": {"entities": {}}, "schema": []}
{"input": "The maximum force exerted by the tip of a force microscope on the sample surface is a critical factor that determines the spatial resolution and the degree of invasiveness of the measurement, in particular, on soft materials.", "output": {"entities": {}}, "schema": []}
{"input": "Here we determine the conditions needed to image soft matter in the 30-500 MPa range while applying very small forces.", "output": {"entities": {}}, "schema": []}
{"input": "Imaging at sub-50 pN in the elastic regime can only be achieved under strict conditions in terms of force constant values (below 0. 1 N/m) and free amplitudes (below 2 nm).", "output": {"entities": {}}, "schema": []}
{"input": "The peak force depends on the operational parameters, probe properties, the elastic and/or viscoelastic response of the sample, and the contact mechanics model.", "output": {"entities": {}}, "schema": []}
{"input": "Images of heterogeneous samples are never taken at a constant peak force.", "output": {"entities": {}}, "schema": []}
{"input": "Under the same operational conditions, smaller forces are obtained on the more compliant materials.", "output": {"entities": {}}, "schema": []}
{"input": "We also find that the viscoelastic response reduces the peak force with respect to the purely elastic regions.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings are summarized in three-dimensional maps that contain the operational conditions for imaging at low forces.", "output": {"entities": {}}, "schema": []}
{"input": "Potent fibrinolysis inhibitor discovered by shape and electrostatic complementarity to the drug tranexamic Acid.", "output": {"entities": {"chemical": [{"text": "tranexamic Acid", "start": 96, "end": 111}]}}, "schema": []}
{"input": "Protein-protein interfaces provide an important class of drug targets currently receiving increased attention.", "output": {"entities": {}}, "schema": []}
{"input": "The typical design strategy to inhibit protein-protein interactions usually involves large molecules such as peptides and macrocycles.", "output": {"entities": {}}, "schema": []}
{"input": "One exception is tranexamic acid (TXA), which, as a lysine mimetic, inhibits binding of plasminogen to fibrin.", "output": {"entities": {"chemical": [{"text": "tranexamic acid", "start": 17, "end": 32}, {"text": "TXA", "start": 34, "end": 37}, {"text": "lysine", "start": 52, "end": 58}]}}, "schema": []}
{"input": "However, the daily dose of TXA is high due to its modest potency and pharmacokinetic properties.", "output": {"entities": {"chemical": [{"text": "TXA", "start": 27, "end": 30}]}}, "schema": []}
{"input": "In this study, we report a computational approach, where the focus was on finding electrostatic potential similarities to TXA.", "output": {"entities": {"chemical": [{"text": "TXA", "start": 122, "end": 125}]}}, "schema": []}
{"input": "Coupling this computational technique with a high-quality low-throughput screen identified 5-(4-piperidyl)-3-isoxazolol (4-PIOL) as a potent plasminogen binding inhibitor with the potential for the treatment of various bleeding disorders.", "output": {"entities": {"chemical": [{"text": "5-(4-piperidyl)-3-isoxazolol", "start": 91, "end": 119}, {"text": "4-PIOL", "start": 121, "end": 127}]}}, "schema": []}
{"input": "Remarkably, 4-PIOL was found to be more than four times as potent as the drug TXA.", "output": {"entities": {"chemical": [{"text": "4-PIOL", "start": 12, "end": 18}, {"text": "TXA", "start": 78, "end": 81}]}}, "schema": []}
{"input": "Scutellarin from Scutellaria baicalensis Suppresses Adipogenesis by Upregulating PPAR alpha in 3T3-L1 Cells.", "output": {"entities": {"chemical": [{"text": "Scutellarin", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Adipocyte dysfunction is a major cause of obesity, which is associated strongly with many disorders including psychological and medical morbidities, metabolic abnormalities, and cardiovascular diseases as well as a series of cancers.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigated the antiadipogenic activity of scutellarin (1) in 3T3-L1 preadipocytes as well as the underlying molecular mechanisms.", "output": {"entities": {"chemical": [{"text": "scutellarin", "start": 55, "end": 66}]}}, "schema": []}
{"input": "It was observed that 1 reduced adipocyte differentiation of 3T3-L1 cells potently, as evidenced by a decrease in cellular lipid accumulation.", "output": {"entities": {}}, "schema": []}
{"input": "At the molecular level, mRNA expression of the master adipogenic transcription factors, PPAR gamma and C/EBP alpha, was decreased markedly.", "output": {"entities": {}}, "schema": []}
{"input": "However, mRNA levels of C/EBP beta, the upstream regulator of PPAR gamma and C/EBP alpha, were not decreased by 1.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, a dose-dependent upregulation of PPAR alpha was observed for 1.", "output": {"entities": {}}, "schema": []}
{"input": "Computational modeling indicated that 1 can bind to PPAR alpha, gamma, and delta each in a distinct manner, while it can activate PPAR alpha only by forming a hydrogen bond with Y464, thus stabilizing the AF-2 helix and activating PPAR alpha.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 159, "end": 167}]}}, "schema": []}
{"input": "Therefore, these results suggest that 1, a major component of Scutellaria baicalensis, attenuates fat cell differentiation by upregulating PPAR alpha as well as downregulating the expression of PPAR gamma and C/EBP alpha, thus showing therapeutic potential for obesity-related diseases.", "output": {"entities": {}}, "schema": []}
{"input": "A Redox Responsive, Fluorescent Supramolecular Metallohydrogel Consists of Nanofibers with Single-Molecule Width.", "output": {"entities": {}}, "schema": []}
{"input": "The integration of a tripeptide derivative, which is a versatile self-assembly motif, with a ruthenium (II) tris (bipyridine) complex affords the first supramolecular metallo-hydrogelator that not only self assembles in water to form a hydrogel but also exhibits gel-sol transition upon oxidation of the metal center.", "output": {"entities": {"chemical": [{"text": "tripeptide", "start": 21, "end": 31}, {"text": "ruthenium (II) tris (bipyridine)", "start": 93, "end": 125}]}}, "schema": []}
{"input": "Surprisingly, the incorporation of the metal complex in the hydrogelator results in the nanofibers, formed by the self-assembly of the hydrogelator in water, to have the width of a single molecule of the hydrogelator.", "output": {"entities": {}}, "schema": []}
{"input": "These results illustrate that metal complexes, besides being able to impart rich optical, electronic, redox, or magnetic properties to supramolecular hydrogels, also offer a unique geometrical control to prearrange the self-assembly motif prior to self-assembling.", "output": {"entities": {}}, "schema": []}
{"input": "The use of metal complexes to modulate the dimensionality of intermolecular interactions may also help elucidate the interactions of the molecular nanofibers with other molecules, thus facilitating the development of supramolecular hydrogel materials for a wide range of applications.", "output": {"entities": {}}, "schema": []}
{"input": "Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson' s disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors.", "output": {"entities": {"chemical": [{"text": "dihydropteridinone", "start": 135, "end": 153}]}}, "schema": []}
{"input": "By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1.", "output": {"entities": {}}, "schema": []}
{"input": "When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-alpha-synuclein levels in the cerebral cortex.", "output": {"entities": {}}, "schema": []}
{"input": "Phellinus linteus mushroom protects against tacrine-induced mitochondrial impairment and oxidative stress in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "tacrine", "start": 44, "end": 51}]}}, "schema": []}
{"input": "Tacrine (THA) was the first drug licensed for the treatment of Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "Tacrine", "start": 0, "end": 7}, {"text": "THA", "start": 9, "end": 12}]}}, "schema": []}
{"input": "Unfortunately, reversible hepatotoxicity is evident in about 30% of patients and limits its clinical use.", "output": {"entities": {}}, "schema": []}
{"input": "The intracellular mechanisms have not yet been elucidated.", "output": {"entities": {}}, "schema": []}
{"input": "Phellinus linteus (PL) is a mushroom that has long been used as a folk medicine.", "output": {"entities": {}}, "schema": []}
{"input": "In our previous study, we found that PL could decrease the reactive oxygen species (ROS) formation in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 68, "end": 74}]}}, "schema": []}
{"input": "Presently, protective effects of PL on tacrine-induced ROS formation and mitochondria dysfunction were evaluated.", "output": {"entities": {"chemical": [{"text": "tacrine", "start": 39, "end": 46}]}}, "schema": []}
{"input": "The results showed that PL significantly reduced tacrine-induced ROS production, disruption of Delta Psi m, 8-OHdG formation in mitochondrial DNA, and cytotoxicity in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "tacrine", "start": 49, "end": 56}, {"text": "8-OHdG", "start": 108, "end": 114}]}}, "schema": []}
{"input": "These data suggest that PL could attenuate the cytotoxicity and mitochondria dysfunction induced by tacrine in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "tacrine", "start": 100, "end": 107}]}}, "schema": []}
{"input": "The protection is probably mediated by an antioxidant protective mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "Consumption of PL may be a plausible way to prevent tacrine-induced hepatotoxicity.", "output": {"entities": {"chemical": [{"text": "tacrine", "start": 52, "end": 59}]}}, "schema": []}
{"input": "System-wide hybrid MPC-PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction.", "output": {"entities": {}}, "schema": []}
{"input": "The next generation of QbD based pharmaceutical products will be manufactured through continuous processing.", "output": {"entities": {}}, "schema": []}
{"input": "This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables, so that the predefined product quality can be achieved consistently.", "output": {"entities": {}}, "schema": []}
{"input": "The direct compaction process considered in this study is highly interactive and involves time delays for a number of process variables due to sensor placements, process equipment dimensions, and the flow characteristics of the solid material.", "output": {"entities": {}}, "schema": []}
{"input": "A simple feedback regulatory control system (e. g., PI (D)) by itself may not be sufficient to achieve the tight process control that is mandated by regulatory authorities.", "output": {"entities": {}}, "schema": []}
{"input": "The process presented herein comprises of coupled dynamics involving slow and fast responses, indicating the requirement of a hybrid control scheme such as a combined MPC-PID control scheme.", "output": {"entities": {}}, "schema": []}
{"input": "In this manuscript, an efficient system-wide hybrid control strategy for an integrated continuous pharmaceutical tablet manufacturing process via direct compaction has been designed.", "output": {"entities": {}}, "schema": []}
{"input": "The designed control system is a hybrid scheme of MPC-PID control.", "output": {"entities": {}}, "schema": []}
{"input": "An effective controller parameter tuning strategy involving an ITAE method coupled with an optimization strategy has been used for tuning of both MPC and PID parameters.", "output": {"entities": {}}, "schema": []}
{"input": "The designed hybrid control system has been implemented in a first-principles model-based flowsheet that was simulated in gPROMS (Process System Enterprise).", "output": {"entities": {}}, "schema": []}
{"input": "Results demonstrate enhanced performance of critical quality attributes (CQAs) under the hybrid control scheme compared to only PID or MPC control schemes, illustrating the potential of a hybrid control scheme in improving pharmaceutical manufacturing operations.", "output": {"entities": {}}, "schema": []}
{"input": "Biodegradation and heart retention of polymeric microparticles in a rat model of myocardial ischemia.", "output": {"entities": {}}, "schema": []}
{"input": "Poly-lactide-co-glycolide (PLGA) microparticles emerged as one of the most promising strategies to achieve site-specific drug delivery.", "output": {"entities": {"chemical": [{"text": "Poly-lactide-co-glycolide", "start": 0, "end": 25}, {"text": "PLGA", "start": 27, "end": 31}]}}, "schema": []}
{"input": "Although these microparticles have been demonstrated to be effective in several wound healing models, their potential in cardiac regeneration has not yet been fully assessed.", "output": {"entities": {}}, "schema": []}
{"input": "The present work sought to explore PLGA microparticles as cardiac drug delivery systems.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 35, "end": 39}]}}, "schema": []}
{"input": "PLGA microparticles were prepared by Total Recirculation One-Machine System (TROMS) after the formation of a multiple emulsion.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Microparticles of different size were prepared and characterized to select the most suitable size for intramyocardial administration.", "output": {"entities": {}}, "schema": []}
{"input": "Next, the potential of PLGA microparticles for administration in the heart was assessed in a MI rat model.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 23, "end": 27}]}}, "schema": []}
{"input": "Particle biodegradation over time and myocardial tissue reaction were studied by routine staining and confocal microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Results showed that microparticles with a diameter of 5 mu m were the most compatible with intramyocardial administration in terms of injectability through a 29-gauge needle and tissue response.", "output": {"entities": {}}, "schema": []}
{"input": "Particles were present in the heart tissue for up to 3months post-implantation and no particle migration toward other solid organs was observed, demonstrating good myocardial retention.", "output": {"entities": {}}, "schema": []}
{"input": "CD68 immunolabeling revealed 31%, 47% and below 4% microparticle uptake by macrophages 1week, 1month, and 3months after injection, respectively (P < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these findings support the feasibility of the developed PLGA microparticles as vehicles for delivering growth factors in the infarcted myocardium.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 72, "end": 76}]}}, "schema": []}
{"input": "Inhibition of the renin-angiotensin system for lowering coronary artery disease risk.", "output": {"entities": {}}, "schema": []}
{"input": "The renin-angiotensin system when activated exerts proliferative and pro-inflammatory actions and thereby contributes to progression of atherosclerosis, including that occurring in the coronary arteries.", "output": {"entities": {}}, "schema": []}
{"input": "It thus contributes as well to coronary artery disease (CAD).", "output": {"entities": {}}, "schema": []}
{"input": "Several clinical trials have examined effects of renin-angiotensin system inhibition for primary and secondary prevention of coronary heart disease.", "output": {"entities": {}}, "schema": []}
{"input": "These include important trials such as HOPE, EUROPA and PEACE using angiotensin converting enzyme inhibitors, VALIANT, OPTIMAAL and TRANSCEND using angiotensin receptor blockers, and the ongoing TOPCAT study in patients with preserved ejection fraction heart failure, many of who also have coronary artery disease.", "output": {"entities": {}}, "schema": []}
{"input": "Data are unavailable as yet of effects of either direct renin inhibitors or the new angiotensin receptor/neprilysin inhibitor agents.", "output": {"entities": {}}, "schema": []}
{"input": "Today, inhibition of the renin-angiotensin system is standard-of-care therapy for lowering cardiovascular risk in secondary prevention in high cardiovascular risk subjects.", "output": {"entities": {}}, "schema": []}
{"input": "GLPG0492, a novel selective androgen receptor modulator, improves muscle performance in the exercised-mdx mouse model of muscular dystrophy.", "output": {"entities": {"chemical": [{"text": "GLPG0492", "start": 0, "end": 8}, {"text": "androgen", "start": 28, "end": 36}]}}, "schema": []}
{"input": "Anabolic drugs may counteract muscle wasting and dysfunction in Duchenne muscular dystrophy (DMD); however, steroids have unwanted side effects.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 108, "end": 116}]}}, "schema": []}
{"input": "We focused on GLPG0492, a new non-steroidal selective androgen receptor modulator that is currently under development for musculo-skeletal diseases such as sarcopenia and cachexia.", "output": {"entities": {"chemical": [{"text": "GLPG0492", "start": 14, "end": 22}, {"text": "androgen", "start": 54, "end": 62}]}}, "schema": []}
{"input": "GLPG0492 was tested in the exercised mdx mouse model of DMD in a 4-week trial at a single high dose (30mg/kg, 6 day/week s. c.), and the results were compared with those from the administration of alpha-methylprednisolone (PDN; 1mg/kg, i. p.) and nandrolone (NAND, 5mg/kg, s. c.).", "output": {"entities": {"chemical": [{"text": "GLPG0492", "start": 0, "end": 8}, {"text": "alpha-methylprednisolone", "start": 197, "end": 221}, {"text": "PDN", "start": 223, "end": 226}, {"text": "nandrolone", "start": 247, "end": 257}, {"text": "NAND", "start": 259, "end": 263}]}}, "schema": []}
{"input": "This assessment was followed by a 12-week dose-dependence study (0. 3-30mg/kg s. c.).", "output": {"entities": {}}, "schema": []}
{"input": "The outcomes were evaluated in vivo and ex vivo on functional, histological and biochemical parameters.", "output": {"entities": {}}, "schema": []}
{"input": "Similar to PDN and NAND, GLPG0492 significantly increased mouse strength.", "output": {"entities": {"chemical": [{"text": "PDN", "start": 11, "end": 14}, {"text": "NAND", "start": 19, "end": 23}, {"text": "GLPG0492", "start": 25, "end": 33}]}}, "schema": []}
{"input": "In acute exhaustion tests, a surrogate of the 6-min walking test used in DMD patients, GLPG0492 preserved running performance, whereas vehicle-or comparator-treated animals showed a significant increase in fatigue (30-50%).", "output": {"entities": {"chemical": [{"text": "GLPG0492", "start": 87, "end": 95}]}}, "schema": []}
{"input": "Ex vivo, all drugs resulted in a modest but significant increase of diaphragm force.", "output": {"entities": {}}, "schema": []}
{"input": "In parallel, a decrease in the non-muscle area and markers of fibrosis was observed in GLPG0492-and NAND-treated mice.", "output": {"entities": {"chemical": [{"text": "GLPG0492", "start": 87, "end": 95}, {"text": "NAND", "start": 100, "end": 104}]}}, "schema": []}
{"input": "The drugs exerted minor effects on limb muscles; however, electrophysiological biomarkers were ameliorated in extensor digitorum longus muscle.", "output": {"entities": {}}, "schema": []}
{"input": "The longer dose-dependence study confirmed the effect on mdx mouse strength and resistance to fatigue and demonstrated the efficacy of lower drug doses on in vivo and ex vivo functional parameters.", "output": {"entities": {}}, "schema": []}
{"input": "These results support the interest of further studies of GLPG0492 as a potential treatment for DMD.", "output": {"entities": {"chemical": [{"text": "GLPG0492", "start": 57, "end": 65}]}}, "schema": []}
{"input": "Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death.", "output": {"entities": {"chemical": [{"text": "dibenzoylmethane", "start": 15, "end": 31}]}}, "schema": []}
{"input": "Screening of a small in-house library of 1863 compounds identified 29 compounds that protected Jurkat cells from hydrogen peroxide-induced cytotoxicity.", "output": {"entities": {"chemical": [{"text": "hydrogen peroxide", "start": 113, "end": 130}]}}, "schema": []}
{"input": "From the cytoprotective compounds eleven proved to possess antioxidant activity (ABTS radical scavenger effect) and two were found to inhibit poly (ADP-ribosyl) ation (PARylation), a cytotoxic pathway operating in severely injured cells.", "output": {"entities": {"chemical": [{"text": "ABTS", "start": 81, "end": 85}, {"text": "poly (ADP-ribosyl)", "start": 142, "end": 160}]}}, "schema": []}
{"input": "Four cytoprotective dibenzoylmethane (DBM) derivatives were investigated in more detail as they did not scavenge hydrogen peroxide nor did they inhibit PARylation.", "output": {"entities": {"chemical": [{"text": "dibenzoylmethane", "start": 20, "end": 36}, {"text": "DBM", "start": 38, "end": 41}, {"text": "hydrogen peroxide", "start": 113, "end": 130}]}}, "schema": []}
{"input": "These compounds protected cells from necrotic cell death while caspase activation, a parameter of apoptotic cell death was not affected.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrogen peroxide activated extracellular signal regulated kinase (ERK1/2) and p38 MAP kinases but not c-Jun N-terminal kinase (JNK).", "output": {"entities": {"chemical": [{"text": "Hydrogen peroxide", "start": 0, "end": 17}, {"text": "N", "start": 109, "end": 110}]}}, "schema": []}
{"input": "The cytoprotective DBMs suppressed the activation of Erk1/2 but not that of p38.", "output": {"entities": {"chemical": [{"text": "DBMs", "start": 19, "end": 23}]}}, "schema": []}
{"input": "Cytoprotection was confirmed in another cell type (A549 lung epithelial cells), indicating that the cytoprotective effect is not cell type specific.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion we identified DBM analogs as a novel class of cytoprotective compounds inhibiting ERK1/2 kinase and protecting from necrotic cell death by a mechanism independent of poly (ADP-ribose) polymerase inhibition.", "output": {"entities": {"chemical": [{"text": "DBM", "start": 28, "end": 31}, {"text": "poly (ADP-ribose)", "start": 180, "end": 197}]}}, "schema": []}
{"input": "Avermectin induces P-glycoprotein expression in S2 cells via the calcium/calmodulin/NF-kappa B pathway.", "output": {"entities": {"chemical": [{"text": "Avermectin", "start": 0, "end": 10}, {"text": "calcium", "start": 65, "end": 72}]}}, "schema": []}
{"input": "Avermectin (AVM) is a macrocyclic lactone agent widely used as a nematicide, acaricide and insecticide in veterinary medicine and plant protection.", "output": {"entities": {"chemical": [{"text": "Avermectin", "start": 0, "end": 10}, {"text": "AVM", "start": 12, "end": 15}, {"text": "lactone", "start": 34, "end": 41}]}}, "schema": []}
{"input": "P-glycoprotein (P-gp) is an ATP-dependent drug efflux pump for xenobiotic compounds, and is involved in multidrug resistance.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 28, "end": 31}]}}, "schema": []}
{"input": "To understand the development of AVM resistance in invertebrates, we investigated the mechanisms by which AVM affected P-gp expression in Drosophila S2 cells.", "output": {"entities": {"chemical": [{"text": "AVM", "start": 33, "end": 36}, {"text": "AVM", "start": 106, "end": 109}]}}, "schema": []}
{"input": "We found that AVM induced upregulation of P-gp protein expression, increased P-gp ATPase activity and enhanced cellular efflux of the P-gp substrate rhodamine 123 from cells.", "output": {"entities": {"chemical": [{"text": "AVM", "start": 14, "end": 17}, {"text": "rhodamine 123", "start": 149, "end": 162}]}}, "schema": []}
{"input": "Furthermore, we observed that AVM-induced expression of P-gp was due to elevation of intracellular calcium concentration ([Ca (2 +)] i).", "output": {"entities": {"chemical": [{"text": "AVM", "start": 30, "end": 33}, {"text": "calcium", "start": 99, "end": 106}, {"text": "Ca (2 +)", "start": 123, "end": 131}]}}, "schema": []}
{"input": "This occurred both directly, by activating calcium ion channels, and indirectly, by activating chloride ion channels.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 43, "end": 50}, {"text": "chloride", "start": 95, "end": 103}]}}, "schema": []}
{"input": "These results are supported by our observations that verapamil, a Ca (2 +) channel blocker, and niflumic acid, a chloride channel antagonist, significantly attenuated AVM-induced [Ca (2 +)] i elevation, thereby reducing P-gp expression.", "output": {"entities": {"chemical": [{"text": "verapamil", "start": 53, "end": 62}, {"text": "Ca (2 +)", "start": 66, "end": 74}, {"text": "niflumic acid", "start": 96, "end": 109}, {"text": "chloride", "start": 113, "end": 121}, {"text": "AVM", "start": 167, "end": 170}, {"text": "Ca (2 +)", "start": 180, "end": 188}]}}, "schema": []}
{"input": "Inhibition of P-gp with anti-P-gp antibody or cyclosporine A (a P-gp inhibitor) reduced the AVM-induced elevation of [Ca (2 +)] i, implying that P-gp and [Ca (2 +)] i regulate each other.", "output": {"entities": {"chemical": [{"text": "cyclosporine A", "start": 46, "end": 60}, {"text": "AVM", "start": 92, "end": 95}, {"text": "Ca (2 +)", "start": 118, "end": 126}, {"text": "Ca (2 +)", "start": 155, "end": 163}]}}, "schema": []}
{"input": "Finally, we found that trifluoperazine, a calmodulin inhibitor, and pyrrolidine dithiocarbamic acid, an NF-kappa B inhibitor, attenuated the AVM-induced expression of P-gp, suggesting that AVM induces P-gp protein expression via the calmodulin/Relish (NF-kappa B) signaling pathway.", "output": {"entities": {"chemical": [{"text": "trifluoperazine", "start": 23, "end": 38}, {"text": "pyrrolidine dithiocarbamic acid", "start": 68, "end": 99}, {"text": "AVM", "start": 141, "end": 144}, {"text": "AVM", "start": 189, "end": 192}]}}, "schema": []}
{"input": "Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells.", "output": {"entities": {"chemical": [{"text": "gefitinib", "start": 43, "end": 52}]}}, "schema": []}
{"input": "Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), has been used to treat numerous cancers; however, evidence has shown that cancer cells can become resistant to gefitinib during therapy.", "output": {"entities": {"chemical": [{"text": "Gefitinib", "start": 0, "end": 9}, {"text": "tyrosine", "start": 13, "end": 21}, {"text": "gefitinib", "start": 198, "end": 207}]}}, "schema": []}
{"input": "Here, we report a human proto-oncogene, securin, which displays resistance to death in cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Gefitinib treatment decreases securin levels at the protein level by inducing protein instability but did not affect on the securin gene expression.", "output": {"entities": {"chemical": [{"text": "Gefitinib", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Treatment with gefitinib induced cytotoxicity in various human cancer cell types, including RKO (colon cancer), A549 (lung cancer), BFTC905 (bladder cancer), MCF7 (breast cancer) and A375 (skin cancer).", "output": {"entities": {"chemical": [{"text": "gefitinib", "start": 15, "end": 24}]}}, "schema": []}
{"input": "BFTC905 and A549 cells expressed relatively high levels of the phosphorylated and total EGFR proteins; however, A375, MCF7 and RKO cells did not markedly express these proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, following treatment with gefitinib, the securin-wild type cancer cells were more resistant to apoptotic induction than the securin-null cancer cells.", "output": {"entities": {"chemical": [{"text": "gefitinib", "start": 35, "end": 44}]}}, "schema": []}
{"input": "Surprisingly, both the securin-wild type and securin-null cancer cells expressed the EGFR protein at similar levels.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment with gefitinib induced mitochondrial dysfunction, cytochrome c release, caspase-3 activation and poly (ADP-ribose) polymerase protein cleavage, indicating that apoptosis occurred in these cancer cells.", "output": {"entities": {"chemical": [{"text": "gefitinib", "start": 15, "end": 24}, {"text": "poly (ADP-ribose)", "start": 107, "end": 124}]}}, "schema": []}
{"input": "The transfection of a GPF-securin expression vector increased both the proliferation rates and resistance to gefitinib-induced death in these cancer cells.", "output": {"entities": {"chemical": [{"text": "gefitinib", "start": 109, "end": 118}]}}, "schema": []}
{"input": "Taken together, these findings demonstrate that the presence of securin promotes resistance to gefitinib-induced apoptosis via an EGFR-independent pathway in human cancer cells.", "output": {"entities": {"chemical": [{"text": "gefitinib", "start": 95, "end": 104}]}}, "schema": []}
{"input": "Copper induces apoptotic cell death through reactive oxygen species-triggered oxidative stress in the intertidal copepod Tigriopus japonicus.", "output": {"entities": {"chemical": [{"text": "Copper", "start": 0, "end": 6}, {"text": "oxygen", "start": 53, "end": 59}]}}, "schema": []}
{"input": "The copepod, Tigriopus japonicus is an important model for toxicity testing.", "output": {"entities": {}}, "schema": []}
{"input": "However, no attempt has been made in analyzing the effect of toxicants at the level of the ROS-mediated signal transduction pathway.", "output": {"entities": {}}, "schema": []}
{"input": "To understand copper-induced cytotoxicity at the molecular level, we employed several cellular and biochemical assays after exposure to copper, and found a significant induction of enzyme activities of antioxidant proteins with increased intracellular reactive oxygen species (ROS) as well as an increase of TUNEL-positive cells, but a decrease of BrdU-positive cells.", "output": {"entities": {"chemical": [{"text": "copper", "start": 14, "end": 20}, {"text": "copper", "start": 136, "end": 142}, {"text": "oxygen", "start": 261, "end": 267}, {"text": "BrdU", "start": 348, "end": 352}]}}, "schema": []}
{"input": "In addition, several important genes such as p38 MAPK, antioxidant-related genes, Hsps, and apoptosis-related genes were significantly modulated by copper exposure.", "output": {"entities": {"chemical": [{"text": "copper", "start": 148, "end": 154}]}}, "schema": []}
{"input": "Taken together, we suggest that copper-induced cytotoxicity is mediated by the formation of intracellular ROS and oxidative stress in T. japonicus.", "output": {"entities": {"chemical": [{"text": "copper", "start": 32, "end": 38}]}}, "schema": []}
{"input": "Whole body biochemical assays such as TUNEL-and BrdU-assay will provide a better understanding of cellular responses such as apoptosis and cell death upon cytotoxic exposure of copper in T. japonicus.", "output": {"entities": {"chemical": [{"text": "BrdU", "start": 48, "end": 52}, {"text": "copper", "start": 177, "end": 183}]}}, "schema": []}
{"input": "Efficient synthesis of new (R)-2-amino-1-butanol derived ureas, thioureas and acylthioureas and in vitro evaluation of their antimycobacterial activity.", "output": {"entities": {"chemical": [{"text": "(R)-2-amino-1-butanol", "start": 27, "end": 48}, {"text": "ureas", "start": 57, "end": 62}, {"text": "thioureas", "start": 64, "end": 73}, {"text": "acylthioureas", "start": 78, "end": 91}]}}, "schema": []}
{"input": "The synthesis of 22 structurally diverse urea, thiourea and acylthiourea derivatives containing the (R)-2-amino-1-butanol motif has been performed.", "output": {"entities": {"chemical": [{"text": "urea", "start": 41, "end": 45}, {"text": "thiourea", "start": 47, "end": 55}, {"text": "acylthiourea", "start": 60, "end": 72}, {"text": "(R)-2-amino-1-butanol", "start": 100, "end": 121}]}}, "schema": []}
{"input": "The evaluation of their in vitro activity against Mycobacterium tuberculosis (H37Rv and strain 43) showed promising results in the case of the acylthiourea derivatives (MIC range 0. 36-7. 46 mu M for H37Rv strain).", "output": {"entities": {"chemical": [{"text": "acylthiourea", "start": 143, "end": 155}]}}, "schema": []}
{"input": "The Crystal Structure of the Lumenal Domain of Erv41p, a Protein Involved in Transport between the Endoplasmic Reticulum and Golgi Apparatus.", "output": {"entities": {}}, "schema": []}
{"input": "Erv41p is a conserved integral membrane protein that is known to play a role in transport between the endoplasmic reticulum and Golgi apparatus, part of the early secretory pathway of eukaryotes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the exact function of the protein is not known, and it shares very low sequence identity with proteins of known structure or function.", "output": {"entities": {}}, "schema": []}
{"input": "Here we present the structure of the full lumenal domain of Erv41p from Saccharomyces cerevisiae, determined by X-ray crystallography to a resolution of 2. 0 A.", "output": {"entities": {}}, "schema": []}
{"input": "The structure reveals the protein to be composed predominantly of two large beta-sheets that form a twisted beta-sandwich.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison to structures in the Protein Data Bank shows that the Erv41p lumenal domain displays only limited similarity to beta-sandwich domains of other proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of the surface properties of the protein identifies an extensive patch of negative electrostatic potential on the exposed surface of one of the beta-sheets, which likely forms a binding site for a ligand or interaction partner.", "output": {"entities": {}}, "schema": []}
{"input": "A predominantly hydrophobic region close to the membrane interface is identified as a likely site for protein-protein interaction.", "output": {"entities": {}}, "schema": []}
{"input": "This structure, the first of Erv41p or any of its homologues, provides a new starting point for studies of the roles of Erv41p and its interaction partners in the eukaryotic secretory pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Placental ABC transporters, cellular toxicity and stress in pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "The human placenta, in addition to its roles as a nutrient transfer and endocrine organ, functions as a selective barrier to protect the fetus against the harmful effects of exogenous and endogenous toxins.", "output": {"entities": {}}, "schema": []}
{"input": "Members of the ATP-binding cassette (ABC) family of transport proteins limit the entry of xenobiotics into the fetal circulation via vectorial efflux from the placenta to the maternal circulation.", "output": {"entities": {}}, "schema": []}
{"input": "Several members of the ABC family, including proteins from the ABCA, ABCB, ABCC and ABCG subfamilies, have been shown to be functional in the placenta with clinically significant roles in xenobiotic efflux.", "output": {"entities": {}}, "schema": []}
{"input": "However, recent findings suggest that these transporters also protect placental tissue by preventing the cellular accumulation of cytotoxic compounds such as lipids, sterols and their derivatives.", "output": {"entities": {}}, "schema": []}
{"input": "Such protective functions are likely to be particularly important in pregnancies complicated by inflammatory or oxidative stress, where the generation of toxic metabolites is enhanced.", "output": {"entities": {}}, "schema": []}
{"input": "For example, ABC transporters have been shown to protect against the harmful effects of hypoxia and oxidative stress through increased expression and efflux of oxysterols and glutathione conjugated xenobiotics.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 160, "end": 170}, {"text": "glutathione", "start": 175, "end": 186}]}}, "schema": []}
{"input": "However, this protective capacity may be diminished in response to the same stressors.", "output": {"entities": {}}, "schema": []}
{"input": "Several studies in primary human trophoblast cells and animal models have demonstrated decreased expression and activity of placental ABC transporters with inflammatory, oxidative or metabolic stress.", "output": {"entities": {}}, "schema": []}
{"input": "Several clinical studies in pregnancies complicated by inflammatory conditions such as preeclampsia and gestational diabetes support these findings, although further studies are required to determine the clinical relevance of the relationships between placental ABC transporter expression and activity, and placental function in stressed pregnancies.", "output": {"entities": {}}, "schema": []}
{"input": "Such studies are necessary to fully understand the consequences of pregnancy disorders on placental function and viability in order to optimise pregnancy care and maximise fetal growth and health.", "output": {"entities": {}}, "schema": []}
{"input": "Thermoreversible in situ gelling poloxamer-based systems with chitosan nanocomplexes for prolonged subcutaneous delivery of heparin: Design and in vitro evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "In situ forming systems including thermoreversible hydrogels, which undergo sol-gel transition upon an increase in temperature have been used for various biomedical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Heparins are the standard of anticoagulation in the prophylaxis and treatment of deep vein thrombosis and pulmonary embolism.", "output": {"entities": {}}, "schema": []}
{"input": "Both conditions require long-lasting treatment with frequent subcutaneous administrations of heparin.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to prepare and evaluate in situ forming gel systems designed by combination of two poloxamers (P407 and P188) and hydroxypropylmethylcellulose (HPMC) for prolonged release of heparin.", "output": {"entities": {"chemical": [{"text": "poloxamers (P407 and P188)", "start": 115, "end": 141}]}}, "schema": []}
{"input": "Thermoreversible hydrogels were prepared with heparin solution and dispersion of heparin/chitosan nanocomplexes.", "output": {"entities": {}}, "schema": []}
{"input": "Nanocomplexes formed by self-assembly of heparin with chitosan at various mass ratios were thoroughly characterized.", "output": {"entities": {}}, "schema": []}
{"input": "A heparin/chitosan mass ratio of 1: 1 with pH 5. 20 was the most appropriate for preparation of small, homogenous and stable nanocomplexes (mean diameter 123nm; polydispersity index 0. 22 and zeta potential + 35. 5mV).", "output": {"entities": {}}, "schema": []}
{"input": "Thermoreversible hydrogels were evaluated by gelation temperature, viscosity over the temperature range 20-40 degrees C, rate of hydrogel dissolution, and heparin release in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "The addition of P188 to P407 gel formulations resulted in an increase in gelation temperature, decrease in viscosity at room temperature and faster gel dissolution.", "output": {"entities": {"chemical": [{"text": "P188", "start": 16, "end": 20}, {"text": "P407", "start": 24, "end": 28}]}}, "schema": []}
{"input": "The opposite effects were observed with formulations containing HPMC which demonstrated 18-day-long gel dissolution and complete heparin release in 9days from gels containing heparin solution.", "output": {"entities": {}}, "schema": []}
{"input": "Considerable prolongation of heparin release was achieved with incorporation of heparin/chitosan nanocomplexes into the gelling systems.", "output": {"entities": {}}, "schema": []}
{"input": "It may be concluded that with poloxamer mixtures at specific concentrations, addition of HPMC and use of heparin/chitosan nanocomplexes dispersions, thermoreversible formulations for prolonged subcutaneous release of heparin are feasible.", "output": {"entities": {}}, "schema": []}
{"input": "Polymer coated liposomes for dental drug delivery-Interactions with parotid saliva and dental enamel.", "output": {"entities": {}}, "schema": []}
{"input": "The interactions between pectin coated liposomes and parotid saliva and dental enamel were studied to investigate their potential to mimic the protective biofilm formed naturally on tooth surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Different pectin coated liposomes with respect to pectin type (LM-, HM-and AM-pectin) and concentration (0. 05% and 0. 2%) were prepared.", "output": {"entities": {}}, "schema": []}
{"input": "Interactions between the pectin coated liposomes and parotid saliva were studied by turbidimetry and imaging by atomic force microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "The liposomes were adsorbed to hydroxyapatite (HA) and human dental enamel using phosphate buffer and parotid saliva as adsorption media.", "output": {"entities": {"chemical": [{"text": "hydroxyapatite", "start": 31, "end": 45}, {"text": "phosphate", "start": 81, "end": 90}]}}, "schema": []}
{"input": "A continuous flow was imposed on the enamel surfaces for various time intervals to examine their retention on the dental enamel.", "output": {"entities": {}}, "schema": []}
{"input": "The results were compared to uncoated, charged liposomes.", "output": {"entities": {}}, "schema": []}
{"input": "No aggregation tendencies for the pectin coated liposomes and parotid saliva were revealed.", "output": {"entities": {}}, "schema": []}
{"input": "This makes them promising as drug delivery systems to be used in the oral cavity.", "output": {"entities": {}}, "schema": []}
{"input": "In phosphate buffer the adsorption to HA of pectin coated liposomes was significantly lower than the negative liposomes.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 3, "end": 12}]}}, "schema": []}
{"input": "The difference diminished in parotid saliva.", "output": {"entities": {}}, "schema": []}
{"input": "Positive liposomes adsorbed better to the dental enamel than the pectin coated liposomes.", "output": {"entities": {}}, "schema": []}
{"input": "However, when subjected to flow for 1h, no significant differences in the retention levels on the enamel were found between the formulations.", "output": {"entities": {}}, "schema": []}
{"input": "For all formulations, more than 40% of the liposomes still remained on the enamel surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "At time point 20min the retention of HM-pectin coated and positive liposomes were significantly higher.", "output": {"entities": {}}, "schema": []}
{"input": "It was concluded that pectin coated liposomes can adsorb to HA as well as to the dental enamel.", "output": {"entities": {}}, "schema": []}
{"input": "Their ability to retain on the enamel surfaces promotes the concept of using them as protective structures for the teeth.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 10, "end": 19}]}}, "schema": []}
{"input": "The aim of this study was to examine whether oral supplementation of quercetin-rich onion peel extract (OPE) influences blood coagulation and arterial thrombosis in Sprague-Dawley (SD) rats.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 69, "end": 78}]}}, "schema": []}
{"input": "24 male rats, 5weeks old, were divided into three groups with different diets (C: control, 2mg OPE: chow diet with 2mg OPE supplementation, 10mg OPE: chow diet with 10mg OPE supplementation) for 6weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet aggregation were examined.", "output": {"entities": {}}, "schema": []}
{"input": "The OPE did not affect blood cholesterol levels but significantly decreased blood triglyceride and glucose levels.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 29, "end": 40}, {"text": "triglyceride", "start": 82, "end": 94}, {"text": "glucose", "start": 99, "end": 106}]}}, "schema": []}
{"input": "PT, aPTT and platelet aggregation were not significantly different among all tested groups.", "output": {"entities": {}}, "schema": []}
{"input": "However, in vivo arterial thrombosis was significantly delayed in groups that were fed 2mg and 10mg OPE diets compared to the control group.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the OPE greatly diminished thrombin-induced expression of tissue factor in human umbilical vein endothelial cells (HUVECs), a coagulation initiator.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways activated by thrombin treatment were prevented by the OPE pre-treatment.", "output": {"entities": {"chemical": [{"text": "N", "start": 67, "end": 68}]}}, "schema": []}
{"input": "These results indicate that OPE may have anti-thrombotic effects through restricting the induced expression of tissue factor via down-regulating mitogen-activated protein kinase (MAPK) activation upon coagulation stimulus, leading to the prolongation of time for arterial thrombosis.", "output": {"entities": {}}, "schema": []}
{"input": "FGFR4 genetic polymorphisms determine the chemotherapy response of Chinese patients with non-small cell lung cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Aim: To investigate the relationship of fibroblast growth factor receptor 4 (FGFR4) gene polymorphisms with the response of Chinese patients with non-small cell lung cancer (NSCLC) to chemotherapy. Methods: A total of 629 patients with Stage III (A + B) or IV NSCLC, as well as 729 age-and gender-matched healthy controls were recruited.", "output": {"entities": {}}, "schema": []}
{"input": "All the patients received platinum-based chemotherapy, and the therapeutic effects were evaluated.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 26, "end": 34}]}}, "schema": []}
{"input": "Three polymorphisms in the FGFR4 gene (rs351855G/A, rs145302848C/G, and rs147603016G/A) were genotyped, and the association between the 3 polymorphisms and the chemotherapy effect was analyzed using SPSS software, version 16. 0. Results: The genotype frequencies of rs145302848C/G and rs147603016G/A were not significantly different between NSCLC patients and healthy controls on one hand, and between the responders and non-responders to the chemotherapy on the other hand.", "output": {"entities": {}}, "schema": []}
{"input": "The distribution of AA genotype and A-allele of rs351855G/A was significantly lower in NSCLC patients than in healthy controls.", "output": {"entities": {}}, "schema": []}
{"input": "Using patients with the GG genotype as a reference, the AA carrier had a significantly reduced risk for the development of NSCLC after normalizing to age, sex and smoking habits.", "output": {"entities": {}}, "schema": []}
{"input": "In NSCLC patients, this genotype occurred more frequently in the responders to the chemotherapy than in non-responders.", "output": {"entities": {}}, "schema": []}
{"input": "The chance of being a responder was significantly increased with the AA genotype as compared to G genotype.", "output": {"entities": {}}, "schema": []}
{"input": "The AA genotype of rs351855G/A had a better prognosis compared with GA and GG genotype carriers: the overall survival of patients with the AA genotype of rs351855G/A was significantly longer than those with the GG + GA genotype (21. 1 vs 16. 5 months). Conclusion: The rs351855G/A polymorphisms of FGFR4 gene can be used to predict the occurrence, chemotherapy response and prognosis of NSCLC.", "output": {"entities": {}}, "schema": []}
{"input": "Amelioration of iron overload-induced liver toxicity by a potent antioxidant and iron chelator, Emblica officinalis Gaertn.", "output": {"entities": {"chemical": [{"text": "iron", "start": 16, "end": 20}, {"text": "iron", "start": 81, "end": 85}]}}, "schema": []}
{"input": "In liver, the major site of iron storage, iron overload is associated with oxidative damage of protein, lipid, and DNA and causes protein oxidation, lipid peroxidation, and rupture of hepatocytes, leading to cell death.", "output": {"entities": {"chemical": [{"text": "iron", "start": 28, "end": 32}, {"text": "iron", "start": 42, "end": 46}]}}, "schema": []}
{"input": "Serum ferritin and liver iron content are the main forecasters of moderate to severe iron overload in the liver.", "output": {"entities": {"chemical": [{"text": "iron", "start": 25, "end": 29}, {"text": "iron", "start": 85, "end": 89}]}}, "schema": []}
{"input": "The sequels of excess iron deposition in the liver are fibrosis and enhanced levels of serum enzymes and bilirubin markers.", "output": {"entities": {"chemical": [{"text": "iron", "start": 22, "end": 26}, {"text": "bilirubin", "start": 105, "end": 114}]}}, "schema": []}
{"input": "Emblica officinalis (EO) fruit extract was found efficient in lessening intraperitoneally injected iron dextran-induced liver toxicity in Swiss albino mice.", "output": {"entities": {"chemical": [{"text": "iron", "start": 99, "end": 103}]}}, "schema": []}
{"input": "Mice administered with different doses of 70% methanol extract of EO (50, 100, and 200 mg kg (-1) body weight) showed significant decrease in liver iron, serum ferritin, and serum enzyme levels, along with the decrease in lipid peroxidation, protein oxidation, and collagen content.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 46, "end": 54}, {"text": "iron", "start": 148, "end": 152}]}}, "schema": []}
{"input": "The activity was further supported by its considerable iron chelation with half-maximal inhibitory concentration of 70. 24 +/- 2. 74 mu g ml (-1) and the protection on ferrous ion-mediated DNA breakdown with 50% protection ([P] 50) of 1. 04 +/- 0. 01 mu g ml (-1).", "output": {"entities": {"chemical": [{"text": "iron", "start": 55, "end": 59}, {"text": "ferrous", "start": 168, "end": 175}]}}, "schema": []}
{"input": "Simultaneously, the extract effectively induced the antioxidant enzyme levels and also exhibited the potential activity of reductive release of ferritin iron.", "output": {"entities": {"chemical": [{"text": "iron", "start": 153, "end": 157}]}}, "schema": []}
{"input": "These findings suggest that the EO extract may be used as a potent drug for the treatment of pathological sequences arisen in the iron overload-induced liver damage.", "output": {"entities": {"chemical": [{"text": "iron", "start": 130, "end": 134}]}}, "schema": []}
{"input": "Ophthalmic findings in acute mercury poisoning in adults: A case series study.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 29, "end": 36}]}}, "schema": []}
{"input": "The aim of this study is to report ophthalmic findings of acute mercury poisoning in 48 adults referred to emergency department.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 64, "end": 71}]}}, "schema": []}
{"input": "Full ophthalmologic examination including the best corrected visual acuity, external eye examination, reaction to light, a slit-lamp examination, funduscopy, intraocular pressure measurements, and visual field (VF) and color vision (CV) tests were performed at the presentation and repeated after 6 months.", "output": {"entities": {}}, "schema": []}
{"input": "The parametric values of VF test, the mean deviation (MD), and pattern standard deviation (PSD) were recorded in order to compare patients and the 30 healthy controls.", "output": {"entities": {}}, "schema": []}
{"input": "The mean parameter of color confusion index in patients was found to be statistically different than controls (p < 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "The MD and PSD in patients were different from controls statistically significant (p < 0. 01 and p < 0. 01, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "There was no correlation between the ocular findings and the urine and blood mercury levels.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 77, "end": 84}]}}, "schema": []}
{"input": "Methyl mercury, held in the school laboratory for experimental purpose, may be a source of poisoning.", "output": {"entities": {"chemical": [{"text": "Methyl mercury", "start": 0, "end": 14}]}}, "schema": []}
{"input": "In this case series, we showed that acute exposure to mercury had hazardous effect on the visual system, especially CV and VF.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 54, "end": 61}]}}, "schema": []}
{"input": "We propose that emphasizing the public education on the potential hazards of mercury is crucial for preventive community health.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 77, "end": 84}]}}, "schema": []}
{"input": "dNTP-dependent conformational transitions in the fingers subdomain of Klentaq1 DNA polymerase: insights into the role of the \" nucleotide binding \" state.", "output": {"entities": {"chemical": [{"text": "dNTP", "start": 0, "end": 4}, {"text": "nucleotide", "start": 127, "end": 137}]}}, "schema": []}
{"input": "DNA polymerases are responsible for the accurate replication of DNA.", "output": {"entities": {}}, "schema": []}
{"input": "Kinetic, single molecule and X-ray studies show that multiple conformational states are important for DNA polymerase fidelity.", "output": {"entities": {}}, "schema": []}
{"input": "Using high-precision FRET we show that Klentaq1 (the Klenow fragment of Thermus aquaticus DNA polymerase 1) is in equilibrium between three structurally distinct states.", "output": {"entities": {}}, "schema": []}
{"input": "In the absence of nucleotide, the enzyme is mostly open, whereas in the presence of DNA and a correctly base-pairing dNTP it re-equilibrates to a closed state.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 18, "end": 28}, {"text": "dNTP", "start": 117, "end": 121}]}}, "schema": []}
{"input": "In the presence of a dNTP alone, with DNA and an incorrect dNTP, or in elevated MgCl2 concentrations, an intermediate state termed'' nucleotide binding'' state predominates.", "output": {"entities": {"chemical": [{"text": "dNTP", "start": 21, "end": 25}, {"text": "dNTP", "start": 59, "end": 63}, {"text": "MgCl2", "start": 80, "end": 85}, {"text": "nucleotide", "start": 133, "end": 143}]}}, "schema": []}
{"input": "Photon distribution and hidden Markov analysis revealed fast dynamic and slow conformational processes occurring between all three states in a complex energy landscape suggesting a mechanism in which dNTP delivery is mediated by the'' nucleotide binding'' state: After nucleotide binding, correct dNTPs are transported to the closed state while incorrect dNTPs are delivered to the open state.", "output": {"entities": {"chemical": [{"text": "dNTP", "start": 200, "end": 204}, {"text": "nucleotide", "start": 235, "end": 245}, {"text": "nucleotide", "start": 269, "end": 279}, {"text": "dNTPs", "start": 297, "end": 302}, {"text": "dNTPs", "start": 355, "end": 360}]}}, "schema": []}
{"input": "One-pot formation of multifunctional Pt-conducting polymer intercalated nanostructures.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 37, "end": 39}]}}, "schema": []}
{"input": "A novel multifunctional Pt nanoparticle @PPy nanofiber intercalated structure (Pt NP @PPy NF) has been synthesized facilely in one-pot.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 24, "end": 26}, {"text": "PPy", "start": 41, "end": 44}, {"text": "Pt", "start": 79, "end": 81}, {"text": "PPy", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Pt NPs, with size and facet control, were nicely assembled and embedded into the polymer nanofiber network.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 0, "end": 2}]}}, "schema": []}
{"input": "Polyvinylpyrrolidone (PVP) was used during the synthesis process which would assist the self-assembly of the metal nanoparticles and polymer backbones into the intercalated structure.", "output": {"entities": {"chemical": [{"text": "Polyvinylpyrrolidone", "start": 0, "end": 20}, {"text": "PVP", "start": 22, "end": 25}]}}, "schema": []}
{"input": "Space-confined distribution of the Pt NPs was achieved within the large dimension PPy nanofiber network, which could enhance the interfacial electron transfer process as well as diminish the catalyst deformation.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 35, "end": 37}, {"text": "PPy", "start": 82, "end": 85}]}}, "schema": []}
{"input": "The as-formed Pt NPs have a cluster-like structure and are mainly composed of 3. 5 nm primary Pt particles with (100) surface atoms.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 14, "end": 16}, {"text": "Pt", "start": 94, "end": 96}]}}, "schema": []}
{"input": "Enhanced electrocatalytic properties were shown by the Pt NP @PPy NF intercalated structure, with sufficiently high enzyme-less glucose biosensitivity and a long linear range from 1-30 mM (R = 0. 9995).", "output": {"entities": {"chemical": [{"text": "Pt", "start": 55, "end": 57}, {"text": "PPy", "start": 62, "end": 65}, {"text": "glucose", "start": 128, "end": 135}]}}, "schema": []}
{"input": "High electrochemical cycling stability, chloride (Cl (-)) tolerance and good selectivity are also obtained for the Pt NP @PPy NF structure, as the electrode showed no obvious response to the common interfering agents, such as ascorbic acid (AA), uric acid (UA), and 4-acetamidophenol (AP).", "output": {"entities": {"chemical": [{"text": "chloride", "start": 40, "end": 48}, {"text": "Cl (-)", "start": 50, "end": 56}, {"text": "Pt", "start": 115, "end": 117}, {"text": "PPy", "start": 122, "end": 125}, {"text": "ascorbic acid", "start": 226, "end": 239}, {"text": "uric acid", "start": 246, "end": 255}, {"text": "4-acetamidophenol", "start": 266, "end": 283}]}}, "schema": []}
{"input": "Furthermore, the Pt NP @PPy NF showed excellent catalytic activity for the methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR), which displayed sufficient CO tolerance, and higher activity compared to the commercial Pt/C catalyst.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 17, "end": 19}, {"text": "PPy", "start": 24, "end": 27}, {"text": "methanol", "start": 75, "end": 83}, {"text": "oxygen", "start": 113, "end": 119}, {"text": "CO", "start": 173, "end": 175}, {"text": "Pt", "start": 234, "end": 236}, {"text": "C", "start": 237, "end": 238}]}}, "schema": []}
{"input": "This intrinsically multifunctional Pt NP @PPy NF with well-controlled Pt facets thus could serve as an advanced electrocatalyst for biosensing and fuel cell applications, surpassing the performance of many existing materials.", "output": {"entities": {"chemical": [{"text": "Pt", "start": 35, "end": 37}, {"text": "PPy", "start": 42, "end": 45}, {"text": "Pt", "start": 70, "end": 72}]}}, "schema": []}
{"input": "Testicular Growth and Regression Are Not Correlated With Dio2 Expression in a Wild Male Songbird, Sturnus vulgaris, Exposed to Natural Changes in Photoperiod.", "output": {"entities": {}}, "schema": []}
{"input": "Timing of seasonal breeding in birds and mammals is regulated by changing the day length and is dependent on the presence of thyroid hormones.", "output": {"entities": {}}, "schema": []}
{"input": "A mechanism for thyroid-dependent control of seasonality has been proposed, in which exposure to long day lengths induces rapid local conversion of T4 to its bioactive form, T3, via the up-regulation of the enzyme type 2 iodothyronine deiodinase (Dio2) in the brain, and the down-regulation of Dio3 (which inactivates T3).", "output": {"entities": {}}, "schema": []}
{"input": "Such changes were correlated with gonadotropin release and gonadal growth in quail.", "output": {"entities": {}}, "schema": []}
{"input": "This mechanism was elucidated in a domesticated species (quail) exposed to unnatural acute changes in day length.", "output": {"entities": {}}, "schema": []}
{"input": "Here we investigated the Dio2/Dio3 mechanism in a wild species, the European starling, under naturally changing day length.", "output": {"entities": {}}, "schema": []}
{"input": "Although Dio2 expression varied seasonally, Dio3 did not.", "output": {"entities": {}}, "schema": []}
{"input": "We found no correlation of Dio2 with photoperiod, seasonal regulation of GnRH, or testicular volume.", "output": {"entities": {}}, "schema": []}
{"input": "The observed differences in data from starlings and quail could be a result of phylogeny, genetic drift from founder populations, or differences in reproductive seasonality in addition to or instead of arising from domestication or use of artificially changing photoperiods.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, the data indicate that in a wild species exposed to natural changes in day length, the current proposed mechanism for photoperiodic timing is less straightforward than is generally accepted and might not be as universally applicable as previously thought.", "output": {"entities": {}}, "schema": []}
{"input": "Free fatty acids induce Lhb mRNA but suppress Fshb mRNA in pituitary L beta T2 gonadotropes and diet-induced obesity reduces FSH levels in male mice and disrupts the proestrus LH/FSH surge in female mice.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 5, "end": 16}]}}, "schema": []}
{"input": "Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that elevated free fatty acids (FFAs) might directly modulate pituitary gonadotropin production.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 35, "end": 46}]}}, "schema": []}
{"input": "FFAs caused a time and dose-dependent increase in phosphorylation of the MAP kinases p38MAPK, JNK1/2 and ERK1/2 in L beta T2 gonadotrope cells.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, FFAs upregulated Lhb mRNA expression acutely, an effect that was blocked by JNK inhibition, but suppressed Fshb mRNA expression, an effect that was independent of MAPK signaling.", "output": {"entities": {}}, "schema": []}
{"input": "FFAs enhanced the activation of the MAPKs in the presence of GnRH although the cotreatment did not alter Lhb induction, but did eliminate the GnRH induction of Fshb.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 61, "end": 65}, {"text": "GnRH", "start": 142, "end": 146}]}}, "schema": []}
{"input": "FFAs also suppressed activin-induced Fshb expression.", "output": {"entities": {}}, "schema": []}
{"input": "Knockdown experiments showed that the FFA effect on the inflammatory kinases p38MAPK and JNK and on Lhb, but not Fshb, mRNA expression is mediated via TLR2 and TLR4 and was mimicked by LPS stimulation.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo, male C57BL/6 mice on a high-fat diet (HFD) showed reduced FSH levels consistent with the suppression of Fshb seen in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Histological analysis of the testes showed an increased number of abnormal seminiferous tubules.", "output": {"entities": {}}, "schema": []}
{"input": "Female mice on HFD lacked the expected proestrus LH and FSH surge, exhibited an increase in the number of days at estrus and a reduced number of days at proestrus, and ovaries had significantly fewer corpora lutea.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, our findings suggest that lipid excess can lead to reproductive defects in both male and female mice.", "output": {"entities": {}}, "schema": []}
{"input": "Doped quantum dots for chemo/biosensing and bioimaging.", "output": {"entities": {}}, "schema": []}
{"input": "Quantum dots (QDs) have received great interest for diverse applications due to their distinct advantages, such as narrow and symmetric emission with tunable colors, broad and strong absorption, reasonable stability, and solution processibility.", "output": {"entities": {}}, "schema": []}
{"input": "Doped QDs not only potentially retain almost all of the above advantages, but also avoid the self-quenching problem due to their substantial ensemble Stokes shift.", "output": {"entities": {}}, "schema": []}
{"input": "Two obvious advantages of doped QDs, especially doped ZnS QDs, over typical CdSe @ZnS and CdTe QDs are longer dopant emission lifetime and potentially lower cytotoxicity.", "output": {"entities": {"chemical": [{"text": "ZnS", "start": 54, "end": 57}, {"text": "CdSe", "start": 76, "end": 80}, {"text": "ZnS", "start": 82, "end": 85}, {"text": "CdTe", "start": 90, "end": 94}]}}, "schema": []}
{"input": "The lifetime of dopant emission from transition-metal ion or lanthanide ion-doped QDs is generally longer than that of the bandgap or defect-related emission of host, and that of biological background fluorescence, providing great opportunities to eliminate background fluorescence for biosensing and bioimaging.", "output": {"entities": {"chemical": [{"text": "lanthanide", "start": 61, "end": 71}]}}, "schema": []}
{"input": "For bioimaging applications, fluorescent dopants may mitigate toxicity problems by producing visible or infrared emission in nanocrystals made from less-harmful elements than those currently used.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, recent advances in utilizing doped QDs for chemo/biosensing and bioimaging are discussed, and the synthetic routes and optical properties of doped QDs that make them excellent probes for various strategies in chemo/biosensing and bioimaging are highlighted.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, perspectives on future exploration of doped QDs for chemo/biosensing and bioimaging are also given.", "output": {"entities": {}}, "schema": []}
{"input": "High-throughput identification of long-range regulatory elements and their target promoters in the human genome.", "output": {"entities": {}}, "schema": []}
{"input": "Enhancer elements are essential for tissue-specific gene regulation during mammalian development.", "output": {"entities": {}}, "schema": []}
{"input": "Although these regulatory elements are often distant from their target genes, they affect gene expression by recruiting transcription factors to specific promoter regions.", "output": {"entities": {}}, "schema": []}
{"input": "Because of this long-range action, the annotation of enhancer element-target promoter pairs remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we developed a novel analysis methodology that takes advantage of Hi-C data to comprehensively identify these interactions throughout the human genome.", "output": {"entities": {}}, "schema": []}
{"input": "To do this, we used a geometric distribution-based model to identify DNA-DNA interaction hotspots that contact gene promoters with high confidence.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that these promoter-interacting hotspots significantly overlap with known enhancer-associated histone modifications and DNase I hypersensitive sites.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, we defined thousands of candidate enhancer elements by incorporating these features, and found that they have a significant propensity to be bound by p300, an enhancer binding transcription factor.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we revealed that their target genes are significantly bound by RNA Polymerase II and demonstrate tissue-specific expression.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we uncovered that these elements are generally found within 1 Mb of their targets, and often regulate multiple genes.", "output": {"entities": {}}, "schema": []}
{"input": "In total, our study presents a novel high-throughput workflow for confident, genome-wide discovery of enhancer-target promoter pairs, which will significantly improve our understanding of these regulatory interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Modelling the surface free energy parameters of polyurethane coats-part 1.", "output": {"entities": {"chemical": [{"text": "polyurethane", "start": 48, "end": 60}]}}, "schema": []}
{"input": "Solvent-based coats obtained from linear polyurethane elastomers.", "output": {"entities": {"chemical": [{"text": "polyurethane", "start": 41, "end": 53}]}}, "schema": []}
{"input": "Polyurethane elastomers coating were synthesised by using typical diisocyanates, polyether and polyester polyols and HO-tertiary amines or diols as a chain extenders.", "output": {"entities": {"chemical": [{"text": "Polyurethane", "start": 0, "end": 12}, {"text": "diisocyanates", "start": 66, "end": 79}, {"text": "polyether", "start": 81, "end": 90}, {"text": "polyester polyols", "start": 95, "end": 112}, {"text": "HO", "start": 117, "end": 119}, {"text": "tertiary amines", "start": 120, "end": 135}, {"text": "diols", "start": 139, "end": 144}]}}, "schema": []}
{"input": "Mole fractions of structural fragments (kappa exp) responsible for the polar interactions within polyurethane chains were calculated by (1) H NMR method.", "output": {"entities": {"chemical": [{"text": "polyurethane", "start": 97, "end": 109}, {"text": "(1) H", "start": 136, "end": 141}]}}, "schema": []}
{"input": "Obtained results were confronted with the analogous parameter values (kappa theor) calculated on the basis of process stoichiometry, considering the stage of the production of isocyanate prepolymers and reaction of their extension for polyurethanes.", "output": {"entities": {"chemical": [{"text": "isocyanate", "start": 176, "end": 186}, {"text": "polyurethanes", "start": 235, "end": 248}]}}, "schema": []}
{"input": "Trials of linear correlation between the kappa exp parameters and surface free energy (SFE) values of investigated coatings were presented.", "output": {"entities": {}}, "schema": []}
{"input": "SFE values were determined by Owens-Wendt method, using contact angles measured with the goniometric method.", "output": {"entities": {}}, "schema": []}
{"input": "Based on achieved results, another empirical models, allowing for prediction the influence of the kind of polyurethane raw materials on SFE values of received coatings were determined.", "output": {"entities": {"chemical": [{"text": "polyurethane", "start": 106, "end": 118}]}}, "schema": []}
{"input": "It was found that it is possible to regulate the SFE in the range millijoules per cubic metre by the selection of appropriate substrates.", "output": {"entities": {}}, "schema": []}
{"input": "It has been found that use of 2, 2, 3, 3-tetrafluoro-1, 4-butanediol as a fluorinated extender of prepolymer chains is essential to obtain coatings with increased hydrophobicity, applied among others as biomaterials-next to diphenylmethane diisocyanate and polyoxyethylene glycol.", "output": {"entities": {"chemical": [{"text": "2, 2, 3, 3-tetrafluoro-1, 4-butanediol", "start": 30, "end": 68}, {"text": "diphenylmethane diisocyanate", "start": 224, "end": 252}, {"text": "polyoxyethylene glycol", "start": 257, "end": 279}]}}, "schema": []}
{"input": "Biocomposites of pHEMA with HA/beta-TCP (60/40) for bone tissue engineering: Swelling, hydrolytic degradation, and in vitro behavior.", "output": {"entities": {"chemical": [{"text": "pHEMA", "start": 17, "end": 22}, {"text": "beta-TCP", "start": 31, "end": 39}]}}, "schema": []}
{"input": "The field of bone and cartilage tissue engineering has a pressing need for novel, biocompatible, biodegradable biocomposites comprising polymers with bioceramics or bioglasses to meet numerous requirements for these applications.", "output": {"entities": {}}, "schema": []}
{"input": "We created hydrolytically degradable hydrogel/bioceramic biocomposites, comprising poly (2-hydroxyethyl methacrylate) (pHEMA) hydrogels and 50 wt% biphasic hydroxyapatite/beta-tricalcium phosphate (60/40) through in situ polymerization.", "output": {"entities": {"chemical": [{"text": "poly (2-hydroxyethyl methacrylate)", "start": 83, "end": 117}, {"text": "pHEMA", "start": 119, "end": 124}, {"text": "hydroxyapatite", "start": 156, "end": 170}, {"text": "beta-tricalcium phosphate", "start": 171, "end": 196}]}}, "schema": []}
{"input": "The hydrolytic degradation starts with hydrolysis of the cross-linker, N, O-dimethacryloyl hydroxylamine, which was synthesized in house.", "output": {"entities": {"chemical": [{"text": "N, O-dimethacryloyl hydroxylamine", "start": 71, "end": 104}]}}, "schema": []}
{"input": "Swelling and degradation were examined in details at a phosphate buffered saline solution at 37 degrees C over a 12-week period of time.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 55, "end": 64}]}}, "schema": []}
{"input": "To vary degradability, a co-monomer, acrylic acid (AA) or 2-hydroxypropyl methacrylamide (HPMA), was introduced, coupled with altering the concentration of the cross-linker and of the bioceramic.", "output": {"entities": {"chemical": [{"text": "acrylic acid", "start": 37, "end": 49}, {"text": "2-hydroxypropyl methacrylamide", "start": 58, "end": 88}, {"text": "HPMA", "start": 90, "end": 94}]}}, "schema": []}
{"input": "The co-monomer HPMA was found to be more effective than AA in enhancing degradation, though AA led to greater swelling ratios.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 15, "end": 19}]}}, "schema": []}
{"input": "33% of weight loss was achieved in some of the biocomposites containing HPMA.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 72, "end": 76}]}}, "schema": []}
{"input": "Porous structures were developed during swelling and degradation in biocomposites with AA but not in those containing HPMA, suggesting different degradation mechanisms: bulk erosion vs. bulk degradation.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 118, "end": 122}]}}, "schema": []}
{"input": "Good biocompatibility, as evidenced by attachment and proliferation of mouse-derived osteoblast precursor cells from the MC3T3-E1 lineage, was observed on these biomaterials, regardless of the type of the co-monomer.", "output": {"entities": {}}, "schema": []}
{"input": "The rationale and approaches employed here open up new opportunities for creating novel, complex organic-inorganic biomaterials in orthopedic tissue engineering.", "output": {"entities": {}}, "schema": []}
{"input": "Use of magnetic forces to promote stem cell aggregation during differentiation, and cartilage tissue modeling.", "output": {"entities": {}}, "schema": []}
{"input": "Magnetic forces induce cell condensation necessary for stem cell differentiation into cartilage and elicit the formation of a tissue-like structure: Magnetically driven fusion of aggregates assembled by micromagnets results in the formation of a continuous tissue layer containing abundant cartilage matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Nicotinic Acid and Nicotinamide: A Review of Their Use for Hyperphosphatemia in Dialysis Patients.", "output": {"entities": {"chemical": [{"text": "Nicotinic Acid", "start": 0, "end": 14}, {"text": "Nicotinamide", "start": 19, "end": 31}]}}, "schema": []}
{"input": "Phosphate binders have traditionally been used to treat hyperphosphatemia, a common complication in patients with end stage renal disease (ESRD).", "output": {"entities": {"chemical": [{"text": "Phosphate", "start": 0, "end": 9}]}}, "schema": []}
{"input": "New evidence suggests that nicotinic acid and its metabolites may effectively decrease phosphorus absorption in the gastrointestinal tract, thereby reducing serum phosphorus concentrations.", "output": {"entities": {"chemical": [{"text": "nicotinic acid", "start": 27, "end": 41}, {"text": "phosphorus", "start": 87, "end": 97}, {"text": "phosphorus", "start": 163, "end": 173}]}}, "schema": []}
{"input": "We conducted a literature search to identify studies of patients with ESRD on dialysis that evaluated the role of niacin and related compounds in decreasing serum phosphorus levels.", "output": {"entities": {"chemical": [{"text": "niacin", "start": 114, "end": 120}, {"text": "phosphorus", "start": 163, "end": 173}]}}, "schema": []}
{"input": "We searched PubMed using the search terms niacin, nicotinic acid, niacinamide, nicotinamide and hyperphosphatemia.", "output": {"entities": {"chemical": [{"text": "niacin", "start": 42, "end": 48}, {"text": "nicotinic acid", "start": 50, "end": 64}, {"text": "niacinamide", "start": 66, "end": 77}, {"text": "nicotinamide", "start": 79, "end": 91}]}}, "schema": []}
{"input": "Limits were set to include only those articles published since 2002, conducted in human subjects, and written in the English language.", "output": {"entities": {}}, "schema": []}
{"input": "Review articles captured through this process were mined for references to other primary literature that may not have been returned through the initial search.", "output": {"entities": {}}, "schema": []}
{"input": "All studies were included if they met the search criteria and were conducted in patients with ESRD who received either hemodialysis or peritoneal dialysis.", "output": {"entities": {}}, "schema": []}
{"input": "To identify current, ongoing studies, another search was conducted through clinicaltrials. gov.", "output": {"entities": {}}, "schema": []}
{"input": "Among the seven studies that met our exclusion criteria, three used nicotinic acid as the therapeutic intervention and four used nicotinamide.", "output": {"entities": {"chemical": [{"text": "nicotinic acid", "start": 68, "end": 82}, {"text": "nicotinamide", "start": 129, "end": 141}]}}, "schema": []}
{"input": "Both nicotinic acid and nicotinamide were effective in significantly reducing serum phosphorus concentrations in patients with ESRD on either hemodialysis or peritoneal dialysis.", "output": {"entities": {"chemical": [{"text": "nicotinic acid", "start": 5, "end": 19}, {"text": "nicotinamide", "start": 24, "end": 36}, {"text": "phosphorus", "start": 84, "end": 94}]}}, "schema": []}
{"input": "Additional, large-scale studies that assess the appropriate dose as well as long-term safety and efficacy are recommended before clinicians can confirm their place in therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple Phytoestrogens Inhibit Cell Growth and Confer Cytoprotection By Inducing Manganese Superoxide Dismutase Expression.", "output": {"entities": {"chemical": [{"text": "Manganese Superoxide", "start": 82, "end": 102}]}}, "schema": []}
{"input": "Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "As data on phytoestrogens continues to accumulate, it is clear that there is significant overlap in the cellular effects elicited by these various compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that one mechanism by which a number of phytoestrogens achieve their growth inhibitory and cytoprotective effects is via induction of the mitochondrial manganese superoxide dismutase (MnSOD).", "output": {"entities": {"chemical": [{"text": "manganese superoxide", "start": 166, "end": 186}]}}, "schema": []}
{"input": "Eight phytoestrogens, including resveratrol, coumestrol, kaempferol, genistein, daidzein, apigenin, isoliquirtigenin and glycitin, were tested for their ability to induce MnSOD expression in mouse C2C12 and primary myoblasts.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 32, "end": 43}, {"text": "coumestrol", "start": 45, "end": 55}, {"text": "kaempferol", "start": 57, "end": 67}, {"text": "genistein", "start": 69, "end": 78}, {"text": "daidzein", "start": 80, "end": 88}, {"text": "apigenin", "start": 90, "end": 98}, {"text": "isoliquirtigenin", "start": 100, "end": 116}, {"text": "glycitin", "start": 121, "end": 129}]}}, "schema": []}
{"input": "Five of these, resveratrol, coumestrol, kaempferol, genistein and daidzein, significantly increased MnSOD expression, slowed proliferative growth and enhanced stress resistance (hydrogen peroxide LD50).", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 15, "end": 26}, {"text": "coumestrol", "start": 28, "end": 38}, {"text": "kaempferol", "start": 40, "end": 50}, {"text": "genistein", "start": 52, "end": 61}, {"text": "daidzein", "start": 66, "end": 74}, {"text": "hydrogen peroxide", "start": 178, "end": 195}]}}, "schema": []}
{"input": "When siRNA was used to prevent the MnSOD induction by genistein, coumestrol or daidzein, none of these compounds exerted any effect on proliferative growth, and only the effect of coumestrol on stress resistance persisted.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 54, "end": 63}, {"text": "coumestrol", "start": 65, "end": 75}, {"text": "daidzein", "start": 79, "end": 87}, {"text": "coumestrol", "start": 180, "end": 190}]}}, "schema": []}
{"input": "The estrogen antagonist ICI182780 prevented the increased MnSOD expression and also the changes in cell growth and stress resistance, indicating that these effects are mediated by estrogen receptors (ER).", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 4, "end": 12}, {"text": "ICI182780", "start": 24, "end": 33}, {"text": "estrogen", "start": 180, "end": 188}]}}, "schema": []}
{"input": "The absence of effects of resveratrol or coumestrol, but not genistein, in ER beta-null cells further indicated that this ER in particular is important in mediating these effects.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 26, "end": 37}, {"text": "coumestrol", "start": 41, "end": 51}, {"text": "genistein", "start": 61, "end": 70}]}}, "schema": []}
{"input": "Thus, an ER-mediated induction of MnSOD expression appears to underlie the growth inhibitory and cytoprotective activities of multiple phytoestrogens.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "The pre-clinical absorption, distribution, metabolism and excretion properties of IPI-926, an orally bioavailable antagonist of the hedgehog signal transduction pathway.", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 82, "end": 89}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "IPI-926 is a novel semisynthetic cyclopamine derivative that is a potent and selective Smoothened inhibitor that blocks the hedgehog signal transduction pathway.", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 0, "end": 7}, {"text": "cyclopamine", "start": 33, "end": 44}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "The in vivo clearance of IPI-926 is low in mouse and dog and moderate in monkey.", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 25, "end": 32}]}}, "schema": []}
{"input": "The volume of distribution is high across species.", "output": {"entities": {}}, "schema": []}
{"input": "Oral bioavailability ranges from moderate in monkey to high in mouse and dog.", "output": {"entities": {}}, "schema": []}
{"input": "Predicted human clearance using simple allometry is low (24 L h (-1)), predicted volume of distribution is high (469 L) and predicted half-life is long (20 h).", "output": {"entities": {}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "IPI-926 is highly bound to plasma proteins and has minimal interaction with human alpha-1-acid glycoprotein.", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 0, "end": 7}]}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro metabolic stability ranges from stable to moderately stable.", "output": {"entities": {}}, "schema": []}
{"input": "Twelve oxidative metabolites were detected in mouse, rat, dog, monkey and human liver microsome incubations and none were unique to human.", "output": {"entities": {}}, "schema": []}
{"input": "5.", "output": {"entities": {}}, "schema": []}
{"input": "IPI-926 is not a potent reversible inhibitor of CYP1A2, 2C8, 2C9 or 3A4 (testosterone).", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 0, "end": 7}, {"text": "testosterone", "start": 73, "end": 85}]}}, "schema": []}
{"input": "IPI-926 is a moderate inhibitor of CYP2C19, 2D6 and 3A4 (midazolam) with KI values of 19, 16 and 4. 5 micro M, respectively.", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 0, "end": 7}, {"text": "midazolam", "start": 57, "end": 66}]}}, "schema": []}
{"input": "IPI-926 is both a substrate and inhibitor (IC50 = 1. 9 micro M) of P-glycoprotein.", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 0, "end": 7}]}}, "schema": []}
{"input": "6.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, IPI-926 has desirable pre-clinical absorption, distribution, metabolism and excretion properties.", "output": {"entities": {"chemical": [{"text": "IPI-926", "start": 12, "end": 19}]}}, "schema": []}
{"input": "A multiple perspectives on atypical polypoid adenomyoma of uterus.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Atypical polypoid adenomyoma (APA) is a rare benign uterine tumor, with less than 200 cases have been reported in English literature.", "output": {"entities": {}}, "schema": []}
{"input": "Although, it is considered as a benign lesion and treated conservatively previously, more and more cases show that APA has a high rate of recurrence or residual, and is found to precede the development of carcinoma.", "output": {"entities": {}}, "schema": []}
{"input": "Given the data from present research on APA, the therapy of APA becomes more complex and must be cautious, especially for the nulliparous and premenopausal patients.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, because of the low incidence, studies on this disease are less, and the etiology and pathogenesis of APA is still unclear.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, we aim to summarize recent researches concerning APA from multiple perspectives, including clinical presentation, histogenesis, immunohistochemistry and molecular features, diagnosis and differential diagnosis, treatment opinion and prognosis, which may provide theory and clinical basis for the future clinical treatment and research of this rare disease.", "output": {"entities": {}}, "schema": []}
{"input": "Path-Branching Representation for Nonadiabatic Electron Dynamics in Conical Intersection.", "output": {"entities": {}}, "schema": []}
{"input": "Path-branching representation (or phase-space averaging and natural branching method (PSANB) as its approximation) of nonadiabatic electron wavepacket dynamics is now known to work well for avoided crossings in many dimensional nonadiabatic transitions [Yonehara, T.; Hanasaki, K.; Takatsuka, K. Chem. Rev. 2012, 112, 499].", "output": {"entities": {}}, "schema": []}
{"input": "In this paper we examine feasibility of the path-branching representation in the theoretical studies of conical intersection (CI).", "output": {"entities": {}}, "schema": []}
{"input": "The most characteristic feature of CI is the Herzberg-Longuet-Higgins phase (or the Berry phase) arising from the electronic part of the total wave function, and accordingly quantum phases of both electronic and nuclear dynamics should be taken into account in a balanced manner.", "output": {"entities": {}}, "schema": []}
{"input": "We first show the PSANB can well capture the essential feature of the phase dynamics of CI.", "output": {"entities": {}}, "schema": []}
{"input": "However, the nuclear phases, the wavelength of which is far shorter than that of the electronic phases, make the computation of nonadiabatic transition extremely oscillatory, resulting in very slow convergence with respect to the number of sampling paths.", "output": {"entities": {}}, "schema": []}
{"input": "A similar difficulty quite often takes place in theoretical chemical dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "To cope with this situation, we devise a simple and tractable approximation in the application of PSANB resting on the fact that a small number of PSANB paths already reproduce accurate nonadiabatic transition probability.", "output": {"entities": {}}, "schema": []}
{"input": "Thiolactone Sulfoxides as New Reactive Metabolites Acting as Bis-Electrophiles: Implication in Clopidogrel and Prasugrel Bioactivation.", "output": {"entities": {"chemical": [{"text": "Thiolactone Sulfoxides", "start": 0, "end": 22}, {"text": "Clopidogrel", "start": 95, "end": 106}, {"text": "Prasugrel", "start": 111, "end": 120}]}}, "schema": []}
{"input": "The antithrombotics of the tetrahydrothienopyridine series, clopidogrel and prasugrel, are prodrugs that must be metabolized in two steps to become pharmacologically active.", "output": {"entities": {"chemical": [{"text": "tetrahydrothienopyridine", "start": 27, "end": 51}, {"text": "clopidogrel", "start": 60, "end": 71}, {"text": "prasugrel", "start": 76, "end": 85}]}}, "schema": []}
{"input": "The first step is the formation of a thiolactone metabolite.", "output": {"entities": {"chemical": [{"text": "thiolactone", "start": 37, "end": 48}]}}, "schema": []}
{"input": "The second step is a cytochrome P450 (P450)-dependent oxidation of this thiolactone resulting in the formation of a sulfenic acid that is eventually reduced into the corresponding active thiol.", "output": {"entities": {"chemical": [{"text": "thiolactone", "start": 72, "end": 83}, {"text": "sulfenic acid", "start": 116, "end": 129}, {"text": "thiol", "start": 187, "end": 192}]}}, "schema": []}
{"input": "It has been postulated that the sulfenic acid metabolite resulted from a nucleophilic attack of water on a highly reactive thiolactone sulfoxide derived from P450-dependent oxidation of the thiolactone primary metabolite.", "output": {"entities": {"chemical": [{"text": "sulfenic acid", "start": 32, "end": 45}, {"text": "thiolactone sulfoxide", "start": 123, "end": 144}, {"text": "thiolactone", "start": 190, "end": 201}]}}, "schema": []}
{"input": "The data described in the present article are in complete agreement with this proposition as they show that it was possible to trap these thiolactone sulfoxides by a series of nucleophiles such as amines, thiols, or cyclopentane-1, 3-dione (CPDH), an equivalent of dimedone that is used as a sulfenic acid trapping agent.", "output": {"entities": {"chemical": [{"text": "thiolactone sulfoxides", "start": 138, "end": 160}, {"text": "amines", "start": 197, "end": 203}, {"text": "thiols", "start": 205, "end": 211}, {"text": "cyclopentane-1, 3-dione", "start": 216, "end": 239}, {"text": "CPDH", "start": 241, "end": 245}, {"text": "dimedone", "start": 265, "end": 273}, {"text": "sulfenic acid", "start": 292, "end": 305}]}}, "schema": []}
{"input": "HPLC-MS studies showed that various bis-adducts having incorporated two nucleophile molecules were formed in these reactions.", "output": {"entities": {}}, "schema": []}
{"input": "One of them that resulted from the oxidation of 2-oxo-prasugrel by human liver microsomes in the presence of ethanolamine and CPDH was isolated and completely characterized by (1) H and (13) C NMR spectroscopy in addition to MS and MS (2) spectrometry.", "output": {"entities": {"chemical": [{"text": "2-oxo-prasugrel", "start": 48, "end": 63}, {"text": "ethanolamine", "start": 109, "end": 121}, {"text": "CPDH", "start": 126, "end": 130}, {"text": "(1) H", "start": 176, "end": 181}, {"text": "(13) C", "start": 186, "end": 192}]}}, "schema": []}
{"input": "All metabolites derived from an attack of H2O or an amine at the CO carbon of the intermediate thiolactone sulfoxide existed as a mixture of two diastereomers having a cis configuration of the double bond, whereas those formed in the presence of thiols appeared as a mixture of four diastereomers with a cis or trans configuration of the double bond.", "output": {"entities": {"chemical": [{"text": "H2O", "start": 42, "end": 45}, {"text": "amine", "start": 52, "end": 57}, {"text": "CO carbon", "start": 65, "end": 74}, {"text": "thiolactone sulfoxide", "start": 95, "end": 116}, {"text": "thiols", "start": 246, "end": 252}]}}, "schema": []}
{"input": "This led us to propose tentative mechanisms for the previously reported formation of trans isomers of the active thiol metabolite of clopidogrel upon microsomal metabolism of this antithrombotic in the presence of thiols.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 113, "end": 118}, {"text": "clopidogrel", "start": 133, "end": 144}, {"text": "thiols", "start": 214, "end": 220}]}}, "schema": []}
{"input": "The results described in this article showed that thiolactone sulfoxides are formed as reactive metabolites during the metabolism of clopidogrel and prasugrel and are able to react as bis-electrophiles with a variety of nucleophiles.", "output": {"entities": {"chemical": [{"text": "thiolactone sulfoxides", "start": 50, "end": 72}, {"text": "clopidogrel", "start": 133, "end": 144}, {"text": "prasugrel", "start": 149, "end": 158}]}}, "schema": []}
{"input": "The possible implications of the formation of these reactive metabolites in the pharmacological and/or secondary toxic effects of these drugs remain to be studied.", "output": {"entities": {}}, "schema": []}
{"input": "Tensile Lattice Strain Accelerates Oxygen Surface Exchange and Diffusion in La1-xSrxCoO3-delta Thin Films.", "output": {"entities": {"chemical": [{"text": "Oxygen", "start": 35, "end": 41}]}}, "schema": []}
{"input": "The influence of lattice strain on the oxygen exchange kinetics and diffusion in oxides was investigated on (100) epitaxial La1-xSrxCoO3-delta (LSC) thin films grown by pulsed laser deposition.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 39, "end": 45}, {"text": "oxides", "start": 81, "end": 87}, {"text": "La1-xSrxCoO3-delta", "start": 124, "end": 142}, {"text": "LSC", "start": 144, "end": 147}]}}, "schema": []}
{"input": "Planar tensile and compressively strained LSC films were obtained on single-crystalline SrTiO3 and LaAlO3.", "output": {"entities": {"chemical": [{"text": "LSC", "start": 42, "end": 45}, {"text": "SrTiO3", "start": 88, "end": 94}, {"text": "LaAlO3", "start": 99, "end": 105}]}}, "schema": []}
{"input": "(18) O isotope exchange depth profiling with ToF-SIMS was employed to simultaneously measure the tracer surface exchange coefficient k * and the tracer diffusion coefficient D * in the temperature range 280-475 degrees C.", "output": {"entities": {"chemical": [{"text": "(18) O", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In accordance with recent theoretical findings, much faster surface exchange (~ 4 times) and diffusion (~ 10 times) were observed for the tensile strained films compared to the compressively strained films in the entire temperature range.", "output": {"entities": {}}, "schema": []}
{"input": "The same strain effect-tensile strain leading to higher k * and D *-was found for different LSC compositions (x = 0. 2 and x = 0. 4) and for surface-etched films.", "output": {"entities": {"chemical": [{"text": "LSC", "start": 92, "end": 95}]}}, "schema": []}
{"input": "The temperature dependence of k * and D * is discussed with respect to the contributions of strain states, formation enthalpy of oxygen vacancies, and vacancy mobility at different temperatures.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 129, "end": 135}]}}, "schema": []}
{"input": "Our findings point toward the control of oxygen surface exchange and diffusion kinetics by means of lattice strain in existing mixed conducting oxides for energy conversion applications.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 41, "end": 47}, {"text": "oxides", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Exciton Coupling Mechanisms Analyzed with Subsystem TDDFT: Direct vs Pseudo Exchange Effects.", "output": {"entities": {}}, "schema": []}
{"input": "The dominant effect in exciton coupling is usually the so-called Coulomb coupling contribution, that is the Coulomb interaction between transition densities of localized excitations.", "output": {"entities": {}}, "schema": []}
{"input": "At short distances, Dexter-type exchange effects are discussed to play a role, which are not well described by (semi) local functionals in time-dependent density functional theory (TDDFT) calculations.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, a large effect of the percentage of exact exchange on the resulting exciton splittings is known.", "output": {"entities": {}}, "schema": []}
{"input": "Subsystem TDDFT allows one to analyze the exciton coupling mechanism by distinguishing direct from indirect effects, that is, changes in the actual coupling mechanism from modifications in the underlying local excitations.", "output": {"entities": {}}, "schema": []}
{"input": "Our analysis shows that the strong influence of exact exchange is not due to a direct Dexter-type (exchange) coupling, but rather to an increased Coulomb (or pseudo-exchange) coupling triggered by a change in transition densities.", "output": {"entities": {}}, "schema": []}
{"input": "This is demonstrated in calculations for 2-pyridone and chlorophyll dimers.", "output": {"entities": {"chemical": [{"text": "2-pyridone", "start": 41, "end": 51}]}}, "schema": []}
{"input": "We finally propose a route to efficient calculations of excited states of large pigment aggregates with hybrid functionals, which so far has been out of reach for quantum chemical methods.", "output": {"entities": {}}, "schema": []}
{"input": "Arylpiperazines as fatty acid transport protein 1 (FATP1) inhibitors with improved potency and pharmacokinetic properties.", "output": {"entities": {"chemical": [{"text": "Arylpiperazines", "start": 0, "end": 15}, {"text": "fatty acid", "start": 19, "end": 29}]}}, "schema": []}
{"input": "The discovery and optimization of a novel series of FATP1 inhibitors are described.", "output": {"entities": {}}, "schema": []}
{"input": "Through the derivatization process, arylpiperazine derivatives 5k and 12a were identified as possessing potent in vitro activity against human and mouse FATP1s as well as excellent pharmacokinetic properties.", "output": {"entities": {"chemical": [{"text": "arylpiperazine", "start": 36, "end": 50}]}}, "schema": []}
{"input": "In vivo evaluation of triglyceride accumulation in the liver, white gastrocnemius muscle and soleus is also described.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 22, "end": 34}]}}, "schema": []}
{"input": "Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors.", "output": {"entities": {"chemical": [{"text": "cyclic imides", "start": 57, "end": 70}, {"text": "benzenesulfonamide", "start": 79, "end": 97}]}}, "schema": []}
{"input": "Part 2.", "output": {"entities": {}}, "schema": []}
{"input": "A group of cyclic imides (1-10) was designed for evaluation as a selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activity.", "output": {"entities": {"chemical": [{"text": "cyclic imides", "start": 11, "end": 24}]}}, "schema": []}
{"input": "Compounds 6a, 6b, 8a, 8b, 9a, 9b, 10a and 10b were proved to be potent COX-2 inhibitors with IC50 range of 0. 1-4. 0 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 8a as a highly potent (IC50 = 0. 1 mu M), and an extremely selective [COX-2 (SI) > 1000] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 72. 4mg/kg) relative to diclofenac (ED50 = 114mg/kg).", "output": {"entities": {"chemical": [{"text": "celecoxib", "start": 182, "end": 191}, {"text": "diclofenac", "start": 308, "end": 318}]}}, "schema": []}
{"input": "Molecular modeling was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "The study showed that the homosulfonamide fragment of 8a inserted deep inside the 2 degrees-pocket of the COX-2 active site, where the SO2NH2 group underwent H-bonding interaction with Gln (192) (2. 95 A), Phe (518) (2. 82 A) and Arg (513) (2. 63 and 2. 73 A).", "output": {"entities": {"chemical": [{"text": "homosulfonamide", "start": 26, "end": 41}, {"text": "SO2NH2", "start": 135, "end": 141}, {"text": "H", "start": 158, "end": 159}, {"text": "Gln", "start": 185, "end": 188}, {"text": "Phe", "start": 206, "end": 209}, {"text": "Arg", "start": 230, "end": 233}]}}, "schema": []}
{"input": "Docking study of the synthesized compound 8a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.", "output": {"entities": {"chemical": [{"text": "SC-558", "start": 110, "end": 116}]}}, "schema": []}
{"input": "Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-kappa B pathway activation in human umbilical vein endothelial cells.", "output": {"entities": {"chemical": [{"text": "glycyrrhizic acid", "start": 14, "end": 31}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Glycyrrhiza uralensis roots) is used as a traditional medicine for the treatment of diabetes mellitus and its vascular complications.", "output": {"entities": {}}, "schema": []}
{"input": "Glycyrrhizic acid (GA, also known as Glycyrrhizin), a triterpenoid saponin glycoside, is considered to be a bioactive component in Licorice and is beneficial to diabetic vascular complications.", "output": {"entities": {"chemical": [{"text": "Glycyrrhizic acid", "start": 0, "end": 17}, {"text": "Glycyrrhizin", "start": 37, "end": 49}, {"text": "triterpenoid saponin glycoside", "start": 54, "end": 84}]}}, "schema": []}
{"input": "AIM OF STUDY: The present study was conducted to evaluate the potential protective activities on AGEs-induced endothelial dysfunction, including anti-apoptosis, antioxidant stress and anti-proinflammatory responses, and explore the underlying mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were incubated and pre-treated with GA (10 (-9)-10 (-6) M) or RAGE-Ab (5 mu g/ml) in the presence or absence of 200 mu g/ml AGEs.", "output": {"entities": {}}, "schema": []}
{"input": "AO/EB fluorescence staining assay was performed to evaluate anti-apoptosis activity.", "output": {"entities": {}}, "schema": []}
{"input": "The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in cell supernatant were detected by kits while the intracellular reactive oxygen species (ROS) generation was determined by 2, 7-dichlorodihydrofluorescin diacetate (DCFH-DA) kit.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 4, "end": 14}, {"text": "malondialdehyde", "start": 44, "end": 59}, {"text": "MDA", "start": 61, "end": 64}, {"text": "oxygen", "start": 147, "end": 153}, {"text": "2, 7-dichlorodihydrofluorescin diacetate", "start": 197, "end": 237}, {"text": "DCFH-DA", "start": 239, "end": 246}]}}, "schema": []}
{"input": "Immunocytochemistry analysis was designed to determine transforming growth factor beta1 (TGF-beta 1) protein expression while immunofluorescence analysis for RAGE and NF-kB.", "output": {"entities": {}}, "schema": []}
{"input": "The protein expressions of TGF-beta 1, RAGE and NF-kB were analyzed by Western blot analysis.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Pretreatment with GA at a concentration of 10 (-8)-10 (-6) M significantly reduced the AGEs-induced apoptosis in HUVECs.", "output": {"entities": {}}, "schema": []}
{"input": "GA significantly increased antioxidant enzyme SOD activity and decreased peroxide degradation product MDA level in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 102, "end": 105}]}}, "schema": []}
{"input": "Furthermore, GA also remarkably inhibited the overgeneration of AGEs-induced ROS.", "output": {"entities": {}}, "schema": []}
{"input": "Both immunocytochemistry analysis and western blot analysis showed that GA significantly decreased the protein expression of poinflammatory cytokine TGF-beta 1 in a similar manner which RAGE-Ab did.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, AGEs-induced RAGE and NF-kB protein expressions were down-regulated significantly by the pretreatment with GA or RAGE-Ab.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: These findings provide evidences that GA possesses protective activity on AGEs-induced endothelial dysfunction, including anti-apoptosis, anti-inflammation and antioxidant stress, via inhibiting RAGE/NF-kB pathway.", "output": {"entities": {}}, "schema": []}
{"input": "GA might be an alternative for the prevention and treatment of diabetic vascular complications in an appropriate dosage.", "output": {"entities": {}}, "schema": []}
{"input": "Complement activation by PEGylated liposomes containing prednisolone.", "output": {"entities": {"chemical": [{"text": "prednisolone", "start": 56, "end": 68}]}}, "schema": []}
{"input": "Infusion of PEGylated liposomes can give rise to hypersensitivity reactions (HSRs) in a relatively large number of patients.", "output": {"entities": {}}, "schema": []}
{"input": "Previously it has been shown that these reactions can be caused by activation of the complement (C) system by a negative charge on the anchor molecule of PEG at the liposomal surface.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 154, "end": 157}]}}, "schema": []}
{"input": "In this study it is tested whether the activation of the C system by PEG-liposomes could be significantly reduced to values comparable to nonreactive liposomal formulations, by changing the PEGylation-profile on the liposomal surface.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 69, "end": 72}]}}, "schema": []}
{"input": "Therefore, the formation of C activation markers SC5b-9, C3a, C4d and Bb in normal human serum by both prednisolone loaded and empty liposomes with a variation of PEG chain length, PEG surface concentration, PEG anchor molecule and liposomal size was determined using in vitro assays.", "output": {"entities": {"chemical": [{"text": "prednisolone", "start": 103, "end": 115}, {"text": "PEG", "start": 163, "end": 166}, {"text": "PEG", "start": 181, "end": 184}, {"text": "PEG", "start": 208, "end": 211}]}}, "schema": []}
{"input": "The tested liposomes caused no or only mild (30%) activation of C except for one formulation wherein the PEG2000 was anchored to cholesterol (CHOL-PEG2000).", "output": {"entities": {"chemical": [{"text": "PEG2000", "start": 105, "end": 112}, {"text": "cholesterol", "start": 129, "end": 140}, {"text": "CHOL-PEG2000", "start": 142, "end": 154}]}}, "schema": []}
{"input": "The latter liposomes caused paralleling rises in SC5b-9 and Bb levels, suggesting excess activation of the alternative pathway.", "output": {"entities": {}}, "schema": []}
{"input": "While the relative safety of weak C activator liposomes remains to be confirmed in vivo, the unique, non-charge and non-antibody-mediated direct conversion of C3 by CHOL-PEG2000 liposomes (although argues against the clinical development of these vesicles) opens new opportunities to understand liposomal C activation at the molecular level.", "output": {"entities": {"chemical": [{"text": "CHOL-PEG2000", "start": 165, "end": 177}]}}, "schema": []}
{"input": "Technological and biopharmaceutical optimization of nystatin release from a multiparticulate based bioadhesive drug delivery system.", "output": {"entities": {"chemical": [{"text": "nystatin", "start": 52, "end": 60}]}}, "schema": []}
{"input": "Formulation considerations of a new drug delivery system include controlling the site of release of the active ingredient, maintaining drug level for a suitable time and decreasing dosage frequency.", "output": {"entities": {}}, "schema": []}
{"input": "In research and development practice, these therapeutic benefits can be attained by selecting suitable active ingredients and optimizing procedure parameters, determining the composition of the medicine, and dissolution properties.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of our study was to design a pharmaceutical preparation with increased local therapeutic effect in the therapy of gastrointestinal candidiasis.", "output": {"entities": {}}, "schema": []}
{"input": "The polyene antibiotic nystatin may be an optimal choice for active agent, incorporated in a bioadhesive multiparticulate system.", "output": {"entities": {"chemical": [{"text": "polyene", "start": 4, "end": 11}, {"text": "nystatin", "start": 23, "end": 31}]}}, "schema": []}
{"input": "Choosing the proper excipients in the proper dosage form and ensuring prolonged residence time may further improve the optimal treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Using an experimental design, the micropellets were prepared with 5% nystatin content, taking the factors average pellet size (~ 200 to ~ 800 mu m) and the amount of applied carbomer and hydroxyethylcellulose (0-5%) into consideration.", "output": {"entities": {"chemical": [{"text": "nystatin", "start": 69, "end": 77}]}}, "schema": []}
{"input": "Dissolution of the active ingredient was detected by UV spectrophotometric and microbiological assay.", "output": {"entities": {}}, "schema": []}
{"input": "The bioadhesive character of the multiparticulate dosage form was examined by ex vivo wash-off test.", "output": {"entities": {}}, "schema": []}
{"input": "The only factor which significantly influenced the examined parameters was average pellet size.", "output": {"entities": {}}, "schema": []}
{"input": "The proportion of applied bioadhesive excipients had significance mostly in interactions with average pellet size.", "output": {"entities": {}}, "schema": []}
{"input": "Eventually, optimized drug release (5-10min mean dissolution time, 50-55% bioadhesion retention) could be achieved with 550 mu m pellet size, containing carbomer and hydroxyethylcellulose in 85: 15 ratio.", "output": {"entities": {}}, "schema": []}
{"input": "The molecular fingerprint of high grade serous ovarian cancer reflects its fallopian tube origin.", "output": {"entities": {}}, "schema": []}
{"input": "High grade serous ovarian cancer (HGSC), the most lethal and frequent type of epithelial ovarian cancer (EOC), has poor long term prognosis due to a combination of factors: late detection, great metastatic potential and the capacity to develop resistance to available therapeutic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, there has been considerable controversy concerning the etiology of this malignancy.", "output": {"entities": {}}, "schema": []}
{"input": "New studies, both clinical and molecular, strongly suggest that HGSC originates not from the surface of the ovary, but from the epithelial layer of the neighboring fallopian tube fimbriae.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper we summarize data supporting the central role of fallopian tube epithelium in the development of HGSC.", "output": {"entities": {}}, "schema": []}
{"input": "Specifically, we address cellular pathways and regulatory mechanisms which are modulated in the process of transformation, but also genetic changes which accumulate during disease progression.", "output": {"entities": {}}, "schema": []}
{"input": "Similarities between fallopian tube mucosa and the malignant tissue of HGSC warrant a closer analysis of homeostatic mechanisms in healthy epithelium in order to elucidate key steps in disease development.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we highlight the importance of the cancer stem cell (CSC) identification and understanding of its niche regulation for improvement of therapeutic strategies.", "output": {"entities": {}}, "schema": []}
{"input": "Systematic review of anticholinergic risk scales in older adults.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: Anticholinergic drugs are often involved in explicit criteria for inappropriate prescribing in older adults.", "output": {"entities": {}}, "schema": []}
{"input": "Several scales were developed for screening of anticholinergic drugs and estimation of the anticholinergic burden.", "output": {"entities": {}}, "schema": []}
{"input": "However, variation exists in scale development, in the selection of anticholinergic drugs, and the evaluation of their anticholinergic load.", "output": {"entities": {}}, "schema": []}
{"input": "This study aims to systematically review existing anticholinergic risk scales, and to develop a uniform list of anticholinergic drugs differentiating for anticholinergic potency.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: We performed a systematic search in MEDLINE.", "output": {"entities": {}}, "schema": []}
{"input": "Studies were included if provided (1) a finite list of anticholinergic drugs; (2) a grading score of anticholinergic potency and, (3) a validation in a clinical or experimental setting.", "output": {"entities": {}}, "schema": []}
{"input": "We listed anticholinergic drugs for which there was agreement in the different scales.", "output": {"entities": {}}, "schema": []}
{"input": "In case of discrepancies between scores we used a reputed reference source (Martindale: The Complete Drug Reference (R)) to take a final decision about the anticholinergic activity of the drug.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: We included seven risk scales, and evaluated 225 different drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Hundred drugs were listed as having clinically relevant anticholinergic properties (47 high potency and 53 low potency), to be included in screening software for anticholinergic burden.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: Considerable variation exists among anticholinergic risk scales, in terms of selection of specific drugs, as well as of grading of anticholinergic potency.", "output": {"entities": {}}, "schema": []}
{"input": "Our selection of 100 drugs with clinically relevant anticholinergic properties needs to be supplemented with validated information on dosing and route of administration for a full estimation of the anticholinergic burden in poly-medicated older adults.", "output": {"entities": {}}, "schema": []}
{"input": "Everolimus in Combination with Exemestane: A Review of its Use in the Treatment of Patients with Postmenopausal Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer.", "output": {"entities": {"chemical": [{"text": "Everolimus", "start": 0, "end": 10}, {"text": "Exemestane", "start": 31, "end": 41}]}}, "schema": []}
{"input": "Oral everolimus (Afinitor ((R))) in combination with exemestane is indicated for the treatment of hormone receptor-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer in postmenopausal women after failure of treatment with letrozole or anastrozole (in the USA) or after recurrence of progression following a nonsteroidal aromatase inhibitor (AI) in women without symptomatic visceral disease (in the EU).", "output": {"entities": {"chemical": [{"text": "everolimus", "start": 5, "end": 15}, {"text": "Afinitor", "start": 17, "end": 25}, {"text": "exemestane", "start": 53, "end": 63}, {"text": "letrozole", "start": 260, "end": 269}, {"text": "anastrozole", "start": 273, "end": 284}]}}, "schema": []}
{"input": "Everolimus, a selective inhibitor of mammalian target of rapamycin (mTOR), inhibits the downstream signalling events of the mTOR pathway.", "output": {"entities": {"chemical": [{"text": "Everolimus", "start": 0, "end": 10}, {"text": "rapamycin", "start": 57, "end": 66}]}}, "schema": []}
{"input": "This review summarizes the pharmacology of everolimus and reviews its efficacy and tolerability when administered in combination with exemestane in postmenopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer refractory to nonsteroidal AIs.", "output": {"entities": {"chemical": [{"text": "everolimus", "start": 43, "end": 53}, {"text": "exemestane", "start": 134, "end": 144}, {"text": "oestrogen", "start": 174, "end": 183}]}}, "schema": []}
{"input": "In the well-designed BOLERO-2 study, the addition of everolimus to exemestane was shown to significantly prolong progression-free survival in this patient population.", "output": {"entities": {"chemical": [{"text": "everolimus", "start": 53, "end": 63}, {"text": "exemestane", "start": 67, "end": 77}]}}, "schema": []}
{"input": "However, treatment-emergent adverse events and treatment discontinuations occurred more frequently with combination therapy than with exemestane alone, suggesting a need for careful benefit/risk assessment prior to initiating therapy.", "output": {"entities": {"chemical": [{"text": "exemestane", "start": 134, "end": 144}]}}, "schema": []}
{"input": "Mature survival data from this study are awaited and additional studies would help to further demonstrate the benefit of combination therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Nevertheless, current evidence suggests that everolimus plus exemestane combination therapy may be a useful treatment option in patients with postmenopausal hormone receptor-positive, HER2-negative, advanced breast cancer refractory to nonsteroidal AIs.", "output": {"entities": {"chemical": [{"text": "everolimus", "start": 45, "end": 55}, {"text": "exemestane", "start": 61, "end": 71}]}}, "schema": []}
{"input": "Lorcaserin: a review of its use in chronic weight management.", "output": {"entities": {"chemical": [{"text": "Lorcaserin", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Oral lorcaserin (BELVIQ ((R))), a selective serotonin 5-HT2C receptor agonist, is indicated in the US as an adjunct to diet and exercise in the chronic weight management of obese adults, or overweight adults with at least one weight-related comorbidity (e. g. dyslipidaemia, hypertension, type 2 diabetes).", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 5, "end": 15}, {"text": "BELVIQ", "start": 17, "end": 23}, {"text": "serotonin", "start": 44, "end": 53}]}}, "schema": []}
{"input": "This article reviews the pharmacological properties, therapeutic efficacy and tolerability of oral lorcaserin in this patient population.", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 99, "end": 109}]}}, "schema": []}
{"input": "In three large randomized, double-blind, multicentre studies, oral lorcaserin was more effective than placebo in the management of obese and overweight adults with or without type 2 diabetes mellitus.", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 67, "end": 77}]}}, "schema": []}
{"input": "Following 12 months' therapy, significantly higher proportions of lorcaserin than placebo recipients achieved a >= 5 and >= 10% reduction from baseline in their bodyweight and a significant between-group difference favouring lorcaserin over placebo was observed for the change from baseline in bodyweight.", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 66, "end": 76}, {"text": "lorcaserin", "start": 225, "end": 235}]}}, "schema": []}
{"input": "Moreover, among patients who had achieved a >= 5% reduction in their bodyweight after 12 months' therapy with lorcaserin, a significantly higher proportion who received lorcaserin for a further 12 months than those who switched to placebo maintained >= 5% weight loss at 24 months.", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 110, "end": 120}, {"text": "lorcaserin", "start": 169, "end": 179}]}}, "schema": []}
{"input": "In general, oral lorcaserin was well tolerated in clinical studies, with hypoglycaemia and headache the most frequently reported adverse events in those with or without type 2 diabetes, respectively.", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 17, "end": 27}]}}, "schema": []}
{"input": "According to a pooled analysis, the risk of US-FDA-defined valvulopathy with lorcaserin is generally low and not statistically significantly different from placebo.", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 77, "end": 87}]}}, "schema": []}
{"input": "From these and other data, the FDA has concluded that lorcaserin is unlikely to elevate the risk of valvulopathy.", "output": {"entities": {"chemical": [{"text": "lorcaserin", "start": 54, "end": 64}]}}, "schema": []}
{"input": "Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1.", "output": {"entities": {}}, "schema": []}
{"input": "COL1A1 haploinsufficiency mutations lead to the mildest form of osteogenesis imperfecta (OI), OI type I.", "output": {"entities": {}}, "schema": []}
{"input": "The skeletal clinical characteristics resulting from such mutations have not been characterized in detail.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we assessed 86 patients (36 male, 50 female; mean age 13. 3 years; range 0. 6 to 54 years) with COL1A1 haploinsufficiency mutations, of whom 70 were aged 21 years or less (' pediatric' patients).", "output": {"entities": {}}, "schema": []}
{"input": "Birth history was positive for fracture or long-bone deformity in 12% of patients.", "output": {"entities": {}}, "schema": []}
{"input": "The average rate of long-bone fracture (femur, tibia/fibula, humerus, radius/ulna) in pediatric patients was 0. 62 fractures per year, half of which affected the tibia/fibula.", "output": {"entities": {}}, "schema": []}
{"input": "Long-bone fracture rate was negatively associated with age and lumbar spine areal bone mineral density.", "output": {"entities": {}}, "schema": []}
{"input": "Vertebral compression fractures were observed in 71% of the 58 pediatric patients who had lateral spine radiographs.", "output": {"entities": {}}, "schema": []}
{"input": "The median number of vertebral fractures was higher for females (median 4; range 0 to 14) than for males (median 1, range 0 to 8) (P = 0. 03).", "output": {"entities": {}}, "schema": []}
{"input": "Lumbar spine areal bone mineral density was negatively associated with the severity of vertebral compression fractures, as reflected in the spine deformity index.", "output": {"entities": {}}, "schema": []}
{"input": "Scoliosis was present in about 30% of pediatric patients but the Cobb angle was < 30 degrees in all cases.", "output": {"entities": {}}, "schema": []}
{"input": "The average final height z-score was-1. 1, representing a deficit of 8 to 10 cm compared to the general population.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, OI patients with COL1A1 haploinsufficiency mutations have high rates of significant skeletal involvement.", "output": {"entities": {}}, "schema": []}
{"input": "Systematic follow up of growing patients with COL1A1 haploinsufficiency mutations including radiographic screening for vertebral compression fractures and scoliosis is warranted.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Broadband Light-Trapping Enhancement in an Ultrathin Film a-Si Absorber Using Whispering Gallery Modes and Guided Wave Modes with Dielectric Surface-Textured Structures.", "output": {"entities": {"chemical": [{"text": "Si", "start": 60, "end": 62}]}}, "schema": []}
{"input": "An embedded nanosphere dielectric structure on an a-Si ultrathin film improves weighted absorption from 23. 8% to 39. 9%.", "output": {"entities": {"chemical": [{"text": "Si", "start": 52, "end": 54}]}}, "schema": []}
{"input": "The PMMA embedding layer offers a guided wave mode as well as mechanical robustness, in addition to the resonant whispering gallery modes coupling.", "output": {"entities": {"chemical": [{"text": "PMMA", "start": 4, "end": 8}]}}, "schema": []}
{"input": "Broadband light-trapping enhancements are observed by dielectric surface textured structures of hemispheres, nanocones, nanospheres, or embedded nanospheres.", "output": {"entities": {}}, "schema": []}
{"input": "Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets.", "output": {"entities": {}}, "schema": []}
{"input": "Increased sympathetic activity is a well-known pathophysiological mechanism in insulin resistance (IR) and hypertension (HT).", "output": {"entities": {}}, "schema": []}
{"input": "The carotid bodies (CB) are peripheral chemoreceptors that classically respond to hypoxia by increasing chemosensory activity in the carotid sinus nerve (CSN), causing hyperventilation and activation of the sympathoadrenal system.", "output": {"entities": {}}, "schema": []}
{"input": "Besides its role in the control of ventilation, the CB has been proposed as a glucose sensor being implicated in the control of energy homeostasis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 78, "end": 85}]}}, "schema": []}
{"input": "However, to date no studies have anticipated its role in the development of IR.", "output": {"entities": {}}, "schema": []}
{"input": "Herein we propose that CB overstimulation is involved in the aetiology of IR and HT, core metabolic and hemodynamic disturbances of highly prevalent diseases like the metabolic syndrome, type 2 diabetes and obstructive sleep apnoea.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrated CB activity is increased in IR animal models and that CSN resection prevents CB-overactivation and diet-induced IR and HT.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover we showed that insulin triggers CB, highlighting a new role for hyperinsulinemia as a stimulus for CB-overactivation.", "output": {"entities": {}}, "schema": []}
{"input": "We propose that CB is implicated in the pathogenesis of metabolic and hemodynamic disturbances through sympathoadrenal overactivation and may represent a novel therapeutic target in these diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Universal rule on chirality-dependent bandgaps in graphene antidot lattices.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 50, "end": 58}]}}, "schema": []}
{"input": "Graphene with periodically patterned antidots has attracted intense research attention as it represents a facile route to open a bandgap for graphene electronics.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 0, "end": 8}, {"text": "graphene", "start": 141, "end": 149}]}}, "schema": []}
{"input": "However, not all graphene antidot lattices (GALs) can open a bandgap and a guiding rule is missing.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 17, "end": 25}]}}, "schema": []}
{"input": "Here, through systematic first-principles calculations, it is found that bandgaps in triangular GALs are surprisingly well defined by a chirality vector R = n a1 + ma2 connecting two neighboring antidots, where a1 and a2 are the basis vectors of graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 246, "end": 254}]}}, "schema": []}
{"input": "The bandgap opens in the GALs with (n-m) mod3 = 0 but remains closed in those with (n-m) mod3 = +/- 1, reminiscent of the gap-chirality rule in carbon nanotubes.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Remarkably, the gap value in GALs allows ample modulation by adjusting the length of chirality vectors, shape and size of the antidots.", "output": {"entities": {}}, "schema": []}
{"input": "The gap-chirality relation in GALs stems from the chirality-dependent atomic structures of GALs as revealed by a super-atom model as well as Clar sextet analyses.", "output": {"entities": {}}, "schema": []}
{"input": "This chirality-dependent bandgap is further shown to be a generic behavior in any parallelogram GAL and thus serves as an essential stepping stone for experimenters to realize graphene devices by antidot engineering.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 176, "end": 184}]}}, "schema": []}
{"input": "Circulating Vitamin D Metabolites and Subclinical Atherosclerosis in Type 1 Diabetes.", "output": {"entities": {"chemical": [{"text": "Vitamin D", "start": 12, "end": 21}]}}, "schema": []}
{"input": "OBJECTIVEPeople with type 1 diabetes are at high risk of premature atherosclerosis.", "output": {"entities": {}}, "schema": []}
{"input": "Existing evidence suggests that impaired vitamin D metabolism may contribute to the development of atherosclerosis.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 41, "end": 50}]}}, "schema": []}
{"input": "We tested associations of circulating vitamin D metabolite concentrations with subclinical atherosclerosis among 1, 193 participants with type 1 diabetes in the DCCT/EDIC study. RESEARCH DESIGN AND METHODSWe measured plasma concentrations of 25-hydroxyvitamin D [25 (OH) D], 1, 25-dihydroxyvitamin D, and 24, 25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 38, "end": 47}, {"text": "25-hydroxyvitamin D", "start": 242, "end": 261}, {"text": "25 (OH) D", "start": 263, "end": 272}, {"text": "1, 25-dihydroxyvitamin D", "start": 275, "end": 299}, {"text": "24, 25-dihydroxyvitamin D", "start": 305, "end": 330}]}}, "schema": []}
{"input": "In a staggered cross-sectional design, we tested associations with coronary artery calcium (CAC), measured by computed tomography a median of 10 years later, and with common and internal carotid intima-media thickness (IMT), measured by B-mode ultrasonography on two occasions a median of 4 years later and a median of 10 years later.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 83, "end": 90}]}}, "schema": []}
{"input": "We hypothesized that lower concentrations of each vitamin D metabolite would be associated with increased risk of CAC and greater carotid IMT. RESULTSAt the time metabolites were measured, mean age was 32. 4 years and mean duration of diabetes was 7. 5 years.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 50, "end": 59}]}}, "schema": []}
{"input": "The prevalence and severity of CAC tended to be lower-not higher-with lower concentrations of each vitamin D metabolite.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 99, "end": 108}]}}, "schema": []}
{"input": "For instance, in a fully adjusted multinomial logistic model, a 25 nmol/L lower 25-hydroxyvitamin D was associated with a 0. 8-fold decrease in the odds of having higher CAC (95% CI 0. 68-0. 96, P = 0. 01).", "output": {"entities": {"chemical": [{"text": "25-hydroxyvitamin D", "start": 80, "end": 99}]}}, "schema": []}
{"input": "No vitamin D metabolite was associated with either common or internal mean IMT. CONCLUSIONSWe did not find evidence linking impaired vitamin D metabolism with increased subclinical atherosclerosis in type 1 diabetes.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 3, "end": 12}, {"text": "vitamin D", "start": 133, "end": 142}]}}, "schema": []}
{"input": "Regulation of the Bone-restricted ifitm-like (Bril) gene transcription by Sp and Gli family members and CpG methylation.", "output": {"entities": {"chemical": [{"text": "CpG", "start": 104, "end": 107}]}}, "schema": []}
{"input": "Bril encodes a small membrane protein present in osteoblasts.", "output": {"entities": {}}, "schema": []}
{"input": "In humans, a single recurrent mutation in the 5' UTR of BRIL causes osteogenesis imperfecta type V.", "output": {"entities": {}}, "schema": []}
{"input": "The exact function of BRIL and the mechanism by which it contributes to disease are still unknown.", "output": {"entities": {}}, "schema": []}
{"input": "The goal of the current study was to characterize the mechanisms governing Bril transcription in the human, rat and mouse.", "output": {"entities": {}}, "schema": []}
{"input": "In the three species, as detected by luciferase reporter assays in UMR106 cells, we found that most of the baseline regulatory activity was localized within =~ 250bp upstream of the coding ATG.", "output": {"entities": {}}, "schema": []}
{"input": "Co-transfection experiments indicated that Sp1 and Sp3 were potent inducers of the promoter activity, through the binding several GC-rich boxes.", "output": {"entities": {}}, "schema": []}
{"input": "Osterix was a weak activator but acted cooperatively with Sp1 and GLI2 to synergistically induce the BRIL promoter.", "output": {"entities": {}}, "schema": []}
{"input": "GLI2, a mediator of hedgehog signaling pathway, was also a potent activator of BRIL through a single GLI binding site.", "output": {"entities": {}}, "schema": []}
{"input": "Correspondingly, agonists of the Hedgehog pathway (purmorphamine and Indian hedgehog) in MC3T3 osteoblasts led to increased BRIL levels.", "output": {"entities": {"chemical": [{"text": "purmorphamine", "start": 51, "end": 64}]}}, "schema": []}
{"input": "The BRIL promoter activity was also found to be negatively modulated through two different mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "First, the ZFP354C zinc finger protein repressed basal and Sp1-induced activity.", "output": {"entities": {}}, "schema": []}
{"input": "Second, CpG methylation of the promoter region correlated with an inactive state, and prevented Sp1 activation.", "output": {"entities": {"chemical": [{"text": "CpG", "start": 8, "end": 11}]}}, "schema": []}
{"input": "The data provide the very first analyses of the cis-and trans-acting factors regulating Bril transcription.", "output": {"entities": {}}, "schema": []}
{"input": "They revealed key roles for the Sp members and GLI2 that possibly cooperate to activate Bril when the promoter becomes demethylated.", "output": {"entities": {}}, "schema": []}
{"input": "E-cadherin polarity is determined by a multi-function motif mediating lateral membrane retention through ankyrin-G and apical-lateral transcytosis through clathrin.", "output": {"entities": {}}, "schema": []}
{"input": "We report a highly conserved motif in the E-cadherin juxtamembrane domain that determines apical-lateral polarity by conferring both restricted mobility at the lateral membrane and transcytosis of apically mis-sorted protein to the lateral membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations causing either increased lateral membrane mobility or loss of apical-lateral transcytosis result in partial mis-sorting of E-cadherin in MDCK cells.", "output": {"entities": {}}, "schema": []}
{"input": "However, loss of both activities results in complete loss of polarity.", "output": {"entities": {}}, "schema": []}
{"input": "We present evidence that residues required for restricted mobility mediate retention at the lateral membrane through interaction with ankyrin-G, while dileucine residues conferring apical-lateral transcytosis act through a clathrin-dependent process and function in an editing pathway.", "output": {"entities": {"chemical": [{"text": "dileucine", "start": 151, "end": 160}]}}, "schema": []}
{"input": "Ankyrin-G interaction with E-cadherin is abolished by the same mutations resulting in increased E-cadherin mobility.", "output": {"entities": {}}, "schema": []}
{"input": "Clathrin heavy chain knockdown and dileucine mutation of E-cadherin both cause the same partial loss of polarity of E-cadherin.", "output": {"entities": {"chemical": [{"text": "dileucine", "start": 35, "end": 44}]}}, "schema": []}
{"input": "Moreover, clathrin knockdown causes no further change in polarity of E-cadherin with dileucine mutation, but does completely randomize E-cadherin mutants lacking ankyrin-binding.", "output": {"entities": {"chemical": [{"text": "dileucine", "start": 85, "end": 94}]}}, "schema": []}
{"input": "Dileucine mutation, but not loss of ankyrin-binding, prevented transcytosis of apically mis-sorted E-cadherin to the lateral membrane.", "output": {"entities": {"chemical": [{"text": "Dileucine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Finally, neurofascin, which binds ankyrin but lacks dileucine residues, exhibited partial apical-lateral polarity that was abolished by mutation of its ankyrin-binding site but was not affected by clathrin knockdown.", "output": {"entities": {"chemical": [{"text": "dileucine", "start": 52, "end": 61}]}}, "schema": []}
{"input": "The polarity motif thus integrates complementary activities of lateral membrane retention through ankyrin-G and apical-lateral transcytosis of mis-localized protein through clathrin.", "output": {"entities": {}}, "schema": []}
{"input": "Together, the combination of retention and editing function to ensure a high fidelity steady state localization of E-cadherin at the lateral membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Biomimetic cryptic site surfaces for reversible chemo-and cyto-mechanoresponsive substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Chemo-mechanotransduction, the way by which mechanical forces are transformed into chemical signals, plays a fundamental role in many biological processes.", "output": {"entities": {}}, "schema": []}
{"input": "The first step of mechanotransduction often relies on exposure, under stretching, of cryptic sites buried in adhesion proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Likewise, here we report the first example of synthetic surfaces allowing for specific and fully reversible adhesion of proteins or cells promoted by mechanical action.", "output": {"entities": {}}, "schema": []}
{"input": "Silicone sheets are first plasma treated and then functionalized by grafting sequentially under stretching poly (ethylene glycol) (PEG) chains and biotin or arginine-glycine-aspartic acid (RGD) peptides.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol)", "start": 107, "end": 129}, {"text": "PEG", "start": 131, "end": 134}, {"text": "biotin", "start": 147, "end": 153}, {"text": "arginine", "start": 157, "end": 165}, {"text": "glycine", "start": 166, "end": 173}, {"text": "aspartic acid", "start": 174, "end": 187}]}}, "schema": []}
{"input": "At unstretched position, these ligands are not accessible for their receptors.", "output": {"entities": {}}, "schema": []}
{"input": "Under a mechanical deformation, the surface becomes specifically interactive to streptavidin, biotin antibodies, or adherent for cells, the interactions both for proteins and cells being fully reversible by stretching/unstretching, revealing a reversible exposure process of the ligands.", "output": {"entities": {"chemical": [{"text": "biotin", "start": 94, "end": 100}]}}, "schema": []}
{"input": "By varying the degree of stretching, the amount of interacting proteins can be varied continuously.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembly of DNA rings from scaffold-free DNA tiles.", "output": {"entities": {}}, "schema": []}
{"input": "We report a scaffold-free approach in which four-and six-helix DNA bundle units, assembled from a small number of single stranded DNA oligonucleotides precisely arranged in networks of contiguous and semicrossover strands, are connected into DNA nano rings.", "output": {"entities": {}}, "schema": []}
{"input": "Nearly uniform structures with well-defined diameters of 53 +/- 7, 81 +/- 9, 85 +/- 8, and 166 +/- 13 nm were achieved by introducing uniform, in-plane curvature to the repeating units.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that precise higher order assemblies can be achieved by fine tuning the particular features of the individual building blocks.", "output": {"entities": {}}, "schema": []}
{"input": "Nickel (II) Dithiocarbamate Complexes Containing Sulforhodamine B as Fluorescent Probes for Selective Detection of Nitrogen Dioxide.", "output": {"entities": {"chemical": [{"text": "Nickel (II) Dithiocarbamate", "start": 0, "end": 27}, {"text": "Sulforhodamine B", "start": 49, "end": 65}, {"text": "Nitrogen Dioxide", "start": 115, "end": 131}]}}, "schema": []}
{"input": "We synthesized complexes of Ni (II) with dithiocarbamate ligands derived from the ortho and para isomers of sulforhodamine B fluorophores and demonstrated they are highly selective in reactions with nitrogen dioxide (NO2).", "output": {"entities": {"chemical": [{"text": "Ni (II)", "start": 28, "end": 35}, {"text": "dithiocarbamate", "start": 41, "end": 56}, {"text": "sulforhodamine B", "start": 108, "end": 124}, {"text": "nitrogen dioxide", "start": 199, "end": 215}, {"text": "NO2", "start": 217, "end": 220}]}}, "schema": []}
{"input": "Compared with the para isomer, the ortho isomer showed a much greater fluorescence increase upon reaction with NO2, which led to oxidation and decomplexation of the dithiocarbamate ligand from Ni (II).", "output": {"entities": {"chemical": [{"text": "NO2", "start": 111, "end": 114}, {"text": "dithiocarbamate", "start": 165, "end": 180}, {"text": "Ni (II)", "start": 193, "end": 200}]}}, "schema": []}
{"input": "We applied this probe for visual detection of 1 ppm NO2 in the gas phase and fluorescence imaging of NO2 in macrophage cells treated with a nitrogen dioxide donor.", "output": {"entities": {"chemical": [{"text": "NO2", "start": 52, "end": 55}, {"text": "NO2", "start": 101, "end": 104}, {"text": "nitrogen dioxide", "start": 140, "end": 156}]}}, "schema": []}
{"input": "Cryptic genetic and wing pattern diversity in a mimetic Heliconius butterfly.", "output": {"entities": {}}, "schema": []}
{"input": "Despite rampant colour pattern diversity in South America, Heliconius erato exhibits a' postman' wing pattern throughout most of Central America.", "output": {"entities": {}}, "schema": []}
{"input": "We examined genetic variation across the range of H. erato, including dense sampling in Central America, and discovered a deep genetic break, centred on the mountain range that runs through Costa Rica.", "output": {"entities": {}}, "schema": []}
{"input": "This break is characterized by a novel mitochondrial lineage, which is nearly fixed in northern Central America, that branches basal to all previously described mitochondrial diversity in the species.", "output": {"entities": {}}, "schema": []}
{"input": "Strong genetic differentiation also appears in Z-linked and autosomal markers, and it is further associated with a distinct, but subtle, shift in wing pattern phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of clines in wing phenotype, mtDNA and nuclear markers indicate they are all centred on the mountains dividing Costa Rica, but that cline width differs among data sets.", "output": {"entities": {}}, "schema": []}
{"input": "Phylogeographical analyses, accounting for this new diversity, rewrite our understanding of mimicry evolution in this system.", "output": {"entities": {}}, "schema": []}
{"input": "For instance, these results suggest that H. erato originated west of the Andes, perhaps in Central America, and as many as 1 million years before its co-mimic, H. melpomene.", "output": {"entities": {}}, "schema": []}
{"input": "Overall our data indicate that neutral genetic markers and colour pattern loci are congruent and converge on the same hypothesis-H. erato originated in northwest South America or Central America with a' postman' phenotype and then radiated into the wealth of colour patterns present today.", "output": {"entities": {}}, "schema": []}
{"input": "Magnetite Biomineralization in Magnetospirillum gryphiswaldense: Time-Resolved Magnetic and Structural Studies.", "output": {"entities": {"chemical": [{"text": "Magnetite", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Magnetotactic bacteria biosynthesize magnetite nanoparticles of high structural and chemical purity that allow them to orientate in the geomagnetic field.", "output": {"entities": {"chemical": [{"text": "magnetite", "start": 37, "end": 46}]}}, "schema": []}
{"input": "In this work we have followed the process of biomineralization of these magnetite nanoparticles.", "output": {"entities": {"chemical": [{"text": "magnetite", "start": 72, "end": 81}]}}, "schema": []}
{"input": "We have performed a time-resolved study on magnetotactic bacteria Magnetospirillum gryphiswaldense strain MSR-1.", "output": {"entities": {}}, "schema": []}
{"input": "From the combination of magnetic and structural studies by means of Fe K-edge X-ray absorption near edge structure (XANES) and high-resolution transmission electron microscopy we have identified and quantified two phases of Fe (ferrihydrite and magnetite) involved in the biomineralization process, confirming the role of ferrihydrite as the source of Fe ions for magnetite biomineralization in M. gryphiswaldense.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 68, "end": 70}, {"text": "ferrihydrite", "start": 228, "end": 240}, {"text": "magnetite", "start": 245, "end": 254}, {"text": "ferrihydrite", "start": 322, "end": 334}, {"text": "Fe", "start": 352, "end": 354}, {"text": "magnetite", "start": 364, "end": 373}]}}, "schema": []}
{"input": "We have distinguished two steps in the biomineralization process: the first, in which Fe is accumulated in the form of ferrihydrite, and the second, in which the magnetite is rapidly biomineralized from ferrihydrite.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 86, "end": 88}, {"text": "ferrihydrite", "start": 119, "end": 131}, {"text": "magnetite", "start": 162, "end": 171}, {"text": "ferrihydrite", "start": 203, "end": 215}]}}, "schema": []}
{"input": "Finally, the XANES analysis suggests that the origin of the ferrihydrite could be at bacterial ferritin cores, characterized by a poorly crystalline structure and high phosphorus content.", "output": {"entities": {"chemical": [{"text": "ferrihydrite", "start": 60, "end": 72}, {"text": "phosphorus", "start": 168, "end": 178}]}}, "schema": []}
{"input": "Exploiting the Unique ATP-Binding Pocket of Toxoplasma Calcium-Dependent Protein Kinase 1 To Identify Its Substrates.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 22, "end": 25}, {"text": "Calcium", "start": 55, "end": 62}]}}, "schema": []}
{"input": "Apicomplexan parasites rely on calcium as a second messenger to regulate a variety of essential cellular processes.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 31, "end": 38}]}}, "schema": []}
{"input": "Calcium-dependent protein kinases (CDPK), which transduce these signals, are conserved among apicomplexans but absent from mammalian hosts, making them attractive targets for therapeutic intervention.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Despite their importance, the signaling pathways CDPK regulate remain poorly characterized, and their protein substrates are completely unknown.", "output": {"entities": {}}, "schema": []}
{"input": "In Toxoplasma gondii, CDPK1 is required for calcium-regulated secretion from micronemes, thereby controlling motility, invasion, and egress from host cells.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 44, "end": 51}]}}, "schema": []}
{"input": "CDPK1 is unique among parasite and mammalian kinases in containing glycine at the key \" gatekeeper \" residue, which results in an expanded ATP-binding pocket.", "output": {"entities": {"chemical": [{"text": "glycine", "start": 67, "end": 74}, {"text": "ATP", "start": 139, "end": 142}]}}, "schema": []}
{"input": "In the present study, we use a synthetic ATP gamma S analogue that displays steric complementarity to the ATP-binding pocket and hence allows identification of protein substrates based on selective thiophosphorylation.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 41, "end": 44}]}}, "schema": []}
{"input": "The specificity of this approach was validated by the concordance between the identified phosphorylation sites and the in vitro substrate preference of CDPK1.", "output": {"entities": {}}, "schema": []}
{"input": "We further demonstrate that the phosphorylation of predicted substrates is dependent on CDPK1 both in vivo and in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "This combined strategy for identifying the targets of specific protein kinases provides a platform for defining the roles of CDPKs in apicomplexans.", "output": {"entities": {}}, "schema": []}
{"input": "In Vivo Degradation and Elimination of Injectable Ricinoleic Acid-Based Poly (ester-anhydride).", "output": {"entities": {"chemical": [{"text": "Ricinoleic Acid", "start": 50, "end": 65}, {"text": "Poly (ester-anhydride)", "start": 72, "end": 94}]}}, "schema": []}
{"input": "The in vivo degradation and elimination after subcutaneous implantation of injectable p (SA-RA) 3: 7 copolymer in rats, followed by characterization of the polymer matrix composition during hydrolysis and erosion, is reported.", "output": {"entities": {"chemical": [{"text": "p (SA-RA) 3: 7", "start": 86, "end": 100}]}}, "schema": []}
{"input": "Major chemical changes were observed during the first few days post implantation, the anhydride bonds hydrolyzed along with about 45% weight loss and a significant decrease in the molecular weight.", "output": {"entities": {}}, "schema": []}
{"input": "(1) H NMR spectral analysis was used to determine the structures and content of ricinoleic acid containing oligomeric chains present in the degraded polymer.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 0, "end": 5}, {"text": "ricinoleic acid", "start": 80, "end": 95}]}}, "schema": []}
{"input": "The polymer degrades into ester oligomers of 2-4 ricinoleic acid units which further degrade to ricinoleic acid, a natural fatty acid.", "output": {"entities": {"chemical": [{"text": "ricinoleic acid", "start": 49, "end": 64}, {"text": "ricinoleic acid", "start": 96, "end": 111}, {"text": "fatty acid", "start": 123, "end": 133}]}}, "schema": []}
{"input": "The polymer hydrolytic degradation process fit the in vitro degradation process.", "output": {"entities": {}}, "schema": []}
{"input": "Multipart Copolyelectrolyte Adhesive of the Sandcastle Worm, Phragmatopoma californica (Fewkes): Catechol Oxidase Catalyzed Curing through Peptidyl-DOPA.", "output": {"entities": {"chemical": [{"text": "Catechol", "start": 97, "end": 105}, {"text": "DOPA", "start": 148, "end": 152}]}}, "schema": []}
{"input": "Tube-building sabellariid polychaetes have major impacts on the geology and ecology of shorelines worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Sandcastle worms, Phragmatopoma californica (Fewkes), live along the western coast of North America.", "output": {"entities": {}}, "schema": []}
{"input": "Individual sabellariid worms build tubular shells by gluing together mineral particles with a multipart polyelectrolytic adhesive.", "output": {"entities": {}}, "schema": []}
{"input": "Distinct sets of oppositely charged components are packaged and stored in concentrated granules in separate cell types.", "output": {"entities": {}}, "schema": []}
{"input": "Homogeneous granules contain sulfated macromolecules as counter-polyanion to polycationic Pc2 and Pc5 proteins, which become major components of the fully cured glue.", "output": {"entities": {}}, "schema": []}
{"input": "Heterogeneous granules contain polyphosphoproteins, Pc3A/B, paired with divalent cations and polycationic Pc1 and Pc4 proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Both types of granules contain catechol oxidase that catalyzes oxidative cross-linking of L-DOPA.", "output": {"entities": {"chemical": [{"text": "catechol", "start": 31, "end": 39}, {"text": "L-DOPA", "start": 90, "end": 96}]}}, "schema": []}
{"input": "Co-secretion of catechol oxidase guarantees rapid and spatially homogeneous curing with limited mixing of the preassembled adhesive packets.", "output": {"entities": {"chemical": [{"text": "catechol", "start": 16, "end": 24}]}}, "schema": []}
{"input": "Catechol oxidase remains active long after the glue is fully cured, perhaps providing an active cue for conspecific larval settlement.", "output": {"entities": {"chemical": [{"text": "Catechol", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Progression to insulin for patients with diabetes mellitus on dual oral antidiabetic therapy using the US Department of Defense Database.", "output": {"entities": {}}, "schema": []}
{"input": "AIM: To compare' progression to insulin' for three cohorts on oral antidiabetic medication combinations: metformin/sulphonylurea (Met/SU), metformin/thiazolidinedione (Met/TZD) and sulphonylurea/thiazolidinedione (SU/TZD).", "output": {"entities": {"chemical": [{"text": "metformin", "start": 105, "end": 114}, {"text": "sulphonylurea", "start": 115, "end": 128}, {"text": "Met", "start": 130, "end": 133}, {"text": "metformin", "start": 139, "end": 148}, {"text": "thiazolidinedione", "start": 149, "end": 166}, {"text": "Met", "start": 168, "end": 171}, {"text": "TZD", "start": 172, "end": 175}, {"text": "sulphonylurea", "start": 181, "end": 194}, {"text": "thiazolidinedione", "start": 195, "end": 212}, {"text": "TZD", "start": 217, "end": 220}]}}, "schema": []}
{"input": "METHODS: Retrospective cohort analysis design was used.", "output": {"entities": {}}, "schema": []}
{"input": "The subjects were US nationwide members of military and their families.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 5608 patients who were on antidiabetic monotherapy for at least 1 year before adding a second agent to their medication regimen between October 2001 and September 2008 participated in this study.", "output": {"entities": {}}, "schema": []}
{"input": "Mean age ranged from 64 to 71 years among the cohorts.", "output": {"entities": {}}, "schema": []}
{"input": "Cox regression compared the progression to insulin, adjusting for demographics, months of follow-up and co-morbidities [measured with Chronic Disease Score (CDS)].", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: By the end of the 2-to 6-year follow-up period, 14. 3% of the Met/TZD cohort, 23. 6% of the Met/SU cohort and 28. 2% of the SU/TZD cohort had insulin added to their regimen.", "output": {"entities": {"chemical": [{"text": "Met", "start": 71, "end": 74}, {"text": "TZD", "start": 75, "end": 78}, {"text": "Met", "start": 101, "end": 104}, {"text": "TZD", "start": 136, "end": 139}]}}, "schema": []}
{"input": "Those in the Met/SU cohort had a 1. 8 times higher probability of progression to insulin than those in the Met/TZD cohort [odds ratio (OR) = 1. 80, 95% confidence interval (CI) = 1. 51-2. 14), and those in the SU/TZD cohort had a 2. 5 times higher probability of progression to insulin than those in the Met/TZD cohort (OR = 2. 51, 95% CI = 2. 04-3. 08).", "output": {"entities": {"chemical": [{"text": "Met", "start": 13, "end": 16}, {"text": "Met", "start": 107, "end": 110}, {"text": "TZD", "start": 111, "end": 114}, {"text": "TZD", "start": 213, "end": 216}, {"text": "Met", "start": 304, "end": 307}, {"text": "TZD", "start": 308, "end": 311}]}}, "schema": []}
{"input": "CONCLUSION: When sensitizers were paired (Met/TZD), a lower percentage of patients progressed to insulin during the study period, as opposed to patients who used a combination of a secretagogue with a sensitizer (SU/TZD or Met/SU).", "output": {"entities": {"chemical": [{"text": "Met", "start": 42, "end": 45}, {"text": "TZD", "start": 46, "end": 49}, {"text": "TZD", "start": 216, "end": 219}, {"text": "Met", "start": 223, "end": 226}]}}, "schema": []}
{"input": "Murabutide revisited: a review of its pleiotropic biological effects.", "output": {"entities": {}}, "schema": []}
{"input": "Despite the great efforts put into their development, the list of clinically approved immunological adjuvants is still very short.", "output": {"entities": {}}, "schema": []}
{"input": "Evolution of the knowledge of the immune system has enabled for rational design of novel adjuvants and has led to the conclusion that more than one type of adjuvant will be required.", "output": {"entities": {}}, "schema": []}
{"input": "Derivatives of muramyl dipeptide (MDP), the minimal immunomodulatory structure of bacterial cell wall peptidoglycan, have gained considerable attention in the past decades, because of their potent adjuvant effects.", "output": {"entities": {}}, "schema": []}
{"input": "Murabutide is a safe derivative of MDP, which interacts with cells of the immune system, both innate and adaptive, and exerts its effect through activation of Nod2.", "output": {"entities": {}}, "schema": []}
{"input": "The transcriptional response of murabutide-stimulated macrophages revealed enhanced expression of genes coding for various proteins such as immune mediators and their receptors, transcription factors and kinases, ion channels/transporters and proteins involved in cell metabolic activity, thus reflecting a broad spectrum of biological effects.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to its well recognized adjuvant effect, murabutide has also been shown to enhance the host' s resistance against microbial infections, nonspecific resistance against tumors and the induction of cytokines and chemokines implicated in enhancing the immune response and hematopoesis.", "output": {"entities": {}}, "schema": []}
{"input": "This article provides an insight into the mechanism of action of murabutide and its interactions with the cells of the immune system in vitro and in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "On account of its numerous biological effects, murabutide has been the subject of several clinical studies.", "output": {"entities": {}}, "schema": []}
{"input": "Many of these have confirmed its potential to synergize with cytokines of therapeutic interest in potentiating the tumoricidal activity of macrophages or targeting chronic viral diseases, as well as reducing the cytokine dosage needed to achieve a therapeutic effect.", "output": {"entities": {}}, "schema": []}
{"input": "This review covers the findings of all relevant studies and focuses on the role of murabutide and its potential in the treatment of several microbial diseases.", "output": {"entities": {}}, "schema": []}
{"input": "The Protective Effects of alpha-Lipoic Acid on Kidneys in Type 2 Diabetic Goto-Kakisaki Rats via Reducing Oxidative Stress.", "output": {"entities": {"chemical": [{"text": "alpha-Lipoic Acid", "start": 26, "end": 43}]}}, "schema": []}
{"input": "To evaluate the protective effects of alpha-lipoic acid on the kidneys of Goto-Kakisaki (GK) diabetic rats, ten GK diabetic rats were randomly divided into a diabetic control group and a lipoic acid-treated diabetic group with alpha-lipoic acid 35 mg. Kg-1 intraperitoneal injections.", "output": {"entities": {"chemical": [{"text": "alpha-lipoic acid", "start": 38, "end": 55}, {"text": "lipoic acid", "start": 187, "end": 198}, {"text": "alpha-lipoic acid", "start": 227, "end": 244}]}}, "schema": []}
{"input": "Four healthy Wistar rats served as normal controls.", "output": {"entities": {}}, "schema": []}
{"input": "Malonaldehyde (MDA), ascorbic acid (vitamin C), vitamin E, glutathione (GSH) and superoxide dismutase (SOD) levels in renal homogenate, and urine protein excretion were measured.", "output": {"entities": {"chemical": [{"text": "Malonaldehyde", "start": 0, "end": 13}, {"text": "MDA", "start": 15, "end": 18}, {"text": "ascorbic acid", "start": 21, "end": 34}, {"text": "vitamin C", "start": 36, "end": 45}, {"text": "vitamin E", "start": 48, "end": 57}, {"text": "glutathione", "start": 59, "end": 70}, {"text": "GSH", "start": 72, "end": 75}, {"text": "superoxide", "start": 81, "end": 91}]}}, "schema": []}
{"input": "The expression of mRNA for NF-kappa B, NADPH oxidase subunits p22phox and p47phox in renal tissue was examined by realtime PCR.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 39, "end": 44}]}}, "schema": []}
{"input": "Pathological changes in renal tissue were evaluated by light and electron microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "There were significant increases in urine protein excretion, MDA levels and the expression of mRNA of NF-kappa B, p22phox and p47phox, and significant decreases in GSH, SOD, vitamin C and vitamin E levels in the diabetic control group compared with the normal control group.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 61, "end": 64}, {"text": "GSH", "start": 164, "end": 167}, {"text": "vitamin C", "start": 174, "end": 183}, {"text": "vitamin E", "start": 188, "end": 197}]}}, "schema": []}
{"input": "Pathological changes of renal tissue were more progressive in the diabetic control group than in the normal control group.", "output": {"entities": {}}, "schema": []}
{"input": "All the parameters above were improved in the alpha-lipoic acid-treated diabetic group.", "output": {"entities": {"chemical": [{"text": "alpha-lipoic acid", "start": 46, "end": 63}]}}, "schema": []}
{"input": "Oxidative stress is increased in the kidney of type 2 diabetic GK rats.", "output": {"entities": {}}, "schema": []}
{"input": "It is associated with the progression of diabetic nephropathy.", "output": {"entities": {}}, "schema": []}
{"input": "alpha-lipoic acid can protect renal function in diabetic rats via its antioxidant activity.", "output": {"entities": {"chemical": [{"text": "alpha-lipoic acid", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 10, "end": 16}]}}, "schema": []}
{"input": "Precision cut liver slices (PCLSs) are widely used as a model to study hepatotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "For culturing of PCLS diverse protocols are used which could affect slices viability and results.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to identify the most optimal culture protocol for mouse PCLS.", "output": {"entities": {}}, "schema": []}
{"input": "Slices were cultured for 24h under different concentrations of serum, glucose, insulin, and oxygen.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 70, "end": 77}, {"text": "oxygen", "start": 92, "end": 98}]}}, "schema": []}
{"input": "Thereafter, slices viability was assessed by biochemical methods.", "output": {"entities": {}}, "schema": []}
{"input": "Transcriptome analysis was performed to identify changes introduced by culture at different oxygen concentrations (20%, 40%, 60%, and 80% of oxygen).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 92, "end": 98}, {"text": "oxygen", "start": 141, "end": 147}]}}, "schema": []}
{"input": "Medium composition did not affect the slices viability.", "output": {"entities": {}}, "schema": []}
{"input": "Although metabolic competence was unaffected by oxygen concentrations, culturing at 80% of oxygen yielded slices with the best biochemical characteristics.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 48, "end": 54}, {"text": "oxygen", "start": 91, "end": 97}]}}, "schema": []}
{"input": "The comparison of uncultured vs. cultured slices revealed 2524 genes to be differentially expressed.", "output": {"entities": {}}, "schema": []}
{"input": "Genes involved in drug metabolism, peroxisomal and mitochondrial functions were down-regulated while several adaptive/stress response processes were up-regulated.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, 80% of oxygen was the most favorable condition with respect to maintenance of expression of genes involved in drug and energy metabolism.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 17, "end": 23}]}}, "schema": []}
{"input": "The outcome of this study indicates that mouse PCLS are a valuable tool in research on hepatic functions and toxicity, particularly if they are cultured under a controlled oxygen concentration of 80%.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 172, "end": 178}]}}, "schema": []}
{"input": "The noncellular reduction of MTT tetrazolium salt by TiO2 nanoparticles and its implications for cytotoxicity assays.", "output": {"entities": {"chemical": [{"text": "MTT tetrazolium salt", "start": 29, "end": 49}, {"text": "TiO2", "start": 53, "end": 57}]}}, "schema": []}
{"input": "We report results of noncellular tests, revealing the occurrence of photocatalytic interactions between titanium dioxide (TiO2, titania) nanoparticles and the MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide] cytotoxicity indicator.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 104, "end": 120}, {"text": "TiO2", "start": 122, "end": 126}, {"text": "titania", "start": 128, "end": 135}, {"text": "MTT", "start": 159, "end": 162}, {"text": "3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide", "start": 164, "end": 226}]}}, "schema": []}
{"input": "These interactions induce the reduction of MTT and formation of purple formazan under biologically relevant conditions.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 43, "end": 46}]}}, "schema": []}
{"input": "Classical MTT assays have been performed to evaluate the production of formazan in DMEM-F12 and RPMI-1640 cell culture media (containing 10% fetal bovine serum-FBS) treated with Degussa-P25 TiO2 nanoparticles, in the absence of cells.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 10, "end": 13}, {"text": "formazan", "start": 71, "end": 79}, {"text": "P25 TiO2", "start": 186, "end": 194}]}}, "schema": []}
{"input": "The colorimetric determinations revealed the noncellular MTT to formazan transformation induced by TiO2 nanoparticles, under conditions commonly used for in vitro cytotoxicity testing of nanomaterials.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 57, "end": 60}, {"text": "formazan", "start": 64, "end": 72}, {"text": "TiO2", "start": 99, "end": 103}]}}, "schema": []}
{"input": "The formazan precipitation was found to be proportional to the TiO2 concentration, being enhanced under laboratory daylight exposure.", "output": {"entities": {"chemical": [{"text": "formazan", "start": 4, "end": 12}, {"text": "TiO2", "start": 63, "end": 67}]}}, "schema": []}
{"input": "The photocatalytic nature of the studied effect was assessed under UV irradiation at 365nm.", "output": {"entities": {}}, "schema": []}
{"input": "The biological significance of the reported reaction was established with respect to cellular reference experiments performed on V79-4, HeLa and B16 cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "The results show false viability increases with up to 14% (for TiO2 concentrations generally higher than 50 mu g/ml), induced by the TiO2-MTT reaction.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 63, "end": 67}, {"text": "TiO2", "start": 133, "end": 137}, {"text": "MTT", "start": 138, "end": 141}]}}, "schema": []}
{"input": "This type of artifacts may lead to underestimated toxicity or false proliferation results.", "output": {"entities": {}}, "schema": []}
{"input": "Streptococcal collagen-like protein A and general stress protein 24 are immunomodulating virulence factors of group A Streptococcus.", "output": {"entities": {}}, "schema": []}
{"input": "In Western countries, invasive infections caused by M1T1 serotype group A Streptococcus (GAS) are epidemiologically linked to mutations in the control of virulence regulatory 2-component operon (covRS).", "output": {"entities": {}}, "schema": []}
{"input": "In indigenous communities and developing countries, severe GAS disease is associated with genetically diverse non-M1T1 GAS serotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Hypervirulent M1T1 covRS mutant strains arise through selection by human polymorphonuclear cells for increased expression of GAS virulence factors such as the DNase Sda1, which promotes neutrophil resistance.", "output": {"entities": {}}, "schema": []}
{"input": "The GAS bacteremia isolate NS88. 2 (emm 98. 1) is a covS mutant that exhibits a hypervirulent phenotype and neutrophil resistance yet lacks the phage-encoded Sda1.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we have employed a comprehensive systems biology (genomic, transcriptomic, and proteomic) approach to identify NS88. 2 virulence determinants that enhance neutrophil resistance in the non-M1T1 GAS genetic background.", "output": {"entities": {}}, "schema": []}
{"input": "Using this approach, we have identified streptococcal collagen-like protein A and general stress protein 24 proteins as NS88. 2 determinants that contribute to survival in whole blood and neutrophil resistance in non-M1T1 GAS.", "output": {"entities": {}}, "schema": []}
{"input": "This study has revealed new factors that contribute to GAS pathogenicity that may play important roles in resisting innate immune defenses and the development of human invasive infections-Tsatsaronis, J.", "output": {"entities": {}}, "schema": []}
{"input": "A., Hollands, A., Cole, J.", "output": {"entities": {}}, "schema": []}
{"input": "N., Maamary, P.", "output": {"entities": {}}, "schema": []}
{"input": "G., Gillen, C.", "output": {"entities": {}}, "schema": []}
{"input": "M., Ben Zakour, N.", "output": {"entities": {}}, "schema": []}
{"input": "L., Kotb, M., Nizet, V., Beatson, S.", "output": {"entities": {}}, "schema": []}
{"input": "A.", "output": {"entities": {}}, "schema": []}
{"input": "Walker, M.", "output": {"entities": {}}, "schema": []}
{"input": "J., Sanderson-Smith, M.", "output": {"entities": {}}, "schema": []}
{"input": "L.", "output": {"entities": {}}, "schema": []}
{"input": "Streptococcal collagen-like protein A and general stress protein 24 are immunomodulating virulence factors of group A Streptococcus.", "output": {"entities": {}}, "schema": []}
{"input": "Systems approaches in risk assessment.", "output": {"entities": {}}, "schema": []}
{"input": "Adverse drug events (ADEs) remain a universal problem in drug development, regulatory review, and clinical practice with a substantial financial burden on the global health-care system.", "output": {"entities": {}}, "schema": []}
{"input": "Recent advances in molecular and \" omics \" technologies, along with online databases and bioinformatics, have enabled a more integrative approach to understanding drug-target (protein) interactions, both desirable and undesirable, within a biological system.", "output": {"entities": {}}, "schema": []}
{"input": "This has led to the development of systems approaches to risk assessment in an attempt to complement and improve on contemporary observational and predictive strategies for assessing risk.", "output": {"entities": {}}, "schema": []}
{"input": "Although still in an evolutionary phase, systems approaches have the potential to markedly advance our understanding of ADEs and ability to predict them.", "output": {"entities": {}}, "schema": []}
{"input": "Systems approaches will also move personalized medicine forward by enabling better identification of individual and subgroup risk factors.", "output": {"entities": {}}, "schema": []}
{"input": "Population structure, migration, and diversifying selection in the Netherlands.", "output": {"entities": {}}, "schema": []}
{"input": "Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data.", "output": {"entities": {}}, "schema": []}
{"input": "PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection.", "output": {"entities": {}}, "schema": []}
{"input": "In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country.", "output": {"entities": {}}, "schema": []}
{"input": "The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to geography, the Dutch North-South PC showed correlations with genome-wide homozygosity (r = 0. 245), which may reflect a serial-founder effect due to northwards migration, and also with height (male: r = 0. 142, female: r = 0. 153).", "output": {"entities": {}}, "schema": []}
{"input": "The divergence between subpopulations identified by PCs is partly driven by selection pressures.", "output": {"entities": {}}, "schema": []}
{"input": "The first three PCs showed significant signals for diversifying selection (545 SNPs-the majority within 184 genes).", "output": {"entities": {}}, "schema": []}
{"input": "The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. European Journal of Human Genetics advance online publication, 27 March 2013; doi: 10. 1038/ejhg. 2013. 48.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of visible-light-active Sn (ii)-TiO2 photocatalysts.", "output": {"entities": {"chemical": [{"text": "Sn (ii)", "start": 33, "end": 40}, {"text": "TiO2", "start": 41, "end": 45}]}}, "schema": []}
{"input": "The influence of Sn (ii) species on TiO2 is investigated.", "output": {"entities": {"chemical": [{"text": "Sn (ii)", "start": 17, "end": 24}, {"text": "TiO2", "start": 36, "end": 40}]}}, "schema": []}
{"input": "The absorption spectra of these materials are red-shifted by 115 nm to the visible region of the solar spectrum compared with P25 TiO2.", "output": {"entities": {"chemical": [{"text": "P25 TiO2", "start": 126, "end": 134}]}}, "schema": []}
{"input": "This prominent red-shift is attributed to the interaction of Sn (ii) 5s orbitals with the TiO2 decreasing the band gap of TiO2 by raising its valence band.", "output": {"entities": {"chemical": [{"text": "Sn (ii)", "start": 61, "end": 68}, {"text": "TiO2", "start": 90, "end": 94}, {"text": "TiO2", "start": 122, "end": 126}]}}, "schema": []}
{"input": "The tin oxidation state and the materials electronic structure are evaluated using M o ssbauer spectroscopy and valence band X-ray photoelectron spectroscopy respectively.", "output": {"entities": {"chemical": [{"text": "tin", "start": 4, "end": 7}]}}, "schema": []}
{"input": "These materials are active for sacrificial photo-generation of hydrogen in visible light.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 63, "end": 71}]}}, "schema": []}
{"input": "A pyrrolidinium nitrate protic ionic liquid-based electrolyte for very low-temperature electrical double-layer capacitors.", "output": {"entities": {"chemical": [{"text": "pyrrolidinium nitrate", "start": 2, "end": 23}]}}, "schema": []}
{"input": "This study describes the use of the pyrrolidinium nitrate ([Pyrr] [NO3]) protic ionic liquid (PIL) in a mixture with gamma butyrolactone (gamma-BL) as an electrolyte for carbon-based supercapacitors with an operating voltage of 2. 0 V and at very low temperature.", "output": {"entities": {"chemical": [{"text": "pyrrolidinium nitrate", "start": 36, "end": 57}, {"text": "[Pyrr] [NO3]", "start": 59, "end": 71}, {"text": "gamma butyrolactone", "start": 117, "end": 136}, {"text": "gamma-BL", "start": 138, "end": 146}, {"text": "carbon", "start": 170, "end": 176}]}}, "schema": []}
{"input": "Thermal and transport properties of this electrolyte were firstly evaluated from-40 degrees C to 80 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "The evolution of conductivity with the addition of gamma-BL rendered it possible to determine the optimal composition for electrochemical application, with a molar fraction of gamma-BL of 0. 6.", "output": {"entities": {"chemical": [{"text": "gamma-BL", "start": 51, "end": 59}, {"text": "gamma-BL", "start": 176, "end": 184}]}}, "schema": []}
{"input": "This mixture shows a Newtonian behavior with a low viscosity value of 5 mPa s at 25 degrees C, and exhibits high conductivity values of up to 65 mS cm (-1) at 80 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, exceptional residual conductivity was measured for this composition at-40 degrees C (9 mS cm (-1)), thanks to the superionic character of pyrrolidinium nitrate PIL.", "output": {"entities": {"chemical": [{"text": "pyrrolidinium nitrate", "start": 156, "end": 177}]}}, "schema": []}
{"input": "Electrochemical characterization of this electrolyte demonstrated, at first, a passivation on the aluminum collector, secondly good cycling performances with an activated carbon electrode from 50 degrees C to-40 degrees C with capacitance up to 132 F g (-1) at room temperature and a wide voltage window (2. 0 V).", "output": {"entities": {"chemical": [{"text": "aluminum", "start": 98, "end": 106}, {"text": "carbon", "start": 171, "end": 177}]}}, "schema": []}
{"input": "Finally at very low temperature (-40 degrees C), this system demonstrates an unprecedented combination of high specific capacitance (up to 117 F g (-1)), and rapid charging-discharging even at high current density, which is very promising for the progress of energy storage systems with environmentally friendly electrolytes at such very low temperatures.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of immunosuppression on alpha and beta cell renewal in transplanted mouse islets.", "output": {"entities": {}}, "schema": []}
{"input": "AIMS/HYPOTHESIS: Immunosuppressive drugs used in human islet transplantation interfere with the balance between beta cell renewal and death, and thus may contribute to progressive graft dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "We analysed the influence of immunosuppressants on the proliferation of transplanted alpha and beta cells after syngeneic islet transplantation in streptozotocin-induced diabetic mice.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 147, "end": 161}]}}, "schema": []}
{"input": "METHODS: C57BL/6 diabetic mice were transplanted with syngeneic islets in the liver and simultaneously abdominally implanted with a mini-osmotic pump delivering BrdU alone or together with an immunosuppressant (tacrolimus, sirolimus, everolimus or mycophenolate mofetil [MMF]).", "output": {"entities": {"chemical": [{"text": "tacrolimus", "start": 211, "end": 221}, {"text": "sirolimus", "start": 223, "end": 232}, {"text": "everolimus", "start": 234, "end": 244}, {"text": "mycophenolate mofetil", "start": 248, "end": 269}, {"text": "MMF", "start": 271, "end": 274}]}}, "schema": []}
{"input": "Glycaemic control was assessed for 4 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "The area and proliferation of transplanted alpha and beta cells were subsequently quantified.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: After 4 weeks, glycaemia was significantly higher in treated mice than in controls.", "output": {"entities": {}}, "schema": []}
{"input": "Insulinaemia was significantly lower in mice treated with everolimus, tacrolimus and sirolimus.", "output": {"entities": {"chemical": [{"text": "everolimus", "start": 58, "end": 68}, {"text": "tacrolimus", "start": 70, "end": 80}, {"text": "sirolimus", "start": 85, "end": 94}]}}, "schema": []}
{"input": "MMF was the only immunosuppressant that did not significantly reduce beta cell area or proliferation, albeit its levels were in a lower range than those used in clinical settings.", "output": {"entities": {"chemical": [{"text": "MMF", "start": 0, "end": 3}]}}, "schema": []}
{"input": "CONCLUSIONS/INTERPRETATION: After transplantation in diabetic mice, syngeneic beta cells have a strong capacity for self-renewal.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast to other immunosuppressants, MMF neither impaired beta cell proliferation nor adversely affected the fractional beta cell area.", "output": {"entities": {"chemical": [{"text": "MMF", "start": 41, "end": 44}]}}, "schema": []}
{"input": "Although human beta cells are less prone to proliferate compared with rodent beta cells, the use of MMF may improve the long-term outcome of islet transplantation.", "output": {"entities": {"chemical": [{"text": "MMF", "start": 100, "end": 103}]}}, "schema": []}
{"input": "Adrenocortical reserves in hyperthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "Explicit data regarding the changes in adrenocortical reserves during hyperthyroidism do not exist.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to document the capability (response) of adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to euthyroidism, and to describe factors associated with these responses.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 75, "end": 83}, {"text": "DHEA", "start": 88, "end": 92}]}}, "schema": []}
{"input": "A standard-dose (0. 25 mg/i. v.) ACTH stimulation test was performed to the same patients before hyperthyroidism treatment, and after attainment of euthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "Baseline cortisol (Cor0), DHEA-S (DHEA-S0), cortisol binding globulin (CBG), ACTH, calculated free cortisol (by Coolen' s equation = CFC), free cortisol index (FCI), 60-min cortisol (Cor60), and DHEA-S (DHEA-S60), delta cortisol (Delta Cor), delta DHEA-S (Delta DHEA-S) responses were evaluated.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 9, "end": 17}, {"text": "DHEA", "start": 26, "end": 30}, {"text": "DHEA", "start": 34, "end": 38}, {"text": "cortisol", "start": 44, "end": 52}, {"text": "cortisol", "start": 99, "end": 107}, {"text": "cortisol", "start": 144, "end": 152}, {"text": "cortisol", "start": 173, "end": 181}, {"text": "DHEA", "start": 195, "end": 199}, {"text": "DHEA", "start": 203, "end": 207}, {"text": "delta cortisol", "start": 214, "end": 228}, {"text": "Delta Cor", "start": 230, "end": 239}, {"text": "delta DHEA", "start": 242, "end": 252}, {"text": "Delta DHEA", "start": 256, "end": 266}]}}, "schema": []}
{"input": "Forty-one patients [22 females, 49. 5 +/- 15. 2 years old, 32 Graves disease, nine toxic nodular goiter] had similar Cor0, DHEA-S0, CFC, FCI, and DHEA-S60 in hyperthyroid and euthyroid states.", "output": {"entities": {"chemical": [{"text": "DHEA", "start": 123, "end": 127}, {"text": "DHEA", "start": 146, "end": 150}]}}, "schema": []}
{"input": "Cor60, Delta Cor, and Delta DHEA-S were lower in hyperthyroidism.", "output": {"entities": {"chemical": [{"text": "Delta Cor", "start": 7, "end": 16}, {"text": "Delta DHEA", "start": 22, "end": 32}]}}, "schema": []}
{"input": "In four (10%) patients the peak ACTH-stimulated cortisol values were lower than 18 mu g/dL.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 48, "end": 56}]}}, "schema": []}
{"input": "When the test repeated after attainment of euthyroidism, all of the patients had normal cortisol response.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 88, "end": 96}]}}, "schema": []}
{"input": "Regression analysis demonstrated an independent association of Cor60 with free T3 in hyperthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "However, the predictors of CFC, FCI, and DHEA-S levels were serum creatinine levels in hyperthyroidism, and both creatinine and transaminase levels in euthyroidism.", "output": {"entities": {"chemical": [{"text": "DHEA", "start": 41, "end": 45}, {"text": "creatinine", "start": 66, "end": 76}, {"text": "creatinine", "start": 113, "end": 123}]}}, "schema": []}
{"input": "ACTH-stimulated peak cortisol, delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 21, "end": 29}, {"text": "delta cortisol", "start": 31, "end": 45}, {"text": "delta DHEA", "start": 51, "end": 61}]}}, "schema": []}
{"input": "Since about 10% of the subjects with hyperthyroidism are at risk for adrenal insufficiency, clinicians dealing with Graves' disease should be alert to the possibility of adrenal insufficiency during hyperthyroid stage.", "output": {"entities": {}}, "schema": []}
{"input": "Tryptophan residue at active-site tunnel entrance of Trichoderma reesei cellobiohydrolase Cel7A is important to initiate degradation of crystalline cellulose.", "output": {"entities": {"chemical": [{"text": "Tryptophan", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Glycoside hydrolase family-7 cellobiohydrolase from Trichoderma reesei (TrCel7A) is one of the best-studied cellulases with the ability to degrade highly crystalline cellulose (HCC).", "output": {"entities": {}}, "schema": []}
{"input": "The catalytic domain (cat) and cellulose-binding domain (CBD) are both necessary for full activity on crystalline substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Our previous high-speed AFM studies showed that mutation of tryptophan residue (Trp40; W40) at the entrance of the catalytic tunnel drastically decreases the ability to degrade crystalline cellulose.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 60, "end": 70}, {"text": "Trp40", "start": 80, "end": 85}]}}, "schema": []}
{"input": "Here, we examined the activities of the wild-type (WT) enzyme and tryptophan to alanine mutant (W40A) enzyme, with and without the CBD, towards various substrates.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 66, "end": 76}, {"text": "alanine", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Evaluation and comparison of the specific activities of the enzymes (WT, WTcat, W40A, and W40Acat) adsorbed on crystalline cellulose indicated that Trp40 is involved in recruiting individual substrate chains into the active site tunnel to initiate processive hydrolysis.", "output": {"entities": {"chemical": [{"text": "Trp40", "start": 148, "end": 153}]}}, "schema": []}
{"input": "This idea was supported by molecular dynamics simulation study, i. e., the reducing-end glucose unit was effectively loaded into the active site of WTcat, but not into that of W40Acat. when the simulation was started from subsite-7.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 88, "end": 95}]}}, "schema": []}
{"input": "However, when the similar simulations were carried out starting from subsite-5, both enzymes hold the substrate in 50 ns, indicating that the major difference between WTcat and W40Acat is the length of free chain-end of the substrate required to allow initiation of processive movements; this also reflects the difference between crystalline and amorphous celluloses.", "output": {"entities": {}}, "schema": []}
{"input": "The CBD is important for enhancing the enzyme population on crystalline substrate, but it also decreases the specific activity of the adsorbed enzyme, possibly by attaching the enzyme to non-optimal places on cellulose surface and/or hindering processive hydrolysis.", "output": {"entities": {}}, "schema": []}
{"input": "A Novel Automethylation Reaction in the Aspergillus nidulans LaeA Protein Generates S-Methylmethionine.", "output": {"entities": {"chemical": [{"text": "S-Methylmethionine", "start": 84, "end": 102}]}}, "schema": []}
{"input": "The filamentous fungi in the genus Aspergillus are opportunistic plant and animal pathogens that can adapt to their environment by producing various secondary metabolites including lovastatin, penicillin, and aflatoxin.", "output": {"entities": {"chemical": [{"text": "lovastatin", "start": 181, "end": 191}, {"text": "penicillin", "start": 193, "end": 203}, {"text": "aflatoxin", "start": 209, "end": 218}]}}, "schema": []}
{"input": "The synthesis of these small molecules is dependent on gene clusters that are globally regulated by the LaeA protein.", "output": {"entities": {}}, "schema": []}
{"input": "Null mutants of LaeA in all pathogenic fungi examined to date show decreased virulence coupled with reduced secondary metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "Although the amino acid sequence of LaeA contains the motifs characteristic of seven-beta-strand methyltransferases, a methyl-accepting substrate of LaeA has not been identified.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 13, "end": 23}, {"text": "methyltransferases", "start": 97, "end": 115}]}}, "schema": []}
{"input": "In this work, we did not find a methyl-accepting substrate in A. nidulans with various assays including in vivo S-adenosyl-[methyl-(3) H] methionine labeling, targeted in vitro methylation experiments using putative protein substrates, or in vitro methylation assays using whole cell extracts grown under different conditions.", "output": {"entities": {"chemical": [{"text": "methyl", "start": 32, "end": 38}, {"text": "S-adenosyl-[methyl-(3) H] methionine", "start": 112, "end": 148}]}}, "schema": []}
{"input": "However, in each experiment LaeA was shown to self-methylate.", "output": {"entities": {}}, "schema": []}
{"input": "Amino acid hydrolysis of radioactively-labeled LaeA followed by cation exchange and reverse phase chromatography identified methionine as the modified residue.", "output": {"entities": {"chemical": [{"text": "Amino acid", "start": 0, "end": 10}, {"text": "methionine", "start": 124, "end": 134}]}}, "schema": []}
{"input": "Point mutations show that the major site of modification of LaeA is on methionine-207.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 71, "end": 81}]}}, "schema": []}
{"input": "However, in vivo complementation showed that methionine-207 is not required for the biological function of LaeA.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 45, "end": 55}]}}, "schema": []}
{"input": "LaeA is the first protein to exhibit automethylation at a methionine residue.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 58, "end": 68}]}}, "schema": []}
{"input": "These findings not only indicate LaeA may perform novel chemistry with S-adenosylmethionine, but also provide new insights into the physiological function of LaeA.", "output": {"entities": {"chemical": [{"text": "S-adenosylmethionine", "start": 71, "end": 91}]}}, "schema": []}
{"input": "Synthesis and in Vitro Characterisation of Ifenprodil-Based Fluorescein Conjugates as GluN1/GluN2B N-Methyl-D-aspartate Receptor Antagonists.", "output": {"entities": {"chemical": [{"text": "Ifenprodil", "start": 43, "end": 53}, {"text": "Fluorescein", "start": 60, "end": 71}, {"text": "N-Methyl-D-aspartate", "start": 99, "end": 119}]}}, "schema": []}
{"input": "GluN2B-containing NMDA receptors are involved in many important physiological functions and play a pivotal role in mediating pain as well as in several neurodegenerative disorders.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 18, "end": 22}]}}, "schema": []}
{"input": "We aimed to develop fluorescent probes to target the GluN2B subunit selectively in order to allow better understanding of the relationships between receptor localisation and physiological importance.", "output": {"entities": {}}, "schema": []}
{"input": "Ifenprodil, known as the GluNR2B antagonist of reference, was chosen as the template for the elaboration of probes.", "output": {"entities": {"chemical": [{"text": "Ifenprodil", "start": 0, "end": 10}]}}, "schema": []}
{"input": "We had previously reported a fluorescein conjugate that was shown (by confocal microscopy imaging of DS-red-labelled cortical neurons) to bind specifically to GluN2B.", "output": {"entities": {"chemical": [{"text": "fluorescein", "start": 29, "end": 40}]}}, "schema": []}
{"input": "To elaborate this probe, we explored the influence of both the nature and the attachment point of the spacer between the fluorophore and the parent compound, ifenprodil.", "output": {"entities": {"chemical": [{"text": "ifenprodil", "start": 158, "end": 168}]}}, "schema": []}
{"input": "We performed chemical modifications of ifenprodil at the benzylic position and on the phenol ring by introducing secondary amine or amide functions and evaluated alkyl chains from two to 20 bonds either including or not including secondary amide functions as spacers.", "output": {"entities": {"chemical": [{"text": "ifenprodil", "start": 39, "end": 49}, {"text": "benzylic", "start": 57, "end": 65}, {"text": "phenol", "start": 86, "end": 92}, {"text": "secondary amine or amide", "start": 113, "end": 137}, {"text": "secondary amide", "start": 230, "end": 245}]}}, "schema": []}
{"input": "The previously developed probe was found to display the greatest activity in the inhibition of NMDA-induced Ca (2 +) influx by calcium imaging experiments on HEK293 cells transfected with the cDNA encoding for GluN1-1A and GluN2B.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 95, "end": 99}, {"text": "Ca (2 +)", "start": 108, "end": 116}, {"text": "calcium", "start": 127, "end": 134}]}}, "schema": []}
{"input": "Further investigations revealed that this probe had a neuroprotective effect equivalent to that of ifenprodil in a standard test for neurotoxicity.", "output": {"entities": {"chemical": [{"text": "ifenprodil", "start": 99, "end": 109}]}}, "schema": []}
{"input": "Despite effects of lesser amplitude with these probes relative to ifenprodil, we demonstrated that they displaced [(3) H] ifenprodil in mouse brain slices in a similar manner.", "output": {"entities": {"chemical": [{"text": "ifenprodil", "start": 66, "end": 76}, {"text": "[(3) H] ifenprodil", "start": 114, "end": 132}]}}, "schema": []}
{"input": "Highly efficient f o rster resonance energy transfer in a fast, serum-compatible immunoassay.", "output": {"entities": {}}, "schema": []}
{"input": "Highly efficient FRET leads to important enhancements for homogeneous immunoassays.", "output": {"entities": {}}, "schema": []}
{"input": "By using the novel phosphorescent dye EuLH and BHQ-10 as a donor-acceptor pair, the FRET efficiency increases to > 99. 5%, leading to significantly improved signal-to-background ratio, precision and linear range.", "output": {"entities": {"chemical": [{"text": "BHQ-10", "start": 47, "end": 53}]}}, "schema": []}
{"input": "The phosphorescence detection enabled full compatibility to serum samples for this fast-responding immunoassay.", "output": {"entities": {}}, "schema": []}
{"input": "Extended h u ckel theory for carbon nanotubes: band structure and transport properties.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 29, "end": 35}]}}, "schema": []}
{"input": "Extended H u ckel theory (EHT) is a well established method for the description of the electronic structure of molecules and solids.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we present a set of extended H u ckel parameters for carbon nanotubes (CNTs), obtained by fitting the ab initio band structure of the (6, 0) CNT.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 70, "end": 76}]}}, "schema": []}
{"input": "The new parameters are highly transferable to different types of CNTs.", "output": {"entities": {}}, "schema": []}
{"input": "To demonstrate the versatility of the approach, we perform self-consistent EHT-based electron transport calculations for finite length CNTs with metal electrodes.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and anti-HIV activities.", "output": {"entities": {"chemical": [{"text": "tricyclic guanidine", "start": 39, "end": 58}, {"text": "batzelladine K", "start": 72, "end": 86}]}}, "schema": []}
{"input": "Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities.", "output": {"entities": {"chemical": [{"text": "batzelladine K", "start": 19, "end": 33}]}}, "schema": []}
{"input": "Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC (50) 1. 25 and 0. 88 mu M and chloroquine-resistant W2 strain with IC (50) 1. 64 and 1. 07 mu M, respectively.", "output": {"entities": {"chemical": [{"text": "chloroquine", "start": 72, "end": 83}, {"text": "chloroquine", "start": 142, "end": 153}]}}, "schema": []}
{"input": "Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC (50) 2. 39 and 2. 78 mu M and IC (90) 11. 27 and 12. 76 mu M, respectively.", "output": {"entities": {"chemical": [{"text": "nonyl", "start": 29, "end": 34}]}}, "schema": []}
{"input": "Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC (50) < 3. 02 mu M and MIC/MBC/MFC < 6 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens.", "output": {"entities": {"chemical": [{"text": "pentyl", "start": 20, "end": 26}, {"text": "methyl", "start": 31, "end": 37}]}}, "schema": []}
{"input": "However, none was found active against HIV-1.", "output": {"entities": {}}, "schema": []}
{"input": "Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.", "output": {"entities": {"chemical": [{"text": "tricyclic guanidine", "start": 32, "end": 51}]}}, "schema": []}
{"input": "Pickering-Emulsion-Polymerized Polystyrene/Fe2O3 Composite Particles and Their Magnetoresponsive Characteristics.", "output": {"entities": {"chemical": [{"text": "Polystyrene", "start": 31, "end": 42}, {"text": "Fe2O3", "start": 43, "end": 48}]}}, "schema": []}
{"input": "Core-shell-structured magnetic polystyrene (PS)/inorganic particles were fabricated by Pickering emulsion polymerization using nanosized Fe2O3 particles as a solid stabilizer.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 31, "end": 42}, {"text": "Fe2O3", "start": 137, "end": 142}]}}, "schema": []}
{"input": "Scanning electron microscopy and transmission electron microscopy confirmed the synthesized PS/Fe2O3 particles to be comprised of a PS surface coated with Fe2O3 nanoparticles.", "output": {"entities": {"chemical": [{"text": "Fe2O3", "start": 95, "end": 100}, {"text": "Fe2O3", "start": 155, "end": 160}]}}, "schema": []}
{"input": "The chemical structure of the composite nanospheres was characterized by Fourier transform infrared spectroscopy and X-ray diffraction.", "output": {"entities": {}}, "schema": []}
{"input": "The thermal properties of composite nanospheres and corresponding pure polymer were examined by thermogravimetric analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The rheological properties of the core-shell-structured magnetic PS/inorganic particles dispersed in silicone oil were investigated under an external magnetic field strength using a rotational rheometer.", "output": {"entities": {}}, "schema": []}
{"input": "The particles with extremely lower density than common magnetic particles exhibited solid-like magnetorheological phase characteristics, and the flow curves were fitted to the Cho-Choi-Jhon model of the rheological equation of state.", "output": {"entities": {}}, "schema": []}
{"input": "Engineering the Microstructure of Electrospun Fibrous Scaffolds by Microtopography.", "output": {"entities": {}}, "schema": []}
{"input": "Controlling the structure and organization of electrospun fibers is desirable for fabricating scaffolds and materials with defined microstructures.", "output": {"entities": {}}, "schema": []}
{"input": "However, the effects of microtopography on the deposition and, in turn, the organization of the electrospun fibers are not well understood.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, conductive polydimethylsiloxane (PDMS) templates with different micropatterns were fabricated by combining photolithography, silicon wet etching, and PDMS molding techniques.", "output": {"entities": {"chemical": [{"text": "polydimethylsiloxane", "start": 26, "end": 46}, {"text": "PDMS", "start": 48, "end": 52}, {"text": "silicon", "start": 140, "end": 147}, {"text": "PDMS", "start": 165, "end": 169}]}}, "schema": []}
{"input": "The fiber organization was varied by fine-tuning the microtopography of the electrospinning collector.", "output": {"entities": {}}, "schema": []}
{"input": "Fiber conformity and alignment were influenced by the depth and the slope of microtopography features, resulting in scaffolds comprising either an array of microdomains with different porosity and fiber alignment or an array of microwells.", "output": {"entities": {}}, "schema": []}
{"input": "Microtopography affected the fiber organization for hundreds of micrometers below the scaffold surface, resulting in scaffolds with distinct surface properties on each side.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the fiber diameter was also affected by the fiber conformity.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of the fiber arrangement in the scaffolds on the morphology, migration, and infiltration of cells were examined by in vitro and in vivo experiments.", "output": {"entities": {}}, "schema": []}
{"input": "Cell morphology and organization were guided by the fibers in the microdomains, and cell migration was enhanced by the aligned fibers and the three-dimensional scaffold structure.", "output": {"entities": {}}, "schema": []}
{"input": "Cell infiltration was correlated with the microdomain porosity.", "output": {"entities": {}}, "schema": []}
{"input": "Microscale control of the fiber organization and the porosity at the surface and through the thickness of the fibrous scaffolds, as demonstrated by the results of this study, provides a powerful means of engineering the three-dimensional structure of electrospun fibrous scaffolds for cell and tissue engineering.", "output": {"entities": {}}, "schema": []}
{"input": "Directing Chondrogenesis of Stem Cells with Specific Blends of Cellulose and Silk.", "output": {"entities": {}}, "schema": []}
{"input": "Biomaterials that can stimulate stem cell differentiation without growth factor supplementation provide potent and cost-effective scaffolds for regenerative medicine.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesize that a scaffold prepared from cellulose and silk blends can direct stem cell chondrogenic fate.", "output": {"entities": {}}, "schema": []}
{"input": "We systematically prepared cellulose blends with silk at different compositions using an environmentally benign processing method based on ionic liquids as a common solvent.", "output": {"entities": {}}, "schema": []}
{"input": "We tested the effect of blend compositions on the physical properties of the materials as well as on their ability to support mesenchymal stem cell (MSC) growth and chondrogenic differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "The stiffness and tensile strength of cellulose was significantly reduced by blending with silk.", "output": {"entities": {}}, "schema": []}
{"input": "The characterized materials were tested using MSCs derived from four different patients.", "output": {"entities": {}}, "schema": []}
{"input": "Growing MSCs on a specific blend combination of cellulose and silk in a 75: 25 ratio significantly upregulated the chondrogenic marker genes SOX9, aggrecan, and type II collagen in the absence of specific growth factors.", "output": {"entities": {}}, "schema": []}
{"input": "This chondrogenic effect was neither found with neat cellulose nor the cellulose/silk 50: 50 blend composition.", "output": {"entities": {}}, "schema": []}
{"input": "No adipogenic or osteogenic differentiation was detected on the blends, suggesting that the cellulose/silk 75: 25 blend induced specific stem cell differentiation into the chondrogenic lineage without addition of the soluble growth factor TGF-beta.", "output": {"entities": {}}, "schema": []}
{"input": "The cellulose/silk blend we identified can be used both for in vitro tissue engineering and as an implantable device for stimulating endogenous stem cells to initiate cartilage repair.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA: cholesterol acyltransferase 2 (ACAT2) inhibitors: Part 2.", "output": {"entities": {"chemical": [{"text": "pyripyropene A", "start": 49, "end": 63}, {"text": "acyl-CoA", "start": 100, "end": 108}, {"text": "cholesterol", "start": 110, "end": 121}]}}, "schema": []}
{"input": "Synthesis and structure-activity relationships of 7-O-p-cyanobenzoyl pyripyropene A derivatives with modification at C1 and 11 are described.", "output": {"entities": {"chemical": [{"text": "7-O-p-cyanobenzoyl pyripyropene A", "start": 50, "end": 83}]}}, "schema": []}
{"input": "Regioselective mono-deprotection of di-tert-butylsilylene acetal was critical in their synthesis.", "output": {"entities": {"chemical": [{"text": "di-tert-butylsilylene acetal", "start": 36, "end": 64}]}}, "schema": []}
{"input": "Disruption of AtWNK8 Enhances Tolerance of Arabidopsis to Salt and Osmotic Stresses via Modulating Proline Content and Activities of Catalase and Peroxidase.", "output": {"entities": {"chemical": [{"text": "Proline", "start": 99, "end": 106}]}}, "schema": []}
{"input": "With no lysine kinases (WNKs) play important roles in plant growth and development.", "output": {"entities": {"chemical": [{"text": "lysine", "start": 8, "end": 14}]}}, "schema": []}
{"input": "However, its role in salt and osmotic stress tolerance is unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report that AtWNK8 is mainly expressed in primary root, hypocotyl, stamen and pistil and is induced by NaCl and sorbitol treatment.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 112, "end": 116}, {"text": "sorbitol", "start": 121, "end": 129}]}}, "schema": []}
{"input": "Compared to the wild-type, the T-DNA knock-out wnk8 mutant was more tolerant to severe salinity and osmotic stresses, as indicated by 27% and 198% more fresh weight in the NaCl and sorbitol treatment, respectively.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 172, "end": 176}, {"text": "sorbitol", "start": 181, "end": 189}]}}, "schema": []}
{"input": "The wnk8 mutant also accumulated 1. 43-fold more proline than the wild-type in the sorbitol treatment.", "output": {"entities": {"chemical": [{"text": "proline", "start": 49, "end": 56}, {"text": "sorbitol", "start": 83, "end": 91}]}}, "schema": []}
{"input": "Under NaCl and sorbitol stresses, catalase (CAT) activity in wnk8 mutant was 1. 92-and 3. 7-times of that in Col-0, respectively.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 6, "end": 10}, {"text": "sorbitol", "start": 15, "end": 23}]}}, "schema": []}
{"input": "Similarly, under salt and osmotic stress conditions, peroxidase (POD) activities in wnk8 mutant were 1. 81-and 1. 58-times of that in Col-0, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, we revealed that maintaining higher CAT and POD activities might be one of the reasons that the disruption of AtWNK8 enhances the tolerance to salt stress, and accumulating more proline and higher activities of CAT and POD might result in the higher tolerance of WNK8 to osmotic stress.", "output": {"entities": {"chemical": [{"text": "proline", "start": 194, "end": 201}]}}, "schema": []}
{"input": "Lipid Status of the Two High Latitude Fish Species, Leptoclinus maculatus and Lumpenus fabricii.", "output": {"entities": {}}, "schema": []}
{"input": "A comparative study of the lipid status (i. e., the total lipid and phospholipid concentrations and the percentage of fatty acids of the total lipids) of adult specimens of daubed shanny (Leptoclinus maculatus) from Svalbard waters (Isfjord) and slender eel blenny (Lumpenus fabricii) from the White Sea (Onega Bay and Tersky shore) was performed to study the metabolism and functions of lipids of these fishes in ontogeny and under various ecological conditions.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 118, "end": 129}]}}, "schema": []}
{"input": "Slender eel blenny from both areas of the White Sea were distinguished by a high level of sphingomyelin compared with the daubed shanny from Svalbard, and the amount of total phospholipids was higher in slender eel blenny from Onega Bay than in slender eel blenny from the Tersky shore.", "output": {"entities": {"chemical": [{"text": "sphingomyelin", "start": 90, "end": 103}]}}, "schema": []}
{"input": "The extent of saturation and the signature of polyenic fatty acids varied according to the specific species of the Stichaeidae family under study.", "output": {"entities": {"chemical": [{"text": "polyenic fatty acids", "start": 46, "end": 66}]}}, "schema": []}
{"input": "These results demonstrate the differences in the trophoecological and hydrobiological conditions of habitations of these species and highlighted the importance of considering certain trends in the lipid profiles of these fishes as specific features of the organization of the ecological and biochemical mechanisms of adaptation.", "output": {"entities": {}}, "schema": []}
{"input": "Further evidence for involvement of the dorsal hippocampus serotonergic and gamma-aminobutyric acid (GABA) ergic pathways in the expression of contextual fear conditioning in rats.", "output": {"entities": {"chemical": [{"text": "gamma-aminobutyric acid", "start": 76, "end": 99}, {"text": "GABA", "start": 101, "end": 105}]}}, "schema": []}
{"input": "Intra-dorsal hippocampus (DH) injections of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin-1A (5-hydroxytryptamine (5-HT)-1A) receptor agonist, were previously shown to inhibit the expression of contextual fear when administered six hours after conditioning.", "output": {"entities": {"chemical": [{"text": "8-hydroxy-2-(di-n-propylamino) tetralin", "start": 44, "end": 83}, {"text": "8-OH-DPAT", "start": 85, "end": 94}, {"text": "serotonin", "start": 99, "end": 108}, {"text": "5-hydroxytryptamine", "start": 113, "end": 132}, {"text": "5-HT", "start": 134, "end": 138}]}}, "schema": []}
{"input": "However, further understanding of the consolidation and expression of aversive memories requires investigations of these and other mechanisms at distinct time points and the regions of the brain to which they are transferred.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the purpose of the present study was to investigate the role of DH serotonergic and gamma-aminobutyric acid (GABA) ergic mechanisms in the expression of contextual fear 24 h after conditioning, reflected by fear-potentiated startle (FPS) and freezing behavior.", "output": {"entities": {"chemical": [{"text": "gamma-aminobutyric acid", "start": 90, "end": 113}, {"text": "GABA", "start": 115, "end": 119}]}}, "schema": []}
{"input": "The recruitment of the amygdala and medial prefrontal cortex (mPFC) in these processes was also evaluated by measuring Fos protein immunoreactivity.", "output": {"entities": {}}, "schema": []}
{"input": "Although intra-DH injections of 8-OH-DPAT did not produce behavioral changes, muscimol reduced both FPS and the freezing response.", "output": {"entities": {"chemical": [{"text": "8-OH-DPAT", "start": 32, "end": 41}]}}, "schema": []}
{"input": "Fos protein immunoreactivity revealed that contextual fear promoted wide activation of the mPFC, which was significantly reduced after intra-DH infusions of muscimol.", "output": {"entities": {"chemical": [{"text": "muscimol", "start": 157, "end": 165}]}}, "schema": []}
{"input": "The present findings, together with previous data, indicate that in contrast to 5-HT, which appears to play a role during the early phases of contextual aversive memory consolidation, longer-lasting GABA-mediated mechanisms are recruited during the expression of contextual fear memories.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 80, "end": 84}, {"text": "GABA", "start": 199, "end": 203}]}}, "schema": []}
{"input": "Risk of ischemic stroke with the use of risperidone, quetiapine and olanzapine in elderly patients: a population-based, case-crossover study.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 40, "end": 51}, {"text": "quetiapine", "start": 53, "end": 63}, {"text": "olanzapine", "start": 68, "end": 78}]}}, "schema": []}
{"input": "We conducted a case-crossover study to evaluate the comparative risk of ischemic stroke associated with the use of risperidone, quetiapine and olanzapine in geriatric patients using the Korean Health Insurance Review and Assessment Service database.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 115, "end": 126}, {"text": "quetiapine", "start": 128, "end": 138}, {"text": "olanzapine", "start": 143, "end": 153}]}}, "schema": []}
{"input": "Cases included elderly patients > 64 years old who had experienced their first ischemic stroke (International Classification of Disease, Tenth Revision (ICD-10), I63) hospitalization from July 2005 to June 2006 and who had been without prior cerebrovascular diseases (ICD-10, I60-I69), or transient ischemic attack (ICD-10, G45).", "output": {"entities": {}}, "schema": []}
{"input": "Exposures to risperidone, quetiapine and olanzapine were assessed during the 30 days prior to the stroke episode.", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 13, "end": 24}, {"text": "quetiapine", "start": 26, "end": 36}, {"text": "olanzapine", "start": 41, "end": 51}]}}, "schema": []}
{"input": "We set two control periods with lengths which were the same as the hazard periods.", "output": {"entities": {}}, "schema": []}
{"input": "Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated by conditional logistic regression.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 1601 cases of ischemic stroke with a mean age of 75. 6 (+/- 6. 7) years were identified, among which 933 (58. 3%) were female.", "output": {"entities": {}}, "schema": []}
{"input": "An increased risk of ischemic stroke was associated with the use of risperidone (aOR = 3. 5, 95% CI 3. 3-4. 6) and quetiapine (aOR = 2. 7, 95% CI 2. 0-3. 6) during the 30 days prior to stroke: however, no significant risk was observed with olanzapine (aOR = 1. 2, 95% CI 0. 7-2. 0).", "output": {"entities": {"chemical": [{"text": "risperidone", "start": 68, "end": 79}, {"text": "quetiapine", "start": 115, "end": 125}, {"text": "olanzapine", "start": 240, "end": 250}]}}, "schema": []}
{"input": "The increased stroke risk in demented patients, assessed within 30 days after exposure, was also observed with olanzapine.", "output": {"entities": {"chemical": [{"text": "olanzapine", "start": 111, "end": 121}]}}, "schema": []}
{"input": "However, the sample of olanzapine users was small and underpowered.", "output": {"entities": {"chemical": [{"text": "olanzapine", "start": 23, "end": 33}]}}, "schema": []}
{"input": "Evaluation of Perturbations in Serum Thyroid Hormones During Human Pregnancy Due to Dietary Iodide and Perchlorate Exposure Using a Biologically Based Dose-Response Model.", "output": {"entities": {"chemical": [{"text": "Iodide", "start": 92, "end": 98}, {"text": "Perchlorate", "start": 103, "end": 114}]}}, "schema": []}
{"input": "A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus.", "output": {"entities": {}}, "schema": []}
{"input": "This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake.", "output": {"entities": {"chemical": [{"text": "iodide", "start": 53, "end": 59}, {"text": "thyroxine", "start": 67, "end": 76}, {"text": "thyroxine", "start": 88, "end": 97}, {"text": "triiodothyronine", "start": 115, "end": 131}, {"text": "iodide", "start": 184, "end": 190}]}}, "schema": []}
{"input": "The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide.", "output": {"entities": {"chemical": [{"text": "perchlorate", "start": 35, "end": 46}, {"text": "sodium iodide", "start": 110, "end": 123}, {"text": "iodide", "start": 166, "end": 172}]}}, "schema": []}
{"input": "Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake.", "output": {"entities": {"chemical": [{"text": "perchlorate", "start": 106, "end": 117}, {"text": "iodide", "start": 204, "end": 210}]}}, "schema": []}
{"input": "Model simulations suggested that a maternal iodide intake of 75 to 250 micro g/day and an environmentally relevant exposure of perchlorate (~ 0. 1 micro g/kg/day) did not result in hypothyroxinemia or hypothyroidism.", "output": {"entities": {"chemical": [{"text": "iodide", "start": 44, "end": 50}, {"text": "perchlorate", "start": 127, "end": 138}]}}, "schema": []}
{"input": "For a daily iodide-sufficient intake of 200 micro g/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32. 2 micro g/kg/day.", "output": {"entities": {"chemical": [{"text": "iodide", "start": 12, "end": 18}, {"text": "perchlorate", "start": 69, "end": 80}]}}, "schema": []}
{"input": "As iodide intake was lowered to 75 micro g/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold.", "output": {"entities": {"chemical": [{"text": "iodide", "start": 3, "end": 9}, {"text": "perchlorate", "start": 74, "end": 85}]}}, "schema": []}
{"input": "Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54. 8 to 21. 5 micro g/kg/day for daily iodide intake of 250-75 micro g/day.", "output": {"entities": {"chemical": [{"text": "perchlorate", "start": 15, "end": 26}, {"text": "iodide", "start": 148, "end": 154}]}}, "schema": []}
{"input": "This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.", "output": {"entities": {}}, "schema": []}
{"input": "Interferon-gamma Promoter Is Hypermethylated in Blood DNA from Workers with Confirmed Diisocyanate Asthma.", "output": {"entities": {"chemical": [{"text": "Diisocyanate", "start": 86, "end": 98}]}}, "schema": []}
{"input": "Risk factors have not been identified that determine susceptibility for development of diisocyanate-induced occupational asthma (DA).", "output": {"entities": {"chemical": [{"text": "diisocyanate", "start": 87, "end": 99}]}}, "schema": []}
{"input": "We hypothesized that diisocyanate (DI) exposure could modify gene promoter regions regulating transcription of cytokine mediators and thereby influence expression of DA.", "output": {"entities": {"chemical": [{"text": "diisocyanate", "start": 21, "end": 33}]}}, "schema": []}
{"input": "A cross-sectional study was designed to investigate the promoter methylation status of candidate genes in DI-exposed workers.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects consisted of 131 workers in three groups: 40 cases with DA confirmed by a positive specific inhalation challenge (SIC) (DA +), 41 exposed workers with lower respiratory symptoms and negative SIC (DA-), and 50 asymptomatic exposed workers (AWs).", "output": {"entities": {}}, "schema": []}
{"input": "We studied four candidate genes (GSTM1, DUSP22, IFN-gamma, and IL-4) for which altered promoter methylation has been previously investigated for relationships with a variety of other environmental exposures.", "output": {"entities": {}}, "schema": []}
{"input": "Methylation status was determined using methylation-specific quantitative PCR performed on genomic DNA extracted from whole blood.", "output": {"entities": {}}, "schema": []}
{"input": "Results showed that relative methylation of IFN-gamma promoter was significantly increased in DA + in comparison with both comparator groups (DA-and AW), and it exhibited good sensitivity (77. 5%) and specificity (80%) for identifying DA workers in a multivariate predictive model after adjusting for type of DI exposure, smoking status, methacholine PC20, and gender.", "output": {"entities": {"chemical": [{"text": "methacholine", "start": 338, "end": 350}]}}, "schema": []}
{"input": "IL-4 promoter was slightly less methylated only in DA + compared with AW among nonsmoking workers.", "output": {"entities": {}}, "schema": []}
{"input": "Both GSTM1 and DUSP22 promoter methylations were found not associated with DA.", "output": {"entities": {}}, "schema": []}
{"input": "Our finding suggests that exposure to occupational chemicals could play a heretofore undefined mechanistic role via epigenetic modification of specific genes in the promoter region.", "output": {"entities": {}}, "schema": []}
{"input": "DNA Adduct Formation of 2-Amino-9H-pyrido [2, 3-b] indole and 2-Amino-3, 4-dimethylimidazo [4, 5-f] quinoline in Mouse Liver and Extrahepatic Tissues During a Subchronic Feeding Study.", "output": {"entities": {"chemical": [{"text": "2-Amino-9H-pyrido [2, 3-b] indole", "start": 24, "end": 57}, {"text": "2-Amino-3, 4-dimethylimidazo [4, 5-f] quinoline", "start": 62, "end": 109}]}}, "schema": []}
{"input": "Tobacco smoking is a risk factor for cancers of the liver and gastrointestinal (GI) tract, but the causal agents responsible for these cancers are uncertain.", "output": {"entities": {}}, "schema": []}
{"input": "2-Amino-9H-pyrido [2, 3-b] indole (A alpha C) is an abundant heterocyclic aromatic amine present in tobacco smoke.", "output": {"entities": {"chemical": [{"text": "2-Amino-9H-pyrido [2, 3-b] indole", "start": 0, "end": 33}, {"text": "heterocyclic aromatic amine", "start": 61, "end": 88}]}}, "schema": []}
{"input": "A alpha C is a liver carcinogen and both a transgene mutagen and inducer of aberrant crypt foci in the colon of mice.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesize that A alpha C may contribute to DNA damage and tumorigenesis in these organs of smokers.", "output": {"entities": {}}, "schema": []}
{"input": "The potential of A alpha C to induce DNA adduct formation in liver, organs of the GI tract, lung, and urinary bladder, which are target organs of cancer in smokers, was examined using the C57BL/6 mouse as an animal model.", "output": {"entities": {}}, "schema": []}
{"input": "A alpha C (400 or 800 ppm) and 2-amino-3, 4-dimethylimidazo [4, 5-f] quinoline (MeIQ) (300 ppm), a liver and colon carcinogen in C57BL/6 mice, were given in the diet for up to 12 weeks.", "output": {"entities": {"chemical": [{"text": "2-amino-3, 4-dimethylimidazo [4, 5-f] quinoline", "start": 31, "end": 78}, {"text": "MeIQ", "start": 80, "end": 84}]}}, "schema": []}
{"input": "Liquid chromatography/mass spectrometry was employed to measure DNA adducts.", "output": {"entities": {}}, "schema": []}
{"input": "The major DNA adducts of both carcinogens were identified as deoxyguanosine-C8 adducts.", "output": {"entities": {"chemical": [{"text": "deoxyguanosine", "start": 61, "end": 75}]}}, "schema": []}
{"input": "The levels of formation of A alpha C-and MeIQ-DNA adducts were similar in liver and extrahepatic tissues when adjusted for dose.", "output": {"entities": {"chemical": [{"text": "MeIQ", "start": 41, "end": 45}]}}, "schema": []}
{"input": "The highest levels of adducts occurred in liver, followed by urinary bladder, and then in cecum and colon; lower DNA adduct levels were formed in the lung and pancreas following 12 weeks of feeding.", "output": {"entities": {}}, "schema": []}
{"input": "The high levels of A alpha C adduct formed in liver, GI tract, and bladder of C57BL/6 mice reinforce the notion that A alpha C may contribute to DNA damage and cancer of these organs in smokers.", "output": {"entities": {}}, "schema": []}
{"input": "Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis) By-Products.", "output": {"entities": {}}, "schema": []}
{"input": "Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides.", "output": {"entities": {}}, "schema": []}
{"input": "The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3.", "output": {"entities": {}}, "schema": []}
{"input": "The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction.", "output": {"entities": {}}, "schema": []}
{"input": "At a protein concentration of 44 micro g/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "At the low protein concentration of only 11 micro g/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids.", "output": {"entities": {"chemical": [{"text": "taurine", "start": 134, "end": 141}, {"text": "methionine", "start": 146, "end": 156}, {"text": "threonine", "start": 179, "end": 188}, {"text": "proline", "start": 190, "end": 197}, {"text": "glycine amino acids", "start": 202, "end": 221}]}}, "schema": []}
{"input": "The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.", "output": {"entities": {}}, "schema": []}
{"input": "Recent developments in design and synthesis of bicyclic azasugars, carbasugars and related molecules as glycosidase inhibitors.", "output": {"entities": {"chemical": [{"text": "bicyclic azasugars", "start": 47, "end": 65}, {"text": "carbasugars", "start": 67, "end": 78}]}}, "schema": []}
{"input": "The importance of glycosidase inhibitors and especially the bicyclic molecules has led to design and assessment of many analogs of naturally occurring molecules.", "output": {"entities": {}}, "schema": []}
{"input": "This review focuses on the synthesis and enzyme inhibitions of a few selected (synthetic or non-naturally occurring) molecules that have been reported in the last decade, which allow one to draw some connection between varying the structural features and their effect on glycosidase inhibitions.", "output": {"entities": {}}, "schema": []}
{"input": "It is expected that further improvements based on these features could lead to improved inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Biomarkers of Lead Exposure Among a Population Under Environmental Stress.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to evaluate the relationship between blood lead and serum creatinine and blood lead and serum urea nitrogen levels as biomarkers of lead exposure from subjects living in a historic polymetallic mining area in China.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 75, "end": 85}, {"text": "urea nitrogen", "start": 111, "end": 124}]}}, "schema": []}
{"input": "Elevated levels were found for blood lead, serum creatinine, and serum urea nitrogen in the mining area with mean values at 245. 65 mu g/l, 74. 16 mu mol/l, and 12. 79 mmol/l, which were significantly higher than those in the control area, respectively.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 49, "end": 59}, {"text": "urea nitrogen", "start": 71, "end": 84}]}}, "schema": []}
{"input": "Moreover, the coefficients between paired results for blood lead and serum creatinine and blood lead and serum urea nitrogen were positively statistically significant (serum creatinine vs. blood lead, r = 0. 35, p < 0. 05; serum urea nitrogen vs. blood lead, r = 0. 48, p < 0. 05).", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 75, "end": 85}, {"text": "urea nitrogen", "start": 111, "end": 124}, {"text": "creatinine", "start": 174, "end": 184}, {"text": "urea nitrogen", "start": 229, "end": 242}]}}, "schema": []}
{"input": "With respect to the effects of sex and age on the blood lead, serum creatinine, and serum urea nitrogen levels, data analysis revealed there was a tendency for higher blood lead, serum creatinine, and serum urea nitrogen levels in females than in males, and the levels of blood lead, serum creatinine, and serum urea nitrogen increased among older residents.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 68, "end": 78}, {"text": "urea nitrogen", "start": 90, "end": 103}, {"text": "creatinine", "start": 185, "end": 195}, {"text": "urea nitrogen", "start": 207, "end": 220}, {"text": "creatinine", "start": 290, "end": 300}, {"text": "urea nitrogen", "start": 312, "end": 325}]}}, "schema": []}
{"input": "We conclude that females and the older population in the mining area are more susceptible to lead exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Blood lead, serum creatinine, and serum urea nitrogen can be useful biomarkers of lead exposure among populations under environmental stress.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 18, "end": 28}, {"text": "urea nitrogen", "start": 40, "end": 53}]}}, "schema": []}
{"input": "Neuroprotective Effects of Cilostazol on Retinal Ganglion Cell damage in Diabetic Rats.", "output": {"entities": {"chemical": [{"text": "Cilostazol", "start": 27, "end": 37}]}}, "schema": []}
{"input": "Neurodegeneration is an important component of diabetic retinopathy with increasing evidence that retinal ganglion cell (RGC) death occurs early in diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the effects of cilostazol, which has been widely used to manage diabetic complications, on retinal ganglion cell death in diabetic retina.", "output": {"entities": {"chemical": [{"text": "cilostazol", "start": 31, "end": 41}]}}, "schema": []}
{"input": "Four-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats as matched nondiabetic controls were treated with daily oral cilostazol at 30mg/kg or 0. 9% saline solution.", "output": {"entities": {"chemical": [{"text": "cilostazol", "start": 166, "end": 176}]}}, "schema": []}
{"input": "In OLETF rats at the age of 40 weeks, glial fibrillary acidic protein (GFAP) immunofluorescence staining was upregulated in vertical sections and showed a more ramified pattern in whole-mount retinas compared with that in LETO rats.", "output": {"entities": {}}, "schema": []}
{"input": "Vascular endothelial growth factor (VEGF) expression was limited to the ganglion cell layer in LETO rats, but extended into the outer plexiform layer in OLETF rats.", "output": {"entities": {}}, "schema": []}
{"input": "Immunofluorescence staining and western blotting demonstrated that cilostazol treatment reduced GFAP and VEGF expression in the retinas of OLETF rats.", "output": {"entities": {"chemical": [{"text": "cilostazol", "start": 67, "end": 77}]}}, "schema": []}
{"input": "Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNLEL) staining revealed an increase in the RGC layer in OLETF compared with LETO rats (P < 0. 05), and cilostazol treatment reduced the number of TUNEL-positive cells in OLETF rats (P < 0. 05).", "output": {"entities": {"chemical": [{"text": "dUTP", "start": 47, "end": 51}, {"text": "cilostazol", "start": 176, "end": 186}]}}, "schema": []}
{"input": "Relieving retinal ischemia by systemic cilostazol treatment had a noticeable protective effect on RGCs in diabetic rats.", "output": {"entities": {"chemical": [{"text": "cilostazol", "start": 39, "end": 49}]}}, "schema": []}
{"input": "Cilostazol treatment may be useful for the management of diabetic retinal vascular dysfunction and neuronal degeneration.", "output": {"entities": {"chemical": [{"text": "Cilostazol", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Chrysin Ameliorates Chemically Induced Colitis in the Mouse Through Modulation of a PXR/NF-kappa B Signaling Pathway.", "output": {"entities": {"chemical": [{"text": "Chrysin", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Targeted activation of pregnane X receptor (PXR) in recent years has become a therapeutic strategy for inflammatory bowel disease (IBD).", "output": {"entities": {}}, "schema": []}
{"input": "Chrysin is a naturally occurring flavonoid with anti-inflammation activity.", "output": {"entities": {"chemical": [{"text": "Chrysin", "start": 0, "end": 7}, {"text": "flavonoid", "start": 33, "end": 42}]}}, "schema": []}
{"input": "The current study investigated the role of chrysin as a putative mouse PXR agonist in preventing experimental colitis.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 43, "end": 50}]}}, "schema": []}
{"input": "Pre-administration of chrysin ameliorated inflammatory symptoms in mouse models of colitis (DSS-and TNBS-induced) and resulted in down-regulation of NF-kappa B target genes (iNOS, ICAM-1, MCP-1, Cox2, TNF-alpha and IL-6) in the colon mucosa.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 22, "end": 29}]}}, "schema": []}
{"input": "Chrysin inhibited the phosphorylation/degradation of I kappa B alpha, which correlated with the decline in the activity of myeloperoxidase (MPO) and the levels of TNF-alpha and IL-6 in the colon.", "output": {"entities": {"chemical": [{"text": "Chrysin", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Consistent with the in vivo results, chrysin blocked LPS-stimulated nuclear translocation of NF-kappa B p65 in mouse macrophage RAW264. 7.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 37, "end": 44}]}}, "schema": []}
{"input": "Furthermore, chrysin dose-dependently activated human/mouse PXR in reporter gene assays and up-regulated xenobiotic detoxification genes in the colon mucosa, but not in the liver.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 13, "end": 20}]}}, "schema": []}
{"input": "Silencing of PXR by RNAi demonstrated necessity of PXR in mediating chrysin' s ability to induce xenobiotic detoxification genes and NF-kappa B inactivation.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 68, "end": 75}]}}, "schema": []}
{"input": "The repression of NF-kappa B transcription activity by chrysin was confirmed by in vitro PXR transduction.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 55, "end": 62}]}}, "schema": []}
{"input": "These findings suggest the effect of chrysin in preventing chemically induced colitis is mediated in large part by a PXR/NF-kappa B pathway.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 37, "end": 44}]}}, "schema": []}
{"input": "The data also suggest that chrysin or chrysin-like flavonoids could be further developed as intestine-specific PXR activators.", "output": {"entities": {"chemical": [{"text": "chrysin", "start": 27, "end": 34}, {"text": "chrysin", "start": 38, "end": 45}, {"text": "flavonoids", "start": 51, "end": 61}]}}, "schema": []}
{"input": "The protective effects of taurine on experimental acute pancreatitis in a rat model.", "output": {"entities": {"chemical": [{"text": "taurine", "start": 26, "end": 33}]}}, "schema": []}
{"input": "The aim of this study was to investigate the protective effects of taurine (Tau) on experimental acute pancreatitis (AP) in a rat model by measuring cytokines and oxidant stress markers. Forty rats were randomly divided into four groups: sham, AP, Tau and AP + Tau.", "output": {"entities": {"chemical": [{"text": "taurine", "start": 67, "end": 74}, {"text": "Tau", "start": 76, "end": 79}, {"text": "Tau", "start": 248, "end": 251}]}}, "schema": []}
{"input": "AP was induced with sodium taurocholate.", "output": {"entities": {"chemical": [{"text": "sodium taurocholate", "start": 20, "end": 39}]}}, "schema": []}
{"input": "No treatment was given to the AP.", "output": {"entities": {}}, "schema": []}
{"input": "All rats were killed 5 days later.", "output": {"entities": {}}, "schema": []}
{"input": "Pancreatic tissues of rats and blood samples were obtained. Tau treatment significantly decreased serum amylase activity (p < 0. 001), total injury score (p < 0. 001), malondialdehyde levels (p < 0. 001) and myeloperoxidase (MPO) activity (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "Tau", "start": 60, "end": 63}, {"text": "malondialdehyde", "start": 168, "end": 183}]}}, "schema": []}
{"input": "There was no significant difference between the Tau and AP + Tau groups in serum and pancreatic tumor necrosis factor-alpha, interleukin (IL)-1 beta and IL-6 levels (p = 1. 000).", "output": {"entities": {"chemical": [{"text": "Tau", "start": 48, "end": 51}, {"text": "Tau", "start": 61, "end": 64}]}}, "schema": []}
{"input": "Histopathologic scores in the AP + Tau and Tau groups were significantly lower compared with the AP group (both p < 0. 001). These results showed that Tau reduces lipid peroxidation, amylase and MPO activities and the concentrations of proinflammatory cytokines secondary to AP and also increases superoxide dismutase and glutathione peroxidase activities in rats with sodium taurocholate-induced AP.", "output": {"entities": {"chemical": [{"text": "Tau", "start": 35, "end": 38}, {"text": "Tau", "start": 43, "end": 46}, {"text": "Tau", "start": 151, "end": 154}, {"text": "superoxide", "start": 297, "end": 307}, {"text": "glutathione", "start": 322, "end": 333}, {"text": "sodium taurocholate", "start": 369, "end": 388}]}}, "schema": []}
{"input": "It also has a marked ameliorative effect at histopathologic lesions.", "output": {"entities": {}}, "schema": []}
{"input": "With these effects, Tau protects the cells from oxidative damage, reduces inflammation and promotes regression of pancreatic damage.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of oily vehicles on fetal testis and lipid profile of rats exposed to di-butyl phthalate.", "output": {"entities": {"chemical": [{"text": "di-butyl phthalate", "start": 80, "end": 98}]}}, "schema": []}
{"input": "It has been hypothesized that oils containing high levels of omega-3 polyunsaturated fatty acids, such as canola and fish oil, could counteract some of the adverse effects induced by phthalates.", "output": {"entities": {"chemical": [{"text": "omega-3 polyunsaturated fatty acids", "start": 61, "end": 96}, {"text": "phthalates", "start": 183, "end": 193}]}}, "schema": []}
{"input": "In the present study, the influence of different oily vehicles on di-butyl phthalate (DBP)-induced testicular toxicity and lipid profile was investigated.", "output": {"entities": {"chemical": [{"text": "di-butyl phthalate", "start": 66, "end": 84}, {"text": "DBP", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Pregnant Wistar rats were treated by oral gavage from gestation days 13 to 20 with DBP (500 mg/kg/day) diluted in three different vehicles: corn, canola or fish oil.", "output": {"entities": {"chemical": [{"text": "DBP", "start": 83, "end": 86}]}}, "schema": []}
{"input": "Male fetuses were analyzed on gestation day 20.", "output": {"entities": {}}, "schema": []}
{"input": "DBP exposure lowered intratesticular testosterone levels and anogenital distance, regardless of the vehicle used.", "output": {"entities": {"chemical": [{"text": "DBP", "start": 0, "end": 3}, {"text": "testosterone", "start": 37, "end": 49}]}}, "schema": []}
{"input": "The percentage of seminiferous cords containing multinucleated gonocytes and cord diameter was increased in DBP-exposed groups, compared with vehicle controls, with no difference between the three DBP-exposed groups.", "output": {"entities": {"chemical": [{"text": "DBP", "start": 108, "end": 111}, {"text": "DBP", "start": 197, "end": 200}]}}, "schema": []}
{"input": "Clustering of Leydig cells was seen in all DBP groups.", "output": {"entities": {"chemical": [{"text": "DBP", "start": 43, "end": 46}]}}, "schema": []}
{"input": "Lipid profile indicated that administration of canola and fish oil can increase the content of omega-3 fatty acids in rat testis.", "output": {"entities": {"chemical": [{"text": "omega-3 fatty acids", "start": 95, "end": 114}]}}, "schema": []}
{"input": "However, content of omega-3 was diminished in DBP-treated groups.", "output": {"entities": {"chemical": [{"text": "omega-3", "start": 20, "end": 27}, {"text": "DBP", "start": 46, "end": 49}]}}, "schema": []}
{"input": "Overall, our results indicate that different oily vehicles did not alter fetal rat testicular toxicity induced by a high DBP dose.", "output": {"entities": {"chemical": [{"text": "DBP", "start": 121, "end": 124}]}}, "schema": []}
{"input": "Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: Calorie restriction is the force to the cytotoxicity.", "output": {"entities": {"chemical": [{"text": "Resveratrol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The aim of this study was to examine the antitumour activity of resveratrol in human colorectal cancer cell lines (HCT116 and Caco2) and to explore its mechanism of action assuming that it is by calorie-restriction effect.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 64, "end": 75}]}}, "schema": []}
{"input": "Resveratrol inhibited the proliferation of colon cancer cells with half maximal inhibitory concentration (IC50) equal to 50 and 130 mu M for HCT116 and Caco2, respectively.", "output": {"entities": {"chemical": [{"text": "Resveratrol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Caco2 cells appeared with significant time-dependent increase in the glycolytic pathway, a behaviour that was absent in HCT116 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Resveratrol (100 mu M) significantly decreased the glycolytic enzymes (pyruvate kinase and lactate dehydrogenase) in Caco2 cells, while an increase in citrate synthase activity and a decrease in glucose consumption were observed in both cell lines.", "output": {"entities": {"chemical": [{"text": "Resveratrol", "start": 0, "end": 11}, {"text": "citrate", "start": 151, "end": 158}, {"text": "glucose", "start": 195, "end": 202}]}}, "schema": []}
{"input": "Moreover, resveratrol downregulated the expressions of leptin and c-Myc, and decreased the content of vascular endothelial growth factor.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 10, "end": 21}]}}, "schema": []}
{"input": "The apoptotic markers, caspases 3 and 8, were activated and the Bax/BCl2 ratio was increased.", "output": {"entities": {}}, "schema": []}
{"input": "The study suggested a promising anticancer activity of resveratrol, calorie-restriction pathway may be one of the driving forces for this activity.", "output": {"entities": {"chemical": [{"text": "resveratrol", "start": 55, "end": 66}]}}, "schema": []}
{"input": "Differential effects of organic and inorganic selenium compounds on adenosine deaminase activity and scavenger capacity in cerebral cortex slices of young rats.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 46, "end": 54}, {"text": "adenosine", "start": 68, "end": 77}]}}, "schema": []}
{"input": "Selenium (Se) has anti-inflammatory and antioxidant properties and is necessary for the development and normal function of the central nervous system.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 0, "end": 8}, {"text": "Se", "start": 10, "end": 12}]}}, "schema": []}
{"input": "This study was aimed to compare the in vitro effects of 3-methyl-1-phenyl-2-(phenylseleno) oct-2-en-1-one (C21H2HOSe; organoselenium) and sodium selenate (inorganic Se) on adenosine deaminase (ADA) activity, cell viability, lipid peroxidation, scavenger of nitric oxide (NO) and nonprotein thiols (NP-SH) content in the cerebral cortex slices of the young rats.", "output": {"entities": {"chemical": [{"text": "3-methyl-1-phenyl-2-(phenylseleno) oct-2-en-1-one", "start": 56, "end": 105}, {"text": "C21H2HOSe", "start": 107, "end": 116}, {"text": "organoselenium", "start": 118, "end": 132}, {"text": "sodium selenate", "start": 138, "end": 153}, {"text": "Se", "start": 165, "end": 167}, {"text": "adenosine", "start": 172, "end": 181}, {"text": "nitric oxide", "start": 257, "end": 269}, {"text": "NO", "start": 271, "end": 273}, {"text": "thiols", "start": 290, "end": 296}, {"text": "SH", "start": 301, "end": 303}]}}, "schema": []}
{"input": "A decrease in ADA activity was observed when the slices were exposed to organoselenium at the concentrations of 1, 10 and 30 micro M.", "output": {"entities": {"chemical": [{"text": "organoselenium", "start": 72, "end": 86}]}}, "schema": []}
{"input": "The same compound showed higher scavenger capacity of NO than the inorganic compound.", "output": {"entities": {"chemical": [{"text": "NO", "start": 54, "end": 56}]}}, "schema": []}
{"input": "Inorganic Se was able to protect against sodium nitroprusside-induced oxidative damage and increased the NP-SH content.", "output": {"entities": {"chemical": [{"text": "Se", "start": 10, "end": 12}, {"text": "sodium nitroprusside", "start": 41, "end": 61}, {"text": "SH", "start": 108, "end": 110}]}}, "schema": []}
{"input": "Both the compounds displayed distinctive antioxidant capacities and were not cytotoxic for the cerebral cortex slices in the conditions tested.", "output": {"entities": {}}, "schema": []}
{"input": "These findings are likely to be related to immunomodulatory and antioxidant properties of this compound.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of the Relative Propensities of Isoamyl Nitrite and Sodium Nitrite to Ameliorate Acute Cyanide Poisoning in Mice and a Novel Antidotal Effect Arising from Anesthetics.", "output": {"entities": {"chemical": [{"text": "Isoamyl Nitrite", "start": 43, "end": 58}, {"text": "Sodium Nitrite", "start": 63, "end": 77}, {"text": "Cyanide", "start": 98, "end": 105}]}}, "schema": []}
{"input": "Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote; therefore, the antidotal utility of this organic nitrite compared with sodium nitrite was investigated.", "output": {"entities": {"chemical": [{"text": "Isoamyl nitrite", "start": 0, "end": 15}, {"text": "cyanide", "start": 72, "end": 79}, {"text": "nitrite", "start": 139, "end": 146}, {"text": "sodium nitrite", "start": 161, "end": 175}]}}, "schema": []}
{"input": "To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally cyanide-challenged mice.", "output": {"entities": {"chemical": [{"text": "sodium nitrite", "start": 55, "end": 69}, {"text": "isoamyl nitrite", "start": 74, "end": 89}, {"text": "cyanide", "start": 155, "end": 162}]}}, "schema": []}
{"input": "Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the isoamyl nitrite to release nitrite anion.", "output": {"entities": {"chemical": [{"text": "isoamyl nitrite", "start": 74, "end": 89}, {"text": "isoamyl alchol", "start": 160, "end": 174}, {"text": "isoamyl nitrite", "start": 209, "end": 224}, {"text": "nitrite", "start": 236, "end": 243}]}}, "schema": []}
{"input": "Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to ameliorate sublethal cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to that of the control animals given only the toxicant.", "output": {"entities": {"chemical": [{"text": "sodium nitrite", "start": 30, "end": 44}, {"text": "cyanide", "start": 94, "end": 101}]}}, "schema": []}
{"input": "Aerosolized sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic nitrites for development as an inhaled cyanide antidote.", "output": {"entities": {"chemical": [{"text": "sodium nitrite", "start": 12, "end": 26}, {"text": "nitrites", "start": 119, "end": 127}, {"text": "cyanide", "start": 158, "end": 165}]}}, "schema": []}
{"input": "The inhaled sodium nitrite led to the production of NO in the bloodstream as determined by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin.", "output": {"entities": {"chemical": [{"text": "sodium nitrite", "start": 12, "end": 26}, {"text": "NO", "start": 52, "end": 54}]}}, "schema": []}
{"input": "The aerosol delivery was performed in an unmetered inhalation chamber, and in this study, no attempt was made to optimize the procedure.", "output": {"entities": {}}, "schema": []}
{"input": "It is argued that administration of an effective inhaled aqueous sodium nitrite dose in humans is possible, though just beyond the capability of current individual metered-dose inhaler designs, such as those used for asthma.", "output": {"entities": {"chemical": [{"text": "sodium nitrite", "start": 65, "end": 79}]}}, "schema": []}
{"input": "Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia leads to significantly prolonged survival compared to that of unanesthetized animals and that (ii) the antidotal activity of nitrite anion was completely abolished under anesthesia.", "output": {"entities": {"chemical": [{"text": "NaCN", "start": 47, "end": 51}, {"text": "nitrite", "start": 235, "end": 242}]}}, "schema": []}
{"input": "Plausible explanations for these effects in mice and their practical consequences in relation to testing putative cyanide antidotes are discussed.", "output": {"entities": {"chemical": [{"text": "cyanide", "start": 114, "end": 121}]}}, "schema": []}
{"input": "Biotransformation of 2, 2', 4, 4'-Tetrabromodiphenyl Ether (BDE-47) by Human Liver Microsomes: Identification of Cytochrome P450 2B6 as the Major Enzyme Involved.", "output": {"entities": {"chemical": [{"text": "2, 2', 4, 4'-Tetrabromodiphenyl Ether", "start": 21, "end": 58}, {"text": "BDE-47", "start": 60, "end": 66}]}}, "schema": []}
{"input": "Polybrominated diphenyl ethers (PBDEs) were widely used flame retardants that have become persistent environmental pollutants.", "output": {"entities": {"chemical": [{"text": "Polybrominated diphenyl ethers", "start": 0, "end": 30}, {"text": "PBDEs", "start": 32, "end": 37}]}}, "schema": []}
{"input": "In the present study, we investigated the in vitro oxidative metabolism of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), a major PBDE detected in human tissue and environmental samples.", "output": {"entities": {"chemical": [{"text": "2, 2', 4, 4'-tetrabromodiphenyl ether", "start": 75, "end": 112}, {"text": "BDE-47", "start": 114, "end": 120}, {"text": "PBDE", "start": 131, "end": 135}]}}, "schema": []}
{"input": "Biotransformation of BDE-47 by pooled and individual human liver microsomes and by human recombinant cytochrome P450 (P450) enzymes was assessed using a liquid chromatography/tandem mass spectrometry-based method.", "output": {"entities": {"chemical": [{"text": "BDE-47", "start": 21, "end": 27}]}}, "schema": []}
{"input": "Of the nine hydroxylated metabolites of BDE-47 produced by human liver microsomes, seven metabolites were identified using authentic standards.", "output": {"entities": {"chemical": [{"text": "BDE-47", "start": 40, "end": 46}]}}, "schema": []}
{"input": "A monohydroxy-tetrabrominated and a dihydroxy-tetrabrominated metabolite remain unidentified.", "output": {"entities": {"chemical": [{"text": "monohydroxy", "start": 2, "end": 13}, {"text": "dihydroxy", "start": 36, "end": 45}]}}, "schema": []}
{"input": "Kinetic analysis of the rates of metabolite formation revealed that the major metabolites were 5-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether (5-OH-BDE-47), 6-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether (6-OH-BDE-47), and possibly the unidentified monohydroxy-tetrabrominated metabolite.", "output": {"entities": {"chemical": [{"text": "5-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether", "start": 95, "end": 142}, {"text": "5-OH-BDE-47", "start": 144, "end": 155}, {"text": "6-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether", "start": 158, "end": 205}, {"text": "6-OH-BDE-47", "start": 207, "end": 218}, {"text": "monohydroxy", "start": 251, "end": 262}]}}, "schema": []}
{"input": "Among the human recombinant P450 enzymes tested, P450 2B6 was the most active enzyme in the formation of the hydroxylated metabolites of BDE-47.", "output": {"entities": {"chemical": [{"text": "BDE-47", "start": 137, "end": 143}]}}, "schema": []}
{"input": "Moreover, the formation of all metabolites of BDE-47 by pooled human liver microsomes was inhibited by a P450 2B6-specific antibody and was highly correlated with P450 2B6-mediated activity in single donor liver microsomes indicating that P450 2B6 was the major P450 responsible for the biotransformation of BDE-47.", "output": {"entities": {"chemical": [{"text": "BDE-47", "start": 46, "end": 52}, {"text": "BDE-47", "start": 308, "end": 314}]}}, "schema": []}
{"input": "Additional experiments involving the incubation of liver microsomes with individual monohydroxy-tetrabrominated metabolites in place of BDE-47 demonstrated that 2, 4-dibromophenol was a product of BDE-47 and several primary metabolites, but the dihydroxy-tetrabrominated metabolite was not formed by sequential hydroxylation of any of the monohydroxy-tetrabrominated metabolites tested.", "output": {"entities": {"chemical": [{"text": "monohydroxy", "start": 84, "end": 95}, {"text": "BDE-47", "start": 136, "end": 142}, {"text": "2, 4-dibromophenol", "start": 161, "end": 179}, {"text": "BDE-47", "start": 197, "end": 203}, {"text": "dihydroxy", "start": 245, "end": 254}, {"text": "monohydroxy", "start": 339, "end": 350}]}}, "schema": []}
{"input": "The present study provides a comprehensive characterization of the oxidative metabolism of BDE-47 by human liver microsomes and P450 2B6.", "output": {"entities": {"chemical": [{"text": "BDE-47", "start": 91, "end": 97}]}}, "schema": []}
{"input": "Flavonoids of Dikamali: A phytochemical reinvestigation.", "output": {"entities": {"chemical": [{"text": "Flavonoids", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Eleven known flavonoids (1-11) were isolated from Dikamali, the gum resin of Gardenia lucida.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 13, "end": 23}]}}, "schema": []}
{"input": "Three of them, desmethylnobiletin, pectolinarigenin and xanthomicrol, are a new report from this source.", "output": {"entities": {"chemical": [{"text": "desmethylnobiletin", "start": 15, "end": 33}, {"text": "pectolinarigenin", "start": 35, "end": 51}, {"text": "xanthomicrol", "start": 56, "end": 68}]}}, "schema": []}
{"input": "Nuclear magnetic resonance (NMR) data are being given for all the isolates.", "output": {"entities": {}}, "schema": []}
{"input": "For two of them, viz., 3', 4'-dimethoxywogonin and 4'-hydroxywogonin, such data have not been reported in literature.", "output": {"entities": {"chemical": [{"text": "3', 4'-dimethoxywogonin", "start": 23, "end": 46}, {"text": "4'-hydroxywogonin", "start": 51, "end": 68}]}}, "schema": []}
{"input": "Furthermore, correct NMR data are being provided for gardenin C as the data reported in literature were found to be incorrect.", "output": {"entities": {"chemical": [{"text": "gardenin C", "start": 53, "end": 63}]}}, "schema": []}
{"input": "New triterpene glycoside and other chemical constituents from the leaves of Swartzia apetala Raddi var. glabra.", "output": {"entities": {"chemical": [{"text": "triterpene glycoside", "start": 4, "end": 24}]}}, "schema": []}
{"input": "A new triterpene saponin (1) was isolated from a methanol extract of Swartzia apetala Raddi var. glabra, together with the flavonoids mauritianin (2), kaempferol (3) and the triterpene saponin beta-D-glucopyranosyl 3 beta-hydroxy-olean-12-en-28-oate (4).", "output": {"entities": {"chemical": [{"text": "triterpene saponin", "start": 6, "end": 24}, {"text": "methanol", "start": 49, "end": 57}, {"text": "flavonoids mauritianin", "start": 123, "end": 145}, {"text": "kaempferol", "start": 151, "end": 161}, {"text": "triterpene saponin beta-D-glucopyranosyl 3 beta-hydroxy-olean-12-en-28-oate", "start": 174, "end": 249}]}}, "schema": []}
{"input": "These compounds were characterised on the basis of their spectral data, mainly one-dimension (1D; (1) H, (13) C, APT) and two-dimension (2D; (1) H-(1) H-COSY, HMQC and HMBC) nuclear magnetic resonance (NMR) and HR-ESI-MS, and comparison with values in the literature.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 98, "end": 103}, {"text": "(13) C", "start": 105, "end": 111}, {"text": "(1) H", "start": 141, "end": 146}, {"text": "(1) H", "start": 147, "end": 152}]}}, "schema": []}
{"input": "The analysis by HR-ESI-MS showed a mass compatible with that of triterpene saponin 1.", "output": {"entities": {"chemical": [{"text": "triterpene saponin", "start": 64, "end": 82}]}}, "schema": []}
{"input": "This proposal was supported by molecular modelling.", "output": {"entities": {}}, "schema": []}
{"input": "LC-HR-ESI-MS experiment was also used to evaluate the purity of 1 and allowed to speculate about the possibility of the presence of 5 in very small quantity.", "output": {"entities": {}}, "schema": []}
{"input": "The extract and four compounds were assayed for antifungal activity against nine strains of Candida spp.", "output": {"entities": {}}, "schema": []}
{"input": "Measurements of Rate Constants for the OH Reactions with Bromoform (CHBr3), CHBr2Cl, CHBrCl2, and Epichlorohydrin (C3H5ClO).", "output": {"entities": {"chemical": [{"text": "OH", "start": 39, "end": 41}, {"text": "Bromoform", "start": 57, "end": 66}, {"text": "CHBr3", "start": 68, "end": 73}, {"text": "CHBr2Cl", "start": 76, "end": 83}, {"text": "CHBrCl2", "start": 85, "end": 92}, {"text": "Epichlorohydrin", "start": 98, "end": 113}, {"text": "C3H5ClO", "start": 115, "end": 122}]}}, "schema": []}
{"input": "Measurements of the rate constants for the gas phase reactions of OH radicals with bromoform (CHBr3) and epichlorohydrin (C3H5ClO) were performed using a flash photolysis resonance-fluorescence technique over the temperature range 230-370 K.", "output": {"entities": {"chemical": [{"text": "OH", "start": 66, "end": 68}, {"text": "bromoform", "start": 83, "end": 92}, {"text": "CHBr3", "start": 94, "end": 99}, {"text": "epichlorohydrin", "start": 105, "end": 120}, {"text": "C3H5ClO", "start": 122, "end": 129}]}}, "schema": []}
{"input": "The temperature dependences of the rate constants can be represented by the following expressions: kBF (230-370 K) = (9. 94 +/- 0. 76) x 10 (-13) exp [-(387 +/- 22)/T] cm (3) molecule (-1) s (-1) and kECH (230-370 K) = 1. 05 x 10 (-14) (T/298) (5. 16) exp (+ 1082/T) cm (3) molecule (-1) s (-1).", "output": {"entities": {}}, "schema": []}
{"input": "Rate constants for the reactions of OH with CHCl2Br and CHClBr2 were measured between 230 and 330 K.", "output": {"entities": {"chemical": [{"text": "OH", "start": 36, "end": 38}, {"text": "CHCl2Br", "start": 44, "end": 51}, {"text": "CHClBr2", "start": 56, "end": 63}]}}, "schema": []}
{"input": "They can be represented by the following expressions: kDCBM (230-330 K) = (9. 4 +/- 1. 3) x 10 (-13) exp [-(513 +/- 37)/T] cm (3) molecule (-1) s (-1) and kCDBM (230-330 K) = (9. 0 +/- 1. 9) x 10 (-13) exp [-(423 +/- 61)/T] cm (3) molecule (-1) s (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The atmospheric lifetimes due to reactions with tropospheric OH were estimated to be 57, 39, 72, and 96 days, respectively.", "output": {"entities": {"chemical": [{"text": "OH", "start": 61, "end": 63}]}}, "schema": []}
{"input": "The total atmospheric lifetimes of the Br-containing methanes due to both reaction with OH and photolysis were calculated to be 22, 50, and 67 days for CHBr3, CHClBr2, and CHCl2Br, respectively.", "output": {"entities": {"chemical": [{"text": "Br", "start": 39, "end": 41}, {"text": "methanes", "start": 53, "end": 61}, {"text": "OH", "start": 88, "end": 90}, {"text": "CHBr3", "start": 152, "end": 157}, {"text": "CHClBr2", "start": 159, "end": 166}, {"text": "CHCl2Br", "start": 172, "end": 179}]}}, "schema": []}
{"input": "Integrated chemical and biological analysis to explain estrogenic potency in bile extracts of red mullet (Mullus barbatus).", "output": {"entities": {}}, "schema": []}
{"input": "A biological screening was performed to establish the total exposure to estrogenic compounds of red mullet (Mullus barbatus) collected at several sites along the Spanish Mediterranean coast by testing male fish bile extracts using the in vitro ER-LUC reporter gene assay.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, major metabolites were identified and measurements of OH-PAHs (1-naphthol, 9-phenantrol, 9-fluorenol, 1-pyrenol, 1OH-BaP and 3OH-BaP) and alkylphenols (4-n-nonylphenol (4-n-NP) and 4-tertoctylphenol (4-tert-OP)) in the same fish bile extracts were taken by gas chromatography-mass spectrometry in electron ionization mode (GC-EI-MS).", "output": {"entities": {"chemical": [{"text": "OH-PAHs", "start": 67, "end": 74}, {"text": "1-naphthol", "start": 76, "end": 86}, {"text": "9-phenantrol", "start": 88, "end": 100}, {"text": "9-fluorenol", "start": 102, "end": 113}, {"text": "1-pyrenol", "start": 115, "end": 124}, {"text": "1OH-BaP", "start": 126, "end": 133}, {"text": "3OH-BaP", "start": 138, "end": 145}, {"text": "alkylphenols", "start": 151, "end": 163}, {"text": "4-n-nonylphenol", "start": 165, "end": 180}, {"text": "4-n-NP", "start": 182, "end": 188}, {"text": "4-tertoctylphenol", "start": 194, "end": 211}, {"text": "4-tert-OP", "start": 213, "end": 222}]}}, "schema": []}
{"input": "Relative in vitro estrogenic potencies of the chemically quantified compounds were also tested.", "output": {"entities": {}}, "schema": []}
{"input": "The highest biliary concentrations of 1-pyrenol, 9-fluorenol and 4-n-NP were found in fish from Barcelona and from the Mar Menor coastal lagoon.", "output": {"entities": {"chemical": [{"text": "1-pyrenol", "start": 38, "end": 47}, {"text": "9-fluorenol", "start": 49, "end": 60}, {"text": "4-n-NP", "start": 65, "end": 71}]}}, "schema": []}
{"input": "However, these concentrations can be considered relatively low compared to values reported in red mullet from other polluted waters in the Mediterranean Sea.", "output": {"entities": {}}, "schema": []}
{"input": "The contribution of 1-pyrenol, 4-n-NP and 4-tert-OP to the total estrogenic potency measured in male fish bile was found to be negligible, indicating the presence of other estrogenic compounds in red mullet bile.", "output": {"entities": {"chemical": [{"text": "1-pyrenol", "start": 20, "end": 29}, {"text": "4-n-NP", "start": 31, "end": 37}, {"text": "4-tert-OP", "start": 42, "end": 51}]}}, "schema": []}
{"input": "Estrogenic potency in bile from male fish was markedly elevated in Mar Menor lagoon (234. 8 +/- 5. 7pgE2EQ/mu l), and further research will be necessary to explain whether the presence of natural and synthetic-hormones in the lagoon contributed to this finding.", "output": {"entities": {}}, "schema": []}
{"input": "Values of approximately 15-16E2EQpg/mg bile can be regarded as preliminary baseline levels of bile estrogenicity in male red mullet from the western Mediterranean Sea.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant and anticancer activities of Chenopodium quinoa leaves extracts-In vitro study.", "output": {"entities": {}}, "schema": []}
{"input": "The nutraceutical potential of Chenopodium quinoa Leaves (ChL) was assessed through analyses of their phenolic content, elucidation of the effect of ChL phenolic compounds on cancer cell properties and estimation of their antioxidative activity, bioaccessibility and bioavailability in vitro.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 102, "end": 110}, {"text": "phenolic", "start": 153, "end": 161}]}}, "schema": []}
{"input": "Considerable amounts of ferulic, sinapinic and gallic acids, kaempferol, isorhamnetin and rutin were observed in the chemical ChL extract and were linked with its inhibitory effect on prostate cancer cell proliferation, motility and cellular competence for gap junctional communication.", "output": {"entities": {"chemical": [{"text": "ferulic, sinapinic and gallic acids", "start": 24, "end": 59}, {"text": "kaempferol", "start": 61, "end": 71}, {"text": "isorhamnetin", "start": 73, "end": 85}, {"text": "rutin", "start": 90, "end": 95}]}}, "schema": []}
{"input": "Both extracts, chemical and obtained after simulated digestion, exerted an inhibitory effect on lipoxygenase activity, paralleled by their considerable chelating, antioxidative, antiradical and reducing power.", "output": {"entities": {}}, "schema": []}
{"input": "These observations indicate that phenolic ChL compounds may exert a chemopreventive and anticarcinogenic effect on oxidative stress and ROS-dependent intracellular signaling via synergic effects.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 33, "end": 41}]}}, "schema": []}
{"input": "The relatively high potential bioaccessibility and bioavailability of the compounds probably responsible for these effects demonstrates the suitability of ChL for dietary supplementation.", "output": {"entities": {}}, "schema": []}
{"input": "An ultra-low dose of tetrahydrocannabinol provides cardioprotection.", "output": {"entities": {"chemical": [{"text": "tetrahydrocannabinol", "start": 21, "end": 41}]}}, "schema": []}
{"input": "Tetrahydrocannabinol (THC), the major psychoactive component of marijuana, is a cannabinoid agonist that exerts its effects by activating at least two specific receptors (CB1 and CB2) that belong to the seven transmembrane G-protein coupled receptor (GPCR) family.", "output": {"entities": {"chemical": [{"text": "Tetrahydrocannabinol", "start": 0, "end": 20}, {"text": "THC", "start": 22, "end": 25}]}}, "schema": []}
{"input": "Both CB1 and CB2 mRNA and proteins are present in the heart.", "output": {"entities": {}}, "schema": []}
{"input": "THC treatment was beneficial against hypoxia in neonatal cardiomyocytes in vitro.", "output": {"entities": {"chemical": [{"text": "THC", "start": 0, "end": 3}]}}, "schema": []}
{"input": "We also observed a neuroprotective effect of an ultra low dose of THC when applied to mice before brain insults.", "output": {"entities": {"chemical": [{"text": "THC", "start": 66, "end": 69}]}}, "schema": []}
{"input": "The present study was aimed to test and characterize the cardioprotective effects of a very low dose (0. 002mg/kg) of THC which is 3-4 orders of magnitude lower than the conventional doses, administered before myocardial infarction in mice in vivo.", "output": {"entities": {"chemical": [{"text": "THC", "start": 118, "end": 121}]}}, "schema": []}
{"input": "Three regimens of THC administration were tested: single THC application 2h or 48h before the induction of infarct, or 3 weeks continuous treatment before MI.", "output": {"entities": {"chemical": [{"text": "THC", "start": 18, "end": 21}, {"text": "THC", "start": 57, "end": 60}]}}, "schema": []}
{"input": "All protocols of THC administration were found to be beneficial.", "output": {"entities": {"chemical": [{"text": "THC", "start": 17, "end": 20}]}}, "schema": []}
{"input": "In the case of THC treatment 2h before MI, fractional shortening was elevated (37 +/- 4% vs. 42 +/- 1%, p < 0. 04), troponin T leakage to the blood was reduced (14 +/- 3ng/ml vs. 10 +/- 4ng/ml, p < 0. 008), infarct size decreased (29 +/- 4% vs. 23 +/- 4%, p < 0. 02), and the accumulation of neutrophils to the infarct area declined (36 +/- 10cells/field vs. 19 +/- 4cells/field, p < 0. 007) in THC-compared to vehicle-pretreated mice, 24h after MI.", "output": {"entities": {"chemical": [{"text": "THC", "start": 15, "end": 18}, {"text": "THC", "start": 395, "end": 398}]}}, "schema": []}
{"input": "ERK1/2 phosphorylation following infarct was also inhibited by pre-treatment with THC (p < 0. 01).", "output": {"entities": {"chemical": [{"text": "THC", "start": 82, "end": 85}]}}, "schema": []}
{"input": "CONCLUSION: A single ultra low dose of THC before ischemia is a safe and effective treatment that reduces myocardial ischemic damage.", "output": {"entities": {"chemical": [{"text": "THC", "start": 39, "end": 42}]}}, "schema": []}
{"input": "Systematic evaluation of 640 FDA drugs for their effect on CD4 (+) Foxp3 (+) regulatory T cells using a novel cell-based high throughput screening assay.", "output": {"entities": {}}, "schema": []}
{"input": "Regulatory T cells (Treg), which play a pivotal role in maintaining immune homeostasis by suppressing the proliferation of effector T cells, have great therapeutic potential for autoimmune diseases and transplantation.", "output": {"entities": {}}, "schema": []}
{"input": "However, progress on their clinical application has been hampered by the lack of high throughput screening (HTS) strategies for the systematic and rapid evaluation of existing drugs and the identification of novel drug candidates.", "output": {"entities": {}}, "schema": []}
{"input": "In this report, we present an innovative in vitro HTS assay using CD4 (+) T cells from Foxp3-GFP transgenic mice that specifically express the GFP signal in Foxp3 (+) Treg cells detectable by FACS analysis in a high throughput manner.", "output": {"entities": {}}, "schema": []}
{"input": "Systematic evaluation of 640 FDA-approved drugs revealed that 70 drugs increased the number of Treg cells with suppression function only in the presence of TGF beta, 75 drugs increased Treg numbers even in the absence of TGF beta, and 32 drugs increased Treg numbers synergistically with TGF beta.", "output": {"entities": {}}, "schema": []}
{"input": "The identified Treg-promoting drugs include those previously known to induce Treg (rapamycin and retinoic acid), statins, glucocorticoids and drugs in many other categories.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 83, "end": 92}, {"text": "retinoic acid)", "start": 97, "end": 111}]}}, "schema": []}
{"input": "Furthermore, Treg cells cultured with the identified drugs possess surface and intracellular markers characteristic of natural Treg cells and possess suppressive function.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that this Treg HTS assay can be used to screen compound libraries to identify novel chemical entities for Treg-based immune therapies.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of a Cimicifuga racemosa extracts Ze 450 in the treatment of climacteric complaints-an observational study.", "output": {"entities": {"chemical": [{"text": "Ze 450", "start": 45, "end": 51}]}}, "schema": []}
{"input": "BACKGROUND: Root extracts of Cimicifuga racemosa (L.) Nutt. have been successfully used in the treatment of climacteric complaints.", "output": {"entities": {}}, "schema": []}
{"input": "METHOD: In this observational study, Cimicifuga racemosa (CR) extract Ze 450 was studied in 442 unselected ambulatory female outpatients with menopausal complaints under daily practice conditions.", "output": {"entities": {"chemical": [{"text": "Ze 450", "start": 70, "end": 76}]}}, "schema": []}
{"input": "Physicians were suggested to treat patients for the first 3 months with 13mg/d CR (high dose, HD) and to continue over additional 6 months either with this treatment or to switch to 6. 5mg/d CR (low dose, LD).", "output": {"entities": {}}, "schema": []}
{"input": "The choice of treatment and its dose, however, was fully at the discretion of the physician.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: After 3-months treatment with HD, symptom severity (Kupperman Menopause Index, KMI) decreased significantly (p < 0. 001) from baseline values.", "output": {"entities": {}}, "schema": []}
{"input": "Continuation of treatment with HD or LD decreased total KMI and its sub-item scores further (HD, LD: p < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "However, more patients (84. 9%) responded to HD than to LD (78. 4%) and showed an improvement of symptoms (p = 0. 011).", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: This observational study demonstrated that treatment with CR in unselected patients with climacteric complaints under the conditions of daily practice resulted in a significant improvement of menopausal symptoms assessed by the total KMI score and its sub-item scores with an effect size similar to that in a previous randomized, controlled clinical trial.", "output": {"entities": {}}, "schema": []}
{"input": "Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria.", "output": {"entities": {"chemical": [{"text": "beta-lactam", "start": 114, "end": 125}]}}, "schema": []}
{"input": "The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution.", "output": {"entities": {}}, "schema": []}
{"input": "The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli.", "output": {"entities": {"chemical": [{"text": "ampicillin", "start": 107, "end": 117}, {"text": "piperacillin", "start": 119, "end": 131}, {"text": "cefazolin", "start": 133, "end": 142}, {"text": "cefuroxime", "start": 144, "end": 154}, {"text": "carbenicillin", "start": 156, "end": 169}, {"text": "ceftazidime", "start": 171, "end": 182}, {"text": "meropenem", "start": 184, "end": 193}]}}, "schema": []}
{"input": "In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations.", "output": {"entities": {}}, "schema": []}
{"input": "Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils.", "output": {"entities": {}}, "schema": []}
{"input": "Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC <= 0. 5) and 31 pairs showed no interaction (FIC > 0. 5-4. 0).", "output": {"entities": {}}, "schema": []}
{"input": "The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0. 26-0. 5.", "output": {"entities": {"chemical": [{"text": "piperacillin", "start": 109, "end": 121}, {"text": "piperacillin", "start": 141, "end": 153}, {"text": "piperacillin", "start": 168, "end": 180}, {"text": "meropenem", "start": 207, "end": 216}]}}, "schema": []}
{"input": "The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent.", "output": {"entities": {}}, "schema": []}
{"input": "Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance.", "output": {"entities": {"chemical": [{"text": "beta-lactam", "start": 131, "end": 142}]}}, "schema": []}
{"input": "Two new tryptophan derivatives from the seed kernels of Entada rheedei: Effects on cell viability and HIV infectivity.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 8, "end": 18}]}}, "schema": []}
{"input": "Two new tryptophan derivatives, N-sulfonyl-L-tryptophan (tryptorheedei A) (1) and 3-(N-sulfonylindolyl)-D-lactic acid (tryptorheedei B) (2) together with the known 5-O-beta-D-glucopyranosyl-2-hydroxyphenylacetic acid (3), 1-O-methylglucopyranoside, entadamide A, homogentisic acid and 3-O-beta-D-glucopyranosyl-beta-sitosterol, were isolated from the seed kernels of Entada rheedei (Mimosaceae).", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 8, "end": 18}, {"text": "N-sulfonyl-L-tryptophan", "start": 32, "end": 55}, {"text": "tryptorheedei A", "start": 57, "end": 72}, {"text": "3-(N-sulfonylindolyl)-D-lactic acid", "start": 82, "end": 117}, {"text": "tryptorheedei B", "start": 119, "end": 134}, {"text": "5-O-beta-D-glucopyranosyl-2-hydroxyphenylacetic acid", "start": 164, "end": 216}, {"text": "1-O-methylglucopyranoside", "start": 222, "end": 247}, {"text": "entadamide A", "start": 249, "end": 261}, {"text": "homogentisic acid", "start": 263, "end": 280}, {"text": "3-O-beta-D-glucopyranosyl-beta-sitosterol", "start": 285, "end": 326}]}}, "schema": []}
{"input": "Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry and by comparison with spectroscopic data reported in the literature.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1 and 2 showed no toxicity to TZM and Human PBMC cells.", "output": {"entities": {}}, "schema": []}
{"input": "Both compounds 1 and 2 were found to promote early infection events in HIV, likely by inhibiting the enzyme indolamine 2, 3-dioxygenase (IDO) and preventing tryptophan depletion.", "output": {"entities": {"chemical": [{"text": "indolamine", "start": 108, "end": 118}, {"text": "tryptophan", "start": 157, "end": 167}]}}, "schema": []}
{"input": "Inhibition of IDO acutely in HIV infection inhibits viral replication, but chronic activation of IDO leads to immune impairment in AIDS.", "output": {"entities": {}}, "schema": []}
{"input": "IDO is also the gatekeeper enzyme for kynurenine metabolism, a pathway involved in serotonin and melatonin biosynthesis and the regulation of glutamate and dopamine levels in the brain.", "output": {"entities": {"chemical": [{"text": "kynurenine", "start": 38, "end": 48}, {"text": "serotonin", "start": 83, "end": 92}, {"text": "glutamate", "start": 142, "end": 151}, {"text": "dopamine", "start": 156, "end": 164}]}}, "schema": []}
{"input": "Therefore inhibition of IDO might explain both the reported medicinal and neuropsychiatric effects of E. rheedei.", "output": {"entities": {}}, "schema": []}
{"input": "The conjugation of microcystin-RR by human recombinant GSTs and hepatic cytosol.", "output": {"entities": {"chemical": [{"text": "microcystin-RR", "start": 19, "end": 33}]}}, "schema": []}
{"input": "Many cyanobacterial species can produce cyanotoxins, among which mycrocistins (MC) are a group of =~ 100 congeners of hepatotoxic cyclic heptapeptides.", "output": {"entities": {"chemical": [{"text": "mycrocistins", "start": 65, "end": 77}, {"text": "cyclic heptapeptides", "start": 130, "end": 150}]}}, "schema": []}
{"input": "MC-RR differs from MC-LR, the most studied congener only for one residue (arginine vs leucine), resulting in a ten-fold difference in the acute toxicity in mice.", "output": {"entities": {"chemical": [{"text": "MC-RR", "start": 0, "end": 5}, {"text": "MC-LR", "start": 19, "end": 24}, {"text": "arginine", "start": 74, "end": 82}, {"text": "leucine", "start": 86, "end": 93}]}}, "schema": []}
{"input": "Although humans may be exposed to MC through several routes and kinetics appeared to be the major factor affecting congener-specific toxicity, little is known on MC metabolism.", "output": {"entities": {}}, "schema": []}
{"input": "The accepted pathway for MC detoxication is GSH conjugation: here the MC-RR conjugation with GSH catalyzed by 5 recombinant human GSTs and human liver cytosol (HLC) has been characterized and appeared to be more efficient than MC-LR conjugation.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 44, "end": 47}, {"text": "MC-RR", "start": 70, "end": 75}, {"text": "GSH", "start": 93, "end": 96}, {"text": "MC-LR", "start": 227, "end": 232}]}}, "schema": []}
{"input": "The catalytic efficiency score is T1-1 > A1-1 =~ P1-1 > M1-1 > A3-3 (0. 161-0. 056pmol GSMC-RR (mu gproteinmin mu M) (-1)).", "output": {"entities": {}}, "schema": []}
{"input": "In HLC the spontaneous reaction is favored vs the enzymatic one (ratio 3: 1) at physiological GSH content.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 94, "end": 97}]}}, "schema": []}
{"input": "However, at low MC-RR concentrations, representative of repeated oral exposure, and low GSH content (down to 0. 05mM), possibly associated to exposure to drugs or in patients affected by several pathologies, the relevance of the enzymatic reaction progressively increases, providing the predominant contribution to MC-RR detoxication.", "output": {"entities": {"chemical": [{"text": "MC-RR", "start": 16, "end": 21}, {"text": "GSH", "start": 88, "end": 91}, {"text": "MC-RR", "start": 315, "end": 320}]}}, "schema": []}
{"input": "Activating glucocorticoid receptor-ERK signaling pathway contributes to ginsenoside Rg1 protection against beta-amyloid peptide-induced human endothelial cells apoptosis.", "output": {"entities": {"chemical": [{"text": "ginsenoside Rg1", "start": 72, "end": 87}]}}, "schema": []}
{"input": "The deposition of beta-amyloid (A beta) in neurons and vascular cells of the brain has been characterized in Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Ginsenoside Rg1 (Rg1) is an active components in Panax ginseng, a famous traditional Chinese medicines recorded in Compendium of Materia Medica.", "output": {"entities": {"chemical": [{"text": "Ginsenoside Rg1", "start": 0, "end": 15}, {"text": "Rg1", "start": 17, "end": 20}]}}, "schema": []}
{"input": "Present study attempted to evaluate the potential mechanisms of A beta-mediated insult and the protective effects of Rg1 on human endothelial cells.", "output": {"entities": {"chemical": [{"text": "Rg1", "start": 117, "end": 120}]}}, "schema": []}
{"input": "Rg1 attenuated the A beta 25-35-associated mitochondrial apoptotic events, accompanied by inhibiting HIF-1 alpha expression followed by intracellular reactive nitrogen species generation, and protein nitrotyrosination.", "output": {"entities": {"chemical": [{"text": "Rg1", "start": 0, "end": 3}, {"text": "nitrogen", "start": 159, "end": 167}]}}, "schema": []}
{"input": "These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or p-ERK inhibitor U0126 rather than estrogen receptor alpha antagonist ICI 82, 780.", "output": {"entities": {"chemical": [{"text": "RU486", "start": 83, "end": 88}, {"text": "U0126", "start": 108, "end": 113}, {"text": "estrogen", "start": 126, "end": 134}, {"text": "ICI 82, 780", "start": 161, "end": 172}]}}, "schema": []}
{"input": "Taken together, our results suggested that Rg1 protected against A beta 25-35-induced apoptosis at least in part by two complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating HIF-1 alpha initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades.", "output": {"entities": {"chemical": [{"text": "Rg1", "start": 43, "end": 46}]}}, "schema": []}
{"input": "These data provided a novel insight to the mechanisms of Rg1protective effects on A beta 25-35-induced endothelial cells apoptosis, suggesting that GR-ERK signaling pathway might play an important role in it.", "output": {"entities": {"chemical": [{"text": "Rg1protective", "start": 57, "end": 70}]}}, "schema": []}
{"input": "Exposure to 2, 4-dichlorophenoxyacetic acid alters glucose metabolism in immature rat Sertoli cells.", "output": {"entities": {"chemical": [{"text": "2, 4-dichlorophenoxyacetic acid", "start": 12, "end": 43}, {"text": "glucose", "start": 51, "end": 58}]}}, "schema": []}
{"input": "The purpose of this study was to determine the effects of 2, 4-D, an herbicide used worldwide also known as endocrine disruptor, in Sertoli cell (SC) metabolism.", "output": {"entities": {"chemical": [{"text": "2, 4-D", "start": 58, "end": 64}]}}, "schema": []}
{"input": "Immature rat SCs were maintained 50h under basal conditions or exposed to 2, 4-D (100nM, 10 mu M and 1mM).", "output": {"entities": {"chemical": [{"text": "2, 4-D", "start": 74, "end": 80}]}}, "schema": []}
{"input": "SCs exposed to 10 mu M and 1mM of 2, 4-D presented lower intracellular glucose and lactate content.", "output": {"entities": {"chemical": [{"text": "2, 4-D", "start": 34, "end": 40}, {"text": "glucose", "start": 71, "end": 78}, {"text": "lactate", "start": 83, "end": 90}]}}, "schema": []}
{"input": "Exposure to 10 mu M of 2, 4-D induced a significant decrease in glucose transporter-3 mRNA levels and phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10 mu M of 2, 4-D.", "output": {"entities": {"chemical": [{"text": "2, 4-D", "start": 23, "end": 29}, {"text": "glucose", "start": 64, "end": 71}, {"text": "2, 4-D", "start": 187, "end": 193}]}}, "schema": []}
{"input": "Exposure to 100nM and 10 mu M also induced a decrease in lactate dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased in cells exposed to 1mM of 2, 4-D.", "output": {"entities": {"chemical": [{"text": "lactate", "start": 57, "end": 64}, {"text": "2, 4-D", "start": 173, "end": 179}]}}, "schema": []}
{"input": "Exposure to 2, 4-D altered glucose uptake and metabolization in SCs, as well as lactate metabolism and export that may result in impaired spermatogenesis.", "output": {"entities": {"chemical": [{"text": "2, 4-D", "start": 12, "end": 18}, {"text": "glucose", "start": 27, "end": 34}, {"text": "lactate", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Synthesis of some novel thieno [3, 2-d] pyrimidines as potential cytotoxic small molecules against breast cancer.", "output": {"entities": {"chemical": [{"text": "thieno [3, 2-d] pyrimidines", "start": 24, "end": 51}]}}, "schema": []}
{"input": "A variety of novel thieno [3, 2-d] pyrimidines with different decorating functional groups were synthesized as a part of a study aiming to enrich the arsenal of chemotherapeutic agents for the treatment of cancer.", "output": {"entities": {"chemical": [{"text": "thieno [3, 2-d] pyrimidines", "start": 19, "end": 46}]}}, "schema": []}
{"input": "The design of synthetic molecules based on DNA-interchelating properties by hydrogen bond formation.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 76, "end": 84}]}}, "schema": []}
{"input": "The reported compounds herein are: 4-aminothienopyrimidine derivatives 4a, b and their 4-substituted phenylamino analogues 8a, b; 4-thienopyrimidin-4-ones 5a, b; N-alkyl thienopyrimidin-4-ones 6a-g; 4-chlorothienopyrimidines 7a, b; and thienopyrimidoquinazolinones 9a, b which are the structural mimics of 8a, b.", "output": {"entities": {"chemical": [{"text": "4-aminothienopyrimidine", "start": 35, "end": 58}, {"text": "4-substituted phenylamino", "start": 87, "end": 112}, {"text": "4-thienopyrimidin-4-ones", "start": 130, "end": 154}, {"text": "N-alkyl thienopyrimidin-4-ones", "start": 162, "end": 192}, {"text": "4-chlorothienopyrimidines", "start": 199, "end": 224}, {"text": "thienopyrimidoquinazolinones", "start": 236, "end": 264}]}}, "schema": []}
{"input": "The synthesized molecules were evaluated for their in vitro cytotoxic activity against human breast cancer cell line (MCF-7).", "output": {"entities": {}}, "schema": []}
{"input": "Biological screening revealed varying cytotoxic potencies of the tested molecules compared with Doxorubicin as a reference drug.", "output": {"entities": {"chemical": [{"text": "Doxorubicin", "start": 96, "end": 107}]}}, "schema": []}
{"input": "The cytotoxicity results from the study suggested that the synthesized molecules are potential antitumor agents and compound 4a was the most potent with an IC 50 2. 04 nM.", "output": {"entities": {}}, "schema": []}
{"input": "Cadmium Tolerance and Removal from Cunninghamella elegans Related to the Polyphosphate Metabolism.", "output": {"entities": {"chemical": [{"text": "Cadmium", "start": 0, "end": 7}]}}, "schema": []}
{"input": "The aim of the present work was to study the cadmium effects on growth, ultrastructure and polyphosphate metabolism, as well as to evaluate the metal removal and accumulation by Cunninghamella elegans (IFM 46109) growing in culture medium.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 45, "end": 52}]}}, "schema": []}
{"input": "The presence of cadmium reduced growth, and a longer lag phase was observed.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 16, "end": 23}]}}, "schema": []}
{"input": "However, the phosphate uptake from the culture medium increased 15% when compared to the control.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 13, "end": 22}]}}, "schema": []}
{"input": "Moreover, C. elegans removed 70%-81% of the cadmium added to the culture medium during its growth.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 44, "end": 51}]}}, "schema": []}
{"input": "The C. elegans mycelia showed a removal efficiency of 280 mg/g at a cadmium concentration of 22. 10 mg/L, and the removal velocity of cadmium was 0. 107 mg/h.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 68, "end": 75}, {"text": "cadmium", "start": 134, "end": 141}]}}, "schema": []}
{"input": "Additionally, it was observed that cadmium induced vacuolization, the presence of electron dense deposits in vacuoles, cytoplasm and cell membranes, as well as the distinct behavior of polyphosphate fractions.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 35, "end": 42}]}}, "schema": []}
{"input": "The results obtained with C. elegans suggest that precipitation, vacuolization and polyphosphate fractions were associated to cadmium tolerance, and this species demonstrated a higher potential for bioremediation of heavy metals.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 126, "end": 133}]}}, "schema": []}
{"input": "Chemical Stability of the Lipid Phase in Concentrated Beverage Emulsions Colored with Natural beta-Carotene.", "output": {"entities": {"chemical": [{"text": "beta-Carotene", "start": 94, "end": 107}]}}, "schema": []}
{"input": "The aim of this study was to examine the oxidation of selected plant oils in concentrated beverage emulsions colored with natural beta-carotene.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 130, "end": 143}]}}, "schema": []}
{"input": "Carotenoid preparations obtained from carrots were dissolved in cold-pressed linseed oil, refined canola oil, and refined palm olein.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative stability of the lipids was examined with and without addition of the pigment to the oil/water (O/W) emulsion.", "output": {"entities": {}}, "schema": []}
{"input": "Carotenoid/lipid hydro peroxide (LOOH) concentration was evaluated using two different methods: LOOH + Fe (2 +) reaction connected with a colored complex of ammonium thiocyanate determined with the help of a spectrophotometer, and LOOH determined with the help of a chemiluminometer.", "output": {"entities": {"chemical": [{"text": "hydro peroxide", "start": 17, "end": 31}, {"text": "Fe (2 +)", "start": 103, "end": 111}, {"text": "ammonium thiocyanate", "start": 157, "end": 177}]}}, "schema": []}
{"input": "It was shown that oxidation rate of lipids in the O/W emulsions strongly depended on chemical composition of the lipid fraction (type of oil used).", "output": {"entities": {}}, "schema": []}
{"input": "Presence of the carotenoid pigment increased the rate.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, if a carotenoid-containing emulsion is to be stable, it should be based on oils of a high oxidative stability.", "output": {"entities": {}}, "schema": []}
{"input": "The Relationship Between Serum Calcium Level, Blood Lipids, and Blood Pressure in Hypertensive and Normotensive Subjects who Come from a Normal University in East of China.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 31, "end": 38}]}}, "schema": []}
{"input": "Previous studies revealed that low calcium intake is related to high prevalence of cardiovascular diseases such as hypertension.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 35, "end": 42}]}}, "schema": []}
{"input": "However, the relationship between serum calcium and blood pressure was unclear.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 40, "end": 47}]}}, "schema": []}
{"input": "The prevalence of hypertension is high in China.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the aim of this study was to evaluate the serum calcium level between hypertensive and normotensive groups and to investigate the correlation between serum calcium, blood pressure, and blood lipid parameters.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 54, "end": 61}, {"text": "calcium", "start": 162, "end": 169}]}}, "schema": []}
{"input": "A total of 1, 135 adult subjects participated in this study and were divide into two study groups: a hypertensive group (n = 316) who had 140 mmHg or higher in systolic blood pressure (SBP) or 90 mmHg or higher in diastolic blood pressure (DBP) and an age-and sex-matched normotensive group (n = 819, 120 mmHg or less SBP and 80 mmHg or less DBP).", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate a significant trend for men (60 years old or older) in the direction of decreasing blood pressure with increasing serum calcium level, but no trend for women was indicated.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 141, "end": 148}]}}, "schema": []}
{"input": "In the normotensive group, a significant positive correlation was found between DBP and total cholesterol (P < 0. 01) and triglyceride (P < 0. 01), Likewise, triglyceride was positively correlated with SBP (P < 0. 01).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 94, "end": 105}, {"text": "triglyceride", "start": 122, "end": 134}, {"text": "triglyceride", "start": 158, "end": 170}]}}, "schema": []}
{"input": "Overall, these data suggest that serum calcium may have an influence in the blood pressure of older male subjects with hypertension and in blood lipid profiles of normotensive subjects.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 39, "end": 46}]}}, "schema": []}
{"input": "Inhibitors of bacterial tubulin target bacterial membranes in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "FtsZ is a homolog of eukaryotic tubulin that is widely conserved among bacteria and coordinates the assembly of the cell division machinery.", "output": {"entities": {}}, "schema": []}
{"input": "FtsZ plays a central role in cell replication and is a target of interest for antibiotic development.", "output": {"entities": {}}, "schema": []}
{"input": "Several FtsZ inhibitors have been reported.", "output": {"entities": {}}, "schema": []}
{"input": "We characterized the mechanism of these compounds in bacteria and found that many of them disrupt the localization of membrane-associated proteins, including FtsZ, by reducing the transmembrane potential or perturbing membrane permeability.", "output": {"entities": {}}, "schema": []}
{"input": "We tested whether the reported phenotypes of a broad collection of FtsZ inhibitors disrupt the transmembrane potential in Bacillus subtilis strain 168.", "output": {"entities": {}}, "schema": []}
{"input": "Using a combination of flow cytometry and microscopy, we found that zantrin Z1, cinnamaldehyde, totarol, sanguinarine, and viriditoxin decreased the B. subtilis transmembrane potential or perturbed membrane permeability, and influenced the localization of the membrane-associated, division protein MinD.", "output": {"entities": {"chemical": [{"text": "zantrin Z1", "start": 68, "end": 78}, {"text": "cinnamaldehyde", "start": 80, "end": 94}, {"text": "totarol", "start": 96, "end": 103}, {"text": "sanguinarine", "start": 105, "end": 117}, {"text": "viriditoxin", "start": 123, "end": 134}]}}, "schema": []}
{"input": "These studies demonstrate that small molecules that disrupt membrane function in bacterial cells produce phenotypes that are similar to the inhibition of proteins associated with membranes in vivo, including bacterial cytoskeleton homologs, such as FtsZ.", "output": {"entities": {}}, "schema": []}
{"input": "The results provide a new dimension for consideration in the design and testing of inhibitors of bacterial targets that are membrane-associated and provide additional insight into the structural characteristics of antibiotics that disrupt the membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Transfer of lipids to high-density lipoprotein (HDL) is altered in patients with familial hypercholesterolemia.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE: In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts.", "output": {"entities": {}}, "schema": []}
{"input": "Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in FH patients.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 109, "end": 120}]}}, "schema": []}
{"input": "METHODS: Seventy-one FH patients (39 +/- 15years, LDL-cholesterol = 274 +/- 101; HDL-cholesterol = 50 +/- 14mg/dl) and 66 normolipidemic subjects (NL) (38 +/- 11years, LDL-cholesterol = 105 +/- 27; HDL-cholesterol = 52 +/- 12mg/dl) were studied.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 54, "end": 65}, {"text": "cholesterol", "start": 85, "end": 96}, {"text": "cholesterol", "start": 172, "end": 183}, {"text": "cholesterol", "start": 202, "end": 213}]}}, "schema": []}
{"input": "In vitro, lipid transfers were evaluated by incubation of plasma samples (37 degrees C, 1h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL).", "output": {"entities": {"chemical": [{"text": "3H-triglycerides", "start": 137, "end": 153}, {"text": "14C", "start": 163, "end": 166}, {"text": "cholesterol", "start": 180, "end": 191}, {"text": "3H-cholesteryl ester", "start": 205, "end": 225}, {"text": "14C", "start": 235, "end": 238}]}}, "schema": []}
{"input": "Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion.", "output": {"entities": {}}, "schema": []}
{"input": "Data are% of total radioactivity measured in the HDL fraction.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Transfer of UC to HDL was lower in FH than in NL (5. 6 +/- 2. 1 vs 6. 7 +/- 2. 0%, p = 0. 0005) whereas TG (5. 5 +/- 3. 1 vs 3. 7 +/- 0. 9%, p = 0. 018) and PL (20. 9 +/- 4. 6 vs 18. 2 +/- 3. 7%, p = 0. 023) transfers were higher in FH.", "output": {"entities": {}}, "schema": []}
{"input": "EC transfer was equal.", "output": {"entities": {}}, "schema": []}
{"input": "By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 75, "end": 86}]}}, "schema": []}
{"input": "CONCLUSION: FH elicited marked changes in three of the four tested lipid transfers to HDL.", "output": {"entities": {}}, "schema": []}
{"input": "The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis and biological activity of multifunctional alpha, beta-unsaturated carbonyl scaffolds for Alzheimer' s disease.", "output": {"entities": {"chemical": [{"text": "alpha, beta-unsaturated carbonyl", "start": 61, "end": 93}]}}, "schema": []}
{"input": "A series of compounds containing an alpha, beta-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer' s disease (AD) agents.", "output": {"entities": {"chemical": [{"text": "alpha, beta-unsaturated carbonyl", "start": 36, "end": 68}, {"text": "chalcones", "start": 85, "end": 94}, {"text": "coumarins", "start": 99, "end": 108}]}}, "schema": []}
{"input": "The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (A beta) self-assembly and the disassembly of preformed A beta oligomers.", "output": {"entities": {}}, "schema": []}
{"input": "Several compounds showed excellent potential as multifunctional compounds for AD.", "output": {"entities": {}}, "schema": []}
{"input": "Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.", "output": {"entities": {"chemical": [{"text": "coumarin", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth.", "output": {"entities": {}}, "schema": []}
{"input": "Glioblastomas (GBMs) are highly vascular and lethal brain tumors that display cellular hierarchies containing self-renewing tumorigenic glioma stem cells (GSCs).", "output": {"entities": {}}, "schema": []}
{"input": "Because GSCs often reside in perivascular niches and may undergo mesenchymal differentiation, we interrogated GSC potential to generate vascular pericytes.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that GSCs give rise to pericytes to support vessel function and tumor growth.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo cell lineage tracing with constitutive and lineage-specific fluorescent reporters demonstrated that GSCs generate the majority of vascular pericytes.", "output": {"entities": {}}, "schema": []}
{"input": "Selective elimination of GSC-derived pericytes disrupts the neovasculature and potently inhibits tumor growth.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of human GBM specimens showed that most pericytes are derived from neoplastic cells.", "output": {"entities": {}}, "schema": []}
{"input": "GSCs are recruited toward endothelial cells via the SDF-1/CXCR4 axis and are induced to become pericytes predominantly by transforming growth factor beta.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, GSCs contribute to vascular pericytes that may actively remodel perivascular niches.", "output": {"entities": {}}, "schema": []}
{"input": "Therapeutic targeting of GSC-derived pericytes may effectively block tumor progression and improve antiangiogenic therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains.", "output": {"entities": {"chemical": [{"text": "Pyridinone", "start": 6, "end": 16}, {"text": "Nucleoside", "start": 36, "end": 46}]}}, "schema": []}
{"input": "Novel 6-substituted-4-cycloalkyloxy-pyridin-2 (1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated.", "output": {"entities": {"chemical": [{"text": "6-substituted-4-cycloalkyloxy-pyridin-2 (1H)-ones", "start": 6, "end": 55}, {"text": "nucleoside", "start": 80, "end": 90}]}}, "schema": []}
{"input": "Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs).", "output": {"entities": {"chemical": [{"text": "3-isopropyl", "start": 55, "end": 66}, {"text": "3-iodine", "start": 71, "end": 79}]}}, "schema": []}
{"input": "The diastereoisomers of 26-trans and 26-cis were synthesized separately and confirmed with HPLC and NOESY spectra.", "output": {"entities": {}}, "schema": []}
{"input": "The 26-trans isomers had an activity about 400-fold more potent than that of 26-cis.", "output": {"entities": {}}, "schema": []}
{"input": "The pair of 26-trans enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity index (SI) of 75000, was highly effective against a panel of RTIs-resistant strains with single (Y181C and K103N) or double (A17) mutations in reverse transcriptase.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest that these novel pyridinone derivatives have the potential to be further developed as new antiretroviral drugs with improved antiviral efficacy and drug resistance profile.", "output": {"entities": {"chemical": [{"text": "pyridinone", "start": 37, "end": 47}]}}, "schema": []}
{"input": "Antiallodynic and Analgesic Effects of Maslinic Acid, a Pentacyclic Triterpenoid from Olea europaea.", "output": {"entities": {"chemical": [{"text": "Maslinic Acid", "start": 39, "end": 52}, {"text": "Pentacyclic Triterpenoid", "start": 56, "end": 80}]}}, "schema": []}
{"input": "The effects of maslinic acid (1), a pentacyclic triterpenoid obtained from Olea europaea, were studied in several tests for nociception in mice.", "output": {"entities": {"chemical": [{"text": "maslinic acid", "start": 15, "end": 28}, {"text": "pentacyclic triterpenoid", "start": 36, "end": 60}]}}, "schema": []}
{"input": "Systemic administration of 1 reduced acetic acid-induced writhing, the inflammatory phase of formalin-induced pain, and capsaicin-induced mechanical allodynia.", "output": {"entities": {"chemical": [{"text": "acetic acid", "start": 37, "end": 48}, {"text": "formalin", "start": 93, "end": 101}, {"text": "capsaicin", "start": 120, "end": 129}]}}, "schema": []}
{"input": "However, it did not induce motor incoordination in the rotarod test.", "output": {"entities": {}}, "schema": []}
{"input": "The topical administration of 1 also reduced the inflammatory phase of the formalin test, indicating that at least some of its effects are mediated peripherally.", "output": {"entities": {"chemical": [{"text": "formalin", "start": 75, "end": 83}]}}, "schema": []}
{"input": "The present results demonstrate for the first time that maslinic acid induces antinociceptive and antiallodynic effects.", "output": {"entities": {"chemical": [{"text": "maslinic acid", "start": 56, "end": 69}]}}, "schema": []}
{"input": "Emergence of Glass-like Behavior in Markov State Models of Protein Folding Dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "The extent to which glass-like kinetics govern dynamics in protein folding has been heavily debated.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we address the subject with an application of space-time perturbation theory to the dynamics of protein folding Markov state models.", "output": {"entities": {}}, "schema": []}
{"input": "Borrowing techniques from the s-ensemble method, we argue that distinct active and inactive phases exist for protein folding dynamics, and that kinetics for specific systems can fall into either dynamical regime.", "output": {"entities": {}}, "schema": []}
{"input": "We do not, however, observe a true glass transition in any system studied.", "output": {"entities": {}}, "schema": []}
{"input": "We go on to discuss how these inactive and active phases might relate to general protein folding properties.", "output": {"entities": {}}, "schema": []}
{"input": "T-Cells from HLA-B * 57: 01 + Human Subjects Are Activated with Abacavir through Two Independent Pathways and Induce Cell Death by Multiple Mechanisms.", "output": {"entities": {"chemical": [{"text": "Abacavir", "start": 64, "end": 72}]}}, "schema": []}
{"input": "Susceptibility to abacavir hypersensitivity has been attributed to possession of the specific human leukocyte antigen allele HLA-B * 57: 01.", "output": {"entities": {}}, "schema": []}
{"input": "HLA-B * 57: 01-restricted activation of CD8 + T-cells provides a link between the genetic association and the iatrogenic disease.", "output": {"entities": {}}, "schema": []}
{"input": "The objectives of this study were to characterize the functionality of drug-responsive CD8 + T-cell clones generated from HLA-B * 57: 01 + drug-naive subjects and to explore the relationship between abacavir accumulation in antigen presenting cells and the T-cell response.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 199, "end": 207}]}}, "schema": []}
{"input": "Seventy-four CD8 + clones expressing different V beta receptors were shown to proliferate and kill target cells via different mechanisms when exposed to abacavir.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 153, "end": 161}]}}, "schema": []}
{"input": "Certain clones were activated with abacavir in the absence of antigen presenting cells.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 35, "end": 43}]}}, "schema": []}
{"input": "Analysis of the remaining clones revealed two pathways of drug-dependent T-cell activation.", "output": {"entities": {}}, "schema": []}
{"input": "Overnight incubation of antigen presenting cells with abacavir, followed by repeated washing to remove soluble drug, activated approximately 50% of the clones, and the response was blocked by glutaraldehyde fixation.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 54, "end": 62}, {"text": "glutaraldehyde", "start": 192, "end": 206}]}}, "schema": []}
{"input": "In contrast, a 1 h antigen presenting cell pulse did not activate any of the clones.", "output": {"entities": {}}, "schema": []}
{"input": "Accumulation of abacavir in antigen presenting cells was rapid (less than 1 h), and the intracellular concentrations were maintained for 16 h.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 16, "end": 24}]}}, "schema": []}
{"input": "However, intracellular abacavir was not detectable by mass spectrometry after pulsing.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 23, "end": 31}]}}, "schema": []}
{"input": "These data suggest that T-cells can be activated by abacavir through a direct interaction with surface and intracellular major histocompatibility complex (MHC) molecules.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 52, "end": 60}]}}, "schema": []}
{"input": "With the former, abacavir seemingly participates in the MHC T-cell receptor binding interaction.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 17, "end": 25}]}}, "schema": []}
{"input": "In contrast, the latter pathway likely involves MHC binding peptides displayed as a consequence of abacavir exposure, but not abacavir itself.", "output": {"entities": {"chemical": [{"text": "abacavir", "start": 99, "end": 107}, {"text": "abacavir", "start": 126, "end": 134}]}}, "schema": []}
{"input": "Activation of Transient Receptor Potential Ankyrin-1 (TRPA1) in Lung Cells by Wood Smoke Particulate Material.", "output": {"entities": {}}, "schema": []}
{"input": "Cigarette smoke, diesel exhaust, and other combustion-derived particles activate the calcium channel transient receptor potential ankyrin-1 (TRPA1), causing irritation and inflammation in the respiratory tract.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 85, "end": 92}]}}, "schema": []}
{"input": "It was hypothesized that wood smoke particulate and select chemical constituents thereof would also activate TRPA1 in lung cells, potentially explaining the adverse effects of wood and other forms of biomass smoke on the respiratory system.", "output": {"entities": {}}, "schema": []}
{"input": "TRPA1 activation was assessed using calcium imaging assays in TRPA1-overexpressing HEK-293 cells, mouse primary trigeminal neurons, and human adenocarcinoma (A549) lung cells.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 36, "end": 43}]}}, "schema": []}
{"input": "Particles from pine and mesquite smoke were less potent agonists of TRPA1 than an equivalent mass concentration of an ethanol extract of diesel exhaust particles; pine particles were comparable in potency to cigarette smoke condensate, and mesquite particles were the least potent.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 118, "end": 125}]}}, "schema": []}
{"input": "The fine particulate (PM < 2. 5 mu m) of wood smoke were the most potent TRPA1 agonists and several chemical constituents of wood smoke particulate, 3, 5-ditert-butylphenol, coniferaldehyde, formaldehyde, perinaphthenone, agathic acid, and isocupressic acid, were TRPA1 agonists.", "output": {"entities": {"chemical": [{"text": "3, 5-ditert-butylphenol", "start": 149, "end": 172}, {"text": "coniferaldehyde", "start": 174, "end": 189}, {"text": "formaldehyde", "start": 191, "end": 203}, {"text": "perinaphthenone", "start": 205, "end": 220}, {"text": "agathic acid", "start": 222, "end": 234}, {"text": "isocupressic acid", "start": 240, "end": 257}]}}, "schema": []}
{"input": "Pine particulate activated TRPA1 in mouse trigeminal neurons and A549 cells in a concentration-dependent manner, which was inhibited by the TRPA1 antagonist HC-030031.", "output": {"entities": {"chemical": [{"text": "HC-030031", "start": 157, "end": 166}]}}, "schema": []}
{"input": "TRPA1 activation by wood smoke particles occurred through the electrophile/oxidant-sensing domain (i. e., C621/C641/C665/K710), based on the inhibition of cellular responses when the particles were pretreated with glutathione; a role for the menthol-binding site of TRPA1 (S873/T874) was demonstrated for 3, 5-ditert-butylphenol.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 214, "end": 225}, {"text": "menthol", "start": 242, "end": 249}, {"text": "3, 5-ditert-butylphenol", "start": 305, "end": 328}]}}, "schema": []}
{"input": "This study demonstrated that TRPA1 is a molecular sensor for wood smoke particulate and several chemical constituents thereof, in sensory neurons and A549 cells, suggesting that TRPA1 may mediate some of the adverse effects of wood smoke in humans.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of exposure to amitraz on noradrenaline, serotonin and dopamine levels in brain regions of 30 and 60 days old male rats.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 23, "end": 30}, {"text": "noradrenaline", "start": 34, "end": 47}, {"text": "serotonin", "start": 49, "end": 58}, {"text": "dopamine", "start": 63, "end": 71}]}}, "schema": []}
{"input": "The effects of amitraz oral exposure (20, 50 and 80mg/kg bw, 5 days) on brain region monoamine levels of male rats at 30 and 60 days of age were examined.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 15, "end": 22}, {"text": "monoamine", "start": 85, "end": 94}]}}, "schema": []}
{"input": "The amitraz-treated rats at the oral doses of 20 and 50mg/kg bw had no visible injury, i. e., any clinical signs of dysfunction observed in any of the animals.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 4, "end": 11}]}}, "schema": []}
{"input": "However, rats treated with amitraz at the highest dose (80mg/kg bw, 5 days) showed a slight motor incoordination after 1-2h of treatment.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 27, "end": 34}]}}, "schema": []}
{"input": "These signs were reversible approximately at 6h after dose.", "output": {"entities": {}}, "schema": []}
{"input": "After the last dose of amitraz, NE, DA and 5-HT and its metabolites levels were determined in the brain regions hypothalamus, midbrain, prefrontal cortex, striatum and hippocampus by HPLC.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 23, "end": 30}, {"text": "5-HT", "start": 43, "end": 47}]}}, "schema": []}
{"input": "Amitraz caused changes in the NE, DA and 5-HT and their metabolite levels in a brain regional-, dose-and age-related manner.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 41, "end": 45}]}}, "schema": []}
{"input": "In the brain regions studied, amitraz induced a statistically significant increase in 5-HT, NE and DA content with age interaction, but the NE increases in prefrontal cortex and hippocampus was without age interaction.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Moreover, in the brain regions studied, amitraz induced a statistically significant decrease in the metabolite 5-HIAA, MHPG, DOPAC and HVA levels displaying an age interaction, excepting the 5-HIAA decrease in midbrain and the DOPAC decrease in hypothalamus and striatum which were without age interaction.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 40, "end": 47}, {"text": "5-HIAA", "start": 111, "end": 117}, {"text": "MHPG", "start": 119, "end": 123}, {"text": "DOPAC", "start": 125, "end": 130}, {"text": "HVA", "start": 135, "end": 138}, {"text": "5-HIAA", "start": 191, "end": 197}, {"text": "DOPAC", "start": 227, "end": 232}]}}, "schema": []}
{"input": "Furthermore, amitraz evoked a statistically significant decrease in 5-HT, NE and DA turnover in the brain regions studied.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 13, "end": 20}, {"text": "5-HT", "start": 68, "end": 72}]}}, "schema": []}
{"input": "The present findings indicate that amitraz significantly altered CNS monoaminergic neurotransmitters in a brain regional-, dose-and age-related manner.", "output": {"entities": {"chemical": [{"text": "amitraz", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks.", "output": {"entities": {"chemical": [{"text": "PVP", "start": 15, "end": 18}, {"text": "PEG", "start": 19, "end": 22}]}}, "schema": []}
{"input": "The effect of plasticizer' s (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 30, "end": 33}, {"text": "PVP", "start": 60, "end": 63}, {"text": "Tibolone", "start": 161, "end": 169}]}}, "schema": []}
{"input": "PEGs with MW of 400, 600, and 2000g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated.", "output": {"entities": {"chemical": [{"text": "PEGs", "start": 0, "end": 4}, {"text": "Tibolone", "start": 146, "end": 154}]}}, "schema": []}
{"input": "PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous.", "output": {"entities": {"chemical": [{"text": "PVP", "start": 0, "end": 3}, {"text": "PEG400", "start": 16, "end": 22}, {"text": "PEG600", "start": 27, "end": 33}]}}, "schema": []}
{"input": "Furthermore, a single Tg recorded in all samples, indicating that Tibolone was dispersed in a molecular lever (or in the form of nanodispersions), varied with varying PEG' s molecular weight, melt mixing temperature, and drug content, while FTIR analysis indicated significant interactions between Tibolone and PVP/PEG matrices.", "output": {"entities": {"chemical": [{"text": "Tibolone", "start": 66, "end": 74}, {"text": "PEG", "start": 167, "end": 170}, {"text": "Tibolone", "start": 298, "end": 306}, {"text": "PVP", "start": 311, "end": 314}, {"text": "PEG", "start": 315, "end": 318}]}}, "schema": []}
{"input": "All prepared solid dispersion showed long-term physical stability (18months in room temperature).", "output": {"entities": {}}, "schema": []}
{"input": "The extent of interaction between mixture components was verified using Fox and Gordon-Taylor equations.", "output": {"entities": {}}, "schema": []}
{"input": "Artificial neural networks, used to correlate the studied factors with selected dissolution characteristics, showed good prediction ability.", "output": {"entities": {}}, "schema": []}
{"input": "Targeting miRNAs to treat Hepatitis C Virus infections and liver pathology: Inhibiting the virus and altering the host.", "output": {"entities": {}}, "schema": []}
{"input": "Hepatitis C Virus (HCV) infection-induced liver disease is a growing problem worldwide, and is the primary cause of liver failure requiring liver transplantation in North America.", "output": {"entities": {}}, "schema": []}
{"input": "Improved therapeutic strategies are required to control and possibly eradicate HCV infections, and to modulate HCV-induced liver disease.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular microRNAs anneal to and regulate mRNA translation and stability and form a regulatory network that modulates virtually every cellular process.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, miRNAs are promising cellular targets for therapeutic intervention for an array of diseases including cancer, metabolic diseases, and virus infections.", "output": {"entities": {}}, "schema": []}
{"input": "In this review we outline the features of miRNA regulation and how miRNAs may be targeted in strategies to modulate HCV replication and pathogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, we highlight miR-122, a miRNA that directly modulates the HCV life cycle using an unusual mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "This miRNA is very important since miR-122 antagonists dramatically reduced HCV titres in HCV-infected chimpanzees and humans and currently represents the most likely candidate to be the first miRNA-based therapy licensed for use.", "output": {"entities": {}}, "schema": []}
{"input": "However, we also discuss other miRNAs that directly or indirectly alter HCV replication efficiency, liver cirrhosis, fibrosis and the development of hepatocellular carcinoma (HCC).", "output": {"entities": {}}, "schema": []}
{"input": "We also discuss a few miRNAs that might be targets to treat HCV in cases of HCV/HIV co-infection.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we review methods to deliver miRNA antagonists and mimics to the liver.", "output": {"entities": {}}, "schema": []}
{"input": "In the future, it may be possible to design and deliver specific combinations of miRNA antagonists and mimics to cure HCV infection or to limit liver pathogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological evaluation of Foscan ((R)) bile acid conjugates to target esophageal cancer cells.", "output": {"entities": {"chemical": [{"text": "Foscan", "start": 39, "end": 45}, {"text": "bile acid", "start": 52, "end": 61}]}}, "schema": []}
{"input": "Porphyrins and chlorins such as Foscan (R) have a natural proclivity to accumulate in cancer cells.", "output": {"entities": {"chemical": [{"text": "Porphyrins", "start": 0, "end": 10}, {"text": "chlorins", "start": 15, "end": 23}, {"text": "Foscan", "start": 32, "end": 38}]}}, "schema": []}
{"input": "This trait has made them good candidates for photosensitizers and as imaging agents in phototherapy.", "output": {"entities": {}}, "schema": []}
{"input": "In order to improve on cellular selectivity to lower post-treatment photosensitivity bile acid porphyrin bioconjugates have been prepared and investigated in esophageal cancer cells.", "output": {"entities": {"chemical": [{"text": "bile acid porphyrin", "start": 85, "end": 104}]}}, "schema": []}
{"input": "Bile acids which are known to selectively bind to, or be readily taken up by cancer cells were chosen as targeting moieties.", "output": {"entities": {"chemical": [{"text": "Bile acids", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Synthesis of the conjugates was achieved via selective nucleophilic monofunctionalization of 5, 10, 15, 20-tetrahydroxyphenylporphyrins with propargyl bromide followed by Cu (I) mediated cycloaddition with bile acid azides in good yields.", "output": {"entities": {"chemical": [{"text": "5, 10, 15, 20-tetrahydroxyphenylporphyrins", "start": 93, "end": 135}, {"text": "propargyl bromide", "start": 141, "end": 158}, {"text": "Cu (I)", "start": 171, "end": 177}, {"text": "bile acid azides", "start": 206, "end": 222}]}}, "schema": []}
{"input": "The compounds were readily taken up by esophageal cancer cells but showed no PDT activity.", "output": {"entities": {}}, "schema": []}
{"input": "A diazen-1-ium-1, 2-diolate analog of 7-azabenzobicyclo [2. 2. 1] heptane: Synthesis, nitric oxide and nitroxyl release, in vitro hemodynamic, and anti-hypertensive studies.", "output": {"entities": {"chemical": [{"text": "diazen-1-ium-1, 2-diolate", "start": 2, "end": 27}, {"text": "7-azabenzobicyclo [2. 2. 1] heptane", "start": 38, "end": 73}, {"text": "nitric oxide", "start": 86, "end": 98}, {"text": "nitroxyl", "start": 103, "end": 111}]}}, "schema": []}
{"input": "1-(7-Azabenzobicyclo [2. 2. 1] heptane) diazen-1-ium-1, 2-diolate (16) was designed with the expectation that it would act as a dual nitric oxide (NO) and nitroxyl (HNO) donor that is not carcinogenic or genotoxic.", "output": {"entities": {"chemical": [{"text": "1-(7-Azabenzobicyclo [2. 2. 1] heptane) diazen-1-ium-1, 2-diolate", "start": 0, "end": 65}, {"text": "nitric oxide", "start": 133, "end": 145}, {"text": "NO", "start": 147, "end": 149}, {"text": "nitroxyl", "start": 155, "end": 163}, {"text": "HNO", "start": 165, "end": 168}]}}, "schema": []}
{"input": "Compound 16, with a suitable half-life (17. 8min) in PBS at pH 7, released NO (19%) and HNO (22%) during a 2h incubation in PBS at pH 7.", "output": {"entities": {"chemical": [{"text": "NO", "start": 75, "end": 77}, {"text": "HNO", "start": 88, "end": 91}]}}, "schema": []}
{"input": "In addition, compound 16 exhibited a significant in vitro positive inotropic effect, increased the rates of contraction and relaxation, and increased coronary flow rate, but did not induce a chronotropic effect.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, compound 16 (13. 7mgkg (-1), po dose) provided a significant reduction in the blood pressure of mice up to 3h post-drug administration.", "output": {"entities": {}}, "schema": []}
{"input": "All these data suggest that compound 16 constitutes an attractive' lead-compound' that could have potential applications to treat cardiovascular disease (s) such as congestive heart failure.", "output": {"entities": {}}, "schema": []}
{"input": "Synthetic oligoureas of metaphenylenediamine mimic host defence peptides in their antimicrobial behaviour.", "output": {"entities": {"chemical": [{"text": "metaphenylenediamine", "start": 24, "end": 44}]}}, "schema": []}
{"input": "Oligomeric ureas of m-phenylenediamine target anionic DMPG (dimyristoylphosphatidylglycerol) and possess promise as antimicrobial agents.", "output": {"entities": {"chemical": [{"text": "ureas", "start": 11, "end": 16}, {"text": "m-phenylenediamine", "start": 20, "end": 38}, {"text": "DMPG", "start": 54, "end": 58}, {"text": "dimyristoylphosphatidylglycerol", "start": 60, "end": 91}]}}, "schema": []}
{"input": "Their similar size, shape and hydrophobicity to helical antimicrobial peptides (AMPs) may be important for activity to exist and the ability of these compounds to insert into a well ordered lipid environment.", "output": {"entities": {}}, "schema": []}
{"input": "PEG mediated synthesis and pharmacological evaluation of some fluoro substituted pyrazoline derivatives as antiinflammatory and analgesic agents.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 0, "end": 3}, {"text": "fluoro substituted pyrazoline", "start": 62, "end": 91}]}}, "schema": []}
{"input": "A new series of fluoro substituted pyrazoline derivatives 5a-g and 6a-g were synthesized in good to excellent yield from the corresponding pyrazole chalcones, 4a-g, by using polyethylene glycol-400 (PEG-400) as an alternative reaction medium.", "output": {"entities": {"chemical": [{"text": "fluoro substituted pyrazoline", "start": 16, "end": 45}, {"text": "pyrazole chalcones", "start": 139, "end": 157}, {"text": "polyethylene glycol-400", "start": 174, "end": 197}, {"text": "PEG-400", "start": 199, "end": 206}]}}, "schema": []}
{"input": "The newly synthesized compounds were characterized and screened for their in vivo antiinflammatory and analgesic activity.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 5g and 6g were found to be more potent than standard drug Diclofenac and six other compounds 5b, 5c, 5f, 6b, 6c and 6f showed significant antiinflammatory activity as compared to standard drug.", "output": {"entities": {"chemical": [{"text": "Diclofenac", "start": 68, "end": 78}]}}, "schema": []}
{"input": "Compounds 5c, 5d, 5e, 5f, 6c, 6d, 6e and 6f showed significant analgesic activity as compared to standard drug Aspirin.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of metal ion binding peptides containing unnatural amino acids by phage display.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 66, "end": 77}]}}, "schema": []}
{"input": "The bidentate metal binding amino acid bipyridylalanine (BpyAla) was incorporated into a disulfide linked cyclic peptide phage displayed library to identify metal ion binding peptides.", "output": {"entities": {"chemical": [{"text": "amino acid bipyridylalanine", "start": 28, "end": 55}, {"text": "BpyAla", "start": 57, "end": 63}, {"text": "disulfide", "start": 89, "end": 98}]}}, "schema": []}
{"input": "Selection against Ni (2 +)-nitrilotriacetic acid (NTA) enriched for sequences containing histidine and BpyAla.", "output": {"entities": {"chemical": [{"text": "Ni (2 +)", "start": 18, "end": 26}, {"text": "nitrilotriacetic acid", "start": 27, "end": 48}, {"text": "NTA", "start": 50, "end": 53}, {"text": "histidine", "start": 89, "end": 98}, {"text": "BpyAla", "start": 103, "end": 109}]}}, "schema": []}
{"input": "BpyAla predominated when selections were carried out at lower pH, consistent with the differential pKa' s of histidine and BpyAla.", "output": {"entities": {"chemical": [{"text": "BpyAla", "start": 0, "end": 6}, {"text": "histidine", "start": 109, "end": 118}, {"text": "BpyAla", "start": 123, "end": 129}]}}, "schema": []}
{"input": "Two peptides containing BpyAla were synthesized and found to bind Ni (2 +) with low micromolar dissociation constants.", "output": {"entities": {"chemical": [{"text": "BpyAla", "start": 24, "end": 30}, {"text": "Ni (2 +)", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Incorporation of BpyAla and other metal binding amino acids into peptide and protein libraries should enable the evolution of novel binding and catalytic activities.", "output": {"entities": {"chemical": [{"text": "BpyAla", "start": 17, "end": 23}, {"text": "amino acids", "start": 48, "end": 59}]}}, "schema": []}
{"input": "Tuning into diversity of homeostatic synaptic plasticity.", "output": {"entities": {}}, "schema": []}
{"input": "Neurons are endowed with the remarkable ability to integrate activity levels over time and tune their excitability such that action potential firing is maintained within a computationally optimal range.", "output": {"entities": {}}, "schema": []}
{"input": "These feedback mechanisms, collectively referred to as \" homeostatic plasticity \", enable neurons to respond and adapt to prolonged alterations in neuronal activity by regulating several determinants of cellular excitability.", "output": {"entities": {}}, "schema": []}
{"input": "Perhaps the best-characterized of these homeostatic responses involves the regulation of excitatory glutamatergic transmission.", "output": {"entities": {}}, "schema": []}
{"input": "This homeostatic synaptic plasticity (HSP) operates bidirectionally, thus providing a means for neurons to tune cellular excitability in response to either elevations or reductions in net activity.", "output": {"entities": {}}, "schema": []}
{"input": "The last decade has seen rapid growth in interest and efforts to understand the mechanistic underpinnings of HSP in part because of the theoretical stabilization that HSP confers to neural network function.", "output": {"entities": {}}, "schema": []}
{"input": "Since the initial reports describing HSP in central neurons, innovations in experimental approaches have permitted the mechanistic dissection of this cellular adaptive response and, as a result, key advances have been made in our understanding of the cellular and molecular basis of HSP.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review recent evidence that outline the presence of distinct forms of HSP at excitatory glutamatergic synapses which operate at different sub-cellular levels.", "output": {"entities": {}}, "schema": []}
{"input": "We further present theoretical considerations on the potential computational roles afforded by local, synapse-specific homeostatic regulation.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Homeostatic Plasticity'.", "output": {"entities": {}}, "schema": []}
{"input": "Impact of flow pulsatility on arterial drug distribution in stent-based therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Drug-eluting stents reside in a dynamic fluid environment where the extent to which drugs are distributed within the arterial wall is critically modulated by the blood flowing through the arterial lumen.", "output": {"entities": {}}, "schema": []}
{"input": "Yet several factors associated with the pulsatile nature of blood flow and their impact on arterial drug deposition have not been fully investigated.", "output": {"entities": {}}, "schema": []}
{"input": "We employed an integrated framework comprising bench-top and computational models to explore the factors governing the time-varying fluid dynamic environment within the vasculature and their effects on arterial drug distribution patterns.", "output": {"entities": {}}, "schema": []}
{"input": "A custom-designed bench-top framework comprising a model of a single drug-eluting stent strut and a poly-vinyl alcohol-based hydrogel as a model tissue bed simulated fluid flow and drug transport under fully apposed strut settings.", "output": {"entities": {"chemical": [{"text": "poly-vinyl alcohol", "start": 100, "end": 118}]}}, "schema": []}
{"input": "Bench-top experiments revealed a relative independence between drug distribution and the factors governing pulsatile flow and these findings were validated with the in silico model.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, computational models simulating suboptimal deployment settings revealed a complex interplay between arterial drug distribution, Womersley number and the extent of malapposition.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, for a stent strut offset from the wall, total drug deposition was sensitive to changes in the pulsatile flow environment, with this dependence increasing with greater wall displacement.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that factors governing pulsatile luminal flow on arterial drug deposition should be carefully considered in conjunction with device deployment settings for better utilization of drug-eluting stent therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Antagonists reversibly reverse chemical LTD induced by group I, group II and group III metabotropic glutamate receptors.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 100, "end": 109}]}}, "schema": []}
{"input": "Metabotropic glutamate (mGlu) receptors are implicated in many neurological and psychiatric diseases and are the targets of therapeutic agents currently in clinical development.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 13, "end": 22}]}}, "schema": []}
{"input": "Their activation has diverse effects in the central nervous system (CNS) that includes an involvement in synaptic plasticity.", "output": {"entities": {}}, "schema": []}
{"input": "We previously reported that the brief exposure of hippocampal slices to dihydroxyphenylglycine (DHPG) can result in a long-term depression (LTD) of excitatory synaptic transmission.", "output": {"entities": {"chemical": [{"text": "dihydroxyphenylglycine", "start": 72, "end": 94}, {"text": "DHPG", "start": 96, "end": 100}]}}, "schema": []}
{"input": "Surprisingly, this LTD could be fully reversed by mGlu receptor antagonists in a manner that was itself fully reversible upon washout of the antagonist.", "output": {"entities": {}}, "schema": []}
{"input": "Here, 15 years after the discovery of DHPG-LTD and its reversible reversibility, we summarise these initial findings.", "output": {"entities": {"chemical": [{"text": "DHPG", "start": 38, "end": 42}]}}, "schema": []}
{"input": "We then present new data on DHPG-LTD, which demonstrates that evoked epileptiform activity triggered by activation of group I mGlu receptors can also be reversibly reversed by mGlu receptor antagonists.", "output": {"entities": {"chemical": [{"text": "DHPG", "start": 28, "end": 32}]}}, "schema": []}
{"input": "Furthermore, we show that the phenomenon of reversible reversibility is not specific to group I mGlu receptors.", "output": {"entities": {}}, "schema": []}
{"input": "We report that activation of group II mGlu receptors in the temporo-ammonic pathway (TAP) and mossy fibre pathway within the hippocampus and in the cortical input to neurons of the lateral amygdala induces an LTD that is reversed by LY341495, a group II mGlu receptor antagonist.", "output": {"entities": {"chemical": [{"text": "LY341495", "start": 233, "end": 241}]}}, "schema": []}
{"input": "We also show that activation of group III mGlu8 receptors induces an LTD at lateral perforant path inputs to the dentate gyrus and that this LTD is reversed by MDCPG, an mGlu8 receptor antagonist.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, we have shown that activation of representative members of each of the three groups of mGlu receptors can induce forms of LTD than can be reversed by antagonists, and that in each case washout of the antagonist is associated with the re-establishment of the LTD.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.", "output": {"entities": {}}, "schema": []}
{"input": "Arsenic trioxide depletes cancer stem-like cells and inhibits repopulation of neurosphere derived from glioblastoma by downregulation of Notch pathway.", "output": {"entities": {"chemical": [{"text": "Arsenic trioxide", "start": 0, "end": 16}]}}, "schema": []}
{"input": "Notch signaling has been demonstrated to have a central role in cancer stem-like cells (CSLCs) in glioblastoma multiforme (GBM).", "output": {"entities": {}}, "schema": []}
{"input": "We have recently demonstrated the inhibitory effect of arsenic trioxide (ATO) on CSLCs in glioblastoma cell lines.", "output": {"entities": {"chemical": [{"text": "arsenic trioxide", "start": 55, "end": 71}, {"text": "ATO", "start": 73, "end": 76}]}}, "schema": []}
{"input": "In this study we used neurosphere recovery assay that measured neurosphere formation at three time points to assess the capacity of the culture to repopulate after ATO treatment.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 164, "end": 167}]}}, "schema": []}
{"input": "Our results provided strong evidence that ATO depleted CSLCs in GBM, and inhibited neurosphere recovery and secondary neurosphere formation.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 42, "end": 45}]}}, "schema": []}
{"input": "ATO inhibited the phosphorylation and activation of AKT and STAT3 through Notch signaling blockade.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 0, "end": 3}]}}, "schema": []}
{"input": "These data show that the ATO is a promising new approach to decrease glioblastoma proliferation and recurrence by downregulation of Notch pathway.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 25, "end": 28}]}}, "schema": []}
{"input": "Structure-activity relationship of 5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole analogues as 5-HT6 receptor agonists.", "output": {"entities": {"chemical": [{"text": "5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole", "start": 35, "end": 100}]}}, "schema": []}
{"input": "To further investigate the structure-activity relationship (SAR) of the 5-hydroxytryptamine type 6 (5-HT6) receptor agonist 5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole (EMD386088, 6), a series of 2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles were synthesized, and in vitro affinity to, and functional activity at 5-HT6 receptors was tested.", "output": {"entities": {"chemical": [{"text": "5-hydroxytryptamine", "start": 72, "end": 91}, {"text": "5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole", "start": 124, "end": 189}, {"text": "EMD386088", "start": 191, "end": 200}, {"text": "2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles", "start": 218, "end": 275}]}}, "schema": []}
{"input": "We focused on substituents made at the indole N (1)-, 2-and 5-positions and these were found to not only influence the affinity at 5-HT6 receptors but also the intrinsic activity leading to antagonists, partial agonists and full agonists.", "output": {"entities": {"chemical": [{"text": "indole", "start": 39, "end": 45}]}}, "schema": []}
{"input": "In order for a compound to demonstrate potent 5-HT6 receptor agonist properties, the indole N (1) should be unsubstituted, an alkyl group such as 2-methyl is needed and finally halogen substituents in the indole 5-position (fluoro, chloro or, bromo) were essential requirements.", "output": {"entities": {"chemical": [{"text": "indole", "start": 85, "end": 91}, {"text": "alkyl", "start": 126, "end": 131}, {"text": "2-methyl", "start": 146, "end": 154}, {"text": "halogen", "start": 177, "end": 184}, {"text": "indole", "start": 205, "end": 211}, {"text": "fluoro", "start": 224, "end": 230}, {"text": "chloro", "start": 232, "end": 238}, {"text": "bromo", "start": 243, "end": 248}]}}, "schema": []}
{"input": "However, the introduction of a benzenesulfonyl group at N (1)-position switched the full agonist 6 to be a 5-HT6 receptor antagonist (30).", "output": {"entities": {"chemical": [{"text": "benzenesulfonyl", "start": 31, "end": 46}]}}, "schema": []}
{"input": "A few compounds within the 2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles were also screened for off-targets and generally they displayed low affinity for other 5-HT subtypes and serotonin transporter protein (SERT).", "output": {"entities": {"chemical": [{"text": "2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles", "start": 27, "end": 84}, {"text": "5-HT", "start": 172, "end": 176}, {"text": "serotonin", "start": 190, "end": 199}]}}, "schema": []}
{"input": "Induction of G2/M arrest, caspase activation and apoptosis by alpha-santonin derivatives in HL-60 cells.", "output": {"entities": {"chemical": [{"text": "alpha-santonin", "start": 62, "end": 76}]}}, "schema": []}
{"input": "Sesquiterpene lactones (SLs) are natural products with a variety of biological activities.", "output": {"entities": {"chemical": [{"text": "Sesquiterpene lactones", "start": 0, "end": 22}, {"text": "SLs", "start": 24, "end": 27}]}}, "schema": []}
{"input": "Previously, we demonstrated the cytotoxic effects of three new alpha-santonin derivatives on different tumor cell lines with low toxic effects upon peripheral human leukocytes.", "output": {"entities": {"chemical": [{"text": "alpha-santonin", "start": 63, "end": 77}]}}, "schema": []}
{"input": "Here, we evaluated the mechanism of action triggered by these derivatives.", "output": {"entities": {}}, "schema": []}
{"input": "HL-60 cell cycle determined after 24h treatment revealed a significant inhibition on cell-cycle progression and leading to an increasing of cells in G2/M [7. 6% and 9. 0% for compound 3% and 9. 0% and 8. 6% for compound 4 (1 and 2 mu M, respectively)].", "output": {"entities": {}}, "schema": []}
{"input": "However, after 48h exposure, all compounds caused G2/M reduction and a significant DNA fragmentation.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 2, 3 and 4 were able to induce apoptosis on leukemia cells, which was corroborated by phosphatidyserine externalization and activation of caspases-3 and-7 after 24h exposure.", "output": {"entities": {}}, "schema": []}
{"input": "None of the derivatives analyzed caused depolarization of mitochondrial membrane within 24h of incubation, suggesting the involvement of the extrinsic apoptotic pathway in the death process.", "output": {"entities": {}}, "schema": []}
{"input": "The antiproliferative action of these compounds is related to the DNA synthesis inhibition and cell cycle arrest, which probably lead to apoptosis activation.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, these santonin derivatives are promising lead candidates for development of new cytotoxic agents.", "output": {"entities": {"chemical": [{"text": "santonin", "start": 17, "end": 25}]}}, "schema": []}
{"input": "Systematic review of the effects of maternal hypertension in pregnancy and antihypertensive therapies on child neurocognitive development.", "output": {"entities": {}}, "schema": []}
{"input": "As many as 15% of women experience hypertension during pregnancy.", "output": {"entities": {}}, "schema": []}
{"input": "Large proportions of them are receiving antihypertensive medications.", "output": {"entities": {}}, "schema": []}
{"input": "This review investigated whether hypertension itself, or the antihypertensive medications, adversely affect long term child neurocognitive development.", "output": {"entities": {}}, "schema": []}
{"input": "The existing evidence suggests that methyldopa and labetalol probably do not adversely affect neurobehavioral development.", "output": {"entities": {"chemical": [{"text": "methyldopa", "start": 36, "end": 46}, {"text": "labetalol", "start": 51, "end": 60}]}}, "schema": []}
{"input": "Although an increasing body of evidence suggests adverse neurocognitive effects of the hypertension itself, none of the existing studies examined simultaneously the effects of both hypertension and the drugs used therapeutically.", "output": {"entities": {}}, "schema": []}
{"input": "The confounding effects by indication must be addressed in future studies.", "output": {"entities": {}}, "schema": []}
{"input": "Tail Tip Proteins Related to Bacteriophage lambda gpL Coordinate an Iron-Sulfur Cluster.", "output": {"entities": {"chemical": [{"text": "Iron-Sulfur", "start": 68, "end": 79}]}}, "schema": []}
{"input": "The assembly of long non-contractile phage tails begins with the formation of the tail tip complex (TTC).", "output": {"entities": {}}, "schema": []}
{"input": "TTCs are multi-functional protein structures that mediate host cell adsorption and genome injection.", "output": {"entities": {}}, "schema": []}
{"input": "The TTC of phage lambda is assembled from multiple copies of eight different proteins, including gpL.", "output": {"entities": {}}, "schema": []}
{"input": "Purified preparations of gpL and several homologues all displayed a distinct reddish color, suggesting the binding of iron by these proteins.", "output": {"entities": {"chemical": [{"text": "iron", "start": 118, "end": 122}]}}, "schema": []}
{"input": "Further characterization of the gpL homologue from phage N15, which was most amenable to in vitro analyses, showed that it contains two domains.", "output": {"entities": {}}, "schema": []}
{"input": "The C-terminal domain was demonstrated to coordinate an iron-sulfur cluster, providing the first example of a viral structural protein binding to this type of metal group.", "output": {"entities": {"chemical": [{"text": "C", "start": 4, "end": 5}, {"text": "iron-sulfur", "start": 56, "end": 67}]}}, "schema": []}
{"input": "We characterized the iron-sulfur cluster using inductively coupled plasma-atomic emission spectroscopy, absorbance spectroscopy, and electron paramagnetic resonance spectroscopy and found that it is an oxygen-sensitive [4Fe-4S] (2 +) cluster.", "output": {"entities": {"chemical": [{"text": "iron-sulfur", "start": 21, "end": 32}, {"text": "oxygen", "start": 202, "end": 208}, {"text": "[4Fe-4S] (2 +)", "start": 219, "end": 233}]}}, "schema": []}
{"input": "Four highly conserved cysteine residues were shown to be required for coordinating the iron-sulfur cluster, and substitution of any of these Cys residues with Ser or Ala within the context of lambda gpL abolished biological activity.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 22, "end": 30}, {"text": "iron-sulfur", "start": 87, "end": 98}, {"text": "Cys", "start": 141, "end": 144}, {"text": "Ser", "start": 159, "end": 162}, {"text": "Ala", "start": 166, "end": 169}]}}, "schema": []}
{"input": "These data imply that the intact iron-sulfur cluster is required for function.", "output": {"entities": {"chemical": [{"text": "iron-sulfur", "start": 33, "end": 44}]}}, "schema": []}
{"input": "The presence of four conserved Cys residues in the C-terminal regions of very diverse gpL homologues suggest that utilization of an iron-sulfur cluster is a widespread feature of non-contractile tailed phages that infect Gram-negative bacteria.", "output": {"entities": {"chemical": [{"text": "Cys", "start": 31, "end": 34}, {"text": "C", "start": 51, "end": 52}, {"text": "iron-sulfur", "start": 132, "end": 143}]}}, "schema": []}
{"input": "In addition, this is the first example of a viral structural protein that binds an iron-sulfur cluster.", "output": {"entities": {"chemical": [{"text": "iron-sulfur", "start": 83, "end": 94}]}}, "schema": []}
{"input": "Cell adhesion and homeostatic synaptic plasticity.", "output": {"entities": {}}, "schema": []}
{"input": "At synapses, pre-and post-synaptic cells get in direct contact with each other via cell adhesion molecules (CAMs).", "output": {"entities": {}}, "schema": []}
{"input": "Several CAMs have been identified at the neuromuscular junction and at central synapses, where they regulate synaptic strength, by recruiting scaffolding proteins, neurotransmitter receptors and synaptic vesicles in response to the binding of counter-receptors across the synaptic cleft.", "output": {"entities": {}}, "schema": []}
{"input": "Many synapses are also surrounded by astrocytic processes and embedded in conspicuous extracellular matrix (ECM).", "output": {"entities": {}}, "schema": []}
{"input": "It is now widely recognized that astrocytes play a central role in regulating the synaptic machinery by exchanging information with the neuronal elements via diffusible molecules and direct physical interactions; this has lead to the concept of the' tri-partite synapse'.", "output": {"entities": {}}, "schema": []}
{"input": "More recently, the term' tetra-partite synapse' has been introduced to underlie the importance of ECM in shaping synaptic function by mediating interaction and signaling between neurons and astrocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we will review how this integrated view of the synapse can help us understand homeostatic synaptic plasticity at the neuromuscular junction and in the central nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "We will explore how synaptic CAMs regulate two forms of homeostatic plasticity: (i) postsynaptic scaling of synaptic currents to counteract changes in neuronal network activity and (ii) the compensatory modulation of presynaptic neurotransmitter release in response to changes in postsynaptic efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "We will discuss recent findings on activity-dependent trans-synaptic signaling events and the role of cell adhesion in the feedback control of network activity.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Homeostatic Plasticity'.", "output": {"entities": {}}, "schema": []}
{"input": "Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: Preparation, characterization and in vivo evaluation.", "output": {"entities": {"chemical": [{"text": "curcumin didecanoate", "start": 62, "end": 82}]}}, "schema": []}
{"input": "The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano-and micro-suspensions after intramuscular (i. m.) administration to rats.", "output": {"entities": {"chemical": [{"text": "curcumin didecanoate", "start": 63, "end": 83}, {"text": "CurDD", "start": 85, "end": 90}]}}, "schema": []}
{"input": "Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~ 500nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions.", "output": {"entities": {"chemical": [{"text": "CurDD", "start": 49, "end": 54}]}}, "schema": []}
{"input": "Although the nanosuspension appeared to exhibit slower clearance from the injection site after i. m. injection, compared to microsuspension (~ 5 mu m), a significantly higher maximum plasma curcumin concentration (69. 0ng/ml) was observed for the former than that for the latter (18. 5ng/ml).", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 190, "end": 198}]}}, "schema": []}
{"input": "In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15days than the microsuspension, except for the initial times.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 67, "end": 75}, {"text": "CurDD", "start": 101, "end": 106}]}}, "schema": []}
{"input": "A single i. m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13days.", "output": {"entities": {"chemical": [{"text": "reserpine", "start": 82, "end": 91}]}}, "schema": []}
{"input": "This study demonstrates that CurDD nanosuspension may act as a long-acting i. m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect.", "output": {"entities": {"chemical": [{"text": "CurDD", "start": 29, "end": 34}, {"text": "curcumin", "start": 118, "end": 126}]}}, "schema": []}
{"input": "Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers: Photophysical and physicochemical characterisation, release and phototoxicity in vitro.", "output": {"entities": {"chemical": [{"text": "Chloroaluminium phthalocyanine", "start": 0, "end": 30}]}}, "schema": []}
{"input": "Nanoparticles of poly (d, l-lactide-co-glycolide), poly (d, l-lactide) and polyethylene glycol-block-poly (d, l-lactide) were developed to encapsulate chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used in photodynamic therapy (PDT).", "output": {"entities": {"chemical": [{"text": "poly (d, l-lactide-co-glycolide)", "start": 17, "end": 49}, {"text": "poly (d, l-lactide)", "start": 51, "end": 70}, {"text": "polyethylene glycol-block-poly (d, l-lactide)", "start": 75, "end": 120}, {"text": "chloroaluminium phthalocyanine", "start": 151, "end": 181}, {"text": "AlClPc", "start": 183, "end": 189}]}}, "schema": []}
{"input": "The mean nanoparticle size varied from 115 to 274nm, and the encapsulation efficiency ranged from 57% to 96% due to drug precipitation induced by different types of polymer.", "output": {"entities": {}}, "schema": []}
{"input": "All nanoparticle formulations presented negative zeta potential values (-37mV to-59mV), explaining their colloidal stability.", "output": {"entities": {}}, "schema": []}
{"input": "The characteristic photophysical parameters were analysed: the absorption spectrum profile, fluorescence quantum yield and transient absorbance decay, with similar values for free and nanoparticles of AlClPc.", "output": {"entities": {"chemical": [{"text": "AlClPc", "start": 201, "end": 207}]}}, "schema": []}
{"input": "The time-resolved spectroscopy measurements for AlClPc triplet excited state lifetimes indicate that encapsulation in nanocapsules increases triplet lifetime, which is advantageous for PDT efficiency.", "output": {"entities": {"chemical": [{"text": "AlClPc", "start": 48, "end": 54}]}}, "schema": []}
{"input": "A sustained release profile over 168h was obtained using external sink method.", "output": {"entities": {}}, "schema": []}
{"input": "An in vitro phototoxic effect higher than 80% was observed in human fibroblasts at low laser light doses (3J/cm (2)) with 10 mu M of AlClPc.", "output": {"entities": {"chemical": [{"text": "AlClPc", "start": 133, "end": 139}]}}, "schema": []}
{"input": "The AlClPc loaded within polymeric nanocapsules presented suitable physical stability, improved photophysical properties, sustained released profile and suitable activity in vitro to be considered a promising formulation for PDT.", "output": {"entities": {"chemical": [{"text": "AlClPc", "start": 4, "end": 10}]}}, "schema": []}
{"input": "A global toxicogenomic analysis investigating the mechanistic differences between tobacco and marijuana smoke condensates in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Like tobacco smoking, habitual marijuana smoking causes numerous adverse pulmonary effects.", "output": {"entities": {}}, "schema": []}
{"input": "However, the mechanisms of action involved, especially as compared to tobacco smoke, are still unclear.", "output": {"entities": {}}, "schema": []}
{"input": "To uncover putative modes of action, this study employed a toxicogenomics approach to compare the toxicological pathways perturbed following exposure to marijuana and tobacco smoke condensate in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Condensates of mainstream smoke from hand-rolled tobacco and marijuana cigarettes were similarly prepared using identical smoking conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Murine lung epithelial cells were exposed to low, medium and high concentrations of the smoke condensates for 6h.", "output": {"entities": {}}, "schema": []}
{"input": "RNA was extracted immediately or after a 4h recovery period and hybridized to mouse whole genome microarrays.", "output": {"entities": {}}, "schema": []}
{"input": "Tobacco smoke condensate (TSC) exposure was associated with changes in xenobiotic metabolism, oxidative stress, inflammation, and DNA damage response.", "output": {"entities": {}}, "schema": []}
{"input": "These same pathways were also significantly affected following marijuana smoke condensate (MSC) exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Although the effects of the condensates were largely similar, dose-response analysis indicates that the MSC is substantially more potent than TSC.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, steroid biosynthesis, apoptosis, and inflammation pathways were more significantly affected following MSC exposure, whereas M phase cell cycle pathways were more significantly affected following TSC exposure.", "output": {"entities": {}}, "schema": []}
{"input": "MSC exposure also appeared to elicit more severe oxidative stress than TSC exposure, which may account for the greater cytotoxicity of MSC.", "output": {"entities": {}}, "schema": []}
{"input": "This study shows that in general MSC impacts many of the same molecular processes as TSC.", "output": {"entities": {}}, "schema": []}
{"input": "However, subtle pathway differences can provide insight into the differential toxicities of the two complex mixtures.", "output": {"entities": {}}, "schema": []}
{"input": "Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy-A meta-analysis of 11 randomized controlled trials involving 21, 295 participants.", "output": {"entities": {}}, "schema": []}
{"input": "The available studies have reported the benefits of statins on all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients.", "output": {"entities": {}}, "schema": []}
{"input": "However studies in end-stage renal disease patients on dialysis yielded conflicting results.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we performed a meta-analysis and provide the most reliable trial data to date on the impact of statin therapy on cardiovascular events and death from all causes in CKD patients.", "output": {"entities": {}}, "schema": []}
{"input": "Data from PubMed, Web of Science, Cochrane Library, and Scopus for the years 1966 to October 2012 were searched.", "output": {"entities": {}}, "schema": []}
{"input": "The final meta-analysis included 11 randomized controlled trials involving 21, 295 participants with CKD.", "output": {"entities": {}}, "schema": []}
{"input": "Among them 6857 were on dialysis.", "output": {"entities": {}}, "schema": []}
{"input": "The use of statins in subjects with non-dialysis-dependent CKD resulted in a marked reduction in death from all causes (relative risk [RR]: 0. 66; 95% confidence interval [CI]: 0. 55-0. 79; p < 0. 0001), cardiac causes (RR: 0. 69; 95% CI: 0. 55-0. 68; p = 0. 0012), cardiovascular events (RR: 0. 55; 95% CI: 0. 4-0. 75; p = 0. 0001) and stroke (RR: 0. 66; 95% CI: 0. 5-0. 88; p = 0. 0022).", "output": {"entities": {}}, "schema": []}
{"input": "The use of statins in dialysis-dependent CKD patients resulted in a non-significant effect on death from all causes (RR: 0. 99; 95% CI: 0. 88-1. 11; p = 0. 85) and stroke (RR: 1. 31; 95% CI: 0. 9-1. 89; p > 0. 05), but had the effect of reducing death from cardiac causes (RR: 0. 79; 95% CI: 0. 64-0. 98; p < 0. 05) and cardiovascular events (RR: 0. 81; 95% CI: 0. 7-0. 94; p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, the use of statins should be indicated in cardiovascular disease prevention especially in patients with non-dialysis-dependent CKD.", "output": {"entities": {}}, "schema": []}
{"input": "According to the very limited data the obtained results suggest caution in expecting a reduction in cardiovascular events in patients on dialysis.", "output": {"entities": {}}, "schema": []}
{"input": "Arsenic trioxide induces cardiac fibroblast apoptosis in vitro and in vivo by up-regulating TGF-beta 1 expression.", "output": {"entities": {"chemical": [{"text": "Arsenic trioxide", "start": 0, "end": 16}]}}, "schema": []}
{"input": "Arsenic trioxide (As2O3; ATO) is clinically effective in treating acute promyelocytic leukemia (APL); however, it frequently causes cardiotoxic effects.", "output": {"entities": {"chemical": [{"text": "Arsenic trioxide", "start": 0, "end": 16}, {"text": "As2O3", "start": 18, "end": 23}, {"text": "ATO", "start": 25, "end": 28}]}}, "schema": []}
{"input": "This study was designed to investigate whether ATO could induce apoptosis of cardiac fibroblasts (CFs) that play very important roles in maintaining the structure integrity and function of the heart.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 47, "end": 50}]}}, "schema": []}
{"input": "Cardiac fibroblasts from guinea pigs administered with ATO (1mg/kgbw) were used to test the pro-apoptotic role of ATO in vivo.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 55, "end": 58}, {"text": "ATO", "start": 114, "end": 117}]}}, "schema": []}
{"input": "The current study demonstrated that ATO induced morphological characteristics of apoptosis and Caspase-3 activation in CFs of guinea pigs along with a significant up-regulation in TGF-beta 1 protein expression, Bax/Bcl-2 ratio and ERK1/2 phosphorylation.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 36, "end": 39}]}}, "schema": []}
{"input": "In vitro MTT assay showed that ATO remarkably reduced the viability of cultured cardiac fibroblasts (NRCFs) from neonatal rat in a concentration-and time-dependent manner.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 9, "end": 12}, {"text": "ATO", "start": 31, "end": 34}]}}, "schema": []}
{"input": "Consistent with the notions in vivo, ATO significantly induced the apoptosis in NRCFs, dramatically up-regulated TGF-beta 1 protein level and Bax/Bcl-2 ratio in a time-dependent fashion and activated Caspase-3 and ERK1/2.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 37, "end": 40}]}}, "schema": []}
{"input": "Finally, pretreatment with LY364947, an inhibitor of TGF-beta signaling could apparently reverse these changes.", "output": {"entities": {"chemical": [{"text": "LY364947", "start": 27, "end": 35}]}}, "schema": []}
{"input": "We therefore conclude that TGF-beta is functionally linked to ERK1/2 and that TGF-beta signaling is responsible for ATO-induced CFs apoptosis, which provides a novel mechanism of ATO related cardiac toxicology.", "output": {"entities": {"chemical": [{"text": "ATO", "start": 116, "end": 119}, {"text": "ATO", "start": 179, "end": 182}]}}, "schema": []}
{"input": "In utero phthalate effects in the female rat: A model for MRKH syndrome.", "output": {"entities": {"chemical": [{"text": "phthalate", "start": 9, "end": 18}]}}, "schema": []}
{"input": "Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology.", "output": {"entities": {}}, "schema": []}
{"input": "Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phenomenon that is better studied in male offspring than females.", "output": {"entities": {"chemical": [{"text": "phthalate esters", "start": 25, "end": 41}, {"text": "PEs", "start": 43, "end": 46}]}}, "schema": []}
{"input": "The current study reports female reproductive tract malformations in the Sprague-Dawley rat similar to those characteristic of MRKH syndrome, following in utero exposure to a mixture of 5 PEs.", "output": {"entities": {"chemical": [{"text": "PEs", "start": 188, "end": 191}]}}, "schema": []}
{"input": "We determined that females are ~ 2-fold less sensitive to the effects of the 5-PE mixture than males for reproductive tract malformations.", "output": {"entities": {}}, "schema": []}
{"input": "We were not fully successful in defining the critical exposure period for females; however, incidence of malformations was 88% following dosing from GD8 to 19 versus 22% and 0% for GD8-13 and GD14-19, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, this study provides valuable information regarding female vulnerability to in utero phthalate exposure and further characterizes a potential model for the human MRKH syndrome.", "output": {"entities": {"chemical": [{"text": "phthalate", "start": 93, "end": 102}]}}, "schema": []}
{"input": "Disruption of the integrity and function of brain microvascular endothelial cells in culture by exposure to diesel engine exhaust particles.", "output": {"entities": {}}, "schema": []}
{"input": "Diesel exhaust particles (DEPs), a by-product of diesel engine exhaust (DEE), are known to produce pro-oxidative and pro-inflammatory effects, thereby leading to oxidative stress-induced damage.", "output": {"entities": {}}, "schema": []}
{"input": "Given the key role of DEPs in inducing oxidative stress, we investigated the role of DEPs in disrupting the integrity and function of immortalized human brain microvascular endothelial cells (HBMVEC).", "output": {"entities": {}}, "schema": []}
{"input": "To study this, HBMVEC cells were exposed to media containing three different concentrations of DEPs or plain media for 24h.", "output": {"entities": {}}, "schema": []}
{"input": "Those exposed to DEPs showed significantly higher oxidative stress than the untreated group, as indicated by the glutathione (GSH) and malondialdehyde (MDA) levels, and the glutathione peroxidase and glutathione reductase activities.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 113, "end": 124}, {"text": "GSH", "start": 126, "end": 129}, {"text": "malondialdehyde", "start": 135, "end": 150}, {"text": "MDA", "start": 152, "end": 155}, {"text": "glutathione", "start": 173, "end": 184}, {"text": "glutathione", "start": 200, "end": 211}]}}, "schema": []}
{"input": "DEPs also induced oxidative stress-related disruption of the HBMVEC cells monolayer, as measured by trans-epithelial electrical resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these data suggest that DEPs induce cell death and disrupt the function and integrity of HBMVEC cells, indicating a potential role of DEPs in neurotoxicities.", "output": {"entities": {}}, "schema": []}
{"input": "The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel.", "output": {"entities": {"chemical": [{"text": "ethylene bis-dithiocarbamate", "start": 4, "end": 32}, {"text": "Mancozeb", "start": 43, "end": 51}, {"text": "potassium", "start": 82, "end": 91}]}}, "schema": []}
{"input": "Mancozeb (manganese/zinc ethylene bis-dithiocarbamate) is an organometallic fungicide that has been associated with human neurotoxicity and neurodegeneration.", "output": {"entities": {"chemical": [{"text": "Mancozeb", "start": 0, "end": 8}, {"text": "manganese/zinc ethylene bis-dithiocarbamate", "start": 10, "end": 53}]}}, "schema": []}
{"input": "In a high-throughput screen for modulators of KCNQ2 channel, a fundamental player modulating neuronal excitability, Mancozeb, was found to significantly potentiate KCNQ2 activity.", "output": {"entities": {"chemical": [{"text": "Mancozeb", "start": 116, "end": 124}]}}, "schema": []}
{"input": "Mancozeb was validated electrophysiologically as a KCNQ2 activator with an EC50 value of 0. 92 +/- 0. 23 mu M.", "output": {"entities": {"chemical": [{"text": "Mancozeb", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Further examination showed that manganese but not zinc ethylene bis-dithiocarbamate is the active component for the positive modulation effects.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 32, "end": 41}, {"text": "zinc ethylene bis-dithiocarbamate", "start": 50, "end": 83}]}}, "schema": []}
{"input": "In addition, the compounds are effective when the metal ions are substituted by iron but lack potentiation activity when the metal ions are substituted by sodium, signifying the importance of the metal ion.", "output": {"entities": {"chemical": [{"text": "iron", "start": 80, "end": 84}, {"text": "sodium", "start": 155, "end": 161}]}}, "schema": []}
{"input": "However, the iron (Fe (3 +)) alone, organic ligands alone or the mixture of iron with the organic ligand did not show any potentiation effect, suggesting as the active ingredient is a specific complex rather than two separate additive or synergistic components.", "output": {"entities": {"chemical": [{"text": "iron", "start": 13, "end": 17}, {"text": "Fe (3 +)", "start": 19, "end": 27}, {"text": "iron", "start": 76, "end": 80}]}}, "schema": []}
{"input": "Our study suggests that potentiation on KCNQ2 potassium channels might be the possible mechanism of Mancozeb toxicity in the nervous system.", "output": {"entities": {"chemical": [{"text": "potassium", "start": 46, "end": 55}, {"text": "Mancozeb", "start": 100, "end": 108}]}}, "schema": []}
{"input": "Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative stress basically defines a condition in which prooxidant-antioxidant balance in the cell is disturbed; cellular biomolecules undergo severe oxidative damage, ultimately compromising cells viability.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years, a number of studies have shown that oxidative stress could cause cellular apoptosis via both the mitochondria-dependent and mitochondria-independent pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Since these pathways are directly related to the survival or death of various cell types in normal as well as pathophysiological situations, a clear picture of these pathways for various active molecules in their biological functions would help designing novel therapeutic strategy.", "output": {"entities": {}}, "schema": []}
{"input": "This review highlights the basic mechanisms of ROS production and their sites of formation; detail mechanism of both mitochondria-dependent and mitochondria-independent pathways of apoptosis as well as their regulation by ROS.", "output": {"entities": {}}, "schema": []}
{"input": "Emphasis has been given on the redox-sensitive ASK1 signalosome and its downstream JNK pathway.", "output": {"entities": {}}, "schema": []}
{"input": "This review also describes the involvement of oxidative stress under various environmental toxin-and drug-induced organ pathophysiology and diabetes-mediated apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "We believe that this review would provide useful information about the most recent progress in understanding the mechanism of oxidative stress-mediated regulation of apoptotic pathways.", "output": {"entities": {}}, "schema": []}
{"input": "It will also help to figure out the complex cross-talks between these pathways and their modulations by oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "The literature will also shed a light on the blind alleys of this field to be explored.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, readers would know about the ROS-regulated and apoptosis-mediated organ pathophysiology which might help to find their probable remedies in future.", "output": {"entities": {}}, "schema": []}
{"input": "Global and MGMT promoter hypomethylation independently associated with genomic instability of lymphocytes in subjects exposed to high-dose polycyclic aromatic hydrocarbon.", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbon", "start": 139, "end": 170}]}}, "schema": []}
{"input": "Global hypomethylation, gene-specific methylation, and genome instability are common events in tumorigenesis.", "output": {"entities": {}}, "schema": []}
{"input": "To date, few studies have examined the aberrant DNA methylation patterns in coke oven workers, who are highly at risk of lung cancer by occupational exposure to polycyclic aromatic hydrocarbons (PAHs).", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbons", "start": 161, "end": 193}, {"text": "PAHs", "start": 195, "end": 199}]}}, "schema": []}
{"input": "We recruited 82 PAH-exposed workers and 62 unexposed controls, assessed exposure levels by urinary 1-hydroxypyrene, and measured genetic damages by comet assay, bleomycin sensitivity, and micronucleus assay.", "output": {"entities": {"chemical": [{"text": "PAH", "start": 16, "end": 19}, {"text": "1-hydroxypyrene", "start": 99, "end": 114}, {"text": "bleomycin", "start": 161, "end": 170}]}}, "schema": []}
{"input": "The PAHs in coke oven emissions (COE) were estimated based on toxic equivalency factors.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 4, "end": 8}]}}, "schema": []}
{"input": "We used bisulfite-PCR pyrosequencing to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and O (6)-methylguanine-DNA methyltransferase (MGMT).", "output": {"entities": {"chemical": [{"text": "bisulfite", "start": 8, "end": 17}, {"text": "O (6)-methylguanine", "start": 119, "end": 138}]}}, "schema": []}
{"input": "Further, the methylation alteration was also investigated in COE-treated human bronchial epithelial (16HBE) cells.", "output": {"entities": {}}, "schema": []}
{"input": "We found there are higher levels of PAHs in COE.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 36, "end": 40}]}}, "schema": []}
{"input": "Among PAH-exposed workers, LINE-1 and MGMT methylation levels (with CpG site specificity) were significantly lowered.", "output": {"entities": {"chemical": [{"text": "PAH", "start": 6, "end": 9}, {"text": "CpG", "start": 68, "end": 71}]}}, "schema": []}
{"input": "LINE-1, MGMT, and its hot CpG site-specific methylation were negatively correlated with urinary 1-hydroxypyrene levels (r =-0. 329, p < 0. 001; r =-0. 164, p = 0. 049 and r =-0. 176, p = 0. 034, respectively).", "output": {"entities": {"chemical": [{"text": "CpG", "start": 26, "end": 29}, {"text": "1-hydroxypyrene", "start": 96, "end": 111}]}}, "schema": []}
{"input": "In addition, LINE-1 methylation was inversely associated with comet tail moment and micronucleus frequency, and a significant increase of micronucleus in low MGMT methylation group.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro study revealed that treatment of COE in 16HBE cells resulted in higher production of BPDE-DNA adducts, LINE-1 hypomethylation, hypomethylation, and suppression of MGMT expression.", "output": {"entities": {"chemical": [{"text": "BPDE", "start": 94, "end": 98}]}}, "schema": []}
{"input": "These findings suggest hypomethylation of LINE-1 and MGMT promoter could be used as markers for PAHs exposure and merit further investigation.", "output": {"entities": {"chemical": [{"text": "PAHs", "start": 96, "end": 100}]}}, "schema": []}
{"input": "Comparison of the Therapeutic Effectiveness of Sustained Low-Efficiency Dialysis (SLED) with Continuous Blood Purification (CBP) in Critically Ill Patients.", "output": {"entities": {}}, "schema": []}
{"input": "The differences in therapeutic effectiveness between sustained low-efficiency dialysis (SLED) and continuous blood purification (CBP) were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "In order to assess the different treatment methods, 56 critically ill patients were divided into two groups, the CBP group and the SLED group.", "output": {"entities": {}}, "schema": []}
{"input": "A comparison was made between all the biochemical indicators, in-hospital duration, hemodynamic parameters, acute physiology and chronic health evaluation (APACHE-II), the survival, and the mortality rates.", "output": {"entities": {}}, "schema": []}
{"input": "After treatment, the levels of serum creatine kinase isozyme MB (CK-MB), creatine kinase, creatinine, glutamate-oxalacetate transaminase (AST), glutamate-pyruvate transaminase (ALT), APACHE II score on the 1st, 2nd, and 7th day in both the treatment groups were lower than that before the treatment (P < 0. 05).", "output": {"entities": {"chemical": [{"text": "creatine", "start": 37, "end": 45}, {"text": "creatine", "start": 73, "end": 81}, {"text": "creatinine", "start": 90, "end": 100}, {"text": "glutamate", "start": 102, "end": 111}, {"text": "oxalacetate", "start": 112, "end": 123}, {"text": "glutamate", "start": 144, "end": 153}, {"text": "pyruvate", "start": 154, "end": 162}]}}, "schema": []}
{"input": "There are no statistical differences in in-hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, the survival rate and the mortality rate between the two groups (P > 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "It was concluded that SLED has similar hemodynamic stability with CBP and the two methods have similar treatment effects in critically ill patients.", "output": {"entities": {}}, "schema": []}
{"input": "However, we noticed that SLED can be relatively economical and convenient for critically ill patients in clinical practice.", "output": {"entities": {}}, "schema": []}
{"input": "The ameliorating effects of 5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one, an oroxylin A derivative, against memory impairment and sensorimotor gating deficit in mice.", "output": {"entities": {"chemical": [{"text": "5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one", "start": 28, "end": 90}, {"text": "oroxylin A", "start": 95, "end": 105}]}}, "schema": []}
{"input": "We previously reported that oroxylin A, a gamma-aminobutyric acid A (GABAA) receptor antagonist, ameliorates drugs-induced memory impairments.", "output": {"entities": {"chemical": [{"text": "oroxylin A", "start": 28, "end": 38}, {"text": "gamma-aminobutyric acid", "start": 42, "end": 65}]}}, "schema": []}
{"input": "We synthesized several oroxylin A derivatives in efforts to find a substance that has pro-cognitive effects as well as improves sensorimotor gating.", "output": {"entities": {"chemical": [{"text": "oroxylin A", "start": 23, "end": 33}]}}, "schema": []}
{"input": "The aim of the present study is to investigate the effect of a novel oroxylin A derivative, 5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one (DMPC), on pharmacological models of schizophrenia, which exhibit memory impairment and sensorimotor gating deficit.", "output": {"entities": {"chemical": [{"text": "oroxylin A", "start": 69, "end": 79}, {"text": "5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one", "start": 92, "end": 154}, {"text": "DMPC", "start": 156, "end": 160}]}}, "schema": []}
{"input": "Memory impairment was induced by scopolamine, a muscarinic receptor antagonist, or MK-801, an N-methyl-D-aspartate receptor antagonist.", "output": {"entities": {"chemical": [{"text": "scopolamine", "start": 33, "end": 44}, {"text": "MK-801", "start": 83, "end": 89}, {"text": "N-methyl-D-aspartate", "start": 94, "end": 114}]}}, "schema": []}
{"input": "Sensorimotor gating deficits were induced by MK-801 and measured by prepulse inhibition (PPI) of the acoustic startle response task.", "output": {"entities": {"chemical": [{"text": "MK-801", "start": 45, "end": 51}]}}, "schema": []}
{"input": "DMPC treatment (20 mg/kg) significantly attenuated scopolamine-or MK-801-induced memory impairment and it even enhanced cognitive performance of normal animals.", "output": {"entities": {"chemical": [{"text": "DMPC", "start": 0, "end": 4}, {"text": "scopolamine", "start": 51, "end": 62}, {"text": "MK-801", "start": 66, "end": 72}]}}, "schema": []}
{"input": "Furthermore, DMPC significantly ameliorated MK-801-induced PPI deficits in the acoustic startle response task.", "output": {"entities": {"chemical": [{"text": "DMPC", "start": 13, "end": 17}, {"text": "MK-801", "start": 44, "end": 50}]}}, "schema": []}
{"input": "In an in vitro study, DMPC (20 mu M) inhibited intracellular Cl (-) influx induced by muscimol, a selective GABAA receptor agonist.", "output": {"entities": {"chemical": [{"text": "DMPC", "start": 22, "end": 26}, {"text": "Cl (-)", "start": 61, "end": 67}, {"text": "muscimol", "start": 86, "end": 94}]}}, "schema": []}
{"input": "These results suggest that DMPC would be a potential candidate for alleviating cognitive dysfunction and sensorimotor gating deficits in schizophrenia, and that its effects may be mediated, in part, via blockade of the GABAergic neurotransmitter system.", "output": {"entities": {"chemical": [{"text": "DMPC", "start": 27, "end": 31}]}}, "schema": []}
{"input": "Progress in the studies on tryptanthrin, an alkaloid of history.", "output": {"entities": {"chemical": [{"text": "tryptanthrin", "start": 27, "end": 39}]}}, "schema": []}
{"input": "Tryptanthrin, an indoloquinazoline alkaloid, was first obtained by sublimation of natural indigo and later isolated from the culture of fungus Candida lipolytica and a variety of other natural sources.", "output": {"entities": {"chemical": [{"text": "Tryptanthrin", "start": 0, "end": 12}, {"text": "indoloquinazoline alkaloid", "start": 17, "end": 43}]}}, "schema": []}
{"input": "Tryptanthrin showed a variety of intriguing biological properties such as antibacterial, antifungal, antiprotozoal, and antiparasitic activities, inhibitory activities against COX-2, 5-LOX, NO synthase and PGE (2) expression, as well as cytotoxic and antitumor activities.", "output": {"entities": {"chemical": [{"text": "Tryptanthrin", "start": 0, "end": 12}, {"text": "NO", "start": 190, "end": 192}, {"text": "PGE (2)", "start": 206, "end": 213}]}}, "schema": []}
{"input": "Present review covers recent studies on the natural sources, biological activities and mechanisms of their actions, synthesis, structure-activity relationship, and metabolism of tryptanthrin.", "output": {"entities": {"chemical": [{"text": "tryptanthrin", "start": 178, "end": 190}]}}, "schema": []}
{"input": "Design, synthesis, in vitro cytotoxicity evaluation and structure-activity relationship of Goniothalamin analogs.", "output": {"entities": {"chemical": [{"text": "Goniothalamin", "start": 91, "end": 104}]}}, "schema": []}
{"input": "A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from commercially available (3, 4-dihydro-2H-pyran-2-yl) methanol/5-(hydroxymethyl) dihydrofuran-2 (3H)-one in three steps with good to moderate overall yields and their cytotoxicity against lymphoblastic leukemic T cell line (Jurkat E6. 1) have been evaluated.", "output": {"entities": {"chemical": [{"text": "(E/Z)-Goniothalamin", "start": 28, "end": 47}, {"text": "(3, 4-dihydro-2H-pyran-2-yl) methanol", "start": 101, "end": 138}, {"text": "5-(hydroxymethyl) dihydrofuran-2 (3H)-one", "start": 139, "end": 180}]}}, "schema": []}
{"input": "Among the synthesized analogs, (Z)-Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 mu M).", "output": {"entities": {"chemical": [{"text": "(Z)-Goniothalamin", "start": 31, "end": 48}]}}, "schema": []}
{"input": "Structure-activity relationship study indicates that introducing substituent in phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the ring size of lactones (from six to five member) do not increase the cytotoxicity.", "output": {"entities": {"chemical": [{"text": "phenyl", "start": 80, "end": 86}, {"text": "pyridine", "start": 120, "end": 128}, {"text": "naphthalene", "start": 129, "end": 140}, {"text": "lactones", "start": 173, "end": 181}]}}, "schema": []}
{"input": "Loss of Calcium/Calmodulin-Dependent Protein Kinase II Activity in Cortical Astrocytes Decreases Glutamate Uptake and Induces Neurotoxic Release of ATP.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 8, "end": 15}, {"text": "Glutamate", "start": 97, "end": 106}, {"text": "ATP", "start": 148, "end": 151}]}}, "schema": []}
{"input": "The extent of calcium/calmodulin-dependent protein kinase II (CaMKII) inactivation in the brain following ischemia correlates with the extent of damage.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 14, "end": 21}]}}, "schema": []}
{"input": "We have previously shown that a loss of CaMKII activity in neurons is detrimental to neuronal viability by inducing excitotoxic glutamate release.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 128, "end": 137}]}}, "schema": []}
{"input": "In the current study, we extend these findings to show that the ability of astrocytes to buffer extracellular glutamate is reduced when CaMKII is inhibited.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 110, "end": 119}]}}, "schema": []}
{"input": "Furthermore, CaMKII inhibition in astrocytes is associated with the rapid onset of intracellular calcium oscillations.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Surprisingly, this rapid calcium influx is blocked by the N-type calcium channel antagonist, omega-conotoxin.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 25, "end": 32}, {"text": "N", "start": 58, "end": 59}, {"text": "calcium", "start": 65, "end": 72}]}}, "schema": []}
{"input": "While the function of N-type calcium channels within astrocytes is controversial, these voltage-gated calcium channels have been linked to calcium-dependent vesicular gliotransmitter release.", "output": {"entities": {"chemical": [{"text": "N", "start": 22, "end": 23}, {"text": "calcium", "start": 29, "end": 36}, {"text": "calcium", "start": 102, "end": 109}, {"text": "calcium", "start": 139, "end": 146}]}}, "schema": []}
{"input": "When extracellular glutamate and ATP levels are measured following CaMKII inhibition within our enriched astrocyte cultures, no alterations in glutamate levels are observed, whereas ATP levels in the extracellular environment significantly increase.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 19, "end": 28}, {"text": "ATP", "start": 33, "end": 36}, {"text": "glutamate", "start": 143, "end": 152}, {"text": "ATP", "start": 182, "end": 185}]}}, "schema": []}
{"input": "Extracellular ATP accumulation associated with CaMKII inhibition contributes both to calcium oscillations within astrocytes and ultimately cortical neuron toxicity.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 14, "end": 17}, {"text": "calcium", "start": 85, "end": 92}]}}, "schema": []}
{"input": "Thus, a loss of CaMKII signaling within astrocytes dysregulates glutamate uptake and supports ATP release, two processes that would compromise neuronal survival following ischemic/excitotoxic insults.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 64, "end": 73}, {"text": "ATP", "start": 94, "end": 97}]}}, "schema": []}
{"input": "Mass and Ion Transport in Ketones and Ketone Electrolytes: Comparison with Acetate Systems.", "output": {"entities": {"chemical": [{"text": "Ketones", "start": 26, "end": 33}, {"text": "Ketone", "start": 38, "end": 44}, {"text": "Acetate", "start": 75, "end": 82}]}}, "schema": []}
{"input": "Self-diffusion coefficient measurements were performed for pure n-alkyl ketone liquids using the pulsed field gradient NMR spin-echo technique.", "output": {"entities": {"chemical": [{"text": "n-alkyl ketone", "start": 64, "end": 78}]}}, "schema": []}
{"input": "Ionic conductivities and dielectric constants of 0. 0055 mol. L (-1) tetrabutylammonium trifluoromethanesulfonate in 2-pentanone, 2-hexanone, 2-heptanone, 2-octanone, 2-nonanone, and 2-decanone were also measured.", "output": {"entities": {"chemical": [{"text": "tetrabutylammonium trifluoromethanesulfonate", "start": 69, "end": 113}, {"text": "2-pentanone", "start": 117, "end": 128}, {"text": "2-hexanone", "start": 130, "end": 140}, {"text": "2-heptanone", "start": 142, "end": 153}, {"text": "2-octanone", "start": 155, "end": 165}, {"text": "2-nonanone", "start": 167, "end": 177}, {"text": "2-decanone", "start": 183, "end": 193}]}}, "schema": []}
{"input": "The temperature-dependent conductivities and diffusion coefficients over the range 5-80 degrees C can be described using the compensated Arrhenius formalism.", "output": {"entities": {}}, "schema": []}
{"input": "Compensated Arrhenius equation plots were used to calculate the average activation energy for both sets of data.", "output": {"entities": {}}, "schema": []}
{"input": "The average activation energy from conductivity data is approximately equal to that from diffusion data.", "output": {"entities": {}}, "schema": []}
{"input": "The data for the pure ketones and ketone-based electrolytes are compared with analogous data for pure n-alkyl acetates and n-alkyl acetate-based electrolytes.", "output": {"entities": {"chemical": [{"text": "ketones", "start": 22, "end": 29}, {"text": "ketone", "start": 34, "end": 40}, {"text": "n-alkyl acetates", "start": 102, "end": 118}, {"text": "n-alkyl acetate", "start": 123, "end": 138}]}}, "schema": []}
{"input": "Synthesis and Pharmacological Characterization of 2-(Acylamino) thiophene Derivatives as Metabolically Stable, Orally Effective, Positive Allosteric Modulators of the GABAB Receptor.", "output": {"entities": {"chemical": [{"text": "2-(Acylamino) thiophene", "start": 50, "end": 73}]}}, "schema": []}
{"input": "Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino) thiophene derivatives.", "output": {"entities": {"chemical": [{"text": "COR627", "start": 37, "end": 43}, {"text": "COR628", "start": 48, "end": 54}, {"text": "2-(acylamino) thiophene", "start": 99, "end": 122}]}}, "schema": []}
{"input": "Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABAB receptor by potentiating GTP gamma S stimulation induced by GABA at 2. 5 and 25 mu M while failing to exhibit intrinsic agonist activity.", "output": {"entities": {"chemical": [{"text": "GABAB", "start": 105, "end": 110}]}}, "schema": []}
{"input": "Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically.", "output": {"entities": {"chemical": [{"text": "baclofen", "start": 64, "end": 72}]}}, "schema": []}
{"input": "Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice.", "output": {"entities": {"chemical": [{"text": "GS39783", "start": 73, "end": 80}, {"text": "baclofen", "start": 216, "end": 224}]}}, "schema": []}
{"input": "Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177.", "output": {"entities": {"chemical": [{"text": "GS39783", "start": 96, "end": 103}, {"text": "BHF177", "start": 107, "end": 113}]}}, "schema": []}
{"input": "Catalytic Asymmetric Synthesis of gamma-Butenolides by Direct Vinylogous Reactions.", "output": {"entities": {"chemical": [{"text": "gamma-Butenolides", "start": 34, "end": 51}]}}, "schema": []}
{"input": "The gamma-butenolide structural motif is a prominent feature in many bioactive natural products and drugs.", "output": {"entities": {"chemical": [{"text": "gamma-butenolide", "start": 4, "end": 20}]}}, "schema": []}
{"input": "This short review summarizes catalytic asymmetric synthesis of gamma-butenolides through direct vinylogous reactions by metal complexes and organocatalysts.", "output": {"entities": {"chemical": [{"text": "gamma-butenolides", "start": 63, "end": 80}]}}, "schema": []}
{"input": "In light of building chiral gamma-tertiary and quaternary carbon centers of butenolides, three synthetic strategies are included: 1) the reactions with furanone derivatives as nucleophiles, 2) olefination of gamma, gamma-disubstituted butenolides and 3) the reactions by using gamma, gamma-disubstituted butenolides as nucleophiles.", "output": {"entities": {"chemical": [{"text": "gamma-tertiary and quaternary carbon", "start": 28, "end": 64}, {"text": "butenolides", "start": 76, "end": 87}, {"text": "gamma, gamma-disubstituted butenolides", "start": 208, "end": 246}, {"text": "gamma, gamma-disubstituted butenolides", "start": 277, "end": 315}]}}, "schema": []}
{"input": "Transition metal-catalyzed efficient and green transformations of p (o)-h compounds to functional organophosphorus compounds.", "output": {"entities": {"chemical": [{"text": "Transition metal", "start": 0, "end": 16}, {"text": "organophosphorus", "start": 98, "end": 114}]}}, "schema": []}
{"input": "Organophosphorus compounds are of high importance in organic synthesis, catalysis, biochemistry, pharmaceuticals, and material science.", "output": {"entities": {"chemical": [{"text": "Organophosphorus", "start": 0, "end": 16}]}}, "schema": []}
{"input": "In this mini review, we summarize our recent studies on transition metal-catalyzed green and atom efficient transformations of P (O)-H bonds to various versatile organophosphorus compounds, including the highly regio-and stereoselective P (O)-H additions to carbon-carbon unsaturated compounds, asymmetric hydrophosphorylation reactions, and dehydrogenative coupling reactions of P (O)-H compounds with carbon-H and heteroatom-H compounds.", "output": {"entities": {"chemical": [{"text": "transition metal", "start": 56, "end": 72}, {"text": "P (O)-H", "start": 127, "end": 134}, {"text": "organophosphorus", "start": 162, "end": 178}, {"text": "P (O)-H", "start": 237, "end": 244}, {"text": "carbon", "start": 258, "end": 264}, {"text": "carbon", "start": 265, "end": 271}, {"text": "P (O)-H", "start": 380, "end": 387}, {"text": "carbon", "start": 403, "end": 409}, {"text": "H", "start": 410, "end": 411}, {"text": "H", "start": 427, "end": 428}]}}, "schema": []}
{"input": "These new reactions provide efficient, general and practical ways for the preparation of a variety of well-defined functional organophosphorus compounds.", "output": {"entities": {"chemical": [{"text": "organophosphorus", "start": 126, "end": 142}]}}, "schema": []}
{"input": "Mechanistic aspects related to the catalytic processes are also discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Organic selenium resin in solid phase synthesis and its application in constructing medicinally relevant small organic molecules.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 8, "end": 16}]}}, "schema": []}
{"input": "Heterocyclic compounds are of high importance in constructing active drug intermediates library.", "output": {"entities": {}}, "schema": []}
{"input": "The emergence of solid-phase and combinatorial chemistry has led to renewed interest in using organoselenium resins to library drug-like production.", "output": {"entities": {"chemical": [{"text": "organoselenium", "start": 94, "end": 108}]}}, "schema": []}
{"input": "In this mini review, we summarize the construction of heterocyclic compounds libraries such as isoxazoles, oxadiazoles, triazoles, pyrimidines, pyrrolines, indolines, benzopyrans, furans etc. using organoselenium resins.", "output": {"entities": {"chemical": [{"text": "isoxazoles", "start": 95, "end": 105}, {"text": "oxadiazoles", "start": 107, "end": 118}, {"text": "triazoles", "start": 120, "end": 129}, {"text": "pyrimidines", "start": 131, "end": 142}, {"text": "pyrrolines", "start": 144, "end": 154}, {"text": "indolines", "start": 156, "end": 165}, {"text": "benzopyrans", "start": 167, "end": 178}, {"text": "furans", "start": 180, "end": 186}, {"text": "organoselenium", "start": 198, "end": 212}]}}, "schema": []}
{"input": "And it provided efficient and practical ways for the preparation of a variety of well-defined functional heterocyclic compounds with the advantages of good yields, high purity, straightforward operations, broad range and high diversity of the products, lack of odor, and good stability of the resins, all of these give expression to green chemistry.", "output": {"entities": {}}, "schema": []}
{"input": "Enzyme-Catalyzed Synthesis of Aliphatic-Aromatic Oligoamides.", "output": {"entities": {}}, "schema": []}
{"input": "Enzymatically catalyzed polycondensation of p-xylylenediamine and diethyl sebacate resulted in oligo (p-xylylene sebacamide) with high melting temperatures (223-230 degrees C) and the enzymatic polycondensation of dimethyl terephthalate and 1, 8-diaminooctane leads to oligo (octamethylene terephthalamide) with two melting temperatures at 186 and 218 degrees C.", "output": {"entities": {"chemical": [{"text": "p-xylylenediamine", "start": 44, "end": 61}, {"text": "diethyl sebacate", "start": 66, "end": 82}, {"text": "oligo (p-xylylene sebacamide)", "start": 95, "end": 124}, {"text": "dimethyl terephthalate", "start": 214, "end": 236}, {"text": "1, 8-diaminooctane", "start": 241, "end": 259}, {"text": "oligo (octamethylene terephthalamide)", "start": 269, "end": 306}]}}, "schema": []}
{"input": "No oligoamides, but products 1 and 2, were formed from the enzymatic reaction of dimethyl terephthalate and p-xylylenediamine.", "output": {"entities": {"chemical": [{"text": "dimethyl terephthalate", "start": 81, "end": 103}, {"text": "p-xylylenediamine", "start": 108, "end": 125}]}}, "schema": []}
{"input": "All reactions were catalyzed by CAL-B, icutinase, or CLEA cutinase.", "output": {"entities": {}}, "schema": []}
{"input": "All reactions catalyzed by CAL-B show higher conversion than reactions catalyzed by icutinase or CLEA cutinase.", "output": {"entities": {}}, "schema": []}
{"input": "The highest DPmax of 15 was achieved in a one-step and two-step synthesis of oligo (p-xylylene sebacamide) catalyzed by CLEA cutinase.", "output": {"entities": {"chemical": [{"text": "oligo (p-xylylene sebacamide)", "start": 77, "end": 106}]}}, "schema": []}
{"input": "Impurity partitioning during colloidal crystallization.", "output": {"entities": {}}, "schema": []}
{"input": "We have found that an impurity partitioning takes place during growth of colloidal crystals, which was recognized by the fact that the impurity concentration in the solid (CS) was different from that in the initial solution (C0).", "output": {"entities": {}}, "schema": []}
{"input": "The effective partition coefficient keff (= CS/C0) was investigated for pure polystyrene and polystyrene dyed with fluorescent particles by changing the ratio of particle diameters dimp/dcryst and growth rate V.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 77, "end": 88}, {"text": "polystyrene", "start": 93, "end": 104}]}}, "schema": []}
{"input": "At each size ratio for the polystyrene impurity, keff was less than unity and increased to unity with increasing V, whereas at a given growth rate, keff increased to unity as dimp/dcryst approached unity.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 27, "end": 38}]}}, "schema": []}
{"input": "These results were consistent with the solute behavior analyzed using the Burton, Prim, and Slichter (BPS) model.", "output": {"entities": {}}, "schema": []}
{"input": "The obtained k0, equilibrium partition coefficient, from a BPS plot increased as dimp/dcryst approached unity.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, while the fluorescent particles also followed the BPS model, they showed higher k0 values than those of the same size of polystyrene particles.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 134, "end": 145}]}}, "schema": []}
{"input": "A k0 value greater than unity was obtained for impurities that were similar in size to the host particle.", "output": {"entities": {}}, "schema": []}
{"input": "This behavior is attributed to the positive free energy of fusion associated with the incorporation of the fluorescent particles into the host matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Such positive free energy of fusion implies the presence of the enthalpy associated with interaction between particles.", "output": {"entities": {}}, "schema": []}
{"input": "Virtual medicinal chemistry: In silico pre-docking functional group transformation for discovery of novel inhibitors of botulinum toxin serotype A light chain.", "output": {"entities": {}}, "schema": []}
{"input": "A novel method for applying high-throughput docking to challenging metalloenzyme targets is described.", "output": {"entities": {}}, "schema": []}
{"input": "The method utilizes information-based virtual transformation of library carboxylates to hydroxamic acids prior to docking, followed by compound acquisition, one-pot (two steps) chemical synthesis and in vitro screening.", "output": {"entities": {"chemical": [{"text": "carboxylates", "start": 72, "end": 84}, {"text": "hydroxamic acids", "start": 88, "end": 104}]}}, "schema": []}
{"input": "In two experiments targeting the botulinum neurotoxin serotype A metalloprotease light chain, hit rates of 32% and 18% were observed.", "output": {"entities": {}}, "schema": []}
{"input": "Antimicrobial activity of southern African medicinal plants with dermatological relevance: From an ethnopharmacological screening approach, to combination studies and the isolation of a bioactive compound.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical reports on more than 100 southern African medicinal plants with dermatological relevance have been highlighted, yet there is still limited scientific data to support claims for their antimicrobial effectiveness against skin pathogens.", "output": {"entities": {}}, "schema": []}
{"input": "Guided by ethnobotanical data, this paper explores the antimicrobial efficacies of southern African medicinal plants used to treat skin ailments.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: To investigate the antimicrobial properties of southern African medicinal plants against dermatologically relevant pathogens.", "output": {"entities": {}}, "schema": []}
{"input": "The study also aimed at providing a scientific rationale for the traditional use of plant combinations to treat skin diseases and the isolation of the bioactive compound from the most active species, Aristea ecklonii (Iridaceae).", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Organic and aqueous extracts (132) were prepared from 47 plant species and screened for antimicrobial properties against dermatologically relevant pathogens using the micro-titre plate dilution method.", "output": {"entities": {}}, "schema": []}
{"input": "Four different plant combinations were investigated for interactive properties and the sum of the fractional inhibitory concentration (Esh FIC) calculated.", "output": {"entities": {}}, "schema": []}
{"input": "Isobolograms were used to further investigate the antimicrobial interactive properties of Pentanisia prunelloides combined with Elephantorrhiza elephantina at varied ratios.", "output": {"entities": {}}, "schema": []}
{"input": "A bioactivity-guided fractionation process was adopted to fractionate the organic leaf extract of Aristea ecklonii.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Plants demonstrating notable broad-spectrum activities (MIC values <= 1. 00mg/ml) against the tested pathogens included extracts from Aristea ecklonii, Chenopodium ambrosioides, Diospyros mespiliformis, Elephantorrhiza elephantina, Eucalyptus camaldulensis, Gunnera perpensa, Harpephyllum caffrum, Hypericum perforatum, Melianthus comosus, Terminalia sericea and Warburgia salutaris.", "output": {"entities": {}}, "schema": []}
{"input": "The organic extract of Elephantorrhiza elephantina, a plant reportedly used to treat acne vulgaris, demonstrated noteworthy antimicrobial activity (MIC value of 0. 05mg/ml) against Propionibacterium acnes.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, Diospyros mespiliformis reported for its traditional use to treat ringworm, also displayed noteworthy antimicrobial activity against Trichophyton mentagrophytes (MIC 0. 10mg/ml) and Microsporum canis (MIC 0. 50mg/ml).", "output": {"entities": {}}, "schema": []}
{"input": "The aqueous root extracts of Pentanisia prunelloides combined (1: 1) with Elephantorrhiza elephantina displayed synergistic interactions (Esh FIC values 0. 31-0. 38) against Staphylococcus aureus, gentamycin-methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans.", "output": {"entities": {"chemical": [{"text": "gentamycin", "start": 197, "end": 207}, {"text": "methicillin", "start": 208, "end": 219}]}}, "schema": []}
{"input": "Fractionation of Aristea ecklonii resulted in the isolation of the known bioactive compound, plumbagin, displaying noteworthy antimicrobial activity (MIC range between 2. 00 mu g/ml and 16. 00 mu g/ml).", "output": {"entities": {"chemical": [{"text": "plumbagin", "start": 93, "end": 102}]}}, "schema": []}
{"input": "CONCLUSION: Most of the plant extracts demonstrated pathogen specific antimicrobial effects with a few exhibiting broad-spectrum activities.", "output": {"entities": {}}, "schema": []}
{"input": "Positive antimicrobial effects noted for plants such as Elephantorrhiza elephantina and Diospyros mespiliformis used for acne vulgaris and ringworm infections, respectively, give some validation to their reported traditiona l uses.", "output": {"entities": {}}, "schema": []}
{"input": "Synergistic interactions noted for Pentanisia prunelloides combined with Elephantorrhiza elephantina validate an enhanced antimicrobial effect when used in combination.", "output": {"entities": {}}, "schema": []}
{"input": "Noteworthy antimicrobial activities (MIC range between 2. 00 mu g/ml and 16. 00 mu g/ml) were observed for plumbagin isolated from Aristea ecklonii.", "output": {"entities": {"chemical": [{"text": "plumbagin", "start": 107, "end": 116}]}}, "schema": []}
{"input": "Stable and high-rate overcharge protection for rechargeable lithium batteries.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 60, "end": 67}]}}, "schema": []}
{"input": "Rechargeable lithium or lithium-ion cells can be overcharge-protected by an electroactive polymer composite separator.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 13, "end": 20}, {"text": "lithium", "start": 24, "end": 31}]}}, "schema": []}
{"input": "The use of non-woven fibrous membranes instead of conventional microporous membranes as the composite substrates allowed better distribution of the electroactive polymer, which led to improved utilization and a 40-fold increase in sustainable current density.", "output": {"entities": {}}, "schema": []}
{"input": "For the first time, stable overcharge protection for hundreds of cycles was demonstrated in several cell chemistries, including LiNi1/3Co1/3Mn1/3O2, LiFePO4, and spinel Li1. 05Mn1. 95O4 half-cells.", "output": {"entities": {"chemical": [{"text": "LiNi1", "start": 128, "end": 133}, {"text": "3Co1", "start": 134, "end": 138}, {"text": "3Mn1", "start": 139, "end": 143}, {"text": "3O2", "start": 144, "end": 147}, {"text": "LiFePO4", "start": 149, "end": 156}, {"text": "Li1. 05Mn1. 95O4", "start": 169, "end": 185}]}}, "schema": []}
{"input": "Protection at a charging rate as high as 5 C was achieved at a steady state cell potential below 4. 85 V.", "output": {"entities": {}}, "schema": []}
{"input": "PD-1, but not PD-L1, expressed by islet-reactive CD4 + T cells suppresses infiltration of the pancreas during Type 1 Diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "The inhibitory receptor PD-1 constrains Type 1 Diabetes (T1D) in the non-obese diabetic (NOD) mouse.", "output": {"entities": {}}, "schema": []}
{"input": "However, how PD-1 influences diabetogenic CD4 (+) T cells during natural diabetes is not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "To address this question we developed a novel model to investigate antigen-specific CD4 (+) T cells under physiological conditions in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "We transferred a low number of na i ve CD4 (+) T cells from the BDC2. 5 mouse into prediabetic NOD mice to mimic a physiological precursor frequency and allowed the cells to become primed by endogenous autoantigen.", "output": {"entities": {}}, "schema": []}
{"input": "Transferred BDC2. 5 T cells became activated, differentiated into T-bet (+) IFN gamma-producing cells, and infiltrated the pancreas.", "output": {"entities": {}}, "schema": []}
{"input": "In this model, loss of PD-1, but not PD-L1, on the antigen-specific CD4 (+) T cell resulted in increased cell numbers in the spleen, pancreas-draining lymph node and pancreas.", "output": {"entities": {}}, "schema": []}
{"input": "PD-1-deficiency also increased expression of the chemokine receptor CXCR3.", "output": {"entities": {}}, "schema": []}
{"input": "Lastly, histological data showed that a loss of PD-1 caused BDC2. 5 cells to penetrate deep into the islet core, resulting in conversion from peri-insulitis to destructive insulitis.", "output": {"entities": {}}, "schema": []}
{"input": "These data support a model by which PD-1 regulates islet-reactive CD4 (+) T cells in a cell intrinsic manner by suppressing proliferation, inhibiting infiltration of the pancreas, and limiting diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "The metabolic profile of mitoxantrone and its relation with mitoxantrone-induced cardiotoxicity.", "output": {"entities": {"chemical": [{"text": "mitoxantrone", "start": 25, "end": 37}, {"text": "mitoxantrone", "start": 60, "end": 72}]}}, "schema": []}
{"input": "Mitoxantrone (MTX) is an antitumor agent that causes cardiotoxicity in 18% patients.", "output": {"entities": {"chemical": [{"text": "Mitoxantrone", "start": 0, "end": 12}, {"text": "MTX", "start": 14, "end": 17}]}}, "schema": []}
{"input": "The metabolic profile of MTX was assessed after incubation of 100 mu M MTX with hepatic S9 fraction isolated from rats.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 25, "end": 28}, {"text": "MTX", "start": 71, "end": 74}]}}, "schema": []}
{"input": "The presence of MTX and its metabolites was also assessed in vivo through the analysis of liver and heart extracts of MTX-treated rats.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 16, "end": 19}, {"text": "MTX", "start": 118, "end": 121}]}}, "schema": []}
{"input": "The cytotoxic effects of MTX and MTX metabolites were evaluated in the H9c2 cells after 24-h incubation with MTX alone and MTX + metabolites.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 25, "end": 28}, {"text": "MTX", "start": 33, "end": 36}, {"text": "MTX", "start": 109, "end": 112}, {"text": "MTX", "start": 123, "end": 126}]}}, "schema": []}
{"input": "The influence of CYP450-and CYP2E1-mediated metabolism for the cytotoxicity of MTX was assessed after 96-h incubation with MTX (100 nM and 1 mu M) in the presence/absence of CYP450 or CYP2E1 inhibitors.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 79, "end": 82}, {"text": "MTX", "start": 123, "end": 126}]}}, "schema": []}
{"input": "After 4-h incubation in supplemented S9 fraction, the MTX content was 35% lower and 5 metabolites were identified: an acetoxy ester derivative (never described before), two glutathione conjugates, a monocarboxylic acid derivative, and the naphtoquinoxaline, the later commonly related to MTX pharmacological effects.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 54, "end": 57}, {"text": "glutathione", "start": 173, "end": 184}, {"text": "monocarboxylic acid", "start": 199, "end": 218}, {"text": "naphtoquinoxaline", "start": 239, "end": 256}, {"text": "MTX", "start": 288, "end": 291}]}}, "schema": []}
{"input": "The presence of MTX and naphtoquinoxaline metabolite was evidenced in vivo in liver and heart of MTX-treated rats.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 16, "end": 19}, {"text": "naphtoquinoxaline", "start": 24, "end": 41}, {"text": "MTX", "start": 97, "end": 100}]}}, "schema": []}
{"input": "The cytotoxicity caused by MTX + metabolites was higher than that observed in the H9c2 cells incubated with non-metabolized MTX group.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 27, "end": 30}, {"text": "MTX", "start": 124, "end": 127}]}}, "schema": []}
{"input": "The co-incubation of MTX with CYP450 and CYP2E1 inhibitors partially prevented the cytotoxicity observed in the MTX groups incubated with H9c2 cells, highlighting that the metabolism of MTX is relevant for its undesirable effects.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 21, "end": 24}, {"text": "MTX", "start": 112, "end": 115}, {"text": "MTX", "start": 186, "end": 189}]}}, "schema": []}
{"input": "The naphtoquinoxaline metabolite is described in heart and liver in vivo, highlighting that this metabolite accumulates in these tissues.", "output": {"entities": {"chemical": [{"text": "naphtoquinoxaline", "start": 4, "end": 21}]}}, "schema": []}
{"input": "It was demonstrated that MTX P450-mediated metabolism contributed to MTX toxicity.", "output": {"entities": {"chemical": [{"text": "MTX", "start": 25, "end": 28}, {"text": "MTX", "start": 69, "end": 72}]}}, "schema": []}
{"input": "Six New Cyclic Peptides from the Roots of Gypsophila oldhamiana.", "output": {"entities": {}}, "schema": []}
{"input": "Six new cyclic peptides, gypsophin A-F (1-6), were isolated from Gypsophila oldhamiana.", "output": {"entities": {"chemical": [{"text": "gypsophin A-F", "start": 25, "end": 38}]}}, "schema": []}
{"input": "Their structures were elucidated by extensive NMR and chemical degradation.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 3 exhibited moderate activity of antiplatelet aggregation in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 71, "end": 78}]}}, "schema": []}
{"input": "The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells.", "output": {"entities": {"chemical": [{"text": "petroleum ether", "start": 103, "end": 118}, {"text": "chloroform", "start": 134, "end": 144}, {"text": "ethyl acetate", "start": 160, "end": 173}, {"text": "ethanol", "start": 296, "end": 303}]}}, "schema": []}
{"input": "Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 mu g/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 113, "end": 120}]}}, "schema": []}
{"input": "After the exposure, cell viability using (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied.", "output": {"entities": {"chemical": [{"text": "3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide", "start": 42, "end": 104}, {"text": "neutral red", "start": 110, "end": 121}]}}, "schema": []}
{"input": "Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 135, "end": 142}]}}, "schema": []}
{"input": "Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 75, "end": 81}, {"text": "glutathione", "start": 138, "end": 149}, {"text": "GSH", "start": 151, "end": 154}, {"text": "ethanol", "start": 174, "end": 181}]}}, "schema": []}
{"input": "Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 133, "end": 136}, {"text": "ethanol", "start": 155, "end": 162}]}}, "schema": []}
{"input": "The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 131, "end": 138}]}}, "schema": []}
{"input": "However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective.", "output": {"entities": {}}, "schema": []}
{"input": "The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia.", "output": {"entities": {}}, "schema": []}
{"input": "Differential propensity of citrate-and polyethylene glycol-coated silver nanoparticles to bovine hemoglobin.", "output": {"entities": {"chemical": [{"text": "citrate", "start": 27, "end": 34}, {"text": "polyethylene glycol", "start": 39, "end": 58}, {"text": "silver", "start": 66, "end": 72}]}}, "schema": []}
{"input": "Propensity of two different silver nanoparticles (Ag-NPs) to bovine hemoglobin (BHb) was investigated by means of spectroscopic methods.", "output": {"entities": {"chemical": [{"text": "silver", "start": 28, "end": 34}, {"text": "Ag", "start": 50, "end": 52}]}}, "schema": []}
{"input": "We have combined spectrophotometric and calorimetric methods to show that there is no significant interaction between citrate-coated Ag-NPs and BHb at physiological pH and 20 degrees C.", "output": {"entities": {"chemical": [{"text": "citrate", "start": 118, "end": 125}, {"text": "Ag", "start": 133, "end": 135}]}}, "schema": []}
{"input": "However, our previous results show that polyethylene glycol-coated Ag-NPs strongly bind to Hb and effect on the secondary and tertiary structures of BHb.", "output": {"entities": {"chemical": [{"text": "polyethylene glycol", "start": 40, "end": 59}, {"text": "Ag", "start": 67, "end": 69}]}}, "schema": []}
{"input": "Thus, a suitable surface coating and modification of surface charge would increase the NPs safety and reduce adverse biological responses.", "output": {"entities": {}}, "schema": []}
{"input": "Excess androgens in utero alters fetal testis development.", "output": {"entities": {"chemical": [{"text": "androgens", "start": 7, "end": 16}]}}, "schema": []}
{"input": "Prenatal androgenization induces a polycystic ovary syndrome-like phenotype in adult female offspring, which is associated with alterations that can be detected in the fetal ovary, suggesting gestational origins of this condition.", "output": {"entities": {}}, "schema": []}
{"input": "We therefore investigated whether increased prenatal androgen exposure also altered testicular development using ovine animal models.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 53, "end": 61}]}}, "schema": []}
{"input": "Biweekly maternal testosterone propionate (TP; 100 mg) from day 62 to day 70/day 90 of gestation altered male developmental trajectory.", "output": {"entities": {"chemical": [{"text": "testosterone propionate", "start": 18, "end": 41}]}}, "schema": []}
{"input": "In male fetuses serum LH was decreased (P <. 01), and testicular STAR, CYP11, and CYP17 abundance were reduced.", "output": {"entities": {}}, "schema": []}
{"input": "Coincident with this, basal testicular T synthesis was decreased in vitro (P <. 001).", "output": {"entities": {}}, "schema": []}
{"input": "Leydig cell distribution was severely perturbed in all testes prenatally exposed to TP (P <. 001).", "output": {"entities": {}}, "schema": []}
{"input": "To examine the contribution of estrogens, fetuses were injected with TP (20 mg), the potent estrogen agonist, diethylstilbestrol (DES; 20 mg), or vehicle control at day 62 and day 82 and assessed at day 90.", "output": {"entities": {"chemical": [{"text": "estrogens", "start": 31, "end": 40}, {"text": "estrogen", "start": 92, "end": 100}, {"text": "diethylstilbestrol", "start": 110, "end": 128}, {"text": "DES", "start": 130, "end": 133}]}}, "schema": []}
{"input": "The effects of fetal (direct) TP treatment, but not DES, paralleled maternal (indirect) TP exposure, supporting a direct androgen effect.", "output": {"entities": {"chemical": [{"text": "DES", "start": 52, "end": 55}, {"text": "androgen", "start": 121, "end": 129}]}}, "schema": []}
{"input": "Cessation of maternal androgenization at day 102 returned Leydig cell distribution to normal but increased basal T output, at day 112, demonstrating Leydig cell developmental plasticity.", "output": {"entities": {}}, "schema": []}
{"input": "Earlier maternal androgen exposure from day 30 similarly influenced Leydig cell development at day 90 but additionally affected the expression of Sertoli and germ cell markers.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 17, "end": 25}]}}, "schema": []}
{"input": "We show in this study that increased prenatal androgen exposure alters development and function of Leydig cells at a time when androgen production is paramount for male development.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 46, "end": 54}]}}, "schema": []}
{"input": "This supports the concept that gestational antecedents associated with polycystic ovary syndrome may have effects on the male fetus.", "output": {"entities": {}}, "schema": []}
{"input": "Budesonide/cyclodextrin complex-loaded lyophilized microparticles for intranasal application.", "output": {"entities": {"chemical": [{"text": "Budesonide", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Abstract Objective: Lyophilized microparticles composed of budesonide (BDS), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and hydroxypropylmethylcellulose (HPMC) or sodium carboxymethylcellulose (CMC-Na) were developed for intranasal delivery and their characteristics were evaluated.", "output": {"entities": {"chemical": [{"text": "budesonide", "start": 59, "end": 69}, {"text": "BDS", "start": 71, "end": 74}, {"text": "hydroxypropyl-beta-cyclodextrin", "start": 77, "end": 108}, {"text": "HP-beta-CD", "start": 110, "end": 120}, {"text": "sodium", "start": 166, "end": 172}, {"text": "Na", "start": 201, "end": 203}]}}, "schema": []}
{"input": "Materials and methods: The particle size and morphology were assessed by mean diameter measurement and scanning electron microscopy (SEM) image, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The solid-state of products was tested by X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC).", "output": {"entities": {}}, "schema": []}
{"input": "In vitro drug release and cytotoxicity to the primary human nasal epithelial (HNE) cells were also evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Results and discussion: Lyophilized microparticles exhibited vanishment of crystallinity of drug in XRPD analysis, the enfeeblement of carbonyl (C = O) stretching bands of carboxyl group in BDS in FT-IR spectra and the disappearance of endothermic peak of drug in the results of DSC study.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 135, "end": 143}, {"text": "C = O", "start": 145, "end": 150}, {"text": "carboxyl", "start": 172, "end": 180}, {"text": "BDS", "start": 190, "end": 193}]}}, "schema": []}
{"input": "Based on the results of solid-state studies, BDS was existed as an amorphous form in the lyophilized microparticles.", "output": {"entities": {"chemical": [{"text": "BDS", "start": 45, "end": 48}]}}, "schema": []}
{"input": "CD complexation enhanced drug solubility and release rate, and HPMC or CMC-Na also improved drug dissolution rates.", "output": {"entities": {"chemical": [{"text": "Na", "start": 75, "end": 77}]}}, "schema": []}
{"input": "Cytotoxicity of developed microparticles to the HNE cells was measured and their safety to HNE cell was identified.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: Developed microparticles can efficiently deliver insoluble drug, such as BDS, to the nasal epithelium and thus it may improve therapeutic efficacy in the respiratory tract.", "output": {"entities": {"chemical": [{"text": "BDS", "start": 85, "end": 88}]}}, "schema": []}
{"input": "Serotonin (5-HT) in the Regulation of Depression-Related Emotionality: Insight from 5-HT Transporter and Tryptophan Hydroxylase-2 Knockout Mouse Models.", "output": {"entities": {"chemical": [{"text": "Serotonin", "start": 0, "end": 9}, {"text": "5-HT", "start": 11, "end": 15}, {"text": "5-HT", "start": 84, "end": 88}, {"text": "Tryptophan", "start": 105, "end": 115}]}}, "schema": []}
{"input": "Disorders of emotion regulation such as anxiety disorders and depression are common and yet debilitating.", "output": {"entities": {}}, "schema": []}
{"input": "Accumulating evidence suggests involvement of serotonin (5-HT) in the regulation of emotion.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 46, "end": 55}, {"text": "5-HT", "start": 57, "end": 61}]}}, "schema": []}
{"input": "Mice with targeted deletion of genes encoding mediators of the serotonergic transmission have proven to be a powerful tool for understanding contributions of such mediators of emotion regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Over the last decade, research on mice with a targeted inactivation of the 5-HT transporter (5-Htt, Sert, Slc6a4) has considerably advanced our knowledge about functions that the 5-HTT plays in the context of emotion related to depression.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 75, "end": 79}]}}, "schema": []}
{"input": "Moreover, the recent advent of knockout (KO) mice for tryptophan hydroxylase 2 (Tph2 KO), which lacks the rate-limiting enzyme for 5-HT synthesis in the brain, has further provided insight to the brain serotonergic system and its role in emotion dysregulation.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 54, "end": 64}, {"text": "5-HT", "start": 131, "end": 135}]}}, "schema": []}
{"input": "Here, we first highlight basic characteristics of the serotonergic system including the biosynthesis of 5-HT as well as the anatomy and firing activity of serotonergic neurons.", "output": {"entities": {"chemical": [{"text": "5-HT", "start": 104, "end": 108}]}}, "schema": []}
{"input": "Furthermore, characteristics of 5-Htt and Tph2 KO mice are covered together with association studies on human variants of 5-HTT and TPH2 in emotional regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Among various targets of serotonergic projections, which originate from the raphe nuclei in the brain stem, particular focus is placed on the hippocampus due to its unique dual role in memory and emotion.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, effects of therapeutic drugs and psychoactive drugs on KO mouse models as well as on synaptic plasticity will be discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Controllable Hydrogen Sulfide Donors and Their Activity against Myocardial Ischemia-Reperfusion Injury.", "output": {"entities": {"chemical": [{"text": "Hydrogen Sulfide", "start": 13, "end": 29}]}}, "schema": []}
{"input": "Hydrogen sulfide (H2S), known as an important cellular signaling molecule, plays critical roles in many physiological and/or pathological processes.", "output": {"entities": {"chemical": [{"text": "Hydrogen sulfide", "start": 0, "end": 16}, {"text": "H2S", "start": 18, "end": 21}]}}, "schema": []}
{"input": "Modulation of H2S levels could have tremendous therapeutic value.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 14, "end": 17}]}}, "schema": []}
{"input": "However, the study on H2S has been hindered due to the lack of controllable H2S releasing agents that could mimic the slow and moderate H2S release in vivo.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 22, "end": 25}, {"text": "H2S", "start": 76, "end": 79}, {"text": "H2S", "start": 136, "end": 139}]}}, "schema": []}
{"input": "In this work we report the design, synthesis, and biological evaluation of a new class of controllable H2S donors.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 103, "end": 106}]}}, "schema": []}
{"input": "Twenty-five donors were prepared and tested.", "output": {"entities": {}}, "schema": []}
{"input": "Their structures were based on a perthiol template, which was suggested to be involved in H2S biosynthesis.", "output": {"entities": {"chemical": [{"text": "perthiol", "start": 33, "end": 41}, {"text": "H2S", "start": 90, "end": 93}]}}, "schema": []}
{"input": "H2S release mechanism from these donors was studied and proved to be thiol-dependent.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 0, "end": 3}, {"text": "thiol", "start": 69, "end": 74}]}}, "schema": []}
{"input": "We also developed a series of cell-based assays to access their H2S-related activities.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 64, "end": 67}]}}, "schema": []}
{"input": "H9c2 cardiac myocytes were used in these experiments.", "output": {"entities": {}}, "schema": []}
{"input": "We tested lead donors' cytotoxicity and confirmed their H2S production in cells.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 56, "end": 59}]}}, "schema": []}
{"input": "Finally we demonstrated that selected donors showed potent protective effects in an in vivo murine model of myocardial ischemia-reperfusion injury, through a H2S-related mechanism.", "output": {"entities": {"chemical": [{"text": "H2S", "start": 158, "end": 161}]}}, "schema": []}
{"input": "Interfacial Nanoarchitectonics: Lateral and Vertical, Static and Dynamic.", "output": {"entities": {}}, "schema": []}
{"input": "The exploration of nanostructures and nanomaterials is essential to the development of advanced functions.", "output": {"entities": {}}, "schema": []}
{"input": "For such innovations, nanoarchitectonics has been proposed as a novel paradigm of nanotechnology aimed at assembling nanoscale structural units into predesigned configurations or arrangements.", "output": {"entities": {}}, "schema": []}
{"input": "In this Feature Article, we provide an overview of several recent research works from the viewpoint of interfacial nanoarchitectonics with features developed in lateral directions or grown in vertical directions with construction on solid, static, or flexible dynamic surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Lateral nanoarchitectonics at a static interface provides molecular organization by bottom-up nanoarchitectonics and can also be used to realize device integration by top-down nanoarchitectonics.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, in the latter case, the fabrication of novel devices, so-called atomic switches, are introduced as a demonstration of atomic-level electronics.", "output": {"entities": {}}, "schema": []}
{"input": "Lateral nanoarchitectonics at dynamic interfaces is exemplified by 2D molecular patterning and molecular machine operation induced by macroscopic motion.", "output": {"entities": {}}, "schema": []}
{"input": "The dynamic nature of interfaces enables us to operate molecular-sized machines by macroscopic mechanical stimuli such as our hand motion, which we refer to as hand-operated nanotechnology.", "output": {"entities": {}}, "schema": []}
{"input": "Vertical nanoarchitectonics is mainly discussed in relation to layer-by-layer (LbL) assembly.", "output": {"entities": {}}, "schema": []}
{"input": "By using this technique, we can assemble a variety of functional materials in ultrathin film structures of defined thickness and layer sequence.", "output": {"entities": {}}, "schema": []}
{"input": "The organization of biomolecules (or even living cells) within thin films and their integration with device structures is exemplified.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, the anticipated research directions of interfacial nanoarchitectonics are described.", "output": {"entities": {}}, "schema": []}
{"input": "Polycyclic Hybrid Isoprenoids from a Reed Rhizosphere Soil Derived Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "Isoprenoids", "start": 18, "end": 29}]}}, "schema": []}
{"input": "CHQ-64.", "output": {"entities": {}}, "schema": []}
{"input": "Two new hybrid isoprenoids, named indotertine B (2) and drimentine H (3), along with the known analogue drimentine C (4), were isolated from the reed rhizosphere soil derived actinomycete Streptomyces sp.", "output": {"entities": {"chemical": [{"text": "isoprenoids", "start": 15, "end": 26}, {"text": "indotertine B", "start": 34, "end": 47}, {"text": "drimentine H", "start": 56, "end": 68}, {"text": "drimentine C", "start": 104, "end": 116}]}}, "schema": []}
{"input": "CHQ-64.", "output": {"entities": {}}, "schema": []}
{"input": "The structures of these compounds, including absolute configurations, were elucidated by extensive NMR, MS, and CD analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Indotertine B (2) exists as a pair of rotamers about the N-C (O) bond with a 2: 1 ratio and displays activities against HCT-8 and A549 tumor cell lines with IC50 values of 6. 96 and 4. 88 mu M, respectively.", "output": {"entities": {"chemical": [{"text": "Indotertine B", "start": 0, "end": 13}, {"text": "N-C (O)", "start": 57, "end": 64}]}}, "schema": []}
{"input": "A mass-tagging approach for enhanced sensitivity of dynamic cytokine detection using a label-free biosensor.", "output": {"entities": {}}, "schema": []}
{"input": "Monitoring cytokine release by cells allows the investigation of cellular response to specific external stimuli, such as pathogens or candidate drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike conventional colorimetric techniques, label-free detection of cytokines enables studying cellular secretions in real time by eliminating additional wash and labeling steps after the binding step.", "output": {"entities": {}}, "schema": []}
{"input": "However, label-free techniques that are based on measuring mass accumulation on a sensor surface are challenging for measuring small cytokines binding to much larger capture agents (usually antibodies) because the relative signal change is small.", "output": {"entities": {}}, "schema": []}
{"input": "This problem is exacerbated when the capturing antibodies desorb from the surface, a phenomenon that almost inevitably occurs in immunoassays but is rarely accounted for.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate a quantitative dynamic detection of interleukine-6 (IL-6), a pro-inflammatory cytokine, using an interferometric reflectance imaging sensor (IRIS).", "output": {"entities": {}}, "schema": []}
{"input": "We improved the accuracy of the quantitative analysis of this relatively small protein (21 kDa) by characterizing the antibody desorption rate and compensating for the antibody loss during the binding experiment.", "output": {"entities": {}}, "schema": []}
{"input": "By correcting for protein desorption, we achieved an analytical limit of detection at 19 ng/mL IL-6 concentration.", "output": {"entities": {}}, "schema": []}
{"input": "We enhanced the sensitivity by 7-fold by using detection antibodies that recognize a different epitope of the cytokine.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that these detection antibodies, which we call \" mass tags \", can be used concurrently with the target analyte to eliminate an additional wash and binding step.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we report successful label-free detection of IL-6 in cell culture medium (with 10% serum) with comparable signal to that obtained in PBS.", "output": {"entities": {}}, "schema": []}
{"input": "This work is the first to report quantitative dynamic label-free detection of small protein in a complex biological fluid using IRIS.", "output": {"entities": {}}, "schema": []}
{"input": "The impact of computer science in molecular medicine: enabling high-throughput research.", "output": {"entities": {}}, "schema": []}
{"input": "The Human Genome Project and the explosion of high-throughput data have transformed the areas of molecular and personalized medicine, which are producing a wide range of studies and experimental results and providing new insights for developing medical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Research in many interdisciplinary fields is resulting in data repositories and computational tools that support a wide diversity of tasks: genome sequencing, genome-wide association studies, analysis of genotype-phenotype interactions, drug toxicity and side effects assessment, prediction of protein interactions and diseases, development of computational models, biomarker discovery, and many others.", "output": {"entities": {}}, "schema": []}
{"input": "The authors of the present paper have developed several inventories covering tools, initiatives and studies in different computational fields related to molecular medicine: medical informatics, bioinformatics, clinical informatics and nanoinformatics.", "output": {"entities": {}}, "schema": []}
{"input": "With these inventories, created by mining the scientific literature, we have carried out several reviews of these fields, providing researchers with a useful framework to locate, discover, search and integrate resources.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper we present an analysis of the state-ofthe-art as it relates to computational resources for molecular medicine, based on results compiled in our inventories, as well as results extracted from a systematic review of the literature and other scientific media.", "output": {"entities": {}}, "schema": []}
{"input": "The present review is based on the impact of their related publications and the available data and software resources for molecular medicine.", "output": {"entities": {}}, "schema": []}
{"input": "It aims to provide information that can be useful to support ongoing research and work to improve diagnostics and therapeutics based on molecular-level insights.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism evolution based on network degrees of orthologous enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "The evolution of orthologous proteins opens a new era of research where the concepts of orthology and paralogy have become more and more substantial, as the whole-genome comparison allows their identification in complete genomes.", "output": {"entities": {}}, "schema": []}
{"input": "Functional specificity of proteins is understood to be conserved among orthologs but it shows much more variability among paralogs.", "output": {"entities": {}}, "schema": []}
{"input": "We used this laying claim to identify inter-species interactions based on orthologous protein networks which are crucial for understanding the evolution of orthologous proteins.", "output": {"entities": {}}, "schema": []}
{"input": "We analyzed six classes of enzymatic protein sequence data using the node degrees of orthologous proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The results demonstrated the evolutionary importance of the fatty acid syntheses and the photosynthetic system in algae.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 60, "end": 70}]}}, "schema": []}
{"input": "Methods which have successfully exploited network structure at many different levels of detail are a cornerstone of systems biology.", "output": {"entities": {}}, "schema": []}
{"input": "Multi-classifier based on hard instances-new method for prediction of human immunodeficiency virus drug resistance.", "output": {"entities": {}}, "schema": []}
{"input": "There are several classification problems, which are difficult to solve using a single classifier because of the complexity of the decision boundary.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas a wide variety of multiple classifier systems have been built with the purpose of improving the recognition process, there is no universal method performing the best.", "output": {"entities": {}}, "schema": []}
{"input": "This paper provides a review of different multi-classifiers and some application of them.", "output": {"entities": {}}, "schema": []}
{"input": "Also it is shown a novel model of combining classifiers and its application to predicting human immunodeficiency virus drug resistance from genotype.", "output": {"entities": {}}, "schema": []}
{"input": "The proposal is based on the use of different classifier models.", "output": {"entities": {}}, "schema": []}
{"input": "It clusters the dataset considering the performance of the base classifiers.", "output": {"entities": {}}, "schema": []}
{"input": "The system learns how to decide from the groups, by using a meta-classifier, which are the best classifiers for a given pattern.", "output": {"entities": {}}, "schema": []}
{"input": "The proposed model is compared with well-known classifier ensembles and individual classifiers as well resulting the novel model in similar or even better performance.", "output": {"entities": {}}, "schema": []}
{"input": "A Coupling of Benzamides and Donor/Acceptor Diazo Compounds To Form gamma-Lactams via Rh (III)-Catalyzed C-H Activation.", "output": {"entities": {"chemical": [{"text": "Benzamides", "start": 14, "end": 24}, {"text": "Diazo", "start": 44, "end": 49}, {"text": "gamma-Lactams", "start": 68, "end": 81}, {"text": "Rh (III)", "start": 86, "end": 94}, {"text": "C-H", "start": 105, "end": 108}]}}, "schema": []}
{"input": "The coupling of O-pivaloyl benzhydroxamic acids with donor/acceptor diazo compounds provides isoindolones in high yield.", "output": {"entities": {"chemical": [{"text": "O-pivaloyl benzhydroxamic acids", "start": 16, "end": 47}, {"text": "diazo", "start": 68, "end": 73}, {"text": "isoindolones", "start": 93, "end": 105}]}}, "schema": []}
{"input": "The reaction tolerates a broad range of benzhydroxamic acids and diazo compounds, including substituted 2, 2, 2-trifluorodiazoethanes.", "output": {"entities": {"chemical": [{"text": "benzhydroxamic acids", "start": 40, "end": 60}, {"text": "diazo", "start": 65, "end": 70}, {"text": "2, 2, 2-trifluorodiazoethanes", "start": 104, "end": 133}]}}, "schema": []}
{"input": "Mechanistic experiments suggested that C-H activation is turnover-limiting and irreversible and that insertion of the diazo compound favors electron-deficient substrates.", "output": {"entities": {"chemical": [{"text": "C-H", "start": 39, "end": 42}, {"text": "diazo", "start": 118, "end": 123}]}}, "schema": []}
{"input": "Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer.", "output": {"entities": {"chemical": [{"text": "pazopanib", "start": 52, "end": 61}]}}, "schema": []}
{"input": "1. Pazopanib (Votrient) is an oral tyrosine kinase inhibitor that was recently approved for the treatment of renal cell carcinoma and soft tissue sarcoma.", "output": {"entities": {"chemical": [{"text": "Pazopanib", "start": 3, "end": 12}, {"text": "Votrient", "start": 14, "end": 22}, {"text": "tyrosine", "start": 35, "end": 43}]}}, "schema": []}
{"input": "2. In this two-part study, we investigated the metabolism, disposition of [(14) C] pazopanib, and the oral bioavailability of pazopanib tablets in patients with advanced cancer.", "output": {"entities": {"chemical": [{"text": "[(14) C] pazopanib", "start": 74, "end": 92}, {"text": "pazopanib", "start": 126, "end": 135}]}}, "schema": []}
{"input": "3. In part A, three men each received a single oral dose of [(14) C] pazopanib in suspension (400 mg, 70 micro Ci).", "output": {"entities": {"chemical": [{"text": "[(14) C] pazopanib", "start": 60, "end": 78}]}}, "schema": []}
{"input": "Pazopanib was the predominant drug-related component in circulation.", "output": {"entities": {"chemical": [{"text": "Pazopanib", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Two metabolites derived from hydroxylation and one from N-demethylation were also circulating, but were minor, each accounting for < 5% of plasma radioactivity.", "output": {"entities": {"chemical": [{"text": "N", "start": 56, "end": 57}]}}, "schema": []}
{"input": "Faecal elimination predominated, accounting for 82. 2% of the administered radio-dose, with negligible renal elimination (2. 6% of dose).", "output": {"entities": {}}, "schema": []}
{"input": "Pazopanib was primarily excreted as the unchanged drug in faeces (67% of dose).", "output": {"entities": {"chemical": [{"text": "Pazopanib", "start": 0, "end": 9}]}}, "schema": []}
{"input": "4. In part B, seven additional patients received a single intravenous administration of 5 mg pazopanib (day 1) followed by oral administration of 800 mg pazopanib tablet once daily for 26 days (days 3 or 5-28).", "output": {"entities": {"chemical": [{"text": "pazopanib", "start": 93, "end": 102}, {"text": "pazopanib", "start": 153, "end": 162}]}}, "schema": []}
{"input": "In the three evaluable patients from part B, pazopanib had a slow plasma clearance and a small volume of distribution.", "output": {"entities": {"chemical": [{"text": "pazopanib", "start": 45, "end": 54}]}}, "schema": []}
{"input": "The absolute oral bioavailability of the 800 mg pazopanib tablet ranged from 14% to 39%.", "output": {"entities": {"chemical": [{"text": "pazopanib", "start": 48, "end": 57}]}}, "schema": []}
{"input": "Aqueous extract of Artemisia capillaris exerts hepatoprotective action in alcohol-pyrazole-fed rat model.", "output": {"entities": {"chemical": [{"text": "pyrazole", "start": 82, "end": 90}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGIC RELEVANCE: Artemisia capillaris, also called \" InJin \" in Korean, has been widely used to treat various hepatic disorders in traditional Oriental medicine.", "output": {"entities": {}}, "schema": []}
{"input": "AIMS: The purpose of this study is to evaluate the hepatoprotective effect of Artemisia capillaris (aqueous extract, WAC) on alcoholic liver injury.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Liver injury was induced by oral administration of 30% alcohol (10mL/kg, twice per day) plus pyrazole (PRZ, 30mg/kg) with/without WAC (50, 100mg/kg, orally once per day) or silymarin (50mg/kg) for 10 days.", "output": {"entities": {"chemical": [{"text": "pyrazole", "start": 116, "end": 124}, {"text": "PRZ", "start": 126, "end": 129}]}}, "schema": []}
{"input": "The hepatoprotective effects were assessed by observing histopathological changes, hepatic transaminase enzymes, hepatic oxidation and antioxidant parameters, inflammatory cytokines, and alcohol metabolic enzymes in serum and hepatic gene expression level, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Alcohol-PRZ treatment drastically increased the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels in serum and liver tissues while these changes were significantly ameliorated by WAC administration (p < 0. 05 or 0. 01).", "output": {"entities": {"chemical": [{"text": "PRZ", "start": 17, "end": 20}, {"text": "aspartate", "start": 73, "end": 82}, {"text": "alanine", "start": 103, "end": 110}, {"text": "malondialdehyde", "start": 135, "end": 150}, {"text": "MDA", "start": 152, "end": 155}]}}, "schema": []}
{"input": "The prominent microvesicular steatosis and mild necrosis in hepatic histopathology were induced by alcohol-PRZ treatment, but notably attenuated by WAC administration.", "output": {"entities": {"chemical": [{"text": "PRZ", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Moreover, the alcohol-PRZ treatment-induced depletions of the antioxidant components including glutathione content, total antioxidant capacity (TAC), activities of glutathione peroxidase (GSH-Px), reductase (GSH-Rd), catalase, and superoxide dismutase (SOD) were significantly ameliorated by WAC administration (p < 0. 05, except GSH-Rd).", "output": {"entities": {"chemical": [{"text": "PRZ", "start": 22, "end": 25}, {"text": "glutathione", "start": 95, "end": 106}, {"text": "glutathione", "start": 164, "end": 175}, {"text": "superoxide", "start": 231, "end": 241}]}}, "schema": []}
{"input": "These results were in accordance with the modulation of NF-E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) gene expression.", "output": {"entities": {}}, "schema": []}
{"input": "Alcohol-PRZ treatment increased the levels of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) in hepatic tissues.", "output": {"entities": {"chemical": [{"text": "PRZ", "start": 8, "end": 11}]}}, "schema": []}
{"input": "However they were significantly normalized by WAC administration (p < 0. 05 or 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, WAC administration significantly attenuated the alterations of aldehyde dehydrogenase (ALDH) level in serum and hepatic gene expressions of ALDH and alcohol dehydrogenase (ADH).", "output": {"entities": {"chemical": [{"text": "aldehyde", "start": 76, "end": 84}]}}, "schema": []}
{"input": "CONCLUSIONS: These results support the relevance in clinical use of Artemisia capillaris for alcohol-associated hepatic disorders.", "output": {"entities": {}}, "schema": []}
{"input": "The underlying mechanisms may involve both enhancement of antioxidant activities and modulation of proinflammatory cytokines.", "output": {"entities": {}}, "schema": []}
{"input": "Novel quinolone substituted thiazolidin-4-ones as anti-inflammatory, anticancer agents: Design, synthesis and biological screening.", "output": {"entities": {"chemical": [{"text": "quinolone", "start": 6, "end": 15}, {"text": "thiazolidin-4-ones", "start": 28, "end": 46}]}}, "schema": []}
{"input": "Nuclear factor-kappaB (NF-kappa B) has been reported to regulate various genes involved in cancer and inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, drugs suppressing or inhibiting NF-kappa B may possess both anti-inflammatory and anticancer properties.", "output": {"entities": {}}, "schema": []}
{"input": "A library of quinolone substituted thiazolidin-4-ones was docked into the active site of NF-kappa B and the top-ranked 31 compounds were synthesized and evaluated for anti-inflammatory and anticancer activity.", "output": {"entities": {"chemical": [{"text": "quinolone", "start": 13, "end": 22}, {"text": "thiazolidin-4-ones", "start": 35, "end": 53}]}}, "schema": []}
{"input": "The best-ranked compound 6b showed highest anti-inflammatory activity in carrageenan-induced paw edema model.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro anticancer studies revealed 1a and 16a as most active compounds against BT-549, HeLa, COLO-205 and ACHN human cancer cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1a and 16a exhibited NF-kappa B dependent anticancer properties and apoptosis mediated cell death.", "output": {"entities": {}}, "schema": []}
{"input": "In vivo Ehrlich ascites carcinoma study further confirmed the antitumor activity of 1a and 16a.", "output": {"entities": {}}, "schema": []}
{"input": "A central role for thiols in plant tolerance to abiotic stress.", "output": {"entities": {"chemical": [{"text": "thiols", "start": 19, "end": 25}]}}, "schema": []}
{"input": "Abiotic stress poses major problems to agriculture and increasing efforts are being made to understand plant stress response and tolerance mechanisms and to develop new tools that underpin successful agriculture.", "output": {"entities": {}}, "schema": []}
{"input": "However, the molecular mechanisms of plant stress tolerance are not fully understood, and the data available is incomplete and sometimes contradictory.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review the significance of protein and non-protein thiol compounds in relation to plant tolerance of abiotic stress.", "output": {"entities": {}}, "schema": []}
{"input": "First, the roles of the amino acids cysteine and methionine, are discussed, followed by an extensive discussion of the low-molecular-weight tripeptide, thiol glutathione, which plays a central part in plant stress response and oxidative signalling and of glutathione-related enzymes, including those involved in the biosynthesis of non-protein thiol compounds.", "output": {"entities": {"chemical": [{"text": "cysteine", "start": 36, "end": 44}, {"text": "methionine", "start": 49, "end": 59}, {"text": "tripeptide", "start": 140, "end": 150}, {"text": "thiol glutathione", "start": 152, "end": 169}, {"text": "glutathione", "start": 255, "end": 266}, {"text": "thiol", "start": 344, "end": 349}]}}, "schema": []}
{"input": "Special attention is given to the glutathione redox state, to phytochelatins and to the role of glutathione in the regulation of the cell cycle.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 34, "end": 45}, {"text": "glutathione", "start": 96, "end": 107}]}}, "schema": []}
{"input": "The protein thiol section focuses on glutaredoxins and thioredoxins, proteins with oxidoreductase activity, which are involved in protein glutathionylation.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 12, "end": 17}]}}, "schema": []}
{"input": "The review concludes with a brief overview of and future perspectives for the involvement of plant thiols in abiotic stress tolerance.", "output": {"entities": {"chemical": [{"text": "thiols", "start": 99, "end": 105}]}}, "schema": []}
{"input": "Cytokines as biomarkers of nanoparticle immunotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications.", "output": {"entities": {}}, "schema": []}
{"input": "However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention.", "output": {"entities": {}}, "schema": []}
{"input": "Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function.", "output": {"entities": {}}, "schema": []}
{"input": "Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing.", "output": {"entities": {}}, "schema": []}
{"input": "The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of exogenous thiocyanate on mineral nutrients, antioxidative responses and free amino acids in rice seedlings.", "output": {"entities": {"chemical": [{"text": "thiocyanate", "start": 21, "end": 32}, {"text": "amino acids", "start": 88, "end": 99}]}}, "schema": []}
{"input": "The effects of exogenous thiocyanate (SCN (-)) on amino acids composition, content of mineral nutrients and antioxidative systems in plants were investigated.", "output": {"entities": {"chemical": [{"text": "thiocyanate", "start": 25, "end": 36}, {"text": "SCN (-)", "start": 38, "end": 45}, {"text": "amino acids", "start": 50, "end": 61}]}}, "schema": []}
{"input": "Young rice seedlings (Oryza sativa L. cv. XZX 45) were grown in nutrient solutions amended with potassium thiocyanate (KSCN).", "output": {"entities": {"chemical": [{"text": "potassium thiocyanate", "start": 96, "end": 117}, {"text": "KSCN", "start": 119, "end": 123}]}}, "schema": []}
{"input": "Activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in plant materials were analyzed in vivo.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 14, "end": 24}, {"text": "ascorbate", "start": 80, "end": 89}]}}, "schema": []}
{"input": "Mineral nutrients and free amino acids in rice seedlings were also measured to determine metabolic responses to SCN (-) exposure.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 27, "end": 38}, {"text": "SCN (-)", "start": 112, "end": 119}]}}, "schema": []}
{"input": "A significant reduction in transpiration and relative growth was recorded with all treatments (p < 0. 05), while changes of total chlorophyll content in leaves was negligible (p > 0. 05).", "output": {"entities": {"chemical": [{"text": "chlorophyll", "start": 130, "end": 141}]}}, "schema": []}
{"input": "SCN-induced toxicity appeared to be more sensitive to activities of POD in shoots and APX activities in roots than the others.", "output": {"entities": {"chemical": [{"text": "SCN", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The content of nutrient elements in rice seedlings exposed to exogenous SCN (-) was variable, while the effects were more evident at the highest SCN-treatment (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "SCN (-)", "start": 72, "end": 79}, {"text": "SCN", "start": 145, "end": 148}]}}, "schema": []}
{"input": "Although the change of total free amino acids in shoots of SCN-exposed seedlings was negligible (p > 0. 05), responses of different amino acids to SCN (-) application were quite different.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 34, "end": 45}, {"text": "SCN", "start": 59, "end": 62}, {"text": "amino acids", "start": 132, "end": 143}, {"text": "SCN (-)", "start": 147, "end": 154}]}}, "schema": []}
{"input": "Among fifteen free amino acids detected, serine (Ser), proline (Pro), and methionine (Met) increased, while asparagine (Asp) decreased with an increase of the doses of SCN (-) supplied.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 19, "end": 30}, {"text": "serine", "start": 41, "end": 47}, {"text": "Ser", "start": 49, "end": 52}, {"text": "proline", "start": 55, "end": 62}, {"text": "Pro", "start": 64, "end": 67}, {"text": "methionine", "start": 74, "end": 84}, {"text": "Met", "start": 86, "end": 89}, {"text": "asparagine", "start": 108, "end": 118}, {"text": "Asp", "start": 120, "end": 123}, {"text": "SCN (-)", "start": 168, "end": 175}]}}, "schema": []}
{"input": "Phyto-transport of SCN (-) was apparent and the removal rates were positively correlated to the doses, suggesting that phyto-assimilation of SCN (-) is an enzymatic process through a potentially un-identified degradation pathway.", "output": {"entities": {"chemical": [{"text": "SCN (-)", "start": 19, "end": 26}, {"text": "SCN (-)", "start": 141, "end": 148}]}}, "schema": []}
{"input": "2-Hydroxy-3-methylanthraquinone from Hedyotis diffusa Willd induces apoptosis in human leukemic U937 cells through modulation of MAPK pathways.", "output": {"entities": {"chemical": [{"text": "2-Hydroxy-3-methylanthraquinone", "start": 0, "end": 31}]}}, "schema": []}
{"input": "The herb of Hedyotis diffusa Willd (H. diffusa Willd), an annual herb distributed in northeastern Asia, has been known as a traditional oriental medicine for the treatment of cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, Chinese researchers have discovered that two anthraquinones isolated from a water extract of H. diffusa Willd showed apoptosis-inducing effects against cancer cells.", "output": {"entities": {"chemical": [{"text": "anthraquinones", "start": 55, "end": 69}]}}, "schema": []}
{"input": "However, the cellular and molecular mechanisms responsible for this phenomenon are poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "The current study determines the role of mitogen-activated protein kinases (MAPK) in human leukemic U937 cells apoptosis induced by 2-hydroxy-3-methylanthraquinone from H. diffusa.", "output": {"entities": {"chemical": [{"text": "2-hydroxy-3-methylanthraquinone", "start": 132, "end": 163}]}}, "schema": []}
{"input": "Our results showed that 2-hydroxy-3-methylanthraquinone decreased phosphorylation-ERK1/2 (p-ERK1/2), and increased p-p38MAPK, but did not affect expressions of p-JNK1/2 in U937 cells.", "output": {"entities": {"chemical": [{"text": "2-hydroxy-3-methylanthraquinone", "start": 24, "end": 55}]}}, "schema": []}
{"input": "Moreover, treatment of U937 cells with 2-hydroxy-3-methylanthraquinone resulted in activation of caspase-3.", "output": {"entities": {"chemical": [{"text": "2-hydroxy-3-methylanthraquinone", "start": 39, "end": 70}]}}, "schema": []}
{"input": "Furthermore, PD98059 (ERK1/2 inhibitor) significantly enhanced 2-hydroxy-3-methylanthraquinone-induced apoptosis in U937 cells, whereas caspase-3 inhibitor or SB203580 (p-p38MAPK inhibitor), decreased apoptosis in U937 cells.", "output": {"entities": {"chemical": [{"text": "PD98059", "start": 13, "end": 20}, {"text": "2-hydroxy-3-methylanthraquinone", "start": 63, "end": 94}, {"text": "SB203580", "start": 159, "end": 167}]}}, "schema": []}
{"input": "Taken together, our study for the first time suggests that 2-hydroxy-3-methylanthraquinone is able to enhance apoptosis of U937 cells, at least in part, through activation of p-p38MAPK and downregulation of p-ERK1/2.", "output": {"entities": {"chemical": [{"text": "2-hydroxy-3-methylanthraquinone", "start": 59, "end": 90}]}}, "schema": []}
{"input": "Moreover, the triggering of caspase-3 activation mediated apoptotic induction.", "output": {"entities": {}}, "schema": []}
{"input": "Monocarbonyl Curcumin Analogues: Heterocyclic Pleiotropic Kinase Inhibitors That Mediate Anticancer Properties.", "output": {"entities": {"chemical": [{"text": "Monocarbonyl Curcumin", "start": 0, "end": 21}]}}, "schema": []}
{"input": "Curcumin is a biologically active component of curry powder.", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "A structurally related class of mimetics possesses similar anti-inflammatory and anticancer properties.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanism has been examined by exploring kinase inhibition trends.", "output": {"entities": {}}, "schema": []}
{"input": "In a screen of 50 kinases relevant to many forms of cancer, one member of the series (4, EF31) showed >= 85% inhibition for 10 of the enzymes at 5 mu M, while 22 of the proteins were blocked at >= 40%.", "output": {"entities": {}}, "schema": []}
{"input": "IC50 values for an expanded set of curcumin analogues established a rank order of potencies, and analyses of IKK beta and AKT2 enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition dominating.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 35, "end": 43}, {"text": "ATP", "start": 184, "end": 187}]}}, "schema": []}
{"input": "Our curcumin mimetics are generally selective for Ser/Thr kinases.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 4, "end": 12}, {"text": "Ser", "start": 50, "end": 53}, {"text": "Thr", "start": 54, "end": 57}]}}, "schema": []}
{"input": "Both selectivity and potency trends are compatible with protein sequence comparisons, while modeled kinase binding site geometries deliver a reasonable correlation with mixed inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, these analogues are shown to be pleiotropic inhibitors that operate at multiple points along cell signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxic, Antitopoisomerase II alpha, and Anti-HIV-1 Activities of Triterpenoids Isolated from Leaves and Twigs of Gardenia carinata.", "output": {"entities": {"chemical": [{"text": "Triterpenoids", "start": 68, "end": 81}]}}, "schema": []}
{"input": "Eight new cycloartane triterpenoids (1-8), named carinatins A-H, and the known compounds secaubryolide (9) and dikamaliartane D (10) were isolated from the leaves and twigs of Gardenia carinata.", "output": {"entities": {"chemical": [{"text": "cycloartane triterpenoids", "start": 10, "end": 35}, {"text": "carinatins A-H", "start": 49, "end": 63}, {"text": "secaubryolide", "start": 89, "end": 102}, {"text": "dikamaliartane D", "start": 111, "end": 127}]}}, "schema": []}
{"input": "Their structures were determined on the basis of spectroscopic methods.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxic, antitopoisomerase II alpha, and anti-HIV-1 activities of compounds 1-7, 9, and 10 were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "A high throughput assay for the glucuronidation of 7-hydroxy-4-trifluoromethylcoumarin by recombinant human UDP-glucuronosyltransferases and liver microsomes.", "output": {"entities": {"chemical": [{"text": "7-hydroxy-4-trifluoromethylcoumarin", "start": 51, "end": 86}, {"text": "UDP", "start": 108, "end": 111}]}}, "schema": []}
{"input": "Abstract 1. UDP-glucuronosyltransferases (UGTs) are versatile and important conjugation enzymes in the metabolism of drugs and other xenobiotics.", "output": {"entities": {"chemical": [{"text": "UDP", "start": 12, "end": 15}]}}, "schema": []}
{"input": "2. We have developed a convenient quantitative multi-well plate assay to measure the glucuronidation rate of 7-hydroxy-4-trifluoromethylcoumarin (HFC) for several UGTs.", "output": {"entities": {"chemical": [{"text": "7-hydroxy-4-trifluoromethylcoumarin", "start": 109, "end": 144}, {"text": "HFC", "start": 146, "end": 149}]}}, "schema": []}
{"input": "3. We have used this method to screen 11 recombinant human UGTs for HFC glucuronidation activity and studied the reaction kinetics with the most active enzymes.", "output": {"entities": {"chemical": [{"text": "HFC", "start": 68, "end": 71}]}}, "schema": []}
{"input": "We have also examined the HFC glucuronidation activity of liver microsomes from human, pig, rabbit and rat.", "output": {"entities": {"chemical": [{"text": "HFC", "start": 26, "end": 29}]}}, "schema": []}
{"input": "4. At a substrate concentration of 20 micro M, the most active HFC glucuronidation catalysts were UGT1A10 followed by UGT1A6 > UGT1A7 > UGT2A1, whereas at 300 micro M UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "output": {"entities": {"chemical": [{"text": "HFC", "start": 63, "end": 66}]}}, "schema": []}
{"input": "The activities of UGTs 1A3, 1A8, 1A9, 2B4 and 2B7 were low, whereas UGT1A1 and UGT2B17 exhibited no HFC glucuronidation activity.", "output": {"entities": {"chemical": [{"text": "HFC", "start": 100, "end": 103}]}}, "schema": []}
{"input": "UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and UDP-glucuronic acid than the other UGTs.", "output": {"entities": {"chemical": [{"text": "HFC", "start": 71, "end": 74}, {"text": "UDP", "start": 79, "end": 82}, {"text": "glucuronic acid", "start": 83, "end": 98}]}}, "schema": []}
{"input": "5. Human, pig and rabbit, but not rat liver microsomes, catalyzed HFC glucuronidation at high rates.", "output": {"entities": {"chemical": [{"text": "HFC", "start": 66, "end": 69}]}}, "schema": []}
{"input": "6. This new method is particularly suitable for fast activity screenings of UGTs 1A6, 1A7, 1A10 and 2A1 and HFC glucuronidation activity determination from various samples.", "output": {"entities": {"chemical": [{"text": "HFC", "start": 108, "end": 111}]}}, "schema": []}
{"input": "Ion Distributions at the Water/1, 2-Dichloroethane Interface: Potential of Mean Force Approach to Analyzing X-ray Reflectivity and Interfacial Tension Measurements.", "output": {"entities": {"chemical": [{"text": "1, 2-Dichloroethane", "start": 31, "end": 50}]}}, "schema": []}
{"input": "We present X-ray reflectivity and interfacial tension measurements of the electrified liquid/liquid interface between two immiscible electrolyte solutions for the purpose of understanding the dependence of interfacial ion distributions on the applied electric potential difference across the interface.", "output": {"entities": {}}, "schema": []}
{"input": "The aqueous phase contains alkali-metal chlorides, including LiCl, NaCl, RbCl, or CsCl, and the organic phase is a 1, 2-dichloroethane solution of bis (triphenylphosphor anylidene) ammonium tetrakis (pentafluorophenyl) borate (BTPPATPFB).", "output": {"entities": {"chemical": [{"text": "alkali-metal chlorides", "start": 27, "end": 49}, {"text": "LiCl", "start": 61, "end": 65}, {"text": "NaCl", "start": 67, "end": 71}, {"text": "RbCl", "start": 73, "end": 77}, {"text": "CsCl", "start": 82, "end": 86}, {"text": "1, 2-dichloroethane", "start": 115, "end": 134}, {"text": "bis (triphenylphosphor anylidene) ammonium tetrakis (pentafluorophenyl) borate", "start": 147, "end": 225}, {"text": "BTPPATPFB", "start": 227, "end": 236}]}}, "schema": []}
{"input": "Selected data for a subset of electric potential differences are analyzed to determine the potentials of mean force for Li (+), Rb (+), Cs (+), BTPPA (+), and TPFB (-).", "output": {"entities": {"chemical": [{"text": "Li (+)", "start": 120, "end": 126}, {"text": "Rb (+)", "start": 128, "end": 134}, {"text": "Cs (+)", "start": 136, "end": 142}, {"text": "BTPPA (+)", "start": 144, "end": 153}, {"text": "TPFB (-)", "start": 159, "end": 167}]}}, "schema": []}
{"input": "These potentials of mean force are then used to analyze both X-ray reflectivity and interfacial tension data measured over a wide range of electric potential differences.", "output": {"entities": {}}, "schema": []}
{"input": "Comparison of X-ray reflectivity data for strongly hydrated alkali-metal ions (Li (+) and Na (+)), for which ion pairing to TPFB (-) ions across the interface is not expected, to data for weakly hydrated alkali-metal ions (Rb (+) and Cs (+)) indicates that the Gibbs energy of adsorption due to ion pairing at the interface must be small (< 1 kBT per ion pair) for both the CsCl and RbCl samples.", "output": {"entities": {"chemical": [{"text": "alkali-metal", "start": 60, "end": 72}, {"text": "Li (+)", "start": 79, "end": 85}, {"text": "Na (+)", "start": 90, "end": 96}, {"text": "TPFB (-)", "start": 124, "end": 132}, {"text": "alkali-metal", "start": 204, "end": 216}, {"text": "Rb (+)", "start": 223, "end": 229}, {"text": "Cs (+)", "start": 234, "end": 240}, {"text": "CsCl", "start": 374, "end": 378}, {"text": "RbCl", "start": 383, "end": 387}]}}, "schema": []}
{"input": "This paper demonstrates the applicability of the Poisson-Boltzmann potential of mean force approach to the analysis of X-ray reflectivity measurements that probe the nanoscale ion distribution and the consequences of these underlying distributions for thermodynamic studies, such as interfacial tension measurements, that yield quantities related to the integrated ion distribution.", "output": {"entities": {}}, "schema": []}
{"input": "Immobilizing Individual Atoms beneath a Corrugated Single Layer of Boron Nitride.", "output": {"entities": {"chemical": [{"text": "Boron Nitride", "start": 67, "end": 80}]}}, "schema": []}
{"input": "Single atoms, and in particular the least reactive noble gases, are difficult to immobilize at room temperature.", "output": {"entities": {"chemical": [{"text": "noble gases", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Ion implantation into a crystal lattice has this capability, but the randomness of the involved processes does not permit much control over their distribution within the solid.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that the boron nitride nanomesh, a corrugated single layer of hexagonal boron nitride (h-BN) with a 3. 2 nm honeycomb superstructure formed on a Rh (111) surface, can trap individual argon atoms at distinct subsurface sites at room temperature.", "output": {"entities": {"chemical": [{"text": "boron nitride", "start": 29, "end": 42}, {"text": "boron nitride", "start": 92, "end": 105}, {"text": "h-BN", "start": 107, "end": 111}, {"text": "Rh (111)", "start": 165, "end": 173}, {"text": "argon", "start": 203, "end": 208}]}}, "schema": []}
{"input": "A kinetic energy window for implantation is identified where the argon ions can penetrate the h-BN layer but not enter the Rh lattice.", "output": {"entities": {"chemical": [{"text": "argon", "start": 65, "end": 70}, {"text": "h-BN", "start": 94, "end": 98}, {"text": "Rh", "start": 123, "end": 125}]}}, "schema": []}
{"input": "Scanning tunneling microscopy and photoemission data show the presence of argon atoms at two distinct sites within the nanomesh unit cell, confirmed also by density functional theory calculations.", "output": {"entities": {"chemical": [{"text": "argon", "start": 74, "end": 79}]}}, "schema": []}
{"input": "The single atom implants are stable in air.", "output": {"entities": {}}, "schema": []}
{"input": "Annealing of implanted structures to 900 K induces the formation of highly regular holes of 2 nm diameter in the h-BN layer with adjacent flakes of the same size found on top of the layer.", "output": {"entities": {"chemical": [{"text": "h-BN", "start": 113, "end": 117}]}}, "schema": []}
{"input": "We explain this \" can-opener \" effect by the presence of a vacancy defect, generated during the penetration of the Ar ion through the h-BN lattice, and propagating along the rim of a nanomesh pore where the h-BN lattice is highly bent.", "output": {"entities": {"chemical": [{"text": "Ar", "start": 115, "end": 117}, {"text": "h-BN", "start": 134, "end": 138}, {"text": "h-BN", "start": 207, "end": 211}]}}, "schema": []}
{"input": "The reported effects are also observed in graphene on ruthenium and for neon atoms.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 42, "end": 50}, {"text": "ruthenium", "start": 54, "end": 63}, {"text": "neon", "start": 72, "end": 76}]}}, "schema": []}
{"input": "Low-Dose Dexamethasone Treatment Promotes Pro-Survival Signalling Pathway In Adult Rat Prefrontal Cortex.", "output": {"entities": {"chemical": [{"text": "Dexamethasone", "start": 9, "end": 22}]}}, "schema": []}
{"input": "Synthetic glucocorticoid dexamethasone (DEX), a highly potent anti-inflammatory and immunosuppressive agent, is widely used in treatments of brain cancer, inflammatory and autoimmune diseases.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 25, "end": 38}, {"text": "DEX", "start": 40, "end": 43}]}}, "schema": []}
{"input": "The objective of the current study was to determine whether a low-dose subchronic DEX treatment (100 mu g/kg for 8 consecutive days) exerts long-term effects on apoptosis in the adult rat prefrontal cortex (PFC) by examining the expression of cell death-promoting molecules (poly (ADP-ribose) polymerase (PARP), p53, procaspase 3, cleaved caspase 3, Bax) and cell-survival molecules (AKT, Bcl-2).", "output": {"entities": {"chemical": [{"text": "DEX", "start": 82, "end": 85}, {"text": "poly (ADP-ribose)", "start": 275, "end": 292}]}}, "schema": []}
{"input": "Our results revealed that body, thymus and adrenal weight as well corticosterone level in the serum and PFC were reduced a day following last DEX injection.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 66, "end": 80}, {"text": "DEX", "start": 142, "end": 145}]}}, "schema": []}
{"input": "In PFC, DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to mitochondria.", "output": {"entities": {"chemical": [{"text": "DEX", "start": 8, "end": 11}]}}, "schema": []}
{"input": "The unaltered profile in the protein expression of apoptotic molecules PARP, procaspase 3 and Bax was detected, while the p53 protein was decreased.", "output": {"entities": {}}, "schema": []}
{"input": "Results of RT-PCR analysis showed decrease of p53 mRNA level and no significant difference in Bcl-2 and Bax mRNA expressions in DEX-treated rats.", "output": {"entities": {"chemical": [{"text": "DEX", "start": 128, "end": 131}]}}, "schema": []}
{"input": "Finally, the DNA fragmentation assay and Fluoro-Jade staining demonstrated no considerable changes in the apoptosis in rat PFC.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings support the concept that a low-dose DEX creates the hypocorticoid state in the brain and indicate that subchronic DEX treatment activates pro-survival signalling pathway but does not change apoptotic markers in rat PFC.", "output": {"entities": {"chemical": [{"text": "DEX", "start": 49, "end": 52}, {"text": "DEX", "start": 127, "end": 130}]}}, "schema": []}
{"input": "This mechanism might be relevant for DEX-induced apoptosis resistance observed during and after chemotherapy of patients with brain tumours.", "output": {"entities": {"chemical": [{"text": "DEX", "start": 37, "end": 40}]}}, "schema": []}
{"input": "(c) 2013 British Society for Neuroendocrinology.", "output": {"entities": {}}, "schema": []}
{"input": "Hypoxia, energy balance and obesity: from pathophysiological mechanisms to new treatment strategies.", "output": {"entities": {}}, "schema": []}
{"input": "High altitude exposure is often accompanied by weight loss.", "output": {"entities": {}}, "schema": []}
{"input": "Postulated mechanisms are a reduction of nutritional energy intake, a reduction of intestinal energy uptake from impaired intestinal function and increased energy expenditure.", "output": {"entities": {}}, "schema": []}
{"input": "Beyond the field of altitude, there are good reasons for renewed interest in the relationship between hypoxia and energy balance.", "output": {"entities": {}}, "schema": []}
{"input": "The increasing prevalence of obesity and associated comorbidities represent a major health concern.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity is frequently associated with sleep disorders leading to intermittent systemic hypoxia with deleterious cardiovascular and metabolic consequences.", "output": {"entities": {}}, "schema": []}
{"input": "Hypoxic regions may be present within hypertrophic white adipose tissue leading to chronic systemic inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Among the increasing number of people commuting to altitude for work or leisure, obesity is a risk factor for acute mountain sickness.", "output": {"entities": {}}, "schema": []}
{"input": "Paradoxically, exposure to intermittent hypoxia might be considered as a means to lose body mass and to improve metabolic risk factors.", "output": {"entities": {}}, "schema": []}
{"input": "Daytime exposure to intermittent hypoxia has been used to treat hypertension in former Soviet Union countries and is now being experimented elsewhere.", "output": {"entities": {}}, "schema": []}
{"input": "Such intermittent hypoxic exposure at rest or during exercise may lead to improvement in body composition and health status with improved exercise tolerance, metabolism and systemic arterial pressure.", "output": {"entities": {}}, "schema": []}
{"input": "Future research should confirm whether hypoxic training could be a new treatment strategy for weight loss and comorbidities in obese subjects and elucidate the underlying mechanisms and signalling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Histological, ultrastructural and immunohistochemical studies on the protective effect of ginger extract against cisplatin-induced nephrotoxicity in male rats.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 113, "end": 122}]}}, "schema": []}
{"input": "Cisplatin (CP) is a widely used anticancer drug; however, it has several side effects such as nephrotoxicity.", "output": {"entities": {"chemical": [{"text": "Cisplatin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Ginger, the rhizome of Zingiber officinale, consumed since ancient times has numerous health benefits.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this work was to evaluate the protective effect of ginger extract (GE) against CP-induced nephrotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "CP group displayed a marked renal failure characterized by a significant increase in serum creatinine and blood urea nitrogen (BUN) levels in addition to severe histopathological and ultrastructural renal alterations.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 91, "end": 101}, {"text": "urea nitrogen", "start": 112, "end": 125}]}}, "schema": []}
{"input": "Also, CP group showed an increase in the immunohistochemical expression of Bax proapoptotic protein.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, GE + CP group showed significant decrease in the elevated serum creatinine and BUN levels and an improvement in the histopathological and ultrastructural renal injury induced by CP.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 77, "end": 87}]}}, "schema": []}
{"input": "The overexpression of Bax proapoptotic protein was significantly decreased in the GE + CP group.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, the present results indicated that GE has a protective effect against CP-induced renal damage in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Thereby, such findings recommended the usage of GE to prevent and/or decrease the renal damage induced by CP chemotherapeutic treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Lipoxygenase and urease inhibition of the aerial parts of the Polygonatum verticillatum.", "output": {"entities": {}}, "schema": []}
{"input": "Over expression of lipoxygenase (LOX) and urease has already contributed to the pathology of different human disease.", "output": {"entities": {}}, "schema": []}
{"input": "Targeting the inhibition of these enzymes has proved great clinical utility.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to scrutinised the inhibitory profile of the aerial parts of the Polygonatum verticillatum enzyme against LOX, urease, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using standard experimental protocols.", "output": {"entities": {}}, "schema": []}
{"input": "When checked against lipoxygenase, the extracts revealed significant attenuation.", "output": {"entities": {}}, "schema": []}
{"input": "Of the tested extracts, the ethyl acetate fraction was the most potent (half-maximal inhibitory concentration (IC50): 97 micro g/mL) followed by aqueous fraction IC50: 109 micro g/mL).", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 28, "end": 41}]}}, "schema": []}
{"input": "Regarding urease inhibition, n-butanol was the most potent fraction (IC50: 97 micro g/mL).", "output": {"entities": {"chemical": [{"text": "n-butanol", "start": 29, "end": 38}]}}, "schema": []}
{"input": "However, the extracts did not show significant inhibition on AChE and BChE.", "output": {"entities": {}}, "schema": []}
{"input": "In the preliminary phytochemical tests, the aerial parts of the plant showed the presence of saponins, alkaloids, flavonoids, phenols, tannins and terpenoids.", "output": {"entities": {"chemical": [{"text": "saponins", "start": 93, "end": 101}, {"text": "flavonoids", "start": 114, "end": 124}, {"text": "phenols", "start": 126, "end": 133}, {"text": "tannins", "start": 135, "end": 142}, {"text": "terpenoids", "start": 147, "end": 157}]}}, "schema": []}
{"input": "The current findings could be attributed to these groups of compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Trace and major element levels in rats after oral administration of diesel and biodiesel derived from opium poppy (Papaver somniferum L.) seeds.", "output": {"entities": {}}, "schema": []}
{"input": "The study investigated the toxic effects of diesel and biodiesel derived from opium poppy (Papaver somniferum L.) oil seeds on the trace and major elements in kidney, lung, liver, and serum of rats.", "output": {"entities": {}}, "schema": []}
{"input": "By the end of 21 days, trace and major element concentrations in kidney, lung, and liver tissues and the serum were measured using inductively coupled plasma-optical emission spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that trace and major element levels in kidney, lung, and liver tissues and the serum changed.", "output": {"entities": {}}, "schema": []}
{"input": "Especially, important differences were detected in trace and major element concentrations in kidney and lung tissues.", "output": {"entities": {}}, "schema": []}
{"input": "In kidney tissue, the concentration differences of calcium, sodium, and zinc (Zn) were found between diesel and biodiesel groups.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 51, "end": 58}, {"text": "sodium", "start": 60, "end": 66}, {"text": "zinc", "start": 72, "end": 76}, {"text": "Zn", "start": 78, "end": 80}]}}, "schema": []}
{"input": "In lung tissue, the concentration differences of cadmium, lithium, magnesium, manganese, and Zn were found between diesel and biodiesel groups.", "output": {"entities": {"chemical": [{"text": "cadmium", "start": 49, "end": 56}, {"text": "lithium", "start": 58, "end": 65}, {"text": "magnesium", "start": 67, "end": 76}, {"text": "manganese", "start": 78, "end": 87}, {"text": "Zn", "start": 93, "end": 95}]}}, "schema": []}
{"input": "Among the significant findings, Zn concentration in serum and liver tissue of diesel and biodiesel were different from control (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "Zn", "start": 32, "end": 34}]}}, "schema": []}
{"input": "However, the metal levels of biodiesel group were similar to control group.", "output": {"entities": {}}, "schema": []}
{"input": "Due to lesser toxicity of biodiesel, it could be considered as an alternate fuel.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of sugammadex on rocuronium induced changes in pancreatic mast cells.", "output": {"entities": {"chemical": [{"text": "sugammadex", "start": 10, "end": 20}, {"text": "rocuronium", "start": 24, "end": 34}]}}, "schema": []}
{"input": "Mast cells play a vital role in hypersensitivity reactions.", "output": {"entities": {}}, "schema": []}
{"input": "Rocuronium is known to cause mast cell mobilization, hypersensitivity, and pancreatitis.", "output": {"entities": {"chemical": [{"text": "Rocuronium", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The aim of this study was to investigate the effects of sugammadex on pancreatic changes due to rocuronium.", "output": {"entities": {"chemical": [{"text": "sugammadex", "start": 56, "end": 66}, {"text": "rocuronium", "start": 96, "end": 106}]}}, "schema": []}
{"input": "A total of 42 Sprague-Dawley male rats were divided into six equal groups to receive either rocuronium 1 mg/kg intravenously (i. v., R group), rocuronium 1 mg/kg + sugammadex 16 mg/kg i. v. (RS16 group), rocuronium 1 mg/kg + sugammadex 96 mg/kg i. v. (RS96 group), sugammadex 16 mg/kg (S16), sugammadex 96 mg/kg i. v. (S96 group), or 0. 9% sodium chloride (control group).", "output": {"entities": {"chemical": [{"text": "rocuronium", "start": 92, "end": 102}, {"text": "rocuronium", "start": 143, "end": 153}, {"text": "sugammadex", "start": 164, "end": 174}, {"text": "rocuronium", "start": 204, "end": 214}, {"text": "sugammadex", "start": 225, "end": 235}, {"text": "sugammadex", "start": 265, "end": 275}, {"text": "sugammadex", "start": 292, "end": 302}, {"text": "sodium chloride", "start": 340, "end": 355}]}}, "schema": []}
{"input": "Sugammadex was administered 5s later following rocuronium.", "output": {"entities": {"chemical": [{"text": "Sugammadex", "start": 0, "end": 10}, {"text": "rocuronium", "start": 47, "end": 57}]}}, "schema": []}
{"input": "In R group, mast count was higher, and the distribution rate of granules and nuclear changes were different compared with other groups.", "output": {"entities": {}}, "schema": []}
{"input": "Distribution rate of granules in groups S16 and S96 were similar to the control group and lower compared with other groups.", "output": {"entities": {}}, "schema": []}
{"input": "The amount of mast cells and granule density in groups RS16 and RS96 was lower compared with R group.", "output": {"entities": {}}, "schema": []}
{"input": "The amount of mast cells in groups RS16 and RS96 was significantly lower compared with other treatment groups.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that sugammadex may have an inhibitory effect on mobilization and morphological changes in pancreatic mast cells induced by administration of rocuronium and sugammadex in rats.", "output": {"entities": {"chemical": [{"text": "sugammadex", "start": 27, "end": 37}, {"text": "rocuronium", "start": 164, "end": 174}, {"text": "sugammadex", "start": 179, "end": 189}]}}, "schema": []}
{"input": "Synthesis and characterization of naphthalenediimide-functionalized flavin derivatives.", "output": {"entities": {"chemical": [{"text": "naphthalenediimide", "start": 34, "end": 52}, {"text": "flavin", "start": 68, "end": 74}]}}, "schema": []}
{"input": "Two acceptor-acceptor dyads have been synthesized featuring a flavin moiety and a naphthalenediimide (NDI) unit.", "output": {"entities": {"chemical": [{"text": "flavin", "start": 62, "end": 68}, {"text": "naphthalenediimide", "start": 82, "end": 100}, {"text": "NDI", "start": 102, "end": 105}]}}, "schema": []}
{"input": "The NDI unit is linked to the flavin through a short spacer group via either the N (3) or N (10) positions of the flavin.", "output": {"entities": {"chemical": [{"text": "NDI", "start": 4, "end": 7}, {"text": "flavin", "start": 30, "end": 36}, {"text": "flavin", "start": 114, "end": 120}]}}, "schema": []}
{"input": "We have investigated the UV-Vis and redox properties of these multi-electron accepting systems which indicate that these materials display the collective properties of their component systems.", "output": {"entities": {}}, "schema": []}
{"input": "Fluorescence spectroscopy measurements have revealed that their emission properties are dominated by the flavin unit.", "output": {"entities": {"chemical": [{"text": "flavin", "start": 105, "end": 111}]}}, "schema": []}
{"input": "On the Vibrational linear and nonlinear optical properties of compounds involving noble gas atoms: HXeOXeH, HXeOXeF, and FXeOXeF.", "output": {"entities": {"chemical": [{"text": "HXeOXeH", "start": 99, "end": 106}, {"text": "HXeOXeF", "start": 108, "end": 115}, {"text": "FXeOXeF", "start": 121, "end": 128}]}}, "schema": []}
{"input": "The vibrational (hyper) polarizabilities of some selected Xe derivatives are studied in the context of Bishop-Kirtman perturbation theory (BKPT) and numerical finite field methodology.", "output": {"entities": {"chemical": [{"text": "Xe", "start": 58, "end": 60}]}}, "schema": []}
{"input": "It was found that for this set of rare gas compounds, the static vibrational properties are quite large, in comparison to the corresponding electronic ones, especially those of the second hyperpolarizability.", "output": {"entities": {}}, "schema": []}
{"input": "This also holds for the dc-Pockels beta (-omega; omega, 0), Kerr gamma (-omega; omega, 0, 0) and electric field second harmonic generation gamma (-2 omega; omega, omega, 0) effects, although the computed nuclear relaxation (nr) vibrational contributions are smaller in magnitude than the static ones.", "output": {"entities": {}}, "schema": []}
{"input": "HXeOXeH was used to study the effects of electron correlation, basis set, and geometry.", "output": {"entities": {"chemical": [{"text": "HXeOXeH", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Geometry effects were found to lead to noticeable changes of the vibrational and electronic second hyperpolarizability.", "output": {"entities": {}}, "schema": []}
{"input": "A limited study of the effect of Xe insertion to the nr vibrational properties is also reported.", "output": {"entities": {"chemical": [{"text": "Xe", "start": 33, "end": 35}]}}, "schema": []}
{"input": "Assessment of the results revealed that Xe insertion has a remarkable effect on the nr (hyper) polarizabilities.", "output": {"entities": {"chemical": [{"text": "Xe", "start": 40, "end": 42}]}}, "schema": []}
{"input": "In terms of the BKPT, this is associated with a remarkable increase of the electrical and mechanical anharmonicity terms.", "output": {"entities": {}}, "schema": []}
{"input": "The latter is consistent with the anharmonic character of several vibrational modes reported for rare gas compounds.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 Wiley Periodicals, Inc.", "output": {"entities": {}}, "schema": []}
{"input": "Once-Weekly Exenatide: An Extended-Duration Glucagon-Like Peptide Agonist for the Treatment of Type 2 Diabetes Mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Type 2 diabetes affects over 25 million people in the United States.", "output": {"entities": {}}, "schema": []}
{"input": "There are many treatment options for patients with type 2 diabetes, but current treatments must be administered on a daily basis.", "output": {"entities": {}}, "schema": []}
{"input": "Once-weekly exenatide, an extended-duration glucagon-like peptide-1 (GLP-1) agonist, provides an option for patients to take a drug weekly, with pharmacotherapeutic effects that are superior to twice-daily exenatide and sitagliptin and comparable to insulin glargine.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 220, "end": 231}]}}, "schema": []}
{"input": "The DURATION trials provide evidence that once-weekly exenatide reduces hemoglobin A1c, and may result in weight loss.", "output": {"entities": {}}, "schema": []}
{"input": "Once-weekly exenatide is marketed as a 2-mg injection administered subcutaneously once every 7 days.", "output": {"entities": {}}, "schema": []}
{"input": "Adverse effects of once-weekly exenatide include gastrointestinal effects, hypoglycemia, injection-site reactions, pancreatitis, and antibody development.", "output": {"entities": {}}, "schema": []}
{"input": "Patients with a self history or family history of thyroid tumors should avoid using once-weekly exenatide.", "output": {"entities": {}}, "schema": []}
{"input": "Delayed gastric absorption with orally administered drugs is possible, and monitoring should occur to avoid loss in therapeutic effect.", "output": {"entities": {}}, "schema": []}
{"input": "Once-weekly exenatide is a new extended-duration agent with efficacy and tolerability profiles comparative to older therapies.", "output": {"entities": {}}, "schema": []}
{"input": "Appropriate patients for once-weekly exenatide would be those who are concerned about weight gain, hypoglycemia, or those who do not wish to administer injections daily.", "output": {"entities": {}}, "schema": []}
{"input": "Baseline Albumin Is Associated with Worsening Renal Function in Patients with Acute Decompensated Heart Failure Receiving Continuous Infusion Loop Diuretics.", "output": {"entities": {}}, "schema": []}
{"input": "STUDY OBJECTIVES: To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics.", "output": {"entities": {}}, "schema": []}
{"input": "DESIGN: Retrospective observational analysis.", "output": {"entities": {}}, "schema": []}
{"input": "SETTING: Academic tertiary medical center.", "output": {"entities": {}}, "schema": []}
{"input": "PATIENTS: A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009.", "output": {"entities": {}}, "schema": []}
{"input": "MEASUREMENTS AND MAIN RESULTS: The mean patient age was 61 years, 63% were male, ~ 45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days.", "output": {"entities": {}}, "schema": []}
{"input": "Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization.", "output": {"entities": {}}, "schema": []}
{"input": "Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables.", "output": {"entities": {}}, "schema": []}
{"input": "Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2. 87, 95% confidence interval [CI] 1. 60-5. 16, p = 0. 0004), which remained significant despite adjustments for other covariates.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics.", "output": {"entities": {}}, "schema": []}
{"input": "Bone Health and Human Immunodeficiency Virus Infection.", "output": {"entities": {}}, "schema": []}
{"input": "Low bone mineral density is common among persons with human immunodeficiency virus (HIV) infection, and studies reporting increased fracture rates in this patient population are emerging.", "output": {"entities": {}}, "schema": []}
{"input": "The causes of low bone mineral density, osteoporosis, and fractures in persons with HIV are likely multifactorial, involving traditional risk factors, HIV infection, and exposure to antiretroviral treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Specific antiretrovirals such as tenofovir may cause a greater loss of bone mineral density compared with other agents and have recently been linked to an increased risk for fracture.", "output": {"entities": {"chemical": [{"text": "tenofovir", "start": 33, "end": 42}]}}, "schema": []}
{"input": "As a result, recent treatment guidelines suggest that clinicians consider avoiding tenofovir as initial therapy in postmenopausal women.", "output": {"entities": {"chemical": [{"text": "tenofovir", "start": 83, "end": 92}]}}, "schema": []}
{"input": "Evaluating bone mineral density and vitamin D status in persons with HIV may be important steps in identifying those requiring pharmacotherapy; however, the appropriate timing for bone mineral density and vitamin D screening is uncertain, as is the appropriate method of replacing vitamin D in HIV-positive patients who are deficient.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 36, "end": 45}, {"text": "vitamin D", "start": 205, "end": 214}, {"text": "vitamin D", "start": 281, "end": 290}]}}, "schema": []}
{"input": "Further study is necessary to definitively determine the approach to evaluating bone health and managing low bone mineral density and vitamin D deficiency in patients with HIV infection.", "output": {"entities": {"chemical": [{"text": "vitamin D", "start": 134, "end": 143}]}}, "schema": []}
{"input": "Package-Free Flexible Organic Solar Cells with Graphene top Electrodes.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 47, "end": 55}]}}, "schema": []}
{"input": "Package-free flexible organic solar cells were fabricated with multilayer graphene as top transparent electrodes, which show the highest power conversion efficiency of about 3. 2% and excellent flexibility and bending stability.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 74, "end": 82}]}}, "schema": []}
{"input": "The devices also show good air stability, indicating that multilayer graphene is a promising environmental barrier that can protect the organic solar cells from air contamination.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 69, "end": 77}]}}, "schema": []}
{"input": "High Mobility Field-Effect Transistors with Versatile Processing from a Small-Molecule Organic Semiconductor.", "output": {"entities": {}}, "schema": []}
{"input": "Trialkylgermyl functionalization allows development of high-performance soluble small-molecule organic semiconductors with mobilities greater than 5 cm (2) V (-1) s (-1).", "output": {"entities": {"chemical": [{"text": "Trialkylgermyl", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Spray-deposited organic thin-film transistors show a record mobility of 2. 2 cm (2) V (-1) s (-1) and demonstrate the potential for incorporation in large-area, low-cost electronic applications.", "output": {"entities": {}}, "schema": []}
{"input": "Bone remodeling is regulated by inner ear vestibular signals.", "output": {"entities": {}}, "schema": []}
{"input": "Bone remodeling allows the conservation of normal bone mass despite constant changes in internal and external environments.", "output": {"entities": {}}, "schema": []}
{"input": "The adaptation of the skeleton to these various stimuli led credence to the notion that bone remodeling is a true homeostatic function, and as such is under the control of specific centers in the central nervous system (CNS).", "output": {"entities": {}}, "schema": []}
{"input": "Hypothalamic and brainstem centers, as well as the sympathetic nervous system (SNS), have been identified as regulators of bone remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "However, the nature of the afferent CNS stimuli that may modulate CNS centers involved in the control of bone remodeling, with the exception of leptin, remains unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the partial efficacy of exercise and mechanical stimulation regimens to prevent microgravity-induced bone loss and the known alterations in vestibular functions associated with space flights, we hypothesized that inner ear vestibular signals may contribute to the regulation of bone remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Using an established model of bilateral vestibular lesions and microtomographic and histomorphometric bone analyses, we show here that induction of bilateral vestibular lesion in rats generates significant bone loss, which is restricted to weight-bearing bones and associated with a significant reduction in bone formation, as observed in rats under microgravity conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, this bone loss was not associated with reduced locomotor activity or metabolic abnormalities, was accompanied with molecular signs of increased sympathetic outflow, and could be prevented by the beta-blocker propranolol.", "output": {"entities": {"chemical": [{"text": "propranolol", "start": 221, "end": 232}]}}, "schema": []}
{"input": "Collectively, these data suggest that the homeostatic process of bone remodeling has a vestibulo-sympathetic regulatory component and that vestibular system pathologies might be accompanied by bone fragility.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 American Society for Bone and Mineral Research.", "output": {"entities": {}}, "schema": []}
{"input": "Tunable 3D Extended Self-Assembled Gold Metamaterials with Enhanced Light Transmission.", "output": {"entities": {}}, "schema": []}
{"input": "The optical properties of metamaterials made by block copolymer self-assembly are tuned by structural and environmental variations.", "output": {"entities": {}}, "schema": []}
{"input": "The plasma frequency red-shifts with increasing lattice constant and blue-shifts as the network filling fraction increases.", "output": {"entities": {}}, "schema": []}
{"input": "Infiltration with dielectric liquids leads also to a red-shift of the plasma edge.", "output": {"entities": {}}, "schema": []}
{"input": "A 300 nm-thick slab of gyroid-structured gold has a remarkable transmission of 20%.", "output": {"entities": {}}, "schema": []}
{"input": "The Glucuronidation of R-and S-Lorazepam: Human Liver Microsomal Kinetics, UDP-Glucuronosyltransferase Enzyme Selectivity, and Inhibition by Drugs.", "output": {"entities": {"chemical": [{"text": "R-and S-Lorazepam", "start": 23, "end": 40}, {"text": "UDP", "start": 75, "end": 78}]}}, "schema": []}
{"input": "The widely used hypnosedative-anxiolytic agent R, S-lorazepam is cleared predominantly by conjugation with glucuronic acid in humans, but the enantioselective glucuronidation of lorazepam has received little attention.", "output": {"entities": {"chemical": [{"text": "R, S-lorazepam", "start": 47, "end": 61}, {"text": "glucuronic acid", "start": 107, "end": 122}, {"text": "lorazepam", "start": 178, "end": 187}]}}, "schema": []}
{"input": "The present study characterized the kinetics of the separate R-and S-enantiomers of lorazepam by human liver microsomes (HLM) and by a panel of recombinant human UDP-glucuronosyltransferase (UGT) enzymes.", "output": {"entities": {"chemical": [{"text": "lorazepam", "start": 84, "end": 93}, {"text": "UDP", "start": 162, "end": 165}]}}, "schema": []}
{"input": "Respective mean Km and Vmax values for R-and S-lorazepam by HLM were 29 +/- 8. 9 and 36 +/- 10 mu M, and 7. 4 +/- 1. 9 and 10 +/- 3. 8 pmol/min. mg.", "output": {"entities": {"chemical": [{"text": "R-and S-lorazepam", "start": 39, "end": 56}]}}, "schema": []}
{"input": "Microsomal intrinsic clearances were not significantly different, suggesting the in vivo clearances of R-and S-lorazepam are likely to be similar.", "output": {"entities": {"chemical": [{"text": "R-and S-lorazepam", "start": 103, "end": 120}]}}, "schema": []}
{"input": "Both R-and S-lorazepam were glucuronidated by UGT 2B4, 2B7, and 2B15, while R-lorazepam was additionally metabolized by the extra-hepatic enzymes UGT 1A7 and 1A10.", "output": {"entities": {"chemical": [{"text": "R-and S-lorazepam", "start": 5, "end": 22}, {"text": "R-lorazepam", "start": 76, "end": 87}]}}, "schema": []}
{"input": "Based on in vitro clearances and consideration of available in vivo and in vitro data, UGT2B15 is likely to play an important role in the glucuronidation of R-and S-lorazepam.", "output": {"entities": {"chemical": [{"text": "R-and S-lorazepam", "start": 157, "end": 174}]}}, "schema": []}
{"input": "However, the possible contribution of other enzymes and the low activities observed in vitro indicate that the lorazepam enantiomers are of limited use as substrate probes for UGT2B15.", "output": {"entities": {"chemical": [{"text": "lorazepam", "start": 111, "end": 120}]}}, "schema": []}
{"input": "In order to identify potential drug-drug interactions, codeine, fluconazole, ketamine, ketoconazole, methadone, morphine, valproic acid, and zidovudine were screened as inhibitors of R-and S-lorazepam glucuronidation by HLM.", "output": {"entities": {"chemical": [{"text": "codeine", "start": 55, "end": 62}, {"text": "fluconazole", "start": 64, "end": 75}, {"text": "ketamine", "start": 77, "end": 85}, {"text": "ketoconazole", "start": 87, "end": 99}, {"text": "methadone", "start": 101, "end": 110}, {"text": "morphine", "start": 112, "end": 120}, {"text": "valproic acid", "start": 122, "end": 135}, {"text": "zidovudine", "start": 141, "end": 151}, {"text": "R-and S-lorazepam", "start": 183, "end": 200}]}}, "schema": []}
{"input": "Of these drugs, in vitro-in vivo extrapolation suggested that only ketoconazole had the potential to inhibit lorazepam clearance to a clinically significant extent.", "output": {"entities": {"chemical": [{"text": "ketoconazole", "start": 67, "end": 79}, {"text": "lorazepam", "start": 109, "end": 118}]}}, "schema": []}
{"input": "Notch Signaling in Skeletal Health and Disease.", "output": {"entities": {}}, "schema": []}
{"input": "Notch receptors are single-pass transmembrane proteins that determine cell fate.", "output": {"entities": {}}, "schema": []}
{"input": "Upon Notch-ligand interactions, proteolytic cleavages release the Notch intracellular domain (NICD) which translocates to the nucleus to regulate the transcription of target genes, including Hairy enhancer of split (Hes) and Hes-related with YRPW-motif (Hey).", "output": {"entities": {}}, "schema": []}
{"input": "Notch is critical for skeletal development and activity of skeletal cells, and dysregulation of Notch signaling is associated with human diseases affecting the skeleton.", "output": {"entities": {}}, "schema": []}
{"input": "Inherited or sporadic mutations in components of the Notch signaling pathway are associated with spondylocostal and spondylothoracic dysostoses, and recessive brachydactyly, diseases characterized by skeletal patterning defects.", "output": {"entities": {}}, "schema": []}
{"input": "Inactivating mutations of the Notch ligand JAG1 or of NOTCH2 are associated with Alagille syndrome, and activating mutations in NOTCH2 are associated with Hajdu-Cheney syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Individuals affected by Hajdu-Cheney syndrome exhibit osteolysis in distal phalanges, and osteoporosis.", "output": {"entities": {}}, "schema": []}
{"input": "NOTCH is activated in selected tumors, such as osteosarcoma, and in breast cancer cells that form osteolytic bone metastases.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, Notch regulates skeletal development and bone remodeling, and gain-or loss-of-function mutations of Notch signaling result in important skeletal diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Selecting One of Several Mating Types through Gene Segment Joining and Deletion in Tetrahymena thermophila.", "output": {"entities": {}}, "schema": []}
{"input": "The unicellular eukaryote Tetrahymena thermophila has seven mating types.", "output": {"entities": {}}, "schema": []}
{"input": "Cells can mate only when they recognize cells of a different mating type as non-self.", "output": {"entities": {}}, "schema": []}
{"input": "As a ciliate, Tetrahymena separates its germline and soma into two nuclei.", "output": {"entities": {}}, "schema": []}
{"input": "During growth the somatic nucleus is responsible for all gene transcription while the germline nucleus remains silent.", "output": {"entities": {}}, "schema": []}
{"input": "During mating, a new somatic nucleus is differentiated from a germline nucleus and mating type is decided by a stochastic process.", "output": {"entities": {}}, "schema": []}
{"input": "We report here that the somatic mating type locus contains a pair of genes arranged head-to-head.", "output": {"entities": {}}, "schema": []}
{"input": "Each gene encodes a mating type-specific segment and a transmembrane domain that is shared by all mating types.", "output": {"entities": {}}, "schema": []}
{"input": "Somatic gene knockouts showed both genes are required for efficient non-self recognition and successful mating, as assessed by pair formation and progeny production.", "output": {"entities": {}}, "schema": []}
{"input": "The germline mating type locus consists of a tandem array of incomplete gene pairs representing each potential mating type.", "output": {"entities": {}}, "schema": []}
{"input": "During mating, a complete new gene pair is assembled at the somatic mating type locus; the incomplete genes of one gene pair are completed by joining to gene segments at each end of germline array.", "output": {"entities": {}}, "schema": []}
{"input": "All other germline gene pairs are deleted in the process.", "output": {"entities": {}}, "schema": []}
{"input": "These programmed DNA rearrangements make this a fascinating system of mating type determination.", "output": {"entities": {}}, "schema": []}
{"input": "Liquid chromatography-mass spectrometry method for the quantification of posaconazole in human plasma: application to pharmacokinetics following single-dose administration in the fasted state and with a high-fat meal.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 73, "end": 85}]}}, "schema": []}
{"input": "A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed to determine concentrations of posaconazole in human plasma precipitated by acetonitrile including internal standard.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 112, "end": 124}, {"text": "acetonitrile", "start": 157, "end": 169}]}}, "schema": []}
{"input": "Rapid chromatographic separation was achieved in the mobile phase composition of acetonitrile, water and formic acid (v/v/v, 55: 45: 0. 1) with a flow rate of 0. 25 ml/min.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 81, "end": 93}, {"text": "formic acid", "start": 105, "end": 116}]}}, "schema": []}
{"input": "Posaconazole-d4 was used as internal standard.", "output": {"entities": {"chemical": [{"text": "Posaconazole-d4", "start": 0, "end": 15}]}}, "schema": []}
{"input": "Detection was undertaken with cation electrospray tandem mass spectrometry on a Sciex/API3000.", "output": {"entities": {}}, "schema": []}
{"input": "The method was accurate, specific and sensitive for the analysis of posaconazole in human plasma in the concentration range of 2-1000 ng/ml.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 68, "end": 80}]}}, "schema": []}
{"input": "The inter-and intra-batch accuracy was within +/-10% and the lower limit of quantification was 2 ng/ml.", "output": {"entities": {}}, "schema": []}
{"input": "The method facilitated a clinical pharmacokinetic study after oral administration of a single-dose of posaconazole suspension in the fasted state and with a high-fat meal in a two-period crossover design.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 102, "end": 114}]}}, "schema": []}
{"input": "Cmax (maximum concentration) and AUC (area under serum drug concentration) were significantly increased, and Tmax (time to maximum plasma concentration) was delayed under fed condition, which suggested that simultaneous administration of posaconazole with food may help to achieve higher plasma concentrations and result in better antifungal efficacy.", "output": {"entities": {"chemical": [{"text": "posaconazole", "start": 238, "end": 250}]}}, "schema": []}
{"input": "Interspecies difference of luteolin and apigenin after oral administration of Chrysanthemum morifolium extract and prediction of human pharmacokinetics.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 27, "end": 35}, {"text": "apigenin", "start": 40, "end": 48}]}}, "schema": []}
{"input": "The aims of the present study were to study the interspecies difference in the pharmacokinetics of luteolin and apigenin occurring in Chrysanthemum morifolium extract (CME) among rats, beagle dogs, mini-pigs, and humans, and compared the human pharmacokinetic parameters with the data predicted from the above three animals.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 99, "end": 107}, {"text": "apigenin", "start": 112, "end": 120}]}}, "schema": []}
{"input": "The plasma concentrations of luteolin and apigenin were determined with a RP-HPLC method.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 29, "end": 37}, {"text": "apigenin", "start": 42, "end": 50}]}}, "schema": []}
{"input": "An interspecies difference of pharmacokinetics was found, especially between rats and other species, the plasma concentration of luteolin was much lower than that of apigenin in rats, although the content of luteolin in CME was higherthan that of apigenin, whereas the plasma concentration of luteolin was much higher than that of apigenin in dogs, mini-pigs and humans.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 129, "end": 137}, {"text": "apigenin", "start": 166, "end": 174}, {"text": "luteolin", "start": 208, "end": 216}, {"text": "apigenin", "start": 247, "end": 255}, {"text": "luteolin", "start": 293, "end": 301}, {"text": "apigenin", "start": 331, "end": 339}]}}, "schema": []}
{"input": "Animal scale-up of some pharmacokinetic parameters of luteolin and apigenin were also performed after rats, beagle dogs, mini-pigs and humans were orally given CME at dosages of 400 mg/kg, 102 mg/kg, 90 mg/kg, and 20 mg/kg, respectively.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 54, "end": 62}, {"text": "apigenin", "start": 67, "end": 75}]}}, "schema": []}
{"input": "Linear relationships were obtained between log mean retention time (MRT) and log species body weight (W) (kg), and log elimination half-life (t1/2) (h) and logW.", "output": {"entities": {}}, "schema": []}
{"input": "The corresponding allometric equations were MRT = 9. 382W (0. 1711) (R2 = 0. 9999) and t1/2 = 4. 811W (0. 1093) (R2 = 0. 9013) for luteolin, MRT = 12. 53W (0. 0356) (R2 = 0. 9980) and t1/2 = 7. 940W (0. 0294) (R2 = 0. 9258) for apigenin, respectively.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 131, "end": 139}, {"text": "apigenin", "start": 228, "end": 236}]}}, "schema": []}
{"input": "The predicted human pharmacokinetic parameters (MRT and t1/2) by an allometric approach were 18. 6 h and 7. 46 h for luteolin, 14. 3 h and 8. 95 h for apigenin, respectively, which were close to the values obtained from humans (20 mg CME/kg) in the present study.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 117, "end": 125}, {"text": "apigenin", "start": 151, "end": 159}]}}, "schema": []}
{"input": "The study has demonstrated the possibility to extrapolate the pharmacokinetic behavior of flavonoids from animals to humans.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 90, "end": 100}]}}, "schema": []}
{"input": "Genes involved in hemorrhagic transformations that follow recombinant t-PA treatment in stroke patients.", "output": {"entities": {}}, "schema": []}
{"input": "Aim: Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Our objective is to study the transcriptomics of HTs patients.", "output": {"entities": {}}, "schema": []}
{"input": "Methods: We studied by microarrays 11 blood samples from patients with stroke that had received rt-PA of whom six of them had suffered a HT.", "output": {"entities": {}}, "schema": []}
{"input": "For replication step RNA was collected from 14 new subjects (seven with HT, seven without) and then analyzed by real-time PCR.", "output": {"entities": {}}, "schema": []}
{"input": "Four proteins were measured by ELISA in 72 new subjects to analyze their role as potential protein biomarkers.", "output": {"entities": {}}, "schema": []}
{"input": "Results: The microarray analysis revealed that 14 genes were altered among the HT patients.", "output": {"entities": {}}, "schema": []}
{"input": "The replication study confirmed these results for six genes.", "output": {"entities": {}}, "schema": []}
{"input": "Two of them (BCL2 and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil processes.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: Our data revealed that genes related to apoptosis and neutrophil regulation pathways could be associated with HTs after rt-PA.", "output": {"entities": {}}, "schema": []}
{"input": "Original submitted 7 September 2012; Revision submitted 23 January 2013.", "output": {"entities": {}}, "schema": []}
{"input": "Interactions of PAMAM Dendrimers with SDS at the Solid-Liquid Interface.", "output": {"entities": {"chemical": [{"text": "PAMAM", "start": 16, "end": 21}, {"text": "SDS", "start": 38, "end": 41}]}}, "schema": []}
{"input": "This work addresses structural and nonequilibrium effects of the interactions between well-defined cationic poly (amidoamine) PAMAM dendrimers of generations 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) at the hydrophilic silica-water interface.", "output": {"entities": {"chemical": [{"text": "poly (amidoamine) PAMAM", "start": 108, "end": 131}, {"text": "sodium dodecyl sulfate", "start": 193, "end": 215}, {"text": "SDS", "start": 217, "end": 220}, {"text": "silica", "start": 241, "end": 247}]}}, "schema": []}
{"input": "Neutron reflectometry and quartz crystal microbalance with dissipation monitoring were used to reveal the adsorption from premixed dendrimer/surfactant solutions as well as sequential addition of the surfactant to preadsorbed layers of dendrimers.", "output": {"entities": {}}, "schema": []}
{"input": "PAMAM dendrimers of both generations adsorb to hydrophilic silica as a compact monolayer, and the adsorption is irreversible upon rinsing with salt solution.", "output": {"entities": {"chemical": [{"text": "PAMAM", "start": 0, "end": 5}, {"text": "silica", "start": 59, "end": 65}]}}, "schema": []}
{"input": "SDS adsorbs on the dendrimer layer and at low bulk concentrations causes the expansion of the dendrimer layers on the surface.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 0, "end": 3}]}}, "schema": []}
{"input": "When the bulk concentration of SDS is increased, the surfactant layer consists of aggregates or bilayer-like structures.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 31, "end": 34}]}}, "schema": []}
{"input": "The adsorption of surfactant is reversible upon rinsing, but slight changes of the structure of the preadsorbed PAMAM monolayer were observed.", "output": {"entities": {"chemical": [{"text": "PAMAM", "start": 112, "end": 117}]}}, "schema": []}
{"input": "The adsorption from premixed solutions close to charge neutrality results in thick multilayers, but the surface excess is lower when the bulk complexes have a net negative charge.", "output": {"entities": {}}, "schema": []}
{"input": "A critical examination of the pathway of adsorption for the interactions of SDS with preadsorbed PAMAM monolayers and premixed PAMAM/SDS solutions with hydrophilic silica revealed that nonequilibrium effects are important only in the latter case, and the application of a thermodynamic model to such experimental data would be inappropriate.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 76, "end": 79}, {"text": "PAMAM", "start": 97, "end": 102}, {"text": "PAMAM", "start": 127, "end": 132}, {"text": "SDS", "start": 133, "end": 136}, {"text": "silica", "start": 164, "end": 170}]}}, "schema": []}
{"input": "Gravitational drainage of foam films.", "output": {"entities": {}}, "schema": []}
{"input": "Gravitational drainage from thick plane vertical soap films and hemispherical bubbles is studied experimentally and theoretically.", "output": {"entities": {}}, "schema": []}
{"input": "The experiments involve microinterferometry kindred to the one used in the experiments in the Scheludko cell.", "output": {"entities": {}}, "schema": []}
{"input": "The following surfactants were used in the experiments: cationic dodecyltrimethylammonium bromide (DTAB), anionic sodium dodecyl sulfate (SDS), anionic Pantene shampoo which primarily contains sodium lauryl sulfate, nonionic tetraethylene glycol monooctyl ether (C8E4), and nonionic Pluronic (P-123) surfactants at different concentrations.", "output": {"entities": {"chemical": [{"text": "dodecyltrimethylammonium bromide", "start": 65, "end": 97}, {"text": "DTAB", "start": 99, "end": 103}, {"text": "sodium dodecyl sulfate", "start": 114, "end": 136}, {"text": "SDS", "start": 138, "end": 141}, {"text": "sodium lauryl sulfate", "start": 193, "end": 214}, {"text": "tetraethylene glycol monooctyl ether", "start": 225, "end": 261}, {"text": "C8E4", "start": 263, "end": 267}, {"text": "Pluronic (P-123)", "start": 283, "end": 299}]}}, "schema": []}
{"input": "The theoretical results explain the drainage mechanism and are used to develop a new method of measurement of the surface elasticity and to test it on the above-mentioned surfactants.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of Specific Binding Interactions at l-Cystine Crystal Surfaces with Chemical Force Microscopy.", "output": {"entities": {"chemical": [{"text": "l-Cystine", "start": 50, "end": 59}]}}, "schema": []}
{"input": "The pathogenesis of l-cystine kidney stones involves four critical steps: nucleation, crystal growth, crystal aggregation, and crystal adhesion to cells.", "output": {"entities": {"chemical": [{"text": "l-cystine", "start": 20, "end": 29}]}}, "schema": []}
{"input": "Although inhibition of crystal growth by l-cystine \" imposters \" at l-cystine crystal surfaces has been suggested as a plausible route for the suppression of stones, understanding the factors that govern crystal-crystal aggregation and adhesion of crystals to epithelial cells also is essential for devising strategies to mitigate l-cystine stone formation.", "output": {"entities": {"chemical": [{"text": "l-cystine", "start": 41, "end": 50}, {"text": "l-cystine", "start": 68, "end": 77}, {"text": "l-cystine", "start": 331, "end": 340}]}}, "schema": []}
{"input": "Chemical force microscopy performed with atomic force microscope tips decorated with functional groups commonly found in urinary constituents that likely mediate aggregation and attachment (e. g., COOH, NH2, SH, CH3, OH) revealed signatures that reflect differences in the chemical affinity of these groups for the (001) and {100} faces of the naturally occurring hexagonal form of l-cystine single crystals and the {110} faces of the non-native tetragonal form.", "output": {"entities": {"chemical": [{"text": "COOH", "start": 197, "end": 201}, {"text": "NH2", "start": 203, "end": 206}, {"text": "SH", "start": 208, "end": 210}, {"text": "CH3", "start": 212, "end": 215}, {"text": "OH", "start": 217, "end": 219}, {"text": "l-cystine", "start": 382, "end": 391}]}}, "schema": []}
{"input": "These signatures can be explained by the different chemical compositions of the crystal faces, and they reveal a remarkable binding specificity of the thiol group for the sulfur-rich {100} and {110} faces of the hexagonal and tetragonal forms, respectively.", "output": {"entities": {"chemical": [{"text": "sulfur", "start": 171, "end": 177}]}}, "schema": []}
{"input": "Collectively, these observations suggest that alterations of the crystal habit and polymorph by crystal growth inhibitors may not affect crystal aggregation or adhesion to cells significantly.", "output": {"entities": {}}, "schema": []}
{"input": "Screening and evaluation of traditional Chinese medicine by microarray expression analysis.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza is a Chinese medicinal herb, which is widely used for the treatment of cardiovascular disorders.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we investigated the effects of Salvia miltiorrhiza and its hydrophilic and lipophilic components (HCS and LCS) on human umbilical vein endothelial cells (HUVECs), and the molecular mechanism was explored by microarray gene expression profiling.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Cell proliferation and migration were used to evaluate the angiogenic effects of HCS, LCS and total extract of Salvia miltiorrhiza (TES).", "output": {"entities": {}}, "schema": []}
{"input": "Microarray technology was applied to detect the gene expression of HUVECs treated with TES, HCS and LCS.", "output": {"entities": {}}, "schema": []}
{"input": "Besides, quantitative real-time PCR was used to verify the microarray results.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Our results showed that LCS inhibited the proliferation and migration of HUVECs, HCS promoted the proliferation and migration of HUVECs, and TES did not affect the viability of HUVECs at the concentration of 5 micro g/mL.", "output": {"entities": {}}, "schema": []}
{"input": "From the result of principle component analysis (PCA) of microarray data, the effect of LCS on HUVECs was significantly different from the other components.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, there were more differentially expression genes in LCS group than in the other groups, which meant LCS had a strong influence on HUVECs.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with untreated cells, 511 significantly changed genes had been detected in LCS treated cells and 236 (approximately 46%) of them were up-regulated.", "output": {"entities": {}}, "schema": []}
{"input": "The mRNA expression of IL-6 was found to be increased significantly in LCS group.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: In Salvia miltiorrhiza, HCS and LCS had opposite effects on HUVECs.", "output": {"entities": {}}, "schema": []}
{"input": "LCS showed significantly inhibitory action on HUVECs proliferation and migration.", "output": {"entities": {}}, "schema": []}
{"input": "It was proposed that LCS could apply in the diseases caused by vascular anomaly hyperplasia.", "output": {"entities": {}}, "schema": []}
{"input": "In the mechanism of action of LCS on HUVECs, the pathways of ErbB, MAPK, p53, oxidative phosphorylation and inflammatory response were involved.", "output": {"entities": {}}, "schema": []}
{"input": "Global gene expression analysis reveals pathway differences between teratogenic and non-teratogenic exposure concentrations of bisphenol A and 17 beta-estradiol in embryonic zebrafish.", "output": {"entities": {"chemical": [{"text": "bisphenol A", "start": 127, "end": 138}, {"text": "17 beta-estradiol", "start": 143, "end": 160}]}}, "schema": []}
{"input": "Transient developmental exposure to 0. 1 mu M bisphenol A (BPA) results in larval zebrafish hyperactivity and learning impairments in the adult, while exposure to 80 mu M BPA results in teratogenic responses, including craniofacial abnormalities and edema.", "output": {"entities": {"chemical": [{"text": "bisphenol A", "start": 46, "end": 57}, {"text": "BPA", "start": 59, "end": 62}, {"text": "BPA", "start": 171, "end": 174}]}}, "schema": []}
{"input": "The mode of action underlying these effects is unclear.", "output": {"entities": {}}, "schema": []}
{"input": "We used global gene expression analysis to identify candidate genes and signaling pathways that mediate BPA' s developmental toxicity in zebrafish.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 104, "end": 107}]}}, "schema": []}
{"input": "Exposure concentrations were selected and anchored to the positive control, 17 beta-estradiol (E2), based on previously determined behavioral or teratogenic phenotypes.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 76, "end": 93}]}}, "schema": []}
{"input": "Functional analysis of differentially expressed genes revealed distinct expression profiles at 24h post fertilization for 0. 1 mu M versus 80 mu M BPA and 0. 1 mu M versus 15 mu M E2 exposure, identification of prothrombin activation as a top canonical pathway impacted by both 0. 1 mu M BPA and 0. 1 mu M E2 exposure, and suppressed expression of several genes involved in nervous system development and function following 0. 1 mu M BPA exposure.", "output": {"entities": {"chemical": [{"text": "BPA", "start": 147, "end": 150}, {"text": "BPA", "start": 288, "end": 291}, {"text": "BPA", "start": 434, "end": 437}]}}, "schema": []}
{"input": "Environmental pesticide exposure modulates cytokines, arginase and ornithine decarboxylase expression in human placenta.", "output": {"entities": {"chemical": [{"text": "ornithine", "start": 67, "end": 76}]}}, "schema": []}
{"input": "To evaluate the cytokine balance and enzymatic alterations induced by environmental pesticide exposure during pregnancy, this transversal study explored placentas derived from non-exposed women (control group-CG), and from women living in a rural area (rural group-RG), collected during intensive organophosphate (OP) pesticide spraying season (RG-SS) and during non-spraying season (RG-NSS).", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 297, "end": 312}]}}, "schema": []}
{"input": "The exposure biomarkers blood cholinesterase and placental carboxylesterase (CaE) were significantly decreased in RG-SS.", "output": {"entities": {}}, "schema": []}
{"input": "Among the cytokines studied IL-8, IL-6, TNF alpha, IL-10, TGF beta and IL-13, the expression frequency of IL-13 increased in RG-SS.", "output": {"entities": {}}, "schema": []}
{"input": "Arginase and ornithine decarboxylase (ODC) enzymes were induced in syncytiotrophoblast and endothelial cells.", "output": {"entities": {"chemical": [{"text": "ornithine", "start": 13, "end": 22}]}}, "schema": []}
{"input": "Interestingly, the decrease in CaE activity was associated with arginase and ODC activity induction.", "output": {"entities": {}}, "schema": []}
{"input": "These findings suggest that environmental pesticide exposure impacts the placenta by increasing the expression frequency of the anti-inflammatory cytokine IL-13, which may be related to the up-regulation of enzymes implicated in tissue repair.", "output": {"entities": {}}, "schema": []}
{"input": "Replication Dynamics: Biases and Robustness of DNA Fiber Analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The factors that govern replication programs are still poorly identified in metazoans, especially in mammalian cells.", "output": {"entities": {}}, "schema": []}
{"input": "Thanks to molecular combing, the dynamics of DNA replication can be assessed at the genome-scale level from the cumulative analysis of single DNA fibers.", "output": {"entities": {}}, "schema": []}
{"input": "This technique notably enables measurement of replication fork speed and fork asymmetry and that of distances separating either initiation or termination events.", "output": {"entities": {}}, "schema": []}
{"input": "The results presented here aim to evaluate requirements critical to accurate measurement of replication parameters by molecular combing.", "output": {"entities": {}}, "schema": []}
{"input": "We show that sample size, fiber length and DNA counterstaining are crucial to gain robust information concerning replication dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "Our results thus provide a methodological frame to investigate the DNA replication program through molecular combing analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Dissolution enhancement of Deflazacort using hollow crystals prepared by antisolvent crystallization process.", "output": {"entities": {"chemical": [{"text": "Deflazacort", "start": 27, "end": 38}]}}, "schema": []}
{"input": "Deflazacort (DFZ), a derivate of prednisolone, is a poorly soluble drug which has been proposed to have major advantages over other corticosteroids.", "output": {"entities": {"chemical": [{"text": "Deflazacort", "start": 0, "end": 11}, {"text": "DFZ", "start": 13, "end": 16}, {"text": "prednisolone", "start": 33, "end": 45}, {"text": "corticosteroids", "start": 132, "end": 147}]}}, "schema": []}
{"input": "Poorly soluble drugs present limited bioavailability due to their low solubility and dissolution rate and several strategies have been developed in order to find ways to improve them.", "output": {"entities": {}}, "schema": []}
{"input": "In general, pharmaceutical laboratories use a micronized process to reduce the particle size in order to increase the dissolution of the drugs.", "output": {"entities": {}}, "schema": []}
{"input": "However, this process causes changes such as polymorphic transitions, particle agglomeration and a reduction in fluidity and wettability.", "output": {"entities": {}}, "schema": []}
{"input": "These solid-state properties affect the dissolution behavior and stability performance of drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Crystallization techniques are widely used in the pharmaceutical industry and antisolvent crystallization has been used to obtain ultrafine particles.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, DFZ was investigated in terms of its antisolvent crystallization in different solvents and under various preparation conditions (methanol/water ratio, stirring and evaporation rate, etc.), in order to compare the physicochemical properties between crystallized samples and raw materials available on the Brazilian market with and without micronization.", "output": {"entities": {"chemical": [{"text": "DFZ", "start": 15, "end": 18}, {"text": "methanol", "start": 144, "end": 152}]}}, "schema": []}
{"input": "Crystalline structure, morphology, and particle size, and their correlation with the Intrinsic Dissolution Rate (IDR) and dissolution profile as relevant biopharmaceutical properties were studied.", "output": {"entities": {}}, "schema": []}
{"input": "Crystallization conditions were achieved which provided crystalline samples of hollow-shaped crystals with internal channels, which increased the dissolution rate of DFZ.", "output": {"entities": {"chemical": [{"text": "DFZ", "start": 166, "end": 169}]}}, "schema": []}
{"input": "The antisolvent crystallization process allowed the formation of hollow crystals, which demonstrated a better dissolution profile than the raw material (crystalline and micronized), making this a promising technique as a crystallization strategy for improving the dissolution and thus the bioavailability of poorly soluble drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Trichostatin A protects against cisplatin-induced ototoxicity by regulating expression of genes related to apoptosis and synaptic function.", "output": {"entities": {"chemical": [{"text": "Trichostatin A", "start": 0, "end": 14}, {"text": "cisplatin", "start": 32, "end": 41}]}}, "schema": []}
{"input": "OBJECTIVE: Although inhibition of histone deacetylases (HDACs) has been shown to protect against cisplatin-induced hearing loss, the underlying mechanism is still poorly understood.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 97, "end": 106}]}}, "schema": []}
{"input": "In the present study, we aim to investigate the protective effect of trichostatin A (TSA), a specific inhibitor of HDACs, on cisplatin-induced ototoxicity and to determine the differentially expressed genes involved in this process.", "output": {"entities": {"chemical": [{"text": "trichostatin A", "start": 69, "end": 83}, {"text": "TSA", "start": 85, "end": 88}, {"text": "cisplatin", "start": 125, "end": 134}]}}, "schema": []}
{"input": "METHODS: The basilar membrane of the cochlea was isolated from 3-day newborn Wistar rats.", "output": {"entities": {}}, "schema": []}
{"input": "Organotypic cultures were treated with 150 mu M cisplatin or 200nM TSA.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 48, "end": 57}, {"text": "TSA", "start": 67, "end": 70}]}}, "schema": []}
{"input": "For combination treatment, cells were pre-incubated with TSA for 1h, followed by TSA plus cisplatin treatment.", "output": {"entities": {"chemical": [{"text": "TSA", "start": 57, "end": 60}, {"text": "TSA", "start": 81, "end": 84}, {"text": "cisplatin", "start": 90, "end": 99}]}}, "schema": []}
{"input": "Rhodamine-phalloidin staining was used to label hair cells, and immunocytochemistry with an anti-neurofilament-200 antibody was applied to label spiral ganglion neurons (SGNs).", "output": {"entities": {"chemical": [{"text": "Rhodamine", "start": 0, "end": 9}, {"text": "phalloidin", "start": 10, "end": 20}]}}, "schema": []}
{"input": "Global expression profile microarray analysis was used to identify differentially expressed genes.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular function and signal pathway analysis were performed using a protein analysis through evolutionary relationships (PANTHER) classification system.", "output": {"entities": {}}, "schema": []}
{"input": "Real-time quantitative PCR (qPCR) was carried out for data validation.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Severe loss of hair cells and SGNs occurred after 48h of cisplatin incubation, while TSA significantly increased the number of hair cells and SGNs in the combination treatment group (P < 0. 05).", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 66, "end": 75}, {"text": "TSA", "start": 94, "end": 97}]}}, "schema": []}
{"input": "Compared with control, expression of 71 genes were up-regulated and 383 genes were down-regulated upon cisplatin treatment.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 103, "end": 112}]}}, "schema": []}
{"input": "Addition of TSA induced the up-regulation of 1387 genes and down-regulation of 1226 genes as compared with cisplatin administration alone.", "output": {"entities": {"chemical": [{"text": "TSA", "start": 12, "end": 15}, {"text": "cisplatin", "start": 107, "end": 116}]}}, "schema": []}
{"input": "After cisplatin treatment, we observed significant down-regulation of mRNA for several genes related to synaptic function genes, including Camk2a, Camk2b, Vglut1, Snap25 and Rab3b, whereas pretreatment with TSA elevated mRNA levels of these genes.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 6, "end": 15}, {"text": "TSA", "start": 207, "end": 210}]}}, "schema": []}
{"input": "TSA greatly decreased expression of genes related to the calcium signaling pathway (Capn1 and Capn2) and apoptosis signaling pathway (Tnfrsf1a and Tp53), while addition of TSA significantly reduced levels of Tnfrsf1a and Tp53 compared with cisplatin alone (P < 0. 01).", "output": {"entities": {"chemical": [{"text": "TSA", "start": 0, "end": 3}, {"text": "calcium", "start": 57, "end": 64}, {"text": "TSA", "start": 172, "end": 175}, {"text": "cisplatin", "start": 240, "end": 249}]}}, "schema": []}
{"input": "CONCLUSIONS: Our results suggested that TSA might protect against cisplatin-induced ototoxicity via mediating expression of genes responsible for regulating apoptosis, intracellular calcium homeostasis, neurotransmitter synthesis and release, and synaptic plasticity.", "output": {"entities": {"chemical": [{"text": "TSA", "start": 40, "end": 43}, {"text": "cisplatin", "start": 66, "end": 75}, {"text": "calcium", "start": 182, "end": 189}]}}, "schema": []}
{"input": "A novel series of histamine H4 receptor antagonists based on the pyrido [3, 2-d] pyrimidine scaffold: Comparison of hERG binding and target residence time with PF-3893787.", "output": {"entities": {"chemical": [{"text": "histamine", "start": 18, "end": 27}, {"text": "pyrido [3, 2-d] pyrimidine", "start": 65, "end": 91}, {"text": "PF-3893787", "start": 160, "end": 170}]}}, "schema": []}
{"input": "In this work we describe the optimization of a lead compound based on the quinazoline template to give a new series of potent pyrido [3, 2-d] pyrimidines as histamine H4 receptor antagonists.", "output": {"entities": {"chemical": [{"text": "quinazoline", "start": 74, "end": 85}, {"text": "pyrido [3, 2-d] pyrimidines", "start": 126, "end": 153}, {"text": "histamine", "start": 157, "end": 166}]}}, "schema": []}
{"input": "The pyrido [3, 2-d] pyrimidine ligands have significantly reduced hERG binding compared to clinical stage compound PF-3893787 while showing good affinities at the human and rodent histamine receptors.", "output": {"entities": {"chemical": [{"text": "pyrido [3, 2-d] pyrimidine", "start": 4, "end": 30}, {"text": "PF-3893787", "start": 115, "end": 125}, {"text": "histamine", "start": 180, "end": 189}]}}, "schema": []}
{"input": "The receptor residence time of several of these new compounds was determined for the human H4R and compared with JNJ7777120 and PF-3893787.", "output": {"entities": {"chemical": [{"text": "JNJ7777120", "start": 113, "end": 123}, {"text": "PF-3893787", "start": 128, "end": 138}]}}, "schema": []}
{"input": "The pyrido [3, 2-d] pyrimidines showed residence times lower than JNJ7777120 but comparable to the residence time of PF-3893787.", "output": {"entities": {"chemical": [{"text": "pyrido [3, 2-d] pyrimidines", "start": 4, "end": 31}, {"text": "JNJ7777120", "start": 66, "end": 76}, {"text": "PF-3893787", "start": 117, "end": 127}]}}, "schema": []}
{"input": "Overall, the pyrido [3, 2-d] pyrimidines show an excellent in vitro profile that warrants their further investigation in relevant models of human disease.", "output": {"entities": {"chemical": [{"text": "pyrido [3, 2-d] pyrimidines", "start": 13, "end": 40}]}}, "schema": []}
{"input": "Characterization of a gap-junctional intercellular communication (GJIC) assay using cigarette smoke.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of gap-junctional intercellular communication (GJIC) via exposure to various toxic substances has been implicated in tumor promotion.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, cigarette smoke total particulate matter (TPM), a known inhibitor of GJIC, were used to characterize a new GJIC screening assay in three independent experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The main features of this assay were automated fluorescence microscopy combined with non-invasive parachute technique.", "output": {"entities": {}}, "schema": []}
{"input": "Rat liver epithelial cells (WB-F344) were stained with the fluorescent dye Calcein AM (acetoxymethyl) and exposed to TPM from the Kentucky Reference Cigarette 2R4F (a blend of Bright and Burley tobaccos) and from two single-tobacco cigarettes (Bright and Burley) for 3h.", "output": {"entities": {"chemical": [{"text": "Calcein AM", "start": 75, "end": 85}, {"text": "acetoxymethyl", "start": 87, "end": 100}]}}, "schema": []}
{"input": "Phorbol-12-myristate-13-acetate (TPA) was used as positive control and 0. 5% dimethyl sulfoxide (DMSO) as solvent control.", "output": {"entities": {"chemical": [{"text": "Phorbol-12-myristate-13-acetate", "start": 0, "end": 31}, {"text": "TPA", "start": 33, "end": 36}, {"text": "dimethyl sulfoxide", "start": 77, "end": 95}, {"text": "DMSO", "start": 97, "end": 101}]}}, "schema": []}
{"input": "The transfer of dye to adjacent cells (percentage of stained cells) was used as a measure of cellular communication.", "output": {"entities": {}}, "schema": []}
{"input": "A clear and reproducible dose-response of GJIC inhibition following TPM exposure was seen.", "output": {"entities": {}}, "schema": []}
{"input": "Reproducibility and repeatability measurements for the 2R4F cigarette were 3. 7% and 6. 9%, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The half-maximal effective concentration values were 0. 34ng/ml for TPA, 0. 050mg/ml for the 2R4F, 0. 044mg/ml for the Bright cigarette, and 0. 060mg/ml for the Burley cigarette.", "output": {"entities": {"chemical": [{"text": "TPA", "start": 68, "end": 71}]}}, "schema": []}
{"input": "The assay was able to discriminate between the two single-tobacco cigarettes (P < 0. 0001), and between the single-tobacco cigarettes and the 2R4F (P = 0. 0008, 2R4F vs. Burley and P < 0. 0001, 2R4F vs. Bright).", "output": {"entities": {}}, "schema": []}
{"input": "Thus, this assay can be used to determine the activity of complex mixtures such as cigarette smoke with high throughput and high precision.", "output": {"entities": {}}, "schema": []}
{"input": "Vinclozolin: A case study on the identification of endocrine active substances in the past and a future perspective.", "output": {"entities": {"chemical": [{"text": "Vinclozolin", "start": 0, "end": 11}]}}, "schema": []}
{"input": "In the late 1980s vinclozolin was tested for prenatal developmental toxicity in rats for registration purposes in USA.", "output": {"entities": {"chemical": [{"text": "vinclozolin", "start": 18, "end": 29}]}}, "schema": []}
{"input": "At 1000mg/kgbw, 95% of all fetuses were female upon visual inspection (ano-genital distance determination).", "output": {"entities": {}}, "schema": []}
{"input": "Anti-androgenic effects (AA) were also noted in a subsequent 2-generation study.", "output": {"entities": {}}, "schema": []}
{"input": "These findings triggered mechanistic investigations at BASF and at US-EPA.", "output": {"entities": {}}, "schema": []}
{"input": "Results published by the latter were the starting point of the endocrine disruption (ED) discussion in the 1990s.", "output": {"entities": {}}, "schema": []}
{"input": "AA effects of vinclozolin are mediated by two metabolites, which have an antagonistic effect on the androgen receptor.", "output": {"entities": {"chemical": [{"text": "vinclozolin", "start": 14, "end": 25}]}}, "schema": []}
{"input": "Currently, determination of ED has become a major end-point in toxicology testing and the US-EPA has set up an elaborated testing paradigm to fulfill this requirement.", "output": {"entities": {}}, "schema": []}
{"input": "Future screening for ED can be improved making use of new technologies.", "output": {"entities": {}}, "schema": []}
{"input": "ED modes of action can be determined by three alternative (3R) methods.", "output": {"entities": {}}, "schema": []}
{"input": "Steroid synthesis in H295R cells (1), androgen-receptor binding in modified yeast (2) and metabolomics (3).", "output": {"entities": {"chemical": [{"text": "androgen", "start": 38, "end": 46}]}}, "schema": []}
{"input": "Using vinclozolin as a case study, results indicate: (1) an effect on steroid synthesis in vitro, (2) an antagonistic effect on the androgen receptor and (3) that the metabolome profile of vinclozolin is similar to that of other receptor mediated anti-androgens (e. g. flutamide).", "output": {"entities": {"chemical": [{"text": "vinclozolin", "start": 6, "end": 17}, {"text": "steroid", "start": 70, "end": 77}, {"text": "androgen", "start": 132, "end": 140}, {"text": "vinclozolin", "start": 189, "end": 200}, {"text": "androgens", "start": 252, "end": 261}, {"text": "flutamide", "start": 269, "end": 278}]}}, "schema": []}
{"input": "Association of serum adiponectin and IGF-I levels with parameters of cardiac remodeling in severely obese patients.", "output": {"entities": {}}, "schema": []}
{"input": "Background.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity is associated with various changes in cardiac geometry and this process involves both hemodynamic and non-hemodynamic factors, among which adipocitokines and growth factors may play an important role The aim of this study was to identify the extent and pattern of cardiac remodeling in a group of severely obese patients and analyze the relationship between adiponectin, IGF-I and cardiac parameters reflecting obesity associated structural changes.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects and methods.", "output": {"entities": {}}, "schema": []}
{"input": "Our study included 344 patients (104 men) with severe obesity (mean body mass index (BMI) = 45. 7 +/- 8. 5 kg/m2), extensively evaluated clinically and biologically (complete metabolic tests, serum adiponectin and IGF-I measurements).", "output": {"entities": {}}, "schema": []}
{"input": "Left ventricular mass index (LVMI), left atrium (LA) size and LV geometry were determined by means of cardiac ultrasound.", "output": {"entities": {}}, "schema": []}
{"input": "Results.", "output": {"entities": {}}, "schema": []}
{"input": "The most prevalent pattern of LV geometry was eccentric hypertrophy (28. 7% of patients).", "output": {"entities": {}}, "schema": []}
{"input": "In a gender, age, BMI, diabetes and hypertension adjusted general linear model, patients with concentric or eccentric hypertrophy had significantly lower values of adiponectin than those with normal geometry (6. 75 +/- 0. 41, 6. 96 +/- 0. 53, versus 9. 04 +/- 0. 42 mg/l, p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "In multivariate analysis, independent determinants for LVMI were BMI (B = 0. 364, p < 0. 001), systolic blood pressure (BP) (beta = 0. 187, p = 0. 004), age (beta = 0. 246, p < 0. 001), adiponectin (beta =-0. 151, p = 0. 012) and IGF-I z-score (beta = 0. 134, p = 0. 025) while factors independently related to LA size were systolic BP (beta = 0. 218, p < 0. 001), BMI (beta = 0. 194, p < 0. 001), age (beta = 0. 273, p < 0. 001), gender (beta =-0. 195, p < 0. 001) and adiponectin (beta =-0. 180, p = 0. 005).", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: In patients with severe obesity, IGF-I z score and adiponectin correlate with parameters of cardiac remodeling independently of anthropometric, hemodynamic or metabolic factors.", "output": {"entities": {}}, "schema": []}
{"input": "Straight talk with... Miyoung Chun.", "output": {"entities": {}}, "schema": []}
{"input": "It was a single tweet.", "output": {"entities": {}}, "schema": []}
{"input": "In February, after US President Barack Obama made a subtle nod to a new neuroscience project in his annual State of the Union address, Francis Collins, director of the country' s National Institutes of Health (NIH), posted on the @NIHDirector Twitter feed: \" Obama mentions the #NIH Brain Activity Map in #SOTU. \" Instantly, scientists were buzzing with rumors that the Brain Activity Map could be the next moon shot, with a budget and timeline similar to the Human Genome Project.", "output": {"entities": {}}, "schema": []}
{"input": "The brain map began as a brief white paper and has grown into a large-and still largely undefined-collaboration of several government agencies, nonprofit foundations and private companies.", "output": {"entities": {}}, "schema": []}
{"input": "As the stakeholders describe in a commentary published last month (339, 1284-1285, 2013 10. 1126/science. 1236939), the goal of the initiative is to understand how thousands of neurons work in concert to control behavior and trigger disease.", "output": {"entities": {}}, "schema": []}
{"input": "Miyoung Chun, vice president for science programs at The Kavli Foundation in Oxnard, California, has been developing the project since the beginning and is the self-described \" glue \" between its many diverse stakeholders.", "output": {"entities": {}}, "schema": []}
{"input": "Chun spoke with Virginia Hughes about the evolution of the project and what it might mean for biomedicine.", "output": {"entities": {}}, "schema": []}
{"input": "Drosophila homologues of Adenomatous polyposis coli (APC) and the formin Diaphanous collaborate by a conserved mechanism to stimulate actin filament assembly.", "output": {"entities": {}}, "schema": []}
{"input": "Adenomatous polyposis coli (APC) is a large multi-domain protein that regulates the cytoskeleton.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, it was shown that vertebrate APC through its Basic domain directly collaborates with the formin mDia1 to stimulate actin filament assembly in the presence of nucleation barriers.", "output": {"entities": {}}, "schema": []}
{"input": "However, it has been unclear whether these activities extend to homologues of APC and Dia in other organisms.", "output": {"entities": {}}, "schema": []}
{"input": "Drosophila APC and Dia are each required to promote actin furrow formation in the syncytial embryo, suggesting a potential collaboration in actin assembly, but low sequence homology between the Basic domains of Drosophila and vertebrate APC has left their functional and mechanistic parallels uncertain.", "output": {"entities": {}}, "schema": []}
{"input": "To address this question, we purified Drosophila APC1 and Dia and determined their individual and combined effects on actin assembly using both bulk fluorescence assays and total internal reflection fluorescence (TIRF) microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Our data show that APC1, similar to its vertebrate homologue, bound to actin monomers and nucleated and bundled filaments.", "output": {"entities": {}}, "schema": []}
{"input": "Further, Drosophila Dia nucleated actin assembly, and protected growing filament barbed ends from capping protein.", "output": {"entities": {}}, "schema": []}
{"input": "Drosophila APC1 and Dia directly interacted and collaborated to promote actin assembly in the combined presence of profilin and capping protein.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, despite limited sequence homology, Drosophila and vertebrate APCs exhibit highly related activities and mechanisms, and directly collaborate with formins.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that APC-Dia interactions in actin assembly are conserved and may underlie important in vivo functions in a broad range of animal phyla.", "output": {"entities": {}}, "schema": []}
{"input": "Norepinephrine and impulsivity: effects of acute yohimbine.", "output": {"entities": {"chemical": [{"text": "Norepinephrine", "start": 0, "end": 14}, {"text": "yohimbine", "start": 49, "end": 58}]}}, "schema": []}
{"input": "RATIONALE: Rapid-response impulsivity, characterized by inability to withhold response to a stimulus until it is adequately appraised, is associated with risky behavior and may be increased in a state-dependent manner by norepinephrine.", "output": {"entities": {"chemical": [{"text": "norepinephrine", "start": 221, "end": 235}]}}, "schema": []}
{"input": "OBJECTIVE: We assessed effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenergic receptors, on plasma catecholamine metabolites, blood pressure, subjective symptoms, and laboratory-measured rapid-response impulsivity.", "output": {"entities": {"chemical": [{"text": "yohimbine", "start": 34, "end": 43}, {"text": "norepinephrine", "start": 61, "end": 75}, {"text": "catecholamine", "start": 139, "end": 152}]}}, "schema": []}
{"input": "METHODS: Subjects were 23 healthy controls recruited from the community, with normal physical examination and ECG, and negative history for hypertension, cardiovascular illness, and axis I or II disorder.", "output": {"entities": {}}, "schema": []}
{"input": "Blood pressure, pulse, and behavioral measures were obtained before and periodically after 0. 4 mg/kg oral yohimbine or placebo in a randomized, counterbalanced design.", "output": {"entities": {"chemical": [{"text": "yohimbine", "start": 107, "end": 116}]}}, "schema": []}
{"input": "Metabolites of norepinephrine [3-methoxy-4-hydroxyphenylglycol (MHPG) and vanillylmandelic acid (VMA)] and dopamine [homovanillic acid (HVA)] were measured by high-pressure liquid chromatography with electrochemical detection.", "output": {"entities": {"chemical": [{"text": "norepinephrine", "start": 15, "end": 29}, {"text": "3-methoxy-4-hydroxyphenylglycol", "start": 31, "end": 62}, {"text": "MHPG", "start": 64, "end": 68}, {"text": "vanillylmandelic acid", "start": 74, "end": 95}, {"text": "VMA", "start": 97, "end": 100}, {"text": "dopamine", "start": 107, "end": 115}, {"text": "homovanillic acid", "start": 117, "end": 134}, {"text": "HVA", "start": 136, "end": 139}]}}, "schema": []}
{"input": "Rapid-response impulsivity was measured by commission errors and reaction times on the immediate memory task (IMT), a continuous performance test designed to measure impulsivity and attention.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Yohimbine increased plasma MHPG and VMA but not HVA.", "output": {"entities": {"chemical": [{"text": "Yohimbine", "start": 9, "end": 18}, {"text": "MHPG", "start": 36, "end": 40}, {"text": "VMA", "start": 45, "end": 48}, {"text": "HVA", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Yohimbine increased systolic and diastolic blood pressure and pulse rate.", "output": {"entities": {"chemical": [{"text": "Yohimbine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "On the IMT, yohimbine increased impulsive errors and impulsive response bias and accelerated reaction times.", "output": {"entities": {"chemical": [{"text": "yohimbine", "start": 12, "end": 21}]}}, "schema": []}
{"input": "Yohimbine-associated increase in plasma MHPG correlated with increased impulsive response rates.", "output": {"entities": {"chemical": [{"text": "Yohimbine", "start": 0, "end": 9}, {"text": "MHPG", "start": 40, "end": 44}]}}, "schema": []}
{"input": "Time courses varied; effects on blood pressure generally preceded those on metabolites and test performance.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: These effects are consistent with increased rapid-response impulsivity after pharmacological noradrenergic stimulation in healthy controls.", "output": {"entities": {}}, "schema": []}
{"input": "Labile noradrenergic responses, or increased sensitivity to norepinephrine, may increase risk for impulsive behavior.", "output": {"entities": {"chemical": [{"text": "norepinephrine", "start": 60, "end": 74}]}}, "schema": []}
{"input": "Using waste Li ion batteries as cathodes in rechargeable Li-liquid batteries.", "output": {"entities": {"chemical": [{"text": "Li", "start": 12, "end": 14}, {"text": "Li", "start": 57, "end": 59}]}}, "schema": []}
{"input": "The rechargeable Li-liquid battery was developed using waste Li ion battery materials immersed in water and used as the liquid cathode.", "output": {"entities": {"chemical": [{"text": "Li", "start": 17, "end": 19}, {"text": "Li", "start": 61, "end": 63}]}}, "schema": []}
{"input": "Either the Li metal or Li ions (by the formation LixC6 or Li4 + xTi5O12) was harvested from waste Li ion source materials such as a waste anode (LixC6), cathode (LixFePO4), and electrolyte (LiPF6 in EC: DEC) by charging the cell, which then discharged with the waste products in the liquid cathode solution to produce electric energy.", "output": {"entities": {"chemical": [{"text": "Li", "start": 11, "end": 13}, {"text": "Li", "start": 23, "end": 25}, {"text": "LixC6", "start": 49, "end": 54}, {"text": "Li4 + xTi5O12", "start": 58, "end": 71}, {"text": "Li", "start": 98, "end": 100}, {"text": "LixC6", "start": 145, "end": 150}, {"text": "LixFePO4", "start": 162, "end": 170}, {"text": "LiPF6", "start": 190, "end": 195}]}}, "schema": []}
{"input": "When the Li4Ti5O12 was used as the anode with the waste products as the cathode in the proposed battery system, a good cycle-life with high coulombic efficiency was observed.", "output": {"entities": {"chemical": [{"text": "Li4Ti5O12", "start": 9, "end": 18}]}}, "schema": []}
{"input": "Obesity Modulates the Immune Response to Oxidized LDL in Hypertensive Patients.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity and hypertension have been recognized as inflammatory diseases capable of activating the immune system, thus contributing to an increased cardiovascular risk.", "output": {"entities": {}}, "schema": []}
{"input": "However, the link between adaptive immunity, obesity, and hypertension is poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the relationship of the body mass index (BMI) on the inflammatory, vascular, and immune responses in patients with hypertension na i ve of anti-hypertensive treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Hypertensive patients (N = 88) were divided into three groups: normal weight (NW), overweight (OW), and obese (OB) subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-oxidized LDL autoantibodies (anti-oxLDL Abs), anti-ApoB-D peptide (anti-ApoB-D) Abs, interleukin (IL)-8 and IL-10, flow-mediated dilation (FMD) of the brachial artery, and 24-h ambulatory blood pressure monitoring (ABPM) were assessed.", "output": {"entities": {}}, "schema": []}
{"input": "OB patients presented lower levels of anti-oxLDL Abs and IL-10, higher levels of IL-8, and impaired FMD, when compared to NW and OW (P < 0. 05), without differences between groups regarding anti-ApoB-D Abs.", "output": {"entities": {}}, "schema": []}
{"input": "After adjusting for age, systolic and diastolic blood pressure, anti-oxLDL Abs were inversely correlated with BMI and waist circumference (r =-0. 24, P = 0. 02 and r =-0. 25, P = 0. 02, respectively), whereas ApoB-D correlated with 24-h ABPM (r = 0. 22, P = 0. 05 for systolic, and r = 0. 29, P = 0. 01 for diastolic blood pressure).", "output": {"entities": {}}, "schema": []}
{"input": "Regression analyses showed inverse associations of anti-oxLDL Abs with BMI (beta =-0. 05, P = 0. 01) and waist circumference (beta =-0. 01, P = 0. 02); anti-ApoB-D Abs were associated with systolic and diastolic 24-h ABPM (beta = 0. 96, P = 0. 04; beta = 1. 02, P = 0. 005, for systolic and diastolic 24-h ABPM, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "Among hypertensive patients, obesity modulates the immune and inflammatory milieu, determining an unfavorable balance of cytokines and reduction in titers of anti-oxLDL Abs.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-four hour ABPM is associated with titers of anti-ApoB-D Abs.", "output": {"entities": {}}, "schema": []}
{"input": "In Vitro Inhibition of the Transcription Factor NF-kappa B and Cyclooxygenase by Bamboo Extracts.", "output": {"entities": {}}, "schema": []}
{"input": "Several bamboo species have been used in traditional medicine for the treatment of inflammatory conditions.", "output": {"entities": {}}, "schema": []}
{"input": "The present study evaluates the in vitro anti-inflammatory properties of the traditionally used bamboo species Phyllostachys nigra (Lodd.) Munro and Sasa veitchii (Carr.) Rehder to explore their future research opportunities and therapeutic potential as anti-inflammatory agents.", "output": {"entities": {}}, "schema": []}
{"input": "The extracts were evaluated for their potential inhibitory activity at the level of NF-kappa B-induced gene expression and suppression of cyclooxygenase (COX)-1 and COX-2 enzyme activities, representative pharmacological targets for the anti-inflammatory action of glucocorticoids and non-steroidal anti-inflammatory drugs, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The activity of P. nigra (Lodd.) Munro and S. veitchii (Carr.) Rehder was compared with bamboo species without traditional anti-inflammatory indications.", "output": {"entities": {}}, "schema": []}
{"input": "High-performance liquid chromatography with diode-array detection and liquid chromatography-tandem mass spectrometry analyses were performed to phytochemically characterize the extracts.", "output": {"entities": {}}, "schema": []}
{"input": "P. nigra (Lodd.) Munro leaf extract potently inhibited NF-kappa B-induced gene expression, while S. veitchii (Carr.) Rehder leaf extract exerted a selective COX-2 inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "The crude extracts consistently showed a more potent bioactivity than the solid phase extraction fractions.", "output": {"entities": {}}, "schema": []}
{"input": "P. nigra (Lodd.) Munro and S. veitchii (Carr.) Rehder both exert anti-inflammatory properties, but act via a different molecular mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "A solar rechargeable flow battery based on photoregeneration of two soluble redox couples.", "output": {"entities": {}}, "schema": []}
{"input": "Storable sunshine, reusable rays: A solar rechargeable redox flow battery is proposed based on the photoregeneration of I3 (-)/I (-) and [Fe (C10 H15) 2] (+)/Fe (C10 H15) 2 soluble redox couples, which can be regenerated by flowing from a discharged redox flow battery (RFB) into a dye-sensitized solar cell (DSSC) and then stored in tanks for subsequent RFB applications This technology enables effective solar-to-chemical energy conversion.", "output": {"entities": {"chemical": [{"text": "I3 (-)", "start": 120, "end": 126}, {"text": "I (-)", "start": 127, "end": 132}, {"text": "[Fe (C10 H15) 2] (+)", "start": 137, "end": 157}, {"text": "Fe (C10 H15) 2", "start": 158, "end": 172}]}}, "schema": []}
{"input": "Temperature-Induced Emission Enhancement of Star Conjugated Copolymers with Poly (2-(dimethylamino) ethyl methacrylate) Coronas for Detection of Bacteria.", "output": {"entities": {"chemical": [{"text": "Poly (2-(dimethylamino) ethyl methacrylate)", "start": 76, "end": 119}]}}, "schema": []}
{"input": "A facile strategy for temperature-induced emission enhancement of star conjugated copolymers has been developed for biodetection.", "output": {"entities": {}}, "schema": []}
{"input": "The star copolymers (HCP-star-PDMAEMAs) with different poly (2-(dimethylamino) ethyl methacrylate) (PDMAEMA) chain lengths were synthesized from the hyperbranched conjugated polymer (HCP) macroinitiator by atom transfer radical polymerization (ATRP).", "output": {"entities": {"chemical": [{"text": "PDMAEMAs", "start": 30, "end": 38}, {"text": "poly (2-(dimethylamino) ethyl methacrylate)", "start": 55, "end": 98}, {"text": "PDMAEMA", "start": 100, "end": 107}]}}, "schema": []}
{"input": "The star conjugated copolymers exhibited interesting thermoresponsive phase transitions with adjustable lower critical solution temperature (LCST) depending on the pH of copolymer solution.", "output": {"entities": {}}, "schema": []}
{"input": "Above the LCST, the emission of HCP-star-PDMAEMAs was enhanced greatly through restriction of intermolecular aggregation of conjugated polymer cores by the collapse of PDMAEMA arms.", "output": {"entities": {"chemical": [{"text": "PDMAEMAs", "start": 41, "end": 49}, {"text": "PDMAEMA", "start": 168, "end": 175}]}}, "schema": []}
{"input": "By changing the PDMAEMA length, the emission performance of HCP-star-PDMAEMAs could be readily adjusted.", "output": {"entities": {"chemical": [{"text": "PDMAEMA", "start": 16, "end": 23}, {"text": "PDMAEMAs", "start": 69, "end": 77}]}}, "schema": []}
{"input": "Correspondingly, this temperature-dependent emission enhancement of HCP-star-PDMAEMAs was successfully applied in the highly sensitive detection of bacteria.", "output": {"entities": {"chemical": [{"text": "PDMAEMAs", "start": 77, "end": 85}]}}, "schema": []}
{"input": "Due to the existence of a hyperbranched conjugated core and many thermo-responsive PDMAEMA arms, the detection limit of E. coli could reach 10 (2) cfu mL (-1).", "output": {"entities": {"chemical": [{"text": "PDMAEMA", "start": 83, "end": 90}]}}, "schema": []}
{"input": "Poly (vinyl alcohol) Physical Hydrogel Nanoparticles, Not Polymer Solutions, Exert Inhibition of Nitric Oxide Synthesis in Cultured Macrophages.", "output": {"entities": {"chemical": [{"text": "Poly (vinyl alcohol)", "start": 0, "end": 20}, {"text": "Nitric Oxide", "start": 97, "end": 109}]}}, "schema": []}
{"input": "Hydrogel nanoparticles (HNP) are an emerging tool of biomedicine with unique materials characteristics, scope, and utility.", "output": {"entities": {}}, "schema": []}
{"input": "These hydrated, soft colloidal carriers can penetrate through voids with dimensions narrower than the size of the particle, provide stabilization for fragile biological cargo and allow diffusion and exchange of solutes with external phase.", "output": {"entities": {}}, "schema": []}
{"input": "However, techniques to assemble HNP are few; solitary examples exist of biocompatible polymers being formulated into HNP; and knowledge on the biomedical properties of HNP remains rather cursory.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we investigate assembly of HNP based on a polymer with decades of prominence in the biomedical field, poly (vinyl alcohol), PVA.", "output": {"entities": {"chemical": [{"text": "poly (vinyl alcohol)", "start": 116, "end": 136}, {"text": "PVA", "start": 138, "end": 141}]}}, "schema": []}
{"input": "We develop a novel method for production of PVA HNP through nanoprecipitation-based assembly of polymer nanoparticles and subsequent physical hydrogelation of the polymer.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 44, "end": 47}]}}, "schema": []}
{"input": "Polymer nanoparticles and HNP were visualized using scanning electron microscopy and fluorescence imaging, and characterized using dynamic light scattering and zeta potential measurements.", "output": {"entities": {}}, "schema": []}
{"input": "Interaction of PVA HNP with mammalian cells was investigated using flow cytometry, viability screening, and measurements of nitric oxide production by cultured macrophages.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 15, "end": 18}, {"text": "nitric oxide", "start": 124, "end": 136}]}}, "schema": []}
{"input": "The latter analyses revealed that PVA administered as a polymer solution or in the form of HNP resulted in no measurable increase in production of the inflammation marker.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 34, "end": 37}]}}, "schema": []}
{"input": "Unexpectedly, PVA HNP exerted a pronounced inhibition of NO synthesis by stimulated macrophages, that is, had an anti-inflammatory activity.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 14, "end": 17}, {"text": "NO", "start": 57, "end": 59}]}}, "schema": []}
{"input": "This effect was accomplished with a negligible change in the cell viability and was not observed when PVA was administered as a polymer solution.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 102, "end": 105}]}}, "schema": []}
{"input": "To the best of our knowledge, this is the first observation of inhibition of NO synthesis in macrophages by administered nanoparticles and specifically hydrogel nanoparticles.", "output": {"entities": {"chemical": [{"text": "NO", "start": 77, "end": 79}]}}, "schema": []}
{"input": "Taken together, our results present PVA HNP as promising colloidal hydrogel nanocarriers for biomedical applications, specifically drug delivery and assembly of intracellular biosensors.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 36, "end": 39}]}}, "schema": []}
{"input": "Enhancing Raman Scattering without Plasmons: Unprecedented Sensitivity Achieved by TiO2 Shell-Based Resonators.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 83, "end": 87}]}}, "schema": []}
{"input": "A remarkable enhancement of Raman scattering is achieved by TiO2 shell-based spherical resonators in the absence of plasmonic enhancers.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 60, "end": 64}]}}, "schema": []}
{"input": "This effect is ascribed to the synergistic combination of high refractive index of the shell layer, multiple light scattering through the spheres, and related geometrical factors and can be exploited to fabricate a new generation of self-diagnostic, recyclable SERS-active substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Graphene MEMS: AFM Probe Performance Improvement.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 0, "end": 8}]}}, "schema": []}
{"input": "We explore the feasibility of growing a continuous layer of graphene in prepatterned substrates, like an engineered silicon wafer, and we apply this as a mold for the fabrication of AFM probes.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 60, "end": 68}, {"text": "silicon", "start": 116, "end": 123}]}}, "schema": []}
{"input": "This fabrication method proves the fabrication of SU-8 devices coated with graphene in a full-wafer parallel technology and with high yield.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 75, "end": 83}]}}, "schema": []}
{"input": "It also demonstrates that graphene coating enhances the functionality of SU-8 probes, turning them conductive and more resistant to wear.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 26, "end": 34}]}}, "schema": []}
{"input": "Furthermore, it opens new experimental possibilities such as studying graphene-graphene interaction at the nanoscale with the precision of an AFM or the exploration of properties in nonplanar graphene layers.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 70, "end": 78}, {"text": "graphene", "start": 79, "end": 87}, {"text": "graphene", "start": 192, "end": 200}]}}, "schema": []}
{"input": "3D Spectroscopy of Vibrational Coherences in Quantum Dots: Theory.", "output": {"entities": {}}, "schema": []}
{"input": "In semiconductor nanocrystals, called quantum dots (QD), electronic transition energies, phonon frequencies, and electron-phonon coupling strengths are all reported to depend on the size of the crystals.", "output": {"entities": {}}, "schema": []}
{"input": "The size dependencies of the transition energies and the mode frequencies are well characterized and understood.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, the electron-phonon coupling dependence on size is controversial-even the sign of the change is not settled.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, third-order response functions of a model QD resembling CdSe are calculated.", "output": {"entities": {"chemical": [{"text": "CdSe", "start": 73, "end": 77}]}}, "schema": []}
{"input": "The longitudinal optical (LO) mode is included as a relatively narrow Lorentzian contribution to the spectral density.", "output": {"entities": {}}, "schema": []}
{"input": "A novel version of electronic 2D spectroscopy is investigated where a third Fourier transform is taken over a so-called population time, leading to 3D spectral representation.", "output": {"entities": {}}, "schema": []}
{"input": "The amplitude and phase of the 2D cuts of the 3D spectral body around the LO mode frequency are analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "The analytical power and sensitivity of the cuts in determining the possible Huang-Rhys factor (electron-phonon coupling strength) and the LO mode frequency dependence on the QD size are investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Peak structures in the cuts with a tilt relative to the diagonal are identified as sensitive signatures for the size dependencies.", "output": {"entities": {}}, "schema": []}
{"input": "The study elucidates the 3D representation of the electronic 2D spectroscopy as a powerful tool for obtaining insight into otherwise hardly accessible characteristics of the system.", "output": {"entities": {}}, "schema": []}
{"input": "Peptide-Directed Preparation and X-ray Structural Study of Au Nanoparticles on Titanium Surfaces.", "output": {"entities": {"chemical": [{"text": "Au", "start": 59, "end": 61}, {"text": "Titanium", "start": 79, "end": 87}]}}, "schema": []}
{"input": "We report the peptide-directed preparation and X-ray structural study of biofunctionalized Au nanoparticles (NPs) deposited on Ti surfaces.", "output": {"entities": {"chemical": [{"text": "Au", "start": 91, "end": 93}, {"text": "Ti", "start": 127, "end": 129}]}}, "schema": []}
{"input": "Au NPs were prepared by reduction of Au (3 +) compound onto HCl-refreshed Ti in the presence of thiol-functionalized small peptides.", "output": {"entities": {"chemical": [{"text": "Au", "start": 0, "end": 2}, {"text": "Au (3 +)", "start": 37, "end": 45}, {"text": "HCl", "start": 60, "end": 63}, {"text": "Ti", "start": 74, "end": 76}, {"text": "thiol", "start": 96, "end": 101}]}}, "schema": []}
{"input": "A modified extended X-ray absorption fine-structure (EXAFS) technique, equipped with a rotating-stage and glancing-angle setup, was able to more sensitively detect the structure and bonding of Au NPs on Ti with low surface coverage.", "output": {"entities": {"chemical": [{"text": "Au", "start": 193, "end": 195}, {"text": "Ti", "start": 203, "end": 205}]}}, "schema": []}
{"input": "It was found that the use of the tripeptide glutathione (GSH) results in smaller NP size when compared to N-(2-mercapto-propionyl) glycine (MPG), a pseudodipeptide, over a wide range of Au/peptide molar ratios (20: 1, 10: 1, 5: 1, and 2: 1).", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 44, "end": 55}, {"text": "GSH", "start": 57, "end": 60}, {"text": "N-(2-mercapto-propionyl) glycine", "start": 106, "end": 138}, {"text": "MPG", "start": 140, "end": 143}, {"text": "Au", "start": 186, "end": 188}]}}, "schema": []}
{"input": "By varying the ligand concentration, the Au NP structure in both systems can be controlled, generating nanocrystals, nanoclusters, and Au-thiolate polymer, which is unique for substrate-supported NP synthesis.", "output": {"entities": {"chemical": [{"text": "Au", "start": 41, "end": 43}, {"text": "Au", "start": 135, "end": 137}, {"text": "thiolate", "start": 138, "end": 146}]}}, "schema": []}
{"input": "This work presents a facile preparation of Au-peptide nanoparticles on biocompatible surfaces, and illustrates the high sensitivity of this modified EXAFS technique for structural studies of substrate-supported nanoparticles with low coverage.", "output": {"entities": {"chemical": [{"text": "Au", "start": 43, "end": 45}]}}, "schema": []}
{"input": "Synergistic Interactions between Grafted Hyaluronic Acid and Lubricin Provide Enhanced Wear Protection and Lubrication.", "output": {"entities": {}}, "schema": []}
{"input": "Normal (e. g., adhesion) and lateral (friction) forces were measured between physisorbed and chemically grafted layers of hyaluronic acid (HA), an anionic polyelectrolyte in the presence of lubricin (Lub), a mucinous glycoprotein, on mica surfaces using a surface forces apparatus (SFA).", "output": {"entities": {}}, "schema": []}
{"input": "This work demonstrates that high friction coefficients between the surfaces do not necessarily correlate with surface damage and that chemically grafted HA acts synergistically with Lub to provide friction reduction and enhanced wear protection to the surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Surface immobilization of HA by grafting is necessary for such wear protection.", "output": {"entities": {}}, "schema": []}
{"input": "Increasing the concentration of Lub enhances the threshold load that a chemically grafted HA surface can be subjected to before the onset of wear.", "output": {"entities": {}}, "schema": []}
{"input": "Addition of Lub does not have any beneficial effect if HA is physisorbed to the mica surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Damage occurs at loads less than 1 mN regardless of the amount of Lub, indicating that the molecules in the bulk play little or no role in protecting the surfaces from damage.", "output": {"entities": {}}, "schema": []}
{"input": "Lub penetrates into the chemically bound HA to form a visco-elastic gel that reduces the coefficient of friction as well as boosts the strength of the surface against abrasive wear (damage).", "output": {"entities": {}}, "schema": []}
{"input": "Effects of combination processes on the extraction of pectins from rapeseed cake (Brassica napus L.).", "output": {"entities": {}}, "schema": []}
{"input": "In this study, rapeseed cake (RSC) was used as a source of pectins due to its high carbohydrate content.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 83, "end": 95}]}}, "schema": []}
{"input": "Different combinations of treatments were applied to investigate the effect of combination processes on the extraction of pectin from RSC.", "output": {"entities": {}}, "schema": []}
{"input": "The treatments chosen for combination were a fat removal process (FRP) (solvent extraction using an alcohol-benzene mixture), a chemical treatment (CT) (hydrolysis using 1% hydrochloric acid), and an enzymatic hydrolysis (EH).", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 100, "end": 107}, {"text": "benzene", "start": 108, "end": 115}, {"text": "hydrochloric acid", "start": 173, "end": 190}]}}, "schema": []}
{"input": "After the combined processes, pectins were extracted by isopropanol/ethanol precipitation and the residues were analysed by HPLC or an elemental analyser.", "output": {"entities": {"chemical": [{"text": "isopropanol", "start": 56, "end": 67}, {"text": "ethanol", "start": 68, "end": 75}]}}, "schema": []}
{"input": "The pectin yields and galacturonic acid contents were increased by FRP because 72. 13% of the total fat was removed; additionally, EH had a similar effect.", "output": {"entities": {"chemical": [{"text": "galacturonic acid", "start": 22, "end": 39}]}}, "schema": []}
{"input": "However, CT decreased the yields because the treatment was too harsh and the galacturonic acid broke down.", "output": {"entities": {"chemical": [{"text": "galacturonic acid", "start": 77, "end": 94}]}}, "schema": []}
{"input": "Pectin yields and galacturonic acid contents were highest in the combination process FRP/EH (6. 23% and 64. 23%, respectively).", "output": {"entities": {"chemical": [{"text": "galacturonic acid", "start": 18, "end": 35}]}}, "schema": []}
{"input": "Microencapsulation of aspartame by double emulsion followed by complex coacervation to provide protection and prolong sweetness.", "output": {"entities": {"chemical": [{"text": "aspartame", "start": 22, "end": 31}]}}, "schema": []}
{"input": "The objective of this work was to microencapsulate aspartame by double emulsion followed by complex coacervation, aiming to protect it and control its release.", "output": {"entities": {"chemical": [{"text": "aspartame", "start": 51, "end": 60}]}}, "schema": []}
{"input": "Six treatments were prepared using sunflower oil to prepare the primary emulsion and gelatin and gum Arabic as the wall materials.", "output": {"entities": {}}, "schema": []}
{"input": "The microcapsules were evaluated structurally with respect to their sorption isotherms and release into water (36 degrees C and 80 degrees C).", "output": {"entities": {}}, "schema": []}
{"input": "The microcapsules were multinucleated, not very water-soluble or hygroscopic and showed reduced rates of equilibrium moisture content and release at both temperatures.", "output": {"entities": {}}, "schema": []}
{"input": "FTIR confirmed complexation between the wall materials and the intact nature of aspartame.", "output": {"entities": {"chemical": [{"text": "aspartame", "start": 80, "end": 89}]}}, "schema": []}
{"input": "The results indicated it was possible to encapsulate aspartame with the techniques employed and that these protected the sweetener even at 80 degrees C.", "output": {"entities": {"chemical": [{"text": "aspartame", "start": 53, "end": 62}]}}, "schema": []}
{"input": "The reduced solubility and low release rates indicated the enormous potential of the vehicle developed in controlling the release of the aspartame into the food, thus prolonging its sweetness.", "output": {"entities": {"chemical": [{"text": "aspartame", "start": 137, "end": 146}]}}, "schema": []}
{"input": "Enrichment of two isoflavone aglycones in black soymilk by using spent coffee grounds as an immobiliser for beta-glucosidase.", "output": {"entities": {"chemical": [{"text": "isoflavone aglycones", "start": 18, "end": 38}]}}, "schema": []}
{"input": "Spent coffee grounds, discarded as environmental pollutants, were adopted as enzyme immobilisation solid carriers instead of commercialised solid supports to establish an economical catalytic system.", "output": {"entities": {}}, "schema": []}
{"input": "beta-Glucosidase was covalently immobilised onto spent coffee grounds for the conversion of isoflavone glycosides into their aglycones in black soymilk.", "output": {"entities": {"chemical": [{"text": "isoflavone glycosides", "start": 92, "end": 113}]}}, "schema": []}
{"input": "Optimum conditions were determined to be 40 degrees C and pH 6 using 4-nitrophenyl beta-d-glucuronide as an indicator.", "output": {"entities": {"chemical": [{"text": "4-nitrophenyl beta-d-glucuronide", "start": 69, "end": 101}]}}, "schema": []}
{"input": "Operational reusability was confirmed for more than 30 batch reactions and the storage stability was capable of sustaining its highest catalytic activity for 20days.", "output": {"entities": {}}, "schema": []}
{"input": "The kinetic parameters including rate constant (K), time (tau 50) in which 50% of isoflavone deglycosylation was reached, and time (tau complete) required to achieve complete isoflavone deglycosylation, were0. 16 +/- 0. 02min (-1), 4. 54 +/- 0. 32min, 60min for daidzin and 0. 16 +/- 0. 02min (-1), 2. 28 +/- 0. 11min, 60min for genistin, respectively.", "output": {"entities": {"chemical": [{"text": "isoflavone", "start": 82, "end": 92}, {"text": "isoflavone", "start": 175, "end": 185}, {"text": "daidzin", "start": 262, "end": 269}, {"text": "genistin", "start": 329, "end": 337}]}}, "schema": []}
{"input": "The total aglycone content in black soymilk was enriched by 67. 14 +/- 0. 60% in the enzymatic treatment of 60min duration.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activity-guided separation of coumarins and lignan from Melicope glabra (Rutaceae).", "output": {"entities": {"chemical": [{"text": "coumarins", "start": 42, "end": 51}, {"text": "lignan", "start": 56, "end": 62}]}}, "schema": []}
{"input": "The ethyl acetate and methanol bark extracts of Melicope glabra were evaluated for their antioxidant capacities by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and beta-carotene bleaching/linoleic acid system.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 4, "end": 17}, {"text": "methanol", "start": 22, "end": 30}, {"text": "1, 1-diphenyl-2-picrylhydrazyl", "start": 115, "end": 145}, {"text": "DPPH", "start": 147, "end": 151}, {"text": "beta-carotene", "start": 190, "end": 203}, {"text": "linoleic acid", "start": 214, "end": 227}]}}, "schema": []}
{"input": "Both extracts exhibited strong inhibition against the DPPH radical (IC50 values of 24. 81 and 13. 01 mu gml (-1), respectively) and strong antioxidant activity in beta-carotene bleaching assay.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 54, "end": 58}, {"text": "beta-carotene", "start": 163, "end": 176}]}}, "schema": []}
{"input": "Both samples were found to have high phenolic content with values of 39 and 44mg GAE/g as indicated by Follin-Ciocalteau' s reagent.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant TLC assay-guided isolation on the methanol extract led to the isolation of a new pyranocoumarin, glabranin (1), umbelliferone (2), scopoletin (3) and sesamin (4), and their structures were determined by spectroscopy.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 46, "end": 54}, {"text": "pyranocoumarin", "start": 93, "end": 107}, {"text": "glabranin", "start": 109, "end": 118}, {"text": "umbelliferone", "start": 124, "end": 137}, {"text": "scopoletin", "start": 143, "end": 153}, {"text": "sesamin", "start": 162, "end": 169}]}}, "schema": []}
{"input": "Compounds (1-3) showed significant activities on DPPH free radical with the IC50 of 240. 20, 810. 02 and 413. 19 mu gml (-1), respectively.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 49, "end": 53}]}}, "schema": []}
{"input": "However, in beta-carotene bleaching assay, sesamin (4) showed higher inhibitory activity (1mgml (-1), 95%) than glabranin (1) (1mgml (-1), 74%), whilst umbelliferone (2) and scopoletin (3) were slightly pro-oxidant.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 12, "end": 25}, {"text": "sesamin", "start": 43, "end": 50}, {"text": "glabranin", "start": 112, "end": 121}, {"text": "umbelliferone", "start": 152, "end": 165}, {"text": "scopoletin", "start": 174, "end": 184}]}}, "schema": []}
{"input": "Free phenolics and polyphenol oxidase (PPO): The factors affecting post-cut browning in eggplant (Solanum melongena).", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 5, "end": 14}, {"text": "polyphenol", "start": 19, "end": 29}]}}, "schema": []}
{"input": "Polyphenol oxidase (PPO) catalyses oxidation of phenolics, which results in instant but differential browning in many cut fruits and vegetables, including eggplant.", "output": {"entities": {"chemical": [{"text": "Polyphenol", "start": 0, "end": 10}, {"text": "phenolics", "start": 48, "end": 57}]}}, "schema": []}
{"input": "Eight cultivars of eggplant were characterised by their PPO specific activity, phenolic content, browning index, and PPO polymorphism.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 79, "end": 87}]}}, "schema": []}
{"input": "In fresh eggplant, browning was found to be dependent on both the phenolic content and PPO specific activity, whereas, total phenolic content played a major role in browning of stored fruits.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 66, "end": 74}, {"text": "phenolic", "start": 125, "end": 133}]}}, "schema": []}
{"input": "Interestingly, although browning index increased in stored eggplant fruits, PPO activity reduced in four out of eight cultivars studied.", "output": {"entities": {}}, "schema": []}
{"input": "Phenolic level was found to increase in all these cultivars during storage.", "output": {"entities": {"chemical": [{"text": "Phenolic", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Although a significant level of homology was observed in PPO nucleotide and conceptually translated protein sequence, two cultivars, which displayed highest PPO specific activity, differed in the 38 amino acid stretch in the peptide region 301-338.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 61, "end": 71}, {"text": "amino acid", "start": 199, "end": 209}]}}, "schema": []}
{"input": "Characteristics of antioxidant activity and composition of pumpkin seed oils in 12 cultivars.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to determine the antioxidant properties, and provide characteristics, of the oil obtained from the seeds of 12 pumpkin varieties belonging to the species Cucurbita maxima Duch. and Cucurbita pepo L.", "output": {"entities": {}}, "schema": []}
{"input": "Another objective was to establish which of the two extracting agents, ethanol or methanol, is more effective.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 71, "end": 78}, {"text": "methanol", "start": 82, "end": 90}]}}, "schema": []}
{"input": "The seeds of the pumpkin varieties examined differ in chemical composition and antioxidant activity.", "output": {"entities": {}}, "schema": []}
{"input": "The seeds of the cultivars belonging to the species C. maxima are characterised by a higher content of fatty acids than are the cultivars of the species C. pepo.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 103, "end": 114}]}}, "schema": []}
{"input": "In the seed oil, unsaturated acids are dominant (oleic and linoleic), and their proportion depends on the pumpkin variety.", "output": {"entities": {"chemical": [{"text": "oleic", "start": 49, "end": 54}, {"text": "linoleic", "start": 59, "end": 67}]}}, "schema": []}
{"input": "The highest content of unsaturated acids has been measured in the oil extracted from the seeds of the cultivar, Jet F1 (C. pepo).", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activity analysis has produced the following findings.", "output": {"entities": {}}, "schema": []}
{"input": "The seeds of the pumpkin varieties that belong to the species C. pepo exhibit better antioxidant properties, regardless of the extraction solvent used.", "output": {"entities": {}}, "schema": []}
{"input": "50% ethanol is more efficient than 80% methanol when used as an extracting agent.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 4, "end": 11}, {"text": "methanol", "start": 39, "end": 47}]}}, "schema": []}
{"input": "The antioxidant activity values obtained with 50% ethanol are higher than those achieved with 80% methanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 50, "end": 57}, {"text": "methanol", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Owing to the considerable differences in composition among the fatty acids examined, it is possible to choose the desired pumpkin variety for the intended use.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 63, "end": 74}]}}, "schema": []}
{"input": "An integrated approach for flavour quality evaluation in muskmelon (Cucumis melo L. reticulatus group) during ripening.", "output": {"entities": {}}, "schema": []}
{"input": "Numerous and diverse physiological changes occur during fruit ripening and maturity at harvest is one of the key factors influencing the flavour quality of fruits.", "output": {"entities": {}}, "schema": []}
{"input": "The effect of ripening on chemical composition, physical parameters and sensory perception of three muskmelon (Cucumis melo L. reticulatus group) cultivars was evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Significant correlations emerging from this extensive data set are discussed in the context of identifying potential targets for melon sensory quality improvement.", "output": {"entities": {}}, "schema": []}
{"input": "A portable ultra-fast gas-chromatograph coupled with a surface acoustic wave sensor (UFGC-SAW) was also used to monitor aroma volatile concentrations during fruit ripening and evaluated for its ability to predict the sensory perception of melon flavour.", "output": {"entities": {}}, "schema": []}
{"input": "UFGC-SAW analysis allowed the discrimination of melon maturity stage based on six measured peaks, whose abundance was positively correlated to maturity-specific sensory attributes.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest that this technology shows promise for future applications in rapid flavour quality evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "Studies of isothermal crystallisation kinetics of sunflower hard stearin-based confectionery fats.", "output": {"entities": {"chemical": [{"text": "stearin", "start": 65, "end": 72}]}}, "schema": []}
{"input": "The crystallisation and polymorphic properties of three sunflower hard stearins (SHSs) and cocoa butter equivalents (CBEs) formulated by blending SHSs and palm mid fraction (PMF) were studied and compared with those from cocoa butter (CB), to explore their possibilities as confectionery fats.", "output": {"entities": {"chemical": [{"text": "stearins", "start": 71, "end": 79}]}}, "schema": []}
{"input": "The isothermal crystallisation kinetics of these fats were examined by pNMR and DSC at three different temperatures.", "output": {"entities": {}}, "schema": []}
{"input": "All samples studied displayed a two-step crystallisation profile that could be fitted to an exponential-Gompertz equation.", "output": {"entities": {}}, "schema": []}
{"input": "Stop-and-return DSC studies showed that SHSs and CBEs exhibited different crystallisation mechanisms according to their triacylglycerol composition, with a quick formation of metastable crystals, followed by a polymorphic transition to the more stable beta or beta' forms.", "output": {"entities": {"chemical": [{"text": "triacylglycerol", "start": 120, "end": 135}]}}, "schema": []}
{"input": "X-ray diffraction (XRD) was used to investigate the polymorphic forms of tempered SHSs and CBEs in the long term.", "output": {"entities": {}}, "schema": []}
{"input": "In all cases the resulting fats displayed short spacing patterns associated with beta polymorphism.", "output": {"entities": {}}, "schema": []}
{"input": "These formulations based on SHSs and PMF met all the requirements to be considered as CBEs; therefore they could be used as an alternative to traditional confectionery fats.", "output": {"entities": {}}, "schema": []}
{"input": "Simulated digestion of proanthocyanidins in grape skin and seed extracts and the effects of digestion on the angiotensin I-converting enzyme (ACE) inhibitory activity.", "output": {"entities": {"chemical": [{"text": "proanthocyanidins", "start": 23, "end": 40}]}}, "schema": []}
{"input": "This study investigated the effect of in vitro gastrointestinal digestion on the stability and composition of flavan-3-ols from red grape skin and seed extracts (raw and purified, which are high in proanthocyanidins (PAs)).", "output": {"entities": {"chemical": [{"text": "flavan-3-ols", "start": 110, "end": 122}, {"text": "proanthocyanidins", "start": 198, "end": 215}, {"text": "PAs", "start": 217, "end": 220}]}}, "schema": []}
{"input": "In addition, the effects of digestion on the angiotensin I-converting enzyme (ACE) inhibitory activities of these extracts were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "The extracts were digested with a mixture of pepsin-HCl for 2h, followed by a 2h incubation with pancreatin and bile salts including a cellulose dialysis tubing (molecular weight cut-off 12kDa) at 37 degrees C with shaking in the dark and under N2.", "output": {"entities": {"chemical": [{"text": "HCl", "start": 52, "end": 55}, {"text": "bile salts", "start": 112, "end": 122}]}}, "schema": []}
{"input": "Under gastric conditions, the mean degree of polymerisation (mDP) of seed extracts, raw (mDP =~ 6, p < 0. 05), and purified (mDP =~ 10, p < 0. 05) was stable.", "output": {"entities": {}}, "schema": []}
{"input": "The mDP of the raw skin extracts increased from 19 to 25 towards the end of the digestion.", "output": {"entities": {}}, "schema": []}
{"input": "The PAs were significantly degraded (up to 80%) during the pancreatic digestion, yielding low-molecular-weight compounds that diffused into the serum-available fraction (mDP =~ 2).", "output": {"entities": {"chemical": [{"text": "PAs", "start": 4, "end": 7}]}}, "schema": []}
{"input": "The overall mass transfer coefficient (K) of the seed extracts was 10 (-7) m (2)/s.", "output": {"entities": {}}, "schema": []}
{"input": "After simulated gastrointestinal digestion, over 80% of ACE inhibition by raw seed and skin extracts was preserved.", "output": {"entities": {}}, "schema": []}
{"input": "However, the purified seed and skin extracts lost their ability to inhibit ACE after intestinal digestion.", "output": {"entities": {}}, "schema": []}
{"input": "Transport across Caco-2 monolayers of peptides arising from in vitro digestion of bovine milk proteins.", "output": {"entities": {}}, "schema": []}
{"input": "The entire panel of peptides produced from caseins (CN) and whey proteins (WP) that survive in vitro sequential gastro-pancreatic digestion and translocate across monolayers of Caco-2 cells, used as a model of the intestinal epithelium, has been characterised by HPLC and mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "Among the milk-derived bioactive peptides, only minor amounts of mono-phosphorylated peptides arising from alpha s1-and beta-CN were detected.", "output": {"entities": {}}, "schema": []}
{"input": "The absorption behaviour of two resistant beta-lactoglobulin (beta-Lg) domains, beta-Lg 125-135 and beta-Lg 40-60, was studied in detail using synthetic peptides.", "output": {"entities": {}}, "schema": []}
{"input": "The IgE-binding properties of the digests recovered from the apical and basolateral monolayer compartments were evaluated by dot-blot, using the sera of milk allergic children (N = 5).", "output": {"entities": {}}, "schema": []}
{"input": "Outcomes indicated beta-Lg 127-135 as a possible \" immune sensitising factor \" in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "The almost complete loss of the IgE-affinity of CN and WP after digestion points out the need to design in vivo experiments to track the metabolic fate of dietary proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Purification and characterisation of sarcoplasmic calcium-binding protein, a novel allergen of red swamp crayfish (Procambarus clarkii).", "output": {"entities": {"chemical": [{"text": "calcium", "start": 50, "end": 57}]}}, "schema": []}
{"input": "Crayfish sarcoplasmic calcium-binding protein (SCP) was purified.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 22, "end": 29}]}}, "schema": []}
{"input": "The physicochemical and polymorphic characterisations were also analysed.", "output": {"entities": {}}, "schema": []}
{"input": "SCP was purified by column chromatography to reveal a single band with molecular mass of 22kDa and further confirmed by mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The results of physicochemical characterisation showed that SCP was stable in the processes of thermal or acid/alkali treatment, and could be digested by simulate gastrointestinal fluid.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, the comparison of SCP polymorphism using sera from crustacean-allergic patients demonstrated SCP-II had a weaker IgE-binding activity.", "output": {"entities": {}}, "schema": []}
{"input": "The isoelectric points of SCP subunits a, b and c were 4. 6, 4. 7, and 4. 8, respectively, as determined by two-dimensional electrophoresis and IgE immunoblotting analysis showed that patients' sera reacted to three subunits of SCP.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, it can be concluded that SCP is a stable polymorphic allergen in crayfish, and all of its isotypes and subunits have allergenicity.", "output": {"entities": {}}, "schema": []}
{"input": "Enzymatic modification enhances the protective activity of citrus flavonoids against alcohol-induced liver disease.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 66, "end": 76}, {"text": "alcohol", "start": 85, "end": 92}]}}, "schema": []}
{"input": "Alcoholic liver disease (ALD) can be developed by a prolonged or large intake of alcohol in a short period of time.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 81, "end": 88}]}}, "schema": []}
{"input": "ALD is considered as a leading cause for a liver injury in modern dietary life.", "output": {"entities": {}}, "schema": []}
{"input": "This study was aimed to investigate the effects of orally administrated citrus flavonoids (CFs) and their enzymatically modified ones (EM-CFs) to prevent ALD.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 79, "end": 89}]}}, "schema": []}
{"input": "Hesperidin and narirutin were extracted from peels of Citrus unshiu by ultra-sonication and purified further.", "output": {"entities": {"chemical": [{"text": "Hesperidin", "start": 0, "end": 10}, {"text": "narirutin", "start": 15, "end": 24}]}}, "schema": []}
{"input": "These CFs were modified enzymatically through glycosylation and de-rhamnosylation by the actions of cyclodextrin glucanotransferase (CGTase) and hesperidinase, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "CFs and EM-CFs were fed to ICR mouse along with ethanol for 8weeks, and changes in lipid contents, lipid peroxidation, GSH, antioxidant enzymes activity and proinflammatory cytokines in hepatic tissues were observed.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 48, "end": 55}, {"text": "GSH", "start": 119, "end": 122}]}}, "schema": []}
{"input": "Administration of CFs and EM-CFs along with alcohol significantly suppressed increases in prognostic parameters of a hepatocellular injury.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 44, "end": 51}]}}, "schema": []}
{"input": "Especially, EM-CFs fed groups maintained malondialdehyde, GSH levels and catalase activity in hepatic tissues close to those of the normal diet fed group.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 41, "end": 56}, {"text": "GSH", "start": 58, "end": 61}]}}, "schema": []}
{"input": "Abrupt increases in proinflammatory cytokines such as I kappa B-alpha, TNF-alpha, IL-1 beta and IL-6 in hepatocytes due to a chronic alcohol uptake were significantly suppressed by co-administration of EM-CFs.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 133, "end": 140}]}}, "schema": []}
{"input": "These results indicate that although the administration of CFs can alleviate ALD through preventing excessive lipid formation, protecting the antioxidant system and suppressing induction of inflammation in hepatocytes, their effectiveness can be further improved by glycosylation and de-rhamnosylation.", "output": {"entities": {}}, "schema": []}
{"input": "Carbon nanotubes-reinforced hollow fibre solid-phase microextraction coupled with high performance liquid chromatography for the determination of carbamate pesticides in apples.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 0, "end": 6}, {"text": "carbamate", "start": 146, "end": 155}]}}, "schema": []}
{"input": "An effective and sensitive method to determinate five carbamate pesticides in apples was developed by using carbon nanotubes-reinforced hollow fibre solid-phase microextraction (CNTs-HF-SPME) combined with high performance liquid chromatography-photodiode array detection (HPLC-DAD).", "output": {"entities": {"chemical": [{"text": "carbamate", "start": 54, "end": 63}, {"text": "carbon", "start": 108, "end": 114}]}}, "schema": []}
{"input": "The CNTs were dispersed in water via adding surfactant, and then were held in the pores of HF supported by capillary forces and sonification.", "output": {"entities": {}}, "schema": []}
{"input": "The SPME device, which was wetted with 1-octanol, was placed in a stirred apple samples to extract target analytes.", "output": {"entities": {"chemical": [{"text": "1-octanol", "start": 39, "end": 48}]}}, "schema": []}
{"input": "After extraction, analytes were desorbed and analyzed using HPLC-DAD.", "output": {"entities": {}}, "schema": []}
{"input": "Under the optimized extraction conditions, the enrichment factors were achieved in the range from 49 to 308 with good inter-fibre repeatability and batch-to-batch reproducibility, while good linearity ranges and recoveries were obtained.", "output": {"entities": {}}, "schema": []}
{"input": "The limits of detection ranged from 0. 09 to 6. 00ng/g.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the results demonstrated that this novel method was an efficient pretreatment and enrichment procedure for the determination of trace carbamate pesticides in apples.", "output": {"entities": {"chemical": [{"text": "carbamate", "start": 145, "end": 154}]}}, "schema": []}
{"input": "A sensitive and selective imprinted solid phase extraction coupled to HPLC for simultaneous detection of trace quinoxaline-2-carboxylic acid and methyl-3-quinoxaline-2-carboxylic acid in animal muscles.", "output": {"entities": {"chemical": [{"text": "quinoxaline-2-carboxylic acid", "start": 111, "end": 140}, {"text": "methyl-3-quinoxaline-2-carboxylic acid", "start": 145, "end": 183}]}}, "schema": []}
{"input": "A new molecularly imprinted polymer (MIP), selective for major metabolites of quinoxaline-1, 4-dioxides, was prepared through bulk polymerisation using quinoxaline-2-carboxylic acid (QCA) as template, diethylaminoethylmethacrylate as functional monomer and ethylene glycol dimethacrylate as cross-linker in tetrahydrofuran.", "output": {"entities": {"chemical": [{"text": "quinoxaline-1, 4-dioxides", "start": 78, "end": 103}, {"text": "quinoxaline-2-carboxylic acid", "start": 152, "end": 181}, {"text": "QCA", "start": 183, "end": 186}, {"text": "diethylaminoethylmethacrylate", "start": 201, "end": 230}, {"text": "ethylene glycol dimethacrylate", "start": 257, "end": 287}, {"text": "tetrahydrofuran", "start": 307, "end": 322}]}}, "schema": []}
{"input": "The synthesised MIP was characterised by Fourier transform infrared and adsorption experiments.", "output": {"entities": {}}, "schema": []}
{"input": "MIP exhibited high affinity, fast kinetics for QCA and good selectivity for QCA and methyl-3-quinoxaline-2-carboxylic acid (MQCA).", "output": {"entities": {"chemical": [{"text": "QCA", "start": 47, "end": 50}, {"text": "QCA", "start": 76, "end": 79}, {"text": "methyl-3-quinoxaline-2-carboxylic acid", "start": 84, "end": 122}, {"text": "MQCA", "start": 124, "end": 128}]}}, "schema": []}
{"input": "MIP obtained was used as a selective sorbent for molecularly imprinted solid phase extraction (MISPE) coupled with HPLC to detect QCA and MQCA.", "output": {"entities": {"chemical": [{"text": "QCA", "start": 130, "end": 133}, {"text": "MQCA", "start": 138, "end": 142}]}}, "schema": []}
{"input": "Under the optimal conditions, the limits of detection (S/N = 3) of porcine, chicken and fish muscles were 0. 1, 0. 3, 0. 1 mu g/kg for QCA and 0. 2, 0. 3, 0. 1 mu g/kg for MQCA, respectively and good recoveries were obtained in the range from 60. 0 to 119. 4%.", "output": {"entities": {"chemical": [{"text": "QCA", "start": 135, "end": 138}, {"text": "MQCA", "start": 172, "end": 176}]}}, "schema": []}
{"input": "These results indicated the MISPE-HPLC procedure could be successfully used for the determination QCA and MQCA in animal muscles.", "output": {"entities": {"chemical": [{"text": "QCA", "start": 98, "end": 101}, {"text": "MQCA", "start": 106, "end": 110}]}}, "schema": []}
{"input": "Synthesis of amino acid conjugates of tetrahydrocurcumin and evaluation of their antibacterial and anti-mutagenic properties.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 13, "end": 23}, {"text": "tetrahydrocurcumin", "start": 38, "end": 56}]}}, "schema": []}
{"input": "Tetrahydrocurcumin (THC), the hydrogenated and stable form of curcumin, exhibits physiological and pharmacological activities similar to curcumin.", "output": {"entities": {"chemical": [{"text": "Tetrahydrocurcumin", "start": 0, "end": 18}, {"text": "THC", "start": 20, "end": 23}, {"text": "curcumin", "start": 62, "end": 70}, {"text": "curcumin", "start": 137, "end": 145}]}}, "schema": []}
{"input": "A protocol has been developed for the synthesis of novel conjugates of THC with alanine (2a), isoleucine (2b), proline (2c), valine (2d), phenylalanine (2e), glycine (2f) and leucine (2g) in high yields (43-82%).", "output": {"entities": {"chemical": [{"text": "THC", "start": 71, "end": 74}, {"text": "alanine", "start": 80, "end": 87}, {"text": "isoleucine", "start": 94, "end": 104}, {"text": "proline", "start": 111, "end": 118}, {"text": "valine", "start": 125, "end": 131}, {"text": "phenylalanine", "start": 138, "end": 151}, {"text": "glycine", "start": 158, "end": 165}, {"text": "leucine", "start": 175, "end": 182}]}}, "schema": []}
{"input": "All the derivatives of THC exhibited more potent anti-microbial activity than THC against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Yersinia enterocolitica.", "output": {"entities": {"chemical": [{"text": "THC", "start": 23, "end": 26}, {"text": "THC", "start": 78, "end": 81}]}}, "schema": []}
{"input": "The MIC values of the derivatives were 24-37% of those for THC in case of both Gram-positive and Gram-negative bacteria.", "output": {"entities": {"chemical": [{"text": "THC", "start": 59, "end": 62}]}}, "schema": []}
{"input": "Derivatives 2g and 2d exhibited maximum anti-mutagenicity against Salmonella typhimurium TA 98 and TA 1538, respectively at a low concentration of 313 mu g/plate, with comparable activity for THC evident only at 3750 mu g/plate.", "output": {"entities": {"chemical": [{"text": "THC", "start": 192, "end": 195}]}}, "schema": []}
{"input": "These results clearly demonstrated that the conjugation of THC at the phenolic position with amino acids led to significant improvement of its in vitro biological attributes.", "output": {"entities": {"chemical": [{"text": "THC", "start": 59, "end": 62}, {"text": "phenolic", "start": 70, "end": 78}, {"text": "amino acids", "start": 93, "end": 104}]}}, "schema": []}
{"input": "Influence of triterpenoids present in apple peel on inflammatory gene expression associated with inflammatory bowel disease (IBD).", "output": {"entities": {"chemical": [{"text": "triterpenoids", "start": 13, "end": 26}]}}, "schema": []}
{"input": "Various ursanic, oleanic and lupanic pentacyclic triterpenoids found in apple peel were studied for anti-inflammatory effects in vitro using T84 colon carcinoma cells.", "output": {"entities": {"chemical": [{"text": "ursanic, oleanic and lupanic pentacyclic triterpenoids", "start": 8, "end": 62}]}}, "schema": []}
{"input": "After pretreatment with single triterpenoids, cells were stimulated with pro-inflammatory cytokines (TNF-alpha, INF-gamma, IL-1 beta).", "output": {"entities": {"chemical": [{"text": "triterpenoids", "start": 31, "end": 44}]}}, "schema": []}
{"input": "Regulation of mRNA expression was analysed for three specific inflammation-associated marker genes (TNF-alpha, IL-8, IP-10) using qRT-PCR.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the effects of ursolic acid (UA) and oleanolic acid (OA) on the synthesis of certain pro-inflammatory proteins were examined.", "output": {"entities": {"chemical": [{"text": "ursolic acid", "start": 28, "end": 40}, {"text": "oleanolic acid", "start": 50, "end": 64}]}}, "schema": []}
{"input": "IP-10 expression was inhibited in a dose-dependent manner by all the tested compounds at concentrations <= 25 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "The mRNA expression of TNF-alpha was slightly affected and the IL-8 level was increased.", "output": {"entities": {}}, "schema": []}
{"input": "At the protein level, UA and OA (25 mu M) reduced the synthesis of IP-10; sICAM-1, IL-23 and GRO alpha were slightly repressed.", "output": {"entities": {}}, "schema": []}
{"input": "The TNF-alpha level was not modulated, whereas induction of IL-8 was increased.", "output": {"entities": {}}, "schema": []}
{"input": "UA also enhanced the synthesis of IL-1ra, while OA suppressed the level of I-TAC.", "output": {"entities": {}}, "schema": []}
{"input": "The present study confirms that triterpenoids present in apple peel and beta-damascone may be implicated in the anti-inflammatory properties of apple constituents, suggesting that these substances might be helpful in the treatment of IBD as nutrient supplements.", "output": {"entities": {"chemical": [{"text": "triterpenoids", "start": 32, "end": 45}, {"text": "beta-damascone", "start": 72, "end": 86}]}}, "schema": []}
{"input": "Characteristics and antioxidant activity of water-soluble Maillard reaction products from interactions in a whey protein isolate and sugars system.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to determine antioxidant activities of water-soluble MRPs (Maillard reaction products) from the reactions between whey protein isolate (WPI) and xylose (X), glucose (G), fructose (F), lactose (L), maltose (M) and sucrose (S) at different initial pH values (3, 4, 5, 6, 7, 8 and 9).", "output": {"entities": {"chemical": [{"text": "xylose", "start": 177, "end": 183}, {"text": "glucose", "start": 189, "end": 196}, {"text": "fructose", "start": 202, "end": 210}, {"text": "lactose", "start": 216, "end": 223}, {"text": "maltose", "start": 229, "end": 236}, {"text": "sucrose", "start": 245, "end": 252}]}}, "schema": []}
{"input": "MRPs derived from the WPI-X system with increasing of pH rendered the highest browning, reducing power and DPPH radical-scavenging activity.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 107, "end": 111}]}}, "schema": []}
{"input": "SDS-PAGE analyses indicated formation of cross-linked proteins of large molecular mass produced from WPI-X systems.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Results of FT-IR analysis indicated that the amide I, II and III bands of WPI from the WPI-X and WPI-G systems were changed by the Maillard reaction.", "output": {"entities": {"chemical": [{"text": "amide", "start": 45, "end": 50}]}}, "schema": []}
{"input": "CD spectroscopy showed that beta-sheet, beta-turns and random coil were increased while the alpha-helix was decreased after the WPI-G and WPI-X system aqueous solutions were heated.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, MRPs obtained from the WPI-X system had high antioxidant activity.", "output": {"entities": {}}, "schema": []}
{"input": "Alternanthera paronychioides protects pancreatic beta-cells from glucotoxicity by its antioxidant, antiapoptotic and insulin secretagogue actions.", "output": {"entities": {}}, "schema": []}
{"input": "The antioxidant and antiglucotoxic effects of Alternanthera paronychioides on pancreatic beta-cell were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant assays demonstrated that ethanol extracts of A. paronychioides (EEAP) exhibited the highest antioxidant activity, which also had the highest phenolic and flavonoid contents.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 37, "end": 44}, {"text": "phenolic", "start": 153, "end": 161}, {"text": "flavonoid", "start": 166, "end": 175}]}}, "schema": []}
{"input": "Two major polyphenolics, ferulic acid and quercetin, were identified from EEAP by HPLC-DAD.", "output": {"entities": {"chemical": [{"text": "polyphenolics", "start": 10, "end": 23}, {"text": "ferulic acid", "start": 25, "end": 37}, {"text": "quercetin", "start": 42, "end": 51}]}}, "schema": []}
{"input": "Effects of EEAP, ferulic acid and quercetin on high glucose (25mmol/L)-induced pancreatic beta-cell apoptosis and dysfunction were further evaluated.", "output": {"entities": {"chemical": [{"text": "ferulic acid", "start": 17, "end": 29}, {"text": "quercetin", "start": 34, "end": 43}]}}, "schema": []}
{"input": "Results showed that EEAP and quercetin but not ferulic acid protected beta-cells from glucotoxicity through several mechanisms, including: (1) maintaining beta-cell viability; (2) suppressing reactive oxygen species production; (3) reducing characteristic features of apoptosis; (4) inhibiting the activation of caspase-9 and caspase-3 and the cleavage of poly (ADP-ribose) polymerase; (5) upregulating pancreatic and duodenal homeobox 1 gene expression and the insulin secretagogue action of pancreatic beta-cells.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 29, "end": 38}, {"text": "ferulic acid", "start": 47, "end": 59}, {"text": "oxygen", "start": 201, "end": 207}, {"text": "poly (ADP-ribose)", "start": 356, "end": 373}]}}, "schema": []}
{"input": "These findings may shed light on the preventive actions of A. paronychioides on diabetic glucotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Peach (Prunus persica) extract inhibits angiotensin II-induced signal transduction in vascular smooth muscle cells.", "output": {"entities": {"chemical": [{"text": "angiotensin II", "start": 40, "end": 54}]}}, "schema": []}
{"input": "Angiotensin II (Ang II) is a vasoactive hormone that has been implicated in cardiovascular diseases.", "output": {"entities": {"chemical": [{"text": "Angiotensin II", "start": 0, "end": 14}, {"text": "Ang II", "start": 16, "end": 22}]}}, "schema": []}
{"input": "Here, the effect of peach, Prunus persica L.", "output": {"entities": {}}, "schema": []}
{"input": "Batsch, pulp extract on Ang II-induced intracellular Ca (2 +) mobilization, reactive oxygen species (ROS) production and signal transduction events in cultured vascular smooth muscle cells (VSMCs) was investigated.", "output": {"entities": {"chemical": [{"text": "Ang II", "start": 24, "end": 30}, {"text": "Ca (2 +)", "start": 53, "end": 61}, {"text": "oxygen", "start": 85, "end": 91}]}}, "schema": []}
{"input": "Pretreatment of peach ethyl acetate extract inhibited Ang II-induced intracellular Ca (2 +) elevation in VSMCs.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 22, "end": 35}, {"text": "Ang II", "start": 54, "end": 60}, {"text": "Ca (2 +)", "start": 83, "end": 91}]}}, "schema": []}
{"input": "Furthermore, Ang II-induced ROS generation, essential for signal transduction events, was diminished by the peach ethyl acetate extract.", "output": {"entities": {"chemical": [{"text": "Ang II", "start": 13, "end": 19}, {"text": "ethyl acetate", "start": 114, "end": 127}]}}, "schema": []}
{"input": "The peach ethyl acetate extract also attenuated the Ang II-induced phosphorylation of epidermal growth factor receptor and myosin phosphatase target subunit 1, both of which are associated with atherosclerosis and hypertension.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 10, "end": 23}, {"text": "Ang II", "start": 52, "end": 58}]}}, "schema": []}
{"input": "These results suggest that peach ethyl acetate extract may have clinical potential for preventing cardiovascular diseases by interfering with Ang II-induced intracellular Ca (2 +) elevation, the generation of ROS, and then blocking signal transduction events.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 33, "end": 46}, {"text": "Ang II", "start": 142, "end": 148}, {"text": "Ca (2 +)", "start": 171, "end": 179}]}}, "schema": []}
{"input": "mu-Calpain is involved in the postmortem proteolysis of gizzard smooth muscle.", "output": {"entities": {}}, "schema": []}
{"input": "Postmortem changes in proteins that have been implicated in affecting muscle integrity were examined in goose (GG) and duck (DG) gizzard smooth muscle stored at 5 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "GG and DG smooth muscles were sampled at 0, 1, 3 and 7day of storage.", "output": {"entities": {}}, "schema": []}
{"input": "The pH was approximately 7 in both GG and DG samples during postmortem storage.", "output": {"entities": {}}, "schema": []}
{"input": "Casein zymograms showed that 0-day mu-calpain activity was higher (p < 0. 05) in GG than in DG samples.", "output": {"entities": {}}, "schema": []}
{"input": "As postmortem time progressed, mu-calpain was activated and autolyzed more extensively in GG than in DG samples.", "output": {"entities": {}}, "schema": []}
{"input": "However, mu/m-calpain remained relatively stable in both samples.", "output": {"entities": {}}, "schema": []}
{"input": "Western blots indicated that postmortem desmin degradation was more rapid in GG than in DG samples.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, alpha-actinin remained nearly unchanged in both samples.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, our results suggest that mu-calpain has an important role in the postmortem proteolysis of gizzard smooth muscle.", "output": {"entities": {}}, "schema": []}
{"input": "Free fatty acid profiles of emulsified lipids during in vitro digestion with pancreatic lipase.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 5, "end": 15}]}}, "schema": []}
{"input": "Individual free fatty acids released from milk protein-stabilized emulsions prepared with milk fat, soya bean oil or tuna fish oil during in vitro digestion with pancreatic lipase were monitored using gas chromatography.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 16, "end": 27}]}}, "schema": []}
{"input": "The results showed that saturated fatty acids (C16: 0 and C18: 0) were released faster than unsaturated fatty acids (C18: 1n9, C18: 2n6 and C18: 3n3) from soya bean oil emulsions; short chain fatty acids were released faster than long chain fatty acids from milk fat emulsions; long chain polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, were released more slowly than other fatty acids from fish oil emulsions.", "output": {"entities": {"chemical": [{"text": "saturated fatty acids", "start": 24, "end": 45}, {"text": "C16: 0", "start": 47, "end": 53}, {"text": "C18: 0", "start": 58, "end": 64}, {"text": "unsaturated fatty acids", "start": 92, "end": 115}, {"text": "C18: 1n9", "start": 117, "end": 125}, {"text": "C18: 2n6", "start": 127, "end": 135}, {"text": "C18: 3n3", "start": 140, "end": 148}, {"text": "fatty acids", "start": 192, "end": 203}, {"text": "fatty acids", "start": 241, "end": 252}, {"text": "polyunsaturated fatty acids", "start": 289, "end": 316}, {"text": "eicosapentaenoic acid", "start": 326, "end": 347}, {"text": "docosahexaenoic acid", "start": 352, "end": 372}, {"text": "fatty acids", "start": 411, "end": 422}]}}, "schema": []}
{"input": "The results confirm that the release behaviour of fatty acids from emulsions during digestion is related not only to the position of the fatty acids in the triglycerides in the fat/oil, but also to the length of the carbon chain of the fatty acid.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 50, "end": 61}, {"text": "fatty acids", "start": 137, "end": 148}, {"text": "triglycerides", "start": 156, "end": 169}, {"text": "carbon", "start": 216, "end": 222}, {"text": "fatty acid", "start": 236, "end": 246}]}}, "schema": []}
{"input": "The rates and the extents of the digestion of lipids consisting of short chain fatty acids are higher than those of lipids consisting of long chain fatty acids.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 79, "end": 90}, {"text": "fatty acids", "start": 148, "end": 159}]}}, "schema": []}
{"input": "Characterisation of muscles from Frigate mackerel (Auxis thazard) and catfish (Clarias macrocephalus).", "output": {"entities": {}}, "schema": []}
{"input": "Frigate mackerel (Auxis thazard) and catfish (Clarias macrocephalus) can be used as alternative sources for surimi production.", "output": {"entities": {}}, "schema": []}
{"input": "However, the functionality of surimi is species-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to characterise certain chemical and physical compositions of dark and ordinary muscles from these species.", "output": {"entities": {}}, "schema": []}
{"input": "Catfish, particularly ordinary muscle, was composed of higher contents of lipid and carotenoid than Frigate mackerel muscle (p < 0. 05) but ordinary muscle from Frigate mackerel had the highest phospholipid content (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Both dark and ordinary muscles of Frigate mackerel had greater contents of myofibrillar proteins than had catfish muscle (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Myosin heavy chain and actin were predominant proteins found in both muscle types of both species.", "output": {"entities": {}}, "schema": []}
{"input": "Dark muscle from Frigate mackerel had the highest sarcoplasmic protein content, especially extractable myoglobin (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Muscles from Frigate mackerel had greater content of sodium chloride than had catfish (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "sodium chloride", "start": 53, "end": 68}]}}, "schema": []}
{"input": "The highest contents of iron, copper and selenium were found in Frigate mackerel dark muscle (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "iron", "start": 24, "end": 28}, {"text": "copper", "start": 30, "end": 36}, {"text": "selenium", "start": 41, "end": 49}]}}, "schema": []}
{"input": "The pH of ordinary muscle from both species was higher than that of dark muscle (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Frigate mackerel, especilly dark muscle, exhibited the most dark-red colour, as shown by the lowest L (*) and b (*) values with the highest a (*) value and redness index (a (*)/b (*)) (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "In vitro antioxidant capacity and anti-inflammatory activity of seven common oats.", "output": {"entities": {}}, "schema": []}
{"input": "Oats are gaining increasing scientific and public interest for their purported antioxidant-associated health benefits.", "output": {"entities": {}}, "schema": []}
{"input": "Most reported studies focused on specific oat extracts or particular oat components, such as beta-glucans, tocols (vitamin E), or avenanthramides.", "output": {"entities": {"chemical": [{"text": "tocols", "start": 107, "end": 113}, {"text": "vitamin E", "start": 115, "end": 124}, {"text": "avenanthramides", "start": 130, "end": 145}]}}, "schema": []}
{"input": "Studies on whole oats with respect to antioxidant and anti-inflammatory activities are still lacking.", "output": {"entities": {}}, "schema": []}
{"input": "Here the antioxidant and anti-inflammatory activities from whole oat groats of seven common varieties were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "All oat varieties had very similar oxygen radical absorption capacity compared with other whole grains.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 35, "end": 41}]}}, "schema": []}
{"input": "In an anti-inflammatory assay, oat variety CDC Dancer inhibited tumor necrosis factor-alpha induced nuclear factor-kappa B activation by 27. 5% at 2mg/ml, whereas variety Deiter showed 13. 7% inhibition at a comparable dose.", "output": {"entities": {}}, "schema": []}
{"input": "Avenanthramide levels did not correlate with the observed antioxidant and anti-inflammatory activities.", "output": {"entities": {"chemical": [{"text": "Avenanthramide", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Further investigations are needed to pinpoint the specific antioxidant and anti-inflammatory compounds, and potential synergistic and/or matrix effects that may help explain the mechanisms of oat' s anti-inflammatory actions.", "output": {"entities": {}}, "schema": []}
{"input": "Microcapsule production employing chickpea or lentil protein isolates and maltodextrin: Physicochemical properties and oxidative protection of encapsulated flaxseed oil.", "output": {"entities": {}}, "schema": []}
{"input": "Flaxseed oil was microencapsulated, employing a wall material matrix of either chickpea (CPI) or lentil protein isolate (LPI) and maltodextrin, followed by freeze-drying.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of oil concentration (5. 3-21. 0%), protein source (CPI vs. LPI) and maltodextrin type (DE 9 and 18) and concentration (25. 0-40. 7%), on both the physicochemical characteristics and microstructure of the microcapsules, were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that an increase in emulsion oil concentration resulted in a concomitant increase in oil droplet diameter and microcapsule surface oil content, and a decrease in oil encapsulation efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Optimum flaxseed oil encapsulation efficiency (~ 83. 5%), minimum surface oil content (~ 2. 8%) and acceptable mean droplet diameter (3. 0 mu m) were afforded with 35. 5% maltodextrin-DE 9 and 10. 5% oil.", "output": {"entities": {}}, "schema": []}
{"input": "Microcapsules, formed by employing these experimental conditions, showed a protective effect against oxidation versus free oil over a storage period of 25d at room temperature.", "output": {"entities": {}}, "schema": []}
{"input": "Assay of phenolic compounds from four species of ber (Ziziphus mauritiana L.) fruits: Comparison of three base hydrolysis procedure for quantification of total phenolic acids.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 9, "end": 17}, {"text": "phenolic acids", "start": 160, "end": 174}]}}, "schema": []}
{"input": "The present study was undertaken to investigate the flavonoid profile in four species of ber (Ziziphus mauritiana Lamk.) fruit.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 52, "end": 61}]}}, "schema": []}
{"input": "The 12 flavonoids identified were quercetin 3-O-robinobioside, quercetin 3-O-rutinoside, quercetin 3'-O-galactoside, quercetin 3'-O-glucoside, quercetin 3'-O-rhamnoside, quercetin 3'-O-pentosylhexoside, quercetin 3-O-6' malonylglucoside, quercetin 3'-O-malonylglucoside, luteolin 7-O-6' malonylglucoside, luteolin 7-O-malonylglucoside, myricetin 3-O-galactoside, and naringenin tri glycoside.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 7, "end": 17}, {"text": "quercetin 3-O-robinobioside", "start": 34, "end": 61}, {"text": "quercetin 3-O-rutinoside", "start": 63, "end": 87}, {"text": "quercetin 3'-O-galactoside", "start": 89, "end": 115}, {"text": "quercetin 3'-O-glucoside", "start": 117, "end": 141}, {"text": "quercetin 3'-O-rhamnoside", "start": 143, "end": 168}, {"text": "quercetin 3'-O-pentosylhexoside", "start": 170, "end": 201}, {"text": "quercetin 3-O-6' malonylglucoside", "start": 203, "end": 236}, {"text": "quercetin 3'-O-malonylglucoside", "start": 238, "end": 269}, {"text": "luteolin 7-O-6' malonylglucoside", "start": 271, "end": 303}, {"text": "luteolin 7-O-malonylglucoside", "start": 305, "end": 334}, {"text": "myricetin 3-O-galactoside", "start": 336, "end": 361}, {"text": "naringenin tri glycoside", "start": 367, "end": 391}]}}, "schema": []}
{"input": "This is the first report on extraction of nine additional flavonoids from the ber fruits.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 58, "end": 68}]}}, "schema": []}
{"input": "In addition, we also compared the impact of three different base hydrolysis techniques namely ultrasonic assisted base hydrolysis (UABH), microwave assisted base hydrolysis (MWABH), and pressurised liquid assisted base hydrolysis (PLABH) for the quantification of total phenolic acids.", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 270, "end": 284}]}}, "schema": []}
{"input": "Nine phenolic acids, protocatechuic acid, p-hydroxybenzoic acid, ferulic acid, chlorogenic acid, vanillic acid, caffeic acid, vanillin, ortho-and para-coumaric acids, were identified and quantified.", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 5, "end": 19}, {"text": "protocatechuic acid", "start": 21, "end": 40}, {"text": "p-hydroxybenzoic acid", "start": 42, "end": 63}, {"text": "ferulic acid", "start": 65, "end": 77}, {"text": "chlorogenic acid", "start": 79, "end": 95}, {"text": "vanillic acid", "start": 97, "end": 110}, {"text": "caffeic acid", "start": 112, "end": 124}, {"text": "vanillin", "start": 126, "end": 134}, {"text": "ortho-and para-coumaric acids", "start": 136, "end": 165}]}}, "schema": []}
{"input": "The three major phenolic acids identified in all four ber species were p-coumaric acid, vanillin and ferulic acids.", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 16, "end": 30}, {"text": "p-coumaric acid", "start": 71, "end": 86}, {"text": "vanillin", "start": 88, "end": 96}, {"text": "ferulic acids", "start": 101, "end": 114}]}}, "schema": []}
{"input": "Higher amounts (p < 0. 05) of total phenolic acids in all cultivars were obtained with the PLABH technique as compared to other two procedures (UABH and MWABH).", "output": {"entities": {"chemical": [{"text": "phenolic acids", "start": 36, "end": 50}]}}, "schema": []}
{"input": "Physico-chemical characteristics and sensory evaluation of wheat bread partially substituted with banana (Musa acuminata X balbisiana cv. Awak) pseudo-stem flour.", "output": {"entities": {}}, "schema": []}
{"input": "The physico-chemical and sensorial properties of the control (BCtr), commercial wheat flour (CWF) bread substituted with 10% BPF (banana pseudo-stem flour) (B10BPF) and B10BPF with added 0. 8% w/w (flour weight basis) xanthan gum (XG) or sodium carboxymethylcellulose (CMC) (B10BPFXG and B10BPFCMC, respectively) were examined.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 238, "end": 244}]}}, "schema": []}
{"input": "The proximate analyses revealed that the composite bread had significantly higher moisture, ash, crude fibre, soluble, insoluble and total dietary fibre contents but lower protein, fat and carbohydrate contents than the BCtr.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 189, "end": 201}]}}, "schema": []}
{"input": "Bread incorporated with BPF resulted in a lower volume, darker crumb and lighter crust colour than the BCtr.", "output": {"entities": {}}, "schema": []}
{"input": "The addition of CMC improved the bread volume.", "output": {"entities": {}}, "schema": []}
{"input": "All breads containing BPF had greater total phenolics, and antioxidant properties than the control bread.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 44, "end": 53}]}}, "schema": []}
{"input": "Sensory evaluation indicated that the B10BPFCMC bread had the highest acceptability.", "output": {"entities": {}}, "schema": []}
{"input": "Variation in nutritionally relevant components in retail Jersey and Guernsey whole milk.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigates the quality of retail milk labelled as Jersey & Guernsey (JG) when compared with milk without breed specifications (NS) and repeatability of differences over seasons and years.", "output": {"entities": {}}, "schema": []}
{"input": "16 different brands of milk (4 Jersey & Guernsey, 12 non specified breed) were sampled over 2years on 4 occasions.", "output": {"entities": {}}, "schema": []}
{"input": "JG milk was associated with both favourable traits for human health, such as the higher total protein, total casein, alpha-casein, beta-casein, kappa-casein and alpha-tocopherol contents, and unfavourable traits, such as the higher concentrations of saturated fat, C12: 0, C14: 0 and lower concentrations of monounsaturated fatty acids.", "output": {"entities": {"chemical": [{"text": "alpha-tocopherol", "start": 161, "end": 177}, {"text": "monounsaturated fatty acids", "start": 308, "end": 335}]}}, "schema": []}
{"input": "In summer, JG milk had a higher omega-3: omega-6 ratio than had NS milk.", "output": {"entities": {}}, "schema": []}
{"input": "Also, the relative increase in omega-3 fatty acids and alpha-tocopherol, from winter to summer, was greater in JG milk.", "output": {"entities": {"chemical": [{"text": "omega-3 fatty acids", "start": 31, "end": 50}, {"text": "alpha-tocopherol", "start": 55, "end": 71}]}}, "schema": []}
{"input": "The latter characteristic could be of use in breeding schemes and farming systems producing niche dairy products.", "output": {"entities": {}}, "schema": []}
{"input": "Seasonality had a more marked impact on the fatty acid composition of JG milk than had NS milk, while the opposite was found for protein composition.", "output": {"entities": {"chemical": [{"text": "fatty acid", "start": 44, "end": 54}]}}, "schema": []}
{"input": "Potential implication for the findings in human health, producers, industry and consumers are considered.", "output": {"entities": {}}, "schema": []}
{"input": "Preparative isolation and purification of seven main antioxidants from Eucommia ulmoides Oliv.", "output": {"entities": {}}, "schema": []}
{"input": "(Du-zhong) leaves using HSCCC guided by DPPH-HPLC experiment.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 40, "end": 44}]}}, "schema": []}
{"input": "Seven antioxidants were purified from Eucommia ulmoides Oliv. leaves using HSCCC guided by DPPH-HPLC experiment.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 91, "end": 95}]}}, "schema": []}
{"input": "HSCCC was successfully used to separate target antioxidants by three runs with different solvent systems after D101 column chromatography fractionation.", "output": {"entities": {}}, "schema": []}
{"input": "Ethyl acetate-n-butanol-water (1: 2: 3, v/v/v) was selected as the optimum solvent system to purify geniposidic acid.", "output": {"entities": {"chemical": [{"text": "Ethyl acetate", "start": 0, "end": 13}, {"text": "n-butanol", "start": 14, "end": 23}, {"text": "geniposidic acid", "start": 100, "end": 116}]}}, "schema": []}
{"input": "Ethyl acetate-ethanol-water (4: 1: 5, v/v/v) was used to isolate caffeic acid, chlorogenic acid and ferulic acid.", "output": {"entities": {"chemical": [{"text": "Ethyl acetate", "start": 0, "end": 13}, {"text": "ethanol", "start": 14, "end": 21}, {"text": "caffeic acid", "start": 65, "end": 77}, {"text": "chlorogenic acid", "start": 79, "end": 95}, {"text": "ferulic acid", "start": 100, "end": 112}]}}, "schema": []}
{"input": "While three flavonoids, quercetin-3-O-sambubioside, rutin and isoquercitrin were purified by petroleum ether-ethyl acetate-methanol-water (1: 5: 1: 5, v/v/v/v).", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 12, "end": 22}, {"text": "quercetin-3-O-sambubioside", "start": 24, "end": 50}, {"text": "rutin", "start": 52, "end": 57}, {"text": "isoquercitrin", "start": 62, "end": 75}, {"text": "petroleum ether", "start": 93, "end": 108}, {"text": "ethyl acetate", "start": 109, "end": 122}, {"text": "methanol", "start": 123, "end": 131}]}}, "schema": []}
{"input": "The structures were identified by MS and NMR.", "output": {"entities": {}}, "schema": []}
{"input": "Antioxidant activities were assessed, and compounds 2-7 showed strong antioxidant activities.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first report about separation of antioxidants from E. ulmoides leaves by HSCCC.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicated that the combinative methods using DPPH-HPLC and HSCCC could be widely applied for screening and isolation of antioxidants from complex extracts.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 57, "end": 61}]}}, "schema": []}
{"input": "Ellagic acid derivatives, ellagitannins, proanthocyanidins and other phenolics, vitamin C and antioxidant capacity of two powder products from camu-camu fruit (Myrciaria dubia).", "output": {"entities": {"chemical": [{"text": "Ellagic acid", "start": 0, "end": 12}, {"text": "proanthocyanidins", "start": 41, "end": 58}, {"text": "phenolics", "start": 69, "end": 78}, {"text": "vitamin C", "start": 80, "end": 89}]}}, "schema": []}
{"input": "The aims of this study were the evaluation of polyphenols and vitamin C content, and antioxidant capacity of dehydrated pulp powder and the dried flour obtained from the skin and seeds residue remaining after pulp preparation from camu-camu (Myrciaria dudia).", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 46, "end": 57}, {"text": "vitamin C", "start": 62, "end": 71}]}}, "schema": []}
{"input": "Fifty-three different phenolics were characterised by HPLC-DAD-ESI-MS-MS and UPLC-HR-QTOF-MS-MS.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 22, "end": 31}]}}, "schema": []}
{"input": "The phenolic content of camu-camu flour was higher than that of the pulp powder (4007. 95mg/100g vs. 48. 54mg/100g).", "output": {"entities": {}}, "schema": []}
{"input": "In both products the flavonol myricetin and conjugates, ellagic acid and conjugates and ellagitannins were detected.", "output": {"entities": {"chemical": [{"text": "flavonol myricetin", "start": 21, "end": 39}, {"text": "ellagic acid", "start": 56, "end": 68}]}}, "schema": []}
{"input": "Cyanidin 3-glucoside, and quercetin and its glycosides were only found in the pulp powder, while proanthocyanidins were only present in the flour (3. 5g/100g, mean degree of polymerisation 3).", "output": {"entities": {"chemical": [{"text": "Cyanidin 3-glucoside", "start": 0, "end": 20}, {"text": "quercetin", "start": 26, "end": 35}, {"text": "proanthocyanidins", "start": 97, "end": 114}]}}, "schema": []}
{"input": "The vitamin C content was lower in pulp powder (3. 5%) than in the flour (9. 1%).", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 4, "end": 13}]}}, "schema": []}
{"input": "The radical-scavenging capacity of both powders was determined by the DPPH, ABTS and ORAC assays, and was higher for camu-camu flour as could be expected for its higher phenolics and vitamin C content.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 70, "end": 74}, {"text": "ABTS", "start": 76, "end": 80}, {"text": "phenolics", "start": 169, "end": 178}, {"text": "vitamin C", "start": 183, "end": 192}]}}, "schema": []}
{"input": "Comparative analyses with fresh camu-camu berries indicate that some transformations occur during processing.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of fresh berries showed that ellagic acid derivatives and ellagitannins were mainly present in the seeds, while proanthocyanidins were present both in the seeds and skin.", "output": {"entities": {"chemical": [{"text": "ellagic acid", "start": 38, "end": 50}, {"text": "proanthocyanidins", "start": 121, "end": 138}]}}, "schema": []}
{"input": "Tenderization effect of soy sauce on beef M. biceps femoris.", "output": {"entities": {}}, "schema": []}
{"input": "This study was conducted to evaluate the tenderization effect of soy sauce on beef M. biceps femoris (BF).", "output": {"entities": {}}, "schema": []}
{"input": "Five marinades were prepared with 4% (w/v) sodium chloride and 25% (w/v) soy sauce solutions (4% salt concentration) and mixed with the ratios of 100: 0 (S0, pH 6. 52), 75: 25 (S25, 5. 40) 50: 50 (S50, 5. 24), 25: 75 (S75, 5. 05), and 0: 100 (S100, 4. 85), respectively.", "output": {"entities": {"chemical": [{"text": "sodium chloride", "start": 43, "end": 58}]}}, "schema": []}
{"input": "The BF samples which were obtained from Hanwoo cows at 48h postmortem (n = 24) were marinated with five marinades for 72h at 4 degrees C (1: 4 w/w), and the effects of soy sauce on tenderness were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Soy sauce marination resulted in a decrease in the pH value of the BF sample.", "output": {"entities": {}}, "schema": []}
{"input": "However, there were no significant differences in the water holding capacity (P < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "The S100 treatment showed the significant (P < 0. 05) increase in collagen solubility and myofibrillar fragmentation index, contributing to decreased shear force compared to S0 (control).", "output": {"entities": {}}, "schema": []}
{"input": "Reduction in intensity of few myofibrillar protein bands were observed for S100 treatment compared to control using SDS-PAGE.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 116, "end": 119}]}}, "schema": []}
{"input": "Scanning electron microscopy revealed breakdown of connective tissue surrounding muscle fibers of the S100 treatment.", "output": {"entities": {}}, "schema": []}
{"input": "The tenderization effect of soy sauce may attribute various mechanisms such as increased collagen solubility or proteolysis which depend on soy sauce level in marinade.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of NaCl and pH on the structural conformations of kidney bean vicilin.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 11, "end": 15}]}}, "schema": []}
{"input": "Structural changes as a result of variations in pH value and salt concentration were determined for purified vicilin, the major globular protein in kidney beans using intrinsic fluorescence and circular dichroism (CD).", "output": {"entities": {}}, "schema": []}
{"input": "The vicilin consisted of two polypeptide chains of about 43 and 45kDa in size when analysed under reducing SDS-PAGE.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Amino acid analysis showed that the vicilin had high contents of acidic amino acids and a low lysine/arginine ratio.", "output": {"entities": {"chemical": [{"text": "Amino acid", "start": 0, "end": 10}, {"text": "acidic amino acids", "start": 65, "end": 83}, {"text": "lysine", "start": 94, "end": 100}, {"text": "arginine", "start": 101, "end": 109}]}}, "schema": []}
{"input": "Intrinsic fluorescence measurements were performed to measure exposure of tyrosine and tryptophan as a means of estimating protein conformational changes.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 74, "end": 82}, {"text": "tryptophan", "start": 87, "end": 97}]}}, "schema": []}
{"input": "Generally, the vicilin showed an unfolded structure at pH 3. 0, 5. 0, 7. 0, and 9. 0 as evident by the extensive red shift (> 350nm) of the wavelength of maximum tryptophan fluorescence intensity.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 162, "end": 172}]}}, "schema": []}
{"input": "At pH 3. 0 and 5. 0, the fluorescence intensity (FI) was greater than values obtained at pH 7. 0 and 9. 0, which suggests that the microenvironment of tryptophan was less hydrophilic at acidic pH.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 151, "end": 161}]}}, "schema": []}
{"input": "Addition of NaCl also led to increased FI, an indication of structural changes of tryptophan in response to the hydrophilic environment.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 12, "end": 16}, {"text": "tryptophan", "start": 82, "end": 92}]}}, "schema": []}
{"input": "These changes in FI were due mostly to tryptophan emission because tyrosine emission (at 303nm) was suppressed.", "output": {"entities": {"chemical": [{"text": "tryptophan", "start": 39, "end": 49}, {"text": "tyrosine", "start": 67, "end": 75}]}}, "schema": []}
{"input": "The far-UV CD spectra showed that vicilin had minimal measurable secondary structures at pH 3. 0 and 5. 0 when compared to pH 7. 0 and 9. 0.", "output": {"entities": {}}, "schema": []}
{"input": "Addition of NaCl led to an increase in the tertiary structure conformation of vicilin as determined from the near-UV CD spectra.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 12, "end": 16}]}}, "schema": []}
{"input": "Biosynthesis of highly enriched (13) C-lycopene for human metabolic studies using repeated batch tomato cell culturing with (13) C-glucose.", "output": {"entities": {"chemical": [{"text": "(13) C-lycopene", "start": 32, "end": 47}, {"text": "(13) C-glucose", "start": 124, "end": 138}]}}, "schema": []}
{"input": "While putative disease-preventing lycopene metabolites are found in both tomato (Solanum lycopersicum) products and in their consumers, mammalian lycopene metabolism is poorly understood.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 34, "end": 42}, {"text": "lycopene", "start": 146, "end": 154}]}}, "schema": []}
{"input": "Advances in tomato cell culturing techniques offer an economical tool for generation of highly-enriched (13) C-lycopene for human bioavailability and metabolism studies.", "output": {"entities": {"chemical": [{"text": "(13) C-lycopene", "start": 104, "end": 119}]}}, "schema": []}
{"input": "To enhance the (13) C-enrichment and yields of labelled lycopene from the hp-1 tomato cell line, cultures were first grown in (13) C-glucose media for three serial batches and produced increasing proportions of uniformly labelled lycopene (14. 3 +/- 1. 2%, 39. 6 +/- 0. 5%, and 48. 9 +/- 1. 5%) with consistent yields (from 5. 8 to 9mg/L).", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 15, "end": 21}, {"text": "lycopene", "start": 56, "end": 64}, {"text": "(13) C-glucose", "start": 126, "end": 140}, {"text": "lycopene", "start": 230, "end": 238}]}}, "schema": []}
{"input": "An optimised 9-day-long (13) C-loading and 18-day-long labelling strategy developed based on glucose utilisation and lycopene yields, yielded (13) C-lycopene with 93% (13) C isotopic purity, and 55% of isotopomers were uniformly labelled.", "output": {"entities": {"chemical": [{"text": "(13) C", "start": 24, "end": 30}, {"text": "glucose", "start": 93, "end": 100}, {"text": "lycopene", "start": 117, "end": 125}, {"text": "(13) C-lycopene", "start": 142, "end": 157}, {"text": "(13) C", "start": 167, "end": 173}]}}, "schema": []}
{"input": "Furthermore, an optimised acetone and hexane extraction led to a fourfold increase in lycopene recovery from cultures compared to a standard extraction.", "output": {"entities": {"chemical": [{"text": "acetone", "start": 26, "end": 33}, {"text": "hexane", "start": 38, "end": 44}, {"text": "lycopene", "start": 86, "end": 94}]}}, "schema": []}
{"input": "Effect of recovery methods on the oxidative and physical stability of oil body emulsions.", "output": {"entities": {}}, "schema": []}
{"input": "Three natural oil body emulsions of a similar fat content (~ 5%), but differing in their protein composition were obtained from an aqueous maize germ extract.", "output": {"entities": {}}, "schema": []}
{"input": "The first was prepared by concentrating the aqueous oil body extract with ultrafiltration to a fat content of ~ 5%.", "output": {"entities": {}}, "schema": []}
{"input": "The other two were prepared by initially recovering the oil bodies from the extract by centrifugation, either in the presence of sucrose or by applying isoelectric precipitation at pH 5. 0 and then diluting the resulting oil body creams with deionized water.", "output": {"entities": {"chemical": [{"text": "sucrose", "start": 129, "end": 136}]}}, "schema": []}
{"input": "The oxidative and physical stability of the three emulsions, either as they were or after submission to thermal treatment (100 degrees C for 15min), were studied following storage at 45 degrees C.", "output": {"entities": {}}, "schema": []}
{"input": "The emulsions differed both in their oxidative and physical stability, depending on the recovery method that in turn influenced their continuous phase and/or interfacial membrane protein and/or polar antioxidant composition.", "output": {"entities": {}}, "schema": []}
{"input": "Ultrafiltration resulted in the most stable emulsion.", "output": {"entities": {}}, "schema": []}
{"input": "Mixtures of the natural oil body emulsions with green tea extracts, aiming to serve as a base for functional beverages, were then prepared and studied for their creaming behaviour.", "output": {"entities": {}}, "schema": []}
{"input": "The green tea polyphenols seem to interact with the oil bodies leading to intensive dispersion destabilisation which, however, was halted following carrageenan addition at a relatively very low level.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 14, "end": 25}]}}, "schema": []}
{"input": "Effect of temperature on the release of intentionally and non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: Chemical analysis and potential toxicity.", "output": {"entities": {"chemical": [{"text": "polyethylene terephthalate", "start": 98, "end": 124}, {"text": "PET", "start": 126, "end": 129}]}}, "schema": []}
{"input": "The purpose of this study was to investigate the impact of temperature on the release of PET-bottle constituents into water and to assess the potential health hazard using in vitro bioassays with bacteria and human cell lines.", "output": {"entities": {"chemical": [{"text": "PET", "start": 89, "end": 92}]}}, "schema": []}
{"input": "Aldehydes, trace metals and other compounds found in plastic packaging were analysed in PET-bottled water stored at different temperatures: 40, 50, and 60 degrees C.", "output": {"entities": {"chemical": [{"text": "Aldehydes", "start": 0, "end": 9}, {"text": "PET", "start": 88, "end": 91}]}}, "schema": []}
{"input": "In this study, temperature and the presence of CO2 increased the release of formaldehyde, acetaldehyde and antimony (Sb).", "output": {"entities": {"chemical": [{"text": "CO2", "start": 47, "end": 50}, {"text": "formaldehyde", "start": 76, "end": 88}, {"text": "acetaldehyde", "start": 90, "end": 102}, {"text": "antimony", "start": 107, "end": 115}, {"text": "Sb", "start": 117, "end": 119}]}}, "schema": []}
{"input": "In parallel, genotoxicity assays (Ames and micronucleus assays) and transcriptional-reporter gene assays for estrogenic and anti-androgenic activity were performed on bottled water extracts at relevant consumer exposure levels.", "output": {"entities": {}}, "schema": []}
{"input": "As expected, and in accordance with the chemical formulations specified for PET bottles, neither phthalates nor UV stabilisers were present in the water extracts.", "output": {"entities": {"chemical": [{"text": "PET", "start": 76, "end": 79}, {"text": "phthalates", "start": 97, "end": 107}]}}, "schema": []}
{"input": "However, 2, 4-di-tert-butylphenol, a degradation compound of phenolic antioxidants, was detected.", "output": {"entities": {"chemical": [{"text": "2, 4-di-tert-butylphenol", "start": 9, "end": 33}, {"text": "phenolic", "start": 61, "end": 69}]}}, "schema": []}
{"input": "In addition, an intermediary monomer, bis (2-hydroxyethyl) terephthalate, was found but only in PET-bottled waters.", "output": {"entities": {"chemical": [{"text": "bis (2-hydroxyethyl) terephthalate", "start": 38, "end": 72}, {"text": "PET", "start": 96, "end": 99}]}}, "schema": []}
{"input": "None of the compounds are on the positive list of EU Regulation No. 10/2011.", "output": {"entities": {}}, "schema": []}
{"input": "However, the PET-bottled water extracts did not induce any cytotoxic, genotoxic or endocrine-disruption activity in the bioassays after exposure.", "output": {"entities": {"chemical": [{"text": "PET", "start": 13, "end": 16}]}}, "schema": []}
{"input": "Congeners in sugar cane spirits aged in casks of different woods.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 13, "end": 18}]}}, "schema": []}
{"input": "The profile of volatile compounds and aging markers in sugar cane spirits aged for 36months in casks made of 10 types of wood were studied.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 55, "end": 60}]}}, "schema": []}
{"input": "The ethanol content, volatile acidity, aldehydes, esters, higher alcohols, and methanol were determined.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 4, "end": 11}, {"text": "aldehydes", "start": 39, "end": 48}, {"text": "esters", "start": 50, "end": 56}, {"text": "alcohols", "start": 65, "end": 73}, {"text": "methanol", "start": 79, "end": 87}]}}, "schema": []}
{"input": "In addition, gallic, vanilic and syringic acids, siringaldehyde, coniferaldehyde, sinapaldehyde, vanillin, 5-hydroxymethylfurfural and furfural were identified and quantified.", "output": {"entities": {"chemical": [{"text": "gallic, vanilic and syringic acids", "start": 13, "end": 47}, {"text": "siringaldehyde", "start": 49, "end": 63}, {"text": "coniferaldehyde", "start": 65, "end": 80}, {"text": "sinapaldehyde", "start": 82, "end": 95}, {"text": "vanillin", "start": 97, "end": 105}, {"text": "5-hydroxymethylfurfural", "start": 107, "end": 130}, {"text": "furfural", "start": 135, "end": 143}]}}, "schema": []}
{"input": "The profile of volatile compounds characterised aging in each type of wood.", "output": {"entities": {}}, "schema": []}
{"input": "The beverage aged in oak cask achieved the highest contents of maturation-related congeners.", "output": {"entities": {}}, "schema": []}
{"input": "The Brazilian woods, similar to oak, were jequitib a rosa and cerejeira, which presented the highest contents of some maturation-related compounds, such as vanillin, vanilic acid, syringaldehyde and sinapaldehyde.", "output": {"entities": {"chemical": [{"text": "vanillin", "start": 156, "end": 164}, {"text": "vanilic acid", "start": 166, "end": 178}, {"text": "syringaldehyde", "start": 180, "end": 194}, {"text": "sinapaldehyde", "start": 199, "end": 212}]}}, "schema": []}
{"input": "Although oak wood conferred more chemical complexity to the beverage, Brazilian woods, singly or complementarily, present potential for spirit characterisation and for improving the quality of sugar cane spirits.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 193, "end": 198}]}}, "schema": []}
{"input": "Effects of fisetin supplementation on hepatic lipogenesis and glucose metabolism in Sprague-Dawley rats fed on a high fat diet.", "output": {"entities": {"chemical": [{"text": "fisetin", "start": 11, "end": 18}, {"text": "glucose", "start": 62, "end": 69}]}}, "schema": []}
{"input": "The modulatory effects of daily fisetin supplementation for 8weeks on genes involved in hepatic lipogenesis and gluconeogenesis and hyperglycemia in rats fed a high fat (HF) diet were evaluated.", "output": {"entities": {"chemical": [{"text": "fisetin", "start": 32, "end": 39}]}}, "schema": []}
{"input": "Elevated levels of triglyceride (TG), along with hepatic TG content and glucose concentrations in a high fat diet group were found to be reduced by fisetin supplementation.", "output": {"entities": {"chemical": [{"text": "triglyceride", "start": 19, "end": 31}, {"text": "glucose", "start": 72, "end": 79}, {"text": "fisetin", "start": 148, "end": 155}]}}, "schema": []}
{"input": "The high fat diet significantly increased hepatic mRNA expressions of PPAR gamma, SREBP1C and SCD-1 genes in comparison to the control diet, which was subsequently reversed by supplementation with fisetin.", "output": {"entities": {"chemical": [{"text": "fisetin", "start": 197, "end": 204}]}}, "schema": []}
{"input": "In addition, fisetin supplementation significantly reduced hepatic mRNA abundance of FAS, ATPCL and G6Pase compared to the control group.", "output": {"entities": {"chemical": [{"text": "fisetin", "start": 13, "end": 20}]}}, "schema": []}
{"input": "Finally, epididymal mRNA abundance of GLUT4 was significantly increased by fisetin supplementation, compared to levels in the control and HF groups.", "output": {"entities": {"chemical": [{"text": "fisetin", "start": 75, "end": 82}]}}, "schema": []}
{"input": "Enhancement of GLUT4 expression by fisetin was further confirmed in differentiated 3T3-L1 adipocytes.", "output": {"entities": {"chemical": [{"text": "fisetin", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Fisetin supplementation decreases cardiovascular risks by ameliorating hepatic steatosis and lowering circulating glucose concentrations.", "output": {"entities": {"chemical": [{"text": "Fisetin", "start": 0, "end": 7}, {"text": "glucose", "start": 114, "end": 121}]}}, "schema": []}
{"input": "Enrichment of polyphenol contents and antioxidant activities of Irish brown macroalgae using food-friendly techniques based on polarity and molecular size.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 14, "end": 24}]}}, "schema": []}
{"input": "An efficient, food-friendly process for the enrichment of macroalgal phlorotannins from solid-liquid extracts (SLE) of three brown macroalgae, namely Fucus spiralis Linnaeus, Pelvetia canaliculata (Linnaeus) Decaisne & Thuret and Ascophyllum nodosum (Linnaeus) Le Jolis, has been demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "The initial utilisation of molecular weight cut-off (MWCO) dialysis generated fractions of low molecular weight (LMW) (< 3. 5kDa) and of high molecular weight (HMW) (3. 5-100kDa and > 100kDa) from cold water, hot water and aqueous ethanolic SLE extracts.", "output": {"entities": {}}, "schema": []}
{"input": "An enhancement of the total phenolic content (TPC), radical scavenging abilities (RSA) and ferric reducing antioxidant power (FRAP) in the HMW fractions of 3. 5-100kDa and/or > 100kDa from the cold water and aqueous ethanolic extracts was observed.", "output": {"entities": {"chemical": [{"text": "ferric", "start": 91, "end": 97}]}}, "schema": []}
{"input": "The initial weak TPC, RSA and FRAP observed in the LMW fractions relative to the HMW fractions were substantially enhanced following a reverse-phase flash chromatography fractionation method.", "output": {"entities": {}}, "schema": []}
{"input": "Quadrupole time-of-flight mass spectrometry (Q-Tof-MS) suggests that phlorotannins of varying degrees of phloroglucinol polymerisation are present in LMW fractions of the three brown macroalgal species.", "output": {"entities": {"chemical": [{"text": "phloroglucinol", "start": 105, "end": 119}]}}, "schema": []}
{"input": "The development of a food-friendly process for the extraction and enrichment of phlorotannins from Irish macroalgae is vital to facilitate the use of this valuable resource in future developments of macroalgal-based functional foods.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of cold pre-fermentation treatments on the major volatile compounds of three wine varieties.", "output": {"entities": {}}, "schema": []}
{"input": "The volatile compounds of wines made from three grape varieties (Monastrell, Cabernet Sauvignon and Syrah) using three pre-fermentation techniques (grape freezing, dry-ice and cold maceration) and a control treatment were measured.", "output": {"entities": {"chemical": [{"text": "dry-ice", "start": 164, "end": 171}]}}, "schema": []}
{"input": "The different winemaking practices, which are intended to increase the aromatic properties of wines, produced results that depended on the variety concerned.", "output": {"entities": {}}, "schema": []}
{"input": "For example, freezing the Cabernet Sauvignon and Syrah grapes produced different results compared with the respective controls, whereas few changes were found on freezing the Monastrell wine.", "output": {"entities": {}}, "schema": []}
{"input": "Differences were significant in the case of some volatile compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Linear discriminant analysis allowed some grouping of the varieties at sampling but not of the pre-fermentation techniques used.", "output": {"entities": {}}, "schema": []}
{"input": "Characterisation of chlorophyll oxidation mediated by peroxidative activity in olives (Olea europaea L.) cv.", "output": {"entities": {"chemical": [{"text": "chlorophyll", "start": 20, "end": 31}]}}, "schema": []}
{"input": "Hojiblanca.", "output": {"entities": {}}, "schema": []}
{"input": "The oxidation of chlorophyll a (chl a) catalysed by peroxidase (POD) from mesocarp of the olive fruit (Olea europaea L., cv Hojiblanca) in the presence of H2O2 and 2, 4-dichlorophenol (2, 4-DCP), is characterised via the individualised quantification of the products of the enzymatic reaction using a new methodology of HPLC-UV spectrometry.", "output": {"entities": {"chemical": [{"text": "chlorophyll a", "start": 17, "end": 30}, {"text": "chl a", "start": 32, "end": 37}, {"text": "H2O2", "start": 155, "end": 159}, {"text": "2, 4-dichlorophenol", "start": 164, "end": 183}, {"text": "2, 4-DCP", "start": 185, "end": 193}]}}, "schema": []}
{"input": "This innovation has allowed the discovery that, in addition to 13 (2) OH chl a and 15 (1) OH lactone chl a, which are the first products of POD on chl a, the reaction process sequentially creates another series of oxidised chlorophyll derivatives which have not been previously described.", "output": {"entities": {"chemical": [{"text": "13 (2) OH chl a", "start": 63, "end": 78}, {"text": "15 (1) OH lactone chl a", "start": 83, "end": 106}, {"text": "chl a", "start": 147, "end": 152}, {"text": "chlorophyll", "start": 223, "end": 234}]}}, "schema": []}
{"input": "Their origins have been linked to POD activity in the presence of 2, 4-DCP.", "output": {"entities": {"chemical": [{"text": "2, 4-DCP", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Likewise, a study of the effect of the concentration of the various cosubstrates on the POD reaction rate demonstrated that the correct establishment of the relative concentrations of the same ([H2O2]/[2, 4-DCP]/[Chl] = 1: 3: 0. 02) is crucial to explaining inhibition effects by substrates and carrying out optimum measurements.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 195, "end": 199}, {"text": "2, 4-DCP", "start": 202, "end": 210}, {"text": "Chl", "start": 213, "end": 216}]}}, "schema": []}
{"input": "Therefore, new essential parameters for the determination of POD activity on a chlorophyll substrate are established.", "output": {"entities": {"chemical": [{"text": "chlorophyll", "start": 79, "end": 90}]}}, "schema": []}
{"input": "Oil composition and characterisation of phenolic compounds of Opuntia ficus-indica seeds.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 40, "end": 48}]}}, "schema": []}
{"input": "The seed composition of four varieties of Opuntia ficus-indica growing in Algeria was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Seeds ground into a fine powder were first, subjected to oil extraction and fatty acids analysis.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 76, "end": 87}]}}, "schema": []}
{"input": "The phenolic compounds were then extracted from the defatted powder of seeds in order to be quantified and characterised by liquid chromatography coupled to mass spectrometry (LC-MS (n)) and to nuclear magnetic resonance (LC-NMR) approaches.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 4, "end": 12}]}}, "schema": []}
{"input": "In addition, an evaluation of the antioxidant activity of the phenolic extracts was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Gas chromatography analysis of the seed oil showed high percentages of linoleic acid in the four varieties ranging from 58% to 63%.", "output": {"entities": {"chemical": [{"text": "linoleic acid", "start": 71, "end": 84}]}}, "schema": []}
{"input": "The phenolic profile of the Opuntia ficus-indica seeds displayed a high complexity, with more than 20 compounds detected at 330nm after the LC separation.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, three isomers of feruloyl-sucrose were firmly identified and another was strongly supposed to be a sinapoyl-diglycoside.", "output": {"entities": {"chemical": [{"text": "feruloyl-sucrose", "start": 29, "end": 45}, {"text": "sinapoyl-diglycoside", "start": 111, "end": 131}]}}, "schema": []}
{"input": "High correlations were found between phenolic content in the defatted seed extracts and their antioxidant activity.", "output": {"entities": {}}, "schema": []}
{"input": "The data indicate that the defatted cactus seed wastes still contain various components that constitute a source for natural foods.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition kinetics of lipid oxidation of model foods by using antioxidant extract of fermented soybeans.", "output": {"entities": {}}, "schema": []}
{"input": "Fermentation by using Aspergillus oryzae has been reported to increase antioxidant activity of soybeans significantly.", "output": {"entities": {}}, "schema": []}
{"input": "The effectiveness of the extract from fermented soybeans was studied in 3 model foods with different complexities, i. e., linoleic acid emulsion, sunflower oil emulsions and bulk sunflower oil.", "output": {"entities": {"chemical": [{"text": "linoleic acid", "start": 122, "end": 135}]}}, "schema": []}
{"input": "For the emulsion systems, oxidation at two different pH values (4. 5 and 7) was also compared.", "output": {"entities": {}}, "schema": []}
{"input": "A reparameterised logistic equation was used to describe and to predict the experimental data.", "output": {"entities": {}}, "schema": []}
{"input": "In general, a good agreement between experimental trends and simulated data from the model was found.", "output": {"entities": {}}, "schema": []}
{"input": "A crude antioxidant extract (5mg/g) showed a comparable antioxidant activity to 0. 26mg/g of butylated hydroxytoluene (BHT) in the linoleic acid emulsions.", "output": {"entities": {"chemical": [{"text": "butylated hydroxytoluene", "start": 93, "end": 117}, {"text": "BHT", "start": 119, "end": 122}, {"text": "linoleic acid", "start": 131, "end": 144}]}}, "schema": []}
{"input": "The extract exhibited a better capability to retard primary products in the linoleic acid systems than the secondary products.", "output": {"entities": {"chemical": [{"text": "linoleic acid", "start": 76, "end": 89}]}}, "schema": []}
{"input": "The opposite effect was observed in the bulk sunflower oil and its emulsion systems.", "output": {"entities": {}}, "schema": []}
{"input": "A dipeptide and an amino acid present in whey protein hydrolysate increase translocation of GLUT-4 to the plasma membrane in Wistar rats.", "output": {"entities": {"chemical": [{"text": "dipeptide", "start": 2, "end": 11}, {"text": "amino acid", "start": 19, "end": 29}]}}, "schema": []}
{"input": "Whey protein hydrolysate (WPH) is capable of increasing muscle glycogen reserves and of concentrating the glucose transporter in the plasma membrane (PM).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 106, "end": 113}]}}, "schema": []}
{"input": "The objective of this study was to determine which WPH components could modulate translocation of the glucose transporter GLUT-4 to the PM of animal skeletal muscle.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 102, "end": 109}]}}, "schema": []}
{"input": "Forty-nine animals were divided into 7 groups (n = 7) and received by oral gavage 30% glucose plus 0. 55g/kg body mass of the following WPH components: (a) control; (b) WPH; (c) l-isoleucine; (d) l-leucine; (e) l-leucine plus l-isoleucine; (f) l-isoleucyl-l-leucine dipeptide; (g) l-leucyl-l-isoleucine dipeptide.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 86, "end": 93}, {"text": "l-isoleucine", "start": 178, "end": 190}, {"text": "l-leucine", "start": 196, "end": 205}, {"text": "l-leucine", "start": 211, "end": 220}, {"text": "l-isoleucine", "start": 226, "end": 238}, {"text": "l-isoleucyl-l-leucine dipeptide", "start": 244, "end": 275}, {"text": "l-leucyl-l-isoleucine dipeptide", "start": 281, "end": 312}]}}, "schema": []}
{"input": "After receiving these solutions, the animals were sacrificed and the GLUT-4 analysed by western blot.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, glycogen, glycaemia, insulin and free amino acids were also determined by standard methods.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 52, "end": 63}]}}, "schema": []}
{"input": "Of the WPH components tested, the amino acid l-isoleucine and the peptide l-leucyl-l-isoleucine showed greater efficiency in translocating GLUT-4 to the PM and of increasing glucose capture by skeletal muscle.", "output": {"entities": {"chemical": [{"text": "l-isoleucine", "start": 45, "end": 57}, {"text": "l-leucyl-l-isoleucine", "start": 74, "end": 95}, {"text": "glucose", "start": 174, "end": 181}]}}, "schema": []}
{"input": "Antioxidant, free radical scavenging and liver protective effects of friedelin isolated from Azima tetracantha Lam. leaves.", "output": {"entities": {"chemical": [{"text": "friedelin", "start": 69, "end": 78}]}}, "schema": []}
{"input": "The aim of the present study was to evaluate the antioxidant, free radical scavenging and liver protective effects of friedelin isolated from Azima tetracantha Lam. leaves.", "output": {"entities": {"chemical": [{"text": "friedelin", "start": 118, "end": 127}]}}, "schema": []}
{"input": "In in vitro antioxidant study, the free radical scavenging effect of friedelin on 2, 2-diphenyl-picrylhydrazyl (DPPH), hydroxyl, nitric oxide and superoxide radicals were evaluated.", "output": {"entities": {"chemical": [{"text": "friedelin", "start": 69, "end": 78}, {"text": "2, 2-diphenyl-picrylhydrazyl", "start": 82, "end": 110}, {"text": "DPPH", "start": 112, "end": 116}, {"text": "hydroxyl", "start": 119, "end": 127}, {"text": "nitric oxide", "start": 129, "end": 141}, {"text": "superoxide", "start": 146, "end": 156}]}}, "schema": []}
{"input": "Friedelin showed very good scavenging effect on DPPH (IC50 21. 1mM), hydroxyl (IC50 19. 8mM), nitric oxide (IC50 22. 1mM) and superoxide (IC50 21. 9mM) radicals.", "output": {"entities": {"chemical": [{"text": "Friedelin", "start": 0, "end": 9}, {"text": "DPPH", "start": 48, "end": 52}, {"text": "hydroxyl", "start": 69, "end": 77}, {"text": "nitric oxide", "start": 94, "end": 106}, {"text": "superoxide", "start": 126, "end": 136}]}}, "schema": []}
{"input": "Friedelin also showed strong suppressive effect on lipid peroxidation.", "output": {"entities": {"chemical": [{"text": "Friedelin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In in vivo antioxidant study, CCl4 induced oxidative stress on rats produced significant increase in serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH) levels along with reduction in liver superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione peroxidase (GPx) levels.", "output": {"entities": {"chemical": [{"text": "CCl4", "start": 30, "end": 34}, {"text": "glutamate oxaloacetate", "start": 107, "end": 129}, {"text": "glutamate pyruvate", "start": 157, "end": 175}, {"text": "lactate", "start": 200, "end": 207}, {"text": "superoxide", "start": 265, "end": 275}, {"text": "reduced glutathione", "start": 309, "end": 328}, {"text": "GSH", "start": 330, "end": 333}, {"text": "glutathione", "start": 339, "end": 350}]}}, "schema": []}
{"input": "Pre-treatment of rats with friedelin at 40mg/kg for 7days restored these levels to normality and showed liver protection, comparable to the standard, silymarin (25mg/kg).", "output": {"entities": {"chemical": [{"text": "friedelin", "start": 27, "end": 36}]}}, "schema": []}
{"input": "These results clearly demonstrated that friedelin possessed marked antioxidant and liver protective effects.", "output": {"entities": {"chemical": [{"text": "friedelin", "start": 40, "end": 49}]}}, "schema": []}
{"input": "In vitro bioavailability of total selenium and selenium species from seafood.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 34, "end": 42}, {"text": "selenium", "start": 47, "end": 55}]}}, "schema": []}
{"input": "In vitro bioavailability of total selenium and selenium species from different raw seafood has been assessed by using a simulated gastric and intestinal digestion/dialysis method.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 34, "end": 42}, {"text": "selenium", "start": 47, "end": 55}]}}, "schema": []}
{"input": "Inductively coupled plasma-mass spectrometry (ICP-MS) was used to assess total selenium contents after a microwave assisted acid digestion, and also to quantify total selenium in the dialyzable and non-dialyzable fractions.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 79, "end": 87}, {"text": "selenium", "start": 167, "end": 175}]}}, "schema": []}
{"input": "Selenium speciation in the dialyzates was assessed by high performance liquid chromatography (HPLC) coupled with ICP-MS detection.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Major Se species (selenium methionine and oxidized selenium methionine) from dialyzate were identified and characterized by HPLC coupled to mass spectrometry (HPLC-MS).", "output": {"entities": {"chemical": [{"text": "Se", "start": 6, "end": 8}, {"text": "selenium methionine", "start": 18, "end": 37}, {"text": "oxidized selenium methionine", "start": 42, "end": 70}]}}, "schema": []}
{"input": "Selenocystine was detected at low concentrations while Se-(Methyl) selenocysteine and inorganic selenium species (selenite and selenate) were not detected in the dialyzate.", "output": {"entities": {"chemical": [{"text": "Selenocystine", "start": 0, "end": 13}, {"text": "Se", "start": 55, "end": 57}, {"text": "(Methyl) selenocysteine", "start": 58, "end": 81}, {"text": "selenium", "start": 96, "end": 104}, {"text": "selenite", "start": 114, "end": 122}, {"text": "selenate", "start": 127, "end": 135}]}}, "schema": []}
{"input": "Low bioavailability percentages for total selenium (6. 69 +/- 3. 39 and 5. 45 +/- 2. 44% for fish and mollusk samples, respectively) were obtained.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Similar bioavailability percentages was achieved for total selenium as a sum of selenium species (selenocystine plus oxidized selenium methionine and selenium methionine, mainly).", "output": {"entities": {"chemical": [{"text": "selenium", "start": 59, "end": 67}, {"text": "selenium", "start": 80, "end": 88}, {"text": "selenocystine", "start": 98, "end": 111}, {"text": "oxidized selenium methionine", "start": 117, "end": 145}, {"text": "selenium methionine", "start": 150, "end": 169}]}}, "schema": []}
{"input": "HPLC-MS data confirmed SeMet oxidation during the in vitro procedure.", "output": {"entities": {"chemical": [{"text": "SeMet", "start": 23, "end": 28}]}}, "schema": []}
{"input": "Oregon' Pinot noir' grape anthocyanin enhancement by early leaf removal.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 26, "end": 37}]}}, "schema": []}
{"input": "Complete cluster zone leaf removal of' Pinot noir' was initiated at three separate pre-v e raison growth stages (bloom, grain-pea size, and bunch closure) and maintained leaf free until harvest, for four growing seasons (2008-2011).", "output": {"entities": {}}, "schema": []}
{"input": "Fruit anthocyanin composition was examined at harvest for the last two vintages (2010 and 2011) and compared to a control-no cluster zone leaf removal.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 6, "end": 17}]}}, "schema": []}
{"input": "Experiments were conducted at two commercially operating Oregon vineyards (site A = 420 rootstock/' Pinot noir' 115 scion and site B = 3309C rootstock/' Pinot noir' 777 scion).", "output": {"entities": {}}, "schema": []}
{"input": "All clusters contained the five anthocyanins typically found in' Pinot noir'.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 32, "end": 44}]}}, "schema": []}
{"input": "Leaf removal at bloom and maintained until harvest produced maximum anthocyanin accumulation in' Pinot noir' grapes (site A = 85. 24mg/100g and site B = 125. 06mg/100g), compared to no leaf removal (control; site A = 57. 91mg/100g and site B = 97. 56mg/100g).", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 68, "end": 79}]}}, "schema": []}
{"input": "Even leaf removal at bunch closure (last leaf removal initiation period) increased grape anthocyanin (site A = 73. 22mg/100g and site B = 118. 93mg/100g) compared to control, but total anthocyanins were lower than grapes from bloom leaf removal (first time period).", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 89, "end": 100}, {"text": "anthocyanins", "start": 185, "end": 197}]}}, "schema": []}
{"input": "Results differed slightly by vineyard site and rootstock/scion combination.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitory effects of myricetin on mammalian DNA polymerase, topoisomerase and human cancer cell proliferation.", "output": {"entities": {"chemical": [{"text": "myricetin", "start": 22, "end": 31}]}}, "schema": []}
{"input": "In this study, the inhibitory activities against mammalian DNA polymerases (pols) of 16 major bioflavonoids were investigated.", "output": {"entities": {"chemical": [{"text": "bioflavonoids", "start": 94, "end": 107}]}}, "schema": []}
{"input": "Myricetin (3, 3', 4', 5, 5', 7-hexahydroxyflavone) was the most potent inhibitor of pols amongst the compounds tested, with IC50 values of 21. 3-40. 9 mu M.", "output": {"entities": {"chemical": [{"text": "Myricetin", "start": 0, "end": 9}, {"text": "3, 3', 4', 5, 5', 7-hexahydroxyflavone", "start": 11, "end": 49}]}}, "schema": []}
{"input": "This compound did not affect the activities of plant (cauliflower) pol alpha or prokaryotic pols.", "output": {"entities": {}}, "schema": []}
{"input": "Myricetin also inhibited human DNA topoisomerase II (topo II) activity with an IC50 value of 27. 5 mu M, but did not inhibit the activities of other DNA metabolic enzymes tested.", "output": {"entities": {"chemical": [{"text": "Myricetin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Myricetin also did not influence the direct binding to double stranded DNA as determined by thermal transition analysis.", "output": {"entities": {"chemical": [{"text": "Myricetin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "It was found to prevent the proliferation of human colon HCT116 carcinoma cells with an LD50 of 28. 2 mu M, halt the cell cycle in G2/M phase, and induce apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that the decrease of proliferation may be a result of the inhibition of cellular topoisomerase (topo) II rather than pols.", "output": {"entities": {}}, "schema": []}
{"input": "Extra virgin olive oil bitterness evaluation by sensory and chemical analyses.", "output": {"entities": {}}, "schema": []}
{"input": "An experimental investigation was performed on blend extra virgin olive oils (EVOOs) from different cultivars and EVOO from different olive monovarieties (Coratina, Leccino, Maiatica, Ogliarola) with the aim to evaluate the possibility of estimating the perceived bitterness intensity by using chemical indices, such as the total phenol content and the compounds responsible for oil bitterness measured spectrophotometrically at 225nm (K225 value), as bitterness predictors in different EVOO.", "output": {"entities": {"chemical": [{"text": "phenol", "start": 330, "end": 336}]}}, "schema": []}
{"input": "Therefore, a bitterness predictive model, based on the relationship between the perceived bitterness intensity of the selected stimuli and the chosen chemicals parameters has been built and validated.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicated that the oil bitterness intensity could be satisfactorily predicted by using the K225 values of oil samples.", "output": {"entities": {}}, "schema": []}
{"input": "Polycyclic aromatic hydrocarbons (PAH) and phenolic substances in meat products smoked with different types of wood and smoking spices.", "output": {"entities": {"chemical": [{"text": "Polycyclic aromatic hydrocarbons", "start": 0, "end": 32}, {"text": "PAH", "start": 34, "end": 37}, {"text": "phenolic", "start": 43, "end": 51}]}}, "schema": []}
{"input": "The contents of polycyclic aromatic hydrocarbons (15 + 1 EU PAH) and phenolic substances (guaiacol, 4-methylguaiacol, syringol, eugenol, and trans-isoeugenol) were investigated in smouldering-smoked Frankfurters and mini-salamis.", "output": {"entities": {"chemical": [{"text": "polycyclic aromatic hydrocarbons", "start": 16, "end": 48}, {"text": "PAH", "start": 60, "end": 63}, {"text": "phenolic", "start": 69, "end": 77}, {"text": "guaiacol", "start": 90, "end": 98}, {"text": "4-methylguaiacol", "start": 100, "end": 116}, {"text": "syringol", "start": 118, "end": 126}, {"text": "eugenol", "start": 128, "end": 135}, {"text": "trans-isoeugenol", "start": 141, "end": 157}]}}, "schema": []}
{"input": "For the 51 smoking experiments wood chips of oak, poplar, hickory, spruce, fir, alder, beech, and beech with an apple-smoking spice mix, cherry-smoking spice mix, and a mix of juniper berries and bay leaves were tested.", "output": {"entities": {}}, "schema": []}
{"input": "The use of poplar and hickory led to a decrease in the PAH contents in the range of 35-55% compared to the commonly used beech wood.", "output": {"entities": {"chemical": [{"text": "PAH", "start": 55, "end": 58}]}}, "schema": []}
{"input": "Higher PAH contents by using softwood were not observed.", "output": {"entities": {"chemical": [{"text": "PAH", "start": 7, "end": 10}]}}, "schema": []}
{"input": "The use of the rapidly growing poplar seems to be a reasonable approach for reducing the PAH contents in smoked meat products.", "output": {"entities": {"chemical": [{"text": "PAH", "start": 89, "end": 92}]}}, "schema": []}
{"input": "Furthermore, the sum contents of the five phenolic substances in sausages smoked with poplar were higher, or only slightly lower, when compared to the use of beech.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 42, "end": 50}]}}, "schema": []}
{"input": "Inhibitory effects of water extract of Flos Inulae on mutation and tyrosinase.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, the effects of a water extract of Flos Inulae (WFI) on antioxidant, antimutation and antityrosinase were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that WFI inhibited the mutagenicity of 2-aminoanthracene (2-AA), an indirect mutagen; and 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen toward Salmonella typhimurium TA 98 and TA 100.", "output": {"entities": {"chemical": [{"text": "2-aminoanthracene", "start": 58, "end": 75}, {"text": "2-AA", "start": 77, "end": 81}, {"text": "4-nitroquinoline-N-oxide", "start": 109, "end": 133}, {"text": "4-NQO", "start": 135, "end": 140}]}}, "schema": []}
{"input": "In addition, WFI, in the range of 0. 2-0. 6mg/ml, showed radical scavenging, reducing activities and chelating activity as well as decreased lipid oxidative damage.", "output": {"entities": {}}, "schema": []}
{"input": "Meanwhile, WFI also inhibited tyrosinase activity and NO generation in lipopolysaccharide (LPS) stimulated macrophages.", "output": {"entities": {"chemical": [{"text": "NO", "start": 54, "end": 56}]}}, "schema": []}
{"input": "High performance liquid chromatography analysis suggests that the major phenolic constituents in WFI are chlorogenic acid, rutin, quercetin, luteolin and kaempferol.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 72, "end": 80}, {"text": "chlorogenic acid", "start": 105, "end": 121}, {"text": "rutin", "start": 123, "end": 128}, {"text": "quercetin", "start": 130, "end": 139}, {"text": "luteolin", "start": 141, "end": 149}, {"text": "kaempferol", "start": 154, "end": 164}]}}, "schema": []}
{"input": "These bioactive components may contribute to the protective effects of WFI.", "output": {"entities": {}}, "schema": []}
{"input": "The obtained data suggests that Flos Inulae can be applied to antimutation, antityrosinase and anti-inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Evolution of the aromatic profile in Garnacha Tintorera grapes during raisining and comparison with that of the naturally sweet wine obtained.", "output": {"entities": {}}, "schema": []}
{"input": "The postharvest dehydration is one of the most important steps in obtaining a high quality naturally sweet wine and it can play an important role in modulating the production and the release of volatile compounds.", "output": {"entities": {}}, "schema": []}
{"input": "However, only a few studies have analysed the changes in the free and bound volatile compounds of grapes throughout the process.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, GC-MS was applied to determine the aromatic composition of Garnacha Tintorera grapes subjected to off-vine dehydration or raisining at several points during the process.", "output": {"entities": {}}, "schema": []}
{"input": "The total water loss in 83days was about 62% and the sugar concentration rose from 225 to 464g/L.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 53, "end": 58}]}}, "schema": []}
{"input": "Within the free volatile compounds, isoamyl alcohols, benzaldehyde and guaiacol registered the largest increase above the concentration effect due to water loss; while within the bound volatile compounds were isoamyl alcohols, ethyl vanillate and benzoic acid.", "output": {"entities": {"chemical": [{"text": "isoamyl alcohols", "start": 36, "end": 52}, {"text": "benzaldehyde", "start": 54, "end": 66}, {"text": "guaiacol", "start": 71, "end": 79}, {"text": "isoamyl alcohols", "start": 209, "end": 225}, {"text": "ethyl vanillate", "start": 227, "end": 242}, {"text": "benzoic acid", "start": 247, "end": 259}]}}, "schema": []}
{"input": "The aromatic profile of the raisins obtained were mainly caramelised, floral, phenolic and burned.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 78, "end": 86}]}}, "schema": []}
{"input": "LC-ESI-TOF-MS identification of bioactive secondary metabolites involved in the antioxidant, anti-inflammatory and anticancer activities of the edible halophyte Zygophyllum album Desf.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, liquid chromatography coupled to electrospray time-of-flight mass spectrometry (LC-ESI-TOF-MS) has been applied to screen bioactive metabolites in shoot extract of the medicinal halophyte Zygophyllum album.", "output": {"entities": {}}, "schema": []}
{"input": "Among 10 compounds identified (saponins, flavonoids and sterols) five were reported for the first time in Z. album.", "output": {"entities": {"chemical": [{"text": "saponins", "start": 31, "end": 39}, {"text": "flavonoids", "start": 41, "end": 51}, {"text": "sterols", "start": 56, "end": 63}]}}, "schema": []}
{"input": "Furthermore, novel biological activities of hexane, dichloromethane and methanolic extracts were assessed.", "output": {"entities": {"chemical": [{"text": "hexane", "start": 44, "end": 50}, {"text": "dichloromethane", "start": 52, "end": 67}]}}, "schema": []}
{"input": "Results showed that methanolic extract exhibit the highest antioxidant activity using in vitro ORAC test and anti-inflammatory activity, inhibiting by 84. 8% NO release in RAW264. 7 macrophages.", "output": {"entities": {"chemical": [{"text": "NO", "start": 158, "end": 160}]}}, "schema": []}
{"input": "However, dichloromethane extract proved the utmost antioxidant activity in cell (WS1) based-assay (IC50 = 57 mu g/ml) and interesting anticancer capacity against human lung carcinoma (A-549) and colon adenocarcinoma (DLD-1) cells (IC50 = 37 and 48 mu g/ml, respectively).", "output": {"entities": {"chemical": [{"text": "dichloromethane", "start": 9, "end": 24}]}}, "schema": []}
{"input": "These findings can be attributed to the presence of triterpenes, flavonoids and sterols in Z. album, which are widely known as powerful antioxidants and used in various industrial fields.", "output": {"entities": {"chemical": [{"text": "triterpenes", "start": 52, "end": 63}, {"text": "flavonoids", "start": 65, "end": 75}, {"text": "sterols", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Degradation of complex carbohydrate: Immobilization of pectinase from Bacillus licheniformis KIBGE-IB21 using calcium alginate as a support.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 23, "end": 35}, {"text": "calcium", "start": 110, "end": 117}]}}, "schema": []}
{"input": "Pectinases are heterogeneous group of enzymes that catalyse the hydrolysis of pectin substances which is responsible for the turbidity and undesirable cloudiness in fruits juices.", "output": {"entities": {}}, "schema": []}
{"input": "In current study, partially purified pectinase from Bacillus licheniformis KIBGE-IB21 was immobilized in calcium alginate beads.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 105, "end": 112}]}}, "schema": []}
{"input": "The effect of sodium alginate and calcium chloride concentration on immobilization was studied and it was found that the optimal sodium alginate and calcium chloride concentration was 3. 0% and 0. 2M, respectively.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 14, "end": 20}, {"text": "calcium chloride", "start": 34, "end": 50}, {"text": "sodium", "start": 129, "end": 135}, {"text": "calcium chloride", "start": 149, "end": 165}]}}, "schema": []}
{"input": "It was found that immobilization increases the optimal reaction time for pectin degradation from 5 to 10min and temperature from 45 to 55 degrees C, whereas, the optimal pH remained same with reference to free enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Thermal stability of enzyme increased after immobilization and immobilized pectinase retained more than 80% of its initial activity after 5days at 30 degrees C as compared with free enzyme which showed only 30% of residual activity.", "output": {"entities": {}}, "schema": []}
{"input": "The immobilized enzyme also exhibited good operational stability and 65% of its initial activity was observed during third cycle.", "output": {"entities": {}}, "schema": []}
{"input": "In term of pectinase immobilization efficiency and stability, this calcium alginate beads approach seemed to permit good results and can be used to make a bioreactor for various applications in food industries.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 67, "end": 74}]}}, "schema": []}
{"input": "Influence of pH, metal chelator, free radical scavenger and interfacial characteristics on the oxidative stability of beta-carotene in conjugated whey protein-pectin stabilised emulsion.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 118, "end": 131}]}}, "schema": []}
{"input": "The influence of whey protein isolate (WPI)-beet pectin conjugates formed by dry-heating on the oxidative stability of beta-carotene in O/W emulsions was studied.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 119, "end": 132}]}}, "schema": []}
{"input": "It was mainly focused on the influence of pH, metal chelator, free radical scavenger and interfacial characteristics on the degradation of beta-carotene in the emulsion stabilised by conjugate.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 139, "end": 152}]}}, "schema": []}
{"input": "The conjugate increased the oxidative stability of beta-carotene in the emulsion as compared to their unconjugated mixture at pH 7. 0.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 51, "end": 64}]}}, "schema": []}
{"input": "The desferoxamine retarded beta-carotene degradation at pH 4. 0 more effectively than pH 7. 0 and more effectively in the emulsion with the conjugate than the unconjugated mixture (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "desferoxamine", "start": 4, "end": 17}, {"text": "beta-carotene", "start": 27, "end": 40}]}}, "schema": []}
{"input": "The addition of 200mg/kg alpha-tocopherol significantly improved the stability of beta-carotene in the conjugate stabilised emulsion.", "output": {"entities": {"chemical": [{"text": "alpha-tocopherol", "start": 25, "end": 41}, {"text": "beta-carotene", "start": 82, "end": 95}]}}, "schema": []}
{"input": "The emulsions were washed to remove conjugate not absorbed to the emulsion droplet interface, indicating that unabsorbed emulsifiers could protect beta-carotene.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 147, "end": 160}]}}, "schema": []}
{"input": "It suggested that WPI-pectin conjugate could be used to protect bioactive lipids in emulsions.", "output": {"entities": {}}, "schema": []}
{"input": "Phospholipids in rice: Significance in grain quality and health benefits: A review.", "output": {"entities": {}}, "schema": []}
{"input": "Phospholipids (PLs) are a major class of lipid in rice grain.", "output": {"entities": {}}, "schema": []}
{"input": "Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance.", "output": {"entities": {}}, "schema": []}
{"input": "We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling.", "output": {"entities": {}}, "schema": []}
{"input": "Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice.", "output": {"entities": {"chemical": [{"text": "Phosphatidylcholine", "start": 0, "end": 19}, {"text": "phosphatidylethanolamine", "start": 26, "end": 50}, {"text": "phosphatidylinositol", "start": 57, "end": 77}]}}, "schema": []}
{"input": "The deterioration of PC in rice bran during storage was considered as a trigger for the degradation of rice lipids with associated rancid flavour in paddy and brown rice.", "output": {"entities": {}}, "schema": []}
{"input": "The lyso forms in rice endosperm represent the major starch lipid, and may form inclusion complexes with amylose, affecting the physicochemical properties and digestibility of starch, and hence its cooking and eating quality.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary PLs have a positive impact on several human diseases and reduce the side-effects of some drugs.", "output": {"entities": {}}, "schema": []}
{"input": "As rice has long been consumed as a staple food in many Asian countries, rice PLs may have significant health benefits for those populations.", "output": {"entities": {}}, "schema": []}
{"input": "Rice PLs may be influenced both by genetic (G) and environmental (E) factors, and resolving G x E interactions may allow future exploitation of PL composition and content, thus boosting rice eating quality and health benefits for consumers.", "output": {"entities": {}}, "schema": []}
{"input": "We have identified and summarised the different methods used for rice PL analysis, and discussed the consequences of variation in reported PL values due to inconsistencies between methods.", "output": {"entities": {}}, "schema": []}
{"input": "This review enhances the understanding of the nature and importance of PLs in rice and outlines potential approaches for manipulating PLs to improve the quality of rice grain and other cereals.", "output": {"entities": {}}, "schema": []}
{"input": "On the origin of sharp peaks in the X-ray diffraction patterns of xanthan powders.", "output": {"entities": {}}, "schema": []}
{"input": "A series of xanthans containing different levels of the charged group pyruvate has been examined.", "output": {"entities": {"chemical": [{"text": "pyruvate", "start": 70, "end": 78}]}}, "schema": []}
{"input": "The X-ray diffraction patterns of the powders of these materials had different levels of a sharp pattern superimposed on an amorphous background.", "output": {"entities": {}}, "schema": []}
{"input": "As the moisture content increased so the intensity of the sharp pattern increased up to a level between 20% and 40% moisture content where the sharp pattern disappeared.", "output": {"entities": {}}, "schema": []}
{"input": "X-ray diffraction pattern identification software and an inorganic X-ray diffraction database showed the origin of the sharp peaks to be due to sodium sulphate polymorphs.", "output": {"entities": {"chemical": [{"text": "sodium sulphate", "start": 144, "end": 159}]}}, "schema": []}
{"input": "The behaviour of the xanthans was thought to be due to the differences in charge on the molecule; however, the increase in the crystalline component observed with increased amounts of water was unexpected.", "output": {"entities": {}}, "schema": []}
{"input": "The possibility of the drying of samples was considered but the interplay between ions, the charged polymer and the water present was considered necessary to more closely describe the results.", "output": {"entities": {}}, "schema": []}
{"input": "Impact of pectin type on the storage stability of black currant (Ribes nigrum L.) anthocyanins in pectic model solutions.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 82, "end": 94}]}}, "schema": []}
{"input": "The effects of different pectins on the stabilisation of black currant anthocyanins in viscous model solutions at pH 3. 0 were investigated.", "output": {"entities": {"chemical": [{"text": "anthocyanins", "start": 71, "end": 83}]}}, "schema": []}
{"input": "For this purpose, low esterified amidated (AM), low (LM) and high (HM) methoxylated citrus and apple pectins and a sugar beet pectin were added to a purified anthocyanin extract (ACN-E) and to an extract containing anthocyanins and non-anthocyanin phenolics (PP-E).", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 158, "end": 169}, {"text": "ACN", "start": 179, "end": 182}, {"text": "anthocyanins", "start": 215, "end": 227}, {"text": "anthocyanin phenolics", "start": 236, "end": 257}]}}, "schema": []}
{"input": "Model systems were stored at 20 +/- 0. 5 degrees C in the dark.", "output": {"entities": {}}, "schema": []}
{"input": "Anthocyanin contents were monitored by HPLC analysis over a period of 18weeks, and half-life and destruction values were calculated.", "output": {"entities": {"chemical": [{"text": "Anthocyanin", "start": 0, "end": 11}]}}, "schema": []}
{"input": "In all pectic model solutions anthocyanin stability was significantly improved compared to stability of the extracts without added pectins (blank).", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 30, "end": 41}]}}, "schema": []}
{"input": "Best stabilisation was obtained with AM pectin, followed by LM and HM pectins.", "output": {"entities": {}}, "schema": []}
{"input": "In model systems containing citrus pectins, anthocyanin stabilisation was better compared to that of apple pectins having similar degrees of esterification and amidation, respectively.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 44, "end": 55}]}}, "schema": []}
{"input": "This was primarily due to the strong interaction of delphinidin glycosides with the citrus pectins, whereas stabilisation of cyanidin derivatives was less important.", "output": {"entities": {"chemical": [{"text": "delphinidin glycosides", "start": 52, "end": 74}, {"text": "cyanidin", "start": 125, "end": 133}]}}, "schema": []}
{"input": "Sugar beet pectin improved anthocyanin stability only to a limited extent.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 27, "end": 38}]}}, "schema": []}
{"input": "In the presence of non-anthocyanin phenolics (PP-E) the impact of the pectin source was even more pronounced than the effect of the pectin type.", "output": {"entities": {"chemical": [{"text": "anthocyanin phenolics", "start": 23, "end": 44}]}}, "schema": []}
{"input": "Addition of citrate to pectic systems accelerated anthocyanin decay.", "output": {"entities": {"chemical": [{"text": "anthocyanin", "start": 50, "end": 61}]}}, "schema": []}
{"input": "Stabilising effects of pectins were hardly noticeable when evaluating total phenolic content (TPC, Folin-Ciocalteu) and antioxidant capacity during storage.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 76, "end": 84}]}}, "schema": []}
{"input": "Highest TPC, TEAC-and FRAP values were observed in systems containing citrus pectin, which was in contrast to sugar beet pectin, where values fell below those of the blank after storage.", "output": {"entities": {}}, "schema": []}
{"input": "Conformational restriction approach to BACE1 inhibitors II: SAR study of the isocytosine derivatives fixed with a cis-cyclopropane ring.", "output": {"entities": {"chemical": [{"text": "isocytosine", "start": 77, "end": 88}, {"text": "cis-cyclopropane", "start": 114, "end": 130}]}}, "schema": []}
{"input": "To improve the efficacy of the conformationally restricted BACE1 inhibitors, structural modifications were investigated using two strategies: (a) modification of the terminal aromatic ring and (b) insertion of a spacer between the aromatic rings.", "output": {"entities": {}}, "schema": []}
{"input": "In the latter approach, another type of inhibitor 17 bearing an ethylene spacer between two aromatic rings was found to exhibit good BACE1 inhibitory activity, while the corresponding conformationally unrestricted compound 25 showed no activity.", "output": {"entities": {"chemical": [{"text": "ethylene", "start": 64, "end": 72}]}}, "schema": []}
{"input": "This result revealed an interesting effect of a conformational restriction with a cyclopropane ring.", "output": {"entities": {"chemical": [{"text": "cyclopropane", "start": 82, "end": 94}]}}, "schema": []}
{"input": "Discovery of ML326: The first sub-micromolar, selective M5 PAM.", "output": {"entities": {"chemical": [{"text": "ML326", "start": 13, "end": 18}]}}, "schema": []}
{"input": "This Letter describes the further chemical optimization of the M5 PAM MLPCN probes ML129 and ML172.", "output": {"entities": {"chemical": [{"text": "ML129", "start": 83, "end": 88}, {"text": "ML172", "start": 93, "end": 98}]}}, "schema": []}
{"input": "A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172.", "output": {"entities": {"chemical": [{"text": "isatin", "start": 73, "end": 79}, {"text": "ML129", "start": 167, "end": 172}, {"text": "ML172", "start": 177, "end": 182}]}}, "schema": []}
{"input": "An HTS campaign identified several weak M5 PAMs (M5 EC50 > 10 mu M) with a structurally related isatin core that possessed a southern phenethyl ether linkage.", "output": {"entities": {"chemical": [{"text": "isatin", "start": 96, "end": 102}, {"text": "phenethyl ether", "start": 134, "end": 149}]}}, "schema": []}
{"input": "While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M5 PAM, ML326 (VU0467903), (human and rat M5 EC50s of 409nM and 500nM, respectively) with excellent mAChR selectivity (M1-M4 EC50s > 30 mu M) and a robust 20-fold leftward shift of the ACh CRC.", "output": {"entities": {"chemical": [{"text": "phenethyl ether", "start": 90, "end": 105}, {"text": "ML129", "start": 123, "end": 128}, {"text": "ML172", "start": 129, "end": 134}, {"text": "ML326", "start": 181, "end": 186}, {"text": "VU0467903", "start": 188, "end": 197}]}}, "schema": []}
{"input": "The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported.", "output": {"entities": {}}, "schema": []}
{"input": "This candidate, (S)-3-[4-(1-{3, 5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl] phenoxy} butyl) benzamido] propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing.", "output": {"entities": {"chemical": [{"text": "(S)-3-[4-(1-{3, 5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl] phenoxy} butyl) benzamido] propanoic acid", "start": 16, "end": 124}]}}, "schema": []}
{"input": "Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs.", "output": {"entities": {}}, "schema": []}
{"input": "In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 80, "end": 87}]}}, "schema": []}
{"input": "Its properties make it an excellent candidate for further investigation.", "output": {"entities": {}}, "schema": []}
{"input": "Altered cholesterol homeostasis in aged macrophages linked to neovascular macular degeneration.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 8, "end": 19}]}}, "schema": []}
{"input": "Abnormal lipid metabolism has been linked to age-related macular degeneration (AMD); choroidal neovascularization in late AMD commonly causes blindness.", "output": {"entities": {}}, "schema": []}
{"input": "Sene et al.", "output": {"entities": {}}, "schema": []}
{"input": "(2013) now demonstrate that in aged macrophages decreased ABCA1 expression, regulated by liver X receptor and miR-33, impairs export of intracellular cholesterol, which promotes neovascular AMD.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 150, "end": 161}]}}, "schema": []}
{"input": "Learning from our mistakes: The' unknown knowns' in fragment screening.", "output": {"entities": {}}, "schema": []}
{"input": "In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry.", "output": {"entities": {}}, "schema": []}
{"input": "The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads.", "output": {"entities": {}}, "schema": []}
{"input": "Because the affinities of the initial fragments are often low, detection methods are pushed to their limits, leading to a variety of artifacts, false positives, and false negatives that too often go unrecognized.", "output": {"entities": {}}, "schema": []}
{"input": "This Digest discusses some of these problems and offers suggestions to avoid them.", "output": {"entities": {}}, "schema": []}
{"input": "Although the primary focus is on FBLD, many of the lessons also apply to more established approaches such as high-throughput screening.", "output": {"entities": {}}, "schema": []}
{"input": "Lignans extracted from Vitex negundo possess cytotoxic activity by G2/M phase cell cycle arrest and apoptosis induction.", "output": {"entities": {"chemical": [{"text": "Lignans", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Evn-50 is a lignan compounds mixture extracted from Vitex negundo, a widely used herb in traditional Chinese medicine.", "output": {"entities": {"chemical": [{"text": "Evn-50", "start": 0, "end": 6}, {"text": "lignan", "start": 12, "end": 18}]}}, "schema": []}
{"input": "This study is aimed to define the spectrum of cytotoxic activity of EVn-50, and also to investigate mechanisms underlying the anticancer actions via assessing the influence on cell cycle using EVn-50, and the lignan compound VB1 purified from EVn-50.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 68, "end": 74}, {"text": "EVn-50", "start": 193, "end": 199}, {"text": "lignan", "start": 209, "end": 215}, {"text": "VB1", "start": 225, "end": 228}, {"text": "EVn-50", "start": 243, "end": 249}]}}, "schema": []}
{"input": "The cytotoxic effect of EVn-50 and VB1 was determined with SRB assay using a panel of cancer cell lines.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 24, "end": 30}, {"text": "VB1", "start": 35, "end": 38}]}}, "schema": []}
{"input": "Breast cancer cell line MDA-MB-435 and liver cancer cell line SMMC-7721 were selected for further evaluating the effect of EVn-50 or VB1 on cell cycle by flow cytometric analysis.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 123, "end": 129}, {"text": "VB1", "start": 133, "end": 136}]}}, "schema": []}
{"input": "Apoptosis exerted by EVn-50 or VB1 was measured by TUNEL assay and DAPI staining, and Western blot analysis was utilized to assess the influence on expression and phosphorylation of proteins which are closely related to cell cycle and apoptosis.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 21, "end": 27}, {"text": "VB1", "start": 31, "end": 34}]}}, "schema": []}
{"input": "EVn-50 possessed a broad spectrum of in vitro anticancer activity for those tested cancer cells, especially sensitive to MDA-MB-435, SKOV-3, BXPC-3, SMMC-7721, MCF-7, HO-8910, SGC-7901, BEL-7402, HCT-116, and 786-O, with the respective IC50 below 10 mu g/ml.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Treatment with EVn-50 or VB1 resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of Cdk1 at Tyr15, expression of cyclin B1, and decreased expression of Cdc25c.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 15, "end": 21}, {"text": "VB1", "start": 25, "end": 28}, {"text": "Ser10", "start": 190, "end": 195}, {"text": "Tyr15", "start": 224, "end": 229}]}}, "schema": []}
{"input": "Moreover, we found that exposure of MDA-MB-435 cells to EVn-50 or VB1 caused obvious apoptosis of MDA-MB-435 cells.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 56, "end": 62}, {"text": "VB1", "start": 66, "end": 69}]}}, "schema": []}
{"input": "Our data show that EVn-50, lignan compounds extracted from Vitex negundo, possesses a broad spectrum cytotoxic effect via arresting cancer cells at G2/M phase cell cycle and subsequently inducing apoptosis.", "output": {"entities": {"chemical": [{"text": "EVn-50", "start": 19, "end": 25}, {"text": "lignan", "start": 27, "end": 33}]}}, "schema": []}
{"input": "Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 12, "end": 21}]}}, "schema": []}
{"input": "In our previous studies we described functional expression of organic cation transporter 3 (OCT3) and multidrug and toxin extrusion 1 (MATE1) protein in the rat placenta.", "output": {"entities": {}}, "schema": []}
{"input": "Since metformin is a substrate of both OCT3 and MATE1, in this study we used the model of dually perfused rat placenta to investigate the role of these transporters in metformin passage across the placenta.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 6, "end": 15}, {"text": "metformin", "start": 168, "end": 177}]}}, "schema": []}
{"input": "We observed concentration-dependent transplacental clearance of metformin in both maternal-to-fetal and fetal-to-maternal directions; in addition metformin crossed the placenta from the fetal to maternal compartment even against its concentration gradient.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 64, "end": 73}, {"text": "metformin", "start": 146, "end": 155}]}}, "schema": []}
{"input": "This transport was completely inhibited by MPP (+), a common OCT3 and MATE1 inhibitor.", "output": {"entities": {"chemical": [{"text": "MPP (+)", "start": 43, "end": 50}]}}, "schema": []}
{"input": "Furthermore, we observed that the oppositely directed H (+)-gradient can drive the secretion of metformin from placenta to maternal circulation, confirming apical efflux of metformin from trophoblast by MATE1.", "output": {"entities": {"chemical": [{"text": "H (+)", "start": 54, "end": 59}, {"text": "metformin", "start": 96, "end": 105}, {"text": "metformin", "start": 173, "end": 182}]}}, "schema": []}
{"input": "In conclusion, we suggest an important role of OCT3 and MATE1 in the transplacental transfer of metformin.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 96, "end": 105}]}}, "schema": []}
{"input": "2-Hydroxychalcone and xanthohumol inhibit invasion of triple negative breast cancer cells.", "output": {"entities": {"chemical": [{"text": "2-Hydroxychalcone", "start": 0, "end": 17}, {"text": "xanthohumol", "start": 22, "end": 33}]}}, "schema": []}
{"input": "Breast cancer is estimated as one of the most common causes of cancer death among women.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, triple negative breast cancers (TNBCs), which do not express the genes for estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2), have been associated with poor prognosis and metastasis.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 90, "end": 98}, {"text": "progesterone", "start": 99, "end": 111}]}}, "schema": []}
{"input": "Chalcones, the biosynthetic precursors of flavonoids present in edible plants, exert cytotoxic and chemopreventive activities.", "output": {"entities": {"chemical": [{"text": "Chalcones", "start": 0, "end": 9}, {"text": "flavonoids", "start": 42, "end": 52}]}}, "schema": []}
{"input": "Although mounting evidence suggests the anticancer properties of chalcones, limited information is available regarding the inhibitory effects of chalcones on the aggressiveness of breast cancer cells.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 65, "end": 74}, {"text": "chalcones", "start": 145, "end": 154}]}}, "schema": []}
{"input": "The present study aimed to investigate the effects of chalcone and its derivatives on the growth and the invasiveness of TNBC cells.", "output": {"entities": {"chemical": [{"text": "chalcone", "start": 54, "end": 62}]}}, "schema": []}
{"input": "Here, we showed that treatment with chalcone, 2-hydroxychalcone, and xanthohumol for 24h inhibited the growth of MDA-MB-231cells with IC50 values of 18. 1, 4. 6, and 6. 7 mu M, respectively.", "output": {"entities": {"chemical": [{"text": "chalcone", "start": 36, "end": 44}, {"text": "2-hydroxychalcone", "start": 46, "end": 63}, {"text": "xanthohumol", "start": 69, "end": 80}]}}, "schema": []}
{"input": "Similarly, Chalcone, 2-hydroxychalcone, and xanthohumol also exerted cytotoxicity in another TNBC cell line, Hs578T.", "output": {"entities": {"chemical": [{"text": "Chalcone", "start": 11, "end": 19}, {"text": "2-hydroxychalcone", "start": 21, "end": 38}, {"text": "xanthohumol", "start": 44, "end": 55}]}}, "schema": []}
{"input": "Neohesperidin dihydrochalcone, 4-methoxychalcone, and hesperidin methylchalcone did not show the cytotoxicity on the MDA-MB-231cells.", "output": {"entities": {"chemical": [{"text": "Neohesperidin dihydrochalcone", "start": 0, "end": 29}, {"text": "4-methoxychalcone", "start": 31, "end": 48}, {"text": "hesperidin methylchalcone", "start": 54, "end": 79}]}}, "schema": []}
{"input": "Xanthohumol and 2-hydroxychalcone induced apoptosis by Bcl-2 downregulation.", "output": {"entities": {"chemical": [{"text": "Xanthohumol", "start": 0, "end": 11}, {"text": "2-hydroxychalcone", "start": 16, "end": 33}]}}, "schema": []}
{"input": "Importantly, 2-hydroxychalcone and xanthohumol exerted more potent inhibitory effects on the proliferation, MMP-9 expression and invasive phenotype of MDA-MB-231 than chalcone.", "output": {"entities": {"chemical": [{"text": "2-hydroxychalcone", "start": 13, "end": 30}, {"text": "xanthohumol", "start": 35, "end": 46}, {"text": "chalcone", "start": 167, "end": 175}]}}, "schema": []}
{"input": "These results suggest a potential application of these chalcones as anticancer agents that can alleviate malignant progression of TNBC.", "output": {"entities": {"chemical": [{"text": "chalcones", "start": 55, "end": 64}]}}, "schema": []}
{"input": "Increased dissolution and oral absorption of itraconazole/Soluplus extrudate compared with itraconazole nanosuspension.", "output": {"entities": {"chemical": [{"text": "itraconazole", "start": 45, "end": 57}, {"text": "Soluplus", "start": 58, "end": 66}, {"text": "itraconazole", "start": 91, "end": 103}]}}, "schema": []}
{"input": "The purpose of this article was to compare the in vitro and in vivo profiles of itraconazole (ITZ) extrudates and nanosuspension separately prepared by two different methods.", "output": {"entities": {"chemical": [{"text": "itraconazole", "start": 80, "end": 92}, {"text": "ITZ", "start": 94, "end": 97}]}}, "schema": []}
{"input": "And it was proved truly to form nanocrystalline and amorphous ITZ characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrum (FTIR), transmission electron microscope (TEM), and scanning electron microscope (SEM).", "output": {"entities": {"chemical": [{"text": "ITZ", "start": 62, "end": 65}]}}, "schema": []}
{"input": "The release of ITZ/Soluplus solid dispersions with amorphous ITZ was almost complete while only 40% release was obtained with ITZ nanocrystals.", "output": {"entities": {"chemical": [{"text": "ITZ", "start": 15, "end": 18}, {"text": "Soluplus", "start": 19, "end": 27}, {"text": "ITZ", "start": 61, "end": 64}, {"text": "ITZ", "start": 126, "end": 129}]}}, "schema": []}
{"input": "The amorphous state need not to cross over the crystal lattice energy upon dissolution while the crystalline need to overcome it.", "output": {"entities": {}}, "schema": []}
{"input": "In the in vivo assay, the AUC (0-t) and Cmax of ITZ/Soluplus were 6. 9-and 11. 6-time higher than those of pure ITZ.", "output": {"entities": {"chemical": [{"text": "ITZ", "start": 48, "end": 51}, {"text": "Soluplus", "start": 52, "end": 60}, {"text": "ITZ", "start": 112, "end": 115}]}}, "schema": []}
{"input": "The formulation of the extrudate had an AUC (0-t) and Cmax similar to those of ITZ and also OH-ITZ compared with the commercial capsule (Sporanox (R)).", "output": {"entities": {"chemical": [{"text": "ITZ", "start": 79, "end": 82}, {"text": "OH-ITZ", "start": 92, "end": 98}, {"text": "Sporanox", "start": 137, "end": 145}]}}, "schema": []}
{"input": "The relative bioavailability values with their 95% confidence limit were calculated to be 98. 3% (92. 5-104. 1%) and 101. 3% (97. 9-104. 1%), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study showed increased dissolution and bioavailability of the solid dispersion of Soluplus-based carrier loading ITZ prepared by HME compared with the ITZ nanosuspension prepared by wet milling.", "output": {"entities": {"chemical": [{"text": "Soluplus", "start": 102, "end": 110}, {"text": "ITZ", "start": 133, "end": 136}, {"text": "ITZ", "start": 171, "end": 174}]}}, "schema": []}
{"input": "Beneficial effects of asiaticoside on cognitive deficits in senescence-accelerated mice.", "output": {"entities": {"chemical": [{"text": "asiaticoside", "start": 22, "end": 34}]}}, "schema": []}
{"input": "The effect of asiaticoside isolated from Hydrocotyle sibthorpioides (AHS) on the promotion of cognition in senescence-accelerated mice (SAMP) was evaluated.", "output": {"entities": {"chemical": [{"text": "asiaticoside", "start": 14, "end": 26}]}}, "schema": []}
{"input": "Six-month old male SAMP8 mice were orally administered 20, 40 or 80mg/kg AHS daily for three months.", "output": {"entities": {}}, "schema": []}
{"input": "SAMR1 mice were used as a \" normal aging \" control.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that treatment with AHS significantly improved learning and memory abilities in behavioral tests.", "output": {"entities": {}}, "schema": []}
{"input": "AHS-treated mice showed higher antioxidant enzyme activity and lower lipid oxidation in serum compared with untreated SAMP8 mice.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistically, studies showed that AHS markedly reduced the content and deposition of beta-amyloid peptide (A beta) by inhibiting the expression of mRNA for amyloid protein precursor, beta-site amyloid cleaving enzyme-1 and cathepsin B and promoting the expression of mRNA for neprilysin and insulin degrading enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, AHS significantly increased the expression of plasticity-related proteins including postsynaptic density-95, phosphor-N-methyl-d-aspartate receptor 1, phospho-calcium-calmodulin dependent kinase II, phospho-protein kinase A Catalytic beta subunit, protein kinase C gamma subunit, phospho-CREB and brain derived neurotrophic factor.", "output": {"entities": {"chemical": [{"text": "N-methyl-d-aspartate", "start": 131, "end": 151}, {"text": "phospho", "start": 164, "end": 171}, {"text": "calcium", "start": 172, "end": 179}, {"text": "phospho", "start": 212, "end": 219}, {"text": "phospho", "start": 293, "end": 300}]}}, "schema": []}
{"input": "Furthermore, AHS increased the levels of acetylcholine (Ach), but decreased cholinesterase (AchE) activity.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 41, "end": 54}, {"text": "Ach", "start": 56, "end": 59}]}}, "schema": []}
{"input": "These results demonstrated that AHS administration may prevent spatial learning and memory decline by scavenging free radicals, up-regulating the activity of antioxidant enzymes, decreasing the level of A beta, ameliorating dysfunction in synaptic plasticity, and reversing abnormal changes in Ach level and AchE activity.", "output": {"entities": {"chemical": [{"text": "Ach", "start": 294, "end": 297}]}}, "schema": []}
{"input": "Thus, AHS should be developed as a new drug to prevent age-related cognitive deficits.", "output": {"entities": {}}, "schema": []}
{"input": "Bioreducible alginate-poly (ethylenimine) nanogels as an antigen-delivery system robustly enhance vaccine-elicited humoral and cellular immune responses.", "output": {"entities": {"chemical": [{"text": "poly (ethylenimine)", "start": 22, "end": 41}]}}, "schema": []}
{"input": "Although polysaccharide nanogels have emerged as a novel antigen delivery system for vaccine development, whether modulating the redox sensitivity of nanogels could improve vaccine efficacy remains unclear.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we generated bioreducible cationic alginate-polyethylenimine (PEI) nanogels as a novel vaccine delivery system.", "output": {"entities": {"chemical": [{"text": "polyethylenimine", "start": 66, "end": 82}, {"text": "PEI", "start": 84, "end": 87}]}}, "schema": []}
{"input": "Briefly, nanogels were prepared by the electrostatic interaction of negatively charged alginate sodium with branched PEI2k, followed by disulfide cross-linking to generate bioreducible nanogels (AP-SS).", "output": {"entities": {"chemical": [{"text": "sodium", "start": 96, "end": 102}, {"text": "disulfide", "start": 136, "end": 145}]}}, "schema": []}
{"input": "The AP-SS nanogels demonstrated great antigen-loading capacity and minimal cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro study showed that reducible AP-SS nanogels not only facilitated antigen uptake by mouse bone marrow dendritic cells (BMDCs), but also promoted intracellular antigen degradation and cytosolic release.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, AP-SS nanogels significantly enhanced both MHC class I and II antigen presentation by BMDCs.", "output": {"entities": {}}, "schema": []}
{"input": "Compared with the non-reducible nanogels, AP-SS nanogels more potently enhanced vaccine-induced antibody production and CD8 (+) T cell-mediated tumor cell lysis.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, the bioreducible alginate-PEI nanogels could serve as a potent adjuvant to improve vaccine-elicited humoral and cellular immune responses.", "output": {"entities": {}}, "schema": []}
{"input": "Transcellular transport of aconitine across human intestinal Caco-2 cells.", "output": {"entities": {"chemical": [{"text": "aconitine", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Aconitine (AC) is a highly toxic compound present in plants of the genus Aconitum.", "output": {"entities": {"chemical": [{"text": "Aconitine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "The transcellular transport mechanism of AC was investigated using Caco-2 cells.", "output": {"entities": {}}, "schema": []}
{"input": "The flux of AC was time-and concentration-dependent in both apical-to-basolateral and the reverse direction.", "output": {"entities": {}}, "schema": []}
{"input": "The efflux of AC was more than two-fold that in the opposite direction.", "output": {"entities": {}}, "schema": []}
{"input": "The influx of AC was temperature-, pH-and Na (+)-dependent.", "output": {"entities": {"chemical": [{"text": "Na (+)", "start": 42, "end": 48}]}}, "schema": []}
{"input": "Glucose markedly decreased the absorption of AC.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}]}}, "schema": []}
{"input": "However, the efflux of AC was temperature-and pH-dependent, but Na (+)-independent.", "output": {"entities": {"chemical": [{"text": "Na (+)", "start": 64, "end": 70}]}}, "schema": []}
{"input": "Cyclosporin A and verapamil, both inhibitors of P-glycoprotein (P-gp), significantly decreased the efflux of AC.", "output": {"entities": {"chemical": [{"text": "Cyclosporin A", "start": 0, "end": 13}, {"text": "verapamil", "start": 18, "end": 27}]}}, "schema": []}
{"input": "In addition, MK-571, an inhibitor of multidrug resistance-associated protein 2 (MRP2), exhibited the same trend but to a lesser extent.", "output": {"entities": {"chemical": [{"text": "MK-571", "start": 13, "end": 19}]}}, "schema": []}
{"input": "These results indicate that both the influx and efflux of AC across Caco-2 monolayers were through an active process.", "output": {"entities": {}}, "schema": []}
{"input": "A pH-dependent carrier-mediated transport system was the major absorption mechanism and a sodium-dependent glucose transporter may be involved.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 90, "end": 96}, {"text": "glucose", "start": 107, "end": 114}]}}, "schema": []}
{"input": "The active efflux of AC across Caco-2 cells was mediated mainly by ABC-transporter P-gp.", "output": {"entities": {}}, "schema": []}
{"input": "It is involved in reducing the toxicity of AC to organisms and is the major reasons for the poor absorption of AC in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Retrospective exposure data for baby and children care products: An analysis of 48 clinical studies.", "output": {"entities": {}}, "schema": []}
{"input": "To conduct a reliable safety assessment, accurate exposure information for cosmetic products and ingredients is needed.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present retrospective study was to determine the amount per application and the daily exposure for some of the most commonly used baby cosmetic products.", "output": {"entities": {}}, "schema": []}
{"input": "Consumption data from 48 clinical studies performed on 1481 babies and children (from 0 to 10years old) were reviewed and used to conduct a probabilistic evaluation of dermal exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Six categories of products were reviewed: rinseoff products for hair and body; rinse-off products for the whole body; leave-on products for face and body; cleansers for face and body; diaper dermatitis treatment products; shampoos.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects were provided with products and recorded detailed daily usage information over a 1-4-week period, depending on the study.", "output": {"entities": {}}, "schema": []}
{"input": "Products were weighed at the start and upon completion of each study in order to determine the total amount of product used.", "output": {"entities": {}}, "schema": []}
{"input": "The mean, median, standard deviation and 95th percentile were calculated for daily consumption and exposure, for several age groups from 0 to 10years old.", "output": {"entities": {}}, "schema": []}
{"input": "This study provides current baby cosmetic exposure information for commonly used products which will be useful for risk assessment purposes.", "output": {"entities": {}}, "schema": []}
{"input": "A protocol for the classification of wet mass in extrusion-spheronization.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, a structured protocol for the classification of wet mass in extrusion-spheronization was developed to predict formation and pellet quality.", "output": {"entities": {}}, "schema": []}
{"input": "The wet masses of 120 formulae were prepared taking microcrystalline celluloses as pelletization aid and lactose, hydroxypropyl methylcellulose grades, herbal medicines as model drugs.", "output": {"entities": {"chemical": [{"text": "lactose", "start": 105, "end": 112}, {"text": "hydroxypropyl", "start": 114, "end": 127}]}}, "schema": []}
{"input": "Physical properties of the wet masses such as hardness, adhesiveness, springiness, cohesiveness, chewiness, and resilience were tested, respectively, using a texture analyzer.", "output": {"entities": {}}, "schema": []}
{"input": "Particles were produced by spheronization process, and the quality of spherical pellets was also evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Data were analyzed by principal component analysis, factor analysis, and classification analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The wet masses could be classified into five groups taking the ratio of hardness to springiness (Ha/Sp) as the first classification index and chewiness, resilience as the second and the third classification index.", "output": {"entities": {}}, "schema": []}
{"input": "The wet masses of different classification could correspondingly form the different shapes.", "output": {"entities": {}}, "schema": []}
{"input": "So, a new protocol could be devised, for example, if the range of Ha/Sp of the wet masses was 30, 992-47, 689g, at the same time, the value of chewiness was less than 4842, and the value of resilience was no more than 0. 139; it would form spherical pellets under the experimental condition.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate that the proposed protocol could be a valuable asset in a formulation development project to assess the physical properties of wet masses and to predict formation and pellet quality.", "output": {"entities": {}}, "schema": []}
{"input": "So, the tedious and expensive pre-production (pre-formulation and optimization) work could be considerably reduced.", "output": {"entities": {}}, "schema": []}
{"input": "Frequency of the GPR7 Tyr135Phe allelic variant in lean and obese subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Background: GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the Central Nervous System (CNS), which are involved in the regulation of feeding behaviour.", "output": {"entities": {}}, "schema": []}
{"input": "GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Aim: Aim of this study was to investigate whether GPR7 gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects and Methods: The coding region of GPR7 were sequenced in 150 obese patients and 100 normal-weight unrelated controls.", "output": {"entities": {}}, "schema": []}
{"input": "Functional studies of the allelic variants were performed.", "output": {"entities": {}}, "schema": []}
{"input": "Results: One genetic GPR7 variant was found (Tyr135Phe-rs33977775) in obese subjects (13, 3%) and lean control (25%).", "output": {"entities": {}}, "schema": []}
{"input": "Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW mediated capacity to inhibit forskolin-induced cAMP production.", "output": {"entities": {"chemical": [{"text": "forskolin", "start": 157, "end": 166}, {"text": "cAMP", "start": 175, "end": 179}]}}, "schema": []}
{"input": "Conclusions: Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population.", "output": {"entities": {}}, "schema": []}
{"input": "As indicated by in vitro and in silico studies, this variant is unlikely to cause a functional derangement of the receptor.", "output": {"entities": {}}, "schema": []}
{"input": "Resolving the phylogenetic history of the short-necked turtles, genera Elseya and Myuchelys (Testudines: Chelidae) from Australia and New Guinea.", "output": {"entities": {}}, "schema": []}
{"input": "Phylogenetic relationships and taxonomy of the short-necked turtles of the genera Elseya, Myuchelys, and Emydura in Australia and New Guinea have long been debated as a result of conflicting hypotheses supported by different data sets and phylogenetic analyses.", "output": {"entities": {}}, "schema": []}
{"input": "To resolve this contentious issue, we analyzed sequences from two mitochondrial genes (cytochrome b and ND4) and one nuclear intron gene (R35) from all species of the genera Elseya, Myuchelys, Emydura, and their relatives.", "output": {"entities": {}}, "schema": []}
{"input": "Phylogenetic analyses using three methods (maximum parsimony, maximum likelihood, and Bayesian inference) produce a single, well resolved, and strongly corroborated hypothesis, which provides support for the three genera, with the exception that the genus Myuchelys is paraphyletic-Myuchelys purvisi is the sister taxon to the remaining Elseya, Myuchelys and Emydura.", "output": {"entities": {}}, "schema": []}
{"input": "A new genus is proposed for the species Myuchelys purvisi to address this paraphyletic relationship.", "output": {"entities": {}}, "schema": []}
{"input": "Time-calibration analysis suggests that diversification of the group in Australia coincides with periods of aridification in the late Eocene and between the mid-Miocene and early Pliocene.", "output": {"entities": {}}, "schema": []}
{"input": "Other speciation events occurred during the faunal exchange between Australia and the island of New Guinea during the late Miocene and early Pliocene.", "output": {"entities": {}}, "schema": []}
{"input": "Lineages distributed in New Guinea are likely influenced by the complex geologic history of the island, and include cryptic species diversity.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of pediatric reference levels of FT3, FT4 and TSH measured with ECLusys kits.", "output": {"entities": {}}, "schema": []}
{"input": "Reference ranges for serum thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in children were set using the assay kits currently used in clinical settings.", "output": {"entities": {"chemical": [{"text": "triiodothyronine", "start": 49, "end": 65}, {"text": "thyroxine", "start": 78, "end": 87}]}}, "schema": []}
{"input": "A total of 342 children (111 males and 231 females) who were negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonographic examination of the thyroid gland were divided into 6 age groups: 4-6 years (45 children), 7-8 years (40), 9-10 years (53), 11-12 years (65), 13-14 years (83), and 15 years (56) for the study.", "output": {"entities": {}}, "schema": []}
{"input": "FT3, FT4 and TSH levels were determined by electrochemiluminescence immunoassay (ECLIA) (ECLusys FT3, FT4 and TSH). The reference range for FT3 (pg/mL) was 2. 91-4. 70 for the age group of 4-6 years, 3. 10-5. 10 for the age group of 7-8 years, 3. 10-4. 87 for the age group of 9-10 years, 2. 78-4. 90 for the age group of 11-12 years, 2. 77-4. 59 for the age group of 13-14 years, and 2. 50-4. 64 for the age group of 15 years.", "output": {"entities": {}}, "schema": []}
{"input": "The reference range for FT4 (ng/dL) was 1. 12-1. 67, 1. 07-1. 61, 0. 96-1. 60, 1. 02-1. 52, 0. 96-1. 52, 0. 95-1. 53.", "output": {"entities": {}}, "schema": []}
{"input": "The reference range for TSH (mu U/mL) was 0. 62-4. 90, 0. 53-5. 16, 0. 67-4. 52, 0. 62-3. 36, 0. 54-2. 78, 0. 32-3. 00.", "output": {"entities": {}}, "schema": []}
{"input": "Serum FT3, FT4 and TSH levels in children differ from those in adults.", "output": {"entities": {}}, "schema": []}
{"input": "It is, therefore, of importance to perform evaluation of thyroid function in children using reference values appropriate for the chronological ages, because misdiagnosis of hypothyroidism or inappropriate secretion of TSH (SITSH) and oversight of mild subclinical hypothyroidism could occur if the diagnosis is made using reference values for adults.", "output": {"entities": {}}, "schema": []}
{"input": "Polybetaine modification of PDMS microfluidic devices to resist thrombus formation in whole blood.", "output": {"entities": {"chemical": [{"text": "PDMS", "start": 28, "end": 32}]}}, "schema": []}
{"input": "Assembled polydimethylsiloxane microfluidic devices were modified with a sulfobetaine polymer through continuous \" tip-to-tip \" modification, significantly reducing blood clotting and extending device patency under blood flow.", "output": {"entities": {"chemical": [{"text": "polydimethylsiloxane", "start": 10, "end": 30}, {"text": "sulfobetaine", "start": 73, "end": 85}]}}, "schema": []}
{"input": "This technology can be designed to enable the development of devices that can continuously work in whole blood, especially in an extracorporeal or in vivo environment.", "output": {"entities": {}}, "schema": []}
{"input": "Assessing triclosan-induced ecological and trans-generational effects in natural phytoplankton communities: a trait-based field method.", "output": {"entities": {"chemical": [{"text": "triclosan", "start": 10, "end": 19}]}}, "schema": []}
{"input": "We exposed replicated phytoplankton communities confined in semi-permeable membrane-based mesocosms to 0, 0. 1, 1 and 10 mu g L (-1) triclosan (TCS) and placed them back in their original environment to investigate the occurrence of trans-generational responses at individual, population and community levels.", "output": {"entities": {"chemical": [{"text": "triclosan", "start": 133, "end": 142}, {"text": "TCS", "start": 144, "end": 147}]}}, "schema": []}
{"input": "TCS diffused out of mesocosms with a half-life of less than 8 h, so that only the parental generation was directly stressed.", "output": {"entities": {"chemical": [{"text": "TCS", "start": 0, "end": 3}]}}, "schema": []}
{"input": "At the beginning of the experiment and after 7 days (approximately 2 generations) we analysed responses in the phytoplankton using scanning flow-cytometry.", "output": {"entities": {}}, "schema": []}
{"input": "We acquired information on several individually expressed phenotypic traits, such as size, biovolume, pigment fluorescence and packaging, for thousands of individuals per replicated population and derived population and community aggregated traits.", "output": {"entities": {}}, "schema": []}
{"input": "We found significant changes in community functioning (increased productivity in terms of biovolume and total fluorescence), with maximal effects at 1 mu g L (-1) TCS.", "output": {"entities": {"chemical": [{"text": "TCS", "start": 163, "end": 166}]}}, "schema": []}
{"input": "We detected significant and dose-dependent responses on population traits, such as changes in abundance for several populations, increased average size and fluorescence of cells, and strong changes in within-population trait mean and variance (suggesting micro-evolutionary effects).", "output": {"entities": {}}, "schema": []}
{"input": "We applied the Price equation approach to partition community effects (changes in biovolume or fluorescence) in their physiological and ecological components, and quantified the residual component (including also evolutionary responses).", "output": {"entities": {}}, "schema": []}
{"input": "Our results suggested that evolutionary or inheritable phenotypic plasticity responses may represent a significant component of the total observed change following exposure and over relatively small temporal scales.", "output": {"entities": {}}, "schema": []}
{"input": "Radiolabeled Heterobivalent Peptidic Ligands: an Approach with High Future Potential for in vivo Imaging and Therapy of Malignant Diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Two-pronged synergism: We review the recently developed approach of using heterobivalent peptide ligands that interact concomitantly with different receptors on tumor cells.", "output": {"entities": {}}, "schema": []}
{"input": "These ligands exhibit highly favorable tumor-targeting properties and pave the way for the development of drugs for specific, sensitive, and noninvasive tumor imaging and therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolic response demonstrated by 18F-FDG-PET/CT in metastatic medullary thyroid carcinoma under sorafenib therapy.", "output": {"entities": {"chemical": [{"text": "18F-FDG", "start": 35, "end": 42}, {"text": "sorafenib", "start": 98, "end": 107}]}}, "schema": []}
{"input": "A 51-year-old woman with a medullary thyroid carcinoma (MTC) presented with a palpable nodule in the right breast.", "output": {"entities": {}}, "schema": []}
{"input": "Serum calcitonin was 1, 453 pg/ml and carcinoembryonic antigen was 201 ng/ml.", "output": {"entities": {}}, "schema": []}
{"input": "Cervical ultrasound and bone scintigraphy were normal.", "output": {"entities": {}}, "schema": []}
{"input": "Computed tomography (CT) showed nodules in the right breast and anterior thoracic wall and a hypodense lesion in the right hepatic lobe.", "output": {"entities": {}}, "schema": []}
{"input": "Histology of the breast nodule confirmed metastasis from MTC.", "output": {"entities": {}}, "schema": []}
{"input": "To evaluate the metabolic activity of these lesions, 18F-fluorodeoxiglucose positron emission tomography-CT (FDG-PET/CT) scan was requested.", "output": {"entities": {"chemical": [{"text": "18F-fluorodeoxiglucose", "start": 53, "end": 75}, {"text": "FDG", "start": 109, "end": 112}]}}, "schema": []}
{"input": "Axial fused images revealed high FDG uptake by the breast and thoracic wall nodules and the right hepatic lobe.", "output": {"entities": {"chemical": [{"text": "FDG", "start": 33, "end": 36}]}}, "schema": []}
{"input": "FDG-PET/CT also showed uptake in sacrum and right iliac bone, undetected by CT and bone scintigraphy.", "output": {"entities": {"chemical": [{"text": "FDG", "start": 0, "end": 3}]}}, "schema": []}
{"input": "After seven cycles of sorafenib PET/CT became negative.", "output": {"entities": {"chemical": [{"text": "sorafenib", "start": 22, "end": 31}]}}, "schema": []}
{"input": "Calcitonin decreased to 82. 5.", "output": {"entities": {}}, "schema": []}
{"input": "A PET/CT performed 6 months later remained negative.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first published image of the complete metabolic response of MTC to sorafenib therapy using FDG-PET/CT.", "output": {"entities": {"chemical": [{"text": "sorafenib", "start": 79, "end": 88}, {"text": "FDG", "start": 103, "end": 106}]}}, "schema": []}
{"input": "Detection of Statin Cytotoxicity Is Increased in Cells Expressing the OATP1B1 Transporter.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxicity of a compound is determined by the intracellular concentration mediated both by passive permeability and active uptake through drug transporters.", "output": {"entities": {}}, "schema": []}
{"input": "However, the major liver uptake transporters were either absent or expressed at significantly lower levels in human liver cell lines than in human liver.", "output": {"entities": {}}, "schema": []}
{"input": "When comparing cytotoxicity of five statins, the organic anion transporting polypeptide 1B1 (OATP1B1) expressing HEK cells showed a significantly higher sensitivity than the wild-type HEK cells.", "output": {"entities": {}}, "schema": []}
{"input": "The IC50 shifts ranged from 9-to > 100-fold, and the potency shifts collapsed in the presence of rifampicin, the inhibitor for OATPs.", "output": {"entities": {"chemical": [{"text": "rifampicin", "start": 97, "end": 107}]}}, "schema": []}
{"input": "The extent of the IC50 shift correlated with the permeability of the statins with high permeable compounds having smaller shifts and low permeable compounds having larger shifts.", "output": {"entities": {}}, "schema": []}
{"input": "The changes in statin potency in transporter transfected cells reflect the active uptake of statins into the cells and the increased intracellular drug concentration lead to increased toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The data suggested that uptake transporters have a significant impact on the outcomes of a cell-based assay and should be considered during the early stages of compound toxicity screening in drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "For compounds with low permeability which are likely to undergo transporter-mediated uptake, it is important to test them in transporter-competent cell models.", "output": {"entities": {}}, "schema": []}
{"input": "Expression of a novel mRNA transcript for human microsomal epoxide hydrolase (EPHX1) is regulated by short open reading frames within its 5'-untranslated region.", "output": {"entities": {"chemical": [{"text": "epoxide", "start": 59, "end": 66}]}}, "schema": []}
{"input": "Microsomal epoxide hydrolase (mEH, EPHX1) is a critical xenobiotic-metabolizing enzyme, catalyzing both detoxification and bioactivation reactions that direct the disposition of chemical epoxides, including the carcinogenic metabolites of several polycyclic aromatic hydrocarbons.", "output": {"entities": {"chemical": [{"text": "epoxide", "start": 11, "end": 18}, {"text": "epoxides", "start": 187, "end": 195}, {"text": "polycyclic aromatic hydrocarbons", "start": 247, "end": 279}]}}, "schema": []}
{"input": "Recently, we discovered that a previously unrecognized and primate-specific EPHX1 transcript, termed E1-b, was actually the predominant driver of EPHX1 expression in all human tissues.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we identify another human EPHX1 transcript, designated as E1-b'.", "output": {"entities": {}}, "schema": []}
{"input": "Unusually, both the E1-b and E1-b' mRNA transcripts are generated from the use of a far upstream gene promoter, localized ~ 18. 5 kb 5'-upstream of the EPHX1 protein-coding region.", "output": {"entities": {}}, "schema": []}
{"input": "Although expressed at comparatively lower levels than E1-b, the novel E1-b' transcript is readily detected in all tissues examined, with highest levels maintained in human ovary.", "output": {"entities": {}}, "schema": []}
{"input": "The E1-b' mRNA possesses unusual functional features in its 5'-untranslated region, including a GC-rich leader sequence and two upstream AUGs that encode for short peptides of 26 and 17 amino acids in length, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Results from in vitro transcription/translation assays and direct transfection in mammalian cells of either the E1-b' transcript or the encoded peptides demonstrated that the E1-b' upstream open reading frames (uORFs) are functional, with their presence markedly inhibiting the translation of EPHX1 protein, both in cis and in trans configurations.", "output": {"entities": {}}, "schema": []}
{"input": "These unique uORF peptides exhibit no homology to any other known uORF sequences but likely function to mediate post-transcription regulation of EPHX1 and perhaps more broadly as translational regulators in human cells.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of Intraduodenal Glutamine on Incretin Hormone and Insulin Release, the Glycemic Response to an Intraduodenal Glucose Infusion, and Antropyloroduodenal Motility in Health and Type 2 Diabetes.", "output": {"entities": {"chemical": [{"text": "Glutamine", "start": 25, "end": 34}, {"text": "Glucose", "start": 118, "end": 125}]}}, "schema": []}
{"input": "OBJECTIVEGlutamine reduces postprandial glycemia when given before oral glucose.", "output": {"entities": {"chemical": [{"text": "OBJECTIVEGlutamine", "start": 0, "end": 18}, {"text": "glucose", "start": 72, "end": 79}]}}, "schema": []}
{"input": "We evaluated whether this is mediated by stimulation of insulin and/or slowing of gastric emptying. RESEARCH DESIGN AND METHODSTen healthy subjects were studied during intraduodenal (ID) infusion of glutamine (7. 5 or 15 g) or saline over 30 min, followed by glucose (75 g over 100 min), while recording antropyloroduodenal pressures.", "output": {"entities": {"chemical": [{"text": "glutamine", "start": 199, "end": 208}, {"text": "glucose", "start": 259, "end": 266}]}}, "schema": []}
{"input": "Ten patients with type 2 diabetes mellitus (T2DM) were also studied with 15 g glutamine or saline. RESULTSID glutamine stimulated glucagon-like peptide 1 (GLP-1; healthy: P < 0. 05; T2DM: P < 0. 05), glucose-dependent insulinotropic polypeptide (GIP; P = 0. 098; P < 0. 05), glucagon (P < 0. 01; P < 0. 001), insulin (P = 0. 05; P < 0. 01), and phasic pyloric pressures (P < 0. 05; P < 0. 05), but did not lower blood glucose (P = 0. 077; P = 0. 5). CONCLUSIONSGlutamine does not lower glycemia after ID glucose, despite stimulating GLP-1, GIP, and insulin, probably due to increased glucagon.", "output": {"entities": {"chemical": [{"text": "glutamine", "start": 78, "end": 87}, {"text": "glutamine", "start": 109, "end": 118}, {"text": "glucose", "start": 200, "end": 207}, {"text": "glucose", "start": 418, "end": 425}, {"text": "CONCLUSIONSGlutamine", "start": 450, "end": 470}, {"text": "glucose", "start": 504, "end": 511}]}}, "schema": []}
{"input": "Its capacity for pyloric stimulation suggests that delayed gastric emptying is a major mechanism for lowering glycemia when glutamine is given before oral glucose.", "output": {"entities": {"chemical": [{"text": "glutamine", "start": 124, "end": 133}, {"text": "glucose", "start": 155, "end": 162}]}}, "schema": []}
{"input": "Low-Carbohydrate Diet for the Treatment of Gestational Diabetes: A randomized controlled trial.", "output": {"entities": {"chemical": [{"text": "Carbohydrate", "start": 4, "end": 16}]}}, "schema": []}
{"input": "OBJECTIVEMedical nutrition therapy based on the control of the amount and distribution of carbohydrates (CHO) is the initial treatment for gestational diabetes mellitus (GDM), but there is a need for randomized controlled trials comparing different dietary strategies.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 90, "end": 103}, {"text": "CHO", "start": 105, "end": 108}]}}, "schema": []}
{"input": "The purpose of this study was to test the hypothesis that a low-CHO diet for the treatment of GDM would lead to a lower rate of insulin treatment with similar pregnancy outcomes compared with a control diet. RESEARCH DESIGN AND METHODSA total of 152 women with GDM were included in this open, randomized controlled trial and assigned to follow either a diet with low-CHO content (40% of the total diet energy content as CHO) or a control diet (55% of the total diet energy content as CHO).", "output": {"entities": {"chemical": [{"text": "CHO", "start": 64, "end": 67}, {"text": "CHO", "start": 367, "end": 370}, {"text": "CHO", "start": 420, "end": 423}, {"text": "CHO", "start": 484, "end": 487}]}}, "schema": []}
{"input": "CHO intake was assessed by 3-day food records.", "output": {"entities": {"chemical": [{"text": "CHO", "start": 0, "end": 3}]}}, "schema": []}
{"input": "The main pregnancy outcomes were also assessed. RESULTSThe rate of women requiring insulin was not significantly different between the treatment groups (low CHO 54. 7% vs. control 54. 7%; P = 1).", "output": {"entities": {"chemical": [{"text": "CHO", "start": 157, "end": 160}]}}, "schema": []}
{"input": "Daily food records confirmed a difference in the amount of CHO consumed between the groups (P = 0. 0001).", "output": {"entities": {"chemical": [{"text": "CHO", "start": 59, "end": 62}]}}, "schema": []}
{"input": "No differences were found in the obstetric and perinatal outcomes between the treatment groups. CONCLUSIONSTreatment of women with GDM using a low-CHO diet did not reduce the number of women needing insulin and produced similar pregnancy outcomes.", "output": {"entities": {"chemical": [{"text": "CHO", "start": 147, "end": 150}]}}, "schema": []}
{"input": "In GDM, CHO amount (40 vs. 55% of calories) did not influence insulin need or pregnancy outcomes.", "output": {"entities": {"chemical": [{"text": "CHO", "start": 8, "end": 11}]}}, "schema": []}
{"input": "Expansion of the Homeostasis Model Assessment of beta-Cell Function and Insulin Resistance to Enable Clinical Trial Outcome Modeling Through the Interactive Adjustment of Physiology and Treatment Effects--iHOMA2.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVETo describe and make available an interactive, 24-variable homeostasis model assessment (iHOMA2) that extends the HOMA2 model, enabling the modeling of physiology and treatment effects, to present equations of the HOMA2 and iHOMA2 models, and to exemplify iHOMA2 in two widely differing scenarios: changes in insulin sensitivity with thiazolidinediones and changes in renal threshold with sodium glucose transporter (SGLT2) inhibition. RESEARCH DESIGN AND METHODSiHOMA2 enables a user of the available software to examine and modify the mathematical functions describing the organs and tissues involved in the glucose and hormonal compartments.", "output": {"entities": {"chemical": [{"text": "thiazolidinediones", "start": 343, "end": 361}, {"text": "sodium glucose", "start": 398, "end": 412}, {"text": "glucose", "start": 619, "end": 626}]}}, "schema": []}
{"input": "We exemplify this with SGLT2 inhibition modeling (by changing the renal threshold parameters) using published data of renal effect, showing that the modeled effect is concordant with the effects on fasting glucose from independent data. RESULTSiHOMA2 modeling of thiazolidinediones effect suggested that changes in insulin sensitivity in the fasting state are predominantly hepatic.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 206, "end": 213}, {"text": "thiazolidinediones", "start": 263, "end": 281}]}}, "schema": []}
{"input": "SGLT2 inhibition modeled by iHOMA2 resulted in a decrease in mean glucose of 1. 1 mmol/L.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 66, "end": 73}]}}, "schema": []}
{"input": "Observed data showed a decrease in glucose of 0. 9 mmol/L.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 35, "end": 42}]}}, "schema": []}
{"input": "There was no significant difference between the model and the independent data.", "output": {"entities": {}}, "schema": []}
{"input": "Manipulation of iHOMA2s renal excretion threshold variable suggested that a decrease of 17% was required to obtain a 0. 9 mmol/L decrease in mean glucose. CONCLUSIONSiHOMA2 is an extended mathematical model for the assessment of insulin resistance and beta-cell function.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 146, "end": 153}]}}, "schema": []}
{"input": "The model can be used to evaluate therapeutic agents and predict effects on fasting glucose and insulin and on beta-cell function and insulin sensitivity.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 84, "end": 91}]}}, "schema": []}
{"input": "The C-terminus of Botulinum A Protease Has Profound and Unanticipated Kinetic Consequences Upon the Catalytic Cleft.", "output": {"entities": {}}, "schema": []}
{"input": "Botulinum neurotoxins (BoNTs) are among the most deadly poisons known though ironically, they also are of great therapeutic utility.", "output": {"entities": {}}, "schema": []}
{"input": "A number of research programs have been initiated to discover small molecule inhibitors of BoNTs metalloprotease activity.", "output": {"entities": {}}, "schema": []}
{"input": "Many, though not all of these programs have screened against a truncated and more stable form of the enzyme, that possess comparable catalytic properties to the full length enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, several classes of inhibitors notably the hydroxamates, display a large shift in potency between the two enzyme forms.", "output": {"entities": {"chemical": [{"text": "hydroxamates", "start": 57, "end": 69}]}}, "schema": []}
{"input": "In this report we compare the kinetics of active-site, alpha-exosite and beta-exosite inhibitors versus truncated and full length enzyme.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular dynamics simulations conducted with the truncated and homology models of the fully length BoNT LC/A indicate the flexibility of the C-terminus of the full length enzyme is responsible for the potency shifts of active-site proximally binding inhibitors while distal binding (alpha-exosite) inhibitors remain equipotent.", "output": {"entities": {}}, "schema": []}
{"input": "Human Precision-Cut Liver Slices as an ex Vivo Model to Study Idiosyncratic Drug-Induced Liver Injury.", "output": {"entities": {}}, "schema": []}
{"input": "Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings.", "output": {"entities": {}}, "schema": []}
{"input": "Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict IDILI in humans.", "output": {"entities": {}}, "schema": []}
{"input": "According to the inflammatory stress hypothesis, the effects of inflammation interact with the effects of a drug or its reactive metabolite, precipitating toxic reactions in the liver.", "output": {"entities": {}}, "schema": []}
{"input": "As a follow-up to our recently published mouse precision-cut liver slices model, an ex vivo model involving human precision-cut liver slices (hPCLS), co-incubated for 24 h with IDILI-related drugs and lipopolysaccharide (LPS), was developed to study IDILI mechanisms related to inflammatory stress in humans and to detect potential biomarkers.", "output": {"entities": {}}, "schema": []}
{"input": "LPS exacerbated the effects of ketoconazole and clozapine toxicity but not those of their non-IDILI-related comparators, voriconazole and olanzapine.", "output": {"entities": {"chemical": [{"text": "ketoconazole", "start": 31, "end": 43}, {"text": "clozapine", "start": 48, "end": 57}, {"text": "voriconazole", "start": 121, "end": 133}, {"text": "olanzapine", "start": 138, "end": 148}]}}, "schema": []}
{"input": "However, the IDILI-related drugs diclofenac, carbamazepine, and troglitazone did not show synergistic toxicity with LPS after incubation for 24 h.", "output": {"entities": {"chemical": [{"text": "diclofenac", "start": 33, "end": 43}, {"text": "carbamazepine", "start": 45, "end": 58}, {"text": "troglitazone", "start": 64, "end": 76}]}}, "schema": []}
{"input": "Co-incubation of ketoconazole and clozapine with LPS decreased the levels of glutathione in hPCLS, but this was not seen for the other drugs.", "output": {"entities": {"chemical": [{"text": "ketoconazole", "start": 17, "end": 29}, {"text": "clozapine", "start": 34, "end": 43}, {"text": "glutathione", "start": 77, "end": 88}]}}, "schema": []}
{"input": "All drugs affected LPS-induced cytokine release, but interestingly, only ketoconazole and clozapine increased the level of LPS-induced TNF release.", "output": {"entities": {"chemical": [{"text": "ketoconazole", "start": 73, "end": 85}, {"text": "clozapine", "start": 90, "end": 99}]}}, "schema": []}
{"input": "Decreased levels of glutathione and cysteine conjugates of clozapine were detected in IDILI-responding livers following cotreatment with LPS.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 20, "end": 31}, {"text": "cysteine", "start": 36, "end": 44}, {"text": "clozapine", "start": 59, "end": 68}]}}, "schema": []}
{"input": "In conclusion, we identified ketoconazole and clozapine as drugs that exhibited synergistic toxicity with LPS, while glutathione and TNF were found to be potential biomarkers for IDILI-inducing drugs mediated by inflammatory stress.", "output": {"entities": {"chemical": [{"text": "ketoconazole", "start": 29, "end": 41}, {"text": "clozapine", "start": 46, "end": 55}, {"text": "glutathione", "start": 117, "end": 128}]}}, "schema": []}
{"input": "hPCLS appear to be suitable for further unraveling the mechanisms of inflammatory stress-associated IDILI.", "output": {"entities": {}}, "schema": []}
{"input": "Controlling the Effective Surface Area and Pore Size Distribution of sp (2) Carbon Materials and Their Impact on the Capacitance Performance of These Materials.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 76, "end": 82}]}}, "schema": []}
{"input": "A series of sp (2) carbon materials with different specific surface area (SSA) and controlled pore size distribution (PSD) were synthesized at large scale through a facile and low-cost method.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 19, "end": 25}]}}, "schema": []}
{"input": "The SSA and PSD of these carbon materials were controlled by using different carbon sources and preparation methods.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 25, "end": 31}, {"text": "carbon", "start": 77, "end": 83}]}}, "schema": []}
{"input": "With different total and effective SSA (E-SSA) and PSD, the impacts on their capacitance performance were investigated thoroughly, which demonstrated that both E-SSA and PSD played the most important roles in their capacitance performance.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, theoretical modeling was performed, and the results are in agreement with the experimental results for the influence of E-SSA and PSD on their capacitance performance.", "output": {"entities": {}}, "schema": []}
{"input": "Based on these, a general model using the slit/cylindrical NL-DFT approach is proposed for the estimation of the specific capacitance of sp (2) carbon materials, which offers a simple but reliable method to predict the capacitance performance of these materials, thus speeding up the design and screening of the materials for high-performance supercapacitor and other surface area related devices.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 144, "end": 150}]}}, "schema": []}
{"input": "Approach to dark spin cooling in a diamond nanocrystal.", "output": {"entities": {"chemical": [{"text": "diamond", "start": 35, "end": 42}]}}, "schema": []}
{"input": "Using a Hartman-Hahn protocol, we demonstrate spin polarization transfer from a single, optically polarized nitrogen-vacancy (NV) center to the ensemble of paramagnetic defects hosted by an individual diamond nanocrystal.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 108, "end": 116}, {"text": "diamond", "start": 201, "end": 208}]}}, "schema": []}
{"input": "Owing to the strong NV-bath coupling, the transfer takes place on a short, microsecond time scale.", "output": {"entities": {}}, "schema": []}
{"input": "Upon fast repetition of the pulse sequence, we observe strong polarization transfer blockade, which we interpret as an indication of spin bath cooling.", "output": {"entities": {}}, "schema": []}
{"input": "Numerical simulations indicate that the spin bath polarization is nonuniform throughout the nanoparticle, averaging approximately 5% over the crystal volume, but reaching up to 25% in the immediate vicinity of the NV.", "output": {"entities": {}}, "schema": []}
{"input": "These observations may prove relevant to the planning of future bath-assisted magnetometry tests.", "output": {"entities": {}}, "schema": []}
{"input": "The role of intracrine androgen metabolism, androgen receptor and apoptosis in the survival and recurrence of prostate cancer during androgen deprivation therapy.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 23, "end": 31}, {"text": "androgen", "start": 44, "end": 52}, {"text": "androgen", "start": 133, "end": 141}]}}, "schema": []}
{"input": "Prostate cancer (CaP) is the most frequently diagnosed cancer and leading cause of cancer death in American men.", "output": {"entities": {}}, "schema": []}
{"input": "Almost all men present with advanced CaP and some men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT).", "output": {"entities": {"chemical": [{"text": "androgen", "start": 109, "end": 117}]}}, "schema": []}
{"input": "ADT is not curative and CaP recurs as the lethal phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "The goal of this review is to apply our current understanding of CaP and castration-recurrent CaP (CR-CaP) to earlier studies that characterized ADT and the molecular mechanisms that facilitate the transition from androgen-stimulated CaP to CR-CaP.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 214, "end": 222}]}}, "schema": []}
{"input": "Reexamination of earlier studies also may provide a better understanding of how more newly recognized mechanisms, such as intracrine metabolism, may be involved with the early events that allow CaP survival after initiation of ADT and subsequent development of CR-CaP.", "output": {"entities": {}}, "schema": []}
{"input": "Real-time evaluation of binding mechanisms in multivalent interactions: a surface plasmon resonance kinetic approach.", "output": {"entities": {}}, "schema": []}
{"input": "Multivalency is a key, ubiquitous phenomenon in nature characterized by a complex combination of binding mechanisms, with special relevance in carbohydrate-lectin recognition.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 143, "end": 155}]}}, "schema": []}
{"input": "Herein we introduce an original surface plasmon resonance kinetic approach to analyze multivalent interactions that has been validated with dendrimers as monodisperse multivalent analytes binding to lectin clusters.", "output": {"entities": {}}, "schema": []}
{"input": "The method, based on the analysis of early association and late dissociation phases of the sensorgrams provides robust information of the glycoconjugate binding efficiency and real-time structural data of the binding events under the complex scenario of the glyco-cluster effect.", "output": {"entities": {}}, "schema": []}
{"input": "Notably, it reveals the dynamic nature of the interaction and offers experimental evidence on the contribution of binding mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Enhancing Catalytic Performance of Palladium in Gold and Palladium Alloy Nanoparticles for Organic Synthesis Reactions through Visible Light Irradiation at Ambient Temperatures.", "output": {"entities": {"chemical": [{"text": "Palladium", "start": 35, "end": 44}, {"text": "Palladium", "start": 57, "end": 66}]}}, "schema": []}
{"input": "The intrinsic catalytic activity of palladium (Pd) is significantly enhanced in gold (Au)-Pd alloy nanoparticles (NPs) under visible light irradiation at ambient temperatures.", "output": {"entities": {"chemical": [{"text": "palladium", "start": 36, "end": 45}, {"text": "Pd", "start": 47, "end": 49}, {"text": "Au", "start": 86, "end": 88}, {"text": "Pd", "start": 90, "end": 92}]}}, "schema": []}
{"input": "The alloy NPs strongly absorb light and efficiently enhance the conversion of several reactions, including Suzuki-Miyaura cross coupling, oxidative addition of benzylamine, selective oxidation of aromatic alcohols to corresponding aldehydes and ketones, and phenol oxidation.", "output": {"entities": {"chemical": [{"text": "benzylamine", "start": 160, "end": 171}, {"text": "aromatic alcohols", "start": 196, "end": 213}, {"text": "aldehydes", "start": 231, "end": 240}, {"text": "ketones", "start": 245, "end": 252}, {"text": "phenol", "start": 258, "end": 264}]}}, "schema": []}
{"input": "The Au/Pd molar ratio of the alloy NPs has an important impact on performance of the catalysts since it determines both the electronic heterogeneity and the distribution of Pd sites at the NP surface, with these two factors playing key roles in the catalytic activity.", "output": {"entities": {"chemical": [{"text": "Au", "start": 4, "end": 6}, {"text": "Pd", "start": 7, "end": 9}, {"text": "Pd", "start": 173, "end": 175}]}}, "schema": []}
{"input": "Irradiating with light produces an even more profound enhancement in the catalytic performance of the NPs.", "output": {"entities": {}}, "schema": []}
{"input": "For example, the best conversion rate achieved thermally at 30 degrees C for Suzuki-Miyaura cross coupling was 37% at a Au/Pd ratio of 1: 1. 86, while under light illumination the yield increased to 96% under the same conditions.", "output": {"entities": {"chemical": [{"text": "Au", "start": 120, "end": 122}, {"text": "Pd", "start": 123, "end": 125}]}}, "schema": []}
{"input": "The catalytic activity of the alloy NPs depends on the intensity and wavelength of incident light.", "output": {"entities": {}}, "schema": []}
{"input": "Light absorption due to the Localized Surface Plasmon Resonance of gold nanocrystals plays an important role in enhancing catalyst performance.", "output": {"entities": {}}, "schema": []}
{"input": "We believe that the conduction electrons of the NPs gain the light absorbed energy producing energetic electrons at the surface Pd sites, which enhances the sites' intrinsic catalytic ability.", "output": {"entities": {"chemical": [{"text": "Pd", "start": 128, "end": 130}]}}, "schema": []}
{"input": "These findings provide useful guidelines for designing efficient catalysts composed of alloys of a plasmonic metal and a catalytically active transition metal for various organic syntheses driven by sunlight.", "output": {"entities": {"chemical": [{"text": "transition metal", "start": 142, "end": 158}]}}, "schema": []}
{"input": "Effects of Curcumin on Apoptosis and Oxidoinflammatory Regulation in a Rat Model of Acetic Acid-Induced Colitis: The Roles of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase.", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 11, "end": 19}, {"text": "Acetic Acid", "start": 84, "end": 95}, {"text": "N", "start": 132, "end": 133}]}}, "schema": []}
{"input": "Abstract The present study evaluated the effects of curcumin on epithelial cell apoptosis, the immunoreactivity of the phospho-c-Jun N-terminal kinase (JNK) and phospho-p38 mitogen-activated protein kinases (MAPKs) in inflamed colon mucosa, and oxidative stress in a rat model of ulcerative colitis induced by acetic acid.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 52, "end": 60}, {"text": "N", "start": 133, "end": 134}, {"text": "acetic acid", "start": 310, "end": 321}]}}, "schema": []}
{"input": "Rats were randomly divided into three groups: control, acetic acid, and acetic acid + curcumin.", "output": {"entities": {"chemical": [{"text": "acetic acid", "start": 55, "end": 66}, {"text": "acetic acid", "start": 72, "end": 83}, {"text": "curcumin", "start": 86, "end": 94}]}}, "schema": []}
{"input": "Curcumin (100 mg/kg per day, intragastrically) was administered 10 days before the induction of colitis and was continued for two additional days.", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Acetic acid-induced colitis caused a significant increase in the macroscopic and microscopic tissue ranking scores as well as an elevation in colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and the number of apoptotic epithelial cells in colon tissue compared to controls.", "output": {"entities": {"chemical": [{"text": "Acetic acid", "start": 0, "end": 11}, {"text": "malondialdehyde", "start": 182, "end": 197}, {"text": "MDA", "start": 199, "end": 202}]}}, "schema": []}
{"input": "In the rat colon, immunoreactivity of phospho-p38 MAPK was increased, whereas the phospho-JNK activity was decreased following the induction of colitis.", "output": {"entities": {}}, "schema": []}
{"input": "Curcumin treatment was associated with amelioration of macroscopic and microscopic colitis sores, decreased MPO activity, and decreased MDA levels in acetic acid-induced colitis.", "output": {"entities": {"chemical": [{"text": "Curcumin", "start": 0, "end": 8}, {"text": "MDA", "start": 136, "end": 139}, {"text": "acetic acid", "start": 150, "end": 161}]}}, "schema": []}
{"input": "Furthermore, oral curcumin supplementation clearly prevented programmed cell death and restored immunreactivity of MAPKs in the colons of colitic rats.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 18, "end": 26}]}}, "schema": []}
{"input": "The results of this study suggest that oral curcumin treatment decreases colon injury and is associated with decreased inflammatory reactions, lipid peroxidation, apoptotic cell death, and modulating p38-and JNK-MAPK pathways.", "output": {"entities": {"chemical": [{"text": "curcumin", "start": 44, "end": 52}]}}, "schema": []}
{"input": "Oligonol supplementation attenuates body temperature and the circulating levels of prostaglandin e2 and cyclooxygenase-2 after heat stress in humans.", "output": {"entities": {"chemical": [{"text": "prostaglandin e2", "start": 83, "end": 99}]}}, "schema": []}
{"input": "Abstract Oligonol, a phenolic production from lychee, has been reported to exhibit anti-oxidative and anti-inflammatory effects.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 21, "end": 29}]}}, "schema": []}
{"input": "This study investigated the effect of Oligonol supplementation on circulating levels of prostaglandin E2 (PGE2) and cyclooxygenase (COX)-2, as well as body temperature, after heat stress in 17 healthy human male volunteers (age, 21. 6 +/- 2. 1 years).", "output": {"entities": {"chemical": [{"text": "prostaglandin E2", "start": 88, "end": 104}, {"text": "PGE2", "start": 106, "end": 110}]}}, "schema": []}
{"input": "All experiments were performed in an automated climate chamber (26. 0 degrees C +/- 0. 5 degrees C, relative humidity 60% +/- 3. 0%, air velocity less than 1 m/sec) between 2 and 5 p. m.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects ingested an Oligonol (100 mg)-containing beverage or placebo beverage before half-body immersion into hot water (42 degrees C +/- 0. 5 degrees C for 30 min).", "output": {"entities": {}}, "schema": []}
{"input": "Tympanic and skin temperatures were measured and mean body temperatures were calculated.", "output": {"entities": {}}, "schema": []}
{"input": "Serum concentrations of PGE2 and COX-2 were analyzed before, immediately after, and 60 min after immersion.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 24, "end": 28}]}}, "schema": []}
{"input": "Oligonol intake significantly prevented elevation of tympanic (temperature difference: 0. 17 degrees C at Post, P <. 05; 0. 17 degrees C at Re-60, P <. 05) and mean body temperatures (temperature difference: 0. 18 degrees C at Post, P <. 05; 0. 15 degrees C at Re-60, P <. 05), and lowered concentrations of serum PGE2 (increased by 13. 3% vs. 29. 6% at Post, P <. 05) and COX-2 (increased by 15. 6% vs. 21. 8% at Post, P <. 05), compared to placebo beverage.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 314, "end": 318}]}}, "schema": []}
{"input": "Our result suggests that Oligonol has the potential to suppress increases in body temperature under heat stress, and this is associated with decreases in serum levels of PGE2 and COX-2.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 170, "end": 174}]}}, "schema": []}
{"input": "Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer.", "output": {"entities": {"chemical": [{"text": "enterolactone", "start": 17, "end": 30}]}}, "schema": []}
{"input": "Abstract Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B (NF kappa B) and vascular endothelial growth factor (VEGF).", "output": {"entities": {"chemical": [{"text": "Enterolactone", "start": 9, "end": 22}, {"text": "enterodiol", "start": 27, "end": 37}, {"text": "lignans", "start": 49, "end": 56}]}}, "schema": []}
{"input": "We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of NF kappa B, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for ~ 30 days.", "output": {"entities": {"chemical": [{"text": "enterolactone", "start": 45, "end": 58}, {"text": "enterodiol", "start": 63, "end": 73}]}}, "schema": []}
{"input": "Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively.", "output": {"entities": {"chemical": [{"text": "enterolignans", "start": 8, "end": 21}]}}, "schema": []}
{"input": "After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (rho = 0. 677, P <. 0001), enterolactone (rho = 0. 676, P <. 0001), and enterodiol (rho = 0. 628, P <. 0001).", "output": {"entities": {"chemical": [{"text": "lignan", "start": 85, "end": 91}, {"text": "enterolignans", "start": 128, "end": 141}, {"text": "enterolactone", "start": 169, "end": 182}, {"text": "enterodiol", "start": 214, "end": 224}]}}, "schema": []}
{"input": "Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (rho =-0. 217, P =. 011, and rho =-0. 230, P =. 007, respectively), and a near-significant inverse association was observed for enterodiol (rho =-0. 159, P =. 064).", "output": {"entities": {"chemical": [{"text": "enterolignans", "start": 44, "end": 57}, {"text": "enterolactone", "start": 62, "end": 75}, {"text": "enterodiol", "start": 278, "end": 288}]}}, "schema": []}
{"input": "An inverse association was observed between enterolactone and VEGF (rho =-0. 143, P =. 141), although this did not reach statistical significance.", "output": {"entities": {"chemical": [{"text": "enterolactone", "start": 44, "end": 57}]}}, "schema": []}
{"input": "We did not observe an association between enterolignans and NF kappa B.", "output": {"entities": {"chemical": [{"text": "enterolignans", "start": 42, "end": 55}]}}, "schema": []}
{"input": "In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.", "output": {"entities": {"chemical": [{"text": "enterolignans", "start": 32, "end": 45}]}}, "schema": []}
{"input": "Synthesis and structure-activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors.", "output": {"entities": {"chemical": [{"text": "2-amino-3-carboxy-4-phenylthiophenes", "start": 50, "end": 86}]}}, "schema": []}
{"input": "Recent evidence suggests atypical protein kinase C (aPKC) isoforms are required for both TNF-and VEGF-induced breakdown of the blood-retinal barrier (BRB) and endothelial permeability to 70kDa dextran or albumin.", "output": {"entities": {"chemical": [{"text": "retinal", "start": 133, "end": 140}]}}, "schema": []}
{"input": "A chemical library screen revealed a series of novel small molecule phenylthiophene based inhibitors of aPKC isoforms that effectively block permeability in cell culture and in vivo.", "output": {"entities": {"chemical": [{"text": "phenylthiophene", "start": 68, "end": 83}]}}, "schema": []}
{"input": "In an effort to further elucidate the structural requirements of this series of inhibitors, we detail in this study a structure-activity relationship (SAR) built on screening hit 1, which expands on our initial pharmacophore model.", "output": {"entities": {}}, "schema": []}
{"input": "The biological activity of our analogues was evaluated in models of bona fide aPKC-dependent signaling including NF kappa B driven-gene transcription as a marker for an inflammatory response and VEGF/TNF-induced vascular endothelial permeability.", "output": {"entities": {}}, "schema": []}
{"input": "The EC50 for the most efficacious inhibitors (6, 32) was in the low nanomolar range in these two cellular assays.", "output": {"entities": {}}, "schema": []}
{"input": "Our study demonstrates the key structural elements that confer inhibitory activity and highlights the requirement for electron-donating moieties off the C-4 aryl moiety of the 2-amino-3-carboxy-4-phenylthiophene backbone.", "output": {"entities": {"chemical": [{"text": "2-amino-3-carboxy-4-phenylthiophene", "start": 176, "end": 211}]}}, "schema": []}
{"input": "These studies suggest that this class has potential for further development into small molecule aPKC inhibitors with therapeutic efficacy in a host of diseases involving increased vascular permeability and inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, cytotoxicity and topoisomerase II inhibitory activity of lomefloxacin derivatives.", "output": {"entities": {"chemical": [{"text": "lomefloxacin", "start": 68, "end": 80}]}}, "schema": []}
{"input": "A novel series of amide derivatives of lomefloxacin were synthesized and evaluated for their topoisomerase I and II inhibitory activity as well as cytotoxicity against a panel of five human cancer cell lines.", "output": {"entities": {"chemical": [{"text": "amide", "start": 18, "end": 23}, {"text": "lomefloxacin", "start": 39, "end": 51}]}}, "schema": []}
{"input": "Of the compounds prepared compounds 9d and 9g exhibited strong inhibition against topoisomerase II at 100 mu M.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, docking studies were performed to predict the inhibition mode.", "output": {"entities": {}}, "schema": []}
{"input": "Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression.", "output": {"entities": {"chemical": [{"text": "Tomatidine", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Tomatidine is an aglycone of glycoalkaloid tomatine in tomato.", "output": {"entities": {"chemical": [{"text": "Tomatidine", "start": 0, "end": 10}, {"text": "tomatine", "start": 43, "end": 51}]}}, "schema": []}
{"input": "Tomatidine is found to possess anti-inflammatory properties and may serve as a chemosensitizer in multidrug-resistant tumor cells.", "output": {"entities": {"chemical": [{"text": "Tomatidine", "start": 0, "end": 10}]}}, "schema": []}
{"input": "However, the effect of tomatidine on cancer cell metastasis remains unclear.", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 23, "end": 33}]}}, "schema": []}
{"input": "This study examines the effect of tomatidine on the migration and invasion of human lung adenocarcinoma A549 cell in vitro.", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 34, "end": 44}]}}, "schema": []}
{"input": "The data demonstrates that tomatidine does not effectively inhibit the viability of A549 cells.", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 27, "end": 37}]}}, "schema": []}
{"input": "When treated with non-toxic doses of tomatidine, cell invasion is markedly suppressed by Boyden chamber invasion assay, while cell migration is not affected.", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 37, "end": 47}]}}, "schema": []}
{"input": "Tomatidine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1).", "output": {"entities": {"chemical": [{"text": "Tomatidine", "start": 0, "end": 10}, {"text": "cysteine", "start": 130, "end": 138}]}}, "schema": []}
{"input": "The immunoblotting assays indicate that tomatidine is very effective in suppressing the phosphorylation of Akt and extracellular signal regulating kinase (ERK).", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 40, "end": 50}]}}, "schema": []}
{"input": "In addition, tomatidine significantly decreases the nuclear level of nuclear factor kappa B (NF-kappa B), which suggests that tomatidine inhibits NF-kappa B activity.", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 13, "end": 23}, {"text": "tomatidine", "start": 126, "end": 136}]}}, "schema": []}
{"input": "Furthermore, the treatment of inhibitors specific for PI3K/Akt (LY294002), ERK (U0126), or NF-kappa B (pyrrolidine dithiocarbamate) to A549 cells reduced cell invasion and MMP-2/9 expression.", "output": {"entities": {"chemical": [{"text": "LY294002", "start": 64, "end": 72}, {"text": "U0126", "start": 80, "end": 85}, {"text": "pyrrolidine dithiocarbamate", "start": 103, "end": 130}]}}, "schema": []}
{"input": "The results suggest that tomatidine inhibits the invasion of A549 cells by reducing the expression of MMPs.", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 25, "end": 35}]}}, "schema": []}
{"input": "It also inhibits ERK and Akt signaling pathways and NF-kappa B activity.", "output": {"entities": {}}, "schema": []}
{"input": "These findings demonstrate a new therapeutic potential for tomatidine in anti-metastatic therapy.", "output": {"entities": {"chemical": [{"text": "tomatidine", "start": 59, "end": 69}]}}, "schema": []}
{"input": "Phylogenetic relationship among genera of Polymorphidae (Acanthocephala), inferred from nuclear and mitochondrial gene sequences.", "output": {"entities": {}}, "schema": []}
{"input": "Acanthocephalans of the family Polymorphidae Meyer, 1931 are obligate endoparasites with complex life cycles.", "output": {"entities": {}}, "schema": []}
{"input": "These worms use vertebrates (marine mammals, fish-eating birds and waterfowl) as definitive hosts and invertebrates (amphipods, decapods and euphausiids) as intermediate hosts to complete their life cycle.", "output": {"entities": {}}, "schema": []}
{"input": "Polymorphidae has a wordwide distribution, containing 12 genera, with approximately 127 species.", "output": {"entities": {}}, "schema": []}
{"input": "The family is diagnosed by having a spinose trunk, bulbose proboscis, double-walled proboscis receptacle, and usually four to eight tubular cement glands.", "output": {"entities": {}}, "schema": []}
{"input": "To conduct a phylogenetic analysis, in the current study sequences of the small (18S) and large-subunit (28S) ribosomal RNA, and cytochrome c oxidase subunit 1 (cox 1) were generated for 27 taxa representing 10 of 12 genera of Polymorphidae, plus three additional species of acanthocephalans that were used as outgroups.", "output": {"entities": {}}, "schema": []}
{"input": "Maximum likelihood (ML), maximum parsimony (MP), and Bayesian analyses were conducted on a combined nuclear rRNA (18S + 28S) data set and on a concatenated dataset of nuclear plus one mitochondrial gene (18S + 28S + cox 1).", "output": {"entities": {}}, "schema": []}
{"input": "Phylogenetic analyses inferred with the concatenated dataset of three genes support the monophyly of nine genera (Andracantha, Corynosoma, Bolbosoma, Profilicollis, Pseudocorynosoma, Southwellina, Arhythmorhynchus, Hexaglandula and Ibirhynchus).", "output": {"entities": {}}, "schema": []}
{"input": "However, the four sampled species of Polymorphus were nested within several clades, indicating that these species do not share a common ancestor, requiring further taxonomic revision using phylogenetic systematics, and reexamination of morphological and ecological data.", "output": {"entities": {}}, "schema": []}
{"input": "By mapping definitive and intermediate host association onto the resulting cladogram, we observe that aquatic birds were the ancestral definitive hosts for the family with a secondary colonization and diversification to marine mammals.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas amphipods were ancestral intermediate hosts and that the association with decapods represent episodes of secondary colonization that arose several times during the evolutionary history of the family.", "output": {"entities": {}}, "schema": []}
{"input": "Our results are useful to start testing hypothesis about the evolutionary history of this highly diverse family of acanthocephalans.", "output": {"entities": {}}, "schema": []}
{"input": "The influence of Bauhinia forficata Link subsp. pruinosa tea on lipid peroxidation and non-protein SH groups in human erythrocytes exposed to high glucose concentrations.", "output": {"entities": {"chemical": [{"text": "SH", "start": 99, "end": 101}, {"text": "glucose", "start": 147, "end": 154}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia forficata (BF) has been traditionally used as tea in folk medicine of Brazil for treatment of Diabetes mellitus (DM).", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: To evaluate the effects of BF leaf tea on markers of oxidative damage and antioxidant levels in an experimental model of hyperglycemia in human erythrocytes in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Human erythrocytes were incubated with high glucose concentrations or glucose and BF tea for 24h and 48h.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 67, "end": 74}, {"text": "glucose", "start": 93, "end": 100}]}}, "schema": []}
{"input": "After incubation lipid peroxidation and non-protein SH levels were analyzed.", "output": {"entities": {"chemical": [{"text": "SH", "start": 52, "end": 54}]}}, "schema": []}
{"input": "Moreover, quantification of polyphenols and flavonoids, iron chelating property, scavenging of DPPH, and prevention of lipid peroxidation in isolated lipids were also assessed.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 28, "end": 39}, {"text": "flavonoids", "start": 44, "end": 54}, {"text": "iron", "start": 56, "end": 60}, {"text": "DPPH", "start": 95, "end": 99}]}}, "schema": []}
{"input": "RESULTS: A significant amount of polyphenols and flavonoids was observed.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 33, "end": 44}, {"text": "flavonoids", "start": 49, "end": 59}]}}, "schema": []}
{"input": "The main components found by LC-MS analysis were quercetin-3-O-(2-rhamnosyl) rutinoside, kaempferol-3-O-(2-rhamnosyl) rutinoside, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside.", "output": {"entities": {"chemical": [{"text": "quercetin-3-O-(2-rhamnosyl) rutinoside", "start": 49, "end": 87}, {"text": "kaempferol-3-O-(2-rhamnosyl) rutinoside", "start": 89, "end": 128}, {"text": "quercetin-3-O-rutinoside", "start": 130, "end": 154}, {"text": "kaempferol-3-O-rutinoside", "start": 159, "end": 184}]}}, "schema": []}
{"input": "BF tea presents important antioxidant and chelating properties.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, BF tea was effective to increase non-protein SH levels and reduce lipid peroxidation induced by high glucose concentrations in human erythrocytes.", "output": {"entities": {"chemical": [{"text": "SH", "start": 55, "end": 57}, {"text": "glucose", "start": 111, "end": 118}]}}, "schema": []}
{"input": "CONCLUSION: The antioxidant effects of BF tea could be related to the presence of different phenolic and flavonoids components.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 92, "end": 100}, {"text": "flavonoids", "start": 105, "end": 115}]}}, "schema": []}
{"input": "We believe that these components can be responsible to protect human erythrocytes exposed to high glucose concentrations against oxidative damage.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 98, "end": 105}]}}, "schema": []}
{"input": "In vitro and in vivo anti-diabetic activity of Swertia kouitchensis extract.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Swertia kouitchensis has long been used as a folk medicine to treat hepatitis and diabetes in central-western China.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, this study was aimed to evaluate the anti-diabetic activity of the plant ethanol extract.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 84, "end": 91}]}}, "schema": []}
{"input": "MATERIALS AND METHODS: Firstly, the extract was tested for its inhibitory activity on alpha-amylase and alpha-glucosidase in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Following that, insulin secretion test in NIT-1cell was performed.", "output": {"entities": {}}, "schema": []}
{"input": "Then, oral sucrose or starch tolerance test of the extract were carried out in normal mice.", "output": {"entities": {}}, "schema": []}
{"input": "After that, acute effect of the extract was executed in normal and streptozotocin-induced (60mg/kg) diabetic mice.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 67, "end": 81}]}}, "schema": []}
{"input": "Eventually, long term effect of the extract was performed in diabetic mice for 4 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Oral glucose tolerance test and biochemical parameters were estimated at the end of the study.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 5, "end": 12}]}}, "schema": []}
{"input": "RESULTS: Swertia kouitchensis extract could remarkably inhibit the activity of alpha-amylase and alpha-glucosidase and stimulate insulin secretion in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "And also the extract displayed anti-hyperglycemic activity, improved antioxidant capacity, ameliorated the hyperlipidemia and carbohydrate metabolism in diabetic mice.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 126, "end": 138}]}}, "schema": []}
{"input": "CONCLUSIONS: Swertia kouitchensis exhibits considerable anti-diabetic activity and metabolic alterations in diabetic mice.", "output": {"entities": {}}, "schema": []}
{"input": "These results provide a rationale for the use of Swertia kouitchensis to treat diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Safety assessment of the standardized extract of Carissa edulis root bark in rats.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Preparations of Carissa edulis (Vahl) have been used in the Nigerian traditional medicine for the management of fever, sickle cell disease, epilepsy, pain and inflammation for many years and their efficacy is widely acclaimed among the Hausa communities of northern Nigeria.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: The present studies aimed at evaluating the toxicological properties of the standardized ethanol extract of C. edulis root bark in rats, in order to determine its safety and to complement earlier efficacy studies on this widely used medicinal plant.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 107, "end": 114}]}}, "schema": []}
{"input": "MATERIALS AND METHODS: High performance liquid chromatography (HPLC) and preliminary phytochemical analysis of the extract were conducted and its oral median lethal dose (LD50) determined.", "output": {"entities": {}}, "schema": []}
{"input": "Signs of toxicity, body weight changes, relative organs weight, feed and water consumption were monitored following 28 days of daily oral administration of graded doses of the extract in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of the extract on sex hormones, low-and high-density lipids, hematological and biochemical parameters were examined and pathological changes of the vital organs after treatment with the extract were also investigated.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The oral LD50 of the extract was estimated to be > 5000mg/kg.", "output": {"entities": {}}, "schema": []}
{"input": "The body weights of treated rats increased progressively, but the changes were not significantly different from the control groups.", "output": {"entities": {}}, "schema": []}
{"input": "The extract neither produces significant changes in feed and water consumption nor affected the relative organs weight.", "output": {"entities": {}}, "schema": []}
{"input": "Although some variations were observed in hormonal and lipid profiles hematological and biochemical indices, these important parameters were normal and within acceptable limits.", "output": {"entities": {}}, "schema": []}
{"input": "No lesions or pathological changes of the organs attributable to treatment with the extract were observed from the pathological examinations.", "output": {"entities": {}}, "schema": []}
{"input": "The HPLC fingerprint of the extract shows a spectrum profile characteristic of C. edulis, while the preliminary phytochemical screening revealed the presence of saponins, flavonoids, tannins, anthraquinones and cardiac glycosides.", "output": {"entities": {"chemical": [{"text": "saponins", "start": 161, "end": 169}, {"text": "flavonoids", "start": 171, "end": 181}, {"text": "tannins", "start": 183, "end": 190}, {"text": "anthraquinones", "start": 192, "end": 206}]}}, "schema": []}
{"input": "CONCLUSION: Our results provided evidence that short-term administration of the standardized ethanol extract of C. edulis root bark at doses lower than 1000mg/kg is safe in rats and may not exert severe toxic effects.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 93, "end": 100}]}}, "schema": []}
{"input": "Identification of microcystins in a Lake Victoria cyanobacterial bloom using LC-MS with thiol derivatization.", "output": {"entities": {"chemical": [{"text": "microcystins", "start": 18, "end": 30}, {"text": "thiol", "start": 88, "end": 93}]}}, "schema": []}
{"input": "Microcystins are cyclic heptapeptides from cyanobacteria which are responsible for poisonings of livestock and humans.", "output": {"entities": {"chemical": [{"text": "Microcystins", "start": 0, "end": 12}, {"text": "cyclic heptapeptides", "start": 17, "end": 37}]}}, "schema": []}
{"input": "Cyanobacteria also produce a range of peptides and other compounds that can result in complex chromatograms when samples are analysed by LC-MS.", "output": {"entities": {}}, "schema": []}
{"input": "Thiol derivatization of the alpha, beta-unsaturated amide present in most microcystins was recently shown to simplify analysis of LC-MS chromatograms of a Microcystis culture, making it easier to identify peaks corresponding to microcystins in complex mixtures.", "output": {"entities": {"chemical": [{"text": "Thiol", "start": 0, "end": 5}, {"text": "alpha, beta-unsaturated amide", "start": 28, "end": 57}, {"text": "microcystins", "start": 74, "end": 86}, {"text": "microcystins", "start": 228, "end": 240}]}}, "schema": []}
{"input": "This method was applied to analysis of extracts taken from a natural cyanobacteria bloom in Mwanza Gulf, Lake Victoria, Tanzania, in 2010, revealing the presence of numerous putative microcystin analogues in the sample.", "output": {"entities": {"chemical": [{"text": "microcystin", "start": 183, "end": 194}]}}, "schema": []}
{"input": "Results were verified using LC-MS (2), LC-MS/MS with precursor-ion scanning, and LC-HRMS, leading to identification of 8 major and 17 minor microcystins in the sample, including analogues of microcystin-RY,-RL and-RA.", "output": {"entities": {"chemical": [{"text": "microcystins", "start": 140, "end": 152}, {"text": "microcystin-RY,-RL and-RA", "start": 191, "end": 216}]}}, "schema": []}
{"input": "Microcystin-YR (2),-RR (3), and-RY (9) were isolated from bloom material from Lake Victoria, and the structure of 9 was confirmed by NMR spectroscopic analysis and NMR spectral comparison with 2 and 3.", "output": {"entities": {"chemical": [{"text": "Microcystin-YR (2),-RR (3), and-RY (9)", "start": 0, "end": 38}]}}, "schema": []}
{"input": "Confirmation of the structure of MC-RY (9) facilitated detailed analysis of its MS (2) spectrum, thereby supporting the structures of related analogues tentatively established on the basis of MS analyses.", "output": {"entities": {"chemical": [{"text": "MC-RY", "start": 33, "end": 38}]}}, "schema": []}
{"input": "Intra-articular drug delivery from an optimized topical patch containing teriflunomide and lornoxicam for rheumatoid arthritis treatment: Does the topical patch really enhance a local treatment?", "output": {"entities": {"chemical": [{"text": "teriflunomide", "start": 73, "end": 86}, {"text": "lornoxicam", "start": 91, "end": 101}]}}, "schema": []}
{"input": "Patients with rheumatoid arthritis (RA) often bear joint destruction and symptomatic pain.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this work is to develop a compound transdermal patch containing teriflunomide (TEF) and lornoxicam (LOX) to transport these drugs across the skin with the isochronous permeation rates for RA therapy and investigate intra-articular delivery of TEF and LOX following transdermal patches applied topically.", "output": {"entities": {"chemical": [{"text": "teriflunomide", "start": 75, "end": 88}, {"text": "TEF", "start": 90, "end": 93}, {"text": "lornoxicam", "start": 99, "end": 109}, {"text": "LOX", "start": 111, "end": 114}, {"text": "TEF", "start": 254, "end": 257}, {"text": "LOX", "start": 262, "end": 265}]}}, "schema": []}
{"input": "The salts of TEF and LOX with organic amines diethylamine (DEtA), triethylamine (TEtA), diethanolamine (DEA), triethanolamine (TEA) and N-(2'-hydroxy-ethanol)-piperdine (NP) were prepared to improve the skin permeation of the parent drug.", "output": {"entities": {"chemical": [{"text": "TEF", "start": 13, "end": 16}, {"text": "LOX", "start": 21, "end": 24}, {"text": "organic amines diethylamine", "start": 30, "end": 57}, {"text": "DEtA", "start": 59, "end": 63}, {"text": "triethylamine", "start": 66, "end": 79}, {"text": "TEtA", "start": 81, "end": 85}, {"text": "diethanolamine", "start": 88, "end": 102}, {"text": "DEA", "start": 104, "end": 107}, {"text": "triethanolamine", "start": 110, "end": 125}, {"text": "TEA", "start": 127, "end": 130}, {"text": "N-(2'-hydroxy-ethanol)-piperdine", "start": 136, "end": 168}]}}, "schema": []}
{"input": "The optimized patch formulation is obtained from a 3-factor, 2-level central composite design.", "output": {"entities": {}}, "schema": []}
{"input": "After topical application of the optimized compound patch to only one knee joint in rabbit, intra-articular delivery of TEF and LOX on the application site was compared with that on the non-application site.", "output": {"entities": {"chemical": [{"text": "TEF", "start": 120, "end": 123}, {"text": "LOX", "start": 128, "end": 131}]}}, "schema": []}
{"input": "Anti-inflammatory and analgesic effects of the optimized compound patch were evaluated using the adjuvant arthritis model and the pain model induced by acetic acid, respectively.", "output": {"entities": {"chemical": [{"text": "acetic acid", "start": 152, "end": 163}]}}, "schema": []}
{"input": "The in vitro experiment results showed that the amine salts of TEF and LOX, especially TEF-TEtA and LOX-TEtA, enhanced the skin permeation of TEF and LOX from the transdermal patch system.", "output": {"entities": {"chemical": [{"text": "amine salts", "start": 48, "end": 59}, {"text": "TEF", "start": 63, "end": 66}, {"text": "LOX", "start": 71, "end": 74}, {"text": "TEF-TEtA", "start": 87, "end": 95}, {"text": "LOX-TEtA", "start": 100, "end": 108}, {"text": "TEF", "start": 142, "end": 145}, {"text": "LOX", "start": 150, "end": 153}]}}, "schema": []}
{"input": "The optimal formulation successfully displayed isochronous permeation rates for TEF and LOX across rabbit skin, and was defined with 5% of TEF-TEtA, 10% of LOX-TEtA and 15% of azone.", "output": {"entities": {"chemical": [{"text": "TEF", "start": 80, "end": 83}, {"text": "LOX", "start": 88, "end": 91}, {"text": "TEF-TEtA", "start": 139, "end": 147}, {"text": "LOX-TEtA", "start": 156, "end": 164}]}}, "schema": []}
{"input": "The in vivo study showed that TEF and LOX from transdermal patches were transferred into skin, ligament and fat pad on the application site by direct diffusion and on the non-application site by the redistribution of systemic blood supply, while local absorption of TEF and LOX in synovial fluid originated from the systemic blood supply rather than direct diffusion.", "output": {"entities": {"chemical": [{"text": "TEF", "start": 30, "end": 33}, {"text": "LOX", "start": 38, "end": 41}, {"text": "TEF", "start": 266, "end": 269}, {"text": "LOX", "start": 274, "end": 277}]}}, "schema": []}
{"input": "In the RA rat model, the results of swelling inhibition on primary arthritis of bilateral hind paws further confirmed the above-mentioned point.", "output": {"entities": {}}, "schema": []}
{"input": "The optimal formulation displayed a double response on joint inflammation and symptomatic pain.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, although transdermal administration applied topically can provide a local enhanced drug delivery for the superficial joint tissues by direct diffusion, it seemed unlikely to do that for the deeper tissue synovial fluid.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of UVB-induced skin phototoxicity by a grape seed extract as modulator of nitrosative stress, ERK/NF-kB signaling pathway and apoptosis, in SKH-1 mice.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular mechanisms concerning the modulation of nitrosative stress, signal transduction and proliferation/apoptosis by a grape seed extract, Burgund Mare variety (BM), in SKH-1 mice exposed to UVB, were investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The animals were irradiated with single and multiple doses of UVB in 10 consecutive days.", "output": {"entities": {}}, "schema": []}
{"input": "In each experiment were used five groups of animals: control, vehicle, UVB irradiated, vehicle + UVB, BM + UVB.", "output": {"entities": {}}, "schema": []}
{"input": "The extract was applied topically, 30min before each UVB exposure, in a dose of 4mg total polyphenols/cm (2).", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 90, "end": 101}]}}, "schema": []}
{"input": "BM remarkably inhibited UVB-induced activation of inducible nitric oxide synthase (iNOS) and therefore generation of nitric oxide (NO) and nitrotyrosine, in a UVB single dose regimen.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 60, "end": 72}, {"text": "nitric oxide", "start": 117, "end": 129}, {"text": "NO", "start": 131, "end": 133}, {"text": "nitrotyrosine", "start": 139, "end": 152}]}}, "schema": []}
{"input": "BM also suppressed NF-kB activation by UVB but did not affect the activity of total ERK 1/2.", "output": {"entities": {}}, "schema": []}
{"input": "In multiple UVB irradiations, BM increased NO formation and total ERK 1/2 activity and reduced iNOS activity and nitrotyrosine levels, inhibited cell proliferation, diminished p53 and caspase-3 immunoreactivities and increased the percentage of Bcl-2 positive cells.", "output": {"entities": {"chemical": [{"text": "NO", "start": 43, "end": 45}, {"text": "nitrotyrosine", "start": 113, "end": 126}]}}, "schema": []}
{"input": "We concluded that BM modulates the apoptotic response of SKH-1 mice skin in UVB irradiation by the inhibition of p53, caspase-3, Bax/Bcl-2 and proliferating cell nuclear antigen expressions, as well as by reducing the activation of iNOS and NF-kB.", "output": {"entities": {}}, "schema": []}
{"input": "Neonatal exposure to lipopolysaccharide enhances accumulation of alpha-synuclein aggregation and dopamine transporter protein expression in the substantia nigra in responses to rotenone challenge in later life.", "output": {"entities": {"chemical": [{"text": "dopamine", "start": 97, "end": 105}, {"text": "rotenone", "start": 177, "end": 185}]}}, "schema": []}
{"input": "Brain inflammation in early life may enhance adult susceptibility to develop neurodegenerative disorders triggered by environmental toxins.", "output": {"entities": {}}, "schema": []}
{"input": "Our previous studies show that perinatal lipopolysaccharide (LPS) exposure enhances adult susceptibility to rotenone-induced injury to the dopaminergic system in the substantia nigra (SN) of the adult rat brain.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 108, "end": 116}]}}, "schema": []}
{"input": "To further investigate the enhanced adult susceptibility by neonatal LPS exposure to rotenone neurotoxicity, we used our neonatal rat model of LPS exposure (1mg/kg, intracerebral injection in postnatal day 5, P5, neonatal rats) to examine the protein levels of alpha-synuclein and dopamine transporters (DAT) in the adult rat.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 85, "end": 93}, {"text": "dopamine", "start": 281, "end": 289}]}}, "schema": []}
{"input": "By P70, rats from the saline-or LPS-exposed group were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1. 25mg/kg/day for 14 days.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 71, "end": 79}]}}, "schema": []}
{"input": "The accumulation of alpha-synuclein aggregation and increment of DAT protein content were found in the SN of LPS-exposed rats.", "output": {"entities": {}}, "schema": []}
{"input": "Neonatal LPS exposure enhanced rotenone-stimulated accumulation of alpha-synuclein aggregation and increment in DAT protein expression in the cytoplasmic compartment of the SN, and in the synaptosomal compartment of the striatum of adult rats.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 31, "end": 39}]}}, "schema": []}
{"input": "Rotenone treatment also resulted in reduction of [(3) H] dopamine uptake and mitochondrial complex I activity in the striatum of rats with neonatal LPS exposure, but not in those without this exposure.", "output": {"entities": {"chemical": [{"text": "Rotenone", "start": 0, "end": 8}, {"text": "[(3) H] dopamine", "start": 49, "end": 65}]}}, "schema": []}
{"input": "The current study suggests possible roles of alpha-synuclein aggregate and DAT distribution in the cytoplasm and synaptosome triggered by environmental toxins in later life in the development of neurodegenerative disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Our model may be useful in studying mechanisms involved in the pathogenesis of nonfamilial Parkinson' s disease and for developing potential therapeutic treatments for this disease.", "output": {"entities": {}}, "schema": []}
{"input": "Lyophilization of a triply unsaturated phospholipid: Effects of trace metal contaminants.", "output": {"entities": {}}, "schema": []}
{"input": "As liquid liposomal formulations are prone to chemical degradation and aggregation, these formulations often require freeze drying (e. g., lyophilization) to achieve sufficient shelf-life.", "output": {"entities": {}}, "schema": []}
{"input": "However, liposomal formulations may undergo oxidation during lyophilization and/or during prolonged storage.", "output": {"entities": {}}, "schema": []}
{"input": "The goal of the current study was to characterize the degradation of 1, 2-dilinolenoyl-sn-glycero-3-phosphocholine (DLPC) during lyophilization and to also probe the influence of metal contaminants in promoting the observed degradation.", "output": {"entities": {"chemical": [{"text": "1, 2-dilinolenoyl-sn-glycero-3-phosphocholine", "start": 69, "end": 114}, {"text": "DLPC", "start": 116, "end": 120}]}}, "schema": []}
{"input": "Aqueous sugar formulations containing DLPC (0. 01mg/ml) were lyophilized, and DLPC degradation was monitored using HPLC/UV and GC/MS methods.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 8, "end": 13}, {"text": "DLPC", "start": 38, "end": 42}, {"text": "DLPC", "start": 78, "end": 82}]}}, "schema": []}
{"input": "The effect of ferrous ion and sucrose concentration, as well as lyophilization stage promoting lipid degradation, was investigated.", "output": {"entities": {"chemical": [{"text": "ferrous", "start": 14, "end": 21}, {"text": "sucrose", "start": 30, "end": 37}]}}, "schema": []}
{"input": "DLPC degradation increased with higher levels of ferrous ion.", "output": {"entities": {"chemical": [{"text": "DLPC", "start": 0, "end": 4}, {"text": "ferrous", "start": 49, "end": 56}]}}, "schema": []}
{"input": "After lyophilization, 103. 1 +/- 1. 1%, 66. 9 +/- 0. 8%, and 28. 7 +/- 0. 7% DLPC remained in the sucrose samples spiked with 0. 0ppm, 0. 2ppm, and 1. 0ppm ferrous ion, respectively.", "output": {"entities": {"chemical": [{"text": "DLPC", "start": 77, "end": 81}, {"text": "sucrose", "start": 98, "end": 105}, {"text": "ferrous", "start": 156, "end": 163}]}}, "schema": []}
{"input": "Lipid degradation predominantly occurs during the freezing stage of lyophilization.", "output": {"entities": {}}, "schema": []}
{"input": "Sugar concentration and buffer ionic strength also influence the extent of lipid degradation, and DLPC loss correlated with degradation product formation.", "output": {"entities": {"chemical": [{"text": "Sugar", "start": 0, "end": 5}, {"text": "DLPC", "start": 98, "end": 102}]}}, "schema": []}
{"input": "We conclude that DLPC oxidation during the freezing stage of lyophilization dramatically compromises the stability of lipid-based formulations.", "output": {"entities": {"chemical": [{"text": "DLPC", "start": 17, "end": 21}]}}, "schema": []}
{"input": "In addition, we demonstrate that metal contaminants in sugars can become highly active when lyophilized in the presence of a reducing agent.", "output": {"entities": {"chemical": [{"text": "sugars", "start": 55, "end": 61}]}}, "schema": []}
{"input": "The cyclin D1 (CCND1) rs9344 G > A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy.", "output": {"entities": {"chemical": [{"text": "5-FU", "start": 121, "end": 125}]}}, "schema": []}
{"input": "Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated the effect of cyclin D1 (CCND1) rs9344 G > A in stage II/III colon cancer patients and validated the findings in an independent study cohort.", "output": {"entities": {}}, "schema": []}
{"input": "For evaluation and validation set, a total of 264 and 234 patients were included.", "output": {"entities": {}}, "schema": []}
{"input": "Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2. 47; 95% confidence interval (CI) 1. 16-5. 29; P = 0. 019).", "output": {"entities": {"chemical": [{"text": "5-fluorouracil", "start": 22, "end": 36}]}}, "schema": []}
{"input": "There was no significant association between CCND1 rs9344 G > A and TTR in patients with curative surgery alone.", "output": {"entities": {}}, "schema": []}
{"input": "In the validation set, the A allele of CCND1 rs9344 G > A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1. 94; 95% CI 1. 05-3. 58; P = 0. 035).", "output": {"entities": {}}, "schema": []}
{"input": "CCND1 rs9344 G > A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings. The Pharmacogenomics Journal advance online publication, 9 April 2013; doi: 10. 1038/tpj. 2013. 15.", "output": {"entities": {}}, "schema": []}
{"input": "DNA-binding, photocleavage, cytotoxicity in vitro, apoptosis and cell cycle arrest studies of symmetric ruthenium (II) complexes.", "output": {"entities": {"chemical": [{"text": "ruthenium (II)", "start": 104, "end": 118}]}}, "schema": []}
{"input": "Two novel ruthenium (II) complexes [Ru (dmb) 2 (addppn)] (ClO4) 2 (1) and [Ru (bpy) 2 (addppn)] (ClO4) 2 (2) were synthesized.", "output": {"entities": {"chemical": [{"text": "ruthenium (II)", "start": 10, "end": 24}, {"text": "[Ru (dmb) 2 (addppn)] (ClO4) 2", "start": 35, "end": 65}, {"text": "[Ru (bpy) 2 (addppn)] (ClO4) 2", "start": 74, "end": 104}]}}, "schema": []}
{"input": "The DNA-binding constants of complexes 1 and 2 were determined to be 4. 78 (+/- 0. 49) x 10 (5) and 7. 42 (+/- 0. 53) x 10 (5) M (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that complexes 1 and 2 interact with CT DNA through intercalative mode.", "output": {"entities": {}}, "schema": []}
{"input": "The cytotoxicity in vitro of the complexes toward BEL-7402, HeLa, MG-63 and SKBR-3 cells was assessed by MTT assay.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 105, "end": 108}]}}, "schema": []}
{"input": "The apoptosis was carried out with Hoechst 33258 staining method and flow cytometry.", "output": {"entities": {"chemical": [{"text": "Hoechst 33258", "start": 35, "end": 48}]}}, "schema": []}
{"input": "The cellular uptake was observed under fluorescence microscope.", "output": {"entities": {}}, "schema": []}
{"input": "The cell cycle arrest shows that the antiproliferative mechanism induced by complexes 1 and 2 on BEL-7402 cells is G0/G1 phase arrest.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of novel 1, 3, 4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.", "output": {"entities": {"chemical": [{"text": "1, 3, 4-trisubstituted pyrazoles", "start": 19, "end": 51}]}}, "schema": []}
{"input": "Some novel 1, 3, 4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability.", "output": {"entities": {"chemical": [{"text": "1, 3, 4-trisubstituted pyrazoles", "start": 11, "end": 43}]}}, "schema": []}
{"input": "They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone.", "output": {"entities": {"chemical": [{"text": "phenylbutazone", "start": 104, "end": 118}]}}, "schema": []}
{"input": "In addition, IC50 values for 5e and 8e were recorded.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of the antioxidant properties of differently substituted 2-and 3-indolyl carbohydrazides and related derivatives.", "output": {"entities": {"chemical": [{"text": "2-and 3-indolyl carbohydrazides", "start": 66, "end": 97}]}}, "schema": []}
{"input": "Herein, we report the antioxidant properties of some selected substituted 2-indolyl carbohydrazides (JL34, JL40, JL71, JL87, JL317, JL432, JL436), the substituted 3-indolyl carbohydrazide JL344, 3-(3-hydrazinylpropyl)-1H-indole (JL72) and 3-(1H-indol-3-yl) propanehydrazide (JL418), throughout the assessment of their antioxidative potential using different antioxidant assays such as DPPH, lipid peroxidation in the APPH, or the DMSO method.", "output": {"entities": {"chemical": [{"text": "2-indolyl carbohydrazides", "start": 74, "end": 99}, {"text": "JL34", "start": 101, "end": 105}, {"text": "JL40", "start": 107, "end": 111}, {"text": "JL71", "start": 113, "end": 117}, {"text": "JL87", "start": 119, "end": 123}, {"text": "JL317", "start": 125, "end": 130}, {"text": "JL432", "start": 132, "end": 137}, {"text": "JL436", "start": 139, "end": 144}, {"text": "3-indolyl carbohydrazide JL344", "start": 163, "end": 193}, {"text": "3-(3-hydrazinylpropyl)-1H-indole", "start": 195, "end": 227}, {"text": "JL72", "start": 229, "end": 233}, {"text": "3-(1H-indol-3-yl) propanehydrazide", "start": 239, "end": 273}, {"text": "JL418", "start": 275, "end": 280}, {"text": "DPPH", "start": 385, "end": 389}, {"text": "DMSO", "start": 430, "end": 434}]}}, "schema": []}
{"input": "We conclude that these compounds are convenient templates for the design of useful drugs in to treat Alzheimer' s disease (AD), a pathology characterized by extensive oxidative stress and inflammation, thus essentially affected by reactive oxygen species (ROS).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 240, "end": 246}]}}, "schema": []}
{"input": "Most of them are potent hydroxyl radical scavengers and inhibit in vitro lipid peroxidation.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Compounds JL40 and JL432 presenting higher lipoxygenase inhibitory activity among the tested derivatives, were found to present a promising anti-inflammatory in vivo result, as well as antioxidant and LOX inhibitory profile.", "output": {"entities": {"chemical": [{"text": "JL40", "start": 10, "end": 14}, {"text": "JL432", "start": 19, "end": 24}]}}, "schema": []}
{"input": "These results in combination to their known AChE/BuChE inhibitory activities led us to propose these indolyl carbohydrazides as new multifunctional compounds against AD.", "output": {"entities": {"chemical": [{"text": "indolyl carbohydrazides", "start": 101, "end": 124}]}}, "schema": []}
{"input": "Biological evaluation of bisbenzaldehydes against four Mycobacterium species.", "output": {"entities": {"chemical": [{"text": "bisbenzaldehydes", "start": 25, "end": 41}]}}, "schema": []}
{"input": "A series of bisbenzaldehydes and structurally related analogs, conveniently synthesized via microwave-assisted reactions, were evaluated in vitro against drug susceptible and multi-drug resistant Mycobacterium tuberculosis, against virulent Mycobacterium bovis, against Mycobacterium ulcerans and against two Mycobacterium avium subspecies.", "output": {"entities": {"chemical": [{"text": "bisbenzaldehydes", "start": 12, "end": 28}]}}, "schema": []}
{"input": "Among the 33 substances that were tested, compound 12, i. e. 4, 4'-[1, 12-dodecanediyl (oxy)] bisbenzaldehyde, emerged as the most promising hit.", "output": {"entities": {"chemical": [{"text": "4, 4'-[1, 12-dodecanediyl (oxy)] bisbenzaldehyde", "start": 61, "end": 109}]}}, "schema": []}
{"input": "Its activity was further confirmed in an intracellular growth inhibition assay of M. tb in murine J774 A. 1 macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "None of the compounds showed significant cytotoxicity on human C3A hepatocytes in a neutral red dye uptake assay and no genotoxicity or mutagenicity was observed as demonstrated by a VITOTOX (TM) test and confirmed with a comet assay.", "output": {"entities": {"chemical": [{"text": "neutral red", "start": 84, "end": 95}]}}, "schema": []}
{"input": "Small-molecule regulators of autophagy and their potential therapeutic applications.", "output": {"entities": {}}, "schema": []}
{"input": "Autophagy is a highly conserved process in which damaged proteins and organelles are sequestered in double-membrane autophagosomes and delivered to lysosomes for degradation and recycling.", "output": {"entities": {}}, "schema": []}
{"input": "As an efficient response to cellular stress, autophagy is essential for the maintenance of cellular homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Defective autophagy is associated with a variety of diseases, including cancer.", "output": {"entities": {}}, "schema": []}
{"input": "This article summarizes current knowledge about the molecular mechanism of autophagy and its role in tumorigenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Particular focus is placed on the development of small-molecule regulators of autophagy and their potential application as anticancer therapeutic agents.", "output": {"entities": {}}, "schema": []}
{"input": "Thin films: organic vapor passivation of silicon at room temperature (adv. Mater. 14/2013).", "output": {"entities": {"chemical": [{"text": "silicon", "start": 41, "end": 48}]}}, "schema": []}
{"input": "Initiated chemical vapor deposition is used to achieve air-stable organic passivation of silicon, as reported by Karen K. Gleason and co-workers on page 2078.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 89, "end": 96}]}}, "schema": []}
{"input": "This layer also functions as an anti-reflection coating.", "output": {"entities": {}}, "schema": []}
{"input": "Resistively heated wires produce reactive gas phase species, including methyl radicals, while the silicon surface below remains near room temperature.", "output": {"entities": {"chemical": [{"text": "methyl", "start": 71, "end": 77}, {"text": "silicon", "start": 98, "end": 105}]}}, "schema": []}
{"input": "Photoshop enhanced image by Felice C. Frankel.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclic AMP responsive element binding protein-a vital link in embryonic hormonal adaptation.", "output": {"entities": {"chemical": [{"text": "Cyclic AMP", "start": 0, "end": 10}]}}, "schema": []}
{"input": "The transcription factor cyclic AMP responsive element binding protein (CREB) and activating transcription factors (ATFs) are downstream components of the insulin/IGF cascade, playing crucial roles in maintaining cell viability and embryo survival.", "output": {"entities": {"chemical": [{"text": "cyclic AMP", "start": 25, "end": 35}]}}, "schema": []}
{"input": "One of the CREB target genes is adiponectin which acts synergistically with insulin.", "output": {"entities": {}}, "schema": []}
{"input": "We have studied the CREB-ATF-adiponectin network in rabbit preimplantation development in vivo and in vitro. From the blastocyst stage onwards CREB and ATF1, 3 and 4 are present with increasing expression for CREB, ATF1 and 3 during gastrulation and with a dominant expression in the embryoblast (EB).", "output": {"entities": {}}, "schema": []}
{"input": "In vitro stimulation with insulin and IGF1 reduced CREB and ATF1 transcripts by approx. 50%, while CREB phosphorylation was increased.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of CREB was accompanied by subsequent reduction in adiponectin and adiponectin receptor 1 (adipoR1) expression. Under in vivo conditions of diabetes type 1, maternal adiponectin levels were up-regulated in serum and endometrium.", "output": {"entities": {}}, "schema": []}
{"input": "Embryonic CREB expression was altered in a cell lineage-specific pattern.", "output": {"entities": {}}, "schema": []}
{"input": "While in EB cells CREB localization did not change, it was translocated from the nucleus into the cytosol in trophoblast (TB) cells.", "output": {"entities": {}}, "schema": []}
{"input": "In TB adiponectin expression was increased [diabetic 427. 8 +/- 59. 3 pg/ml versus normoinsulinaemic 143. 9 +/- 26. 5 pg/ml], while it was no longer measureable in the EB.", "output": {"entities": {}}, "schema": []}
{"input": "Analysis of embryonic adiponectin receptors showed an increased expression of adipoR1 and no changes in adipoR2 transcription. We conclude that the transcription factors CREB and ATFs vitally participate in embryo-maternal crosstalk prior to implantation in a cell lineage-specific manner.", "output": {"entities": {}}, "schema": []}
{"input": "Embryonic CREB/ATFs act as insulin/IGF sensors.", "output": {"entities": {}}, "schema": []}
{"input": "Lack of insulin is compensated by a CREB-mediated adiponectin expression which may maintain glucose uptake in blastocysts grown in diabetic mothers.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 92, "end": 99}]}}, "schema": []}
{"input": "Highly Stretchable Patterned Gold Electrodes Made of Au Nanosheets.", "output": {"entities": {"chemical": [{"text": "Au", "start": 53, "end": 55}]}}, "schema": []}
{"input": "Multilayered Au nanosheets are suggested as a novel class of material for fabricating stretchable electrodes suitable for organic-based electronic devices.", "output": {"entities": {"chemical": [{"text": "Au", "start": 13, "end": 15}]}}, "schema": []}
{"input": "The electrodes show no difference in resistivity during repeated stretching cycles up to epsilon = 40%.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of Topical Application of Chlorogenic Acid on Excision Wound Healing in Rats.", "output": {"entities": {"chemical": [{"text": "Chlorogenic Acid", "start": 33, "end": 49}]}}, "schema": []}
{"input": "This study was undertaken to evaluate the therapeutic effects of topical chlorogenic acid on excision wounds in Wistar rats.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 73, "end": 89}]}}, "schema": []}
{"input": "A 1% (w/w) chlorogenic acid or silver sulfadiazine ointment was applied topically once a day for 15 days on full-thickness excision wounds created on rats.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 11, "end": 27}, {"text": "silver sulfadiazine", "start": 31, "end": 50}]}}, "schema": []}
{"input": "The 1% (w/w) chlorogenic acid ointment had potent wound healing capacity as evident from the wound contraction on the 15th post-surgery day, which was similar to that produced by 1% (w/w) silver sulfadiazine ointment.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 13, "end": 29}, {"text": "silver sulfadiazine", "start": 188, "end": 207}]}}, "schema": []}
{"input": "Increased rates of epithelialization were observed in the treated rats.", "output": {"entities": {}}, "schema": []}
{"input": "It also improved cellular proliferation, increased tumor necrosis factor-alpha levels during the inflammatory phase (12 h, 24 h, 48 h, and 72 h post-wounding) of wound healing, upregulated transforming growth factor-beta 1 and elevated collagen IV synthesis in the chlorogenic acid-treated group.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 265, "end": 281}]}}, "schema": []}
{"input": "The results also indicated that chlorogenic acid possesses potent antioxidant activity by increasing superoxide dismutase, catalase, and glutathione, and decreasing lipid peroxidation.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 32, "end": 48}, {"text": "superoxide", "start": 101, "end": 111}, {"text": "glutathione", "start": 137, "end": 148}]}}, "schema": []}
{"input": "In conclusion, these results demonstrate that topical application of chlorogenic acid can accelerate the process of excision wound healing by its ability to increase collagen synthesis through upregulation of key players such as tumor necrosis factor-alpha and transforming growth factor-beta 1 in different phases of wound healing as well as by its antioxidant potential.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 69, "end": 85}]}}, "schema": []}
{"input": "Signaling mechanism of tumor cell-induced up-regulation of E3 ubiquitin ligase UBR2.", "output": {"entities": {}}, "schema": []}
{"input": "The N-end rule pathway contributes significantly to accelerated muscle proteolysis mediated by the ubiquitin-proteasome pathway in various catabolic conditions.", "output": {"entities": {"chemical": [{"text": "N", "start": 4, "end": 5}]}}, "schema": []}
{"input": "UBR2 (aka E3 alpha-II) is the only known E3 ubiquitin ligase of the N-end rule pathway that is up-regulated by cachectic stimuli including proinflammatory cytokines and tumors.", "output": {"entities": {"chemical": [{"text": "N", "start": 68, "end": 69}]}}, "schema": []}
{"input": "However, the signaling mechanism through which UBR2 is up-regulated remains undetermined.", "output": {"entities": {}}, "schema": []}
{"input": "Here we identify a signaling pathway that mediates tumor cell-induced up-regulation of UBR2.", "output": {"entities": {}}, "schema": []}
{"input": "UBR2 expression in C2C12 myotubes was up-regulated by conditioned medium from Lewis lung carcinoma cells or C26 colon adenocarcinoma cells, which was blocked by a pharmacological inhibitor of p38 alpha/beta mitogen-activated protein kinase (MAPK), SB202190.", "output": {"entities": {"chemical": [{"text": "SB202190", "start": 248, "end": 256}]}}, "schema": []}
{"input": "Similarly, SB202190 administration (i. p.) abolished UBR2 up-regulation in the tibialis anterior of LLC tumor-bearing mice.", "output": {"entities": {"chemical": [{"text": "SB202190", "start": 11, "end": 19}]}}, "schema": []}
{"input": "Genetic gain and loss of function assays in C2C12 myotubes indicated that tumor-induced activation of the p38 beta isoform is sufficient and necessary for UBR2 up-regulation.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, UBR2 up-regulation required p38 beta-mediated phosphorylation of CCAAT/enhancer binding protein (C/EBP)-beta Thr-188, which was critical to C/EBP beta binding to the UBR2 promoter.", "output": {"entities": {"chemical": [{"text": "Thr", "start": 122, "end": 125}]}}, "schema": []}
{"input": "Furthermore, luciferase reporter assay revealed that the C/EBP beta binding motif in the UBR2 promoter is a functional C/EBP beta-responsive cis-element that enhances the promoter activity on activation by p38 beta.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, genetic ablation of C/EBP beta blocked UBR2 up-regulation in LLC tumor-bearing mice.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that UBR2 up-regulation in cachectic muscle is mediated by the p38 beta-C/EBP beta signaling pathway responsible for the bulk of tumor-induced muscle proteolysis.-Zhang, G., Lin, R.-K., Kwon, Y.", "output": {"entities": {}}, "schema": []}
{"input": "T., Li, Y.-P.", "output": {"entities": {}}, "schema": []}
{"input": "Signaling mechanism of tumor cell-induced up-regulation of E3 ubiquitin ligase UBR2.", "output": {"entities": {}}, "schema": []}
{"input": "Minor Compensatory Changes in SAGE Mdr1a (P-gp), Bcrp, and Mrp2 Knockout Rats do not Detract from their General Utility in the Study of Transporter-mediated Pharmacokinetics.", "output": {"entities": {}}, "schema": []}
{"input": "Mdr1a-, Bcrp-, and Mrp2-knockout rats are a more practical species for ADME studies than murine models and previously demonstrated expected alterations in pharmacokinetics of various probe substrates.", "output": {"entities": {}}, "schema": []}
{"input": "At present, gene expression and pathology changes were systematically studied in small intestine, liver, kidney, and brain tissue from male SAGE Mdr1a-, Bcrp-, and Mrp2-knockout rats versus wild-type Sprague Dawley controls.", "output": {"entities": {}}, "schema": []}
{"input": "Gene expression data supported the relevant knockout genotype.", "output": {"entities": {}}, "schema": []}
{"input": "As expected, Mrp2-knockout rats were hyperbilirubinemic and exhibited upregulation of hepatic Mrp3.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, few alterations were observed within 112 ADME-relevant genes.", "output": {"entities": {}}, "schema": []}
{"input": "The two potentially most consequential changes were upregulation of intestinal carboxylesterase in Mdr1a-knockouts and catechol-O-methyltransferase in all tissues of Bcrp-knockout rats.", "output": {"entities": {"chemical": [{"text": "catechol", "start": 119, "end": 127}, {"text": "O", "start": 128, "end": 129}]}}, "schema": []}
{"input": "Previously reported upregulation of hepatic Mdr1b P-glycoprotein in proprietary Wistar Mdr1a-knockout rats was not observed in the SAGE counterpart investigated herein.", "output": {"entities": {}}, "schema": []}
{"input": "Relative liver and kidney weights were 22-53% higher in all three knockouts, with microscopic increases in hepatocyte size in Mdr1a-and Mrp2-knockout rats, and glomerular size in Bcrp-and Mrp2-knockouts.", "output": {"entities": {}}, "schema": []}
{"input": "Increased relative weight of clearing organs is quantitatively consistent with reported increases in clearance of drugs that are not substrates of the knocked-out transporter.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, SAGE knockout rats demonstrated modest compensatory changes, which do not preclude their general application to study transporter-mediated pharmacokinetics.", "output": {"entities": {}}, "schema": []}
{"input": "However, until future studies elucidate the magnitude of functional change, caution is warranted in rare instances of extensive metabolism by catechol-O-methyltransferase in Bcrp-knockouts and intestinal carboxylesterase in Mdr1a-knockout rats, specifically for molecules with free catechol groups and esters subject to gut wall hydrolysis.", "output": {"entities": {"chemical": [{"text": "catechol", "start": 142, "end": 150}, {"text": "O", "start": 151, "end": 152}, {"text": "catechol", "start": 282, "end": 290}]}}, "schema": []}
{"input": "Structural and functional characterization of a phosphatase domain within yeast general transcription factor TFIIIC.", "output": {"entities": {}}, "schema": []}
{"input": "Saccharomyces cerevisiae tau 55, a subunit of the RNA polymerase III-specific general transcription factor TFIIIC, comprises an N-terminal histidine phosphatase domain (tau 55-HPD) whose catalytic activity and cellular function is poorly understood.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 139, "end": 148}]}}, "schema": []}
{"input": "We solved the crystal structures of tau 55-HPD and its closely related paralogue Huf and used in silico docking methods to identify phospho-serine and phospho-tyrosine containing peptides as possible substrates that were subsequently validated using in vitro phosphatase assays.", "output": {"entities": {"chemical": [{"text": "phospho-serine", "start": 132, "end": 146}, {"text": "phospho-tyrosine", "start": 151, "end": 167}]}}, "schema": []}
{"input": "A comparative phospho-proteomic study identified additional phosphopeptides as possible targets, which show the involvement of these two phosphatases in the regulation of a variety of cellular functions.", "output": {"entities": {"chemical": [{"text": "phospho", "start": 14, "end": 21}]}}, "schema": []}
{"input": "Our results identify tau 55-HPD and Huf as bona fide protein phosphatases, characterize their substrate specificities and provide a small set of regulated phosphosite targets in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Adenine-DNA Adducts Derived from the Highly Tumorigenic Dibenzo [a, l] pyrene Are Resistant to Nucleotide Excision Repair while Guanine Adducts Are Not.", "output": {"entities": {"chemical": [{"text": "Adenine", "start": 0, "end": 7}, {"text": "Dibenzo [a, l] pyrene", "start": 56, "end": 77}, {"text": "Nucleotide", "start": 95, "end": 105}, {"text": "Guanine", "start": 128, "end": 135}]}}, "schema": []}
{"input": "The structural origins of differences in susceptibilities of various DNA lesions to nucleotide excision repair (NER) are poorly understood.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 84, "end": 94}]}}, "schema": []}
{"input": "Here we compared, in the same sequence context, the relative NER dual incision efficiencies elicited by two stereochemically distinct pairs of guanine (N (2)-dG) and adenine (N (6)-dA) DNA lesions, derived from enantiomeric genotoxic diol epoxides of the highly tumorigenic fjord region polycyclic aromatic hydrocarbon dibenzo [a, l] pyrene (DB [a, l] P).", "output": {"entities": {"chemical": [{"text": "guanine", "start": 143, "end": 150}, {"text": "adenine", "start": 166, "end": 173}, {"text": "diol epoxides", "start": 234, "end": 247}, {"text": "dibenzo [a, l] pyrene", "start": 319, "end": 340}, {"text": "DB [a, l] P", "start": 342, "end": 353}]}}, "schema": []}
{"input": "Remarkably, in cell-free HeLa cell extracts, the guanine adduct with R absolute chemistry at the N (2)-dG linkage site is ~ 35 times more susceptible to NER dual incisions than the stereochemically identical N (6)-dA adduct.", "output": {"entities": {"chemical": [{"text": "guanine", "start": 49, "end": 56}]}}, "schema": []}
{"input": "For the guanine and adenine adducts with S stereochemistry, a similar but somewhat smaller effect (factor of ~ 15) is observed.", "output": {"entities": {"chemical": [{"text": "guanine", "start": 8, "end": 15}, {"text": "adenine", "start": 20, "end": 27}]}}, "schema": []}
{"input": "The striking resistance of the bulky N (6)-dA in contrast to the modest to good susceptibilities of the N (2)-dG adducts to NER is interpreted in terms of the balance between lesion-induced DNA distorting and DNA stabilizing van der Waals interactions in their structures, that are partly reflected in the overall thermal stabilities of the modified duplexes.", "output": {"entities": {}}, "schema": []}
{"input": "Our results are consistent with the hypothesis that the high genotoxic activity of DB [a, l] P is related to the formation of NER-resistant and persistent DB [a, l] P-derived adenine adducts in cellular DNA.", "output": {"entities": {"chemical": [{"text": "DB [a, l] P", "start": 83, "end": 94}, {"text": "DB [a, l] P", "start": 155, "end": 166}, {"text": "adenine", "start": 175, "end": 182}]}}, "schema": []}
{"input": "Reactions of Hydrocarbon Radicals and Biradicals.", "output": {"entities": {"chemical": [{"text": "Hydrocarbon Radicals and Biradicals", "start": 13, "end": 48}]}}, "schema": []}
{"input": "Experimental measurements of the rate coefficients for several types of gas phase radical reactions are reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "They include radical isomerization and dissociation, radical + radical association, and unimolecular reactions of peroxy radicals.", "output": {"entities": {"chemical": [{"text": "peroxy", "start": 114, "end": 120}]}}, "schema": []}
{"input": "Some reactions of methylene in its lowest singlet state are also considered.", "output": {"entities": {"chemical": [{"text": "methylene", "start": 18, "end": 27}]}}, "schema": []}
{"input": "The links to theories of chemical reaction rates and especially of capture rates for radical + radical reactions are examined.", "output": {"entities": {}}, "schema": []}
{"input": "Many of the reactions involve formation of adducts, which can isomerize and dissociate.", "output": {"entities": {}}, "schema": []}
{"input": "Such reactions frequently involve energy distributions of the adducts that are far from Boltzmann, and the interpretation of measurements requires the use of master equation techniques.", "output": {"entities": {}}, "schema": []}
{"input": "The basis of these methods and the use of matrix diagonalization and eigenvector/eigenvalue analysis to extract phenomenological rate coefficients are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "The relevance of the measurements to applications in atmospheric chemistry and, especially, in combustion is briefly considered.", "output": {"entities": {}}, "schema": []}
{"input": "Ion impacts on graphene/ir (111): interface channeling, vacancy funnels, and a nanomesh.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 15, "end": 23}, {"text": "ir (111)", "start": 24, "end": 32}]}}, "schema": []}
{"input": "By combining ion beam experiments and atomistic simulations we study the production of defects in graphene on Ir (111) under grazing incidence of low energy Xe ions.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 98, "end": 106}, {"text": "Ir (111)", "start": 110, "end": 118}, {"text": "Xe", "start": 157, "end": 159}]}}, "schema": []}
{"input": "We demonstrate that the ions are channeled in between graphene and the substrate, giving rise to chains of vacancy clusters with their edges bending down toward the substrate.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 54, "end": 62}]}}, "schema": []}
{"input": "These clusters self-organize to a graphene nanomesh via thermally activated diffusion as their formation energy varies within the graphene moir e supercell.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 34, "end": 42}, {"text": "graphene", "start": 130, "end": 138}]}}, "schema": []}
{"input": "A facile strategy to design zeolite L crystals with tunable morphology and surface architecture.", "output": {"entities": {"chemical": [{"text": "zeolite L", "start": 28, "end": 37}]}}, "schema": []}
{"input": "Tailoring the anisotropic growth rates of materials to achieve desired structural outcomes is a pervasive challenge in synthetic crystallization.", "output": {"entities": {}}, "schema": []}
{"input": "Here we discuss a method to selectively control the growth of zeolite crystals, which are used extensively in a wide range of industrial applications.", "output": {"entities": {"chemical": [{"text": "zeolite", "start": 62, "end": 69}]}}, "schema": []}
{"input": "This facile method cooperatively tunes crystal properties, such as morphology and surface architecture, through the use of inexpensive, commercially available chemicals with specificity for binding to crystallographic surfaces and mediating anisotropic growth.", "output": {"entities": {}}, "schema": []}
{"input": "We examined over 30 molecules as potential zeolite growth modifiers (ZGMs) of zeolite L (LTL type) crystallization.", "output": {"entities": {"chemical": [{"text": "zeolite", "start": 43, "end": 50}, {"text": "zeolite L", "start": 78, "end": 87}]}}, "schema": []}
{"input": "ZGM efficacy was quantified through a combination of macroscopic (bulk) and microscopic (surface) investigations that identified modifiers capable of dramatically altering the cylindrical morphology of LTL crystals.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate an ability to tailor properties critical to zeolite performance, such as external porous surface area, crystal shape, and pore length, which can enhance sorbate accessibility to LTL pores, tune the supramolecular organization of guest-host composites, and minimize the diffusion path length, respectively.", "output": {"entities": {"chemical": [{"text": "zeolite", "start": 59, "end": 66}, {"text": "sorbate", "start": 168, "end": 175}]}}, "schema": []}
{"input": "We report that a synergistic combination of ZGMs and the judicious adjustment of synthesis parameters produce LTL crystals with unique surface features, and a range of length-to-diameter aspect ratios spanning 3 orders of magnitude.", "output": {"entities": {}}, "schema": []}
{"input": "A systematic examination of different ZGM structures and molecular compositions (i. e., hydrophobicity and binding moieties) reveal interesting physicochemical properties governing their efficacy and specificity.", "output": {"entities": {}}, "schema": []}
{"input": "Results of this study suggest this versatile strategy may prove applicable for a host of framework types to produce unrivaled materials that have eluded more conventional techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Silver Nanoparticles Induced RNA Polymerase-Silver Binding and RNA Transcription Inhibition in Erythroid Progenitor Cells.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}, {"text": "Silver", "start": 44, "end": 50}]}}, "schema": []}
{"input": "Due to its antimicrobial activity, nanosilver (nAg) has become the most widely used nanomaterial.", "output": {"entities": {}}, "schema": []}
{"input": "Thus far, the mechanisms responsible for nAg-induced antimicrobial properties and nAg-mediated toxicity to organisms have not been clearly recognized.", "output": {"entities": {}}, "schema": []}
{"input": "Silver (Ag) ions certainly play a crucial role, and the form of nanoparticles can change the dissolution rate, bioavailability, biodistribution, and cellular uptake of Ag.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}, {"text": "Ag", "start": 8, "end": 10}, {"text": "Ag", "start": 168, "end": 170}]}}, "schema": []}
{"input": "However, whether nAg exerts direct \" particle-specific \" effects has been under debate.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrated that nAg exhibited a robust inhibition on RNA polymerase activity and overall RNA transcription through direct Ag binding to RNA polymerase, which is separated from the cytotoxicity pathway induced by Ag ions.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 132, "end": 134}]}}, "schema": []}
{"input": "nAg treatment in vitro resulted in reduced hemoglobin concentration in erythroid cells; in vivo administration of nAg in mice caused profound reduction of hemoglobin content in embryonic erythrocytes, associated with anemia in the embryos.", "output": {"entities": {}}, "schema": []}
{"input": "Embryonic anemia and general proliferation deficit due to the significant inhibition on RNA synthesis, at least partially, accounted for embryonic developmental retardation upon nAg administration.", "output": {"entities": {}}, "schema": []}
{"input": "To date, there is no conclusive answer to the sources of nAg-mediated toxicity: Ag ions or \" particle-specific \" effects, or both.", "output": {"entities": {}}, "schema": []}
{"input": "We here demonstrated that both Ag ions and nAg particles simultaneously existed inside cells, demonstrating the \" Trojan horse \" effects of nAg particles in posing biological impacts on erythroid cells.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 31, "end": 33}]}}, "schema": []}
{"input": "Moreover, our results suggested that \" particle-specific \" effects could be the predominant mediator in eliciting biological influences on erythroid cells under relatively low concentrations of nAg exposure.", "output": {"entities": {}}, "schema": []}
{"input": "The combined data highlighted the inhibitory effect of nAg on RNA polymerase activity through a direct reciprocal interaction.", "output": {"entities": {}}, "schema": []}
{"input": "New genetic associations in thiopurine-related bone marrow toxicity among inflammatory bowel disease patients.", "output": {"entities": {"chemical": [{"text": "thiopurine", "start": 28, "end": 38}]}}, "schema": []}
{"input": "Background: The toxicity related to thiopurine drug therapy for inflammatory bowel disease (IBD) varies widely among patients.", "output": {"entities": {"chemical": [{"text": "thiopurine", "start": 36, "end": 46}]}}, "schema": []}
{"input": "Almost 15-30% of patients with IBD develop side effects during treatment, often bone marrow suppression.", "output": {"entities": {}}, "schema": []}
{"input": "Several factors have been implicated in determining this toxicity, mainly individual genetic variation related to formation of active thiopurine metabolites.", "output": {"entities": {"chemical": [{"text": "thiopurine", "start": 134, "end": 144}]}}, "schema": []}
{"input": "The aim was to identify genes involved in thiopurine-related myelosuppression.", "output": {"entities": {"chemical": [{"text": "thiopurine", "start": 42, "end": 52}]}}, "schema": []}
{"input": "Materials & methods: A two-stage investigation of 19, 217 coding SNPs (cSNPs) was performed in a Spanish (Inflammatory Bowel Disease Group of Galicia [EIGA]) cohort of 173 IBD patients, 15 with bone marrow suppression.", "output": {"entities": {}}, "schema": []}
{"input": "The top 20 cSNPs identified in the first stage with p < 10 (-3) for allelic test association and SNPs that define the common TPMT alleles were replicated in a different Spanish (ENEIDA) cohort (87 patients, 29 with bone marrow suppression).", "output": {"entities": {}}, "schema": []}
{"input": "Results: Several cSNPs showed a significant p-value in the allelic joint analysis (p-Cochran-Mantel-Haenszel test <= 2. 55 x 10 (-3)) despite no cSNP passing correction for multiple testing in the first cohort.", "output": {"entities": {}}, "schema": []}
{"input": "Of note is rs3729961 in the gene IL6ST, a transducer signal chain shared by many cytokines including IL6 (p-value combined = 2. 36 x 10 (-4), odds ratio [95% CI]: 3. 41 [1. 71-6. 78]).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we detected association with rs3749598 in the FSTL5 gene that appears to interact with metalloproteases at the extracellular matrix level (p-value combined = 4. 89 x 10 (-4)), odds ratio (95% CI): 3. 67 (1. 68-8. 01).", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: We have identified IL6ST and FSLT5 as new bone marrow suppression susceptibility candidate genes after thiopurine treatment in IBD patients.", "output": {"entities": {"chemical": [{"text": "thiopurine", "start": 115, "end": 125}]}}, "schema": []}
{"input": "This is the first report of variants associated with thiopurine-related myelosuppression that was identified by a genome-wide association study.", "output": {"entities": {"chemical": [{"text": "thiopurine", "start": 53, "end": 63}]}}, "schema": []}
{"input": "Its validation awaits functional analyses and replication in additional studies.", "output": {"entities": {}}, "schema": []}
{"input": "Original submitted 14 September 2012; Revision submitted 13 February 2013.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacogenomics of bipolar disorder.", "output": {"entities": {}}, "schema": []}
{"input": "Bipolar disorder (BD) is a lifelong severe psychiatric condition with high morbidity, disability and excess mortality.", "output": {"entities": {}}, "schema": []}
{"input": "The longitudinal clinical trajectory of BD is significantly modified by pharmacological treatment (s), both in acute and in long-term stages.", "output": {"entities": {}}, "schema": []}
{"input": "However, a large proportion of BD patients have inadequate response to pharmacological treatments.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacogenomic research may lead to the identification of molecular predictors of treatment response.", "output": {"entities": {}}, "schema": []}
{"input": "When integrated with clinical information, pharmacogenomic findings may be used in the future to determine the probability of response/nonresponse to treatment on an individual basis.", "output": {"entities": {}}, "schema": []}
{"input": "Here we present a selective review of pharmacogenomic findings in BD.", "output": {"entities": {}}, "schema": []}
{"input": "In light of the evidence suggesting a genetic effect of lithium reponse in BD, we focused particularly on the pharmacogenomic literature relevant to this trait.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 56, "end": 63}]}}, "schema": []}
{"input": "The article contributes a detailed overview of the current status of pharmacogenomics in BD and offers a perspective on the challenges that can hinder its transition to personalized healthcare.", "output": {"entities": {}}, "schema": []}
{"input": "Adsorption of small organic molecules on graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 41, "end": 49}]}}, "schema": []}
{"input": "We present a combined experimental and theoretical quantification of the adsorption enthalpies of seven organic molecules (acetone, acetonitrile, dichloromethane, ethanol, ethyl acetate, hexane, and toluene) on graphene.", "output": {"entities": {"chemical": [{"text": "acetone", "start": 123, "end": 130}, {"text": "acetonitrile", "start": 132, "end": 144}, {"text": "dichloromethane", "start": 146, "end": 161}, {"text": "ethanol", "start": 163, "end": 170}, {"text": "ethyl acetate", "start": 172, "end": 185}, {"text": "hexane", "start": 187, "end": 193}, {"text": "toluene", "start": 199, "end": 206}, {"text": "graphene", "start": 211, "end": 219}]}}, "schema": []}
{"input": "Adsorption enthalpies were measured by inverse gas chromatography and ranged from-5. 9 kcal/mol for dichloromethane to-13. 5 kcal/mol for toluene.", "output": {"entities": {"chemical": [{"text": "dichloromethane", "start": 100, "end": 115}, {"text": "toluene", "start": 138, "end": 145}]}}, "schema": []}
{"input": "The strength of interaction between graphene and the organic molecules was estimated by density functional theory (PBE, B97D, M06-2X, and optB88-vdW), wave function theory (MP2, SCS (MI)-MP2, MP2. 5, MP2. X, and CCSD (T)), and empirical calculations (OPLS-AA) using two graphene models: coronene and infinite graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 36, "end": 44}, {"text": "graphene", "start": 270, "end": 278}, {"text": "coronene", "start": 287, "end": 295}, {"text": "graphene", "start": 309, "end": 317}]}}, "schema": []}
{"input": "Symmetry-adapted perturbation theory calculations indicated that the interactions were governed by London dispersive forces (amounting to ~ 60% of attractive interactions), even for the polar molecules.", "output": {"entities": {}}, "schema": []}
{"input": "The results also showed that the adsorption enthalpies were largely controlled by the interaction energy.", "output": {"entities": {}}, "schema": []}
{"input": "Adsorption enthalpies obtained from ab initio molecular dynamics employing non-local optB88-vdW functional were in excellent agreement with the experimental data, indicating that the functional can cover physical phenomena behind adsorption of organic molecules on graphene sufficiently well.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 265, "end": 273}]}}, "schema": []}
{"input": "Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci.", "output": {"entities": {}}, "schema": []}
{"input": "Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein coding regions.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types.", "output": {"entities": {}}, "schema": []}
{"input": "We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage.", "output": {"entities": {"chemical": [{"text": "formaldehyde", "start": 8, "end": 20}]}}, "schema": []}
{"input": "In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types, and associate with the cell type-specific gene expression patterns.", "output": {"entities": {}}, "schema": []}
{"input": "Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site and ontology classes of nearby genes.", "output": {"entities": {}}, "schema": []}
{"input": "Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices.", "output": {"entities": {}}, "schema": []}
{"input": "The majority (63. 6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis.", "output": {"entities": {}}, "schema": []}
{"input": "We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs, and found that 10 (76. 9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits.", "output": {"entities": {}}, "schema": []}
{"input": "Structure-activity relationship of potent antimicrobial peptide analogs of Ixosin-B amide.", "output": {"entities": {"chemical": [{"text": "amide", "start": 84, "end": 89}]}}, "schema": []}
{"input": "There is a great urgency in developing a new generation of antibiotics and antimicrobial agents since the bacterial resistance to antibiotics have increased dramatically.", "output": {"entities": {}}, "schema": []}
{"input": "A series of overlapped peptide fragments of Ixosin-B, an antimicrobial peptide with amino acid sequence of QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY, was designed, synthesized and examined for their antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 84, "end": 94}]}}, "schema": []}
{"input": "A potent 11-mer peptide TSG-8-1, WWSYVRRWRSR-amide, was developed, which exhibited antimicrobial activity against E. coli and S. aureus while very little hemolytic activity in human erythrocytes was observed at high dose level.", "output": {"entities": {"chemical": [{"text": "TSG-8-1", "start": 24, "end": 31}, {"text": "amide", "start": 45, "end": 50}]}}, "schema": []}
{"input": "This peptide could be further modified for the development of a potent antimicrobial agent in the future.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of miRNA modulators to PARP inhibitor response.", "output": {"entities": {}}, "schema": []}
{"input": "Based on the principle of synthetic lethality, PARP inhibitors have been shown to be very effective in killing cells deficient in homologous recombination (HR), such as those bearing mutations in BRCA1/2.", "output": {"entities": {}}, "schema": []}
{"input": "However, questions regarding their wider use persist and other determinants of responsiveness to PARP inhibitor remain to be fully explored.", "output": {"entities": {}}, "schema": []}
{"input": "MicroRNAs (miRNAs) are small non-coding RNAs, which serve as post-transcriptional regulators of gene expression and are involved in a wide variety of cellular processes, including the DNA damage response (DDR).", "output": {"entities": {}}, "schema": []}
{"input": "However, little is known about whether miRNAs might influence sensitivity to PARP inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "To investigate this, we performed a high throughput miRNA mimetic screen, which identified several miRNAs whose over-expression results in sensitization to the clinical PARP inhibitor olaparib.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, our findings indicate that hsa-miR-107 and hsa-miR-222 regulate the DDR and sensitise tumour cells to olaparib by repressing expression of RAD51, thus impairing DSB repair by HR.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, elevated expression of hsa-miR-107 has been observed in a subset of ovarian clear cell carcinomas, which correlates with PARP inhibitor sensitivity and reduced RAD51 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these observations raise the possibility that these miRNAs could be used as biomarkers to identify patients that may benefit from treatment with PARP inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo.", "output": {"entities": {"chemical": [{"text": "Pyranocycloartobiloxanthone A", "start": 0, "end": 29}, {"text": "ethanol", "start": 105, "end": 112}]}}, "schema": []}
{"input": "Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia.", "output": {"entities": {"chemical": [{"text": "Pyranocycloartobiloxanthone A", "start": 0, "end": 29}, {"text": "xanthone", "start": 38, "end": 46}]}}, "schema": []}
{"input": "In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 86, "end": 93}]}}, "schema": []}
{"input": "The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 103, "end": 110}]}}, "schema": []}
{"input": "The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 78, "end": 89}, {"text": "GSH", "start": 91, "end": 94}, {"text": "malondialdehyde", "start": 104, "end": 119}, {"text": "MDA", "start": 127, "end": 130}, {"text": "nitric oxide", "start": 133, "end": 145}, {"text": "NO", "start": 147, "end": 149}, {"text": "sulfhydryl", "start": 167, "end": 177}, {"text": "SH", "start": 188, "end": 190}]}}, "schema": []}
{"input": "The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 83, "end": 90}]}}, "schema": []}
{"input": "PA pretreatment significantly (p < 0. 05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 64, "end": 67}, {"text": "SH", "start": 72, "end": 74}, {"text": "NO", "start": 79, "end": 81}]}}, "schema": []}
{"input": "Moreover, PA significantly (p < 0. 05) reduced the elevated MDA level due to ethanol administration.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 60, "end": 63}, {"text": "ethanol", "start": 77, "end": 84}]}}, "schema": []}
{"input": "The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium.", "output": {"entities": {}}, "schema": []}
{"input": "The efficacy of PA was accomplished safely without the presence of any toxicological parameters.", "output": {"entities": {}}, "schema": []}
{"input": "The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori.", "output": {"entities": {}}, "schema": []}
{"input": "Plant High-Affinity Potassium (HKT) Transporters Involved in Salinity Tolerance: Structural Insights to Probe Differences in Ion Selectivity.", "output": {"entities": {"chemical": [{"text": "Potassium", "start": 20, "end": 29}]}}, "schema": []}
{"input": "High-affinity Potassium Transporters (HKTs) belong to an important class of integral membrane proteins (IMPs) that facilitate cation transport across the plasma membranes of plant cells.", "output": {"entities": {"chemical": [{"text": "Potassium", "start": 14, "end": 23}]}}, "schema": []}
{"input": "Some members of the HKT protein family have been shown to be critical for salinity tolerance in commercially important crop species, particularly in grains, through exclusion of Na + ions from sensitive shoot tissues in plants.", "output": {"entities": {"chemical": [{"text": "Na +", "start": 178, "end": 182}]}}, "schema": []}
{"input": "However, given the number of different HKT proteins expressed in plants, it is likely that different members of this protein family perform in a range of functions.", "output": {"entities": {}}, "schema": []}
{"input": "Plant breeders and biotechnologists have attempted to manipulate HKT gene expression through genetic engineering and more conventional plant breeding methods to improve the salinity tolerance of commercially important crop plants.", "output": {"entities": {}}, "schema": []}
{"input": "Successful manipulation of a biological trait is more likely to be effective after a thorough understanding of how the trait, genes and proteins are interconnected at the whole plant level.", "output": {"entities": {}}, "schema": []}
{"input": "This article examines the current structural and functional knowledge relating to plant HKTs and how their structural features may explain their transport selectivity.", "output": {"entities": {}}, "schema": []}
{"input": "We also highlight specific areas where new knowledge of plant HKT transporters is needed.", "output": {"entities": {}}, "schema": []}
{"input": "Our goal is to present how knowledge of the structure of HKT proteins is helpful in understanding their function and how this understanding can be an invaluable experimental tool.", "output": {"entities": {}}, "schema": []}
{"input": "As such, we assert that accurate structural information of plant IMPs will greatly inform functional studies and will lead to a deeper understanding of plant nutrition, signalling and stress tolerance, all of which represent factors that can be manipulated to improve agricultural productivity.", "output": {"entities": {}}, "schema": []}
{"input": "Sphingomyelin in high-density lipoproteins: structural role and biological function.", "output": {"entities": {"chemical": [{"text": "Sphingomyelin", "start": 0, "end": 13}]}}, "schema": []}
{"input": "High-density lipoprotein (HDL) levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM) is the second most abundant phospholipid component and the major sphingolipid in HDL.", "output": {"entities": {"chemical": [{"text": "sphingomyelin", "start": 98, "end": 111}, {"text": "sphingolipid", "start": 182, "end": 194}]}}, "schema": []}
{"input": "Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 290, "end": 301}]}}, "schema": []}
{"input": "In addition, plasma enzymes involved in HDL metabolism such as lecithin-cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 72, "end": 83}]}}, "schema": []}
{"input": "Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat), drugs (statins or diuretics) and modified in diseases such as diabetes, renal failure or Niemann-Pick disease.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease.", "output": {"entities": {}}, "schema": []}
{"input": "The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future.", "output": {"entities": {}}, "schema": []}
{"input": "Bioinspired design and macroscopic assembly of poly (vinyl alcohol)-coated graphene into kilometers-long fibers.", "output": {"entities": {"chemical": [{"text": "poly (vinyl alcohol)", "start": 47, "end": 67}, {"text": "graphene", "start": 75, "end": 83}]}}, "schema": []}
{"input": "Nacre is characterized by its excellent mechanical performance due to the well-recognized \" brick and mortar \" structure.", "output": {"entities": {}}, "schema": []}
{"input": "Many efforts have been applied to make nacre-mimicking materials, but it is still a big challenge to realize their continuous production.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we prepared sandwich-like building blocks of poly (vinyl alcohol) (PVA)-coated graphene, and achieved high-nanofiller-content kilometers-long fibers by continuous wet-spinning assembly technology.", "output": {"entities": {"chemical": [{"text": "poly (vinyl alcohol)", "start": 51, "end": 71}, {"text": "PVA", "start": 73, "end": 76}, {"text": "graphene", "start": 85, "end": 93}]}}, "schema": []}
{"input": "The fibers have a strict \" brick and mortar \" layered structure, with graphene sheet as rigid brick and PVA as soft mortar.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 70, "end": 78}, {"text": "PVA", "start": 104, "end": 107}]}}, "schema": []}
{"input": "The mortar thickness can be precisely tuned from 2. 01 to 3. 31 nm by the weight feed ratio of PVA to graphene, as demonstrated by both atomic force microscopy and X-ray diffraction measurements.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 102, "end": 110}]}}, "schema": []}
{"input": "The mechanical strength of the nacre-mimicking fibers increases with increasing the content of PVA, and it rises gradually from 81 MPa for the fiber with 53. 1 wt% PVA to 161 MPa for the fiber with 65. 8 wt% PVA.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 95, "end": 98}, {"text": "PVA", "start": 164, "end": 167}, {"text": "PVA", "start": 208, "end": 211}]}}, "schema": []}
{"input": "The mechanical performance of our fibers was independent of the molecular weight (MW) of PVA in the wide range of 2-100 kDa, indicating that low MW polymers can also be used to make strong nanocomposites.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 89, "end": 92}]}}, "schema": []}
{"input": "The tensile stress of fibers immersed in PVA 5 wt% solution reached ca.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 41, "end": 44}]}}, "schema": []}
{"input": "200 MPa, surpassing the values of nacre and most of other nacre-mimicking materials.", "output": {"entities": {}}, "schema": []}
{"input": "The nacre-mimicking fibers are highly electrically conductive (~ 350 S m (-1)) after immersing in hydroiodic acid, enabling them to connect a circuit to illuminate an LED lamp.", "output": {"entities": {"chemical": [{"text": "hydroiodic acid", "start": 98, "end": 113}]}}, "schema": []}
{"input": "A capture approach for supercoiled plasmid DNA using a triplex-forming oligonucleotide.", "output": {"entities": {}}, "schema": []}
{"input": "Proteins that recognize and bind specific sites in DNA are essential for regulation of numerous biological functions.", "output": {"entities": {}}, "schema": []}
{"input": "Such proteins often require a negative supercoiled DNA topology to function correctly.", "output": {"entities": {}}, "schema": []}
{"input": "In current research, short linear DNA is often used to study DNA-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Although linear DNA can easily be modified, for capture on a surface, its relaxed topology does not accurately resemble the natural situation in which DNA is generally negatively supercoiled.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, specific binding sequences are flanked by large stretches of non-target sequence in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present a straightforward method for capturing negatively supercoiled plasmid DNA on a streptavidin surface.", "output": {"entities": {}}, "schema": []}
{"input": "It relies on the formation of a temporary parallel triplex, using a triple helix forming oligonucleotide containing locked nucleic acid nucleotides.", "output": {"entities": {"chemical": [{"text": "nucleotides", "start": 136, "end": 147}]}}, "schema": []}
{"input": "All materials required for this method are commercially available.", "output": {"entities": {}}, "schema": []}
{"input": "Lac repressor binding to its operator was used as model system.", "output": {"entities": {}}, "schema": []}
{"input": "Although the dissociation constants for both the linear and plasmid-based operator are in the range of 4 nM, the association and dissociation rates of Lac repressor binding to the plasmid-based operator are ~ 18 times slower than on a linear fragment.", "output": {"entities": {}}, "schema": []}
{"input": "This difference underscores the importance of using a physiologically relevant DNA topology for studying DNA-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical Pharmacology and the Catalysis of Regulatory Science: Opportunities for the Advancement of Drug Development and Evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "The \" regulatory paradox \" is a tension between aversion to uncertainty and willingness to accept unknowns about a drug before its approval.", "output": {"entities": {}}, "schema": []}
{"input": "Finding the right balance may mean the difference between fostering and stifling innovation.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical pharmacology applied in the drug development and regulatory contexts can bridge mechanistic reasoning and empiricism to help reconcile the regulatory paradox.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we propose that the discipline of clinical pharmacology, in the regulatory setting, is well positioned to build on its past successes in the advancement and acceleration of drug development. Clinical Pharmacology & Therapeutics (2013); advance online publication 10 April 2013. doi: 10. 1038/clpt. 2013. 32.", "output": {"entities": {}}, "schema": []}
{"input": "Generic Development of Topical Dermatologic Products, Part II: Quality by Design for Topical Semisolid Products.", "output": {"entities": {}}, "schema": []}
{"input": "The emergence of quality by design as a relatively new systematic science and risk-based approach has added a new dimension to pharmaceutical development and manufacturing.", "output": {"entities": {}}, "schema": []}
{"input": "This review attempts to discuss the quality by design elements and concepts applied for topical semisolid products.", "output": {"entities": {}}, "schema": []}
{"input": "Quality by design begins with defining a quality target product profile as well as critical quality attributes.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, this is followed by risk identification/risk analysis/risk evaluation to recognize critical material attributes and critical process parameters, in conjunction with design of experiments or other appropriate methods to establish control strategies for the drug product.", "output": {"entities": {}}, "schema": []}
{"input": "Several design-of-experiment examples are included as practical strategies for the development and optimization of formulation and process for topical drug products.", "output": {"entities": {}}, "schema": []}
{"input": "Hypermethylation of P15, P16, and E-cadherin genes in ovarian cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Both p16 and p15 proteins are inhibitors of cyclin-dependent kinases that prevent the cell going through the G1/S phase transaction.", "output": {"entities": {}}, "schema": []}
{"input": "E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent interactions between adjacent epithelial cells.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 57, "end": 64}]}}, "schema": []}
{"input": "Two groups of patients were selected: the first group suffered from epithelial serous ovarian tumors and the second group suffered from benign ovarian lesions; ovarian tissue samples from all the subjects (benign and malignant) were subjected to methylation-specific polymerase chain reaction for methylated and unmethylated alleles of the genes (E-cadherin, p15, and p16).", "output": {"entities": {}}, "schema": []}
{"input": "Results obtained showed that aberrant methylation of p15 and p16 genes were detected in 64. 29 and 50% of ovarian cancer patients, while E-cadherin hypermethylation was detected in 78. 57% of ovarian cancer patients.", "output": {"entities": {}}, "schema": []}
{"input": "Methylation of E-cadherin was significantly correlated with different stage of disease (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "It was found that the risk of E-cadherin hypermethylation was 1. 347-fold, while risk of p15 hypermethylation was 1. 543-fold and p16 was 1. 2-fold among patients with ovarian cancer than that among patients with benign ovarian lesions.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, Dysfunction of the cell cycle and/or the cell-cell adhesion molecule plays a role in the pathogenesis of ovarian cancer and that the analysis of the methylation of p15 and E-cadherin genes can provide clinically important evidence on which to base the treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Physiological and biochemical mechanisms of allelopathy mediated by the allelochemical extracts of Phytolacca latbenia (Moq.) H.", "output": {"entities": {}}, "schema": []}
{"input": "Walter.", "output": {"entities": {}}, "schema": []}
{"input": "In allelopathy, one plant suppresses the growth and development of other plant/plants by negatively affecting a variety of physiological and biochemical reactions.", "output": {"entities": {}}, "schema": []}
{"input": "We checked the effects of methanolic extracts (allelochemical extracts) of Phytolacca latbenia (Moq.) H.", "output": {"entities": {}}, "schema": []}
{"input": "Walter on antioxidant enzyme activities such as peroxidases (PODs), super oxide dismutases (SODs) and catalase (CAT) and on total protein contents (TPC), cellular injury (CI), and malondialdehyde (MDA) in the germinating seeds of Brassica napus L.", "output": {"entities": {"chemical": [{"text": "super oxide", "start": 68, "end": 79}, {"text": "malondialdehyde", "start": 180, "end": 195}, {"text": "MDA", "start": 197, "end": 200}]}}, "schema": []}
{"input": "(dicot) and Triticum aestivum L.", "output": {"entities": {}}, "schema": []}
{"input": "(monocot).", "output": {"entities": {}}, "schema": []}
{"input": "Both the crude methanolic extract root (CMER) and crude methanolic extract aerial (CMEA) of P. latbenia at 10000 ppm significantly reduced the POD activity in both the test seeds.", "output": {"entities": {}}, "schema": []}
{"input": "The activity of SODs was significantly decreased by both CMER and CMEA in B. napus germinating seeds.", "output": {"entities": {}}, "schema": []}
{"input": "A linear increase in the activity of CAT, CI, and MDA contents was found in both the test seeds with the increasing concentrations of CMEA and CMER, while TPC of the germinating seeds was found decreased.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 50, "end": 53}]}}, "schema": []}
{"input": "It is inferred that both the CMEA and CMER inhibited/delayed the seed germination, reduced the seedling growth by affecting a variety of biochemical and physiological attributes, and also caused cellular membrane injury in the germinating seeds of both the monocot and dicot seeds.", "output": {"entities": {}}, "schema": []}
{"input": "Ultrasonic synthesis, characterization of beta-aminoketones by bismuth (III) triflate and determination of antigenotoxic properties.", "output": {"entities": {"chemical": [{"text": "beta-aminoketones", "start": 42, "end": 59}, {"text": "bismuth (III) triflate", "start": 63, "end": 85}]}}, "schema": []}
{"input": "Direct-type catalytic Mannich reaction for the synthesis of beta-aminoketones from cyclohexanone, substituted aromatic amines and aromatic or hetero-aromatic aldehydes has been applied in water with bismuth triflate under ultrasound.", "output": {"entities": {"chemical": [{"text": "beta-aminoketones", "start": 60, "end": 77}, {"text": "cyclohexanone", "start": 83, "end": 96}, {"text": "aromatic amines and aromatic or hetero-aromatic aldehydes", "start": 110, "end": 167}, {"text": "bismuth triflate", "start": 199, "end": 215}]}}, "schema": []}
{"input": "Good yields of the expected beta-aminoketones were obtained from available substrates, at room temperature in 1-2 hours.", "output": {"entities": {"chemical": [{"text": "beta-aminoketones", "start": 28, "end": 45}]}}, "schema": []}
{"input": "This study was designed to evaluate the mutagenic and antimutagenic potential of synthesized beta-aminoketones compounds using Ames/Salmonella and Escherichia coli WP2 bacterial reverse mutation assay systems.", "output": {"entities": {"chemical": [{"text": "beta-aminoketones", "start": 93, "end": 110}]}}, "schema": []}
{"input": "Ameliorative effect of lycopene against 2, 3, 7, 8-tetrachlorodibenzo-pdioxin-induced rat liver microsomal toxicity: An in vitro study.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 23, "end": 31}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-pdioxin", "start": 40, "end": 77}]}}, "schema": []}
{"input": "The objective of the current study was to investigate the potential oxidative damage of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in hepatic microsomal fractions in vitro and to further elucidate the potential modulatory effect of lycopene.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 88, "end": 126}, {"text": "TCDD", "start": 128, "end": 132}, {"text": "lycopene", "start": 235, "end": 243}]}}, "schema": []}
{"input": "Rat liver microsomes were divided into four groups.", "output": {"entities": {}}, "schema": []}
{"input": "Group I served as a control and is incubated with vehicle (toluene).", "output": {"entities": {"chemical": [{"text": "toluene", "start": 59, "end": 66}]}}, "schema": []}
{"input": "Groups II and IV were incubated with 20 micro M lycopene for 1 h before further incubating; groups III and IV with 15 nM of TCDD for further 1 h.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 48, "end": 56}, {"text": "TCDD", "start": 124, "end": 128}]}}, "schema": []}
{"input": "Hydrogen peroxide (H2O2) production, lipid peroxidation (LPO), protein carbonyl content and activities of uridine 5'-diphospho-glucuronyltransferase (UDPGT) and P450 were significantly increased.", "output": {"entities": {"chemical": [{"text": "Hydrogen peroxide", "start": 0, "end": 17}, {"text": "H2O2", "start": 19, "end": 23}, {"text": "carbonyl", "start": 71, "end": 79}, {"text": "uridine 5'-diphospho", "start": 106, "end": 126}]}}, "schema": []}
{"input": "Moreover, the activity of antioxidant enzymes superoxide dismutase, glutathione peroxidase, catalse, glutathione-S-transferase and glutathione reductase as well as the microsomal thiol content were significantly decreased.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 68, "end": 79}, {"text": "glutathione", "start": 101, "end": 112}, {"text": "S", "start": 113, "end": 114}, {"text": "glutathione", "start": 131, "end": 142}]}}, "schema": []}
{"input": "Incubation with lycopene (group IV) maintained near normal activities of the enzymes, normalized thiol and carbonyl content and significantly reduced LPO and H2O2 production.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 16, "end": 24}, {"text": "thiol", "start": 97, "end": 102}, {"text": "carbonyl", "start": 107, "end": 115}, {"text": "H2O2", "start": 158, "end": 162}]}}, "schema": []}
{"input": "In conclusion, the findings of the study indicate that TCDD induces a significant oxidative stress in liver microsomes as manifested by increased LPO, H2O2 production, protein carbonyl content and activities of UDPGT and P450 and decreased antioxidant enzymes activities and thiol content.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 55, "end": 59}, {"text": "H2O2", "start": 151, "end": 155}, {"text": "carbonyl", "start": 176, "end": 184}, {"text": "thiol", "start": 275, "end": 280}]}}, "schema": []}
{"input": "By the reversal of biochemical and oxidative markers toward normalcy, the protective role of lycopene is illuminated in rat liver microsomal toxicity.", "output": {"entities": {"chemical": [{"text": "lycopene", "start": 93, "end": 101}]}}, "schema": []}
{"input": "Circulating glucagon to ghrelin ratio as a determinant of insulin resistance in hyperthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "Due to stimulated overall metabolism, a state of nutritional inadequacy often ensues, during thyrotoxicosis.", "output": {"entities": {}}, "schema": []}
{"input": "We aimed to investigate circulating levels of some major components of the system that regulates energy stores, glucose, and fat metabolism, during thyrotoxicosis compared to euthyroidism.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 112, "end": 119}]}}, "schema": []}
{"input": "Fasting serum ghrelin, leptin, adiponectin, insulin, glucagon, glucose, as well as body fat composition were analyzed during thyrotoxicosis in 40 hyperthyroid patients (50. 5 +/- 15. 2 years old, 22 females, 31 with Graves disease, and 9 with toxic nodular goiter).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 63, "end": 70}]}}, "schema": []}
{"input": "The same measurements were repeated an average 3 months later, when all patients achieved euthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to euthyroidism, in thyrotoxicosis, patients had lower ghrelin and fat mass; had comparable insulin, HOMA-IR, glucagon, and leptin levels; higher levels of circulating adiponectin.", "output": {"entities": {}}, "schema": []}
{"input": "Fasting serum glucose tended to be higher during thyrotoxicosis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 14, "end": 21}]}}, "schema": []}
{"input": "The unique correlation of HOMA-IR was with the-glucagon to ghrelin ratio-(r = 0. 801, p < 0. 001) in hyperthyrodism, and with glucagon itself in euthyroidism (r =-0. 844, p < 0. 001).", "output": {"entities": {}}, "schema": []}
{"input": "Circulating levels of ghrelin are decreased; leptin, insulin, glucagon are unchanged; adiponectin are increased during hyperthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "The fasting HOMA-IR tends to be higher, despite the decreased adiposity in hyperthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "The-glucagon to ghrelin ratio-strongly correlates with fasting HOMA-IR in hyperthyroidism.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical strategies to enhance the efficacy of nicotine replacement therapy for smoking cessation: a review of the literature.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 47, "end": 55}]}}, "schema": []}
{"input": "A number of smoking cessation pharmacotherapies have led to increases in quitting and thus to significant benefits to public health.", "output": {"entities": {}}, "schema": []}
{"input": "Among existing medications, nicotine replacement therapy (NRT) has been available the longest, has the largest literature base in support, and is the only option for over-the-counter access.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 28, "end": 36}]}}, "schema": []}
{"input": "While the short-term efficacy of NRT is well documented in clinical trials, long-term abstinence rates associated with using NRT are modest, as most smokers will relapse.", "output": {"entities": {}}, "schema": []}
{"input": "This literature review examines emerging clinical strategies to improve NRT efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "After an initial overview of NRT and its FDA-approved indications for use, we review randomized trials in which clinical delivery of NRT was manipulated and tested, in an attempt to enhance efficacy, through (1) duration of use (pre-quit and extended use), (2) amount of use (high-dose and combination NRT), (3) tailoring to specific smoker groups (genotype and phenotype), or (4) use of NRT for novel purposes (relapse prevention, temporary abstinence, cessation induction).", "output": {"entities": {}}, "schema": []}
{"input": "Outcomes vary within and across topic area, and we highlight areas that offer stronger promise.", "output": {"entities": {}}, "schema": []}
{"input": "Combination NRT likely represents the most promising strategy moving forward; other clinical strategies offer conflicting evidence but deserve further testing (pre-quit NRT or tailored treatment) or offer potential utility but are in need of further, direct tests.", "output": {"entities": {}}, "schema": []}
{"input": "Some areas, though based on a limited set of studies, do not offer great promise (high-dose and extended treatment NRT).", "output": {"entities": {}}, "schema": []}
{"input": "We conclude with a brief discussion of emergent NRT products (e. g., oral nicotine spray, among others), which may ultimately offer greater efficacy than current formulations.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 74, "end": 82}]}}, "schema": []}
{"input": "In order to further lower the prevalence of smoking, novel strategies designed to optimize NRT efficacy are needed.", "output": {"entities": {}}, "schema": []}
{"input": "Optimal management of metastatic renal cell carcinoma: current status.", "output": {"entities": {}}, "schema": []}
{"input": "The armamentarium for the systemic therapy of advanced renal cell carcinoma (RCC) has undergone dramatic changes over the past 6 years.", "output": {"entities": {}}, "schema": []}
{"input": "While high-dose interleukin (IL)-2 remains an option for highly selected good and intermediate risk patients with clear-cell histology because of durable complete responses in a small fraction of patients, cytokine-based therapy including interferon (IFN) has been supplanted by vascular-endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 345, "end": 354}]}}, "schema": []}
{"input": "Treatment decision is initially based on prognostication of the disease.", "output": {"entities": {}}, "schema": []}
{"input": "As metastatic RCC (mRCC) is commonly an indolent disease, a period of observation should always been considered.", "output": {"entities": {}}, "schema": []}
{"input": "For good and intermediate risk disease, pazopanib, sunitinib or the combination of bevacizumab plus IFN are considered.", "output": {"entities": {"chemical": [{"text": "pazopanib", "start": 40, "end": 49}, {"text": "sunitinib", "start": 51, "end": 60}]}}, "schema": []}
{"input": "Notably, recent data suggest non-inferiority for the efficacy of pazopanib compared to sunitinib coupled with a better toxicity profile.", "output": {"entities": {"chemical": [{"text": "pazopanib", "start": 65, "end": 74}, {"text": "sunitinib", "start": 87, "end": 96}]}}, "schema": []}
{"input": "A novel VEGF receptor inhibitor, tivozanib, is expected to be approved based on improvement in PFS when compared to sorafenib in the first-line setting.", "output": {"entities": {"chemical": [{"text": "tivozanib", "start": 33, "end": 42}, {"text": "sorafenib", "start": 116, "end": 125}]}}, "schema": []}
{"input": "The use of temsirolimus for poor risk disease is supported by a phase III trial dedicated to this group of patients.", "output": {"entities": {"chemical": [{"text": "temsirolimus", "start": 11, "end": 23}]}}, "schema": []}
{"input": "The role of cytoreductive nephrectomy in the context of VEGF and mTOR inhibitors is being studied in randomized trials.", "output": {"entities": {}}, "schema": []}
{"input": "Selected patients with solitary or oligometastatic disease may be eligible for metastatectomy.", "output": {"entities": {}}, "schema": []}
{"input": "Following first-line VEGF inhibitors, second-line therapy with everolimus and axitinib have demonstrated benefits in progression-free survival (PFS).", "output": {"entities": {"chemical": [{"text": "everolimus", "start": 63, "end": 73}, {"text": "axitinib", "start": 78, "end": 86}]}}, "schema": []}
{"input": "One phase III trial comparing sorafenib and temsirolimus in the post-sunitinib setting showed no difference in PFS, the primary endpoint, but did show a superior overall survival for sorafenib.", "output": {"entities": {"chemical": [{"text": "sorafenib", "start": 30, "end": 39}, {"text": "temsirolimus", "start": 44, "end": 56}, {"text": "sunitinib", "start": 69, "end": 78}, {"text": "sorafenib", "start": 183, "end": 192}]}}, "schema": []}
{"input": "Sorafenib, pazopanib and axitinib have all demonstrated clinical benefit following cytokines.", "output": {"entities": {"chemical": [{"text": "Sorafenib", "start": 0, "end": 9}, {"text": "pazopanib", "start": 11, "end": 20}, {"text": "axitinib", "start": 25, "end": 33}]}}, "schema": []}
{"input": "Therapy following first-line mTOR inhibitors remains undefined, although VEGF inhibitors have demonstrated activity in this setting.", "output": {"entities": {}}, "schema": []}
{"input": "Optimal sequencing of agents and individualized therapy based on biomarkers is undergoing investigation.", "output": {"entities": {}}, "schema": []}
{"input": "Today, the choice of therapy is based on patient and physician decision, which is a function of comorbidities, toxicity profiles and costs.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical trials evaluating novel agents and combinations should be preferred when available since agents in the current therapeutic arsenal have not yielded cures despite extending median survival to greater than 2 years.", "output": {"entities": {}}, "schema": []}
{"input": "One noteworthy new class of agents that has yielded durable responses is programmed death (PD)-1 inhibitors, which target a T-lymphocyte checkpoint and are heralding a resurgence of immunotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, optimal therapy for non-clear cell RCC remains to be delineated, although sunitinib, everolimus and other VEGFR-TKI or mTOR inhibitors have all demonstrated modest benefit.", "output": {"entities": {"chemical": [{"text": "sunitinib", "start": 83, "end": 92}, {"text": "everolimus", "start": 94, "end": 104}]}}, "schema": []}
{"input": "Multiple gene polymorphisms can improve prediction of non-vertebral fracture in postmenopausal women.", "output": {"entities": {}}, "schema": []}
{"input": "Clinical risk factors (CRFs), with or without bone mineral density (BMD), are used to determine the risk of osteoporotic fracture (OF), which has a heritable component.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigated whether genetic profiling can additionally improve the ability to predict OF.", "output": {"entities": {}}, "schema": []}
{"input": "Using 1, 229 unrelated Korean postmenopausal women, 39 single-nucleotide polymorphisms (SNPs) in 30 human genomic loci were tested for association with osteoporosis-related traits, such as BMD, osteoporosis, vertebral fracture (VF), non-vertebral fracture (NVF), and any fracture.", "output": {"entities": {}}, "schema": []}
{"input": "To estimate the effects of genetic profiling, the genetic risk score (GRS) was calculated using five prediction models: (model I) GRSs only; (model II) BMD only; (model III) CRFs only; (model IV) CRFs and BMD; and (model V) CRFs, BMD and GRS.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 21 SNPs within 19 genes associated with one or more osteoporosis-related traits and were included for GRS calculation.", "output": {"entities": {}}, "schema": []}
{"input": "GRS associated with BMD before and after adjustment for CRFs (P = < 0. 001 to 0. 018).", "output": {"entities": {}}, "schema": []}
{"input": "GRS associated with NVF before and after adjustment for CRFs and BMD (P = 0. 017 to 0. 045), and with any fracture after adjustment for CRFs and femur neck BMD (P = 0. 049).", "output": {"entities": {}}, "schema": []}
{"input": "In terms of predicting NVF, the area under the receptor-operator characteristics curve (AUC) for model I was 0. 55, which was lower than the AUCs of models II (0. 60), III (0. 64), and IV (0. 65).", "output": {"entities": {}}, "schema": []}
{"input": "Adding GRS to model IV (in model V) increased the AUC to 0. 67, and improved the accuracy of NVF classification by 11. 5% (P = 0. 014).", "output": {"entities": {}}, "schema": []}
{"input": "In terms of predicting any fracture, the AUC of model V (0. 68) was similar to that of model IV (0. 68), and model V did not significantly improve the accuracy of any fracture classification (P = 0. 39).", "output": {"entities": {}}, "schema": []}
{"input": "Thus, genetic profiling may enhance the accuracy of NVF predictions and help to delineate the intervention threshold.", "output": {"entities": {}}, "schema": []}
{"input": "Design and in vitro evaluation of a novel polymeric excipient for buccal applications.", "output": {"entities": {}}, "schema": []}
{"input": "Background: The objective of this study was to develop and evaluate a more effective mucoadhesive thiomer for buccal drug-delivery systems.", "output": {"entities": {}}, "schema": []}
{"input": "Methods: 2-iminothiolane was covalently attached to a chitosan backbone.", "output": {"entities": {"chemical": [{"text": "2-iminothiolane", "start": 9, "end": 24}]}}, "schema": []}
{"input": "A preactivation step followed, mediated by 6, 6' dithionicotinamide, thiol groups were modified by disulfide bonds formation.", "output": {"entities": {"chemical": [{"text": "6, 6' dithionicotinamide", "start": 43, "end": 67}, {"text": "thiol", "start": 69, "end": 74}, {"text": "disulfide", "start": 99, "end": 108}]}}, "schema": []}
{"input": "Mucoadhesion studies were performed on buccal mucosa.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, water-uptake capacity, disintegration, release and cytotoxicity studies were completed.", "output": {"entities": {}}, "schema": []}
{"input": "Results: The obtained chitosan-thiobutylamidine conjugate displayed 647. 4 +/- 85. 23 micro mol/g immobilized thiol groups.", "output": {"entities": {"chemical": [{"text": "thiobutylamidine", "start": 31, "end": 47}]}}, "schema": []}
{"input": "Due to the preactivation, approximately 60% of thiol groups were modified by formation of disulfide bonds.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 90, "end": 99}]}}, "schema": []}
{"input": "Chitosan-thiobutylamidine-mercaptonicotinamide displayed 1. 8-fold higher stability and 1. 6-fold higher mucoadhesive properties, respectively.", "output": {"entities": {"chemical": [{"text": "thiobutylamidine", "start": 9, "end": 25}, {"text": "mercaptonicotinamide", "start": 26, "end": 46}]}}, "schema": []}
{"input": "The release study demonstrated a 1. 4-fold more prolonged drug release compared with corresponding thiomers.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: According to these results, preactivated thiomers demonstrate an improved stability and increased mucoadhesive properties.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, they seem to be advantageous for buccal administration over corresponding thiomers and chitosan.", "output": {"entities": {}}, "schema": []}
{"input": "Present and future approaches to screening of G-protein-coupled receptors.", "output": {"entities": {}}, "schema": []}
{"input": "As G-protein-coupled receptors (GPCRs) mediate a multitude of cellular signal transduction events, affecting more or less all human disease areas, it is, therefore, no surprise that they comprise the largest family of current drug targets.", "output": {"entities": {}}, "schema": []}
{"input": "Screening of compounds interacting with GPCRs has developed during the past decade from receptor binding assays, to various functional determination of coupling to G-proteins, and, more recently, G-protein-independent signal transduction events.", "output": {"entities": {}}, "schema": []}
{"input": "Additional opportunities have been presented in drug discovery through novel pharmacological properties obtained for receptor dimers and by identification of ligands for orphan GPCRs.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, high-throughput formats and automation has substantially facilitated and accelerated the screening process providing powerful tools in improving modern drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "Organic Solvent-Based Graphene Oxide Liquid Crystals: A Facile Route toward the Next Generation of Self-Assembled Layer-by-Layer Multifunctional 3D Architectures.", "output": {"entities": {"chemical": [{"text": "Graphene Oxide", "start": 22, "end": 36}]}}, "schema": []}
{"input": "We introduce soft self-assembly of ultralarge liquid crystalline (LC) graphene oxide (GO) sheets in a wide range of organic solvents overcoming the practical limitations imposed on LC GO processing in water.", "output": {"entities": {"chemical": [{"text": "graphene oxide", "start": 70, "end": 84}]}}, "schema": []}
{"input": "This expands the number of known solvents which can support amphiphilic self-assembly to ethanol, acetone, tetrahydrofuran, N-dimethylformamide, N-cyclohexyl-2-pyrrolidone, and a number of other organic solvents, many of which were not known to afford solvophobic self-assembly prior to this report.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 89, "end": 96}, {"text": "acetone", "start": 98, "end": 105}, {"text": "tetrahydrofuran", "start": 107, "end": 122}, {"text": "N-dimethylformamide", "start": 124, "end": 143}, {"text": "N-cyclohexyl-2-pyrrolidone", "start": 145, "end": 171}]}}, "schema": []}
{"input": "The LC behavior of the as-prepared GO sheets in organic solvents has enabled us to disperse and organize substantial amounts of aggregate-free single-walled carbon nanotubes (SWNTs, up to 10 wt%) without compromise in LC properties.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 157, "end": 163}]}}, "schema": []}
{"input": "The as-prepared LC GO-SWNT dispersions were employed to achieve self-assembled layer-by-layer multifunctional 3D hybrid architectures comprising SWNTs and GO with unrivalled superior mechanical properties (Young' s modulus in excess of 50 GPa and tensile strength of more than 500 MPa).", "output": {"entities": {}}, "schema": []}
{"input": "Helicity as a Steric Force: Stabilization and Helicity-Dependent Reversion of Colored o-Quinonoid Intermediates of Helical Chromenes.", "output": {"entities": {"chemical": [{"text": "o-Quinonoid", "start": 86, "end": 97}]}}, "schema": []}
{"input": "Photolysis of regioisomeric helical chromenes 1 and 2 leads to colored reactive intermediates.", "output": {"entities": {}}, "schema": []}
{"input": "While the latter generally decay quite rapidly, they are found to be longer lived in 1 and highly persistent in 2.", "output": {"entities": {}}, "schema": []}
{"input": "The remarkable stability of the otherwise fleeting transient in 2 allowed isolation and structural characterization by X-ray crystallography.", "output": {"entities": {}}, "schema": []}
{"input": "The structural analyses revealed that steric force inherent to the helical scaffold is the origin of stability as well as differentiation in the persistence of the intermediates of 1 and 2 (1Q and 2Q).", "output": {"entities": {}}, "schema": []}
{"input": "The structure further shows that diphenylvinyl moiety in the TT isomer of 2Q gets splayed over the helical scaffold such that it is fraught with a huge steric strain to undergo required bond rotations to regenerate the precursor chromene.", "output": {"entities": {"chemical": [{"text": "diphenylvinyl", "start": 33, "end": 46}]}}, "schema": []}
{"input": "Otherwise, reversion of 2Q was found to occur at higher temperatures.", "output": {"entities": {}}, "schema": []}
{"input": "Aazahelical chromenes 3 and 4 with varying magnitudes of helicity were designed in pursuit of o-quinonoid intermediates with graded activation barriers.", "output": {"entities": {"chemical": [{"text": "o-quinonoid", "start": 94, "end": 105}]}}, "schema": []}
{"input": "Their photogenerated intermediates 3Q and 4Q were also isolated and structurally characterized.", "output": {"entities": {}}, "schema": []}
{"input": "The activation barriers for thermal reversion of 2Q-4Q, as determined from Arrhenius and Eyring plots, are found to correlate nicely with the helical turn, which decisively determines the steric force.", "output": {"entities": {}}, "schema": []}
{"input": "The exploitation of helicity is thus demonstrated to develop a novel set of photoresponsive helicenes 2-4 that lead to colored intermediates exhibiting graded stability.", "output": {"entities": {}}, "schema": []}
{"input": "It is further shown that the photochromism of 2-4 in conjunction with response of 2Q-4Q to external stimuli (acid, heat, and visible radiation) permits development of molecular logic gates with INHIBIT function.", "output": {"entities": {}}, "schema": []}
{"input": "Screening and Structural Analysis of Flavones Inhibiting Tankyrases.", "output": {"entities": {"chemical": [{"text": "Flavones", "start": 37, "end": 45}]}}, "schema": []}
{"input": "Flavonoids are known for their beneficial effects on human health, and therefore the therapeutic potential of these compounds have been extensively studied.", "output": {"entities": {"chemical": [{"text": "Flavonoids", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Flavone has been previously identified as a tankyrase inhibitor, and to further elucidate whether tankyrases would be inhibited by other flavonoids, we performed a systematic screening of tankyrase 2 inhibitory activity using 500 natural and naturally derived flavonoids covering nine different flavonoid classes.", "output": {"entities": {"chemical": [{"text": "Flavone", "start": 0, "end": 7}, {"text": "flavonoids", "start": 137, "end": 147}, {"text": "flavonoids", "start": 260, "end": 270}, {"text": "flavonoid", "start": 295, "end": 304}]}}, "schema": []}
{"input": "All identified tankyrase inhibitors were flavones.", "output": {"entities": {"chemical": [{"text": "flavones", "start": 41, "end": 49}]}}, "schema": []}
{"input": "We report crystal structures of all the hit compounds in complex with the catalytic domain of human tankyrase 2.", "output": {"entities": {}}, "schema": []}
{"input": "Flavone derivatives in all 10 crystal structures bind to the nicotinamide binding site of tankyrase 2.", "output": {"entities": {"chemical": [{"text": "Flavone", "start": 0, "end": 7}, {"text": "nicotinamide", "start": 61, "end": 73}]}}, "schema": []}
{"input": "Potencies of the active flavones toward tankyrases vary between 50 nM and 1. 1 mu M, and flavones show up to 200-fold selectivity for tankyrases over ARTD1.", "output": {"entities": {"chemical": [{"text": "flavones", "start": 24, "end": 32}, {"text": "flavones", "start": 89, "end": 97}]}}, "schema": []}
{"input": "The molecular details of the interactions revealed by cocrystal structures efficiently describe the properties of potent flavone derivatives inhibiting tankyrases.", "output": {"entities": {"chemical": [{"text": "flavone", "start": 121, "end": 128}]}}, "schema": []}
{"input": "Alexander b o hm (1971-2012).", "output": {"entities": {}}, "schema": []}
{"input": "On November 28, 2012 Alexander (Alex) B o hm, a bacterial geneticist, died at age 41, only a few months after taking up a position as an assistant professor at the LOEWE Center for Synthetic Microbiology in Marburg, Germany.", "output": {"entities": {}}, "schema": []}
{"input": "Earlier in 2012 Alex had been diagnosed with an aggressive form of thyroid cancer that left him little time to live his scientific and personal dreams.", "output": {"entities": {}}, "schema": []}
{"input": "Water-Mediated Interactions Influence the Binding of Thapsigargin to Sarco/Endoplasmic Reticulum Calcium Adenosinetriphosphatase.", "output": {"entities": {"chemical": [{"text": "Thapsigargin", "start": 53, "end": 65}, {"text": "Calcium", "start": 97, "end": 104}]}}, "schema": []}
{"input": "A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA).", "output": {"entities": {"chemical": [{"text": "thapsigargin", "start": 87, "end": 99}, {"text": "calcium", "start": 131, "end": 138}]}}, "schema": []}
{"input": "Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 91, "end": 99}, {"text": "thapsigargin", "start": 124, "end": 136}]}}, "schema": []}
{"input": "The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions.", "output": {"entities": {"chemical": [{"text": "thapsigargin", "start": 23, "end": 35}]}}, "schema": []}
{"input": "The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 175, "end": 183}]}}, "schema": []}
{"input": "Water-Soluble Polymer Exfoliated Graphene: As Catalyst Support and Sensor.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 33, "end": 41}]}}, "schema": []}
{"input": "In this paper, we obtained various water-soluble polymer functionalized graphene in dimethyl sulfoxide under ultrasonication.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 72, "end": 80}, {"text": "dimethyl sulfoxide", "start": 84, "end": 102}]}}, "schema": []}
{"input": "The atomic force microscope analysis and control experiment shows the water-soluble polymer is the crucial part to help solvent molecules separate interlayer.", "output": {"entities": {}}, "schema": []}
{"input": "Such polymer/graphene exhibits high conductivity and tunable surface property, as confirmed by the selected area electron diffraction and Raman and electrochemical impedance spectroscopy.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 13, "end": 21}]}}, "schema": []}
{"input": "As a result, a catalyst based on polyvinyl pyrrolidone (PVP)/graphene shows better methanol oxidation performance than that based on PVP/reduced graphene oxide.", "output": {"entities": {"chemical": [{"text": "polyvinyl pyrrolidone", "start": 33, "end": 54}, {"text": "PVP", "start": 56, "end": 59}, {"text": "graphene", "start": 61, "end": 69}, {"text": "methanol", "start": 83, "end": 91}, {"text": "PVP", "start": 133, "end": 136}, {"text": "graphene oxide", "start": 145, "end": 159}]}}, "schema": []}
{"input": "By changing to another polymer, poly (4-vinylpyridine)/graphene shows a stable and reversible response to pH, and demonstrates its potential for sensor application.", "output": {"entities": {"chemical": [{"text": "poly (4-vinylpyridine)", "start": 32, "end": 54}, {"text": "graphene", "start": 55, "end": 63}]}}, "schema": []}
{"input": "Detection of Nitrogen-Protonated Nitrous Oxide (HNNO (+)) by Rotational Spectroscopy.", "output": {"entities": {"chemical": [{"text": "Nitrogen", "start": 13, "end": 21}, {"text": "Protonated Nitrous Oxide", "start": 22, "end": 46}, {"text": "HNNO (+)", "start": 48, "end": 56}]}}, "schema": []}
{"input": "The rotational spectrum of nitrogen-protonated nitrous oxide (HNNO (+)), an isomer whose existence was first inferred from kinetic studies more than 30 years ago, has now been detected by Fourier transform microwave spectroscopy, guided by new high-level coupled-cluster calculations of its molecular structure.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 27, "end": 35}, {"text": "protonated nitrous oxide", "start": 36, "end": 60}, {"text": "HNNO (+)", "start": 62, "end": 70}]}}, "schema": []}
{"input": "From high-resolution measurements of the hyperfine splitting in its fundamental rotational transition, the rotational constant (B + C)/2 and the quadrupole tensor element chi aa (N) for both nitrogen atoms have been precisely determined.", "output": {"entities": {"chemical": [{"text": "N", "start": 179, "end": 180}, {"text": "nitrogen", "start": 191, "end": 199}]}}, "schema": []}
{"input": "The derived constants agree well with quantum-chemical calculations here and others in the literature.", "output": {"entities": {}}, "schema": []}
{"input": "The chi aa (N) values for the two isomers of protonated nitrous oxide are qualitatively consistent with the valence bond description of H-N = N (+) = O for the electronic structure of the nitrogen-protonated form and N = N (+)-O-H for the oxygen-protonated form.", "output": {"entities": {"chemical": [{"text": "N", "start": 12, "end": 13}, {"text": "protonated nitrous oxide", "start": 45, "end": 69}, {"text": "H-N = N (+) = O", "start": 136, "end": 151}, {"text": "nitrogen", "start": 188, "end": 196}, {"text": "N = N (+)-O-H", "start": 217, "end": 230}, {"text": "oxygen", "start": 239, "end": 245}]}}, "schema": []}
{"input": "HNNO (+) is found to be 2-4 times less abundant than NNOH (+) under a range of experimental conditions, as might be expected because this metastable isomer is known to be only ~ 6 kcal mol (-1) less stable than ground-state NNOH (+) from kinetic measurements by Ferguson and co-workers.", "output": {"entities": {"chemical": [{"text": "HNNO (+)", "start": 0, "end": 8}, {"text": "NNOH (+)", "start": 53, "end": 61}, {"text": "NNOH (+)", "start": 224, "end": 232}]}}, "schema": []}
{"input": "Immunopathology of rheumatoid arthritis.", "output": {"entities": {}}, "schema": []}
{"input": "Rheumatoid arthritis (RA) is one of the most common autoimmune diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Genetic and epidemiologic studies point to a relevant role of adaptive T-cell response interactions with environmental factors such as smoking in the immunopathogenesis of the disease.", "output": {"entities": {}}, "schema": []}
{"input": "These interactions result in a specific systemic autoantibody response that seems to contribute to the synovial inflammatory process.", "output": {"entities": {}}, "schema": []}
{"input": "The reasons for specific localization of the autoimmune proinflammatory process to synovial tissue remain poorly known, but relevant local effector mechanisms have been recently unveiled and successfully targeted by new specific therapies.", "output": {"entities": {}}, "schema": []}
{"input": "A relevant role for cytokine networks, where TNF-alpha displays a pivotal role, has been confirmed.", "output": {"entities": {}}, "schema": []}
{"input": "The local pathology is hallmarked by immune cell accumulation and expansion of resident stromal and vascular cells.", "output": {"entities": {}}, "schema": []}
{"input": "Crosstalk between these elements generates an aggressive environment that leads to cartilage and bone destruction. RA provides represents a model for systemic T-cell mediated systemic autoimmunity leading to local cellular and autoantibody mediated chronic inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas targeting of these elements with specific antagonists may interfere with the disease process, reestablishing tolerance and preventing further synovial inflammation has not been achieved.", "output": {"entities": {}}, "schema": []}
{"input": "Safety evaluation of desloratadine in allergic rhinitis.", "output": {"entities": {"chemical": [{"text": "desloratadine", "start": 21, "end": 34}]}}, "schema": []}
{"input": "Introduction: Desloratadine is a biologically active metabolite of second-generation antihistamine loratadine.", "output": {"entities": {"chemical": [{"text": "Desloratadine", "start": 14, "end": 27}, {"text": "loratadine", "start": 99, "end": 109}]}}, "schema": []}
{"input": "It is also indicated for the treatment of allergic diseases, including allergic rhinitis.", "output": {"entities": {}}, "schema": []}
{"input": "Areas covered: A Medline search was conducted to identify preclinical and clinical studies of desloratadine.", "output": {"entities": {"chemical": [{"text": "desloratadine", "start": 94, "end": 107}]}}, "schema": []}
{"input": "This was supplemented with additional articles obtained from online sources.", "output": {"entities": {}}, "schema": []}
{"input": "The focus of this review is on the safety profile of desloratadine.", "output": {"entities": {"chemical": [{"text": "desloratadine", "start": 53, "end": 66}]}}, "schema": []}
{"input": "Expert opinion: The review of these data indicates that the safety profile of desloratadine is similar to other second-generation antihistamines.", "output": {"entities": {"chemical": [{"text": "desloratadine", "start": 78, "end": 91}]}}, "schema": []}
{"input": "Desloratadine is highly selective for histamine H1-receptors, does not cross the blood-brain barrier (BBB), and has minimal adverse events (very low sedation rate), with a better safety and tolerability than first-generation antihistamines.", "output": {"entities": {"chemical": [{"text": "Desloratadine", "start": 0, "end": 13}, {"text": "histamine", "start": 38, "end": 47}]}}, "schema": []}
{"input": "Desloratadine is safe and well tolerated without having central nervous system (CNS) or cardiovascular effects and with low drug interaction.", "output": {"entities": {"chemical": [{"text": "Desloratadine", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Proposed diagnostic criteria for subclinical Cushing' s syndrome associated with adrenal incidentaloma.", "output": {"entities": {}}, "schema": []}
{"input": "Subclinical Cushing' s syndrome (SCS) associated with adrenal incidentaloma is usually characterized by autonomous cortisol secretion without overt symptoms of Cushing' s syndrome (CS).", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 115, "end": 123}]}}, "schema": []}
{"input": "Although the diagnostic criteria for SCS differ among countries, the 1 mg dexamethasone suppression test (DST) is essential to confirm the presence and the extent of cortisol overproduction.", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 74, "end": 87}, {"text": "cortisol", "start": 166, "end": 174}]}}, "schema": []}
{"input": "Since 1995, SCS has been diagnosed in Japan based on serum cortisol levels >= 3 mu g/dl (measured by radioimmunoassay [RIA]) after a 1 mg DST.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 59, "end": 67}]}}, "schema": []}
{"input": "However, the increasing use of enzyme immunoassays (EIA) instead of RIA has hindered the diagnosis of SCS because of the differing sensitivities of commercially available assays, particularly for serum cortisol levels of around 3 mu g/dl.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 202, "end": 210}]}}, "schema": []}
{"input": "One way to overcome this problem is to lower the cortisol threshold level after a 1 mg DST.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 49, "end": 57}]}}, "schema": []}
{"input": "In the present study, we examined the clinical applicability of lowering the cortisol threshold to 1. 8 mu g/dl, similar to the American Endocrine Society' s guidelines for CS, by reanalyzing 119 patients with adrenal incidentaloma.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 77, "end": 85}]}}, "schema": []}
{"input": "Our findings indicate that serum cortisol levels >= 1. 8 mu g/dl after 1 mg DST are useful to confirm the diagnosis of SCS if both of the following criteria are met: (1) basal ACTH level < 10 pg/ml (or poor plasma ACTH response to corticotrophin-releasing hormone) and (2) serum cortisol >= 5 mu g/dl at 21: 00 to 23: 00 h.", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 33, "end": 41}, {"text": "cortisol", "start": 279, "end": 287}]}}, "schema": []}
{"input": "If only one of (1) and (2) are met, we recommend that other clinical features are considered in the diagnosis of SCS, including serum dehydroepiandrosterone sulfate levels, urine free cortisol levels, adrenal scintigraphy, and clinical manifestation.", "output": {"entities": {"chemical": [{"text": "dehydroepiandrosterone sulfate", "start": 134, "end": 164}, {"text": "cortisol", "start": 184, "end": 192}]}}, "schema": []}
{"input": "Synthesis, Antidepressant Evaluation and Docking Studies of Long-Chain Alkylnitroquipazines as Serotonin Transporter Inhibitors.", "output": {"entities": {"chemical": [{"text": "Alkylnitroquipazines", "start": 71, "end": 91}, {"text": "Serotonin", "start": 95, "end": 104}]}}, "schema": []}
{"input": "Twelve alkyl analogues (1-12) of the high-affinity serotonin transporter (SERT) inhibitor 6-nitroquipazine (6-NQ) were synthesized and studied using in vitro radioligand competition binding assays to determine their binding affinity (Ki).", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 7, "end": 12}, {"text": "serotonin", "start": 51, "end": 60}, {"text": "6-nitroquipazine", "start": 90, "end": 106}, {"text": "6-NQ", "start": 108, "end": 112}]}}, "schema": []}
{"input": "The putative antidepressant activity of five of the binders with the highest SERT binding affinities was studied by the forced swim and locomotor activity mouse tests.", "output": {"entities": {}}, "schema": []}
{"input": "The three-dimensional (3D) structures of 8 and 9 were determined using NOE NMR technique.", "output": {"entities": {}}, "schema": []}
{"input": "Flexible docking of the compounds was undertaken to illustrate the binding of the compounds in the SERT model.", "output": {"entities": {}}, "schema": []}
{"input": "Our results showed that several of the 6-NQ analogues are high-affinity SERT inhibitors and indicated that the octyl (8), decyl (10) and dodecyl (12) 6-NQ analogues exhibit moderate antidepressant activity.", "output": {"entities": {"chemical": [{"text": "6-NQ", "start": 39, "end": 43}, {"text": "octyl", "start": 111, "end": 116}, {"text": "decyl", "start": 122, "end": 127}, {"text": "dodecyl", "start": 137, "end": 144}, {"text": "6-NQ", "start": 150, "end": 154}]}}, "schema": []}
{"input": "Vortex domain structures of an epitaxial ferroelectric nanodot and its temperature-misfit strain phase diagram.", "output": {"entities": {}}, "schema": []}
{"input": "Phase field simulations were conducted to investigate the effect of misfit strain on the vortex domain structure (VDS) in a BaTiO3 nanodot.", "output": {"entities": {"chemical": [{"text": "BaTiO3", "start": 124, "end": 130}]}}, "schema": []}
{"input": "Taking into account the effect of inhomogeneous eletromechanical fields, ambient temperature and surface effects, our calculations demonstrate a strong effect of misfit strain on the orientation and magnitude of the polarization dipoles.", "output": {"entities": {}}, "schema": []}
{"input": "As a consequence, fruitful equilibrium vortex domain patterns can be obtained by adjusting the epitaxial misfit strain between the substrate and the nanodot.", "output": {"entities": {}}, "schema": []}
{"input": "While the nanodot exhibits a single transition from a paraelectric to a near-rhombohedral vortex state at zero misfit strain with the decrease of temperature, complicated transformations of vortex domain patterns are found under nonzero misfit strain.", "output": {"entities": {}}, "schema": []}
{"input": "Typically, orthorhombic, tetragonal and several unreported vortex domain patterns (e. g., with zero toroidal moment) are found.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, misfit strain-induced transformations into these domain patterns are also predicted for a ferroelectric nanodot with initial near-rhombohedral vortex state.", "output": {"entities": {}}, "schema": []}
{"input": "Combining effects of the ambient temperature and misfit strain, a \" temperature-misfit strain \" phase-diagram depicting the fruitful vortex domain patterns of the nanodot was obtained.", "output": {"entities": {}}, "schema": []}
{"input": "Our simulations indicate promising application of strain engineering in controlling the VDS in ferroelectric nanostructures.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolomics reveals trichloroacetate as a major contributor to trichloroethylene-induced metabolic alterations in mouse urine and serum.", "output": {"entities": {"chemical": [{"text": "trichloroacetate", "start": 21, "end": 37}, {"text": "trichloroethylene", "start": 64, "end": 81}]}}, "schema": []}
{"input": "Trichloroethylene (TCE)-induced liver toxicity and carcinogenesis is believed to be mediated in part by activation of the peroxisome proliferator-activated receptor alpha (PPAR alpha).", "output": {"entities": {"chemical": [{"text": "Trichloroethylene", "start": 0, "end": 17}, {"text": "TCE", "start": 19, "end": 22}]}}, "schema": []}
{"input": "However, the contribution of the two TCE metabolites, dichloroacetate (DCA) and trichloroacetate (TCA) to the toxicity of TCE, remains unclear.", "output": {"entities": {"chemical": [{"text": "TCE", "start": 37, "end": 40}, {"text": "dichloroacetate", "start": 54, "end": 69}, {"text": "DCA", "start": 71, "end": 74}, {"text": "trichloroacetate", "start": 80, "end": 96}, {"text": "TCA", "start": 98, "end": 101}, {"text": "TCE", "start": 122, "end": 125}]}}, "schema": []}
{"input": "The aim of the present study was to determine the metabolite profiles in serum and urine upon exposure of mice to TCE, to aid in determining the metabolic response to TCE exposure and the contribution of DCA and TCA to TCE toxicity.", "output": {"entities": {"chemical": [{"text": "TCE", "start": 114, "end": 117}, {"text": "TCE", "start": 167, "end": 170}, {"text": "DCA", "start": 204, "end": 207}, {"text": "TCA", "start": 212, "end": 215}, {"text": "TCE", "start": 219, "end": 222}]}}, "schema": []}
{"input": "C57BL/6 mice were administered TCE, TCA, or DCA, and urine and serum subjected to ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based global metabolomics analysis.", "output": {"entities": {"chemical": [{"text": "TCE", "start": 31, "end": 34}, {"text": "TCA", "start": 36, "end": 39}, {"text": "DCA", "start": 44, "end": 47}]}}, "schema": []}
{"input": "The ions were identified through searching metabolomics databases and by comparison with authentic standards, and quantitated using multiple reactions monitoring.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative polymerase chain reaction of mRNA, biochemical analysis, and liver histology were also performed.", "output": {"entities": {}}, "schema": []}
{"input": "TCE exposure resulted in a decrease in urine of metabolites involved in fatty acid metabolism, resulting from altered expression of PPAR alpha target genes.", "output": {"entities": {"chemical": [{"text": "TCE", "start": 0, "end": 3}, {"text": "fatty acid", "start": 72, "end": 82}]}}, "schema": []}
{"input": "TCE treatment also induced altered phospholipid homeostasis in serum, as revealed by increased serum lysophosphatidylcholine 18: 0 and 18: 1, and phosphatidylcholine metabolites.", "output": {"entities": {"chemical": [{"text": "TCE", "start": 0, "end": 3}, {"text": "lysophosphatidylcholine 18: 0 and 18: 1", "start": 101, "end": 140}, {"text": "phosphatidylcholine", "start": 146, "end": 165}]}}, "schema": []}
{"input": "TCA administration revealed similar metabolite profiles in urine and serum upon TCE exposure, which correlated with a more robust induction of PPAR alpha target gene expression associated with TCA than DCA treatment.", "output": {"entities": {"chemical": [{"text": "TCA", "start": 0, "end": 3}, {"text": "TCE", "start": 80, "end": 83}, {"text": "TCA", "start": 193, "end": 196}, {"text": "DCA", "start": 202, "end": 205}]}}, "schema": []}
{"input": "These data show the metabolic response to TCE exposure and demonstrate that TCA is the major contributor to TCE-induced metabolite alterations observed in urine and serum.", "output": {"entities": {"chemical": [{"text": "TCE", "start": 42, "end": 45}, {"text": "TCA", "start": 76, "end": 79}, {"text": "TCE", "start": 108, "end": 111}]}}, "schema": []}
{"input": "Boron Enhances Odontogenic and Osteogenic Differentiation of Human Tooth Germ Stem Cells (hTGSCs) In Vitro.", "output": {"entities": {"chemical": [{"text": "Boron", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Stem cell technology has been a great hope for the treatment of many common problems such as Parkinson' s disease, Alzheimer' s disease, diabetes, cancer, and tissue regeneration.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the main challenge in hard tissue engineering is to make a successful combination of stem cells and efficient inductors in the concept of stem cell differentiation into odontogenic and osteogenic cell types.", "output": {"entities": {}}, "schema": []}
{"input": "Although some boron derivatives have been reported to promote bone and teeth growth in vivo, the molecular mechanism of bone formation has not been elucidated yet.", "output": {"entities": {"chemical": [{"text": "boron", "start": 14, "end": 19}]}}, "schema": []}
{"input": "Different concentrations of sodium pentaborate pentahydrate (NaB) were prepared for the analysis of cell toxicity and differentiation evaluations.", "output": {"entities": {"chemical": [{"text": "sodium pentaborate pentahydrate", "start": 28, "end": 59}, {"text": "NaB", "start": 61, "end": 64}]}}, "schema": []}
{"input": "The odontogenic, osteogenic differentiation and biomineralization of human tooth germ stem cells (hTGSCs) were evaluated by analyzing the mRNA expression levels, odontogenic and osteogenic protein expressions, alkaline phosphatase (ALP) activity, mineralization, and calcium deposits.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 267, "end": 274}]}}, "schema": []}
{"input": "The NaB-treated group displayed the highest ALP activity and expression of osteo-and odontogenic-related genes and proteins compared to the other groups and baseline.", "output": {"entities": {"chemical": [{"text": "NaB", "start": 4, "end": 7}]}}, "schema": []}
{"input": "In the current study, increased in vitro odontogenic and osteogenic differentiation capacity of hTGSCs by NaB application has been shown for the first time.", "output": {"entities": {"chemical": [{"text": "NaB", "start": 106, "end": 109}]}}, "schema": []}
{"input": "The study offers considerable promise for the development of new scaffold systems combined with NaB in both functional bone and tooth tissue engineering.", "output": {"entities": {"chemical": [{"text": "NaB", "start": 96, "end": 99}]}}, "schema": []}
{"input": "Cryptococcal infections: changing epidemiology and implications for therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Although the incidence of HIV-associated cryptococcosis has decreased in developed countries since the introduction of antiretroviral therapy, this disease continues to cause significant morbidity and mortality in sub-Saharan Africa among patients with AIDS.", "output": {"entities": {}}, "schema": []}
{"input": "Important strides have been made in an attempt to decrease the burden of disease, particularly the development of the lateral flow assay cryptococcal antigen (LFA CrAg) as a diagnostic tool in resource-limited settings, coupled with the introduction of pre-emptive treatment with fluconazole for HIV-positive patients at risk for cryptococcosis with a positive LFA CrAg.", "output": {"entities": {"chemical": [{"text": "fluconazole", "start": 280, "end": 291}]}}, "schema": []}
{"input": "Among solid organ transplant recipients, recent prospective studies have identified cryptococcosis as the third most common invasive fungal infection, and progress is being made toward earlier diagnosis and more effective therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, the Cryptococcus gattii outbreak in British Columbia, Canada and the US Pacific Northwest is providing important new insights into the emergence of this pathogen in geographic areas previously considered low risk for acquisition of infection.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the similarities and differences among C. gattii and C. neoformans infections will provide critical insights into the behavior of these organisms in the human host.", "output": {"entities": {}}, "schema": []}
{"input": "Both pathogens affect immunocompetent and immunosuppressed hosts, causing pulmonary, central nervous system and widely disseminated infections.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment recommendations in the future will necessarily take into account the site of infection, clinical severity of the infection, Cryptococcus species, host immune status and economic resources.", "output": {"entities": {}}, "schema": []}
{"input": "Protective effects of green tea on antioxidative biomarkers in chemical laboratory workers.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical materials are environmental contaminants, are extensively used in laboratories, and may cause various forms of health hazards in laboratory workers.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, this toxicity most likely is a result of the oxidative metabolism of chemical to reactive products.", "output": {"entities": {}}, "schema": []}
{"input": "As green tea (GT) possesses antioxidant effects, the objective of this study was to examine any amelioration oxidative stress in chemical laboratory workers drinking one cup (3 g/300 ml water) of freshly prepared tea once daily.", "output": {"entities": {}}, "schema": []}
{"input": "Baseline characteristics including age, sex, smoking, fruit consumption, and duration of exposure were recorded via questionnaire to the subjects.", "output": {"entities": {}}, "schema": []}
{"input": "Saliva level oxidative stress parameters such as total antioxidant capacity (TAC), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were estimated before and after consumption of GT in these workers.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 83, "end": 94}, {"text": "superoxide", "start": 133, "end": 143}]}}, "schema": []}
{"input": "Treatment of subjects with GT induced a significant reduction in saliva GPx activity (406. 61 +/- 22. 07 vs. 238. 96 +/- 16. 26 U/l p = 0. 001) and induction in TAC (0. 46 +/- 0. 029 mu mol/ml vs. 0. 56 +/- 0. 031, p = 0. 016).", "output": {"entities": {}}, "schema": []}
{"input": "No statistically significant alteration was found for saliva SOD (0. 080 +/- 0. 0019 vs. 0. 079 +/- 0. 0014, p > 0. 05) and CAT (20. 36 +/- 0. 69 vs. 19. 78 +/- 0. 71, p > 0. 05) after 28 days treatment by GT.", "output": {"entities": {}}, "schema": []}
{"input": "These results demonstrate that drinking GT during chemical exposure can reduce several parameters indicative of oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, using GT as a dietary supplement can be a rational protocol to control source of hazards in chemical laboratory workers.", "output": {"entities": {}}, "schema": []}
{"input": "Attenuation of Gouty Arthritis by Emodinol in Monosodium Urate Crystal-Treated Mice.", "output": {"entities": {"chemical": [{"text": "Emodinol", "start": 34, "end": 42}, {"text": "Monosodium Urate", "start": 46, "end": 62}]}}, "schema": []}
{"input": "A series of studies have recently demonstrated that the release of interleukin 1 beta induced by monosodium urate crystals is central to the experimental gouty arthritis.", "output": {"entities": {"chemical": [{"text": "monosodium urate", "start": 97, "end": 113}]}}, "schema": []}
{"input": "Elaeagnus pungens has been traditionally used for the treatment of gouty arthritis in China for more than thousands years.", "output": {"entities": {}}, "schema": []}
{"input": "However, there is still little known about the active ingredients and mechanisms of E. pungens against gouty arthritis.", "output": {"entities": {}}, "schema": []}
{"input": "Emodinol, as a major triterpene compound in E. pungens, has been seldom reported to have an effect on gouty arthritis.", "output": {"entities": {"chemical": [{"text": "Emodinol", "start": 0, "end": 8}, {"text": "triterpene", "start": 21, "end": 31}]}}, "schema": []}
{"input": "Therefore, the potential beneficial effects and mechanisms of emodinol on gouty arthritis were investigated in this study.", "output": {"entities": {"chemical": [{"text": "emodinol", "start": 62, "end": 70}]}}, "schema": []}
{"input": "Results showed that it significantly ameliorated the hyperalgesia, inflammation, and levels of multiple proinflammatory cytokines in monosodium urate crystals-treated mice.", "output": {"entities": {"chemical": [{"text": "monosodium urate", "start": 133, "end": 149}]}}, "schema": []}
{"input": "These findings elucidate that emodinol exhibits a prominent effect on improving symptoms of acute gouty arthritis induced by monosodium urate crystals through inhibiting the generation of proinflammatory cytokines.", "output": {"entities": {"chemical": [{"text": "emodinol", "start": 30, "end": 38}, {"text": "monosodium urate", "start": 125, "end": 141}]}}, "schema": []}
{"input": "Dioecy in Plants-Is It an Important Factor for Phytochemists to Consider?", "output": {"entities": {}}, "schema": []}
{"input": "Plants with separate male and female flowers are termed dioecious.", "output": {"entities": {}}, "schema": []}
{"input": "Dioecy is not rare, yet is a characteristic that could potentially impact the phytochemical and subsequent pharmacological properties of a species.", "output": {"entities": {}}, "schema": []}
{"input": "This is a brief insight which highlights why the sex of the plant might be an important factor to consider for researchers within phytochemistry related fields.", "output": {"entities": {}}, "schema": []}
{"input": "Scanning protein analysis of electrofocusing gels using X-ray fluorescence.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, \" metallomics, \" in addition to genomics and proteomics, has become a focus as a novel approach to identify sensitive fluctuations in homeostasis that accompany metabolic processes, such as stress responses, differentiation, and proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular elements and associated protein behavior provide important clues for understanding cellular and disease mechanism (s).", "output": {"entities": {}}, "schema": []}
{"input": "It is important to develop a system for measuring the native status of the protein.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we developed an original freeze-dried electrofocusing native gel over polyimide film (native-gel film) for scanning protein analysis using synchrotron radiation excited X-ray fluorescence (SPAX).", "output": {"entities": {"chemical": [{"text": "polyimide", "start": 85, "end": 94}]}}, "schema": []}
{"input": "To our knowledge, this is the first report detailing the successful mapping of metal-associated proteins of electrofocusing gels using X-ray fluorescence.", "output": {"entities": {}}, "schema": []}
{"input": "SPAX can provide detection sensitivity equivalent to that of LA-ICP-MS.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to this increased sensitivity, SPAX has the potential to be combined with other X-ray spectroscopies.", "output": {"entities": {}}, "schema": []}
{"input": "Our system is useful for further applications in proteomics investigating cellular element-associated protein behaviors and disease mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Simultaneous two and three photon resonant enhancement of third-order NLO susceptibility in an azo-dye functionalized polymer film.", "output": {"entities": {"chemical": [{"text": "azo", "start": 95, "end": 98}]}}, "schema": []}
{"input": "We report the observation of simultaneous two and three photon resonances, enhancing the third-order NLO susceptibility in a thin film of an azo-dye polymer.", "output": {"entities": {"chemical": [{"text": "azo", "start": 141, "end": 144}]}}, "schema": []}
{"input": "The possibility of 2-3 orders of magnitude increase in chi ((3)) susceptibility is sustained by quantum mechanical calculations.", "output": {"entities": {}}, "schema": []}
{"input": "This improves the applications of azo-polymers in all optical signal processing as well as in nonlinear optical imaging.", "output": {"entities": {"chemical": [{"text": "azo", "start": 34, "end": 37}]}}, "schema": []}
{"input": "The lifetime and efficiency of triplet-triplet fluorescence from the excited state of a TMM biradical determined using transient emission spectroscopy by two-color two-laser flash photolysis.", "output": {"entities": {"chemical": [{"text": "TMM", "start": 88, "end": 91}]}}, "schema": []}
{"input": "The single laser flash photolysis (FP) of 2-(4-benzoylphenyl)-2-phenyl-1-methylenecyclopropane gave rise to a ground state trimethylenemethane (TMM) biradical with absorption bands at 362 and 545 nm and an excited state of this biradical that displays triplet-triplet fluorescence at 580 nm.", "output": {"entities": {"chemical": [{"text": "2-(4-benzoylphenyl)-2-phenyl-1-methylenecyclopropane", "start": 42, "end": 94}, {"text": "trimethylenemethane", "start": 123, "end": 142}, {"text": "TMM", "start": 144, "end": 147}]}}, "schema": []}
{"input": "The excited biradical is likely formed via an expected two-photon process as well as an unexpected one-photon process.", "output": {"entities": {}}, "schema": []}
{"input": "The fluorescence quantum yield of the excited biradical, 0. 021, was successfully determined by employing a two-color two-laser FP technique.", "output": {"entities": {}}, "schema": []}
{"input": "The PIM Family of Serine/Threonine Kinases in Cancer.", "output": {"entities": {"chemical": [{"text": "Serine", "start": 18, "end": 24}, {"text": "Threonine", "start": 25, "end": 34}]}}, "schema": []}
{"input": "The proviral insertion site in Moloney murine leukemia virus, or PIM proteins, are a family of serine/threonine kinases composed of three different isoforms (PIM1, PIM2, and PIM3) that are highly evolutionarily conserved.", "output": {"entities": {"chemical": [{"text": "serine", "start": 95, "end": 101}, {"text": "threonine", "start": 102, "end": 111}]}}, "schema": []}
{"input": "These proteins are regulated primarily by transcription and stability through pathways that are controlled by Janus kinase/Signal transducer and activator of transcription, JAK/STAT, transcription factors.", "output": {"entities": {}}, "schema": []}
{"input": "The PIM family proteins have been found to be overexpressed in hematological malignancies and solid tumors, and their roles in these tumors were confirmed in mouse tumor models.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, the PIM family proteins have been implicated in the regulation of apoptosis, metabolism, cell cycle, and homing and migration, which has led to the postulation of these proteins as interesting targets for anticancer drug discovery.", "output": {"entities": {}}, "schema": []}
{"input": "In the present work, we review the importance of PIM kinases in tumor growth and as drug targets.", "output": {"entities": {}}, "schema": []}
{"input": "Congruence of Phytochemical and Morphological Profiles along an Altitudinal Gradient in Origanum vulgare ssp. vulgare from Venetian Region (NE Italy).", "output": {"entities": {}}, "schema": []}
{"input": "Plants of Origanum vulgare L. ssp.", "output": {"entities": {}}, "schema": []}
{"input": "vulgare from the Veneto region (NE Italy) were selected to study the variability of the essential-oil composition from leaves and inflorescences throughout an elevation gradient.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated also the morphology of non-glandular and glandular trichomes, their distribution on the vegetative and reproductive organs, as well as the histochemistry of the secreted products, with special focus on the terpenoidic fraction.", "output": {"entities": {}}, "schema": []}
{"input": "Since glandular trichomes are prerequisite for the essential-oil synthesis, the second objective was to establish whether its production is related to glandular hair number, and density.", "output": {"entities": {}}, "schema": []}
{"input": "Essential-oil contents decline with increasing altitude, and the micromorphological observations revealed a decrease in trichome density along the same direction.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, GC/MS analysis together with principal component analysis (PCA) showed that the three investigated populations were significantly different in chemical composition.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, an important interpopulation variability for low-, mid-, and high-altitude sites was established, suggesting the likely occurrence of different biotypes associated with altitudinal levels.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, the involvement of abiotic factors such as temperature and drought in the chemical polymorphism of O. vulgare associated with elevation is briefly discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Configurational Assignment of Secondary Hydroxyl Groups and Methyl Branches in Polyketide Natural Products through Bioinformatic Analysis of the Ketoreductase Domain.", "output": {"entities": {"chemical": [{"text": "Hydroxyl", "start": 40, "end": 48}, {"text": "Methyl", "start": 60, "end": 66}]}}, "schema": []}
{"input": "Profile hidden Markov models (HMMs) were used to predict the configuration of secondary alcohols and alpha-methyl branches of modular polyketides.", "output": {"entities": {"chemical": [{"text": "secondary alcohols", "start": 78, "end": 96}, {"text": "alpha-methyl", "start": 101, "end": 113}]}}, "schema": []}
{"input": "Based on the configurations of two chiral centers in these polyketides, 78 ketoreductases were classified into four different types of polyketide producers.", "output": {"entities": {}}, "schema": []}
{"input": "The identification of positions that discriminate between these protein families was followed by fitting six profile HMMs to the data set and the corresponding subsets, to model the conserved regions of the protein types.", "output": {"entities": {}}, "schema": []}
{"input": "Ultimately, the profile HMMs described herein predict protein subtypes based on the complete information-rich region; consequently, slight changes in a multiple sequence alignment do not significantly alter the outcome of this classification method.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, Viterbi scores can be used to assess the reliability of the classification.", "output": {"entities": {}}, "schema": []}
{"input": "Identification and Characterization of a Cellulose Binding Heptapeptide Revealed by Phage Display.", "output": {"entities": {"chemical": [{"text": "Heptapeptide", "start": 59, "end": 71}]}}, "schema": []}
{"input": "Cellulose nanowhiskers (CNWs) were used in conjunction with phage display technology to identify polypeptides which bind the crystalline region of cellulose.", "output": {"entities": {}}, "schema": []}
{"input": "A consensus peptide WHWTYYW was identified to efficiently bind the CNWs.", "output": {"entities": {}}, "schema": []}
{"input": "The binding affinities of specific phage particles were assessed using biopanning assays and enzyme-linked immunosorbent assay (ELISA).", "output": {"entities": {}}, "schema": []}
{"input": "The WHWTYYW peptide was synthesized and isothermal titration calorimetry (ITC) analysis showed that the peptide exhibited a binding constant of ~ 10 (5) M (-1) toward the crystalline CNWs.", "output": {"entities": {}}, "schema": []}
{"input": "In order to understand how the affinity of this peptide differs for non-crystalline cellulose, binding properties were characterized using cello-oligosaccharides as substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Binding analysis was performed using UV spectroscopy and fluorescence quenching experiments.", "output": {"entities": {}}, "schema": []}
{"input": "The specific molecular interactions of the WHWTYYW peptide with cellohexaose were examined using nuclear magnetic resonance (NMR).", "output": {"entities": {"chemical": [{"text": "cellohexaose", "start": 64, "end": 76}]}}, "schema": []}
{"input": "Interactions of this peptide with crystalline cellulose were also investigated using computational molecular modeling (MM) studies.", "output": {"entities": {}}, "schema": []}
{"input": "The MM and NMR experiments indicate that the WHWTYYW peptide exhibits a bent structure when bound, allowing the Y5 amino acid to form a CH/pi stacking interaction and H-bond with the glucose ring of cellulose.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 115, "end": 125}, {"text": "CH", "start": 136, "end": 138}, {"text": "H", "start": 167, "end": 168}, {"text": "glucose", "start": 183, "end": 190}]}}, "schema": []}
{"input": "Probing the Mechanism of TBAF-Catalyzed Deacylation of Cellulose Esters.", "output": {"entities": {"chemical": [{"text": "TBAF", "start": 25, "end": 29}, {"text": "Esters", "start": 65, "end": 71}]}}, "schema": []}
{"input": "The mechanism of the recently discovered, unusual tetrabutylammonium fluoride (TBAF) deacylation of cellulose esters has been investigated by methods including kinetic isotope effect (KIE) studies.", "output": {"entities": {"chemical": [{"text": "tetrabutylammonium fluoride", "start": 50, "end": 77}, {"text": "TBAF", "start": 79, "end": 83}]}}, "schema": []}
{"input": "The secondary KIE (kH/kD = 1. 26 +/- 0. 04) measured for deacylation at C-2/3 suggests a mechanism involving a ketene intermediate for those positions.", "output": {"entities": {}}, "schema": []}
{"input": "An inverse KIE (kH/kD = 0. 87 +/- 0. 03) for the deacylation at C-6 indicates the involvement of a tetrahedral intermediate in the mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "Additional studies suggest the possibility that TBAF chelation by neighboring acyl groups may account for the unexpected regioselectivity at the secondary alcohol esters that is observed in the TBAF deacylation of cellulose esters.", "output": {"entities": {"chemical": [{"text": "TBAF", "start": 48, "end": 52}, {"text": "acyl", "start": 78, "end": 82}, {"text": "secondary alcohol esters", "start": 145, "end": 169}, {"text": "TBAF", "start": 194, "end": 198}, {"text": "esters", "start": 224, "end": 230}]}}, "schema": []}
{"input": "Liquid/Gas and Liquid/Liquid Phase Equilibria of the System Water/Bovine Serum Albumin.", "output": {"entities": {}}, "schema": []}
{"input": "The thermodynamic behavior of the system H2O/BSA was studied at 25 degrees C within the entire composition range: vapor pressure measurements via head space sampling gas chromatography demonstrate that the attainment of equilibria takes more than one week.", "output": {"entities": {"chemical": [{"text": "H2O", "start": 41, "end": 44}]}}, "schema": []}
{"input": "A miscibility gap was detected via turbidity and the coexisting phases were analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "At 6 degrees C the two phase region extends from ca.", "output": {"entities": {}}, "schema": []}
{"input": "34 to 40 wt% BSA; it shrinks upon heating.", "output": {"entities": {}}, "schema": []}
{"input": "The polymer rich phase is locally ordered, as can be seen under the optical microscope using crossed polarizers.", "output": {"entities": {}}, "schema": []}
{"input": "The Flory-Huggins theory turns out to be inappropriate for the modeling of experimental results.", "output": {"entities": {}}, "schema": []}
{"input": "A phenomenological expression is employed which uses three adjustable parameters and describes the vapor pressures quantitatively; it also forecasts the existence of a miscibility gap.", "output": {"entities": {}}, "schema": []}
{"input": "Monitoring Controlled Release of Payload from Gold Nanocages Using Surface Enhanced Raman Scattering.", "output": {"entities": {}}, "schema": []}
{"input": "Novel organic and inorganic nanostructures for localized and externally triggered delivery of therapeutic agents at a target site have received immense attention over the past decade owing to their enormous potential in treating complex diseases such as cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Gold nanocages, a novel class of hollow plasmonic nanostructures, have been recently demonstrated to serve as carriers for the delivery of payload with external trigger such as light or ultrasound.", "output": {"entities": {}}, "schema": []}
{"input": "In this article, we demonstrate that surface enhanced Raman spectroscopy (SERS) can be employed to noninvasively monitor the release of payload from these hollow plasmonic nanostructures.", "output": {"entities": {}}, "schema": []}
{"input": "The large enhancement of electromagnetic (EM) field at the interior surface of these nanostructures enables us to monitor the controlled release of Raman-active cargo from nanocages.", "output": {"entities": {}}, "schema": []}
{"input": "Considering that SERS can be excited and collected in near-infrared (NIR) therapeutic window, this technique can serve as a powerful tool to monitor the drug release in vivo, providing additional control over externally triggered drug administration.", "output": {"entities": {}}, "schema": []}
{"input": "Carcinogenicity Prediction of Noncongeneric Chemicals by a Support Vector Machine.", "output": {"entities": {}}, "schema": []}
{"input": "The ability to identify carcinogenic compounds is of fundamental importance to the safe application of chemicals.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we generated an array of in silico models allowing the classification of compounds into carcinogenic and noncarcinogenic agents based on a data set of 852 noncongeneric chemicals collected from the Carcinogenic Potency Database (CPDBAS).", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-four molecular descriptors were selected by Pearson correlation, F-score, and stepwise regression analysis.", "output": {"entities": {}}, "schema": []}
{"input": "These descriptors cover a range of physicochemical properties, including electrophilicity, geometry, molecular weight, size, and solubility.", "output": {"entities": {}}, "schema": []}
{"input": "The descriptor mutagenic showed the highest correlation coefficient with carcinogenicity.", "output": {"entities": {}}, "schema": []}
{"input": "On the basis of these descriptors, a support vector machine-based (SVM) classification model was developed and fine-tuned by a 10-fold cross-validation approach.", "output": {"entities": {}}, "schema": []}
{"input": "Both the SVM model (Model A1) and the best model from the 10-fold cross-validation (Model B3) runs gave good results on the test set with prediction accuracy over 80%, sensitivity over 76%, and specificity over 82%.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, extended connectivity fingerprints (ECFPs) and the Toxtree software were used to analyze the functional groups and substructures linked to carcinogenicity.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that the results of both methods are in good agreement.", "output": {"entities": {}}, "schema": []}
{"input": "Natural Products Containing a Nitrogen-Nitrogen Bond.", "output": {"entities": {"chemical": [{"text": "Nitrogen", "start": 30, "end": 38}, {"text": "Nitrogen", "start": 39, "end": 47}]}}, "schema": []}
{"input": "As of early 2013, over 200 natural products are known to contain a nitrogen-nitrogen (N-N) bond.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 67, "end": 75}, {"text": "nitrogen", "start": 76, "end": 84}, {"text": "N-N", "start": 86, "end": 89}]}}, "schema": []}
{"input": "This report categorizes these compounds by structural class and details their isolation and biological activity.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and Self-assembly of Amphiphilic Homoglycopolypeptide.", "output": {"entities": {}}, "schema": []}
{"input": "The synthesis of the amphiphilic homoglycopolypeptide was carried out by a combination of NCA polymerization and click chemistry to yield a well-defined polypeptide having an amphiphilic carbohydrate on its side chain.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 187, "end": 199}]}}, "schema": []}
{"input": "The amphiphilicity of the carbohydrate was achieved by incorporation of an alkyl chain at the C-6 position of the carbohydrate thus also rendering the homoglycopolypeptide amphiphilic.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 26, "end": 38}, {"text": "alkyl", "start": 75, "end": 80}, {"text": "carbohydrate", "start": 114, "end": 126}]}}, "schema": []}
{"input": "The homoglycopolypeptide formed multimicellar aggregates in water above a critical concentration of 0. 9 mu M due to phase separation.", "output": {"entities": {}}, "schema": []}
{"input": "The multimicellar aggregates were characterized by DLS, TEM, and AFM.", "output": {"entities": {}}, "schema": []}
{"input": "It is proposed that hydrophobic interactions of the aliphatic chains at the 6-position of the sugar moieties drives the assembly of these rod-like homoglycopolypeptide into large spherical aggregates.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 94, "end": 99}]}}, "schema": []}
{"input": "These multimicellar aggregates encapsulate both hydrophilic as well as hydrophobic dye as was confirmed by confocal microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, amphiphilic random polypeptides containing 10% and 20% alpha-d-mannose in addition to glucose containing a hydrophobic alkyl chain at its 6 position were synthesized by our methodology, and these polymers were also found to assemble into spherical nanostructures.", "output": {"entities": {"chemical": [{"text": "alpha-d-mannose", "start": 64, "end": 79}, {"text": "glucose", "start": 95, "end": 102}, {"text": "alkyl", "start": 128, "end": 133}]}}, "schema": []}
{"input": "The spherical assemblies of amphiphilic random glycopolypeptides containing 10% and 20% mannose were found to be surface bioactive and were found to interact with the lectin Con-A.", "output": {"entities": {"chemical": [{"text": "mannose", "start": 88, "end": 95}]}}, "schema": []}
{"input": "The time point of beta-catenin knockout in hepatocytes determines their response to xenobiotic activation of the constitutive androstane receptor.", "output": {"entities": {"chemical": [{"text": "androstane", "start": 126, "end": 136}]}}, "schema": []}
{"input": "The constitutive androstane receptor (CAR) controls the expression of drug-metabolizing enzymes and regulates hepatocyte proliferation.", "output": {"entities": {"chemical": [{"text": "androstane", "start": 17, "end": 27}]}}, "schema": []}
{"input": "Studies with transgenic mice with an early postnatal conditional hepatocyte-specific knockout of the beta-catenin gene Ctnnb1 revealed that beta-catenin deficiency decreases the magnitude of induction of drug-metabolizing enzymes by CAR activators, abrogates zonal differences in the hepatocytes' susceptibility to these compounds, and impacts on hepatocyte proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "These data, however, do not allow distinguishing between effects caused by beta-catenin deficiency during postnatal liver development and acute effects of beta-catenin deficiency in the adult animal at the time point of CAR activation.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, CAR activation was now studied in a different mouse model allowing for the hepatocyte-specific knockout of beta-catenin in adult mice.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment of these mice with 3mg/kg body weight of the model CAR activator 1, 4-bis-[2-(3, 5-dichloropyridyloxy)] benzene (TCPOBOP) confirmed previous findings related to the coordinate regulation of drug metabolism by beta-catenin and CAR.", "output": {"entities": {"chemical": [{"text": "1, 4-bis-[2-(3, 5-dichloropyridyloxy)] benzene", "start": 75, "end": 121}, {"text": "TCPOBOP", "start": 123, "end": 130}]}}, "schema": []}
{"input": "More importantly, the present study clarified that the impact of beta-catenin signaling on CAR-mediated enzyme induction in the liver is not merely due to developmental defects caused by a postnatal lack of beta-catenin, but depends on the presence of beta-catenin at the time point of xenobiotic treatment.", "output": {"entities": {}}, "schema": []}
{"input": "The study also revealed interesting differences between the two mouse models: hepatic zonation of TCPOBOP-dependent induction of drug-metabolizing enzymes was restored in mice with late knockout of beta-catenin, and the strong proliferative response of female mice was exclusively abolished when using animals with a late beta-catenin knockout.", "output": {"entities": {"chemical": [{"text": "TCPOBOP", "start": 98, "end": 105}]}}, "schema": []}
{"input": "This suggests a beta-catenin-dependent postnatal priming of hepatocytes during postnatal liver development, later affecting the proliferative response of adult animals to CAR-activating xenobiotics.", "output": {"entities": {}}, "schema": []}
{"input": "Glutathione conjugation attenuates biological activities of 6-dehydroshogaol from ginger.", "output": {"entities": {"chemical": [{"text": "Glutathione", "start": 0, "end": 11}, {"text": "6-dehydroshogaol", "start": 60, "end": 76}]}}, "schema": []}
{"input": "6-Dehydroshogaol (6-DHSG) is a bioactive alpha, beta-unsaturated carbonyl compound isolated from fresh ginger with anti-inflammatory and phase II enzyme inducing activities.", "output": {"entities": {"chemical": [{"text": "6-Dehydroshogaol", "start": 0, "end": 16}, {"text": "6-DHSG", "start": 18, "end": 24}, {"text": "alpha, beta-unsaturated carbonyl", "start": 41, "end": 73}]}}, "schema": []}
{"input": "Here we describe the glutathione (GSH)-dependent metabolism and the effect of this metabolic transformation on the biological activities of 6-DHSG.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 21, "end": 32}, {"text": "GSH", "start": 34, "end": 37}, {"text": "6-DHSG", "start": 140, "end": 146}]}}, "schema": []}
{"input": "Compared with other ginger compounds, such as 6-gingerol and 6-shogaol, 6-DHSG showed the most potent anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264. 7 cells.", "output": {"entities": {"chemical": [{"text": "6-gingerol", "start": 46, "end": 56}, {"text": "6-shogaol", "start": 61, "end": 70}, {"text": "6-DHSG", "start": 72, "end": 78}]}}, "schema": []}
{"input": "The biological activities of 6-DHSG were attenuated by sulfhydryl antioxidants such as glutathione (GSH) or N-acetyl cysteine (NAC), but not ascorbic acid (ASC).", "output": {"entities": {"chemical": [{"text": "6-DHSG", "start": 29, "end": 35}, {"text": "sulfhydryl", "start": 55, "end": 65}, {"text": "glutathione", "start": 87, "end": 98}, {"text": "GSH", "start": 100, "end": 103}, {"text": "N-acetyl cysteine", "start": 108, "end": 125}, {"text": "NAC", "start": 127, "end": 130}, {"text": "ascorbic acid", "start": 141, "end": 154}, {"text": "ASC", "start": 156, "end": 159}]}}, "schema": []}
{"input": "6-DHSG was metabolised by GSH to form a GSH conjugate (GS-6-DHSG) in RAW 264. 7 cells, via a potential mechanism involving the catalytic activity of glutathione-S-transferase (GST).", "output": {"entities": {"chemical": [{"text": "6-DHSG", "start": 0, "end": 6}, {"text": "GSH", "start": 26, "end": 29}, {"text": "GSH", "start": 40, "end": 43}, {"text": "GS-6-DHSG", "start": 55, "end": 64}, {"text": "glutathione", "start": 149, "end": 160}, {"text": "S", "start": 161, "end": 162}]}}, "schema": []}
{"input": "GS-6-DHSG showed reduced biological activities compared with 6-DHSG in multiple biological assays.", "output": {"entities": {"chemical": [{"text": "GS-6-DHSG", "start": 0, "end": 9}, {"text": "6-DHSG", "start": 61, "end": 67}]}}, "schema": []}
{"input": "Together, these results indicate that GSH conjugation attenuates the biological activities of 6-DHSG and other alpha, beta-unsaturated carbonyl compounds.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 38, "end": 41}, {"text": "6-DHSG", "start": 94, "end": 100}, {"text": "alpha, beta-unsaturated carbonyl", "start": 111, "end": 143}]}}, "schema": []}
{"input": "Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters.", "output": {"entities": {}}, "schema": []}
{"input": "Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxybenoic, and chlorogenic acids.", "output": {"entities": {"chemical": [{"text": "Polyphenols", "start": 0, "end": 11}, {"text": "phenolic acids", "start": 54, "end": 68}, {"text": "gentisic, p-hydroxybenoic, and chlorogenic acids", "start": 77, "end": 125}]}}, "schema": []}
{"input": "To investigate the beneficial effects of NJ on the liver, hamsters were fed with two diets, normal-fat and high-fat diets.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, high-fat dietary hamsters were received distilled water, and 3, 6, and 9mL NJ/kg BW, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "After a 6-week feeding period, the increased (p < 0. 05) sizes of liver and visceral fat in high-fat dietary hamsters compared to the control hamsters were ameliorated (p < 0. 05) by NJ supplementation.", "output": {"entities": {}}, "schema": []}
{"input": "NJ also decreased (p < 0. 05) serum/liver lipids but enhanced (p < 0. 05) daily faecal lipid/bile acid outputs in the high-fat dietary hamsters.", "output": {"entities": {"chemical": [{"text": "bile acid", "start": 93, "end": 102}]}}, "schema": []}
{"input": "High-fat dietary hamsters supplemented with NJ had higher (p < 0. 05) liver antioxidant capacities but lowered (p < 0. 05) liver iNOS, COX-2, TNF-alpha, and IL-1 beta expressions, gelatinolytic levels of MMP9, and serum ALT values compared to those without NJ.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, NJ protects liver against a high-fat dietary habit via regulations of antioxidative and anti-inflammatory responses.", "output": {"entities": {}}, "schema": []}
{"input": "Proposal of mechanism of the freeze-thaw fractionation of 7S and 11S globulins in soymilk.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism underlying the freeze-thaw fractionation of 7S and 11S globulins in soymilk was investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Freeze-thawed soymilk demonstrated an increased particle size compared with raw soymilk.", "output": {"entities": {}}, "schema": []}
{"input": "Further, when defatted raw soymilk was freeze-thawed, it was fractionated into 7S (supernatant) and 11S (precipitate) globulins, similar to what is found with freeze-thaw of raw soymilk.", "output": {"entities": {}}, "schema": []}
{"input": "When raw soymilk samples with different ratios of 11S/7S were freeze-thawed, the 11S-deficient variety showed no precipitate.", "output": {"entities": {}}, "schema": []}
{"input": "The addition of sodium sulphite or sodium dodecyl sulphate also inhibited precipitate formation after freeze-thawing, resulting in no fractionation.", "output": {"entities": {"chemical": [{"text": "sodium sulphite", "start": 16, "end": 31}, {"text": "sodium dodecyl sulphate", "start": 35, "end": 58}]}}, "schema": []}
{"input": "These results suggest that the fractionation is due to selective precipitation of aggregates of 11S globulins and/or 11S globulins and lipid complexes, in which the protein molecules interact through disulphide bonds and/or hydrophobic interactions.", "output": {"entities": {"chemical": [{"text": "disulphide", "start": 200, "end": 210}]}}, "schema": []}
{"input": "Novel water-resistant UV-activated oxygen indicator for intelligent food packaging.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 35, "end": 41}]}}, "schema": []}
{"input": "For the first time, alginate polymer has been applied to prevent dyes from leaching out of colorimetric oxygen indicator films, which enable people to notice the presence of oxygen in the package in an economic and simple manner.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 104, "end": 110}, {"text": "oxygen", "start": 174, "end": 180}]}}, "schema": []}
{"input": "The dye-based oxygen indicator film suffers from dye leaching upon contact with water.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 14, "end": 20}]}}, "schema": []}
{"input": "In this work, UV-activated visual oxygen indicator films were fabricated using thionine, glycerol, P25 TiO2, and zein as a redox dye, a sacrificial electron donor, UV-absorbing semiconducting photocatalyst, and an encapsulation polymer, respectively.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 34, "end": 40}, {"text": "thionine", "start": 79, "end": 87}, {"text": "glycerol", "start": 89, "end": 97}, {"text": "P25 TiO2", "start": 99, "end": 107}]}}, "schema": []}
{"input": "When this zein-coated film was immersed in water for 24h, the dye leakage was as high as 80. 80 +/- 0. 45%.", "output": {"entities": {}}, "schema": []}
{"input": "However, introduction of alginate (1. 25%) as the coating polymer considerably diminished the dye leaching to only 5. 80 +/- 0. 06%.", "output": {"entities": {}}, "schema": []}
{"input": "This is because the ion-binding ability of alginate could prevent the cation dye from leaching into water.", "output": {"entities": {}}, "schema": []}
{"input": "This novel water-resistant UV-activated oxygen indicator was also successfully photo-bleached and regained colour fast in the presence of oxygen.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 40, "end": 46}, {"text": "oxygen", "start": 138, "end": 144}]}}, "schema": []}
{"input": "Influence of phenolic compounds on the sensorial perception and volatility of red wine esters in model solution: An insight at the molecular level.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 13, "end": 21}, {"text": "esters", "start": 87, "end": 93}]}}, "schema": []}
{"input": "Impact of (+)-catechin and gallic acid on sensory perception and volatility of isoamyl acetate, ethyl isobutyrate, ethyl butyrate and ethyl octanoate was investigated in model solutions, by means of triangle tests, detection threshold determination and HS-GC-MS analyses.", "output": {"entities": {"chemical": [{"text": "(+)-catechin", "start": 10, "end": 22}, {"text": "gallic acid", "start": 27, "end": 38}, {"text": "isoamyl acetate", "start": 79, "end": 94}, {"text": "ethyl isobutyrate", "start": 96, "end": 113}, {"text": "ethyl butyrate", "start": 115, "end": 129}, {"text": "ethyl octanoate", "start": 134, "end": 149}]}}, "schema": []}
{"input": "Catechin significantly altered the sensory perception of most esters (ethyl isobutyrate, ethyl butyrate and ethyl octanoate) while gallic acid displayed no impact.", "output": {"entities": {"chemical": [{"text": "Catechin", "start": 0, "end": 8}, {"text": "esters", "start": 62, "end": 68}, {"text": "ethyl isobutyrate", "start": 70, "end": 87}, {"text": "ethyl butyrate", "start": 89, "end": 103}, {"text": "ethyl octanoate", "start": 108, "end": 123}, {"text": "gallic acid", "start": 131, "end": 142}]}}, "schema": []}
{"input": "Ethyl butyrate and ethyl octanoate odour thresholds doubled or tripled in the presence of catechin, underlining a retention impact of phenolic compounds in liquid matrix.", "output": {"entities": {"chemical": [{"text": "Ethyl butyrate", "start": 0, "end": 14}, {"text": "ethyl octanoate", "start": 19, "end": 34}, {"text": "catechin", "start": 90, "end": 98}, {"text": "phenolic", "start": 134, "end": 142}]}}, "schema": []}
{"input": "The headspace analyses displayed a decrease only in ethyl octanoate volatility in presence of catechin, whereas no significant difference in other esters concentrations was observed.", "output": {"entities": {"chemical": [{"text": "ethyl octanoate", "start": 52, "end": 67}, {"text": "catechin", "start": 94, "end": 102}, {"text": "esters", "start": 147, "end": 153}]}}, "schema": []}
{"input": "This study indicated that phenolic compounds have a variable impact on aroma compounds' volatility and their sensory perception.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 26, "end": 34}]}}, "schema": []}
{"input": "The polarity of phenolic and volatile compounds as well as their spatial conformation also appeared to influence the interaction strength.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 16, "end": 24}]}}, "schema": []}
{"input": "Fast determination of sulfonamides from egg samples using magnetic multiwalled carbon nanotubes as adsorbents followed by liquid chromatography-tandem mass spectrometry.", "output": {"entities": {"chemical": [{"text": "sulfonamides", "start": 22, "end": 34}, {"text": "carbon", "start": 79, "end": 85}]}}, "schema": []}
{"input": "A simple and effective method based on magnetic separation has been developed for the extraction of sulfonamides (SAs) from egg samples using magnetic multiwalled carbon nanotubes (MMWCNTs) as an adsorbent.", "output": {"entities": {"chemical": [{"text": "sulfonamides", "start": 100, "end": 112}, {"text": "SAs", "start": 114, "end": 117}, {"text": "carbon", "start": 163, "end": 169}]}}, "schema": []}
{"input": "The MMWCNTs were simply prepared by depositing Fe3O4 onto MWCNTs that had been previously oxidised.", "output": {"entities": {"chemical": [{"text": "Fe3O4", "start": 47, "end": 52}]}}, "schema": []}
{"input": "The extraction procedure was carried out in a single step by blending and subsequently stirring the mixture of MMWCNTs and aqueous egg samples.", "output": {"entities": {}}, "schema": []}
{"input": "The SAs were first extracted as described above, adsorbed onto the MMWCNTs directly and finally analysed by liquid chromatography-tandem mass spectrometry.", "output": {"entities": {"chemical": [{"text": "SAs", "start": 4, "end": 7}]}}, "schema": []}
{"input": "The limits of detection obtained are in the range of 1. 4-2. 8ngg (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The proposed method was successfully applied in determining SAs in the eggs obtained from laying hens fed with SA standards, and compared to eggs purchased from local markets.", "output": {"entities": {"chemical": [{"text": "SAs", "start": 60, "end": 63}]}}, "schema": []}
{"input": "The results demonstrate that SAs were detectable in the incurred egg samples.", "output": {"entities": {"chemical": [{"text": "SAs", "start": 29, "end": 32}]}}, "schema": []}
{"input": "Investigation of tocotrienol biosynthesis in rice (Oryza sativa L.).", "output": {"entities": {"chemical": [{"text": "tocotrienol", "start": 17, "end": 28}]}}, "schema": []}
{"input": "Rice tocotrienol (T3) has gained attention due to its physiological activities (e. g., antiangiogenesis).", "output": {"entities": {"chemical": [{"text": "tocotrienol", "start": 5, "end": 16}]}}, "schema": []}
{"input": "However, the biosynthetic pathway for T3 production in rice grain has not been well studied.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that T3 biosynthesis enzymes and/or precursors play an important role in T3 production in whole grain.", "output": {"entities": {}}, "schema": []}
{"input": "This proposal was evaluated in rice (Oryza sativa L.) by PCR and HPLC techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Grain tocopherol as well as flag leaf vitamin E levels were also investigated for comparison.", "output": {"entities": {"chemical": [{"text": "tocopherol", "start": 6, "end": 16}, {"text": "vitamin E", "start": 38, "end": 47}]}}, "schema": []}
{"input": "For rice samples 14days after flowering, grain was abundant in T3, but not in flag leaf.", "output": {"entities": {}}, "schema": []}
{"input": "Expression of a gene encoding homogentisate geranylgeranyltransferase (HGGT, which has long been believed to be important for T3 production) differed significantly between grain and flag leaf.", "output": {"entities": {}}, "schema": []}
{"input": "We then investigated rice samples during the grain maturation period, and found that grain T3 and HGGT levels increased in the early stage and then reached a plateau.", "output": {"entities": {}}, "schema": []}
{"input": "T3 precursors such as homogentisate and geranylgeranyl pyrophosphate decreased during maturation.", "output": {"entities": {"chemical": [{"text": "geranylgeranyl pyrophosphate", "start": 40, "end": 68}]}}, "schema": []}
{"input": "No increase in grain T3 from the middle to late stages of maturation and a decrease in T3 precursors during maturation suggest that HGGT would be an essential, but not limiting factor for T3 biosynthesis, and T3 precursors could regulate the T3 level in grain.", "output": {"entities": {}}, "schema": []}
{"input": "The results of this study would be useful for nutraceutical purposes (e. g., development of T3-overproducing rice for the prevention of angiogenic disorders).", "output": {"entities": {}}, "schema": []}
{"input": "Thermal analysis of some natural polysaccharide materials by isoconversional method.", "output": {"entities": {}}, "schema": []}
{"input": "Isoconversional thermal analysis of some important polysaccharides from functional foods is reported.", "output": {"entities": {}}, "schema": []}
{"input": "Various thermal parameters including apparent activation energy (Ea), pre-exponential factor (A) were worked out, and the fitness of data to different models describing the degradation kinetics of polysaccharides was studied.", "output": {"entities": {}}, "schema": []}
{"input": "The polysaccharides from Mimosa pudica (MP), Plantago ovata (PO), Argyreia speciosa (AS), Acacia nilotica (AN), P. ovata husk (HK) and Acacia modesta (AM) exhibited multistep degradation while those from Astragalus gummifer (AG), Salvia aegyptiaca (SA) and Ocimum basicilicum (OB) degraded mainly in single step.", "output": {"entities": {}}, "schema": []}
{"input": "Generally, the degradation was exothermal.", "output": {"entities": {}}, "schema": []}
{"input": "The average Ea values as determined by Flynn-Wall-Ozawa method were found to be in the range 132-187kJmol (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The mean comprehensive index of thermal stability (ITS) fell in the range 0. 33-0. 43.", "output": {"entities": {}}, "schema": []}
{"input": "All the materials under investigation except those from SA and AS appear to be as stable as some of the important commercial materials used as pharmaceutical ingredients.", "output": {"entities": {}}, "schema": []}
{"input": "Model-fitting analysis revealed that the major degradation step follows first-order kinetics.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of alpha-keto acids in pork meat and Iberian ham via tandem mass spectrometry.", "output": {"entities": {"chemical": [{"text": "alpha-keto acids", "start": 17, "end": 33}]}}, "schema": []}
{"input": "An analytical method which offers accurate determination and identification of eight alpha-keto acids (alpha-ketoglutaric acid, pyruvic acid, 4-hydroxyphenylpyruvic acid, 3-methyl-2-oxobutyric acid, alpha-keto-gamma-methylthiobutyric acid, 4-methyl-2-oxovaleric acid, 3-methyl-2-oxovaleric acid, and phenylpyruvic acid) in pork meat and Iberian ham samples is reported.", "output": {"entities": {"chemical": [{"text": "alpha-keto acids", "start": 85, "end": 101}, {"text": "alpha-ketoglutaric acid", "start": 103, "end": 126}, {"text": "pyruvic acid", "start": 128, "end": 140}, {"text": "4-hydroxyphenylpyruvic acid", "start": 142, "end": 169}, {"text": "3-methyl-2-oxobutyric acid", "start": 171, "end": 197}, {"text": "alpha-keto-gamma-methylthiobutyric acid", "start": 199, "end": 238}, {"text": "4-methyl-2-oxovaleric acid", "start": 240, "end": 266}, {"text": "3-methyl-2-oxovaleric acid", "start": 268, "end": 294}, {"text": "phenylpyruvic acid", "start": 300, "end": 318}]}}, "schema": []}
{"input": "The method utilises a highly selective and sensitive method of multiple reaction monitoring (MRM) by mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The analytical method is simple (although the chemical derivatisation of the alpha-keto acids with dansylhydrazine is required), precise (< 18% RSD), accurate (90-110%), sensitive (0. 01-0. 34mg/kg of defatted and freeze-dried meat depending on the alpha-keto acid) and linear (R > 0. 99) over several orders of magnitude (until 0. 01-146. 1mg/kg of defatted and freeze-dried meat depending on the alpha-keto acid).", "output": {"entities": {"chemical": [{"text": "alpha-keto acids", "start": 77, "end": 93}, {"text": "dansylhydrazine", "start": 99, "end": 114}, {"text": "alpha-keto acid", "start": 249, "end": 264}, {"text": "alpha-keto acid", "start": 398, "end": 413}]}}, "schema": []}
{"input": "Using this methodology, alpha-keto acids were found to be present in pork meat to a low extent, and their concentration increased when they were determined in Iberian ham.", "output": {"entities": {"chemical": [{"text": "alpha-keto acids", "start": 24, "end": 40}]}}, "schema": []}
{"input": "This is the first report of the presence of alpha-keto acids in both pork meats and Iberian hams.", "output": {"entities": {"chemical": [{"text": "alpha-keto acids", "start": 44, "end": 60}]}}, "schema": []}
{"input": "Amino acid profiles and quantitative structure-property relationship models as markers for Merlot and Torront e s wines.", "output": {"entities": {"chemical": [{"text": "Amino acid", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Quantitative structure-property relationships (QSPRs) were applied to the aminograms obtained by HPLC in our laboratories for Torront e s and Merlot wines.", "output": {"entities": {}}, "schema": []}
{"input": "Dragon theoretical descriptors were derived for a set of optimized amino acid structures with the purpose of establishing QSPR models.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 67, "end": 77}]}}, "schema": []}
{"input": "The statistical Replacement Method was used for designing the best multi-parametric linear regression models, which included structural features selected from a pool containing 1497 constitutional, topological, geometrical or electronic molecular descriptors.", "output": {"entities": {}}, "schema": []}
{"input": "Predicted QSPR results were in good agreement with experimental amino acid profiles.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 64, "end": 74}]}}, "schema": []}
{"input": "The developed QSPR approach showed to be of practical value for distinguishing each wine varietal, and for calculating experimentally non-available amino acid concentrations of Torront e s and Merlot wines.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 148, "end": 158}]}}, "schema": []}
{"input": "It was also useful for assessing wine authenticity; the models were especially suitable for Merlot and Torront e s wines.", "output": {"entities": {}}, "schema": []}
{"input": "Prooxidative and antioxidative properties of beta-carotene in chlorophyll and riboflavin photosensitized oil-in-water emulsions.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 45, "end": 58}, {"text": "chlorophyll", "start": 62, "end": 73}, {"text": "riboflavin", "start": 78, "end": 88}]}}, "schema": []}
{"input": "Effects of beta-carotene on the oxidative stability of chlorophyll or riboflavin photosensitized oil-in-water (O/W) emulsions were determined by analysing the depleted headspace oxygen content, lipid hydroperoxides, fluorescence intensity, and headspace volatiles.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 11, "end": 24}, {"text": "chlorophyll", "start": 55, "end": 66}, {"text": "riboflavin", "start": 70, "end": 80}, {"text": "oxygen", "start": 178, "end": 184}, {"text": "hydroperoxides", "start": 200, "end": 214}]}}, "schema": []}
{"input": "As the concentration of beta-carotene increased from 0 to 10, 100, and 1000 mu M, the oxidative stability of samples containing chlorophylls decreased in a concentration-dependent manner under light, indicating that beta-carotene acted as a prooxidant.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 24, "end": 37}, {"text": "chlorophylls", "start": 128, "end": 140}, {"text": "beta-carotene", "start": 216, "end": 229}]}}, "schema": []}
{"input": "However, in riboflavin photosensitized O/W emulsions, 100 and 1000 mu M beta-carotene inhibited lipid oxidation.", "output": {"entities": {"chemical": [{"text": "riboflavin", "start": 12, "end": 22}, {"text": "beta-carotene", "start": 72, "end": 85}]}}, "schema": []}
{"input": "Although beta-carotene protected both photosensitisers in O/W emulsions, beta-carotene displayed antioxidative or prooxidative properties, which depended on the polarity of the photosensitisers.", "output": {"entities": {"chemical": [{"text": "beta-carotene", "start": 9, "end": 22}, {"text": "beta-carotene", "start": 73, "end": 86}]}}, "schema": []}
{"input": "The development of t-2-heptenal and 1-octen-3-ol increased greatly in chlorophyll sensitised O/W emulsions with an increase in beta-carotene concentration, implying that more singlet oxygen oxidation occurred due to the higher levels of remaining chlorophylls.", "output": {"entities": {"chemical": [{"text": "t-2-heptenal", "start": 19, "end": 31}, {"text": "1-octen-3-ol", "start": 36, "end": 48}, {"text": "chlorophyll", "start": 70, "end": 81}, {"text": "beta-carotene", "start": 127, "end": 140}, {"text": "oxygen", "start": 183, "end": 189}, {"text": "chlorophylls", "start": 247, "end": 259}]}}, "schema": []}
{"input": "However, the content of t-2-heptenal and 1-octen-3-ol in the riboflavin sensitised O/W emulsions was not significantly correlated with the beta-carotene concentration, which indicates that beta-carotene in the lipid particles effectively quenched singlet oxygen.", "output": {"entities": {"chemical": [{"text": "t-2-heptenal", "start": 24, "end": 36}, {"text": "1-octen-3-ol", "start": 41, "end": 53}, {"text": "riboflavin", "start": 61, "end": 71}, {"text": "beta-carotene", "start": 139, "end": 152}, {"text": "beta-carotene", "start": 189, "end": 202}, {"text": "oxygen", "start": 255, "end": 261}]}}, "schema": []}
{"input": "Conjugated linoleic acid and calcium co-supplementation improves bone health in ovariectomised mice.", "output": {"entities": {"chemical": [{"text": "linoleic acid", "start": 11, "end": 24}, {"text": "calcium", "start": 29, "end": 36}]}}, "schema": []}
{"input": "Osteoporosis is a significant health concern for the elderly; conjugated linoleic acid (CLA) has been shown to improve overall bone mass when calcium is included as a co-supplement.", "output": {"entities": {"chemical": [{"text": "linoleic acid", "start": 73, "end": 86}, {"text": "calcium", "start": 142, "end": 149}]}}, "schema": []}
{"input": "However, potential effects of CLA and calcium on bone mass during a period of bone loss have not been reported.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 38, "end": 45}]}}, "schema": []}
{"input": "The purpose of this study was to determine how dietary calcium modulates the effects of conjugated linoleic acid (CLA) in preventing bone loss, using an ovariectomised mouse model.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 55, "end": 62}, {"text": "linoleic acid", "start": 99, "end": 112}]}}, "schema": []}
{"input": "CLA supplementation significantly prevented ovariectomy-associated weight and fat mass gain, compared to non-supplemented controls.", "output": {"entities": {}}, "schema": []}
{"input": "CLA significantly increased bone markers without major changes in bone mineral composition in the femur compared to respective controls.", "output": {"entities": {}}, "schema": []}
{"input": "CLA treatment increased serum parathyroid hormone (PTH) significantly (p = 0. 0172), while serum 1, 25-dihydroxyvitamin D3 concentration was not changed by CLA.", "output": {"entities": {"chemical": [{"text": "1, 25-dihydroxyvitamin D3", "start": 97, "end": 122}]}}, "schema": []}
{"input": "Meanwhile, CLA significantly reduced femur tartrate resistant acid phosphatase (TRAP) activity, suggesting potential reduction of osteoclastogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "The data suggest that CLA, along with dietary calcium, has great potential to be used to prevent bone loss and weight gain associated with menopause.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 46, "end": 53}]}}, "schema": []}
{"input": "The oestrogenic and anti-platelet activities of dihydrobenzofuroisocoumarins and homoisoflavonoids from Liriope platyphylla roots.", "output": {"entities": {"chemical": [{"text": "dihydrobenzofuroisocoumarins", "start": 48, "end": 76}, {"text": "homoisoflavonoids", "start": 81, "end": 98}]}}, "schema": []}
{"input": "The ethanolic extract of Liriope platyphylla (Liliaceae) roots showed potential oestrogenic and anti-platelet activities.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-six compounds were isolated and classified as 10 skeletons, including two unusual new dihydrobenzofuroisocoumarins, (+)-platyphyllarin A (1) and B (2), one new butanoate, ethyltributanoate (3), and two new homoisoflavanones, (-)-liriopein A (4) and B (5), along with 21 known compounds, including six homoisoflavonoids, one chalcone, six amides, one lignan, one fatty acid derivative, one alkaloid, three benzenoids, and two steroids.", "output": {"entities": {"chemical": [{"text": "dihydrobenzofuroisocoumarins", "start": 93, "end": 121}, {"text": "(+)-platyphyllarin A (1) and B", "start": 123, "end": 153}, {"text": "butanoate", "start": 167, "end": 176}, {"text": "ethyltributanoate", "start": 178, "end": 195}, {"text": "homoisoflavanones", "start": 213, "end": 230}, {"text": "(-)-liriopein A (4) and B", "start": 232, "end": 257}, {"text": "homoisoflavonoids", "start": 308, "end": 325}, {"text": "chalcone", "start": 331, "end": 339}, {"text": "amides", "start": 345, "end": 351}, {"text": "lignan", "start": 357, "end": 363}, {"text": "fatty acid", "start": 369, "end": 379}, {"text": "benzenoids", "start": 412, "end": 422}, {"text": "steroids", "start": 432, "end": 440}]}}, "schema": []}
{"input": "The biosynthetic pathway of compounds 1 and 2 was proposed in the current investigation.", "output": {"entities": {}}, "schema": []}
{"input": "The oestrogenic activity of the isolates was evaluated utilising the pER8: GUS reporter assay system in transgenic Arabidopsis plant as well as the SEAP reporter assay system in MCF-7 breast cancer cell-line; the anti-platelet activity was evaluated using the anti-platelet aggregation assay.", "output": {"entities": {}}, "schema": []}
{"input": "Several components exhibited significant oestrogenic and anti-platelet activities; demonstrating for the first time the potential use of L. platyphylla as a nutritional supplement for cardiovascular and endocrine diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride.", "output": {"entities": {}}, "schema": []}
{"input": "The study investigated the role of Spirulina platensis in reversing sodium fluoride-induced thyroid, neurodevelopment and oxidative alterations in offspring of pregnant rats.", "output": {"entities": {"chemical": [{"text": "sodium fluoride", "start": 68, "end": 83}]}}, "schema": []}
{"input": "The total antioxidant activity, phycocyanins, and beta carotene content were quantified in Spirulina.", "output": {"entities": {"chemical": [{"text": "beta carotene", "start": 50, "end": 63}]}}, "schema": []}
{"input": "Thirty female pregnant rats were allocated to six groups and treatment initiated orally from embryonic day (ED) 6 to postnatal day (PND) 15.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment groups included control, Spirulina alone, sodium fluoride (20mg/kg) alone, and sodium fluoride along with Spirulina (250 and 500mg/kg).", "output": {"entities": {"chemical": [{"text": "sodium fluoride", "start": 52, "end": 67}, {"text": "sodium fluoride", "start": 89, "end": 104}]}}, "schema": []}
{"input": "Serum fluoride levels were determined on ED 20 and PND 11.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 6, "end": 14}]}}, "schema": []}
{"input": "Offspring were subjected to behavioural testing, estimation of thyroid levels, oxidative measurements in brain mitochondrial fraction and histological evaluation of the cerebellum.", "output": {"entities": {}}, "schema": []}
{"input": "Fluoride-induced alterations in thyroid hormones, behaviour and increased oxidative stress.", "output": {"entities": {"chemical": [{"text": "Fluoride", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Spirulina augmented the displacement of fluoride, facilitated antioxidant formation, improved behaviour and protected Purkinje cells.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 40, "end": 48}]}}, "schema": []}
{"input": "Supplementing Spirulina during pregnancy could reduce the risk of fluoride toxicity in offspring.", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 66, "end": 74}]}}, "schema": []}
{"input": "Impact of blanching on polyphenol stability and antioxidant capacity of innovative coriander (Coriandrum sativum L.) pastes.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 23, "end": 33}]}}, "schema": []}
{"input": "Fresh coriander leaves were steam-and water-blanched at 100 degrees C and at 90 and 100 degrees C, respectively, for 1-10min, and subsequently comminuted to form a paste.", "output": {"entities": {}}, "schema": []}
{"input": "Pasty products obtained from coriander fruits were processed after water-blanching applying the same time-temperature regimes.", "output": {"entities": {}}, "schema": []}
{"input": "Among the 11 phenolics characterised in leaves by high-performance liquid chromatography coupled to mass spectrometric detection, several caffeic acid derivatives, 5-feruloylquinic and 5-p-coumaroylquinic acids were tentatively identified for the first time.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 13, "end": 22}, {"text": "caffeic acid", "start": 138, "end": 150}, {"text": "5-feruloylquinic and 5-p-coumaroylquinic acids", "start": 164, "end": 210}]}}, "schema": []}
{"input": "In fruits, 10 phenolics were detected, whereas rutin, a dicaffeic acid derivative and two feruloylquinic and caffeoylquinic acid isomers were newly detected.", "output": {"entities": {"chemical": [{"text": "phenolics", "start": 14, "end": 23}, {"text": "rutin", "start": 47, "end": 52}, {"text": "dicaffeic acid", "start": 56, "end": 70}, {"text": "feruloylquinic and caffeoylquinic acid", "start": 90, "end": 128}]}}, "schema": []}
{"input": "Upon steam-blanching for 1min, phenolic contents and antioxidant capacities remained virtually unchanged.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 31, "end": 39}]}}, "schema": []}
{"input": "In contrast, water-blanching and extended steam-blanching even yielded increased levels compared to the unheated control, whereas short-time water-blanching resulted in higher values than prolonged heat treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, short-time water-blanching is recommended as the initial unit in the processing of coriander leaves and fruits into novel pasty products.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38 alpha inhibitor.", "output": {"entities": {"chemical": [{"text": "carbamoylmethylene", "start": 28, "end": 46}, {"text": "BMS-582949", "start": 66, "end": 76}]}}, "schema": []}
{"input": "A series of carbamoylmethylene linked prodrugs of 1 (BMS-582949), a clinical p38 alpha inhibitor, were synthesized and evaluated.", "output": {"entities": {"chemical": [{"text": "carbamoylmethylene", "start": 12, "end": 30}, {"text": "BMS-582949", "start": 53, "end": 63}]}}, "schema": []}
{"input": "Though the phosphoryloxymethylene carbamates (3, 4, and 5) and alpha-aminoacyloxymethylene carbamates (22, 23, and 26) were found unstable at neutral pH values, fumaric acid derived acyloxymethylene carbamates (2, 28, and 31) were highly stable under both acidic and neutral conditions.", "output": {"entities": {"chemical": [{"text": "phosphoryloxymethylene carbamates", "start": 11, "end": 44}, {"text": "alpha-aminoacyloxymethylene carbamates", "start": 63, "end": 101}, {"text": "fumaric acid", "start": 161, "end": 173}, {"text": "acyloxymethylene carbamates", "start": 182, "end": 209}]}}, "schema": []}
{"input": "Prodrugs 2 and 31 were also highly soluble at both acidic and neutral pH values.", "output": {"entities": {}}, "schema": []}
{"input": "At a solution dose of 14. 2mpk (equivalent to 10mpk of 1), 2 gave essentially the same exposure of 1 compared to dosing 10mpk of 1 itself.", "output": {"entities": {}}, "schema": []}
{"input": "At a suspension dose of 142mpk (equivalent to 100mpk of 1), 2 demonstrated that it could overcome the solubility issue associated with 1 and provide a much higher exposure of 1.", "output": {"entities": {}}, "schema": []}
{"input": "To our knowledge, the unique type of prodrugs like 2, 28, and 31 was not reported in the past and could represent a novel prodrug approach for secondary amides, a class of molecules frequently identified as drug candidates.", "output": {"entities": {"chemical": [{"text": "secondary amides", "start": 143, "end": 159}]}}, "schema": []}
{"input": "Conformationally restricted homotryptamines.", "output": {"entities": {"chemical": [{"text": "homotryptamines", "start": 28, "end": 43}]}}, "schema": []}
{"input": "Part 6: Indole-5-cycloalkyl methylamines as selective serotonin reuptake inhibitors.", "output": {"entities": {"chemical": [{"text": "Indole-5-cycloalkyl methylamines", "start": 8, "end": 40}, {"text": "serotonin", "start": 54, "end": 63}]}}, "schema": []}
{"input": "Racemic 5-(trans-2-aminomethylcyclopropyl) indoles, 5-(trans-2-aminomethylcyclopentyl) indoles, and 5-(cis-2-aminomethylcyclopentyl) indoles were synthesized and evaluated as selective serotonin reuptake inhibitors.", "output": {"entities": {"chemical": [{"text": "Racemic 5-(trans-2-aminomethylcyclopropyl) indoles", "start": 0, "end": 50}, {"text": "5-(trans-2-aminomethylcyclopentyl) indoles", "start": 52, "end": 94}, {"text": "5-(cis-2-aminomethylcyclopentyl) indoles", "start": 100, "end": 140}, {"text": "serotonin", "start": 185, "end": 194}]}}, "schema": []}
{"input": "These analogs followed SAR trends similar to those previously reported for 3-cycloalkyl substituted indoles.", "output": {"entities": {"chemical": [{"text": "3-cycloalkyl substituted indoles", "start": 75, "end": 107}]}}, "schema": []}
{"input": "The most potent analogs exhibited single digit nanomolar inhibition at the human serotonin transporter but were 10-fold less active than the previously reported compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Biodegradable microparticles for strictly regulating the release of neurotrophic factors.", "output": {"entities": {}}, "schema": []}
{"input": "A lot of research has been carried out in the last decade to find a cure for neurodegenerative diseases especially Parkinson' s disease but to little avail.", "output": {"entities": {}}, "schema": []}
{"input": "In this study we have demonstrated the use of poly (lactic acid-co-glycolic acid) (PLGA)/collagen biodegradable microparticles formed using water-in-oil-in-water (W/O/W) double emulsion method, as a neurotrophic factor delivery vehicle.", "output": {"entities": {"chemical": [{"text": "poly (lactic acid-co-glycolic acid)", "start": 46, "end": 81}, {"text": "PLGA", "start": 83, "end": 87}]}}, "schema": []}
{"input": "The microparticles were encapsulated with glial cell-derived neurotrophic factor (GDNF) fused with collagen binding peptide (CBP) immobilized to the inner collagen phase.", "output": {"entities": {}}, "schema": []}
{"input": "The novelty lies in the strict regulation of release of GDNF-CBP from the microparticles as compared to a burst release from standard microparticles.", "output": {"entities": {}}, "schema": []}
{"input": "The microparticles were demonstrated to be non-cytotoxic till 300 mu g/2 x 10 (5) cells and revealed a maximum release of 250ng GDNF-CBP/mg microparticles in 0. 3% collagenase.", "output": {"entities": {}}, "schema": []}
{"input": "Differentiation of neural progenitor cells (NPCs) into mature neurons was demonstrated by co-culturing microparticles with cells in a medium containing collagenase which enabled the release of encapsulated GDNF-CBP, signaling the differentiation of NPCs into microtubule-associated protein 2 (MAP2)-expressing neurons.", "output": {"entities": {}}, "schema": []}
{"input": "The successful ability of these microparticles to deliver neurotrophic factors and allow differentiation of NPCs into mature neurons provides some scope in its use for the treatment of Parkinson' s disease and other neurodegenerative diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Cell biology: notch recycling is numbed.", "output": {"entities": {}}, "schema": []}
{"input": "During asymmetric cell division, the Notch regulator Numb segregates unequally to establish different cell fates in the two daughter cells.", "output": {"entities": {}}, "schema": []}
{"input": "Numb is thought to act as an endocytic protein.", "output": {"entities": {}}, "schema": []}
{"input": "Two new studies show that Numb antagonizes Notch signaling by also regulating recycling of Sanpodo-Notch complexes via AP-1.", "output": {"entities": {}}, "schema": []}
{"input": "Monoacylglycerol lipase inhibition-induced changes in plasma corticosterone levels, anxiety and locomotor activity in male CD1 mice.", "output": {"entities": {"chemical": [{"text": "Monoacylglycerol", "start": 0, "end": 16}, {"text": "corticosterone", "start": 61, "end": 75}]}}, "schema": []}
{"input": "The hypothalamus-pituitary-adrenal-axis is strongly controlled by the endocannabinoid system.", "output": {"entities": {}}, "schema": []}
{"input": "The specific impact of enhanced 2-arachidonoylglycerol signaling on corticosterone plasma levels, however, was not investigated so far.", "output": {"entities": {"chemical": [{"text": "2-arachidonoylglycerol", "start": 32, "end": 54}, {"text": "corticosterone", "start": 68, "end": 82}]}}, "schema": []}
{"input": "Here we studied the effects of the recently developed monoacylglycerol lipase inhibitor JZL184 on basal and stress-induced corticosterone levels in male CD1 mice, and found that this compound dramatically increased basal levels without affecting stress responses.", "output": {"entities": {"chemical": [{"text": "monoacylglycerol", "start": 54, "end": 70}, {"text": "JZL184", "start": 88, "end": 94}, {"text": "corticosterone", "start": 123, "end": 137}]}}, "schema": []}
{"input": "Since acute changes in corticosterone levels can affect behavior, JZL184 was administered concurrently with the corticosterone synthesis inhibitor metyrapone, to investigate whether the previously shown behavioral effects of JZL184 are dependent on corticosterone.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 23, "end": 37}, {"text": "JZL184", "start": 66, "end": 72}, {"text": "corticosterone", "start": 112, "end": 126}, {"text": "metyrapone", "start": 147, "end": 157}, {"text": "JZL184", "start": 225, "end": 231}, {"text": "corticosterone", "start": 249, "end": 263}]}}, "schema": []}
{"input": "We found that in the elevated plus-maze, the effects of JZL184 on \" classical \" anxiety-related measures were abolished by corticosterone synthesis blockade.", "output": {"entities": {"chemical": [{"text": "JZL184", "start": 56, "end": 62}, {"text": "corticosterone", "start": 123, "end": 137}]}}, "schema": []}
{"input": "By contrast, effects on the \" ethological \" measures of anxiety (i. e. risk assessment) were not affected by metyrapone.", "output": {"entities": {"chemical": [{"text": "metyrapone", "start": 109, "end": 119}]}}, "schema": []}
{"input": "In the open-field, the locomotion-enhancing effects of the compound were not changed either.", "output": {"entities": {}}, "schema": []}
{"input": "These findings show that monoacylglycerol lipase inhibition dramatically increases basal levels of corticosterone.", "output": {"entities": {"chemical": [{"text": "monoacylglycerol", "start": 25, "end": 41}, {"text": "corticosterone", "start": 99, "end": 113}]}}, "schema": []}
{"input": "This endocrine effect partly affects the anxiolytic, but not the locomotion-enhancing effects of monoacylglycerol lipase blockade.", "output": {"entities": {"chemical": [{"text": "monoacylglycerol", "start": 97, "end": 113}]}}, "schema": []}
{"input": "Effect of N-acetyl cysteine (NAC), an organosulfur compound from Allium plants, on experimentally induced hepatic prefibrogenic events in wistar rat.", "output": {"entities": {"chemical": [{"text": "N-acetyl cysteine", "start": 10, "end": 27}, {"text": "NAC", "start": 29, "end": 32}, {"text": "organosulfur", "start": 38, "end": 50}]}}, "schema": []}
{"input": "Aim of present study was to investigate the effect of NAC on experimental chronic hepatotoxicity models induced by carbon tetrachloride (CCl4) and thioacetamide (TAA).", "output": {"entities": {"chemical": [{"text": "NAC", "start": 54, "end": 57}, {"text": "carbon tetrachloride", "start": 115, "end": 135}, {"text": "CCl4", "start": 137, "end": 141}, {"text": "thioacetamide", "start": 147, "end": 160}, {"text": "TAA", "start": 162, "end": 165}]}}, "schema": []}
{"input": "CCl4 toxicity was induced by administering 200 mu l CCl4 (diluted 2: 3 in coconut oil)/100g body weight, p. o., twice weekly for 8 weeks.", "output": {"entities": {"chemical": [{"text": "CCl4", "start": 0, "end": 4}]}}, "schema": []}
{"input": "TAA toxicity was induced by administering 150mg/kg b.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 0, "end": 3}]}}, "schema": []}
{"input": "wt. of TAA i. p., twice weekly for 8 weeks.", "output": {"entities": {"chemical": [{"text": "TAA", "start": 7, "end": 10}]}}, "schema": []}
{"input": "NAC treatment was started along with toxicants (CCl4 and TAA) for 8 weeks and continued for further 4 weeks.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 0, "end": 3}, {"text": "CCl4", "start": 48, "end": 52}, {"text": "TAA", "start": 57, "end": 60}]}}, "schema": []}
{"input": "Self reversal group was kept without any treatment for 4 weeks after completion of toxicant treatments.", "output": {"entities": {}}, "schema": []}
{"input": "Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Bilirubin were measured in serum.", "output": {"entities": {"chemical": [{"text": "Alanine", "start": 0, "end": 7}, {"text": "Aspartate", "start": 32, "end": 41}, {"text": "Bilirubin", "start": 94, "end": 103}]}}, "schema": []}
{"input": "Hydroxyproline (HP), lipid peroxidation (LPO), catalase (CAT), Glutathione peroxidase (GPx) and Glutathione (GSH) were determined in liver samples by colorimetric methods.", "output": {"entities": {"chemical": [{"text": "Hydroxyproline", "start": 0, "end": 14}, {"text": "Glutathione", "start": 63, "end": 74}, {"text": "Glutathione", "start": 96, "end": 107}, {"text": "GSH", "start": 109, "end": 112}]}}, "schema": []}
{"input": "Cytochrome P450 2E1 (CYP 450 2E1), activity was determined as hydroxylation of aniline in liver microsomes.", "output": {"entities": {"chemical": [{"text": "aniline", "start": 79, "end": 86}]}}, "schema": []}
{"input": "General examination and histological analysis were also performed.", "output": {"entities": {}}, "schema": []}
{"input": "Serum markers of liver damage (AST, ALT, ALP and Bilirubin) were increased by CCl4 and TAA intoxication (p < 0. 001), whereas co-treatment with NAC reversed such changes (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "Bilirubin", "start": 49, "end": 58}, {"text": "CCl4", "start": 78, "end": 82}, {"text": "TAA", "start": 87, "end": 90}, {"text": "NAC", "start": 144, "end": 147}]}}, "schema": []}
{"input": "HP was enhanced in toxicant groups (p < 0. 001 in CCl4 and TAA), but inhibited by NAC (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "CCl4", "start": 50, "end": 54}, {"text": "TAA", "start": 59, "end": 62}, {"text": "NAC", "start": 82, "end": 85}]}}, "schema": []}
{"input": "LPO was increased while as GSH, CAT and GPx decreased by the administration of CCl4 and TAA (p < 0. 001); co-administration of NAC restored these liver markers to normal levels (p < 0. 001).", "output": {"entities": {"chemical": [{"text": "GSH", "start": 27, "end": 30}, {"text": "NAC", "start": 127, "end": 130}]}}, "schema": []}
{"input": "Biochemical determinations were corroborated by general and histological findings.", "output": {"entities": {}}, "schema": []}
{"input": "Keeping in view the biochemical and histopathological studies, it was concluded that CCl4 and TAA are strong hepatotoxic agents that produce liver fibrosis with close proximity to human etiology (micronodular cirrhosis) and NAC has a significant protective activity against CCl4 and TAA.", "output": {"entities": {"chemical": [{"text": "CCl4", "start": 85, "end": 89}, {"text": "TAA", "start": 94, "end": 97}, {"text": "NAC", "start": 224, "end": 227}, {"text": "CCl4", "start": 274, "end": 278}, {"text": "TAA", "start": 283, "end": 286}]}}, "schema": []}
{"input": "NAC has also been validated as a model against oxidative burden in chronic liver pathology.", "output": {"entities": {"chemical": [{"text": "NAC", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Pancreatic beta-cell response to increased metabolic demand and to pharmacologic secretagogues requires EPAC2A.", "output": {"entities": {}}, "schema": []}
{"input": "Incretin hormone action on beta-cells stimulates in parallel two different intracellular cyclic AMP-dependent signaling branches mediated by PKA and EPAC2A.", "output": {"entities": {"chemical": [{"text": "cyclic AMP", "start": 89, "end": 99}]}}, "schema": []}
{"input": "Both pathways contribute towards potentiation of glucose-stimulated insulin secretion (GSIS).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 49, "end": 56}]}}, "schema": []}
{"input": "However, the overall functional role of EPAC2A in beta-cells as it relates to in vivo glucose homeostasis remains incompletely understood.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 86, "end": 93}]}}, "schema": []}
{"input": "Therefore, we have examined in vivo GSIS in global EPAC2A knockout mice.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, we have conducted in vitro studies of GSIS and calcium dynamics in isolated EPAC2A-deficient islets.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 61, "end": 68}]}}, "schema": []}
{"input": "EPAC2A deficiency does not impact glucose-stimulated insulin secretion in mice under basal conditions.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 34, "end": 41}]}}, "schema": []}
{"input": "However, when mice are exposed to diet-induced insulin resistance, pharmacologic secretagogue stimulation of beta-cells with an incretin hormone glucagon-like peptide-1 analogue or with a Fatty Acid Receptor 1/GPR40 selective activator, EPAC2A is required for the increased beta-cell response to secretory demand.", "output": {"entities": {"chemical": [{"text": "Fatty Acid", "start": 188, "end": 198}]}}, "schema": []}
{"input": "Under these circumstances, EPAC2A is required for potentiating the early dynamic increase in islet calcium levels after glucose stimulation, which is reflected in potentiated first phase insulin secretion.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 99, "end": 106}, {"text": "glucose", "start": 120, "end": 127}]}}, "schema": []}
{"input": "These studies broaden our understanding of EPAC2A function and highlight its significance during increased secretory demand or drive on beta-cells.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings advance the rationale for developing EPAC2A selective pharmacologic activators for beta-cell targeted pharmacotherapy in type 2 diabetes mellitus.", "output": {"entities": {}}, "schema": []}
{"input": "Salicylic acid alleviates copper toxicity in rice (Oryza sativa L.) seedlings by up-regulating antioxidative and glyoxalase systems.", "output": {"entities": {"chemical": [{"text": "Salicylic acid", "start": 0, "end": 14}, {"text": "copper", "start": 26, "end": 32}]}}, "schema": []}
{"input": "The present study investigated the effect of salicylic acid (SA) on toxic symptoms, lipid peroxidation, reactive oxygen species generation and responses of antioxidative and glyoxalase systems in rice seedlings grown hydroponically under copper (Cu) stress for 48 h.", "output": {"entities": {"chemical": [{"text": "salicylic acid", "start": 45, "end": 59}, {"text": "oxygen", "start": 113, "end": 119}, {"text": "copper", "start": 238, "end": 244}, {"text": "Cu", "start": 246, "end": 248}]}}, "schema": []}
{"input": "Exposures of 75 and 150 mu M Cu (2 +) caused toxicity symptoms (chlorosis, necrosis and rolling in leaves), sharp increases in malondialdehyde (MDA), hydrogen peroxide (H2O2) contents and lipoxygenase (LOX) activity with concomitant reductions of chlorophyll (Chl) and relative water content (RWC).", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 29, "end": 37}, {"text": "malondialdehyde", "start": 127, "end": 142}, {"text": "MDA", "start": 144, "end": 147}, {"text": "hydrogen peroxide", "start": 150, "end": 167}, {"text": "H2O2", "start": 169, "end": 173}]}}, "schema": []}
{"input": "Both levels of Cu decreased ascorbic acid (AsA), glutathione (GSH), non-protein thiol (NPT) and proline contents in roots but rather increased in leaves except that AsA decreased in leaves too.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 15, "end": 17}, {"text": "ascorbic acid", "start": 28, "end": 41}, {"text": "AsA", "start": 43, "end": 46}, {"text": "glutathione", "start": 49, "end": 60}, {"text": "GSH", "start": 62, "end": 65}, {"text": "thiol", "start": 80, "end": 85}, {"text": "proline", "start": 96, "end": 103}, {"text": "AsA", "start": 165, "end": 168}]}}, "schema": []}
{"input": "These results together with overaccumulation of superoxide (O 2 (*-)) and H2O2 in leaves revealed that Cu exposures induced oxidative stress.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 48, "end": 58}, {"text": "O 2 (*-)", "start": 60, "end": 68}, {"text": "H2O2", "start": 74, "end": 78}, {"text": "Cu", "start": 103, "end": 105}]}}, "schema": []}
{"input": "Contrary, SA-pretreatment (100 mu M for 24 h) reduced toxicity symptoms and diminished Cu-induced increases in LOX activity, H2O2, MDA and proline contents while the levels of RWC, Chl, AsA and redox ratios were elevated.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 87, "end": 89}, {"text": "H2O2", "start": 125, "end": 129}, {"text": "MDA", "start": 131, "end": 134}, {"text": "proline", "start": 139, "end": 146}, {"text": "AsA", "start": 186, "end": 189}]}}, "schema": []}
{"input": "Higher levels of GSH and NPT were also observed in roots of SA-pretreated Cu-exposed seedlings.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 17, "end": 20}, {"text": "Cu", "start": 74, "end": 76}]}}, "schema": []}
{"input": "SA-pretreatment also exerted its beneficial role by inhibiting the Cu upward process.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 67, "end": 69}]}}, "schema": []}
{"input": "Studies on antioxidant enzymes showed that SA further enhanced the activities of superoxide dismutase, ascorbate peroxidase, glutathione reductase and glutathione peroxidase, and also elevated the depressed activities of catalase, dehydroascorbate reductase and glutathione S-transferase particularly at 150 mu M Cu (2 +) stress.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 81, "end": 91}, {"text": "ascorbate", "start": 103, "end": 112}, {"text": "glutathione", "start": 125, "end": 136}, {"text": "glutathione", "start": 151, "end": 162}, {"text": "dehydroascorbate", "start": 231, "end": 247}, {"text": "glutathione S", "start": 262, "end": 275}, {"text": "Cu (2 +)", "start": 313, "end": 321}]}}, "schema": []}
{"input": "In addition, the activity of glyoxalase system (glyoxalase I and II) was further elevated by SA pretreatment in the Cu-exposed seedlings.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 116, "end": 118}]}}, "schema": []}
{"input": "These results concluded that SA-mediated retention of Cu in roots and enhanced capacity of both antioxidative and glyoxalase systems might be associated with the alleviation of Cu-toxicity in rice seedlings.", "output": {"entities": {"chemical": [{"text": "Cu", "start": 54, "end": 56}, {"text": "Cu", "start": 177, "end": 179}]}}, "schema": []}
{"input": "Endowing carbon nanotubes with superparamagnetic properties: applications for cell labeling, MRI cell tracking and magnetic manipulations.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 9, "end": 15}]}}, "schema": []}
{"input": "Coating of carbon nanotubes (CNTs) with magnetic nanoparticles (NPs) imparts novel magnetic, optical, and thermal properties with potential applications in the biomedical domain.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 11, "end": 17}]}}, "schema": []}
{"input": "Multi-walled CNTs have been decorated with iron oxide superparamagnetic NPs.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 43, "end": 53}]}}, "schema": []}
{"input": "Two different approaches have been investigated based on ligand exchange or \" click chemistry \".", "output": {"entities": {}}, "schema": []}
{"input": "The presence of the NPs on the nanotube surface allows conferring magnetic properties to CNTs.", "output": {"entities": {}}, "schema": []}
{"input": "We have evaluated the potential of the NP/CNT hybrids as a contrast agent for magnetic resonance imaging (MRI) and their interactions with cells.", "output": {"entities": {}}, "schema": []}
{"input": "The capacity of the hybrids to magnetically monitor and manipulate cells has also been investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The NP/CNTs can be manipulated by a remote magnetic field with enhanced contrast in MRI.", "output": {"entities": {}}, "schema": []}
{"input": "They are internalized into tumor cells without showing cytotoxicity.", "output": {"entities": {}}, "schema": []}
{"input": "The labeled cells can be magnetically manipulated as they display magnetic mobility and are detected at a single cell level through high resolution MRI.", "output": {"entities": {}}, "schema": []}
{"input": "The lack of association between components of metabolic syndrome and treatment resistance in depression.", "output": {"entities": {}}, "schema": []}
{"input": "RATIONALE: Although a number of studies investigated the link between major depressive disorder (MDD) and metabolic syndrome (MetS), the association between MetS and treatment-resistant depression (TRD) is still not clear.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVES: The aim of the study was to investigate the relationship between TRD and MetS and/or components of MetS and cardiovascular risk factors.", "output": {"entities": {}}, "schema": []}
{"input": "Given the high prevalence of both conditions, the hypothesis was that TRD would be significantly associated with MetS.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: This cross-sectional study included 203 inpatients with MDD, assessed for the treatment resistance, MetS and its components, and severity of MDD.", "output": {"entities": {}}, "schema": []}
{"input": "Diagnoses and evaluations were made with SCID based on DSM-IV, National Cholesterol Education Program Adult Treatment Panel III criteria, and the Hamilton Depression Rating Scale.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 72, "end": 83}]}}, "schema": []}
{"input": "RESULTS: TRD prior to study entry was found in 26. 1% of patients, while MetS was observed in 33. 5% of patients.", "output": {"entities": {}}, "schema": []}
{"input": "The prevalence of MetS did not differ significantly between TRD and non-TRD patients.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the frequency of the altered values of particular components of the MetS or cardiovascular risk factors was not associated with treatment resistance in depressed patients.", "output": {"entities": {}}, "schema": []}
{"input": "Patients with TRD were older, had a higher number of lifetime episodes of depression and suicide attempts, and longer duration of MDD compared to non-TRD patients.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: The occurrence of either MetS or the particular components of the MetS and other cardiovascular risk factors was similar between TRD and non-TRD patients.", "output": {"entities": {}}, "schema": []}
{"input": "Although there is a bidirectional relationship between depression and MetS, neither MetS nor its components appear to influence treatment resistance to antidepressants.", "output": {"entities": {}}, "schema": []}
{"input": "The efficacy of metformin in pregnant women with polycystic ovary syndrome: a meta-analysis of clinical trials.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 16, "end": 25}]}}, "schema": []}
{"input": "Objectives: The role of metformin in the treatment of pregnant women with polycystic ovary syndrome is controversial.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 24, "end": 33}]}}, "schema": []}
{"input": "Therefore, we evaluated whether the use of metformin during pregnancy in women with polycystic ovary syndrome could reduce pregnancy-related complications.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 43, "end": 52}]}}, "schema": []}
{"input": "Research design and methods: MEDLINE was searched to retrieve relevant trials.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, reviews and reference lists of the retrieved articles were scanned for further appropriate studies.", "output": {"entities": {}}, "schema": []}
{"input": "The primary outcome measure was the incidence of complications of pregnancy, which included early pregnancy loss, gestational diabetes, preeclampsia and preterm delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Results: In total, eight studies with 1106 patients were included.", "output": {"entities": {}}, "schema": []}
{"input": "The pooled ORs (95% CIs) of outcome for pregnant women with polycystic ovary syndrome prescribed metformin were 0. 32 (0. 19-0. 55) for early pregnancy loss, 0. 37 (0. 25-0. 56) for gestational diabetes, 0. 53 (0. 30-0. 95) for preeclampsia and 0. 30 (0. 13-0. 68) for preterm delivery.", "output": {"entities": {"chemical": [{"text": "metformin", "start": 97, "end": 106}]}}, "schema": []}
{"input": "Conclusions: Metformin therapy throughout pregnancy decreased the ORs of early pregnancy loss, gestational diabetes, preeclampsia and preterm delivery in pregnant PCOS women with no serious detrimental sideeffects.", "output": {"entities": {"chemical": [{"text": "Metformin", "start": 13, "end": 22}]}}, "schema": []}
{"input": "Application of Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabonomic Techniques to Analyze the Joint Toxic Action of Long-Term Low-Level Exposure to a Mixture of Organophosphate Pesticides on Rat Urine Profile.", "output": {"entities": {"chemical": [{"text": "Organophosphate", "start": 184, "end": 199}]}}, "schema": []}
{"input": "In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL).", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 68, "end": 83}, {"text": "dichlorvos", "start": 101, "end": 111}, {"text": "dimethoate", "start": 113, "end": 123}, {"text": "acephate", "start": 125, "end": 133}, {"text": "phorate", "start": 138, "end": 145}]}}, "schema": []}
{"input": "Results show that a single pesticide elicits no toxic response.", "output": {"entities": {}}, "schema": []}
{"input": "The present study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology.", "output": {"entities": {}}, "schema": []}
{"input": "Pesticides were administered daily to rats through drinking water for 24 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide.", "output": {"entities": {}}, "schema": []}
{"input": "The metabonomic profiles of rats urine were analyzed by ultra-performance liquid chromatography/mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The 16 metabolites statistically significantly changed in all treated groups compared with the control group.", "output": {"entities": {}}, "schema": []}
{"input": "Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides.", "output": {"entities": {"chemical": [{"text": "Dimethylphosphate", "start": 0, "end": 17}, {"text": "dimethyldithiophosphate", "start": 22, "end": 45}]}}, "schema": []}
{"input": "Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid and citric acid.", "output": {"entities": {"chemical": [{"text": "7-methylguanine", "start": 62, "end": 77}, {"text": "ribothymidine", "start": 79, "end": 92}, {"text": "cholic acid", "start": 94, "end": 105}, {"text": "4-pyridoxic acid", "start": 107, "end": 123}, {"text": "kynurenine", "start": 125, "end": 135}, {"text": "indoxyl sulfate", "start": 140, "end": 155}, {"text": "hippuric acid", "start": 185, "end": 198}, {"text": "creatinine", "start": 200, "end": 210}, {"text": "uric acid", "start": 212, "end": 221}, {"text": "gentisic acid", "start": 223, "end": 236}, {"text": "C18-dihydrosphingosine", "start": 238, "end": 260}, {"text": "phytosphingosine", "start": 262, "end": 278}, {"text": "suberic acid", "start": 280, "end": 292}, {"text": "citric acid", "start": 297, "end": 308}]}}, "schema": []}
{"input": "The results indicated that a mixture of OP pesticides induced DNA damage, oxidative stress, disturbed the metabolism of lipids as well as interfered with the tricarboxylic acid cycle.", "output": {"entities": {"chemical": [{"text": "tricarboxylic acid", "start": 158, "end": 176}]}}, "schema": []}
{"input": "Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake, but also the joint toxic action.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-Ulcerative Colitis Activity of Compounds from Euphorbia granuleta Forssk.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of the present study was to evaluate the anti-ulcerative colitis (UC) activity of the total alcohol extracts of Euphorbia granuleta Forssk.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 100, "end": 107}]}}, "schema": []}
{"input": "(Euphorpiaceae), isolate and identify the active compounds that could be responsible for the activity, in addition to determination of the possible mechanism of action.", "output": {"entities": {}}, "schema": []}
{"input": "Six compounds were isolated and identified from this plant: three phenolic compounds (kampferol, kampferol-3-glucoside and kampferol-3-galactoside) in addition to three steroidal compounds (1-ethoxypentacosane, heptacosan-1-ol and beta-sitosterol).", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 66, "end": 74}, {"text": "kampferol", "start": 86, "end": 95}, {"text": "kampferol-3-glucoside", "start": 97, "end": 118}, {"text": "kampferol-3-galactoside", "start": 123, "end": 146}, {"text": "1-ethoxypentacosane", "start": 190, "end": 209}, {"text": "heptacosan-1-ol", "start": 211, "end": 226}, {"text": "beta-sitosterol", "start": 231, "end": 246}]}}, "schema": []}
{"input": "Three compounds (heptacosan-1-ol, beta-sitosterol and kampferol-3-galactoside) were found to be responsible for the anti-UC activity of E. granuleta extract.", "output": {"entities": {"chemical": [{"text": "heptacosan-1-ol", "start": 17, "end": 32}, {"text": "beta-sitosterol", "start": 34, "end": 49}, {"text": "kampferol-3-galactoside", "start": 54, "end": 77}]}}, "schema": []}
{"input": "The anti-UC activity of these compounds may be explained by reducing the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), in addition to reduction of colonic malondialdehyde (MDA) contents.", "output": {"entities": {"chemical": [{"text": "malondialdehyde", "start": 176, "end": 191}, {"text": "MDA", "start": 193, "end": 196}]}}, "schema": []}
{"input": "No side effects were reported on liver and kidney functions.", "output": {"entities": {}}, "schema": []}
{"input": "The active compounds reduced both serum TNF-alpha and mucosal MDA levels.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 62, "end": 65}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Decursin Exerts Anti-cancer Activity in MDA-MB-231 Breast Cancer Cells Via Inhibition of the Pin1 Activity and Enhancement of the Pin1/p53 Association.", "output": {"entities": {"chemical": [{"text": "Decursin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The peptidyl-prolyl cis/trans isomerase Pin1 is overexpressed in a wide variety of cancer cells and thus considered as an important target molecule for cancer therapy.", "output": {"entities": {"chemical": [{"text": "prolyl", "start": 13, "end": 19}]}}, "schema": []}
{"input": "This study demonstrates that decursin, a bioactive compound from Angelica gigas, exert the anti-cancer effect against breast cancer cells via regulation of Pin1 and its related signaling molecules.", "output": {"entities": {"chemical": [{"text": "decursin", "start": 29, "end": 37}]}}, "schema": []}
{"input": "We observed that decursin induced G1 arrest with decrease in cyclin D1 level in Pin1-expressing breast cancer cells MDA-MB-231, but not Pin1-non-expressing breast cancer cells MDA-MB-157.", "output": {"entities": {"chemical": [{"text": "decursin", "start": 17, "end": 25}]}}, "schema": []}
{"input": "In addition, decursin significantly reduced protein expression and enzymatic activity of Pin1 in MDA-MB-231 cells.", "output": {"entities": {"chemical": [{"text": "decursin", "start": 13, "end": 21}]}}, "schema": []}
{"input": "Further, we found that decursin treatment enhanced the p53 expression level and failed to down-regulate Pin1 in the cells transfected with p53 siRNA, indicating the importance of p53 in the decursin-mediated Pin1 inhibition in MDA-MB-231 cells.", "output": {"entities": {"chemical": [{"text": "decursin", "start": 23, "end": 31}, {"text": "decursin", "start": 190, "end": 198}]}}, "schema": []}
{"input": "Decursin stimulated association between Pin1 to p53.", "output": {"entities": {"chemical": [{"text": "Decursin", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Moreover, decursin facilitated p53 transcription in MDA-MB-231 cells.", "output": {"entities": {"chemical": [{"text": "decursin", "start": 10, "end": 18}]}}, "schema": []}
{"input": "Overall, our current study suggests the potential of decursin as an attractive cancer therapeutic agent for breast cancer by targeting Pin1 protein.", "output": {"entities": {"chemical": [{"text": "decursin", "start": 53, "end": 61}]}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmacological Inhibition of Platelet-tumor Cell Cross-talk Prevents Platelet-induced Overexpression of Cyclooxygenase-2 in HT29 Human Colon Carcinoma Cells.", "output": {"entities": {}}, "schema": []}
{"input": "Cyclooxygenase (COX)-2-derived prostanoids can influence several processes that are linked to carcinogenesis.", "output": {"entities": {"chemical": [{"text": "prostanoids", "start": 31, "end": 42}]}}, "schema": []}
{"input": "We aimed to address the hypothesis that platelets contribute to aberrant COX-2 expression in HT29 colon carcinoma cells and to reveal the role of platelet-induced COX-2 on the expression of proteins involved in malignancy and marker genes of epithelial-mesenchymal transition (EMT).", "output": {"entities": {}}, "schema": []}
{"input": "Human platelets co-cultured with HT29 cells rapidly adhered to cancer cells and induced COX-2 mRNA expression, but not protein synthesis which required the late release of platelet PDGF and COX-2 mRNA stabilization.", "output": {"entities": {}}, "schema": []}
{"input": "Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21 (WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by rofecoxib (a selective COX-2 inhibitor) and rescued by exogenous PGE2.", "output": {"entities": {"chemical": [{"text": "PGE2", "start": 33, "end": 37}, {"text": "rofecoxib", "start": 180, "end": 189}, {"text": "PGE2", "start": 245, "end": 249}]}}, "schema": []}
{"input": "Galectin-3, highly expressed in HT29 cells, is unique among galectins because it contains a collagen-like domain.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, we studied the role of galectin-3 and platelet collagen receptors in platelet-induced COX-2 overexpression.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitors of galectin-3 function (beta-lactose, a dominant-negative form of galectin-3, Gal-3C, and anti-galectin-3 antibody M3/38) or collagen receptor-mediated platelet adhesion (revacept, a dimeric collagen receptor GPVI-Fc) prevented aberrant COX-2 expression.", "output": {"entities": {"chemical": [{"text": "beta-lactose", "start": 35, "end": 47}]}}, "schema": []}
{"input": "Inhibition of platelet-cancer cell interaction by revacept was more effective than rofecoxib in preventing platelet-induced mRNA changes of EMT markers suggesting that direct cell-cell contact and aberrant COX-2 expression synergistically induced gene expression modifications associated with EMT.", "output": {"entities": {"chemical": [{"text": "rofecoxib", "start": 83, "end": 92}]}}, "schema": []}
{"input": "In conclusion, our findings provide the rationale for testing blockers of collagen binding sites, such as revacept, and galectin-3 inhibitors in the prevention of colon cancer metastasis in animal models followed by studies in patients.", "output": {"entities": {}}, "schema": []}
{"input": "The absence of ER beta results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles.", "output": {"entities": {}}, "schema": []}
{"input": "Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 145, "end": 153}]}}, "schema": []}
{"input": "Estrogen receptor (ER) beta is highly expressed in ovarian granulosa cells and mice lacking ER beta (beta ERKO) are subfertile due to inefficient ovulation.", "output": {"entities": {"chemical": [{"text": "Estrogen", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we isolated preovulatory granulosa cells from WT and ER beta-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation.", "output": {"entities": {}}, "schema": []}
{"input": "This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ER beta-null ovaries.", "output": {"entities": {}}, "schema": []}
{"input": "ER beta-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells.", "output": {"entities": {}}, "schema": []}
{"input": "Our analysis also identified 304 genes not previously associated with ER beta in granulosa cells.", "output": {"entities": {}}, "schema": []}
{"input": "LH responsive genes including Abcb1b and Fam110c show reduced expression in ER beta-null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, our data suggests that granulosa cells from ER beta-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation.", "output": {"entities": {}}, "schema": []}
{"input": "Caspase-14 suppresses GCM1 acetylation and inhibits placental cell differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Glial cell missing 1 (GCM1) transcription factor regulates placental cell fusion into the syncytiotrophoblast.", "output": {"entities": {}}, "schema": []}
{"input": "Caspase-14 is proteolytically activated to mediate filaggrin processing during keratinocyte differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, altered expression of nonactivated caspase-14 proenzyme is associated with tumorigenesis and diabetic retinopathy, suggesting that caspase-14 may perform physiological functions independently of its protease activity.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we performed tandem affinity purification coupled with mass spectrometry analysis to identify caspase-14 proenzyme as a GCM1-interacting protein that suppresses GCM1 activity and syncytiotrophoblast differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Immunohistochemistry revealed that caspase-14 and GCM1 colocalize to placental cytotrophoblast cells at 8 wk of gestation and syncytiotrophoblast layer at term.", "output": {"entities": {}}, "schema": []}
{"input": "Further, we demonstrated that caspase-14 mRNA level is decreased by 40% in placental BeWo cells treated with forskolin (FSK).", "output": {"entities": {"chemical": [{"text": "forskolin", "start": 109, "end": 118}, {"text": "FSK", "start": 120, "end": 123}]}}, "schema": []}
{"input": "To the contrary, stimulation of GCM1-regulated placental cell fusion and human chorionic gonadotropin beta (hCG beta) expression by FSK is enhanced by caspase-14 knockdown.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, GCM1 protein level is increased by 40% in the caspase-14-knockdown BeWo cells.", "output": {"entities": {}}, "schema": []}
{"input": "Because GCM1 is stabilized by acetylation, we subsequently showed that caspase-14 impedes the interaction between GCM1 and cAMP response element-binding protein (CREB)-binding protein (CBP) to suppress CBP-mediated acetylation and transcriptional coactivation of GCM1.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 123, "end": 127}]}}, "schema": []}
{"input": "Therefore, caspase-14 can suppress placental cell differentiation through down-regulation of GCM1 activity.-Wu, Y.-H., Lo, H.-F., Chen, S.-H., Chen, H.", "output": {"entities": {}}, "schema": []}
{"input": "Caspase-14 suppresses GCM1 acetylation and inhibits placental cell differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Patchy surfaces stabilize dextran-polyethylene glycol aqueous two-phase system liquid patterns.", "output": {"entities": {"chemical": [{"text": "polyethylene glycol", "start": 34, "end": 53}]}}, "schema": []}
{"input": "This paper analyzes surface chemistry effects to stably pattern aqueous two-phase system (ATPS) droplets on chemically modified poly (dimethylsiloxane) (PDMS).", "output": {"entities": {"chemical": [{"text": "poly (dimethylsiloxane)", "start": 128, "end": 151}, {"text": "PDMS", "start": 153, "end": 157}]}}, "schema": []}
{"input": "Polyethylene glycol (PEG) and dextran (DEX) are used as phase-forming polymers for the ATPS.", "output": {"entities": {"chemical": [{"text": "Polyethylene glycol", "start": 0, "end": 19}, {"text": "PEG", "start": 21, "end": 24}]}}, "schema": []}
{"input": "PDMS surface modifications studied include primary amine groups, carboxylic acid groups, and neutral polymer surfaces.", "output": {"entities": {"chemical": [{"text": "PDMS", "start": 0, "end": 4}, {"text": "primary amine", "start": 43, "end": 56}, {"text": "carboxylic acid", "start": 65, "end": 80}]}}, "schema": []}
{"input": "The PDMS surfaces were characterized by fluorescent measurement, water and DEX contact angle measurements, and X-ray photoelectron spectroscopy (XPS) analysis to confirm surface properties.", "output": {"entities": {"chemical": [{"text": "PDMS", "start": 4, "end": 8}]}}, "schema": []}
{"input": "While homogeneous surfaces of different functional groups affect DEX droplet pinning somewhat, the most stable patterns were realized using surfaces with chemical heterogeneity.", "output": {"entities": {}}, "schema": []}
{"input": "Arbitrary DEX solution patterning was achieved on a chemically patchy surface.", "output": {"entities": {}}, "schema": []}
{"input": "A Butterfly-Shaped Pyrene Derivative of Cholesterol and Its Uses as a Fluorescent Probe.", "output": {"entities": {"chemical": [{"text": "Pyrene", "start": 19, "end": 25}, {"text": "Cholesterol", "start": 40, "end": 51}]}}, "schema": []}
{"input": "A butterfly-shaped pyrene derivative of cholesterol, namely, N, N'-(ethane-1, 2-diyl)-bis (N-(2-(chol-amino) ethyl) pyrene-1-sulfonamide) (ECPS), has been designed and synthesized.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 40, "end": 51}, {"text": "N, N'-(ethane-1, 2-diyl)-bis (N-(2-(chol-amino) ethyl) pyrene-1-sulfonamide)", "start": 61, "end": 137}, {"text": "ECPS", "start": 139, "end": 143}]}}, "schema": []}
{"input": "Solvent effect studies revealed that in good solvents such as n-hexane, benzene, and 1, 4-dioxane, the profile of the fluorescence emission of the compound is characterized by pyrene monomer emission, but in poor solvent such as water, the emission is dominated by pyrene excimer emission.", "output": {"entities": {"chemical": [{"text": "n-hexane", "start": 62, "end": 70}, {"text": "benzene", "start": 72, "end": 79}, {"text": "1, 4-dioxane", "start": 85, "end": 97}, {"text": "pyrene", "start": 176, "end": 182}]}}, "schema": []}
{"input": "Quantitatively speaking, the ratio of the excimer emission to monomer emission changes from 50 to 0 when ECPS is dissolved in water and n-hexane, respectively.", "output": {"entities": {"chemical": [{"text": "n-hexane", "start": 136, "end": 144}]}}, "schema": []}
{"input": "In contrast, for a commonly used polarity probe pyrene, the ratio of I3/I1 varies only from ~ 0. 6 to ~ 1. 7, where I3 and I1 stand for the intensities of the fluorescence emission at peak 3 and peak 1, respectively.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 48, "end": 54}]}}, "schema": []}
{"input": "This value suggests that a more powerful discriminating ability of the new compound in polarity sensing.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, unlike the main components of the compound, pyrene and cholesterol, its main chain is composed of multiple hydrophilic structures, and it is this structure that makes the emission of the compound in organic solvents sensitive to the presence of water.", "output": {"entities": {"chemical": [{"text": "pyrene", "start": 57, "end": 63}, {"text": "cholesterol", "start": 68, "end": 79}]}}, "schema": []}
{"input": "Accordingly, the applicability of the compound in determination of the trace amount of water in some organic solvents was evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "As expected, the detection limit of the compound toward water in acetonitrile reaches 7 ppm, a result never reached before.", "output": {"entities": {"chemical": [{"text": "acetonitrile", "start": 65, "end": 77}]}}, "schema": []}
{"input": "Furthermore, the fluorescence emission of the compound is also sensitive to viscosity variation.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, it is assumed that ECPS may be used both as a polarity probe and a viscosity probe.", "output": {"entities": {"chemical": [{"text": "ECPS", "start": 30, "end": 34}]}}, "schema": []}
{"input": "On the bases of a series of steady-state and time-resolved fluorescence, as well as dynamic light scattering studies, a structural model was proposed to rationalize the fluorescence behavior of the compound in different solvents and its polarity and viscosity probing performances.", "output": {"entities": {}}, "schema": []}
{"input": "Enhanced Optical Second-Harmonic Generation from the Current-Biased Graphene/SiO2/Si (001) Structure.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 68, "end": 76}, {"text": "SiO2", "start": 77, "end": 81}, {"text": "Si", "start": 82, "end": 84}]}}, "schema": []}
{"input": "We find that optical second-harmonic generation (SHG) in reflection from a chemical-vapor-deposition graphene monolayer transferred onto a SiO2/Si (001) substrate is enhanced about 3 times by the flow of direct current electric current in graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 101, "end": 109}, {"text": "SiO2", "start": 139, "end": 143}, {"text": "Si", "start": 144, "end": 146}, {"text": "graphene", "start": 239, "end": 247}]}}, "schema": []}
{"input": "Measurements of rotational-anisotropy SHG revealed that the current-induced SHG from the current-biased graphene/SiO2/Si (001) structure undergoes a phase inversion as the measurement location on graphene is shifted laterally along the current flow direction.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 104, "end": 112}, {"text": "SiO2", "start": 113, "end": 117}, {"text": "Si", "start": 118, "end": 120}, {"text": "graphene", "start": 196, "end": 204}]}}, "schema": []}
{"input": "The enhancement is due to current-associated charge trapping at the graphene/SiO2 interface, which introduces a vertical electric field across the SiO2/Si interface that produces electric field-induced SHG.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 68, "end": 76}, {"text": "SiO2", "start": 77, "end": 81}, {"text": "SiO2", "start": 147, "end": 151}, {"text": "Si", "start": 152, "end": 154}]}}, "schema": []}
{"input": "The phase inversion is due to the positive-to-negative polarity switch in the current direction of the trapped charges at the current-biased graphene/SiO2 interface.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 141, "end": 149}, {"text": "SiO2", "start": 150, "end": 154}]}}, "schema": []}
{"input": "Exciplex Formation in Blended Spin-Cast Films of Fluorene-Linked Dyes and Bisphthalimide Quenchers.", "output": {"entities": {"chemical": [{"text": "Fluorene", "start": 49, "end": 57}, {"text": "Bisphthalimide", "start": 74, "end": 88}]}}, "schema": []}
{"input": "Spin-cast films of dyes (donor-pi-donor, donor-pi-acceptor, and acceptor-pi-acceptor type, where the donor is Ph2N-, the acceptor is 2-benzothiazoyl, and the pi-linker is 9, 9-diethylfluorene) blended with nonconjugated bisphthalimides were prepared.", "output": {"entities": {"chemical": [{"text": "Ph2N", "start": 110, "end": 114}, {"text": "2-benzothiazoyl", "start": 133, "end": 148}, {"text": "9, 9-diethylfluorene", "start": 171, "end": 191}, {"text": "bisphthalimides", "start": 220, "end": 235}]}}, "schema": []}
{"input": "Upon visible-light excitation of the dyes, quenching of the excited state occurs by exciplex formation between dye and bisphthalimide molecules or, in some cases, by excimer formation or aggregation-induced emission between two dye molecules.", "output": {"entities": {"chemical": [{"text": "bisphthalimide", "start": 119, "end": 133}]}}, "schema": []}
{"input": "The extent of exciplex formation is dependent on the driving force, which can be calculated using the energy difference between the lowest unoccupied molecular orbitals (LUMOs) of the dyes and bisphthalimides.", "output": {"entities": {"chemical": [{"text": "bisphthalimides", "start": 193, "end": 208}]}}, "schema": []}
{"input": "The results show that complete exciplex formation occurs when this driving force is greater than 0. 57 eV whereas partial exciplex formation occurs when the driving force is between 0. 28 and 0. 57 eV.", "output": {"entities": {}}, "schema": []}
{"input": "The exciplex emission energies can also be predicted by calculating the difference between the LUMO level of the bisphthalimide and the highest occupied molecular orbital (HOMO) of the dye.", "output": {"entities": {"chemical": [{"text": "bisphthalimide", "start": 113, "end": 127}]}}, "schema": []}
{"input": "These calculated values, which were obtained from the electrochemically determined energy levels, showed good agreement with the observed emission energies.", "output": {"entities": {}}, "schema": []}
{"input": "The exciplex lifetimes were found to be significantly longer than the lifetimes of the lone dyes.", "output": {"entities": {}}, "schema": []}
{"input": "These exciplexes formed from nonlinked donors and acceptors in the solid state might have potential uses in nonlinear photonics.", "output": {"entities": {}}, "schema": []}
{"input": "Condensation of DNA-A putative obstruction for repair process in abasic clustered DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "Clustered DNA damages are defined as two or more closely located DNA damage lesions that may be present within a few helical turns of the DNA double strand.", "output": {"entities": {}}, "schema": []}
{"input": "These damages are potential signatures of ionizing radiation and are often found to be repair resistant.", "output": {"entities": {}}, "schema": []}
{"input": "Types of damaged lesions frequently found inside clustered DNA damage sites include oxidized bases, abasic sites, nucleotide dimers, strand breaks or their complex combinations.", "output": {"entities": {"chemical": [{"text": "nucleotide dimers", "start": 114, "end": 131}]}}, "schema": []}
{"input": "In this study, we used a bistranded two-lesion abasic cluster DNA damage model to access the repair process of DNA in condensate form.", "output": {"entities": {}}, "schema": []}
{"input": "Oligomer DNA duplexes (47bp) were designed to have two deoxyuridine in the middle of the sequences, three bases apart in opposite strands.", "output": {"entities": {"chemical": [{"text": "deoxyuridine", "start": 55, "end": 67}]}}, "schema": []}
{"input": "The deoxyuridine residues were converted into abasic sites by treatment with UDG enzyme creating an abasic clustered damage site in a precise position in each of the single strand of the DNA duplex.", "output": {"entities": {"chemical": [{"text": "deoxyuridine", "start": 4, "end": 16}]}}, "schema": []}
{"input": "This oligomer duplex having compatible cohesive ends was ligated to pUC19 plasmid, linearized with HindIII restriction endonuclease.", "output": {"entities": {}}, "schema": []}
{"input": "The plasmid-oligomer conjugate was transformed into condensates by treating them with spermidine.", "output": {"entities": {"chemical": [{"text": "spermidine", "start": 86, "end": 96}]}}, "schema": []}
{"input": "The efficiency of strand cleavage action of ApeI enzyme on the abasic sites was determined by denaturing PAGE after timed incubation of the oligomer duplex and the oligomer-plasmid conjugate in presence and absence of spermidine.", "output": {"entities": {"chemical": [{"text": "spermidine", "start": 218, "end": 228}]}}, "schema": []}
{"input": "The efficiency of double strand breaks was determined similarly by native PAGE.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative gel analysis revealed that rate of abasic site cleavage is reduced in the DNA condensates as compared to the oligomer DNA duplex or the linear ligated oligomer-plasmid conjugates.", "output": {"entities": {}}, "schema": []}
{"input": "Generation of double strand break is significantly reduced also, suggesting that their creation is not proportionate to the number of abasic sites cleaved in the condensate model.", "output": {"entities": {}}, "schema": []}
{"input": "All these suggest that the ApeI enzyme have difficulty to access the abasic sites located deep into the condensates leading to repair refractivity of the damages.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we found that presence of a polyamine such as spermidine has no notable effect in the incision activity of ApeI enzyme in linear oligomer DNA duplexes in our experimental concentration.", "output": {"entities": {"chemical": [{"text": "polyamine", "start": 41, "end": 50}, {"text": "spermidine", "start": 59, "end": 69}]}}, "schema": []}
{"input": "Synthesis and antitumor activity of 1, 3, 4-oxadiazole possessing 1, 4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors.", "output": {"entities": {"chemical": [{"text": "1, 3, 4-oxadiazole", "start": 36, "end": 54}, {"text": "1, 4-benzodioxan", "start": 66, "end": 82}, {"text": "methionine", "start": 117, "end": 127}]}}, "schema": []}
{"input": "A series of 1, 3, 4-oxadiazole derivatives containing 1, 4-benzodioxan moiety (7a-7q) have been designed, synthesized and evaluated for their antitumor activity.", "output": {"entities": {"chemical": [{"text": "1, 3, 4-oxadiazole", "start": 12, "end": 30}, {"text": "1, 4-benzodioxan", "start": 54, "end": 70}]}}, "schema": []}
{"input": "Most of the synthesized compounds were proved to have potent antitumor activity and low toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, compound 7a showed the most potent biological activity against Human Umbilical Vein Endothelial cells, which was comparable to the positive control.", "output": {"entities": {}}, "schema": []}
{"input": "The results of apoptosis and flow cytometry (FCM) demonstrated that compound 7a induce cell apoptosis by the inhibition of MetAP2 pathway.", "output": {"entities": {"chemical": [{"text": "MetAP2", "start": 123, "end": 129}]}}, "schema": []}
{"input": "Molecular docking was performed to position compound 7a into MetAP2 binding site in order to explore the potential target.", "output": {"entities": {"chemical": [{"text": "MetAP2", "start": 61, "end": 67}]}}, "schema": []}
{"input": "Nr4a1-Dependent Ly6C (low) Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal.", "output": {"entities": {}}, "schema": []}
{"input": "The functions of Nr4a1-dependent Ly6C (low) monocytes remain enigmatic.", "output": {"entities": {}}, "schema": []}
{"input": "We show that they are enriched within capillaries and scavenge microparticles from their lumenal side in a steady state.", "output": {"entities": {}}, "schema": []}
{"input": "In the kidney cortex, perturbation of homeostasis by a TLR7-dependent nucleic acid \" danger \" signal, which may signify viral infection or local cell death, triggers G alpha i-dependent intravascular retention of Ly6C (low) monocytes by the endothelium.", "output": {"entities": {}}, "schema": []}
{"input": "Then, monocytes recruit neutrophils in a TLR7-dependent manner to mediate focal necrosis of endothelial cells, whereas the monocytes remove cellular debris.", "output": {"entities": {}}, "schema": []}
{"input": "Prevention of Ly6C (low) monocyte development, crawling, or retention in Nr4a1 (-/-), Itgal (-/-), and Tlr7 (host-/-BM +/+) and Cx3cr1 (-/-) mice, respectively, abolished neutrophil recruitment and endothelial killing.", "output": {"entities": {}}, "schema": []}
{"input": "Prevention of neutrophil recruitment in Tlr7 (host +/+ BM-/-) mice or by neutrophil depletion also abolished endothelial cell necrosis.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, Ly6C (low) monocytes are intravascular housekeepers that orchestrate the necrosis by neutrophils of endothelial cells that signal a local threat sensed via TLR7 followed by the in situ phagocytosis of cellular debris.", "output": {"entities": {}}, "schema": []}
{"input": "The anti-diabetic effects and pharmacokinetic profiles of berberine in mice treated with Jiao-Tai-Wan and its compatibility.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 58, "end": 67}]}}, "schema": []}
{"input": "Jiao-Tai-Wan (JTW), a classical Chinese prescription, has been clinically employed to treat diabetes mellitus in recent years.", "output": {"entities": {}}, "schema": []}
{"input": "To investigate the comparative evaluations on anti-diabetic effects and pharmacokinetics of the active ingredient berberine in mice treated with JTW in various combinations of its constituent herbs.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 114, "end": 123}]}}, "schema": []}
{"input": "In our study, the anti-diabetic study was carried out in diabetic mice induced by intraperitoneal injection of streptozotocin.", "output": {"entities": {"chemical": [{"text": "streptozotocin", "start": 111, "end": 125}]}}, "schema": []}
{"input": "The diabetic mice were randomly assigned to three therapy groups and orally administered with different prescription proportions of Rhizoma Coptidis and Cinnamomum cassia respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The level of plasma glucose, lipid profile and parameters related to oxidative stress were determined.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 20, "end": 27}]}}, "schema": []}
{"input": "The concentrations of berberine in non-diabetic mice plasma were determined using HPLC, and main pharmacokinetic parameters were investigated.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 22, "end": 31}]}}, "schema": []}
{"input": "The results indicated that the compatibility effects of ingredients present in Cinnamomum cassia could affect the anti-diabetic ability and pharmacokinetics of berberine in JTW.", "output": {"entities": {"chemical": [{"text": "berberine", "start": 160, "end": 169}]}}, "schema": []}
{"input": "Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}, {"text": "ethanol", "start": 38, "end": 45}, {"text": "CO", "start": 99, "end": 101}]}}, "schema": []}
{"input": "Naturally occuring quercetin protects hepatocytes from ethanol-induced oxidative stress, and heme oxygenase-1 (HO-1) induction and carbon monoxide (CO) metabolite may be implicated in the beneficial effect.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 19, "end": 28}, {"text": "ethanol", "start": 55, "end": 62}, {"text": "heme", "start": 93, "end": 97}, {"text": "carbon monoxide", "start": 131, "end": 146}, {"text": "CO", "start": 148, "end": 150}]}}, "schema": []}
{"input": "However, the precise mechanism by which quercetin counteracts CYP2E1-mediated ethanol hepatotoxicity through HO-1 system is still remained unclear.", "output": {"entities": {"chemical": [{"text": "quercetin", "start": 40, "end": 49}, {"text": "ethanol", "start": 78, "end": 85}]}}, "schema": []}
{"input": "To explore the potential mechanism, herein, ethanol (4. 0g/kg. bw.) was administrated to rats for 90 days.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 44, "end": 51}]}}, "schema": []}
{"input": "Our data showed that chronic ethanol over-activated CYP2E1 but suppressed HO-1 with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg. bw.).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 29, "end": 36}, {"text": "quercetin", "start": 155, "end": 164}]}}, "schema": []}
{"input": "Quercetin (100 mu M) induced HO-1 and depleted heme pool when incubated to human hepatocytes.", "output": {"entities": {"chemical": [{"text": "Quercetin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Ethanol-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by HO-1 inhibition with resultant heme accumulation.", "output": {"entities": {"chemical": [{"text": "Ethanol", "start": 0, "end": 7}, {"text": "quercetin", "start": 65, "end": 74}, {"text": "heme", "start": 130, "end": 134}]}}, "schema": []}
{"input": "CO scavenging blocked the suppression of quercetin only on CYP2E1 activity.", "output": {"entities": {"chemical": [{"text": "CO", "start": 0, "end": 2}, {"text": "quercetin", "start": 41, "end": 50}]}}, "schema": []}
{"input": "CO donor dose-dependently inactivated CYP2E1 of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger.", "output": {"entities": {"chemical": [{"text": "CO", "start": 0, "end": 2}, {"text": "ethanol", "start": 48, "end": 55}, {"text": "CO", "start": 131, "end": 133}]}}, "schema": []}
{"input": "Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by quercetin through HO-1 induction.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 22, "end": 29}, {"text": "quercetin", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Depleted heme pool and CO releasing limited protein synthesis and inhibited enzymatic activity of CYP2E1, respectively.", "output": {"entities": {"chemical": [{"text": "CO", "start": 23, "end": 25}]}}, "schema": []}
{"input": "Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4.", "output": {"entities": {"chemical": [{"text": "Quinone", "start": 0, "end": 7}, {"text": "NADPH", "start": 62, "end": 67}]}}, "schema": []}
{"input": "NADPH oxidase Nox4 is expressed in a wide range of tissues and plays a role in cellular signaling by providing reactive oxygen species (ROS) as intracellular messengers.", "output": {"entities": {"chemical": [{"text": "NADPH", "start": 0, "end": 5}, {"text": "oxygen", "start": 120, "end": 126}]}}, "schema": []}
{"input": "Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity.", "output": {"entities": {"chemical": [{"text": "quinone", "start": 163, "end": 170}]}}, "schema": []}
{"input": "In fact, we demonstrated a significant stimulation of Nox4 activity by 4 quinone derivatives (AA-861, tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx (TM), and chondrocyte cell lines.", "output": {"entities": {"chemical": [{"text": "quinone", "start": 73, "end": 80}, {"text": "AA-861", "start": 94, "end": 100}, {"text": "tBuBHQ", "start": 102, "end": 108}, {"text": "tBuBQ", "start": 110, "end": 115}, {"text": "duroquinone", "start": 121, "end": 132}]}}, "schema": []}
{"input": "Our results indicate that the effect is specific toward Nox4 versus Nox2.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we showed that NAD (P) H: quinone oxidoreductase (NQO1) may participate in this stimulation.", "output": {"entities": {"chemical": [{"text": "NAD (P) H", "start": 28, "end": 37}, {"text": "quinone", "start": 39, "end": 46}]}}, "schema": []}
{"input": "Interestingly, Nox4 activity is also stimulated by reducing agents that possibly act by reducing the disulfide bridge (Cys226, Cys270) located in the extracellular E-loop of Nox4.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 101, "end": 110}, {"text": "Cys226", "start": 119, "end": 125}, {"text": "Cys270", "start": 127, "end": 133}]}}, "schema": []}
{"input": "Such model of Nox4 activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i. e., its potential redox regulation, and could also define new therapeutic targets in diseases in which quinones and Nox4 are implicated.", "output": {"entities": {"chemical": [{"text": "quinones", "start": 266, "end": 274}]}}, "schema": []}
{"input": "Phenolic compounds present in Sardinian wine extracts protect against the production of inflammatory cytokines induced by oxysterols in CaCo-2 human enterocyte-like cells.", "output": {"entities": {"chemical": [{"text": "Phenolic", "start": 0, "end": 8}, {"text": "oxysterols", "start": 122, "end": 132}]}}, "schema": []}
{"input": "Cholesterol auto-oxidation products, namely oxysterols, are widely present in cholesterol-rich foods.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 0, "end": 11}, {"text": "oxysterols", "start": 44, "end": 54}, {"text": "cholesterol", "start": 78, "end": 89}]}}, "schema": []}
{"input": "They are thought to potentially interfere with homeostasis of the human digestive tract, playing a role in intestinal mucosal damage.", "output": {"entities": {}}, "schema": []}
{"input": "This report concerns the marked up-regulation in differentiated CaCo-2 colonic epithelial cells of two key inflammatory interleukins, IL-6 and IL-8, caused by a mixture of oxysterols representative of a high cholesterol diet.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 172, "end": 182}, {"text": "cholesterol", "start": 208, "end": 219}]}}, "schema": []}
{"input": "This strong pro-inflammatory effect appeared to be dependent on the net imbalance of red-ox equilibrium with the production of excessive levels of reactive oxygen species through the colonic NADPH-oxidase NOX1 activation.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 156, "end": 162}, {"text": "NADPH", "start": 191, "end": 196}]}}, "schema": []}
{"input": "Induction of NOX1 was markedly while not fully inhibited by CaCo-2 cell pre-incubation with phenolic extracts obtained from well-selected wines from typical grape varieties grown in Sardinia.", "output": {"entities": {}}, "schema": []}
{"input": "Oxysterol-dependent NOX1 activation, as well as interleukin synthesis, were completely prevented by Cannonau red wine extract that contains an abundant phenolic fraction, in particular phenolic acids and flavonoids.", "output": {"entities": {"chemical": [{"text": "Oxysterol", "start": 0, "end": 9}, {"text": "phenolic acids", "start": 185, "end": 199}, {"text": "flavonoids", "start": 204, "end": 214}]}}, "schema": []}
{"input": "Conversely, cell pre-treatment with Vermentino white wine extract with smaller phenolic fraction showed only a partial NOX1 down-regulation and was ineffective in interleukin synthesis induced by dietary oxysterols.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 204, "end": 214}]}}, "schema": []}
{"input": "It is thus likely that the effects of Sardinian wine extracts against intestinal inflammation induced by dietary oxysterols are mainly due to their high phenolic content: low doses of phenolics would be responsible only for direct scavenging oxysterol-dependent ROS production.", "output": {"entities": {"chemical": [{"text": "oxysterols", "start": 113, "end": 123}, {"text": "phenolics", "start": 184, "end": 193}, {"text": "oxysterol", "start": 242, "end": 251}]}}, "schema": []}
{"input": "Besides this direct activity, an excess of phenolic compounds detectable in red wine, may exert an additional indirect action by blocking oxysterol-related NOX1 induction, thus totally preventing the pro-oxidant and pro-inflammatory events triggered by dietary oxysterols.", "output": {"entities": {"chemical": [{"text": "phenolic", "start": 43, "end": 51}, {"text": "oxysterol", "start": 138, "end": 147}, {"text": "oxysterols", "start": 261, "end": 271}]}}, "schema": []}
{"input": "Simonols A and B, two novel sesqui-neolignans from the fruits of Illicium simonsii.", "output": {"entities": {"chemical": [{"text": "Simonols A and B", "start": 0, "end": 16}, {"text": "sesqui-neolignans", "start": 28, "end": 45}]}}, "schema": []}
{"input": "Two new sesqui-neolignans with novel conjugation way, simonol A (1), featuring a unique motif of a 5, 5-dihydro-pyran with a hemiketal carbon, while simonol B (2) possessing two dihydronfuran rings in the same direction, were isolated from the ethanol extract of the fruits of Illicium simonii.", "output": {"entities": {"chemical": [{"text": "sesqui-neolignans", "start": 8, "end": 25}, {"text": "simonol A", "start": 54, "end": 63}, {"text": "5, 5-dihydro-pyran", "start": 99, "end": 117}, {"text": "hemiketal carbon", "start": 125, "end": 141}, {"text": "simonol B", "start": 149, "end": 158}, {"text": "dihydronfuran", "start": 178, "end": 191}, {"text": "ethanol", "start": 244, "end": 251}]}}, "schema": []}
{"input": "Their structures were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and calculation of electronic circular dichroism (ECD) using density functional theory (DFT).", "output": {"entities": {}}, "schema": []}
{"input": "The two isolates were evaluated for their inhibitory activities against the growth of four lines of human cancer cells (NCI-H460, SMMC-7721, MCF-7, BGC-823): 1 showed strong activities comparable to 5-Fluorouracil, and 2 to a less content.", "output": {"entities": {"chemical": [{"text": "5-Fluorouracil", "start": 199, "end": 213}]}}, "schema": []}
{"input": "In addition, plausible biosynthetic routes for the two compounds were also proposed.", "output": {"entities": {}}, "schema": []}
{"input": "A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 55, "end": 66}]}}, "schema": []}
{"input": "Cholesterol biosynthesis serves as a central metabolic hub for numerous biological processes in health and disease.", "output": {"entities": {"chemical": [{"text": "Cholesterol", "start": 0, "end": 11}]}}, "schema": []}
{"input": "A detailed, integrative single-view description of how the cholesterol pathway is structured and how it interacts with other pathway systems is lacking in the existing literature.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 59, "end": 70}]}}, "schema": []}
{"input": "Here we provide a systematic review of the existing literature and present a detailed pathway diagram that describes the cholesterol biosynthesis pathway (the mevalonate, the Kandutch-Russell and the Bloch pathway) and shunt pathway that leads to 24 (S), 25-epoxycholesterol synthesis.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 121, "end": 132}, {"text": "mevalonate", "start": 159, "end": 169}, {"text": "24 (S), 25-epoxycholesterol", "start": 247, "end": 274}]}}, "schema": []}
{"input": "The diagram has been produced using the Systems Biology Graphical Notation (SBGN) and is available in the SBGN-ML format, a human readable and machine semantically parsable open community file format.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular mechanisms for the anti-cancer effects of diallyl disulfide.", "output": {"entities": {"chemical": [{"text": "diallyl disulfide", "start": 52, "end": 69}]}}, "schema": []}
{"input": "Considerable evidence in recent years suggests that garlic has anti-proliferative effects against various types of cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Garlic contains water-soluble and oil-soluble sulfur compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Oil-soluble compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS) and ajoene are more effective than water-soluble compounds in protection against cancer.", "output": {"entities": {"chemical": [{"text": "diallyl sulfide", "start": 30, "end": 45}, {"text": "DAS", "start": 47, "end": 50}, {"text": "diallyl disulfide", "start": 53, "end": 70}, {"text": "DADS", "start": 72, "end": 76}, {"text": "diallyl trisulfide", "start": 79, "end": 97}, {"text": "DATS", "start": 99, "end": 103}, {"text": "ajoene", "start": 109, "end": 115}]}}, "schema": []}
{"input": "DADS, a major organosulfur compound derived from garlic, can decrease carcinogen-induced cancers in experimental animals and inhibit the proliferation of various types of cancer cells.", "output": {"entities": {"chemical": [{"text": "DADS", "start": 0, "end": 4}, {"text": "organosulfur", "start": 14, "end": 26}]}}, "schema": []}
{"input": "Its mechanisms of action include: the activation of metabolizing enzymes that detoxify carcinogens; suppression of the formation of DNA adducts; antioxidant effects; regulation of cell-cycle arrest; induction of apoptosis and differentiation; histone modification; and inhibition of angiogenesis and invasion.", "output": {"entities": {}}, "schema": []}
{"input": "These topics are discussed in depth in this review.", "output": {"entities": {}}, "schema": []}
{"input": "Particle sizing measurements in pharmaceutical applications: Comparison of in-process methods versus off-line methods.", "output": {"entities": {}}, "schema": []}
{"input": "It has been previously described that when a sample' s particle size is determined using different sizing techniques, the results can differ considerably.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to review several in-process techniques for particle size determination (Spatial Filtering Velocimetry, Focused Beam Reflectance Measurements, Photometric Stereo Imaging, and the Eyecon (R) technology) and compare them to well-known and widespread off-line reference methods (laser diffraction and sieve analysis).", "output": {"entities": {}}, "schema": []}
{"input": "To start with, a theoretical explanation of the working mechanism behind each sizing technique is presented, and a comparison between them is established.", "output": {"entities": {}}, "schema": []}
{"input": "Secondly, six batches of granules and pellets (i. e., spherical particles) having different sizes were measured using these techniques.", "output": {"entities": {}}, "schema": []}
{"input": "The obtained size distributions and related D10, D50, and D90 values were compared using the laser diffraction wet dispersion method as reference technique.", "output": {"entities": {}}, "schema": []}
{"input": "As expected, each technique provided different size distributions with different D values.", "output": {"entities": {}}, "schema": []}
{"input": "These dissimilarities were examined and explained considering the measurement principles behind each sizing technique.", "output": {"entities": {}}, "schema": []}
{"input": "The particle property measured by each particle size analyzer (particle size or chord length) and how it is measured as well as the way in which size information is derived and calculated from this measured property and how results are presented (e. g., volume or mass distributions) are essential for the interpretation of the particle size data.", "output": {"entities": {}}, "schema": []}
{"input": "Interdependency of protein-release completeness and polymer degradation in PLGA-based implants.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 75, "end": 79}]}}, "schema": []}
{"input": "Release of BSA (model protein) from hot-melt extruded poly (lactide-co-glycolide) (PLGA)-based implants was incomplete.", "output": {"entities": {"chemical": [{"text": "poly (lactide-co-glycolide)", "start": 54, "end": 81}, {"text": "PLGA", "start": 83, "end": 87}]}}, "schema": []}
{"input": "A residual mass of covalent BSA-PLGA adducts was still present after 6months.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 32, "end": 36}]}}, "schema": []}
{"input": "The objective of this study was to increase the completeness of BSA release.", "output": {"entities": {}}, "schema": []}
{"input": "BSA reduced the PLGA degradation and erosion rate as well as the extent of erosion.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 16, "end": 20}]}}, "schema": []}
{"input": "An increased uptake of release medium in the presence of BSA in addition to the early outflux of PLGA oligomers resulted in a reduction of the matrix acidity and thus reduction of autocatalysis effects.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 97, "end": 101}]}}, "schema": []}
{"input": "PLGA mass loss was incomplete at 60% and 80% for 10% and 25% BSA-containing implants.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 0, "end": 4}]}}, "schema": []}
{"input": "The extent of PLGA mass loss was correlated with the total releasable protein.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 14, "end": 18}]}}, "schema": []}
{"input": "The same release was obtained from implants prepared with pre-degraded PLGA suggesting that the induction phase did not affect the release completeness.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 71, "end": 75}]}}, "schema": []}
{"input": "Thus, the focus was on the erosion phase to enhance outflux of soluble oligomers.", "output": {"entities": {}}, "schema": []}
{"input": "BSA release completeness increased by increasing the porosity of the implants at the onset of erosion phase.", "output": {"entities": {}}, "schema": []}
{"input": "This could be obtained with a higher initial porosity, formation of porosity upon higher diffusional release and/or incorporation of pore-formers/plasticizers.", "output": {"entities": {}}, "schema": []}
{"input": "Accordingly, the BSA release completeness could be improved by enhancing the outflux of soluble PLGA degradation products.", "output": {"entities": {"chemical": [{"text": "PLGA", "start": 96, "end": 100}]}}, "schema": []}
{"input": "Thermal stability of oligodeoxynucleotide duplexes containing l-deoxynucleotide at termini.", "output": {"entities": {"chemical": [{"text": "l-deoxynucleotide", "start": 62, "end": 79}]}}, "schema": []}
{"input": "The effects of substituting l-deoxynucleotide for d-deoxynucleotide at duplex termini were evaluated and the terminal substitutions were found to show much less effects on duplex destabilization and to show a similar tendency in base pairing selectivity, compared with internal chiral substitutions.", "output": {"entities": {"chemical": [{"text": "l-deoxynucleotide", "start": 28, "end": 45}, {"text": "d-deoxynucleotide", "start": 50, "end": 67}]}}, "schema": []}
{"input": "Agonistic activity of ICI 182 780 on activation of GSK 3 beta/AKT pathway in the rat uterus during the estrous cycle.", "output": {"entities": {"chemical": [{"text": "ICI 182 780", "start": 22, "end": 33}]}}, "schema": []}
{"input": "We examined the ability of ICI 182, 780 (ICI) to block uterine cell proliferation via protein kinase b/AKT pathway in the uterus of the rat during the estrous cycle.", "output": {"entities": {"chemical": [{"text": "ICI 182, 780", "start": 27, "end": 39}, {"text": "ICI", "start": 41, "end": 44}]}}, "schema": []}
{"input": "Intact rats, with regular estrous cycles, received a subcutaneous (s. c.) injection of either vehicle or ICI at 08: 00h on the day of proestrus or at 00: 00h on the day of estrus and sacrificed at 13: 00h of metaestrus.", "output": {"entities": {"chemical": [{"text": "ICI", "start": 105, "end": 108}]}}, "schema": []}
{"input": "Estradiol (E2) and progesterone (P4) plasma levels were measured by radioimmunoassay.", "output": {"entities": {"chemical": [{"text": "Estradiol", "start": 0, "end": 9}, {"text": "progesterone", "start": 19, "end": 31}]}}, "schema": []}
{"input": "Both ICI treatments, induced a significant decrease (p < 0. 01) in uterine estrogen receptor alpha (ER alpha) content, had no effect on uterine progesterone receptor (PR) protein expression and caused marked nuclear localization of cyclin D1, in both luminal and glandular uterine epithelium, as compared to vehicle-treated animals.", "output": {"entities": {"chemical": [{"text": "ICI", "start": 5, "end": 8}, {"text": "estrogen", "start": 75, "end": 83}, {"text": "progesterone", "start": 144, "end": 156}]}}, "schema": []}
{"input": "Furthermore, we detected that ICI treatment induced glycogen synthase kinase (Gsk3-beta) Ser 9 phosphorylation, which correlates with cyclin D1 nuclear localization.", "output": {"entities": {"chemical": [{"text": "ICI", "start": 30, "end": 33}]}}, "schema": []}
{"input": "However, some differences were observed between the two different time schedules of administration.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that the administration of ICI at 08: 00h on proestrus day produced a 15% inhibition of luminal epithelial cell proliferation, reduced uterine wet weight by 21% and caused reduction of Akt phosphorylation at Ser 473 as compared to vehicle-treated animals, whereas ICI treatment at 00: 00h on estrus day had no effect on these parameters.", "output": {"entities": {"chemical": [{"text": "ICI", "start": 39, "end": 42}, {"text": "Ser", "start": 220, "end": 223}, {"text": "ICI", "start": 276, "end": 279}]}}, "schema": []}
{"input": "The overall results indicate that ICI may exert agonistic and antagonistic effects on uterine cell proliferation through differential activation of the Akt pathway depending on the administration period during the estrous cycle, and indicates that the mechanism of cell proliferation during the physiological conditions of the estrous cycle, is under a different and more complex regulation than in the ovariectomized + E2 animal model.", "output": {"entities": {"chemical": [{"text": "ICI", "start": 34, "end": 37}]}}, "schema": []}
{"input": "Skin penetration enhancing properties of the plant N-alkylamide spilanthol.", "output": {"entities": {"chemical": [{"text": "N-alkylamide spilanthol", "start": 51, "end": 74}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Plants are often used for skin diseases in different ethnopharmacological systems.", "output": {"entities": {}}, "schema": []}
{"input": "Local and systemic effects of topically applied compounds can be significantly increased by plant constituents having skin penetration enhancers.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: In this study, we examined the proposed penetration enhancing properties of spilanthol, an N-alkylamide abundantly present in several Asteraceae plants like Spilanthes acmella L., on three model drugs (caffeine, testosterone and ibuprofen).", "output": {"entities": {"chemical": [{"text": "spilanthol", "start": 99, "end": 109}, {"text": "N-alkylamide", "start": 114, "end": 126}, {"text": "caffeine", "start": 225, "end": 233}, {"text": "testosterone", "start": 235, "end": 247}, {"text": "ibuprofen", "start": 252, "end": 261}]}}, "schema": []}
{"input": "Moreover, as plants are frequently contaminated with toxic environmental substances, the mutual influence on the transdermal behavior between spilanthol and six model mycotoxins (aflatoxin B1, ochratoxin A, fumonisin B1, citrinin, zearalenone, T-2 toxin) was investigated.", "output": {"entities": {"chemical": [{"text": "spilanthol", "start": 142, "end": 152}, {"text": "aflatoxin B1", "start": 179, "end": 191}, {"text": "ochratoxin A", "start": 193, "end": 205}, {"text": "fumonisin B1", "start": 207, "end": 219}, {"text": "citrinin", "start": 221, "end": 229}, {"text": "zearalenone", "start": 231, "end": 242}, {"text": "T-2 toxin", "start": 244, "end": 253}]}}, "schema": []}
{"input": "RESULTS: Spilanthol exhibits component and concentration dependent penetration enhancing effects.", "output": {"entities": {"chemical": [{"text": "Spilanthol", "start": 9, "end": 19}]}}, "schema": []}
{"input": "No significant penetration enhancing effect for ibuprofen has been observed, but with increasing spilanthol concentration (from 0 up to 1w/V%), the permeability of caffeine increased, resulting in an enhancing ratio (ER) of 4. 60.", "output": {"entities": {"chemical": [{"text": "ibuprofen", "start": 48, "end": 57}, {"text": "spilanthol", "start": 97, "end": 107}, {"text": "caffeine", "start": 164, "end": 172}]}}, "schema": []}
{"input": "For testosterone, a maximal penetration enhancing concentration of 0. 5% spilanthol was found (ER = 4. 13).", "output": {"entities": {"chemical": [{"text": "testosterone", "start": 4, "end": 16}, {"text": "spilanthol", "start": 73, "end": 83}]}}, "schema": []}
{"input": "Next to its beneficial applicability to increase local as well as systemic pharmacological effects of dermally co-administrated drug, this N-alkylamide negatively influences human health risk if spilanthol containing formulations are polluted with mycotoxins: the presence of spilanthol (0. 3w/V%) induced a significant increase of permeability coefficient Kp of five investigated mycotoxins, with ER values ranging between 1. 57 and 6. 37.", "output": {"entities": {"chemical": [{"text": "N-alkylamide", "start": 139, "end": 151}, {"text": "spilanthol", "start": 195, "end": 205}, {"text": "spilanthol", "start": 276, "end": 286}]}}, "schema": []}
{"input": "On the other hand, mycotoxins themselves do not significantly influence the transdermal behavior of spilanthol.", "output": {"entities": {"chemical": [{"text": "spilanthol", "start": 100, "end": 110}]}}, "schema": []}
{"input": "CONCLUSIONS: The existence of a significant mutual influence of compounds towards skin penetration should always be considered during the development or as part of the functional quality evaluation of topical products.", "output": {"entities": {}}, "schema": []}
{"input": "Biopharmaceutical classification of poorly soluble drugs with respect to \" enabling formulations \"", "output": {"entities": {}}, "schema": []}
{"input": "The large number of drug candidates with poor dissolution characteristics seen in the past decade, has fostered interest in so-called \" enabling formulations \", i. e., formulations which shall make such drugs bio-available.", "output": {"entities": {}}, "schema": []}
{"input": "Development of enabling formulations is currently being guided by the following (simplified) hypothesis: If a poorly soluble drug (BCS class II drug) can be transferred into a solubilized state, one can achieve an absorption profile close to that of a soluble drug (BCS class I drug).", "output": {"entities": {}}, "schema": []}
{"input": "Thus, formulation development typically endeavors to achieve the most robust solubility enhancement.", "output": {"entities": {}}, "schema": []}
{"input": "Here we critically review both common in vitro approaches and experimental data available in literature pertaining to the solubility and permeability of poorly soluble drugs from enabling formulations, and discuss their interplay.", "output": {"entities": {}}, "schema": []}
{"input": "Recent in vitro data indicate, that commonly employed surfactants as well as endogenous surfactants present in the intestine, although enhancing drug solubility, mostly hamper drug permeation.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistic studies demonstrate a direct correlation between passive transcellular diffusion and the concentration of molecularly dissolved drug.", "output": {"entities": {}}, "schema": []}
{"input": "The latter may be reduced due to partitioning into micelles or other solubilizing carriers, but enhanced in supersaturating formulations.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude thus that biopharmaceutical assessment approaches that rely on the amount of molecularly dissolved drug should guide us towards successful enabling formulations.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary nimodipine delays the onset of methylmercury neurotoxicity in mice.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 8, "end": 18}, {"text": "methylmercury", "start": 39, "end": 52}]}}, "schema": []}
{"input": "Adult-onset exposure is thought to result primarily in sensory and motor deficits but effects on learning are poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "One mechanism by which chronic MeHg may exert its neurotoxicity is via sustained disruption of intracellular calcium homeostasis, with a consequent increase of intracellular Ca (2 +) ions in vulnerable neurons.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 31, "end": 35}, {"text": "calcium", "start": 109, "end": 116}, {"text": "Ca (2 +)", "start": 174, "end": 182}]}}, "schema": []}
{"input": "A biochemically heterogeneous group of compounds, calcium channel blockers, have been shown in vitro to attenuate MeHg' s toxicity.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 50, "end": 57}, {"text": "MeHg", "start": 114, "end": 118}]}}, "schema": []}
{"input": "To evaluate the role of calcium antagonism in MeHg toxicity in vivo, adult BALB/c mice were exposed chronically to 0 or 15ppm of Hg (as MeHg) via drinking water and to nimodipine, a dihydropryidine, L-type Ca (2 +) channel blocker with action in the CNS.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 24, "end": 31}, {"text": "MeHg", "start": 46, "end": 50}, {"text": "Hg", "start": 129, "end": 131}, {"text": "MeHg", "start": 136, "end": 140}, {"text": "nimodipine", "start": 168, "end": 178}, {"text": "dihydropryidine", "start": 182, "end": 197}, {"text": "Ca (2 +)", "start": 206, "end": 214}]}}, "schema": []}
{"input": "Nimodipine was administered orally in diets (0, 20, or 200ppm, producing approximately 0, 2, or 20mg/kg/day of nimodipine).", "output": {"entities": {"chemical": [{"text": "Nimodipine", "start": 0, "end": 10}, {"text": "nimodipine", "start": 111, "end": 121}]}}, "schema": []}
{"input": "An incremental repeated acquisition (IRA) of response chains procedure was used to detect MeHg-induced deficits in learning or motoric function and to evaluate possible neuroprotection by nimodipine.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 90, "end": 94}, {"text": "nimodipine", "start": 188, "end": 198}]}}, "schema": []}
{"input": "MeHg impaired performance on the IRA task, and this was partially or completely blocked by dietary nimodipine, depending on dose.", "output": {"entities": {"chemical": [{"text": "MeHg", "start": 0, "end": 4}, {"text": "nimodipine", "start": 99, "end": 109}]}}, "schema": []}
{"input": "Measures of learning co-varied with measures of motoric function as indicated by overall response rate.", "output": {"entities": {}}, "schema": []}
{"input": "Nimodipine delayed or prevented the behavioral toxicity of MeHg exposure as evidenced by IRA performance; effects on learning seemed secondary to response rate decreases.", "output": {"entities": {"chemical": [{"text": "Nimodipine", "start": 0, "end": 10}, {"text": "MeHg", "start": 59, "end": 63}]}}, "schema": []}
{"input": "Acute and subacute toxicity studies on triptolide and triptolide-loaded polymeric micelles following intravenous administration in rodents.", "output": {"entities": {"chemical": [{"text": "triptolide", "start": 39, "end": 49}, {"text": "triptolide", "start": 54, "end": 64}]}}, "schema": []}
{"input": "Except its anti-tumour effects, triptolide (TP) also shows multiple pharmacological side activities, such as immune-suppressive and male anti-fertility.", "output": {"entities": {"chemical": [{"text": "triptolide", "start": 32, "end": 42}]}}, "schema": []}
{"input": "To increase the therapeutic index of TP, a novel polymeric micelle system containing TP (TP-PM) has been developed to treat tumour.", "output": {"entities": {}}, "schema": []}
{"input": "Our previous studies have demonstrated the good anti-tumour efficacy of TP-PM.", "output": {"entities": {}}, "schema": []}
{"input": "This paper investigated the acute toxicity in mice and subacute toxicity in rats of TP-PM and TP.", "output": {"entities": {}}, "schema": []}
{"input": "Results demonstrated that the LD50 for TP-PM and TP administered intravenously were 1. 06mg/kg and 0. 83mg/kg in mice, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In subacute toxicity study, TP-PM and TP were administered intravenously at the dose levels of 0. 1mg/kg and 0. 3mg/kg for 14d.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to the control, there was significant decrease in the serum AST activities, the testis ACP activities, thymus index, testis index, and significant increase in spleen index, and obvious histopathological changes in rats treated with TP, however, the toxicities of TP-PM on liver, kidney, testis and spleen are slighter than TP.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to TP, TP-PM significantly increased the ACP activity of the testis and decreased the MDA level in serum.", "output": {"entities": {"chemical": [{"text": "MDA", "start": 95, "end": 98}]}}, "schema": []}
{"input": "So, the polymeric micelles may be a novel drug delivery carrier of TP for reducing the toxicities of TP.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-kappa B pathway inhibition: Contribution of chlorogenic acid.", "output": {"entities": {"chemical": [{"text": "chlorogenic acid", "start": 144, "end": 160}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC) Stapf leaves infusion is used in traditional medicine for the treatment of inflammatory conditions, however little is known about their bio-active compounds.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: Investigate the compounds responsible for anti-inflammatory potential of Cymbopogon citratus (Cy) on cytokines production induced by lipopolysaccharide in human and mouse macrophages, and the action mechanisms involved.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: An essential oil-free infusion of Cy was prepared and polyphenol-rich fractions (PFs) were obtained from it by column chromatography.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 77, "end": 87}]}}, "schema": []}
{"input": "Chlorogenic acid was identified, by HPLC/PDA/ESI-MS (n).", "output": {"entities": {"chemical": [{"text": "Chlorogenic acid", "start": 0, "end": 16}]}}, "schema": []}
{"input": "The expression of cytokines, namely TNF-alpha and CCL5, was analyzed by real-time RT-PCR, on lipopolysaccharide-stimulated human macrophages.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of nuclear factor-kappa B, a master regulator of inflammation, was investigated by western blot and gene reporter assay.", "output": {"entities": {}}, "schema": []}
{"input": "Proteasome activity was assessed using a fluorogenic peptide.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Cymbopogon citratus extract and its polyphenols inhibited the cytokine production on human macrophages.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 45, "end": 56}]}}, "schema": []}
{"input": "This supports the anti-inflammatory activity of Cy polyphenols in physiologically relevant cells.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Concerning the effect on the activation of nuclear factor (NF)-kappa B pathway, the results pointed to an inhibition of LPS-induced NF-kappa B activation by Cy and PFs.", "output": {"entities": {}}, "schema": []}
{"input": "Chlorogenic acid was identified, by HPLC/PDA/ESI-MS (n), as the main phenolic acid of the Cy infusion, and it demonstrated to be, at least in part, responsible by that effect.", "output": {"entities": {"chemical": [{"text": "Chlorogenic acid", "start": 0, "end": 16}, {"text": "phenolic acid", "start": 69, "end": 82}]}}, "schema": []}
{"input": "Additionally, it was verified for the first time that Cy and PFs inhibited the proteasome activity, a complex that controls NF-kappa B activation, having CGA a strong contribution.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: The results evidenced, for the first time, the anti-inflammatory properties of Cymbopogon citratus through proteasome inhibition and, consequently NF-kappa B pathway and cytokine expression.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, Cy polyphenols, in particular chlorogenic acid, were highlighted as bio-active compounds.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 17, "end": 28}, {"text": "chlorogenic acid", "start": 44, "end": 60}]}}, "schema": []}
{"input": "Effect of bioactive peptide of Carapax Trionycis on TGF-beta 1-induced intracellular events in hepatic stellate cells.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicines for hepatic fibrosis therapy, Carapax Trionycis is used usually as an indispensable component and has a long history of medical use in China.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies have demonstrated that extracts of Carapax Trionycis were able to protect liver against fibrosis in CCl4 animal models.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: The purpose of this study is to verify the inhibitory effect and the underlying mechanisms of Carapax Trionycis extract peptide (CTEP) on activated hepatic stellate cells which play a central role in liver fibrogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Hepatic stellate cells induced by TGF-beta 1 were applied to evaluate the anti-fibrotic effect of CTEP in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "MTS assay, enzyme-linked immunosorbent assay and western blotting were then used to further investigate the molecular mechanisms.", "output": {"entities": {"chemical": [{"text": "MTS", "start": 0, "end": 3}]}}, "schema": []}
{"input": "RESULTS: The results show that the contents of collagen I, collagen III and TIMP-1 were significantly inhibited and the level of collagen I, collagen III, p-Smad 3, TIMP-1 and alpha-SMA proteins decreased significantly in a concentration-dependence manner after treatment with CTEP.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, the level of Smad 3 protein was not different significantly.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: Our data indicate that CTEP efficiently inhibits cultured HSC-T6 cell activation and proliferation via the TGF-beta 1/Smad pathway as well as by the elimination of the extracellular matrix.", "output": {"entities": {}}, "schema": []}
{"input": "Design, synthesis and biological evaluation of new classes of thieno [3, 2-d] pyrimidinone and thieno [1, 2, 3] triazine as inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2).", "output": {"entities": {"chemical": [{"text": "thieno [3, 2-d] pyrimidinone", "start": 62, "end": 90}, {"text": "thieno [1, 2, 3] triazine", "start": 95, "end": 120}]}}, "schema": []}
{"input": "Driven by a multidisciplinary approach combination (Structure-Based (SB) Three-Dimensional Quantitative Structure-Activity Relationships (3-D QSAR), molecular modeling, organic chemistry and various biological evaluations) here is reported the disclosure of new thienopyrimidines 1-3 as inhibitors of KDR activity and human umbilical vein endothelial cell (HUVEC) proliferation.", "output": {"entities": {"chemical": [{"text": "thienopyrimidines", "start": 262, "end": 279}]}}, "schema": []}
{"input": "More specifically, compound 2f represents a new lead compound that inhibits VEGFR-2 and HUVEC at mu M concentration.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover by the mean of an endothelial cell tube formation in vitro model 2f tartaric acid salt proved to block angiogenesis of HUVEC at mu M level.", "output": {"entities": {"chemical": [{"text": "tartaric acid", "start": 77, "end": 90}]}}, "schema": []}
{"input": "A microfluidic D-subminiature connector.", "output": {"entities": {}}, "schema": []}
{"input": "Standardized, affordable, user-friendly world-to-chip interfaces represent one of the major barriers to the adoption of microfluidics.", "output": {"entities": {}}, "schema": []}
{"input": "We present a connector system for plug-and-play interfacing of microfluidic devices to multiple input and output lines.", "output": {"entities": {}}, "schema": []}
{"input": "The male connectors are based on existing standardized housings from electronics that are inexpensive and widely available.", "output": {"entities": {}}, "schema": []}
{"input": "The female connectors are fabricated using familiar replica molding techniques that can easily be adopted by microfluidic developers.", "output": {"entities": {}}, "schema": []}
{"input": "Meclofenamic acid blocks the gap junction communication between the retinal pigment epithelial cells.", "output": {"entities": {"chemical": [{"text": "Meclofenamic acid", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Aim: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage the pain and inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "NSAIDs can cause serious side effects, including vision problems.", "output": {"entities": {}}, "schema": []}
{"input": "However, the underlying mechanisms are still unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we aimed to investigate the effect of meclofenamic acid (MFA) on retinal pigment epithelium (RPE).", "output": {"entities": {"chemical": [{"text": "meclofenamic acid", "start": 49, "end": 66}, {"text": "MFA", "start": 68, "end": 71}]}}, "schema": []}
{"input": "Materials and methods: In our study, we applied image analysis and whole-cell patch clamp recording to directly measure the effect of MFA on the gap junctional coupling between RPE cells.", "output": {"entities": {"chemical": [{"text": "MFA", "start": 134, "end": 137}]}}, "schema": []}
{"input": "Results: Analysis of Lucifer yellow (LY) transfer revealed that the gap junction communication existed between RPE cells.", "output": {"entities": {"chemical": [{"text": "Lucifer yellow", "start": 21, "end": 35}]}}, "schema": []}
{"input": "Functional experiments using the whole-cell configuration of the patch clamp technique showed that a gap junction conductance also existed between this kind of cells.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, MFA largely inhibited the gap junction conductance and induced the uncoupling of RPE cells. Other NSAIDs, like aspirin and flufenamic acid (FFA), had the same effect.", "output": {"entities": {"chemical": [{"text": "MFA", "start": 13, "end": 16}, {"text": "aspirin", "start": 124, "end": 131}, {"text": "flufenamic acid", "start": 136, "end": 151}, {"text": "FFA", "start": 153, "end": 156}]}}, "schema": []}
{"input": "Conclusion: The gap junction functionally existed in RPE cells, which can be blocked by MFA.", "output": {"entities": {"chemical": [{"text": "MFA", "start": 88, "end": 91}]}}, "schema": []}
{"input": "These findings may explain, at least partially, the vision problems with certain clinically used NSAIDs.", "output": {"entities": {}}, "schema": []}
{"input": "A simple, sensitive and accurate method for rat paw volume measurement and its expediency in preclinical animal studies.", "output": {"entities": {}}, "schema": []}
{"input": "Several methods are used to evaluate the inflammatory changes.", "output": {"entities": {}}, "schema": []}
{"input": "Measurement of edema is the most commonly used method for evaluating artificially induced inflammation in rat model.", "output": {"entities": {}}, "schema": []}
{"input": "In this context, we present a method for the measurement of volume of rat paw, in which two glass columns containing fluid are connected by a glass tube.", "output": {"entities": {}}, "schema": []}
{"input": "Paw is immersed in one column and the other column is placed on weighing balance.", "output": {"entities": {}}, "schema": []}
{"input": "Upon immersion of paw, equal volume of fluid displaced applies a force F, which shows specific and proportional increment in the level of fluid in both the columns, which could then be detected by weighing balance, as' Force = Weight' of displaced fluid, using the specific gravity of the fluid and the volume of paw, and thus the change in the volume of paw can be calculated.", "output": {"entities": {}}, "schema": []}
{"input": "The rat paw immersed in column without touching the wall of the column facilitates the accurate measurement of volume of paw when measured several times.", "output": {"entities": {}}, "schema": []}
{"input": "Present method is validated for its accuracy and reproducibility when internal radii of both the columns were same or different.", "output": {"entities": {}}, "schema": []}
{"input": "Presented method is also cost-effective and hence can be used for the academic and the commercial animal research purpose, without compromising the precision of the evaluation.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin-and glucagon-like peptide-1-induced changes in heart rate and vagosympathetic activity: why they matter.", "output": {"entities": {}}, "schema": []}
{"input": "Heart rate (HR) predicts cardiovascular morbidity and mortality in individuals either with or without diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "In type 2 diabetic patients, cardiac autonomic neuropathy is a risk marker for cardiac morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "A major pathogenic potential may be attributed to vagal depression and sympathetic predominance.", "output": {"entities": {}}, "schema": []}
{"input": "In this issue of Diabetologia, Berkelaar et al (DOI: 10. 1007/s00125-013-2848-6) examined the effects of euglycaemic, and hyperglycaemic clamp with the addition of glucagon-like-peptide-1 (GLP-1) and arginine, on cardiac vagal control in a large number of healthy subjects.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 200, "end": 208}]}}, "schema": []}
{"input": "After adjustments for age, BMI and insulin sensitivity, insulin associations with HR remained partially intact while those with vagal control disappeared.", "output": {"entities": {}}, "schema": []}
{"input": "This suggested that BMI and insulin sensitivity, but not insulin levels, were the main drivers of cardiac vagal control.", "output": {"entities": {}}, "schema": []}
{"input": "GLP-1 infusion during hyperglycaemia increased HR and BP and produced a statistically non-significant decrease in measures of cardiac vagal control compared with values before any manipulation of insulin levels.", "output": {"entities": {}}, "schema": []}
{"input": "This commentary summarises how, and to what extent, insulin and GLP-1 affect autonomic nervous system activity, HR and BP.", "output": {"entities": {}}, "schema": []}
{"input": "More information is needed on the mechanisms through which acute administration of, and long-term treatment with, GLP-1 may affect haemodynamics and autonomic activity in diabetic and obese patients, since this may influence cardiovascular outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Photocytotoxicity of copper (II) complexes of curcumin and N-ferrocenylmethyl-l-amino acids.", "output": {"entities": {"chemical": [{"text": "copper (II)", "start": 21, "end": 32}, {"text": "curcumin", "start": 46, "end": 54}, {"text": "N-ferrocenylmethyl-l-amino acids", "start": 59, "end": 91}]}}, "schema": []}
{"input": "Copper (II) complexes [Cu (Fc-aa) (cur)] (1-3) of curcumin (Hcur) and N-ferrocenylmethyl-l-amino acids (Fc-aa), viz., ferrocenylmethyl-l-tyrosine (Fc-TyrH), ferrocenylmethyl-l-tryptophan (Fc-TrpH) and ferrocenylmethyl-l-methionine (Fc-MetH), were prepared and characterized.", "output": {"entities": {"chemical": [{"text": "Copper (II)", "start": 0, "end": 11}, {"text": "[Cu (Fc-aa) (cur)]", "start": 22, "end": 40}, {"text": "curcumin", "start": 50, "end": 58}, {"text": "Hcur", "start": 60, "end": 64}, {"text": "N-ferrocenylmethyl-l-amino acids", "start": 70, "end": 102}, {"text": "Fc-aa", "start": 104, "end": 109}, {"text": "ferrocenylmethyl-l-tyrosine", "start": 118, "end": 145}, {"text": "Fc-TyrH", "start": 147, "end": 154}, {"text": "ferrocenylmethyl-l-tryptophan", "start": 157, "end": 186}, {"text": "Fc-TrpH", "start": 188, "end": 195}, {"text": "ferrocenylmethyl-l-methionine", "start": 201, "end": 230}, {"text": "Fc-MetH", "start": 232, "end": 239}]}}, "schema": []}
{"input": "The DNA photocleavage activity, photocytotoxicity and cellular localization in HeLa and MCF-7 cancer cells of these complexes were studied.", "output": {"entities": {}}, "schema": []}
{"input": "Acetylacetonate (acac) complexes [Cu (Fc-aa) (acac)] (4-6) were prepared and used as controls.", "output": {"entities": {"chemical": [{"text": "Acetylacetonate", "start": 0, "end": 15}, {"text": "acac", "start": 17, "end": 21}, {"text": "[Cu (Fc-aa) (acac)]", "start": 33, "end": 52}]}}, "schema": []}
{"input": "The chemical nuclease inactive complexes showed efficient pUC19 DNA cleavage activity in visible light.", "output": {"entities": {}}, "schema": []}
{"input": "Complexes 1-3 showed high photocytotoxicity with low dark toxicity thus giving remarkable photodynamic effect.", "output": {"entities": {}}, "schema": []}
{"input": "FACScan analysis showed apoptosis of the cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Fluorescence microscopic studies revealed primarily cytosolic localization of the complexes.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic Administration of Small Non-Erythropoietic Peptide Sequence of Erythropoietin Effectively Ameliorates the Progression of Post Myocardial Infarction Dilated Cardiomyopathy.", "output": {"entities": {}}, "schema": []}
{"input": "The cardioprotective properties of erythropoietin (EPO) in pre-clinical studies are well documented, but erythropoietic and prothrombotic properties of EPO preclude its use in chronic heart failure (CHF).", "output": {"entities": {}}, "schema": []}
{"input": "We tested the effect of long-term treatment with a small peptide sequence within the EPO molecule, Helix B surface peptide (HBSP), that possess tissue-protective, but not erythropoietic properties of EPO, on mortality and cardiac remodeling in post-myocardial infarction dilated cardiomyopaty in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Starting two weeks after permanent left coronary artery ligation, rats received i. p. injections of HBSP (60 micro g/kg) or saline 2 times/week for 10 months.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment did not elicit an immune response, and did not affect the hematocrit.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to untreated rats, HBSP treatment reduced mortality by 50% (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Repeated echocardiography demonstrated remarkable attenuation of left ventricular dilatation (EDV: 41% vs. 86%; ESV: 44% vs. 135%; p < 0. 05), LV functional deterioration (EF:-4% vs.-63%; p < 0. 05) and MI expansion (3% vs. 38%; p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "A hemodynamic assessment at study termination demonstrated normal preload independent stroke work (63 +/- 5 vs. 40 +/- 4; p < 0. 05) and arterio-ventricular coupling (1. 2 +/- 0. 2 vs. 2. 7 +/- 0. 7; p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Histological analysis revealed reduced apoptosis (p < 0. 05) and fibrosis (p < 0. 05), increased cardiomyocyte density (p < 0. 05), and increased number of cardiomyocytes in myocardium among HBSP-treated rats.", "output": {"entities": {}}, "schema": []}
{"input": "The results indicate that HBSP effectively reduces mortality, ameliorates the MI expansion and CHF progression, and preserves systolic reserve in the rat post MI model.", "output": {"entities": {}}, "schema": []}
{"input": "There is also a suggestion that HBSP promoted the increase of the myocytes number in the myocardial wall remote from the infarct.", "output": {"entities": {}}, "schema": []}
{"input": "Thus HBSP peptide merits consideration for clinical testing.", "output": {"entities": {}}, "schema": []}
{"input": "Diamond-Lipid Hybrids Enhance Chemotherapeutic Tolerance and Mediate Tumor Regression.", "output": {"entities": {"chemical": [{"text": "Diamond", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Self-assembled nanodiamond-lipid hybrid particles (NDLPs) harness the potent interaction between the nanodiamond (ND)-surface and small molecules, while providing a mechanism for cell-targeted imaging and therapy of triple negative breast cancers.", "output": {"entities": {}}, "schema": []}
{"input": "Epidermal growth factor receptor-targeted NDLPs are highly biocompatible particles that provide cell-specific imaging, promote tumor retention of ND-complexes, prevent epirubicin toxicities and mediate regression of triple negative breast cancers.", "output": {"entities": {"chemical": [{"text": "epirubicin", "start": 168, "end": 178}]}}, "schema": []}
{"input": "Alkane Oxidation by an Immobilized Nickel Complex Catalyst: Structural and Reactivity Differences Induced by Surface-Ligand Density on Mesoporous Silica.", "output": {"entities": {"chemical": [{"text": "Alkane", "start": 0, "end": 6}, {"text": "Nickel", "start": 35, "end": 41}, {"text": "Silica", "start": 146, "end": 152}]}}, "schema": []}
{"input": "Immobilized nickel catalysts SBA *-L-x/Ni (L = bis (2-pyridylmethyl) (1H-1, 2, 3-triazol-4-ylmethyl) amine) with various ligand densities (L content (x) = 0. 5, 1, 2, 4 mol% Si) have been prepared from azidopropyl-functionalized mesoporous silicas SBA-N3-x.", "output": {"entities": {"chemical": [{"text": "nickel", "start": 12, "end": 18}, {"text": "Ni", "start": 39, "end": 41}, {"text": "bis (2-pyridylmethyl) (1H-1, 2, 3-triazol-4-ylmethyl) amine", "start": 47, "end": 106}, {"text": "Si", "start": 174, "end": 176}, {"text": "azidopropyl", "start": 202, "end": 213}, {"text": "silicas", "start": 240, "end": 247}]}}, "schema": []}
{"input": "Related homogeneous ligand L (t) (Bu) and its Ni (II) complexes, [Ni (L (t) (Bu)) (OAc) 2 (H2 O)] (L (t) (Bu)/Ni) and [Ni (L (t) (Bu)) 2] BF4 (2 L (t) (Bu)/Ni), have been synthesized.", "output": {"entities": {"chemical": [{"text": "L (t) (Bu)", "start": 27, "end": 37}, {"text": "Ni (II)", "start": 46, "end": 53}, {"text": "[Ni (L (t) (Bu)) (OAc) 2 (H2 O)] (L (t) (Bu)/Ni)", "start": 65, "end": 113}, {"text": "[Ni (L (t) (Bu)) 2] BF4 (2 L (t) (Bu)/Ni)", "start": 118, "end": 159}]}}, "schema": []}
{"input": "The L/Ni ratio (0. 9-1. 7: 1) in SBA *-L-x/Ni suggests the formation of an inert [NiL2] site on the surface at higher ligand loadings.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 6, "end": 8}, {"text": "Ni", "start": 43, "end": 45}, {"text": "NiL2", "start": 82, "end": 86}]}}, "schema": []}
{"input": "SBA *-L-x/Ni has been applied to the catalytic oxidation of cyclohexane with m-chloroperbenzoic acid (mCPBA).", "output": {"entities": {"chemical": [{"text": "Ni", "start": 10, "end": 12}, {"text": "cyclohexane", "start": 60, "end": 71}, {"text": "m-chloroperbenzoic acid", "start": 77, "end": 100}, {"text": "mCPBA", "start": 102, "end": 107}]}}, "schema": []}
{"input": "The catalyst with the lowest loading shows high activity in its initial use as the homogeneous L (t) (Bu)/Ni catalyst, with some metal leaching.", "output": {"entities": {"chemical": [{"text": "L (t) (Bu)", "start": 95, "end": 105}, {"text": "Ni", "start": 106, "end": 108}]}}, "schema": []}
{"input": "As the ligand loading increases, the activity and Ni leaching are suppressed.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 50, "end": 52}]}}, "schema": []}
{"input": "The importance of site-density control for the development of immobilized catalysts has been demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "Simulating Lifetime Outcomes Associated with Complications for People with Type 1 Diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVES: The aim of this study was to develop a discrete-time simulation model for people with type 1 diabetes mellitus, to estimate and compare mean life expectancy and quality-adjusted life-years (QALYs) over a lifetime between intensive and conventional blood glucose treatment groups.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 266, "end": 273}]}}, "schema": []}
{"input": "METHODS: We synthesized evidence on type 1 diabetes patients using several published sources.", "output": {"entities": {}}, "schema": []}
{"input": "The simulation model was based on 13 equations to estimate risks of events and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiovascular disease (CVD) risk was obtained from results of the DCCT (diabetes control and complications trial).", "output": {"entities": {}}, "schema": []}
{"input": "Mortality post-CVD event was based on a study using linked administrative data on people with diabetes from Western Australia.", "output": {"entities": {}}, "schema": []}
{"input": "Information on incidence of renal disease and the progression to CVD was obtained from studies in Finland and Italy.", "output": {"entities": {}}, "schema": []}
{"input": "Lower-extremity amputation (LEA) risk was based on the type 1 diabetes Swedish inpatient registry, and the risk of blindness was obtained from results of a German-based study.", "output": {"entities": {}}, "schema": []}
{"input": "Where diabetes-specific data were unavailable, information from other populations was used.", "output": {"entities": {}}, "schema": []}
{"input": "We examine the degree and source of parameter uncertainty and illustrate an application of the model in estimating lifetime outcomes of using intensive and conventional treatments for blood glucose control.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 190, "end": 197}]}}, "schema": []}
{"input": "RESULTS: From 15 years of age, male and female patients had an estimated life expectancy of 47. 2 (95% CI 35. 2-59. 2) and 52. 7 (95% CI 41. 7-63. 6) years in the intensive treatment group.", "output": {"entities": {}}, "schema": []}
{"input": "The model produced estimates of the lifetime benefits of intensive treatment for blood glucose from the DCCT of 4. 0 (95% CI 1. 2-6. 8) QALYs for women and 4. 6 (95% CI 2. 7-6. 9) QALYs for men.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 87, "end": 94}]}}, "schema": []}
{"input": "Absolute risk per 1, 000 person-years for fatal CVD events was simulated to be 1. 37 and 2. 51 in intensive and conventional treatment groups, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: The model incorporates diabetic complications risk data from a type 1 diabetes population and synthesizes other type 1-specific data to estimate long-term outcomes of CVD, end-stage renal disease, LEA and risk of blindness, along with life expectancy and QALYs.", "output": {"entities": {}}, "schema": []}
{"input": "External validation was carried out using life expectancy and absolute risk for fatal CVD events.", "output": {"entities": {}}, "schema": []}
{"input": "Because of the flexible and transparent nature of the model, it has many potential future applications.", "output": {"entities": {}}, "schema": []}
{"input": "tert-Butylhydroquinone reduces lipid accumulation in C57BL/6 mice with lower body weight gain.", "output": {"entities": {"chemical": [{"text": "tert-Butylhydroquinone", "start": 0, "end": 22}]}}, "schema": []}
{"input": "tert-Butylhydroquinone (tBHQ) is a commonly used antioxidant additive that is approved for human use by both the Food and Agriculture Organization and the World Health Organization (FAO/WHO).", "output": {"entities": {"chemical": [{"text": "tert-Butylhydroquinone", "start": 0, "end": 22}, {"text": "tBHQ", "start": 24, "end": 28}]}}, "schema": []}
{"input": "In this study, we examined the effect of tBHQ on body weight gain and found that food supplementation with 0. 001% (w/w) tBHQ inhibited 61. 4% (P < 0. 01) of body weight gain in high-fat diet (HFD)-induced C57BL/6 mice, and the oral administration of tBHQ (1. 5 mg/kg) reduced 47. 5% (P < 0. 05) of body weight gain in normal diet fed db/db mice.", "output": {"entities": {"chemical": [{"text": "tBHQ", "start": 41, "end": 45}, {"text": "tBHQ", "start": 121, "end": 125}, {"text": "tBHQ", "start": 251, "end": 255}]}}, "schema": []}
{"input": "The HFD increased lipid deposit in adipocytes, but these were reduced significantly by tBHQ treatment in C57BL/6 mice.", "output": {"entities": {"chemical": [{"text": "tBHQ", "start": 87, "end": 91}]}}, "schema": []}
{"input": "tBHQ supplementation significantly lowered the plasma triglyceride and total cholesterol, with reduced size of accumulated fat mass.", "output": {"entities": {"chemical": [{"text": "tBHQ", "start": 0, "end": 4}, {"text": "triglyceride", "start": 54, "end": 66}, {"text": "cholesterol", "start": 77, "end": 88}]}}, "schema": []}
{"input": "The rate limiting enzyme of beta-oxidation (ACOX1) was significantly over-expressed in the liver with tBHQ treatment.", "output": {"entities": {"chemical": [{"text": "tBHQ", "start": 102, "end": 106}]}}, "schema": []}
{"input": "These results indicate that tBHQ suppresses body weight gain in mice, possibly at least related to the up-regulation of ACOX1 gene expression.", "output": {"entities": {"chemical": [{"text": "tBHQ", "start": 28, "end": 32}]}}, "schema": []}
{"input": "Tandem Assays of Protein and Glucose with Functionalized Core/Shell Particles Based on Magnetic Separation and Surface-Enhanced Raman Scattering.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 29, "end": 36}]}}, "schema": []}
{"input": "Tandem assays of protein and glucose in combination with mannose-functionalized Fe3 O4 @SiO2 and Ag @SiO2 tag particles have promising potential in effective magnetic separation and highly sensitive and selective SERS assays of biomaterials.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 29, "end": 36}, {"text": "mannose", "start": 57, "end": 64}, {"text": "Fe3 O4", "start": 80, "end": 86}, {"text": "SiO2", "start": 88, "end": 92}, {"text": "Ag", "start": 97, "end": 99}, {"text": "SiO2", "start": 101, "end": 105}]}}, "schema": []}
{"input": "It is for the first time that tandem assay of glucose is developed using SERS based on the Con A-sandwiched microstructures between the functionalized magnetic and tag particles.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 46, "end": 53}]}}, "schema": []}
{"input": "De-repression of FOXO3a death axis by microRNA-132 and-212 causes neuronal apoptosis in Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "Alzheimer' s disease (AD) is a multifactorial and fatal neurodegenerative disorder for which the mechanisms leading to profound neuronal loss are incompletely recognized.", "output": {"entities": {}}, "schema": []}
{"input": "MicroRNAs (miRNAs) are recently discovered small regulatory RNA molecules that repress gene expression and are increasingly acknowledged as prime regulators involved in human brain pathologies.", "output": {"entities": {}}, "schema": []}
{"input": "Here we identified two homologous miRNAs, miR-132 and miR-212, downregulated in temporal cortical areas and CA1 hippocampal neurons of human AD brains.", "output": {"entities": {}}, "schema": []}
{"input": "Sequence-specific inhibition of miR-132 and miR-212 induces apoptosis in cultured primary neurons, whereas their overexpression is neuroprotective against oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "Using primary neurons and PC12 cells, we demonstrate that miR-132/212 controls cell survival by direct regulation of PTEN, FOXO3a and P300, which are all key elements of AKT signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Silencing of these three target genes by RNAi abrogates apoptosis caused by the miR-132/212 inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "We further demonstrate that mRNA and protein levels of PTEN, FOXO3a, P300 and most of the direct pro-apoptotic transcriptional targets of FOXO3a are significantly elevated in human AD brains.", "output": {"entities": {}}, "schema": []}
{"input": "These results indicate that the miR-132/miR-212/PTEN/FOXO3a signaling pathway contributes to AD neurodegeneration.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of Ras-Effector Interaction by Cyclic Peptides.", "output": {"entities": {}}, "schema": []}
{"input": "A combinatorial library of 6 x 10 (6) cyclic peptides was synthesized in the one bead-two compound format, with each bead displaying a unique cyclic peptide on its surface and a linear peptide encoding tag in its interior.", "output": {"entities": {}}, "schema": []}
{"input": "Screening of the library against K-Ras identified compounds that bound K-Ras with submicromolar affinity and disrupted its interaction with effector proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Using in Situ X-ray Reflectivity to Study Protein Adsorption on Hydrophilic and Hydrophobic Surfaces: Benefits and Limitations.", "output": {"entities": {}}, "schema": []}
{"input": "We have employed in situ X-ray reflectivity (IXRR) to study the adsorption of a variety of proteins (lysozyme, cytochrome c, myoglobin, hemoglobin, serum albumin, and immunoglobulin G) on model hydrophilic (silicon oxide) and hydrophobic surfaces (octadecyltrichlorosilane self-assembled monolayers), evaluating this recently developed technique for its applicability in the area of biomolecular studies.", "output": {"entities": {"chemical": [{"text": "silicon oxide", "start": 207, "end": 220}, {"text": "octadecyltrichlorosilane", "start": 248, "end": 272}]}}, "schema": []}
{"input": "We report herein the highest resolution depiction of adsorbed protein films, greatly improving on the precision of previous neutron reflectivity (NR) results and previous IXRR studies.", "output": {"entities": {}}, "schema": []}
{"input": "We were able to perform complete scans in 5 min or less with the maximum momentum transfer of at least 0. 52 A (-1), allowing for some time-resolved information about the evolution of the protein film structure.", "output": {"entities": {}}, "schema": []}
{"input": "The three smallest proteins (lysozyme, cytochrome c, and myoglobin) were seen to deposit as fully hydrated, nondenatured molecules onto hydrophilic surfaces, with indications of particular preferential orientations.", "output": {"entities": {}}, "schema": []}
{"input": "Time evolution was observed for both lysozyme and myoglobin films.", "output": {"entities": {}}, "schema": []}
{"input": "The larger proteins were not observed to deposit on the hydrophilic substrates, perhaps because of contrast limitations.", "output": {"entities": {}}, "schema": []}
{"input": "On hydrophobic surfaces, all proteins were seen to denature extensively in a qualitatively similar way but with a rough trend that the larger proteins resulted in lower coverage.", "output": {"entities": {}}, "schema": []}
{"input": "We have generated high-resolution electron density profiles of these denatured films, including capturing the growth of a lysozyme film.", "output": {"entities": {}}, "schema": []}
{"input": "Because the solution interface of these denatured films is diffuse, IXRR cannot unambiguously determine the film extent and coverage, a drawback compared to NR.", "output": {"entities": {}}, "schema": []}
{"input": "X-ray radiation damage was systematically evaluated, including the controlled exposure of protein films to high-intensity X-rays and exposure of the hydrophobic surface to X-rays before adsorption.", "output": {"entities": {}}, "schema": []}
{"input": "Our analysis showed that standard measuring procedures used for XRR studies may lead to altered protein films; therefore, we used modified procedures to limit the influence of X-ray damage.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative Determination of Lateral Concentration and Depth Profile of Histidine-Tagged Recombinant Proteins Probed by Grazing Incidence X-ray Fluorescence.", "output": {"entities": {"chemical": [{"text": "Histidine", "start": 73, "end": 82}]}}, "schema": []}
{"input": "We have demonstrated that the complementary combination of grazing incidence X-ray fluorescence (GIXF) with specular X-ray reflectivity (XRR) can be used to quantitatively determine the density profiles of Ni (2) (+) ions complexed with chelator headgroups as well as S atoms in recombinant proteins anchored to lipid monolayers at the air/water interface.", "output": {"entities": {"chemical": [{"text": "Ni (2) (+)", "start": 206, "end": 216}, {"text": "S", "start": 268, "end": 269}]}}, "schema": []}
{"input": "First, we prepared phospholipid monolayers incorporating chelator lipid anchors at different molar fractions at the air/water interface.", "output": {"entities": {}}, "schema": []}
{"input": "The fine-structures perpendicular to the global plane of monolayers were characterized by XRR in the presence of Ni (2) (+) ions, yielding the thickness, roughness, and electron density of the stratified lipid monolayers.", "output": {"entities": {"chemical": [{"text": "Ni (2) (+)", "start": 113, "end": 123}]}}, "schema": []}
{"input": "X-ray fluorescence intensities from Ni K alpha core levels recorded at the incidence angles below and above the critical angle of total reflection allow for the determination of the position and lateral density of Ni (2) (+) ions associated with chelator headgroups with a high spatial accuracy (+/- 5 A).", "output": {"entities": {"chemical": [{"text": "Ni", "start": 36, "end": 38}, {"text": "Ni (2) (+)", "start": 214, "end": 224}]}}, "schema": []}
{"input": "The coupling of histidine-tagged Xenopus cadherin 11 (Xcad-11) can also be identified by changes in the fines-structures using XRR.", "output": {"entities": {"chemical": [{"text": "histidine", "start": 16, "end": 25}]}}, "schema": []}
{"input": "Although fluorescence intensities from S K alpha level were much weaker than Ni K alpha signals, we could detect the location of S atoms in recombinant Xcad-11 proteins.", "output": {"entities": {"chemical": [{"text": "S", "start": 39, "end": 40}, {"text": "Ni", "start": 77, "end": 79}, {"text": "S", "start": 129, "end": 130}]}}, "schema": []}
{"input": "Ligand Based Approach to L-Type Calcium Channel by Imidazo [2, 1-b] thiazole-1, 4-Dihydropyridines: from Heart Activity to Brain Affinity.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 32, "end": 39}, {"text": "Imidazo [2, 1-b] thiazole-1, 4-Dihydropyridines", "start": 51, "end": 98}]}}, "schema": []}
{"input": "The synthesis, characterization, and functional in vitro assay in cardiac and smooth muscle (vascular and nonvascular) of a series of 4-imidazo [2, 1-b] thiazole-1, 4-dihydropyridines are reported.", "output": {"entities": {"chemical": [{"text": "4-imidazo [2, 1-b] thiazole-1, 4-dihydropyridines", "start": 134, "end": 183}]}}, "schema": []}
{"input": "To define the calcium blocker nature of the imidazo [2, 1-b] thiazole-1, 4-DHPs and their selectivity on Cav1. 2 and Cav1. 3 isoforms we performed binding studies on guinea pig atrial and ventricular membranes, on intact cells expressing the cloned Cav1. 2a subunit and on rat brain cortex.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 14, "end": 21}, {"text": "imidazo [2, 1-b] thiazole-1, 4-DHPs", "start": 44, "end": 79}]}}, "schema": []}
{"input": "To get major insights into the reasons for the affinity for Cav1. 2 and/or Cav1. 3 molecular modelling studies were also undertaken.", "output": {"entities": {}}, "schema": []}
{"input": "Some physicochemical and pharmacokinetic properties of selected compounds were calculated and compared.", "output": {"entities": {}}, "schema": []}
{"input": "All the biological data collected and reported herein allowed us to rationalize the structure-activity relationship of the 4-imidazo [2, 1-b] thiazole-1, 4-DHPs and to identify which of these enhanced the activity at the central level.", "output": {"entities": {"chemical": [{"text": "4-imidazo [2, 1-b] thiazole-1, 4-DHPs", "start": 123, "end": 160}]}}, "schema": []}
{"input": "Synthesis of chemicals using solar energy with stable photoelectrochemically active heterostructures.", "output": {"entities": {}}, "schema": []}
{"input": "Efficient and cost-effective conversion of solar energy to useful chemicals and fuels could lead to a significant reduction in fossil hydrocarbon use.", "output": {"entities": {"chemical": [{"text": "hydrocarbon", "start": 134, "end": 145}]}}, "schema": []}
{"input": "Artificial systems that use solar energy to produce chemicals have been reported for more than a century.", "output": {"entities": {}}, "schema": []}
{"input": "However the most efficient devices demonstrated, based on traditionally fabricated compound semiconductors, have extremely short working lifetimes due to photocorrosion by the electrolyte.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report a stable, scalable design and molecular level fabrication strategy to create photoelectrochemically active heterostructure (PAH) units consisting of an efficient semiconductor light absorber in contact with oxidation and reduction electrocatalysts and otherwise protected by alumina.", "output": {"entities": {"chemical": [{"text": "alumina", "start": 290, "end": 297}]}}, "schema": []}
{"input": "The functional heterostructures are fabricated by layer-by-layer, template-directed, electrochemical synthesis in porous anodic aluminum oxide membranes to produce high density arrays of electronically autonomous, nanostructured, corrosion resistant, photoactive units (~ 10 (9)-10 (10) PAHs per cm (2)).", "output": {"entities": {"chemical": [{"text": "aluminum oxide", "start": 128, "end": 142}]}}, "schema": []}
{"input": "Each PAH unit is isolated from its neighbor by the transparent electrically insulating oxide cellular enclosure that makes the overall assembly fault tolerant.", "output": {"entities": {"chemical": [{"text": "oxide", "start": 87, "end": 92}]}}, "schema": []}
{"input": "When illuminated with visible light, the free floating devices have been demonstrated to produce hydrogen at a stable rate for over 24 h in corrosive hydroiodic acid electrolyte with light as the only input.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 97, "end": 105}, {"text": "hydroiodic acid", "start": 150, "end": 165}]}}, "schema": []}
{"input": "The quantum efficiency (averaged over the solar spectrum) for absorbed photons-to-hydrogen conversion was 7. 4% and solar-to-hydrogen energy efficiency of incident light was 0. 9%.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 82, "end": 90}, {"text": "hydrogen", "start": 125, "end": 133}]}}, "schema": []}
{"input": "The fabrication approach is scalable for commercial manufacturing and readily adaptable to a variety of earth abundant semiconductors which might otherwise be unstable as photoelectrocatalysts.", "output": {"entities": {}}, "schema": []}
{"input": "The role of external defects in chemical sensing of graphene field-effect transistors.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 52, "end": 60}]}}, "schema": []}
{"input": "A fundamental understanding of chemical sensing mechanisms in graphene-based chemical field-effect transistors (chemFETs) is essential for the development of next generation chemical sensors.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 62, "end": 70}]}}, "schema": []}
{"input": "Here we explore the hidden sensing modalities responsible for tailoring the gas detection ability of pristine graphene sensors by exposing graphene chemFETs to electron donor and acceptor trace gas vapors.", "output": {"entities": {"chemical": [{"text": "pristine graphene", "start": 101, "end": 118}, {"text": "graphene", "start": 139, "end": 147}]}}, "schema": []}
{"input": "We uncover that the sensitivity (in terms of modulation in electrical conductivity) of pristine graphene chemFETs is not necessarily intrinsic to graphene, but rather it is facilitated by external defects in the insulating substrate, which can modulate the electronic properties of graphene.", "output": {"entities": {"chemical": [{"text": "pristine graphene", "start": 87, "end": 104}, {"text": "graphene", "start": 146, "end": 154}, {"text": "graphene", "start": 282, "end": 290}]}}, "schema": []}
{"input": "We disclose a mixing effect caused by partial overlap of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of adsorbed gas molecules to explain graphene' s ability to detect adsorbed molecules.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 187, "end": 195}]}}, "schema": []}
{"input": "Our results open a new design space, suggesting that control of external defects in supporting substrates can lead to tunable graphene chemical sensors, which could be developed without compromising the intrinsic electrical and structural properties of graphene.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 126, "end": 134}]}}, "schema": []}
{"input": "Study of the microcharacter of ultrastable aqueous foam stabilized by a kind of flexible connecting bipolar-headed surfactant with existence of magnesium ion.", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 144, "end": 153}]}}, "schema": []}
{"input": "In this paper, ultrastable aqueous foam stabilized by a kind of flexible connecting bipolar-headed surfactant alkyl polyoxyethylene sulfate (AE3S) with coexisting Mg (2 +) was reported.", "output": {"entities": {"chemical": [{"text": "alkyl polyoxyethylene sulfate", "start": 110, "end": 139}, {"text": "AE3S", "start": 141, "end": 145}, {"text": "Mg (2 +)", "start": 163, "end": 171}]}}, "schema": []}
{"input": "Detailed molecular behaviors of AE3S in foam film with coexisting divalent cationic Ca (2 +) or Mg (2 +) were investigated by molecular dynamic simulation, comparing with the traditional surfactant sodium dodecyl sulfate (SDS), to find out how the microcharacter and array behavior of molecules in the foam film determined by molecular interaction effect the foam stability.", "output": {"entities": {"chemical": [{"text": "AE3S", "start": 32, "end": 36}, {"text": "Ca (2 +)", "start": 84, "end": 92}, {"text": "Mg (2 +)", "start": 96, "end": 104}, {"text": "sodium dodecyl sulfate", "start": 198, "end": 220}, {"text": "SDS", "start": 222, "end": 225}]}}, "schema": []}
{"input": "It was found that the ultrastable foam film obtained by the cooperation of magnesium ions and AE3S was driven from two aspects: one is the favorable arrangement of surfactant molecules, and the other is the increase of capacity of foam films for resolutely holding water molecules deduced by a dipolar pair formed by the flexible connecting head groups of AE3S and hydrated Mg (2 +) via intermolecular coactions, both related to the presence of magnesium ions.", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 75, "end": 84}, {"text": "AE3S", "start": 94, "end": 98}, {"text": "AE3S", "start": 356, "end": 360}, {"text": "hydrated Mg (2 +)", "start": 365, "end": 382}, {"text": "magnesium", "start": 445, "end": 454}]}}, "schema": []}
{"input": "Foam lamella stability measurement and foam decay method were both used to evaluate the stability of foam.", "output": {"entities": {}}, "schema": []}
{"input": "Fourier transform infrared (FT-IR) was used to detect the composition variation of foam film in the drainage process; the vibration peak of OH for water molecule shifted from the 3390 cm (-1) (being assigned to the bulk water integrated by hydrogen bonds) to 3685 cm (-1) (being assigned to the vibration of isolated water molecules) for the ultrastable foam film after complete drainage, which agreed very well with the molecular simulation results.", "output": {"entities": {"chemical": [{"text": "OH", "start": 140, "end": 142}, {"text": "hydrogen", "start": 240, "end": 248}]}}, "schema": []}
{"input": "Quinoline Drug-Heme Interactions and Implications for Antimalarial Cytostatic versus Cytocidal Activities.", "output": {"entities": {"chemical": [{"text": "Quinoline", "start": 0, "end": 9}, {"text": "Heme", "start": 15, "end": 19}]}}, "schema": []}
{"input": "Historically, the most successful molecular target for antimalarial drugs has been heme biomineralization within the malarial parasite digestive vacuole.", "output": {"entities": {}}, "schema": []}
{"input": "Heme released from catabolized host red blood cell hemoglobin is toxic, so malarial parasites crystallize heme to nontoxic hemozoin.", "output": {"entities": {"chemical": [{"text": "Heme", "start": 0, "end": 4}, {"text": "heme", "start": 106, "end": 110}]}}, "schema": []}
{"input": "For years it has been accepted that a number of effective quinoline antimalarial drugs (e. g., chloroquine, quinine, amodiaquine) function by preventing hemozoin crystallization.", "output": {"entities": {"chemical": [{"text": "quinoline", "start": 58, "end": 67}, {"text": "chloroquine", "start": 95, "end": 106}, {"text": "quinine", "start": 108, "end": 115}, {"text": "amodiaquine", "start": 117, "end": 128}]}}, "schema": []}
{"input": "However, recent studies over the past decade have revealed a surprising molecular diversity in quinoline-heme molecular interactions.", "output": {"entities": {"chemical": [{"text": "quinoline", "start": 95, "end": 104}, {"text": "heme", "start": 105, "end": 109}]}}, "schema": []}
{"input": "This diversity shows that even closely related quinoline drugs may have quite different molecular pharmacology.", "output": {"entities": {"chemical": [{"text": "quinoline", "start": 47, "end": 56}]}}, "schema": []}
{"input": "This paper reviews the molecular diversity and highlights important implications for understanding quinoline antimalarial drug resistance and for future drug design.", "output": {"entities": {"chemical": [{"text": "quinoline", "start": 99, "end": 108}]}}, "schema": []}
{"input": "Interactions between oral antineoplastic agents and concomitant medication: a systematic review.", "output": {"entities": {}}, "schema": []}
{"input": "Introduction: In recent years, the number of oral antitumoral agents has considerably increased.", "output": {"entities": {}}, "schema": []}
{"input": "Oral administration increases the risk of interactions, because most oral anticancer drugs are taken on a daily basis.", "output": {"entities": {}}, "schema": []}
{"input": "Interactions can increase exposure to antitumoral agents or cause treatment failure.", "output": {"entities": {}}, "schema": []}
{"input": "Many antitumoral drugs undergo enzymatic metabolism by cytochrome P450.", "output": {"entities": {}}, "schema": []}
{"input": "As some act as inducers or inhibitors of one or more isoenzymes, they can lead to decreases or increases in plasma concentrations of concomitant drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, cytostatic drugs can act not only as victims but also as perpetrators.", "output": {"entities": {}}, "schema": []}
{"input": "P-glycoprotein, an efflux transporter, can also be involved in pharmacokinetic interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Areas covered: A Medline search was performed to summarize the available evidence of the most clinically relevant interactions between oral chemotherapy agents and other drugs.", "output": {"entities": {}}, "schema": []}
{"input": "The search covered the period from 1966 until August 2012 for each antitumoral drug using the medical subject headings' Drug Interactions' OR' Pharmacokinetics'.", "output": {"entities": {}}, "schema": []}
{"input": "While the present review is not exhaustive, it aims to increase clinicians' awareness of potential drug-drug interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Expert opinion: As cancer patients are often polymedicated and treated by different physicians, the risk of drug interactions between antitumoral agents and other medications is high.", "output": {"entities": {}}, "schema": []}
{"input": "More clinical interaction studies are encouraged to ensure appropriate antineoplastic pharmacokinetics in clinical practice.", "output": {"entities": {}}, "schema": []}
{"input": "Structure and Absolute Configuration of Fumiquinazoline L, an Alkaloid from a Gorgonian-Derived Scopulariopsis sp.", "output": {"entities": {"chemical": [{"text": "Fumiquinazoline L", "start": 40, "end": 57}]}}, "schema": []}
{"input": "Fungus.", "output": {"entities": {}}, "schema": []}
{"input": "Fumiquinazoline L (1), an alkaloid with a heptacyclic skeleton formed via a bridging hemiaminal linkage, was isolated from a gorgonian-derived Scopulariopsis sp. fungus.", "output": {"entities": {"chemical": [{"text": "Fumiquinazoline L", "start": 0, "end": 17}]}}, "schema": []}
{"input": "The structure and absolute configuration of the new compound were identified by comprehensive spectroscopic data and X-ray diffraction analysis.", "output": {"entities": {}}, "schema": []}
{"input": "During acid hydrolysis of 1, the isomerization of the valine residue was observed and also studied in different conditions.", "output": {"entities": {"chemical": [{"text": "valine", "start": 54, "end": 60}]}}, "schema": []}
{"input": "Fumiquinazoline L (1) showed no cytotoxic or antibacterial activities.", "output": {"entities": {"chemical": [{"text": "Fumiquinazoline L", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Identification of the Post-Polyketide Synthase Modification Enzymes for Fostriecin Biosynthesis in Streptomyces pulveraceus.", "output": {"entities": {"chemical": [{"text": "Fostriecin", "start": 72, "end": 82}]}}, "schema": []}
{"input": "Fostriecin (FST, 1) is a natural product with promising antitumor activity produced by Streptomyces pulveraceus.", "output": {"entities": {"chemical": [{"text": "Fostriecin", "start": 0, "end": 10}, {"text": "FST", "start": 12, "end": 15}]}}, "schema": []}
{"input": "Its antitumor activity is associated with the selective inhibition of protein phosphatase activities.", "output": {"entities": {}}, "schema": []}
{"input": "The biosynthetic gene cluster for FST has recently been cloned and sequenced.", "output": {"entities": {}}, "schema": []}
{"input": "To better understand the post-polyketide synthase (PKS) modification steps in the biosynthetic pathway of FST, we constructed and characterized three post-PKS modification gene mutants of fosG, fosK, and fosM by knockout inactivation in S. pulveraceus.", "output": {"entities": {}}, "schema": []}
{"input": "As a result, we determined that a fosK-encoded cytochrome P450 monooxygenase is responsible for C-18 hydroxylation, formation of an unsaturated lactone is dependent upon FosM, and the fosG gene product is involved in hydroxylation at C-4 after the action of FosM to yield PD 113, 271 from FST.", "output": {"entities": {"chemical": [{"text": "unsaturated lactone", "start": 132, "end": 151}, {"text": "PD 113, 271", "start": 272, "end": 283}, {"text": "FST", "start": 289, "end": 292}]}}, "schema": []}
{"input": "The accumulated analogues from the Delta fosK and Delta fosM mutant strains possessed a malonyl ester moiety that suggested that all the post-PKS modification steps in FST biosynthesis occur with the polyketide chain bearing a malonyl ester at the C-3 position, with formation of the unsaturated six-membered lactone as the last step in FST biosynthesis.", "output": {"entities": {"chemical": [{"text": "malonyl ester", "start": 88, "end": 101}, {"text": "malonyl ester", "start": 227, "end": 240}, {"text": "lactone", "start": 309, "end": 316}, {"text": "FST", "start": 337, "end": 340}]}}, "schema": []}
{"input": "Does Colloid Shape Affect Detachment of Colloids by a Moving Air-Water Interface?", "output": {"entities": {}}, "schema": []}
{"input": "Air-water interfaces interact strongly with colloidal particles by capillary forces.", "output": {"entities": {}}, "schema": []}
{"input": "The magnitude of the interaction force depends on, among other things, the particle shape.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we investigate the effects of particle shape on colloid detachment by a moving air-water interface.", "output": {"entities": {}}, "schema": []}
{"input": "We used hydrophilic polystyrene colloids with four different shapes (spheres, barrels, rods, and oblong disks), but otherwise identical surface properties.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 20, "end": 31}]}}, "schema": []}
{"input": "The nonspherical shapes were created by stretching spherical microspheres on a film of polyvinyl alcohol (PVA).", "output": {"entities": {"chemical": [{"text": "polyvinyl alcohol", "start": 87, "end": 104}, {"text": "PVA", "start": 106, "end": 109}]}}, "schema": []}
{"input": "The colloids were then deposited onto the inner surface of a glass channel.", "output": {"entities": {}}, "schema": []}
{"input": "An air bubble was introduced into the channel and passed through, thereby generating a receding followed by an advancing air-water interface.", "output": {"entities": {}}, "schema": []}
{"input": "The detachment of colloids by the air-water interfaces was visualized with a confocal microscope, quantified by image analysis, and analyzed statistically to determine significant differences.", "output": {"entities": {}}, "schema": []}
{"input": "For all colloid shapes, the advancing air-water interface caused pronounced colloid detachment (> 63%), whereas the receding interface was ineffective in colloid detachment (< 1. 5%).", "output": {"entities": {}}, "schema": []}
{"input": "Among the different colloid shapes, the barrels were most readily removed (94%) by the advancing interface, followed by the spheres and oblong disks (80%) and the rods (63%).", "output": {"entities": {}}, "schema": []}
{"input": "Colloid detachment was significantly affected by colloid shape.", "output": {"entities": {}}, "schema": []}
{"input": "The presence of an edge, as it occurs in a barrel-shaped colloid, promoted colloid detachment because the air-water interface is being pinned at the edge of the colloid.", "output": {"entities": {}}, "schema": []}
{"input": "This suggests that the magnitude of colloid mobilization and transport in porous media is underestimated for edged particles and overestimated for rodlike particles when a sphere is used as a model colloid.", "output": {"entities": {}}, "schema": []}
{"input": "Biomimetic Silicification of Demineralized Hierarchical Collagenous Tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike man-made composite materials, natural biominerals containing composites usually demonstrate different levels of sophisticated hierarchical structures which are responsible for their mechanical properties and other metabolic functions.", "output": {"entities": {}}, "schema": []}
{"input": "However, the complex spatial organizations of the organic-inorganic phases are far beyond what they achieved by contemporary engineering techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we demonstrate that carbonated apatite present in collagen matrices derived from fish scale and bovine bone may be replaced by amorphous silica, using an approach that simulates what is utilized by phylogenetically ancient glass sponges.", "output": {"entities": {"chemical": [{"text": "silica", "start": 143, "end": 149}]}}, "schema": []}
{"input": "The structural hierarchy of these collagen-based biomaterials is replicated by the infiltration and condensation of fluidic polymer-stabilized silicic acid precursors within the intrafibrillar milieu of type I collagen fibrils.", "output": {"entities": {"chemical": [{"text": "silicic acid", "start": 143, "end": 155}]}}, "schema": []}
{"input": "This facile biomimetic silicification strategy may be used for fabricating silica-based, three-dimensional functional materials with specific morphological and hierarchical requirements.", "output": {"entities": {"chemical": [{"text": "silica", "start": 75, "end": 81}]}}, "schema": []}
{"input": "Nocardiamides A and B, Two Cyclohexapeptides from the Marine-Derived Actinomycete Nocardiopsis sp.", "output": {"entities": {"chemical": [{"text": "Nocardiamides A and B", "start": 0, "end": 21}, {"text": "Cyclohexapeptides", "start": 27, "end": 44}]}}, "schema": []}
{"input": "CNX037.", "output": {"entities": {}}, "schema": []}
{"input": "Two new cyclic hexapeptides, nocardiamides A (1) and B (2), were isolated from the culture broth of marine-derived actinomycete CNX037 strain that was identified as a Nocardiopsis species.", "output": {"entities": {"chemical": [{"text": "cyclic hexapeptides", "start": 8, "end": 27}, {"text": "nocardiamides", "start": 29, "end": 42}]}}, "schema": []}
{"input": "The planar structures of nocardiamides A (1) and B (2) were assigned on the basis of 1D and 2D NMR and HRESIMS spectroscopic analyses.", "output": {"entities": {"chemical": [{"text": "nocardiamides", "start": 25, "end": 38}]}}, "schema": []}
{"input": "Their absolute configurations were deduced by the advanced Marfey' s method and chiral-phase HPLC analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The challenge of locating two d-and one l-valine residue in 1 and 2 was accomplished by total synthesis using solid-phase peptide synthetic methods.", "output": {"entities": {"chemical": [{"text": "d-and one l-valine", "start": 30, "end": 48}]}}, "schema": []}
{"input": "Both 1 and 2 showed negligible antimicrobial activities against seven indicator strains and exhibited no cytotoxicity against HCT-116.", "output": {"entities": {}}, "schema": []}
{"input": "Potency switch between CHK1 and MK2: Discovery of imidazo [1, 2-a] pyrazine-and imidazo [1, 2-c] pyrimidine-based kinase inhibitors.", "output": {"entities": {"chemical": [{"text": "imidazo [1, 2-a] pyrazine", "start": 50, "end": 75}, {"text": "imidazo [1, 2-c] pyrimidine", "start": 80, "end": 107}]}}, "schema": []}
{"input": "Chemistry has been developed to access both imidazo [1, 2-a] pyrazines and imidazo [1, 2-c] pyrimidines.", "output": {"entities": {"chemical": [{"text": "imidazo [1, 2-a] pyrazines", "start": 44, "end": 70}, {"text": "imidazo [1, 2-c] pyrimidines", "start": 75, "end": 103}]}}, "schema": []}
{"input": "Small structural modifications in both series led to a switch of potency between two kinases involved in mediating cell cycle checkpoint control, CHK1 and MK2.", "output": {"entities": {}}, "schema": []}
{"input": "The in vitro effect of duroquinone on functional competence, genomic integrity, and oxidative stress indices of sterlet (Acipenser ruthenus) spermatozoa.", "output": {"entities": {"chemical": [{"text": "duroquinone", "start": 23, "end": 34}]}}, "schema": []}
{"input": "The sturgeon is a highly endangered fish species mostly due to over-fishing, habitat destruction, and water pollution.", "output": {"entities": {}}, "schema": []}
{"input": "Duroquinone (derivative of 1, 4-benzoquinone) is a xenobiotic compound widespread in the environment.", "output": {"entities": {"chemical": [{"text": "Duroquinone", "start": 0, "end": 11}, {"text": "1, 4-benzoquinone", "start": 27, "end": 44}]}}, "schema": []}
{"input": "The effect of duroquinone on motility, DNA integrity, and oxidative stress indices in sterlet, Acispenser ruthenus, spermatozoa was investigated.", "output": {"entities": {"chemical": [{"text": "duroquinone", "start": 14, "end": 25}]}}, "schema": []}
{"input": "Sterlet sperm was exposed for 2h to duroquinone at concentrations of 25, 50, 100, and 150 mu M.", "output": {"entities": {"chemical": [{"text": "duroquinone", "start": 36, "end": 47}]}}, "schema": []}
{"input": "Spermatozoa motility, velocity, and ATP content were significantly decreased with exposure to duroquinone.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 36, "end": 39}, {"text": "duroquinone", "start": 94, "end": 105}]}}, "schema": []}
{"input": "The level of DNA damage significantly increased at concentrations of 50 mu M and above.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative stress indices (lipid peroxidation and content of carbonyl proteins) and superoxide dismutase (SOD) activity increased significantly with increasing concentrations of duroquinone.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 60, "end": 68}, {"text": "superoxide", "start": 83, "end": 93}, {"text": "duroquinone", "start": 177, "end": 188}]}}, "schema": []}
{"input": "Oxidative stress in sterlet spermatozoa induced by duroquinone was shown to impair spermatozoa DNA integrity, motility parameters, and the antioxidant defense system.", "output": {"entities": {"chemical": [{"text": "duroquinone", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Spermatozoa motility, content of carbonyl proteins, and SOD activity were shown to be sensitive biomarkers, exhibiting strong responses to low concentrations of the xenobiotic.", "output": {"entities": {"chemical": [{"text": "carbonyl", "start": 33, "end": 41}]}}, "schema": []}
{"input": "Results also suggested that fish spermatozoa in vitro assays may provide a simple and efficient means of monitoring residual pollutants in the aquatic environment.", "output": {"entities": {}}, "schema": []}
{"input": "Kappa opioid receptors in the central amygdala regulate ethanol actions at presynaptic GABAergic sites.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 56, "end": 63}]}}, "schema": []}
{"input": "Human and animal studies indicate that kappa opioid receptor (KOR) systems are involved in ethanol drinking and dependence (Xuei et al., 2006; Walker and Koob, 2008; Walker et al., 2011).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 91, "end": 98}]}}, "schema": []}
{"input": "The central amygdala (CeA) is a critical brain region mediating anxiety-related behavior and drug reward and is a likely site for the interaction of the KOR system and ethanol, although few studies have explored this interaction.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 168, "end": 175}]}}, "schema": []}
{"input": "Using in vitro single-cell recording techniques in mouse brain slices, we examined the physiological effects of KOR activation in CeA on GABAergic neurotransmission and its interaction with acute ethanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 196, "end": 203}]}}, "schema": []}
{"input": "A selective KOR agonist (U69593, 1 mu M) diminished evoked GABAergic inhibitory postsynaptic currents (IPSCs) by 18% (n = 10) in the CeA, whereas blockade of KORs with a selective antagonist (nor-binaltorphimine, 1 mu M) augmented the baseline evoked GABAergic IPSCs by 14% (p < 0. 01; n = 34), suggesting that the KOR system contributes to tonic inhibition of GABAergic neurotransmission in the CeA.", "output": {"entities": {"chemical": [{"text": "U69593", "start": 25, "end": 31}, {"text": "nor-binaltorphimine", "start": 192, "end": 211}]}}, "schema": []}
{"input": "In addition, the enhancement by acute ethanol of GABAergic IPSC amplitudes in the CeA was further augmented by pharmacological blockade of KORs, from 14% (n = 36) to 27% (n = 26; p < 0. 01), or by genetic deletion of KORs, from 14% in WT mice (n = 19) to 34% in KOR knockout (KO) mice (n = 13, p < 0. 01), suggesting that the KOR system regulates acute ethanol actions in the CeA.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 38, "end": 45}, {"text": "ethanol", "start": 353, "end": 360}]}}, "schema": []}
{"input": "Subsequent experiments using tetrodotoxin to block activity-dependent neurotransmission suggest that KORs regulate GABA release at presynaptic sites.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 115, "end": 119}]}}, "schema": []}
{"input": "Thus, KOR activation modulates GABAergic neurotransmission and ethanol effects in CeA in a manner similar to other subtypes of opioid receptors, i. e., mu and delta opioid receptors (Kang-Park et al., 2007; Kang-Park et al., 2009).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Our data support the idea that KORs modulate GABAergic synaptic responses and ethanol effects as one of multiple opioid system-dependent actions of ethanol in the CeA, possibly in a circuit-specific manner.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 78, "end": 85}, {"text": "ethanol", "start": 148, "end": 155}]}}, "schema": []}
{"input": "Application of the combinative particle size reduction technology H 42 to produce fast dissolving glibenclamide tablets.", "output": {"entities": {"chemical": [{"text": "glibenclamide", "start": 98, "end": 111}]}}, "schema": []}
{"input": "Standard particle size reduction techniques such as high pressure homogenization or wet bead milling are frequently used in the production of nanosuspensions.", "output": {"entities": {}}, "schema": []}
{"input": "The need for micronized starting material and long process times are their evident disadvantages.", "output": {"entities": {}}, "schema": []}
{"input": "Combinative particle size reduction technologies have been developed to overcome the drawbacks of the standard techniques.", "output": {"entities": {}}, "schema": []}
{"input": "The H 42 combinative technology consists of a drug pre-treatment by means of spray-drying followed by standard high pressure homogenization.", "output": {"entities": {}}, "schema": []}
{"input": "In the present paper, spray-drying process parameters influencing the diminution effectiveness, such as drug and surfactant concentration, were systematically analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, the untreated and pre-treated drug powders were homogenized for 20 cycles at 1500bar.", "output": {"entities": {}}, "schema": []}
{"input": "For untreated, micronized glibenclamide, the particle size analysis revealed a mean particle size of 772nm and volume-based size distribution values of 2. 686 mu m (d50%) and 14. 423 mu m (d90%).", "output": {"entities": {"chemical": [{"text": "glibenclamide", "start": 26, "end": 39}]}}, "schema": []}
{"input": "The use of pre-treated material (10: 1 glibenclamide/docusate sodium salt ratio spray-dried as ethanolic solution) resulted in a mean particle size of 236nm and volume-based size distribution values of 0. 131 mu m (d50%) and 0. 285 mu m (d90%).", "output": {"entities": {"chemical": [{"text": "glibenclamide", "start": 39, "end": 52}, {"text": "docusate sodium", "start": 53, "end": 68}]}}, "schema": []}
{"input": "These results were markedly improved compared to the standard process.", "output": {"entities": {}}, "schema": []}
{"input": "The nanosuspensions were further transferred into tablet formulations.", "output": {"entities": {}}, "schema": []}
{"input": "Wet granulation, freeze-drying and spray-drying were investigated as downstream methods to produce dry intermediates.", "output": {"entities": {}}, "schema": []}
{"input": "Regarding the dissolution rate, the rank order of the downstream processes was as follows: Spray-drying > freeze-drying > wet granulation.", "output": {"entities": {}}, "schema": []}
{"input": "The best drug release (90% within 10min) was obtained for tablets produced with spray-dried nanosuspension containing 2% mannitol as matrix former.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 121, "end": 129}]}}, "schema": []}
{"input": "In comparison, the tablets processed with micronized glibenclamide showed a drug release of only 26% after 10min.", "output": {"entities": {"chemical": [{"text": "glibenclamide", "start": 53, "end": 66}]}}, "schema": []}
{"input": "The H 42 combinative technology could be successfully applied in the production of small drug nanocrystals.", "output": {"entities": {}}, "schema": []}
{"input": "A nanosuspension transfer to tablets that maintained the fast dissolution properties of the drug nanocrystals was successfully achieved.", "output": {"entities": {}}, "schema": []}
{"input": "Regulation of connexin hemichannel activity by membrane potential and the extracellular calcium in health and disease.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 88, "end": 95}]}}, "schema": []}
{"input": "Connexins are thought to solely mediate cell-to-cell communication by forming gap junction channels composed of two membrane-spanning hemichannels positioned end-to-end.", "output": {"entities": {}}, "schema": []}
{"input": "However, many if not all connexin isoforms also form functional hemichannels (i. e., the precursors of complete channels) that mediate the rapid exchange of ions, second messengers and metabolites between the cell interior and the interstitial space.", "output": {"entities": {}}, "schema": []}
{"input": "Electrical and molecular signaling via connexin hemichannels is now widely recognized to be important in many physiological scenarios and pathological conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Indeed, mutations in connexins that alter hemichannel function have been implicated in several diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present a comprehensive overview of how hemichannel activity is tightly regulated by membrane potential and the external calcium concentration.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 130, "end": 137}]}}, "schema": []}
{"input": "In addition, we discuss the genetic mutations known to alter hemichannel function and their deleterious effects, of which a better understanding is necessary to develop novel therapeutic approaches for diseases caused by hemichannel dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' Connexin based channels'.", "output": {"entities": {}}, "schema": []}
{"input": "Cyp1a reporter zebrafish reveals target tissues for dioxin.", "output": {"entities": {"chemical": [{"text": "dioxin", "start": 52, "end": 58}]}}, "schema": []}
{"input": "2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin", "start": 0, "end": 38}, {"text": "TCDD", "start": 40, "end": 44}]}}, "schema": []}
{"input": "Induction of cyp1a1 is used as an indicator of TCDD exposure.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 47, "end": 51}]}}, "schema": []}
{"input": "We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 54, "end": 58}]}}, "schema": []}
{"input": "We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering.", "output": {"entities": {}}, "schema": []}
{"input": "The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 120, "end": 124}]}}, "schema": []}
{"input": "Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, exposure of the embryos to TCDD at as low as 10pM for 72h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 40, "end": 44}]}}, "schema": []}
{"input": "Furthermore, the reporter embryos responded to other AhR ligands as well.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 27, "end": 31}, {"text": "TCDD", "start": 252, "end": 256}]}}, "schema": []}
{"input": "Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 136, "end": 140}]}}, "schema": []}
{"input": "In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 77, "end": 81}]}}, "schema": []}
{"input": "Reduction of the enniatins A, A1, B, B1 by an in vitro degradation employing different strains of probiotic bacteria: Identification of degradation products by LC-MS-LIT.", "output": {"entities": {"chemical": [{"text": "enniatins A, A1, B, B1", "start": 17, "end": 39}]}}, "schema": []}
{"input": "The degradation of the Fusarium mycotoxins ENs by 9 bacterial strains characteristic of the gastrointestinal tract like Bb. longum, Bb. bifidum, Bb. breve, Bb. adolescentes, Lb. rhamnosus, Lb. casei-casei, S. termofilus, Lb. ruminis, Lb. casei and twenty two strains of Saccharomyces cerevisiae was studied.", "output": {"entities": {"chemical": [{"text": "ENs", "start": 43, "end": 46}]}}, "schema": []}
{"input": "The fermentations were carried out in the liquid medium of De Man Rogosa Sharpe (MRS) under anaerobic conditions for Bifidobacteria Streptococcus and Lactobacillus, and in Potato Dextrose Broth (PDB) for Saccharomyces strains, during 48 h.", "output": {"entities": {"chemical": [{"text": "Dextrose", "start": 179, "end": 187}]}}, "schema": []}
{"input": "The degradation of the bioactive compounds ENs was also studied in a food system composed by wheat flour naturally contaminated by ENs through fermentation by a strain of Fusarium tricinctum.", "output": {"entities": {"chemical": [{"text": "ENs", "start": 43, "end": 46}, {"text": "ENs", "start": 131, "end": 134}]}}, "schema": []}
{"input": "The determination of the ENs in the fermentation mediums was performed using the technique of the liquid chromatography coupled to the mass spectrometry detector in tandem (LC-MS/MS), whereas the identification of the degradation products produced by microbial fermentation was carried out using the technique of the LC coupled to the linear ion trap (LIT).", "output": {"entities": {"chemical": [{"text": "ENs", "start": 25, "end": 28}]}}, "schema": []}
{"input": "All the bacteria analyzed in this study showed a significant ENs reduction in vitro during the fermentation processes, with degradation data ranging from 5 to the 99%.", "output": {"entities": {"chemical": [{"text": "ENs", "start": 61, "end": 64}]}}, "schema": []}
{"input": "In the food system, the ENs degradation data evidenced ranged from 1. 3 to 49. 2%.", "output": {"entities": {"chemical": [{"text": "ENs", "start": 24, "end": 27}]}}, "schema": []}
{"input": "Also three ENs degradation products were identified.", "output": {"entities": {"chemical": [{"text": "ENs", "start": 11, "end": 14}]}}, "schema": []}
{"input": "Antimicrobial interactions of Khoi-San poly-herbal remedies with emphasis on the combination; Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Plants are often combined in traditional herbal remedies to increase medicinal efficacy, thus this investigation provides some insight into the antimicrobial efficacies of selected combinations.", "output": {"entities": {}}, "schema": []}
{"input": "AIMS OF THE STUDY: The first aim was to scientifically validate antibacterial efficacy of plant mixtures that are traded within peri-urban centres of Cape Town (Western Cape, South Africa).", "output": {"entities": {}}, "schema": []}
{"input": "This was followed by an in-depth evaluation of the most antimicrobially active mixture; Agathosma crenulata, Dodonaea viscosa with Eucalyptus globulus.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Methanol and aqueous extracts of six plant mixtures were screened for antibacterial properties against two Gram-negative and two Gram-positive bacteria using the minimum inhibitory microdilution method.", "output": {"entities": {"chemical": [{"text": "Methanol", "start": 23, "end": 31}]}}, "schema": []}
{"input": "Thereafter, chloroform: methanol (1: 1; v/v) extracts, essential oils and aqueous extracts of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus were assayed for antimicrobial activity independently and in various combinations.", "output": {"entities": {"chemical": [{"text": "chloroform", "start": 12, "end": 22}, {"text": "methanol", "start": 24, "end": 32}]}}, "schema": []}
{"input": "The fractional inhibitory concentration indices (Esh FIC) were determined for double and triple plant combinations to establish antimicrobial interactions.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: From the six plant mixtures prepared by herbalists, a methanol extract derived from combining Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus showed the best antibacterial activity.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 63, "end": 71}]}}, "schema": []}
{"input": "The MIC values of 49 mu g/ml for Staphylococcus aureus and Bacillus subtilis, and 98 mu g/ml for Klebsiella pneumoniae and Escherichia coli were recorded.", "output": {"entities": {}}, "schema": []}
{"input": "When Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus were mixed in various 1: 1 combinations, mostly additive and synergistic interactions were noted.", "output": {"entities": {}}, "schema": []}
{"input": "The most noteworthy synergistic (Sigma FIC value 0. 07) 1: 1 combinations were observed for the chloroform: methanol extracts of Agathosma crenulata mixed with Eucalyptus globulus against Klebsiella pneumoniae, Staphylococcus aureus and Bacillus subtilis.", "output": {"entities": {"chemical": [{"text": "chloroform", "start": 96, "end": 106}, {"text": "methanol", "start": 108, "end": 116}]}}, "schema": []}
{"input": "When combined in a mixture of three plants (1: 1: 1), enhanced efficacy was evident against most of the pathogens, for both organic and aqueous extracts.", "output": {"entities": {}}, "schema": []}
{"input": "The triple combination against Bacillus subtilis demonstrated the greatest synergy (Sigma FIC values of 0. 03).", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: The enhanced antimicrobial efficacy and synergistic interactions noted for some of the mixtures, particularly the combination of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus support the Western Cape Khoi-San traditional medicinal practices of combining plants for enhanced efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in mRNA and protein expression in the renal cortex of male and female F344 rats treated with bromate.", "output": {"entities": {"chemical": [{"text": "bromate", "start": 101, "end": 108}]}}, "schema": []}
{"input": "Bromate (BrO3 (-)), a by-product of ozonation of drinking water, induces nephrotoxicity in male rats at much lower doses than in female rats.", "output": {"entities": {"chemical": [{"text": "Bromate", "start": 0, "end": 7}, {"text": "BrO3 (-)", "start": 9, "end": 17}]}}, "schema": []}
{"input": "This difference appears to be related to the development of alpha-2u-globulin nephropathy in males.", "output": {"entities": {}}, "schema": []}
{"input": "To determine sex-dependent changes in mRNA and protein expression in the renal cortex attributable to alpha-2u-globulin nephropathy, we performed microarray and immunohistochemical analyses in proximal renal tubules of male and female F344 rats treated with KBrO3 for 28 days.", "output": {"entities": {"chemical": [{"text": "KBrO3", "start": 258, "end": 263}]}}, "schema": []}
{"input": "Particular attention was paid to molecular biomarkers of renal tubular injury.", "output": {"entities": {}}, "schema": []}
{"input": "Microarray analysis of male and female rats treated with BrO3 (-) at low doses (125 mg/L KBrO3) displayed marked sex-dependent changes in renal gene expression.", "output": {"entities": {"chemical": [{"text": "BrO3 (-)", "start": 57, "end": 65}, {"text": "KBrO3", "start": 89, "end": 94}]}}, "schema": []}
{"input": "The greatest differences were seen in genes encoding for cellular differentiation, apoptosis, ion transport, and cell proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Differences by sex were especially prominent for the cell cycle checkpoint gene p21, the renal injury protein Kim-1, and the kidney injury and cancer biomarker protein osteopontin.", "output": {"entities": {}}, "schema": []}
{"input": "Dose-related nephrotoxicity, assessed by hematoxylin and eosin staining, was greater in males compared to female rats, as was cellular proliferation, assessed by bromodeoxyuridine staining.", "output": {"entities": {"chemical": [{"text": "hematoxylin", "start": 41, "end": 52}, {"text": "eosin", "start": 57, "end": 62}, {"text": "bromodeoxyuridine", "start": 162, "end": 179}]}}, "schema": []}
{"input": "The fraction of proximal renal cells with elevated 8-oxodeoxyguanosine (8-OH-dG) was only increased at the high dose and did not differ by sex.", "output": {"entities": {"chemical": [{"text": "8-oxodeoxyguanosine", "start": 51, "end": 70}, {"text": "8-OH-dG", "start": 72, "end": 79}]}}, "schema": []}
{"input": "Dose-dependent increases in the expression of osteopontin were detected immunohistochemically only in male rats and were localized in proximal tubule cells.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, BrO3 (-) treatment increased clusterin and Kim-1 staining in the proximal tubules; however, staining for these proteins did not differ appreciably between males and females.", "output": {"entities": {"chemical": [{"text": "BrO3 (-)", "start": 11, "end": 19}]}}, "schema": []}
{"input": "These data demonstrate both qualitative and quantitative differences in the response of male versus female kidneys to BrO3 (-)-treatment.", "output": {"entities": {"chemical": [{"text": "BrO3 (-)", "start": 118, "end": 126}]}}, "schema": []}
{"input": "These sex-dependent effects likely contribute to renal carcinogenesis of BrO3 (-) in the male rat.", "output": {"entities": {"chemical": [{"text": "BrO3 (-)", "start": 73, "end": 81}]}}, "schema": []}
{"input": "Why Clinical Inhibition of Efflux Transport at the Blood-Brain Barrier is Unlikely: The ITC Evidence-Based Position.", "output": {"entities": {}}, "schema": []}
{"input": "Drug interactions due to efflux transporter inhibition at the blood-brain barrier have been receiving increasing scrutiny due to the theoretical possibility of adverse CNS effects based on findings from preclinical studies.", "output": {"entities": {}}, "schema": []}
{"input": "In this commentary, evidence from pharmacokinetic, pharmacodynamic, imaging, pharmacogenetic, and pharmacovigilance studies, along with drug safety reports, is presented supporting a low probability of inhibiting efflux transporters at the human blood-brain barrier by currently marketed drugs. Clinical Pharmacology & Therapeutics (2013); accepted article preview 14 February 2013 doi: 10. 1038/clpt. 2013. 34.", "output": {"entities": {}}, "schema": []}
{"input": "A Physiologically-Based Pharmacokinetic Modelling Approach to Predict Disease-Drug Interactions: Suppression of CYP3A by IL-6.", "output": {"entities": {}}, "schema": []}
{"input": "Elevated cytokine levels can down-regulate expression of cytochrome P450 enzymes (CYPs) and suppress their activity.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment of inflammation or infection with cytokine-modulating therapeutic proteins (TP) could reverse suppression manifesting as therapeutic protein-drug drug interactions (TP-DDI).", "output": {"entities": {}}, "schema": []}
{"input": "A physiologically-based pharmacokinetic model was used to quantitatively predict the impact of IL-6 on sensitive CYP3A4 substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Elevated simvastatin AUC in virtual rheumatoid arthritis patients, following 100 pg/mL of IL-6 was comparable to observed clinical data (59% versus 58%).", "output": {"entities": {"chemical": [{"text": "simvastatin", "start": 9, "end": 20}]}}, "schema": []}
{"input": "In virtual bone marrow transplant (BMT) patients, 500 pg/ml of IL-6 resulted in increase in cyclosporine AUC that was in good agreement with the observed data (45% versus 39%).", "output": {"entities": {"chemical": [{"text": "cyclosporine", "start": 92, "end": 104}]}}, "schema": []}
{"input": "In a different group of BMT patients treated with cyclosporine, the magnitude of interaction with IL-6 was under predicted ~ 3-fold.", "output": {"entities": {"chemical": [{"text": "cyclosporine", "start": 50, "end": 62}]}}, "schema": []}
{"input": "The complexity of TP-DDI highlights underlying pathophysiological factors to be considered but these simulations provide valuable first steps towards predictions of TP-DDI risk. Clinical Pharmacology & Therapeutics (2013); accepted article preview online 10 April 2013 doi: 10. 1038/clpt. 2013. 79.", "output": {"entities": {}}, "schema": []}
{"input": "Model-Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmaceutical industry continues to face significant challenges.", "output": {"entities": {}}, "schema": []}
{"input": "Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1. 8 billion.", "output": {"entities": {}}, "schema": []}
{"input": "Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines.", "output": {"entities": {}}, "schema": []}
{"input": "With costs increasing exponentially through each development phase, it is failure in phase II and phase III that is most wasteful.", "output": {"entities": {}}, "schema": []}
{"input": "In today' s development paradigm, late-stage failure is principally a result of insufficient efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "This is manifested as either a failure to differentiate sufficiently from placebo (shown for both novel and precedented mechanisms) or a failure to demonstrate sufficient differentiation from existing compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Set in this context, this article will discuss the role model-based drug development (MBDD) approaches can and do play in accelerating and optimizing compound development strategies through a series of illustrative examples. Clinical Pharmacology & Therapeutics (2013); advance online publication 1 May 2013. doi: 10. 1038/clpt. 2013. 54.", "output": {"entities": {}}, "schema": []}
{"input": "Aspects of physicians' attitudes towards the rational use of drugs at a training and research hospital: a survey study.", "output": {"entities": {}}, "schema": []}
{"input": "PURPOSE: The rational use of drugs (RUD) is primarily the responsibility of physicians.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was to investigate whether physicians are aware of RUD principles and how they apply them in daily medical practice.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: A total 136 physicians working at the Kartal Training and Research Hospital in Istanbul were enrolled in the study between February and March 2012.", "output": {"entities": {}}, "schema": []}
{"input": "A face-to-face interview was conducted with physicians to assess their knowledge and attitude regarding RUD.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: A large majority of the physicians declared that consultation time was insufficient (84%).", "output": {"entities": {}}, "schema": []}
{"input": "The data obtained from the survey indicate that 54% of the enrolled physicians monitored the therapeutic outcome and that 27% found the information given to the patient to be sufficient.", "output": {"entities": {}}, "schema": []}
{"input": "Participating physicians stated that the less known characteristics of the drugs they prescribed were drug interactions, traceability in market, and price.", "output": {"entities": {}}, "schema": []}
{"input": "The most preferred reference source was Vademecum (a drug guideline prepared by the private sector).", "output": {"entities": {}}, "schema": []}
{"input": "Two major factors contributing to prescribing patterns were \" self study \" and \" observation of teachers \" at clinical training.", "output": {"entities": {}}, "schema": []}
{"input": "There was a significant difference between internists-surgeons and residents-specialists in the number of prescribed drugs per prescription (p < 0. 001) and in the information provided to the patient on the prescribed drugs (name, effect, dose, instructions, possible side effect) (p < 0. 05), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: Our findings overall show that the principles of RUD were not fully applied in daily medical practice by the participating physicians.", "output": {"entities": {}}, "schema": []}
{"input": "One important reason for this is a heavy patient load, which requires a change in managerial practices within the healthcare system.", "output": {"entities": {}}, "schema": []}
{"input": "The other, more essential explanation is education; consequently, serious consideration should be given to including effective clinical pharmacotherapy training and RUD courses in the medical education curriculum.", "output": {"entities": {}}, "schema": []}
{"input": "Factors Influencing Magnitude and Duration of Target Inhibition Following Antibody Therapy: Implications in Drug Discovery and Development.", "output": {"entities": {}}, "schema": []}
{"input": "Antibodies or antibody-related fusion proteins binding to soluble antigens in plasma form an important subclass of approved therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Pharmaceutical companies are constantly trying to accelerate the pace of drug discovery and development of these antibodies and identify superior candidates in face of significant attrition rates.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the interplay between drug-and target-related factors on magnitude and duration of target inhibition is imperative for successful advancement of these therapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Simulations using a target-mediated drug disposition model were performed to evaluate the influence of antibody-target binding affinity, baseline target concentration, and target turnover on magnitude and duration of soluble target inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "These simulations assumed intravenous dosing of the antibody and evaluated multiple parameters over a wide range.", "output": {"entities": {}}, "schema": []}
{"input": "These simulations reveal that improvement in affinity reaches a point of diminishing returns following which further improvement in affinity does not alter the magnitude and more importantly the duration of target inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of unbound antibody and target kinetics indicated that point of diminishing returns in duration of inhibition was due to target-mediated binding and subsequent elimination of antibody at later time points.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, influence of baseline target concentration and target turnover on magnitude and duration of target inhibition in plasma is shown.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, the fraction of dose eliminated via target mediated elimination (Fel ((TM))) can be a useful tool to enable selection of strategies to increase duration of target inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "The implications of these simulations in drug discovery and development with regard to target identification, antibody optimization, and backup candidate selection are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer.", "output": {"entities": {"chemical": [{"text": "Silibinin", "start": 24, "end": 33}]}}, "schema": []}
{"input": "Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged deleterious effects on quality of patient life.", "output": {"entities": {}}, "schema": []}
{"input": "Prostate cancer chemoprevention is one potential avenue to alleviate these burdens.", "output": {"entities": {}}, "schema": []}
{"input": "It is a regime whereby long-term treatments are intended to prevent or arrest cancer development, in contrast to more direct intervention upon disease diagnosis.", "output": {"entities": {}}, "schema": []}
{"input": "Based on this intention, cancer chemoprevention generally focuses on the use of nontoxic chemical agents which are well-tolerated for prolonged usage that is necessary to address prostate cancer' s multistage and lengthy period of progression.", "output": {"entities": {}}, "schema": []}
{"input": "One such nontoxic natural agent is the flavonoid silibinin, derived from the milk thistle plant (Silybum marianum), which has ancient medicinal usage and potent antioxidant activity.", "output": {"entities": {"chemical": [{"text": "silibinin", "start": 49, "end": 58}]}}, "schema": []}
{"input": "Based on these properties, silibinin has been investigated in a host of cancer models where it exhibits broad-spectrum efficacy against cancer progression both in vitro and in vivo without noticeable toxicity.", "output": {"entities": {"chemical": [{"text": "silibinin", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Specifically in prostate cancer models, silibinin has shown the ability to modulate cell signaling, proliferation, apoptosis, epithelial to mesenchymal transition, invasion, metastasis, and angiogenesis, which taken together provides strong support for silibinin as a candidate prostate cancer chemopreventive agent.", "output": {"entities": {"chemical": [{"text": "silibinin", "start": 40, "end": 49}, {"text": "silibinin", "start": 253, "end": 262}]}}, "schema": []}
{"input": "The Fer tyrosine kinase is important for platelet-derived growth factor-BB-induced Stat3 phosphorylation, colony formation in soft agar and tumor growth in vivo.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 8, "end": 16}]}}, "schema": []}
{"input": "Fer is a cytoplasmic tyrosine kinase that is activated in response to platelet-derived growth factor (PDGF) stimulation.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 21, "end": 29}]}}, "schema": []}
{"input": "In the present report, we show that Fer associates with the activated PDGFbeta receptor (PDGFRbeta) through multiple autophosphorylation sites, i. e. Tyr579, Tyr581, Tyr740 and Tyr1021.", "output": {"entities": {"chemical": [{"text": "Tyr579", "start": 150, "end": 156}, {"text": "Tyr581", "start": 158, "end": 164}, {"text": "Tyr740", "start": 166, "end": 172}, {"text": "Tyr1021", "start": 177, "end": 184}]}}, "schema": []}
{"input": "Using low molecular weight inhibitors, we found that PDGF-BB-induced Fer activation is dependent on PDGFRbeta kinase activity, but not on the enzymatic activity of Src or Jak kinases.", "output": {"entities": {}}, "schema": []}
{"input": "In cells in which Fer was downregulated using siRNA, PDGF-BB was unable to induce phosphorylation of Stat3, whereas phosphorylations of Stat5, Erk1/2 and Akt were unaffected.", "output": {"entities": {}}, "schema": []}
{"input": "PDGF-BB-induced activation of Stat3 occurred also in cells expressing kinase-dead Fer, suggesting a kinase-independent adaptor role of Fer.", "output": {"entities": {}}, "schema": []}
{"input": "Expression of Fer was dispensable for PDGF-BB-induced proliferation and migration, but essential for colony formation in soft agar.", "output": {"entities": {}}, "schema": []}
{"input": "Tumor growth in vivo was delayed in cells depleted of Fer expression.", "output": {"entities": {}}, "schema": []}
{"input": "Our data suggests a critical role of Fer in PDGF-BB-induced Stat3 activation and cell transformation.", "output": {"entities": {}}, "schema": []}
{"input": "Exposure to mercury among dental health workers in Turkey: Correlation with amalgam work and own fillings.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 12, "end": 19}, {"text": "amalgam", "start": 76, "end": 83}]}}, "schema": []}
{"input": "PURPOSE: To investigate the current status of exposure to mercury (Hg) among dental health workers in Turkey.", "output": {"entities": {"chemical": [{"text": "mercury", "start": 58, "end": 65}, {"text": "Hg", "start": 67, "end": 69}]}}, "schema": []}
{"input": "METHODS: A total of 115 persons working in the same hospital were included in the study and were divided into three groups.", "output": {"entities": {}}, "schema": []}
{"input": "Group 1 consisted of 67 dentists; group 2 consisted of 21 dental personnel who work with amalgam, and group 3 consisted of 27 control subjects who work in the same hospital but are non-dental personnel.", "output": {"entities": {"chemical": [{"text": "amalgam", "start": 89, "end": 96}]}}, "schema": []}
{"input": "The number of amalgam fillings that have been made by the dentists and the number of own fillings of the subjects were recorded.", "output": {"entities": {"chemical": [{"text": "amalgam", "start": 14, "end": 21}]}}, "schema": []}
{"input": "RESULTS: Plasma Hg levels were found to be 3. 76 +/- 1. 84, 3. 54 +/- 1. 83, and 2. 69 +/- 0. 97 micro g/L in groups 1, 2, and 3, respectively.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 16, "end": 18}]}}, "schema": []}
{"input": "Hg concentrations in group 1 were significantly higher than the control group.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 0, "end": 2}]}}, "schema": []}
{"input": "There was no significant difference between groups 1 and 2.", "output": {"entities": {}}, "schema": []}
{"input": "The number of amalgam fillings made by the dentists in the previous year correlated significantly with plasma Hg levels (r = 0. 378, p < 0. 01).", "output": {"entities": {"chemical": [{"text": "amalgam", "start": 14, "end": 21}, {"text": "Hg", "start": 110, "end": 112}]}}, "schema": []}
{"input": "There was no significant correlation between the own amalgam fillings in the teeth of the subjects and Hg levels.", "output": {"entities": {"chemical": [{"text": "amalgam", "start": 53, "end": 60}, {"text": "Hg", "start": 103, "end": 105}]}}, "schema": []}
{"input": "CONCLUSION: Preventive measures for protection from exposure to Hg are necessary for occupational health in dentistry and proper industrial hygiene rules should be emphasized to avoid contamination during work.", "output": {"entities": {"chemical": [{"text": "Hg", "start": 64, "end": 66}]}}, "schema": []}
{"input": "Amelioration of hepatotoxicity induced by aflatoxin using citrus fruit oil in broilers (Gallus domesticus).", "output": {"entities": {"chemical": [{"text": "aflatoxin", "start": 42, "end": 51}]}}, "schema": []}
{"input": "This study was conducted to evaluate the efficacy of citrus fruit oil (CFO; 2. 5 g kg (-) (1)) on the clinicopathological changes in broilers fed with diets containing 1 ppm of aflatoxin (AF).", "output": {"entities": {"chemical": [{"text": "aflatoxin", "start": 177, "end": 186}]}}, "schema": []}
{"input": "A total of 160 Ross 308 broiler chicks of 1-day-old were procured from a commercial hatchery, divided randomly on 7th day of age into four groups with two replicates of 20 birds each and fed with basal diet (group A), basal diet + CFO (group B), basal diet + AF (group C) and CFO + basal diet + AF (group D).", "output": {"entities": {}}, "schema": []}
{"input": "The gross and histopathological changes in the liver, kidney, spleen, thymus and bursa of Fabricius were investigated and relative organ weights were calculated.", "output": {"entities": {}}, "schema": []}
{"input": "Slight to moderate hydropic degeneration, fatty change with the formation of cyst in some cases, periportal necrosis, infiltration of heterophils and mononuclear cells and bile duct hyperplasia were observed in chicks fed with 1 ppm AF-containing diet.", "output": {"entities": {}}, "schema": []}
{"input": "The addition of CFO to AF-containing diet moderately decreased the magnitude and severity of lesions (hydropic degeneration and bile duct hyperplasia) in the liver.", "output": {"entities": {}}, "schema": []}
{"input": "The supplementation of CFO to the basal diet did not produce any adverse effects in birds.", "output": {"entities": {}}, "schema": []}
{"input": "MAO Inhibitory Activity of 2-Arylbenzofurans versus 3-Arylcoumarins: Synthesis, in vitro Study, and Docking Calculations.", "output": {"entities": {"chemical": [{"text": "2-Arylbenzofurans", "start": 27, "end": 44}, {"text": "3-Arylcoumarins", "start": 52, "end": 67}]}}, "schema": []}
{"input": "Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders.", "output": {"entities": {"chemical": [{"text": "Monoamine", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Several 3-arylcoumarin derivatives were previously described as interesting selective MAO-B inhibitors.", "output": {"entities": {"chemical": [{"text": "3-arylcoumarin", "start": 8, "end": 22}]}}, "schema": []}
{"input": "Preserving the trans-stilbene structure, a series of 2-arylbenzofuran and corresponding 3-arylcoumarin derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO-A and MAO-B.", "output": {"entities": {"chemical": [{"text": "trans-stilbene", "start": 15, "end": 29}, {"text": "2-arylbenzofuran", "start": 53, "end": 69}, {"text": "3-arylcoumarin", "start": 88, "end": 102}]}}, "schema": []}
{"input": "In general, both types of derivatives were found to be selective MAO-B inhibitors, with IC50 values in the nano-to micromolar range.", "output": {"entities": {}}, "schema": []}
{"input": "5-Nitro-2-(4-methoxyphenyl) benzofuran (8) is the most active compound of the benzofuran series, presenting MAO-B selectivity and reversible inhibition (IC50 = 140 nM).", "output": {"entities": {"chemical": [{"text": "5-Nitro-2-(4-methoxyphenyl) benzofuran", "start": 0, "end": 38}, {"text": "benzofuran", "start": 78, "end": 88}]}}, "schema": []}
{"input": "3-(4'-Methoxyphenyl)-6-nitrocoumarin (15), with the same substitution pattern as that of compound 8, was found to be the most active MAO-B inhibitor of the coumarin series (IC50 = 3 nM).", "output": {"entities": {"chemical": [{"text": "3-(4'-Methoxyphenyl)-6-nitrocoumarin", "start": 0, "end": 36}, {"text": "coumarin", "start": 156, "end": 164}]}}, "schema": []}
{"input": "However, 3-phenylcoumarin 14 showed activity in the same range (IC50 = 6 nM), is reversible, and also severalfold more selective than compound 15.", "output": {"entities": {"chemical": [{"text": "3-phenylcoumarin", "start": 9, "end": 25}]}}, "schema": []}
{"input": "Docking experiments for the most active compounds into the MAO-B and MAO-A binding pockets highlighted different interactions between the derivative classes (2-arylbenzofurans and 3-arylcoumarins), and provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of these scaffolds.", "output": {"entities": {"chemical": [{"text": "2-arylbenzofurans", "start": 158, "end": 175}, {"text": "3-arylcoumarins", "start": 180, "end": 195}]}}, "schema": []}
{"input": "Direct Laser-Patterned Micro-Supercapacitors from Paintable MoS2 Films.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 60, "end": 64}]}}, "schema": []}
{"input": "Micrometer-sized electrochemical capacitors have recently attracted attention due to their possible applications in micro-electronic devices.", "output": {"entities": {}}, "schema": []}
{"input": "Here, a new approach to large-scale fabrication of high-capacitance, two-dimensional MoS2 film-based micro-supercapacitors is demonstrated via simple and low-cost spray painting of MoS2 nanosheets on Si/SiO2 chip and subsequent laser patterning.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 85, "end": 89}, {"text": "MoS2", "start": 181, "end": 185}, {"text": "Si", "start": 200, "end": 202}, {"text": "SiO2", "start": 203, "end": 207}]}}, "schema": []}
{"input": "The obtained micro-supercapacitors are well defined by ten interdigitated electrodes (five electrodes per polarity) with 4. 5 mm length, 820 mu m wide for each electrode, 200 mu m spacing between two electrodes and the thickness of electrode is ~ 0. 45 mu m.", "output": {"entities": {}}, "schema": []}
{"input": "The optimum MoS2-based micro-supercapacitor exhibits excellent electrochemical performance for energy storage with aqueous electrolytes, with a high area capacitance of 8 mF cm (-2) (volumetric capacitance of 178 F cm (-3)) and excellent cyclic performance, superior to reported graphene-based micro-supercapacitors.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 12, "end": 16}, {"text": "graphene", "start": 279, "end": 287}]}}, "schema": []}
{"input": "This strategy could provide a good opportunity to develop various micro-/nanosized energy storage devices to satisfy the requirements of portable, flexible, and transparent micro-electronic devices.", "output": {"entities": {}}, "schema": []}
{"input": "Vortex-induced amyloid superstructures of insulin and its component a and B chains.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin is an amyloid-forming polypeptide built of two disulfide-linked chains (A and B), both themselves amyloidogenic.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 55, "end": 64}]}}, "schema": []}
{"input": "An interesting property of insulin is that agitation strongly influences the course of its aggregation, resulting in characteristic chiral superstructures of amyloid fibrils.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we investigate the self-assembly of these superstructures by comparing the quiescent and vortex-assisted aggregation of insulin and its individual A and B chains in the presence or absence of reducing agent tris (2-carboxyethyl) phosphine (TCEP).", "output": {"entities": {"chemical": [{"text": "tris (2-carboxyethyl) phosphine", "start": 213, "end": 244}, {"text": "TCEP", "start": 246, "end": 250}]}}, "schema": []}
{"input": "Our study shows that only the B chain in the presence of TCEP is converted into aggregates with morphology (according to atomic force microscopy) and optical activity (manifested as an extrinsic Cotton effect induced in bound thioflavin T) characteristic of amyloid superstructures that are normally formed by insulin in the absence of TCEP.", "output": {"entities": {"chemical": [{"text": "TCEP", "start": 57, "end": 61}, {"text": "thioflavin T", "start": 226, "end": 238}, {"text": "TCEP", "start": 336, "end": 340}]}}, "schema": []}
{"input": "In contrast to more rigid B-peptide fibrils, elongated aggregates of the A peptide become amorphous upon agitation.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the aggregation of equimolar mixture of both peptides does not produce highly ordered entities.", "output": {"entities": {}}, "schema": []}
{"input": "Our results suggest that the dynamics of the B chain are the driving force for the assembly of superstructures, with the A chain being complicit as long as its own dynamics are controlled by the firm attachment to the B chain provided by the intact covalent structure of insulin.", "output": {"entities": {}}, "schema": []}
{"input": "Determination of urinary 6-mercaptopurine and three of its metabolites by HPLC-UV coupled with the iodine-azide reaction.", "output": {"entities": {"chemical": [{"text": "6-mercaptopurine", "start": 25, "end": 41}, {"text": "iodine", "start": 99, "end": 105}, {"text": "azide", "start": 106, "end": 111}]}}, "schema": []}
{"input": "Background: The presented method is able to determine 6-mercaptopurine (6-MP), 6-thioguanine, 6-mercaptopurine riboside and 6-thioguanine riboside in urine, and is thereby dedicated to control of thiopurine therapy of children with acute lymphoblastic leukemia.", "output": {"entities": {"chemical": [{"text": "6-mercaptopurine", "start": 54, "end": 70}, {"text": "6-MP", "start": 72, "end": 76}, {"text": "6-thioguanine", "start": 79, "end": 92}, {"text": "6-mercaptopurine riboside", "start": 94, "end": 119}, {"text": "6-thioguanine riboside", "start": 124, "end": 146}, {"text": "thiopurine", "start": 196, "end": 206}]}}, "schema": []}
{"input": "Good separation of the mentioned compounds was achieved on a C18 stationary phase with a sodium azide and sodium heptane sulfonate solution, acetonitrile and water at ratio of 50: 1: 49 (v/v/v).", "output": {"entities": {"chemical": [{"text": "sodium azide", "start": 89, "end": 101}, {"text": "sodium heptane sulfonate", "start": 106, "end": 130}, {"text": "acetonitrile", "start": 141, "end": 153}]}}, "schema": []}
{"input": "Results: Coefficient of regression is > 0. 99 for all linearity ranges.", "output": {"entities": {}}, "schema": []}
{"input": "LOD and LOQ are 0. 3, 0. 4, 0. 3, 0. 8 and 0. 4, 0. 6, 0. 5 and 0. 9 nmol/ml of urine for 6-MP, 6-thioguanine, 6-mercaptopurine riboside and 6-thioguanine riboside, respectively.", "output": {"entities": {"chemical": [{"text": "6-MP", "start": 90, "end": 94}, {"text": "6-thioguanine", "start": 96, "end": 109}, {"text": "6-mercaptopurine riboside", "start": 111, "end": 136}, {"text": "6-thioguanine riboside", "start": 141, "end": 163}]}}, "schema": []}
{"input": "Intra-and inter-day recovery and RSD are close to 100% and less than 10%, respectively, for all investigated thiopurines.", "output": {"entities": {"chemical": [{"text": "thiopurines", "start": 109, "end": 120}]}}, "schema": []}
{"input": "Conclusion: The elaborated method was successfully applied for detection and quantitation of 6-MP and its selected metabolites in patients' urine samples.", "output": {"entities": {"chemical": [{"text": "6-MP", "start": 93, "end": 97}]}}, "schema": []}
{"input": "A dried blood spot update: still an important bioanalytical technique?", "output": {"entities": {}}, "schema": []}
{"input": "This article discusses the benefits of dried blood spot sampling and the recent issues that have emerged when this technique is used in the regulated quantitative bioanalytical environment.", "output": {"entities": {}}, "schema": []}
{"input": "The author explores what the way forward might be for this important technique and what some of the unexpected benefits of this change in sampling methodologies have been.", "output": {"entities": {}}, "schema": []}
{"input": "Use of Monte Carlo simulations in the assessment of calibration strategies-Part III: an evaluation of linear calibration.", "output": {"entities": {}}, "schema": []}
{"input": "Background: The acceptance criteria for chromatographic bioassays are generally based upon the specifications found in the US FDA Guidance for Industry document, whereas regression analysis is a statistical process and, thus, most suited to large data populations, rather than the small populations used in assay calibration.", "output": {"entities": {}}, "schema": []}
{"input": "Data that form part of the statistical population are often excluded in order that calibrations meet these acceptance criteria.", "output": {"entities": {}}, "schema": []}
{"input": "Results/discussion: Monte Carlo simulations of various linear regression calibration strategies, which take into account guidance acceptance criteria, have been used to quantify calibration errors.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: It is concluded that 1/x (2) weighting generally produces results that meet both theoretical and regulatory requirements, and that use of single, rather than duplicate, calibrators can result in misleading statistics at the LLOQ.", "output": {"entities": {}}, "schema": []}
{"input": "Polyelectrolyte-Surfactant Complexes of Poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide) and Sodium Dodecyl Sulfate: Anomalous Self-Assembly Behavior.", "output": {"entities": {"chemical": [{"text": "Poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide)", "start": 40, "end": 122}, {"text": "Sodium Dodecyl Sulfate", "start": 127, "end": 149}]}}, "schema": []}
{"input": "Polyelectrolyte-surfactant complexes (PE-S) formed by double hydrophilic cationic polyelectrolyte poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide) (NPHOS-PEO) and anionic surfactant sodium dodecyl sulfate (SDS) in acidic aqueous solutions were studied by light scattering, SAXS, and scanning transmission electron microcopy in the environmental mode (wet-STEM) for various stoichiometric ratios between the numbers of SDS anions and dimethylaminomethyl groups of NPHOS in the complex.", "output": {"entities": {"chemical": [{"text": "poly [3, 5-bis (dimethylaminomethyl)-4-hydroxystyrene]-block-poly (ethylene oxide)", "start": 98, "end": 180}, {"text": "NPHOS-PEO", "start": 182, "end": 191}, {"text": "sodium dodecyl sulfate", "start": 216, "end": 238}, {"text": "SDS", "start": 240, "end": 243}, {"text": "dimethylaminomethyl", "start": 467, "end": 486}, {"text": "NPHOS", "start": 497, "end": 502}]}}, "schema": []}
{"input": "The obtained results show that the NPHOS-PEO/SDS system behaves differently from other systems of double hydrophilic block polyelectrolyte and oppositely charged ionic surfactant because it forms water-insoluble PE-S for compositions close to the zero net charge of the complex.", "output": {"entities": {"chemical": [{"text": "NPHOS-PEO", "start": 35, "end": 44}, {"text": "SDS", "start": 45, "end": 48}]}}, "schema": []}
{"input": "This phase separation occurs, instead of the PE-S rearrangement to core-shell particles, which is hindered due to conformational rigidity of the NPHOS blocks.", "output": {"entities": {"chemical": [{"text": "NPHOS", "start": 145, "end": 150}]}}, "schema": []}
{"input": "For the surfactant amounts below and above the precipitation region, large spherical aggregates and their clusters are present in the solution.", "output": {"entities": {}}, "schema": []}
{"input": "SAXS measurements indicate that although the NPHOS-PEO/SDS system does not form the core-shell particles with the NPHOS/SDS core and the PEO shell as other PE-S of double hydrophilic polyelectrolytes, the aggregates contain domains of closely packed surfactant micelles which bind to both NPHOS polyelectrolyte blocks and PEO blocks.", "output": {"entities": {"chemical": [{"text": "NPHOS-PEO", "start": 45, "end": 54}, {"text": "SDS", "start": 55, "end": 58}, {"text": "NPHOS", "start": 114, "end": 119}, {"text": "SDS", "start": 120, "end": 123}, {"text": "PEO", "start": 137, "end": 140}, {"text": "NPHOS", "start": 289, "end": 294}, {"text": "PEO", "start": 322, "end": 325}]}}, "schema": []}
{"input": "Structure in the Visible Absorption Bands of Jet-Cooled Phenylperoxy Radicals.", "output": {"entities": {"chemical": [{"text": "Phenylperoxy", "start": 56, "end": 68}]}}, "schema": []}
{"input": "The visible absorption bands of the phenylperoxy radical in the gas phase have been investigated using cavity ring-down spectroscopy.", "output": {"entities": {"chemical": [{"text": "phenylperoxy", "start": 36, "end": 48}]}}, "schema": []}
{"input": "Jet-cooling was used to reduce the spectral congestion.", "output": {"entities": {}}, "schema": []}
{"input": "Structured spectra spanning the range from 17 500 to 19 000 cm (-1) are reported for the first time.", "output": {"entities": {}}, "schema": []}
{"input": "Analyses of these data have been guided by the results from time-dependent density functional calculations.", "output": {"entities": {}}, "schema": []}
{"input": "The observed spectrum was found to be dominated by the bands of the B (2) A''-X (2) A'' transition.", "output": {"entities": {}}, "schema": []}
{"input": "An analysis of the rotational contour for the origin band yielded a homogeneous line width of 2. 2 cm (-1), corresponding to a decay rate of 4. 1 x 10 (11) s (-1).", "output": {"entities": {}}, "schema": []}
{"input": "The results provide a rationale for the lack of structure in room temperature spectra that have been previously attributed to phenylperoxy.", "output": {"entities": {"chemical": [{"text": "phenylperoxy", "start": 126, "end": 138}]}}, "schema": []}
{"input": "They also indicate that the lower energy region of the spectrum may show resolvable structure at room temperature.", "output": {"entities": {}}, "schema": []}
{"input": "If so, this would provide a more definitive signature for monitoring phenylperoxy in kinetic measurements.", "output": {"entities": {"chemical": [{"text": "phenylperoxy", "start": 69, "end": 81}]}}, "schema": []}
{"input": "pH-Responsive Nanoparticle Vaccines for Dual-Delivery of Antigens and Immunostimulatory Oligonucleotides.", "output": {"entities": {}}, "schema": []}
{"input": "Protein subunit vaccines offer important potential advantages over live vaccine vectors but generally elicit weaker and shorter-lived cellular immune responses.", "output": {"entities": {}}, "schema": []}
{"input": "Here we investigate the use of pH-responsive, endosomolytic polymer nanoparticles that were originally developed for RNA delivery as vaccine delivery vehicles for enhancing cellular and humoral immune responses.", "output": {"entities": {}}, "schema": []}
{"input": "Micellar nanoparticles were assembled from amphiphilic diblock copolymers composed of an ampholytic core-forming block and a redesigned polycationic corona block doped with thiol-reactive pyridyl disulfide groups to enable dual-delivery of antigens and immunostimulatory CpG oligodeoxynucleotide (CpG ODN) adjuvants.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 173, "end": 178}, {"text": "pyridyl disulfide", "start": 188, "end": 205}, {"text": "CpG", "start": 271, "end": 274}, {"text": "CpG", "start": 297, "end": 300}]}}, "schema": []}
{"input": "Polymers assembled into 23 nm particles with simultaneous packaging of CpG ODN and a thiolated protein antigen, ovalbumin (ova).", "output": {"entities": {"chemical": [{"text": "CpG", "start": 71, "end": 74}]}}, "schema": []}
{"input": "Conjugation of ova to nanoparticles significantly enhanced antigen cross-presentation in vitro relative to free ova or an unconjugated, physical mixture of the parent compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Subcutaneous vaccination of mice with ova-nanoparticle conjugates elicited a significantly higher CD8 (+) T cell response (0. 5% IFN-gamma (+) of CD8 (+)) compared to mice vaccinated with free ova or a physical mixture of the two components.", "output": {"entities": {}}, "schema": []}
{"input": "Significantly, immunization with ova-nanoparticle conjugates electrostatically complexed with CpG ODN (dual-delivery) enhanced CD8 (+) T cell responses (3. 4% IFN-gamma (+) of CD8 (+)) 7-, 18-, and 8-fold relative to immunization with conjugates, ova administered with free CpG, or a formulation containing free ova and CpG complexed to micelles, respectively.", "output": {"entities": {"chemical": [{"text": "CpG", "start": 94, "end": 97}, {"text": "CpG", "start": 274, "end": 277}, {"text": "CpG", "start": 320, "end": 323}]}}, "schema": []}
{"input": "Similarly, dual-delivery carriers significantly increased CD4 (+) IFN-gamma (+) (Th1) responses and elicited a balanced IgG1/IgG2c antibody response.", "output": {"entities": {}}, "schema": []}
{"input": "Intradermal administration further augmented cellular immune responses, with dual-delivery carriers inducing ~ 7% antigen-specific CD8 (+) T cells.", "output": {"entities": {}}, "schema": []}
{"input": "This work demonstrates the ability of pH-responsive, endosomolytic nanoparticles to actively promote antigen cross-presentation and augment cellular and humoral immune responses via dual-delivery of protein antigens and CpG ODN.", "output": {"entities": {"chemical": [{"text": "CpG", "start": 220, "end": 223}]}}, "schema": []}
{"input": "Hence, pH-responsive polymeric nanoparticles offer promise as a delivery platform for protein subunit vaccines.", "output": {"entities": {}}, "schema": []}
{"input": "Improved Carrier Mobility in Few-Layer MoS2 Field-Effect Transistors with Ionic-Liquid Gating.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 39, "end": 43}]}}, "schema": []}
{"input": "We report the fabrication of ionic liquid (IL)-gated field-effect transistors (FETs) consisting of bilayer and few-layer MoS2.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 121, "end": 125}]}}, "schema": []}
{"input": "Our transport measurements indicate that the electron mobility mu =~ 60 cm (2) V (-1) s (-1) at 250 K in IL-gated devices exceeds significantly that of comparable back-gated devices.", "output": {"entities": {}}, "schema": []}
{"input": "IL-FETs display a mobility increase from =~ 100 cm (2) V (-1) s (-1) at 180 K to =~ 220 cm (2) V (-1) s (-1) at 77 K in good agreement with the true channel mobility determined from four-terminal measurements, ambipolar behavior with a high ON/OFF ratio > 10 (7) (10 (4)) for electrons (holes), and a near ideal subthreshold swing of =~ 50 mV/dec at 250 K.", "output": {"entities": {}}, "schema": []}
{"input": "We attribute the observed performance enhancement, specifically the increased carrier mobility that is limited by phonons, to the reduction of the Schottky barrier at the source and drain electrode by band bending caused by the ultrathin IL dielectric layer.", "output": {"entities": {}}, "schema": []}
{"input": "pH-Responsive Aggregation States of Chiral Polymerizable Amphiphiles from l-Tyrosine and l-Phenyl Alanine in Water.", "output": {"entities": {"chemical": [{"text": "l-Tyrosine", "start": 74, "end": 84}, {"text": "l-Phenyl Alanine", "start": 89, "end": 105}]}}, "schema": []}
{"input": "Sodium salts of maleamic acid derivatives of lauryl ester of tyrosine (MTNa) and phenyl alanine (MPNa) in water exhibited strong pH-responsive behaviors of viscosity and specific conductivity that originate from the concentration and pH dependence of their aggregation states.", "output": {"entities": {"chemical": [{"text": "Sodium", "start": 0, "end": 6}, {"text": "maleamic acid", "start": 16, "end": 29}, {"text": "lauryl ester", "start": 45, "end": 57}, {"text": "tyrosine", "start": 61, "end": 69}, {"text": "phenyl alanine", "start": 81, "end": 95}]}}, "schema": []}
{"input": "The aggregates were characterized by a novel spin-probe-partitioning electron paramagnetic resonance (SPPEPR) method and dynamic light scattering (DLS).", "output": {"entities": {}}, "schema": []}
{"input": "Results of high-precision fitting of the second-harmonic EPR spectra of the small spin probe di-tert-butyl nitroxide (DTBN) in these aggregates together with viscosity, conductivity, and DLS showed that, at pH ~ 7. 54, MTNa formed micelles and MPNa vesicles and MTNa exhibited a pH-induced micelle to vesicle transition as pH was lowered toward 6.", "output": {"entities": {"chemical": [{"text": "di-tert-butyl nitroxide", "start": 93, "end": 116}, {"text": "DTBN", "start": 118, "end": 122}]}}, "schema": []}
{"input": "MTNa, at pH ~ 7. 54, formed small micelles at low concentrations that transformed to long worm-like micelles for concentrations >= 0. 05 M, accompanied by a 30-fold increase in solution viscosity.", "output": {"entities": {}}, "schema": []}
{"input": "The hydrodynamic radii from DLS confirmed the presence of small micellar aggregates of radius ~ 2 nm in MTNa at pH ~ 7. 54 at the lower concentrations, with coexisting micelles (~ 2 nm) and vesicles (~ 50 nm) at pH near 6. 5, vesicles (radii ~ 70 nm) at pH near 6, and large vesicles (85 nm) in MPNa at pH ~ 7. 60.", "output": {"entities": {}}, "schema": []}
{"input": "Both MTNa and MPNa precipitated upon reduction of pH below 6 and below 7, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The rate of transfer of DTBN between the aqueous phase and the aggregate was calculated from the high-field Lorentzian linewidths of the electron paramagnetic resonance (EPR) spectra.", "output": {"entities": {"chemical": [{"text": "DTBN", "start": 24, "end": 28}]}}, "schema": []}
{"input": "The activation energy for the transfer determined from the temperature dependence of the rate of transfer is 12. 7 kJ/mol for MTNa vesicles (pH ~ 6) and 20. 6 +/- 1. 3 kJ/mol for MPNa (pH ~ 7. 60).", "output": {"entities": {}}, "schema": []}
{"input": "The pH-induced transformations were reversible.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of aryl ureas and aryl amides as potent and selective histamine H3 receptor antagonists for the treatment of obesity (Part I).", "output": {"entities": {"chemical": [{"text": "aryl ureas", "start": 13, "end": 23}, {"text": "aryl amides", "start": 28, "end": 39}, {"text": "histamine", "start": 64, "end": 73}]}}, "schema": []}
{"input": "A series of structurally novel aryl ureas was derived from optimization of the HTS lead as selective histamine H3 receptor (H3R) antagonists.", "output": {"entities": {"chemical": [{"text": "aryl ureas", "start": 31, "end": 41}, {"text": "histamine", "start": 101, "end": 110}]}}, "schema": []}
{"input": "The SAR was explored and the data obtained set up the starting point and foundation for further optimization.", "output": {"entities": {}}, "schema": []}
{"input": "The most potent tool compounds, as exemplified by compounds 2l, 5b, 5d, and 5e, displayed antagonism potencies in the subnanomolar range in in vitro human-H3R FLIPR assays and rhesus monkey H3R binding assays.", "output": {"entities": {}}, "schema": []}
{"input": "Phenanthroimidazole-based thiobenzamide as an effective sensor for highly selective detection of mercury (II).", "output": {"entities": {"chemical": [{"text": "Phenanthroimidazole", "start": 0, "end": 19}, {"text": "thiobenzamide", "start": 26, "end": 39}, {"text": "mercury (II)", "start": 97, "end": 109}]}}, "schema": []}
{"input": "Based on highly selective and irreversible Hg (2 +)-promoted desulfurization reaction, a new and simple phenanthroimidazole-type sensor was prepared and exhibited high selectivity towards Hg (2 +) ion over other metal ions, accompanied by transformation of a weakly fluorescent thioamide moiety (colorless) to a highly fluorescent amide one (blue), with a 136-fold increase in fluorescent intensity in aqueous solution with a pH span 2. 57-9. 12.", "output": {"entities": {"chemical": [{"text": "Hg (2 +)", "start": 43, "end": 51}, {"text": "phenanthroimidazole", "start": 104, "end": 123}, {"text": "Hg (2 +)", "start": 188, "end": 196}, {"text": "thioamide", "start": 278, "end": 287}, {"text": "amide", "start": 331, "end": 336}]}}, "schema": []}
{"input": "Cerebral ischemia-induced difference in sensitivity to depression and potential therapeutics in rats.", "output": {"entities": {}}, "schema": []}
{"input": "The' vascular depression' hypothesis has recently attracted significant research attention, although the causal relationship between vascular-related injuries and depression has not been established.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that one episode of cerebral ischemia was sufficient to greatly increase the sensitivity of rats to potentially depressogenic events, evaluated at below-threshold intensities in the open space swim test.", "output": {"entities": {}}, "schema": []}
{"input": "The induced' ischemic depression' was lasting and sensitive to an acute administration of brain-derived neurotrophic factor or bryostatin-1, a relatively selective activator of protein kinase C epsilon, during the induction phase.", "output": {"entities": {"chemical": [{"text": "bryostatin-1", "start": 127, "end": 139}]}}, "schema": []}
{"input": "Chronic treatment with bryostatin-1 (5 weeks) after the induction of depressive behavior reversed the depressive immobility and produced a lasting therapeutic effect, which remained effective 3 weeks after discontinuation of the treatment.", "output": {"entities": {"chemical": [{"text": "bryostatin-1", "start": 23, "end": 35}]}}, "schema": []}
{"input": "Similar treatment with alaproclate, a selective serotonin reuptake inhibitor, in contrast, produced temporary relief from the depressive symptoms, with the therapeutic effect disappearing soon after the end of the treatment.", "output": {"entities": {"chemical": [{"text": "alaproclate", "start": 23, "end": 34}, {"text": "serotonin", "start": 48, "end": 57}]}}, "schema": []}
{"input": "The results strongly suggest that cerebral ischemia has a direct role in shaping the sensitivity of an individual to depressogenic events and that bryostatin-1-like agents may be developed as therapeutics for treating ischemic depression in humans.", "output": {"entities": {"chemical": [{"text": "bryostatin-1", "start": 147, "end": 159}]}}, "schema": []}
{"input": "Current status of liposomal porphyrinoid photosensitizers.", "output": {"entities": {"chemical": [{"text": "porphyrinoid", "start": 28, "end": 40}]}}, "schema": []}
{"input": "The complete eradication of various targets, such as infectious agents or cancer cells, while leaving healthy host cells untouched, is still a great challenge faced in the field of medicine.", "output": {"entities": {}}, "schema": []}
{"input": "Photodynamic therapy (PDT) seems to be a promising approach for anticancer treatment, as well as to combat various dermatologic and ophthalmic diseases and microbial infections.", "output": {"entities": {}}, "schema": []}
{"input": "The application of liposomes as delivery systems for porphyrinoids has helped overcome many drawbacks of conventional photosensitizers and facilitated the development of novel effective photosensitizers that can be encapsulated in liposomes.", "output": {"entities": {"chemical": [{"text": "porphyrinoids", "start": 53, "end": 66}]}}, "schema": []}
{"input": "The development, preclinical studies and future directions for liposomal delivery of conventional and novel photosensitizers are reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "Structure and energetics of gas phase halogen-bonding in mono-, bi-, and tri-dentate anion receptors as studied by BIRD.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 38, "end": 45}]}}, "schema": []}
{"input": "Complexes of mono-, bi-(RB), and tridentate (RT) receptors with a range of anions (Cl (-), Br (-), I (-), NO3 (-), H2PO4 (-), HSO4 (-), and tosylate (TsO (-))) have been studied in the gas phase by both experimental and theoretical methods.", "output": {"entities": {"chemical": [{"text": "Cl (-)", "start": 83, "end": 89}, {"text": "Br (-)", "start": 91, "end": 97}, {"text": "I (-)", "start": 99, "end": 104}, {"text": "NO3 (-)", "start": 106, "end": 113}, {"text": "H2PO4 (-)", "start": 115, "end": 124}, {"text": "HSO4 (-)", "start": 126, "end": 134}, {"text": "tosylate", "start": 140, "end": 148}, {"text": "TsO (-)", "start": 150, "end": 157}]}}, "schema": []}
{"input": "Temperature dependent blackbody infrared radiative dissociation (BIRD) experiments were performed on complexes of C8F17I with Br (-) and I (-), RB with I (-), NO3 (-), HSO4 (-), H2PO4 (-), and TsO (-), and RT with I (-), HSO4 (-) and TsO (-) and the observed Arrhenius parameters are reported here.", "output": {"entities": {"chemical": [{"text": "C8F17I", "start": 114, "end": 120}, {"text": "Br (-)", "start": 126, "end": 132}, {"text": "I (-)", "start": 137, "end": 142}, {"text": "I (-)", "start": 152, "end": 157}, {"text": "NO3 (-)", "start": 159, "end": 166}, {"text": "HSO4 (-)", "start": 168, "end": 176}, {"text": "H2PO4 (-)", "start": 178, "end": 187}, {"text": "TsO (-)", "start": 193, "end": 200}, {"text": "I (-)", "start": 214, "end": 219}, {"text": "HSO4 (-)", "start": 221, "end": 229}, {"text": "TsO (-)", "start": 234, "end": 241}]}}, "schema": []}
{"input": "Master equation modeling of the BIRD kinetics data was carried out to determine threshold dissociation energies.", "output": {"entities": {}}, "schema": []}
{"input": "Geometry optimizations and thermochemistry calculations were performed using the B3LYP/6-31 + G (d, p) level of theory.", "output": {"entities": {}}, "schema": []}
{"input": "Additional single point energies were calculated using MP2/6-311 + + G (2d, p).", "output": {"entities": {}}, "schema": []}
{"input": "Results were examined in terms of the binding order of various anions as well as the added binding strength from additional halogen bonding (XB) interactions.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 124, "end": 131}]}}, "schema": []}
{"input": "The relative binding energies of ions were generally consistent with the ordering previously reported from solution phase experiments; however, the relatively strong binding of H2PO4 (-) to the bidentate receptor contrasted the solution phase observation of oxoanions having weaker interactions when compared to halides.", "output": {"entities": {"chemical": [{"text": "H2PO4 (-)", "start": 177, "end": 186}, {"text": "oxoanions", "start": 258, "end": 267}, {"text": "halides", "start": 312, "end": 319}]}}, "schema": []}
{"input": "An increase in the energy required to remove the same anion from the tridentate receptor when compared to the bidentate and monodentate receptors is explained as being due to the increase in halogen bonding interactions.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 191, "end": 198}]}}, "schema": []}
{"input": "The possibility of mixed halogen and hydrogen bonded complexes were considered.", "output": {"entities": {"chemical": [{"text": "halogen", "start": 25, "end": 32}, {"text": "hydrogen", "start": 37, "end": 45}]}}, "schema": []}
{"input": "A new potential nano-oncological therapy based on polyamino acid nanocapsules.", "output": {"entities": {"chemical": [{"text": "polyamino acid", "start": 50, "end": 64}]}}, "schema": []}
{"input": "A critical objective in cancer therapy is to reduce the systemic toxicity through the modification of the biodistribution of anticancer drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we disclose a new biodegradable nanocarrier, polyglutamic acid (PGA) nanocapsules, and present the in vivo pharmacokinetics/toxicity proof-of-concept for the anticancer drug plitidepsin.", "output": {"entities": {"chemical": [{"text": "polyglutamic acid", "start": 53, "end": 70}, {"text": "PGA", "start": 72, "end": 75}, {"text": "plitidepsin", "start": 182, "end": 193}]}}, "schema": []}
{"input": "These novel nanocapsules were prepared using a modified solvent displacement technique where the polyamino acid was electrostatically deposited onto the lipid core.", "output": {"entities": {"chemical": [{"text": "polyamino acid", "start": 97, "end": 111}]}}, "schema": []}
{"input": "The nanocapsules exhibited an average size of 200nm, a negative zeta potential and a great capacity for the encapsulation of plitidepsin (encapsulation efficiency above 90%).", "output": {"entities": {"chemical": [{"text": "plitidepsin", "start": 125, "end": 136}]}}, "schema": []}
{"input": "In addition, the nanocapsules could be freeze-dried and showed an adequate stability profile upon storage.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, the in vivo proof-of-concept studies performed in mice indicated that the encapsulation provided the drug with a prolonged blood circulation and a significantly reduced toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "In fact, the maximum tolerated dose of the nanoencapsulated drug was more than 3 times that of the reference formulation (Cremophor (R) EL plitidepsin solution).", "output": {"entities": {"chemical": [{"text": "Cremophor", "start": 122, "end": 131}, {"text": "plitidepsin", "start": 139, "end": 150}]}}, "schema": []}
{"input": "Overall, beyond the value of this specific formulation, the work reported here represents the evidence of the potential of polyamino acid nanocapsules in nano-oncological therapy.", "output": {"entities": {"chemical": [{"text": "polyamino acid", "start": 123, "end": 137}]}}, "schema": []}
{"input": "Effects of Selenium Intervention on Chronic Fluorosis-Induced Renal Cell Apoptosis in Rats.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 11, "end": 19}]}}, "schema": []}
{"input": "This study aims to explore the effect of selenium in fluoride-induced renal cell apoptosis in rats and determine the optimal level of selenium in drinking water to prevent fluorosis.", "output": {"entities": {"chemical": [{"text": "selenium", "start": 41, "end": 49}, {"text": "fluoride", "start": 53, "end": 61}, {"text": "selenium", "start": 134, "end": 142}]}}, "schema": []}
{"input": "Experimental animals were divided into a control group, a sodium fluoride-treated group (NaF, 50 mg/L), three sodium selenite-treated groups (Na2SeO3, 0. 375, 0. 75, and 1. 5 mg/L), and three selenium + NaF-treated groups (Na2SeO3, 0. 375, 0. 75, and 1. 5 mg/L; NaF, 50 mg/L).", "output": {"entities": {"chemical": [{"text": "sodium fluoride", "start": 58, "end": 73}, {"text": "NaF", "start": 89, "end": 92}, {"text": "sodium selenite", "start": 110, "end": 125}, {"text": "Na2SeO3", "start": 142, "end": 149}, {"text": "selenium", "start": 192, "end": 200}, {"text": "NaF", "start": 203, "end": 206}, {"text": "Na2SeO3", "start": 223, "end": 230}, {"text": "NaF", "start": 262, "end": 265}]}}, "schema": []}
{"input": "Ultrastructural changes in the kidney tissues of each group were observed by transmission electron microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and the expressions of Bcl-2 and Bax proteins were detected by immunohistochemical methods.", "output": {"entities": {"chemical": [{"text": "dUTP", "start": 73, "end": 77}]}}, "schema": []}
{"input": "The expressions of Bcl-2 and Bax mRNA were detected by reverse transcription-polymerase chain reaction.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the fluoride and high selenium groups were highly elevated compared with the control group (P < 0. 01).", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 77, "end": 85}, {"text": "selenium", "start": 95, "end": 103}]}}, "schema": []}
{"input": "Bax expression in the low selenium group and Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the moderate selenium groups were observably elevated (P < 0. 05).", "output": {"entities": {"chemical": [{"text": "selenium", "start": 26, "end": 34}, {"text": "selenium", "start": 107, "end": 115}]}}, "schema": []}
{"input": "Bax and Bax/Bcl-2 expressions in the fluoride group and Bax mRNA expression in the high selenium group were highly elevated (P < 0. 01).", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 37, "end": 45}, {"text": "selenium", "start": 88, "end": 96}]}}, "schema": []}
{"input": "Bax/Bcl-2 mRNA expression in the high selenium group was also highly elevated (P < 0. 05).", "output": {"entities": {"chemical": [{"text": "selenium", "start": 38, "end": 46}]}}, "schema": []}
{"input": "Compared with the fluoride group, the group treated with low selenium has Bax protein expression that was observably reduced (P < 0. 05); the group treated with moderate selenium has Bcl-2 protein expression that was observably elevated (P < 0. 05), Bax protein expression that was highly reduced (P < 0. 01), and Bax/Bcl-2 protein expression that was observably reduced (P < 0. 05); the group treated with high selenium has Bcl-2 protein expression that was highly elevated (P < 0. 01), Bax protein expression that was highly elevated (P < 0. 01), and Bax/Bcl-2 protein expression that was highly reduced (P < 0. 01); the groups treated with moderate selenium and high selenium have Bax mRNA expression that was highly reduced (P < 0. 01), and the groups treated with high selenium have Bax/Bcl-2 mRNA expression that was observably reduced (P < 0. 05).", "output": {"entities": {"chemical": [{"text": "fluoride", "start": 18, "end": 26}, {"text": "selenium", "start": 61, "end": 69}, {"text": "selenium", "start": 170, "end": 178}, {"text": "selenium", "start": 412, "end": 420}, {"text": "selenium", "start": 652, "end": 660}, {"text": "selenium", "start": 670, "end": 678}, {"text": "selenium", "start": 774, "end": 782}]}}, "schema": []}
{"input": "Selenium may inhibit the apoptosis of renal cells in fluorosis rats by regulating the expressions of Bcl-2 and Bax.", "output": {"entities": {"chemical": [{"text": "Selenium", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The optimal dose of Na2SeO3 to protect against fluoride-induced renal cell apoptosis was determined to be 1. 5 mg/L.", "output": {"entities": {"chemical": [{"text": "Na2SeO3", "start": 20, "end": 27}, {"text": "fluoride", "start": 47, "end": 55}]}}, "schema": []}
{"input": "Melatonin and its analogue 5-MCA-NAT potentiate adrenergic receptor-mediated ocular hypotensive effects in rabbits: Significance for combination therapy in glaucoma.", "output": {"entities": {"chemical": [{"text": "Melatonin", "start": 0, "end": 9}, {"text": "5-MCA-NAT", "start": 27, "end": 36}]}}, "schema": []}
{"input": "Melatonin is currently considered as a promising drug for glaucoma treatment due to its ocular hypotensive and neuroprotective effects.", "output": {"entities": {"chemical": [{"text": "Melatonin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "We have investigated the effect of melatonin and its analogue 5-methoxycarbonylamino-N-acetyltryptamine, 5-MCA-NAT, on beta 2/alpha 2A-adrenergic receptor mRNA as well as protein expression in cultured rabbit non-pigmented ciliary epithelial cells.", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 35, "end": 44}, {"text": "5-methoxycarbonylamino-N-acetyltryptamine", "start": 62, "end": 103}, {"text": "5-MCA-NAT", "start": 105, "end": 114}]}}, "schema": []}
{"input": "Quantitative PCR and immunocytochemical assays revealed a significant beta 2-adrenergic receptor down-regulation as well as alpha 2A-adrenergic receptor up-regulation of treated cells (p < 0. 001, maximal significant effect).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we have studied the effect of these drugs upon the ocular hypotensive action of a non-selective beta-adrenergic receptor (timolol) and a selective alpha 2-adrenergic receptor agonist (brimonidine) in normotensive rabbits.", "output": {"entities": {"chemical": [{"text": "timolol", "start": 135, "end": 142}, {"text": "brimonidine", "start": 197, "end": 208}]}}, "schema": []}
{"input": "IOP experiments showed that the administration of timolol in rabbits pre-treated with melatonin or 5-MCA-NAT evoked an additional IOP reduction of 14. 02 +/- 5. 8% or 16. 75 +/- 5. 48% (p < 0. 01) in comparison with rabbits treated with timolol alone for 24 hours.", "output": {"entities": {"chemical": [{"text": "timolol", "start": 50, "end": 57}, {"text": "melatonin", "start": 86, "end": 95}, {"text": "5-MCA-NAT", "start": 99, "end": 108}, {"text": "timolol", "start": 237, "end": 244}]}}, "schema": []}
{"input": "Concerning brimonidine hypotensive action, an additional IOP reduction of 29. 26 +/- 5. 21% or 39. 07 +/- 5. 81% (p < 0. 001) was observed in rabbits pretreated with melatonin or 5-MCA-NAT when compared with animals treated with brimonidine alone for 24 hours.", "output": {"entities": {"chemical": [{"text": "brimonidine", "start": 11, "end": 22}, {"text": "melatonin", "start": 166, "end": 175}, {"text": "5-MCA-NAT", "start": 179, "end": 188}, {"text": "brimonidine", "start": 229, "end": 240}]}}, "schema": []}
{"input": "Additionally, a sustained potentiating effect of a single dose of 5-MCA-NAT was seen in rabbits treated with brimonidine once daily for up four days (extra IOP decrease of 15. 57 +/- 5. 15%, p < 0. 05, compared to brimonidine alone).", "output": {"entities": {"chemical": [{"text": "5-MCA-NAT", "start": 66, "end": 75}, {"text": "brimonidine", "start": 109, "end": 120}, {"text": "brimonidine", "start": 214, "end": 225}]}}, "schema": []}
{"input": "These data confirm the indirect action of melatoninergic compounds on adrenergic receptors and their remarkable effect upon the ocular hypotensive action mainly of alpha 2-adrenergic receptor agonists but also of beta-adrenergic antagonists.", "output": {"entities": {}}, "schema": []}
{"input": "Focal adhesion kinase regulates collagen I-induced airway smooth muscle phenotype switching.", "output": {"entities": {}}, "schema": []}
{"input": "Increased extracellular matrix (ECM) deposition and airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, we have demonstrated that the ECM protein collagen I, which is increased surrounding asthmatic ASM, induces a proliferative, hypocontractile ASM phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "Little is known, however, on the signaling pathways involved.", "output": {"entities": {}}, "schema": []}
{"input": "Using bovine tracheal smooth muscle, we investigated the role of focal adhesion kinase (FAK) and downstream signaling pathways in collagen I-induced ASM phenotype modulation.", "output": {"entities": {}}, "schema": []}
{"input": "Phosphorylation of FAK was increased during adhesion to both uncoated and collagen I-coated culture dishes, without differences between these matrices.", "output": {"entities": {}}, "schema": []}
{"input": "No differences in cellular adhesion were found either.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of FAK activity by overexpression of the FAK deletion mutants FAT (focal adhesion targeting domain) and FRNK (FAK-related non-kinase) attenuated adhesion.", "output": {"entities": {}}, "schema": []}
{"input": "After attachment, FAK phosphorylation was time-dependently increased in cells cultured on collagen I, whereas no activation was found on an uncoated plastic matrix.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, collagen I time-and concentration-dependently increased cell proliferation, which was fully inhibited by FAT and FRNK.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, the specific pharmacological FAK inhibitor PF-573, 228 as well as specific inhibitors of p38 MAPK and Src also fully inhibited collagen I-induced proliferation, whereas partial inhibition was observed by inhibition of PI3-kinase and MEK.", "output": {"entities": {"chemical": [{"text": "PF-573, 228", "start": 54, "end": 65}]}}, "schema": []}
{"input": "The inhibition of cell proliferation by these inhibitors was associated with attenuation of the collagen I-induced hypocontractility.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, the results indicate that induction of a proliferative, hypocontractile ASM phenotype by collagen I is mediated by FAK and downstream signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Selective Smad4 Knockout in Ovarian Preovulatory Follicles Results in Multiple Defects in Ovulation.", "output": {"entities": {}}, "schema": []}
{"input": "The TGF-beta signaling pathway is involved with multiple processes in the mammalian ovary, including primordial follicle formation, granulosa cell (GC) proliferation, follicle atresia, ovulation, and feedback regulation between the pituitary and ovary.", "output": {"entities": {}}, "schema": []}
{"input": "The transcriptional factor SMAD4 is the central component of the canonical TGF-beta signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Smad4 knockout using Amhr2-Cre, which is expressed in GCs of immature developing follicles, causes premature luteinization.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we specifically depleted Smad4 in GCs of preovulatory follicles using Cyp19-Cre mice.", "output": {"entities": {}}, "schema": []}
{"input": "As different from results with Smad4 (fl/fl); Amhr2-Cre mice, Smad4 depletion in preovulatory follicles did not cause premature luteinization or suppress GC proliferation; rather, it increased follicle atresia.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, Nppc and Npr2 expressions were reduced by Smad4 depletion; thus, their effect of maintaining oocyte meiotic arrest was weakened in Smad4 conditional knockout mice.", "output": {"entities": {}}, "schema": []}
{"input": "Smad4 (fl/fl); Cyp19-Cre female mice were subfertile and had irregular estrous cycles and ovulation defects.", "output": {"entities": {}}, "schema": []}
{"input": "Smad4 knockout also blocked luteinizing hormone (LH)-induced cumulus expansion and follicle rupture, but not oocyte meiotic resumption.", "output": {"entities": {}}, "schema": []}
{"input": "Our results also indicated that SMAD4 was required for LH-stimulated activation of ERK1/2 and the expressions of ovulation-related genes.", "output": {"entities": {}}, "schema": []}
{"input": "The defects arising from SMAD4 depletion could not be rescued by intra-ovarian mediators of LH actions, such as EGF-like factors and prostaglandin E2.", "output": {"entities": {"chemical": [{"text": "prostaglandin E2", "start": 133, "end": 149}]}}, "schema": []}
{"input": "Furthermore, corpus lutea did not form in Smad4 (fl/fl); Cyp19-Cre female mice, indicating that SMAD4 was crucial for GCs terminal differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, by characterizing the ovarian phenotypes of preovulatory follicle-specific Smad4 knockout mice, we identified the developmental stage-specific functions of the canonical TGF-beta signaling pathway in ovulation and luteinization.", "output": {"entities": {}}, "schema": []}
{"input": "Charge-Transfer Interaction between Few-Layer MoS2 and Tetrathiafulvalene.", "output": {"entities": {"chemical": [{"text": "MoS2", "start": 46, "end": 50}, {"text": "Tetrathiafulvalene", "start": 55, "end": 73}]}}, "schema": []}
{"input": "Graphene look-alike: MoS2 has a layered structure similar to graphene.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 0, "end": 8}, {"text": "MoS2", "start": 21, "end": 25}, {"text": "graphene", "start": 61, "end": 69}]}}, "schema": []}
{"input": "Tetrathiafulvalene (TTF) interacts with thin, few-layer MoS2 material by donating an electron, resulting in the formation of TTF radical cation and n-type doping of MoS2.", "output": {"entities": {"chemical": [{"text": "Tetrathiafulvalene", "start": 0, "end": 18}, {"text": "TTF", "start": 20, "end": 23}, {"text": "MoS2", "start": 56, "end": 60}, {"text": "TTF", "start": 125, "end": 128}, {"text": "MoS2", "start": 165, "end": 169}]}}, "schema": []}
{"input": "Electron-withdrawing tetracyanoethylene, in contrast, does not cause p-type doping in MoS2.", "output": {"entities": {"chemical": [{"text": "tetracyanoethylene", "start": 21, "end": 39}, {"text": "MoS2", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Protective effect of wogonin on proinflammatory cytokine generation via Jak1/3-STAT1/3 pathway in lipopolysaccharide stimulated BV2 microglial cells.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 21, "end": 28}]}}, "schema": []}
{"input": "Wogonin is a flavonoid compound which exhibits antioxidation, anti-inflammation, neuroprotection, and antitumorgenesis functions.", "output": {"entities": {"chemical": [{"text": "Wogonin", "start": 0, "end": 7}, {"text": "flavonoid", "start": 13, "end": 22}]}}, "schema": []}
{"input": "However, the mechanism of how wogonin reduces proinflammatory cytokine generation in activated microglia is unclear.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 30, "end": 37}]}}, "schema": []}
{"input": "At present, we found wogonin inhibited lipopolysaccharide (LPS)-/interferon-gamma (INF-gamma)-induced generation of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 21, "end": 28}]}}, "schema": []}
{"input": "Wogonin exhibited parallel inhibition on LPS-/INF-gamma-induced expression of IL-6 and TNF-alpha messenger RNA at the same concentration range.", "output": {"entities": {"chemical": [{"text": "Wogonin", "start": 0, "end": 7}]}}, "schema": []}
{"input": "LPS-/INF-gamma-induced phosphorylation of signal transduction and transcription 1 and 3 (STAT1/3) were also inhibited by wogonin.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 121, "end": 128}]}}, "schema": []}
{"input": "Although wogonin expressed only weak inhibitory effect on LPS-/INF-gamma-induced phosphorylation of Janus kinase-2 (Jak-2) and tyrosine kinase (Tyk)-2, it significantly attenuated the phosphorylation of Jak-1 and Jak-3.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 9, "end": 16}, {"text": "tyrosine", "start": 127, "end": 135}]}}, "schema": []}
{"input": "These results indicated that the blockade of IL-6 and TNF-alpha production by wogonin in LPS-/INF-gamma-stimulated BV2 microglial cells was attributed mainly to the interference in Jak-1/-3-STAT1/3 signaling pathway.", "output": {"entities": {"chemical": [{"text": "wogonin", "start": 78, "end": 85}]}}, "schema": []}
{"input": "Structural mechanism of ring opening reaction of glucose by human serum albumin.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 49, "end": 56}]}}, "schema": []}
{"input": "Glucose reacts with proteins non-enzymatically under physiological conditions.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Such glycation is exacerbated in diabetic patients with high level of blood sugar, and induces various complications.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 76, "end": 81}]}}, "schema": []}
{"input": "Human albumin serum (HSA) is the most abundant protein in plasma and is glycated by glucose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 84, "end": 91}]}}, "schema": []}
{"input": "The glycation sites on HSA remain controversial among different studies.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report two protein crystal structures of HSA in complex with either glucose or fructose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 77, "end": 84}, {"text": "fructose", "start": 88, "end": 96}]}}, "schema": []}
{"input": "These crystal structures reveal that the presence of linear forms of sugar for both monosaccharides.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 69, "end": 74}, {"text": "monosaccharides", "start": 84, "end": 99}]}}, "schema": []}
{"input": "The linear form of glucose forms a covalent bond to Lys195 of HSA, but not the case for fructose.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 19, "end": 26}, {"text": "Lys195", "start": 52, "end": 58}, {"text": "fructose", "start": 88, "end": 96}]}}, "schema": []}
{"input": "Based on these structures, we propose a mechanism for glucose ring opening involving both residues Lys195 and Lys199.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 54, "end": 61}, {"text": "Lys195", "start": 99, "end": 105}, {"text": "Lys199", "start": 110, "end": 116}]}}, "schema": []}
{"input": "These results provide mechanistic insights to understand the glucose ring opening reaction and the glycation of proteins by monosaccharides.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 61, "end": 68}, {"text": "monosaccharides", "start": 124, "end": 139}]}}, "schema": []}
{"input": "AP-1/Fos-TGase2 axis mediates wounding-induced Plasmodium falciparum killing in Anopheles gambiae.", "output": {"entities": {}}, "schema": []}
{"input": "Anopheline mosquitoes are the only vectors of human malaria worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "It is now widely accepted that mosquito immune responses play a crucial role in restricting Plasmodium development within the vector, therefore further dissection of the molecular mechanisms underlying these processes should inform new vector control strategies urgently needed to roll back the disease.", "output": {"entities": {}}, "schema": []}
{"input": "Here, using genome-wide transcriptional profiling, bioinformatics and functional gene analysis we identify a new axis of mosquito resistance to monoclonal P. falciparum infections that includes the AP-1 transcription factor Fos and the transglutaminase 2 (TGase2), a cross-linking enzyme with known roles in wound responses.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that Fos regulates induction of TGase2 expression after wounding but does not affect expression of the components of the well-characterized complement-like system.", "output": {"entities": {}}, "schema": []}
{"input": "Silencing of Fos or of TGase2 aborts the wounding-induced mosquito killing of P. falciparum.", "output": {"entities": {}}, "schema": []}
{"input": "These results reveal multiple signaling pathways that are required for efficient Plasmodium killing in A. gambiae.", "output": {"entities": {}}, "schema": []}
{"input": "Nutrient signaling in protein homeostasis: an increase in quantity at the expense of quality.", "output": {"entities": {}}, "schema": []}
{"input": "The discovery that rapamycin extends the life span of diverse organisms has triggered many studies aimed at identifying the underlying molecular mechanisms.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 19, "end": 28}]}}, "schema": []}
{"input": "Mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and may regulate organismal aging by controlling mRNA translation.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 20, "end": 29}]}}, "schema": []}
{"input": "However, how inhibiting mTORC1 and decreasing protein synthesis can extend life span remains an unresolved issue.", "output": {"entities": {}}, "schema": []}
{"input": "We showed that constitutively active mTORC1 signaling increased general protein synthesis but unexpectedly reduced the quality of newly synthesized polypeptides.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrated that constitutively active mTORC1 decreased translation fidelity by increasing the speed of ribosomal elongation.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, rapamycin treatment restored the quality of newly synthesized polypeptides mainly by slowing the rate of ribosomal elongation.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 12, "end": 21}]}}, "schema": []}
{"input": "We also found distinct roles for mTORC1 downstream targets in maintaining protein homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Loss of S6 kinases, but not 4E-BP family proteins, which are both involved in regulation of translation, attenuated the effects of rapamycin on the quality of newly translated proteins.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 131, "end": 140}]}}, "schema": []}
{"input": "Our results reveal a mechanistic connection between mTORC1 and protein quality, highlighting the central role of nutrient signaling in growth and aging.", "output": {"entities": {}}, "schema": []}
{"input": "DFT Modeling of 45S5 and 77S Soda-Lime Phospho-Silicate Glass Surfaces: Clues on Different Bioactivity Mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "The reactivity of bioglasses, which is related to the dissolution of cations and orthosilicate groups in the physiological fluid, strongly depends on the key structural features present at the glass surfaces.", "output": {"entities": {"chemical": [{"text": "orthosilicate", "start": 81, "end": 94}]}}, "schema": []}
{"input": "On the basis of the composition and the synthetic routes employed to make the glass, surfaces with very different characteristics and thus presenting different mechanisms of dissolution can be observed.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, the surface structures of two very different bioglass compositions, namely 45S5 (46. 1 SiO2, 24. 4 Na2O, 26. 9 CaO, and 2. 6 P2O5 mol%) and 77S (80. 0 SiO2, 16. 0 CaO, and 4. 0 P2O5 mol%), have been investigated by means of periodic DFT calculations based on a PBE functional and localized Gaussian basis set as encoded in the CRYSTAL code.", "output": {"entities": {"chemical": [{"text": "SiO2", "start": 102, "end": 106}, {"text": "Na2O", "start": 114, "end": 118}, {"text": "CaO", "start": 126, "end": 129}, {"text": "P2O5", "start": 140, "end": 144}, {"text": "SiO2", "start": 166, "end": 170}, {"text": "CaO", "start": 178, "end": 181}, {"text": "P2O5", "start": 192, "end": 196}]}}, "schema": []}
{"input": "Our calculations show that the two glass surfaces differ by the relative amount of key structural sites such as NBOs, exposed ions, orthosilicate units, and small rings.", "output": {"entities": {"chemical": [{"text": "orthosilicate", "start": 132, "end": 145}]}}, "schema": []}
{"input": "We have demonstrated how the number of these sites affects the surface stability and reactivity (bioactivity).", "output": {"entities": {}}, "schema": []}
{"input": "Formation Mechanism of TiO 2 Nanotubes and Their Applications in Photoelectrochemical Water Splitting and Supercapacitors.", "output": {"entities": {"chemical": [{"text": "TiO 2", "start": 23, "end": 28}]}}, "schema": []}
{"input": "Structural observations of the transition of TiO 2 nanopores into nanotubes by increasing the OH (-) concentration in the electrolyte challenge the validity of existing formation mechanisms of anodic TiO 2 nanotubes.", "output": {"entities": {"chemical": [{"text": "TiO 2", "start": 45, "end": 50}, {"text": "OH (-)", "start": 94, "end": 100}, {"text": "TiO 2", "start": 200, "end": 205}]}}, "schema": []}
{"input": "In this study, dehydration of titanium hydroxide in the cell wall is proposed as the mechanism that leads to the separation of neighboring nanotubes.", "output": {"entities": {"chemical": [{"text": "titanium hydroxide", "start": 30, "end": 48}]}}, "schema": []}
{"input": "Based on this understanding, bamboo-type TiO 2 nanotubes with large surface area and excellent interconnectivity are achieved by cycling high and low applied potentials.", "output": {"entities": {"chemical": [{"text": "TiO 2", "start": 41, "end": 46}]}}, "schema": []}
{"input": "After thermal treatment in a H 2 atmosphere, the bamboo-type TiO 2 nanotubes show large photoelectrochemical water splitting efficiency and supercapacitors performace.", "output": {"entities": {"chemical": [{"text": "H 2", "start": 29, "end": 32}, {"text": "TiO 2", "start": 61, "end": 66}]}}, "schema": []}
{"input": "Ultralow Thermal Conductivity in Organoclay Nanolaminates Synthesized via Simple Self-Assembly.", "output": {"entities": {}}, "schema": []}
{"input": "Because interfaces impede phonon transport of thermal energy, nanostructuring can transform fully dense solids into ultralow thermal conductivity materials.", "output": {"entities": {}}, "schema": []}
{"input": "Here we report a simple self-assembly approach to synthesizing organoclay nanolaminates with cross-planar thermal conductivities below 0. 10 W m (-1) K (-1)-a 5-fold decrease compared to unmodified clay.", "output": {"entities": {}}, "schema": []}
{"input": "These organoclays are produced via alkylammonium cation exchange with colloidally dispersed montmorillonite clay sheets followed by solvent casting.", "output": {"entities": {"chemical": [{"text": "alkylammonium", "start": 35, "end": 48}, {"text": "montmorillonite", "start": 92, "end": 107}]}}, "schema": []}
{"input": "Time-domain thermoreflectance (TDTR) is used to evaluate the thermal conductivity of the organoclay nanolaminates.", "output": {"entities": {}}, "schema": []}
{"input": "Variations in both organic layer thickness and cation chemistry are investigated.", "output": {"entities": {}}, "schema": []}
{"input": "At these interface densities (1. 0-1. 5 interfaces/nm), we demonstrate that thermal conductivity is relatively independent of nanolaminate spacing.", "output": {"entities": {}}, "schema": []}
{"input": "A simple series resistance model describes the behavior and gives an interfacial thermal conductance value of =~ 150 MW m (-2) K (-1) for the organic/clay interface, consistent with similar organic-inorganic interfaces.", "output": {"entities": {}}, "schema": []}
{"input": "The wide range of compositional substitutions and structural variations possible in these materials, make organoclays a versatile new platform for investigating the underlying physics of nanolaminate structures.", "output": {"entities": {}}, "schema": []}
{"input": "Matrix Isolation Spectroscopy and Nuclear Spin Conversion of NH3 and ND3 in Solid Parahydrogen.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 61, "end": 64}, {"text": "ND3", "start": 69, "end": 72}, {"text": "Parahydrogen", "start": 82, "end": 94}]}}, "schema": []}
{"input": "We present matrix isolation infrared absorption spectra of NH3 and ND3 trapped in solid parahydrogen (pH2) at temperatures around 1. 8 K.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 59, "end": 62}, {"text": "ND3", "start": 67, "end": 70}, {"text": "parahydrogen", "start": 88, "end": 100}, {"text": "pH2", "start": 102, "end": 105}]}}, "schema": []}
{"input": "We used the relatively slow nuclear spin conversion (NSC) of NH3 and ND3 in freshly deposited pH2 samples as a tool to assign the sparse vibration-inversion-rotation (VIR) spectra of NH3 in the regions of the nu 2, nu 4, 2 nu 4, nu 1, and nu 3 bands and ND3 in the regions of the nu 2, nu 4, nu 1, and nu 3 fundamentals.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 61, "end": 64}, {"text": "ND3", "start": 69, "end": 72}, {"text": "pH2", "start": 94, "end": 97}, {"text": "NH3", "start": 183, "end": 186}, {"text": "ND3", "start": 254, "end": 257}]}}, "schema": []}
{"input": "Partial assignments are also presented for various combination bands of NH3.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 72, "end": 75}]}}, "schema": []}
{"input": "Detailed analysis of the nu 2 bands of NH3 and ND3 indicates that both isotopomers are nearly free rotors; that the vibrational energy is blue-shifted by 1-2%; and that the rotational constants and inversion tunneling splitting are 91-94% and 67-75%, respectively, of the gas-phase values.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 39, "end": 42}, {"text": "ND3", "start": 47, "end": 50}]}}, "schema": []}
{"input": "The line shapes of the VIR absorptions are narrow (0. 2-0. 4 cm (-1)) for upper states that cannot rotationally relax and broad (> 1 cm (-1)) for upper states that can rotationally relax.", "output": {"entities": {}}, "schema": []}
{"input": "We report and assign a number of NH3-induced infrared absorption features of the pH2 host near 4150 cm (-1), along with a cooperative transition that involves simultaneous vibrational excitation of a pH2 molecule and rotation-inversion excitation of NH3.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 33, "end": 36}, {"text": "pH2", "start": 81, "end": 84}, {"text": "pH2", "start": 200, "end": 203}, {"text": "NH3", "start": 250, "end": 253}]}}, "schema": []}
{"input": "The NSCs of NH3 and ND3 were found to follow first-order kinetics with rate constants at 1. 8 K of k = 1. 88 (16) x 10 (-3) s (-1) and k = 1. 08 (8) x 10 (-3) s (-1), respectively.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 12, "end": 15}, {"text": "ND3", "start": 20, "end": 23}]}}, "schema": []}
{"input": "These measured rate constants are compared to previous measurements for NH3 in an Ar matrix and with the rate constants measured for other dopant molecules isolated in solid pH2.", "output": {"entities": {"chemical": [{"text": "NH3", "start": 72, "end": 75}, {"text": "pH2", "start": 174, "end": 177}]}}, "schema": []}
{"input": "Development and validation of NIR-chemometric methods for chemical and pharmaceutical characterization of meloxicam tablets.", "output": {"entities": {"chemical": [{"text": "meloxicam", "start": 106, "end": 115}]}}, "schema": []}
{"input": "Abstract Context: Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets.", "output": {"entities": {}}, "schema": []}
{"input": "Objective: The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets.", "output": {"entities": {"chemical": [{"text": "meloxicam", "start": 248, "end": 257}]}}, "schema": []}
{"input": "Materials and methods: The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method.", "output": {"entities": {"chemical": [{"text": "meloxicam", "start": 153, "end": 162}]}}, "schema": []}
{"input": "Results: The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets.", "output": {"entities": {"chemical": [{"text": "meloxicam", "start": 269, "end": 278}]}}, "schema": []}
{"input": "Discussion: The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time).", "output": {"entities": {"chemical": [{"text": "meloxicam", "start": 156, "end": 165}]}}, "schema": []}
{"input": "Conclusion: The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.", "output": {"entities": {"chemical": [{"text": "meloxicam", "start": 266, "end": 275}]}}, "schema": []}
{"input": "Physicochemical characterization of phyllanthin from Phyllanthus amarus Schum.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 36, "end": 47}]}}, "schema": []}
{"input": "et Thonn.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Phyllanthin is a major bioactive lignan component of Phyllanthus amarus, with several known biological activities.", "output": {"entities": {"chemical": [{"text": "Phyllanthin", "start": 9, "end": 20}, {"text": "lignan", "start": 42, "end": 48}]}}, "schema": []}
{"input": "This study dealt with the isolation and physicochemical characterization of phyllanthin.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 76, "end": 87}]}}, "schema": []}
{"input": "Phyllanthin was isolated from P. amarus leaves by column chromatography and purified by recrystallization to obtain phyllanthin crystals with a purity of more than 98%.", "output": {"entities": {"chemical": [{"text": "Phyllanthin", "start": 0, "end": 11}, {"text": "phyllanthin", "start": 116, "end": 127}]}}, "schema": []}
{"input": "UV, IR, MS, (1) H NMR and (13) C NMR spectra were employed to identify phyllanthin.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 12, "end": 17}, {"text": "(13) C", "start": 26, "end": 32}, {"text": "phyllanthin", "start": 71, "end": 82}]}}, "schema": []}
{"input": "The physicochemical properties of phyllanthin were characterized using differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, pH-solubility, ionization property and lipophilicity.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 34, "end": 45}]}}, "schema": []}
{"input": "The results indicated that phyllanthin crystals had the melting point and melting enthalpy range of 96. 67-97. 03 degrees C and 109. 61-116. 34 J/g, respectively.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 27, "end": 38}]}}, "schema": []}
{"input": "Three kinds of phyllanthin crystals, recrystallized by petroleum ether, absolute ethanol and 25% ethanol solution, showed only one polymorph and no polymorphic impurity.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 15, "end": 26}, {"text": "petroleum ether", "start": 55, "end": 70}, {"text": "ethanol", "start": 81, "end": 88}, {"text": "ethanol", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Phyllanthin in a solid state was found to undergo significant thermal decomposition above 200 degrees C.", "output": {"entities": {"chemical": [{"text": "Phyllanthin", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The compound demonstrated good stability in aqueous solution over a pH range of 1. 07-10. 02 for at least 4 h.", "output": {"entities": {}}, "schema": []}
{"input": "The solubility of phyllanthin appeared to be pH-independent of pH range from 1. 07 to 10. 26.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 18, "end": 29}]}}, "schema": []}
{"input": "Ionization property studied by absorbance spectroscopy method was in agreement with the result of pH-solubility study, showing that phyllanthin has no pKa over a pH range of 1. 12-10. 02.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 132, "end": 143}]}}, "schema": []}
{"input": "The log Pow value of phyllanthin was found to be 3. 30 +/- 0. 05 at pH 7. 48, suggesting that phyllanthin may have good permeability through biological membranes.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 21, "end": 32}, {"text": "phyllanthin", "start": 94, "end": 105}]}}, "schema": []}
{"input": "The findings could be useful tools for the development of stable and bioavailable oral dosage forms of phyllanthin.", "output": {"entities": {"chemical": [{"text": "phyllanthin", "start": 103, "end": 114}]}}, "schema": []}
{"input": "Genistein-Modified Poly (ethylene oxide)/Poly (d, l-lactic acid) Electrospun Mats with Improved Antioxidant and Anti-inflammatory Properties.", "output": {"entities": {"chemical": [{"text": "Poly (ethylene oxide)", "start": 19, "end": 40}, {"text": "Poly (d, l-lactic acid)", "start": 41, "end": 64}]}}, "schema": []}
{"input": "Genistein is a phytochemical with a broad range of desirable biological activity for wound healing.", "output": {"entities": {"chemical": [{"text": "Genistein", "start": 0, "end": 9}]}}, "schema": []}
{"input": "However, its poor bioavailability requires developing a new method for fabricating an appropriate carrier vehicle to deliver genistein in a sustained manner.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 125, "end": 134}]}}, "schema": []}
{"input": "Based on the guidance afforded by the ternary phase diagram of poly (d, l-lactic acid) (PDLLA), poly (ethylene oxide) (PEO), and genistein blends, certain selective compositions were electrospun.", "output": {"entities": {"chemical": [{"text": "poly (d, l-lactic acid)", "start": 63, "end": 86}, {"text": "PDLLA", "start": 88, "end": 93}, {"text": "poly (ethylene oxide)", "start": 96, "end": 117}, {"text": "PEO", "start": 119, "end": 122}, {"text": "genistein", "start": 129, "end": 138}]}}, "schema": []}
{"input": "We obtained a uniformly smooth surface morphology in unmodified and genistein-modified PEO/PDLLA fibers, documented by scanning electron microscopy.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 68, "end": 77}, {"text": "PEO", "start": 87, "end": 90}, {"text": "PDLLA", "start": 91, "end": 96}]}}, "schema": []}
{"input": "Moreover, wide-angle X-ray diffraction and (1) H NMR studies revealed that the genistein molecules, successfully incorporated in the blends, remained chemically stable after electrospinning.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 43, "end": 48}, {"text": "genistein", "start": 79, "end": 88}]}}, "schema": []}
{"input": "Besides surface wettability and dimensional stability of the electrospun mats, the released genistein amount has been evaluated as a function of PEO concentration.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 92, "end": 101}, {"text": "PEO", "start": 145, "end": 148}]}}, "schema": []}
{"input": "Our biocompatibility investigations suggest that genistein-modified PEO/PDLLA electrospun mats exhibit strong antioxidant and anti-inflammatory activities which indicate they have potential applications for wound dressings.", "output": {"entities": {"chemical": [{"text": "genistein", "start": 49, "end": 58}, {"text": "PEO", "start": 68, "end": 71}, {"text": "PDLLA", "start": 72, "end": 77}]}}, "schema": []}
{"input": "Selective Permeation of Hydrogen Gas Using Cellulose Nanofibril Film.", "output": {"entities": {"chemical": [{"text": "Hydrogen", "start": 24, "end": 32}]}}, "schema": []}
{"input": "Biobased membranes that can selectively permeate hydrogen gas have been developed from aqueous dispersions of 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCN) prepared from wood cellulose: TOCN-coated plastic films and self-standing TOCN films.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 49, "end": 57}, {"text": "2, 2, 6, 6-tetramethylpiperidine-1-oxyl", "start": 110, "end": 149}, {"text": "TEMPO", "start": 151, "end": 156}]}}, "schema": []}
{"input": "Compared with TOCNs with sodium, lithium, potassium, and cesium carboxylate groups, TOCN with free carboxyl groups (TOCN-COOH) had much high and selective H2 gas permeation performance.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 25, "end": 31}, {"text": "lithium", "start": 33, "end": 40}, {"text": "potassium", "start": 42, "end": 51}, {"text": "cesium carboxylate", "start": 57, "end": 75}, {"text": "carboxyl", "start": 99, "end": 107}, {"text": "COOH", "start": 121, "end": 125}, {"text": "H2", "start": 155, "end": 157}]}}, "schema": []}
{"input": "Because permeabilities of H2, N2, O2, and CO2 gases through the membranes primarily depended on their kinetic diameters, the gas permeation behavior of the various TOCNs can be explained in terms of a diffusion mechanism.", "output": {"entities": {"chemical": [{"text": "H2", "start": 26, "end": 28}, {"text": "N2", "start": 30, "end": 32}, {"text": "O2", "start": 34, "end": 36}, {"text": "CO2", "start": 42, "end": 45}]}}, "schema": []}
{"input": "Thus, the selective H2 gas permeability for TOCN-COOH was probably due to a larger average size in free volume holes present between nanofibrils in the layer and film than those of other TOCNs with metal carboxylate groups.", "output": {"entities": {"chemical": [{"text": "H2", "start": 20, "end": 22}, {"text": "COOH", "start": 49, "end": 53}, {"text": "metal carboxylate", "start": 198, "end": 215}]}}, "schema": []}
{"input": "The obtained results indicate that TOCN-COOH membranes are applicable as biobased H2 gas separation membranes in fuel cell electric power generation systems.", "output": {"entities": {"chemical": [{"text": "COOH", "start": 40, "end": 44}, {"text": "H2", "start": 82, "end": 84}]}}, "schema": []}
{"input": "Antimalarial Activity of Axidjiferosides, New beta-Galactosylceramides from the African Sponge Axinyssa djiferi.", "output": {"entities": {"chemical": [{"text": "Axidjiferosides", "start": 25, "end": 40}, {"text": "beta-Galactosylceramides", "start": 46, "end": 70}]}}, "schema": []}
{"input": "The marine sponge, Axinyssa djiferi, collected on mangrove tree roots in Senegal, was investigated for glycolipids.", "output": {"entities": {}}, "schema": []}
{"input": "A mixture containing new glycosphingolipids, named axidjiferoside-A,-B and-C, accounted for 0. 07% of sponge biomass (dry weight) and for 2. 16% of total lipids.", "output": {"entities": {"chemical": [{"text": "glycosphingolipids", "start": 25, "end": 43}, {"text": "axidjiferoside-A,-B and-C", "start": 51, "end": 76}]}}, "schema": []}
{"input": "It showed a significant antimalarial activity, with a 50% inhibitory concentration (IC50) of 0. 53 +/- 0. 2 mu M against a chloroquine-resistant strain of Plasmodium falciparum.", "output": {"entities": {"chemical": [{"text": "chloroquine", "start": 123, "end": 134}]}}, "schema": []}
{"input": "They were identified as homologous beta-galactopyranosylceramides composed of 2-amino-(6E)-octadec-6-en-1, 3, 4-triol, and the major one, axidjiferoside-A (around 60%), contained 2-hydroxytetracosanoic acid.", "output": {"entities": {"chemical": [{"text": "beta-galactopyranosylceramides", "start": 35, "end": 65}, {"text": "2-amino-(6E)-octadec-6-en-1, 3, 4-triol", "start": 78, "end": 117}, {"text": "axidjiferoside-A", "start": 138, "end": 154}, {"text": "2-hydroxytetracosanoic acid", "start": 179, "end": 206}]}}, "schema": []}
{"input": "Cytotoxicity was studied in vitro on human cancer cell lines (multiple myeloma, colorectal adenocarcinoma, glioblastoma and two lung cancer NSCLC-N6 and A549).", "output": {"entities": {}}, "schema": []}
{"input": "Results of this investigation showed that axidjiferosides are of interest, because they proved a good antiplasmodial activity, with only a low cytotoxicity against various human cell lines and no significant antitrypanosomal and antileishmanial activity.", "output": {"entities": {"chemical": [{"text": "axidjiferosides", "start": 42, "end": 57}]}}, "schema": []}
{"input": "Thus, it seems that galactosylceramides with a beta anomeric configuration may be suitable in searching for new antimalarial drugs.", "output": {"entities": {"chemical": [{"text": "galactosylceramides", "start": 20, "end": 39}]}}, "schema": []}
{"input": "Cannabis intoxication inhibits avoidance action tendencies: a field study in the Amsterdam coffee shops.", "output": {"entities": {}}, "schema": []}
{"input": "RATIONALE: Experimental laboratory studies suggest that the approach bias (relatively fast approach responses) toward substance-related materials plays an important role in problematic substance use.", "output": {"entities": {}}, "schema": []}
{"input": "How this bias is moderated by intention to use versus recent use remains unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the relationship between approach bias and other motivational processes (satiation and craving) and executive functioning remains unclear.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVES: The aim of this study was to investigate the cannabis approach bias before and after cannabis use in real-life setting (Amsterdam coffee shops) and to assess the relationship between approach bias, craving, satiation, cannabis use, and response inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Cannabis, tobacco, and neutral approach and avoidance action tendencies were measured with the Approach Avoidance Task and compared between 42 heavy cannabis users with the intention to use and 45 heavy cannabis users shortly after cannabis use.", "output": {"entities": {}}, "schema": []}
{"input": "The classical Stroop was used to measure response inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple regression analyses were conducted to investigate relationships between approach bias, satiation, craving, cannabis use, and response inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: In contrast to the hypotheses, heavy cannabis users with the intention to use did not show a cannabis approach bias, whereas intoxicated cannabis users did show an approach bias regardless of image category.", "output": {"entities": {}}, "schema": []}
{"input": "This could be attributed to a general slowing of avoidance action tendencies.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, craving was negatively associated with the approach bias, and no relationships were observed between the cannabis approach bias, satiation, prior cannabis use, and response inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: Cannabis intoxication in a real-life setting inhibited general avoidance.", "output": {"entities": {}}, "schema": []}
{"input": "Expression of the cannabis approach bias appeared not to be modulated by satiation or response inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "Unraveling the Reaction Mechanisms Governing Methanol-to-Olefins Catalysis by Theory and Experiment.", "output": {"entities": {"chemical": [{"text": "Methanol", "start": 45, "end": 53}, {"text": "Olefins", "start": 57, "end": 64}]}}, "schema": []}
{"input": "The conversion of methanol to olefins (MTO) over a heterogeneous nanoporous catalyst material is a highly complex process involving a cascade of elementary reactions.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 18, "end": 26}, {"text": "olefins", "start": 30, "end": 37}]}}, "schema": []}
{"input": "The elucidation of the reaction mechanisms leading to either the desired production of ethene and/or propene or undesired deactivation has challenged researchers for many decades.", "output": {"entities": {"chemical": [{"text": "ethene", "start": 87, "end": 93}, {"text": "propene", "start": 101, "end": 108}]}}, "schema": []}
{"input": "Clearly, catalyst choice, in particular topology and acidity, as well as the specific process conditions determine the overall MTO activity and selectivity; however, the subtle balances between these factors remain not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, an overview of proposed reaction mechanisms for the MTO process is given, focusing on the archetypal MTO catalysts, H-ZSM-5 and H-SAPO-34.", "output": {"entities": {"chemical": [{"text": "H-ZSM-5", "start": 132, "end": 139}, {"text": "H-SAPO-34", "start": 144, "end": 153}]}}, "schema": []}
{"input": "The presence of organic species, that is, the so-called hydrocarbon pool, in the inorganic framework forms the starting point for the majority of the mechanistic routes.", "output": {"entities": {}}, "schema": []}
{"input": "The combination of theory and experiment enables a detailed description of reaction mechanisms and corresponding reaction intermediates.", "output": {"entities": {}}, "schema": []}
{"input": "The identification of such intermediates occurs by different spectroscopic techniques, for which theory and experiment also complement each other.", "output": {"entities": {}}, "schema": []}
{"input": "Depending on the catalyst topology, reaction mechanisms proposed thus far involve aromatic or aliphatic intermediates.", "output": {"entities": {}}, "schema": []}
{"input": "Ab initio simulations taking into account the zeolitic environment can nowadays be used to obtain reliable reaction barriers and chemical kinetics of individual reactions.", "output": {"entities": {}}, "schema": []}
{"input": "As a result, computational chemistry and by extension computational spectroscopy have matured to the level at which reliable theoretical data can be obtained, supplying information that is very hard to acquire experimentally.", "output": {"entities": {}}, "schema": []}
{"input": "Special emphasis is given to theoretical developments that open new perspectives and possibilities that aid to unravel a process as complex as methanol conversion over an acidic porous material.", "output": {"entities": {"chemical": [{"text": "methanol", "start": 143, "end": 151}]}}, "schema": []}
{"input": "Metabolism and pathways for denitration of organic nitrates in the human liver.", "output": {"entities": {"chemical": [{"text": "nitrates", "start": 51, "end": 59}]}}, "schema": []}
{"input": "Liver first-pass metabolism differs considerably among organic nitrates but little information exists on the mechanism of denitration of these compounds in hepatic tissue.", "output": {"entities": {"chemical": [{"text": "nitrates", "start": 63, "end": 71}]}}, "schema": []}
{"input": "The metabolism of nitrooxybutyl-esters of flurbiprofen and ferulic-acid, a class of organic nitrates with potential therapeutic implication in variety of different conditions, was investigated in comparison with glyceryl trinitrate (GTN) in human liver by a multiple approach, using a spontaneous metabolism-independent NO donor (NOC-5) as a reference tool.", "output": {"entities": {"chemical": [{"text": "nitrooxybutyl-esters", "start": 18, "end": 38}, {"text": "flurbiprofen", "start": 42, "end": 54}, {"text": "ferulic-acid", "start": 59, "end": 71}, {"text": "nitrates", "start": 92, "end": 100}, {"text": "glyceryl trinitrate", "start": 212, "end": 231}, {"text": "GTN", "start": 233, "end": 236}, {"text": "NO", "start": 320, "end": 322}, {"text": "NOC-5", "start": 330, "end": 335}]}}, "schema": []}
{"input": "Nitrooxybutyl-esters were rapidly and quantitatively metabolized to their respective parent compounds and the organic nitrate moiety nitrooxybutyl-alcohol (NOBA).", "output": {"entities": {"chemical": [{"text": "Nitrooxybutyl-esters", "start": 0, "end": 20}, {"text": "nitrate", "start": 118, "end": 125}, {"text": "nitrooxybutyl-alcohol", "start": 133, "end": 154}, {"text": "NOBA", "start": 156, "end": 160}]}}, "schema": []}
{"input": "Differently from GTN which was rapidly and completely metabolized to nitrite, NOBA was slowly metabolized to nitrate.", "output": {"entities": {"chemical": [{"text": "GTN", "start": 17, "end": 20}, {"text": "nitrite", "start": 69, "end": 76}, {"text": "NOBA", "start": 78, "end": 82}, {"text": "nitrate", "start": 109, "end": 116}]}}, "schema": []}
{"input": "In contrast to the spontaneous NO donor NOC-5, NOBA and GTN did not generate detectable NO and failed to suppress the activity of cytochromeP450; an enzyme known to be inhibited by NO.", "output": {"entities": {"chemical": [{"text": "NO", "start": 31, "end": 33}, {"text": "NOC-5", "start": 40, "end": 45}, {"text": "NOBA", "start": 47, "end": 51}, {"text": "GTN", "start": 56, "end": 59}, {"text": "NO", "start": 88, "end": 90}, {"text": "NO", "start": 181, "end": 183}]}}, "schema": []}
{"input": "The direct identification of NOBA following liver metabolism targets this compound as the functional organic nitrate metabolite of nitrooxybutyl-esters.", "output": {"entities": {"chemical": [{"text": "NOBA", "start": 29, "end": 33}, {"text": "nitrate", "start": 109, "end": 116}, {"text": "nitrooxybutyl-esters", "start": 131, "end": 151}]}}, "schema": []}
{"input": "Moreover the investigation of the pathways for denitration of NOBA and GTN suggests that organic nitrates are not primarily metabolized to NO in the liver but to different extents of nitrite or nitrate depending from their different chemical structure.", "output": {"entities": {"chemical": [{"text": "NOBA", "start": 62, "end": 66}, {"text": "GTN", "start": 71, "end": 74}, {"text": "nitrates", "start": 97, "end": 105}, {"text": "NO", "start": 139, "end": 141}, {"text": "nitrite", "start": 183, "end": 190}, {"text": "nitrate", "start": 194, "end": 201}]}}, "schema": []}
{"input": "It follows that cytochromeP450-dependent metabolism of concomitant drugs is not likely to be affected by oral co-administration of organic nitrates.", "output": {"entities": {"chemical": [{"text": "nitrates", "start": 139, "end": 147}]}}, "schema": []}
{"input": "However the first-pass may differently affect the pharmacological profile of organic nitrates in connection with the different extent of denitration and the distinct bioactive species generated and exported from the liver (nitrate or nitrite).", "output": {"entities": {"chemical": [{"text": "nitrates", "start": 85, "end": 93}, {"text": "nitrate", "start": 223, "end": 230}, {"text": "nitrite", "start": 234, "end": 241}]}}, "schema": []}
{"input": "From a Multipotent Stilbene to Soluble Epoxide Hydrolase Inhibitors with Antiproliferative Properties.", "output": {"entities": {"chemical": [{"text": "Stilbene", "start": 19, "end": 27}, {"text": "Epoxide", "start": 39, "end": 46}]}}, "schema": []}
{"input": "Inspired by nature: Natural product isopropylstilbene was identified as an inhibitor of soluble epoxide hydrolase exhibiting antiproliferative properties.", "output": {"entities": {"chemical": [{"text": "isopropylstilbene", "start": 36, "end": 53}, {"text": "epoxide", "start": 96, "end": 103}]}}, "schema": []}
{"input": "Following the natural product inspired design approach, a library of (E)-styryl-1H-benzo [d] imidazoles was synthesized and evaluated with recombinant enzyme and on several cancer cell lines.", "output": {"entities": {"chemical": [{"text": "(E)-styryl-1H-benzo [d] imidazoles", "start": 69, "end": 103}]}}, "schema": []}
{"input": "Temporal Concordance between Apical and Transcriptional Points-of-Departure for Chemical Risk Assessment.", "output": {"entities": {}}, "schema": []}
{"input": "The number of legacy chemicals without toxicity reference values combined with the rate of new chemical development are overwhelming the capacity of the traditional risk assessment paradigm.", "output": {"entities": {}}, "schema": []}
{"input": "More efficient approaches are needed to quantitatively estimate chemical risks.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, rats were dosed orally with multiple doses of six chemicals for 5 days, 2, 4, and 13 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "Target organs were analyzed for traditional histological and organ weight changes and transcriptional changes using microarrays.", "output": {"entities": {}}, "schema": []}
{"input": "Histological and organ weight changes in this study and the tumor incidences in the original cancer bioassays were analyzed using benchmark dose (BMD) methods to identify noncancer and cancer points-of-departure.", "output": {"entities": {}}, "schema": []}
{"input": "The dose-response changes in gene expression were also analyzed using BMD methods and the responses grouped based on signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "A comparison of transcriptional BMD values for the most sensitive pathway with BMD values for the noncancer and cancer apical endpoints showed a high degree of correlation at all time points.", "output": {"entities": {}}, "schema": []}
{"input": "When the analysis included data from an earlier study with 8 additional chemicals, transcriptional BMD values for the most sensitive pathway were significantly correlated with noncancer (r = 0. 830, p = 0. 0016) and cancer-related (r = 0. 943, p = 0. 0001) BMD values at 13 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "The average ratio of apical-to-transcriptional BMD values was less than two suggesting that for the current chemicals, transcriptional perturbation did not occur at significantly lower doses than apical responses.", "output": {"entities": {}}, "schema": []}
{"input": "Based on our results, we propose a practical framework for application of transcriptomic data to chemical risk assessment.", "output": {"entities": {}}, "schema": []}
{"input": "Methamidophos exposure during the early postnatal period of mice: Immediate and late-emergent effects on the cholinergic and serotonergic systems and on behavior.", "output": {"entities": {"chemical": [{"text": "Methamidophos", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Organophosphates (OPs) are among the most used pesticides.", "output": {"entities": {"chemical": [{"text": "Organophosphates", "start": 0, "end": 16}, {"text": "OPs", "start": 18, "end": 21}]}}, "schema": []}
{"input": "While some OPs have had their use progressively more restricted, other OPs are being used without sufficient investigation of their effects.", "output": {"entities": {"chemical": [{"text": "OPs", "start": 11, "end": 14}, {"text": "OPs", "start": 71, "end": 74}]}}, "schema": []}
{"input": "Here, we investigated the immediate neurochemical and delayed neurochemical and behavioral actions of the OP methamidophos to verify whether there are concerns regarding exposure during early postnatal development.", "output": {"entities": {"chemical": [{"text": "methamidophos", "start": 109, "end": 122}]}}, "schema": []}
{"input": "From the 3 (rd) to the 9 (th) postnatal day (PN), Swiss mice were subcutaneously injected with methamidophos (1 mg/kg).", "output": {"entities": {"chemical": [{"text": "methamidophos", "start": 95, "end": 108}]}}, "schema": []}
{"input": "At PN10, we assessed cholinergic and serotonergic biomarkers in the cerebral cortex and brainstem.", "output": {"entities": {}}, "schema": []}
{"input": "From PN60 to PN63, mice were submitted to a battery of behavioral tests and subsequently to biochemical analyses.", "output": {"entities": {}}, "schema": []}
{"input": "At PN10, the effects were restricted to females and to the cholinergic system: Methamidophos promoted increased choline transporter binding in the brainstem.", "output": {"entities": {"chemical": [{"text": "Methamidophos", "start": 79, "end": 92}, {"text": "choline", "start": 112, "end": 119}]}}, "schema": []}
{"input": "At PN63, in the brainstem, there was a decrease in choline transporter, a female-only decrease in 5HT1A and a male-only increase in 5HT2 receptor binding.", "output": {"entities": {"chemical": [{"text": "choline", "start": 51, "end": 58}]}}, "schema": []}
{"input": "In the cortex, choline acetyltransferase activity was decreased and 5HT2 receptor binding was increased both in males and females.", "output": {"entities": {"chemical": [{"text": "choline", "start": 15, "end": 22}]}}, "schema": []}
{"input": "Methamidophos elicited behavioral alterations suggestive of increased depressive-like behavior and impaired decision-making.", "output": {"entities": {"chemical": [{"text": "Methamidophos", "start": 0, "end": 13}]}}, "schema": []}
{"input": "There were no significant alterations on anxiety-related measures and on memory/learning.", "output": {"entities": {}}, "schema": []}
{"input": "Methamidophos elicited cholinergic and serotonergic alterations that depended on brain region, sex and age of the animals.", "output": {"entities": {"chemical": [{"text": "Methamidophos", "start": 0, "end": 13}]}}, "schema": []}
{"input": "These outcomes, together with the behavioral effects, indicate that this OP is deleterious to the developing brain and that alterations are indeed identified long after the end of exposure.", "output": {"entities": {}}, "schema": []}
{"input": "Pheromone evolution, reproductive genes, and comparative transcriptomics in Mediterranean earthworms (Annelida, Oligochaeta, Hormogastridae).", "output": {"entities": {}}, "schema": []}
{"input": "Animals inhabiting cryptic environments are often subjected to morphological stasis due to the lack of obvious agents driving selection, and hence chemical cues may be important drivers of sexual selection and individual recognition.", "output": {"entities": {}}, "schema": []}
{"input": "Here we provide a comparative analysis of de novo assembled transcriptomes in two Mediterranean earthworm species with the objective to detect pheromone proteins and other reproductive genes that could be involved in cryptic speciation processes, as recently characterized in other earthworm species.", "output": {"entities": {}}, "schema": []}
{"input": "cDNA libraries of unspecific tissue of Hormogaster samnitica and three different tissues of Hormogaster elisae were sequenced in an Illumina Genome Analyzer II or Hi-Seq.", "output": {"entities": {}}, "schema": []}
{"input": "Two pheromones, Attractin and Temptin were detected in all tissue samples and both species.", "output": {"entities": {}}, "schema": []}
{"input": "Attractin resulted in a reliable marker for phylogenetic inference.", "output": {"entities": {}}, "schema": []}
{"input": "Temptin contained multiple paralogues and was slightly overexpressed in the digestive tissue, suggesting that these pheromones could be released with the casts.", "output": {"entities": {}}, "schema": []}
{"input": "Genes involved in sexual determination and fertilization were highly expressed in reproductive tissue.", "output": {"entities": {}}, "schema": []}
{"input": "This is thus the first detailed analysis of the molecular machinery of sexual reproduction in earthworms.", "output": {"entities": {}}, "schema": []}
{"input": "Determining osmotic pressure of drug solutions by air humidity in equilibrium method.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Objective: To establish a new osmotic pressure measuring method with a wide measuring range.", "output": {"entities": {}}, "schema": []}
{"input": "Method: The osmotic pressure of drug solutions is determined by measuring the relative air humidity in equilibrium with the solution.", "output": {"entities": {}}, "schema": []}
{"input": "The freezing point osmometry is used as a control.", "output": {"entities": {}}, "schema": []}
{"input": "Results: The data obtained by the proposed method are comparable to those by the control method, and the measuring range of the proposed method is significantly wider than that of the control method.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: The proposed method is performed in an isothermal and equilibrium state, so it overcomes the defects of the freezing point and dew point osmometries which result from the heterothermal process in the measurement, and therefore is not limited to diluted solutions.", "output": {"entities": {}}, "schema": []}
{"input": "Enhanced Triboelectric Nanogenerators and Triboelectric Nanosensor Using Chemically Modified TiO2 Nanomaterials.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 93, "end": 97}]}}, "schema": []}
{"input": "Mechanical energy harvesting based on triboelectric effect has been proven to be a simple, cost-effective, and robust method for electricity generation.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we developed a rationally designed triboelectric nanogenerator (TENG) by utilizing the contact electrification between a polytetrafluoroethylene (PTFE) thin film and a layer of TiO2 nanomaterial (nanowire and nanosheet) array.", "output": {"entities": {"chemical": [{"text": "polytetrafluoroethylene", "start": 136, "end": 159}, {"text": "PTFE", "start": 161, "end": 165}, {"text": "TiO2", "start": 192, "end": 196}]}}, "schema": []}
{"input": "The as-developed TENG was systematically studied and demonstrated as a self-powered nanosensor toward catechin detection.", "output": {"entities": {"chemical": [{"text": "catechin", "start": 102, "end": 110}]}}, "schema": []}
{"input": "The high sensitivity (detection limit of 5 mu M) and selectivity are achieved through a strong interaction between Ti atoms of TiO2 nanomaterial and enediol group of catechin.", "output": {"entities": {"chemical": [{"text": "Ti", "start": 115, "end": 117}, {"text": "TiO2", "start": 127, "end": 131}, {"text": "catechin", "start": 166, "end": 174}]}}, "schema": []}
{"input": "The output voltage and current density were increased by a factor of 5. 0 and 2. 9, respectively, when adsorbed with catechin of a saturated concentration, because of the charge transfer from catechin to TiO2.", "output": {"entities": {"chemical": [{"text": "catechin", "start": 117, "end": 125}, {"text": "catechin", "start": 192, "end": 200}, {"text": "TiO2", "start": 204, "end": 208}]}}, "schema": []}
{"input": "This study demonstrates the possibility of improving the electrical output of TENG through chemical modification.", "output": {"entities": {}}, "schema": []}
{"input": "Investigation of Protein Detection Parameters Using Nanofunctionalized Organic Field-Effect Transistors.", "output": {"entities": {}}, "schema": []}
{"input": "Biodetection using organic field-effect transistors (OFETs) is gaining increasing interest for applications as diverse as food security, environmental monitoring, and medical diagnostics.", "output": {"entities": {}}, "schema": []}
{"input": "However, there still lacks a comprehensive, empirical study on the fundamental limits of OFET sensors.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, we present a thorough study of the various parameters affecting biosensing using an OFET decorated with gold nanoparticle (AuNP) binding sites.", "output": {"entities": {}}, "schema": []}
{"input": "These parameters include the spacing between receptors, pH of the buffer, and ionic strength of the buffer.", "output": {"entities": {}}, "schema": []}
{"input": "To this end, we employed the thrombin protein and its corresponding DNA binding aptamer to form our model detection system.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate a detection limit of 100 pM for this protein with high selectivity over other proteases in situ.", "output": {"entities": {}}, "schema": []}
{"input": "We describe herein a feasible approach for protein detection with OFETs and a thorough investigation of parameters governing biodetection events using OFETs.", "output": {"entities": {}}, "schema": []}
{"input": "Our obtained results should provide important guidelines to tailor the sensor' s dynamic range to suit other desired OFET-based biodetection applications.", "output": {"entities": {}}, "schema": []}
{"input": "Magnetic-Nanoparticle-Decorated Polypyrrole Microvessels: Toward Encapsulation of mRNA Cap Analogues.", "output": {"entities": {"chemical": [{"text": "Polypyrrole", "start": 32, "end": 43}]}}, "schema": []}
{"input": "Many phosphorylated nucleoside derivatives have therapeutic potential, but their application is limited by problems with membrane permeability and with intracellular delivery.", "output": {"entities": {"chemical": [{"text": "nucleoside", "start": 20, "end": 30}]}}, "schema": []}
{"input": "Here, we prepared polypyrrole microvessel structures modified with superparamagnetic nanoparticles for use as potential carriers of nucleotides.", "output": {"entities": {"chemical": [{"text": "polypyrrole", "start": 18, "end": 29}, {"text": "nucleotides", "start": 132, "end": 143}]}}, "schema": []}
{"input": "The microvessels were prepared via the photochemical polymerization of the monomer onto the surface of aqueous ferrofluidic droplets.", "output": {"entities": {}}, "schema": []}
{"input": "A complementary physicochemical analysis revealed that a fraction of the nanoparticles was embedded in the microvessel walls, while the other nanoparticles were in the core of the vessel.", "output": {"entities": {}}, "schema": []}
{"input": "SQUID (superconducting quantum interference device) measurements indicated that the incorporated nanoparticles retained their superparamagnetic properties; thus, the resulting nanoparticle-modified microvessels can be directed by an external magnetic field.", "output": {"entities": {}}, "schema": []}
{"input": "As a result of these features, these microvessels may be useful as drug carriers in biomedical applications.", "output": {"entities": {}}, "schema": []}
{"input": "To demonstrate the encapsulation of drug molecules, two labeled mRNA cap analogues, nucleotide-derived potential anticancer agents, were used.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 84, "end": 94}]}}, "schema": []}
{"input": "It was shown that the cap analogues are located in the aqueous core of the microvessels and can be released to the external solution by spontaneous permeation through the polymer walls.", "output": {"entities": {}}, "schema": []}
{"input": "Mass spectrometry analysis confirmed that the cap analogues were preserved during encapsulation, storage, and release.", "output": {"entities": {}}, "schema": []}
{"input": "This finding provides a foundation for the future development of anticancer therapies and for the delivery of nucleotide-based therapeutics.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 110, "end": 120}]}}, "schema": []}
{"input": "Enantioselective thiourea-catalyzed intramolecular cope-type hydroamination.", "output": {"entities": {"chemical": [{"text": "thiourea", "start": 17, "end": 25}]}}, "schema": []}
{"input": "Catalysis of Cope-type rearrangements of bis-homoallylic hydroxylamines is demonstrated using chiral thiourea derivatives.", "output": {"entities": {"chemical": [{"text": "bis-homoallylic hydroxylamines", "start": 41, "end": 71}]}}, "schema": []}
{"input": "This formal intramolecular hydroamination reaction provides access to highly enantioenriched alpha-substituted pyrrolidine products and represents a complementary approach to metal-catalyzed methods.", "output": {"entities": {"chemical": [{"text": "pyrrolidine", "start": 111, "end": 122}]}}, "schema": []}
{"input": "Comparative study on effects of two different types of titanium dioxide nanoparticles on human neuronal cells.", "output": {"entities": {"chemical": [{"text": "titanium dioxide", "start": 55, "end": 71}]}}, "schema": []}
{"input": "Titanium dioxide (TiO2) are among most frequently used nanoparticles (NPs).", "output": {"entities": {"chemical": [{"text": "Titanium dioxide", "start": 0, "end": 16}, {"text": "TiO2", "start": 18, "end": 22}]}}, "schema": []}
{"input": "They are present in a variety of consumer products, including food industry in which they are employed as an additive.", "output": {"entities": {}}, "schema": []}
{"input": "The potential toxic effects of these NPs on mammal cells have been extensively studied.", "output": {"entities": {}}, "schema": []}
{"input": "However, studies regarding neurotoxicity and specific effects on neuronal systems are very scarce and, to our knowledge, no studies on human neuronal cells have been reported so far.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the main objective of this work was to investigate the effects of two types of TiO2 NPs, with different crystalline structure, on human SHSY5Y neuronal cells.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 90, "end": 94}]}}, "schema": []}
{"input": "After NPs characterization, a battery of assays was performed to evaluate the viability, cytotoxicity, genotoxicity and oxidative damage in TiO2 NP-exposed SHSY5Y cells.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 140, "end": 144}]}}, "schema": []}
{"input": "Results obtained showed that the behaviour of both types of NPs resulted quite comparable.", "output": {"entities": {}}, "schema": []}
{"input": "They did not reduce the viability of neuronal cells but were effectively internalized by the cells and induced dose-dependent cell cycle alterations, apoptosis by intrinsic pathway, and genotoxicity not related with double strand break production.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, all these effects were not associated with oxidative damage production and, consequently, further investigations on the specific mechanisms underlying the effects observed in this study are required.", "output": {"entities": {}}, "schema": []}
{"input": "Complex mixtures: Relevance of combined exposure to substances at low dose levels.", "output": {"entities": {}}, "schema": []}
{"input": "Upon analysis of chemically complex food matrices a forest of peaks is likely to be found.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of these peaks and concurrent determination of the toxicological relevance upon exposure is very time consuming, expensive and often requires animal studies.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, a safety assessment framework based on the Threshold of Toxicological Concern (TTC) was published to assess the safety of chemically complex matrices more efficiently.", "output": {"entities": {}}, "schema": []}
{"input": "In this safety assessment framework, the toxicological relevance of exposure to unidentified substances in chemically complex food matrices can be related to the Cramer class III TTC threshold, currently set at 90 mu g/day.", "output": {"entities": {}}, "schema": []}
{"input": "However, possible additive or synergistic effects of combined exposure is not covered.", "output": {"entities": {}}, "schema": []}
{"input": "The current evaluation describes the relevance of combined low dose exposure to unidentified substances in chemically complex food matrices.", "output": {"entities": {}}, "schema": []}
{"input": "It is concluded that to some extent cumulative effects at exposure levels for each substance at or below the Cramer class III TTC threshold, being present in a complex mixture including food, might occur.", "output": {"entities": {}}, "schema": []}
{"input": "However the health relevance of possible cumulative effects at this dose level is considered to be that low that a need for a correction factor to cover possible cumulative effects is very low to absent.", "output": {"entities": {}}, "schema": []}
{"input": "Anandamide deficiency and heightened neuropathic pain in aged mice.", "output": {"entities": {"chemical": [{"text": "Anandamide", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Damaging of peripheral nerves may result in chronic neuropathic pain for which the likelihood is increased in the elderly.", "output": {"entities": {}}, "schema": []}
{"input": "We assessed in mice if age-dependent alterations of endocannabinoids contributed to the heightened vulnerability to neuropathic pain at old age.", "output": {"entities": {}}, "schema": []}
{"input": "We assessed nociception, endocannabinoids and the therapeutic efficacy of R-flurbiprofen in young and aged mice in the spared nerve injury model of neuropathic pain.", "output": {"entities": {"chemical": [{"text": "R-flurbiprofen", "start": 74, "end": 88}]}}, "schema": []}
{"input": "R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.", "output": {"entities": {"chemical": [{"text": "R-flurbiprofen", "start": 0, "end": 14}, {"text": "anandamide", "start": 106, "end": 116}]}}, "schema": []}
{"input": "Aged mice developed stronger nociceptive hypersensitivity after sciatic nerve injury than young mice.", "output": {"entities": {}}, "schema": []}
{"input": "This was associated with low anandamide levels in the dorsal root ganglia, spinal cord, thalamus and cortex, which further decreased after nerve injury.", "output": {"entities": {"chemical": [{"text": "anandamide", "start": 29, "end": 39}]}}, "schema": []}
{"input": "In aged mice, R-flurbiprofen had only weak antinociceptive efficacy and it failed to restore normal anandamide levels after nerve injury.", "output": {"entities": {"chemical": [{"text": "R-flurbiprofen", "start": 14, "end": 28}, {"text": "anandamide", "start": 100, "end": 110}]}}, "schema": []}
{"input": "In terms of the mechanisms, we found that fatty acid amide hydrolase (FAAH) which degrades anandamide, was upregulated after nerve injury at both ages, so that this upregulation likely did not account for the age-dependent differences.", "output": {"entities": {"chemical": [{"text": "fatty acid amide", "start": 42, "end": 58}, {"text": "anandamide", "start": 91, "end": 101}]}}, "schema": []}
{"input": "However, enzymes contributing to oxidative metabolism of anandamide, namely cyclooxygenase-1 and Cyp2D6, were increased in the brain of aged mice, possibly enhancing the oxidative breakdown of anandamide.", "output": {"entities": {"chemical": [{"text": "anandamide", "start": 57, "end": 67}, {"text": "anandamide", "start": 193, "end": 203}]}}, "schema": []}
{"input": "This may overwhelm the capacity of R-flurbiprofen to restore anandamide homeostasis and may contribute to the heightened risk for neuropathic pain at old age.", "output": {"entities": {"chemical": [{"text": "R-flurbiprofen", "start": 35, "end": 49}, {"text": "anandamide", "start": 61, "end": 71}]}}, "schema": []}
{"input": "The novel recreational drug 3, 4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: Self-administration and locomotor activity in rats.", "output": {"entities": {"chemical": [{"text": "3, 4-methylenedioxypyrovalerone", "start": 28, "end": 59}, {"text": "MDPV", "start": 61, "end": 65}]}}, "schema": []}
{"input": "Recreational use of the cathinone derivative 3, 4-methylenedioxypyrovalerone (MDPV; \" bath salts \") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions.", "output": {"entities": {"chemical": [{"text": "3, 4-methylenedioxypyrovalerone", "start": 45, "end": 76}, {"text": "MDPV", "start": 78, "end": 82}]}}, "schema": []}
{"input": "Minimal information exists on the effects of MDPV in laboratory models.", "output": {"entities": {"chemical": [{"text": "MDPV", "start": 45, "end": 49}]}}, "schema": []}
{"input": "This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity.", "output": {"entities": {"chemical": [{"text": "MDPV", "start": 37, "end": 41}, {"text": "d-methamphetamine", "start": 91, "end": 108}, {"text": "METH", "start": 110, "end": 114}]}}, "schema": []}
{"input": "Male Wistar rats were trained to self-administer MDPV or METH (0. 05 mg/kg/infusion, i. v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5. 6 mg/kg s. c.).", "output": {"entities": {"chemical": [{"text": "MDPV", "start": 49, "end": 53}, {"text": "METH", "start": 57, "end": 61}, {"text": "MDPV", "start": 203, "end": 207}, {"text": "METH", "start": 211, "end": 215}]}}, "schema": []}
{"input": "METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/h; METH Mean = 0. 4 and Max = 1. 15; MDPV Mean = 0. 9 and Max = 5. 8).", "output": {"entities": {"chemical": [{"text": "METH", "start": 0, "end": 4}, {"text": "MDPV", "start": 9, "end": 13}, {"text": "METH", "start": 88, "end": 92}, {"text": "MDPV", "start": 122, "end": 126}]}}, "schema": []}
{"input": "Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0. 01-0. 50 mg/kg/inf) showed greater potency and efficacy than METH (0. 1-0. 25 mg/kg/inf).", "output": {"entities": {"chemical": [{"text": "MDPV", "start": 95, "end": 99}, {"text": "METH", "start": 165, "end": 169}]}}, "schema": []}
{"input": "In addition, both MDPV and METH increased locomotor activity at lower doses (0. 5-1. 0 mg/kg, s. c.) and transiently decreased activity at the highest dose (5. 6 mg/kg, s. c.).", "output": {"entities": {"chemical": [{"text": "MDPV", "start": 18, "end": 22}, {"text": "METH", "start": 27, "end": 31}]}}, "schema": []}
{"input": "Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature.", "output": {"entities": {"chemical": [{"text": "METH", "start": 66, "end": 70}, {"text": "MDPV", "start": 75, "end": 79}]}}, "schema": []}
{"input": "Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (~ 1. 5 mg/kg/h) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased.", "output": {"entities": {"chemical": [{"text": "MDPV", "start": 85, "end": 89}, {"text": "MDPV", "start": 138, "end": 142}, {"text": "MDPV", "start": 220, "end": 224}]}}, "schema": []}
{"input": "Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH.", "output": {"entities": {"chemical": [{"text": "MDPV", "start": 6, "end": 10}, {"text": "METH", "start": 99, "end": 103}]}}, "schema": []}
{"input": "Discovery of potent selective bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model.", "output": {"entities": {}}, "schema": []}
{"input": "Part II: Optimization studies and demonstration of in vivo efficacy.", "output": {"entities": {}}, "schema": []}
{"input": "Selective phosphodiesterase 2 (PDE2) inhibitors are shown to have efficacy in a rat model of osteoarthritis (OA) pain.", "output": {"entities": {}}, "schema": []}
{"input": "We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of phosphodiesterase 4 (PDE4) inhibitors, while minimizing PDE4 inhibitory activity.", "output": {"entities": {}}, "schema": []}
{"input": "These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like binding mode orthogonal to the cAMP-like binding mode found in PDE4.", "output": {"entities": {"chemical": [{"text": "cGMP", "start": 66, "end": 70}, {"text": "cAMP", "start": 107, "end": 111}]}}, "schema": []}
{"input": "Extensive structure activity relationship studies ultimately led to identification of pyrazolodiazepinone, 22, which was > 1000-fold selective for PDE2 over recombinant, full length PDEs 1B, 3A, 3B, 4A, 4B, 4C, 7A, 7B, 8A, 8B, 9, 10 and 11.", "output": {"entities": {"chemical": [{"text": "pyrazolodiazepinone", "start": 86, "end": 105}]}}, "schema": []}
{"input": "Compound 22 also retained excellent PDE2 selectivity (241-fold to 419-fold) over the remaining recombinant, full length PDEs, 1A, 4D, 5, and 6.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 22 exhibited good pharmacokinetic properties and excellent oral bioavailability (F = 78%, rat).", "output": {"entities": {}}, "schema": []}
{"input": "In an in vivo rat model of OA pain, compound 22 had significant analgesic activity 1 and 3h after a single, 10mg/kg, subcutaneous dose.", "output": {"entities": {}}, "schema": []}
{"input": "Microglial disruption in young mice with early chronic lead exposure.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 44, "end": 46}]}}, "schema": []}
{"input": "We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 61, "end": 63}]}}, "schema": []}
{"input": "Pups were exposed via dams' drinking water from birth to post-natal day 28 to low, high or no Pb conditions.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 94, "end": 96}]}}, "schema": []}
{"input": "We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2).", "output": {"entities": {}}, "schema": []}
{"input": "Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2. 66 to 20. 31 mu g/dL.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 6, "end": 8}]}}, "schema": []}
{"input": "Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Microglia cell body number also differed between groups and reductions were dose-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low-and high-dose animals were reduced.", "output": {"entities": {}}, "schema": []}
{"input": "The results did not support a model of increased neuroinflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals.", "output": {"entities": {"chemical": [{"text": "Pb", "start": 35, "end": 37}, {"text": "Pb", "start": 148, "end": 150}]}}, "schema": []}
{"input": "Nrp2 deficiency leads to trabecular bone loss and is accompanied by enhanced osteoclast and reduced osteoblast numbers.", "output": {"entities": {}}, "schema": []}
{"input": "Neuropilin 1 (Nrp1) and Nrp2 are transmembrane receptors that can bind class 3 semaphorins (Sema3A-G) in addition to VEGF family members to play important roles in axonal guidance, vascularization and angiogenesis, as well as immune responses.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, recent evidence implicates Sema3A/Nrp-mediated signaling in bone regulation.", "output": {"entities": {}}, "schema": []}
{"input": "However, to date the expression of Nrp2 in bone has not been investigated and a possible role for Nrp2 in the maintenance of bone homeostasis in vivo remains unexplored.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that Nrp2, together with its possible coreceptors (Plexin A family members and Plexin D1) and class 3 semaphorin ligands, were expressed during in vitro osteogenic differentiation of bone marrow stromal cells.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, Nrp2 transcript and protein levels were highly induced in hematopoietic bone marrow cell-derived osteoclast cultures.", "output": {"entities": {}}, "schema": []}
{"input": "Osteoblastic as well as osteoclastic Nrp2 expression was confirmed by immunohistochemistry of the long bones of mice.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, Nrp2 knockout mice were characterized by a low bone mass phenotype which was accompanied by an increased number of osteoclasts and a decreased osteoblast count.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these data point to a physiological role for Nrp2 in bone homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network.", "output": {"entities": {"chemical": [{"text": "platinum", "start": 10, "end": 18}]}}, "schema": []}
{"input": "Non-proliferating oocytes within avascular regions of the ovary are exquisitely susceptible to chemotherapy.", "output": {"entities": {}}, "schema": []}
{"input": "Early menopause and sterility are unintended consequences of chemotherapy, and efforts to understand the oocyte apoptotic pathway may provide new targets for mitigating this outcome.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, the c-Abl kinase inhibitor imatinib mesylate (imatinib) has become the focus of research as a fertoprotective drug against cisplatin.", "output": {"entities": {"chemical": [{"text": "imatinib mesylate", "start": 37, "end": 54}, {"text": "imatinib", "start": 56, "end": 64}, {"text": "cisplatin", "start": 133, "end": 142}]}}, "schema": []}
{"input": "However, the mechanism by which imatinib protects oocytes is not fully understood, and reports of the drug' s efficacy have been contradictory.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 32, "end": 40}]}}, "schema": []}
{"input": "Using in vitro culture and subrenal grafting of mouse ovaries, we demonstrated that imatinib inhibits the cisplatin-induced apoptosis of oocytes within primordial follicles.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 84, "end": 92}, {"text": "cisplatin", "start": 106, "end": 115}]}}, "schema": []}
{"input": "We found that, before apoptosis, cisplatin induces c-Abl and TAp73 expression in the oocyte.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 33, "end": 42}]}}, "schema": []}
{"input": "Oocytes undergoing apoptosis showed downregulation of TAp63 and upregulation of Bax.", "output": {"entities": {}}, "schema": []}
{"input": "While imatinib was unable to block cisplatin-induced DNA damage and damage response, such as the upregulation of p53, imatinib inhibited the cisplatin-induced nuclear accumulation of c-Abl/TAp73 and the subsequent downregulation of TAp63 and upregulation of Bax, thereby abrogating oocyte cell death.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 6, "end": 14}, {"text": "cisplatin", "start": 35, "end": 44}, {"text": "imatinib", "start": 118, "end": 126}, {"text": "cisplatin", "start": 141, "end": 150}]}}, "schema": []}
{"input": "Surprisingly, the conditional deletion of Trp63, but not Delta Np63, in oocytes inhibited apoptosis, as well as the accumulation of c-Abl and TAp73 caused by cisplatin.", "output": {"entities": {"chemical": [{"text": "Trp63", "start": 42, "end": 47}, {"text": "cisplatin", "start": 158, "end": 167}]}}, "schema": []}
{"input": "These data suggest that TAp63 is the master regulator of cisplatin-induced oocyte death.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 57, "end": 66}]}}, "schema": []}
{"input": "The expression kinetics of TAp63, c-Abl and TAp73 suggest that cisplatin activates TAp63-dependent expression of c-Abl and TAp73 and, in turn, the activation of TAp73 by c-Abl-induced BAX expression.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 63, "end": 72}]}}, "schema": []}
{"input": "Our findings indicate that imatinib protects oocytes from cisplatin-induced cell death by inhibiting c-Abl kinase, which would otherwise activate TAp73-BAX-mediated apoptosis.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 27, "end": 35}, {"text": "cisplatin", "start": 58, "end": 67}]}}, "schema": []}
{"input": "Thus, imatinib and other c-Abl kinase inhibitors provide an intriguing new way to halt cisplatin-induced oocyte death in early follicles and perhaps conserve the endocrine function of the ovary against chemotherapy. Cell Death and Differentiation advance online publication, 19 April 2013; doi: 10. 1038/cdd. 2013. 31.", "output": {"entities": {"chemical": [{"text": "imatinib", "start": 6, "end": 14}, {"text": "cisplatin", "start": 87, "end": 96}]}}, "schema": []}
{"input": "Use of' split waves' for the measurement of electrocatalytic kinetics: methyl viologen mediated oxygen reduction on a boron-doped diamond electrode.", "output": {"entities": {"chemical": [{"text": "methyl viologen", "start": 71, "end": 86}, {"text": "oxygen", "start": 96, "end": 102}, {"text": "boron", "start": 118, "end": 123}, {"text": "diamond", "start": 130, "end": 137}]}}, "schema": []}
{"input": "The mediated reduction of oxygen via the reduced form of methyl viologen is studied voltammetrically.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 26, "end": 32}, {"text": "methyl viologen", "start": 57, "end": 72}]}}, "schema": []}
{"input": "The investigation is facilitated through the use of a boron-doped diamond electrode, allowing the catalytic response to be clearly delineated from that of the direct oxygen reduction process at the electrode surface.", "output": {"entities": {"chemical": [{"text": "boron", "start": 54, "end": 59}, {"text": "diamond", "start": 66, "end": 73}, {"text": "oxygen", "start": 166, "end": 172}]}}, "schema": []}
{"input": "From simulation a high homogeneous electron transfer rate (6 x 10 (9) M (-1) s (-1)) is found for the one-electron reduction of oxygen to superoxide.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 128, "end": 134}, {"text": "superoxide", "start": 138, "end": 148}]}}, "schema": []}
{"input": "This value is in close agreement with that found using non-electrochemical methods and is significantly higher than the values previously reported in electrochemical studies.", "output": {"entities": {}}, "schema": []}
{"input": "In the latter case it is demonstrated that the underestimation of the electron transfer rate arises due to oversimplification of the reaction mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "Reaction kinetics of CO2 absorption in to phosphonium based anion-functionalized ionic liquids.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 21, "end": 24}, {"text": "phosphonium", "start": 42, "end": 53}]}}, "schema": []}
{"input": "The reaction kinetics between CO2 and trihexyl (tetradecyl) phosphonium ([P66614])-based ionic liquids (ILs) with prolinate ([Pro]), 2-cyanopyrrolide ([2-CNpyr]), and 3-(trifluoromethyl) pyrazolide ([3-CF3pyra]) anions are studied at temperatures from 22-60 degrees C.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 30, "end": 33}, {"text": "trihexyl (tetradecyl) phosphonium", "start": 38, "end": 71}, {"text": "[P66614]", "start": 73, "end": 81}, {"text": "prolinate", "start": 114, "end": 123}, {"text": "[Pro]", "start": 125, "end": 130}, {"text": "2-cyanopyrrolide", "start": 133, "end": 149}, {"text": "[2-CNpyr]", "start": 151, "end": 160}, {"text": "3-(trifluoromethyl) pyrazolide", "start": 167, "end": 197}, {"text": "[3-CF3pyra]", "start": 199, "end": 210}]}}, "schema": []}
{"input": "The absorption of CO2 is carried out in a stirred reactor under pseudo first order conditions.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 18, "end": 21}]}}, "schema": []}
{"input": "ILs are diluted to concentrations of 0. 05, 0. 1 and 0. 15 M with tetraglyme-a nonreactive, low volatility solvent with much lower viscosity than the ILs.", "output": {"entities": {"chemical": [{"text": "tetraglyme", "start": 66, "end": 76}]}}, "schema": []}
{"input": "Physical solubility of CO2 in the mixtures is calculated using correlations developed from CO2 solubility measurements in tetraglyme and the N2O-analogy for ILs and dilute IL solutions.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 23, "end": 26}, {"text": "CO2", "start": 91, "end": 94}, {"text": "tetraglyme", "start": 122, "end": 132}, {"text": "N2O", "start": 141, "end": 144}]}}, "schema": []}
{"input": "The diffusivity of CO2 is estimated from viscosity-dependent correlations chosen after a thorough literature review.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 19, "end": 22}]}}, "schema": []}
{"input": "The results indicate partial first order reaction kinetics with respect to IL with values ranging from 19 500 L mol (-1) s (-1) ([P66614] [Pro]) to 3200 L mol (-1) s (-1) ([P66614] [3-CF3pyra]) at 22 degrees C.", "output": {"entities": {"chemical": [{"text": "[P66614] [Pro]", "start": 129, "end": 143}, {"text": "[P66614] [3-CF3pyra]", "start": 172, "end": 192}]}}, "schema": []}
{"input": "The second order reaction rate constants follow Arrhenius behavior with the highest activation energy of 43 kJ mol (-1) measured for [P66614] [Pro].", "output": {"entities": {"chemical": [{"text": "[P66614] [Pro]", "start": 133, "end": 147}]}}, "schema": []}
{"input": "ILs with aprotic heterocylic anions (AHA), on the other hand, show small activation energies of 18 and 11 kJ mol (-1) for [P66614] [3-CF3pyra] and [P66614] [2-CNpyr], respectively.", "output": {"entities": {"chemical": [{"text": "[P66614] [3-CF3pyra]", "start": 122, "end": 142}, {"text": "[P66614] [2-CNpyr]", "start": 147, "end": 165}]}}, "schema": []}
{"input": "The ILs studied in this work exhibit reactivity comparable to or higher than common aqueous amines.", "output": {"entities": {}}, "schema": []}
{"input": "High reaction rates and tunable capacity make ILs, and AHA ILs in particular, attractive solvents for CO2 separations.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 102, "end": 105}]}}, "schema": []}
{"input": "P300 during response inhibition is associated with ad-lib alcohol consumption in social drinkers.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 58, "end": 65}]}}, "schema": []}
{"input": "Reduced amplitude of the cortical P300 event-related potential (ERP) component during response inhibition is associated with vulnerability to alcohol use disorders.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 142, "end": 149}]}}, "schema": []}
{"input": "In the current study, we investigated the effect of an experimental manipulation of response conflict on the amplitude of the P300 component during response inhibition, and examined whether individual differences in the amplitude of this P300 component would predict voluntary ad-lib alcohol consumption, in social drinkers.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 284, "end": 291}]}}, "schema": []}
{"input": "Using a repeated measures design, 16 participants performed a stop-signal task after receiving instructions that either emphasised or de-emphasised response conflict while their electroencephalogram (EEG) was concurrently recorded, before their ad-lib drinking was assessed.", "output": {"entities": {}}, "schema": []}
{"input": "Results revealed that task instructions had the predicted effects on behavioural indices of response inhibition and the associated P300 components.", "output": {"entities": {}}, "schema": []}
{"input": "Most importantly, individual differences in the amplitude of P300 subcomponents during response inhibition were negatively correlated with ad-lib alcohol consumption.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 146, "end": 153}]}}, "schema": []}
{"input": "Results provide the first experimental support for theoretical models that posit that reduced amplitude of the P300 during response inhibition is associated with alcohol-seeking behaviour in humans.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 162, "end": 169}]}}, "schema": []}
{"input": "Npas4 is activated by melatonin, and drives the clock gene Cry1 in the ovine pars tuberalis.", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 22, "end": 31}]}}, "schema": []}
{"input": "Seasonal mammals integrate changes in the duration of nocturnal melatonin secretion to drive annual physiological cycles.", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 64, "end": 73}]}}, "schema": []}
{"input": "Melatonin receptors within the proximal pituitary region, the pars tuberalis (PT), are essential in regulating seasonal neuroendocrine responses.", "output": {"entities": {"chemical": [{"text": "Melatonin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "In the ovine PT, melatonin is known to influence acute changes in transcriptional dynamics coupled to the onset (dusk) and offset (dawn) of melatonin secretion, leading to a potential interval-timing mechanism capable of decoding changes in day-length (photoperiod).", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 17, "end": 26}, {"text": "melatonin", "start": 140, "end": 149}]}}, "schema": []}
{"input": "Melatonin offset at dawn is linked to cAMP accumulation, which directly induces transcription of the clock gene Per1.", "output": {"entities": {"chemical": [{"text": "Melatonin", "start": 0, "end": 9}, {"text": "cAMP", "start": 38, "end": 42}]}}, "schema": []}
{"input": "The rise of melatonin at dusk induces a separate and distinct cohort, including the clock-regulated genes Cry1 and Nampt, but little is known of the up-stream mechanisms involved.", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 12, "end": 21}]}}, "schema": []}
{"input": "Here, we used next generation sequencing of the ovine PT transcriptome at melatonin onset, and identified Npas4 as a rapidly induced bHLH-PAS domain transcription factor.", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 74, "end": 83}]}}, "schema": []}
{"input": "In vivo we show nuclear localisation of NPAS4 protein in presumptive melatonin target cells of the PT (alpha GSU-expressing cells), while in situ hybridisation studies identified acute and transient expression in the PT of Npas4 in response to melatonin.", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 69, "end": 78}, {"text": "melatonin", "start": 244, "end": 253}]}}, "schema": []}
{"input": "In vitro, NPAS4 forms functional dimers with bHLH-PAS domain co-factors ARNT, ARNT2 and ARNTL, transactivating both Cry1 and Nampt ovine promoter reporters.", "output": {"entities": {}}, "schema": []}
{"input": "Using a combination of 5 `deletions and site-directed mutagenesis we show NPAS4: ARNT transactivation to be co-dependent upon two conserved central midline elements (CMEs) within the Cry1 promoter.", "output": {"entities": {}}, "schema": []}
{"input": "Our data thus reveal NPAS4 as a candidate immediate early-response gene in the ovine PT, driving molecular responses to melatonin.", "output": {"entities": {"chemical": [{"text": "melatonin", "start": 120, "end": 129}]}}, "schema": []}
{"input": "Clinical implementation of pharmacogenetics: more than one gene at a time.", "output": {"entities": {}}, "schema": []}
{"input": "Tricyclic antidepressant (TCA) clinical pharmacogenetic implementation guidelines for CYP2D6 and CYP2C19 genotypes highlight the importance of both genes.", "output": {"entities": {}}, "schema": []}
{"input": "However, studies of the combined impact of the two genes are sparse, limiting the ability to make strong recommendations based on both genes.", "output": {"entities": {}}, "schema": []}
{"input": "The warfarin pharmacogenetics literature highlights the strength of a multigenic approach for discovery and clinical implementation.", "output": {"entities": {}}, "schema": []}
{"input": "For optimal impact and interpretation, investigators are encouraged to conduct studies in the context of previously well-defined pharmacogenetics markers.", "output": {"entities": {}}, "schema": []}
{"input": "Flavone C-glycosides from the flowers of Trollius chinensis and their anti-complementary activity.", "output": {"entities": {"chemical": [{"text": "Flavone C-glycosides", "start": 0, "end": 20}]}}, "schema": []}
{"input": "Phytochemical investigation of ethanol extract from the flowers of Trollius chinensis Bunge resulted in the isolation of two new flavone C-glycosides (1-2), along with 10 known compounds (3-12).", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 31, "end": 38}, {"text": "flavone C-glycosides", "start": 129, "end": 149}]}}, "schema": []}
{"input": "The structures of the new compounds were established as 6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl orientin (1) and 6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl vitexin (2) on the basis of various spectroscopic analysis (including different 1D and 2D NMR spectroscopies, high-resolution electrospray ionization mass spectrometry) and chemical evidences.", "output": {"entities": {"chemical": [{"text": "6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl orientin", "start": 56, "end": 129}, {"text": "6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl vitexin", "start": 138, "end": 210}]}}, "schema": []}
{"input": "Bioassay showed that eight flavonoids inhibited complement activation on the classic pathway in vitro, with their IC50 values ranging from 0. 88 to 4. 02 mM, which may contribute to the applications of the herb in treatment of acute respiratory distress syndrome, etc.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 27, "end": 37}]}}, "schema": []}
{"input": "Spatially-Resolved EELS Analysis of Antibody Distribution on Biofunctionalized Magnetic Nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "Spatially resolved electron energy loss spectroscopy (SR-EELS) using scanning transmission electron microscope (STEM) allows the identification and determination of the spatial distribution of the components/elements of immuno-functionalized core-shell superparamagnetic magnetite nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we report that SR-EELS measurements allow the direct identification and study of the biological moieties (protein G and anti-HRP antibody) in complex bionanocarriers of relevance for biomedical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings show that the biomacromolecules are located on specific areas on the nanoparticles' surface.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, efficiency of this functionalization was evaluated by means of biochemical techniques.", "output": {"entities": {}}, "schema": []}
{"input": "The receptor binding fragment of alpha-fetoprotein is a promising new vector for the selective delivery of antineoplastic agents.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract The alpha-fetoprotein (AFP) binding protein, a putative AFP receptor, is a tumour marker that is present on the surfaces of malignant cells.", "output": {"entities": {}}, "schema": []}
{"input": "AFP enters cells through receptor-mediated endocytosis.", "output": {"entities": {}}, "schema": []}
{"input": "The recombinant C-terminal fragment of AFP (AFP-3BC, which consists of amino acid residues 473-596) was obtained by the expression in Escherichia coli.", "output": {"entities": {"chemical": [{"text": "C", "start": 16, "end": 17}, {"text": "amino acid", "start": 71, "end": 81}]}}, "schema": []}
{"input": "AFP-3BC was shown to be bound specifically to the AFP putative receptor on tumour cells and accumulated by endocytosis in these cells in a similar manner to that of full-length human AFP.", "output": {"entities": {}}, "schema": []}
{"input": "In lymphocytes, the binding and endocytosis of AFP-3BC were absent.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the AFP receptor binding site was shown experimentally to be located within the AFP-3BC sequence.", "output": {"entities": {}}, "schema": []}
{"input": "A conjugate of synthesised AFP-3BC with the antitumour antibiotic doxorubicin (DOX-AFP-3BC) demonstrated high antitumour activity in vitro.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 66, "end": 77}, {"text": "DOX", "start": 79, "end": 82}]}}, "schema": []}
{"input": "Thus, AFP-3BC can be used successfully as a vector for the targeted selective delivery of drugs into tumour cells.", "output": {"entities": {}}, "schema": []}
{"input": "Pyranoflavones: A Group of Small-Molecule Probes for Exploring the Active Site Cavities of Cytochrome P450 Enzymes 1A1, 1A2, and 1B1.", "output": {"entities": {"chemical": [{"text": "Pyranoflavones", "start": 0, "end": 14}]}}, "schema": []}
{"input": "Selective inhibition of P450 enzymes is the key to block the conversion of environmental procarcinogens to their carcinogenic metabolites in both animals and humans.", "output": {"entities": {}}, "schema": []}
{"input": "To discover highly potent and selective inhibitors of P450s 1A1, 1A2, and 1B1, as well as to investigate active site cavities of these enzymes, 14 novel flavone derivatives were prepared as chemical probes.", "output": {"entities": {"chemical": [{"text": "flavone", "start": 153, "end": 160}]}}, "schema": []}
{"input": "Fluorimetric enzyme inhibition assays were used to determine the inhibitory activities of these probes toward P450s 1A1, 1A2, 1B1, 2A6, and 2B1.", "output": {"entities": {}}, "schema": []}
{"input": "A highly selective P450 1B1 inhibitor 5-hydroxy-4'-propargyloxyflavone (5H4' FPE) was discovered.", "output": {"entities": {"chemical": [{"text": "5-hydroxy-4'-propargyloxyflavone", "start": 38, "end": 70}, {"text": "5H4' FPE", "start": 72, "end": 80}]}}, "schema": []}
{"input": "Some tested compounds also showed selectivity between P450s 1A1 and 1A2.", "output": {"entities": {}}, "schema": []}
{"input": "alpha-Naphthoflavone-like and 5-hydroxyflavone derivatives preferentially inhibited P450 1A2, while beta-naphthoflavone-like flavone derivatives showed selective inhibition of P450 1A1.", "output": {"entities": {"chemical": [{"text": "alpha-Naphthoflavone", "start": 0, "end": 20}, {"text": "5-hydroxyflavone", "start": 30, "end": 46}, {"text": "beta-naphthoflavone", "start": 100, "end": 119}, {"text": "flavone", "start": 125, "end": 132}]}}, "schema": []}
{"input": "On the basis of structural analysis, the active site cavity models of P450 enzymes 1A1 and 1A2 were generated, demonstrating a planar long strip cavity and a planar triangular cavity, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Sustainable diets: Harnessing the nutrition agenda.", "output": {"entities": {}}, "schema": []}
{"input": "There has been rapid growth in the global population over the last century and estimates for 2050 are a global population of over 9billion.", "output": {"entities": {}}, "schema": []}
{"input": "These mouths need to be fed and the nutritional quality of the food received will be a key determinant of future health.", "output": {"entities": {}}, "schema": []}
{"input": "Alongside this expansion in the world' s population, rapid economic growth in China, India and South America is increasing demand for protein-rich foods, especially meat and dairy products, causing concern about the impact this may have on green house gas emissions.", "output": {"entities": {}}, "schema": []}
{"input": "As economies strengthen and dietary and lifestyle patterns become more westernised, the so-called diseases of affluence are becoming ever more evident, often alongside malnutrition.", "output": {"entities": {}}, "schema": []}
{"input": "This paper considers these challenges and the need to embed thinking about nutrition into discussions about sustainability of the food supply.", "output": {"entities": {}}, "schema": []}
{"input": "FAO/INFOODS food composition database for biodiversity.", "output": {"entities": {}}, "schema": []}
{"input": "Nutrient content can vary as much between different varieties of the same foods, as they do among different foods.", "output": {"entities": {}}, "schema": []}
{"input": "Knowledge of varietal differences can therefore mean the difference between nutrient adequacy and inadequacy.", "output": {"entities": {}}, "schema": []}
{"input": "The FAO/INFOODS food composition database for biodiversity has been developed with analytical data for foods described at the level of variety, cultivar and breed, and for underutilized and wild foods.", "output": {"entities": {}}, "schema": []}
{"input": "It contains 6411 food entries and values for 451 components together with the bibliographic references and other information.", "output": {"entities": {}}, "schema": []}
{"input": "The database is in MS Excel format and can be downloaded free-of-charge from the INFOODS website http://www. fao. org/infoods/biodiversity/index _ en. stm.", "output": {"entities": {}}, "schema": []}
{"input": "It is intended to annually publish new editions, making these data available for national and regional food composition databases.", "output": {"entities": {}}, "schema": []}
{"input": "This database could be used to raise the awareness, promote and investigate food biodiversity and help to better estimate nutrient intakes.", "output": {"entities": {}}, "schema": []}
{"input": "Trans fatty acids in a range of UK processed foods.", "output": {"entities": {"chemical": [{"text": "Trans fatty acids", "start": 0, "end": 17}]}}, "schema": []}
{"input": "A survey to determine the trans fatty acid content of a range of processed foods was carried out in response to recent reformulation work by the food industry to lower the artificial trans fatty acid content of processed products.", "output": {"entities": {"chemical": [{"text": "trans fatty acid", "start": 26, "end": 42}, {"text": "trans fatty acid", "start": 183, "end": 199}]}}, "schema": []}
{"input": "Sixty two composite samples, made up of between 5 and 12 sub-samples, were collected in 2010 and were analysed for fatty acids, and a range of nutrients.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 115, "end": 126}]}}, "schema": []}
{"input": "The foods analysed included pizza, garlic bread, breakfast cereals, quiche, fat spreads, a range of fish and meat products, chips, savoury snacks, confectionery and ice cream.", "output": {"entities": {}}, "schema": []}
{"input": "Levels of trans fatty acids were reduced considerably compared with previous UK analyses of similar foods where comparisons are possible.", "output": {"entities": {"chemical": [{"text": "trans fatty acids", "start": 10, "end": 27}]}}, "schema": []}
{"input": "Concentrations of trans elaidic acid (t9-C18: 1) from hydrogenated oils in all samples were < 0. 2g/100g food.", "output": {"entities": {"chemical": [{"text": "trans elaidic acid", "start": 18, "end": 36}, {"text": "t9-C18: 1", "start": 38, "end": 47}]}}, "schema": []}
{"input": "These results confirm information provided by the food industry in 2007 on the levels of trans fats in key processed food sectors.", "output": {"entities": {}}, "schema": []}
{"input": "Application of ethnic food composition data for understanding the diet and nutrition of South Asians in the UK.", "output": {"entities": {}}, "schema": []}
{"input": "Lack of food composition data, recipe information and portion sizes for ethnic foods are commonly reported problems for dietary assessment of ethnic minority groups.", "output": {"entities": {}}, "schema": []}
{"input": "One of the main aims of this study was to use food composition data to validate portion sizes, identify important sources of nutrients and describe the characteristics of the South Asian diet.", "output": {"entities": {}}, "schema": []}
{"input": "The top five ethnic foods containing highest levels of selected nutrients were lamb balti (3mg/100g iron), lamb kebab (3. 2mg/100g zinc), mixed dhal (62 mu g/100g folate), fish curry (1. 4 mu g/100g vitamin D), ghee (968 mu g/100g retinol) and toor dhal (9. 1g/100g dietary fibre).", "output": {"entities": {"chemical": [{"text": "iron", "start": 100, "end": 104}, {"text": "zinc", "start": 131, "end": 135}, {"text": "folate", "start": 163, "end": 169}, {"text": "vitamin D", "start": 199, "end": 208}, {"text": "retinol", "start": 231, "end": 238}]}}, "schema": []}
{"input": "Typical adult South Asian diets included traditional cereals (chapatti, rice and paratha) and low consumption of meat dishes; with vegetable curries contributing most towards energy intake.", "output": {"entities": {}}, "schema": []}
{"input": "A higher consumption of full fat milk and fruit juices by toddlers and school children were observed when compared with the National Diet and Nutrition Survey of the UK.", "output": {"entities": {}}, "schema": []}
{"input": "Food composition activities in South Africa.", "output": {"entities": {}}, "schema": []}
{"input": "Researchers at the South African Medical Research Council used the Bangkok Declaration, Thailand, 2009, as a guideline for their food composition activities.", "output": {"entities": {}}, "schema": []}
{"input": "The vision is to build a comprehensive food composition database for the country.", "output": {"entities": {}}, "schema": []}
{"input": "Activities are directed at increasing the number of food items with country-specific nutrient information; encouraging research organisations, universities and the food industry to become involved in nutrient data generation and the generation of yield factors for South African dishes.", "output": {"entities": {}}, "schema": []}
{"input": "The introduction of the South African Food Data System (SAFOODS) website and a symposium were major food composition activities.", "output": {"entities": {}}, "schema": []}
{"input": "Educating users on the correct application of food composition data is an important endeavour.", "output": {"entities": {}}, "schema": []}
{"input": "The national South African Food Data Advisory Group (SAFDAG) formed in 2008, advises and supports food composition activities at SAFOODS.", "output": {"entities": {}}, "schema": []}
{"input": "In conclusion, with the support of SAFDAG, SAFOODS activities are aimed at compiling a country-specific food composition database and promoting its scientific use.", "output": {"entities": {}}, "schema": []}
{"input": "The nutrient composition of three cuts obtained from P-class South African pork carcasses.", "output": {"entities": {}}, "schema": []}
{"input": "The shoulder, loin and leg from P-class pork carcasses were used to determine the nutrient composition of both raw and cooked cuts.", "output": {"entities": {}}, "schema": []}
{"input": "Significantly lower fat content were observed in the current study for the leg (5. 21g/100g) and loin (6. 99g/100g) compared to the shoulder cut (10. 32g/100g).", "output": {"entities": {}}, "schema": []}
{"input": "The overall percentage fat for all three cuts was less than 10% which is recommended by the South African Heart Mark.", "output": {"entities": {}}, "schema": []}
{"input": "The cooked loin cut contained the most protein (27. 50g/100g) of the three cooked cuts.", "output": {"entities": {}}, "schema": []}
{"input": "When compared to other meat products (beef, mutton and chicken) it is clear that pork is a good source of B vitamins, especially vitamin B3.", "output": {"entities": {"chemical": [{"text": "B vitamins", "start": 106, "end": 116}, {"text": "vitamin B3", "start": 129, "end": 139}]}}, "schema": []}
{"input": "The cooked loin cut contained the least vitamin B1 (0. 22mg/100g), B2 (0. 02mg/100g) but the most vitamin B3 (7. 09mg/100g), of the three cooked cuts.", "output": {"entities": {"chemical": [{"text": "vitamin B1", "start": 40, "end": 50}, {"text": "vitamin B3", "start": 98, "end": 108}]}}, "schema": []}
{"input": "The 100g cooked shoulder, loin and leg cuts provide on average 40. 11% protein, 5. 19% magnesium, 3. 37% calcium, 24. 29% phosphorus, 18. 22% zinc, 22. 33% iron and 22. 50% vitamin B1, 2. 57% vitamin B2 and 42. 6% vitamin B3 of Recommended Daily Allowances for males, age 25-50.", "output": {"entities": {"chemical": [{"text": "magnesium", "start": 87, "end": 96}, {"text": "calcium", "start": 105, "end": 112}, {"text": "phosphorus", "start": 122, "end": 132}, {"text": "zinc", "start": 142, "end": 146}, {"text": "iron", "start": 156, "end": 160}, {"text": "vitamin B1", "start": 173, "end": 183}, {"text": "vitamin B2", "start": 192, "end": 202}, {"text": "vitamin B3", "start": 214, "end": 224}]}}, "schema": []}
{"input": "Energy from a 100g portion provides 5. 81% of the Recommended Daily Allowances.", "output": {"entities": {}}, "schema": []}
{"input": "To conclude, the pork cuts are undoubtedly a good source of nutrients that is required for good health because it is high in protein, have a low fat content and are a nutrient-packed choice for the family and compares favourably with the fat, energy, and cholesterol content of many other meats and poultry.", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 255, "end": 266}]}}, "schema": []}
{"input": "Variability in the contents of pork meat nutrients and how it may affect food composition databases.", "output": {"entities": {}}, "schema": []}
{"input": "Pork meat is generally recognised as a food with relevant nutritional properties because of its content in high biological value proteins, group B vitamins, minerals especially heme iron, trace elements and other bioactive compounds.", "output": {"entities": {"chemical": [{"text": "heme iron", "start": 177, "end": 186}]}}, "schema": []}
{"input": "But pork meat also contributes to the intake of fat, saturated fatty acids, cholesterol, and other substances that, in inappropriate amounts, may result in negative physiologically effects.", "output": {"entities": {"chemical": [{"text": "saturated fatty acids", "start": 53, "end": 74}, {"text": "cholesterol", "start": 76, "end": 87}]}}, "schema": []}
{"input": "However, there are relevant factors affecting the content of many of these substances and somehow such variability should be taken into consideration.", "output": {"entities": {}}, "schema": []}
{"input": "So, genetics, age and even type of muscle have a relevant influence on the amount of fat and the contents in heme iron.", "output": {"entities": {"chemical": [{"text": "heme iron", "start": 109, "end": 118}]}}, "schema": []}
{"input": "Also the composition in fatty acids of triacylglycerols is very sensitive to the contents of cereals in the feed; for instance, polyunsaturated fatty acids may range from 10% to 22% in pork meat.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 24, "end": 35}, {"text": "triacylglycerols", "start": 39, "end": 55}, {"text": "polyunsaturated fatty acids", "start": 128, "end": 155}]}}, "schema": []}
{"input": "The content of other nutrients, like vitamins E and A, are also depending on the type of feed.", "output": {"entities": {"chemical": [{"text": "vitamins E and A", "start": 37, "end": 53}]}}, "schema": []}
{"input": "Some bioactive substances like coenzyme Q10, taurine, glutamine, creatine, creatinine, carnosine and anserine show a large dependence on the type of muscle.", "output": {"entities": {"chemical": [{"text": "coenzyme Q10", "start": 31, "end": 43}, {"text": "taurine", "start": 45, "end": 52}, {"text": "glutamine", "start": 54, "end": 63}, {"text": "creatine", "start": 65, "end": 73}, {"text": "creatinine", "start": 75, "end": 85}, {"text": "carnosine", "start": 87, "end": 96}, {"text": "anserine", "start": 101, "end": 109}]}}, "schema": []}
{"input": "This manuscript describes the main factors affecting the composition of pork meat nutrients and how these changes may affect the general food composition databases.", "output": {"entities": {}}, "schema": []}
{"input": "The new on-line Czech Food Composition Database.", "output": {"entities": {}}, "schema": []}
{"input": "The new on-line Czech Food Composition Database (FCDB) was launched on http://www. czfcdb. cz in December 2010 as a main freely available channel for dissemination of Czech food composition data.", "output": {"entities": {}}, "schema": []}
{"input": "The application is based on a complied FCDB documented according to the EuroFIR standardised procedure for full value documentation and indexing of foods by the LanguaL (TM) Thesaurus.", "output": {"entities": {}}, "schema": []}
{"input": "A content management system was implemented for administration of the website and performing data export (comma-separated values or EuroFIR XML transport package formats) by a compiler.", "output": {"entities": {}}, "schema": []}
{"input": "Reference/s are provided for each published value with linking to available freely accessible on-line sources of data (e. g. full texts, EuroFIR Document Repository, on-line national FCDBs).", "output": {"entities": {}}, "schema": []}
{"input": "LanguaL (TM) codes are displayed within each food record as searchable keywords of the database.", "output": {"entities": {}}, "schema": []}
{"input": "A photo (or a photo gallery) is used as a visual descriptor of a food item.", "output": {"entities": {}}, "schema": []}
{"input": "The application is searchable on foods, components, food groups, alphabet and a multi-field advanced search.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary fibre: Challenges in production and use of food composition data.", "output": {"entities": {}}, "schema": []}
{"input": "Dietary fibre is a heterogeneous group of components for which several definitions and analytical methods were developed over the past decades, causing confusion among users and producers of dietary fibre data in food composition databases.", "output": {"entities": {}}, "schema": []}
{"input": "An overview is given of current definitions and analytical methods.", "output": {"entities": {}}, "schema": []}
{"input": "Some of the issues related to maintaining dietary fibre values in food composition databases are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Newly developed AOAC methods (2009. 01 or modifications) yield higher dietary fibre values, due to the inclusion of low molecular weight dietary fibre and resistant starch.", "output": {"entities": {}}, "schema": []}
{"input": "For food composition databases procedures need to be developed to combine' classic' and' new' dietary fibre values since re-analysing all foods on short notice is impossible due to financial restrictions.", "output": {"entities": {}}, "schema": []}
{"input": "Standardised value documentation procedures are important to evaluate dietary fibre values from several sources before exchanging and using the data, e. g. for dietary intake research.", "output": {"entities": {}}, "schema": []}
{"input": "Codex dietary fibre definition-Justification for inclusion of carbohydrates from 3 to 9 degrees of polymerisation.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 62, "end": 75}]}}, "schema": []}
{"input": "The main controversy about the DF definition, adopted by the commission of Codex Alimentarius, refers to the inclusion of carbohydrates of 3-9 degrees of polymerisation (DP), decision which may be made individually by the authorities of each country.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 122, "end": 135}]}}, "schema": []}
{"input": "Due to the possibility of having two definitions and the negative impact it would cause over the harmonisation of nutritional information, a bibliographic review was carried, from 2009 to 2011, aiming to gather justifications for the inclusion of carbohydrates of 3-9 DP in the definition.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 247, "end": 260}]}}, "schema": []}
{"input": "The current review presents scientific bases that are directed to three topics: physiological aspects; repercussion over the analytical method; and impact on consumers and other users.", "output": {"entities": {}}, "schema": []}
{"input": "The decision of including unavailable carbohydrates of 3-9 DP in the definition of DF may cause effective global harmonisation in the nutritional labelling, considering that the main goal is to help consumers choose healthy foods.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 38, "end": 51}]}}, "schema": []}
{"input": "Biogenic amines content as a measure of the quality of wines of Abruzzo (Italy).", "output": {"entities": {"chemical": [{"text": "amines", "start": 9, "end": 15}]}}, "schema": []}
{"input": "Aim of this research was to study the effect of some agronomic and oenological factors on the content of biogenic amines as quality index of sixty-five Abruzzo wines.", "output": {"entities": {"chemical": [{"text": "amines", "start": 114, "end": 120}]}}, "schema": []}
{"input": "Sum of amines was found to be decreasing in the order: red (19. 3 +/- 12. 8mgL (-1)), ros e (9. 20 +/- 6. 34mgL (-1)), white (7. 67 +/- 3. 84mgL (-1)) wine.", "output": {"entities": {"chemical": [{"text": "amines", "start": 7, "end": 13}]}}, "schema": []}
{"input": "Significant differences in relationship among amines levels and chemical and chemico-physical characteristics of red, white and ros e wine are due to their different biotechnological process and winemaking.", "output": {"entities": {"chemical": [{"text": "amines", "start": 46, "end": 52}]}}, "schema": []}
{"input": "Besides the aging treatment, influential seems to be the effect of the winery, regardless of the area in which it is situated.", "output": {"entities": {}}, "schema": []}
{"input": "The single amines significantly correlated with their sum were putrescine, histamine and tyramine, even if reached levels were below toxicity threshold, demonstrating a good quality of the wines of Abruzzo whose consumption is no risk to the health of the consumer following the rules of proper nutrition.", "output": {"entities": {"chemical": [{"text": "amines", "start": 11, "end": 17}, {"text": "putrescine", "start": 63, "end": 73}, {"text": "histamine", "start": 75, "end": 84}, {"text": "tyramine", "start": 89, "end": 97}]}}, "schema": []}
{"input": "Laboratory performance on analysis of mandatory nutrients and preparation of nutrition labelling.", "output": {"entities": {}}, "schema": []}
{"input": "This study assessed the performance of 17 laboratories in Thailand in analysing mandatory nutrients in salted, fried broad bean and in using data to prepare nutrition labels.", "output": {"entities": {}}, "schema": []}
{"input": "Nutrient levels in the test material, as robust mean (x (*)) and robust standard deviation (s (*)), were assigned in line with ISO 13528.", "output": {"entities": {}}, "schema": []}
{"input": "Data obtained from the laboratories were statistically evaluated against these values.", "output": {"entities": {}}, "schema": []}
{"input": "Laboratories with satisfactory, questionable and unsatisfactory results for each nutrient were identified based on robust z-score.", "output": {"entities": {}}, "schema": []}
{"input": "Laboratories achieving satisfactory analytical results (z-score >= 2) were for lipid, 82%; protein, 85%; Na, 82%; Ca, 62%; Fe, 81%; ash, 70%; and moisture, 62%.", "output": {"entities": {"chemical": [{"text": "Na", "start": 105, "end": 107}, {"text": "Ca", "start": 114, "end": 116}, {"text": "Fe", "start": 123, "end": 125}]}}, "schema": []}
{"input": "Reference values for some nutrients in broad bean powder were developed using data from satisfactorily performing laboratories.", "output": {"entities": {}}, "schema": []}
{"input": "Less than 20% of the laboratories demonstrated good performance in preparing nutrition labels.", "output": {"entities": {}}, "schema": []}
{"input": "Common mistakes were the nutrition information format, estimation of serving size and serving (s) per package.", "output": {"entities": {}}, "schema": []}
{"input": "An electrophoretic mobility shift assay identifies a mechanistically unique inhibitor of protein sumoylation.", "output": {"entities": {}}, "schema": []}
{"input": "The dynamic, posttranslational modification of proteins with a small ubiquitin-like modifier (SUMO) tag has been recognized as an important cellular regulatory mechanism relevant to a number of cancers as well as normal embryonic development.", "output": {"entities": {}}, "schema": []}
{"input": "As part of a program aimed toward the identification of inhibitors of SUMO-conjugating enzymes, we developed a microfluidic electrophoretic mobility shift assay to monitor sumoylation events in real time.", "output": {"entities": {}}, "schema": []}
{"input": "We disclose herein the use of this assay to identify a cell-permeable compound capable of blocking the transfer of SUMO-1 from the E2 enzyme Ubc9 to the substrate.", "output": {"entities": {}}, "schema": []}
{"input": "We screened a small collection of compounds and identified an oxygenated flavonoid derivative that inhibits sumoylation in vitro.", "output": {"entities": {"chemical": [{"text": "oxygenated flavonoid", "start": 62, "end": 82}]}}, "schema": []}
{"input": "Next, we carried out an in-depth mechanistic analysis that ruled out many common false-positive mechanisms such as aggregation or alkylation.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, we report that this flavonoid inhibits a single step in the sumoylation cascade: the transfer of SUMO from the E2 enzyme (Ubc9) thioester conjugate to the substrate.", "output": {"entities": {"chemical": [{"text": "flavonoid", "start": 33, "end": 42}]}}, "schema": []}
{"input": "In addition to having a unique mechanism of action, this inhibitor has a discrete structure-activity relationship uncharacteristic of a promiscuous inhibitor.", "output": {"entities": {}}, "schema": []}
{"input": "Cell-based studies showed that the flavonoid inhibits the sumoylation of topoisomerase-I in response to camptothecin treatment in two different breast cancer cell lines, while isomeric analogs are inactive.", "output": {"entities": {"chemical": [{"text": "camptothecin", "start": 104, "end": 116}]}}, "schema": []}
{"input": "Importantly, this compound blocks sumoylation while not affecting ubiquitylation in cells.", "output": {"entities": {}}, "schema": []}
{"input": "This work identifies a point of entry for pharmacologic inhibition of the sumoylation cascade and may serve as the basis for continued study of additional pharmacophores that modulate SUMO-conjugating enzymes such as Ubc9.", "output": {"entities": {}}, "schema": []}
{"input": "In Vitro Reconstitution of Complexes between proMatrix Metalloproteinase-9 and the Proteoglycans Serglycin and Versican.", "output": {"entities": {}}, "schema": []}
{"input": "Previously we have shown that a fraction of the matrix metalloproteinase-9 (MMP-9) synthesized by the macrophage cell line THP-1 was bound to a chondroitin sulphate proteoglycan (CSPG) core protein as a reduction sensitive heteromer.", "output": {"entities": {}}, "schema": []}
{"input": "It was also shown that the hemopexin-like (PEX) domain and the fibronectin-like (FnII) module in the enzyme are involved in the heteromer formation.", "output": {"entities": {}}, "schema": []}
{"input": "In the present work we show that reduction sensitive and SDS-stable heteromers can be reconstituted in vitro by mixing proMMP-9 with either serglycin, versican or CSPGs isolated from various monocytic cell lines.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 57, "end": 60}]}}, "schema": []}
{"input": "In addition, a strong but SDS-soluble proMMP-9. CSPG heteromer was formed.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 26, "end": 29}]}}, "schema": []}
{"input": "The two macromolecules in the SDS-stable reduction sensitive heteromers were not linked together by disulphide bonds.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 30, "end": 33}, {"text": "disulphide", "start": 100, "end": 110}]}}, "schema": []}
{"input": "As for the heteromer isolated from THP-1 cells, the in vitro reconstituted SDS-stable and SDS-soluble heteromers had a weaker binding to gelatin than the proMMP-9 monomer.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 75, "end": 78}, {"text": "SDS", "start": 90, "end": 93}]}}, "schema": []}
{"input": "Furthermore, gelatin inhibited the in vitro reconstitution of the heteromers, showing that the FnII module is involved in the complex formation.", "output": {"entities": {}}, "schema": []}
{"input": "TIMP-1 could not be detected in the formed proMMP-9. CSPG complexes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the presence of TIMP-1 inhibited the formation of the SDS-soluble heteromer, but not the SDS-stable reduction sensitive heteromer.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 63, "end": 66}, {"text": "SDS", "start": 98, "end": 101}]}}, "schema": []}
{"input": "This indicates that different regions in the PEX domain are involved the formation of these heteromers.", "output": {"entities": {}}, "schema": []}
{"input": "This article is protected by copyright.", "output": {"entities": {}}, "schema": []}
{"input": "All rights reserved.", "output": {"entities": {}}, "schema": []}
{"input": "Robust autoactivation, chymotrypsin C independence and diminished secretion define a subset of hereditary pancreatitis associated cationic trypsinogen mutants.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations in human cationic trypsinogen cause hereditary pancreatitis by altering its proteolytic regulation of activation and degradation by chymotrypsin C (CTRC).", "output": {"entities": {}}, "schema": []}
{"input": "CTRC stimulates trypsinogen autoactivation by processing the activation peptide to a shorter form but also promotes degradation by cleaving the calcium binding loop in trypsinogen.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 144, "end": 151}]}}, "schema": []}
{"input": "Mutations render trypsinogen resistant to CTRC-mediated degradation and/or increase processing of the activation peptide by CTRC.", "output": {"entities": {}}, "schema": []}
{"input": "Here we demonstrate that activation peptide mutations D19A, D22G, K23R and K23 _ I24insIDK robustly increased the rate of trypsinogen autoactivation, both in the presence and absence of CTRC.", "output": {"entities": {}}, "schema": []}
{"input": "Degradation of the mutants by CTRC was unchanged and processing of the activation peptide was increased only in the D19A mutant by 4-fold.", "output": {"entities": {}}, "schema": []}
{"input": "Surprisingly, however, this increased processing had only a minimal effect on autoactivation.", "output": {"entities": {}}, "schema": []}
{"input": "The tetra-aspartate motif in the trypsinogen activation peptide binds calcium (KD ~ 1. 6 mM), which stimulates autoactivation.", "output": {"entities": {"chemical": [{"text": "aspartate", "start": 10, "end": 19}, {"text": "calcium", "start": 70, "end": 77}]}}, "schema": []}
{"input": "Unexpectedly, calcium binding was not compromised by any of the activation peptide mutations.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 14, "end": 21}]}}, "schema": []}
{"input": "Despite normal binding, autoactivation of mutants D22G and K23 _ I24insIDK was not stimulated by calcium.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Finally, the activation peptide mutants exhibited reduced secretion from transfected cells, and secreted trypsinogen levels were inversely proportional with autoactivation rates.", "output": {"entities": {}}, "schema": []}
{"input": "We conclude that D19A, D22G, K23R and K23 _ I24insIDK form a mechanistically distinct subset of hereditary pancreatitis associated mutations, which exert their effect primarily through direct stimulation of autoactivation, independently of CTRC.", "output": {"entities": {}}, "schema": []}
{"input": "The potentially severe clinical impact of the markedly increased autoactivation is offset by diminished secretion, resulting in a clinical phenotype indistinguishable from typical hereditary pancreatitis.", "output": {"entities": {}}, "schema": []}
{"input": "This article is protected by copyright.", "output": {"entities": {}}, "schema": []}
{"input": "All rights reserved.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological evaluation of phosphorylated flavonoids as potent and selective inhibitors of cholesterol esterase.", "output": {"entities": {"chemical": [{"text": "phosphorylated flavonoids", "start": 39, "end": 64}, {"text": "cholesterol", "start": 103, "end": 114}]}}, "schema": []}
{"input": "A series of phosphorylated flavonoids were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and acetylcholinesterase (AChE).", "output": {"entities": {"chemical": [{"text": "phosphorylated flavonoids", "start": 12, "end": 37}, {"text": "cholesterol", "start": 109, "end": 120}]}}, "schema": []}
{"input": "The results showed that most of the synthesized compounds exhibited nanomolar potency against CEase, much better than the parent flavonoids.", "output": {"entities": {"chemical": [{"text": "flavonoids", "start": 129, "end": 139}]}}, "schema": []}
{"input": "Furthermore, these phosphorylated flavonoids demonstrated good to high selectivity for CEase over AChE, which only showed micromolar potency inhibition of AChE.", "output": {"entities": {"chemical": [{"text": "phosphorylated flavonoids", "start": 19, "end": 44}]}}, "schema": []}
{"input": "The most selective and potent inhibitor of CEase (3e) had IC50 value of 0. 72 nM and 11800-fold selectivity for CEase over AChE.", "output": {"entities": {}}, "schema": []}
{"input": "The structure-activity relationships revealed that the free hydroxyl group at position 5 and phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of CEase.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 60, "end": 68}, {"text": "phosphate", "start": 93, "end": 102}, {"text": "phosphorylated flavonoids", "start": 130, "end": 155}]}}, "schema": []}
{"input": "The inhibition mechanism and kinetic characterization studies indicated that they are irreversible competitive inhibitors of CEase.", "output": {"entities": {}}, "schema": []}
{"input": "Flies Cope with Uncontrollable Stress by Learned Helplessness.", "output": {"entities": {}}, "schema": []}
{"input": "In a wide range of animals, uncontrollable stressful events can induce a condition called \" learned helplessness. \" In mammals it is associated with low general activity, poor learning, disorders of sleep and feeding, ulcers, and reduced immune status, as well as with increased serotonin in parts of the brain.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 279, "end": 288}]}}, "schema": []}
{"input": "It is considered an animal model of depression in humans [1-4].", "output": {"entities": {}}, "schema": []}
{"input": "Here we investigate learned helplessness in Drosophila, showing that this behavioral state consists of a cognitive and a modulatory, possibly mood-like, component.", "output": {"entities": {}}, "schema": []}
{"input": "A fly, getting heated as soon as it stops walking, reliably resumes walking to escape the heat.", "output": {"entities": {}}, "schema": []}
{"input": "If, in contrast, the fly is not in control of the heat, it learns that its behavior has no effect and quits responding.", "output": {"entities": {}}, "schema": []}
{"input": "In this state, the fly walks slowly and takes longer and more frequent rests, as if it were \" depressed. \" This downregulation of walking behavior is more pronounced in females than in males.", "output": {"entities": {}}, "schema": []}
{"input": "Learned helplessness in Drosophila is an example of how, in a certain situation, behavior is organized according to its expected consequences.", "output": {"entities": {}}, "schema": []}
{"input": "Trimming of damaged 3' overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases.", "output": {"entities": {}}, "schema": []}
{"input": "Both Metnase and Artemis possess endonuclease activities that trim 3' overhangs of duplex DNA.", "output": {"entities": {}}, "schema": []}
{"input": "To assess the potential of these enzymes for facilitating resolution of damaged ends during double-strand break rejoining, substrates bearing a variety of normal and structurally modified 3' overhangs were constructed, and treated either with Metnase or with Artemis plus DNA-dependent protein kinase (DNA-PK).", "output": {"entities": {}}, "schema": []}
{"input": "Unlike Artemis, which trims long overhangs to 4-5 bases, cleavage by Metnase was more evenly distributed over the length of the overhang, but with significant sequence dependence.", "output": {"entities": {}}, "schema": []}
{"input": "In many substrates, Metnase also induced marked cleavage in the double-stranded region within a few bases of the overhang.", "output": {"entities": {}}, "schema": []}
{"input": "Like Artemis, Metnase efficiently trimmed overhangs terminated in 3'-phosphoglycolates (PGs), and in some cases the presence of 3'-PG stimulated cleavage and altered its specificity.", "output": {"entities": {"chemical": [{"text": "3'-phosphoglycolates", "start": 66, "end": 86}, {"text": "PGs", "start": 88, "end": 91}, {"text": "3'-PG", "start": 128, "end": 133}]}}, "schema": []}
{"input": "The nonplanar base thymine glycol in a 3' overhang severely inhibited cleavage by Metnase in the vicinity of the modified base, while Artemis was less affected.", "output": {"entities": {"chemical": [{"text": "thymine glycol", "start": 19, "end": 33}]}}, "schema": []}
{"input": "Nevertheless, thymine glycol moieties could be removed by Metnase-or Artemis-mediated cleavage at sites farther from the terminus than the lesion itself.", "output": {"entities": {"chemical": [{"text": "thymine glycol", "start": 14, "end": 28}]}}, "schema": []}
{"input": "In in vitro end-joining systems based on human cell extracts, addition of Artemis, but not Metnase, effected robust trimming of an unligatable 3'-PG overhang, resulting in a dramatic stimulation of ligase IV-and XLF-dependent end joining.", "output": {"entities": {"chemical": [{"text": "3'-PG", "start": 143, "end": 148}]}}, "schema": []}
{"input": "Thus, while both Metnase and Artemis are biochemically capable of resolving a variety of damaged DNA ends for the repair of complex double-strand breaks, Artemis appears to act more efficiently in the context of other nonhomologous end joining proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Pathogenesis, current treatments and future directions for idiopathic pulmonary fibrosis.", "output": {"entities": {}}, "schema": []}
{"input": "Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) of unknown origin characterized by epithelial cell dysfunctions, accumulation of fibroblasts and myofibroblasts and relentless deposition of extracellular matrix (ECM).", "output": {"entities": {}}, "schema": []}
{"input": "Improved diagnostic accuracy and better trial design have provided important insights from recent clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "Perhaps the most important insight was the realization that' standard therapy' was actually harmful!", "output": {"entities": {}}, "schema": []}
{"input": "This review summarizes the current understanding of the cell types that are altered in IPF and the pathogenic mechanisms that have been identified.", "output": {"entities": {}}, "schema": []}
{"input": "It also reviews recent clinical trial results and interpretations.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, we highlight attractive biologic targets and therapies in development with recommendations for future therapeutic avenues.", "output": {"entities": {}}, "schema": []}
{"input": "Synergistic enhancement of cancer therapy using a combination of heat shock protein targeted HPMA copolymer-drug conjugates and gold nanorod induced hyperthermia.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 93, "end": 97}]}}, "schema": []}
{"input": "In the field of nanomedicine, selective delivery to cancer cells is a common goal, where active targeting strategies are often employed to increase tumor accumulation.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, tumor hyperthermia was utilized as a means to increase the active delivery of heat shock protein (HSP) targeted N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-drug conjugates.", "output": {"entities": {"chemical": [{"text": "N-(2-hydroxypropyl) methacrylamide", "start": 127, "end": 161}, {"text": "HPMA", "start": 163, "end": 167}]}}, "schema": []}
{"input": "Following hyperthermia, induced expression of cell surface heat shock protein (HSP) glucose regulated protein 78kDa (GRP78) was utilized for targeted drug therapy.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 84, "end": 91}]}}, "schema": []}
{"input": "Conjugates bearing the anticancer agents aminohexylgeldanamycin (AHGDM), docetaxel (DOC), or cisplatin and the GRP78 targeting peptide WDLAWMFRLPVG were synthesized and characterized.", "output": {"entities": {"chemical": [{"text": "aminohexylgeldanamycin", "start": 41, "end": 63}, {"text": "AHGDM", "start": 65, "end": 70}, {"text": "docetaxel", "start": 73, "end": 82}, {"text": "DOC", "start": 84, "end": 87}, {"text": "cisplatin", "start": 93, "end": 102}]}}, "schema": []}
{"input": "Binding to cell surface expressed heat shock protein GRP78 on the surface of human prostate cancer DU145 cells was evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "HSP targeted AHGDM and DOC conjugates demonstrated active binding comparable to native targeting peptide.", "output": {"entities": {"chemical": [{"text": "AHGDM", "start": 13, "end": 18}, {"text": "DOC", "start": 23, "end": 26}]}}, "schema": []}
{"input": "They were then assessed in vitro for the ability to synergistically induce cytotoxicity in combination with moderate hyperthermia (43 degrees C, 30min).", "output": {"entities": {}}, "schema": []}
{"input": "HSP targeted DOC conjugates exhibited high potency against DU145 cells with an IC50 of 2. 4nM.", "output": {"entities": {"chemical": [{"text": "DOC", "start": 13, "end": 16}]}}, "schema": []}
{"input": "HSP targeted AHGDM and DOC conjugates demonstrated synergistic effects in combination with hyperthermia with combination index values of 0. 65 and 0. 45 respectively.", "output": {"entities": {"chemical": [{"text": "AHGDM", "start": 13, "end": 18}, {"text": "DOC", "start": 23, "end": 26}]}}, "schema": []}
{"input": "Based on these results, HSP targeted DOC conjugates were selected for in vivo evaluation.", "output": {"entities": {"chemical": [{"text": "DOC", "start": 37, "end": 40}]}}, "schema": []}
{"input": "In DU145 tumor bearing mice, a single treatment of tumor hyperthermia, induced via gold nanorod mediated plasmonic photothermal therapy, and intravenous administration of HSP targeted HPMA copolymer-docetaxel at 10mg/kg resulted in maintained tumor regression for a period of 30days.", "output": {"entities": {"chemical": [{"text": "HPMA", "start": 184, "end": 188}, {"text": "docetaxel", "start": 199, "end": 208}]}}, "schema": []}
{"input": "These results demonstrate the potential for tumor hyperthermia to increase the delivery of HSP targeted macromolecular chemotherapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "Cannabinoids increase type 1 cannabinoid receptor expression in a cell culture model of striatal neurons: Implications for Huntington' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "The type 1 cannabinoid receptor (CB1) is a G protein-coupled receptor that is expressed at high levels in the striatum.", "output": {"entities": {}}, "schema": []}
{"input": "Activation of CB1 increases expression of neuronal trophic factors and inhibits neurotransmitter release from GABA-ergic striatal neurons.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 110, "end": 114}]}}, "schema": []}
{"input": "CB1 mRNA levels can be elevated by treatment with cannabinoids in non-neuronal cells.", "output": {"entities": {}}, "schema": []}
{"input": "We wanted to determine whether cannabinoid treatment could induce CB1 expression in a cell culture model of striatal neurons and, if possible, determine the molecular mechanism by which this occurred.", "output": {"entities": {}}, "schema": []}
{"input": "We found that treatment of STHdh (7/7) cells with the cannabinoids ACEA, mAEA, and AEA produced a CB1 receptor-dependent increase in CB1 promoter activity, mRNA, and protein expression.", "output": {"entities": {}}, "schema": []}
{"input": "This response was Akt-and NF-kappa B-dependent.", "output": {"entities": {}}, "schema": []}
{"input": "Because decreased CB1 expression is thought to contribute to the pathogenesis of Huntington' s disease (HD), we wanted to determine whether cannabinoids could increase CB1 expression in STHdh (7/111) and (111/111) cells expressing the mutant huntingtin protein.", "output": {"entities": {}}, "schema": []}
{"input": "We observed that cannabinoid treatment increased CB1 mRNA levels approximately 10-fold in STHdh (7/111) and (111/111) cells, compared to vehicle treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, cannabinoid treatment improved ATP production, increased the expression of the trophic factor BDNF-2, and the mitochondrial regulator PGC1 alpha, and reduced spontaneous GABA release, in HD cells.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 44, "end": 47}, {"text": "GABA", "start": 183, "end": 187}]}}, "schema": []}
{"input": "Therefore, cannabinoid-mediated increases in CB1 levels could reduce the severity of some molecular pathologies observed in HD.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic social stress during adolescence: Interplay of paroxetine treatment and ageing.", "output": {"entities": {"chemical": [{"text": "paroxetine", "start": 55, "end": 65}]}}, "schema": []}
{"input": "Exposure to chronic stress during developmental periods is a risk factor for a number of psychiatric disorders.", "output": {"entities": {}}, "schema": []}
{"input": "While the direct effects of stress exposure have been studied extensively, little is known about the long-lasting effects and the interaction with ageing.", "output": {"entities": {}}, "schema": []}
{"input": "The same holds true for the treatment with selective serotonin reuptake inhibitors (SSRIs), which have been shown to prevent or reverse some stress-induced effects.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 53, "end": 62}]}}, "schema": []}
{"input": "Here, we studied the direct and long-lasting impact of chronic social stress during adolescence and the impact of chronic treatment with the SSRI paroxetine in adulthood and aged animals.", "output": {"entities": {"chemical": [{"text": "paroxetine", "start": 146, "end": 156}]}}, "schema": []}
{"input": "Therefore, male CD1 mice at the age of 28 days were subjected to 7 weeks of chronic social stress.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment with paroxetine was performed per os with a dosage of 20 mg/g BW.", "output": {"entities": {"chemical": [{"text": "paroxetine", "start": 15, "end": 25}]}}, "schema": []}
{"input": "We were able to reverse most of the effects of chronic social stress in adult mice (4 months old) and to some extend in aged animals (15 months old) with the SSRI treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Especially the regulation of the HPA axis seems to be affected in aged mice with a shift to the use of vasopressin.", "output": {"entities": {"chemical": [{"text": "vasopressin", "start": 103, "end": 114}]}}, "schema": []}
{"input": "Our results demonstrate that chronic stress exposure and antidepressant treatment at the end of the developmental period can have a significant and long-lasting impact, highly relevant for healthy ageing.", "output": {"entities": {}}, "schema": []}
{"input": "Evaluation of the suitability of chromatographic systems to predict human skin permeation of neutral compounds.", "output": {"entities": {}}, "schema": []}
{"input": "Several chromatographic systems (three systems of high-performance liquid chromatography and two micellar electrokinetic chromatography systems) besides the reference octanol-water partition system are evaluated by a systematic procedure previously proposed in order to know their ability to model human skin permeation.", "output": {"entities": {"chemical": [{"text": "octanol", "start": 167, "end": 174}]}}, "schema": []}
{"input": "The precision achieved when skin-water permeability coefficients are correlated against chromatographic retention factors is predicted within the framework of the solvation parameter model.", "output": {"entities": {}}, "schema": []}
{"input": "It consists in estimating the contribution of error due to the biological and chromatographic data, as well as the error coming from the dissimilarity between the human skin permeation and the chromatographic systems.", "output": {"entities": {}}, "schema": []}
{"input": "Both predictions and experimental tests show that all correlations are greatly affected by the considerable uncertainty of the skin permeability data and the error associated to the dissimilarity between the systems.", "output": {"entities": {}}, "schema": []}
{"input": "Correlations with much better predictive abilities are achieved when the volume of the solute is used as additional variable, which illustrates the main roles of both lipophilicity and size of the solute to penetrate through the skin.", "output": {"entities": {}}, "schema": []}
{"input": "In this way, the considered systems are able to give precise estimations of human skin permeability coefficients.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, the HPLC systems with common C18 columns provide the best performances in emulating the permeation of neutral compounds from aqueous solution through the human skin.", "output": {"entities": {}}, "schema": []}
{"input": "As a result, a methodology based on easy, fast, and economical HPLC measurements in a common C18 column has been developed.", "output": {"entities": {}}, "schema": []}
{"input": "After a validation based on training and test sets, the method has been applied with good results to the estimation of skin permeation of several hormones and pesticides.", "output": {"entities": {}}, "schema": []}
{"input": "Targeting intracellular compartments by magnetic polymeric nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "Superparamagnetic iron oxide nanoparticles (SPIONs) show a great promise for a wide specter of bioapplications, due to their characteristic magnetic properties exhibited only in the presence of magnetic field.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 18, "end": 28}]}}, "schema": []}
{"input": "Their advantages in the fields of magnetic drug targeting and imaging are well established and their safety is assumed, since iron oxide nanoparticles have already been approved for in vivo application, however, according to many literature reports the bare metal oxide nanoparticles may cause toxic effects on treated cells.", "output": {"entities": {"chemical": [{"text": "iron oxide", "start": 126, "end": 136}]}}, "schema": []}
{"input": "Therefore, it is reasonable to prevent the direct interactions between metal oxide core and surrounding environment.", "output": {"entities": {}}, "schema": []}
{"input": "In the current research ricinoleic acid coated maghemite nanoparticles were successfully synthesized, characterized and incorporated in the polymeric matrix, resulting in nanosized magnetic polymeric particles.", "output": {"entities": {"chemical": [{"text": "ricinoleic acid", "start": 24, "end": 39}, {"text": "maghemite", "start": 47, "end": 56}]}}, "schema": []}
{"input": "The carrier system was shown to exhibit superparamagnetic properties and was therefore responsive towards external magnetic field.", "output": {"entities": {}}, "schema": []}
{"input": "Bioevaluation using T47-D breast cancer cells confirmed internalization of magnetic polymeric nanoparticles (MNPs) and their intracellular localization in various subcellular compartments, depending on presence/absence of external magnetic field.", "output": {"entities": {}}, "schema": []}
{"input": "However, the number of internalized MNPs observed by fluorescent and transmission electron microscopy was relatively low, making such way of targeting effective only for delivery of highly potent drugs.", "output": {"entities": {}}, "schema": []}
{"input": "The scanning electron microscopy of treated cells revealed that MNPs influenced the cell adhesion, when external magnetic field was applied, and that treatment resulted in damaged apical plasma membrane right after exposure to the magnetic carrier.", "output": {"entities": {}}, "schema": []}
{"input": "On the other hand, MNPs showed only reversibly reduced cellular metabolic activity in concentrations up to 200 mu g/ml and, in the tested concentration the cell cycle distribution was within the normal range, indicating safety of the established magnetic carrier system for the treated cells.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis, radioiodination and in vivo screening of novel potent iodinated and fluorinated radiotracers as melanoma imaging and therapeutic probes.", "output": {"entities": {}}, "schema": []}
{"input": "In order to develop new iodinated and fluorinated matched-pair radiotracers for Single-Photon Emission Computed Tomography (SPECT)/Positron Emission Tomography (PET) imaging and targeted radionuclide therapy of melanoma, we successfully synthesized and radiolabelled with iodine-125 seven new derivatives, starting from our previously described lead structure 3.", "output": {"entities": {"chemical": [{"text": "iodine-125", "start": 272, "end": 282}]}}, "schema": []}
{"input": "The relevance of these radiotracers for gamma scintigraphic imaging of melanoma in rodent was assessed.", "output": {"entities": {}}, "schema": []}
{"input": "The tumoural radioactivity uptake was most often high and specific even at early time points (12. 1-18. 3% ID/g at 3 h p. i. for [(125) I] 39-42) and a fast clearance from the non-target organs was observed.", "output": {"entities": {"chemical": [{"text": "(125) I", "start": 130, "end": 137}]}}, "schema": []}
{"input": "Also, calculated effective doses that could be delivered to tumours when using corresponding [(131) I]-labelled analogues were generally higher than 100 cGy/MBq injected (98. 9-150. 5 cGy/MBq for [(131) I] 39-42).", "output": {"entities": {"chemical": [{"text": "(131) I", "start": 94, "end": 101}, {"text": "(131) I", "start": 197, "end": 204}]}}, "schema": []}
{"input": "These results make compounds 39-42 suitable candidates for (i) PET imaging of melanoma after labelling with fluorine-18 and (ii) targeted radionuclide therapy of disseminated melanoma after labelling with iodine-131.", "output": {"entities": {"chemical": [{"text": "fluorine-18", "start": 108, "end": 119}, {"text": "iodine-131", "start": 205, "end": 215}]}}, "schema": []}
{"input": "Triazolothiadiazoles and triazolothiadiazines-Biologically attractive scaffolds.", "output": {"entities": {"chemical": [{"text": "Triazolothiadiazoles", "start": 0, "end": 20}, {"text": "triazolothiadiazines", "start": 25, "end": 45}]}}, "schema": []}
{"input": "Contemporary medicinal chemistry faces diverse challenges from several directions, including the need for both potency and specificity of any therapeutic agent.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, in the present perspective, the triazolothiadiazoles and triazolothiadiazines with broad spectrum biological profile have matured into indispensable heterocyclic scaffolds.", "output": {"entities": {"chemical": [{"text": "triazolothiadiazoles", "start": 43, "end": 63}, {"text": "triazolothiadiazines", "start": 68, "end": 88}]}}, "schema": []}
{"input": "This review article is an effort to summarize medicinal chemistry investigations over the last decade, in search for new N-bridged heterocycles which can be a rich source of promising biological activities.", "output": {"entities": {"chemical": [{"text": "N", "start": 121, "end": 122}]}}, "schema": []}
{"input": "The Fusarium toxin deoxynivalenol (DON) modulates the LPS induced acute phase reaction in pigs.", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 19, "end": 33}, {"text": "DON", "start": 35, "end": 38}]}}, "schema": []}
{"input": "The systemic effects of the Fusarium toxin deoxynivalenol (DON) and of bacterial lipopolysaccharides (LPS) were studied in male castrated pigs (40. 4 +/- 3. 7kg) infused intravenously with either DON or LPS alone (100 mu gDON/kg/h, 7. 5 mu g/LPS/kg/h), or together (100 mu gDON plus 7. 5 mu g/LPS/kg/h).", "output": {"entities": {"chemical": [{"text": "deoxynivalenol", "start": 43, "end": 57}, {"text": "DON", "start": 59, "end": 62}, {"text": "DON", "start": 196, "end": 199}, {"text": "gDON", "start": 221, "end": 225}, {"text": "gDON", "start": 273, "end": 277}]}}, "schema": []}
{"input": "The Control group received a saline infusion (n = 6/treatment, 24h observation period).", "output": {"entities": {}}, "schema": []}
{"input": "An additional DON infusion did not exacerbate the clinical signs observed in LPS-infused pigs.", "output": {"entities": {"chemical": [{"text": "DON", "start": 14, "end": 17}]}}, "schema": []}
{"input": "For example, rectal temperature climaxed after 4h (40. 4 +/- 0. 2 degrees C) and 5h (40. 1 +/- 0. 3 degrees C), in the LPS and LPS + DON groups, respectively.", "output": {"entities": {"chemical": [{"text": "DON", "start": 133, "end": 136}]}}, "schema": []}
{"input": "Saline and DON alone did not induce an acute phase reaction as indicated by unaltered plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) while LPS caused a significant rise of both cytokines.", "output": {"entities": {"chemical": [{"text": "DON", "start": 11, "end": 14}]}}, "schema": []}
{"input": "TNF-alpha plasma peak concentrations were significantly higher in the LPS compared to the DON + LPS group (94. 3 +/- 17. 2ng/mL vs. 79. 2 +/- 15. 7ng/mL) while IL-6 climaxed earlier in the latter group (3h p. i. vs. 2h p. i.).", "output": {"entities": {"chemical": [{"text": "DON", "start": 90, "end": 93}]}}, "schema": []}
{"input": "From the tested clinical-chemical plasma characteristics the total bilirubin concentration and the ASAT activity were strongly elevated by the LPS infusion and additionally increased and decreased by DON, respectively.", "output": {"entities": {"chemical": [{"text": "bilirubin", "start": 67, "end": 76}, {"text": "DON", "start": 200, "end": 203}]}}, "schema": []}
{"input": "In conclusion, the LPS-induced effects were only marginally modified by DON.", "output": {"entities": {"chemical": [{"text": "DON", "start": 72, "end": 75}]}}, "schema": []}
{"input": "Thermal inactivation reaction rates for ricin are influenced by pH and carbohydrates.", "output": {"entities": {"chemical": [{"text": "carbohydrates", "start": 71, "end": 84}]}}, "schema": []}
{"input": "Ricin is a lethal protein toxin produced by the castor bean plant.", "output": {"entities": {}}, "schema": []}
{"input": "Ricin is known to possess significant heat resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, we placed it in a variety of foods to study the influence of the food matrix on behavior of a thermally stable protein toxin.", "output": {"entities": {}}, "schema": []}
{"input": "First order rate constants for the thermal inactivation of ricin in foods and simple buffers were measured using cytotoxicity assays.", "output": {"entities": {}}, "schema": []}
{"input": "We observed greater thermal stability at 75 degrees C for the cytotoxic activity of ricin when it was placed in a yogurt-containing fruit drink compared to its stability when placed in the other foods tested.", "output": {"entities": {}}, "schema": []}
{"input": "We found that galactose and high molecular weight exopolysaccharides present in various dairy products contributed to the thermal stability of ricin.", "output": {"entities": {"chemical": [{"text": "galactose", "start": 14, "end": 23}]}}, "schema": []}
{"input": "Differential scanning calorimetry also showed enhanced thermal stability for ricin at pH 4. 5.", "output": {"entities": {}}, "schema": []}
{"input": "Our results demonstrate the importance of considering pH and the presence of stabilizing ligands in the thermal inactivation of protein toxins in foods.", "output": {"entities": {}}, "schema": []}
{"input": "Short-term toxicity of hexavalent-chromium to epipsammic diatoms of a microtidal estuary (R i o de la Plata): Responses from the individual cell to the community structure.", "output": {"entities": {"chemical": [{"text": "hexavalent-chromium", "start": 23, "end": 42}]}}, "schema": []}
{"input": "Diatoms are an integral and often dominant component of the benthic microalgal assemblage in estuarine and shallow coastal environments.", "output": {"entities": {}}, "schema": []}
{"input": "Different toxic substances discharged into these ecosystems persist in the water, sediments, and biota for long periods.", "output": {"entities": {}}, "schema": []}
{"input": "Among these pernicious agents, the toxicity in diatoms by metal is linked to different steps in the transmembrane and internal movements of the toxicant, causing perturbations in the normal structural and functional cellular components.", "output": {"entities": {}}, "schema": []}
{"input": "These changes constitute an early, nontaxonomic warning signal that could potentially serve as an indicator of this type of pollution.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this work was to study the environment-reflecting short-term responses at different levels of organization of epipsammic diatoms from the R i o de la Plata estuary, Argentina that had been exposed to hexavalent chromium within experimental microcosms.", "output": {"entities": {"chemical": [{"text": "hexavalent chromium", "start": 211, "end": 230}]}}, "schema": []}
{"input": "To this end we monitored: (i) changes in the proportion of the diatoms in relation to other algal groups at the biofilm community level; (ii) shifts in species composition at the diatom-assemblage level; (iii) projected changes in the densities of the most representative species at the population level through comparison of relative growth rates and generation times; and (iv) the cytological changes at the cellular and subcellular levels as indicated by the appearance of teratological effects on individuals and nuclear alterations.", "output": {"entities": {}}, "schema": []}
{"input": "The epipsammic biofilms were exposed for 96h to chromium at a concentration similar to that measured in highly impacted sites along the coast (80 mu gL (-1)).", "output": {"entities": {"chemical": [{"text": "chromium", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Chromium pollution, at this concentration and short exposure time did not affect the algal biomass and density of these mature biofilms.", "output": {"entities": {"chemical": [{"text": "Chromium", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The biofilm composition, however, did change, as reflected in a decline in cyanophytes and an increment in the proportions of diatoms and chlorophytes; with Hippodonta hungarica, Navicula novaesiberica, Nitzschia palea, and Sellaphora pupula being the most frequent and abundant species.", "output": {"entities": {}}, "schema": []}
{"input": "The most notable shifts related to chromium exposure were a decrease in the relative abundance of H. hungarica and a significant increase in the proportion of N. palea.", "output": {"entities": {"chemical": [{"text": "chromium", "start": 35, "end": 43}]}}, "schema": []}
{"input": "Moreover, the species analyzed in the treatment microcosms showed higher growth rates than in the controls-N. palea grew faster, while H. hungarica replicated more slowly.", "output": {"entities": {}}, "schema": []}
{"input": "The total nuclear abnormalities-as recorded in Fallacia pygmaea and N. novaesiberica-were significantly higher in the treatment microcosms; whereas in N. palea, the dominant species in treatment microcosms, neither nuclear alterations nor abnormal frustules were observed.", "output": {"entities": {}}, "schema": []}
{"input": "MicroRNAs as pharmacological targets in endothelial cell function and dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions, including impairment of the barrier functions, control of vascular tone, disturbance of proliferative, migratory and morphogenic capacities of endothelial cells, as well as control of leukocyte trafficking.", "output": {"entities": {}}, "schema": []}
{"input": "MicroRNAs (miRNAs) are short non-coding RNAs that have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level.", "output": {"entities": {}}, "schema": []}
{"input": "This review summarizes the latest insights in the identification of endothelial-specific miRNAs and their targets, as well as their roles in controlling endothelial cell functions in both autocrine and paracrine manner.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we discuss the therapeutic potential for the treatment of endothelial cell dysfunction and associated vascular pathophysiological conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Effect of a Garcinia garderiana (Planchon and Triana) Zappi hydroalcoholic extract on melanogenesis in B16F10 melanoma cells.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGY RELEVANCE: Garcinia gardneriana (Planchon and Triana) Zappi (Clusiaceae) is popularly called \" bacopari \" in southern Brazil.", "output": {"entities": {}}, "schema": []}
{"input": "The leaves of this plant are traditionally used to treat skin disorders.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF STUDY: This study evaluated the effects of a hydroalcoholic extract of Garcinia gardneriana leaves (HEGG) on B16F10 murine melanoma cells in order to search for new depigmenting agents.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: The effects of HEGG were assessed in melanin content assays in B16F10 melanoma cells compared with the reference drug kojic acid (500mM).", "output": {"entities": {"chemical": [{"text": "kojic acid", "start": 141, "end": 151}]}}, "schema": []}
{"input": "Melanin content was measured after spontaneous melanogenesis, UVB-induced melanogenesis and melanogenesis induced by alpha-MSH.", "output": {"entities": {}}, "schema": []}
{"input": "At the same time, cell viability assays were conducted.", "output": {"entities": {}}, "schema": []}
{"input": "Intracellular and mushroom tyrosinase activity assays were employed to evaluate the effect of HEGG on tyrosinase activity.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: HEGG decreased the level of melanin under all three experimental conditions of melanin content evaluation without reducing cell viability.", "output": {"entities": {}}, "schema": []}
{"input": "In intracellular tyrosinase assays, the enzyme' s activity was reduced about 19% with extract concentrations ranging 0. 1-10 micro g/mL.", "output": {"entities": {}}, "schema": []}
{"input": "In the mushroom tyrosinase activity assay a maximal inhibition of 35% (1000 micro g/mL) was observed.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: These results suggest that HEGG inhibition relates to its tyrosinase activity.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the hydroalcoholic extract of Garcinia gardneriana shows great potential for use as a depigmenting agent in hyperpigmentation disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Anti-diarrhoeal activity of aqueous extract of Ocimum kilimandscharicum.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum kilimandscharicum Baker ex G u erke, commonly referred to as Kapur Tulsi, is a medicinal herb that belongs to the family of Lamiaceae.", "output": {"entities": {}}, "schema": []}
{"input": "It is traditionally popular for its gastroprotective effects, including its use as a digestive and anti-diarrhoeal.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: The present study aims to prove the anti-diarrhoeal activity of aqueous extract of leaves of Ocimum kilimandscharicum in animal models.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: The aqueous extract was tested at three different dose levels (100, 200 and 400mg/kg, p. o. in rats and the corresponding doses in mice) against castor-oil induced diarrhoea model and castor oil induced enteropooling assay in rats; and charcoal meal test/intestinal motility test in mice.", "output": {"entities": {}}, "schema": []}
{"input": "The parameters observed were the onset of defecation, cumulative faecal weight and consistency of faeces in the castor oil induced diarrhoea model; the weight of intestinal content in castor oil induced enteropooling assay; and the distance travelled by charcoal in the intestinal motility test.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: A significant delay in the onset of defecation (p < 0. 05), reduction in the cumulative faecal weight (p < 0. 001), along with a change in the faecal consistency from watery to solid form was observed at the dose of 200mg/kg in the castor oil-induced diarrhoea model.", "output": {"entities": {}}, "schema": []}
{"input": "Similarly, the extract at the doses of 100mg/kg (p < 0. 01) and 200mg/kg (p < 0. 001) significantly decreased the weight of intestinal content in castor oil induced enteropooling assay.", "output": {"entities": {}}, "schema": []}
{"input": "In the charcoal meal test the extract at the dose of 280mg/kg (corresponding to 200mg/kg in rats) significantly (p < 0. 01) reduced the distance travelled by charcoal.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: The aqueous extract of leaves of Ocimum kilimandscharicum showed anti-diarrhoeal activity, which may be due to its anti-motility and anti-secretory effects, which thus proved the traditional claims.", "output": {"entities": {}}, "schema": []}
{"input": "Electroconvulsive seizures activate anorexigenic signals in the ventromedial nuclei of the hypothalamus.", "output": {"entities": {}}, "schema": []}
{"input": "The ventromedial nucleus of the hypothalamus (VMH) plays an important role in feeding and energy homeostasis.", "output": {"entities": {}}, "schema": []}
{"input": "Electroconvulsive seizure (ECS) therapy is highly effective in the treatment of several psychiatric diseases, including depression, but may also have beneficial effects in other neurological diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Although it has been reported that the neurons of the VMH are strongly activated by ECS stimulation, the specific effects of ECS in this hypothalamic subnucleus remain unknown.", "output": {"entities": {}}, "schema": []}
{"input": "To address this issue, we investigated the changes in gene expression in microdissected-VMH samples in response to ECS in mice, and examined the behavioral effects of ECS on feeding behavior.", "output": {"entities": {}}, "schema": []}
{"input": "ECS significantly induced the expression of immediate-early genes such as Fos, Fosb, and Jun, as well as Bdnf, Adcyap1, Hrh1, and Crhr2 in the VMH.", "output": {"entities": {}}, "schema": []}
{"input": "Given that signals of these gene products are suggested to have anorexigenic roles in the VMH, we also examined the effect of ECS on food intake and body weight.", "output": {"entities": {}}, "schema": []}
{"input": "Repeated ECS had a suppressive effect on food intake and body weight gain under both regular and high-fat diet conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, gold-thioglucose-induced hypothalamic lesions, including the VMH and the arcuate nucleus, abolished the anorexigenic effects of ECS, indicating the requirement for the activation of the hypothalamus.", "output": {"entities": {"chemical": [{"text": "gold-thioglucose", "start": 13, "end": 29}]}}, "schema": []}
{"input": "Our data show an effect of ECS on increased expression of anorexigenic factors in the VMH, and suggest a role in the regulation of energy homeostasis by ECS.", "output": {"entities": {}}, "schema": []}
{"input": "Isolation and in vitro partial characterization of hemolytic proteins from the nematocyst venom of the jellyfish Stomolophus meleagris.", "output": {"entities": {}}, "schema": []}
{"input": "Jellyfish venom contains various toxins and can cause itching, edema, muscle aches, shortness of breath, blood pressure depression, shock or even death after being stung.", "output": {"entities": {}}, "schema": []}
{"input": "Hemolytic protein is one of the most hazardous components in the venom.", "output": {"entities": {}}, "schema": []}
{"input": "The present study investigated the hemolytic activity of the nematocyst venom from jellyfish Stomolophus meleagris.", "output": {"entities": {}}, "schema": []}
{"input": "Anion exchange chromatography, DEAE Sepharose Fast Flow, and gel filtration chromatography, Superdex200 had been employed to isolate hemolytic proteins from the nematocyst venom of jellyfish S. meleagris.", "output": {"entities": {"chemical": [{"text": "DEAE", "start": 31, "end": 35}]}}, "schema": []}
{"input": "Hemolysis of chicken red blood cells was used to quantify hemolytic potency of crude nematocyst venom and chromatography fractions during the purification process.", "output": {"entities": {}}, "schema": []}
{"input": "Native-PAGE profile displayed one protein band in the purified hemolytic protein (SmTX); however, two protein bands with apparent molecular weights of ~ 45kDa and 52kDa were observed in the reducing SDS-PAGE analysis.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 199, "end": 202}]}}, "schema": []}
{"input": "Approximately 70 mu g/mL of SmTX caused 50% hemolysis (HU50) of the erythrocyte suspension.", "output": {"entities": {}}, "schema": []}
{"input": "The hemolytic activity of SmTX was shown to be temperature and pH dependent, with the optimum temperature and pH being 37 degrees C and pH 5. 0.", "output": {"entities": {}}, "schema": []}
{"input": "The present study is the first report of isolation and partial characterization of hemolytic proteins from the nematocyst venom of the jellyfish S. meleagris.", "output": {"entities": {}}, "schema": []}
{"input": "The mechanism of the hemolytic activity of SmTX is not clear and deserves further investigation.", "output": {"entities": {}}, "schema": []}
{"input": "Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation.", "output": {"entities": {}}, "schema": []}
{"input": "The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2, 3, 7, 8-tetrachlorodibenzo-[p]-dioxin (TCDD), 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2, 2', 4, 4'-tetrabrominated diphenyl ether (BDE-47), perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS).", "output": {"entities": {"chemical": [{"text": "tributyltin", "start": 110, "end": 121}, {"text": "TBT", "start": 123, "end": 126}, {"text": "diethylstilbestrol", "start": 129, "end": 147}, {"text": "DES", "start": 149, "end": 152}, {"text": "bisphenol A", "start": 155, "end": 166}, {"text": "BPA", "start": 168, "end": 171}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-[p]-dioxin", "start": 174, "end": 214}, {"text": "TCDD", "start": 216, "end": 220}, {"text": "2, 2', 4, 4', 5, 5'-hexachlorobiphenyl", "start": 223, "end": 261}, {"text": "PCB-153", "start": 263, "end": 270}, {"text": "hexachlorobenzene", "start": 273, "end": 290}, {"text": "HCB", "start": 292, "end": 295}, {"text": "hexabromocyclododecane", "start": 298, "end": 320}, {"text": "HBCD", "start": 322, "end": 326}, {"text": "2, 2', 4, 4'-tetrabrominated diphenyl ether", "start": 329, "end": 372}, {"text": "BDE-47", "start": 374, "end": 380}, {"text": "perfluorinated octyl acid", "start": 383, "end": 408}, {"text": "PFOA", "start": 410, "end": 414}, {"text": "perfluorinated octyl sulfonate", "start": 420, "end": 450}, {"text": "PFOS", "start": 452, "end": 456}]}}, "schema": []}
{"input": "A modest decrease in global DNA methylation was observed in N2A cells exposed to 10 mu M DES, BPA, TCDD, BDE-47, PCB-153 and 1 mu M HCB, but no changes were found in the human SK-N-AS cells.", "output": {"entities": {"chemical": [{"text": "DES", "start": 89, "end": 92}, {"text": "BPA", "start": 94, "end": 97}, {"text": "TCDD", "start": 99, "end": 103}, {"text": "BDE-47", "start": 105, "end": 111}, {"text": "PCB-153", "start": 113, "end": 120}, {"text": "HCB", "start": 132, "end": 135}]}}, "schema": []}
{"input": "We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2. 5-25 mu M).", "output": {"entities": {"chemical": [{"text": "BDE-47", "start": 34, "end": 40}]}}, "schema": []}
{"input": "Adipocyte differentiation was also enhanced by TBT (<= 10nM) and BPA (> 10 mu M) and inhibited by TCDD (<= 0. 1nM).", "output": {"entities": {"chemical": [{"text": "TBT", "start": 47, "end": 50}, {"text": "BPA", "start": 65, "end": 68}, {"text": "TCDD", "start": 98, "end": 102}]}}, "schema": []}
{"input": "The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10 mu M; PCB-153, 3. 4 mu M and HCB, 1 mu M).", "output": {"entities": {"chemical": [{"text": "PFOA", "start": 114, "end": 118}, {"text": "PFOS", "start": 120, "end": 124}, {"text": "HBCD", "start": 129, "end": 133}, {"text": "PCB-153", "start": 146, "end": 153}, {"text": "HCB", "start": 169, "end": 172}]}}, "schema": []}
{"input": "This study demonstrates that, selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation.", "output": {"entities": {}}, "schema": []}
{"input": "Cardiovascular effects of Boophone disticha aqueous ethanolic extract on early maternally separated BALB/C mice.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: There are a number of reports from traditional medical practice in Zimbabwe and neighboring countries and few in vitro studies suggesting an effect with extracts of Boophone disticha in some forms of anxiety disorders.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: In order to validate the use of Boophone disticha in treatment of anxiety, this study was set to determine the effects of the plant extracts on blood pressure (BP) and heart rate (HR) in adult BALB/c mice subjected to repeated early maternal separation (MS) stress.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: To test whether early life stress increases anxiety in mice, non-invasive tail cuff method was used to examine the autonomic nervous system activity by assessing cardiovascular reactivity and response to acute mixing stress (AMS) and restraint stress (RS) in adult mice subjected to early postnatal stress as compared to control.", "output": {"entities": {}}, "schema": []}
{"input": "AMS-induced cardiovascular response was then evaluated in adult MS mice treated with Boophone disticha as compared to vehicle and diazepam.", "output": {"entities": {"chemical": [{"text": "diazepam", "start": 130, "end": 138}]}}, "schema": []}
{"input": "RESULTS: Comparisons of the BP and HR measurements indicated that MS significantly reduced AMS-induced HR responses in BALB/c mice when compared with control.", "output": {"entities": {}}, "schema": []}
{"input": "Boophone disticha treatment significantly reduced AMS-induced BP response in BALB/c MS as compared to vehicle and diazepam treatments.", "output": {"entities": {"chemical": [{"text": "diazepam", "start": 114, "end": 122}]}}, "schema": []}
{"input": "CONCLUSIONS: Our findings demonstrate for the first time that postnatal stress can induce short-term changes in the sensitivity of the cardiovascular system to subsequent stress which can be reduced by treatment with a freeze dried aqueous ethanolic extract of Boophone disticha.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple treatments with liposomal doxorubicin and ultrasound-induced disruption of blood-tumor and blood-brain barriers improve outcomes in a rat glioma model.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 35, "end": 46}]}}, "schema": []}
{"input": "The blood-brain-barrier (BBB) prevents the transport of most anticancer agents to the central nervous system and restricts delivery to infiltrating brain tumors.", "output": {"entities": {}}, "schema": []}
{"input": "The heterogeneous vascular permeability in tumor vessels, along with several other factors, creates additional barriers for drug treatment of brain tumors.", "output": {"entities": {}}, "schema": []}
{"input": "Focused ultrasound (FUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and the \" blood-tumor barrier \".", "output": {"entities": {}}, "schema": []}
{"input": "Here, we tested the impact of three weekly sessions of FUS and liposomal doxorubicin (DOX) in 9L rat glioma tumors.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 73, "end": 84}, {"text": "DOX", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Animals that received FUS + DOX (N = 8) had a median survival time that was increased significantly (P < 0. 001) compared to animals who received DOX only (N = 6), FUS only (N = 8), or no treatment (N = 7).", "output": {"entities": {"chemical": [{"text": "DOX", "start": 28, "end": 31}, {"text": "DOX", "start": 146, "end": 149}]}}, "schema": []}
{"input": "Median survival for animals that received FUS + DOX was increased by 100% relative to untreated controls, whereas animals who received DOX alone had only a 16% improvement.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 48, "end": 51}, {"text": "DOX", "start": 135, "end": 138}]}}, "schema": []}
{"input": "Animals who received only FUS showed no improvement.", "output": {"entities": {}}, "schema": []}
{"input": "No tumor cells were found in histology in 4/8 animals in the FUS + DOX group, and in two animals, only a few tumor cells were detected.", "output": {"entities": {"chemical": [{"text": "DOX", "start": 67, "end": 70}]}}, "schema": []}
{"input": "Adverse events in the treatment group included skin toxicity, impaired activity, damage to surrounding brain tissue, and tissue loss at the tumor site.", "output": {"entities": {}}, "schema": []}
{"input": "In one animal, intratumoral hemorrhage was observed.", "output": {"entities": {}}, "schema": []}
{"input": "These events are largely consistent with known side effects of doxorubicin and with an extensive tumor burden.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 63, "end": 74}]}}, "schema": []}
{"input": "Overall this work demonstrates that multiple sessions using this FUS technique to enhance the delivery of liposomal doxorubicin have a pronounced therapeutic effect in this rat glioma model.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 116, "end": 127}]}}, "schema": []}
{"input": "Global analytical strategy to measure drug-plasma protein interactions: from high-throughput to in-depth analysis.", "output": {"entities": {}}, "schema": []}
{"input": "The selection of drug candidates with improved pharmacokinetics is essential to reduce the attrition rates during drug development and represents one of the big challenges faced by the pharmaceutical industry.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma protein binding (PPB) is an important parameter with significant implications for in vivo drug performance.", "output": {"entities": {}}, "schema": []}
{"input": "Today, the most widely used techniques for PPB measurement in the pharmaceutical community are equilibrium dialysis (ED) and ultrafiltration (UF).", "output": {"entities": {}}, "schema": []}
{"input": "However, these techniques have some limitations.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, we emphasize an alternative strategy, based on a global, new and easy-to-follow methodology, to screen and perform determination of PPB, using orthogonal techniques (i. e. liquid chromatography, capillary electrophoresis (CE), surface plasmon resonance (SPR) based biosensor).", "output": {"entities": {}}, "schema": []}
{"input": "We anticipate that the increased knowledge gained through this strategy will lead to improved drug candidates.", "output": {"entities": {}}, "schema": []}
{"input": "Secular Changes in U. S.", "output": {"entities": {}}, "schema": []}
{"input": "Prediabetes Prevalence Defined by Hemoglobin A1c and Fasting Plasma Glucose: National Health and Nutrition Examination Surveys, 1999-2010.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 68, "end": 75}]}}, "schema": []}
{"input": "OBJECTIVEUsing a nationally representative sample of the civilian noninstitutionalized U. S. population, we estimated prediabetes prevalence and its changes during 1999-2010. RESEARCH DESIGN AND METHODSData were from 19, 182 nonpregnant individuals aged >= 12 years who participated in the 1999-2010 National Health and Nutrition Examination Surveys.", "output": {"entities": {}}, "schema": []}
{"input": "We defined prediabetes as hemoglobin A1c 5. 7 to < 6. 5% (39 to < 48 mmol/mol, A1C5. 7) or fasting plasma glucose (FPG) 100 to < 126 mg/dL (impaired fasting glucose [IFG]).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 106, "end": 113}, {"text": "glucose", "start": 157, "end": 164}]}}, "schema": []}
{"input": "We estimated the prevalence of prediabetes, A1C5. 7, and IFG for 1999-2002, 2003-2006, and 2007-2010.", "output": {"entities": {}}, "schema": []}
{"input": "We calculated estimates age-standardized to the 2000 U. S. census population and used logistic regression to compute estimates adjusted for age, sex, race/ethnicity, poverty-to-income ratio, and BMI.", "output": {"entities": {}}, "schema": []}
{"input": "Participants with self-reported diabetes, A1C >= 6. 5% (>= 48 mmol/mol), or FPG >= 126 mg/dL were included. RESULTSAmong those aged >= 12 years, age-adjusted prediabetes prevalence increased from 27. 4% (95% CI 25. 1-29. 7) in 1999-2002 to 34. 1% (32. 5-35. 8) in 2007-2010.", "output": {"entities": {}}, "schema": []}
{"input": "Among adults aged >= 18 years, the prevalence increased from 29. 2% (26. 8-31. 8) to 36. 2% (34. 5-38. 0).", "output": {"entities": {}}, "schema": []}
{"input": "As single measures among individuals aged >= 12 years, A1C5. 7 prevalence increased from 9. 5% (8. 4-10. 8) to 17. 8% (16. 6-19. 0), a relative increase of 87%, whereas IFG remained stable.", "output": {"entities": {}}, "schema": []}
{"input": "These prevalence changes were similar among the total population, across subgroups, and after controlling for covariates. CONCLUSIONSDuring 1999-2010, U. S. prediabetes prevalence increased because of increases in A1C5. 7.", "output": {"entities": {}}, "schema": []}
{"input": "Continuous monitoring of prediabetes is needed to identify, quantify, and characterize the population of high-risk individuals targeted for ongoing diabetes primary prevention efforts.", "output": {"entities": {}}, "schema": []}
{"input": "BID-induced structural changes in BAK promote apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "The BCL-2-family protein BAK is responsible for mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "The BCL-2 homology 3 (BH3)-only protein BID activates BAK to perform this function.", "output": {"entities": {}}, "schema": []}
{"input": "We report the NMR solution structure of the human BID BH3-BAK complex, which identified the activation site at the canonical BH3-binding groove of BAK.", "output": {"entities": {}}, "schema": []}
{"input": "Mutating the BAK BH1 in the groove prevented activation and MOMP but not the binding of BID.", "output": {"entities": {}}, "schema": []}
{"input": "BAK BH3 mutations allowed BID binding and activation but blunted function by blocking BAK oligomerization.", "output": {"entities": {}}, "schema": []}
{"input": "BAK activation follows a' hit-and-run' mechanism whereby BID dissociates from the trigger site, which allows BAK oligomerization at an overlapping interface.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, the BH3-only proteins NOXA and BAD are predicted to clash with the trigger site and are not activators of BAK.", "output": {"entities": {}}, "schema": []}
{"input": "These findings provide insights into the early stages of BAK activation.", "output": {"entities": {}}, "schema": []}
{"input": "Thermal and electrical conduction in 6. 4 nm thin gold films.", "output": {"entities": {}}, "schema": []}
{"input": "For sub-10 nm thin metallic films, very little knowledge is available so far on how electron scattering at surface and grain boundaries reduces the thermal transport.", "output": {"entities": {}}, "schema": []}
{"input": "This work reports on the first time characterization of the thermal and electrical conductivities of gold films of 6. 4 nm average thickness.", "output": {"entities": {}}, "schema": []}
{"input": "The electrical (sigma) and thermal (k) conductivities of the Au film are found to be reduced dramatically from their bulk counterparts by 93. 7% (sigma) and 80. 5% (k).", "output": {"entities": {"chemical": [{"text": "Au", "start": 61, "end": 63}]}}, "schema": []}
{"input": "Its Lorenz number is measured as 7. 44 x 10 (-8) W Omega K (-2), almost a twofold increase from the bulk value.", "output": {"entities": {}}, "schema": []}
{"input": "The Mayadas-Shatzkes model is used to interpret the experimental results and reveals very strong electron reflection (77%) at grain boundaries.", "output": {"entities": {}}, "schema": []}
{"input": "The relationship between cocaine self-administration and actigraphy-based measures of sleep in adult rhesus monkeys.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 25, "end": 32}]}}, "schema": []}
{"input": "RATIONALE: Clinical trials show that chronic cocaine users suffer from sleep disturbances and preclinical research has shown that acute sleep deprivation increases the rate of cocaine self-administration in rats.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 45, "end": 52}, {"text": "cocaine", "start": 176, "end": 183}]}}, "schema": []}
{"input": "OBJECTIVE: This study examined the effect of cocaine self-administration on behavioral indices of sleep and alternatively the effect of sleep disruption on cocaine-maintained responding by rhesus monkeys.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 45, "end": 52}, {"text": "cocaine", "start": 156, "end": 163}]}}, "schema": []}
{"input": "METHODS: Seven adult rhesus monkeys, fitted with Actical (R) activity monitors, were trained to respond under a concurrent choice paradigm with food (three 1. 0-g pellets) and cocaine (0. 003-0. 3 mg/kg) or saline presentation.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 176, "end": 183}]}}, "schema": []}
{"input": "For each monkey, the lowest preferred dose of cocaine (> 80% cocaine choice) was determined.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 46, "end": 53}, {"text": "cocaine", "start": 61, "end": 68}]}}, "schema": []}
{"input": "Activity data were analyzed during lights out (2000-0600) to determine sleep efficiency, sleep latency, and total activity counts.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, the monkeys' sleep was disrupted (every hour during lights-out period) the night prior to food-cocaine choice sessions.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 109, "end": 116}]}}, "schema": []}
{"input": "RESULTS: Self-administration of the preferred dose of cocaine resulted in a significant decrease in sleep efficiency, with a significant increase in total lights-out activity.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 54, "end": 61}]}}, "schema": []}
{"input": "Sleep disruption significantly altered behavioral indices of sleep, similar to those seen following cocaine self-administration.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 100, "end": 107}]}}, "schema": []}
{"input": "However, sleep disruption did not affect cocaine self-administration under concurrent choice conditions.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 41, "end": 48}]}}, "schema": []}
{"input": "CONCLUSIONS: Based on these findings, cocaine self-administration does appear to disrupt behavioral indices of sleep, although it remains to be determined if treatments that improve sleep measures can affect future cocaine taking.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 38, "end": 45}, {"text": "cocaine", "start": 215, "end": 222}]}}, "schema": []}
{"input": "Contaminant driven genetic erosion and associated hypotheses on alleles loss, reduced population growth rate and increased susceptibility to future stressors: an essay.", "output": {"entities": {}}, "schema": []}
{"input": "Microevolution due to pollution can occur mainly through genetic drift bottlenecks, especially of small sized populations facing intense lethal pulses of contaminants, through mutations, increasing allelic diversity, and through natural selection, with the disappearance of the most sensitive genotypes.", "output": {"entities": {}}, "schema": []}
{"input": "This loss of genotypes can lead to serious effects if coupled to specific hypothetical scenarios.", "output": {"entities": {}}, "schema": []}
{"input": "These may be categorized as leading, first, to the loss of alleles-the recessive tolerance inheritance hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "Second, leading to a reduction of the population growth rate-the mutational load and fitness costs hypotheses.", "output": {"entities": {}}, "schema": []}
{"input": "Third, leading to an increased susceptibility of further genetic erosion both at future inputs of the same contaminant-differential physiological recovery, endpoints (dis) association, and differential phenotypic plasticity hypotheses-and at sequential or simultaneous inputs of other contaminants-the multiple stressors differential tolerance hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "Species in narrowly fluctuating environments (tropics and deep sea) may have a particularly high susceptibility to genetic erosion-the Plus c a change (plus c' est la meme chose) hypothesis.", "output": {"entities": {}}, "schema": []}
{"input": "A discussion on the consequences of these hypotheses is what this essay aimed at.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibitory action of salicylideneamino-2-thiophenol on NF-kappa B signaling cascade and cyclooxygenase-2 in HNE-treated endothelial cells.", "output": {"entities": {"chemical": [{"text": "salicylideneamino-2-thiophenol", "start": 21, "end": 51}, {"text": "HNE", "start": 108, "end": 111}]}}, "schema": []}
{"input": "In the present study, the anti-inflammatory effect of salicylideneamino-2-thiophenol (SAL-2), a derivative of salicylate, on a potent oxidant 4-hydroxynonenal (HNE)-induced oxidative stress was investigated using rat prostate endothelial (YPEN-1) cells.", "output": {"entities": {"chemical": [{"text": "salicylideneamino-2-thiophenol", "start": 54, "end": 84}, {"text": "SAL-2", "start": 86, "end": 91}, {"text": "salicylate", "start": 110, "end": 120}, {"text": "4-hydroxynonenal", "start": 142, "end": 158}, {"text": "HNE", "start": 160, "end": 163}]}}, "schema": []}
{"input": "We focused on anti-inflammatory activity of SAL-2 which was determined by its ability to suppress COX-2 and iNOS gene expression through suppression of NF-kappa B and redox regulation.", "output": {"entities": {"chemical": [{"text": "SAL-2", "start": 44, "end": 49}]}}, "schema": []}
{"input": "We found that SAL-2 effectively inhibited HNE-induced reactive species generation, while upregulated GSH/GSSG ratio.", "output": {"entities": {"chemical": [{"text": "SAL-2", "start": 14, "end": 19}, {"text": "HNE", "start": 42, "end": 45}, {"text": "GSH", "start": 101, "end": 104}, {"text": "GSSG", "start": 105, "end": 109}]}}, "schema": []}
{"input": "Prostagrandin (PG) E2 production stimulated by arachidonic acid was suppressed by SAL-2.", "output": {"entities": {"chemical": [{"text": "(PG) E2", "start": 14, "end": 21}, {"text": "arachidonic acid", "start": 47, "end": 63}, {"text": "SAL-2", "start": 82, "end": 87}]}}, "schema": []}
{"input": "SAL-2 also downregulated COX-2 and iNOS expression induced by HNE, but salicylate did not.", "output": {"entities": {"chemical": [{"text": "SAL-2", "start": 0, "end": 5}, {"text": "HNE", "start": 62, "end": 65}, {"text": "salicylate", "start": 71, "end": 81}]}}, "schema": []}
{"input": "We found that SAL-2 inhibited HNE-mediated IKK phosphorylation, I kappa B alpha degradation and nuclear translocation of p65 which are linked to NF-kappa B activation.", "output": {"entities": {"chemical": [{"text": "SAL-2", "start": 14, "end": 19}, {"text": "HNE", "start": 30, "end": 33}]}}, "schema": []}
{"input": "Furthermore, SAL-2 inhibited HNE-induced activation of mitogen-activated protein kinases.", "output": {"entities": {"chemical": [{"text": "SAL-2", "start": 13, "end": 18}, {"text": "HNE", "start": 29, "end": 32}]}}, "schema": []}
{"input": "Collectively, SAL-2 inhibited COX-2 and iNOS gene expression through suppression of NF-kappa B leading to the inhibition of PGE2 synthesis.", "output": {"entities": {"chemical": [{"text": "SAL-2", "start": 14, "end": 19}, {"text": "PGE2", "start": 124, "end": 128}]}}, "schema": []}
{"input": "Based on these data, we propose that with its combined effect on strong anti-oxidant and anti-inflammatory action, SAL-2 can be a potent anti-inflammatory agent for treatment of inflammatory-related diseases.", "output": {"entities": {"chemical": [{"text": "SAL-2", "start": 115, "end": 120}]}}, "schema": []}
{"input": "Aldose Reductase Inhibitory Compounds from Xanthium strumarium.", "output": {"entities": {}}, "schema": []}
{"input": "As part of our ongoing search for natural sources of therapeutic and preventive agents for diabetic complications, we evaluated the inhibitory effects of components of the fruit of Xanthium strumarium (X. strumarium) on aldose reductase (AR) and galactitol formation in rat lenses with high levels of glucose.", "output": {"entities": {"chemical": [{"text": "aldose", "start": 220, "end": 226}, {"text": "galactitol", "start": 246, "end": 256}, {"text": "glucose", "start": 301, "end": 308}]}}, "schema": []}
{"input": "To identify the bioactive components of X. strumarium, 7 caffeoylquinic acids and 3 phenolic compounds were isolated and their chemical structures were elucidated on the basis of spectroscopic evidence and comparison with published data.", "output": {"entities": {"chemical": [{"text": "caffeoylquinic acids", "start": 57, "end": 77}, {"text": "phenolic", "start": 84, "end": 92}]}}, "schema": []}
{"input": "The abilities of 10 X. strumarium-derived components to counteract diabetic complications were investigated by means of inhibitory assays with rat lens AR (rAR) and recombinant human AR (rhAR).", "output": {"entities": {}}, "schema": []}
{"input": "From the 10 isolated compounds, methyl-3, 5-di-O-caffeoylquinate showed the most potent inhibition, with IC50 values of 0. 30 and 0. 67 mu M for rAR and rhAR, respectively.", "output": {"entities": {"chemical": [{"text": "methyl-3, 5-di-O-caffeoylquinate", "start": 32, "end": 64}]}}, "schema": []}
{"input": "In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate, methyl-3, 5-di-O-caffeoylquinate showed competitive inhibition of rhAR.", "output": {"entities": {"chemical": [{"text": "methyl-3, 5-di-O-caffeoylquinate", "start": 83, "end": 115}]}}, "schema": []}
{"input": "Furthermore, methyl-3, 5-di-O-caffeoylquinate inhibited galactitol formation in the rat lens and in erythrocytes incubated with a high concentration of glucose, indicating that this compound may be effective in preventing diabetic complications.", "output": {"entities": {"chemical": [{"text": "methyl-3, 5-di-O-caffeoylquinate", "start": 13, "end": 45}, {"text": "galactitol", "start": 56, "end": 66}, {"text": "glucose", "start": 152, "end": 159}]}}, "schema": []}
{"input": "Fructose-1, 6-bisphosphate ameliorates lipopolysaccharide-induced dysfunction of blood-brain barrier.", "output": {"entities": {"chemical": [{"text": "Fructose-1, 6-bisphosphate", "start": 0, "end": 26}]}}, "schema": []}
{"input": "Fructose-1, 6-bisphosphate (FBP), a glycolytic intermediate, has neuroprotective effects in various brain injury models.", "output": {"entities": {"chemical": [{"text": "Fructose-1, 6-bisphosphate", "start": 0, "end": 26}, {"text": "FBP", "start": 28, "end": 31}]}}, "schema": []}
{"input": "However, its effects on blood-brain barrier (BBB) are largely unknown.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, we investigated the effects of FBP on lipopolysaccharide (LPS)-induced BBB dysfunction in in vitro BBB model comprising co-culture of mouse brain endothelial cell line, bEnd. 3 and mouse primary astrocyte and explored its action mechanism therein involved.", "output": {"entities": {"chemical": [{"text": "FBP", "start": 46, "end": 49}]}}, "schema": []}
{"input": "LPS induced the impairment of endothelial permeability and transendothelial electrical resistance (TEER).", "output": {"entities": {}}, "schema": []}
{"input": "The functional changes were confirmed by alterations in immunostaining for junctional proteins occludin, ZO-1 and VE-cadherin, such as the loss of cortical staining pattern and appearance of intercellular gaps in endothelial cells.", "output": {"entities": {}}, "schema": []}
{"input": "Co-administration of FBP alleviated the deleterious effects of LPS on BBB permeability and TEER in a dose dependent manner.", "output": {"entities": {"chemical": [{"text": "FBP", "start": 21, "end": 24}]}}, "schema": []}
{"input": "And also FBP inhibited the LPS-induced changes in the distribution of endothelial junctional proteins, resulting in the better preservation of monolayer integrity.", "output": {"entities": {"chemical": [{"text": "FBP", "start": 9, "end": 12}]}}, "schema": []}
{"input": "FBP suppressed the production of reactive oxygen species (ROS) but did not affect cyclooxygenase-2 expression and prostaglandin E2 production in endothelial cells stimulated with LPS.", "output": {"entities": {"chemical": [{"text": "FBP", "start": 0, "end": 3}, {"text": "oxygen", "start": 42, "end": 48}, {"text": "prostaglandin E2", "start": 114, "end": 130}]}}, "schema": []}
{"input": "Taken together, these data suggest that FBP could ameliorate LPS-induced BBB dysfunction through the maintenance of junctional integrity, which might be mediated by downregulation of ROS production.", "output": {"entities": {"chemical": [{"text": "FBP", "start": 40, "end": 43}]}}, "schema": []}
{"input": "The regulation of epidermal melanogenesis via cAMP and/or PKC signaling pathways: insights for the development of hypopigmenting agents.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 46, "end": 50}]}}, "schema": []}
{"input": "Abnormal pigmentation, particularly hyperpigmentation, is major issue of concern for people with colored skin.", "output": {"entities": {}}, "schema": []}
{"input": "Several hypopigmenting agents, which exert their action by inhibiting tyrosinase activity and/or transcription, have been used for treatment.", "output": {"entities": {}}, "schema": []}
{"input": "However, results have been discouraging.", "output": {"entities": {}}, "schema": []}
{"input": "To manage abnormal pigmentation properly, the mechanisms of melanogenesis should be understood.", "output": {"entities": {}}, "schema": []}
{"input": "Endogenous and exogenous factors affect melanogenesis via intracellular machineries.", "output": {"entities": {}}, "schema": []}
{"input": "cAMP and PKC are critical factors of important transduction pathways and cross-talk between them could amplify the melanogenic effect.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Here, factors involved in melanogenesis regulation via cAMP and/or PKC pathways are reviewed with their action mechanisms.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 55, "end": 59}]}}, "schema": []}
{"input": "The Analog of Ginkgo biloba Extract 761 is a Protective Factor of Cognitive Impairment Induced by Chronic Fluorosis.", "output": {"entities": {}}, "schema": []}
{"input": "Ginkgo biloba extract EGb761 is widely used to treat patients with learning and memory impairment in Alzheimer' s disease and Parkinson' s disease in China.", "output": {"entities": {}}, "schema": []}
{"input": "However, it is not yet clear whether the analog of EGb761 (EGb) has a protective effect on the learning and memory damage induced by chronic fluorosis.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, 30 Wistar rats were randomly divided into three groups: a control group, a sodium fluoride (NaF) + EGb group, and a NaF group.", "output": {"entities": {"chemical": [{"text": "sodium fluoride", "start": 90, "end": 105}, {"text": "NaF", "start": 107, "end": 110}, {"text": "NaF", "start": 131, "end": 134}]}}, "schema": []}
{"input": "The rats were administered 0. 5 ml water containing NaF (100 mg/l) and EGb (120 mg/kg) per day via gavage.", "output": {"entities": {"chemical": [{"text": "NaF", "start": 52, "end": 55}]}}, "schema": []}
{"input": "After 3 months, the rats' capacity for learning and memory was tested using a Y-maze.", "output": {"entities": {}}, "schema": []}
{"input": "Damage to hippocampal neurons was evaluated by histological examination of the CA3 area.", "output": {"entities": {}}, "schema": []}
{"input": "Superoxide dismutase (SOD) activity and the levels of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured.", "output": {"entities": {"chemical": [{"text": "Superoxide", "start": 0, "end": 10}, {"text": "glutathione", "start": 54, "end": 65}, {"text": "GSH", "start": 78, "end": 81}, {"text": "malondialdehyde", "start": 90, "end": 105}, {"text": "MDA", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Furthermore, the expression levels of Bcl-2 and Bax and the levels of cleaved Caspase3 in the hippocampus were evaluated by RT-PCR and Western blotting.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that EGb could improve learning and memory abilities, enhance the activities of SOD and GSH-Px, attenuate the level of MDA, upregulate the ratio of Bcl-2/Bax, and downregulate the level of cleaved Caspase3.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 107, "end": 110}]}}, "schema": []}
{"input": "Effects of High Iron and Glucose Concentrations over the Relative Expression of Bcl2, Bax, and Mfn2 in MIN6 Cells.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 16, "end": 20}, {"text": "Glucose", "start": 25, "end": 32}]}}, "schema": []}
{"input": "Type 2 diabetes is characterized by hyperglycemia and oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperglycemia is linked to mitochondrial dysfunction and reduced beta-cell mass due to the reduced expression of genes such as Mfn2 as well as the participation of the Bcl2 gene family, responsible for increased apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this study was to describe the effect of different iron and/or glucose concentrations over Mfn2, Bax, and Bcl2 expressions in a beta-pancreatic cell line (MIN6 cells).", "output": {"entities": {"chemical": [{"text": "iron", "start": 66, "end": 70}, {"text": "glucose", "start": 78, "end": 85}]}}, "schema": []}
{"input": "MIN6 cells were pre-incubated with different iron and/or glucose concentrations, and the relative mRNA abundance of the Bcl2/Bax ratio and of Mfn2 genes was measured by qRT-PCR.", "output": {"entities": {"chemical": [{"text": "iron", "start": 45, "end": 49}, {"text": "glucose", "start": 57, "end": 64}]}}, "schema": []}
{"input": "Heme oxygenase (HO) activity, iron uptake, superoxide dismutase activity, and glutathione content were also determined.", "output": {"entities": {"chemical": [{"text": "iron", "start": 30, "end": 34}, {"text": "superoxide", "start": 43, "end": 53}, {"text": "glutathione", "start": 78, "end": 89}]}}, "schema": []}
{"input": "The Bcl2/Bax ratio increased and Mfn2 expression decreased in MIN6 cells after glucose stimulation.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 79, "end": 86}]}}, "schema": []}
{"input": "These effects were higher when glucose and iron were incubated together.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 31, "end": 38}, {"text": "iron", "start": 43, "end": 47}]}}, "schema": []}
{"input": "Additionally, treatment with glucose/iron showed a higher HO activity.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 29, "end": 36}, {"text": "iron", "start": 37, "end": 41}]}}, "schema": []}
{"input": "Our study revealed that high glucose/Fe concentrations in MIN6 cells induced an increase of the Bcl2/Bax ratio, an indicator of increased cell apoptosis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 29, "end": 36}, {"text": "Fe", "start": 37, "end": 39}]}}, "schema": []}
{"input": "Ospemifene: first global approval.", "output": {"entities": {"chemical": [{"text": "Ospemifene", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Ospemifene (Osphena (TM)) is an oral selective estrogen receptor modulator (SERM), with tissue-specific estrogenic agonist/antagonist effects.", "output": {"entities": {"chemical": [{"text": "Ospemifene", "start": 0, "end": 10}, {"text": "Osphena", "start": 12, "end": 19}, {"text": "estrogen", "start": 47, "end": 55}]}}, "schema": []}
{"input": "QuatRx Pharmaceuticals conducted the global development of the agent before licensing it to Shionogi for regulatory filing and commercialization worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy.", "output": {"entities": {"chemical": [{"text": "Ospemifene", "start": 0, "end": 10}, {"text": "estrogen", "start": 28, "end": 36}]}}, "schema": []}
{"input": "The drug is approved in the USA, and application for EU regulatory approval is underway.", "output": {"entities": {}}, "schema": []}
{"input": "This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy.", "output": {"entities": {"chemical": [{"text": "ospemifene", "start": 61, "end": 71}]}}, "schema": []}
{"input": "Pasireotide: A Review of Its Use in Cushing' s Disease.", "output": {"entities": {"chemical": [{"text": "Pasireotide", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Pasireotide (Signifor ((R))) is a new subcutaneous somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of corticotropin from the pituitary adenoma in patients with Cushing' s disease.", "output": {"entities": {"chemical": [{"text": "Pasireotide", "start": 0, "end": 11}, {"text": "Signifor", "start": 13, "end": 21}, {"text": "somatostatin", "start": 51, "end": 63}, {"text": "somatostatin", "start": 87, "end": 99}]}}, "schema": []}
{"input": "Pasireotide has a receptor binding profile that is distinct from that of other somatostatin analogues, binding with high affinity to somatostatin receptor subtype 5, which is strongly over expressed in corticotroph adenoma cells.", "output": {"entities": {"chemical": [{"text": "Pasireotide", "start": 0, "end": 11}, {"text": "somatostatin", "start": 79, "end": 91}, {"text": "somatostatin", "start": 133, "end": 145}]}}, "schema": []}
{"input": "Pasireotide is the first pituitary-directed agent to be approved for use in Cushing' s disease.", "output": {"entities": {"chemical": [{"text": "Pasireotide", "start": 0, "end": 11}]}}, "schema": []}
{"input": "In a phase III clinical trial in patients with Cushing' s disease, twice-daily pasireotide 600 or 900 mu g for 6 months led to normalization of urinary free cortisol (UFC) levels in up to a quarter of all patients (primary endpoint) and significantly reduced mean UFC levels.", "output": {"entities": {"chemical": [{"text": "pasireotide", "start": 79, "end": 90}, {"text": "cortisol", "start": 157, "end": 165}]}}, "schema": []}
{"input": "The reduction in UFC levels is rapid (within one to two months) and sustained (up to 24 months).", "output": {"entities": {}}, "schema": []}
{"input": "Most patients who do not have an early response to pasireotide do not respond at a later time point.", "output": {"entities": {"chemical": [{"text": "pasireotide", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Decreases in UFC levels achieved during pasireotide treatment are accompanied by decreases in serum and salivary cortisol levels, as well as improvements in clinical signs and symptoms, including body weight, blood pressure and health-related quality-of-life.", "output": {"entities": {"chemical": [{"text": "pasireotide", "start": 40, "end": 51}, {"text": "cortisol", "start": 113, "end": 121}]}}, "schema": []}
{"input": "Pasireotide has a generally similar tolerability profile to that of other somatostatin analogues, but is associated with a relatively high incidence of hyperglycaemia, requiring the addition or intensification of glucose-lowering medication in a substantial proportion of patients.", "output": {"entities": {"chemical": [{"text": "Pasireotide", "start": 0, "end": 11}, {"text": "somatostatin", "start": 74, "end": 86}, {"text": "glucose", "start": 213, "end": 220}]}}, "schema": []}
{"input": "Thus, pasireotide, together with on-going patient monitoring, provides a promising new option for the medical management of Cushing' s disease.", "output": {"entities": {"chemical": [{"text": "pasireotide", "start": 6, "end": 17}]}}, "schema": []}
{"input": "Bicyclic Derivatives of L-Idonojirimycin as Pharmacological Chaperones for Neuronopathic Forms of Gaucher Disease.", "output": {"entities": {"chemical": [{"text": "L-Idonojirimycin", "start": 24, "end": 40}]}}, "schema": []}
{"input": "New human beta-glucocerebrosidase (GCase) ligands with rigid 1, 6-anhydro-beta-L-idonojirimycin cores have been designed with the aid of molecular modeling.", "output": {"entities": {"chemical": [{"text": "1, 6-anhydro-beta-L-idonojirimycin", "start": 61, "end": 95}]}}, "schema": []}
{"input": "Efficient pharmacological chaperones for the L444P (trafficking-incompetent) mutant GCase enzyme associated with type 2 and 3 Gaucher disease (GD) were identified.", "output": {"entities": {}}, "schema": []}
{"input": "Proteomic identification of the candidate target proteins of 15-deoxy-delta (12, 14)-prostaglandin J2.", "output": {"entities": {"chemical": [{"text": "15-deoxy-delta (12, 14)-prostaglandin J2", "start": 61, "end": 101}]}}, "schema": []}
{"input": "15-deoxy-delta12, 14-prostaglandin J2 (15d-PGJ2) is an endogenous anti-inflammatory lipid derived from PGD2.", "output": {"entities": {"chemical": [{"text": "15-deoxy-delta12, 14-prostaglandin J2", "start": 0, "end": 37}, {"text": "15d-PGJ2", "start": 39, "end": 47}, {"text": "PGD2", "start": 103, "end": 107}]}}, "schema": []}
{"input": "One potential mechanism for its activity is the covalent modification of cellular proteins, via a reactive alpha, beta-unsaturated carbonyl group in its cyclopentenone ring, which in turn alters protein function.", "output": {"entities": {"chemical": [{"text": "alpha, beta-unsaturated carbonyl", "start": 107, "end": 139}, {"text": "cyclopentenone", "start": 153, "end": 167}]}}, "schema": []}
{"input": "In order to identify the candidate target proteins covalently modified by 15d-PGJ2 in human aortic endothelial cell (EC), EC were treated with biotinylated-15d-PGJ2, the modified proteins extracted by Neutravidin affinity-purification and the proteins identified by LTQ Orbitrap mass spectrometer.", "output": {"entities": {"chemical": [{"text": "15d-PGJ2", "start": 74, "end": 82}, {"text": "biotinylated-15d-PGJ2", "start": 143, "end": 164}]}}, "schema": []}
{"input": "Classification of the 358 identified proteins was performed using PANTHER classification system (www. pantherdb. org), showing that the proteins mapped to metabolic process, cellular process and transport activity.", "output": {"entities": {}}, "schema": []}
{"input": "This protein data set highlights the potential for 15d-PGJ2 to covalently modify cellular proteins and provides a source of data that will aid further studies on the mechanism of action of this endogenous regulator of inflammation.", "output": {"entities": {"chemical": [{"text": "15d-PGJ2", "start": 51, "end": 59}]}}, "schema": []}
{"input": "This article is protected by copyright.", "output": {"entities": {}}, "schema": []}
{"input": "All rights reserved.", "output": {"entities": {}}, "schema": []}
{"input": "Emergent Renal Dysfunction with Colistin Pharmacotherapy.", "output": {"entities": {"chemical": [{"text": "Colistin", "start": 32, "end": 40}]}}, "schema": []}
{"input": "STUDY OBJECTIVE: To evaluate the association between the administration of intravenous (IV) colistin and the emergence of renal dysfunction.", "output": {"entities": {"chemical": [{"text": "colistin", "start": 92, "end": 100}]}}, "schema": []}
{"input": "DESIGN: A retrospective medical record review.", "output": {"entities": {}}, "schema": []}
{"input": "SETTING: A tertiary care academic medical center.", "output": {"entities": {}}, "schema": []}
{"input": "PATIENTS: A total of 174 critically ill patients who received at least one dose of IV colistin between 2004 and 2007.", "output": {"entities": {"chemical": [{"text": "colistin", "start": 86, "end": 94}]}}, "schema": []}
{"input": "MEASUREMENTS AND MAIN RESULTS: The primary outcome was development of renal dysfunction, defined as an increase in serum creatinine of 50% or more during therapy or the initiation of renal replacement therapy (RRT), in patients who received at least one dose of colistin and were not already on RRT.", "output": {"entities": {"chemical": [{"text": "creatinine", "start": 121, "end": 131}, {"text": "colistin", "start": 262, "end": 270}]}}, "schema": []}
{"input": "The severity of renal dysfunction was further categorized by the RIFLE criteria.", "output": {"entities": {}}, "schema": []}
{"input": "Demographic and clinical characteristics were analyzed by logistic regression for association with new renal dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 174 patients were evaluated for renal dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "Of these patients, 84 (48%) experienced renal dysfunction on colistin.", "output": {"entities": {"chemical": [{"text": "colistin", "start": 61, "end": 69}]}}, "schema": []}
{"input": "On multivariate analysis, age in years (odds ratio [OR] 1. 03, 95% confidence interval [CI] 1. 01-1. 05) and receipt of concurrent nephrotoxin (s) (OR 3. 35, 95% CI 1. 34-8. 36) significantly increased the risk of developing renal dysfunction.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: In this critically ill population, renal dysfunction occurred frequently and was associated with older age and receipt of nephrotoxins.", "output": {"entities": {}}, "schema": []}
{"input": "Patterning Surfaces for Controlled Platelet Adhesion and Detection of Dysfunctional Platelets.", "output": {"entities": {}}, "schema": []}
{"input": "Platelets play a fundamental role in thrombus formation and in the pathogenesis of arterial thrombosis.", "output": {"entities": {}}, "schema": []}
{"input": "Patterning surfaces for controlled platelet adhesion paves the way for adhesion and activation mechanisms in platelets and detection of platelet functional defects.", "output": {"entities": {}}, "schema": []}
{"input": "Here, a new and simple method based on controlled polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) on the surface of styrene-block-(ethylene-co-butylene)-block-styrene (SEBS) is shown.", "output": {"entities": {"chemical": [{"text": "2-methacryloyloxyethyl phosphorylcholine", "start": 68, "end": 108}, {"text": "MPC", "start": 110, "end": 113}, {"text": "styrene-block-(ethylene-co-butylene)-block-styrene", "start": 133, "end": 183}, {"text": "SEBS", "start": 185, "end": 189}]}}, "schema": []}
{"input": "The competition between polymerization and degradation enables platelet adhesion on SEBS to be switched on and off.", "output": {"entities": {"chemical": [{"text": "SEBS", "start": 84, "end": 88}]}}, "schema": []}
{"input": "The adhesive sites of the platelets can be down to single cell level, and the dysfunctional platelets can be quantitatively detected.", "output": {"entities": {}}, "schema": []}
{"input": "Thermal and Electrical Transport in Ultralow Density Single-Walled Carbon Nanotube Networks.", "output": {"entities": {"chemical": [{"text": "Carbon", "start": 67, "end": 73}]}}, "schema": []}
{"input": "The thermal, electrical, and thermoelectric properties of aerogels of single-walled carbon nanotubes are characterized.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 84, "end": 90}]}}, "schema": []}
{"input": "Their ultralow density enables the transport properties of the junctions to be distinguished from those of the nanotubes themselves.", "output": {"entities": {}}, "schema": []}
{"input": "Junction thermal and electrical conductances are found to be orders of magnitude larger than those found in typical dense SWCNT networks.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, the average junction thermal conductance is close to the theoretical maximum for a van der Waals bonded SWCNT junction.", "output": {"entities": {}}, "schema": []}
{"input": "A Tunable Spherical Cap Microfluidic Electrically Small Antenna.", "output": {"entities": {}}, "schema": []}
{"input": "A highly efficient microfluidic 3D electrically small antenna is created using a simple fabrication technique.", "output": {"entities": {}}, "schema": []}
{"input": "It is easy to construct simply by pneumatically inflating a planar microfluidic antenna into a spherical cap.", "output": {"entities": {}}, "schema": []}
{"input": "It has premium performance around its hemispherical shape, combining a wide working band with high efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Receptor-Specific Delivery of Protein Antigen to Dendritic Cells by a Nanoemulsion Formed Using Top-Down Non-Covalent Click Self-Assembly.", "output": {"entities": {}}, "schema": []}
{"input": "A new class of targeted and immune-evading nanocarrier made using only biological components and facile processes is assembled in a bottom-up fashion.", "output": {"entities": {}}, "schema": []}
{"input": "Simple top-down sequential addition of immune-evading or receptor-specific antibody elements conjugated to biosurfactant protein DAMP4 promotes self-assembly at an interface previously formed in the presence of peptide surfactant AM1, leading to a functional display at the interface through non-covalent molecular self-assembly.", "output": {"entities": {}}, "schema": []}
{"input": "A Dual Enzyme Microgel with High Antioxidant Ability Based on Engineered Seleno-Ferritin and Artificial Superoxide Dismutase.", "output": {"entities": {"chemical": [{"text": "Superoxide", "start": 104, "end": 114}]}}, "schema": []}
{"input": "An antioxidant microgel with both glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities is reported.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 34, "end": 45}, {"text": "superoxide", "start": 67, "end": 77}]}}, "schema": []}
{"input": "Using computational design and genetic engineering methods, the main catalytic components of GPx are fabricated onto the surface of ferritin.", "output": {"entities": {}}, "schema": []}
{"input": "The resulting seleno-ferritin (Se-Fn) monomers can self-assemble into nanocomposites that exhibit remarkable GPx activity due to the well organized multi-GPx catalytic centers.", "output": {"entities": {"chemical": [{"text": "Se", "start": 31, "end": 33}]}}, "schema": []}
{"input": "Subsequently, a porphyrin derivative is synthesized as an SOD mimic, and is employed to construct a synergistic dual enzyme system by crosslinking Se-Fn nanocomposites into a microgel.", "output": {"entities": {"chemical": [{"text": "porphyrin", "start": 16, "end": 25}, {"text": "Se", "start": 147, "end": 149}]}}, "schema": []}
{"input": "Significantly, this dual enzyme microgel is demonstrated to display better antioxidant ability than single GPx or SOD mimics in protecting cells from oxidative damage.", "output": {"entities": {}}, "schema": []}
{"input": "A Model-Based Approach to Predict Longitudinal HbA1c, Using Early Phase Glucose Data From Type 2 Diabetes Mellitus Patients After Anti-Diabetic Treatment.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 72, "end": 79}]}}, "schema": []}
{"input": "Predicting late phase outcomes from early-phase findings can help inform decisions in drug development.", "output": {"entities": {}}, "schema": []}
{"input": "If the measurements in early-phase differ from those in late phase, forecasting is more challenging.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, we present a model-based approach for predicting glycosylated hemoglobin (HbA1c) in late phase using glucose and insulin concentrations from an early-phase study, investigating an anti-diabetic treatment.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 116, "end": 123}]}}, "schema": []}
{"input": "Two previously published models were used; an integrated glucose and insulin (IGI) model for meal tolerance tests and an integrated glucose-red blood cell-HbA1c (IGRH) model predicting the formation of HbA1c from the average glucose concentration (Cg, av).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 57, "end": 64}, {"text": "glucose", "start": 132, "end": 139}, {"text": "glucose", "start": 225, "end": 232}]}}, "schema": []}
{"input": "Output from the IGI model was used as input to the IGRH model.", "output": {"entities": {}}, "schema": []}
{"input": "Parameters of the IGI model and drug effects were estimated using data from a phase1 study in 59 diabetic patients receiving various doses of a glucokinase activator.", "output": {"entities": {}}, "schema": []}
{"input": "Cg, av values were simulated according to a Phase 2 study design and used in the IGRH model for predictions of HbA1c.", "output": {"entities": {}}, "schema": []}
{"input": "The performance of the model-based approach was assessed by comparing the predicted to the actual outcome of the Phase 2 study.", "output": {"entities": {}}, "schema": []}
{"input": "We have shown that this approach well predicts the longitudinal HbA1c response in a 12-week study using only information from a 1-week study where glucose and insulin concentrations were measured.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 147, "end": 154}]}}, "schema": []}
{"input": "Transient, Biocompatible Electronics and Energy Harvesters Based on ZnO.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 68, "end": 71}]}}, "schema": []}
{"input": "The combined use of ZnO, Mg, MgO, and silk provides routes to classes of thin-film transistors and mechanical energy harvesters that are soluble in water and biofluids.", "output": {"entities": {"chemical": [{"text": "ZnO", "start": 20, "end": 23}, {"text": "Mg", "start": 25, "end": 27}, {"text": "MgO", "start": 29, "end": 32}]}}, "schema": []}
{"input": "Experimental and theoretical studies of the operational aspects and dissolution properties of this type of transient electronics technology illustrate its various capabilities.", "output": {"entities": {}}, "schema": []}
{"input": "Application opportunities range from resorbable biomedical implants, to environmentally dissolvable sensors, and degradable consumer electronics.", "output": {"entities": {}}, "schema": []}
{"input": "Cell Surface Receptor Targeted Biomimetic Apatite Nanocrystals for Cancer Therapy.", "output": {"entities": {"chemical": [{"text": "Apatite", "start": 42, "end": 49}]}}, "schema": []}
{"input": "Nanosized drug carriers functionalized with moieties specifically targeting tumor cells are promising tools in cancer therapy, due to their ability to circulate in the bloodstream for longer periods and their selectivity for tumor cells, enabling the sparing of healthy tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Because of its biocompatibility, high bioresorbability, and responsiveness to pH changes, synthetic biomimetic nanocrystalline apatites are used as nanocarriers to produce multifunctional nanoparticles, by coupling them with the chemotherapeutic drug doxorubicin (DOXO) and the DO-24 monoclonal antibody (mAb) directed against the Met/Hepatocyte Growth Factor receptor (Met/HGFR), which is over-expressed on different types of carcinomas and thus represents a useful tumor target.", "output": {"entities": {"chemical": [{"text": "apatites", "start": 127, "end": 135}, {"text": "doxorubicin", "start": 251, "end": 262}, {"text": "DOXO", "start": 264, "end": 268}]}}, "schema": []}
{"input": "The chemical-physical features of the nanoparticles are fully investigated and their interaction with cells expressing (GTL-16 gastric carcinoma line) or not expressing (NIH-3T3 fibroblasts) the Met/HGFR is analyzed.", "output": {"entities": {}}, "schema": []}
{"input": "Functionalized nanoparticles specifically bind to and are internalized in cells expressing the receptor (GTL-16) but not in the ones that do not express it (NIH-3T3).", "output": {"entities": {}}, "schema": []}
{"input": "Moreover they discharge DOXO in the targeted GTL-16 cells that reach the nucleus and display cytotoxicity as assessed in an MTT assay.", "output": {"entities": {"chemical": [{"text": "DOXO", "start": 24, "end": 28}, {"text": "MTT", "start": 124, "end": 127}]}}, "schema": []}
{"input": "Two different types of ternary nanoparticles are prepared, differing for the sequence of the functionalization steps (adsorption of DOXO first and then mAb or vice versa), and it is found that the ones in which mAb is adsorbed first are more efficient under all the examined aspects (binding, internalization, cytotoxicity), possibly because of a better mAb orientation on the nanoparticle surface.", "output": {"entities": {"chemical": [{"text": "DOXO", "start": 132, "end": 136}]}}, "schema": []}
{"input": "These multifunctional nanoparticles could thus be useful instruments for targeted local or systemic drug delivery, allowing a reduction in the therapeutic dose of the drug and thus adverse side effects.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, this work opens new perspectives in the use of nanocrystalline apatites as a new platform for theranostic applications in nanomedicine.", "output": {"entities": {"chemical": [{"text": "apatites", "start": 73, "end": 81}]}}, "schema": []}
{"input": "Facile Preparation of Ordered Porous Graphene-Metal Oxide @C Binder-Free Electrodes with High Li Storage Performance.", "output": {"entities": {"chemical": [{"text": "Graphene", "start": 37, "end": 45}, {"text": "Metal Oxide", "start": 46, "end": 57}, {"text": "Li", "start": 94, "end": 96}]}}, "schema": []}
{"input": "A facile and general method is reported to prepare ordered porous graphene-based binder-free electrodes on a large scale.", "output": {"entities": {"chemical": [{"text": "graphene", "start": 66, "end": 74}]}}, "schema": []}
{"input": "This preparation process allows the easy adjustment of the selected components, weight ratio of componets, and the thickness of the electrodes.", "output": {"entities": {}}, "schema": []}
{"input": "Such ordered porous electrodes demonstrate superior Li storage properties; for example, graphene-Fe3 O4 @C depicts high capacities of 1123. 8 and 505 mAh g (-1) at current densities of 0. 5 and 10 A g (-1), respectively.", "output": {"entities": {"chemical": [{"text": "Li", "start": 52, "end": 54}, {"text": "graphene", "start": 88, "end": 96}, {"text": "Fe3 O4", "start": 97, "end": 103}]}}, "schema": []}
{"input": "On the association between Hashimoto' s thyroiditis and papillary thyroid carcinoma.", "output": {"entities": {}}, "schema": []}
{"input": "Looking 100 years back and, hopefully, fewer years ahead to sort out this association.", "output": {"entities": {}}, "schema": []}
{"input": "NOT required for a LETTER TO THE EDITOR.", "output": {"entities": {}}, "schema": []}
{"input": "The Relationship between Charge Density and Polyelectrolyte Brush Profile Using Simultaneous Neutron Reflectivity and In Situ Attenuated Total Internal Reflection FTIR.", "output": {"entities": {}}, "schema": []}
{"input": "We report on a novel experimental study of a pH-responsive polyelectrolyte brush at the silicon/D2O interface.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 88, "end": 95}, {"text": "D2O", "start": 96, "end": 99}]}}, "schema": []}
{"input": "A poly [2-(diethylamino) ethyl methacrylate] brush was grown on a large silicon crystal which acted as both a substrate for a neutron reflectivity solid/liquid experiment but also as an FTIR-ATR spectroscopy crystal.", "output": {"entities": {"chemical": [{"text": "poly [2-(diethylamino) ethyl methacrylate]", "start": 2, "end": 44}, {"text": "silicon", "start": 72, "end": 79}]}}, "schema": []}
{"input": "This arrangement has allowed for both neutron reflectivities and FTIR spectroscopic information to be measured in parallel.", "output": {"entities": {}}, "schema": []}
{"input": "The chosen polybase brush shows strong IR bands which can be assigned to the N-D (+) stretch, D2O, and a carbonyl group.", "output": {"entities": {"chemical": [{"text": "D2O", "start": 94, "end": 97}, {"text": "carbonyl", "start": 105, "end": 113}]}}, "schema": []}
{"input": "From such FTIR data, we are able to closely monitor the degree of protonation along the polymer chain as well as revealing information concerning the D2O concentration at the interface.", "output": {"entities": {"chemical": [{"text": "D2O", "start": 150, "end": 153}]}}, "schema": []}
{"input": "The neutron reflectivity data allows us to determine the physical brush profile normal to the solid/liquid interface along with the corresponding degree of hydration.", "output": {"entities": {}}, "schema": []}
{"input": "This combined approach makes it possible to quantify the charge on a polymer brush alongside the morphology adopted by the polymer chains.", "output": {"entities": {}}, "schema": []}
{"input": "Total Synthesis of the Marine Cyclic Depsipeptide Viequeamide A.", "output": {"entities": {"chemical": [{"text": "Viequeamide A", "start": 50, "end": 63}]}}, "schema": []}
{"input": "The first total synthesis of viequeamide A, a natural cyclic depsipeptide isolated from a marine button cyanobacterium, was achieved with the N-Me-Val-Thr peptide bond as the final macrocyclization site.", "output": {"entities": {"chemical": [{"text": "viequeamide A", "start": 29, "end": 42}, {"text": "N-Me-Val-Thr", "start": 142, "end": 154}]}}, "schema": []}
{"input": "The synthetic product gave nearly identical spectroscopic data to that reported for the natural product.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular Binoculars: How to Spatially Resolve Environmental Fluctuations by Following Two or More Single-Molecule Spectral Trails at a Time.", "output": {"entities": {}}, "schema": []}
{"input": "We propose a novel type of spectral diffusion experiment that enables one to decouple spatial characteristics of the environmental fluctuations, such as their concentration, from the interaction with the chromophore.", "output": {"entities": {}}, "schema": []}
{"input": "Traditional hole broadening experiments do not allow for such decoupling in the common case when the chromophore-environment interaction is scale invariant.", "output": {"entities": {}}, "schema": []}
{"input": "Here we propose to simultaneously follow the spectral trails of a small number of nearby chromophores---two or more---which thereby sense a highly overlapping set of the fluctuations.", "output": {"entities": {}}, "schema": []}
{"input": "To this end, we estimate the combined probability distribution for the frequencies of a set of chromophores contained within the {\\em same} sample.", "output": {"entities": {}}, "schema": []}
{"input": "The present setup introduces a new length scale, i. e., the inter-chromophore distance, which breaks the aforementioned scale invariance and enables one to determine independently the concentration of the environmental fluctuations and their coupling to the chromophores, by monitoring the time after which spectral diffusion of distinct chromophores becomes uncorrelated.", "output": {"entities": {}}, "schema": []}
{"input": "We illustrate these results with structural excitations in low temperature glasses.", "output": {"entities": {}}, "schema": []}
{"input": "Plasmonic resonances in self-assembled reduced symmetry gold nanorod structures.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembled plasmonic Dolmen structures consisting of small gold nanorods (length = 50 nm and diameter = 20 nm) with a few nanometer gaps are observed to show coherent effects of super-radiance and characteristics of Fano resonance due to the significantly reduced symmetry of the structure.", "output": {"entities": {}}, "schema": []}
{"input": "Relative to previous larger structures from top-down electron-beam lithography, the single crystallinity and atomically smooth surfaces of these self-assembled plasmonic structures result in 50% narrower resonances, and the small gaps with associated strong coupling enable observation of multiple dark and bright modes.", "output": {"entities": {}}, "schema": []}
{"input": "By tilting the cap monomer with respect to the base dimer an order of magnitude increase in E-field enhancement at the Fano dip is obtained.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, a spectrally broad mode is observed indicating the strong impact of the geometry of the structure on the nature of coupled modes.", "output": {"entities": {}}, "schema": []}
{"input": "The highly localized electric near-fields in the gaps will enable strong light matter interactions and the narrow resonances will be useful for improved figure of merits in inexpensive chemical and biosensing.", "output": {"entities": {}}, "schema": []}
{"input": "Insight into the Structure of Single Antheraea pernyi Silkworm Fibers Using Synchrotron FTIR Microspectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "Synchrotron FTIR (S-FTIR) microspectroscopy was used to monitor both protein secondary structures (conformations) and their orientations in single cocoon silk fibers of the Chinese Tussah silk moth (Antheraea pernyi).", "output": {"entities": {}}, "schema": []}
{"input": "In addition, to understand further the relationship between structure and properties of single silk fibers, we studied the changes of orientation and content of different secondary structures in single A. pernyi silk fibers when subjected to different strains.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that the content and orientation of beta-sheet was almost unchanged for strains from 0 to 0. 3.", "output": {"entities": {}}, "schema": []}
{"input": "However, the orientation of alpha-helix and random coil improved progressively with increasing strain, with a parallel decrease in alpha-helix content and an increase in random coil.", "output": {"entities": {}}, "schema": []}
{"input": "This clearly indicates that most of the deformation upon stretching of the single fiber is due to the change of orientation in the amorphous regions coupled with a conversion of some of the alpha-helix to random coil.", "output": {"entities": {}}, "schema": []}
{"input": "These observations provide an explanation for the supercontraction behavior of certain animal silks and are likely to facilitate understanding and optimization of postdrawing used in the conjunction with the wet-spinning of silk fibers from regenerated silk solutions.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, our work demonstrates the power of S-FTIR microspectroscopy for studying biopolymers.", "output": {"entities": {}}, "schema": []}
{"input": "Statins Protect Human Endothelial Cells from TNF-induced Inflammation via ERK5 Activation.", "output": {"entities": {}}, "schema": []}
{"input": "3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) exert pleiotropic effects on the cardiovascular system, in part through a decrease in reactive oxygen species (ROS) formation and reduction of vascular inflammation.", "output": {"entities": {"chemical": [{"text": "3-Hydroxy-3-methylglutaryl coenzyme A", "start": 0, "end": 37}, {"text": "oxygen", "start": 164, "end": 170}]}}, "schema": []}
{"input": "To elucidate the molecular mechanisms involved in these effects, we investigated the effect of statins on TNF-alpha-induced ROS production, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression in human aortic endothelial cells (HAECs).", "output": {"entities": {}}, "schema": []}
{"input": "Exposure of HAECs to TNF-alpha caused production of ROS via Rac-1 membrane translocation and activation.", "output": {"entities": {}}, "schema": []}
{"input": "The Rac-1 activation and ROS liberation mediated TNF-stimulated NF-kappa B activation and the subsequent VCAM-1 and ICAM-1 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Extracellular-signal-regulated kinase 5 (ERK5) plays a central role in inhibiting endothelial inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "Immune complex kinase assay of protein extracts from HAECs treated with atorvastatin revealed increased ERK5 activity in a time-and dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 72, "end": 84}]}}, "schema": []}
{"input": "In addition, pretreatment with atorvastatin inhibited TNF-alpha-induced ROS production and VCAM-1 and ICAM-1 expression.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 31, "end": 43}]}}, "schema": []}
{"input": "Chemical or genetic inhibition of ERK5 ablated the statins inhibition of Rac-1 activation, ROS formation, NF-kappa B, VCAM-1 and ICAM-1 expression induced by TNF-alpha.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, statins, via ERK5 activation, suppress TNF-stimulated Rac-1 activation, ROS generation, NF-kappa B activation and VCAM-1 and ICAM-1 expression in human ECs, which provides a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system.", "output": {"entities": {}}, "schema": []}
{"input": "Protective effect of ethyl acetate fraction of Acacia ferruginea DC. against ethanol-induced gastric ulcer in rats.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 21, "end": 34}, {"text": "ethanol", "start": 77, "end": 84}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: In traditional systems of medicine, stem bark of Acacia ferruginea DC.", "output": {"entities": {}}, "schema": []}
{"input": "is used for the treatment of itching, leucoderma, ulcers, stomatitis and diseases of the blood.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, we determined antioxidant and anti-ulcerogenic activities of Acacia ferruginea stem bark.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: Acetone extract and its sub-fractions of Acacia ferruginea stem bark were subjected to assess their antioxidant potential using various in vitro systems such as DPPH (*), ABTS (* +) scavenging, FRAP and phosphomolybdenum reduction activities.", "output": {"entities": {"chemical": [{"text": "Acetone", "start": 23, "end": 30}, {"text": "DPPH (*)", "start": 184, "end": 192}, {"text": "ABTS (* +)", "start": 194, "end": 204}, {"text": "phosphomolybdenum", "start": 226, "end": 243}]}}, "schema": []}
{"input": "Based on the antioxidant potential, the ethyl acetate fraction was used to evaluate the protective effect of ethanol-induced gastric damage in rat model.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 109, "end": 116}]}}, "schema": []}
{"input": "Enzyme activities such as superoxide dismutase, glutathione, catalase and lipid peroxidation were also determined in the stomach tissues.", "output": {"entities": {"chemical": [{"text": "superoxide", "start": 26, "end": 36}, {"text": "glutathione", "start": 48, "end": 59}]}}, "schema": []}
{"input": "RESULTS: Ethyl acetate fraction (AFE) of Acacia ferruginea stem bark registered higher antioxidant and free radical scavenging activities than the crude acetone extract and other fractions.", "output": {"entities": {"chemical": [{"text": "Ethyl acetate", "start": 9, "end": 22}, {"text": "acetone", "start": 153, "end": 160}]}}, "schema": []}
{"input": "In addition, AFE exhibited that the IC50 values of DPPH (2. 5 micro g/ml) and ABTS (1. 8 micro g/ml) were lower when compared to the standard quercetin (12. 4 micro g/ml and 4. 7 micro g/ml, respectively).", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 51, "end": 55}, {"text": "ABTS", "start": 78, "end": 82}, {"text": "quercetin", "start": 142, "end": 151}]}}, "schema": []}
{"input": "In ethanol induced gastric ulcer, administration of AFE at doses of 10mg/kg, 50mg/kg and 100mg/kg body weight prior to ethanol ingestion significantly protected the stomach ulceration.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 3, "end": 10}, {"text": "ethanol", "start": 119, "end": 126}]}}, "schema": []}
{"input": "Consequently significant changes were observed in enzyme activities such as SOD, CAT, GSH and LPO in the stomach tissues when compared with ethanol control group.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 86, "end": 89}, {"text": "ethanol", "start": 140, "end": 147}]}}, "schema": []}
{"input": "CONCLUSION: It is concluded that the ethyl acetate fraction of Acacia ferruginea stem bark possessed higher antioxidant and anti-ulcerogenic activities.", "output": {"entities": {"chemical": [{"text": "ethyl acetate", "start": 37, "end": 50}]}}, "schema": []}
{"input": "Based on the results we suggest that Acacia ferruginea stem bark has potential to provide a therapeutic approach to ethanol mediated ulcer as an effective anti-ulcer agent.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 116, "end": 123}]}}, "schema": []}
{"input": "Botany, traditional uses, phytochemistry and pharmacology of Waltheria indica L.", "output": {"entities": {}}, "schema": []}
{"input": "(syn. Waltheria americana): A review.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Waltheria indica L.", "output": {"entities": {}}, "schema": []}
{"input": "(syn. Waltheria americana) is commonly used in traditional medicine in Africa, South America and Hawaii, mainly against pain, inflammation, conditions of inflammation, diarrhea, dysentery, conjunctivitis, wounds, abscess, epilepsy, convulsions, anemia, erectile dysfunctions, bladder ailments and asthma.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE REVIEW: To provide an up-to-date overview of the botany, phytochemistry, traditional uses, pharmacological activities and toxicity data of Waltheria indica.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, studies providing an evidence for local and traditional uses of Waltheria indica are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Further phytochemical and pharmacological potential of this species are suggested for future investigations.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: The information was collected from scientific journals, books, theses and reports via academic libraries and electronic search.", "output": {"entities": {}}, "schema": []}
{"input": "These sources include Pubmed, Web of Science, Portal de Portales-Latindex, Science Research. com and Google scholar.", "output": {"entities": {}}, "schema": []}
{"input": "These studies about the medical botanical, traditional uses, chemical, pharmacological and toxicological data on Waltheria indica were published in English, Portuguese, Spanish, German and French.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Crude extracts and isolated compounds from Waltheria indica were investigated and showed analgesic, anti-inflammatory, antibacterial, antifungal, antimalarial, anti-anemic, anti-oxidant, sedative and anticonvulsant activities.", "output": {"entities": {}}, "schema": []}
{"input": "The phytochemical investigations showed the presence of cyclopeptid alkaloids, flavonoids (e. g., (-)-epicatechin, quercetin, kaempferol, kaempferol-3-O-beta-d-(6''-E-p-coumaryl)-glucopyranoside), tannins, sterols, terpenes, saponins, anthraquinones.", "output": {"entities": {"chemical": [{"text": "cyclopeptid alkaloids", "start": 56, "end": 77}, {"text": "flavonoids", "start": 79, "end": 89}, {"text": "(-)-epicatechin", "start": 98, "end": 113}, {"text": "quercetin", "start": 115, "end": 124}, {"text": "kaempferol", "start": 126, "end": 136}, {"text": "kaempferol-3-O-beta-d-(6''-E-p-coumaryl)-glucopyranoside)", "start": 138, "end": 195}, {"text": "tannins", "start": 197, "end": 204}, {"text": "sterols", "start": 206, "end": 213}, {"text": "terpenes", "start": 215, "end": 223}, {"text": "saponins", "start": 225, "end": 233}, {"text": "anthraquinones", "start": 235, "end": 249}]}}, "schema": []}
{"input": "Studies of acute toxicity in animal indicated that Waltheria indica can be toxic.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: Waltheria indica possess therapeutic potential in the treatment of inflammation, malaria, infectious diseases (e. g., lungs infection due to Klebsiella pneumoniae, diarrhea due to Candida albicans or Escherichia coli) and prevention of oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "Further studies are necessary to explore pure compounds responsible for the pharmacological effects and the mechanisms of action.", "output": {"entities": {}}, "schema": []}
{"input": "Further investigations are also needed to provide an evidence base for traditional uses of this species against pain, anemia, convulsions and epilepsy.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, there is a pressing need to investigate the other traditional uses such as dysentery, syphilis, erectile dysfunctions and asthma.", "output": {"entities": {}}, "schema": []}
{"input": "beta-estradiol 17-valerate affects embryonic development and sexual differentiation in Japanese medaka (Oryzias latipes).", "output": {"entities": {"chemical": [{"text": "beta-estradiol 17-valerate", "start": 0, "end": 26}]}}, "schema": []}
{"input": "beta-estradiol 17-valerate (EV) is a synthetic estrogen widely used in combination with other steroid hormones in hormone replacement therapy drugs and is detected in natural waters.", "output": {"entities": {"chemical": [{"text": "beta-estradiol 17-valerate", "start": 0, "end": 26}, {"text": "estrogen", "start": 47, "end": 55}, {"text": "steroid hormones", "start": 94, "end": 110}]}}, "schema": []}
{"input": "Although EV is known as an estrogenic chemical, there is still a lack of data on its developmental and reproductive toxicities in fish following exposure to EV during embryo-larval-, juvenile-and adult-life stages in Japanese medaka (Oryzias latipes).", "output": {"entities": {}}, "schema": []}
{"input": "At the early life stage, the fertilized eggs of medaka were exposed to 1, 10, 100 and 1000ng/L EV for 15 days, and hatched larval fish were continually exposed to the same concentration range for an additional 15 days.", "output": {"entities": {}}, "schema": []}
{"input": "The results showed that exposure to 10ng/L or above resulted in adverse effects on hatchability and time to hatching, and the number of hatched females was twice that of males at 10ng/L or above.", "output": {"entities": {}}, "schema": []}
{"input": "When the hatched fish were continually exposed to 1, 10 and 100ng/L of EV for another 40 days, the hepatosomatic index (HSI) was increased in both males and females, and the gonadosomatic index (GSI) was decreased in females, and increased in males.", "output": {"entities": {}}, "schema": []}
{"input": "Sex reversal was found in fish exposed to 1ng/L and above.", "output": {"entities": {}}, "schema": []}
{"input": "Quantitative real-time RT-PCR showed that mRNA levels of estrogen receptor alpha (ER-alpha) and vitellogenin-I (VTG-I) in the liver of females were significantly down-regulated, while those of vitellogenin-I (VTG-I) in the liver of males were significantly up-regulated at all concentrations.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 57, "end": 65}]}}, "schema": []}
{"input": "These findings suggest that EV is a reproductive toxicant and estrogenic chemical in both male and female fish.", "output": {"entities": {}}, "schema": []}
{"input": "Estradiol replacement enhances cocaine-stimulated locomotion in female C57BL/6 mice through estrogen receptor alpha.", "output": {"entities": {"chemical": [{"text": "Estradiol", "start": 0, "end": 9}, {"text": "cocaine", "start": 31, "end": 38}, {"text": "estrogen", "start": 92, "end": 100}]}}, "schema": []}
{"input": "Psychostimulant effects are enhanced by ovarian hormones in women and female rodents.", "output": {"entities": {}}, "schema": []}
{"input": "Estradiol increases behavioral responses to psychostimulants in women and female rats, although the underlying mechanism is unknown.", "output": {"entities": {"chemical": [{"text": "Estradiol", "start": 0, "end": 9}]}}, "schema": []}
{"input": "This study utilized mice to investigate the time frame and receptor mediation of estradiol' s enhancement of cocaine-induced behavior as mice enable parallel use of genetic, surgical and pharmacological methods.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 81, "end": 90}, {"text": "cocaine", "start": 109, "end": 116}]}}, "schema": []}
{"input": "The spontaneous behavior of Sham and Ovariectomized (Ovx) female wildtype (WT) mice was determined during habituation to a novel environment and after cocaine administration.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 151, "end": 158}]}}, "schema": []}
{"input": "Ovx mice were replaced with vehicle (sesame oil) or 17 beta-estradiol (E2) for 2 days or 30 min prior to a cocaine challenge to investigate the time course of E2' s effects.", "output": {"entities": {"chemical": [{"text": "17 beta-estradiol", "start": 52, "end": 69}, {"text": "cocaine", "start": 107, "end": 114}]}}, "schema": []}
{"input": "To examine receptor mediation of estradiol effects, Ovx mice replaced for 2 days with either the ER alpha-selective agonist PPT or the ER beta-selective agonist DPN were compared to Sham mice, and mice lacking either ER alpha (alpha ERKO) or ER beta (beta ERKO) were compared to WT littermates.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 33, "end": 42}, {"text": "PPT", "start": 124, "end": 127}, {"text": "DPN", "start": 161, "end": 164}]}}, "schema": []}
{"input": "Ovx mice exhibited fewer ambulations during habituation than Sham females.", "output": {"entities": {}}, "schema": []}
{"input": "Cocaine-induced increases in behavioral ratings were greater in Sham than in Ovx mice.", "output": {"entities": {"chemical": [{"text": "Cocaine", "start": 0, "end": 7}]}}, "schema": []}
{"input": "Two days but not 30 min of E2 replacement in Ovx mice increased cocaine responses to Sham levels.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 64, "end": 71}]}}, "schema": []}
{"input": "PPT replacement also increased the cocaine response relative to vehicle-or DPN-treated Ovx mice.", "output": {"entities": {"chemical": [{"text": "PPT", "start": 0, "end": 3}, {"text": "cocaine", "start": 35, "end": 42}, {"text": "DPN", "start": 75, "end": 78}]}}, "schema": []}
{"input": "alpha ERKO mice displayed modestly attenuated behavioral responses to novelty and cocaine compared to alpha WT littermates, but no behavioral differences were found between beta ERKO and beta WT mice.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 82, "end": 89}]}}, "schema": []}
{"input": "These results suggest that E2 enhances cocaine-stimulated locomotion in mice predominantly through ER alpha.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 39, "end": 46}]}}, "schema": []}
{"input": "Discovery of natural estrogen receptor modulators with structure-based virtual screening.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 21, "end": 29}]}}, "schema": []}
{"input": "Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ER alpha and ER beta.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 36, "end": 44}]}}, "schema": []}
{"input": "Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2. 55 and 4. 68 mu M for ER alpha and ER beta, respectively.", "output": {"entities": {"chemical": [{"text": "cycloartane triterpenoids", "start": 33, "end": 58}]}}, "schema": []}
{"input": "Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation.", "output": {"entities": {}}, "schema": []}
{"input": "Designing degradable hydrogels for orthogonal control of cell microenvironments.", "output": {"entities": {}}, "schema": []}
{"input": "Degradable and cell-compatible hydrogels can be designed to mimic the physical and biochemical characteristics of native extracellular matrices and provide tunability of degradation rates and related properties under physiological conditions.", "output": {"entities": {}}, "schema": []}
{"input": "Hence, such hydrogels are finding widespread application in many bioengineering fields, including controlled bioactive molecule delivery, cell encapsulation for controlled three-dimensional culture, and tissue engineering.", "output": {"entities": {}}, "schema": []}
{"input": "Cellular processes, such as adhesion, proliferation, spreading, migration, and differentiation, can be controlled within degradable, cell-compatible hydrogels with temporal tuning of biochemical or biophysical cues, such as growth factor presentation or hydrogel stiffness.", "output": {"entities": {}}, "schema": []}
{"input": "However, thoughtful selection of hydrogel base materials, formation chemistries, and degradable moieties is necessary to achieve the appropriate level of property control and desired cellular response.", "output": {"entities": {}}, "schema": []}
{"input": "In this review, hydrogel design considerations and materials for hydrogel preparation, ranging from natural polymers to synthetic polymers, are overviewed.", "output": {"entities": {}}, "schema": []}
{"input": "Recent advances in chemical and physical methods to crosslink hydrogels are highlighted, as well as recent developments in controlling hydrogel degradation rates and modes of degradation.", "output": {"entities": {}}, "schema": []}
{"input": "Special attention is given to spatial or temporal presentation of various biochemical and biophysical cues to modulate cell response in static (i. e., non-degradable) or dynamic (i. e., degradable) microenvironments.", "output": {"entities": {}}, "schema": []}
{"input": "This review provides insight into the design of new cell-compatible, degradable hydrogels to understand and modulate cellular processes for various biomedical applications.", "output": {"entities": {}}, "schema": []}
{"input": "Phytoestrogenic Potential of Cyclopia Extracts and Polyphenols.", "output": {"entities": {"chemical": [{"text": "Polyphenols", "start": 51, "end": 62}]}}, "schema": []}
{"input": "Cyclopia Vent. species, commonly known as honeybush, are endemic to Southern Africa.", "output": {"entities": {}}, "schema": []}
{"input": "The plant is traditionally used as an herbal tea but several health benefits have recently been recorded.", "output": {"entities": {}}, "schema": []}
{"input": "This minireview presents an overview of polyphenols found in Cyclopia and focusses on the phytoestrogenic potential of selected polyphenols and of extracts prepared from the plant.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 40, "end": 51}, {"text": "polyphenols", "start": 128, "end": 139}]}}, "schema": []}
{"input": "Large lateral movement of transmembrane helix S5 is not required for substrate access to the active site of rhomboid intramembrane protease.", "output": {"entities": {}}, "schema": []}
{"input": "Rhomboids represent an evolutionarily ancient protease family.", "output": {"entities": {}}, "schema": []}
{"input": "Unlike most other proteases, they are polytopic membrane proteins, and specialize in cleaving transmembrane protein substrates.", "output": {"entities": {}}, "schema": []}
{"input": "Rhomboid protease' s polar active site is embedded in the membrane, and normally closed.", "output": {"entities": {}}, "schema": []}
{"input": "For bacterial rhomboid GlpG, it has been proposed that one of the protease' s transmembrane helices (S5) can rotate to open a lateral gate, enabling substrate to enter the protease from inside the membrane.", "output": {"entities": {}}, "schema": []}
{"input": "Here we study GlpG' s conformational change by solving the cocrystal structure of the protease with a mechanism-based inhibitor.", "output": {"entities": {}}, "schema": []}
{"input": "We also examine the lateral gating model by crosslinking S5 to a neighboring helix (S2).", "output": {"entities": {}}, "schema": []}
{"input": "The crystal structure shows that inhibitor binding displaces a capping loop (L5) from the active site, but causes only minor shifts of the transmembrane helices.", "output": {"entities": {}}, "schema": []}
{"input": "Crosslinking S5 and S2, which not only restricts S5' s lateral movement, but also prevents substrate from passing between the two helices, does not hinder the protease' s ability to cleave a membrane protein substrate in detergent solution and in reconstituted membrane vesicles.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these data suggest that a large lateral movement of S5 helix is not required for substrate access to rhomboid protease' s active site.", "output": {"entities": {}}, "schema": []}
{"input": "Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea undertaking estrogen replacement therapy.", "output": {"entities": {"chemical": [{"text": "gonadotropin-releasing hormone", "start": 53, "end": 83}, {"text": "estrogen", "start": 134, "end": 142}]}}, "schema": []}
{"input": "Background: Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations.", "output": {"entities": {}}, "schema": []}
{"input": "Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Aim: To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA.", "output": {"entities": {"chemical": [{"text": "gonadotropin-releasing hormone", "start": 101, "end": 131}, {"text": "GnRH", "start": 133, "end": 137}]}}, "schema": []}
{"input": "Materials and Methods: Thirty cases with FHA were recruited.", "output": {"entities": {}}, "schema": []}
{"input": "All subjects were put on continuous 1mg/day estradiol valerate orally and followed up monthly.", "output": {"entities": {"chemical": [{"text": "estradiol valerate", "start": 44, "end": 62}]}}, "schema": []}
{"input": "Recovery was defined as the occurrence of at least three consecutive regular cycles.", "output": {"entities": {}}, "schema": []}
{"input": "Responder referred to those who recovered within two years of therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Gonadotropin response to the 50 microgram GnRH challenge was tested every three months.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 42, "end": 46}]}}, "schema": []}
{"input": "Results: Nineteen (63. 3%) subjects recovered with a mean time to recovery of 26. 8 months.", "output": {"entities": {}}, "schema": []}
{"input": "Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-one cases had undertaken therapy for more than two years and ten of them recovered.", "output": {"entities": {}}, "schema": []}
{"input": "BMI before and by amenorrhea were negatively correlated with the recovery.", "output": {"entities": {}}, "schema": []}
{"input": "Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 74, "end": 78}]}}, "schema": []}
{"input": "Conclusions: Menstrual resumption was common in FHA undertaking ERT.", "output": {"entities": {}}, "schema": []}
{"input": "The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 43, "end": 47}]}}, "schema": []}
{"input": "The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.", "output": {"entities": {"chemical": [{"text": "GnRH", "start": 99, "end": 103}]}}, "schema": []}
{"input": "CHRONIC IDIOPATIC URTICARIA AND GRAVES' DISEASE.", "output": {"entities": {}}, "schema": []}
{"input": "Chronic urticaria is a common condition characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions lasting for more than 6 weeks.", "output": {"entities": {}}, "schema": []}
{"input": "In about 75% of cases, the underlying causes remain unknown, and the term chronic idiopathic urticaria (CIU) is used to emphasize that wheals develop independently of identified external stimuli.", "output": {"entities": {}}, "schema": []}
{"input": "Although CIU affects about 1. 0% of the general population, its etiopathogenesis is not yet well understood.", "output": {"entities": {}}, "schema": []}
{"input": "It is now widely accepted that in many cases CIU should be regarded as an autoimmune disorder caused by circulating and functionally active IgG autoantibodies specific for the IgE receptor (FceRI) present on mast cells and basophils or for IgE itself.", "output": {"entities": {}}, "schema": []}
{"input": "The well-known association of CIU with other autoimmune processes/diseases represents further indirect evidence of its autoimmune origin.", "output": {"entities": {}}, "schema": []}
{"input": "Autoimmune thyroid diseases, especially autoimmune thyroiditis, represent the most frequently investigated diseases in association with CIU.", "output": {"entities": {}}, "schema": []}
{"input": "Here we review this topic with particular regard to the association between Graves' disease and CIU.", "output": {"entities": {}}, "schema": []}
{"input": "The possible pathogenetic mechanisms and the clinical implications of such an association are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "The Beneficial Effect of Total Glucosides of Paeony on Psoriatic Arthritis Links to Circulating Tregs and Th1 Cell Function.", "output": {"entities": {}}, "schema": []}
{"input": "Total glycosides of peony (TGP) is a natural immuno-modulatory drug extracted from traditional Chinese herb peony.", "output": {"entities": {}}, "schema": []}
{"input": "It has been approved by State Food and Drug Administration for the treatment of rheumatoid arthritis.", "output": {"entities": {}}, "schema": []}
{"input": "However, data of TGP effect on psoriatic arthritis (PsA) is still scarce.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, 19 patients with PsA received 12-week treatment of TGP, and clinical efficacy in joint manifestations was evaluated by DAS28 at weeks 0, 4, 8 and 12.", "output": {"entities": {}}, "schema": []}
{"input": "Peripheral percentages of Tregs, Th1, Th2 and NK cells were analyzed, and serum Th1-type cytokines (IL-12, IFN-gamma and TNF-alpha), Th2-type cytokines (IL-4, IL-5 and IL-10) as well as pro-inflammatory factors (IL-2, IL-6 and IL-8) were concomitantly examined.", "output": {"entities": {}}, "schema": []}
{"input": "Six patients (32%) exhibited >= 25% decrease of DAS28 (responders).", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, all responders displayed a continuous decrease in Treg and Th1 numbers during TGP treatment, concomitant with significant decreases in Th1-type cytokine levels.", "output": {"entities": {}}, "schema": []}
{"input": "Serum IL-6 also showed a significant decline in responders.", "output": {"entities": {}}, "schema": []}
{"input": "Non-responders lacked these sequential alterations.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, TGP merits further consideration as a promising therapeutic option for PsA.", "output": {"entities": {}}, "schema": []}
{"input": "The result indicated that recovery of Tregs and Th1 may serve as prognostic markers to assess responsiveness to TGP treatment in PsA.", "output": {"entities": {}}, "schema": []}
{"input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": {"entities": {}}, "schema": []}
{"input": "Amphiphilic Polypeptides as a Bifunctional Template in the Mineralization of Calcium Carbonate at the Air/Water Interface.", "output": {"entities": {"chemical": [{"text": "Calcium Carbonate", "start": 77, "end": 94}]}}, "schema": []}
{"input": "A well-defined amphiphilic polypeptide, poly (glutamic acid) 22-block-poly (alanine) 8 (PGlu22-b-PAla8), which plays the roles of both soluble (functional) additive and insoluble (structural) matrix, is employed to mediate the mineralization of CaCO3 at the air/water interface.", "output": {"entities": {"chemical": [{"text": "poly (glutamic acid) 22-block-poly (alanine) 8", "start": 40, "end": 86}, {"text": "PGlu22-b-PAla8", "start": 88, "end": 102}, {"text": "CaCO3", "start": 245, "end": 250}]}}, "schema": []}
{"input": "X-ray diffraction (XRD) and Raman spectroscopy, for example, show that the polymorph of CaCO3 particles obtained is calcite.", "output": {"entities": {"chemical": [{"text": "CaCO3", "start": 88, "end": 93}, {"text": "calcite", "start": 116, "end": 123}]}}, "schema": []}
{"input": "The observations from SEM and TEM suggest that PGlu22-b-PAla8 initiates the amorphous precursor phase and heterogeneous nucleation of CaCO3 at the air/water interface, while temporarily stabilizes the gelatinous precursors as a process-directing agent; nevertheless, the initial concentration of Ca (2 +) controls the procedure of crystallization and the final morphology of CaCO3 particles.", "output": {"entities": {"chemical": [{"text": "PGlu22-b-PAla8", "start": 47, "end": 61}, {"text": "CaCO3", "start": 134, "end": 139}, {"text": "Ca (2 +)", "start": 296, "end": 304}, {"text": "CaCO3", "start": 375, "end": 380}]}}, "schema": []}
{"input": "Such \" bifunctional \" amphiphilic-polypeptide-regulated mineralization at the air/water interface may be applied to the synthesis of many kinds of symmetrical inorganic/organic hybrids.", "output": {"entities": {}}, "schema": []}
{"input": "Very Low Calorie Diet Mimics the Early Beneficial Effect of Roux-en-Y Gastric Bypass on Insulin Sensitivity and Beta-Cell Function in Type 2 Diabetic Patients.", "output": {"entities": {}}, "schema": []}
{"input": "Marked improvement in glycemic control occurs in patients with type 2 diabetes (T2DM) shortly after Roux-en-Y gastric bypass surgery (RYGB) and before there is major weight loss.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to determine if the magnitude of this change is primarily due to caloric restriction or is unique to the surgical procedure.", "output": {"entities": {}}, "schema": []}
{"input": "We studied eleven subjects who underwent RYGB and fourteen subjects mean-matched for BMI, HbA1c and diabetes duration who were admitted to our inpatient research unit and given a very low calorie diet (VLCD) of 500 kcal/day with a macronutrient content similar to that consumed by patients after RYGB.", "output": {"entities": {}}, "schema": []}
{"input": "Frequently sampled intravenous glucose tolerance tests were performed before and after interventions.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 31, "end": 38}]}}, "schema": []}
{"input": "Both groups lost an equivalent amount of weight over a mean study period of 21 days.", "output": {"entities": {}}, "schema": []}
{"input": "Insulin sensitivity, acute insulin secretion after intravenous glucose administration and beta-cell function as determined by disposition index improved to a similar extent in both groups.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Likewise, changes in fasting glucose and fructosamine levels were similar.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 29, "end": 36}, {"text": "fructosamine", "start": 41, "end": 53}]}}, "schema": []}
{"input": "Based on these data, VLCD improves insulin sensitivity and beta-cell function just as well as RYGB in the short term.", "output": {"entities": {}}, "schema": []}
{"input": "This study was registered in ClinicalTrials. gov NCT00627484.", "output": {"entities": {}}, "schema": []}
{"input": "Central Pulse Pressure and Its Hemodynamic Determinants in Middle-Aged Adults With Impaired Fasting Glucose and Diabetes: The Asklepios study.", "output": {"entities": {"chemical": [{"text": "Glucose", "start": 100, "end": 107}]}}, "schema": []}
{"input": "OBJECTIVEPulse pressure (PP), a strong predictor of cardiovascular events in type 2 diabetes, is a composite measure affected by several hemodynamic factors.", "output": {"entities": {}}, "schema": []}
{"input": "Little is known about the hemodynamic determinants of central PP in type 2 diabetes or whether abnormalities in central pulsatile hemodynamics are already present in individuals with impaired fasting glucose (IFG).", "output": {"entities": {"chemical": [{"text": "glucose", "start": 200, "end": 207}]}}, "schema": []}
{"input": "In a population-based study, we aimed to compare central PP and its hemodynamic determinants among adults with normal fasting glucose (n = 1654), IFG (n = 240), and type 2 diabetes (n = 33). RESEARCH DESIGN AND METHODSWe measured carotid pressure, left ventricular outflow, aortic root diameter, carotid artery flow, and distension in order to measure various structural and hemodynamic arterial parameters. RESULTSIFG was associated with a greater mean arterial pressure (MAP) but was not associated with intrinsic aortic stiffening or abnormal aortic pulsatile indices after adjustment for MAP.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 126, "end": 133}]}}, "schema": []}
{"input": "After adjustment for age, sex, and MAP, type 2 diabetes was associated with a higher aortic root characteristic impedance (Zc), aortic root elastance-thickness product (Eh), and aortic root pulse wave velocity (but not aortic root diameter), a greater carotid-femoral pulse wave velocity, and lower total arterial compliance and wave reflection magnitude.", "output": {"entities": {}}, "schema": []}
{"input": "Carotid size, Zc, distensibility, or Eh did not significantly differ between the groups. CONCLUSIONSType 2 diabetes, but not IFG, is associated with greater large artery stiffness, without abnormalities in aortic root diameter or carotid stiffness.", "output": {"entities": {}}, "schema": []}
{"input": "Subjects with type 2 diabetes demonstrate a decreased reflection magnitude, which may indicate an increased penetration of pulsatile energy to distal vascular beds.", "output": {"entities": {}}, "schema": []}
{"input": "Genetics of mineralocorticoid excess: an update for clinicians.", "output": {"entities": {}}, "schema": []}
{"input": "Aldosterone plays a major role in regulating sodium and potassium homeostasis, and blood pressure.", "output": {"entities": {"chemical": [{"text": "Aldosterone", "start": 0, "end": 11}, {"text": "sodium", "start": 45, "end": 51}, {"text": "potassium", "start": 56, "end": 65}]}}, "schema": []}
{"input": "More recently aldosterone has emerged as a key hormone in mediating end organ damage.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 14, "end": 25}]}}, "schema": []}
{"input": "In extreme cases, dysregulated aldosterone production leads to primary aldosteronism, the most common form of secondary hypertension.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 31, "end": 42}]}}, "schema": []}
{"input": "However, even within the physiological range, high levels of aldosterone are associated with an increased risk of developing hypertension over time.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 61, "end": 72}]}}, "schema": []}
{"input": "Primary aldosteronism represents the most common and curable form of hypertension, with a prevalence that increases with the severity of hypertension.", "output": {"entities": {}}, "schema": []}
{"input": "Although genetic causes underlying glucocorticoid remediable aldosteronism, one of the three Mendelian forms of primary aldosteronism, were established some time ago, somatic and inherited mutations in the potassium channel GIRK4 have only recently been implicated in the formation of aldosterone producing adenoma and in familial hyperaldosteronism type 3.", "output": {"entities": {"chemical": [{"text": "potassium", "start": 206, "end": 215}, {"text": "aldosterone", "start": 285, "end": 296}]}}, "schema": []}
{"input": "Moreover, recent findings have identified somatic mutations in two additional genes, involved in maintaining intracellular ionic homeostasis and cell membrane potential, in a subset of aldosterone producing adenoma. This review summarizes our current knowledge on the genetic determinants that contribute to variations in plasma aldosterone and renin levels in the general population, and the genetics of familial and sporadic primary aldosteronism.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 185, "end": 196}, {"text": "aldosterone", "start": 329, "end": 340}]}}, "schema": []}
{"input": "Various animal models that have significantly improved our understanding of the pathophysiology of excess aldosterone production will also be discussed.", "output": {"entities": {"chemical": [{"text": "aldosterone", "start": 106, "end": 117}]}}, "schema": []}
{"input": "Finally, we will outline the cardiovascular, renal and metabolic consequences of mineralocorticoid excess beyond blood pressure regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of Atactic and Isotactic Poly (1, 2-glycerol carbonate) s: Degradable Polymers for Biomedical and Pharmaceutical Applications.", "output": {"entities": {"chemical": [{"text": "Poly (1, 2-glycerol carbonate) s", "start": 35, "end": 67}]}}, "schema": []}
{"input": "The synthesis and characterization of atactic and isotactic linear poly (benzyl 1, 2-glycerol carbonate) s are reported.", "output": {"entities": {"chemical": [{"text": "poly (benzyl 1, 2-glycerol carbonate) s", "start": 67, "end": 106}]}}, "schema": []}
{"input": "The poly (benzyl 1, 2-glycerol carbonate) s were obtained via the ring-opening copolymerization of rac-/(R)-benzyl glycidyl ether with CO2 using [SalcyCo (III) X] complexes with high carbonate linkage selectivity and polymer/cyclic carbonate selectivity (> 99%).", "output": {"entities": {"chemical": [{"text": "poly (benzyl 1, 2-glycerol carbonate) s", "start": 4, "end": 43}, {"text": "rac-/(R)-benzyl glycidyl ether", "start": 99, "end": 129}, {"text": "CO2", "start": 135, "end": 138}, {"text": "[SalcyCo (III) X]", "start": 145, "end": 162}, {"text": "carbonate", "start": 183, "end": 192}, {"text": "carbonate", "start": 232, "end": 241}]}}, "schema": []}
{"input": "Deprotection of the resultant polymers afforded poly (1, 2-glycerol carbonate) s with a functionalizable pendant primary hydroxyl group.", "output": {"entities": {"chemical": [{"text": "poly (1, 2-glycerol carbonate) s", "start": 48, "end": 80}, {"text": "primary hydroxyl", "start": 113, "end": 129}]}}, "schema": []}
{"input": "Poly (1, 2-glycerol carbonate) showed a remarkable increase in degradation rate compared to poly (1, 3-glycerol carbonate) with a t1/2 =~ 2-3 days.", "output": {"entities": {"chemical": [{"text": "Poly (1, 2-glycerol carbonate)", "start": 0, "end": 30}, {"text": "poly (1, 3-glycerol carbonate)", "start": 92, "end": 122}]}}, "schema": []}
{"input": "These polymers fulfill an unmet need for a readily degradable biocompatible polycarbonate.", "output": {"entities": {"chemical": [{"text": "polycarbonate", "start": 76, "end": 89}]}}, "schema": []}
{"input": "A New Face for Old Antibiotics: Tetracyclines in Treatment of Amyloidoses.", "output": {"entities": {"chemical": [{"text": "Tetracyclines", "start": 32, "end": 45}]}}, "schema": []}
{"input": "The use of tetracyclines has declined because of the appearance of resistant bacterial strains.", "output": {"entities": {"chemical": [{"text": "tetracyclines", "start": 11, "end": 24}]}}, "schema": []}
{"input": "However, the indications of nonantimicrobial activities of these drugs have considerably raised interest and triggered clinical trials for a number of different pathologies.", "output": {"entities": {}}, "schema": []}
{"input": "About 10 years ago we first reported that tetracyclines inhibited the aggregation of prion protein fragments and Alzheimer' s beta peptides, destabilizing their aggregates and promoting their degradation by proteases.", "output": {"entities": {"chemical": [{"text": "tetracyclines", "start": 42, "end": 55}]}}, "schema": []}
{"input": "On the basis of these observations, the antiamyloidogenic effects of tetracyclines on a variety of amyloidogenic proteins were studied and confirmed by independent research groups.", "output": {"entities": {"chemical": [{"text": "tetracyclines", "start": 69, "end": 82}]}}, "schema": []}
{"input": "In this review we comment on the data available on their antiamyloidogenic activity in preclinical and clinical studies.", "output": {"entities": {}}, "schema": []}
{"input": "We also put forward that the beneficial effects of these drugs are a result of a peculiar pleiotropic action, comprising their interaction with oligomers and disruption of fibrils, as well as their antioxidant, anti-inflammatory, antiapoptotic, and matrix metalloproteinase inhibitory activities.", "output": {"entities": {}}, "schema": []}
{"input": "Physicochemical characterization of nimodipine-polyethylene glycol solid dispersion systems.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 36, "end": 46}, {"text": "polyethylene glycol", "start": 47, "end": 66}]}}, "schema": []}
{"input": "Abstract This study investigates the solid-solid interactions between nimodipine (NIM) and polyethylene glycol (PEG) of different mean molecular weights (PEG 2000, 4000 and 6000), in solid dispersion systems, applying differential scanning calorimetry (DSC), Fourier-Transform infrared spectroscopy, powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and theoretical modeling by the Flory-Huggins (FH) solution theory.", "output": {"entities": {"chemical": [{"text": "nimodipine", "start": 70, "end": 80}, {"text": "NIM", "start": 82, "end": 85}, {"text": "polyethylene glycol", "start": 91, "end": 110}, {"text": "PEG", "start": 112, "end": 115}, {"text": "PEG 2000, 4000 and 6000", "start": 154, "end": 177}]}}, "schema": []}
{"input": "Phase diagrams constructed with the aid of DSC and FH solution theory showed sensitivity on the estimated values of the FH interaction parameter (chi).", "output": {"entities": {}}, "schema": []}
{"input": "When chi is considered a constant number (chi = alpha, alpha != 0), formation of a eutectic mixture is predicted in the 70-80% w/w PEG concentration region, while when chi was considered as a function of concentration and temperature (chi = f (phi, Tau)), the model predicts the formation of monotectic systems.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 131, "end": 134}]}}, "schema": []}
{"input": "Construction of more precise phase diagrams by HSM to the aid of Kofler' s \" contact preparation \" method confirmed the monotectic nature of the examined systems.", "output": {"entities": {}}, "schema": []}
{"input": "Studies on NIM' s re-crystallization process in the solid dispersions revealed a strong dependence of the crystallization rate, as well as the resulting crystal form, on the mean molecular weight and concentration of PEG: NIM crystallization rates decrease as PEG' s MW increases, while NIM mod II crystals predominate in dispersions prepared at temperatures above NIM' s liquidus and growth of NIM mod I prevailing in PEG-rich samples.", "output": {"entities": {"chemical": [{"text": "NIM", "start": 11, "end": 14}, {"text": "PEG", "start": 217, "end": 220}, {"text": "NIM", "start": 222, "end": 225}, {"text": "PEG", "start": 260, "end": 263}, {"text": "NIM", "start": 287, "end": 290}, {"text": "NIM", "start": 365, "end": 368}, {"text": "NIM", "start": 395, "end": 398}, {"text": "PEG", "start": 419, "end": 422}]}}, "schema": []}
{"input": "Discovery of a New Class of Natural Product-Inspired Quinazolinone Hybrid as Potent Antileishmanial agents.", "output": {"entities": {"chemical": [{"text": "Quinazolinone", "start": 53, "end": 66}]}}, "schema": []}
{"input": "The high potential of quinazolinone containing natural products and their derivatives in medicinal chemistry led us to discover four novel series of 53 compounds of quinazolinone based on the concept of molecular hybridization.", "output": {"entities": {"chemical": [{"text": "quinazolinone", "start": 22, "end": 35}, {"text": "quinazolinone", "start": 165, "end": 178}]}}, "schema": []}
{"input": "Most of the synthesized analogues exhibited potent leishmanicidal activity against intracellular amastigotes (IC50 from 0. 65 +/- 0. 2 to 7. 76 +/- 2. 1 mu M) as compared to miltefosine (IC50 = 8. 4 +/- 2. 1 mu M) and nontoxic toward the J-774A. 1 cell line and Vero cells.", "output": {"entities": {"chemical": [{"text": "miltefosine", "start": 174, "end": 185}]}}, "schema": []}
{"input": "Moreover, activation of Th1 type and suppression of Th2 type immune responses and induction in nitric oxide generation proved that 8a and 8g induce murine macrophages to prevent survival of parasites.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 95, "end": 107}]}}, "schema": []}
{"input": "Compounds 8a and 8g exhibited significant in vivo inhibition of parasite 73. 15 +/- 12. 69% and 80. 93 +/- 10. 50% against Leishmania donovani/hamster model.", "output": {"entities": {}}, "schema": []}
{"input": "Our results indicate that compounds 8a, 8g, and 9f represent a new structural lead for this serious and neglected disease.", "output": {"entities": {}}, "schema": []}
{"input": "A road map for molecular ecology.", "output": {"entities": {}}, "schema": []}
{"input": "The discipline of molecular ecology has undergone enormous changes since the journal bearing its name was launched approximately two decades ago.", "output": {"entities": {}}, "schema": []}
{"input": "The field has seen great strides in analytical methods development, made groundbreaking discoveries and experienced a revolution in genotyping technology.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we provide brief perspectives on the main subdisciplines of molecular ecology, describe key questions and goals, discuss common challenges, predict future research directions and suggest research priorities for the next 20 years.", "output": {"entities": {}}, "schema": []}
{"input": "New trifluoromethyl quinolone derivatives: Synthesis and investigation of antimicrobial properties.", "output": {"entities": {"chemical": [{"text": "trifluoromethyl quinolone", "start": 4, "end": 29}]}}, "schema": []}
{"input": "A series of quinolone derivatives, containing different heterocyclic amines were prepared.", "output": {"entities": {"chemical": [{"text": "quinolone", "start": 12, "end": 21}, {"text": "heterocyclic amines", "start": 56, "end": 75}]}}, "schema": []}
{"input": "Synthesized compounds were evaluated for their in vitro antimicrobial activities against two Gram-positive bacteria, three Gram-negative bacteria as well as four fungi.", "output": {"entities": {}}, "schema": []}
{"input": "All the derivatives showed good activity towards Gram-positive bacteria and less activity towards Gram-negative bacteria.", "output": {"entities": {}}, "schema": []}
{"input": "They also showed moderate to comparable activity against Aspergillus niger and Candida albicans and low to moderate antifungal activity against Aspergillus fumigatus and Aspergillus flavus.", "output": {"entities": {}}, "schema": []}
{"input": "In vitro antiproliferative effect of a water-soluble Laminaria japonica polysaccharide on human melanoma cell line A375.", "output": {"entities": {}}, "schema": []}
{"input": "A water-soluble polysaccharide WPS-2-1, purified from Laminaria japonica, has been found to have antitumor activity.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, WPS-2-1 exhibited high anti-proliferative activity on A375 cells in a dosedependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Further investigation indicated that WPS-2-1 induced A375 cells apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, WPS-2-1-induced apoptosis was associated with the alteration in expressions of Bcl-2 family proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochonadrial apoptotic pathway was involved in WPS-2-1-induced apoptosis, which included the loss of mitochondrial membrane and activation of caspase-3/9.", "output": {"entities": {}}, "schema": []}
{"input": "The results in this study suggested that WPS-2-1 could effectively inhibit proliferation of A375 cells in vitro and induce apoptosis via mitochondrial apoptotic pathway.", "output": {"entities": {}}, "schema": []}
{"input": "It might serve as a potential anti-tumor agent.", "output": {"entities": {}}, "schema": []}
{"input": "Body composition assessment for the definition of cardiometabolic risk.", "output": {"entities": {}}, "schema": []}
{"input": "Obesity is associated with a major prevalence of cardiovascular risk factors and high risk of cardiovascular events and contributes to the increase in cardiovascular morbidity and mortality worldwide.", "output": {"entities": {}}, "schema": []}
{"input": "Beyond the fat mass per se, the pattern of fat distribution has a profound influence on cardiometabolic risk.", "output": {"entities": {}}, "schema": []}
{"input": "The increase in abdominal adipose tissue confers an independent risk, while the amount of gluteofemoral body fat is thought to be protective.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in the capacity of different depots to store and release fatty acids and to produce adipocytokines are important determinants of fat distribution and its metabolic consequences.", "output": {"entities": {"chemical": [{"text": "fatty acids", "start": 65, "end": 76}]}}, "schema": []}
{"input": "Because of the complexity of the assessment of body fat with imaging techniques, great attention has been paid to other measures of adiposity, such as waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), which provide information on body fat distribution, although BMI is the established clinical measure to estimate the cardiovascular risk disease associated with excessive body weight.", "output": {"entities": {}}, "schema": []}
{"input": "Abdominal obesity is a main predictive factor of the Metabolic Syndrome, so it is certain that it represents a better marker of cardiovascular risk than BMI.", "output": {"entities": {}}, "schema": []}
{"input": "Visceral adiposity index (VAI) has recently proven to be a marker of visceral adipose distribution and function, associated with insulin sensitivity in patients at metabolic risk; however, the evidence needs to be further confirmed.", "output": {"entities": {}}, "schema": []}
{"input": "In summary, BMI, WC, WHR, WHtR and VAI are all useful tools for assessing adiposity/obesity in clinical practice, and should be evaluated along with other cardiometabolic risk factors to define cardiovascular risk stratification.", "output": {"entities": {}}, "schema": []}
{"input": "Unusual glycosaminoglycans from a deep sea hydrothermal bacterium improve fibrillar collagen structuring and fibroblast activities in engineered connective tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Biopolymers produced by marine organisms can offer useful tools for regenerative medicine.", "output": {"entities": {}}, "schema": []}
{"input": "Particularly, HE800 exopolysaccharide (HE800 EPS) secreted by a deep-sea hydrothermal bacterium displays an interesting glycosaminoglycan-like feature resembling hyaluronan.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies demonstrated its effectiveness to enhance in vivo bone regeneration and to support osteoblastic cell metabolism in culture.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, in order to assess the usefulness of this high-molecular weight polymer in tissue engineering and tissue repair, in vitro reconstructed connective tissues containing HE800 EPS were performed.", "output": {"entities": {}}, "schema": []}
{"input": "We showed that this polysaccharide promotes both collagen structuring and extracellular matrix settle by dermal fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, from the native HE800 EPS, a low-molecular weight sulfated derivative (HE800 DROS) displaying chemical analogy with heparan-sulfate, was designed.", "output": {"entities": {"chemical": [{"text": "sulfated", "start": 63, "end": 71}]}}, "schema": []}
{"input": "Thus, it was demonstrated that HE800 DROS mimics some properties of heparan-sulfate, such as promotion of fibroblast proliferation and inhibition of matrix metalloproteinase (MMP) secretion.", "output": {"entities": {"chemical": [{"text": "sulfate", "start": 76, "end": 83}]}}, "schema": []}
{"input": "Therefore, we suggest that the HE800EPS family can be considered as an innovative biotechnological source of glycosaminoglycan-like compounds useful to design biomaterials and drugs for tissue engineering and repair.", "output": {"entities": {}}, "schema": []}
{"input": "Antiprotozoal screening and cytotoxicity of extracts and fractions from the leaves, stem bark and root bark of Alstonia congensis.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: To evaluate the antiprotozoal activity and cytotoxicity of extracts and fractions from the leaves, root bark and stem bark of Alstonia congensis (Apocynaceae), used in traditional medicine against parasitic diseases.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: The aqueous and 80% MeOH extracts, and a series of fractions and subfractions from the leaves, stem and root bark of Alstonia congensis were tested in vitro for their antiprotozoal activity against Trypanosoma brucei brucei, Trypanosoma cruzi, Lesihamania infantum and the chloroquine and pyrimethamine-resitant K1 strain of Plasmodium falciparum.", "output": {"entities": {"chemical": [{"text": "MeOH", "start": 43, "end": 47}, {"text": "chloroquine", "start": 296, "end": 307}, {"text": "pyrimethamine", "start": 312, "end": 325}]}}, "schema": []}
{"input": "Their cytotoxicity on MRC-5 cells (human lung fibroblasts) was evaluated as well.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The aqueous and 80% MeOH extracts and a series of subfractions of each plant part exhibited pronounced antiprotozoal activity against the K1 strain of Plasmodium falciparum with IC50 values ranging from 2 to 5 micro g/ml, and good activity against Trypanosoma brucei brucei and Trypanosoma cruzi with IC50 values ranging between 5 and 10 micro g/ml.", "output": {"entities": {"chemical": [{"text": "MeOH", "start": 29, "end": 33}]}}, "schema": []}
{"input": "The residual 80% MeOH extract from the leaves, and the total alkaloid extract from stem and root bark were the only subfractions active against Leishmania infantum with IC50 values < 10 micro g/ml.", "output": {"entities": {"chemical": [{"text": "MeOH", "start": 17, "end": 21}]}}, "schema": []}
{"input": "None of the samples from the root bark was cytotoxic against MRC-cell lines (CC50 > 64 micro g/ml).", "output": {"entities": {}}, "schema": []}
{"input": "In general, the aqueous extracts (traditional decoctions) showed the highest selectivity, especially against Plasmodium falciparum.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: These results can partly support and justify the traditional use of these plant parts of Alstonina congensis as raw materials for the preparation of traditional remedies to treat parasitic diseases such as malaria and trypanosomiasis.", "output": {"entities": {}}, "schema": []}
{"input": "Structure of hydrated cobalt ions confined in the nanospace of single-walled carbon nanotubes.", "output": {"entities": {"chemical": [{"text": "cobalt", "start": 22, "end": 28}, {"text": "carbon", "start": 77, "end": 83}]}}, "schema": []}
{"input": "The structure of hydrated Co ions confined in the nanospace of single-walled carbon nanotubes (SWNTs) has been studied using the X-ray absorption fine structure (XAFS) technique.", "output": {"entities": {"chemical": [{"text": "Co", "start": 26, "end": 28}, {"text": "carbon", "start": 77, "end": 83}]}}, "schema": []}
{"input": "Water adsorption isotherms on Co-impregnated SWNTs indicate a high affinity of Co ions to water molecules.", "output": {"entities": {"chemical": [{"text": "Co", "start": 30, "end": 32}, {"text": "Co", "start": 79, "end": 81}]}}, "schema": []}
{"input": "The results of XAFS analysis provided the information on the proportion of dissolved species in nanospaces against the total amount of cobalt ions adsorbed on the open-pored SWNT.", "output": {"entities": {"chemical": [{"text": "cobalt", "start": 135, "end": 141}]}}, "schema": []}
{"input": "The structural information of the first shell around a Co ion was expressed in terms of the hydration number, Co-O distance and Debye-Waller factor.", "output": {"entities": {"chemical": [{"text": "Co", "start": 55, "end": 57}, {"text": "Co-O", "start": 110, "end": 114}]}}, "schema": []}
{"input": "The actual coordination number and the interatomic distance of Co-O for the dissolved species were remarkably reduced compared to the bulk aqueous solution indicating the dehydration of water molecules from Co ions and a compact hydrated structure in the micropore of SWNTs.", "output": {"entities": {"chemical": [{"text": "Co-O", "start": 63, "end": 67}, {"text": "Co", "start": 207, "end": 209}]}}, "schema": []}
{"input": "Comparative phosphoproteomic analysis of checkpoint recovery identifies new regulators of the DNA damage response.", "output": {"entities": {}}, "schema": []}
{"input": "How cells recover from a DNA damage-induced arrest is currently poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "We performed large-scale quantitative phosphoproteomics to identify changes in protein phosphorylation that occurred during recovery from arrest in the G2 phase of the cell cycle caused by DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "We identified 154 proteins that were differentially phosphorylated, and systematic depletion of each of these differentially phosphorylated proteins by small interfering RNA (siRNA) identified at least 10 potential regulators of recovery.", "output": {"entities": {}}, "schema": []}
{"input": "Astrin, a protein associated with the mitotic spindle, was among the potential regulators of recovery.", "output": {"entities": {"chemical": [{"text": "Astrin", "start": 0, "end": 6}]}}, "schema": []}
{"input": "We found that astrin controlled the abundance of the cell cycle regulator p53 during DNA damage-induced arrest.", "output": {"entities": {}}, "schema": []}
{"input": "Cells in which astrin was depleted had decreased murine double minute 2 (MDM2) abundance and increased p53 at the later stages of the DNA damage response.", "output": {"entities": {"chemical": [{"text": "astrin", "start": 15, "end": 21}]}}, "schema": []}
{"input": "Astrin was required for continued expression of genes encoding proteins that promote cell cycle progression in arrested cells.", "output": {"entities": {"chemical": [{"text": "Astrin", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Thus, by controlling p53 abundance in cells recovering from DNA damage, astrin maintains the cells in a state competent to resume the cell cycle.", "output": {"entities": {}}, "schema": []}
{"input": "A molecular mechanism for therapeutic effects of cGMP-elevating agents in pulmonary arterial hypertension.", "output": {"entities": {"chemical": [{"text": "cGMP", "start": 49, "end": 53}]}}, "schema": []}
{"input": "Pulmonary arterial hypertension (PAH) 5 is a progressive, usually fatal disease with abnormal vascular remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Pulmonary artery smooth muscle cells (PASMCs) from PAH patients are hyper-proliferative and apoptosis-resistant, and demonstrate decreased signaling in response to bone morphogenetic proteins (BMPs).", "output": {"entities": {}}, "schema": []}
{"input": "Cyclic GMP-elevating agents are beneficial in PAH, but their mechanism (s) of action are incompletely understood.", "output": {"entities": {"chemical": [{"text": "Cyclic GMP", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Here we show that BMP signaling via Smad1/5/8 requires cGMP-dependent protein kinase isotype I (PKGI) to maintain PASMCs in a differentiated, low-proliferative state.", "output": {"entities": {"chemical": [{"text": "cGMP", "start": 55, "end": 59}]}}, "schema": []}
{"input": "BMP cooperation with cGMP/PKGI was crucial for transcription of contractile genes, and suppression of pro-proliferative and anti-apoptotic genes.", "output": {"entities": {"chemical": [{"text": "cGMP", "start": 21, "end": 25}]}}, "schema": []}
{"input": "Lungs from mice with low or absent PKGI (Prkg1 +/-and Prkg1-/-mice) exhibited impaired BMP signaling, decreased contractile gene expression, and abnormal vascular remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, cGMP stimulation of PKGI restored defective BMP signaling in rats with hypoxia-induced PAH, consistent with cGMP-elevating agents reversing vascular remodeling in this PAH model.", "output": {"entities": {"chemical": [{"text": "cGMP", "start": 12, "end": 16}, {"text": "cGMP", "start": 120, "end": 124}]}}, "schema": []}
{"input": "Our results provide a mechanism for the therapeutic effects of cGMP-elevating agents in PAH, and suggest that combining them with BMP mimetics may provide a novel, disease-modifying approach to PAH therapy.", "output": {"entities": {"chemical": [{"text": "cGMP", "start": 63, "end": 67}]}}, "schema": []}
{"input": "The in vivo TRPV6 protein starts at a non-AUG triplet decoded as methionine upstream the canonical initiation at AUG.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 65, "end": 75}]}}, "schema": []}
{"input": "TRPV6 channels function as epithelial Ca2 + entry pathways in the epididymis, prostate and placenta.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 38, "end": 43}]}}, "schema": []}
{"input": "However, like of most proteins the identity of the endogenous TRPV6 protein relies on predicted gene coding regions and is only known to a certain level of approximation.", "output": {"entities": {}}, "schema": []}
{"input": "We show that in vivo the TRPV6 protein has an extended N-terminus.", "output": {"entities": {"chemical": [{"text": "N", "start": 55, "end": 56}]}}, "schema": []}
{"input": "Translation initiates at a non-AUG codon, at ACG, which is decoded by methionine and which is upstream of the annotated AUG which is not used for initiation.", "output": {"entities": {"chemical": [{"text": "methionine", "start": 70, "end": 80}]}}, "schema": []}
{"input": "The in vitro properties of channels formed by the extended full length TRPV6 proteins and the so far annotated and shorter TRPV6 are similar, but the extended N-terminus increases trafficking to the plasma membrane and represents an additional scaffold for channel assembly.", "output": {"entities": {"chemical": [{"text": "N", "start": 159, "end": 160}]}}, "schema": []}
{"input": "The increased translation of the shorter TRPV6 cDNA version may overestimate the in vivo situation where translation efficiency may represent an additional mechanism to tightly control the TRPV6-mediated Ca2 + entry in order to prevent deleterious Ca2 + overload.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 204, "end": 209}, {"text": "Ca2 +", "start": 248, "end": 253}]}}, "schema": []}
{"input": "One-Pot in Situ Mixed Film Formation by Azo Coupling and Diazonium Salt Electrografting.", "output": {"entities": {"chemical": [{"text": "Azo", "start": 40, "end": 43}, {"text": "Diazonium Salt", "start": 57, "end": 71}]}}, "schema": []}
{"input": "So simple: The in situ synthesis of an aryldiazonium salt and an azo-aryldiazonium salt by azo coupling from sulfanilic acid and aniline is reported.", "output": {"entities": {"chemical": [{"text": "aryldiazonium salt", "start": 39, "end": 57}, {"text": "azo-aryldiazonium salt", "start": 65, "end": 87}, {"text": "azo", "start": 91, "end": 94}, {"text": "sulfanilic acid", "start": 109, "end": 124}, {"text": "aniline", "start": 129, "end": 136}]}}, "schema": []}
{"input": "Formation of a mixed organic layer is monitored by cyclic voltammetry and atomic force microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "A compact mixed layer is obtained with a global roughness of 0. 4 nm and 10-15% vertical extension in the range 1. 5-6 nm.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative Study of Metals Accumulation in Cultured In Vitro Mycelium and Naturally Grown Fruiting Bodies of Boletus badius and Cantharellus cibarius.", "output": {"entities": {}}, "schema": []}
{"input": "Cantharellus cibarius Fr.", "output": {"entities": {}}, "schema": []}
{"input": "(chanterelle) and Boletus badius Pers.", "output": {"entities": {}}, "schema": []}
{"input": "(bay bolete) harvested from natural sites in Poland were used to derive in vitro cultures.", "output": {"entities": {}}, "schema": []}
{"input": "The optimal medium composition for cultures was developed.", "output": {"entities": {}}, "schema": []}
{"input": "Concentrations of the chosen elements (Zn, Cu, Fe, Mg, Ni, and Cd) in mycelium samples were measured by means of atomic absorption spectrometry.", "output": {"entities": {"chemical": [{"text": "Zn", "start": 39, "end": 41}, {"text": "Cu", "start": 43, "end": 45}, {"text": "Fe", "start": 47, "end": 49}, {"text": "Mg", "start": 51, "end": 53}, {"text": "Ni", "start": 55, "end": 57}, {"text": "Cd", "start": 63, "end": 65}]}}, "schema": []}
{"input": "Fe concentration in the analyzed mushroom materials was in the range 215. 4-680. 3 mu g/g dry weight.", "output": {"entities": {"chemical": [{"text": "Fe", "start": 0, "end": 2}]}}, "schema": []}
{"input": "Mean values of Mg were respectively (in micrograms per gram dry weight) 541. 8 for mycelium of C. cibarius cultured in vitro and 1, 004. 1 for C. cibarius fruiting bodies and 928. 9 for the mycelium of B. badius cultured in vitro and 906. 4 for B. badius fruiting bodies.", "output": {"entities": {"chemical": [{"text": "Mg", "start": 15, "end": 17}]}}, "schema": []}
{"input": "The mean concentrations of Zn were 442. 7 mu g/g dry weight in mycelium from in vitro cultures of B. badius and 172. 1 in B. badius fruiting bodies and 131. 9 in the case of C. cibarius in mycelium from in vitro cultures and 95. 5 for the C. cibarius fruiting bodies.", "output": {"entities": {"chemical": [{"text": "Zn", "start": 27, "end": 29}]}}, "schema": []}
{"input": "Cu exhibited a reversal tendency, i. e., the element concentrations in naturally grown mushrooms were significantly higher (43. 57 mu g/g dry weight for C. cibarius and 43. 54 mu g/g for B. badius) than in cultured in vitro mycelium (12. 47 mu g/g for C. cibarius and 4. 17 mu g/g for B. badius).", "output": {"entities": {"chemical": [{"text": "Cu", "start": 0, "end": 2}]}}, "schema": []}
{"input": "Ni was found in lowest concentrations ranging from 0. 33 to 1. 88 mu g/g dry weight.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 0, "end": 2}]}}, "schema": []}
{"input": "Toxic metal Cd was found in relatively high concentrations in naturally grown species (0. 79 mu g/g dry weight-1. 02).", "output": {"entities": {"chemical": [{"text": "Cd", "start": 12, "end": 14}]}}, "schema": []}
{"input": "The lowest was the concentration of Cd in C. cibarius mycelium from in vitro culture-0. 06 mu g/g dry weight-a bit higher than it was in the B. badius mycelium (0. 21 mu g/g).", "output": {"entities": {"chemical": [{"text": "Cd", "start": 36, "end": 38}]}}, "schema": []}
{"input": "Biodegradable Polysilsesquioxane Nanoparticles as Efficient Contrast Agents for Magnetic Resonance Imaging.", "output": {"entities": {"chemical": [{"text": "Polysilsesquioxane", "start": 14, "end": 32}]}}, "schema": []}
{"input": "Polysilsesquioxane (PSQ) nanoparticles are crosslinked homopolymers formed by condensation of functionalized trialkoxysilanes, and provide an interesting platform for developing biologically and biomedically relevant nanomaterials.", "output": {"entities": {"chemical": [{"text": "Polysilsesquioxane", "start": 0, "end": 18}, {"text": "PSQ", "start": 20, "end": 23}, {"text": "trialkoxysilanes", "start": 109, "end": 125}]}}, "schema": []}
{"input": "In this work, the design and synthesis of biodegradable PSQ particles with extremely high payloads of paramagnetic Gd (III) centers is explored, for use as efficient contrast agents for magnetic resonance imaging (MRI).", "output": {"entities": {"chemical": [{"text": "PSQ", "start": 56, "end": 59}, {"text": "Gd (III)", "start": 115, "end": 123}]}}, "schema": []}
{"input": "Two new bis (trialkoxysilyl) derivatives of Gd (III) diethylenetriamine pentaacetate (Gd-DTPA) containing disulfide linkages are synthesized and used to form biodegradable Gd-PSQ particles by base-catalyzed condensation reactions in reverse microemulsions.", "output": {"entities": {"chemical": [{"text": "bis (trialkoxysilyl)", "start": 8, "end": 28}, {"text": "Gd (III) diethylenetriamine pentaacetate", "start": 44, "end": 84}, {"text": "Gd-DTPA", "start": 86, "end": 93}, {"text": "disulfide", "start": 106, "end": 115}, {"text": "Gd-PSQ", "start": 172, "end": 178}]}}, "schema": []}
{"input": "The Gd-PSQ particles, PSQ-1 and PSQ-2, carry 53. 8 wt% and 49. 3 wt% of Gd-DTPA derivatives, respectively.", "output": {"entities": {"chemical": [{"text": "Gd-PSQ", "start": 4, "end": 10}, {"text": "Gd-DTPA", "start": 72, "end": 79}]}}, "schema": []}
{"input": "In addition, the surface carboxy groups on the PSQ-2 particles can be modified with polyethylene glycol (PEG) and the anisamide (AA) ligand to enhance biocompatibility and cell uptake, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "The Gd-PSQ particles are readily degradable to release the constituent Gd (III) chelates in the presence of endogenous reducing agents such as cysteine and glutathione.", "output": {"entities": {"chemical": [{"text": "Gd-PSQ", "start": 4, "end": 10}, {"text": "Gd (III)", "start": 71, "end": 79}, {"text": "cysteine", "start": 143, "end": 151}, {"text": "glutathione", "start": 156, "end": 167}]}}, "schema": []}
{"input": "The MR relaxivities of the Gd-PSQ particles are determined using a 3T MR scanner, with r1 values ranging from 5. 9 to 17. 8 mMs (-1) on a per-Gd basis.", "output": {"entities": {"chemical": [{"text": "Gd-PSQ", "start": 27, "end": 33}, {"text": "Gd", "start": 142, "end": 144}]}}, "schema": []}
{"input": "Finally, the high sensitivity of the Gd-PSQ particles as T1-weighted MR contrast agents is demonstrated with in vitro MR imaging of human lung and pancreatic cancer cells.", "output": {"entities": {"chemical": [{"text": "Gd-PSQ", "start": 37, "end": 43}]}}, "schema": []}
{"input": "The enhanced efficiency of the anisamide-functionalized PSQ-2 particles as a contrast agent is corroborated by both confocal laser scanning microscopy imaging and ICP-MS analysis of Gd content in vitro.", "output": {"entities": {"chemical": [{"text": "anisamide", "start": 31, "end": 40}, {"text": "Gd", "start": 182, "end": 184}]}}, "schema": []}
{"input": "Diaion HP-2MG modified with 2-(2, 6-dichlorobenzylideneamino) benzenethiol as new adsorbent for solid phase extraction and flame atomic absorption spectrometric determination of metal ions.", "output": {"entities": {"chemical": [{"text": "2-(2, 6-dichlorobenzylideneamino) benzenethiol", "start": 28, "end": 74}]}}, "schema": []}
{"input": "A solid phase extraction method for enrichment-separation and the determination of cobalt (Co (2 +)), copper (Cu (2 +)), nickel (Ni (2 +)), zinc (Zn (2 +)) and lead (Pb (2 +)) ions in real samples has been proposed.", "output": {"entities": {"chemical": [{"text": "cobalt", "start": 83, "end": 89}, {"text": "Co (2 +)", "start": 91, "end": 99}, {"text": "copper", "start": 102, "end": 108}, {"text": "Cu (2 +)", "start": 110, "end": 118}, {"text": "nickel", "start": 121, "end": 127}, {"text": "Ni (2 +)", "start": 129, "end": 137}, {"text": "zinc", "start": 140, "end": 144}, {"text": "Zn (2 +)", "start": 146, "end": 154}, {"text": "Pb (2 +)", "start": 166, "end": 174}]}}, "schema": []}
{"input": "The influences of some analytical parameters like pH, flow rate, eluent type and interference of matrix ions on recoveries of analytes were optimized.", "output": {"entities": {}}, "schema": []}
{"input": "The limits of detection were found in the range of 1. 6-3. 9 micro g L (-1), while preconcentration factor for all understudy metal ions were found to be 166 with loading half time (t 1/2) less than 10 min.", "output": {"entities": {}}, "schema": []}
{"input": "The procedure was applied for the enrichment-separation of analyte ions in environmental samples with recoveries higher than 94. 8% and relative SD < 4. 9% (N = 5).", "output": {"entities": {}}, "schema": []}
{"input": "Grb10-mediated Negative Regulation of IGF1R-Activated Signalling Pathway Results in Cognitive Disorder in Diabetic Rats.", "output": {"entities": {}}, "schema": []}
{"input": "Growth factor receptor-bound protein 10 (Grb10) is a Src homology 2 (SH2) domain-containing protein and one of the binding partners for several trans-membrane tyrosine-kinase receptors, including insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1-R).", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 159, "end": 167}]}}, "schema": []}
{"input": "The hippocampus, which is critical for cognitive functions, is one of the main distribution areas of Grb10 in the central nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "In recent years, diabetic encephalopathy has been defined as a third type of diabetes and the IGF1-IR pathway has been shown to be critical for the neuropathogenic process of cognitive disorder in diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "However, the role of endogenous Grb10 in regulating the IGF1-IR pathway and neurobehavioral changes is not explicit.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study was to determine the in vivo function of endogenous Grb10 in diabetic encephalopathy and the underlying mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Using stereotaxic surgical techniques and lentiviral vectors expressing specific short hairpin RNA (shRNA), we could steadily knock down Grb10 expression in the hippocampus.", "output": {"entities": {}}, "schema": []}
{"input": "More importantly, we demonstrated that hippocampus-specific modulation of Grb10 protein levels led to a prominent remission of cognitive disorder, including improvements in both ultrastructural pathology and abnormal neurobehavioural changes.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings indicate that endogenous overexpression of Grb10 functions as a suppressor of the IGF1-IR pathway, which may represent an important mechanism that regulates cognitive disorder in diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "This article is protected by copyright.", "output": {"entities": {}}, "schema": []}
{"input": "All rights reserved.", "output": {"entities": {}}, "schema": []}
{"input": "A new ent-kaurane diterpenoid glycoside from Isodon japonica var. glaucocalyx.", "output": {"entities": {"chemical": [{"text": "ent-kaurane diterpenoid glycoside", "start": 6, "end": 39}]}}, "schema": []}
{"input": "A new ent-kaurane diterpenoid glycoside (1), named glaucocalyxin G, has been isolated from the n-butanol-soluble fraction of the dried whole plants of Isodon japonica var. glaucocalyx along with two known compounds, namely arjunglucoside (2) and kaempferol-3-O-rutinoside (3).", "output": {"entities": {"chemical": [{"text": "ent-kaurane diterpenoid glycoside", "start": 6, "end": 39}, {"text": "glaucocalyxin G", "start": 51, "end": 66}, {"text": "n-butanol", "start": 95, "end": 104}, {"text": "arjunglucoside", "start": 223, "end": 237}, {"text": "kaempferol-3-O-rutinoside", "start": 246, "end": 271}]}}, "schema": []}
{"input": "The structures of the isolated compounds were assigned on the basis of their (1) H and (13) C NMR spectra including two-dimensional NMR techniques such as HMQC, HMBC, and NOESY experiments and comparison with the literature data.", "output": {"entities": {"chemical": [{"text": "(1) H", "start": 77, "end": 82}, {"text": "(13) C", "start": 87, "end": 93}]}}, "schema": []}
{"input": "Potential role of CYP2D6 in the central nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "Cytochrome P450 2D6 (CYP2D6) is a pivotal enzyme responsible for a major drug oxidation polymorphism in human populations.", "output": {"entities": {}}, "schema": []}
{"input": "Distribution of CYP2D6 in brain and its role in serotonin metabolism suggest that CYP2D6 may have a function in the central nervous system.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 48, "end": 57}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "To establish an efficient and accurate platform for the study of CYP2D6 in vivo, a human CYP2D6 (Tg-2D6) model was generated by transgenesis in wild-type (WT) C57BL/6 mice using a P1 phage artificial chromosome clone containing the complete human CYP2D locus, including the CYP2D6 gene and 5'-and 3'-flanking sequences.", "output": {"entities": {}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "Human CYP2D6 was expressed not only in the liver but also in the brain.", "output": {"entities": {}}, "schema": []}
{"input": "The abundance of serotonin and 5-hydroxyindoleacetic acid in brain of Tg-2D6 is higher than in WT mice, either basal levels or after harmaline induction.", "output": {"entities": {"chemical": [{"text": "serotonin", "start": 17, "end": 26}, {"text": "5-hydroxyindoleacetic acid", "start": 31, "end": 57}, {"text": "harmaline", "start": 133, "end": 142}]}}, "schema": []}
{"input": "Metabolomics of brain homogenate and cerebrospinal fluid revealed a significant up-regulation of L-carnitine, acetyl-L-carnitine, pantothenic acid, 2'-deoxycytidine diphosphate (dCDP), anandamide, N-acetylglucosaminylamine and a down-regulation of stearoyl-L-carnitine in Tg-2D6 mice compared with WT mice.", "output": {"entities": {"chemical": [{"text": "L-carnitine", "start": 97, "end": 108}, {"text": "acetyl-L-carnitine", "start": 110, "end": 128}, {"text": "pantothenic acid", "start": 130, "end": 146}, {"text": "2'-deoxycytidine diphosphate", "start": 148, "end": 176}, {"text": "dCDP", "start": 178, "end": 182}, {"text": "anandamide", "start": 185, "end": 195}, {"text": "N-acetylglucosaminylamine", "start": 197, "end": 222}, {"text": "stearoyl-L-carnitine", "start": 248, "end": 268}]}}, "schema": []}
{"input": "Anxiety tests indicate Tg-2D6 mice have a higher capability to adapt to anxiety.", "output": {"entities": {}}, "schema": []}
{"input": "4.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, these findings indicate that the Tg-2D6 mouse model may serve as a valuable in vivo tool to determine CYP2D6-involved neurophysiological metabolism and function.", "output": {"entities": {}}, "schema": []}
{"input": "Two Substrate-Confined Sol-Gel Coassembled Ordered Macroporous Silica Structures with an Open Surface.", "output": {"entities": {"chemical": [{"text": "Silica", "start": 63, "end": 69}]}}, "schema": []}
{"input": "A sol-gel cooperative assembly method was demonstrated for the fabrication of inverse opal films with an open surface.", "output": {"entities": {}}, "schema": []}
{"input": "In this method, a sol-gel silicate precursor was cooperatively assembled into the interstitial spaces of microspheres at the same time when polystyrene templates formed in between two desired substrates.", "output": {"entities": {"chemical": [{"text": "silicate", "start": 26, "end": 34}]}}, "schema": []}
{"input": "Silica inverse opals with a three-dimensional ordered macroporous (3DOM) structure were obtained after selective removing the colloidal templates by calcination.", "output": {"entities": {"chemical": [{"text": "Silica", "start": 0, "end": 6}]}}, "schema": []}
{"input": "The open surfaces with a high degree of interconnected porosity and extremely uniform pore size were characterized by scanning electron microscope (SEM).", "output": {"entities": {}}, "schema": []}
{"input": "Optical transmission spectra reveals the existence of considerable deep band gaps of up to 70% and steep band edges of up to 6%/nm in the [111] directions of the 3DOM silica samples.", "output": {"entities": {"chemical": [{"text": "silica", "start": 167, "end": 173}]}}, "schema": []}
{"input": "A little shrinkage confirmed by transmission spectra is not larger than 3%, in consistent with the results measured by SEM, which revealing the sufficient and compact infiltration into the interstitial spaces by our confined sol-gel coassembly method.", "output": {"entities": {}}, "schema": []}
{"input": "With different incidence angles, the positions of pseudogaps can be easily tuned in the wide range from 720 nm to 887 nm, agreed well with the calculated values by the Bragg law.", "output": {"entities": {}}, "schema": []}
{"input": "All the results prove that the sol-gel coassembly method with two substrates confinement is a simple, low cost, convenient and versatile method for the fabrication of silica inverse opals without overlayers in large domains.", "output": {"entities": {"chemical": [{"text": "silica", "start": 167, "end": 173}]}}, "schema": []}
{"input": "Toxicological impact of inhaled electric mosquito-repellent liquid on the rat: a hematological, cytokine indications, oxidative stress and tumor markers.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Context: High malaria burden has led to the increased use of insecticides in the tropics and subtropics.", "output": {"entities": {}}, "schema": []}
{"input": "This study thus aimed at assessing the hematological effects alteration of pyrethroid insecticide exposure using the experimental animal model.", "output": {"entities": {"chemical": [{"text": "pyrethroid", "start": 75, "end": 85}]}}, "schema": []}
{"input": "Objective: A commonly available Electric Mosquito-Repellent Liquid pyrethroid insecticide containing prallethrin 1. 6% w/w is widely used for mosquito control in Saudi Arabia.", "output": {"entities": {"chemical": [{"text": "pyrethroid", "start": 67, "end": 77}, {"text": "prallethrin", "start": 101, "end": 112}]}}, "schema": []}
{"input": "The immunotoxic effects after inhalation exposures to the preparation for a continuous period of 24, 48, and 72 h were investigated in rats.", "output": {"entities": {}}, "schema": []}
{"input": "Methods and materials: Rats were exposed to prallethrin 1. 6% w/w by inhalation for 72 consecutive hours.", "output": {"entities": {"chemical": [{"text": "prallethrin", "start": 44, "end": 55}]}}, "schema": []}
{"input": "Total blood count, blood indices of creatine kinase (CK), gamma-glutamyltranspeptidase (gamma-GT), superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA), interleukin (IL)-2, tumor necrosis factors (TNF) alpha, alpha-fetoprotein (AFP), carbohydrate antigen (CA) 19. 9 and carcinoembrionic antigen (CEA) were assayed.", "output": {"entities": {"chemical": [{"text": "creatine", "start": 36, "end": 44}, {"text": "superoxide", "start": 99, "end": 109}, {"text": "nitric oxide", "start": 127, "end": 139}, {"text": "NO", "start": 141, "end": 143}, {"text": "malondialdehyde", "start": 146, "end": 161}, {"text": "MDA", "start": 163, "end": 166}, {"text": "carbohydrate", "start": 250, "end": 262}]}}, "schema": []}
{"input": "Results: The administration of prallethrin 1. 6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, hemoglobin, packed cell volume, platelets, mean corpuscular volume, and mean corpuscular hemoglobin in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h.", "output": {"entities": {"chemical": [{"text": "prallethrin", "start": 31, "end": 42}]}}, "schema": []}
{"input": "Significant increases in the levels of CK, gamma-GT, SOD, NO, MDA, AFP, IL-2, and TNF alpha were recorded.", "output": {"entities": {"chemical": [{"text": "NO", "start": 58, "end": 60}, {"text": "MDA", "start": 62, "end": 65}]}}, "schema": []}
{"input": "CA and CEA did not exhibit any change.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusions: Continuous inhalation to prallethrin 1. 6% insecticides poses toxicity on hematological variables.", "output": {"entities": {"chemical": [{"text": "prallethrin", "start": 38, "end": 49}]}}, "schema": []}
{"input": "It is also concluded that pyrethroid group of insecticide may cause hematological, biochemical, cytokine disturbances and possible mutagenic damage to the tissues.", "output": {"entities": {"chemical": [{"text": "pyrethroid", "start": 26, "end": 36}]}}, "schema": []}
{"input": "Identification of novel Gyrase B inhibitors as potential anti-TB drugs: Homology modeling, hybrid virtual screening and molecular dynamics simulations.", "output": {"entities": {}}, "schema": []}
{"input": "Using an integrated computational approach involving homology modeling, Pharmacophore/Structure-Based virtual screening, molecular dynamics simulations and per-residue energy contribution, ten compounds were proposed as potential TB inhibitors.", "output": {"entities": {}}, "schema": []}
{"input": "Via validated docking calculations, binding free energy calculations showed that the proposed compounds presented better binding affinity with DNA Gyrase B when compared to Novobiocin.", "output": {"entities": {"chemical": [{"text": "Novobiocin", "start": 173, "end": 183}]}}, "schema": []}
{"input": "The compiled in-silico approach employed in this study may serve as a useful tool in the process of the design and development of drugs, not only against TB, but also for a wide range of biological systems.", "output": {"entities": {}}, "schema": []}
{"input": "This article is protected by copyright.", "output": {"entities": {}}, "schema": []}
{"input": "All rights reserved.", "output": {"entities": {}}, "schema": []}
{"input": "Vitamin C forestalls cigarette smoke induced NF-kappa B activation in alveolar epithelial cells.", "output": {"entities": {"chemical": [{"text": "Vitamin C", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Cigarette smoking causes cellular oxidative stress resulting in inflammatory diseases of lung wherein transcription factor NF-kappa B plays an important role.", "output": {"entities": {}}, "schema": []}
{"input": "It is possible that vitamin C, an antioxidant, may prevent cigarette smoke (CS)-induced NF-kappa B activation that involves degradation of I-kappa B epsilon and nuclear translocation of c-Rel/p50 in alveolar epithelial cells.", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 20, "end": 29}]}}, "schema": []}
{"input": "Therefore, to examine the hypothesis, we verified the effect of vitamin C on CS-induced expression of NF-kappa B driven luciferase reporter and NF-kappa B binding at its target DNA by EMSA in alveolar epithelial A549 cells.", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 64, "end": 73}]}}, "schema": []}
{"input": "We also examined the level of I-kappa B epsilon and sub-cellular distribution of c-Rel by western blotting and immunofluorescence respectively in CSE-treated A549 cells with or without vitamin C pretreatment.", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 185, "end": 194}]}}, "schema": []}
{"input": "We observed a significant reduction in CSE induced luciferase expression, NF-kappa B DNA binding, I-kappa B epsilon degradation and c-Rel nuclear translocation in cells pretreated with vitamin C.", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 185, "end": 194}]}}, "schema": []}
{"input": "To further validate the result, we examined sub-cellular distribution of c-Rel in lungs of CS-exposed guinea pigs treated or untreated with vitamin C.", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 140, "end": 149}]}}, "schema": []}
{"input": "Result showed that vitamin C treatment resulted in markedly reduced c-Rel nuclear translocation.", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 19, "end": 28}]}}, "schema": []}
{"input": "All these results demonstrate that vitamin C prevents CS (E)-induced NF-kappa B activation and thus it could be used for the prevention of CS-induced inflammatory diseases.", "output": {"entities": {"chemical": [{"text": "vitamin C", "start": 35, "end": 44}]}}, "schema": []}
{"input": "Screening for polyphenols, antioxidant and antimicrobial activitiesof extracts from eleven Helianthemum taxa (Cistaceae) used in folk medicine in south-eastern Spain.", "output": {"entities": {"chemical": [{"text": "polyphenols", "start": 14, "end": 25}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: The Helianthemum genus contains approximately one hundred taxa.", "output": {"entities": {}}, "schema": []}
{"input": "Some of them are important medicinal plants used in several countries for many different purposes.", "output": {"entities": {}}, "schema": []}
{"input": "However, studies addressing the phytochemistry of many of these species or their biological activities are currently nonexistent.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: To perform a comparative analysis of the qualitative composition of secondary metabolites and biological activities of the leaves of the most commonly distributed and used Spanish Helianthemum taxa in order to find a relationship between chemotype, biological activity and uses.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: water and 80% methanolic extracts derived from 11 different Helianthemum taxa were analyzed for their phytochemical composition using standard methods.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, HPLC analysis was performed for the estimation of gallic acid, ellagic acid, tannins and flavonols as marker compounds.", "output": {"entities": {"chemical": [{"text": "gallic acid", "start": 63, "end": 74}, {"text": "ellagic acid", "start": 76, "end": 88}, {"text": "tannins", "start": 90, "end": 97}, {"text": "flavonols", "start": 102, "end": 111}]}}, "schema": []}
{"input": "The antioxidant activity was measured by employing the scavenging activity on DPPH (2, 2-diphenyl-1-picrylhydrazyl) and ABTS (2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonate) radicals.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 78, "end": 82}, {"text": "2, 2-diphenyl-1-picrylhydrazyl", "start": 84, "end": 114}, {"text": "ABTS", "start": 120, "end": 124}, {"text": "2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonate", "start": 126, "end": 175}]}}, "schema": []}
{"input": "The 80% methanolic extracts were evaluated for antibacterial (Gram-positive Staphylococcus aureus, Enterococcus faecalis and Listeria monocytogenes and Gram-negative Escherichia coli and Salmonella enterica) activity using the micro dilution technique.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The total polyphenolic content and antioxidant capabilities differed significantly among the Helianthemum leaf extracts.", "output": {"entities": {}}, "schema": []}
{"input": "A strong correlation between total phenolic content, antioxidant properties and antimicrobial activity was found.", "output": {"entities": {}}, "schema": []}
{"input": "The polyphenolic profile was specific for each taxon.", "output": {"entities": {}}, "schema": []}
{"input": "Whereas Helianthemum alypoides, Helianthemum cinereum subsp. rotundifolium, Helianthemum hirtum, Helianthemum asperum, and Helianthemum marifolium subsp. marifolium were characterized by the presence of gallic acid, egallic derivatives and ellagitannins; the polyphenolic profile of Helianthemum apenninum subsp. cavanillesianum, Helianthemum syriacum and Helianthemum polygonoides was mostly based on flavonoids.", "output": {"entities": {"chemical": [{"text": "gallic acid", "start": 203, "end": 214}, {"text": "egallic", "start": 216, "end": 223}, {"text": "flavonoids", "start": 402, "end": 412}]}}, "schema": []}
{"input": "Helianthemum cinereum, Helianthemum alypoides and Helianthemum marifolium consistently presented the strongest radical scavenging activity (in water extracts EC50 ranges from 29. 88 to 38. 1 against DPPH and from 8. 11 to 20. 8 against ABTS, and in 80% MeOH extracts from 25. 3 to 31. 8 against DPPH and from 6. 15 to 8. 6 against ABTS), total phenol content (> 117mg GAE/l) and antimicrobial activities.", "output": {"entities": {"chemical": [{"text": "DPPH", "start": 199, "end": 203}, {"text": "ABTS", "start": 236, "end": 240}, {"text": "MeOH", "start": 253, "end": 257}, {"text": "DPPH", "start": 295, "end": 299}, {"text": "ABTS", "start": 331, "end": 335}]}}, "schema": []}
{"input": "CONCLUSION: The Helianthemum taxa used in folk medicine did not cluster in a unique section, being equally distributed in two out of the four sections analysed.", "output": {"entities": {}}, "schema": []}
{"input": "There was not a clear relationship between the chemotype, based on the polyphenolic composition of the taxa, and their taxonomical classification.", "output": {"entities": {}}, "schema": []}
{"input": "However, the composition of the methanolic and water extracts from the leaves of plants belonging to the Helianthemum genus was strongly related to their medicinal uses.", "output": {"entities": {}}, "schema": []}
{"input": "Caffeic Acid Phenethyl Ester Suppresses Proliferation and Survival of TW2. 6 Human Oral Cancer Cells via Inhibition of Akt Signaling.", "output": {"entities": {"chemical": [{"text": "Caffeic Acid Phenethyl Ester", "start": 0, "end": 28}]}}, "schema": []}
{"input": "Caffeic acid phenethyl ester (CAPE) is a bioactive component extracted from honeybee hive propolis.", "output": {"entities": {"chemical": [{"text": "Caffeic acid phenethyl ester", "start": 0, "end": 28}, {"text": "CAPE", "start": 30, "end": 34}]}}, "schema": []}
{"input": "Our observations indicated that CAPE treatment suppressed cell proliferation and colony formation of TW2. 6 human oral squamous cell carcinoma (OSCC) cells dose-dependently.", "output": {"entities": {"chemical": [{"text": "CAPE", "start": 32, "end": 36}]}}, "schema": []}
{"input": "CAPE treatment decreased G1 phase cell population, increased G2/M phase cell population, and induced apoptosis in TW2. 6 cells.", "output": {"entities": {"chemical": [{"text": "CAPE", "start": 0, "end": 4}]}}, "schema": []}
{"input": "Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3 beta, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-kappa B, phospho-NF-kappa B Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip.", "output": {"entities": {"chemical": [{"text": "CAPE", "start": 15, "end": 19}, {"text": "phospho", "start": 74, "end": 81}, {"text": "Ser473", "start": 86, "end": 92}, {"text": "phospho", "start": 94, "end": 101}, {"text": "phospho", "start": 141, "end": 148}, {"text": "phospho", "start": 162, "end": 169}, {"text": "phospho", "start": 196, "end": 203}, {"text": "phospho", "start": 227, "end": 234}, {"text": "Ser807", "start": 238, "end": 244}]}}, "schema": []}
{"input": "Overexpression of Akt1 or Akt2 in TW2. 6 cells rescued growth inhibition caused by CAPE treatment.", "output": {"entities": {"chemical": [{"text": "CAPE", "start": 83, "end": 87}]}}, "schema": []}
{"input": "Co-treating TW2. 6 cells with CAPE and 5-fluorouracil, a commonly used chemotherapeutic drug for oral cancers, exhibited additive cell proliferation inhibition.", "output": {"entities": {"chemical": [{"text": "CAPE", "start": 30, "end": 34}, {"text": "5-fluorouracil", "start": 39, "end": 53}]}}, "schema": []}
{"input": "Our study suggested that administration of CAPE is a potential adjuvant therapy for patients with OSCC oral cancer.", "output": {"entities": {"chemical": [{"text": "CAPE", "start": 43, "end": 47}]}}, "schema": []}
{"input": "Assessment of genotoxic effects of flumorph by the comet assay in mice organs.", "output": {"entities": {"chemical": [{"text": "flumorph", "start": 35, "end": 43}]}}, "schema": []}
{"input": "The present study investigated the genotoxic effects of flumorph in various organs (brain, liver, spleen, kidney and sperm) of mice.", "output": {"entities": {"chemical": [{"text": "flumorph", "start": 56, "end": 64}]}}, "schema": []}
{"input": "The DNA damage, measured as comet tail length (micro m), was determined using the alkaline comet assay.", "output": {"entities": {}}, "schema": []}
{"input": "The comet assay is a sensitive assay for the detection of genotoxicity caused by flumorph using mice as a model.", "output": {"entities": {"chemical": [{"text": "flumorph", "start": 81, "end": 89}]}}, "schema": []}
{"input": "Statistically significant increases in comet assay for both dose-dependent and duration-dependent DNA damage were observed in all the organs assessed.", "output": {"entities": {}}, "schema": []}
{"input": "The organs exhibited the maximum DNA damage in 96 h at 54 mg/kg body weight.", "output": {"entities": {}}, "schema": []}
{"input": "Brain showed maximum DNA damage followed by spleen > kidney > liver > sperm.", "output": {"entities": {}}, "schema": []}
{"input": "Our data demonstrated that flumorph had induced systemic genotoxicity in mammals as it caused DNA damage in all tested vital organs, especially in brain and spleen.", "output": {"entities": {"chemical": [{"text": "flumorph", "start": 27, "end": 35}]}}, "schema": []}
{"input": "Role of central metabolism in the osmoadaptation of the halophilic bacterium Chromohalobacter salexigens.", "output": {"entities": {}}, "schema": []}
{"input": "Bacterial osmoadaptation involves the cytoplasmic accumulation of compatible solutes in order to counteract extracellular osmolarity.", "output": {"entities": {}}, "schema": []}
{"input": "The halophilic and highly halotolerant bacterium Chromohalobacter salexigens is able to grow up to 3 M NaCl in a minimal medium due to the de novo synthesis of ectoines.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 103, "end": 107}, {"text": "ectoines", "start": 160, "end": 168}]}}, "schema": []}
{"input": "This is an osmoregulated pathway that burdens central metabolic routes by quantitatively drawing off TCA cycle intermediaries.", "output": {"entities": {"chemical": [{"text": "TCA", "start": 101, "end": 104}]}}, "schema": []}
{"input": "Consequently, metabolism in C. salexigens has adapted to support this biosynthetic route.", "output": {"entities": {}}, "schema": []}
{"input": "Metabolism of C. salexigens is more efficient at high salinity than at low salinity, as reflected by lower glucose consumption, lower metabolite overflow and higher biomass yield.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 107, "end": 114}]}}, "schema": []}
{"input": "At low salinity, by-products (mainly gluconate, pyruvate and acetate) accumulate extracellularly.", "output": {"entities": {"chemical": [{"text": "gluconate", "start": 37, "end": 46}, {"text": "pyruvate", "start": 48, "end": 56}, {"text": "acetate", "start": 61, "end": 68}]}}, "schema": []}
{"input": "Using [1-13C]-, [2-13C]-, [6-13C]-and [U-13C6]-glucose as carbon sources, we were able to determine the main central metabolic pathways involved in ectoines biosynthesis from glucose.", "output": {"entities": {"chemical": [{"text": "[1-13C]-, [2-13C]-, [6-13C]-and [U-13C6]-glucose", "start": 6, "end": 54}, {"text": "carbon", "start": 58, "end": 64}, {"text": "ectoines", "start": 148, "end": 156}, {"text": "glucose", "start": 175, "end": 182}]}}, "schema": []}
{"input": "C. salexigens uses the Entner-Doudoroff pathway rather than the standard glycolytic pathway for glucose catabolism, and anaplerotic activity is high to replenish the TCA cycle with the intermediaries withdrawn for ectoines biosynthesis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 96, "end": 103}, {"text": "TCA", "start": 166, "end": 169}, {"text": "ectoines", "start": 214, "end": 222}]}}, "schema": []}
{"input": "Metabolic flux ratios at low and high salinity were similar, revealing a certain metabolic rigidity, probably due to its specialization to support high biosynthetic fluxes and partially explaining why metabolic yields are so highly affected by salinity.", "output": {"entities": {}}, "schema": []}
{"input": "This work represents an im-portant contribution to the elucidation of specific metabolic adaptations in compatible solute accumulating halophilic bacteria.", "output": {"entities": {}}, "schema": []}
{"input": "Selective Bisubstrate Inhibitors with Sub-nanomolar Affinity for Protein Kinase Pim-1.", "output": {"entities": {}}, "schema": []}
{"input": "Potent and selective: The unique nature of the ATP binding pocket structure of Pim family protein kinases (PKs) was used for the development of bisubstrate inhibitors and a fluorescent probe with sub-nanomolar affinity.", "output": {"entities": {"chemical": [{"text": "ATP", "start": 47, "end": 50}]}}, "schema": []}
{"input": "Conjugates of arginine-rich peptides with two ATP mimetic scaffolds were synthesized and tested as inhibitors of Pim-1.", "output": {"entities": {"chemical": [{"text": "arginine", "start": 14, "end": 22}, {"text": "ATP", "start": 46, "end": 49}]}}, "schema": []}
{"input": "Against a panel of 124 protein kinases, a novel ARC-PIM conjugate selectively inhibited PKs of the Pim family.", "output": {"entities": {}}, "schema": []}
{"input": "Side effects associated with psychotropic medications in patients with bipolar disorder: evidence from two independent samples.", "output": {"entities": {}}, "schema": []}
{"input": "Available evidence concerning the side effects experienced by bipolar disorder (BD) patients under naturalistic conditions has been poorly investigated.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study was therefore to investigate side effects related to major psychotropic drugs in two independent samples of BD patients naturalistically treated with mood stabilizers, antidepressants, antipsychotics and/or anxiolytics.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, 3654 patients from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample and 282 patients from the Clinical Outcome and Psycho-Education for Bipolar Disorder (COPE-BD) sample were included.", "output": {"entities": {}}, "schema": []}
{"input": "The primary outcome measure was the influence of each class of psychotropic drugs under investigation on the emergence of any side effect, as measured with the monitoring form in the STEP-BD study and the Udvalg for Kliniske Unders o gelser Side Effect Rating Scale in the COPE-BD study.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary outcome measures included the effects of such drugs on psychic, neurologic, autonomic and other side effects.", "output": {"entities": {}}, "schema": []}
{"input": "Mood stabilizers and antipsychotics were associated with high rates of side effects in both samples.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, antipsychotics were specifically associated with psychic side effects, whereas mood stabilizers were specifically associated with neurologic side effects.", "output": {"entities": {}}, "schema": []}
{"input": "Our results largely confirm in a naturalistic setting results previously observed in randomized controlled trials focusing on BD patients.", "output": {"entities": {}}, "schema": []}
{"input": "In Vitro Activity of Paclitaxel-Loaded Polymeric Expansile Nanoparticles in Breast Cancer Cells.", "output": {"entities": {"chemical": [{"text": "Paclitaxel", "start": 21, "end": 31}]}}, "schema": []}
{"input": "Through a series of in vitro studies, the essential steps for intracellular drug delivery of paclitaxel using a pH-responsive nanoparticle system have been investigated in breast cancer cells.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 93, "end": 103}]}}, "schema": []}
{"input": "We successfully encapsulated paclitaxel within polymeric expansile nanoparticles (Pax-eNPs) at 5% loading via a miniemulsion polymerization procedure.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 29, "end": 39}, {"text": "Pax", "start": 82, "end": 85}]}}, "schema": []}
{"input": "Fluorescently tagged eNPs were readily taken up by MDA-MB-231 breast cancer cells grown in culture as confirmed by confocal microscopy and flow cytometry.", "output": {"entities": {}}, "schema": []}
{"input": "The ability of the encapsulated paclitaxel to reach the cytoplasm was also observed using confocal microscopy and fluorescently labeled paclitaxel.", "output": {"entities": {"chemical": [{"text": "paclitaxel", "start": 32, "end": 42}, {"text": "paclitaxel", "start": 136, "end": 146}]}}, "schema": []}
{"input": "Pax-eNPs were shown to be efficacious against three in vitro human breast adenocarcinoma cell lines (MDA-MB-231, MCF-7 and SK-BR-3) as well as cells isolated from the pleural effusions of two different breast cancer patients.", "output": {"entities": {"chemical": [{"text": "Pax", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Lastly, macropinocytosis was identified as the major cellular pathway responsible for eNP uptake, as confirmed using temperature-sensitive metabolic reduction, pharmacologic inhibitors, and fluid-phase marker co-localization.", "output": {"entities": {}}, "schema": []}
{"input": "LiGen: a High Performance workflow for chemistry driven de novo design.", "output": {"entities": {}}, "schema": []}
{"input": "Tools for molecular de novo design are actively sought incorporating sets of chemical rules for fast and efficient identification of structurally new chemotypes endowed with a desired set of biological properties.", "output": {"entities": {}}, "schema": []}
{"input": "In this paper, we present LiGen, a suite of programs which can be used sequentially or as stand-alone tools for specific purposes.", "output": {"entities": {}}, "schema": []}
{"input": "In its standard application, LiGen modules are used to define input constraints, either structure-based, through active site identification, or ligand-based, through pharmacophore definition, to docking and to de novo generation.", "output": {"entities": {}}, "schema": []}
{"input": "Alternatively, individual modules can be combined in a user-defined manner to generate project-centric workflows.", "output": {"entities": {}}, "schema": []}
{"input": "Specific features of LiGen are the use of a pharmacophore-based docking procedure which allows Flexible docking without conformer enumeration and accurate and flexible reactant mapping coupled with reactant tagging through substructure searching.", "output": {"entities": {}}, "schema": []}
{"input": "The full description of LiGen functionalities is herein presented.", "output": {"entities": {}}, "schema": []}
{"input": "Structures, Dynamics, and Stabilities of Fully Modified Locked Nucleic Acid (beta-d-LNA and alpha-l-LNA) Duplexes in Comparison to Pure DNA and RNA Duplexes.", "output": {"entities": {}}, "schema": []}
{"input": "Locked nucleic acid (LNA) is a chemical modification which introduces a-O-CH2-linkage in the furanose sugar of nucleic acids and blocks its conformation in a particular state.", "output": {"entities": {"chemical": [{"text": "O-CH2", "start": 72, "end": 77}, {"text": "furanose sugar", "start": 93, "end": 107}]}}, "schema": []}
{"input": "Two types of modifications, namely, 2'-O, 4'-C-methylene-beta-d-ribofuranose (beta-d-LNA) and 2'-O, 4'-C-methylene-alpha-l-ribofuranose (alpha-l-LNA), have been shown to yield RNA and DNA duplex-like structures, respectively.", "output": {"entities": {"chemical": [{"text": "2'-O, 4'-C-methylene-beta-d-ribofuranose", "start": 36, "end": 76}, {"text": "2'-O, 4'-C-methylene-alpha-l-ribofuranose", "start": 94, "end": 135}]}}, "schema": []}
{"input": "LNA modifications lead to increased melting temperatures of DNA and RNA duplexes, and have been suggested as potential therapeutic agents in antisense therapy.", "output": {"entities": {}}, "schema": []}
{"input": "In this study, molecular dynamics (MD) simulations were performed on fully modified LNA duplexes and pure DNA and RNA duplexes sharing a similar sequence to investigate their structure, stabilities, and solvation properties.", "output": {"entities": {}}, "schema": []}
{"input": "Both LNA duplexes undergo unwinding of the helical structure compared to the pure DNA and RNA duplexes.", "output": {"entities": {}}, "schema": []}
{"input": "Though the alpha-LNA substituent has been proposed to mimic deoxyribose sugar in its conformational properties, the fully modified duplex was found to exhibit unique structural and dynamic properties with respect to the other three nucleic acid structures.", "output": {"entities": {"chemical": [{"text": "deoxyribose sugar", "start": 60, "end": 77}]}}, "schema": []}
{"input": "Free energy calculations accurately capture the enhanced stabilization of the LNA duplex structures compared to DNA and RNA molecules as observed in experiments.", "output": {"entities": {}}, "schema": []}
{"input": "pi-stacking interaction between bases from complementary strands is shown to be one of the contributors to enhanced stabilization upon LNA substitution.", "output": {"entities": {}}, "schema": []}
{"input": "A combination of two factors, namely, nature of the-O-CH2-linkage in the LNAs vs their absence in the pure duplexes and similar conformations of the sugar rings in DNA and alpha-LNA vs the other two, is suggested to contribute to the stark differences among the four duplexes studied here in terms of their structural, dynamic, and energetic properties.", "output": {"entities": {"chemical": [{"text": "O-CH2", "start": 52, "end": 57}]}}, "schema": []}
{"input": "Interview with m frederick hawthorne.", "output": {"entities": {}}, "schema": []}
{"input": "M Frederick Hawthorne is a world-renowned scientist in the field of molecular medicine and a pioneer in boron chemistry.", "output": {"entities": {"chemical": [{"text": "boron", "start": 104, "end": 109}]}}, "schema": []}
{"input": "He currently serves as the founding Director of the University of Missouri International Institute of Nano and Molecular Medicine (MO, USA).", "output": {"entities": {}}, "schema": []}
{"input": "Prof.", "output": {"entities": {}}, "schema": []}
{"input": "Hawthorne is a University of Missouri Curators' Distinguished Professor and University Professor of Chemistry Emeritus of the University of California, Los Angeles (CA, USA).", "output": {"entities": {}}, "schema": []}
{"input": "He is a member of the US National Academy of Sciences and the recipient of many national and international honors, including the 2003 King Faisal Prize in Science, the American Chemical Society' s 2009 Priestley Medal and the 2011 National Medal of Science.", "output": {"entities": {}}, "schema": []}
{"input": "Prof.", "output": {"entities": {}}, "schema": []}
{"input": "Hawthorne has authored or co-authored more than 540 research articles, 30 patents, ten book chapters and two books.", "output": {"entities": {}}, "schema": []}
{"input": "Prof.", "output": {"entities": {}}, "schema": []}
{"input": "Hawthorne spoke to Future Medicinal Chemistry on how he became involved in the field, the future of boron neutron capture therapy, and provides his advice for the next generation of boron scientists.", "output": {"entities": {"chemical": [{"text": "boron", "start": 100, "end": 105}, {"text": "boron", "start": 182, "end": 187}]}}, "schema": []}
{"input": "Interview conducted by Isaac Bruce, Managing Commissioning Editor.", "output": {"entities": {}}, "schema": []}
{"input": "Boron chemicals in diagnosis and therapeutics.", "output": {"entities": {"chemical": [{"text": "Boron", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Advances in the field of boron chemistry have expanded the application of boron from material use to medicine.", "output": {"entities": {"chemical": [{"text": "boron", "start": 25, "end": 30}, {"text": "boron", "start": 74, "end": 79}]}}, "schema": []}
{"input": "Boron-based drugs represent a new class of molecules that possess several biomedical applications including use as imaging agents for both optical and nuclear imaging as well as therapeutic agents with anticancer, antiviral, antibacterial, antifungal and other disease-specific activities.", "output": {"entities": {"chemical": [{"text": "Boron", "start": 0, "end": 5}]}}, "schema": []}
{"input": "For example, bortezomib (Velcade ((R))), the only drug in clinical use with boron as an active element, was approved in 2003 as a proteasome inhibitor for the treatment of multiple myeloma and non-Hodgkin' s lymphoma.", "output": {"entities": {"chemical": [{"text": "bortezomib", "start": 13, "end": 23}, {"text": "Velcade", "start": 25, "end": 32}, {"text": "boron", "start": 76, "end": 81}]}}, "schema": []}
{"input": "Several other boron-based compounds are in various phases of clinical trials, which illustrates the promise of this approach for medicinal chemists working in the area of boron chemistry.", "output": {"entities": {"chemical": [{"text": "boron", "start": 14, "end": 19}, {"text": "boron", "start": 171, "end": 176}]}}, "schema": []}
{"input": "It is expected that in the near future, several boron-containing drugs should become available in the market with better efficacy and potency than existing drugs.", "output": {"entities": {"chemical": [{"text": "boron", "start": 48, "end": 53}]}}, "schema": []}
{"input": "This article discusses the current status of the development of boron-based compounds as diagnostic and therapeutic agents in humans.", "output": {"entities": {"chemical": [{"text": "boron", "start": 64, "end": 69}]}}, "schema": []}
{"input": "Boronated carbohydrate derivatives as potential boron neutron capture therapy reagents.", "output": {"entities": {"chemical": [{"text": "Boronated carbohydrate", "start": 0, "end": 22}, {"text": "boron", "start": 48, "end": 53}]}}, "schema": []}
{"input": "The treatment of cancer remains one of the most challenging problems for humanity.", "output": {"entities": {}}, "schema": []}
{"input": "Boron neutron capture therapy is a binary approach for cancer treatment that is particularly attractive in treating high-grade gliomas and metastatic brain tumors.", "output": {"entities": {"chemical": [{"text": "Boron", "start": 0, "end": 5}]}}, "schema": []}
{"input": "Among the types of boron-containing molecules used as boron neutron capture therapy agents, boronated carbohydrate derivatives have received significant attention because of their preferential uptake by growing tumor cells.", "output": {"entities": {"chemical": [{"text": "boron", "start": 19, "end": 24}, {"text": "boron", "start": 54, "end": 59}, {"text": "boronated carbohydrate", "start": 92, "end": 114}]}}, "schema": []}
{"input": "This review provides a summary of the recent developments in the chemistry of carborane-containing carbohydrates.", "output": {"entities": {"chemical": [{"text": "carborane", "start": 78, "end": 87}, {"text": "carbohydrates", "start": 99, "end": 112}]}}, "schema": []}
{"input": "Dissecting Colloidal Stabilization Factors in Crowded Polymer Solutions by Forming Self-Assembled Monolayers on Gold Nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "An ideal colloidal system should be highly stable in a diverse range of buffer conditions while still retaining its surface accessibility.", "output": {"entities": {}}, "schema": []}
{"input": "We recently reported that dispersing citrate-capped gold nanoparticles (AuNPs) in polymers such as polyethylene glycol (PEG) can achieve such a goal due to contributions from depletion stabilization.", "output": {"entities": {"chemical": [{"text": "citrate", "start": 37, "end": 44}, {"text": "AuNPs", "start": 72, "end": 77}, {"text": "polyethylene glycol", "start": 99, "end": 118}, {"text": "PEG", "start": 120, "end": 123}]}}, "schema": []}
{"input": "Since AuNPs can weakly adsorb PEG to exert steric stabilization and the remaining citrate can impart charge stabilization, the extent of the contribution of depletion stabilization is unclear.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 30, "end": 33}, {"text": "citrate", "start": 82, "end": 89}]}}, "schema": []}
{"input": "In this work, we aim to dissect the contribution of each stabilizing factor.", "output": {"entities": {}}, "schema": []}
{"input": "This is achieved by coating AuNPs with a layer of thiolated compound, which inhibits the adsorption of PEG and also allows the control of surface charge.", "output": {"entities": {"chemical": [{"text": "AuNPs", "start": 28, "end": 33}, {"text": "PEG", "start": 103, "end": 106}]}}, "schema": []}
{"input": "We found that depletion stabilization alone was insufficient to stabilize AuNPs at room temperature.", "output": {"entities": {"chemical": [{"text": "AuNPs", "start": 74, "end": 79}]}}, "schema": []}
{"input": "However, when working together with other stabilization mechanisms, ultrahigh stability can be achieved.", "output": {"entities": {}}, "schema": []}
{"input": "The size of both AuNPs and PEG was systematically varied and the trend was compared with theoretical calculations.", "output": {"entities": {"chemical": [{"text": "AuNPs", "start": 17, "end": 22}, {"text": "PEG", "start": 27, "end": 30}]}}, "schema": []}
{"input": "Finally, we report the importance of the surface chemistry of commercial AuNPs.", "output": {"entities": {}}, "schema": []}
{"input": "Structural Characterization of a Model Gram-negative Bacterial Surface Using Lipopolysaccharides from Rough Strains of Escherichia coli.", "output": {"entities": {}}, "schema": []}
{"input": "Lipopolysaccharides (LPS) make up approximately 75% of the Gram-negative bacterial outer membrane (OM) surface, however, due to the complexity of the molecule, there are very few model OMs that include LPS.", "output": {"entities": {}}, "schema": []}
{"input": "The LPS molecule consists of lipid A, which anchors the LPS within the OM, a core polysaccharide region and a variable O-antigen polysaccharide chain.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 29, "end": 36}]}}, "schema": []}
{"input": "In this work we used RcLPS (consisting of lipid A plus the first seven sugars of the core polysaccharide) from a rough strain of E. coli to form stable monolayers of LPS at the air-liquid interface.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 42, "end": 49}, {"text": "sugars", "start": 71, "end": 77}]}}, "schema": []}
{"input": "The vertical structure RcLPS monolayers were characterized using neutron and X-ray reflectometry whilst the lateral structure was investigated using grazing incidence X-ray diffraction and Brewster Angle Microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "It was found that RcLPS monolayers at surface pressures of 20 mN m (-1) and above are resolved as hydrocarbon tails, an inner headgroup and an outer headgroup of polysaccharide with increasing solvation from tails to outer headgroups.", "output": {"entities": {"chemical": [{"text": "hydrocarbon", "start": 98, "end": 109}]}}, "schema": []}
{"input": "The lateral organization of the hydrocarbon lipid chains displays an oblique hexagonal unit cell at all surface pressures, with only the chain tilt angle changing with surface pressure.", "output": {"entities": {"chemical": [{"text": "hydrocarbon", "start": 32, "end": 43}]}}, "schema": []}
{"input": "This is in contrast to lipid A which displays hexagonal or, above 20 mN m (-1), distorted hexagonal packing.", "output": {"entities": {"chemical": [{"text": "lipid A", "start": 23, "end": 30}]}}, "schema": []}
{"input": "This work provides the first complete structural analysis of a realistic E. coli OM surface model.", "output": {"entities": {}}, "schema": []}
{"input": "Probing the Role of the Vancomycin E-Ring Aryl Chloride: Selective Divergent Synthesis and Evaluation of Alternatively Substituted E-Ring Analogues.", "output": {"entities": {"chemical": [{"text": "Vancomycin", "start": 24, "end": 34}, {"text": "Aryl Chloride", "start": 42, "end": 55}]}}, "schema": []}
{"input": "The selective functionalization of a vancomycin aglycon derivative through direct conversion of the E-ring aryl chloride to a reactive boronic acid, and its use in the synthesis of a systematic series of vancomycin E-ring analogues are described.", "output": {"entities": {"chemical": [{"text": "vancomycin", "start": 37, "end": 47}, {"text": "aryl chloride", "start": 107, "end": 120}, {"text": "boronic acid", "start": 135, "end": 147}, {"text": "vancomycin", "start": 204, "end": 214}]}}, "schema": []}
{"input": "The series of analogues was used to examine the impact of the E-ring chloride in binding D-Ala-D-Ala and on antimicrobial activity.", "output": {"entities": {"chemical": [{"text": "D-Ala-D-Ala", "start": 89, "end": 100}]}}, "schema": []}
{"input": "In contrast to the reduced activity of the unsubstituted E-ring derivatives, hydrophobic and relatively non-polar substituents approach or match the chloro substituted vancomycin and was insensitive to the electronic character of the substituent (e. g. Cl vs CN or OMe), whereas highly polar substituents fail to provide the enhancements.", "output": {"entities": {"chemical": [{"text": "chloro substituted vancomycin", "start": 149, "end": 178}, {"text": "Cl", "start": 253, "end": 255}, {"text": "CN", "start": 259, "end": 261}, {"text": "OMe", "start": 265, "end": 268}]}}, "schema": []}
{"input": "Moreover, the active permethylated vancomycin aglycon derivatives examined exhibit VanB VRE antimicrobial activity at levels that approach (typically within 2-fold) their activity against sensitive bacteria.", "output": {"entities": {"chemical": [{"text": "vancomycin", "start": 35, "end": 45}, {"text": "VanB", "start": 83, "end": 87}]}}, "schema": []}
{"input": "The robust borylation reaction also enabled the selective functionalization of a minimally protected vancomycin aglycon (N-Boc vancomycin aglycon), and provides a direct method for the preparation of previously inaccessible analogues.", "output": {"entities": {"chemical": [{"text": "vancomycin", "start": 101, "end": 111}, {"text": "N-Boc vancomycin", "start": 121, "end": 137}]}}, "schema": []}
{"input": "Characterization of the nucleation process of lysozyme at physiological pH: Primary but not sole process.", "output": {"entities": {}}, "schema": []}
{"input": "We report on a kinetic study of the heat-induced aggregation process of lysozyme at physiological pH.", "output": {"entities": {}}, "schema": []}
{"input": "The time evolution of the aggregation extent and the conformational changes of the protein were followed by dynamic light scattering (DLS) and FTIR spectroscopy, respectively, whereas the morphology of the aggregates was observed by Atomic Force Microscopy (AFM).", "output": {"entities": {}}, "schema": []}
{"input": "The conformational changes of the secondary and tertiary structures were simultaneous and distinct in time with respect to the formation of aggregates.", "output": {"entities": {}}, "schema": []}
{"input": "Oligomer formation occurred through at least two different aggregation processes: a nucleation process and a homogeneous non-nucleative diffusion-controlled process.", "output": {"entities": {}}, "schema": []}
{"input": "FTIR measurements showed that supramolecular aggregation proceeded without the formation of beta-aggregated structures and AFM images revealed the presence of oligomers and amorphous aggregates; no fibrillar structures were observed.", "output": {"entities": {}}, "schema": []}
{"input": "Expression of WWOX and FHIT is downregulated by exposure to arsenite in human uroepithelial cells.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 60, "end": 68}]}}, "schema": []}
{"input": "Ecological studies in Taiwan, Chile, Argentina, Bangladesh, and Mexico have confirmed significant dose-dependent associations between ingestion of arsenic-contaminated drinking water and the risk of various human malignancies.", "output": {"entities": {"chemical": [{"text": "arsenic", "start": 147, "end": 154}]}}, "schema": []}
{"input": "The FHIT and WWOX genes are active in common fragile sites FRA3B and FRA16D, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Reduced expression of FHIT or WWOX is known to be an early indicator of carcinogen-induced cancers.", "output": {"entities": {}}, "schema": []}
{"input": "However, the effect of arsenite on the expressions and molecular mechanisms of these markers is still unclear.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 23, "end": 31}]}}, "schema": []}
{"input": "The aims of this study were (i) to observe the expression of ATR, WWOX and FHIT proteins in urothelial carcinoma (UC) between endemic and non-endemic areas of blackfoot disease (BFD) by immunohistochemical analyses; (ii) to compare expression of these genes between arsenite-treated SV-HUC-1 human epithelial cells and rat uroepithelial cells; and (iii) to determine the role of DNMT and MEK inhibitors on expressions of WWOX and FHIT in response to arsenite in SV-HUC-1.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 266, "end": 274}, {"text": "arsenite", "start": 450, "end": 458}]}}, "schema": []}
{"input": "The experiments revealed that expressions of ATR, WWOX and FHIT in UC significantly differed between BFD areas and non-BFD areas (p = 0. 003, 0. 009 and 0. 021, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "In fact, the results for the arsenite-treated groups showed that ATR, WWOX and FHIT are downregulated by arsenite in SV-HUC-1.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 29, "end": 37}, {"text": "arsenite", "start": 105, "end": 113}]}}, "schema": []}
{"input": "However, the inhibitors suppressed the effects of arsenite on WWOX and FHIT proteins and mRNA expression.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 50, "end": 58}]}}, "schema": []}
{"input": "In conclusion, arsenite decreased expressions of ATR, WWOX and FHIT via ERK1/2 activation in SV-HUC-1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "These findings confirm that dysregulations of these markers may contribute to arsenite-induced carcinogenesis.", "output": {"entities": {"chemical": [{"text": "arsenite", "start": 78, "end": 86}]}}, "schema": []}
{"input": "Smad3 mediates cigarette smoke extract (CSE) induction of VEGF release by human fetal lung fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Cigarette smoke is the major cause of chronic obstructive pulmonary disease (COPD), yet pathogenic mechanisms are not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "Vascular endothelial growth factor (VEGF) is one of the major regulators of endothelial cell survival and is believed to play a role in the pathogenesis of COPD.", "output": {"entities": {}}, "schema": []}
{"input": "Fibroblasts are a significant source of VEGF in the lungs; however the effect of cigarette smoke exposure on VEGF release by fibroblasts is not fully understood.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that cigarette smoke-induced disturbed VEGF release by human lung fibroblasts is a potential pathogenic mechanism that could contribute to COPD.", "output": {"entities": {}}, "schema": []}
{"input": "Cigarette smoke extract (CSE) was prepared by modification of the methods of Carp and Janoff (American Review of Respiratory Disease, 1978).", "output": {"entities": {}}, "schema": []}
{"input": "Human fetal lung fibroblasts (HFL-1) were exposed to different concentrations of CSE and for different durations.", "output": {"entities": {}}, "schema": []}
{"input": "VEGF release into the media was measured using ELISA.", "output": {"entities": {}}, "schema": []}
{"input": "TGF-beta 1 receptor (T beta R1)/Smad3 as a potential pathway for CSE modulated VEGF release was also investigated using biochemical analyses and siRNA inhibition of Smad3 and siRNA and pharmacologic inhibition of T beta R1.", "output": {"entities": {}}, "schema": []}
{"input": "CSE induced VEGF release by HFL-1 in concentration and time dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "This was confirmed in two additional types of primary human fetal lung fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "CSE induced Smad3 phosphorylation and nuclear translocation in HFL-1 cells.", "output": {"entities": {}}, "schema": []}
{"input": "Silencing of Smad3 by siRNA not only eliminated the stimulatory effect of CSE on VEGF release but also inhibited baseline VEGF production.", "output": {"entities": {}}, "schema": []}
{"input": "Suppression of T beta R1 by the pharmacological inhibitor (SB431542) markedly reduced VEGF release by HFL-1 in response to CSE and this effect was confirmed by T beta R1 siRNA.", "output": {"entities": {"chemical": [{"text": "SB431542", "start": 59, "end": 67}]}}, "schema": []}
{"input": "In contrast, nicotine inhibited VEGF release by HFL-1 in a dose and time dependent manner.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings indicate that CSE stimulates Smad3-mediated VEGF release by lung fibroblasts.", "output": {"entities": {}}, "schema": []}
{"input": "Nicotine does not account for the CSE stimulation of VEGF in HFL-1.", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "The ability of lung fibroblasts to produce VEGF may play a role in pathogenesis of cigarette smoke induced lung disease.", "output": {"entities": {}}, "schema": []}
{"input": "2, 3, 7, 8-TCDD induces neurotoxicity and neuronal apoptosis in the rat brain cortex and PC12 cell line through the down-regulation of the Wnt/beta-catenin signaling pathway.", "output": {"entities": {"chemical": [{"text": "2, 3, 7, 8-TCDD", "start": 0, "end": 15}]}}, "schema": []}
{"input": "TCDD exposure has various toxic effects on in the human nervous system resulting in various developmental and behavioral deficits.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 0, "end": 4}]}}, "schema": []}
{"input": "However the underlying molecular mechanism of TCDD-induced adverse effects on the CNS and associated signaling pathways remains largely unknown.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 46, "end": 50}]}}, "schema": []}
{"input": "Herein we analyzed acute TCDD exposure in the rat brain cortex to investigate whether misregulation of the Wnt/beta-catenin signaling pathway plays a role in neurotoxicity.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 25, "end": 29}]}}, "schema": []}
{"input": "Western blot and immunohistochemical experiments revealed a significant down-regulation of beta-catenin and phospho-glycogen synthase kinase-3 beta (pSer9-GSK-3 beta) after TCDD exposure.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 173, "end": 177}]}}, "schema": []}
{"input": "TUNEL assay results showed apoptosis occurs mainly at day 7 after TCDD treatment.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 66, "end": 70}]}}, "schema": []}
{"input": "Immunofluorescent labeling indicated that beta-catenin was localized mainly in the neurons; co-localization of beta-catenin and active caspase-3 was found following TCDD exposure.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 165, "end": 169}]}}, "schema": []}
{"input": "Further, TCDD exposure decreased the level of pSer9-GSK-3 beta and beta-catenin, and increased apoptosis in the PC12 neuronal cell line in a dose-dependent manner.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 9, "end": 13}]}}, "schema": []}
{"input": "Interestingly the application of lithium chloride, a GSK-3 beta inhibitor, reversed the suppressive effect of TCDD on beta-catenin in PC12 cells and primary cortical neurons restoring cell viability and protecting cells from apoptosis as compared to untreated controls.", "output": {"entities": {"chemical": [{"text": "lithium chloride", "start": 33, "end": 49}, {"text": "TCDD", "start": 110, "end": 114}]}}, "schema": []}
{"input": "Taken together, these results indicate that the canonical Wnt/beta-catenin signaling pathway may play an important role in TCDD-induced neurotoxicity and neuronal apoptosis.", "output": {"entities": {"chemical": [{"text": "TCDD", "start": 123, "end": 127}]}}, "schema": []}
{"input": "Relationships between pharmacokinetics and efficacy of Xie-xin decoction in rats with experimental ulcerative colitis.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Xie-xin decoction (XXD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as ulcerative colitis (UC).", "output": {"entities": {}}, "schema": []}
{"input": "However, no potential action mechanisms and active compounds had been systematically investigated.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: To explore the effectiveness and the material basis of XXD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats.", "output": {"entities": {"chemical": [{"text": "trinitrobenzene sulfonic acid", "start": 80, "end": 109}, {"text": "TNBS", "start": 111, "end": 115}]}}, "schema": []}
{"input": "MATERIALS AND METHODS: XXD was administered orally for 8 days at a dosage of 2 or 4g/kg/day.", "output": {"entities": {}}, "schema": []}
{"input": "Plasma pharmacokinetic properties and colon tissue concentrations of multiple compounds from XXD were detected.", "output": {"entities": {}}, "schema": []}
{"input": "Tissue damage scores, production of interleukin (IL)-10 and myeloperoxidase (MPO), expression of tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappa Bp65 (NF-kappa Bp65) in colon tissues were examined.", "output": {"entities": {}}, "schema": []}
{"input": "Canonical correlation analysis was performed to evaluate the relationships between pharmacokinetics and efficacy to elucidate significantly active compounds of XXD.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: XXD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the level of MPO and the expression of TNF-alpha and NF-kappa Bp65, and increasing the production of IL-10 in colon tissues.", "output": {"entities": {}}, "schema": []}
{"input": "Efficacy of XXD was positively related with AUC of five plasma compounds (baicalin, berberine, wogonoside, wogonin, and rhein) and concentrations of six colon tissue compounds (coptisine, jatrorrhizine, palmatine, berberine, baicalein and emodin), respectively.", "output": {"entities": {"chemical": [{"text": "baicalin", "start": 74, "end": 82}, {"text": "berberine", "start": 84, "end": 93}, {"text": "wogonoside", "start": 95, "end": 105}, {"text": "wogonin", "start": 107, "end": 114}, {"text": "rhein", "start": 120, "end": 125}, {"text": "coptisine", "start": 177, "end": 186}, {"text": "jatrorrhizine", "start": 188, "end": 201}, {"text": "palmatine", "start": 203, "end": 212}, {"text": "berberine", "start": 214, "end": 223}, {"text": "baicalein", "start": 225, "end": 234}, {"text": "emodin", "start": 239, "end": 245}]}}, "schema": []}
{"input": "CONCLUSIONS: The multiple compounds in plasma and colon tissues from XXD might be the main material basis for therapeutic potentials in UC rats.", "output": {"entities": {}}, "schema": []}
{"input": "The anti-cancer activity of Antrodia camphorata against human ovarian carcinoma (SKOV-3) cells via modulation of HER-2/neu signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicinal fungus.", "output": {"entities": {}}, "schema": []}
{"input": "However, the anticancer activity of AC against human HER-2/neu-overexpressing ovarian cancers is poorly understood.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: The aim of this study is to investigate whether a submerged fermentation culture of AC can inhibit human ovarian carcinoma cell (SKOV-3) proliferation by suppressing the HER-2/neu signaling pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Cell viability, colony formation, DCFH-DA fluorescence microscopy, western blotting, HER-2/neu immunofluorescence imaging, flow cytometry, and TUNEL assays were carried out to determine the anti-cancer effects of AC.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: MTT and colony formation assays showed that AC induced a dose-dependent reduction in SKOV-3 cell growth.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 9, "end": 12}]}}, "schema": []}
{"input": "Immunoblot analysis demonstrated that HER-2/neu activity and tyrosine phosphorylation were significantly inhibited by AC.", "output": {"entities": {"chemical": [{"text": "tyrosine", "start": 61, "end": 69}]}}, "schema": []}
{"input": "Furthermore, AC treatment significantly inhibited the activation of PI3K/Akt and their downstream effector beta-catenin.", "output": {"entities": {}}, "schema": []}
{"input": "We also observed that AC caused G2/M arrest mediated by down-regulation of cyclin D1, cyclin A, cyclin B1, and Cdk1 and increased p27 expression.", "output": {"entities": {}}, "schema": []}
{"input": "Notably, AC induced apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9/-3 activation, PARP degradation, and Bcl-2/Bax dysregulation.", "output": {"entities": {}}, "schema": []}
{"input": "An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented AC-induced cell death, HER-2/neu depletion, PI3K/Akt inactivation, and Bcl-2/Bax dysregulation, indicating that AC-induced cell death was mediated by ROS generation.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 38, "end": 44}, {"text": "N-acetylcysteine", "start": 117, "end": 133}, {"text": "NAC", "start": 135, "end": 138}]}}, "schema": []}
{"input": "CONCLUSIONS: These results suggest that AC may exert anti-tumor activity against human ovarian carcinoma by suppressing HER-2/neu signaling pathways.", "output": {"entities": {}}, "schema": []}
{"input": "Comparative effectiveness of dabigatran, rivaroxaban, apixaban and warfarin in the management of patients with non-valvular atrial fibrillation.", "output": {"entities": {"chemical": [{"text": "dabigatran", "start": 29, "end": 39}, {"text": "rivaroxaban", "start": 41, "end": 52}, {"text": "apixaban", "start": 54, "end": 62}, {"text": "warfarin", "start": 67, "end": 75}]}}, "schema": []}
{"input": "Alternative anticoagulants to warfarin (dabigatran, rivaroxaban and apixaban) are becoming available for the prevention of thromboembolic stroke in atrial fibrillation, but there is a lack of information on their comparative effectiveness.", "output": {"entities": {"chemical": [{"text": "warfarin", "start": 30, "end": 38}, {"text": "dabigatran", "start": 40, "end": 50}, {"text": "rivaroxaban", "start": 52, "end": 63}, {"text": "apixaban", "start": 68, "end": 76}]}}, "schema": []}
{"input": "We evaluated this using a discrete event simulation with a lifetime horizon of analysis, based on an indirect comparison of the RE-LY, ROCKET-AF and ARISTOTLE trial results for patients with the characteristics of the US atrial fibrillation population.", "output": {"entities": {}}, "schema": []}
{"input": "Over a lifetime, apixaban, dabigatran and rivaroxaban accrued 0. 130 (95% central range [CR]-0. 030 to 0. 264), 0. 106 (95% CR-0. 048 to 0. 248) and 0. 095 (95% CR-0. 052 to 0. 242) more quality-adjusted life-years than warfarin, respectively, with apixaban having a 55% probability of accruing the highest total lifetime QALYs.", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 17, "end": 25}, {"text": "dabigatran", "start": 27, "end": 37}, {"text": "rivaroxaban", "start": 42, "end": 53}, {"text": "warfarin", "start": 220, "end": 228}, {"text": "apixaban", "start": 249, "end": 257}]}}, "schema": []}
{"input": "In the absence of a definitive trial, and acknowledging the limitations of an indirect comparison, the available evidence suggests apixaban to be the more effective anticoagulant. Clinical Pharmacology & Therapeutics (2013); accepted article preview online 25 April 2013; doi: 10. 1038/clpt. 2013. 83.", "output": {"entities": {"chemical": [{"text": "apixaban", "start": 131, "end": 139}]}}, "schema": []}
{"input": "Tandutinib (MLN518/CT53518) targeted to stem-like cells by inhibiting the function of ATP-binding cassette subfamily G member 2.", "output": {"entities": {"chemical": [{"text": "Tandutinib", "start": 0, "end": 10}, {"text": "MLN518", "start": 12, "end": 18}, {"text": "CT53518", "start": 19, "end": 26}, {"text": "ATP", "start": 86, "end": 89}]}}, "schema": []}
{"input": "Tandutinib is a novel inhibitor of tyrosine kinases FLT3, PDGFR and KIT.", "output": {"entities": {"chemical": [{"text": "Tandutinib", "start": 0, "end": 10}, {"text": "tyrosine", "start": 35, "end": 43}]}}, "schema": []}
{"input": "Our study was to explore the capability of tandutinib to reverse ABC transporter-mediated multidrug resistance.", "output": {"entities": {"chemical": [{"text": "tandutinib", "start": 43, "end": 53}]}}, "schema": []}
{"input": "Tandutinib reversed ABCG2-mediated drug resistance in ABCG2-482-R2, ABCG2-482-G2, ABCG2-482-T7 and S1-M1-80 cells and increased the accumulation of doxorubicin, rhodamine 123 and [H (3)] mitoxantrone in ABCG2-overexpressing cells.", "output": {"entities": {"chemical": [{"text": "Tandutinib", "start": 0, "end": 10}, {"text": "doxorubicin", "start": 148, "end": 159}, {"text": "rhodamine 123", "start": 161, "end": 174}, {"text": "[H (3)] mitoxantrone", "start": 179, "end": 199}]}}, "schema": []}
{"input": "Importantly, tandutinib selectively sensitized side population cells to mitoxantrone.", "output": {"entities": {"chemical": [{"text": "tandutinib", "start": 13, "end": 23}, {"text": "mitoxantrone", "start": 72, "end": 84}]}}, "schema": []}
{"input": "Taken together, our results advocate the potency of tandutinib as an ABCG2 modulator and stem-like cells targeted agent to increase efficiency of anticancer drugs.", "output": {"entities": {"chemical": [{"text": "tandutinib", "start": 52, "end": 62}]}}, "schema": []}
{"input": "How do polymeric micelles cross epithelial barriers?", "output": {"entities": {}}, "schema": []}
{"input": "Non-parenteral delivery of drugs using nanotechnology-based delivery systems is a promising non-invasive way to achieve effective local or systemic drug delivery.", "output": {"entities": {}}, "schema": []}
{"input": "The efficacy of drugs administered non-parenterally is limited by their ability to cross biological barriers, and epithelial tissues particularly present challenges.", "output": {"entities": {}}, "schema": []}
{"input": "Polymeric micelles can achieve transepithelial drug delivery because of their ability to be internalized into cells and/or cross epithelial barriers, thereby delivering drugs either locally or systematically following non-parenteral administration.", "output": {"entities": {}}, "schema": []}
{"input": "This review discusses the particular characteristics of various epithelial barriers and assesses their potential as non-parenteral routes of delivery.", "output": {"entities": {}}, "schema": []}
{"input": "The material characteristics of polymeric micelles (e. g., size, surface charge, and surface decoration) and of unimers dissociated from polymeric micelles determine their interactions (non-specific and/or specific) with mucus and epithelial cells as well as their intracellular fate.", "output": {"entities": {}}, "schema": []}
{"input": "This paper outlines the mechanisms governing the major modes of internalization of polymeric micelles into epithelial cells, with an emphasis on specific recent examples of the transport of drug-loaded polymeric micelles across epithelial barriers.", "output": {"entities": {}}, "schema": []}
{"input": "Rapamycin allosterically inhibits the proteasome.", "output": {"entities": {"chemical": [{"text": "Rapamycin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Rapamycin is a canonical allosteric inhibitor of the mTOR kinase with immunosuppressive and pro-apoptotic activities.", "output": {"entities": {"chemical": [{"text": "Rapamycin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "We found that in vitro rapamycin also regulates the proteasome, an essential intracellular protease of the ubiquitin-proteasome pathway.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 23, "end": 32}]}}, "schema": []}
{"input": "Rapamycin inhibits proteinase and selected peptidase activities of the catalytic core proteasome at low micromolar concentrations.", "output": {"entities": {"chemical": [{"text": "Rapamycin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Moreover, the drug interferes with binding of the 19S cap essential for processing of polyubiquitinylated substrates, and the PA200 activator to the 20S catalytic core proteasome.", "output": {"entities": {}}, "schema": []}
{"input": "These protein complexes are known to bind to specific grooves on the alpha face region of the 20S core.", "output": {"entities": {}}, "schema": []}
{"input": "A treatment with rapamycin affects conformational dynamics of the proteasomal gate, a centrally positioned within the alpha face and allosterically regulated element responsible for the intake of substrates.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 17, "end": 26}]}}, "schema": []}
{"input": "Interestingly, we showed that rapamycin shares all the proteasome targeting properties not only with other two-domain, closed-ring analogs (rapalogs), but also with its single domain mimics, and with seco-rapamycin.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 30, "end": 39}, {"text": "seco-rapamycin", "start": 200, "end": 214}]}}, "schema": []}
{"input": "The latter is the first in vivo open-ring metabolite of rapamycin that does not affect mTOR.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 56, "end": 65}]}}, "schema": []}
{"input": "We hypothesize that the rapamycin and related compounds bind to the alpha face and allosterically impact the proteasome function.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 24, "end": 33}]}}, "schema": []}
{"input": "The implications of our finding for mechanism of in vivo actions of rapamycin and for design of novel allosteric drugs targeting the proteasome are discussed.", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 68, "end": 77}]}}, "schema": []}
{"input": "Insulin-like growth factor 1 (IGF-1) expression is up-regulated in lymphoblastoid cell lines of lithium responsive bipolar disorder patients.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 96, "end": 103}]}}, "schema": []}
{"input": "Bipolar disorder (BD) is a debilitating psychiatric disease characterized by alternating episodes of mania and depression.", "output": {"entities": {}}, "schema": []}
{"input": "Among mood stabilizers, lithium is the mainstay for the treatment of BD, with approximately one-third of patients showing remission from episode recurrence.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 24, "end": 31}]}}, "schema": []}
{"input": "While there is evidence suggesting genetic load for lithium response in BD, its molecular underpinnings are still not completely understood.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 52, "end": 59}]}}, "schema": []}
{"input": "To identify genes potentially involved in (or correlated with) lithium response, we carried out a genome-wide expression analysis on lymphoblastoid cell lines (LCLs) from 10 BD patients responders (R) and 10 non-responders (NR) to lithium.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 63, "end": 70}, {"text": "lithium", "start": 231, "end": 238}]}}, "schema": []}
{"input": "We compared expression levels of the two groups and tested whether in vitro lithium treatment had different effects in LCLs of R compared to NR.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 76, "end": 83}]}}, "schema": []}
{"input": "At basal, 2060 genes were differentially expressed between R and NR while no genes were differentially regulated by lithium in the two groups.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 116, "end": 123}]}}, "schema": []}
{"input": "After pathway analysis based on the 2060 genes, 9 genes were selected for validation with qRT-PCR.", "output": {"entities": {}}, "schema": []}
{"input": "Eight genes were validated in the same sample of LCLs while only insulin-like growth factor 1 (IGF-1) was significantly over-expressed in R compared to NR in the same sample as well as in an independent sample comprised of 6 R and 6 NR (sample 1, fold change = 1. 94; p = 0. 005; sample 2, fold change = 2. 21; p = 0. 005).", "output": {"entities": {}}, "schema": []}
{"input": "IGF-1 was also significantly over-expressed in R but not in NR when compared to a sample of non-psychiatric controls.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest that IGF-1 may be involved in lithium response, supporting further investigation on its potential as a biomarker.", "output": {"entities": {"chemical": [{"text": "lithium", "start": 51, "end": 58}]}}, "schema": []}
{"input": "Polymorphism in porphyrin monolayers: the relation between adsorption configuration and molecular conformation.", "output": {"entities": {"chemical": [{"text": "porphyrin", "start": 16, "end": 25}]}}, "schema": []}
{"input": "Self-assembled monolayers of meso-5, 10, 15, 20-tetrakis (undecyl) porphyrin copper (ii) on a graphite/1-octanoic acid interface have been studied by Scanning Tunnelling Microscopy.", "output": {"entities": {"chemical": [{"text": "meso-5, 10, 15, 20-tetrakis (undecyl) porphyrin copper (ii)", "start": 29, "end": 88}, {"text": "graphite", "start": 94, "end": 102}, {"text": "1-octanoic acid", "start": 103, "end": 118}]}}, "schema": []}
{"input": "Four distinct polymorphs were observed, varying in their unit cell size.", "output": {"entities": {}}, "schema": []}
{"input": "Arrays of unit cells of the various polymorphs seamlessly connect to each other via shared unit cell vectors.", "output": {"entities": {}}, "schema": []}
{"input": "The monolayers are not commensurate, but coincident with the underlying graphite substrate.", "output": {"entities": {"chemical": [{"text": "graphite", "start": 72, "end": 80}]}}, "schema": []}
{"input": "The seamless transition between the polymorphs is proposed to be the result of an adaptation of the molecular conformations in the polymorphs and at the boundaries, which is enabled by the conformational freedom of the alkyl tails of these molecules.", "output": {"entities": {"chemical": [{"text": "alkyl", "start": 219, "end": 224}]}}, "schema": []}
{"input": "Random Regret-Based Discrete-Choice Modelling: An Application to Healthcare.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: A new modelling approach for analysing data from discrete-choice experiments (DCEs) has been recently developed in transport economics based on the notion of regret minimization-driven choice behaviour.", "output": {"entities": {}}, "schema": []}
{"input": "This so-called Random Regret Minimization (RRM) approach forms an alternative to the dominant Random Utility Maximization (RUM) approach.", "output": {"entities": {}}, "schema": []}
{"input": "The RRM approach is able to model semi-compensatory choice behaviour and compromise effects, while being as parsimonious and formally tractable as the RUM approach.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVES: Our objectives were to introduce the RRM modelling approach to healthcare-related decisions, and to investigate its usefulness in this domain.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Using data from DCEs aimed at determining valuations of attributes of osteoporosis drug treatments and human papillomavirus (HPV) vaccinations, we empirically compared RRM models, RUM models and Hybrid RUM-RRM models in terms of goodness of fit, parameter ratios and predicted choice probabilities.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: In terms of model fit, the RRM model did not outperform the RUM model significantly in the case of the osteoporosis DCE data (p = 0. 21), whereas in the case of the HPV DCE data, the Hybrid RUM-RRM model outperformed the RUM model (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Differences in predicted choice probabilities between RUM models and (Hybrid RUM-) RRM models were small.", "output": {"entities": {}}, "schema": []}
{"input": "Derived parameter ratios did not differ significantly between model types, but trade-offs between attributes implied by the two models can vary substantially.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: Differences in model fit between RUM, RRM and Hybrid RUM-RRM were found to be small.", "output": {"entities": {}}, "schema": []}
{"input": "Although our study did not show significant differences in parameter ratios, the RRM and Hybrid RUM-RRM models did feature considerable differences in terms of the trade-offs implied by these ratios.", "output": {"entities": {}}, "schema": []}
{"input": "In combination, our results suggest that RRM and Hybrid RUM-RRM modelling approach hold the potential of offering new and policy-relevant insights for health researchers and policy makers.", "output": {"entities": {}}, "schema": []}
{"input": "Genetic Variants in 2q31 and 5p15 Are Associated With Aggressive Benign Prostatic Hyperplasia in a Chinese Population.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease prevalent in elderly men.", "output": {"entities": {}}, "schema": []}
{"input": "However, the genetic determinants of BPH remain unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Because BPH and prostate cancer (PCa) share some common pathological characteristics, we investigated whether susceptibility loci for PCa contributed to BPH risk and BPH aggressiveness in Chinese men.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Fourteen SNPs associated with PCa risk in a Chinese population were genotyped in 426 BPH cases (184 aggressive and 242 non-aggressive BPH cases) and 1, 008 controls.", "output": {"entities": {}}, "schema": []}
{"input": "The association between the SNPs and BPH risk/aggressiveness was estimated using logistic regression analysis.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, effects of the 14 SNPs on BPH related clinical traits, including International Prostate Symptom Score (IPSS), prostate volume, total PSA, and free PSA were evaluated using linear regression analysis.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Two SNPs, rs12621278 in ITGA6 at 2q31 (OR = 0. 82, P = 0. 05) and rs339331 in RFX6 at 6q22 (OR = 1. 22, P = 0. 04) were significantly associated with BPH.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, rs12621278 (OR = 0. 73, P = 0. 05) and rs12653946, 13 kb upstream of IRX4 at 5p15 (OR = 1. 40, 0. 03), were significantly associated with aggressive BPH.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, the risk allele of rs12621278 (G) and rs12653946 (T) for aggressive BPH were significantly associated with elevated IPSS after treatment (P = 0. 01).", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: This is the first systematic investigation on the contributions of PCa susceptibility loci to risk and aggressiveness of BPH.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings advance our understanding of the genetic basis of BPH, especially aggressive BPH.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, our results provide new insights into the genetic determinants shared between BPH and PCa.", "output": {"entities": {}}, "schema": []}
{"input": "Prostate 9999: XX-XX.", "output": {"entities": {}}, "schema": []}
{"input": "(c) 2013 Wiley Periodicals, Inc.", "output": {"entities": {}}, "schema": []}
{"input": "Chip-scale Mid-Infrared chemical sensors using air-clad pedestal silicon waveguides.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 65, "end": 72}]}}, "schema": []}
{"input": "Towards a future lab-on-a-chip spectrometer, we demonstrate a compact chip-scale air-clad silicon pedestal waveguide as a Mid-Infrared (Mid-IR) sensor capable of in situ monitoring of organic solvents.", "output": {"entities": {}}, "schema": []}
{"input": "The sensor is a planar crystalline silicon waveguide, which is highly transparent, between lambda = 1. 3 and 6. 5 mu m, so that its operational spectral range covers most characteristic chemical absorption bands due to bonds such as C-H, N-H, O-H, C-C, N-O, C [double bond, length as m-dash] O, and C [triple bond, length as m-dash] N, as opposed to conventional UV, Vis, Near-IR sensors, which use weaker overtones of these fundamental bands.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 35, "end": 42}, {"text": "C-H", "start": 233, "end": 236}, {"text": "N-H", "start": 238, "end": 241}, {"text": "O-H", "start": 243, "end": 246}, {"text": "C-C", "start": 248, "end": 251}, {"text": "N-O", "start": 253, "end": 256}, {"text": "C", "start": 258, "end": 259}, {"text": "O", "start": 292, "end": 293}, {"text": "C", "start": 299, "end": 300}, {"text": "N", "start": 333, "end": 334}]}}, "schema": []}
{"input": "To extend light transmission beyond lambda = 3. 7 mu m, a spectral region where a typical silicon dioxide under-clad is absorbing, we fabricate a unique air-clad silicon pedestal waveguide.", "output": {"entities": {"chemical": [{"text": "silicon dioxide", "start": 90, "end": 105}, {"text": "silicon", "start": 162, "end": 169}]}}, "schema": []}
{"input": "The sensing mechanism of our Mid-IR waveguide sensor is based on evanescent wave absorption by functional groups of the surrounding chemical molecules, which selectively absorb specific wavelengths in the mid-IR, depending on the nature of their chemical bonds.", "output": {"entities": {}}, "schema": []}
{"input": "From a measurement of the waveguide mode intensities, we demonstrate in situ identification of chemical compositions and concentrations of organic solvents.", "output": {"entities": {}}, "schema": []}
{"input": "For instance, we show that when testing at lambda = 3. 55 mu m, the Mid-IR sensor can distinguish hexane from the rest of the tested analytes (methanol, toluene, carbon tetrachloride, ethanol and acetone), since hexane has a strong absorption from the aliphatic C-H stretch at lambda = 3. 55 mu m.", "output": {"entities": {"chemical": [{"text": "hexane", "start": 98, "end": 104}, {"text": "methanol", "start": 143, "end": 151}, {"text": "toluene", "start": 153, "end": 160}, {"text": "carbon tetrachloride", "start": 162, "end": 182}, {"text": "ethanol", "start": 184, "end": 191}, {"text": "acetone", "start": 196, "end": 203}, {"text": "hexane", "start": 212, "end": 218}, {"text": "C-H", "start": 262, "end": 265}]}}, "schema": []}
{"input": "Analogously, applying the same technique at lambda = 3. 3 mu m, the Mid-IR sensor is able to determine the concentration of toluene dissolved in carbon tetrachloride, because toluene has a strong absorption at lambda = 3. 3 mu m from the aromatic C-H stretch.", "output": {"entities": {"chemical": [{"text": "toluene", "start": 124, "end": 131}, {"text": "carbon tetrachloride", "start": 145, "end": 165}, {"text": "toluene", "start": 175, "end": 182}, {"text": "C-H", "start": 247, "end": 250}]}}, "schema": []}
{"input": "With our demonstration of an air-clad silicon pedestal waveguide sensor, we move closer towards the ultimate goal of an ultra-compact portable spectrometer-on-a-chip.", "output": {"entities": {"chemical": [{"text": "silicon", "start": 38, "end": 45}]}}, "schema": []}
{"input": "A New Proposed Rodent Model of Chemically Induced Prostate Carcinogenesis: Distinct Time-Course Prostate Cancer Progression in the Dorsolateral and Ventral Lobes.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes.", "output": {"entities": {}}, "schema": []}
{"input": "We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment.", "output": {"entities": {"chemical": [{"text": "MNU", "start": 41, "end": 44}, {"text": "testosterone", "start": 70, "end": 82}]}}, "schema": []}
{"input": "Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle alpha-actin, p63, MGMT, and E-cadherin) were studied in both lobes.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency.", "output": {"entities": {}}, "schema": []}
{"input": "However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups.", "output": {"entities": {"chemical": [{"text": "MNU", "start": 98, "end": 101}]}}, "schema": []}
{"input": "Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration.", "output": {"entities": {"chemical": [{"text": "MNU", "start": 117, "end": 120}, {"text": "testosterone", "start": 123, "end": 135}]}}, "schema": []}
{"input": "Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, VL lesions emerged throughout the entire lobe.", "output": {"entities": {}}, "schema": []}
{"input": "MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining.", "output": {"entities": {"chemical": [{"text": "MNU", "start": 0, "end": 3}]}}, "schema": []}
{"input": "CONCLUSIONS: There are distinct pathways involved in tumor progression in gerbil prostate lobes.", "output": {"entities": {}}, "schema": []}
{"input": "This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes.", "output": {"entities": {}}, "schema": []}
{"input": "Prostate (c) 2013 Wiley Periodicals, Inc.", "output": {"entities": {}}, "schema": []}
{"input": "The Effect of BCRP, MDR1 and OATP1B3 on the Antitumor Efficacy of the Lipophilic Camptothecin AR-67 In Vitro.", "output": {"entities": {"chemical": [{"text": "Camptothecin AR-67", "start": 81, "end": 99}]}}, "schema": []}
{"input": "AR-67 is a lipophilic camptothecin analogue, currently under early stage clinical trials.", "output": {"entities": {"chemical": [{"text": "AR-67", "start": 0, "end": 5}, {"text": "camptothecin", "start": 22, "end": 34}]}}, "schema": []}
{"input": "Transporters are known to have an impact on the disposition of camptothecins and on the response to chemotherapeutics in general due to their expression in tumor tissues.", "output": {"entities": {"chemical": [{"text": "camptothecins", "start": 63, "end": 76}]}}, "schema": []}
{"input": "Therefore, the interplay between the BCRP, MDR1 and OATP1B1/OATP1B3 transporters and AR-67 and their impact on the toxicity profile of AR-67 was investigated.", "output": {"entities": {"chemical": [{"text": "AR-67", "start": 85, "end": 90}, {"text": "AR-67", "start": 135, "end": 140}]}}, "schema": []}
{"input": "Using cell lines expressing the aforementioned transporters, we showed that the lipophilic AR-67 lactone form is a substrate for efflux transporters BCRP and MDR1.", "output": {"entities": {"chemical": [{"text": "AR-67 lactone", "start": 91, "end": 104}]}}, "schema": []}
{"input": "Additionally, OATP1B1 and OATP1B3 facilitated the uptake of AR-67 carboxylate in SLCO1B1 and SLCO1B3-transfected cell systems compared to the mock-transfected ones.", "output": {"entities": {"chemical": [{"text": "AR-67 carboxylate", "start": 60, "end": 77}]}}, "schema": []}
{"input": "Notably, both BCRPand MDR1, conferred resistance to AR-67 lactone.", "output": {"entities": {"chemical": [{"text": "AR-67 lactone", "start": 52, "end": 65}]}}, "schema": []}
{"input": "Prompted by recent studies showing increased OATP1B3 expression in certain cancer types, we investigated the effect of OATP1B3 expression on cell viability after exposure to AR-67 carboxylate.", "output": {"entities": {"chemical": [{"text": "AR-67 carboxylate", "start": 174, "end": 191}]}}, "schema": []}
{"input": "OATP1B3 expressing cells had increased carboxylate uptake as compared to mock transfected cells, but were not sensitized because the intracellular amount of lactone was fifty-fold higher than that of carboxylate and comparable between OATP1B3 expressing and non-expressing cells.", "output": {"entities": {"chemical": [{"text": "carboxylate", "start": 39, "end": 50}, {"text": "lactone", "start": 157, "end": 164}, {"text": "carboxylate", "start": 200, "end": 211}]}}, "schema": []}
{"input": "In conclusion, BCRP-and MDR1-mediated efflux of AR-67 lactone confers resistance to AR-67, but OATP1B3-mediated uptake of the AR-67 carboxylate does not sensitize OATP1B3 expressing tumor cells.", "output": {"entities": {"chemical": [{"text": "AR-67 lactone", "start": 48, "end": 61}, {"text": "AR-67", "start": 84, "end": 89}, {"text": "AR-67 carboxylate", "start": 126, "end": 143}]}}, "schema": []}
{"input": "High salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.", "output": {"entities": {}}, "schema": []}
{"input": "Intrauterine environments are linked to fetal renal development and postnatal health.", "output": {"entities": {}}, "schema": []}
{"input": "Influence of salt diets during pregnancy on renal functions and renin-angiotensin system (RAS) were determined in the ovine fetus and offspring.", "output": {"entities": {}}, "schema": []}
{"input": "Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for two months during middle-later gestation.", "output": {"entities": {}}, "schema": []}
{"input": "Fetal renal functions, plasma hormones, mRNA and protein expressions of the key elements of renal RAS were measured in the fetus and offspring.", "output": {"entities": {}}, "schema": []}
{"input": "Fetal renal excretion of sodium was increased while urine volume decreased in HSD group.", "output": {"entities": {"chemical": [{"text": "sodium", "start": 25, "end": 31}]}}, "schema": []}
{"input": "Fetal blood urea nitrogen was increased, while kidney/body weight ratio decreased in HSD group.", "output": {"entities": {"chemical": [{"text": "urea nitrogen", "start": 12, "end": 25}]}}, "schema": []}
{"input": "The altered ratio also was observed in the offspring at 15-day-old and 90-day-old.", "output": {"entities": {}}, "schema": []}
{"input": "Maternal and fetal plasma antidiuretic hormone was elevated without change in plasma renin activity and Ang I levels, while plasma Ang II was decreased.", "output": {"entities": {}}, "schema": []}
{"input": "The key elements of local renal RAS, including angiotensinogen, ACE, ACE2, AT1 and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake.", "output": {"entities": {}}, "schema": []}
{"input": "The results suggest that High intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Metallothionein gene transfection reverses the phenotype of activated human hepatic stellate cells.", "output": {"entities": {}}, "schema": []}
{"input": "Metallothionein (MT) gene therapy leads to resolution of liver fibrosis in mouse model.", "output": {"entities": {}}, "schema": []}
{"input": "The present study was undertaken to test the hypothesis that reversal of the phenotype of activated hepatic stellate cells (HSC) contributes to the fibrinolysis effect of MT.", "output": {"entities": {}}, "schema": []}
{"input": "Human HSC LX-2 cells were activated after cultured for 24 hrs, as indicated by expression of alpha-smooth muscle actin (alpha-SMA) and collagen-I, and depressed expression of collagenases.", "output": {"entities": {}}, "schema": []}
{"input": "Transfection with a plasmid containing human MT-II gene in the activated HSCs effectively increased the protein level of MT.", "output": {"entities": {}}, "schema": []}
{"input": "The expression of MT was accompanied by the reduction of protein levels of alpha-SMA and collagen-I, and the decrease in their mRNA levels.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, MT gene transfection resulted in upregulation of MMP-1,-8 and-13, which are importantly involved in the resolution of liver fibrosis.", "output": {"entities": {}}, "schema": []}
{"input": "This study demonstrates that reversal of the phenotype of activated HSCs, particularly the upregulation of collagenases, is likely involved in the resolution of liver fibrosis observed in MT gene therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Magnetic Porous Sugar-Functionalized PEG Microgels for Efficient Isolation and Removal of Bacteria from Solution.", "output": {"entities": {"chemical": [{"text": "Sugar", "start": 16, "end": 21}, {"text": "PEG", "start": 37, "end": 40}]}}, "schema": []}
{"input": "Here we present a new microparticle system for the selective detection and magnetic removal of bacteria from contaminated solutions.", "output": {"entities": {}}, "schema": []}
{"input": "The novelty of this system lies in the combination of a biocompatible scaffold reducing unspecific interactions with high capacity for bacteria binding.", "output": {"entities": {}}, "schema": []}
{"input": "We apply highly porous poly (ethylene glycol) (PEG) microparticles and functionalize them introducing both sugar ligands for specific bacteria targeting and cationic moieties for electrostatic loading of superparamagnetic iron oxide nanoparticles.", "output": {"entities": {"chemical": [{"text": "poly (ethylene glycol)", "start": 23, "end": 45}, {"text": "PEG", "start": 47, "end": 50}, {"text": "sugar", "start": 107, "end": 112}, {"text": "iron oxide", "start": 222, "end": 232}]}}, "schema": []}
{"input": "The resulting magnetic, porous, sugar-functionalized (MaPoS) PEG microgels are able to selectively bind and discriminate between different strains of bacteria Escherichia coli.", "output": {"entities": {"chemical": [{"text": "PEG", "start": 61, "end": 64}]}}, "schema": []}
{"input": "Furthermore, they allow for a highly efficient removal of bacteria from solution as their increased surface area can bind three times more bacteria than non-porous particles.", "output": {"entities": {}}, "schema": []}
{"input": "All in all, MaPoS particles represent a novel generation of magnetic beads introducing for the first time a porous, biocompatible and easy to functionalize scaffold and show great potential for various biotechnological applications.", "output": {"entities": {}}, "schema": []}
{"input": "Gliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis.", "output": {"entities": {}}, "schema": []}
{"input": "Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) play an increasing role in the management of type 2 diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Such incretin-based therapies offer some advantages over other glucose-lowering agents, but might be associated with an increased risk of acute pancreatitis.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 63, "end": 70}]}}, "schema": []}
{"input": "Areas covered: An extensive literature search was performed to analyze clinical cases of acute pancreatitis reported in the literature or to the Food and Drug Administration (FDA), in randomized clinical trials, and in observational studies with five DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 269, "end": 280}, {"text": "vildagliptin", "start": 282, "end": 294}, {"text": "saxagliptin", "start": 296, "end": 307}, {"text": "alogliptin", "start": 309, "end": 319}, {"text": "linagliptin", "start": 325, "end": 336}]}}, "schema": []}
{"input": "Expert opinion: An increased risk of pancreatitis has been reported in diabetic versus nondiabetic patients.", "output": {"entities": {}}, "schema": []}
{"input": "Several anecdotal clinical cases of pancreatitis have been reported with sitagliptin and vildagliptin and an increased relative risk reported to the FDA with sitagliptin versus other comparators, but reporting bias cannot be excluded.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 73, "end": 84}, {"text": "vildagliptin", "start": 89, "end": 101}, {"text": "sitagliptin", "start": 158, "end": 169}]}}, "schema": []}
{"input": "In rather short-term clinical trials with well-selected diabetic patients, no increased risk of acute pancreatitis has been observed with any of the five commercialized DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin.", "output": {"entities": {"chemical": [{"text": "sitagliptin", "start": 187, "end": 198}, {"text": "vildagliptin", "start": 200, "end": 212}, {"text": "saxagliptin", "start": 214, "end": 225}, {"text": "alogliptin", "start": 227, "end": 237}, {"text": "linagliptin", "start": 243, "end": 254}]}}, "schema": []}
{"input": "Similarly, real-life cohort studies showed no increased incidence of pancreatitis with gliptins compared with other glucose-lowering agents, a finding recently challenged by a case-control study.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 116, "end": 123}]}}, "schema": []}
{"input": "These results must be confirmed in postmarketing surveillance programs and in ongoing large prospective trials with cardiovascular outcomes.", "output": {"entities": {}}, "schema": []}
{"input": "Microbial degradation of microcystins.", "output": {"entities": {"chemical": [{"text": "microcystins", "start": 25, "end": 37}]}}, "schema": []}
{"input": "Hepatotoxic microcystins that are produced by freshwater cyanobacteria pose a risk to public health.", "output": {"entities": {"chemical": [{"text": "microcystins", "start": 12, "end": 24}]}}, "schema": []}
{"input": "These compounds may be eliminated by enzymatic degradation.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we review the enzymatic pathways for the degradation of these hepatotoxins, some of which are newly discovered processes.", "output": {"entities": {}}, "schema": []}
{"input": "The efficiencies of microcystin biodegradation pathways are documented in several papers and are compared here.", "output": {"entities": {"chemical": [{"text": "microcystin", "start": 20, "end": 31}]}}, "schema": []}
{"input": "Additionally, a comprehensive description of the microcystin enzymatic degradation scheme has been supplemented with a proposal for a new biodegradation pathway.", "output": {"entities": {"chemical": [{"text": "microcystin", "start": 49, "end": 60}]}}, "schema": []}
{"input": "Critical comments on less documented hypotheses are also included in this review.", "output": {"entities": {}}, "schema": []}
{"input": "The genetic aspects of biodegradation activity are discussed in detail.", "output": {"entities": {}}, "schema": []}
{"input": "We also describe some methods that are useful for studying the biological decomposition of microcystins, including screening for microcystin degraders and detecting microcystin degradation products, with an emphasis on mass spectrometric methodology.", "output": {"entities": {"chemical": [{"text": "microcystins", "start": 91, "end": 103}, {"text": "microcystin", "start": 129, "end": 140}, {"text": "microcystin", "start": 165, "end": 176}]}}, "schema": []}
{"input": "Insertion of CO2 and COS into Bi-C Bonds: Reactivity of a Bismuth NCN Pincer Complex of an Oxyaryl Dianionic Ligand, [2, 6-(Me2NCH2) 2C6H3] Bi (C6H2tBu2O).", "output": {"entities": {"chemical": [{"text": "CO2", "start": 13, "end": 16}, {"text": "COS", "start": 21, "end": 24}, {"text": "Bi-C", "start": 30, "end": 34}, {"text": "Bismuth NCN", "start": 58, "end": 69}, {"text": "Oxyaryl", "start": 91, "end": 98}, {"text": "[2, 6-(Me2NCH2) 2C6H3] Bi (C6H2tBu2O)", "start": 117, "end": 154}]}}, "schema": []}
{"input": "The reactivity of the unusual oxyaryl dianionic ligand, (C6H2tBu2-3, 5-O-4) 2-, in the Bi3 + NCN pincer complex Ar' Bi (C6H2tBu2-3, 5-O-4), 1, [Ar' = 2, 6-(Me2NCH2) 2C6H3] has been explored with small molecule substrates and electrophiles.", "output": {"entities": {"chemical": [{"text": "oxyaryl", "start": 30, "end": 37}, {"text": "(C6H2tBu2-3, 5-O-4) 2", "start": 56, "end": 77}, {"text": "Bi3 + NCN", "start": 87, "end": 96}, {"text": "Ar' Bi (C6H2tBu2-3, 5-O-4)", "start": 112, "end": 138}, {"text": "2, 6-(Me2NCH2) 2C6H3", "start": 150, "end": 170}]}}, "schema": []}
{"input": "The first insertion reactions of CO2 and COS into Bi-C bonds are observed with this oxyaryl dianionic ligand complex.", "output": {"entities": {"chemical": [{"text": "CO2", "start": 33, "end": 36}, {"text": "COS", "start": 41, "end": 44}, {"text": "Bi-C", "start": 50, "end": 54}, {"text": "oxyaryl", "start": 84, "end": 91}]}}, "schema": []}
{"input": "These reactions generate new dianions that have quinoidal character similar to the oxyaryl dianionic ligand in 1.", "output": {"entities": {"chemical": [{"text": "oxyaryl", "start": 83, "end": 90}]}}, "schema": []}
{"input": "The oxyarylcarboxy and oxyarylthiocarboxy dianionic ligands were identified by X-ray crystallography in Ar' Bi [O2C (C6H2tBu2-3-5-O-4)-kappa 2O, O'], 2 and Ar' Bi [OSC (C6H2tBu2-3-5-O-4)-kappa 2O, S], 3, respectively.", "output": {"entities": {"chemical": [{"text": "oxyarylcarboxy", "start": 4, "end": 18}, {"text": "oxyarylthiocarboxy", "start": 23, "end": 41}, {"text": "Ar' Bi [O2C (C6H2tBu2-3-5-O-4)-kappa 2O, O']", "start": 104, "end": 148}, {"text": "Ar' Bi [OSC (C6H2tBu2-3-5-O-4)-kappa 2O, S]", "start": 156, "end": 199}]}}, "schema": []}
{"input": "Silyl halides and pseudohalides, R3SiX (X = Cl, CN, N3; R = Me, Ph), react with 1 by attaching X to bismuth and R3Si to the oxyaryl oxygen to form Ar' Bi (X) (C6H2tBu2-3, 5-OSiR3-4) complexes, a formal addition across five bonds.", "output": {"entities": {"chemical": [{"text": "Silyl halides", "start": 0, "end": 13}, {"text": "pseudohalides", "start": 18, "end": 31}, {"text": "R3SiX", "start": 33, "end": 38}, {"text": "Cl", "start": 44, "end": 46}, {"text": "CN", "start": 48, "end": 50}, {"text": "N3", "start": 52, "end": 54}, {"text": "Me", "start": 60, "end": 62}, {"text": "Ph", "start": 64, "end": 66}, {"text": "bismuth", "start": 100, "end": 107}, {"text": "R3Si", "start": 112, "end": 116}, {"text": "oxyaryl oxygen", "start": 124, "end": 138}, {"text": "Ar' Bi (X) (C6H2tBu2-3, 5-OSiR3-4)", "start": 147, "end": 181}]}}, "schema": []}
{"input": "These react with additional R3SiX to generate Ar' BiX2 complexes and R3SiOC6H3tBu2-2, 6.", "output": {"entities": {"chemical": [{"text": "R3SiX", "start": 28, "end": 33}, {"text": "Ar' BiX2", "start": 46, "end": 54}, {"text": "R3SiOC6H3tBu2-2, 6", "start": 69, "end": 87}]}}, "schema": []}
{"input": "The reaction of 1 with I2 forms Ar' BiI2 and the coupled quinone, 3, 3', 5, 5'-tetra-tert-butyl-4, 4'-diphenoquinone, by oxidative coupling.", "output": {"entities": {"chemical": [{"text": "I2", "start": 23, "end": 25}, {"text": "Ar' BiI2", "start": 32, "end": 40}, {"text": "quinone", "start": 57, "end": 64}, {"text": "3, 3', 5, 5'-tetra-tert-butyl-4, 4'-diphenoquinone", "start": 66, "end": 116}]}}, "schema": []}
{"input": "High-Accuracy Estimates for the Vinylidene-Acetylene Isomerization Energy and the Ground State Rotational Constants of: C = CH2.", "output": {"entities": {"chemical": [{"text": "Vinylidene", "start": 32, "end": 42}, {"text": "Acetylene", "start": 43, "end": 52}, {"text": ": C = CH2", "start": 118, "end": 127}]}}, "schema": []}
{"input": "Highly accurate calculations are reported for properties of vinylidene (H2C = C:), specically the position of its zero-point vibrational level relative to that of acetylene and its equilibrium structure and ground state rotational constants.", "output": {"entities": {"chemical": [{"text": "vinylidene", "start": 60, "end": 70}, {"text": "H2C = C:", "start": 72, "end": 80}, {"text": "acetylene", "start": 163, "end": 172}]}}, "schema": []}
{"input": "The isomerization energy of vinylidene calculated at the HEAT-456QP level of theory is 45. 530. 15 kcal mol1, in agreement with the previous best estimate, but associated with a much smaller uncertainty.", "output": {"entities": {"chemical": [{"text": "vinylidene", "start": 28, "end": 38}]}}, "schema": []}
{"input": "In addition, the thermochemical calculations presented here also allow a determination of the: C = CH2 bond energy of the vinyl radical at the HEAT-345 (Q) level of theory, which is 77. 70. 3 kcal mol1.", "output": {"entities": {"chemical": [{"text": ": C = CH2", "start": 93, "end": 102}, {"text": "vinyl", "start": 122, "end": 127}]}}, "schema": []}
{"input": "The equilibrium structure of vinylidene, estimated with an additivity scheme that includes treatment of correlation eects beyond CCSD (T) as well as relativistic and adiabatic (diagonal Born-Oppenheimer correction) contributions is rCC = 1. 29820. 0003 A; rCH = 1. 08440. 0003 A; and CCH = 120. 050. 05o, with zero-point rotational constants (including vibrational contributions and electronic contributions to the moment of inertia) estimated to be A0 = 9. 49250. 0150 cm1; B0 = 1. 32170. 0017 cm1 and C0 = 1. 16020. 0016 cm1.", "output": {"entities": {"chemical": [{"text": "vinylidene", "start": 29, "end": 39}, {"text": "CCH", "start": 284, "end": 287}]}}, "schema": []}
{"input": "INTRODUCTION.", "output": {"entities": {}}, "schema": []}
{"input": "Atomic-Scale Interfacial Band Mapping across Vertically Phased-Separated Polymer/Fullerene Hybrid Solar Cells.", "output": {"entities": {"chemical": [{"text": "Fullerene", "start": 81, "end": 90}]}}, "schema": []}
{"input": "Using cross-sectional scanning tunneling microscope (XSTM) with samples cleaved in situ in an ultrahigh vacuum (UHV) chamber, this study demonstrates the direct visualization of high-resolution interfacial band mapping images across the film thickness in an optimized bulk heterojunction polymer solar cell consisting of nanoscale phase segregated blends of poly (3-hexylthiophene) (P3HT) and [6, 6]-phenyl C61 butyric acid methyl ester (PCBM).", "output": {"entities": {"chemical": [{"text": "poly (3-hexylthiophene)", "start": 358, "end": 381}, {"text": "P3HT", "start": 383, "end": 387}, {"text": "[6, 6]-phenyl C61 butyric acid methyl ester", "start": 393, "end": 436}, {"text": "PCBM", "start": 438, "end": 442}]}}, "schema": []}
{"input": "We were able to achieve the direct observation of the interfacial band alignments at the donor (P3HT)-acceptor (PCBM) interfaces and at the interfaces between the photoactive P3HT: PCBM blends and the poly (3, 4-ethylenedioxythiophene) poly (styrenesulfonate) (PEDOT: PSS) anode modification layer with an atomic-scale spatial resolution.", "output": {"entities": {"chemical": [{"text": "P3HT", "start": 96, "end": 100}, {"text": "PCBM", "start": 112, "end": 116}, {"text": "P3HT", "start": 175, "end": 179}, {"text": "PCBM", "start": 181, "end": 185}, {"text": "poly (3, 4-ethylenedioxythiophene) poly (styrenesulfonate)", "start": 201, "end": 259}, {"text": "PEDOT", "start": 261, "end": 266}, {"text": "PSS", "start": 268, "end": 271}]}}, "schema": []}
{"input": "The unique advantage of using XSTM to characterize polymer: fullerene bulk heterojunction solar cells allows us to explore simultaneously the quantitative link between the vertical morphologies and their corresponding local electronic properties.", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 60, "end": 69}]}}, "schema": []}
{"input": "This provides an atomic insight of interfacial band alignments between the two opposite electrodes, which will be crucial for improving the efficiencies of the charge generation, transport, and collection and the corresponding device performance of polymer solar cells.", "output": {"entities": {}}, "schema": []}
{"input": "Hydrazides/Hydrazones as antimicrobial and anticancer agents in the new millennium.", "output": {"entities": {"chemical": [{"text": "Hydrazides", "start": 0, "end": 10}, {"text": "Hydrazones", "start": 11, "end": 21}]}}, "schema": []}
{"input": "Hydrazide/hydrazone derivatives are of quite interest for medicinal chemists because of their vast spectrum of biological activity.", "output": {"entities": {"chemical": [{"text": "Hydrazide", "start": 0, "end": 9}, {"text": "hydrazone", "start": 10, "end": 19}]}}, "schema": []}
{"input": "Literature reports reveal that the hydrazide derivatives have been extensively studied for their biological profile during the past decade.", "output": {"entities": {"chemical": [{"text": "hydrazide", "start": 35, "end": 44}]}}, "schema": []}
{"input": "The aim of the present work is to collect literature reports focusing the antimicrobial and anticancer study of different hydrazide/hydrazone derivatives carried out during the past decade which will serve as a valuable source of information for the researchers working in the field of antimicrobial and anticancer research.", "output": {"entities": {"chemical": [{"text": "hydrazide", "start": 122, "end": 131}, {"text": "hydrazone", "start": 132, "end": 141}]}}, "schema": []}
{"input": "Evaluation of Chlorpheniramine Maleate microparticles in orally disintegrating film and orally disintegrating tablet for pediatrics.", "output": {"entities": {"chemical": [{"text": "Chlorpheniramine Maleate", "start": 14, "end": 38}]}}, "schema": []}
{"input": "Abstract Objective: To mask the bitterness of Chlorpheniramine Maleate via encapsulating drug into Eudragit EPO microparticles, and then incorporate these microparticles into orally disintegrating films (ODF) and orally disintegrating tablets (ODT) for pediatric uses.", "output": {"entities": {"chemical": [{"text": "Chlorpheniramine Maleate", "start": 46, "end": 70}, {"text": "Eudragit EPO", "start": 99, "end": 111}]}}, "schema": []}
{"input": "Methods: Spray drying of water-in-oil emulsion was utilized to encapsulate Chlorpheniramine Maleate into Eudragit EPO microparticles.", "output": {"entities": {"chemical": [{"text": "Chlorpheniramine Maleate", "start": 75, "end": 99}, {"text": "Eudragit EPO", "start": 105, "end": 117}]}}, "schema": []}
{"input": "Based on an orthogonal experimental design L9 (3 (3)), polynomial regression models were developed to evaluate correlation between microparticle properties (encapsulation efficiency and drug release) and variables (X1: weight ratio of polymer to drug, X2: volume ratio of oil to water and X3: Q-flow of spray dryer).", "output": {"entities": {}}, "schema": []}
{"input": "ODF and ODT formulations were evaluated including weight variation, content uniformity, tensile strength, disintegration time, friability and dissolution profiles.", "output": {"entities": {}}, "schema": []}
{"input": "The bitterness taste test was evaluated in 10 adult volunteers.", "output": {"entities": {}}, "schema": []}
{"input": "Results and discussion: From polynomial regression analysis, the best values of variables leading to the optimized microparticles were X1 = 10, X2 = 3 and X3 = 45.", "output": {"entities": {}}, "schema": []}
{"input": "The optimized microparticles were incorporated into ODF and ODT with satisfactory weight and drug content uniformity, and acceptable physical strength.", "output": {"entities": {}}, "schema": []}
{"input": "Both dosage forms disintegrated immediately (less than 40 s) in simulated saliva solutions.", "output": {"entities": {}}, "schema": []}
{"input": "The outcome of taste-masking test indicated that microparticles alleviated drug bitterness significantly; bitterness was not discernible with microparticles incorporated in ODT, whereas only slight bitterness was detected from microparticles incorporated into ODF.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: Both ODF and ODT are shown to be suitable vehicles for taste masked Chlorpheniramine Maleate microparticles with potential for pediatric uses.", "output": {"entities": {"chemical": [{"text": "Chlorpheniramine Maleate", "start": 80, "end": 104}]}}, "schema": []}
{"input": "Amniotic membrane extract-loaded double-layered wound dressing: evaluation of gel properties and wound healing.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract The conservative single-layered wound dressing system is decomposed when mixed in polyvinyl alcohol (PVA) solution, which means it cannot be used with a temperature-sensitive drug.", "output": {"entities": {"chemical": [{"text": "polyvinyl alcohol", "start": 91, "end": 108}, {"text": "PVA", "start": 110, "end": 113}]}}, "schema": []}
{"input": "The goal of this investigation was to make an amniotic membrane extract (AME)-loaded double-layered wound dressing with an improved healing result compared to the conservative single-layered wound dressing systems.", "output": {"entities": {}}, "schema": []}
{"input": "The double-layered wound dressing was developed with PVA/sodium alginate using a freeze-melting technique; one layer was PVA layer and the other was the drug-loaded sodium alginate layer.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 53, "end": 56}, {"text": "sodium alginate", "start": 57, "end": 72}, {"text": "PVA", "start": 121, "end": 124}, {"text": "sodium alginate", "start": 165, "end": 180}]}}, "schema": []}
{"input": "Its gel properties were assessed compared to single-layered wound dressings.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, in vivo wound-healing effects and histopathology were calculated compared to commercial products.", "output": {"entities": {}}, "schema": []}
{"input": "The double-layered wound dressing gave a similar gel fraction and Young' s module as single-layered wound bandages developed with only PVA, and a similar inflammation ability and WVTR as single-layered wound dressings developed with PVA and sodium alginate.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 135, "end": 138}, {"text": "PVA", "start": 233, "end": 236}, {"text": "sodium alginate", "start": 241, "end": 256}]}}, "schema": []}
{"input": "Our data indicate that these double-layered wound bandages were just as swellable, but more elastic and stronger than single-layered wound dressings comprised of the same polymers and quantities, possibly giving an acceptable level of moisture and accumulation of exudates in the wound zone.", "output": {"entities": {}}, "schema": []}
{"input": "Compared to the commercial product, the double-layered wound dressing comprising 6. 7% PVA, 0. 5% sodium alginate and 0. 01% AME significantly enhanced the wound-healing effect in the wound-healing test.", "output": {"entities": {"chemical": [{"text": "PVA", "start": 87, "end": 90}, {"text": "sodium alginate", "start": 98, "end": 113}]}}, "schema": []}
{"input": "Histological investigations showed that superior full-thickness wound-healing effects compared to the commercial product.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, the double-layered wound dressing would be an outstanding wound-dressing system with improved wound healing and good gel property.", "output": {"entities": {}}, "schema": []}
{"input": "Triterpenes from the Aerial Parts of Cimicifuga yunnanensis and Their Antiproliferative Effects on p53 (N236S) Mouse Embryonic Fibroblasts.", "output": {"entities": {"chemical": [{"text": "Triterpenes", "start": 0, "end": 11}]}}, "schema": []}
{"input": "Nine new triterpene derivatives, yunnanterpenes A-F (1-6), 15, 16-seco-cimiterpenes A and B (7, 8), and cimilactone C (9), and 15 known analogues (10-24) were isolated from the aerial parts of Cimicifuga yunnanensis.", "output": {"entities": {"chemical": [{"text": "triterpene", "start": 9, "end": 19}, {"text": "yunnanterpenes A-F", "start": 33, "end": 51}, {"text": "15, 16-seco-cimiterpenes A and B", "start": 59, "end": 91}, {"text": "cimilactone C", "start": 104, "end": 117}]}}, "schema": []}
{"input": "The new structures were established using a combination of MS, NMR, and single-crystal X-ray diffraction techniques.", "output": {"entities": {}}, "schema": []}
{"input": "WT MEFs (wild-type mouse embryonic fibroblasts) and tumorigenic cell lines p53 (-/-) + H-RasV12 and p53 (-/-) + p53 (N236S) + H-RasV12 were used for evaluating active structures, targeting p53 (N236S) (corresponding to p53 (N239S) in humans) mutation.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 5 showed nonselective activities against these cell lines, with IC50 values of 5. 8, 8. 6, and 6. 0 mu M, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Compound 4 exhibited greater selectivity against the p53 (-/-) + p53 (N236S) + H-RasV12 cells (IC50 5. 5 mu M) than against the WT MEFs cells (IC50 14. 3 mu M).", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxic Bisbenzylisoquinoline Alkaloids from Stephania epigaea.", "output": {"entities": {"chemical": [{"text": "Bisbenzylisoquinoline Alkaloids", "start": 10, "end": 41}]}}, "schema": []}
{"input": "Six new bisbenzylisoquinoline alkaloids (1-6) and seven known compounds (8-14) were isolated from the tubers of Stephania epigaea, in addition to the major alkaloid, cepharanthine (7).", "output": {"entities": {"chemical": [{"text": "bisbenzylisoquinoline alkaloids", "start": 8, "end": 39}, {"text": "cepharanthine", "start": 166, "end": 179}]}}, "schema": []}
{"input": "The structures of 1-6 were elucidated by combined spectroscopic data analysis and chemical methods, with their configurations determined from their optical rotation values and confirmed using circular dichroism.", "output": {"entities": {}}, "schema": []}
{"input": "Compounds 1-6 belong to the oxyacanthine type of bisbenzylisoquinoline alkaloids and have a rare methylenedioxy substituent.", "output": {"entities": {"chemical": [{"text": "oxyacanthine", "start": 28, "end": 40}, {"text": "bisbenzylisoquinoline alkaloids", "start": 49, "end": 80}, {"text": "methylenedioxy", "start": 97, "end": 111}]}}, "schema": []}
{"input": "Compound 1, a dimer composed of benzylisoquinoline and seco-aristolactam units, represents a new type of bisbenzylisoquinoline alkaloid, while compounds 3-6 are bisbenzylisoquinoline N-oxides.", "output": {"entities": {"chemical": [{"text": "benzylisoquinoline", "start": 32, "end": 50}, {"text": "seco-aristolactam", "start": 55, "end": 72}, {"text": "bisbenzylisoquinoline alkaloid", "start": 105, "end": 135}, {"text": "bisbenzylisoquinoline N-oxides", "start": 161, "end": 191}]}}, "schema": []}
{"input": "These compounds were evaluated for their in vitro cytotoxicities against six human cancer cell lines (A-549, ECA109, HL-60, MCF-7, SMMC-7721, and SW480).", "output": {"entities": {}}, "schema": []}
{"input": "Cepharanthine (7), the major component of S. epigaea, exhibited cytotoxicity against all of these cancer cell lines except ECA109, while its known analogue, 10, displayed cytotoxicity against all six cancer cell lines.", "output": {"entities": {"chemical": [{"text": "Cepharanthine", "start": 0, "end": 13}]}}, "schema": []}
{"input": "An archaeal RadA paralog influences presynaptic filament formation.", "output": {"entities": {}}, "schema": []}
{"input": "Recombinases of the RecA family play vital roles in homologous recombination, a high-fidelity mechanism to repair DNA double-stranded breaks.", "output": {"entities": {}}, "schema": []}
{"input": "These proteins catalyze strand invasion and exchange after forming dynamic nucleoprotein filaments on ssDNA.", "output": {"entities": {}}, "schema": []}
{"input": "Increasing evidence suggests that stabilization of these dynamic filaments is a highly conserved function across diverse species.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we analyze the presynaptic filament formation and DNA binding characteristics of the Sulfolobus solfataricus recombinase SsoRadA in conjunction with the SsoRadA paralog SsoRal1.", "output": {"entities": {}}, "schema": []}
{"input": "In addition to constraining SsoRadA ssDNA-dependent ATPase activity, the paralog also enhances SsoRadA ssDNA binding, effectively influencing activities necessary for presynaptic filament formation.", "output": {"entities": {}}, "schema": []}
{"input": "These activities result in enhanced SsoRadA-mediated strand invasion in the presence of SsoRal1 and suggest a filament stabilization function for the SsoRal1 protein.", "output": {"entities": {}}, "schema": []}
{"input": "Melanogenesis inhibitory daphnane diterpenoids from the flower buds of Daphne genkwa.", "output": {"entities": {"chemical": [{"text": "daphnane diterpenoids", "start": 25, "end": 46}]}}, "schema": []}
{"input": "Two new daphnane-type diterpene esters, daphneresiniferins A (1) and B (2), along with seven known diterpenes, yuanhuacine (3), yuanhuadine (4), yuanhuahine (5), genkwadaphnin (6), genkwanine A (7), genkwanine F (8), and genkwanine H (9), were isolated from the methanol extract of the flower buds of Daphne genkwa.", "output": {"entities": {"chemical": [{"text": "daphneresiniferins A (1) and B", "start": 40, "end": 70}, {"text": "diterpenes", "start": 99, "end": 109}, {"text": "yuanhuacine", "start": 111, "end": 122}, {"text": "yuanhuadine", "start": 128, "end": 139}, {"text": "yuanhuahine", "start": 145, "end": 156}, {"text": "genkwadaphnin", "start": 162, "end": 175}, {"text": "genkwanine A", "start": 181, "end": 193}, {"text": "genkwanine F", "start": 199, "end": 211}, {"text": "genkwanine H", "start": 221, "end": 233}, {"text": "methanol", "start": 262, "end": 270}]}}, "schema": []}
{"input": "Their structures were elucidated on the basis of spectroscopic methods, especially 2D NMR spectra such as HMQC, HMBC, and NOESY.", "output": {"entities": {}}, "schema": []}
{"input": "All the isolates were evaluated for their inhibitory effects of the melanogenesis against alpha-melanocyte stimulating hormone (alpha-MSH)-activated B16 melanoma cells.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of pyrazolo [1, 5-a] pyrimidine linked aminobenzothiazole conjugates as potential anticancer agents.", "output": {"entities": {"chemical": [{"text": "pyrazolo [1, 5-a] pyrimidine", "start": 13, "end": 41}, {"text": "aminobenzothiazole", "start": 49, "end": 67}]}}, "schema": []}
{"input": "A series of pyrazolo [1, 5-a] pyrimidine linked 2-aminobenzothizole conjugates (6a-t) were synthesized and evaluated for their anticancer activity against five human cancer cell lines.", "output": {"entities": {"chemical": [{"text": "pyrazolo [1, 5-a] pyrimidine", "start": 12, "end": 40}, {"text": "2-aminobenzothizole", "start": 48, "end": 67}]}}, "schema": []}
{"input": "Among them two compounds 6p and 6m showed significant anticancer activity with IC50 values ranging from 2. 01 to 7. 07 and 1. 94-3. 46 mu M, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, cell cycle arrest in G2/M and reduction in Cdk1 expression level were observed upon treatment of these compounds and they also induced caspase-3 dependent apoptosis.", "output": {"entities": {}}, "schema": []}
{"input": "This was further confirmed by staining as well as DNA fragmentation analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Germ Cell Specification Requires Zygotic Mechanisms Rather Than Germ Plasm in a Basally Branching Insect.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: Primordial germ cell (PGC) specification is a universal process across animals, but the molecular mechanisms specifying PGCs are remarkably diverse.", "output": {"entities": {}}, "schema": []}
{"input": "In Drosophila, PGCs are specified by maternally provided, asymmetrically localized cytoplasmic factors (germ plasm).", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, historical literature on most other arthropods reports that PGCs arise from mesoderm during midembryogenesis, suggesting that an arthropod last common ancestor may have specified PGCs via zygotic mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "However, there has been no direct experimental evidence to date for germ plasm-independent arthropod PGC specification.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Here we show that in a basally branching insect, the cricket Gryllus bimaculatus, conserved germ plasm molecules are ubiquitously, rather than asymmetrically, localized during oogenesis and early embryogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular and cytological analyses suggest that Gryllus PGCs arise from abdominal mesoderm during segmentation, and twist RNAi embryos that lack mesoderm fail to form PGCs.", "output": {"entities": {}}, "schema": []}
{"input": "Using RNA interference we show that vasa and piwi are not required maternally or zygotically for PGC formation but rather are required for primary spermatogonial divisions in adult males.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: These observations suggest that Gryllus lacks a maternally inherited germ plasm, in contrast with many holometabolous insects, including Drosophila.", "output": {"entities": {}}, "schema": []}
{"input": "The mesodermal origin of Gryllus PGCs and absence of instructive roles for vasa and piwi in PGC formation are reminiscent of mouse PGC specification and suggest that zygotic cell signaling may direct PGC specification in Gryllus and other Hemimetabola.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular and functional characterization of flavin-containing monooxygenases in cynomolgus macaque.", "output": {"entities": {"chemical": [{"text": "flavin", "start": 45, "end": 51}]}}, "schema": []}
{"input": "Flavin-containing monooxygenases (FMOs), drug-metabolizing enzymes essential for the metabolism of endogenous biochemicals and foreign compounds, have been characterized in human (including FMO1-5 and FMO6P), but remain to be investigated in cynomolgus macaque.", "output": {"entities": {"chemical": [{"text": "Flavin", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In this study, cDNAs of cynomolgus FMO1-5 and FMO6 were isolated and characterized.", "output": {"entities": {}}, "schema": []}
{"input": "Amino acid sequences of cynomolgus FMO1-5, respectively, shared high sequence identities (94-98%) and were closely clustered in a phylogenetic tree, with human FMO1-5.", "output": {"entities": {"chemical": [{"text": "Amino acid", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Eight different transcripts, due to alternative splicing, were isolated for cynomolgus FMO6, which is highly identical (~ 96%) to human FMO6P.", "output": {"entities": {}}, "schema": []}
{"input": "Among the 10 tissue types analyzed, cynomolgus FMO1, FMO2, FMO4, and FMO6 were most abundantly expressed in kidney, while cynomolgus FMO3 and FMO5 were most abundantly expressed in liver.", "output": {"entities": {}}, "schema": []}
{"input": "In kidney and liver, the most abundantly expressed cynomolgus FMO genes were FMO1 and FMO3 respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Cynomolgus FMO1, FMO2, FMO3, and FMO5 metabolized benzydamine, and FMO1/FMO3 and FMO3 also metabolized methimazole and trimethylamine, respectively.", "output": {"entities": {"chemical": [{"text": "benzydamine", "start": 50, "end": 61}, {"text": "methimazole", "start": 103, "end": 114}, {"text": "trimethylamine", "start": 119, "end": 133}]}}, "schema": []}
{"input": "Rates of benzydamine N-oxygenation (catalyzed by FMO3) varied (approximately 20-fold) among the 28 cynomolgus livers and were significantly correlated with FMO3 protein expression, indicating that the inter-animal variations in benzydamine N-oxygenation might be partly accounted for by the variable FMO3 expression.", "output": {"entities": {"chemical": [{"text": "benzydamine N", "start": 9, "end": 22}, {"text": "benzydamine N", "start": 228, "end": 241}]}}, "schema": []}
{"input": "Cynomolgus FMO6 metabolized benzydamine only slightly, but minimal expression of FMO6 in all tissue precludes the importance of FMO6 in drug metabolism, unlike cynomolgus FMO1, FMO2, FMO3, and FMO5 which were all functional.", "output": {"entities": {"chemical": [{"text": "benzydamine", "start": 28, "end": 39}]}}, "schema": []}
{"input": "Abundant expression of FMO1 and FMO3 in kidney and liver, respectively, suggest their importance in drug metabolism in cynomolgus macaque, similar to human.", "output": {"entities": {}}, "schema": []}
{"input": "Intestinal Organoids as Tissue Surrogates for Toxicological and Pharmacological Studies.", "output": {"entities": {}}, "schema": []}
{"input": "Recently developed cell culture protocols have allowed for the derivation of multi-cellular structures dubbed intestinal \" organoids \" from embryonic stem cells (ESCs), induced pluripotent stem cells (IPSCs), and adult intestinal stem cells (ISCs).", "output": {"entities": {}}, "schema": []}
{"input": "These structures resemble in vivo intestinal crypts, both in structure and developmental processes, and can be grown quickly and in relatively large quantities.", "output": {"entities": {}}, "schema": []}
{"input": "Although much research has focused on developing intestinal organoids for tissue repair, more immediate applications include high-throughput screening for agents that target intestinal epithelium.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe current methods for deriving mouse and human intestinal organoids and discuss some applications aimed at developing novel therapies or preventive agents for diseases of the lower GI tract such as inflammatory bowel diseases and colorectal cancer.", "output": {"entities": {}}, "schema": []}
{"input": "GABAA receptor modulation by piperine and a non-TRPV1 activating derivative.", "output": {"entities": {"chemical": [{"text": "piperine", "start": 29, "end": 37}]}}, "schema": []}
{"input": "The action of piperine (the pungent component of pepper) and its derivative SCT-66 ((2E, 4E)-5-(1, 3-benzodioxol-5-yl))-N, N-diisobutyl-2, 4-pentadienamide) on different gamma-aminobutyric acid (GABA) type A (GABAA) receptors, transient-receptor-potential-vanilloid-1 (TRPV1) receptors and behavioral effects were investigated.", "output": {"entities": {"chemical": [{"text": "piperine", "start": 14, "end": 22}, {"text": "SCT-66 ((2E, 4E)-5-(1, 3-benzodioxol-5-yl))-N, N-diisobutyl-2, 4-pentadienamide)", "start": 76, "end": 156}, {"text": "gamma-aminobutyric acid", "start": 170, "end": 193}, {"text": "GABA", "start": 195, "end": 199}]}}, "schema": []}
{"input": "GABAA receptor subtypes and TRPV1 receptors were expressed in Xenopus laevis oocytes.", "output": {"entities": {}}, "schema": []}
{"input": "Modulation of GABA-induced chloride currents (IGABA) by piperine and SCT-66 and activation of TRPV1 was studied using the two-microelectrode-voltage-clamp technique and fast perfusion.", "output": {"entities": {"chemical": [{"text": "GABA", "start": 14, "end": 18}, {"text": "chloride", "start": 27, "end": 35}, {"text": "piperine", "start": 56, "end": 64}, {"text": "SCT-66", "start": 69, "end": 75}]}}, "schema": []}
{"input": "Their effects on explorative behavior, thermoregulation and seizure threshold were analyzed in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Piperine acted with similar potency on all GABAA receptor subtypes (EC50 range: 42. 8 +/- 7. 6 mu M (alpha 2 beta 2)-59. 6 +/- 12. 3 mu M (alpha 3 beta 2)).", "output": {"entities": {"chemical": [{"text": "Piperine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "IGABA modulation by piperine did not require the presence of a gamma 2S-subunit, suggesting a binding site involving only alpha and beta subunits.", "output": {"entities": {"chemical": [{"text": "piperine", "start": 20, "end": 28}]}}, "schema": []}
{"input": "IGABA activation was slightly more efficacious on receptors formed from beta 2/3 subunits (maximal IGABA stimulation through alpha 1 beta 3 receptors: 332 +/- 64% and alpha 1 beta 2: 271 +/- 36% vs. alpha 1 beta 1: 171 +/- 22%, p < 0. 05) and alpha 3-subunits (alpha 3 beta 2: 375 +/- 51% vs. alpha 5 beta 2: 136 +/- 22%, p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "Replacing the piperidine ring by a N-di-isobutyl residue (SCT-66) prevents interactions with TRPV1 and simultaneously increases the potency and efficiency of GABAA receptor modulation.", "output": {"entities": {"chemical": [{"text": "piperidine", "start": 14, "end": 24}, {"text": "N-di-isobutyl", "start": 35, "end": 48}, {"text": "SCT-66", "start": 58, "end": 64}]}}, "schema": []}
{"input": "SCT-66 displayed greater efficacy on GABAA receptors than piperine, with different subunit-dependence.", "output": {"entities": {"chemical": [{"text": "SCT-66", "start": 0, "end": 6}, {"text": "piperine", "start": 58, "end": 66}]}}, "schema": []}
{"input": "Both compounds induced anxiolytic, anticonvulsant effects and reduced locomotor activity; however, SCT-66 induced stronger anxiolysis without decreasing body temperature and without the proconvulsive effects of TRPV1 activation and thus may serve as a scaffold for the development of novel GABAA receptor modulators.", "output": {"entities": {"chemical": [{"text": "SCT-66", "start": 99, "end": 105}]}}, "schema": []}
{"input": "The accurate measurement of second virial coefficients using self-interaction chromatography: Experimental considerations.", "output": {"entities": {}}, "schema": []}
{"input": "Measurement of B22, the second virial coefficient, is an important technique for describing the solution behaviour of proteins, especially as it relates to precipitation, aggregation and crystallisation phenomena.", "output": {"entities": {}}, "schema": []}
{"input": "This paper describes the best practise for calculating B22 values from self-interaction chromatograms (SIC) for aqueous protein solutions.", "output": {"entities": {}}, "schema": []}
{"input": "Detailed analysis of SIC peak shapes for lysozyme shows that non-Gaussian peaks are commonly encountered for SIC, with typical peak asymmetries of 10%.", "output": {"entities": {}}, "schema": []}
{"input": "This asymmetry reflects a non-linear chromatographic retention process, in this case heterogeneity of the protein-protein interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, it is important to use the centre of mass calculations for determining accurate retention volumes and thus B22 values.", "output": {"entities": {}}, "schema": []}
{"input": "Empirical peak maximum chromatogram analysis, often reported in the literature, can result in errors of up to 50% in B22 values.", "output": {"entities": {}}, "schema": []}
{"input": "A methodology is reported here for determining both the mean and the variance in B22 from SIC experiments, includes a correction for normal longitudinal peak broadening.", "output": {"entities": {}}, "schema": []}
{"input": "The variance in B22 due to chemical effects is quantified statistically and is a measure of the heterogeneity of protein-protein interactions in solution.", "output": {"entities": {}}, "schema": []}
{"input": "In the case of lysozyme, a wide range of B22 values are measured which can vary significantly from the average B22 values.", "output": {"entities": {}}, "schema": []}
{"input": "Recent advances in quantitative neuroproteomics.", "output": {"entities": {}}, "schema": []}
{"input": "The field of proteomics is undergoing rapid development in a number of different areas including improvements in mass spectrometric platforms, peptide identification algorithms and bioinformatics.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, new and/or improved approaches have established robust methods that not only allow for in-depth and accurate peptide and protein identification and modification, but also allow for sensitive measurement of relative or absolute quantitation.", "output": {"entities": {}}, "schema": []}
{"input": "These methods are beginning to be applied to the area of neuroproteomics, but the central nervous system poses many specific challenges in terms of quantitative proteomics, given the large number of different neuronal cell types that are intermixed and that exhibit distinct patterns of gene and protein expression.", "output": {"entities": {}}, "schema": []}
{"input": "This review highlights the recent advances that have been made in quantitative neuroproteomics, with a focus on work published over the last five years that applies emerging methods to normal brain function as well as to various neuropsychiatric disorders including schizophrenia and drug addiction as well as of neurodegenerative diseases including Parkinson' s disease and Alzheimer' s disease.", "output": {"entities": {}}, "schema": []}
{"input": "While older methods such as two-dimensional polyacrylamide electrophoresis continued to be used, a variety of more in-depth MS-based approaches including both label (ICAT, iTRAQ, TMT, SILAC, SILAM), label-free (label-free, MRM, SWATH) and absolute quantification methods, are rapidly being applied to neurobiological investigations of normal and diseased brain tissue as well as of cerebrospinal fluid (CSF).", "output": {"entities": {"chemical": [{"text": "polyacrylamide", "start": 44, "end": 58}]}}, "schema": []}
{"input": "While the biological implications of many of these studies remain to be clearly established, that there is a clear need for standardization of experimental design and data analysis, and that the analysis of protein changes in specific neuronal cell types in the central nervous system remains a serious challenge, it appears that the quality and depth of the more recent quantitative proteomics studies is beginning to shed light on a number of aspects of neuroscience that relates to normal brain function as well as of the changes in protein expression and regulation that occurs in neuropsychiatric and neurodegenerative disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Maternal nicotine exposure during lactation alters hypothalamic neuropeptides expression in the adult rat progeny.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 9, "end": 17}]}}, "schema": []}
{"input": "Maternal exposure to nicotine during lactation causes hyperleptinemia in the pups and, at adulthood, these animals are overweight and hyperleptinemic, while, in their hypothalamus, the leptin signaling pathway is reduced, evidencing a central leptin resistance.", "output": {"entities": {}}, "schema": []}
{"input": "Then, we evaluated the expression of pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone (alpha-MSH), cocaine and amphetamine-regulated transcript (CART), neuropeptide Y (NPY), agouti-related peptide (AgRP) and others in different hypothalamic nuclei in order to better understand the mechanisms underlying the obese phenotype observed in these animals at adulthood.", "output": {"entities": {"chemical": [{"text": "cocaine", "start": 116, "end": 123}, {"text": "amphetamine", "start": 128, "end": 139}]}}, "schema": []}
{"input": "On the 2nd postnatal day (P2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6mg/kg/day) or saline for 14days.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 99, "end": 107}, {"text": "NIC", "start": 109, "end": 112}]}}, "schema": []}
{"input": "Offspring were killed in P180 and immunohistochemistry and Western blot analysis were carried out.", "output": {"entities": {}}, "schema": []}
{"input": "Significance data had p < 0. 05.", "output": {"entities": {}}, "schema": []}
{"input": "Adult NIC offspring showed more intense NPY staining in the paraventricular nucleus (PVN) (+ 21%) and increased number of POMC-positive cells in the: arcuate nucleus (+ 33%), as an increase in fiber density of alpha-MSH in PVN (+ 85%).", "output": {"entities": {"chemical": [{"text": "NIC", "start": 6, "end": 9}]}}, "schema": []}
{"input": "However, the number of CART-positive cells was reduced in the PVN (-25%).", "output": {"entities": {}}, "schema": []}
{"input": "CRH staining was more intense in NIC offspring (+ 136%).", "output": {"entities": {"chemical": [{"text": "NIC", "start": 33, "end": 36}]}}, "schema": []}
{"input": "Orexins and AgRP were not altered.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, maternal nicotine exposure changes hypothalamic neuropeptides in the adult progeny that is partially compatible with leptin resistance.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 15, "end": 23}]}}, "schema": []}
{"input": "Modulation of the peroxiredoxin system by cytokines in insulin-producing RINm5F cells: Down-regulation of PRDX6 increases susceptibility of beta cells to oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "Peroxiredoxins are a family of six antioxidant enzymes (PRDX1-6), and may be an alternative system for the pancreatic beta cells to cope with oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigated whether the main diabetogenic pro-inflammatory cytokines or the anti-inflammatory cytokine IL-4 modulate PRDXs levels and putative intracellular pathways important for this process in the insulin-producing RINm5F cells.", "output": {"entities": {}}, "schema": []}
{"input": "RINm5F cells expressed significant amounts of PRDX1, PRDX3 and PRDX6 enzymes.", "output": {"entities": {}}, "schema": []}
{"input": "Only PRDX6 was modulated by cytokines, showing both mRNA and protein down-regulation following incubation of RINm5F cells with TNF-alpha and IFN-gamma but not with IL-1beta.", "output": {"entities": {}}, "schema": []}
{"input": "Separately IFN-gamma or TNF-alpha decreased PRDX6 protein but not mRNA levels.", "output": {"entities": {}}, "schema": []}
{"input": "The blockage of the JNK signalling and of the calpains and proteasome proteolysis systems restored PRDX6 protein levels.", "output": {"entities": {}}, "schema": []}
{"input": "IL-4 alone did not modulate PRDXs levels.", "output": {"entities": {}}, "schema": []}
{"input": "However, pre/co-incubation with IL-4 substantially prevented the decrease in PRDX6 induced by pro-inflammatory cytokines.", "output": {"entities": {}}, "schema": []}
{"input": "Knockdown of PRDX6 increased susceptibility of RINm5F cells to the deleterious effects of pro-inflammatory cytokines and to oxidative stress.", "output": {"entities": {}}, "schema": []}
{"input": "These results show that, from the PRDXs significantly expressed in RINm5F cells, only PRDX6 is modulated by the diabetogenic cytokines IFN-gamma and TNF-alpha.", "output": {"entities": {}}, "schema": []}
{"input": "This PRDX6 down-regulation depends on the calpain and proteasome systems and JNK signalling.", "output": {"entities": {}}, "schema": []}
{"input": "PRDX6 is an important enzyme for protection against oxidative stress and the interaction between pro-and anti-inflammatory cytokines might be important to determine the antioxidant capacity of the cells.", "output": {"entities": {}}, "schema": []}
{"input": "Developmental immunotoxicity in male rats after juvenile exposure to ethanol.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 69, "end": 76}]}}, "schema": []}
{"input": "The aim of the present study was to determine the sensitivity of the developing immune system to ethanol (EtOH) after exposure from postnatal day (PND) 10 onward.", "output": {"entities": {"chemical": [{"text": "ethanol", "start": 97, "end": 104}, {"text": "EtOH", "start": 106, "end": 110}]}}, "schema": []}
{"input": "Adult Wistar dams and litters were exposed to EtOH via drinking water (0, 0. 25, 1. 5, 2. 75, 4, 5. 25, or 6. 5% (w/v) EtOH ad libitum) and drinking water exposure of the F1 was continued from weaning until sacrifice.", "output": {"entities": {"chemical": [{"text": "EtOH", "start": 46, "end": 50}, {"text": "EtOH", "start": 119, "end": 123}]}}, "schema": []}
{"input": "Immune assessments were performed at postnatal days (PNDs) 21, 42, and 70.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, Keyhole Limpet Hemocyanin (KLH) specific immune responses were evaluated following subcutaneous immunizations on PNDs 21 and 35.", "output": {"entities": {}}, "schema": []}
{"input": "EtOH exposure affected innate immune responses, such as LPS-induced NO-production by adherent splenocytes, as well as adaptive immune responses as represented by KLH-specific parameters.", "output": {"entities": {"chemical": [{"text": "EtOH", "start": 0, "end": 4}, {"text": "NO", "start": 68, "end": 70}]}}, "schema": []}
{"input": "The most sensitive developmental parameters included effects on maternal and pup bodyweight with calculated BMDs of 4. 0% and 4. 3% EtOH, respectively.", "output": {"entities": {"chemical": [{"text": "EtOH", "start": 132, "end": 136}]}}, "schema": []}
{"input": "The most sensitive immune parameters were affected at dose levels lower than those affecting developmental parameters and included KLH-specific immune responses, LPS-induced NO production by adherent splenocytes, and IL-10 production by ConA stimulated splenocytes.", "output": {"entities": {"chemical": [{"text": "NO", "start": 174, "end": 176}]}}, "schema": []}
{"input": "Calculated BMDs for these parameters were between 0. 01% and 0. 1% EtOH.", "output": {"entities": {"chemical": [{"text": "EtOH", "start": 67, "end": 71}]}}, "schema": []}
{"input": "A comparison of the results of this juvenile study with an extended one-generation reproductive toxicity study revealed that the juvenile study design may result in a higher sensitivity related to differences in the exposure design.", "output": {"entities": {}}, "schema": []}
{"input": "These findings demonstrate the relative sensitivity of the developing immune system for EtOH exposure, the additional value of assessing functional immune parameters, and the importance of the juvenile window in developmental immunotoxicity testing.", "output": {"entities": {"chemical": [{"text": "EtOH", "start": 88, "end": 92}]}}, "schema": []}
{"input": "Relationship between protein digestibility and allergenicity: Comparisons of pepsin and cathepsin.", "output": {"entities": {}}, "schema": []}
{"input": "An association between protein allergenicity and resistance to pepsin digestion in the gastrointestinal tract has been proposed.", "output": {"entities": {}}, "schema": []}
{"input": "However, although widely accepted, such an association is inconsistent with known labile allergens and resistant non-allergens.", "output": {"entities": {}}, "schema": []}
{"input": "Given the central role of antigen presenting cells, and in particular dendritic cells (DCs), in the development of allergic responses, the stability of allergens to intracellular processing may be more relevant than resistance to extracellular pepsin digestion.", "output": {"entities": {}}, "schema": []}
{"input": "We have characterised the expression by DC of cathepsins (proteolytic enzymes), and compared the proteolytic activity of the most highly expressed cathepsin with pepsin for a range of 9 allergens and 4 putative nonallergens.", "output": {"entities": {}}, "schema": []}
{"input": "Cathepsin expression in bone marrow-derived DC (BM-DC) derived from BALB/c strain mice was characterised by flow cytometry; cathepsins D, E and S were identified, with cathepsin D being the most highly expressed.", "output": {"entities": {}}, "schema": []}
{"input": "Digestion studies revealed that the majority of allergens (5/9) were pepsin resistant, whereas non-allergens (3/4) were labile.", "output": {"entities": {}}, "schema": []}
{"input": "If the generation of pepsin-resistant fragments was considered as a feature of allergenicity, this increased to 7/9 allergens and 4/4 nonallergens.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, most of the proteins examined were resistant to cathepsin digestion, with significant digestion recorded for only 2/9 allergens and 2/4 non-allergens.", "output": {"entities": {}}, "schema": []}
{"input": "Chemical reduction (to mimic intracellular reducing conditions) increased the susceptibility of proteins to digestion by cathepsins, but did not improve discrimination between allergens and nonallergens on this basis.", "output": {"entities": {}}, "schema": []}
{"input": "These data confirm that there is a general relationship between resistance to digestion with pepsin and allergenicity.", "output": {"entities": {}}, "schema": []}
{"input": "The relationship is not absolute, but the information gained from this characteristic does provide useful information in a weight of evidence approach for allergenicity assessment.", "output": {"entities": {}}, "schema": []}
{"input": "The most abundant cathepsin detected in antigen processing BM-DC, cathepsin D, is not an appropriate substitute for pepsin.", "output": {"entities": {}}, "schema": []}
{"input": "The hypothesis that pepsin stability may be a surrogate for stability to digestion within DC may still hold true, but consideration of a single enzyme in this context is possibly an oversimplification.", "output": {"entities": {}}, "schema": []}
{"input": "Structural requirements within protoporphyrin IX in the inhibition of heat shock protein 90.", "output": {"entities": {"chemical": [{"text": "protoporphyrin IX", "start": 31, "end": 48}]}}, "schema": []}
{"input": "Porphyrins are used for photodynamic therapy for their light-absorbing properties, and some of them were approved for the treatment of certain types of cancers.", "output": {"entities": {"chemical": [{"text": "Porphyrins", "start": 0, "end": 10}]}}, "schema": []}
{"input": "Porphyrins prevent activation of hypoxia inducible factor-1 alpha (HIF-1 alpha) by inhibiting heat shock protein 90 (HSP90).", "output": {"entities": {"chemical": [{"text": "Porphyrins", "start": 0, "end": 10}]}}, "schema": []}
{"input": "This study investigated the structural requirements within protoporphyrin IX (PPIX) for the inhibition of HSP90 activity.", "output": {"entities": {"chemical": [{"text": "protoporphyrin IX", "start": 59, "end": 76}, {"text": "PPIX", "start": 78, "end": 82}]}}, "schema": []}
{"input": "In HCT116, HT29 and DLD-1 cells, PPIX treatment directly hindered the binding between HSP90 and HIF-1 alpha; PPIX treatment inhibited the chaperone activity of HSP90, accelerating protein degradation of HIF-1 alpha.", "output": {"entities": {"chemical": [{"text": "PPIX", "start": 33, "end": 37}, {"text": "PPIX", "start": 109, "end": 113}]}}, "schema": []}
{"input": "In addition, PPIX treatment suppressed cancer cell migration, endothelial cell tube formation, and aortic ring sprouting, being consistent with its anti-tumor and anti-angiogenic activities.", "output": {"entities": {"chemical": [{"text": "PPIX", "start": 13, "end": 17}]}}, "schema": []}
{"input": "In silico analysis, molecular docking model indicated that a tetrapyrrole macrocycle and two propionate chains within PPIX are necessary for the binding to the adenosine triphosphate (ATP)-binding pocket of HSP90.", "output": {"entities": {"chemical": [{"text": "tetrapyrrole macrocycle", "start": 61, "end": 84}, {"text": "propionate", "start": 93, "end": 103}, {"text": "PPIX", "start": 118, "end": 122}, {"text": "adenosine triphosphate", "start": 160, "end": 182}, {"text": "ATP", "start": 184, "end": 187}]}}, "schema": []}
{"input": "The predicted structural requirement was verified by the differential inhibitory effects of PPIX analogs, or the precursor of PPIX, on HIF-1 alpha; compounds lacking either the tetrapyrrole macrocycle or the propionate chains were inactive.", "output": {"entities": {"chemical": [{"text": "PPIX", "start": 92, "end": 96}, {"text": "PPIX", "start": 126, "end": 130}, {"text": "tetrapyrrole macrocycle", "start": 177, "end": 200}, {"text": "propionate", "start": 208, "end": 218}]}}, "schema": []}
{"input": "Our results show that a tetrapyrrole macrocycle and two attached propionate chains in PPIX coordinately interact with the ATP-binding pocket of HSP90, offering structural information on the inhibitory effect of porphyrins on angiogenesis.", "output": {"entities": {"chemical": [{"text": "tetrapyrrole macrocycle", "start": 24, "end": 47}, {"text": "propionate", "start": 65, "end": 75}, {"text": "PPIX", "start": 86, "end": 90}, {"text": "ATP", "start": 122, "end": 125}]}}, "schema": []}
{"input": "Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass-Prediction of viscosity through protein-protein interaction measurements.", "output": {"entities": {}}, "schema": []}
{"input": "The purpose of this work was to explore the relation between protein-protein interactions (PPIs) and solution viscosity at high protein concentration using three monoclonal antibodies (mAbs), two of the IgG4 subclass and one of the IgG1 subclass.", "output": {"entities": {}}, "schema": []}
{"input": "A range of methods was used to quantify the PPI either at low concentration (interaction parameter (kD) obtained from dynamic light scattering, DLS) or at high concentration (solution storage modulus (G') from ultrasonic shear rheology).", "output": {"entities": {}}, "schema": []}
{"input": "We also developed a novel method for the determination of PPI using the apparent radius of the protein at either low or high protein concentration determined using DLS.", "output": {"entities": {}}, "schema": []}
{"input": "The PPI measurements were correlated with solution viscosity (measured by DLS using polystyrene nanospheres and ultrasonic shear rheology) as a function of pH (4-9) and ionic strength (10, 50 and 150mM).", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 84, "end": 95}]}}, "schema": []}
{"input": "Our measurements showed that the highest solution viscosity was observed under conditions with the most negative kD, the highest apparent radius and the lowest net charge.", "output": {"entities": {}}, "schema": []}
{"input": "An increase in ionic strength resulted in a change in the nature of the PPI at low pH from repulsive to attractive.", "output": {"entities": {}}, "schema": []}
{"input": "In the neutral to alkaline pH region the mAbs behaved differently with respect to increase in ionic strength.", "output": {"entities": {}}, "schema": []}
{"input": "Two mAbs (A and B) showed little or no effect of increasing ionic strength, whereas mAb-C showed a remarkable decrease in attractive PPI and viscosity.", "output": {"entities": {}}, "schema": []}
{"input": "Previous studies have mainly investigated mAbs of the IgG1 and IgG2 subclass.", "output": {"entities": {}}, "schema": []}
{"input": "We show here, for the first time, that mAbs of the IgG4 subclass behave similar as the other subclasses.", "output": {"entities": {}}, "schema": []}
{"input": "By comparison of the three tested mAbs with mAbs investigated in other studies a clear linear trend emerges between the pH of strongest attractive PPI and highest solution viscosity.", "output": {"entities": {}}, "schema": []}
{"input": "The determination of PPI using either kD or apparent radius is thus a useful prediction tool in the determination of solution conditions that favors low solution viscosity at high protein concentration of therapeutically used mAb molecules.", "output": {"entities": {}}, "schema": []}
{"input": "The novel methodology using apparent radius is a simple and rapid alternative to determine relative PPI directly under formulation conditions.", "output": {"entities": {}}, "schema": []}
{"input": "The method can potentially serve as a high-throughput screening tool in formulation development.", "output": {"entities": {}}, "schema": []}
{"input": "Pullulan-based nanoparticles as carriers for transmucosal protein delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability.", "output": {"entities": {}}, "schema": []}
{"input": "In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up.", "output": {"entities": {}}, "schema": []}
{"input": "In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation.", "output": {"entities": {}}, "schema": []}
{"input": "As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge.", "output": {"entities": {}}, "schema": []}
{"input": "These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers.", "output": {"entities": {}}, "schema": []}
{"input": "Positively charged nanoparticles of 180-270nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein.", "output": {"entities": {}}, "schema": []}
{"input": "In PBS pH 7. 4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants.", "output": {"entities": {}}, "schema": []}
{"input": "A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT.", "output": {"entities": {"chemical": [{"text": "MTT", "start": 118, "end": 121}]}}, "schema": []}
{"input": "Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3).", "output": {"entities": {}}, "schema": []}
{"input": "Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Liberation of drugs from multi-wall carbon nanotube carriers.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 36, "end": 42}]}}, "schema": []}
{"input": "MWCNTs in the' nanotube-drug' hybrids can play a role of carriers or additives (enhancers) in the more complex formulations.", "output": {"entities": {}}, "schema": []}
{"input": "This work reviews qualitative and quantitative analyses of Drug Delivery Systems (DDSs) based on multi-wall carbon nanotubes (MWCNTs) and their chemically modified analogues (mainly oxidised MWCNTs).", "output": {"entities": {"chemical": [{"text": "carbon", "start": 108, "end": 114}]}}, "schema": []}
{"input": "A special emphasis was placed on the chemical interactions between drug molecules and the nanotube carrier critical both in the stage of preparation/synthesis of the hybrids and liberation of the drug.", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative damage induced by chlorpyrifos in the hepatic and renal tissue of Kunming mice and the antioxidant role of vitamin E.", "output": {"entities": {"chemical": [{"text": "chlorpyrifos", "start": 28, "end": 40}, {"text": "vitamin E", "start": 117, "end": 126}]}}, "schema": []}
{"input": "Chlorpyrifos is a broad-spectrum, chlorinated organophosphate pesticide employed for pest control in various agricultural and animal husbandries.", "output": {"entities": {"chemical": [{"text": "Chlorpyrifos", "start": 0, "end": 12}, {"text": "chlorinated organophosphate", "start": 34, "end": 61}]}}, "schema": []}
{"input": "Acute and chronic exposure to CPF can elicit several adverse effects, including oxidative stress.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 30, "end": 33}]}}, "schema": []}
{"input": "We investigated neurotoxicity of CPF-treated mice, and evaluated the antioxidant effect of vitamin E against oxidative stress and histological changes in the livers and kidneys of CPF-treated mice.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 33, "end": 36}, {"text": "vitamin E", "start": 91, "end": 100}, {"text": "CPF", "start": 180, "end": 183}]}}, "schema": []}
{"input": "Kunming mice were divided randomly into five exposure groups of six: (A) peanut oil; (B) 3mg/kg CPF; (C) 6mg/kg CPF; (D) 12mg/kg CPF; (E) vitamin E (100mg/kg), 3h after administration of CPF (12mg/kg) and used as a post-treatment group.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 96, "end": 99}, {"text": "CPF", "start": 112, "end": 115}, {"text": "CPF", "start": 129, "end": 132}, {"text": "vitamin E", "start": 138, "end": 147}, {"text": "CPF", "start": 187, "end": 190}]}}, "schema": []}
{"input": "Oral administration of high-dose groups (12mg/kg) CPF led to a significant increase in levels of reactive oxygen species, DNA-protein crosslinks, 8-hydroxy-2-deoxyguanosine and malondialdehyde, decreases in acetylcholinesterase activity and glutathione level, as well as causing hepatic and renal histopathological change.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 50, "end": 53}, {"text": "oxygen", "start": 106, "end": 112}, {"text": "8-hydroxy-2-deoxyguanosine", "start": 146, "end": 172}, {"text": "malondialdehyde", "start": 177, "end": 192}, {"text": "glutathione", "start": 241, "end": 252}]}}, "schema": []}
{"input": "Except for AChE activity levels, administration of vitamin E to CPF-treated mice restored these biochemical parameters to within normal levels, and resulted in overall improvement in damage to livers and kidneys.", "output": {"entities": {"chemical": [{"text": "vitamin E", "start": 51, "end": 60}, {"text": "CPF", "start": 64, "end": 67}]}}, "schema": []}
{"input": "These data suggest that oxidative stress is involved in CPF-induced toxicity and that vitamin E can protect against the tissue damage induced by CPF.", "output": {"entities": {"chemical": [{"text": "CPF", "start": 56, "end": 59}, {"text": "vitamin E", "start": 86, "end": 95}, {"text": "CPF", "start": 145, "end": 148}]}}, "schema": []}
{"input": "Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3.", "output": {"entities": {}}, "schema": []}
{"input": "From birth, the vault of the skull grows at a prodigious rate, driven by the activity of osteoblastic cells at the fibrous joints (sutures) that separate the bony calvarial plates.", "output": {"entities": {}}, "schema": []}
{"input": "One in 2500 children is born with a medical condition known as craniosynostosis because of premature bony fusion of the calvarial plates and a cessation of bone growth at the sutures.", "output": {"entities": {}}, "schema": []}
{"input": "Bone morphogenetic proteins (BMPs) are potent growth factors that promote bone formation.", "output": {"entities": {}}, "schema": []}
{"input": "Previously, we found that Glypican-1 (GPC1) and Glypican-3 (GPC3) are expressed in cranial sutures and are decreased during premature suture fusion in children.", "output": {"entities": {}}, "schema": []}
{"input": "Although glypicans are known to regulate BMP signalling, a mechanistic link between GPC1, GPC3 and BMPs and osteogenesis has not yet been investigated.", "output": {"entities": {}}, "schema": []}
{"input": "We now report that human primary suture mesenchymal cells coexpress GPC1 and GPC3 on the cell surface and release them into the media.", "output": {"entities": {}}, "schema": []}
{"input": "We show that they inhibit BMP2, BMP4 and BMP7 activities, which both physically interact with BMP2 and that immunoblockade of endogenous GPC1 and GPC3 potentiates BMP2 activity.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, increased levels of GPC1 and GPC3 as a result of overexpression or the addition of recombinant protein, inhibit BMP2 signalling and BMP2-mediated osteogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that BMP signalling in suture mesenchymal cells is mediated by both SMAD-dependent and SMAD-independent pathways and that GPC1 and GPC3 inhibit both pathways.", "output": {"entities": {}}, "schema": []}
{"input": "GPC3 inhibition of BMP2 activity is independent of attachment of the glypican on the cell surface and post-translational glycanation, and thus appears to be mediated by the core glypican protein.", "output": {"entities": {}}, "schema": []}
{"input": "The discovery that GPC1 and GPC3 regulate BMP2-mediated osteogenesis, and that inhibition of endogenous GPC1 and GPC3 potentiates BMP2 responsiveness of human suture mesenchymal cells, indicates how downregulation of glypican expression could lead to the bony suture fusion that characterizes craniosynostosis.", "output": {"entities": {}}, "schema": []}
{"input": "Method for fabrication and verification of conjugated nanoparticle-antibody tuning elements for multiplexed electrochemical biosensors.", "output": {"entities": {}}, "schema": []}
{"input": "There is a critical need for more accurate, highly sensitive and specific assay for disease diagnosis and management.", "output": {"entities": {}}, "schema": []}
{"input": "A novel, multiplexed, single sensor using rapid and label free electrochemical impedance spectroscopy tuning method has been developed.", "output": {"entities": {}}, "schema": []}
{"input": "The key challenges while monitoring multiple targets is frequency overlap.", "output": {"entities": {}}, "schema": []}
{"input": "Here we describe the methods to circumvent the overlap, tune by use of nanoparticle (NP) and discuss the various fabrication and characterization methods to develop this technique.", "output": {"entities": {}}, "schema": []}
{"input": "First sensors were fabricated using printed circuit board (PCB) technology and nickel and gold layers were electrodeposited onto the PCB sensors.", "output": {"entities": {"chemical": [{"text": "nickel", "start": 79, "end": 85}]}}, "schema": []}
{"input": "An off-chip conjugation of gold NP' s to molecular recognition elements (with verification technique) is described as well.", "output": {"entities": {}}, "schema": []}
{"input": "A standard covalent immobilization of the molecular recognition elements is also discussed with quality control techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Finally use and verification of sensitivity and specificity is also presented.", "output": {"entities": {}}, "schema": []}
{"input": "By use of gold NP' s of various sizes, we have demonstrated the possibility and shown little loss of sensitivity and specificity in the molecular recognition of inflammatory markers as \" model \" targets for our tuning system.", "output": {"entities": {}}, "schema": []}
{"input": "By selection of other sized NP' s or NP' s of various materials, the tuning effect can be further exploited.", "output": {"entities": {}}, "schema": []}
{"input": "The novel platform technology developed could be utilized in critical care, clinical management and at home health and disease management.", "output": {"entities": {}}, "schema": []}
{"input": "Growth and potential damage of human bone-derived cells on fresh and aged fullerene c60 films.", "output": {"entities": {"chemical": [{"text": "fullerene c60", "start": 74, "end": 87}]}}, "schema": []}
{"input": "Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure.", "output": {"entities": {"chemical": [{"text": "Fullerenes", "start": 0, "end": 10}, {"text": "carbon", "start": 41, "end": 47}]}}, "schema": []}
{"input": "Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis.", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 61, "end": 70}]}}, "schema": []}
{"input": "On the other hand, fullerenes are not only able to quench, but also to generate harmful reactive oxygen species.", "output": {"entities": {"chemical": [{"text": "fullerenes", "start": 19, "end": 29}, {"text": "oxygen", "start": 97, "end": 103}]}}, "schema": []}
{"input": "The reactivity of fullerenes may change in time due to the oxidation and polymerization of fullerenes in an air atmosphere.", "output": {"entities": {"chemical": [{"text": "fullerenes", "start": 18, "end": 28}, {"text": "fullerenes", "start": 91, "end": 101}]}}, "schema": []}
{"input": "In this study, we therefore tested the dependence between the age of fullerene films (from one week to one year) and the proliferation, viability and metabolic activity of human osteosarcoma cells (lines MG-63 and U-2 OS).", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 69, "end": 78}]}}, "schema": []}
{"input": "We also monitored potential membrane and DNA damage and morphological changes of the cells.", "output": {"entities": {}}, "schema": []}
{"input": "After seven days of cultivation, we did not observe any cytotoxic morphological changes, such as enlarged cells or cytosolic vacuole formation.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, there was no increased level of DNA damage.", "output": {"entities": {}}, "schema": []}
{"input": "The increasing age of the fullerene films did not cause enhancement of cytotoxicity.", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 26, "end": 35}]}}, "schema": []}
{"input": "On the contrary, it resulted in an improvement in the properties of these materials, which are more suitable for cell cultivation.", "output": {"entities": {}}, "schema": []}
{"input": "Therefore, fullerene films could be considered as a promising material with potential use as a bioactive coating of cell carriers for bone tissue engineering.", "output": {"entities": {"chemical": [{"text": "fullerene", "start": 11, "end": 20}]}}, "schema": []}
{"input": "Excitation and Adaptation in Bacteria-a Model Signal Transduction System that Controls Taxis and Spatial Pattern Formation.", "output": {"entities": {}}, "schema": []}
{"input": "The machinery for transduction of chemotactic stimuli in the bacterium E. coli is one of the most completely characterized signal transduction systems, and because of its relative simplicity, quantitative analysis of this system is possible.", "output": {"entities": {}}, "schema": []}
{"input": "Here we discuss models which reproduce many of the important behaviors of the system.", "output": {"entities": {}}, "schema": []}
{"input": "The important characteristics of the signal transduction system are excitation and adaptation, and the latter implies that the transduction system can function as a \" derivative sensor \" with respect to the ligand concentration in that the DC component of a signal is ultimately ignored if it is not too large.", "output": {"entities": {}}, "schema": []}
{"input": "This temporal sensing mechanism provides the bacterium with a memory of its passage through spatially-or temporally-varying signal fields, and adaptation is essential for successful chemotaxis.", "output": {"entities": {}}, "schema": []}
{"input": "We also discuss some of the spatial patterns observed in populations and indicate how cell-level behavior can be embedded in population-level descriptions.", "output": {"entities": {}}, "schema": []}
{"input": "High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 24, "end": 37}]}}, "schema": []}
{"input": "RATIONALE: Nicotinic acetylcholine receptors (nAChRs) are a critical component of the cholinergic system of neurotransmission in the brain that modulates important physiological processes such as reward, cognition, and mood.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 21, "end": 34}]}}, "schema": []}
{"input": "Abnormalities in this system are accordingly implicated in multiple psychiatric illnesses, including addiction, schizophrenia, and mood disorders.", "output": {"entities": {}}, "schema": []}
{"input": "There is significantly increased tobacco use, and therefore nicotine intake, in patient populations, and pharmacological agents that act on various nicotinic receptor subtypes ameliorate clinical features of these disorders.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 60, "end": 68}]}}, "schema": []}
{"input": "Better understanding of the molecular mechanisms underlying cholinergic dysfunction in psychiatric disease will permit more targeted design of novel therapeutic agents.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The objective of this review is to describe the multiple cellular pathways through which chronic nicotine exposure regulates nAChR expression, and to juxtapose these mechanisms with evidence for altered expression of high-affinity nAChRs in human psychiatric illness.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 106, "end": 114}]}}, "schema": []}
{"input": "Here, we summarize multiple studies from pre-clinical animal models to human in vivo imaging and post-mortem experiments demonstrating changes in nAChR regulation and expression in psychiatric illness.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: We conclude that a mechanistic explanation of nAChR abnormalities in psychiatric illness will arise from a fuller understanding of normal nAChR trafficking, along with the detailed study of human tissue, perhaps using novel biotechnological advances, such as induced pluripotent stem cells.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperphosphataemia: Treatment Options.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperphosphataemia can be induced by three main conditions: a massive acute phosphate load, a primary increase in renal phosphate reabsorption, and an impaired renal phosphate excretion due to acute or chronic renal insufficiency.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 76, "end": 85}, {"text": "phosphate", "start": 120, "end": 129}, {"text": "phosphate", "start": 166, "end": 175}]}}, "schema": []}
{"input": "Renal excretion is so efficient in normal subjects that balance can be maintained with only a minimal rise in serum phosphorus concentration even for a large phosphorus load.", "output": {"entities": {"chemical": [{"text": "phosphorus", "start": 116, "end": 126}, {"text": "phosphorus", "start": 158, "end": 168}]}}, "schema": []}
{"input": "Therefore, acute hyperphosphataemia usually resolves within few hours if renal function is intact.", "output": {"entities": {}}, "schema": []}
{"input": "The most frequent cause of chronic hyperphosphataemia is chronic renal failure.", "output": {"entities": {}}, "schema": []}
{"input": "Hyperphosphataemia in chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality.", "output": {"entities": {}}, "schema": []}
{"input": "Lowering the phosphate load and maintaining serum phosphorus levels within the normal range are considered important therapeutic goals to improve clinical outcomes in CKD patients.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 13, "end": 22}, {"text": "phosphorus", "start": 50, "end": 60}]}}, "schema": []}
{"input": "Treatment consists of diminishing intestinal phosphate absorption by a low phosphate diet and phosphate binders.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 45, "end": 54}, {"text": "phosphate", "start": 75, "end": 84}, {"text": "phosphate", "start": 94, "end": 103}]}}, "schema": []}
{"input": "In CKD patients on dialysis an efficient dialysis removal of phosphate should be ensured.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 61, "end": 70}]}}, "schema": []}
{"input": "Dietary restriction of phosphorus while maintaining adequate protein intake is not sufficient to control serum phosphate levels in most CKD patients; therefore, the prescription of a phosphate binder is required.", "output": {"entities": {"chemical": [{"text": "phosphorus", "start": 23, "end": 33}, {"text": "phosphate", "start": 111, "end": 120}, {"text": "phosphate", "start": 183, "end": 192}]}}, "schema": []}
{"input": "Aluminium-containing agents are efficient but no longer widely used because of their toxicity.", "output": {"entities": {"chemical": [{"text": "Aluminium", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Calcium-based salts are inexpensive, effective and most widely used, but there is now concern about their association with hypercalcaemia, parathyroid gland suppression, adynamic bone disease, and vascular and extraosseous calcification.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 0, "end": 7}]}}, "schema": []}
{"input": "The average daily dose of calcium acetate or carbonate prescribed in the randomised controlled trials to control hyperphosphataemia in dialysis patients ranges between 1. 2 and 2. 3 g of elemental calcium.", "output": {"entities": {"chemical": [{"text": "calcium acetate or carbonate", "start": 26, "end": 54}, {"text": "calcium", "start": 197, "end": 204}]}}, "schema": []}
{"input": "Such doses are greater than the recommended dietary calcium intake and can lead to a positive calcium balance.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 52, "end": 59}, {"text": "calcium", "start": 94, "end": 101}]}}, "schema": []}
{"input": "Although large amounts of calcium salts should probably be avoided, modest doses (< 1 g of elemental calcium) may represent a reasonable initial approach to reduced serum phosphorus levels.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 26, "end": 33}, {"text": "calcium", "start": 101, "end": 108}]}}, "schema": []}
{"input": "A non-calcium-based binder can then be added when large doses of binder are required.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 6, "end": 13}]}}, "schema": []}
{"input": "At present, there are three types of non-calcium-based phosphate binders available: sevelamer, lanthanum carbonate and magnesium salts.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 41, "end": 48}, {"text": "sevelamer", "start": 84, "end": 93}, {"text": "lanthanum carbonate", "start": 95, "end": 114}, {"text": "magnesium", "start": 119, "end": 128}]}}, "schema": []}
{"input": "Each of these compounds is as effective as calcium salts in lowering serum phosphorus levels depending on an adequate prescribed dose and adherence of the patient to treatment.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 43, "end": 50}, {"text": "phosphorus", "start": 75, "end": 85}]}}, "schema": []}
{"input": "Sevelamer is the only non-calcium-containing phosphate binder that does not have potential for systemic accumulation and presents pleiotropic effects that may impact on cardiovascular disease.", "output": {"entities": {"chemical": [{"text": "Sevelamer", "start": 0, "end": 9}, {"text": "calcium", "start": 26, "end": 33}, {"text": "phosphate", "start": 45, "end": 54}]}}, "schema": []}
{"input": "In contrast, lanthanum carbonate and magnesium salts are absorbed in the gut and their route of excretion is biliary for lanthanum and urinary for magnesium.", "output": {"entities": {"chemical": [{"text": "lanthanum carbonate", "start": 13, "end": 32}, {"text": "magnesium", "start": 37, "end": 46}, {"text": "lanthanum", "start": 121, "end": 130}, {"text": "magnesium", "start": 147, "end": 156}]}}, "schema": []}
{"input": "There are insufficient data to establish the comparative superiority of non-calcium binding agents over calcium salts for such important patient-level outcomes as all-cause mortality and cardiovascular end points.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 76, "end": 83}, {"text": "calcium", "start": 104, "end": 111}]}}, "schema": []}
{"input": "Moreover, full adoption of sevelamer and lanthanum by government drug reimbursement agencies in place of calcium salts would lead to a large increase in health-care expenditure.", "output": {"entities": {"chemical": [{"text": "sevelamer", "start": 27, "end": 36}, {"text": "lanthanum", "start": 41, "end": 50}, {"text": "calcium", "start": 105, "end": 112}]}}, "schema": []}
{"input": "Therefore, the choice of phosphate binder should be individualised, considering the clinical context, the costs, and the individual tolerability the concomitant effects on other parameters of mineral metabolism, such as serum calcium and parathyroid hormone, besides those on serum phosphorus.", "output": {"entities": {"chemical": [{"text": "phosphate", "start": 25, "end": 34}, {"text": "calcium", "start": 226, "end": 233}, {"text": "phosphorus", "start": 282, "end": 292}]}}, "schema": []}
{"input": "Solvated protein-DNA docking using HADDOCK.", "output": {"entities": {}}, "schema": []}
{"input": "Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition.", "output": {"entities": {}}, "schema": []}
{"input": "Yet they have been mostly neglected in the computational modeling of these complexes.", "output": {"entities": {}}, "schema": []}
{"input": "We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein-DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein-DNA complexes containing crystallographically-determined water molecules at their interfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Solvated docking leads to an overall improvement in the quality of the generated protein-DNA models for cases with limited conformational change of the partners upon complex formation.", "output": {"entities": {}}, "schema": []}
{"input": "The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints.", "output": {"entities": {}}, "schema": []}
{"input": "As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein-DNA complexes.", "output": {"entities": {}}, "schema": []}
{"input": "The Cost-Effectiveness of Oral Direct Factor Xa Inhibitors Compared with Low-Molecular-Weight Heparin for the Prevention of Venous Thromboembolism Prophylaxis in Total Hip or Knee Replacement Surgery.", "output": {"entities": {}}, "schema": []}
{"input": "INTRODUCTION: Major orthopedic surgery is associated with a high risk of venous thromboembolism (VTE).", "output": {"entities": {}}, "schema": []}
{"input": "Anticoagulants are recommended to prevent VTE, and recently an oral direct factor Xa inhibitor (FXaI) was approved for this indication.", "output": {"entities": {}}, "schema": []}
{"input": "We compared the cost-effectiveness of FXaIs with low-molecular-weight heparin (LMWH) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery.", "output": {"entities": {}}, "schema": []}
{"input": "DESIGN: A decision-tree model was developed to compare the cost-effectiveness of oral direct FXaIs (rivaroxaban, apixaban, and edoxaban) to subcutaneous LMWHs (enoxaparin and dalteparin), with separate models for THR and TKR.", "output": {"entities": {"chemical": [{"text": "rivaroxaban", "start": 100, "end": 111}, {"text": "apixaban", "start": 113, "end": 121}, {"text": "edoxaban", "start": 127, "end": 135}]}}, "schema": []}
{"input": "The analysis was conducted over a 180-day postoperative time horizon from the U. S.", "output": {"entities": {}}, "schema": []}
{"input": "Medicare perspective.", "output": {"entities": {}}, "schema": []}
{"input": "The model was developed using TreeAge Pro 2011 (TreeAge Software Inc., Williamstown, MA, USA).", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: Efficacy and safety data (probabilities of distal and proximal deep vein thrombosis, symptomatic pulmonary embolism, and major bleeding) were derived from a systematic review and meta-analysis of phase II and III clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "Costs and quality-adjusted life-years (QALYs) are reported.", "output": {"entities": {}}, "schema": []}
{"input": "One-way and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: In the THR model, the average costs per patient for FXaIs and LMWHs were $18, 762 and $18, 897, respectively, and the QALYs were 0. 938 and 0. 932.", "output": {"entities": {}}, "schema": []}
{"input": "In the TKR model, the average cost per patient for FXaIs and LMWHs were $18, 804 and $18, 991, respectively, and the QALYs were 0. 935 and 0. 931.", "output": {"entities": {}}, "schema": []}
{"input": "In both models, FXaIs dominated LMWH (less costly and more efficacious).", "output": {"entities": {}}, "schema": []}
{"input": "Neither model was sensitive to changes in any of the variables in the one-way sensitivity analyses.", "output": {"entities": {}}, "schema": []}
{"input": "Probabilistic sensitivity analysis indicated that FXaIs were cost-effective in more than 99% of iterations in the THR population and in 98% of iterations in the TKR population assuming a willingness-to-pay threshold of $50, 000/QALY.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: Oral direct FXaIs may be an economically dominant strategy compared with LMWHs for VTE prophylaxis in patients undergoing either THR or TKR surgery.", "output": {"entities": {}}, "schema": []}
{"input": "Psychologic Disorders and Statin Use: A Propensity Score-Matched Analysis.", "output": {"entities": {}}, "schema": []}
{"input": "STUDY OBJECTIVE: To evaluate the association between statin therapy and the risk of psychologic disorders including schizophrenia, psychosis, major depression, and bipolar disorder in a military population.", "output": {"entities": {}}, "schema": []}
{"input": "DESIGN: Retrospective, observational, population-based, propensity score-matched, cohort study.", "output": {"entities": {}}, "schema": []}
{"input": "SETTING: Database of a patient population enrolled in the San Antonio Military Multi-Market Area as Tricare Prime or Plus.", "output": {"entities": {}}, "schema": []}
{"input": "PATIENTS: Medical records were reviewed from 46, 249 patients aged 30-85 years who were continuously enrolled in the San Antonio Military Multi-Market Area as Tricare Prime or Plus from October 1, 2003-March 1, 2010.", "output": {"entities": {}}, "schema": []}
{"input": "Data were obtained from the Military Health System Management Analysis and Reporting Tool (M2).", "output": {"entities": {}}, "schema": []}
{"input": "Based on drug fills during fiscal year 2005, patients were stratified as statin users (13, 626 patients received at least 90-days supply of statin) or nonusers (32, 623 patients never received a statin during the study period).", "output": {"entities": {}}, "schema": []}
{"input": "A propensity score-matched cohort of 6972 statin users and 6972 nonusers from this population was created.", "output": {"entities": {}}, "schema": []}
{"input": "MEASUREMENTS AND MAIN RESULTS: The occurrence of psychologic disorders between October 1, 2005, and March 1, 2010, was determined using prespecified groups of ICD-9-CM, Psych1: schizophrenia, schizoaffective disorders, and other psychosis; Psych2: major depression and bipolar disorder; Psych3: all psychologic disorders as identified by the Agency for Health Research and Quality-Clinical Classifications (except for categories of childhood or developmental psychiatric disorders).", "output": {"entities": {}}, "schema": []}
{"input": "Between matched pairs of statin users and nonusers, the odds ratios and 95% confidence intervals were as follows: Psych1 (0. 9, 0. 75-1. 05), Psych2 (1. 02, 0. 94-1. 11), and Psych3 (1. 02, 0. 96-1. 1), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: The risk of developing psychologic disorders was similar in this cohort of propensity score-matched statin users and nonusers.", "output": {"entities": {}}, "schema": []}
{"input": "Exciton Dynamics in Semiconductor Nanocrystals.", "output": {"entities": {}}, "schema": []}
{"input": "This review article provides an overview of recent advances in the study and understanding of dynamics of excitons in semiconductor nanocrystals (NCs) or quantum dots (QDs).", "output": {"entities": {}}, "schema": []}
{"input": "Emphasis is placed on the relationship between exciton dynamics and optical properties, both linear and nonlinear.", "output": {"entities": {}}, "schema": []}
{"input": "We also focus on the unique aspects of exciton dynamics in semiconductor NCs as compared to those in bulk crystals.", "output": {"entities": {}}, "schema": []}
{"input": "Various experimental techniques for probing exciton dynamics, particularly time-resolved laser methods, are reviewed.", "output": {"entities": {}}, "schema": []}
{"input": "Relevant models and computational studies are also briefly presented.", "output": {"entities": {}}, "schema": []}
{"input": "By comparing different materials systems, a unifying picture is proposed to account for the major dynamic features of excitons in semiconductor QDs.", "output": {"entities": {}}, "schema": []}
{"input": "While the specific dynamic processes involved are material-dependent, key processes can be identified for all the materials that include electronic dephasing, intraband relaxation, trapping, and interband recombination of free and trapped charge carriers (electron and hole).", "output": {"entities": {}}, "schema": []}
{"input": "Exciton dynamics play a critical role in the fundamental properties and functionalities of nanomaterials of interest for a variety of applications including optical detectors, solar energy conversion, lasers, and sensors.", "output": {"entities": {}}, "schema": []}
{"input": "A better understanding of exciton dynamics in nanomaterials is thus important both fundamentally and technologically.", "output": {"entities": {}}, "schema": []}
{"input": "Mechanistic Aspects of hSOD1 Maturation from the Solution Structure of Cu (I)-Loaded hCCS Domain 1 and Analysis of Disulfide-Free hSOD1 Mutants.", "output": {"entities": {"chemical": [{"text": "Cu (I)", "start": 71, "end": 77}, {"text": "Disulfide", "start": 115, "end": 124}]}}, "schema": []}
{"input": "Superoxide dismutase 1 (SOD1) maturation within the cell is mainly accomplished with the SOD1-specific chaperone, CCS, a dimeric protein with three distinct domains in each monomer.", "output": {"entities": {"chemical": [{"text": "Superoxide", "start": 0, "end": 10}]}}, "schema": []}
{"input": "We recently showed that the first domain of human CCS (hCCSD1) is responsible for copper transfer to its protein partner, human SOD1 (hSOD1).", "output": {"entities": {"chemical": [{"text": "copper", "start": 82, "end": 88}]}}, "schema": []}
{"input": "The NMR solution structure of the copper (I)-loaded form of hCCSD1 reported here contributes further to characterization of the copper-transfer mechanism to hSOD1.", "output": {"entities": {"chemical": [{"text": "copper (I)", "start": 34, "end": 44}]}}, "schema": []}
{"input": "NMR spectroscopy was also used to examine the hSOD1 mutants C57A, C146A, and C57A/C146A, which are unable to form the structurally conserved disulfide bond in SOD1, in order to investigate the role of these cysteines during hSOD1 copper acquisition.", "output": {"entities": {"chemical": [{"text": "disulfide", "start": 141, "end": 150}, {"text": "cysteines", "start": 207, "end": 216}]}}, "schema": []}
{"input": "Together, the information on both hCCS and hSOD1, along with a sequence analysis of eukaryotic CCSD1, allows us to propose important mechanistic aspects regarding the copper-transfer process from hCCS to hSOD1.", "output": {"entities": {"chemical": [{"text": "copper", "start": 167, "end": 173}]}}, "schema": []}
{"input": "Metoprolol and diltiazem ameliorate ziprasidone-induced prolonged corrected QT interval in rats.", "output": {"entities": {"chemical": [{"text": "Metoprolol", "start": 0, "end": 10}, {"text": "diltiazem", "start": 15, "end": 24}, {"text": "ziprasidone", "start": 36, "end": 47}]}}, "schema": []}
{"input": "Ziprasidone, an atypical antipsychotic agent, has been shown to increase the corrected QT (QTc) interval in some patients.", "output": {"entities": {"chemical": [{"text": "Ziprasidone", "start": 0, "end": 11}]}}, "schema": []}
{"input": "The aim of this study was to reveal the effects of metoprolol and diltiazem on ziprasidone drug-induced prolonged QTc interval.", "output": {"entities": {"chemical": [{"text": "metoprolol", "start": 51, "end": 61}, {"text": "diltiazem", "start": 66, "end": 75}, {"text": "ziprasidone", "start": 79, "end": 90}]}}, "schema": []}
{"input": "A total of 24 rats were equally divided into the following four groups: the first group was used as the control and received 1 mL/kg saline; 3 mg/kg ziprasidone and saline were administered to the second group; 3 mg/kg ziprasidone and 1 mg/kg metoprolol were administered to the third group and 3 mg/kg ziprasidone and 2 mg/kg diltiazem were administered to the fourth group.", "output": {"entities": {"chemical": [{"text": "ziprasidone", "start": 149, "end": 160}, {"text": "ziprasidone", "start": 219, "end": 230}, {"text": "metoprolol", "start": 243, "end": 253}, {"text": "ziprasidone", "start": 303, "end": 314}, {"text": "diltiazem", "start": 327, "end": 336}]}}, "schema": []}
{"input": "Two hours following application of the drugs, the QTc was calculated by performing electrocardiography in derivation (D) I.", "output": {"entities": {}}, "schema": []}
{"input": "The duration of QTc interval was compared among the four groups.", "output": {"entities": {}}, "schema": []}
{"input": "The mean QTc intervals were significantly increased in the third and fourth groups compared with the second group (p < 0. 0005 and p < 0. 0001, respectively).", "output": {"entities": {}}, "schema": []}
{"input": "The study demonstrated the effectiveness of metoprolol and diltiazem in the prevention of ziprasidone-induced elongation in the QTc interval.", "output": {"entities": {"chemical": [{"text": "metoprolol", "start": 44, "end": 54}, {"text": "diltiazem", "start": 59, "end": 68}, {"text": "ziprasidone", "start": 90, "end": 101}]}}, "schema": []}
{"input": "Both metoprolol and diltiazem may be considered in the prophylactic therapy of high-risk patients who are using ziprasidone.", "output": {"entities": {"chemical": [{"text": "metoprolol", "start": 5, "end": 15}, {"text": "diltiazem", "start": 20, "end": 29}, {"text": "ziprasidone", "start": 112, "end": 123}]}}, "schema": []}
{"input": "Store-operated Ca2 + Entry (SOCE) Induced by Protease-activated Receptor-1 mediates STIM1 Phosphorylation to inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38beta Mitogen-activated Protein Kinase.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 15, "end": 20}, {"text": "AMP", "start": 151, "end": 154}]}}, "schema": []}
{"input": "The Ca2 + sensor STIM1 is crucial for activation of store-operated Ca2 + entry (SOCE) through TRPC and Orai channels.", "output": {"entities": {"chemical": [{"text": "Ca2 +", "start": 4, "end": 9}, {"text": "Ca2 +", "start": 67, "end": 72}]}}, "schema": []}
{"input": "STIM1 phosphorylation serves as an off-switch for SOCE.", "output": {"entities": {}}, "schema": []}
{"input": "However, the signaling pathway for STIM1 phosphorylation is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "Here we show that SOCE activates AMP-activated protein kinase (AMPK); its effector p38 beta mitogen-activated protein kinase (p38 beta MAPK) phosphorylates STIM1, thus inhibiting SOCE in human lung microvascular endothelial cells (ECs).", "output": {"entities": {"chemical": [{"text": "AMP", "start": 33, "end": 36}]}}, "schema": []}
{"input": "Activation of AMPK using AICAR resulted in STIM1 phosphorylation on serine residues and prevented PAR-1-induced Ca2 + entry.", "output": {"entities": {"chemical": [{"text": "AICAR", "start": 25, "end": 30}, {"text": "serine", "start": 68, "end": 74}, {"text": "Ca2 +", "start": 112, "end": 117}]}}, "schema": []}
{"input": "Further, AICAR pretreatment blocked PAR-1-induced increase in permeability of mouse-lung microvessels.", "output": {"entities": {"chemical": [{"text": "AICAR", "start": 9, "end": 14}]}}, "schema": []}
{"input": "Activation of SOCE with thrombin caused phosphorylation of isoform alpha 1, but not alpha 2 of the AMPK catalytic subunit.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, knockdown of AMPK alpha 1 augmented SOCE induced by thrombin.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, SB203580, a selective inhibitor of p38 MAPK, blocked STIM1 phosphorylation and led to sustained STIM1-puncta formation and Ca2 + entry.", "output": {"entities": {"chemical": [{"text": "SB203580", "start": 15, "end": 23}, {"text": "Ca2 +", "start": 138, "end": 143}]}}, "schema": []}
{"input": "Of the three p38 MAPK isoforms expressed in ECs, p38 beta knockdown prevented PAR-1-mediated STIM1 phosphorylation and potentiated SOCE.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, inhibition of the SOCE downstream target CaMKK beta or knockdown of AMPK alpha 1 suppressed PAR-1-mediated phosphorylation of p38 beta and hence STIM1.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, our findings demonstrate that SOCE activates CaMKK beta-AMPK alpha 1-p38 beta MAPK signaling to phosphorylate STIM1, thereby suppressing endothelial SOCE and permeability responses.", "output": {"entities": {}}, "schema": []}
{"input": "Novel pentablock copolymer (PLA-PCL-PEG-PCL-PLA) based nanoparticles for controlled drug delivery: Effect of copolymer compositions on the crystallinity of copolymers and in vitro drug release profile from nanoparticles.", "output": {"entities": {"chemical": [{"text": "PLA", "start": 28, "end": 31}, {"text": "PCL", "start": 32, "end": 35}, {"text": "PEG", "start": 36, "end": 39}, {"text": "PCL", "start": 40, "end": 43}, {"text": "PLA", "start": 44, "end": 47}]}}, "schema": []}
{"input": "The purpose of this investigation was to design novel pentablock copolymers (polylatide-polycaprolactone-polyethylene glycol-polycaprolactone-polylatide) (PLA-PCL-PEG-PCL-PLA) to prepare nanoparticle formulations which provide continuous delivery of steroids over a longer duration with minimal burst effect.", "output": {"entities": {"chemical": [{"text": "polylatide", "start": 77, "end": 87}, {"text": "polycaprolactone", "start": 88, "end": 104}, {"text": "polyethylene glycol", "start": 105, "end": 124}, {"text": "polycaprolactone", "start": 125, "end": 141}, {"text": "polylatide", "start": 142, "end": 152}, {"text": "PLA", "start": 155, "end": 158}, {"text": "PCL", "start": 159, "end": 162}, {"text": "PEG", "start": 163, "end": 166}, {"text": "PCL", "start": 167, "end": 170}, {"text": "PLA", "start": 171, "end": 174}, {"text": "steroids", "start": 250, "end": 258}]}}, "schema": []}
{"input": "Another purpose was to evaluate the effect of poly (L-lactide) (PLLA) or poly (D, L-lactide) (PDLLA) incorporation on crystallinity of pentablock copolymers and in vitro release profile of triamcinolone acetonide (selected as model drug) from nanoparticles.", "output": {"entities": {"chemical": [{"text": "poly (L-lactide)", "start": 46, "end": 62}, {"text": "PLLA", "start": 64, "end": 68}, {"text": "poly (D, L-lactide)", "start": 73, "end": 92}, {"text": "PDLLA", "start": 94, "end": 99}, {"text": "triamcinolone acetonide", "start": 189, "end": 212}]}}, "schema": []}
{"input": "PLA-PCL-PEG-PCL-PLA copolymers with different block ratio of PCL/PLA segment were synthesized.", "output": {"entities": {"chemical": [{"text": "PLA", "start": 0, "end": 3}, {"text": "PCL", "start": 4, "end": 7}, {"text": "PEG", "start": 8, "end": 11}, {"text": "PCL", "start": 12, "end": 15}, {"text": "PLA", "start": 16, "end": 19}, {"text": "PCL", "start": 61, "end": 64}, {"text": "PLA", "start": 65, "end": 68}]}}, "schema": []}
{"input": "Release of triamcinolone acetonide from nanoparticles was significantly affected by crystallinity of the copolymers.", "output": {"entities": {"chemical": [{"text": "triamcinolone acetonide", "start": 11, "end": 34}]}}, "schema": []}
{"input": "Burst release of triamcinolone acetonide from nanoparticles was significantly minimized with incorporation of proper ratio of PDLLA in the existing triblock (PCL-PEG-PCL) copolymer.", "output": {"entities": {"chemical": [{"text": "triamcinolone acetonide", "start": 17, "end": 40}, {"text": "PDLLA", "start": 126, "end": 131}, {"text": "PCL", "start": 158, "end": 161}, {"text": "PEG", "start": 162, "end": 165}, {"text": "PCL", "start": 166, "end": 169}]}}, "schema": []}
{"input": "Moreover, pentablock copolymer based nanoparticles exhibited continuous release of triamcinolone acetonide.", "output": {"entities": {"chemical": [{"text": "triamcinolone acetonide", "start": 83, "end": 106}]}}, "schema": []}
{"input": "Pentablock copolymer based nanoparticles can be utilized to achieve continuous near zero-order delivery of corticosteroids from nanoparticles without any burst effect.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and Structure Activity Relationship of Tetrahydroisoquinoline-based Potentiators of GluN2C and GluN2D Containing N-Methyl-D-Aspartate Receptors.", "output": {"entities": {"chemical": [{"text": "Tetrahydroisoquinoline", "start": 49, "end": 71}, {"text": "N-Methyl-D-Aspartate", "start": 123, "end": 143}]}}, "schema": []}
{"input": "We describe here the synthesis and evaluation of a series of tetrahydroisoquinolines that show subunit-selective potentiation of NMDA receptors containing the GluN2C or GluN2D subunits.", "output": {"entities": {"chemical": [{"text": "tetrahydroisoquinolines", "start": 61, "end": 84}, {"text": "NMDA", "start": 129, "end": 133}]}}, "schema": []}
{"input": "Bischler-Napieralski conditions were employed in the key step for the conversion of acyclic amides to the corresponding tetrahydroisoquinoline containing analogs.", "output": {"entities": {"chemical": [{"text": "acyclic amides", "start": 84, "end": 98}, {"text": "tetrahydroisoquinoline", "start": 120, "end": 142}]}}, "schema": []}
{"input": "Compounds were evaluated using both two electrode voltage clamp recordings from Xenopus laevis oocytes and imaging of mammalian BHK cells loaded with Ca (2 +)-sensitive dyes.", "output": {"entities": {"chemical": [{"text": "Ca (2 +)", "start": 150, "end": 158}]}}, "schema": []}
{"input": "The most potent analogues had EC50 values of 300 nM and showed over 2-fold potentiation of the response to maximally effective concentrations of glutamate and glycine, but had no effect on responses from NMDA receptors containing the GluN2A or GluN2B subunits, AMPA, kainate, GABA, or glycine receptors or a variety of other potential targets.", "output": {"entities": {"chemical": [{"text": "glutamate", "start": 145, "end": 154}, {"text": "glycine", "start": 159, "end": 166}, {"text": "NMDA", "start": 204, "end": 208}, {"text": "AMPA", "start": 261, "end": 265}, {"text": "kainate", "start": 267, "end": 274}, {"text": "GABA", "start": 276, "end": 280}, {"text": "glycine", "start": 285, "end": 292}]}}, "schema": []}
{"input": "These compounds represent a potent class of small molecule subunit-selective potentiators of NMDA receptors.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 93, "end": 97}]}}, "schema": []}
{"input": "Design, synthesis and molecular modeling of novel pyrido [2, 3-d] pyrimidine analogs as antifolates: Application of Buchwald-Hartwig aminations of heterocycles.", "output": {"entities": {"chemical": [{"text": "pyrido [2, 3-d] pyrimidine", "start": 50, "end": 76}]}}, "schema": []}
{"input": "Opportunistic infections caused by Pneumocystis jirovecii (P. jirovecii, pj), Toxoplasma gondii (T. gondii, tg) and Mycobacterium avium (M. avium, ma) are the principal causes of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS).", "output": {"entities": {}}, "schema": []}
{"input": "The absence of any animal models for human Pneumocystis jirovecii pneumonia and the lack of crystal structures of pjDHFR and tgDHFR make the design of inhibitors challenging.", "output": {"entities": {}}, "schema": []}
{"input": "A novel series of pyrido [2, 3-d] pyrimidines as selective and potent DHFR inhibitors against these opportunistic infections are presented.", "output": {"entities": {"chemical": [{"text": "pyrido [2, 3-d] pyrimidines", "start": 18, "end": 45}]}}, "schema": []}
{"input": "Buchwald-Hartwig coupling reaction of substituted anilines with pivaloyl protected 2, 4-diamino-6-bromo-pyrido [2, 3-d] pyrimidine was successfully explored to synthesize these analogs.", "output": {"entities": {"chemical": [{"text": "pivaloyl", "start": 64, "end": 72}, {"text": "2, 4-diamino-6-bromo-pyrido [2, 3-d] pyrimidine", "start": 83, "end": 130}]}}, "schema": []}
{"input": "Compound 26 was the most selective inhibitor with excellent potency against pjDHFR.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular modeling studies with a pjDHFR homology model explained the potency and selectivity of 26.", "output": {"entities": {}}, "schema": []}
{"input": "Structural data are also reported for 26 with pcDHFR and 16 and 22 with variants of pcDHFR.", "output": {"entities": {}}, "schema": []}
{"input": "Towards Understanding the Bonding Character in Complexes of Coinage Metals with Lone-Pair Ligands.", "output": {"entities": {}}, "schema": []}
{"input": "CCSD (T) and DFT Computations.", "output": {"entities": {}}, "schema": []}
{"input": "We present CCSD (T) interaction energies and the bonding analysis for complexes of Cu, Ag, and Au with the lone-pair ligands, H2O, OF2, OMe2, NH3, NF3, NMe3, H2S, SF2, SMe2, PH3, PF3, PCl3, PMe3 (ML complexes).", "output": {"entities": {"chemical": [{"text": "Cu", "start": 83, "end": 85}, {"text": "Ag", "start": 87, "end": 89}, {"text": "Au", "start": 95, "end": 97}, {"text": "H2O", "start": 126, "end": 129}, {"text": "OF2", "start": 131, "end": 134}, {"text": "OMe2", "start": 136, "end": 140}, {"text": "NH3", "start": 142, "end": 145}, {"text": "NF3", "start": 147, "end": 150}, {"text": "NMe3", "start": 152, "end": 156}, {"text": "H2S", "start": 158, "end": 161}, {"text": "SF2", "start": 163, "end": 166}, {"text": "SMe2", "start": 168, "end": 172}, {"text": "PH3", "start": 174, "end": 177}, {"text": "PF3", "start": 179, "end": 182}, {"text": "PCl3", "start": 184, "end": 188}, {"text": "PMe3", "start": 190, "end": 194}]}}, "schema": []}
{"input": "Both, electron correlation and relativistic effects, are crucial in the bonding of all complexes.", "output": {"entities": {}}, "schema": []}
{"input": "AuPH3, AuPF3 and AuPCl3 (MPX3) complexes exhibit particularly large relativistic effects, 30-46 kJ/mol.", "output": {"entities": {"chemical": [{"text": "AuPH3", "start": 0, "end": 5}, {"text": "AuPF3", "start": 7, "end": 12}, {"text": "AuPCl3", "start": 17, "end": 23}]}}, "schema": []}
{"input": "Upon neglecting relativistic effects the Au-P bonds almost vanish aside from weak long-range van der Waals interactions.", "output": {"entities": {"chemical": [{"text": "Au", "start": 41, "end": 43}, {"text": "P", "start": 44, "end": 45}]}}, "schema": []}
{"input": "Highest binding energies are computed for complexes with Au, followed by Cu and Ag.", "output": {"entities": {"chemical": [{"text": "Au", "start": 57, "end": 59}, {"text": "Cu", "start": 73, "end": 75}, {"text": "Ag", "start": 80, "end": 82}]}}, "schema": []}
{"input": "For all coinage metals the strongest interactions are computed for PX3 ligands followed by SX2 and NX3 OX2 ligands.", "output": {"entities": {"chemical": [{"text": "PX3", "start": 67, "end": 70}, {"text": "SX2", "start": 91, "end": 94}, {"text": "NX3 OX2", "start": 99, "end": 106}]}}, "schema": []}
{"input": "Upon methylation the interaction energy rises significantly.", "output": {"entities": {}}, "schema": []}
{"input": "Metal-thiol complexes, particularly AuSCH3, form a separate class.", "output": {"entities": {"chemical": [{"text": "Metal-thiol", "start": 0, "end": 11}, {"text": "AuSCH3", "start": 36, "end": 42}]}}, "schema": []}
{"input": "Exceptional stability of gold complexes is due to large relativistic enhancement of the electron affinity of Au.", "output": {"entities": {"chemical": [{"text": "Au", "start": 109, "end": 111}]}}, "schema": []}
{"input": "Along with the electron affinity of a metal we link the pattern of interaction energies in ML complexes with ionization potentials (IPs) of ligands.", "output": {"entities": {}}, "schema": []}
{"input": "Strong interaction with P containing ligands is attributed to their lower IP and the lone pair --> metal electron donation accompanied with the back-donation characteristic for P containing ligand.", "output": {"entities": {"chemical": [{"text": "P", "start": 24, "end": 25}]}}, "schema": []}
{"input": "Energy data are accompanied with the Natural Bond Orbital (NBO) analysis.", "output": {"entities": {}}, "schema": []}
{"input": "Computationally less demanding DFT computations with the PBE0 functional provide correct pattern of interaction energies when compared with benchmark CCSD (T) results.", "output": {"entities": {}}, "schema": []}
{"input": "Broad-Range Modulation of Light Emission in Two-Dimensional Semiconductors by Molecular Physisorption Gating.", "output": {"entities": {}}, "schema": []}
{"input": "In the monolayer limit, transition metal dichalcogenides become direct-bandgap, light-emitting semiconductors.", "output": {"entities": {"chemical": [{"text": "transition metal dichalcogenides", "start": 24, "end": 56}]}}, "schema": []}
{"input": "The quantum yield of light emission is low and extremely sensitive to the substrate used, while the underlying physics remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we report over 100 times modulation of light emission efficiency of these two-dimensional semiconductors by physical adsorption of O2 and/or H2O molecules, while inert gases do not cause such effect.", "output": {"entities": {"chemical": [{"text": "O2", "start": 145, "end": 147}, {"text": "H2O", "start": 155, "end": 158}]}}, "schema": []}
{"input": "The O2 and/or H2O pressure acts quantitatively as an instantaneously reversible \" molecular gating \" force, providing orders of magnitude broader control of carrier density and light emission than conventional electric field gating.", "output": {"entities": {"chemical": [{"text": "O2", "start": 4, "end": 6}, {"text": "H2O", "start": 14, "end": 17}]}}, "schema": []}
{"input": "Physi-sorbed O2 and/or H2O molecules electronically deplete n-type materials such as MoS2 and MoSe2, which weakens electrostatic screening that would otherwise destabilize excitons, leading to the drastic enhancement in photoluminescence.", "output": {"entities": {"chemical": [{"text": "O2", "start": 13, "end": 15}, {"text": "H2O", "start": 23, "end": 26}, {"text": "MoS2", "start": 85, "end": 89}, {"text": "MoSe2", "start": 94, "end": 99}]}}, "schema": []}
{"input": "In p-type materials such as WSe2, the molecular physisorption results in the opposite effect.", "output": {"entities": {"chemical": [{"text": "WSe2", "start": 28, "end": 32}]}}, "schema": []}
{"input": "Unique and universal in two-dimensional semiconductors, the effect offers a new mechanism for modulating electronic interactions and implementing optical devices.", "output": {"entities": {}}, "schema": []}
{"input": "Combinatorial Growth and Anisotropy Control of Self-Assembled Epitaxial Ultrathin Alloy Nanowires.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembled vertical epitaxial nanostructures form a new class of heterostructured materials that has emerged in recent years.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, such kind of architectures can be grown using combinatorial processes, implying sequential deposition of distinct materials.", "output": {"entities": {}}, "schema": []}
{"input": "Although opening many perspectives, this combinatorial nature has not been fully exploited yet.", "output": {"entities": {}}, "schema": []}
{"input": "This work demonstrates that the combinatorial character of the growth can be further exploited in order to obtain alloy nanowires coherently embedded in a matrix.", "output": {"entities": {}}, "schema": []}
{"input": "This issue is illustrated in the case of a fully epitaxial system: CoxNi1-x nanowires in CeO2/SrTiO3 (001).", "output": {"entities": {"chemical": [{"text": "CoxNi1-x", "start": 67, "end": 75}, {"text": "CeO2", "start": 89, "end": 93}, {"text": "SrTiO3", "start": 94, "end": 100}]}}, "schema": []}
{"input": "The advantage brought by the ability to grow alloys is illustrated by the control of the magnetic anisotropy of the nanowires when passing from pure Ni wires to CoxNi1-x alloys.", "output": {"entities": {"chemical": [{"text": "Ni", "start": 149, "end": 151}, {"text": "CoxNi1-x", "start": 161, "end": 169}]}}, "schema": []}
{"input": "Further exploitation of this combinatorial approach may pave the way toward full three-dimensional heteroepitaxial architectures through axial structuring of the wires.", "output": {"entities": {}}, "schema": []}
{"input": "Conformational determinants of the activity of Antiproliferative factor glycopeptide.", "output": {"entities": {}}, "schema": []}
{"input": "The antiproliferative factor (APF) involved in interstitial cystitis is a glycosylated nonapeptide (TVPAAVVVA) containing a sialylated core alpha-O-disaccharide linked to the N-terminal threonine.", "output": {"entities": {"chemical": [{"text": "nonapeptide", "start": 87, "end": 98}, {"text": "alpha-O-disaccharide", "start": 140, "end": 160}, {"text": "N", "start": 175, "end": 176}, {"text": "threonine", "start": 186, "end": 195}]}}, "schema": []}
{"input": "The chemical structure of APF was deduced using spectroscopic techniques and confirmed using total syn-thesis.", "output": {"entities": {}}, "schema": []}
{"input": "The synthetic APF provided a platform to study amino acid modifications and their effect on APF activity, based on which a structure-activity relationship (SAR) for APF activity was previously proposed.", "output": {"entities": {"chemical": [{"text": "amino acid", "start": 47, "end": 57}]}}, "schema": []}
{"input": "However, this SAR model could not explain the change in activity associated with minor al-terations in the peptide sequence.", "output": {"entities": {}}, "schema": []}
{"input": "Presented is computational analysis of 14 APF derivatives to identify structural trends from which a more detailed SAR is obtained.", "output": {"entities": {}}, "schema": []}
{"input": "The APF activity is found to be dictated by the close interplay between carbohydrate-peptide and peptide-peptide interactions.", "output": {"entities": {"chemical": [{"text": "carbohydrate", "start": 72, "end": 84}]}}, "schema": []}
{"input": "The former in-volves hydrogen bond and hydrophobic interactions and the latter is dominated by hydrophobic interac-tions.", "output": {"entities": {"chemical": [{"text": "hydrogen", "start": 21, "end": 29}]}}, "schema": []}
{"input": "The highly flexible hydrophobic peptide adopts collapsed conformations separated by low energy barriers.", "output": {"entities": {}}, "schema": []}
{"input": "APF activity correlates with hydrophobic clustering associated with amino acids 4A, 6V and 8V.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 68, "end": 79}]}}, "schema": []}
{"input": "Peptide conformations are highly sensitive to single point mutations, which explain the experi-mental trends.", "output": {"entities": {}}, "schema": []}
{"input": "The presented SAR will act as a guide for lead optimization of more potent APF ana-logues of potential therapeutic utility.", "output": {"entities": {}}, "schema": []}
{"input": "Active Layer-Incorporated, Spectrally-Tuned Au/SiO2 Core/Shell Nanorod-Based Light Trapping for Organic Photovoltaics.", "output": {"entities": {"chemical": [{"text": "Au", "start": 44, "end": 46}, {"text": "SiO2", "start": 47, "end": 51}]}}, "schema": []}
{"input": "We demonstrated that incorporation of octadecyltrimethoxysilane (OTMS) functionalized, spectrally tuned, gold/silica (Au/SiO2) core/shell nanospheres and nanorods into the active layer of an organic photovoltaic (OPV) device led to an in increase photo conversion efficiency (PCE).", "output": {"entities": {"chemical": [{"text": "octadecyltrimethoxysilane", "start": 38, "end": 63}, {"text": "OTMS", "start": 65, "end": 69}, {"text": "silica", "start": 110, "end": 116}, {"text": "Au", "start": 118, "end": 120}, {"text": "SiO2", "start": 121, "end": 125}]}}, "schema": []}
{"input": "A silica shell layer was added onto Au core nanospheres and nanorods in order to provide an electrically insulating surface that does not interfere with carrier generation and transport inside the active layer.", "output": {"entities": {"chemical": [{"text": "silica", "start": 2, "end": 8}, {"text": "Au", "start": 36, "end": 38}]}}, "schema": []}
{"input": "Functionalization of the Au/SiO2 core/shell nanoparticles with the OTMS organic ligand was then necessary in order to transfer the Au/SiO2 core/shell nanoparticles from an ethanol solution into an OPV polymer-compatible solvent, such as dichlorobenzene (DCB).", "output": {"entities": {"chemical": [{"text": "Au", "start": 25, "end": 27}, {"text": "SiO2", "start": 28, "end": 32}, {"text": "OTMS", "start": 67, "end": 71}, {"text": "Au", "start": 131, "end": 133}, {"text": "SiO2", "start": 134, "end": 138}, {"text": "ethanol", "start": 172, "end": 179}, {"text": "dichlorobenzene", "start": 237, "end": 252}, {"text": "DCB", "start": 254, "end": 257}]}}, "schema": []}
{"input": "The OTMS-functionalized Au/SiO2 core/shell nanorods and nanospheres were then incorporated into the active layers of two OPV polymer systems: a poly (3-hexylthiophene): [6, 6]-phenyl-C61-butyric acid methyl ester (P3HT: PCB60M) OPV device and a poly [2, 6-4, 8-di (5-ethylhexylthienyl) benzo [1, 2-b; 3, 4-b] dithiophene-alt-5-dibutyloctyl-3, 6-bis (5-bromothiophen-2-yl) pyrrolo [3, 4-c] pyrrole-1, 4-dione] (PBDTT-DPP: PC60BM) OPV device.", "output": {"entities": {"chemical": [{"text": "OTMS", "start": 4, "end": 8}, {"text": "Au", "start": 24, "end": 26}, {"text": "SiO2", "start": 27, "end": 31}, {"text": "poly (3-hexylthiophene)", "start": 144, "end": 167}, {"text": "[6, 6]-phenyl-C61-butyric acid methyl ester", "start": 169, "end": 212}, {"text": "P3HT", "start": 214, "end": 218}, {"text": "PCB60M", "start": 220, "end": 226}, {"text": "poly [2, 6-4, 8-di (5-ethylhexylthienyl) benzo [1, 2-b; 3, 4-b] dithiophene-alt-5-dibutyloctyl-3, 6-bis (5-bromothiophen-2-yl) pyrrolo [3, 4-c] pyrrole-1, 4-dione]", "start": 245, "end": 408}, {"text": "PBDTT-DPP", "start": 410, "end": 419}, {"text": "PC60BM", "start": 421, "end": 427}]}}, "schema": []}
{"input": "For the P3HT: PC60BM polymer with a band edge of ~ 700 nm, the addition of the core/shell nanorods with an aspect ratio (AR) of ~ 2. 5 (extinction peak ~ 670 nm) resulted in a 7. 1% improvement in PCE, while for the PBDTT-DPP: PC60BM polymer with a band edge ~ 860 nm, the addition of core/shell nanorods with an AR of ~ 4 (extinction peak ~ 830 nm) resulted in a 14. 4% improvement in PCE.", "output": {"entities": {"chemical": [{"text": "P3HT", "start": 8, "end": 12}, {"text": "PC60BM", "start": 14, "end": 20}, {"text": "PBDTT-DPP", "start": 216, "end": 225}, {"text": "PC60BM", "start": 227, "end": 233}]}}, "schema": []}
{"input": "The addition of Au/SiO2 core/shell nanospheres to the P3HT: PC60BM-polymer resulted in a 2. 7% improvement in PCE, while their addition to a PBDTT-DPP: PC60BM polymer resulted in a 9. 1% improvement.", "output": {"entities": {"chemical": [{"text": "Au", "start": 16, "end": 18}, {"text": "SiO2", "start": 19, "end": 23}, {"text": "P3HT", "start": 54, "end": 58}, {"text": "PC60BM", "start": 60, "end": 66}, {"text": "PBDTT-DPP", "start": 141, "end": 150}, {"text": "PC60BM", "start": 152, "end": 158}]}}, "schema": []}
{"input": "The PCE and Jsc enhancements were consistent with external quantum efficiency (EQE) measurements and the EQE enhancements spectrally matched the extinction spectra of Au/SiO2 nanospheres and nanorods in both OPV polymer systems.", "output": {"entities": {"chemical": [{"text": "Au", "start": 167, "end": 169}, {"text": "SiO2", "start": 170, "end": 174}]}}, "schema": []}
{"input": "Interactions between solid surfaces with pre-adsorbed poly (ethylenimine) (PEI) layers: effect of unadsorbed free PEI chains.", "output": {"entities": {"chemical": [{"text": "poly (ethylenimine)", "start": 54, "end": 73}, {"text": "PEI", "start": 75, "end": 78}, {"text": "PEI", "start": 114, "end": 117}]}}, "schema": []}
{"input": "Poly (ethylenimine) (PEI) polyelectrolytes have been widely used to tune the stability, rheology, or adhesion properties of colloidal suspensions due to their strong tendency to adsorb to solid surfaces.", "output": {"entities": {"chemical": [{"text": "Poly (ethylenimine)", "start": 0, "end": 19}, {"text": "PEI", "start": 21, "end": 24}]}}, "schema": []}
{"input": "They have also gained importance as gene carriers in biomedical applications, in which the anionic DNA chains are complexed and condensed to form PEI/DNA polyplexes.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 146, "end": 149}]}}, "schema": []}
{"input": "Some reported literatures have recently shown that the overdosed PEI chains, which are free in the solution mixture, also play a vital role in promoting the gene transfection, but the reason is unclear.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 65, "end": 68}]}}, "schema": []}
{"input": "In this work, we present the results of using total internal reflection microscopy (TIRM) to measure the interaction forces between a Brownian colloidal sphere and a flat glass plate in the presence of overdosed free PEI cationic chains, when both surfaces were saturated adsorbed with the PEI chains.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 217, "end": 220}, {"text": "PEI", "start": 290, "end": 293}]}}, "schema": []}
{"input": "The colloidal sphere pre-adsorbed with PEI chains was chosen to mimic the PEI/DNA polyplex.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 39, "end": 42}, {"text": "PEI", "start": 74, "end": 77}]}}, "schema": []}
{"input": "Results for the potential energy of interaction measured for model polyplex (e. g., PEI-coated sphere) interacting with a PEI-coated glass surface in the presence of overdosed free PEI chains at various pH values and salt concentrations were presented.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 84, "end": 87}, {"text": "PEI", "start": 122, "end": 125}, {"text": "PEI", "start": 181, "end": 184}]}}, "schema": []}
{"input": "As can be shown by direct force measurements, the interaction potentials in NaCl salt solution are dominated by repulsive forces originating from diffuse layer overlap and gravitational attraction.", "output": {"entities": {"chemical": [{"text": "NaCl", "start": 76, "end": 80}]}}, "schema": []}
{"input": "However, the presence of free PEI chains in the solution mixture produces a long-ranged (> 60 nm) attractive force between two PEI-coated surfaces with the range and magnitude tunable by pH value, PEI and salt concentrations.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 30, "end": 33}, {"text": "PEI", "start": 127, "end": 130}, {"text": "PEI", "start": 197, "end": 200}]}}, "schema": []}
{"input": "The possible mechanisms of this long-ranged attractive force are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "A better understanding of this free PEI-induced attractive force will be useful in the development of improved PEI/DNA polyplexes systems for biomedical applications.", "output": {"entities": {"chemical": [{"text": "PEI", "start": 36, "end": 39}, {"text": "PEI", "start": 111, "end": 114}]}}, "schema": []}
{"input": "Evaluation of the In Vitro Cytotoxicity of Cross-Linked Biomaterials.", "output": {"entities": {}}, "schema": []}
{"input": "This study evaluated the in vitro cytotoxicity of poly (propylene fumarate) (PPF).", "output": {"entities": {"chemical": [{"text": "poly (propylene fumarate)", "start": 50, "end": 75}, {"text": "PPF", "start": 77, "end": 80}]}}, "schema": []}
{"input": "PPF is an aliphatic biodegradable polymer that has been well characterized for use in bone tissue engineering scaffolds.", "output": {"entities": {"chemical": [{"text": "PPF", "start": 0, "end": 3}]}}, "schema": []}
{"input": "Four different cell types, human mesenchymal stem cells (hMSC), fibroblasts (L929), preosteoblasts (MC3T3), and canine mesenchymal stem cells (cMSC), were used to evaluate the cytotoxicity of PPF.", "output": {"entities": {"chemical": [{"text": "PPF", "start": 192, "end": 195}]}}, "schema": []}
{"input": "These cell types represent the tissues that PPF would interact with in vivo as a bone tissue scaffold.", "output": {"entities": {"chemical": [{"text": "PPF", "start": 44, "end": 47}]}}, "schema": []}
{"input": "The sol fraction of the PPF films was measured and then utilized to estimate cross-linking density.", "output": {"entities": {"chemical": [{"text": "PPF", "start": 24, "end": 27}]}}, "schema": []}
{"input": "Cytotoxicity was evaluated using XTT assay and fluorescence imaging.", "output": {"entities": {"chemical": [{"text": "XTT", "start": 33, "end": 36}]}}, "schema": []}
{"input": "Results showed that PPF supported similar cell metabolic activities of hMSC, L929, MC3T3, and cMSC compared to the noncytotoxic control, high-density polyethylene (HDPE) and were statistically different than those cultured with the cytotoxic control, a polyurethane film containing 0. 1% zinc diethyldithiocarbamate (ZCF).", "output": {"entities": {"chemical": [{"text": "PPF", "start": 20, "end": 23}, {"text": "polyethylene", "start": 150, "end": 162}, {"text": "polyurethane", "start": 253, "end": 265}, {"text": "zinc diethyldithiocarbamate", "start": 288, "end": 315}, {"text": "ZCF", "start": 317, "end": 320}]}}, "schema": []}
{"input": "Results showed differing cellular responses to ZCF, the cytotoxic control.", "output": {"entities": {"chemical": [{"text": "ZCF", "start": 47, "end": 50}]}}, "schema": []}
{"input": "The L929 cells had the lowest cell metabolic activity levels after exposure to ZCF compared to the cell metabolic activity levels of the MC3T3, hMSC, or cMSC cells.", "output": {"entities": {"chemical": [{"text": "ZCF", "start": 79, "end": 82}]}}, "schema": []}
{"input": "Qualitative verification of the results using fluorescence imaging demonstrated no change in cell morphology, vacuolization, or detachment when cultured with PPF compared to HDPE or blank media cultures.", "output": {"entities": {"chemical": [{"text": "PPF", "start": 158, "end": 161}]}}, "schema": []}
{"input": "Overall, the cytotoxicity response of the cells to PPF was demonstrated to be similar to the cytotoxic response of cells to known noncytotoxic materials (HDPE).", "output": {"entities": {"chemical": [{"text": "PPF", "start": 51, "end": 54}]}}, "schema": []}
{"input": "Fas receptor-deficient lpr mice are protected against acetaminophen hepatotoxicity due to higher glutathione synthesis and enhanced detoxification of oxidant stress.", "output": {"entities": {"chemical": [{"text": "acetaminophen", "start": 54, "end": 67}, {"text": "glutathione", "start": 97, "end": 108}]}}, "schema": []}
{"input": "Acetaminophen (APAP) overdose is a classical model of hepatocellular necrosis; however, the involvement of the Fas receptor in the pathophysiology remains controversial.", "output": {"entities": {"chemical": [{"text": "Acetaminophen", "start": 0, "end": 13}, {"text": "APAP", "start": 15, "end": 19}]}}, "schema": []}
{"input": "Fas receptor-deficient (lpr) and C57BL/6 mice were treated with APAP to compare the mechanisms of hepatotoxicity.", "output": {"entities": {"chemical": [{"text": "APAP", "start": 64, "end": 68}]}}, "schema": []}
{"input": "Lpr mice were partially protected against APAP hepatotoxicity as indicated by reduced plasma ALT and GDH levels and liver necrosis.", "output": {"entities": {"chemical": [{"text": "APAP", "start": 42, "end": 46}]}}, "schema": []}
{"input": "Hepatic Cyp2e1 protein, adduct formation and hepatic glutathione (GSH) depletion were similar, demonstrating equivalent reactive metabolite generation.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 53, "end": 64}, {"text": "GSH", "start": 66, "end": 69}]}}, "schema": []}
{"input": "There was no difference in cytokine formation or hepatic neutrophil recruitment.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, hepatic GSH recovered faster in lpr mice than in wild type animals resulting in enhanced detoxification of reactive oxygen species.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 23, "end": 26}, {"text": "oxygen", "start": 131, "end": 137}]}}, "schema": []}
{"input": "Driving the increased GSH levels, mRNA induction and protein expression of glutamate-cysteine ligase (gclc) were higher in lpr mice.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 22, "end": 25}, {"text": "glutamate", "start": 75, "end": 84}, {"text": "cysteine", "start": 85, "end": 93}]}}, "schema": []}
{"input": "Inducible nitric oxide synthase (iNOS) mRNA and protein levels at 6h were significantly lower in lpr mice, which correlated with reduced nitrotyrosine staining.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 10, "end": 22}, {"text": "nitrotyrosine", "start": 137, "end": 150}]}}, "schema": []}
{"input": "Heat shock protein 70 (Hsp70) mRNA levels were substantially higher in lpr mice after APAP.", "output": {"entities": {"chemical": [{"text": "APAP", "start": 86, "end": 90}]}}, "schema": []}
{"input": "Conclusion: Our data suggest that the faster recovery of hepatic GSH levels during oxidant stress and peroxynitrite formation, reduced iNOS expression and enhanced induction of Hsp70 attenuated the susceptibility to APAP-induced cell death in lpr mice.", "output": {"entities": {"chemical": [{"text": "GSH", "start": 65, "end": 68}, {"text": "peroxynitrite", "start": 102, "end": 115}, {"text": "APAP", "start": 216, "end": 220}]}}, "schema": []}
{"input": "A proteome-wide visual screen identifies fission yeast proteins localizing to DNA double-strand breaks.", "output": {"entities": {}}, "schema": []}
{"input": "DNA double-strand breaks (DSBs) are a major threat to genome integrity.", "output": {"entities": {}}, "schema": []}
{"input": "Proteins involved in DNA damage checkpoint signaling and DSB repair often relocalize and concentrate at DSBs.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we used an ORFeome library of the fission yeast Schizosaccharomyces pombe to systematically identify proteins targeted to DSBs.", "output": {"entities": {}}, "schema": []}
{"input": "We found 51 proteins that, when expressed from a strong exogenous promoter on the ORFeome plasmids, were able to form a distinct nuclear focus at an HO endonuclease-induced DSB.", "output": {"entities": {}}, "schema": []}
{"input": "The majority of these proteins have known connections to DNA damage response, but few have been visualized at a specific DSB before.", "output": {"entities": {}}, "schema": []}
{"input": "Among the screen hits, 37 can be detected at DSBs when expressed from native promoters.", "output": {"entities": {}}, "schema": []}
{"input": "We classified them according to the focus emergence timing of the endogenously tagged proteins.", "output": {"entities": {}}, "schema": []}
{"input": "Eight of these 37 proteins are yet unnamed.", "output": {"entities": {}}, "schema": []}
{"input": "We named these eight proteins DNA-break-localizing proteins (Dbls) and performed preliminary functional analysis on two of them, Dbl1 (SPCC2H8. 05c) and Dbl2 (SPCC553. 01c).", "output": {"entities": {}}, "schema": []}
{"input": "We found that Dbl1 and Dbl2 contribute to the normal DSB targeting of checkpoint protein Rad26 (homolog of human ATRIP) and DNA repair helicase Fml1 (homolog of human FANCM), respectively.", "output": {"entities": {}}, "schema": []}
{"input": "As the first proteome-wide inventory of DSB-localizing proteins, our screen result will be a useful resource for understanding the mechanisms of eukaryotic DSB response.", "output": {"entities": {}}, "schema": []}
{"input": "Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission.", "output": {"entities": {}}, "schema": []}
{"input": "Mitochondria and peroxisomes can be fragmented by the process of fission.", "output": {"entities": {}}, "schema": []}
{"input": "The fission machineries of both organelles share a set of proteins.", "output": {"entities": {}}, "schema": []}
{"input": "GDAP1 is a tail-anchored protein of mitochondria and induces mitochondrial fragmentation.", "output": {"entities": {}}, "schema": []}
{"input": "Mutations in GDAP1 lead to Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy, and affect mitochondrial dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we show that GDAP1 is also targeted to peroxisomes mediated by the import receptor Pex19.", "output": {"entities": {}}, "schema": []}
{"input": "Knockdown of GDAP1 leads to peroxisomal elongation that can be rescued by re-expressing GDAP1 and by missense mutated forms found in CMT patients.", "output": {"entities": {}}, "schema": []}
{"input": "GDAP1-induced peroxisomal fission is dependent on the integrity of its hydrophobic domain 1, and on Drp1 and Mff, as is mitochondrial fission.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, GDAP1 regulates mitochondrial and peroxisomal fission by a similar mechanism.", "output": {"entities": {}}, "schema": []}
{"input": "However, our results reveal also a more critical role of the amino-terminal GDAP1 domains, carrying most CMT-causing mutations, in the regulation of mitochondrial compared to peroxisomal fission.", "output": {"entities": {"chemical": [{"text": "amino", "start": 61, "end": 66}]}}, "schema": []}
{"input": "Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity.", "output": {"entities": {"chemical": [{"text": "manganese", "start": 76, "end": 85}]}}, "schema": []}
{"input": "The extra-pyramidal symptoms associated with manganism often overlap with that seen in Parkinsonism suggesting a common link between the two disorders.", "output": {"entities": {"chemical": [{"text": "manganism", "start": 45, "end": 54}]}}, "schema": []}
{"input": "Since wide deviations are observed in susceptibility and characteristics of the symptoms observed in manganism, these differences may be due to underlying genetic variability.", "output": {"entities": {"chemical": [{"text": "manganism", "start": 101, "end": 110}]}}, "schema": []}
{"input": "Genes linked to early onset of Parkinsonism which includes ATP13A2 and parkin have already been suggested to promote development of Mn toxicity.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 132, "end": 134}]}}, "schema": []}
{"input": "Of the other Parkinson-linked genes, mutations in LRRK2, an autosomal dominant gene, represent another likely candidate involved in the development of manganism.", "output": {"entities": {"chemical": [{"text": "manganism", "start": 151, "end": 160}]}}, "schema": []}
{"input": "In this paper the effect of shRNA LRRK2 knock-down on Mn toxicity was examined in control and DAT transfected HEK293 cells.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 54, "end": 56}]}}, "schema": []}
{"input": "Results demonstrate that LRRK2 down-regulation potentiates Mn toxicity in both control and DAT-transfected cell as well as potentiates DA toxicity.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 59, "end": 61}]}}, "schema": []}
{"input": "Combined treatment of Mn and DA further augments cell toxicity, ROS production and JNK phosphorylation in LRRK2 deficient cells compared to controls.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 22, "end": 24}]}}, "schema": []}
{"input": "Consistent with studies demonstrating that LRRK2 plays a role in the phosphorylation of p38, our results similarly demonstrate a decrease in p38 activation in LRRK2 knock-down cells.", "output": {"entities": {}}, "schema": []}
{"input": "Our findings suggest that null mutations in LRRK2 which cause Parkinsonism potentiate Mn toxicity and increase susceptibility to develop manganism.", "output": {"entities": {"chemical": [{"text": "Mn", "start": 86, "end": 88}, {"text": "manganism", "start": 137, "end": 146}]}}, "schema": []}
{"input": "Dendritic architectures based on bis-MPA: functional polymeric scaffolds for application-driven research.", "output": {"entities": {"chemical": [{"text": "bis-MPA", "start": 33, "end": 40}]}}, "schema": []}
{"input": "Dendritic polymers are highly branched, globular architectures with multiple representations of functional groups.", "output": {"entities": {}}, "schema": []}
{"input": "These nanoscale organic frameworks continue to fascinate researchers worldwide and are today under intensive investigation in application-driven research.", "output": {"entities": {}}, "schema": []}
{"input": "A large number of potential application areas have been suggested for dendritic polymers, including theranostics, biosensors, optics, adhesives and coatings.", "output": {"entities": {}}, "schema": []}
{"input": "The transition from potential to real applications is strongly dictated by their commercial accessibility, scaffolding ability as well as biocompatibility.", "output": {"entities": {}}, "schema": []}
{"input": "A dendritic family that fulfills these requirements is based on the 2, 2-bismethylolpropionic acid (bis-MPA) monomer.", "output": {"entities": {"chemical": [{"text": "2, 2-bismethylolpropionic acid", "start": 68, "end": 98}, {"text": "bis-MPA", "start": 100, "end": 107}]}}, "schema": []}
{"input": "This critical review is the first of its kind to cover most of the research activities generated on aliphatic polyester dendritic architectures based on bis-MPA.", "output": {"entities": {"chemical": [{"text": "bis-MPA", "start": 153, "end": 160}]}}, "schema": []}
{"input": "It is apparent that these scaffolds will continue to be in the forefront of cutting-edge research as their structural variations are endless including dendrons, dendrimers, hyperbranched polymers, dendritic-linear hybrids and their hybridization with inorganic surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Differential Activity of Plasma and Vacuolar Membrane Transporters Contributes to Genotypic Differences in Salinity Tolerance in a Halophyte Species, Chenopodium quinoa.", "output": {"entities": {}}, "schema": []}
{"input": "Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants.", "output": {"entities": {}}, "schema": []}
{"input": "Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity of slow (SV) and fast (FV) tonoplast channels to match specific growth conditions by ensuring that most of accumulated Na + is safely locked in the vacuole (Bonales-Alatorre et al. (2013) Plant Physiology).", "output": {"entities": {"chemical": [{"text": "Na +", "start": 254, "end": 258}]}}, "schema": []}
{"input": "This work extends these finding by comparing the properties of tonoplast FV and SV channels in two quinoa genotypes contrasting in their salinity tolerance.", "output": {"entities": {}}, "schema": []}
{"input": "The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue.", "output": {"entities": {}}, "schema": []}
{"input": "Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa.", "output": {"entities": {}}, "schema": []}
{"input": "These include: (i) a higher rate of Na + exclusion from leaf mesophyll; (ii) maintenance of low cytosolic Na + levels; (iii) better K + retention in the leaf mesophyll; (iv) a high rate of H + pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v) the ability to reduce the activity of SV and FV channels under saline conditions.", "output": {"entities": {"chemical": [{"text": "Na +", "start": 36, "end": 40}, {"text": "Na +", "start": 106, "end": 110}, {"text": "K +", "start": 132, "end": 135}, {"text": "H +", "start": 189, "end": 192}]}}, "schema": []}
{"input": "These mechanisms appear to be highly orchestrated, thus enabling the remarkable overall salinity tolerance of quinoa species.", "output": {"entities": {}}, "schema": []}
{"input": "Basic evidence for epidermal H2O2/ONOO--mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 29, "end": 33}, {"text": "ONOO", "start": 34, "end": 38}, {"text": "H2O2", "start": 173, "end": 177}]}}, "schema": []}
{"input": "Nonsegmental vitiligo (NSV) is characterized by loss of inherited skin color.", "output": {"entities": {}}, "schema": []}
{"input": "The cause of the disease is still unknown despite accumulating in vivo and in vitro evidence of massive epidermal oxidative stress via H2O2 and peroxynitrite (ONOO (-)) in affected individuals.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 135, "end": 139}, {"text": "peroxynitrite", "start": 144, "end": 157}, {"text": "ONOO (-)", "start": 159, "end": 167}]}}, "schema": []}
{"input": "The most favored hypothesis is based on autoimmune mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Strictly segmental vitiligo (SSV) with dermatomal distribution is a rare entity, often associated with stable outcome.", "output": {"entities": {}}, "schema": []}
{"input": "Recently, it was documented that this form can be associated with NSV (mixed vitiligo).", "output": {"entities": {}}, "schema": []}
{"input": "We here asked the question whether ROS and possibly ONOO (-) could be players in the pathogenesis of SSV.", "output": {"entities": {"chemical": [{"text": "ONOO (-)", "start": 52, "end": 60}]}}, "schema": []}
{"input": "Our in situ results demonstrate for the first time epidermal biopterin accumulation together with significantly decreased epidermal catalase, thioredoxin/thioreoxin reductase, and MSRA/MSRB expression.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, we show epidermal ONOO (-) accumulation.", "output": {"entities": {"chemical": [{"text": "ONOO (-)", "start": 28, "end": 36}]}}, "schema": []}
{"input": "In vivo FT-Raman spectroscopy reveals the presence of H2O2, methionine sulfoxide, and tryptophan metabolites; i. e., N-formylkynurenine and kynurenine, implying Fenton chemistry in the cascade (n = 10).", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 54, "end": 58}, {"text": "methionine sulfoxide", "start": 60, "end": 80}, {"text": "tryptophan", "start": 86, "end": 96}, {"text": "N-formylkynurenine", "start": 117, "end": 135}, {"text": "kynurenine", "start": 140, "end": 150}]}}, "schema": []}
{"input": "Validation of the basic data stems from successful repigmentation of skin and eyelashes in affected individuals, regardless of SSV or segmental vitiligo in association with NSV after reduction of epidermal H2O2 (n = 5).", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 206, "end": 210}]}}, "schema": []}
{"input": "Taken together, our contribution strongly supports H2O2/ONOO-mediated stress in the pathogenesis of SSV.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 51, "end": 55}, {"text": "ONOO-", "start": 56, "end": 61}]}}, "schema": []}
{"input": "Our findings offer new treatment intervention for lost skin and hair color.-Schallreuter, K.", "output": {"entities": {}}, "schema": []}
{"input": "U., Salem, M.", "output": {"entities": {}}, "schema": []}
{"input": "A.", "output": {"entities": {}}, "schema": []}
{"input": "E.", "output": {"entities": {}}, "schema": []}
{"input": "L., Holtz, S., Panske, A.", "output": {"entities": {}}, "schema": []}
{"input": "Basic evidence for epidermal H2O2/ONOO (-)-mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 29, "end": 33}, {"text": "ONOO (-)", "start": 34, "end": 42}, {"text": "H2O2", "start": 176, "end": 180}]}}, "schema": []}
{"input": "Caveolae-Mediated Endocytosis of Conjugated Polymer Nanoparticles.", "output": {"entities": {}}, "schema": []}
{"input": "Understanding the cellular entry pathways of synthetic biomaterials is highly important to improve overall labeling and delivery efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, cellular entry mechanisms of conjugated polymer nanoparticles (CPNs) are presented.", "output": {"entities": {}}, "schema": []}
{"input": "CPNs are intrinsic fluorescent materials used for various biological applications.", "output": {"entities": {}}, "schema": []}
{"input": "While CPNs cause no toxicity, decreased CPN uptake is observed from cancer cells pretreated with genistein, which is an inhibitor of caveolae-mediated endocytosis (CvME).", "output": {"entities": {"chemical": [{"text": "genistein", "start": 97, "end": 106}]}}, "schema": []}
{"input": "CvME is further confirmed by high co-localization with caveolin-1 proteins found in the caveolae and caveosomes.", "output": {"entities": {}}, "schema": []}
{"input": "Excellent photophysical properties, non-toxicity, and non-destructive delivery pathways support that CPNs are promising multifunctional carriers minimizing degradation of contents during delivery.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of an Inhibitory Mechanism of Luteolin on the Insulin-Like Growth Factor-1 Ligand-Receptor Interaction.", "output": {"entities": {"chemical": [{"text": "Luteolin", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Using single-molecule force measurement and fluorescence imaging, we have demonstrated that luteolin has an inhibitory effect on IGF-1 ligand-receptor binding, the initial step in IGF-1 signaling.", "output": {"entities": {"chemical": [{"text": "luteolin", "start": 92, "end": 100}]}}, "schema": []}
{"input": "This inhibition mechanism, which was confirmed by flow cytometry and molecular docking, could play a role in cancer therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Strong Parent-of-Origin Effects in the Association of KCNQ1 Variants with Type 2 Diabetes Mellitus in American Indians.", "output": {"entities": {}}, "schema": []}
{"input": "Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, including those in KLF14 (rs4731702), MOB2 (rs2334499) and KCNQ1 (rs2237892, rs231362).", "output": {"entities": {}}, "schema": []}
{"input": "We analyzed parent-of-origin effects for these variants, along with two others in KCNQ1 identified in previous genome-wide association studies (rs2237895, rs2299620), in 7351 Pima Indians from 4549 nuclear families; 34% of participants had diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "In a subset of 287 normoglycemic individuals, acute insulin secretion was measured by an intravenous glucose tolerance test.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 101, "end": 108}]}}, "schema": []}
{"input": "Statistically significant (P < 0. 05) parent-of-origin effects were seen for association with type 2 diabetes for all variants.", "output": {"entities": {}}, "schema": []}
{"input": "The strongest effect was seen at rs2299620 in KCNQ1: the C allele was associated with increased diabetes when maternally-derived (odds ratio = 1. 92, P = 4. 1x10 (-12)), but not when paternally-derived (odds ratio = 0. 93, P = 0. 47; P = 9. 9x10 (-6) for difference in maternal and paternal effects).", "output": {"entities": {}}, "schema": []}
{"input": "A maternally-derived C allele was also associated with a 28% decrease in insulin secretion (P = 0. 002).", "output": {"entities": {}}, "schema": []}
{"input": "This study confirms parent-of-origin effects in the association with type 2 diabetes for variants in KLF14, MOB2 and KCNQ1.", "output": {"entities": {}}, "schema": []}
{"input": "In Pima Indians the effect of maternally-derived KCNQ1 variants appears to be mediated through decreased insulin secretion, and is particularly strong, accounting for 4% of the variance in liability to diabetes.", "output": {"entities": {}}, "schema": []}
{"input": "Matrix Metalloproteinase Inhibitors Based on the 3-Mercaptopyrrolidine Core.", "output": {"entities": {"chemical": [{"text": "3-Mercaptopyrrolidine", "start": 49, "end": 70}]}}, "schema": []}
{"input": "New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamido pyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated.", "output": {"entities": {"chemical": [{"text": "pyrrolidine mercaptosulfide", "start": 14, "end": 41}, {"text": "2-mercaptocyclopentane arylsulfonamide", "start": 43, "end": 81}, {"text": "3-mercapto-4-arylsulfonamido pyrrolidine", "start": 87, "end": 127}]}}, "schema": []}
{"input": "Exhibiting unique properties over other MMPIs (e. g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (~ 2 to 50 nM), MMP-13 (~ 2 to 50 nM), and MMP-14 (~ 4 to 60 nM).", "output": {"entities": {"chemical": [{"text": "hydroxamates", "start": 54, "end": 66}]}}, "schema": []}
{"input": "Additionally these compounds are selective to intermediate-and deep-pocket MMPs but not shallow-pocketed MMPs (e. g., MMP-1, ~ 850 to > 50, 000 nM; MMP-7, ~ 4, 000 to > 25, 000 nM).", "output": {"entities": {}}, "schema": []}
{"input": "Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S, 4R)-stereochemistry was optimal for all of the MMPs tested.", "output": {"entities": {"chemical": [{"text": "mercaptosulfide", "start": 27, "end": 42}, {"text": "cyclopentane", "start": 74, "end": 86}, {"text": "pyrrolidine", "start": 91, "end": 102}]}}, "schema": []}
{"input": "However, in our newest compounds an interesting shift of preference to the trans-form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility.", "output": {"entities": {"chemical": [{"text": "mercaptosulfonamides", "start": 93, "end": 113}]}}, "schema": []}
{"input": "We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.", "output": {"entities": {}}, "schema": []}
{"input": "Design, Synthesis and Biological Evaluation of Aminoalkylindole Derivatives as Cannabinoid Receptor Ligands with Potential for Treatment of Alcohol Abuse.", "output": {"entities": {"chemical": [{"text": "Aminoalkylindole", "start": 47, "end": 63}, {"text": "Alcohol", "start": 140, "end": 147}]}}, "schema": []}
{"input": "Attenuation of increased endocannabinoid signaling with a CB1R neutral antagonist might offer a new therapeutic direction for treatment of alcohol abuse.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 139, "end": 146}]}}, "schema": []}
{"input": "We have recently reported that a mono-hydroxylated metabolite of the synthetic aminoalkylindole cannabinoid JHW-073 (3) exhibits neutral antagonist activity at CB1Rs and thus may serve as a promising lead for the development of novel alcohol abuse therapies.", "output": {"entities": {"chemical": [{"text": "aminoalkylindole", "start": 79, "end": 95}, {"text": "JHW-073", "start": 108, "end": 115}, {"text": "alcohol", "start": 234, "end": 241}]}}, "schema": []}
{"input": "In the current study, we show that systematic modification of an aminoalkylindole scaffold identifies two new compounds with dual CB1R antagonist/CB2R agonist activity.", "output": {"entities": {"chemical": [{"text": "aminoalkylindole", "start": 65, "end": 81}]}}, "schema": []}
{"input": "Similar to the CB1R antagonist/inverse agonist rimonabant, analogues 27 and 30 decrease oral alcohol self-administration, without affecting total fluid intake and block the development of alcohol-conditioned place preference.", "output": {"entities": {"chemical": [{"text": "alcohol", "start": 93, "end": 100}, {"text": "alcohol", "start": 188, "end": 195}]}}, "schema": []}
{"input": "Collectively, these initial findings suggest that design and systematic modification of aminoalkylindoles such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse.", "output": {"entities": {"chemical": [{"text": "aminoalkylindoles", "start": 88, "end": 105}, {"text": "alcohol", "start": 257, "end": 264}]}}, "schema": []}
{"input": "Milk-Derived Peptides, Val-Pro-Pro and Ile-Pro-Pro, Attenuate Atherosclerosis Development in Apolipoprotein E-Deficient Mice: A Preliminary Study.", "output": {"entities": {"chemical": [{"text": "Val-Pro-Pro", "start": 23, "end": 34}, {"text": "Ile-Pro-Pro", "start": 39, "end": 50}]}}, "schema": []}
{"input": "Abstract Milk-derived peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), have angiotensin I-converting enzyme inhibitory activities and blood pressure-lowering effects.", "output": {"entities": {"chemical": [{"text": "Val-Pro-Pro", "start": 32, "end": 43}, {"text": "Ile-Pro-Pro", "start": 54, "end": 65}]}}, "schema": []}
{"input": "We examined the effects of these peptides on the development of atherosclerosis in apolipoprotein E-deficient [apoE (-/-)] mice.", "output": {"entities": {}}, "schema": []}
{"input": "For 31 weeks, six-week-old male apoE (-/-) mice received a diet that included one of the following: fermented milk containing both VPP and IPP; casein hydrolysate containing both of these peptides; synthesized VPP; synthesized IPP; enalapril; captopril; or control diet.", "output": {"entities": {"chemical": [{"text": "enalapril", "start": 232, "end": 241}, {"text": "captopril", "start": 243, "end": 252}]}}, "schema": []}
{"input": "At the end of feeding, blood biochemistry, aortic atherogenesis, and gene expression by DNA microarray analysis were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "There were no significant changes in the plasma lipid levels and 8-isoprostane, a marker of oxidative stress.", "output": {"entities": {"chemical": [{"text": "8-isoprostane", "start": 65, "end": 78}]}}, "schema": []}
{"input": "The area ratio of intima to media in the aortic arch was significantly lower in the fermented milk, casein hydrolysate, synthesized VPP, enalapril, and captopril groups than in the control group.", "output": {"entities": {"chemical": [{"text": "enalapril", "start": 137, "end": 146}, {"text": "captopril", "start": 152, "end": 161}]}}, "schema": []}
{"input": "As is common with diets containing VPP and/or IPP, we observed reductions in mRNA expression of inflammatory cytokines, such as interleukin (IL)-6 and IL-1 beta, oxidized low-density lipoprotein receptor, and transcription regulators.", "output": {"entities": {}}, "schema": []}
{"input": "These results suggest that a continuous intake of VPP and IPP might be beneficial for preventing atherosclerosis caused by hypercholesterolemia.", "output": {"entities": {}}, "schema": []}
{"input": "Inhibition of Foodborne Pathogens by Pomegranate Juice.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract Pomegranates have health-promoting benefits because of their polyphenol constituents.", "output": {"entities": {"chemical": [{"text": "polyphenol", "start": 70, "end": 80}]}}, "schema": []}
{"input": "Previous studies have demonstrated the antimicrobial activity of aqueous and organic extracts of pomegranate components and by-products.", "output": {"entities": {}}, "schema": []}
{"input": "We sought to determine the antimicrobial activity against 40 foodborne pathogens representing eight bacterial species using juice itself.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, we sought to determine the synergistic antimicrobial activity between pomegranate juice and other plant products displaying antimicrobial activity.", "output": {"entities": {}}, "schema": []}
{"input": "The antimicrobial activity of pomegranate juice was dependent on the test organism, which varied to highly susceptible (four Gram-positive species) to unaffected (Salmonella and Escherichia coli O157: H7).", "output": {"entities": {}}, "schema": []}
{"input": "Two Gram-negative species, which were inhibited were Helicobacter pylori and Vibrio parahemolyticus.", "output": {"entities": {}}, "schema": []}
{"input": "No synergistic antimicrobial activity was seen between pomegranate and either barberry, oregano, or cranberry.", "output": {"entities": {}}, "schema": []}
{"input": "The antimicrobial activity of pomegranate juice is dependent on the test organism and extraction method.", "output": {"entities": {}}, "schema": []}
{"input": "The sensitivity of H. pylori suggests that pomegranate juice may be an alternative or supplemental treatment for gastric ulcers caused by this organism.", "output": {"entities": {}}, "schema": []}
{"input": "Designed amphiphilic beta-sheet peptides as templates for paraoxon adsorption and detection.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 58, "end": 66}]}}, "schema": []}
{"input": "Amphiphilic peptides were designed to fold into a beta-sheet monolayer structure while presenting the catalytic triad residues of the enzyme, acetylcholinesterase (Glu, His and Ser), to a solution containing the organophosphate, paraoxon.", "output": {"entities": {"chemical": [{"text": "Glu", "start": 164, "end": 167}, {"text": "His", "start": 169, "end": 172}, {"text": "Ser", "start": 177, "end": 180}, {"text": "organophosphate", "start": 212, "end": 227}, {"text": "paraoxon", "start": 229, "end": 237}]}}, "schema": []}
{"input": "Three peptides, in which the catalytic triad residues were arranged in different orders along the strand, were generated to reveal potential differences in interactions with paraoxon as a function of the order of these amino acids.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 174, "end": 182}, {"text": "amino acids", "start": 219, "end": 230}]}}, "schema": []}
{"input": "One additional peptide with amino acids introduced in random order was studied to highlight the contribution of the beta-sheet secondary structure to any interactions with paraoxon.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 28, "end": 39}, {"text": "paraoxon", "start": 172, "end": 180}]}}, "schema": []}
{"input": "Langmuir isotherms, Brewster angle microscope at interfaces and circular dichroism measurements in bulk showed that both the beta-sheet conformation and the order of the amino acids along the strand influenced the interactions of paraoxon with the peptides.", "output": {"entities": {"chemical": [{"text": "amino acids", "start": 170, "end": 181}, {"text": "paraoxon", "start": 230, "end": 238}]}}, "schema": []}
{"input": "Compression isotherm curves, as well as Brewster-angle microscopy images, provided evidence for enhanced adsorption of the paraoxon to the monolayers of peptides which present neighboring Glu and Ser residues along the hydrophilic face of the beta-strand.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 123, "end": 131}, {"text": "Glu", "start": 188, "end": 191}, {"text": "Ser", "start": 196, "end": 199}]}}, "schema": []}
{"input": "Circular dichroism revealed that the peptide most sensitive to interactions with paraoxon was that with the triad residues in the order Glu, Ser and His, which appears to be appropriate for supporting a catalytic mechanism similar to that in acetylcholinesterase enzyme.", "output": {"entities": {"chemical": [{"text": "paraoxon", "start": 81, "end": 89}, {"text": "Glu", "start": 136, "end": 139}, {"text": "Ser", "start": 141, "end": 144}, {"text": "His", "start": 149, "end": 152}]}}, "schema": []}
{"input": "These rationally designed peptides may be further utilized for the development of technologies for organophosphate adsorption and detection.", "output": {"entities": {"chemical": [{"text": "organophosphate", "start": 99, "end": 114}]}}, "schema": []}
{"input": "Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing.", "output": {"entities": {}}, "schema": []}
{"input": "Abstract A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available.", "output": {"entities": {}}, "schema": []}
{"input": "The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane.", "output": {"entities": {}}, "schema": []}
{"input": "The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear.", "output": {"entities": {}}, "schema": []}
{"input": "Four formulations and a control were examined in this study using cidofovir as the model drug.", "output": {"entities": {"chemical": [{"text": "cidofovir", "start": 66, "end": 75}]}}, "schema": []}
{"input": "Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system.", "output": {"entities": {}}, "schema": []}
{"input": "The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system.", "output": {"entities": {}}, "schema": []}
{"input": "Among the formulations investigated, poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions.", "output": {"entities": {"chemical": [{"text": "poly (lactic-co-glycolic acid)", "start": 37, "end": 67}, {"text": "poly (ethylene glycol)", "start": 68, "end": 90}, {"text": "poly (lactic-co-glycolic acid)", "start": 91, "end": 121}, {"text": "cidofovir", "start": 256, "end": 265}]}}, "schema": []}
{"input": "Membrane fusion-competent virus-like proteoliposomes and proteinaceous supported bilayers made directly from cell plasma membranes.", "output": {"entities": {}}, "schema": []}
{"input": "Virus-like particles are useful materials for studying virus-host interactions in a safe manner.", "output": {"entities": {}}, "schema": []}
{"input": "However, the standard production of pseudovirus based on the Vesicular Stomatitis Virus (VSV) backbone is an intricate procedure that requires trained laboratory personnel.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, a new strategy for creating virus-like proteoliposomes (VLPLs) and virus-like supported bilayers (VLSBs) is presented.", "output": {"entities": {}}, "schema": []}
{"input": "This strategy uses a cell blebbing technique to induce the formation of nanoscale vesicles from the plasma membrane of BHK cells expressing the hemagglutinin (HA) fusion protein of influenza X-31.", "output": {"entities": {}}, "schema": []}
{"input": "These vesicles and supported bilayers contain HA and are used to carry out single particle membrane fusion events, monitored using total internal reflection fluorescence microscopy.", "output": {"entities": {}}, "schema": []}
{"input": "The results of these studies show that the VLPLs and VLSBs contain HA proteins that are fully competent to carry out membrane fusion, including the formation of a fusion pore and the release of fluorophores loaded into vesicles.", "output": {"entities": {}}, "schema": []}
{"input": "This new strategy for creating spherical and planar geometry virus-like membranes has many potential applications.", "output": {"entities": {}}, "schema": []}
{"input": "VLPLs could be used to study fusion proteins of virulent viruses in a safe manner, or they could be used as therapeutic delivery particles to transport beneficial proteins co-expressed in the cells to a target cell.", "output": {"entities": {}}, "schema": []}
{"input": "VLSBs could facilitate high throughput screening of antiviral drugs or pathogen-host cell interactions.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of Amylose-Polystyrene Inclusion Complexes by a Facile Preparation Route.", "output": {"entities": {"chemical": [{"text": "Polystyrene", "start": 21, "end": 32}]}}, "schema": []}
{"input": "The formation of amylose-polystyrene inclusion complexes via a novel two-step approach is described.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 25, "end": 36}]}}, "schema": []}
{"input": "In the first-step, styrene was inserted inside the amylose helical cavity, followed by free radical polymerization in the second step.", "output": {"entities": {}}, "schema": []}
{"input": "The inclusion complexes were characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), Ultraviolet Spectroscopy (UV), X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), and Differential Scanning Calorimetry (DSC).", "output": {"entities": {}}, "schema": []}
{"input": "The formation of polystyrene was confirmed by gel Permeation Chromatography (GPC).", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 17, "end": 28}]}}, "schema": []}
{"input": "The molecular weight of polystyrene can be varied by using amylose bearing different molar masses.", "output": {"entities": {"chemical": [{"text": "polystyrene", "start": 24, "end": 35}]}}, "schema": []}
{"input": "The approach described here is general and could be used to synthesis other host-polymer inclusion complexes for which long chains of polymeric guests are difficult to insert into the host cavity.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of Silver Octahedra with Controlled Sizes and Optical Properties via Seed-Mediated Growth.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 13, "end": 19}]}}, "schema": []}
{"input": "Silver octahedra with edge lengths controlled in the range of 20-72 nm were synthesized via seed-mediated growth.", "output": {"entities": {"chemical": [{"text": "Silver", "start": 0, "end": 6}]}}, "schema": []}
{"input": "The key to the success of this synthesis is the use of single-crystal Ag seeds with uniform and precisely controlled sizes to direct the growth and the use of citrate as a selective capping agent for the {111} facets.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 70, "end": 72}, {"text": "citrate", "start": 159, "end": 166}]}}, "schema": []}
{"input": "Our mechanistic studies demonstrated that Ag seeds with both cubic and quasi-spherical shapes could evolve into octahedra.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 42, "end": 44}]}}, "schema": []}
{"input": "For the first time, we were able to precisely control the edge lengths of Ag octahedra below 100 nm, and the lower limit of size could even be pushed down to 20 nm.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 74, "end": 76}]}}, "schema": []}
{"input": "Using the as-obtained Ag octahedra as sacrificial templates, Au nanocages with an octahedral shape and precisely tunable optical properties were synthesized through a galvanic replacement reaction.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 22, "end": 24}, {"text": "Au", "start": 61, "end": 63}]}}, "schema": []}
{"input": "Such hollow nanostructures are promising candidates for a broad range of applications related to optics, catalysis, and biomedicine.", "output": {"entities": {}}, "schema": []}
{"input": "Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes.", "output": {"entities": {"chemical": [{"text": "Zirconium", "start": 24, "end": 33}, {"text": "Aminoalkenes", "start": 59, "end": 71}]}}, "schema": []}
{"input": "Aminoalkenes are catalytically cyclized in the presence of cyclopentadienylbis (oxazolinyl) borato group 4 complexes {PhB (C5H4) (Ox (R)) 2} M (NMe2) 2 (M = Ti, Zr, Hf; Ox (R) = 4, 4-dimethyl-2-oxazoline, 4S-isopropyl-5, 5-dimethyl-2-oxazoline, 4S-tert-butyl-2-oxazoline) at room temperature and below, affording five-, six-, and seven-membered N-heterocyclic amines with enantiomeric excesses of > 90% in many cases and up to 99%.", "output": {"entities": {"chemical": [{"text": "Aminoalkenes", "start": 0, "end": 12}, {"text": "cyclopentadienylbis (oxazolinyl) borato", "start": 59, "end": 98}, {"text": "{PhB (C5H4) (Ox (R)) 2} M (NMe2) 2", "start": 117, "end": 151}, {"text": "Ti", "start": 157, "end": 159}, {"text": "Zr", "start": 161, "end": 163}, {"text": "Hf", "start": 165, "end": 167}, {"text": "Ox (R)", "start": 169, "end": 175}, {"text": "4, 4-dimethyl-2-oxazoline", "start": 178, "end": 203}, {"text": "4S-isopropyl-5, 5-dimethyl-2-oxazoline", "start": 205, "end": 243}, {"text": "4S-tert-butyl-2-oxazoline", "start": 245, "end": 270}, {"text": "N-heterocyclic amines", "start": 345, "end": 366}]}}, "schema": []}
{"input": "Mechanistic investigations of this highly selective system employed synthetic tests, kinetics, and stereochemistry.", "output": {"entities": {}}, "schema": []}
{"input": "Secondary aminopentene cyclizations require a primary amine (1-2 equiv vs catalyst).", "output": {"entities": {"chemical": [{"text": "Secondary aminopentene", "start": 0, "end": 22}, {"text": "primary amine", "start": 46, "end": 59}]}}, "schema": []}
{"input": "Aminoalkenes are unchanged in the presence of a zirconium monoamido complex {PhB (C5H4) (Ox (4S-iPr, Me2)) 2} Zr (NMe2) Cl or a cyclopentadienylmono (oxazolinyl) borato zirconium diamide {Ph2B (C5H4) (Ox (4S-iPr, Me2))} Zr (NMe2) 2.", "output": {"entities": {"chemical": [{"text": "Aminoalkenes", "start": 0, "end": 12}, {"text": "zirconium monoamido", "start": 48, "end": 67}, {"text": "{PhB (C5H4) (Ox (4S-iPr, Me2)) 2} Zr (NMe2) Cl", "start": 76, "end": 122}, {"text": "cyclopentadienylmono (oxazolinyl) borato zirconium diamide {Ph2B (C5H4) (Ox (4S-iPr, Me2))} Zr (NMe2) 2", "start": 128, "end": 231}]}}, "schema": []}
{"input": "Plots of initial rate versus [substrate] show a rate dependence that evolves from first-order at low concentration to zero-order at high concentration, and this is consistent with a reversible substrate-catalyst interaction preceding an irreversible step.", "output": {"entities": {}}, "schema": []}
{"input": "Primary kinetic isotope effects from substrate conversion measurements (k' obs ((H))/k' obs ((D)) = 3. 3 +/- 0. 3) and from initial rate analysis (k2 ((H))/k2 ((D)) = 2. 3 +/- 0. 4) indicate that a N-H bond is broken in the turnover-limiting and irreversible step of the catalytic cycle.", "output": {"entities": {"chemical": [{"text": "N-H", "start": 198, "end": 201}]}}, "schema": []}
{"input": "Asymmetric hydroamination/cyclization of N-deutero-aminoalkenes provides products with higher optical purities than obtained with N-proteo-aminoalkenes.", "output": {"entities": {"chemical": [{"text": "N-deutero-aminoalkenes", "start": 41, "end": 63}, {"text": "N-proteo-aminoalkenes", "start": 130, "end": 151}]}}, "schema": []}
{"input": "Transition state theory, applied to the rate constant k2 that characterizes the irreversible step, provides activation parameters consistent with a highly organized transition state (Delta S (|=) =-43 (7) cal. mol (-1) K (-1)) and a remarkably low enthalpic barrier (Delta H (|=) = 6. 7 (2) kcal. mol (-1)).", "output": {"entities": {}}, "schema": []}
{"input": "A six-centered, concerted transition state for C-N and C-H bond formation and N-H bond cleavage involving two amidoalkene ligands is proposed as most consistent with the current data.", "output": {"entities": {"chemical": [{"text": "C-N", "start": 47, "end": 50}, {"text": "C-H", "start": 55, "end": 58}, {"text": "N-H", "start": 78, "end": 81}, {"text": "amidoalkene", "start": 110, "end": 121}]}}, "schema": []}
{"input": "Elucidation of the biochemical basis for a clinical drug-drug interaction between atorvastatin and 5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid (CP-778 875), a subtype selective agonist of the peroxisome proliferator-activated receptor alpha.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 82, "end": 94}, {"text": "5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid", "start": 99, "end": 170}, {"text": "CP-778 875", "start": 172, "end": 182}]}}, "schema": []}
{"input": "Abstract 1. 5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid (CP-778 875), an agonist of the peroxisome proliferator-activated receptor alpha, has been evaluated in the clinic to treat dyslipidemia and type 2 diabetes mellitus.", "output": {"entities": {"chemical": [{"text": "5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid", "start": 12, "end": 83}, {"text": "CP-778 875", "start": 85, "end": 95}]}}, "schema": []}
{"input": "Herein, we investigate the effect of CP-778 875 on the pharmacokinetics of atorvastatin acid and its metabolites in humans.", "output": {"entities": {"chemical": [{"text": "CP-778 875", "start": 37, "end": 47}, {"text": "atorvastatin acid", "start": 75, "end": 92}]}}, "schema": []}
{"input": "2. The study incorporated a fixed-sequence design conducted in two groups.", "output": {"entities": {}}, "schema": []}
{"input": "Group A was designed to estimate the effects of multiple doses of CP-778 875 on the single dose pharmacokinetics of atorvastatin.", "output": {"entities": {"chemical": [{"text": "CP-778 875", "start": 66, "end": 76}, {"text": "atorvastatin", "start": 116, "end": 128}]}}, "schema": []}
{"input": "Subjects in group A (n = 26) received atorvastatin (40 mg) on days 1 and 9 and CP-778 875 (1. 0 mg QD) on days 5-12.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 38, "end": 50}, {"text": "CP-778 875", "start": 79, "end": 89}]}}, "schema": []}
{"input": "Group B was designed to examine the effects of multiple doses of atorvastatin on the single dose pharmacokinetics of CP-778 875.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 65, "end": 77}, {"text": "CP-778 875", "start": 117, "end": 127}]}}, "schema": []}
{"input": "Subjects in group B (n = 29) received CP-778 875 (0. 3 mg) on days 1 and 9 and atorvastatin (40 mg QD) on days 5-12.", "output": {"entities": {"chemical": [{"text": "CP-778 875", "start": 38, "end": 48}, {"text": "atorvastatin", "start": 79, "end": 91}]}}, "schema": []}
{"input": "3. Mean maximum serum concentration (Cmax) and area under the curve of atorvastatin were increased by 45% and 20%, respectively, upon co-administration with CP-778 875.", "output": {"entities": {"chemical": [{"text": "atorvastatin", "start": 71, "end": 83}, {"text": "CP-778 875", "start": 157, "end": 167}]}}, "schema": []}
{"input": "Statistically significant increases in the systemic exposure of ortho-and para-hydroxyatorvastatin were also observed upon concomitant dosing with CP-778 875.", "output": {"entities": {"chemical": [{"text": "ortho-and para-hydroxyatorvastatin", "start": 64, "end": 98}, {"text": "CP-778 875", "start": 147, "end": 157}]}}, "schema": []}
{"input": "CP-778 875 pharmacokinetics, however, were not impacted upon concomitant dosing with atorvastatin.", "output": {"entities": {"chemical": [{"text": "CP-778 875", "start": 0, "end": 10}, {"text": "atorvastatin", "start": 85, "end": 97}]}}, "schema": []}
{"input": "4. Inhibition of organic anion transporting polypeptide 1B1 by CP-778 875 (IC50 = 2. 14 +/- 0. 40 mu M) could be the dominant cause of the pharmacokinetic interaction as CP-778 875 did not exhibit significant inhibition of cytochrome P450 3A4/3A5, multidrug resistant protein 1 or breast cancer resistant protein, which are also involved in the hepatobiliary disposition of atorvastatin.", "output": {"entities": {"chemical": [{"text": "CP-778 875", "start": 63, "end": 73}, {"text": "CP-778 875", "start": 170, "end": 180}, {"text": "atorvastatin", "start": 374, "end": 386}]}}, "schema": []}
{"input": "Simultaneous determination by LC-MS/MS of 25-methoxydammarane-3 beta, 12 beta, 20-triol epimers and active metabolites in rat plasma after intravenous administration.", "output": {"entities": {"chemical": [{"text": "25-methoxydammarane-3 beta, 12 beta, 20-triol", "start": 42, "end": 87}]}}, "schema": []}
{"input": "Abstract 1.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacokinetics of the 25-OCH3-PPD epimers and active metabolites in rat plasma after a single intravenous (i. v.) administration were studied by a rapid, selective and sensitive UPLC-MS/MS method.", "output": {"entities": {"chemical": [{"text": "25-OCH3-PPD", "start": 28, "end": 39}]}}, "schema": []}
{"input": "2.", "output": {"entities": {}}, "schema": []}
{"input": "Chromatographic separation was performed on an Acquity UPLC with Agela C18 column, and the solvents of 5 mM ammonium acetate (pH 7. 8)-acetonitrile (65: 35, v/v) were used as mobile phase for elution.", "output": {"entities": {"chemical": [{"text": "ammonium acetate", "start": 108, "end": 124}, {"text": "acetonitrile", "start": 135, "end": 147}]}}, "schema": []}
{"input": "The quantification was performed with the transitions of m/z 493. 5 --> 475. 5 for 20 (R, S)-25-OCH3-PPD, m/z 479. 5 --> 461. 5 for 20 (R, S)-25-OH-PPD.", "output": {"entities": {"chemical": [{"text": "20 (R, S)-25-OCH3-PPD", "start": 83, "end": 104}, {"text": "20 (R, S)-25-OH-PPD", "start": 132, "end": 151}]}}, "schema": []}
{"input": "The Lower Limit Of Quantitation (LLOQ) was 20. 0 ng mL (-1) for 20 (R, S)-25-OCH3-PPD, 2. 0 ng mL (-1) for 20 (R, S)-25-OH-PPD in the plasma samples assay.", "output": {"entities": {"chemical": [{"text": "20 (R, S)-25-OCH3-PPD", "start": 64, "end": 85}, {"text": "20 (R, S)-25-OH-PPD", "start": 107, "end": 126}]}}, "schema": []}
{"input": "3.", "output": {"entities": {}}, "schema": []}
{"input": "The pharmacokinetic parameters of AUC, t1/2 and MRT had no difference between 20 (R)-and (S)-25-OCH3-PPD, but S-epimer has a lower plasma clearance compared to the R-isomer.", "output": {"entities": {"chemical": [{"text": "20 (R)-and (S)-25-OCH3-PPD", "start": 78, "end": 104}]}}, "schema": []}
{"input": "The active metabolite 20 (S)-25-OH-PPD showed significantly higher AUC, MRT and a longer half-life than that of 20 (R)-25-OH-PPD.", "output": {"entities": {"chemical": [{"text": "20 (S)-25-OH-PPD", "start": 22, "end": 38}, {"text": "20 (R)-25-OH-PPD", "start": 112, "end": 128}]}}, "schema": []}
{"input": "These assay results are necessary for the evaluation of the pharmacokinetic behavior of 25-methoxydammarane-3 beta, 12 beta, 20-triol in vivo.", "output": {"entities": {"chemical": [{"text": "25-methoxydammarane-3 beta, 12 beta, 20-triol", "start": 88, "end": 133}]}}, "schema": []}
{"input": "Spatial memory deficits in maternal iron deficiency paradigms are associated with altered glucocorticoid levels.", "output": {"entities": {"chemical": [{"text": "iron", "start": 36, "end": 40}]}}, "schema": []}
{"input": "\" The goal of this study was to examine the effect of maternal iron deficiency on the developing hippocampus in order to define a developmental window for this effect, and to see whether iron deficiency causes changes in glucocorticoid levels.", "output": {"entities": {"chemical": [{"text": "iron", "start": 63, "end": 67}, {"text": "iron", "start": 187, "end": 191}]}}, "schema": []}
{"input": "The study was carried out using pre-natal, post-natal, and pre + post-natal iron deficiency paradigm.", "output": {"entities": {"chemical": [{"text": "iron", "start": 76, "end": 80}]}}, "schema": []}
{"input": "Iron deficient pregnant dams and their pups displayed elevated corticosterone which, in turn, differentially affected glucocorticoid receptor (GR) expression in the CA1 and the dentate gyrus.", "output": {"entities": {"chemical": [{"text": "Iron", "start": 0, "end": 4}, {"text": "corticosterone", "start": 63, "end": 77}]}}, "schema": []}
{"input": "Brain Derived Neurotrophic Factor (BDNF) was reduced in the hippocampi of pups following elevated corticosterone levels.", "output": {"entities": {"chemical": [{"text": "corticosterone", "start": 98, "end": 112}]}}, "schema": []}
{"input": "Reduced neurogenesis at P7 was seen in pups born to iron deficient mothers, and these pups had reduced numbers of hippocampal pyramidal and granule cells as adults.", "output": {"entities": {"chemical": [{"text": "iron", "start": 52, "end": 56}]}}, "schema": []}
{"input": "Hippocampal subdivision volumes also were altered.", "output": {"entities": {}}, "schema": []}
{"input": "The structural and molecular defects in the pups were correlated with radial arm maze performance; reference memory function was especially affected.", "output": {"entities": {}}, "schema": []}
{"input": "Pups from dams that were iron deficient throughout pregnancy and lactation displayed the complete spectrum of defects, while pups from dams that were iron deficient only during pregnancy or during lactation displayed subsets of defects.", "output": {"entities": {"chemical": [{"text": "iron", "start": 25, "end": 29}, {"text": "iron", "start": 150, "end": 154}]}}, "schema": []}
{"input": "These findings show that maternal iron deficiency is associated with altered levels of corticosterone and GR expression, and with spatial memory deficits in their pups. \"", "output": {"entities": {"chemical": [{"text": "iron", "start": 34, "end": 38}, {"text": "corticosterone", "start": 87, "end": 101}]}}, "schema": []}
{"input": "An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine: Thiamine and thiamine pyrophosphate effects on cisplatin neurotoxicity.", "output": {"entities": {"chemical": [{"text": "thiamine pyrophosphate", "start": 34, "end": 56}, {"text": "cisplatin", "start": 60, "end": 69}, {"text": "thiamine", "start": 144, "end": 152}, {"text": "Thiamine", "start": 154, "end": 162}, {"text": "thiamine pyrophosphate", "start": 167, "end": 189}, {"text": "cisplatin", "start": 201, "end": 210}]}}, "schema": []}
{"input": "This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine.", "output": {"entities": {"chemical": [{"text": "thiamine pyrophosphate", "start": 39, "end": 61}, {"text": "TPP", "start": 63, "end": 66}, {"text": "cisplatin", "start": 151, "end": 160}, {"text": "thiamine", "start": 184, "end": 192}]}}, "schema": []}
{"input": "Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses.", "output": {"entities": {"chemical": [{"text": "Cisplatin", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Oxidative stress is considered responsible for cisplatin toxicity.", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 47, "end": 56}]}}, "schema": []}
{"input": "Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD).", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 24, "end": 33}, {"text": "thio barbituric acid", "start": 105, "end": 125}, {"text": "glutathione", "start": 253, "end": 264}, {"text": "GSH", "start": 266, "end": 269}, {"text": "superoxide", "start": 275, "end": 285}]}}, "schema": []}
{"input": "TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels.", "output": {"entities": {"chemical": [{"text": "TPP", "start": 0, "end": 3}, {"text": "cisplatin", "start": 103, "end": 112}, {"text": "thiamine", "start": 146, "end": 154}, {"text": "TPP", "start": 168, "end": 171}, {"text": "GSH", "start": 196, "end": 199}]}}, "schema": []}
{"input": "In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1. 7 +/- 0. 12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0. 97 +/- 0. 03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1. 55 +/- 0. 11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group.", "output": {"entities": {"chemical": [{"text": "8-Gua", "start": 26, "end": 31}, {"text": "guanine", "start": 33, "end": 40}, {"text": "8-hydroxyl guanine", "start": 87, "end": 105}, {"text": "8-OH Gua", "start": 107, "end": 115}, {"text": "Gua", "start": 121, "end": 124}, {"text": "cisplatin", "start": 172, "end": 181}, {"text": "Gua", "start": 218, "end": 221}, {"text": "Gua", "start": 226, "end": 229}, {"text": "thiamine pyrophosphate", "start": 237, "end": 259}, {"text": "8-OH Gua", "start": 297, "end": 305}, {"text": "Gua", "start": 310, "end": 313}, {"text": "thiamine", "start": 321, "end": 329}]}}, "schema": []}
{"input": "These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.", "output": {"entities": {"chemical": [{"text": "thiamine pyrophosphate", "start": 24, "end": 46}, {"text": "cisplatin", "start": 98, "end": 107}, {"text": "thiamine", "start": 156, "end": 164}]}}, "schema": []}
{"input": "Effect of subacute exposure to silver nanoparticle on some hematological and plasma biochemical indices in silver carp (Hypophthalmichthys molitrix).", "output": {"entities": {"chemical": [{"text": "silver", "start": 31, "end": 37}, {"text": "silver", "start": 107, "end": 113}]}}, "schema": []}
{"input": "The use of silver nanoparticles (Ag-NPs) is rapidly increasing, but there are limited data on their effects on the aquatic environment.", "output": {"entities": {"chemical": [{"text": "silver", "start": 11, "end": 17}, {"text": "Ag", "start": 33, "end": 35}]}}, "schema": []}
{"input": "The present study aimed to determine the acute toxicity and evaluate the effect of subacute concentrations of Ag-NPs (Nanocid (R): average particle size of 61 nm) on hematological and plasma biochemical indices of silver carp, Hypophthalmichthys molitrix, after 3, 7 and 14 days.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 110, "end": 112}, {"text": "Nanocid", "start": 118, "end": 125}, {"text": "silver", "start": 214, "end": 220}]}}, "schema": []}
{"input": "The 24-, 48-, 72-and 96-h median lethal concentration (LC50) values of Nanocid for silver carp were estimated at 0. 810, 0. 648, 0. 383 and 0. 202 mg/L, respectively; 20% and 10% of the 96-h LC50 values (0. 04 and 0. 02 mg/L) were selected for subacute study.", "output": {"entities": {"chemical": [{"text": "Nanocid", "start": 71, "end": 78}, {"text": "silver", "start": 83, "end": 89}]}}, "schema": []}
{"input": "Red blood cell (RBC) count, hemoglobin (Hb) count and hematocrit (Hct) level were significantly reduced at both concentrations tested (p < 0. 05).", "output": {"entities": {}}, "schema": []}
{"input": "White blood cell (WBC), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), cortisol and glucose levels in Nanocid-treated groups were significantly higher than the controlled group at experimental periods (p < 0. 05).", "output": {"entities": {"chemical": [{"text": "cortisol", "start": 109, "end": 117}, {"text": "glucose", "start": 122, "end": 129}, {"text": "Nanocid", "start": 140, "end": 147}]}}, "schema": []}
{"input": "In conclusion, Ag-NPs intoxication resulted in erythrocyte reduction, hematological disturbances, leucocytosis and stress response in silver carp and offered a simple tool to evaluate toxicity-derived alterations.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 15, "end": 17}, {"text": "silver", "start": 134, "end": 140}]}}, "schema": []}
{"input": "Non-classic congenital adrenal hyperplasia.", "output": {"entities": {}}, "schema": []}
{"input": "Non-classic or late-onset congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Reported prevalence is approximately 1 in 1000.", "output": {"entities": {}}, "schema": []}
{"input": "Affected individuals typically present due to signs and symptoms of androgen excess.", "output": {"entities": {"chemical": [{"text": "androgen", "start": 68, "end": 76}]}}, "schema": []}
{"input": "The purpose of this review is to provide current information regarding the pathophysiology, molecular genetics, and management of this common disorder.", "output": {"entities": {}}, "schema": []}
{"input": "The treatment of NCAH needs to be directed towards the symptoms.", "output": {"entities": {}}, "schema": []}
{"input": "For affected children, goals of treatment include normal linear growth velocity, normal rate of skeletal maturation, \" on-time \" puberty.", "output": {"entities": {}}, "schema": []}
{"input": "For affected adolescent and adult women, goals of treatment include regular menstrual cycles, prevention or progression of hirsutism and acne, and fertility.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.", "output": {"entities": {}}, "schema": []}
{"input": "Calcium pathways such as cAMP modulate clothianidin action through activation of alpha-bungarotoxin-sensitive and-insensitive nicotinic acetylcholine receptors.", "output": {"entities": {"chemical": [{"text": "Calcium", "start": 0, "end": 7}, {"text": "cAMP", "start": 25, "end": 29}, {"text": "clothianidin", "start": 39, "end": 51}, {"text": "acetylcholine", "start": 136, "end": 149}]}}, "schema": []}
{"input": "Clothianidin is a neonicotinoid insecticide developed in the early 2000s.", "output": {"entities": {"chemical": [{"text": "Clothianidin", "start": 0, "end": 12}]}}, "schema": []}
{"input": "We have recently demonstrated that it was a full agonist of alpha-bungarotoxin-sensitive and-insensitive nicotinic acetylcholine receptors expressed in the cockroach dorsal unpaired median neurons.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 115, "end": 128}]}}, "schema": []}
{"input": "Clothianidin was able to act as an agonist of imidacloprid-insensitive nAChR2 receptor and internal regulation of cAMP concentration modulated nAChR2 sensitivity to clothianidin.", "output": {"entities": {"chemical": [{"text": "Clothianidin", "start": 0, "end": 12}, {"text": "imidacloprid", "start": 46, "end": 58}, {"text": "cAMP", "start": 114, "end": 118}, {"text": "clothianidin", "start": 165, "end": 177}]}}, "schema": []}
{"input": "In the present study, we demonstrated that cAMP modulated the agonist action of clothianidin via alpha-bungarotoxin-sensitive and insensitive receptors.", "output": {"entities": {"chemical": [{"text": "cAMP", "start": 43, "end": 47}, {"text": "clothianidin", "start": 80, "end": 92}]}}, "schema": []}
{"input": "Clothianidin-induced current-voltage curves were dependent to clothianidin concentrations.", "output": {"entities": {"chemical": [{"text": "Clothianidin", "start": 0, "end": 12}, {"text": "clothianidin", "start": 62, "end": 74}]}}, "schema": []}
{"input": "At 10 mu M clothianidin, increasing cAMP concentration induced a linear current-voltage curve.", "output": {"entities": {"chemical": [{"text": "clothianidin", "start": 11, "end": 23}, {"text": "cAMP", "start": 36, "end": 40}]}}, "schema": []}
{"input": "Clothianidin effects were blocked by 0. 5 mu M alpha-bungarotoxin suggesting that cAMP modulation occurred through alpha-bungarotoxin-sensitive receptors.", "output": {"entities": {"chemical": [{"text": "Clothianidin", "start": 0, "end": 12}, {"text": "cAMP", "start": 82, "end": 86}]}}, "schema": []}
{"input": "At 1mM clothianidin, cAMP effects were associated to alpha-bungarotoxin-insensitive receptors because clothianidin-induced currents were blocked by 5 mu M mecamylamine and 20 mu M d-tubocurarine.", "output": {"entities": {"chemical": [{"text": "clothianidin", "start": 7, "end": 19}, {"text": "cAMP", "start": 21, "end": 25}, {"text": "clothianidin", "start": 102, "end": 114}, {"text": "mecamylamine", "start": 155, "end": 167}, {"text": "d-tubocurarine", "start": 180, "end": 194}]}}, "schema": []}
{"input": "In addition, we found that application of 1mM clothianidin induced a strong increase of intracellular calcium concentration.", "output": {"entities": {"chemical": [{"text": "clothianidin", "start": 46, "end": 58}, {"text": "calcium", "start": 102, "end": 109}]}}, "schema": []}
{"input": "These data reinforced the finding that calcium pathways including cAMP modulated clothianidin action on insect nicotinic acetylcholine receptors.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 39, "end": 46}, {"text": "cAMP", "start": 66, "end": 70}, {"text": "clothianidin", "start": 81, "end": 93}, {"text": "acetylcholine", "start": 121, "end": 134}]}}, "schema": []}
{"input": "We proposed that intracellular calcium pathways such as cAMP could be a target to modulate the mode of action of neonicotinoid insecticides.", "output": {"entities": {"chemical": [{"text": "calcium", "start": 31, "end": 38}, {"text": "cAMP", "start": 56, "end": 60}]}}, "schema": []}
{"input": "Immunoregulatory effects of Glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4 (+) CD25 (+) Foxp3 (+) regulatory T cells in ovalbumin-sensitized mice.", "output": {"entities": {"chemical": [{"text": "Glycyrrhizic acid", "start": 28, "end": 45}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra), and has been found to be associated with multiple therapeutic properties.", "output": {"entities": {"chemical": [{"text": "Glycyrrhizic acid", "start": 32, "end": 49}]}}, "schema": []}
{"input": "AIM OF THE STUDY: In this study, we investigated immunoregulatory effects of glycyrrhizic acid on anti-asthmatic effects and underlying mechanisms.", "output": {"entities": {"chemical": [{"text": "glycyrrhizic acid", "start": 77, "end": 94}]}}, "schema": []}
{"input": "MATERIALS AND METHODS: Asthma model was established by ovalbumin-induced.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2mg/kg) and GA (10mg/kg, 20mg/kg, 40mg/kg).", "output": {"entities": {"chemical": [{"text": "dexamethasone", "start": 86, "end": 99}]}}, "schema": []}
{"input": "Airway resistance (Raw) were measured by the forced oscillation technique, histological studies were evaluated by The hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and CD4 (+) CD25 (+) Foxp3 (+) regulatory T cells (Tregs) was evaluated by Flow Cytometry (FCM), the forkhead/winged helix transcription factor (Foxp3) was evaluated by western blotting.", "output": {"entities": {"chemical": [{"text": "hematoxylin", "start": 118, "end": 129}, {"text": "eosin", "start": 134, "end": 139}]}}, "schema": []}
{"input": "RESULTS: Our study demonstrated that, compared with model group, GA inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-gamma level in bronchoalveolar lavage fluid; histological studies demonstrated that GA substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue compared with model group.", "output": {"entities": {}}, "schema": []}
{"input": "Flow cytometry studies demonstrated that GA substantially enhanced Tregs compared with model group.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: These findings suggest that GA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.", "output": {"entities": {}}, "schema": []}
{"input": "Electronic structure analysis of multistate reactivity in transition metal catalyzed reactions: the case of C-H bond activation by non-heme iron (iv)-oxo cores.", "output": {"entities": {"chemical": [{"text": "C-H", "start": 108, "end": 111}]}}, "schema": []}
{"input": "This perspective discusses the principles of the multistate scenario often encountered in transition metal catalyzed reactions, and is organized as follows.", "output": {"entities": {}}, "schema": []}
{"input": "First, several important theoretical concepts (physical versus formal oxidation states, orbital interactions, use of (spin) natural and corresponding orbitals, exchange enhanced reactivity and the connection between valence bond and molecular orbital based electronic structure analysis) are presented.", "output": {"entities": {}}, "schema": []}
{"input": "These concepts are then used to analyze the electronic structure changes occurring in the reaction of C-H bond oxidation by Fe (IV) oxo species.", "output": {"entities": {"chemical": [{"text": "C-H", "start": 102, "end": 105}, {"text": "Fe (IV) oxo", "start": 124, "end": 135}]}}, "schema": []}
{"input": "The analysis reveals that the energy separation and the overlap between the electron donating orbitals and electron accepting orbitals of the Fe (IV) oxo complexes dictate the reaction stereochemistry, and that the manner in which the exchange interaction changes depends on the identity of these orbitals.", "output": {"entities": {"chemical": [{"text": "Fe (IV) oxo", "start": 142, "end": 153}]}}, "schema": []}
{"input": "The electronic reorganization of the Fe (IV) oxo species during the reaction is thoroughly analyzed and it is shown that the Fe (IV) oxo reactant develops oxyl radical character, which interacts effectively with the sigma CH orbital of the alkane.", "output": {"entities": {"chemical": [{"text": "Fe (IV) oxo", "start": 37, "end": 48}, {"text": "Fe (IV) oxo", "start": 125, "end": 136}, {"text": "oxyl", "start": 155, "end": 159}, {"text": "CH", "start": 222, "end": 224}, {"text": "alkane", "start": 240, "end": 246}]}}, "schema": []}
{"input": "The factors that determine the energy barrier for the reaction are discussed in terms of molecular orbital and valence bond concepts.", "output": {"entities": {}}, "schema": []}
{"input": "First principles intensity calculations of the methane rovibrational spectra in the infrared up to 9300 cm (-1.)", "output": {"entities": {"chemical": [{"text": "methane", "start": 47, "end": 54}]}}, "schema": []}
{"input": "We report global calculations of rovibrational spectra and dipole transition intensities of methane using our recent ab initio dipole moment and potential surfaces [Nikitin et al., Chem. Phys. Lett., 2011, 501, 179; 2013, 565, 5].", "output": {"entities": {"chemical": [{"text": "methane", "start": 92, "end": 99}]}}, "schema": []}
{"input": "For the full symmetry account, a recently published variational tensor formalism in normal modes [Rey et al., J. Chem. Phys., 2012, 136, 244106] is applied, the convergence of high-J calculations being improved by the use of vibrational eigenfunctions to make a compressed basis set for solving the rovibrational problem.", "output": {"entities": {}}, "schema": []}
{"input": "Comparisons of theoretical predictions up to J = 25 for various complex polyads of methane involving strongly coupled vibration-rotation bands support the validity of this new approach.", "output": {"entities": {"chemical": [{"text": "methane", "start": 83, "end": 90}]}}, "schema": []}
{"input": "For the first time, positions and line intensities at 80 K and 296 K are shown to be in excellent agreement with raw experimental data, even for high energy ranges.", "output": {"entities": {}}, "schema": []}
{"input": "The theoretical predictions also correctly describe the isotopic effects in line positions and intensities due to the CH4 --> CD4 substitution which is considered as the test for the method.", "output": {"entities": {"chemical": [{"text": "CH4", "start": 118, "end": 121}, {"text": "CD4", "start": 126, "end": 129}]}}, "schema": []}
{"input": "This work is a first step toward the theoretical interpretation of numerous methane bands which remain still unassigned and detailed line-by-line absorption/emission spectra analyses for atmospheric and planetological applications.", "output": {"entities": {"chemical": [{"text": "methane", "start": 76, "end": 83}]}}, "schema": []}
{"input": "A Structural Snapshot of Cytochrome P450 2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States.", "output": {"entities": {"chemical": [{"text": "Paroxetine", "start": 61, "end": 71}]}}, "schema": []}
{"input": "An X-ray crystal structure of cytochrome P450 2B4 in complex with the drug paroxetine was solved at 2. 14 A resolution.", "output": {"entities": {"chemical": [{"text": "paroxetine", "start": 75, "end": 85}]}}, "schema": []}
{"input": "The structure revealed a conformation intermediate to that of the recently solved complex with amlodipine and of the more compact complex with 4-(4-chlorophenyl) imidazole in terms of the placement of the F-G cassette.", "output": {"entities": {"chemical": [{"text": "amlodipine", "start": 95, "end": 105}, {"text": "4-(4-chlorophenyl) imidazole", "start": 143, "end": 171}]}}, "schema": []}
{"input": "Moreover, the comparison of the new structure with 15 previously solved structures of P450 2B4 revealed some new insights into determinants of active site size and shape.", "output": {"entities": {}}, "schema": []}
{"input": "The 2B4-paroxetine structure is nearly superimposable on a previously solved closed structure in a ligand free state.", "output": {"entities": {"chemical": [{"text": "paroxetine", "start": 8, "end": 18}]}}, "schema": []}
{"input": "Despite the overall conformational similarity among multiple closed structures, the active site cavity volume of the paroxetine complex is enlarged.", "output": {"entities": {"chemical": [{"text": "paroxetine", "start": 117, "end": 127}]}}, "schema": []}
{"input": "Further analysis of the accessible space and binding pocket near the heme reveals a new sub-chamber that resulted from the movement of secondary structural elements and rearrangements of active site side chains.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, the results from the comparison of all the 16 structures of P450 2B4 demonstrate a cluster of protein conformations that were observed in the presence or absence of various ligands.", "output": {"entities": {}}, "schema": []}
{"input": "Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1 in Cells.", "output": {"entities": {"chemical": [{"text": "Pyridinylquinazolines", "start": 0, "end": 21}, {"text": "Methionine", "start": 48, "end": 58}]}}, "schema": []}
{"input": "Methionine aminopeptidases (MetAPs), which remove the initiator methionine from nascent peptides, are essential in all organisms.", "output": {"entities": {"chemical": [{"text": "Methionine", "start": 0, "end": 10}, {"text": "methionine", "start": 64, "end": 74}]}}, "schema": []}
{"input": "While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation.", "output": {"entities": {}}, "schema": []}
{"input": "Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (1-4), but all of them failed to inhibit cellular HsMetAP1.", "output": {"entities": {}}, "schema": []}
{"input": "Using Mn (II) or Zn (II) to activate HsMetAP1, we found that 1-4 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co (II).", "output": {"entities": {"chemical": [{"text": "Mn (II)", "start": 6, "end": 13}, {"text": "Zn (II)", "start": 17, "end": 24}, {"text": "Co (II)", "start": 180, "end": 187}]}}, "schema": []}
{"input": "In an effort to seek Co (II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl) quinazoline core has been discovered.", "output": {"entities": {"chemical": [{"text": "Co (II)", "start": 21, "end": 28}, {"text": "2-(pyridin-2-yl) quinazoline", "start": 91, "end": 119}]}}, "schema": []}
{"input": "Many compounds in this class potently and selectively inhibited HsMetAP1 without Co (II).", "output": {"entities": {"chemical": [{"text": "Co (II)", "start": 81, "end": 88}]}}, "schema": []}
{"input": "Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells.", "output": {"entities": {}}, "schema": []}
{"input": "This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells.", "output": {"entities": {}}, "schema": []}
{"input": "Single Ion Channel Recordings with CMOS-Anchored Lipid Membranes.", "output": {"entities": {}}, "schema": []}
{"input": "We present single-ion-channel recordings performed with biomimetic lipid membranes which are directly attached to the surface of a complementary metal-oxide-semiconductor (CMOS) preamplifier chip.", "output": {"entities": {"chemical": [{"text": "metal-oxide", "start": 145, "end": 156}]}}, "schema": []}
{"input": "With this system we resolve single-channel currents from several types of bacterial ion channels, including fluctuations of a single alamethicin channel at a bandwidth of 1 MHz which represent the fastest single-ion-channel recordings reported to date.", "output": {"entities": {}}, "schema": []}
{"input": "The platform is also used for high-resolution alpha-hemolysin nanopore recordings.", "output": {"entities": {}}, "schema": []}
{"input": "These results illustrate the high signal fidelity, fine temporal resolution, small geometry, and multiplexed integration which can be achieved by leveraging integrated semiconductor platforms for advanced ion channel interfaces.", "output": {"entities": {}}, "schema": []}
{"input": "Indazole-based Potent and Cell-Active Mps1 Kinase Inhibitors: Rational Design from Pan-Kinase Inhibitor Anthrapyrazolone (SP600125).", "output": {"entities": {"chemical": [{"text": "Indazole", "start": 0, "end": 8}, {"text": "Anthrapyrazolone", "start": 104, "end": 120}, {"text": "SP600125", "start": 122, "end": 130}]}}, "schema": []}
{"input": "Monopolar spindle 1 (Mps1) is essential for centrosome duplication, the spindle assembly check point, and the maintenance of chromosomal instability.", "output": {"entities": {}}, "schema": []}
{"input": "Mps1 is highly expressed in cancer cells, and its expression levels correlate with the histological grades of cancers.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, selective Mps1 inhibitors offer an attractive opportunity for the development of novel cancer therapies.", "output": {"entities": {}}, "schema": []}
{"input": "To design novel Mps1 inhibitors, we utilized the pan-kinase inhibitor anthrapyrazolone (4, SP600125) and its crystal structure bound to JNK1.", "output": {"entities": {"chemical": [{"text": "anthrapyrazolone", "start": 70, "end": 86}, {"text": "SP600125", "start": 91, "end": 99}]}}, "schema": []}
{"input": "Our design efforts led to the identification of indazole-based lead 6 with an Mps1 IC50 value of 498 nM.", "output": {"entities": {"chemical": [{"text": "indazole", "start": 48, "end": 56}]}}, "schema": []}
{"input": "Optimization of the 3-and 6-positions on the indazole core of 6 resulted in 23c with improved Mps1 activity (IC50 = 3. 06 nM).", "output": {"entities": {"chemical": [{"text": "indazole", "start": 45, "end": 53}]}}, "schema": []}
{"input": "Finally, application of structure-based design using the X-ray structure of 23d bound to Mps1 culminated in the discovery of 32a and 32b with improved potency for cellular Mps1 and A549 lung cancer cells.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, 32a and 32b exhibited reasonable selectivities over 120 and 166 kinases, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "3D Printed Bionic Ears.", "output": {"entities": {}}, "schema": []}
{"input": "The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts.", "output": {"entities": {}}, "schema": []}
{"input": "Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements.", "output": {"entities": {}}, "schema": []}
{"input": "As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles.", "output": {"entities": {"chemical": [{"text": "silver", "start": 206, "end": 212}]}}, "schema": []}
{"input": "This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes.", "output": {"entities": {}}, "schema": []}
{"input": "The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music.", "output": {"entities": {}}, "schema": []}
{"input": "Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis and biological evaluation of (68) Ga labeled bis-DOTA-3, 3'-(benzylidene)-bis-(1H-indole-2-carbohydrazide) as a PET tracer for in vivo visualization of necrosis.", "output": {"entities": {"chemical": [{"text": "(68) Ga labeled bis-DOTA", "start": 39, "end": 63}, {"text": "3, 3'-(benzylidene)-bis-(1H-indole-2-carbohydrazide)", "start": 64, "end": 116}]}}, "schema": []}
{"input": "The aim of the present study was to develop a (68) Ga labeled bis-DOTA derivative of benzylidene-bis-indole and compare the in vivo stability and biodistribution with that of the previously reported bis-DTPA derivate for in vivo imaging of necrosis using PET.", "output": {"entities": {"chemical": [{"text": "(68) Ga labeled bis-DOTA", "start": 46, "end": 70}, {"text": "benzylidene-bis-indole", "start": 85, "end": 107}, {"text": "bis-DTPA", "start": 199, "end": 207}]}}, "schema": []}
{"input": "Uptake of the tracer was evaluated in a mouse model of Fas-mediated hepatic apoptosis in correlation with histochemical stainings.", "output": {"entities": {}}, "schema": []}
{"input": "The novel (68) Ga labeled tracer showed an improved in vivo stability and could therefore be used for selective non-invasive imaging of necrotic cell death using PET.", "output": {"entities": {"chemical": [{"text": "(68) Ga", "start": 10, "end": 17}]}}, "schema": []}
{"input": "Cigarette craving and withdrawal symptoms during temporary abstinence and the effect of nicotine gum.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 88, "end": 96}]}}, "schema": []}
{"input": "RATIONALE: It is widely believed that nicotine withdrawal symptoms appear within a few hours of stopping smoking, but few data exist documenting their emergence in naturalistic settings.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 38, "end": 46}]}}, "schema": []}
{"input": "In several countries, nicotine replacement products are licensed for relief of withdrawal symptoms during temporary abstinence, but again, there are no data supporting this from naturalistic settings.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 22, "end": 30}]}}, "schema": []}
{"input": "OBJECTIVES: To examine the emergence of cigarette craving and withdrawal symptoms during temporary abstinence in a naturalistic setting while using either nicotine or placebo gum.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 155, "end": 163}]}}, "schema": []}
{"input": "METHODS: Double-blind, randomised, placebo-controlled study in which 132 dependent smokers abstained for 6 h with the assistance of either nicotine (2 mg, n = 42 or 4 mg, n = 24) or placebo (n = 66) gum while travelling on a non-smoking train.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 139, "end": 147}]}}, "schema": []}
{"input": "Outcome measures were ratings of craving and mood withdrawal symptoms prior to treatment and at regular intervals during abstinence.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: In a multivariate analysis of all symptoms, there was no interaction between treatment and time [F (21, 110) = 1. 28, p = 0. 20, [Formula: see text] = 0. 20] nor an effect of treatment [F (7, 124) = 0. 45, p = 0. 87, [Formula: see text] = 0. 03].", "output": {"entities": {}}, "schema": []}
{"input": "There was an effect of time [F (21, 110) = 11. 59, p < 0. 001, [Formula: see text] = 0. 69) and univariate analyses revealed that the majority of symptoms increased linearly throughout the period of abstinence with detectable onsets typically between the first 60 and 180 min of abstinence.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: Smokers who temporarily abstain in naturalistic settings experience craving and withdrawal symptoms that emerge linearly over the first 6 h of abstinence.", "output": {"entities": {}}, "schema": []}
{"input": "Changes in craving and several mood withdrawal symptoms can be detected within the first 3 h.", "output": {"entities": {}}, "schema": []}
{"input": "Nicotine gum may not have an acute effect on the development of these symptoms.", "output": {"entities": {"chemical": [{"text": "Nicotine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin in an advanced-aged diet-induced obesity mouse model.", "output": {"entities": {"chemical": [{"text": "vildagliptin", "start": 123, "end": 135}]}}, "schema": []}
{"input": "AIMS/HYPOTHESIS: Studies have shown that dipeptidyl peptidase-4 (DPP4) inhibitors stimulate insulin secretion and increase beta cell mass in rodents.", "output": {"entities": {}}, "schema": []}
{"input": "However, in these models hyperglycaemia has been induced early on in life and the treatment periods have been short.", "output": {"entities": {}}, "schema": []}
{"input": "To explore the long-term effects of DPP4 inhibition on insulin secretion and beta cell mass, we have generated a high-fat diet (HFD)-induced-obesity model in mice of advanced age (10 months old).", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: After 1 month of HFD alone, the mice were given the DPP4 inhibitor vildagliptin for a further 11 months.", "output": {"entities": {"chemical": [{"text": "vildagliptin", "start": 76, "end": 88}]}}, "schema": []}
{"input": "At multiple time points throughout the study, OGTTs were performed and beta cell area and long-term survival were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Beta cell function and glucose tolerance were significantly improved by vildagliptin with both diets.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 32, "end": 39}, {"text": "vildagliptin", "start": 81, "end": 93}]}}, "schema": []}
{"input": "In contrast, in spite of the long treatment period, beta cell area was not significantly different between vildagliptin-treated mice and controls.", "output": {"entities": {"chemical": [{"text": "vildagliptin", "start": 107, "end": 119}]}}, "schema": []}
{"input": "Mice of advanced age chronically fed an HFD displayed clear and extensive pancreatic inflammation and peri-insulitis, mainly formed by CD3-positive T cells, which were completely prevented by vildagliptin treatment.", "output": {"entities": {"chemical": [{"text": "vildagliptin", "start": 192, "end": 204}]}}, "schema": []}
{"input": "Chronic vildagliptin treatment also improved survival rates for HFD-fed mice.", "output": {"entities": {"chemical": [{"text": "vildagliptin", "start": 8, "end": 20}]}}, "schema": []}
{"input": "CONCLUSIONS/INTERPRETATION: In a unique advanced-aged HFD-induced-obesity mouse model, insulin secretion was improved and the extensive peri-insulitis prevented by chronic DPP4 inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "The improved survival rates for obese mice chronically treated with vildagliptin suggest that chronic DPP4 inhibition potentially results in additional quality-adjusted life-years for individuals with type 2 diabetes, which is the primary goal of any diabetes therapy.", "output": {"entities": {"chemical": [{"text": "vildagliptin", "start": 68, "end": 80}]}}, "schema": []}
{"input": "PT-ACRAMTU, A Platinum-Acridine Anticancer Agent, Lengthens and Aggregates, but does not Stiffen or Soften DNA.", "output": {"entities": {"chemical": [{"text": "Platinum", "start": 14, "end": 22}, {"text": "Acridine", "start": 23, "end": 31}]}}, "schema": []}
{"input": "We used atomic force microscopy (AFM) to study the dose-dependent change in conformational and mechanical properties of DNA treated with PT-ACRAMTU ([PtCl (en) (ACRAMTU-S)] (NO3) 2, (en = ethane-1, 2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea.", "output": {"entities": {"chemical": [{"text": "PT-ACRAMTU ([PtCl (en) (ACRAMTU-S)] (NO3) 2", "start": 137, "end": 180}, {"text": "ethane-1, 2-diamine", "start": 188, "end": 207}, {"text": "ACRAMTU", "start": 209, "end": 216}, {"text": "1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea", "start": 219, "end": 272}]}}, "schema": []}
{"input": "PT-ACRAMTU is the parent drug of a family of non-classical platinum-based agents that show potent activity in non-small cell lung cancer in vitro and in vivo.", "output": {"entities": {"chemical": [{"text": "PT-ACRAMTU", "start": 0, "end": 10}, {"text": "platinum", "start": 59, "end": 67}]}}, "schema": []}
{"input": "Its acridine moiety intercalates between DNA bases, while the platinum group forms mono-adducts with DNA bases.", "output": {"entities": {"chemical": [{"text": "acridine", "start": 4, "end": 12}, {"text": "platinum", "start": 62, "end": 70}]}}, "schema": []}
{"input": "AFM images show that PT-ACRAMTU causes some DNA looping and aggregation at drug-to-base pair ratio (r b) of 0. 1 and higher.", "output": {"entities": {"chemical": [{"text": "PT-ACRAMTU", "start": 21, "end": 31}]}}, "schema": []}
{"input": "Very significant lengthening of the DNA was observed with increasing doses of PT-ACRAMTU, and reached saturation at an r b of 0. 15.", "output": {"entities": {"chemical": [{"text": "PT-ACRAMTU", "start": 78, "end": 88}]}}, "schema": []}
{"input": "At r b of 0. 1, lengthening was 0. 6 nm per drug molecule, which is more than one fully stretched base pair stack can accommodate, indicating that ACRAMTU also disturbs the stacking of neighboring base pair stacks.", "output": {"entities": {"chemical": [{"text": "ACRAMTU", "start": 147, "end": 154}]}}, "schema": []}
{"input": "Analysis of the AFM images based on the worm-like chain (WLC) model showed that PT-ACRAMTU did not change the flexibility of (non-aggregated) DNA, despite the extreme lengthening.", "output": {"entities": {"chemical": [{"text": "PT-ACRAMTU", "start": 80, "end": 90}]}}, "schema": []}
{"input": "The persistence length of untreated DNA and DNA treated with PT-ACRAMTU was in the range of 49-65 nm.", "output": {"entities": {"chemical": [{"text": "PT-ACRAMTU", "start": 61, "end": 71}]}}, "schema": []}
{"input": "Potential consequences of the perturbations caused by this agent for the recognition and processing of the DNA adducts it forms are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "The Atrial Natriuretic Peptide Genetic Variant Rs5068 Is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEWe hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODSWe genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTSGenotype frequencies of rs5068 are AA, 93. 5%; AG, 6. 4%; and GG, 0. 1%.", "output": {"entities": {}}, "schema": []}
{"input": "All subsequent analyses are AA versus AG + GG.", "output": {"entities": {}}, "schema": []}
{"input": "After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]:-1. 7 kg/m (2) [0. 8], P = 0. 04).", "output": {"entities": {}}, "schema": []}
{"input": "In the AG + GG group, males with HDL cholesterol levels < 40 mg/dL are less frequent (P = 0. 05) and obesity tends to be less prevalent (P = 0. 07).", "output": {"entities": {"chemical": [{"text": "cholesterol", "start": 37, "end": 48}]}}, "schema": []}
{"input": "Importantly, the G allele is associated with a lower prevalence of metabolic syndrome (P = 0. 02).", "output": {"entities": {}}, "schema": []}
{"input": "After adjusting for BMI, the above associations were attenuated.", "output": {"entities": {}}, "schema": []}
{"input": "Independently of age, sex, and BMI, the minor allele is also associated with lower systolic blood pressure (-6. 0 mmHg [2. 5], P = 0. 02) and lower prevalence of hypertension (odds ratio 0. 41 [95% CI 0. 20-0. 83], P = 0. 01). CONCLUSIONSThe association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U. S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome.", "output": {"entities": {}}, "schema": []}
{"input": "Diabetes Prevention and Treatment Strategies: Are we doing enough?", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVEEffective interventions to prevent, delay, or remit diabetes are currently available.", "output": {"entities": {}}, "schema": []}
{"input": "However, their impact on the prevalence of diabetes at the population level is unknown.", "output": {"entities": {}}, "schema": []}
{"input": "This study aimed to estimate the impact of a range of diabetes interventions on the population prevalence of diabetes for Australian adults between 2010 and 2025. RESEARCH DESIGN AND METHODSWe used the Australian Diabetes Projection Model to estimate the impact of a population-wide strategy, high-risk prevention, surgical diabetes treatment, and a combination strategy on the future population prevalence of diabetes and to estimate the number of diabetes cases that could be potentially prevented in the year 2025. RESULTSWe estimate that a population-wide strategy would reduce the number of diabetes cases by 60, 000-85, 000 in 2025 from an estimated 2 million cases under the status quo scenario.", "output": {"entities": {}}, "schema": []}
{"input": "A high-risk prevention strategy would result in 106, 000 to 150, 000 fewer cases of diabetes in 2025, and surgically induced weight loss would result in 3, 000-6, 000 fewer cases.", "output": {"entities": {}}, "schema": []}
{"input": "No single intervention, or combination of interventions, reversed the increasing trend in diabetes prevalence over the next 15 years. CONCLUSIONSTo reverse upward trends in diabetes prevalence in future years, it is essential that current approaches to diabetes prevention and treatment are optimized and implemented and that alternative approaches to reduce the prevalence of diabetes at a population level are developed.", "output": {"entities": {}}, "schema": []}
{"input": "Charge transfer and Penning ionization of dopants in or on helium nanodroplets exposed to EUV radiation.", "output": {"entities": {"chemical": [{"text": "helium", "start": 59, "end": 65}]}}, "schema": []}
{"input": "Helium nanodroplets are widely used as a cold, weakly interacting matrix for spectroscopy of embedded species.", "output": {"entities": {"chemical": [{"text": "Helium", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In this work we excite or ionize doped He droplets using synchrotron radiation and study the effect onto the dopant atoms depending on their location inside the droplets (rare gases) or outside at the droplet surface (alkali metals).", "output": {"entities": {"chemical": [{"text": "He", "start": 39, "end": 41}, {"text": "alkali metals", "start": 218, "end": 231}]}}, "schema": []}
{"input": "Using photoelectron-photoion coincidence imaging spectroscopy at variable photon energies (20-25eV), we compare the rates of charge-transfer to Penning ionization of the dopants in the two cases.", "output": {"entities": {}}, "schema": []}
{"input": "The surprising finding is that alkali metals, in contrast to the rare gases, are efficiently Penning ionized upon excitation of the (n = 2)-bands of the host droplets.", "output": {"entities": {"chemical": [{"text": "alkali metals", "start": 31, "end": 44}]}}, "schema": []}
{"input": "This indicates rapid migration of the excitation to the droplet surface, followed by relaxation, and eventually energy transfer to the alkali dopants.", "output": {"entities": {}}, "schema": []}
{"input": "Structural revision of methyl tortuoate D, a bis-cembranoid from Hainan Sarcophyton tortuosum and its absolute stereochemistry.", "output": {"entities": {"chemical": [{"text": "methyl tortuoate D", "start": 23, "end": 41}, {"text": "bis-cembranoid", "start": 45, "end": 59}]}}, "schema": []}
{"input": "Methyl tortuoate D (1), together with five other known related bis-cembranoids, was isolated from Hainan soft coral Sarcophyton tortuosum.", "output": {"entities": {"chemical": [{"text": "Methyl tortuoate D", "start": 0, "end": 18}, {"text": "bis-cembranoids", "start": 63, "end": 78}]}}, "schema": []}
{"input": "The structure of methyl tortuoate D (1a), firstly isolated and reported by Li et al. from the title organism, was corrected as 1 by an extensive analysis of its one-dimensional and two-dimensional nuclear magnetic resonance data and by comparison with those reported in the literature.", "output": {"entities": {"chemical": [{"text": "methyl tortuoate D", "start": 17, "end": 35}]}}, "schema": []}
{"input": "In addition, lobophytone K (1b), recently isolated from Hainan soft coral Lobophytum pauciflorum by Lin et al., was proved to be the same compound as 1 and 1a.", "output": {"entities": {"chemical": [{"text": "lobophytone K", "start": 13, "end": 26}]}}, "schema": []}
{"input": "The absolute configuration of 1 was determined by comparing its electronic circular dichroism curve with that of co-occurring ximaolide A (2).", "output": {"entities": {"chemical": [{"text": "ximaolide A", "start": 126, "end": 137}]}}, "schema": []}
{"input": "Non-Contact AFM Imaging in Water Using Electrically-Driven Cantilever Vibration.", "output": {"entities": {}}, "schema": []}
{"input": "An atomic force microscopy (AFM) imaging mode is presented that can simultaneously record surface topography and local electrical properties in aqueous solutions without mechanical contact between the AFM tip and the sample.", "output": {"entities": {}}, "schema": []}
{"input": "The interaction between the electrically biased tip and the grounded sample in aqueous medium causes the AFM cantilever to vibrate.", "output": {"entities": {}}, "schema": []}
{"input": "This operation mode is based on the previously-developed SPFM technique, though using water as the medium instead of air introduces some important practical and theoretical differences, and also greatly extends the applicability of this technique.", "output": {"entities": {}}, "schema": []}
{"input": "There are two vibration modes, one at the frequency of the applied voltage (omega) and one at twice this frequency (2 omega).", "output": {"entities": {}}, "schema": []}
{"input": "The surface topography can be imaged using feedback control of the 2 <F077> vibration amplitude, which is very sensitive to the tip-sample separation distance in the range of 1 ~ 10 nm.", "output": {"entities": {}}, "schema": []}
{"input": "The amplitude and phase of the 1 <F077> vibration can be recorded simultaneously during imaging to obtain information on local surface charge or potential differences.", "output": {"entities": {}}, "schema": []}
{"input": "Similar techniques exist for imaging in air or vacuum, but the addition of a polarizable medium such as water adds significant theoretical and practical complexities.", "output": {"entities": {}}, "schema": []}
{"input": "This paper addresses those complexities, and demonstrates the effectiveness of the technique for surface imaging and analysis in aqueous environments.", "output": {"entities": {}}, "schema": []}
{"input": "Involvement of p-CREB and phase II detoxifying enzyme system in neuroprotection mediated by the flavonoid calycopterin isolated from Dracocephalum kotschyi.", "output": {"entities": {"chemical": [{"text": "calycopterin", "start": 106, "end": 118}]}}, "schema": []}
{"input": "PURPOSE: There is an increasing amount of experimental evidence that oxidative stress has a central role in the neuropathology of neurodegenerative diseases.", "output": {"entities": {}}, "schema": []}
{"input": "It has been suggested that the loss of cell function results from the increased oxidative damage to proteins and DNA.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we investigated the effect of a natural neuroprotective flavonoid, calycopterin, on H2O2-induced disruption of phase II detoxifying enzyme system and cAMP response element binding protein (CREB) phosphorylation.", "output": {"entities": {"chemical": [{"text": "calycopterin", "start": 75, "end": 87}, {"text": "H2O2", "start": 92, "end": 96}, {"text": "cAMP", "start": 158, "end": 162}]}}, "schema": []}
{"input": "METHODS: PC12 cells were treated with 25, 50 and 100 mu M of calycopterin for 3h, followed by adding H2O2 (150 mu M) for 24h.", "output": {"entities": {"chemical": [{"text": "calycopterin", "start": 61, "end": 73}, {"text": "H2O2", "start": 101, "end": 105}]}}, "schema": []}
{"input": "The extent of apoptosis was assessed by comet assay.", "output": {"entities": {}}, "schema": []}
{"input": "The level of phosphorylated CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), glutamylcysteine synthetase (gamma-GCS) and heme oxygenase 1 (HO-1) were measured by western blot method.", "output": {"entities": {"chemical": [{"text": "glutamylcysteine", "start": 86, "end": 102}]}}, "schema": []}
{"input": "The concentration of glutathione (GSH) was determined in whole cell lysate using dithionitrobenzoic acid method.", "output": {"entities": {"chemical": [{"text": "glutathione", "start": 21, "end": 32}, {"text": "GSH", "start": 34, "end": 37}]}}, "schema": []}
{"input": "Superoxide dismutase (SOD) activity was measured by colorimetric assay.", "output": {"entities": {}}, "schema": []}
{"input": "RESULT: Morphological analysis of protection induced by calycopterin, determined by comet assay, showed that calycopterin reduced DNA in tail.", "output": {"entities": {"chemical": [{"text": "calycopterin", "start": 56, "end": 68}, {"text": "calycopterin", "start": 109, "end": 121}]}}, "schema": []}
{"input": "We found that H2O2 decreased mitochondrial membrane potential (MMP), while, calycopterin prevented this decrease in MMP in presence of H2O2.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 14, "end": 18}, {"text": "calycopterin", "start": 76, "end": 88}, {"text": "H2O2", "start": 135, "end": 139}]}}, "schema": []}
{"input": "In H2O2-treated cells, calycopterin also suppressed cytochrome C release to cytosol that is necessary for maintaining mitochondrial homeostasis in survived cells.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 3, "end": 7}, {"text": "calycopterin", "start": 23, "end": 35}]}}, "schema": []}
{"input": "Moreover, calycopterin, in presence of H2O2 inhibited the decrease caused by oxidative stress in stress-sensing transcription factors, CREB and Nrf2, which play an important role in antioxidant capacity of the cell.", "output": {"entities": {"chemical": [{"text": "calycopterin", "start": 10, "end": 22}, {"text": "H2O2", "start": 39, "end": 43}]}}, "schema": []}
{"input": "There was also an increase in gamma-GCS and HO-1 levels in calycopterin pretreated cells.", "output": {"entities": {"chemical": [{"text": "calycopterin", "start": 59, "end": 71}]}}, "schema": []}
{"input": "In the presence of H2O2, calycopterin inhibited decrease in GSH level and SOD activity.", "output": {"entities": {"chemical": [{"text": "H2O2", "start": 19, "end": 23}, {"text": "calycopterin", "start": 25, "end": 37}, {"text": "GSH", "start": 60, "end": 63}]}}, "schema": []}
{"input": "CONCLUSION: We provided documentation of neuroprotective effect of a natural flavone, calycopterin, against H2O2-induced oxidative stress in differentiated PC12 cells by modulating the level of CREB phosphorylation and Nrf2 pathway.", "output": {"entities": {"chemical": [{"text": "calycopterin", "start": 86, "end": 98}, {"text": "H2O2", "start": 108, "end": 112}]}}, "schema": []}
{"input": "Monitoring Conformational Changes in Peroxisome Proliferator-Activated Receptor alpha by a Genetically Encoded Photo-Amino Acid, Cross-Linking, and Mass Spectrometry.", "output": {"entities": {"chemical": [{"text": "Amino Acid", "start": 117, "end": 127}]}}, "schema": []}
{"input": "Chemical cross-linking combined with an enzymatic digestion and mass spectrometric analysis of the reaction products has evolved into an alternative strategy to structurally resolve protein complexes.", "output": {"entities": {}}, "schema": []}
{"input": "We investigated conformational changes in peroxisome proliferator-activated receptor alpha (PPAR alpha) upon ligand binding.", "output": {"entities": {}}, "schema": []}
{"input": "Using E. coli cells with a special tRNA/aminoacyl-tRNA synthetase pair, two PPAR alpha variants were prepared, in which Leu-258 or Phe-273 were site-specifically replaced by the genetically encoded photo-reactive amino acid para-benzoylphenylalanine (Bpa).", "output": {"entities": {"chemical": [{"text": "Leu", "start": 120, "end": 123}, {"text": "Phe", "start": 131, "end": 134}, {"text": "amino acid para-benzoylphenylalanine", "start": 213, "end": 249}, {"text": "Bpa", "start": 251, "end": 254}]}}, "schema": []}
{"input": "PPAR alpha variants were subjected to UV-induced cross-linking, both in the absence and presence of ligands.", "output": {"entities": {}}, "schema": []}
{"input": "After the photo-cross-linking reaction, reaction mixtures were enzymatically digested and peptides were analyzed by mass spectrometry.", "output": {"entities": {}}, "schema": []}
{"input": "The inter-residue distances disclosed by the photo-chemical cross-links served to monitor conformational changes in PPAR alpha upon agonist and antagonist binding.", "output": {"entities": {}}, "schema": []}
{"input": "The data obtained with our strategy underline the potential of genetically encoded internal photo-cross-linkers in combination with mass spectrometry as an alternative method to monitor in-solution 3D-protein structures.", "output": {"entities": {}}, "schema": []}
{"input": "Differential Induction of Cytochrome P450 Isoforms and Peroxisomal Proliferation by Cyfluthrin in Male Wistar Rats.", "output": {"entities": {"chemical": [{"text": "Cyfluthrin", "start": 84, "end": 94}]}}, "schema": []}
{"input": "Cyfluthrin effects on in vivo drug metabolizing enzymes were evaluated using the oxidative substrate antipyrine.", "output": {"entities": {"chemical": [{"text": "Cyfluthrin", "start": 0, "end": 10}, {"text": "antipyrine", "start": 101, "end": 111}]}}, "schema": []}
{"input": "Antipyrine pharmacokinetics in plasma and urinary excretion of its major metabolites with and without cyfluthrin oral treatment (20mg/kg/day for 6 days) were investigated in rats.", "output": {"entities": {"chemical": [{"text": "Antipyrine", "start": 0, "end": 10}, {"text": "cyfluthrin", "start": 102, "end": 112}]}}, "schema": []}
{"input": "Cyfluthrin increased the apparent intrinsic clearance and decreased the antipyrine half-life at beta phase.", "output": {"entities": {"chemical": [{"text": "Cyfluthrin", "start": 0, "end": 10}, {"text": "antipyrine", "start": 72, "end": 82}]}}, "schema": []}
{"input": "Cyfluthrin also increased the clearance of the antipyrine metabolites, norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine and the formation rate constants for each of the three metabolites measured in urine.", "output": {"entities": {"chemical": [{"text": "Cyfluthrin", "start": 0, "end": 10}, {"text": "antipyrine", "start": 47, "end": 57}, {"text": "norantipyrine", "start": 71, "end": 84}, {"text": "4-hydroxyantipyrine", "start": 86, "end": 105}, {"text": "3-hydroxymethylantipyrine", "start": 110, "end": 135}]}}, "schema": []}
{"input": "These results suggest that cyfluthrin affects hepatic cytochrome P450 (CYP) system.", "output": {"entities": {"chemical": [{"text": "cyfluthrin", "start": 27, "end": 37}]}}, "schema": []}
{"input": "In order to confirm, a second experiment was carried out.", "output": {"entities": {}}, "schema": []}
{"input": "We evaluated the effects of repeated exposure to cyfluthrin on hepatic and renal CYP2E, CYP1A and CYP4A subfamilies and peroxisomal proliferation in rats following oral administration (10 and 20mg/kg/day for 6 days).", "output": {"entities": {"chemical": [{"text": "cyfluthrin", "start": 49, "end": 59}]}}, "schema": []}
{"input": "At the highest dose, cyfluthrin increased renal and hepatic O-deethylation of ethoxyresorufin and O-demethylation of methoxyresorufin, metabolism mediated by the CYP1A subfamily.", "output": {"entities": {"chemical": [{"text": "cyfluthrin", "start": 21, "end": 31}, {"text": "O", "start": 60, "end": 61}, {"text": "ethoxyresorufin", "start": 78, "end": 93}, {"text": "O", "start": 98, "end": 99}, {"text": "methoxyresorufin", "start": 117, "end": 133}]}}, "schema": []}
{"input": "Liver and kidney were susceptible to cyfluthrin-dependent induction of 12-and 11-hydroxylation of lauric acid, suggesting CYP4A subfamily induction.", "output": {"entities": {"chemical": [{"text": "cyfluthrin", "start": 37, "end": 47}, {"text": "lauric acid", "start": 98, "end": 109}]}}, "schema": []}
{"input": "Also cyfluthrin increased the beta-oxidation of palmitoyl-coenzyme A and carnitine acetyltransferase activity, supporting cyfluthrin as a peroxisome proliferator.", "output": {"entities": {"chemical": [{"text": "cyfluthrin", "start": 5, "end": 15}, {"text": "palmitoyl", "start": 48, "end": 57}, {"text": "carnitine", "start": 73, "end": 82}, {"text": "cyfluthrin", "start": 122, "end": 132}]}}, "schema": []}
{"input": "In conclusion, the demonstration that cyfluthrin induced hepatic CYP1A, CYP4A subfamilies and peroxisomal proliferation raises the possibility of cyfluthrin could produce changes in oxidative stress.", "output": {"entities": {"chemical": [{"text": "cyfluthrin", "start": 38, "end": 48}, {"text": "cyfluthrin", "start": 146, "end": 156}]}}, "schema": []}
{"input": "Indoxyl 3-sulfate stimulates Th17 differentiation enhancing phosphorylation of c-Src and STAT3 to worsen experimental autoimmune encephalomyelitis.", "output": {"entities": {"chemical": [{"text": "Indoxyl 3-sulfate", "start": 0, "end": 17}]}}, "schema": []}
{"input": "Although AhR activation regulates CD4T cell differentiation, how it works has yet to be elucidated.", "output": {"entities": {}}, "schema": []}
{"input": "In the present study, using in vitro Th17 differentiation model, we examined effects of AhR activation by indoxyl 3-sulfate (I3S), a uremic toxin, on Th17 differentiation and investigated underlying mechanisms.", "output": {"entities": {"chemical": [{"text": "indoxyl 3-sulfate", "start": 106, "end": 123}, {"text": "I3S", "start": 125, "end": 128}]}}, "schema": []}
{"input": "I3S increased expression of ROR gamma t, the master transcription factor for Th17 differentiation, and stimulated Th17 differentiation, in a comparative manner as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), a prototypical AhR ligand.", "output": {"entities": {"chemical": [{"text": "I3S", "start": 0, "end": 3}, {"text": "2, 3, 7, 8-tetrachlorodibenzo-p-dioxin", "start": 163, "end": 201}, {"text": "TCDD", "start": 203, "end": 207}]}}, "schema": []}
{"input": "Activation of STAT3, which is phosphorylated by the IL-6 signaling pathways and thus is necessary for Th17 differentiation, was strongly stimulated by I3S and TCDD.", "output": {"entities": {"chemical": [{"text": "I3S", "start": 151, "end": 154}, {"text": "TCDD", "start": 159, "end": 163}]}}, "schema": []}
{"input": "Phosphorylation of c-Src, which was shown to be activated by AhR ligands, was also increased by I3S and TCDD, and blocking of c-Src activity by 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3, 4-d] pyrimidine (PP2) inhibited phosphorylation of both c-Src and STAT3, raising a possibility that stimulatory activities of I3S and TCDD on Th17 differentiation could be exerted via increased phosphorylation of c-Src, which in turn stimulates STAT3 activation.", "output": {"entities": {"chemical": [{"text": "I3S", "start": 96, "end": 99}, {"text": "TCDD", "start": 104, "end": 108}, {"text": "4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3, 4-d] pyrimidine", "start": 144, "end": 211}, {"text": "I3S", "start": 322, "end": 325}, {"text": "TCDD", "start": 330, "end": 334}]}}, "schema": []}
{"input": "Finally, we found that I3S worsened experimental autoimmune encephalomyelitis (EAE), which is primarily mediated by Th17 cells, enhancing the frequency of IL-17-producing cells in draining lymph nodes.", "output": {"entities": {"chemical": [{"text": "I3S", "start": 23, "end": 26}]}}, "schema": []}
{"input": "Canna indica L. attenuates high-glucose-and lipopolysaccharide-induced inflammatory mediators in monocyte/macrophage.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 32, "end": 39}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Canna indica L.", "output": {"entities": {}}, "schema": []}
{"input": "(CI) has been widely used as a folklore medicine in tropical and subtropical areas with beneficial effects in numerous diseases, including infection, rheumatism, hepatitis, and it has also been identified as an antioxidant.", "output": {"entities": {}}, "schema": []}
{"input": "MATERIALS AND METHODS: The present study aimed to investigate the effect of CI ethanolic extract (CIE) on productions of nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-1 beta (IL-1 beta) in lipopolysaccharide (LPS)-induced RAW264. 7 macrophages.", "output": {"entities": {"chemical": [{"text": "nitric oxide", "start": 121, "end": 133}, {"text": "NO", "start": 135, "end": 137}, {"text": "prostaglandin E2", "start": 140, "end": 156}, {"text": "PGE2", "start": 158, "end": 162}]}}, "schema": []}
{"input": "In addition, the effects of CIE in high glucose (HG)-induced U937 monocytes on mRNA expressions of IL-8 and monocyte chemoattractant protein-1 (MCP-1), and regulation of mitogen-activated protein kinase (MAPK) pathways were also identified.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 40, "end": 47}]}}, "schema": []}
{"input": "RESULTS: CIE was found to inhibit the production of inflammatory mediators including NO, IL-1 beta, and PGE2 from LPS-induced RAW 264. 7 macrophages.", "output": {"entities": {"chemical": [{"text": "NO", "start": 85, "end": 87}, {"text": "PGE2", "start": 104, "end": 108}]}}, "schema": []}
{"input": "The increases in HG-induced mRNA expressions of IL-8 and MCP-1 were also significantly inhibited by CIE.", "output": {"entities": {}}, "schema": []}
{"input": "Stimulation of HG in U937 monocytes resulted in activation of p38 MAPK, ERK1/2, and JNK.", "output": {"entities": {}}, "schema": []}
{"input": "However, CIE treatment significantly decreased phosphorylation of p38 MAPK, ERK1/2, and JNK.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSION: The present study demonstrated that CIE suppressed the LPS-induced inflammatory mediator production and also inhibited HG-induced inflammatory mediator expression by the regulation of MAPK pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Nedd4 is a specific E3 ubiquitin ligase for the NMDA receptor subunit GluN2D.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 48, "end": 52}]}}, "schema": []}
{"input": "NMDA receptors are a family of glutamate-gated ion channels that regulate various CNS functions such as synaptic plasticity and learning.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 0, "end": 4}, {"text": "glutamate", "start": 31, "end": 40}]}}, "schema": []}
{"input": "However hypo-or hyper-activation of NMDA receptors is critically involved in many neurological and psychiatric conditions such as pain, stroke, epilepsy, neurodegeneration, schizophrenia, and depression.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 36, "end": 40}]}}, "schema": []}
{"input": "Thus, it is important to identify mechanisms (such as by targeted ubiquitination) that regulate the levels of individual subtypes of NMDA receptors.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 133, "end": 137}]}}, "schema": []}
{"input": "In this study, we used a series of tagged, carboxy terminal constructs of GluN2D to identify associating proteins from rat brain.", "output": {"entities": {"chemical": [{"text": "carboxy", "start": 43, "end": 50}]}}, "schema": []}
{"input": "Of seven different GluN2D C-terminal fragments used as bait, only the construct containing amino acids 983-1097 associated with an E3 ligase, Nedd4.", "output": {"entities": {"chemical": [{"text": "C", "start": 26, "end": 27}, {"text": "amino acids", "start": 91, "end": 102}]}}, "schema": []}
{"input": "A direct interaction between GluN2D and Nedd4 was confirmed both in vivo and in vitro.", "output": {"entities": {}}, "schema": []}
{"input": "This association is mediated by an interaction between GluN2D' s C-terminal PPXY motif and the 2nd and 3rd WW domains of Nedd4.", "output": {"entities": {"chemical": [{"text": "C", "start": 65, "end": 66}]}}, "schema": []}
{"input": "Of the four GluN2 subunits, Nedd4 directly interacted with GluN2D and also weakly with GluN2A.", "output": {"entities": {}}, "schema": []}
{"input": "Nedd4 coexpression with GluN2D enhances GluN2D ubiquitination and reduces GluN1/GluN2D NMDA receptor responses.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 87, "end": 91}]}}, "schema": []}
{"input": "These results identify Nedd4 as a novel binding partner for GluN2D and suggest a mechanism for the regulation of NMDA receptors that contains GluN2D subunit through ubiquitination-dependent downregulation.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 113, "end": 117}]}}, "schema": []}
{"input": "This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.", "output": {"entities": {}}, "schema": []}
{"input": "Cell-penetrating cationic siRNA and lipophilic derivatives efficient at nanomolar concentrations in the presence of serum and albumin.", "output": {"entities": {}}, "schema": []}
{"input": "Despite its considerable interest in human therapy, in vivo siRNA delivery is still suffering from hurdles of vectorization.", "output": {"entities": {}}, "schema": []}
{"input": "We have shown recently efficient gene silencing by non-vectorized cationic siRNA.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we describe the synthesis and in vitro evaluation of new amphiphilic cationic siRNA.", "output": {"entities": {}}, "schema": []}
{"input": "C12-, (C12) 2-and cholesteryl-sperminex-siRNA were capable of luciferase knockdown at nanomolar concentrations without vectorization (i. e. one to two orders of magnitude more potent than commercially available cholesteryl siRNA).", "output": {"entities": {"chemical": [{"text": "C12", "start": 0, "end": 3}, {"text": "(C12) 2", "start": 6, "end": 13}, {"text": "cholesteryl-sperminex", "start": 18, "end": 39}, {"text": "cholesteryl", "start": 211, "end": 222}]}}, "schema": []}
{"input": "Moreover, incubation in the presence of serum did not impair their efficiency.", "output": {"entities": {}}, "schema": []}
{"input": "Finally, amphiphilic cationic siRNA was pre-loaded on albumin.", "output": {"entities": {}}, "schema": []}
{"input": "In A549Luc cells in the presence of serum, these siRNA conjugates were highly effective and had low toxicity.", "output": {"entities": {}}, "schema": []}
{"input": "A dihydrochalcone and several homoisoflavonoids from Polygonatum odoratum are activators of adenosine monophosphate-activated protein kinase.", "output": {"entities": {"chemical": [{"text": "dihydrochalcone", "start": 2, "end": 17}, {"text": "homoisoflavonoids", "start": 30, "end": 47}, {"text": "adenosine monophosphate", "start": 92, "end": 115}]}}, "schema": []}
{"input": "Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a major cellular energy sensor and master regulator of metabolic homeostasis; thus, AMPK plays a central role in studies on diabetes and related metabolic diseases.", "output": {"entities": {"chemical": [{"text": "Adenosine monophosphate", "start": 0, "end": 23}, {"text": "AMP", "start": 25, "end": 28}]}}, "schema": []}
{"input": "From the rhizomes of Polygonatum odoratum (Mill.) Druce, six homoisoflavonoids (1-6) and one dihydrochalcone (7) were isolated, and the structures of polygonatones A-D (4-7) were elucidated by various spectroscopic analyses.", "output": {"entities": {"chemical": [{"text": "homoisoflavonoids", "start": 61, "end": 78}, {"text": "dihydrochalcone", "start": 93, "end": 108}, {"text": "polygonatones A-D", "start": 150, "end": 167}]}}, "schema": []}
{"input": "Compounds 1-7 were evaluated for their effect on AMPK activation.", "output": {"entities": {}}, "schema": []}
{"input": "The amount of active phosphorylated AMPK and acetyl-CoA carboxylase in rat liver epithelial IAR-20 cells increased when the cells were incubated with the aforementioned compounds.", "output": {"entities": {"chemical": [{"text": "acetyl-CoA", "start": 45, "end": 55}]}}, "schema": []}
{"input": "Specifically, (3R)-5, 7-dihydroxyl-6-methyl-8-methoxyl-3-(4'-hydroxylbenzyl)-chroman-4-one (1), (3R)-5, 7-dihydroxyl-6, 8-dimethyl-3-(4'-hydroxylbenzyl)-chroman-4-one (2), (3R)-5, 7-dihydroxyl-6-methyl-3-(4'-hydroxylbenzyl)-chroman-4-one (3), and polygonatone D (7) exhibited significant activation effects.", "output": {"entities": {"chemical": [{"text": "(3R)-5, 7-dihydroxyl-6-methyl-8-methoxyl-3-(4'-hydroxylbenzyl)-chroman-4-one", "start": 14, "end": 90}, {"text": "(3R)-5, 7-dihydroxyl-6, 8-dimethyl-3-(4'-hydroxylbenzyl)-chroman-4-one", "start": 96, "end": 166}, {"text": "(3R)-5, 7-dihydroxyl-6-methyl-3-(4'-hydroxylbenzyl)-chroman-4-one", "start": 172, "end": 237}, {"text": "polygonatone D", "start": 247, "end": 261}]}}, "schema": []}
{"input": "Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo [1. 5-a] pyrimidine scaffold of Dorsomorphin: The discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe.", "output": {"entities": {"chemical": [{"text": "pyrazolo [1. 5-a] pyrimidine", "start": 141, "end": 169}, {"text": "ML347", "start": 213, "end": 218}]}}, "schema": []}
{"input": "A structure-activity relationship of the 3-and 6-positions of the pyrazolo [1, 5-a] pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 versus ALK3.", "output": {"entities": {"chemical": [{"text": "pyrazolo [1, 5-a] pyrimidine", "start": 66, "end": 94}, {"text": "dorsomorphin", "start": 132, "end": 144}, {"text": "LDN-193189", "start": 149, "end": 159}, {"text": "DMH1", "start": 168, "end": 172}]}}, "schema": []}
{"input": "The potency contributions of several 3-position substituents were evaluated with subtle structural changes leading to significant changes in potency.", "output": {"entities": {}}, "schema": []}
{"input": "From these studies, a novel 5-quinoline molecule was identified and designated an MLPCN probe molecule, ML347, which shows > 300-fold selectivity for ALK2 and presents the community with a selective molecular probe for further biological evaluation.", "output": {"entities": {"chemical": [{"text": "5-quinoline", "start": 28, "end": 39}, {"text": "ML347", "start": 104, "end": 109}]}}, "schema": []}
{"input": "Synthesis and in vitro evaluation of a PDT active BODIPY-NLS conjugate.", "output": {"entities": {}}, "schema": []}
{"input": "Two new photosensitizers based on the BODIPY scaffold have been synthesized, of which one bears an NLS peptide, which is linked to the BODIPY' s core using the copper catalysed azide-alkyne click reaction.", "output": {"entities": {"chemical": [{"text": "BODIPY", "start": 38, "end": 44}, {"text": "copper", "start": 160, "end": 166}, {"text": "azide", "start": 177, "end": 182}, {"text": "alkyne", "start": 183, "end": 189}]}}, "schema": []}
{"input": "The phototoxicities of these BODIPY based photosensitizers have been determined, as well as their dark toxicities.", "output": {"entities": {"chemical": [{"text": "BODIPY", "start": 29, "end": 35}]}}, "schema": []}
{"input": "Although the conjugation of a single NLS peptide to the BODIPY did not lead to any observable nuclear localization, the photosensitizer did exhibit a superior photoxicity.", "output": {"entities": {"chemical": [{"text": "BODIPY", "start": 56, "end": 62}]}}, "schema": []}
{"input": "Cellular co-localization experiments revealed a localization of both dyes in the lysosomes, as well as a partial localization within the ER (for the peptide-bearing BODIPY).", "output": {"entities": {"chemical": [{"text": "BODIPY", "start": 165, "end": 171}]}}, "schema": []}
{"input": "Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 37, "end": 45}]}}, "schema": []}
{"input": "In this study, we investigated the potential protective effects of Valeriana officinalis (V. officinalis) against the toxicity induced by rotenone in Drosophila melanogaster (D. melanogaster).", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 138, "end": 146}]}}, "schema": []}
{"input": "Adult wild-type flies were concomitantly exposed to rotenone (500 mu M) and V. officinalis aqueous extract (10mg/mL) in the food during 7 days.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 52, "end": 60}]}}, "schema": []}
{"input": "Rotenone-fed flies had a worse performance in the negative geotaxis assay (i. e. climbing capability) and open-field test (i. e. mobility time) as well as a higher incidence of mortality when compared to control group.", "output": {"entities": {"chemical": [{"text": "Rotenone", "start": 0, "end": 8}]}}, "schema": []}
{"input": "V. officinalis treatment offered protection against these detrimental effects of rotenone.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 81, "end": 89}]}}, "schema": []}
{"input": "In contrast, the decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis.", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 80, "end": 88}]}}, "schema": []}
{"input": "Rotenone toxicity was also associated with a marked decrease on the total-thiol content in the homogenates and cell viability of flies, which were reduced by V. officinalis treatment.", "output": {"entities": {"chemical": [{"text": "Rotenone", "start": 0, "end": 8}, {"text": "thiol", "start": 74, "end": 79}]}}, "schema": []}
{"input": "Indeed, rotenone exposure caused a significant increase in the mRNA expression of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and also in the tyrosine hydroxylase gene (TH).", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 8, "end": 16}, {"text": "superoxide", "start": 102, "end": 112}, {"text": "tyrosine", "start": 164, "end": 172}]}}, "schema": []}
{"input": "The expression of SOD and CAT mRNAs were normalized by V. officinalis treatment.", "output": {"entities": {}}, "schema": []}
{"input": "Our results suggest that V. officinalis extract was effective in reducing the toxicity induced by rotenone in D. melonogaster as well as confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, including Parkinson disease (PD).", "output": {"entities": {"chemical": [{"text": "rotenone", "start": 98, "end": 106}]}}, "schema": []}
{"input": "Direct methods for detection of protein S-nitrosylation.", "output": {"entities": {"chemical": [{"text": "S", "start": 40, "end": 41}]}}, "schema": []}
{"input": "S-nitrosylation of protein cysteine residues is known to be an important mechanism for nitric oxide signaling.", "output": {"entities": {"chemical": [{"text": "S", "start": 0, "end": 1}, {"text": "cysteine", "start": 27, "end": 35}, {"text": "nitric oxide", "start": 87, "end": 99}]}}, "schema": []}
{"input": "However, the detection of protein S-nitrosylation is still challenging due to technical limitations of current methods.", "output": {"entities": {"chemical": [{"text": "S", "start": 34, "end": 35}]}}, "schema": []}
{"input": "This chapter provides a brief review on recent developments of methods, which directly target S-nitroso moieties for detection.", "output": {"entities": {"chemical": [{"text": "S", "start": 94, "end": 95}, {"text": "nitroso", "start": 96, "end": 103}]}}, "schema": []}
{"input": "We also describe in detail the protocol of an organophosphine-based biotin labeling of protein S-nitroso moieties.", "output": {"entities": {"chemical": [{"text": "organophosphine", "start": 46, "end": 61}, {"text": "biotin", "start": 68, "end": 74}, {"text": "S", "start": 95, "end": 96}, {"text": "nitroso", "start": 97, "end": 104}]}}, "schema": []}
{"input": "Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver.", "output": {"entities": {"chemical": [{"text": "BDE209", "start": 13, "end": 19}, {"text": "glucose", "start": 37, "end": 44}]}}, "schema": []}
{"input": "Several persistent organic pollutants are reported to be potentially associated with the risk of human diabetes that has become rapidly epidemic in China currently.", "output": {"entities": {}}, "schema": []}
{"input": "2, 2', 3, 3', 4, 4', 5, 5', 6, 6'-decabromodiphenyl ether (BDE209) is commercially most important both in the production and in the use of polybrominated diphenyl ethers (PBDEs).", "output": {"entities": {"chemical": [{"text": "2, 2', 3, 3', 4, 4', 5, 5', 6, 6'-decabromodiphenyl ether", "start": 0, "end": 57}, {"text": "BDE209", "start": 59, "end": 65}, {"text": "polybrominated diphenyl ethers", "start": 139, "end": 169}, {"text": "PBDEs", "start": 171, "end": 176}]}}, "schema": []}
{"input": "It might bioaccumulate in wildlife and human and is the only PBDEs mixture still used today.", "output": {"entities": {"chemical": [{"text": "PBDEs", "start": 61, "end": 66}]}}, "schema": []}
{"input": "In the present study, male adult rats treated with BDE209 (0, 0. 05, 1, and 20 mg/kg) for 8 weeks were used to explore the effects of BDE209 on glucose homeostasis and possible mechanisms; 0. 05 mg/kg of BDE209 induced dose-related hyperglycemia.", "output": {"entities": {"chemical": [{"text": "BDE209", "start": 51, "end": 57}, {"text": "BDE209", "start": 134, "end": 140}, {"text": "glucose", "start": 144, "end": 151}, {"text": "BDE209", "start": 204, "end": 210}]}}, "schema": []}
{"input": "Then, we performed the full-genome gene expression microarrays, gene ontology analysis, and pathway analysis in this group and control.", "output": {"entities": {}}, "schema": []}
{"input": "BDE209 induced 1, 257 liver gene transcript changes, and 18 canonical pathways were significantly enriched.", "output": {"entities": {"chemical": [{"text": "BDE209", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Four of them were involved in immune diseases, including autoimmune thyroid disease, graft-versus-host disease, allograft rejection, and type I diabetes mellitus (T1MD), which was confirmed by the decrease in serum insulin.", "output": {"entities": {}}, "schema": []}
{"input": "Subsequently, gene act network and gene co-expression network found that some MHC molecules and TNF-alpha were involved in T1DM pathway, which was then confirmed by the increase in serum TNF-alpha.", "output": {"entities": {}}, "schema": []}
{"input": "Additionally, reduced glutathione and superoxide dismutase in plasma indicated that oxidative damage might partly contribute to BDE209-induced hyperglycemia.", "output": {"entities": {"chemical": [{"text": "reduced glutathione", "start": 14, "end": 33}, {"text": "superoxide", "start": 38, "end": 48}, {"text": "BDE209", "start": 128, "end": 134}]}}, "schema": []}
{"input": "The results of this study provide some new experimental evidence that the exposure to high levels of BDE209 may contribute to the onset of diabetes in human populations.", "output": {"entities": {"chemical": [{"text": "BDE209", "start": 101, "end": 107}]}}, "schema": []}
{"input": "Further work needs to be done to confirm this link.", "output": {"entities": {}}, "schema": []}
{"input": "The Development and Validation of a Decision-Analytic Model Representing the Full Disease Course of Acute Myeloid Leukemia.", "output": {"entities": {}}, "schema": []}
{"input": "BACKGROUND: The treatment of acute myeloid leukemia (AML) is moving towards personalized medicine.", "output": {"entities": {}}, "schema": []}
{"input": "However, due to the low incidence of AML, it is not always feasible to evaluate the cost-effectiveness of personalized medicine using clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "Decision analytic models provide an alternative data source.", "output": {"entities": {}}, "schema": []}
{"input": "OBJECTIVE: The aim of this study was to develop and validate a decision analytic model that represents the full disease course of AML.", "output": {"entities": {}}, "schema": []}
{"input": "METHODS: We used a micro simulation with discrete event components to incorporate both patient and disease heterogeneity.", "output": {"entities": {}}, "schema": []}
{"input": "Input parameters were calculated from patient-level data.", "output": {"entities": {}}, "schema": []}
{"input": "Two hematologists critically evaluated the model to ensure face validity.", "output": {"entities": {}}, "schema": []}
{"input": "Internal and external validity was tested by comparing complete remission (CR) rates and survival outcomes of the model with original data, other clinical trials and a population-based study.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: No significant differences in patient and treatment characteristics, CR rate, 5-year overall and disease-free survival were found between the simulated and original data.", "output": {"entities": {}}, "schema": []}
{"input": "External validation showed no significant differences in survival between simulated data and other clinical trials.", "output": {"entities": {}}, "schema": []}
{"input": "However, differences existed between the simulated data and a population-based study.", "output": {"entities": {}}, "schema": []}
{"input": "CONCLUSIONS: The model developed in this study is proved to be valid for analysis of an AML population participating in a clinical trial.", "output": {"entities": {}}, "schema": []}
{"input": "The generalizability of the model to a broader patient population has not been proven yet.", "output": {"entities": {}}, "schema": []}
{"input": "Further research is needed to identify differences between the clinical trial population and other AML patients and to incorporate these differences in the model.", "output": {"entities": {}}, "schema": []}
{"input": "The design and realization of a large-area flexible nanofiber-based mat for pollutant degradation: an application in photocatalysis.", "output": {"entities": {}}, "schema": []}
{"input": "This work demonstrates a novel multifunctional nanofibrous mat for photocatalytic applications based on TiO2 nanocables functionalized by Ag nanoparticles and coated with a thin (~ 2 nm) graphitic shell.", "output": {"entities": {"chemical": [{"text": "TiO2", "start": 104, "end": 108}, {"text": "Ag", "start": 138, "end": 140}, {"text": "graphitic", "start": 187, "end": 196}]}}, "schema": []}
{"input": "In this mat, which was realized by an electrospinning technique, each component serves a unique function: the carbon coating acts as both an adsorption material for capturing pollutants and as a charge-transfer material, the Ag nanoparticles act as a visible-light sensitizing agent and also as a charge-transfer material, finally the TiO2 nanocable mat acts as a UV sensitive photocatalytic matrix and as the flexible substrate for the other functional components.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 110, "end": 116}, {"text": "Ag", "start": 225, "end": 227}, {"text": "TiO2", "start": 335, "end": 339}]}}, "schema": []}
{"input": "This multicomponent nanocable mat exhibits excellent photocatalytic activity under simulated solar irradiation for the degradation of model pollutants including RhB and phenol.", "output": {"entities": {"chemical": [{"text": "RhB", "start": 161, "end": 164}, {"text": "phenol", "start": 169, "end": 175}]}}, "schema": []}
{"input": "The significant photocatalytic properties are attributed to the synergetic effect of the three functional components and the unique charge transport \" freeway \" property of the nanofibrous mat.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the porous carbon coating infiltrated into the nanocable matrix endows the mat with excellent flexibility and enables robust, large-area (10 x 10 cm) fabrication, representing a significant advantage over previous brittle ceramic nanofibrous mat photocatalyst substrates.", "output": {"entities": {"chemical": [{"text": "carbon", "start": 24, "end": 30}]}}, "schema": []}
{"input": "This study provides new insight into the design and preparation of an advanced, yet commercially practical and scaleable photocatalytic composite membrane material.", "output": {"entities": {}}, "schema": []}
{"input": "The as-prepared photocatalytic mat might also be of interest in solar cell, catalysis, separation technology, biomedical engineering, and nanotechnology.", "output": {"entities": {}}, "schema": []}
{"input": "Toxic Shock Syndrome: Characterization of Human Immune Responses to TSST-1 and Evidence for Sensitivity Thresholds.", "output": {"entities": {}}, "schema": []}
{"input": "Noninvasive vaginal infections by S. aureus strains producing the superantigen TSST-1 can cause menstrual toxic shock syndrome (mTSS).", "output": {"entities": {}}, "schema": []}
{"input": "With the objective of exploring the basis for differential susceptibility to mTSS the relative responsiveness to TSST-1 of healthy women has been investigated.", "output": {"entities": {}}, "schema": []}
{"input": "Peripheral blood mononuclear cells from healthy donors were incubated with purified TSST-1, or with the T cell mitogen phytohaemmaglutinin (PHA), and proliferation measured.", "output": {"entities": {}}, "schema": []}
{"input": "The concentrations of TSST-1 and PHA required to elicit a response equivalent to 15% of the maximal achievable response (EC15) was determined.", "output": {"entities": {}}, "schema": []}
{"input": "Although with PHA EC15 values were comparable between donors, subjects could be classified as being of high, medium or low sensitivity based on responsiveness to TSST-1.", "output": {"entities": {}}, "schema": []}
{"input": "Sensitivity to TSST-1-induced proliferation was associated with increased production of the cytokines interleukin (IL)-2 and interferon gamma (IFN-gamma).", "output": {"entities": {}}, "schema": []}
{"input": "When the entire T lymphocyte population was considered, there were no differences between sensitivity groups with respect to the frequency of cells known to be responsive to TSST-1 (those bearing CD3 (+) V beta 2 (+)).", "output": {"entities": {}}, "schema": []}
{"input": "However, there was an association between sensitivity to TSST-1 and certain HLA-class II haplotypes.", "output": {"entities": {}}, "schema": []}
{"input": "Thus, the frequency of DR7DQ2, DR14DQ5, DR4DQ8, and DR8DQ4 haplotypes were greater among those with high sensitivity; a finding confirmed by analysis of responses to immortalized homozygous B cell lines. Collectively, the results reveal that factors other than neutralising antibody and the frequency of V beta 2 (+) T lymphocytes determine immunological responsiveness to TSST-1.", "output": {"entities": {}}, "schema": []}
{"input": "Differential responsiveness of lymphocytes to TSST-1 may form the basis of inter-individual variations in susceptibility to mTSS.", "output": {"entities": {}}, "schema": []}
{"input": "Distinct role of PYK2 in mediating thromboxane generation downstream of both G12/13 and integrin alpha iib beta in platelets.", "output": {"entities": {"chemical": [{"text": "thromboxane", "start": 35, "end": 46}]}}, "schema": []}
{"input": "Proline-rich tyrosine kinase 2 (Pyk2) is activated by various agonists in platelets.", "output": {"entities": {"chemical": [{"text": "Proline", "start": 0, "end": 7}, {"text": "tyrosine", "start": 13, "end": 21}]}}, "schema": []}
{"input": "We evaluated the signaling mechanism and the functional role of Pyk2 in platelets by using pharmacological inhibitors and Pyk2-deficient platelets.", "output": {"entities": {}}, "schema": []}
{"input": "We found that platelet aggregation and secretion in response to 2-MeSADP and AYPGKF were diminished in the presence of Pyk2 inhibitors or in Pyk2-deficient platelets, suggesting that Pyk2 plays a positive regulatory role in platelet functional responses.", "output": {"entities": {"chemical": [{"text": "2-MeSADP", "start": 64, "end": 72}]}}, "schema": []}
{"input": "It has been shown that ADP-, but not thrombin-, induced thromboxane (TxA2) generation depends on integrin signaling.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 23, "end": 26}, {"text": "thromboxane", "start": 56, "end": 67}, {"text": "TxA2", "start": 69, "end": 73}]}}, "schema": []}
{"input": "Unlike ADP, thrombin activates G12/13 pathways, and G12/13 pathways can substitute for integrin signaling for TxA2 generation.", "output": {"entities": {"chemical": [{"text": "ADP", "start": 7, "end": 10}, {"text": "TxA2", "start": 110, "end": 114}]}}, "schema": []}
{"input": "We found that Pyk2 was activated downstream of both G12/13 and integrin-mediated pathways, and both 2-MeSADP-and AYPGKF-induced TxA2 generation was significantly diminished in Pyk2-deficient platelets.", "output": {"entities": {"chemical": [{"text": "2-MeSADP", "start": 100, "end": 108}, {"text": "TxA2", "start": 128, "end": 132}]}}, "schema": []}
{"input": "In addition, TxA2 generation induced by co-stimulation of Gi and Gz pathways, which is dependent on integrin signaling, was inhibited by blocking Pyk2.", "output": {"entities": {"chemical": [{"text": "TxA2", "start": 13, "end": 17}]}}, "schema": []}
{"input": "Furthermore, inhibition of 2-MeSADP-induced TxA2 generation by fibrinogen receptor antagonist was not rescued by co-stimulation of G12/13 pathways in the presence of Pyk2 inhibitor.", "output": {"entities": {"chemical": [{"text": "2-MeSADP", "start": 27, "end": 35}, {"text": "TxA2", "start": 44, "end": 48}]}}, "schema": []}
{"input": "We conclude that Pyk2 is a common signaling effector downstream of both G12/13 and integrin alpha IIb beta 3 signaling which contributes to thromboxane generation.", "output": {"entities": {"chemical": [{"text": "thromboxane", "start": 140, "end": 151}]}}, "schema": []}
{"input": "Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.", "output": {"entities": {}}, "schema": []}
{"input": "Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker.", "output": {"entities": {}}, "schema": []}
{"input": "These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges.", "output": {"entities": {}}, "schema": []}
{"input": "The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data.", "output": {"entities": {}}, "schema": []}
{"input": "With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving.", "output": {"entities": {}}, "schema": []}
{"input": "Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.", "output": {"entities": {}}, "schema": []}
{"input": "Immunogenicity assays for antibody-drug conjugates: case study with ado-trastuzumab emtansine.", "output": {"entities": {}}, "schema": []}
{"input": "Background: Antibody-drug conjugates (ADCs) such as Kadcyla (TM) (ado-trastuzumab emtansine [T-DM1]) present covalently bound cytotoxic drugs, which may influence their immunogenicity potential compared with antibody therapies.", "output": {"entities": {"chemical": [{"text": "DM1", "start": 95, "end": 98}]}}, "schema": []}
{"input": "Therefore, ADCs require assay strategies that allow measurement of responses to all the molecular components.", "output": {"entities": {}}, "schema": []}
{"input": "Results: The immunogenicity strategy for T-DM1 used a risk-based, tiered approach that included screening and titration to detect antitherapeutic antibodies; confirmation of positive responses; and characterization to assess whether the immune response is primarily to the antibody or to the linker-drug and/or new epitopes in trastuzumab resulting from conjugation.", "output": {"entities": {"chemical": [{"text": "DM1", "start": 43, "end": 46}]}}, "schema": []}
{"input": "Conclusion: The tiered immunogenicity assay strategy for T-DM1 allowed detection of antitherapeutic antibodies to all components of the ADC in multiple nonclinical and clinical studies.", "output": {"entities": {"chemical": [{"text": "DM1", "start": 59, "end": 62}]}}, "schema": []}
{"input": "Characterization strategies implemented in clinical studies provided additional insights into the specificity of the immune response.", "output": {"entities": {}}, "schema": []}
{"input": "Immunogenicity testing strategy and bioanalytical assays for antibody-drug conjugates.", "output": {"entities": {}}, "schema": []}
{"input": "Background: Immunogenicity testing is an important component of clinical development for large-molecule biotherapeutics.", "output": {"entities": {}}, "schema": []}
{"input": "New complex types of large molecules, such as antibody-drug conjugates (ADCs), require careful evaluation of the testing strategy and bioanalytical assays used to monitor the development of antitherapeutic antibodies.", "output": {"entities": {}}, "schema": []}
{"input": "Results: An electrochemiluminescence-based immunoassay for the detection and epitope characterization of anti-ADC antibodies was validated.", "output": {"entities": {}}, "schema": []}
{"input": "Using this assay format, antibodies directed against the monoclonal antibody and linker-drug components of the ADC were successfully detected in a multiple-dose rat toxicity study.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: Immunogenicity assays incorporating epitope determination may provide additional information about the characteristics of induced antitherapeutic antibodies, including the magnitude and timing of the various types of antibody responses.", "output": {"entities": {}}, "schema": []}
{"input": "A novel approach to capillary plasma microsampling for quantitative bioanalysis.", "output": {"entities": {}}, "schema": []}
{"input": "Background: A novel device and procedure for the collection and isolation of microvolumes of plasma have been developed and two pilot rodent PK studies have been completed.", "output": {"entities": {}}, "schema": []}
{"input": "Results: This method involves collection of blood into a plastic-wrapped, EDTA-coated capillary tube, containing a small amount of a thixotropic gel and a porous plug.", "output": {"entities": {"chemical": [{"text": "EDTA", "start": 74, "end": 78}]}}, "schema": []}
{"input": "Following blood collection, the capillary is placed into a secondary labeled container suitable for centrifugation and plasma is generated.", "output": {"entities": {}}, "schema": []}
{"input": "During centrifugation, the thixotropic gel isolates the plasma from the red blood cells and creates a physical barrier between the two matrices.", "output": {"entities": {}}, "schema": []}
{"input": "The plasma is then dispensed from the capillary tube into a separate container for storage or processing.", "output": {"entities": {}}, "schema": []}
{"input": "Conclusion: A simple and robust novel approach for the collection of small plasma volumes from rodent TK studies has been demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "Solution pH and Oligoamine Molecular Weight Dependence of the Transition from Monolayer to Multilayer Adsorption at the Air-Water Interface from Sodium Dodecyl Sulfate/Oligoamine Mixtures.", "output": {"entities": {"chemical": [{"text": "Sodium Dodecyl Sulfate", "start": 145, "end": 167}]}}, "schema": []}
{"input": "Neutron reflectivity and surface tension have been used to investigate the solution pH and oligoamine molecular weight dependence of the adsorption of sodium dodecyl sulfate (SDS)/oligoamine mixtures at the air-water interface.", "output": {"entities": {"chemical": [{"text": "sodium dodecyl sulfate", "start": 151, "end": 173}, {"text": "SDS", "start": 175, "end": 178}]}}, "schema": []}
{"input": "For diethylenetriamine, triamine, or triethylenetetramine, tetramine mixed with SDS, there is monolayer adsorption at pH 7 and 10, and multilayer adsorption at pH 3.", "output": {"entities": {"chemical": [{"text": "diethylenetriamine", "start": 4, "end": 22}, {"text": "triamine", "start": 24, "end": 32}, {"text": "triethylenetetramine", "start": 37, "end": 57}, {"text": "tetramine", "start": 59, "end": 68}, {"text": "SDS", "start": 80, "end": 83}]}}, "schema": []}
{"input": "For the slightly higher molecular weight tetraethylenepentamine, pentamine, and pentaethylenehexamine, hexamine, the adsorption is in the form of a monolayer at pH 3 and multilayers at pH 7 and 10.", "output": {"entities": {"chemical": [{"text": "tetraethylenepentamine", "start": 41, "end": 63}, {"text": "pentamine", "start": 65, "end": 74}, {"text": "pentaethylenehexamine", "start": 80, "end": 101}, {"text": "hexamine", "start": 103, "end": 111}]}}, "schema": []}
{"input": "Hence, there is a pH driven transition from monolayer to multilayer adsorption, which shifts from low pH to higher pH as the oligoamine molecular weight increases from tetramine to pentamine.", "output": {"entities": {"chemical": [{"text": "tetramine", "start": 168, "end": 177}, {"text": "pentamine", "start": 181, "end": 190}]}}, "schema": []}
{"input": "This results from the relative balance between the electrostatic attraction between the SDS and amine nitrogen group which decreases as the charge density decreases with increasing pH, the ion-dipole interaction between the amine nitrogen and SDS sulfate group which is dominant at higher pH, and the hydrophobic interalkyl chain interaction between bound SDS molecules which changes with oligoamine molecular weight.", "output": {"entities": {"chemical": [{"text": "SDS", "start": 88, "end": 91}, {"text": "amine nitrogen", "start": 96, "end": 110}, {"text": "amine nitrogen", "start": 224, "end": 238}, {"text": "SDS sulfate", "start": 243, "end": 254}, {"text": "SDS", "start": 356, "end": 359}]}}, "schema": []}
{"input": "Barnacle Cement as Surface Anchor for' Clicking' of Antifouling and Antimicrobial Polymer Brushes on Stainless Steel.", "output": {"entities": {}}, "schema": []}
{"input": "Barnacle cement (BC) was utilized' beneficially' as a surface anchor on stainless steel (SS) for coupling of functional polymer brushes via' click' reactions in both \" grafting-to \" and \" grafting-from \" processes.", "output": {"entities": {}}, "schema": []}
{"input": "Ethylene sulfide (ES), propargyl carbonylimidazole (PPC) and azidoethyl carbonylimidazole (AEC) reacted with amine and/or hydroxyl groups in BC to introduce the corresponding thiol, alkyne and azide groups on SS surfaces (SS-thiol, SS-alkyne and SS-azide, respectively).", "output": {"entities": {"chemical": [{"text": "Ethylene sulfide", "start": 0, "end": 16}, {"text": "propargyl carbonylimidazole", "start": 23, "end": 50}, {"text": "PPC", "start": 52, "end": 55}, {"text": "azidoethyl carbonylimidazole", "start": 61, "end": 89}, {"text": "AEC", "start": 91, "end": 94}, {"text": "amine", "start": 109, "end": 114}, {"text": "hydroxyl", "start": 122, "end": 130}, {"text": "thiol", "start": 175, "end": 180}, {"text": "alkyne", "start": 182, "end": 188}, {"text": "azide", "start": 193, "end": 198}, {"text": "thiol", "start": 225, "end": 230}, {"text": "alkyne", "start": 235, "end": 241}, {"text": "azide", "start": 249, "end": 254}]}}, "schema": []}
{"input": "Antifouling zwitterionic SS-PMPC surface was prepared by thiol-ene photopolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) from the SS-thiol surface.", "output": {"entities": {"chemical": [{"text": "thiol", "start": 57, "end": 62}, {"text": "2-methacryloyloxyethyl phosphorylcholine", "start": 90, "end": 130}, {"text": "MPC", "start": 132, "end": 135}, {"text": "thiol", "start": 149, "end": 154}]}}, "schema": []}
{"input": "Protein-resistant SS-PPEGMA and protein-adsorbing SS-PPFS surfaces were prepared by coupling of the respective azide-functionalized poly (poly (ethylene glycol) methyl ether methacrylate) (azido-PPEGMA) and poly (2, 3, 4, 5, 6-pentafluorostyrene) (azido-PPFS) polymer brushes in azide-alkyne' click' reaction.", "output": {"entities": {"chemical": [{"text": "PPEGMA", "start": 21, "end": 27}, {"text": "PPFS", "start": 53, "end": 57}, {"text": "azide", "start": 111, "end": 116}, {"text": "poly (poly (ethylene glycol) methyl ether methacrylate)", "start": 132, "end": 187}, {"text": "azido-PPEGMA", "start": 189, "end": 201}, {"text": "poly (2, 3, 4, 5, 6-pentafluorostyrene)", "start": 207, "end": 246}, {"text": "azido-PPFS", "start": 248, "end": 258}, {"text": "azide", "start": 279, "end": 284}, {"text": "alkyne", "start": 285, "end": 291}]}}, "schema": []}
{"input": "Antifouling alkyne-functionalized poly (N-hydroxyethyl acrylamide) (alkynyl-PHEAA) and antibacterial alkyne-functionalized poly (2-(methacryloyloxy) ethyl trimethylammonium chloride) (alkynyl-PMETA) polymer brushes were clicked on the SS-azide surface.", "output": {"entities": {"chemical": [{"text": "alkyne", "start": 12, "end": 18}, {"text": "poly (N-hydroxyethyl acrylamide)", "start": 34, "end": 66}, {"text": "alkynyl-PHEAA", "start": 68, "end": 81}, {"text": "alkyne", "start": 101, "end": 107}, {"text": "poly (2-(methacryloyloxy) ethyl trimethylammonium chloride)", "start": 123, "end": 182}, {"text": "alkynyl-PMETA", "start": 184, "end": 197}, {"text": "azide", "start": 238, "end": 243}]}}, "schema": []}
{"input": "Adsorption of bovine serum albumin and bacteria fouling of Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus epidermidis (S. epidermidis) were investigated on the polymer-functionalized SS surfaces.", "output": {"entities": {}}, "schema": []}
{"input": "The versatile bio-anchor and functional polymer brush coatings are stable in abiotic aqueous environment for over a month.", "output": {"entities": {}}, "schema": []}
{"input": "Revisiting the Mechanism of Neutral Hydrolysis of Esters: Water Autoionization Mechanisms with Acid or Base Initiation Pathways.", "output": {"entities": {"chemical": [{"text": "Esters", "start": 50, "end": 56}]}}, "schema": []}
{"input": "The mechanism of neutral hydrolysis of ester has long been explored by theoretical studies.", "output": {"entities": {"chemical": [{"text": "ester", "start": 39, "end": 44}]}}, "schema": []}
{"input": "However, reliable theoretical calculations show that the usual bifunctional catalysis mechanism reported by different authors cannot explain the experimental kinetics.", "output": {"entities": {}}, "schema": []}
{"input": "An important advance was recently reported by Gunaydin and Houk, suggesting that ions are involved in the mechanism and the process initiates by water autoionization followed by protonation of the ester (WAIA mechanism).", "output": {"entities": {"chemical": [{"text": "ester", "start": 197, "end": 202}]}}, "schema": []}
{"input": "However, this mechanism does not explain the hydrolysis of activated esters.", "output": {"entities": {"chemical": [{"text": "esters", "start": 69, "end": 75}]}}, "schema": []}
{"input": "In this work, we have used ab initio calculations, continuum solvation models and ab initio classical trajectory to support the WAIA mechanism for normal ester.", "output": {"entities": {"chemical": [{"text": "ester", "start": 154, "end": 159}]}}, "schema": []}
{"input": "In the case of activated esters, the process can also be viewed as water autoionization with formation of hydroxide ion aided by a second water moleculeacting as a general base (WAIB mechanism).", "output": {"entities": {"chemical": [{"text": "hydroxide", "start": 106, "end": 115}]}}, "schema": []}
{"input": "This is the mechanism proposed by Jencks and Carriuolo fifty years ago.", "output": {"entities": {}}, "schema": []}
{"input": "Our analysis point out that the usual method for exploring mechanisms, searching for saddle points, may not work for problems like the present one, since there are no saddle points on the reaction pathway.", "output": {"entities": {}}, "schema": []}
{"input": "Rather, the formation of a pair of ions from a neutral species may have an asymptotic barrier.", "output": {"entities": {}}, "schema": []}
{"input": "The approach used in this paper allows the calculation of the free energy profile and enable us to explain the mechanism and kinetics of the neutral hydrolysis of normal (methyl acetate) and activated (methyl trifluoroacetate) esters.", "output": {"entities": {"chemical": [{"text": "methyl acetate", "start": 171, "end": 185}, {"text": "methyl trifluoroacetate", "start": 202, "end": 225}, {"text": "esters", "start": 227, "end": 233}]}}, "schema": []}
{"input": "In addition, the present study suggests that formation of a pair of ions should be always considered in reactions in aqueous solution.", "output": {"entities": {}}, "schema": []}
{"input": "Nanoscale Patterning of Membrane-Bound Proteins Formed through Curvature-Induced Partitioning of Phase-Specific Receptor Lipids.", "output": {"entities": {}}, "schema": []}
{"input": "This work describes a technique for forming high-density arrays and patterns of membrane-bound proteins through binding to a curvature-organized compositional pattern of metal-chelating lipids (Cu (2 +)-DOIDA or Cu (2 +)-DSIDA).", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 194, "end": 202}, {"text": "Cu (2 +)", "start": 212, "end": 220}]}}, "schema": []}
{"input": "In this bottom-up approach, the underlying support is an e-beam formed, square lattice pattern of hemispheres.", "output": {"entities": {}}, "schema": []}
{"input": "This curvature pattern sorts Cu (2 +)-DOIDA to the 200 nm hemispherical lattice sites of a 600 nm X 600 nm unit cell in Ld-Lo phase separated lipid multibilayers.", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Binding of histidine-tagged green fluorescent protein (His-GFP) creates a high density array of His-GFP-bound pixels localized to the square lattice sites.", "output": {"entities": {}}, "schema": []}
{"input": "In comparison, the negative pixel pattern is created by sorting Cu (2 +)-DSIDA in Ld-L beta' phase separated lipid multibilayers to the flat grid between the lattice sites followed by binding to His-GFP.", "output": {"entities": {"chemical": [{"text": "Cu (2 +)", "start": 64, "end": 72}]}}, "schema": []}
{"input": "Lattice defects in the His-GFP pattern lead to interesting features such as pattern circularity.", "output": {"entities": {}}, "schema": []}
{"input": "We also observe defect-free arrays of His-GFP that demonstrate perfect arrays can be formed by this method suggesting the possibility of using this approach for the localization of various active molecules to form protein, DNA, or optically active molecular arrays.", "output": {"entities": {}}, "schema": []}
{"input": "A Minimal Transcriptional Controlling Network of Regulatory T Cell Development.", "output": {"entities": {}}, "schema": []}
{"input": "Regulatory T cells (Treg) are a subpopulation of T cells that are central to immune homeostasis and develop under the control of a complex regulatory network consisting of FoxP3 and its partner factors.", "output": {"entities": {}}, "schema": []}
{"input": "A central question about this network is how does it enable T cells to robustly specify and stably maintain their states despite intrinsic and environmental fluctuations.", "output": {"entities": {}}, "schema": []}
{"input": "Inspired by recent experimental advances, we propose here a minimal transcriptional controlling network and use it to illustrate the robustness and dynamic features of Treg development.", "output": {"entities": {}}, "schema": []}
{"input": "Our study shows that the controlling network may exhibit distinct dynamics depending on its parameter regimes and that the maintenance of multistability requires the orchestration of both its positive and negative feedback loops.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, system volume contributes monotonically to the increase of the network' s robustness.", "output": {"entities": {}}, "schema": []}
{"input": "We further show that the dynamics of our model varies with the alteration of FoxP3-DNA binding affinity, consistent with recent experimental findings.", "output": {"entities": {}}, "schema": []}
{"input": "This minimal model thereby offers new insights into the dynamics and robustness of Treg development and may serve as a platform for future exploration towards a more quantitative and systematic understanding of the immune system.", "output": {"entities": {}}, "schema": []}
{"input": "Synthesis of Hollow Ag-Au Bimetallic Nanoparticles in Polyelectrolyte Multilayers.", "output": {"entities": {"chemical": [{"text": "Ag-Au", "start": 20, "end": 25}]}}, "schema": []}
{"input": "Ag nanoparticles of ~ 20 nm size and rather uniform size distribution were synthesized in polyelectrolyte multilayers (PEMs) via an ion-exchange/reduction process in two stages (seeding and growth), which were used as sacrificial templates to fabricate Ag-Au bimetallic hollow nanoparticles via galvanic replacement reaction.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 0, "end": 2}, {"text": "Ag-Au", "start": 253, "end": 258}]}}, "schema": []}
{"input": "The reaction process was monitored by UV-vis spectroscopy.", "output": {"entities": {}}, "schema": []}
{"input": "The morphology and structure of the nanoparticles were characterized by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy, which confirmed the formation of hollow Ag-Au bimetallic nanoparticles.", "output": {"entities": {"chemical": [{"text": "Ag-Au", "start": 193, "end": 198}]}}, "schema": []}
{"input": "UV-vis absorbance spectroscopy and TEM results indicated that both size and optical properties of the Ag nanoparticles in the PEM can be controlled by manipulating ion content in the PEM and the number of the ion-exchange/reduction cycle, whereas that of Ag-Au bimetallic nanoparticles were dependent on size of the Ag templates and the replacement reaction kinetics.", "output": {"entities": {"chemical": [{"text": "Ag", "start": 102, "end": 104}, {"text": "Ag-Au", "start": 255, "end": 260}, {"text": "Ag", "start": 316, "end": 318}]}}, "schema": []}
{"input": "The hollow Ag-Au bimetallic nanoparticles exhibited a significant red shift in the surface plasmon resonance to the near-infrared region.", "output": {"entities": {"chemical": [{"text": "Ag-Au", "start": 11, "end": 16}]}}, "schema": []}
{"input": "The strategy enables facile preparation of hollow bimetallic nanoparticles in situ in polymer matrices.", "output": {"entities": {}}, "schema": []}
{"input": "Vibrational Perturbations of W (CO) 6 Trapped in a Molecular Lattice Probed by Linear and Non Linear Spectroscopy.", "output": {"entities": {"chemical": [{"text": "W (CO) 6", "start": 29, "end": 37}]}}, "schema": []}
{"input": "Vibrational dynamics of the T1u CO stretching mode of tungsten hexacarbonyl is explored when the molecule is embedded in a nitrogen matrix at low temperature.", "output": {"entities": {"chemical": [{"text": "CO", "start": 32, "end": 34}, {"text": "tungsten hexacarbonyl", "start": 54, "end": 75}, {"text": "nitrogen", "start": 123, "end": 131}]}}, "schema": []}
{"input": "Experiments combined IR absorption spectroscopy and IR stimulated photon echoes at the femtosecond timescale.", "output": {"entities": {}}, "schema": []}
{"input": "W (CO) 6 is found to be trapped in two main families of sites differing by their symmetries (called hereafter Oh and D2h).", "output": {"entities": {"chemical": [{"text": "W (CO) 6", "start": 0, "end": 8}]}}, "schema": []}
{"input": "In Oh sites, the vibrational coherence is strongly temperature dependent, exhibiting a coupling with librational phonons of the nitrogen lattice.", "output": {"entities": {"chemical": [{"text": "nitrogen", "start": 128, "end": 136}]}}, "schema": []}
{"input": "Perturbation in D2h sites results in the splitting of the T1u band in three components.", "output": {"entities": {}}, "schema": []}
{"input": "Each component is inhomogeneously broadened, with dephasing times in the tens of picoseconds, weakly coupled to the lattice phonons.", "output": {"entities": {}}, "schema": []}
{"input": "Experiments in solid krypton are performed to compare the effect of atomic and diatomic host lattices.", "output": {"entities": {"chemical": [{"text": "krypton", "start": 21, "end": 28}]}}, "schema": []}
{"input": "Dephasing time in Kr does not depend on temperature and remains in the hundreds of picosecond, highlighting the molecular origin of dephasing process in N2.", "output": {"entities": {"chemical": [{"text": "Kr", "start": 18, "end": 20}, {"text": "N2", "start": 153, "end": 155}]}}, "schema": []}
{"input": "Additionally, non linear signals show oscillations due to quantum beats and polarization interferences between different frequency components of the induced third order polarization, giving information, in particular, on the overtone vibrational transition.", "output": {"entities": {}}, "schema": []}
{"input": "Base-Specific Ionization of Deprotonated Nucleotides by Resonance Enhanced Two-Photon Detachment.", "output": {"entities": {"chemical": [{"text": "Nucleotides", "start": 41, "end": 52}]}}, "schema": []}
{"input": "The intrinsic ionization energy of a base in DNA plays a critical role in determining the energies at which damage mechanisms may emerge.", "output": {"entities": {}}, "schema": []}
{"input": "Here, a two-photon resonance-enhanced ionization scheme is presented that utilizes the 1 pi pi * transition, localized on the DNA base, to elucidate the base-specific ionization in a deprotonated nucleotide.", "output": {"entities": {"chemical": [{"text": "nucleotide", "start": 196, "end": 206}]}}, "schema": []}
{"input": "In contrast to previous reports, the scheme is insensitive to competing ionization channels arising from the sugar-phosphate backbone.", "output": {"entities": {"chemical": [{"text": "sugar", "start": 109, "end": 114}, {"text": "phosphate", "start": 115, "end": 124}]}}, "schema": []}
{"input": "Using this approach, we demonstrate that for all bases except guanine, the lowest electron detachment energy corresponds to detachment from the sugar-phosphate backbone and allows us to determine the lowest adiabatic ionization energy for the other three bases for the first time in an isolated nucleotide.", "output": {"entities": {"chemical": [{"text": "guanine", "start": 62, "end": 69}, {"text": "sugar", "start": 144, "end": 149}, {"text": "phosphate", "start": 150, "end": 159}, {"text": "nucleotide", "start": 295, "end": 305}]}}, "schema": []}
{"input": "The Pyrimidyn compounds: dual-action small molecule pyrimidine-based dynamin inhibitors.", "output": {"entities": {"chemical": [{"text": "Pyrimidyn", "start": 4, "end": 13}, {"text": "pyrimidine", "start": 52, "end": 62}]}}, "schema": []}
{"input": "Dynamin is required for clathrin-mediated endocytosis (CME).", "output": {"entities": {}}, "schema": []}
{"input": "Its GTPase activity stimulated by phospholipid binding to its PH domain which induces helical oligomerization.", "output": {"entities": {}}, "schema": []}
{"input": "We have designed a series of novel pyrimidine-based' PyrimidynTM' compounds which inhibit the lipid stimulated GTPase activity of full length dynamin I and II with similar potency.", "output": {"entities": {"chemical": [{"text": "pyrimidine", "start": 35, "end": 45}]}}, "schema": []}
{"input": "The most potent analogue, Pyrimidyn 7, has an IC50 of 1. 1 mu M for dynamin I and 1. 8 mu M for dynamin II, making it among the most potent dynamin inhibitors identified to date.", "output": {"entities": {"chemical": [{"text": "Pyrimidyn", "start": 26, "end": 35}]}}, "schema": []}
{"input": "We investigated the mechanism of action of the Pyrimidyn compounds in detail by examining the kinetics of Pyrimidyn 7 inhibition of dynamin.", "output": {"entities": {"chemical": [{"text": "Pyrimidyn", "start": 47, "end": 56}, {"text": "Pyrimidyn", "start": 106, "end": 115}]}}, "schema": []}
{"input": "The compound competitively inhibits both GTP and phospholipid interactions with dynamin I.", "output": {"entities": {"chemical": [{"text": "GTP", "start": 41, "end": 44}]}}, "schema": []}
{"input": "While both mechanisms of action have been previously observed separately, this is the first inhibitor series to incorporate both and thereby targets two distinct domains of dynamin.", "output": {"entities": {}}, "schema": []}
{"input": "Pyrimidyn 6 and 7 reversibly inhibit CME of both transferrin and EGF in a number of non-neuronal cell lines as well as inhibiting synaptic vesicle endocytosis (SVE) in nerve terminals.", "output": {"entities": {"chemical": [{"text": "Pyrimidyn", "start": 0, "end": 9}]}}, "schema": []}
{"input": "Therefore, Pyrimidyn compounds block endocytosis by directly competing with GTP and lipid binding to dynamin, limiting both the recruitment of dynamin to membranes and its activation.", "output": {"entities": {"chemical": [{"text": "Pyrimidyn", "start": 11, "end": 20}, {"text": "GTP", "start": 76, "end": 79}]}}, "schema": []}
{"input": "This dual mode of action provides an important new tool for molecular dissection of dynamin' s role in endocytosis.", "output": {"entities": {}}, "schema": []}
{"input": "Interactive effects of smoking and glutathione S-transferase polymorphisms on the development of non-alcoholic fatty liver disease.", "output": {"entities": {"chemical": [{"text": "glutathione S", "start": 35, "end": 48}]}}, "schema": []}
{"input": "Glutathione S-transferases (GSTs) protect cells against exogenous and endogenous oxidative stress.", "output": {"entities": {"chemical": [{"text": "Glutathione S", "start": 0, "end": 13}]}}, "schema": []}
{"input": "GST polymorphisms are associated with the development of cardiovascular disease (CVD) and diabetes mellitus (DM), especially in current-smokers.", "output": {"entities": {}}, "schema": []}
{"input": "Non-alcoholic fatty liver disease (NAFLD) is a predictor of future CVD or DM, because oxidative stress contributes to their pathogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "This study investigated whether the combination of smoking status and GST genotypes could affect the risk for NAFLD.", "output": {"entities": {}}, "schema": []}
{"input": "A cross-sectional analysis was conducted among 713 Japanese participants (458 males and 255 females) during a health screening program.", "output": {"entities": {}}, "schema": []}
{"input": "The GSTM1 null, GSTT1 null, GSTP1 * A/* B or * B/* B and GSTA1 * A/* B or * B/* B genotypes were determined and deemed to be high-risk genotypes.", "output": {"entities": {}}, "schema": []}
{"input": "The prevalence of NAFLD was 18. 7%.", "output": {"entities": {}}, "schema": []}
{"input": "Among never-smokers, carriers of one, and those of two or more high-risk GSTM1, GSTP1 or GSTA1 genotypes were at a higher risk for NAFLD than those who were not carriers [odds ratio (95% confidence interval): 2. 6 (1. 1-5. 9) and 3. 3 (1. 3-8. 1), respectively], and the risk was further increased among current-smokers [4. 6 (1. 6-13. 0) and 5. 4 (1. 2-23. 7), respectively].", "output": {"entities": {}}, "schema": []}
{"input": "This is the first report to show that the combination of current-smoking and harboring high-risk GSTM1, GSTP1 and/or GSTA1 genotypes is interactively associated with the risk of NAFLD.", "output": {"entities": {}}, "schema": []}
{"input": "Melamine activates NF kappa B/COX-2/PGE2 pathway and increases NADPH oxidase-dependent ROS production in macrophages and human embryonic kidney cells.", "output": {"entities": {"chemical": [{"text": "Melamine", "start": 0, "end": 8}, {"text": "NADPH", "start": 63, "end": 68}]}}, "schema": []}
{"input": "Melamine is a wildly used compound in manufactures of plastics and resins.", "output": {"entities": {"chemical": [{"text": "Melamine", "start": 0, "end": 8}]}}, "schema": []}
{"input": "A variety of toxic effects from melamine, including nephrolithiasis, chronic kidney inflammation, and bladder carcinoma, have been mentioned.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 32, "end": 40}]}}, "schema": []}
{"input": "Oxidative stress is considered to be an important pathogenic mechanism of kidney disease which may develop from an increasing free radical production through inflammation.", "output": {"entities": {}}, "schema": []}
{"input": "The aim of this study is to investigate melamine-induced oxidative stress and inflammation in macrophage-like cell line RAW 264. 7 and human embryonic kidney cell line HEK293.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 40, "end": 48}]}}, "schema": []}
{"input": "Results indicated melamine activated nuclear factor (NF)-kappa B through increasing I kappa B-alpha degradation and NF-kappa B p65/p50 DNA-binding activity.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 18, "end": 26}]}}, "schema": []}
{"input": "In addition, melamine significantly increased COX-2 expression and prostaglandin E2 (PGE2) production.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 13, "end": 21}, {"text": "prostaglandin E2", "start": 67, "end": 83}, {"text": "PGE2", "start": 85, "end": 89}]}}, "schema": []}
{"input": "Moreover, melamine activated NADPH oxidase (NOX), including NOX1, 2 and 4, accompanied with an increase in reactive oxygen species (ROS) production.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 10, "end": 18}, {"text": "NADPH", "start": 29, "end": 34}, {"text": "oxygen", "start": 116, "end": 122}]}}, "schema": []}
{"input": "Furthermore, melamine-induced ROS production could be attenuated by apocynin, a NOX inhibitor.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 13, "end": 21}, {"text": "apocynin", "start": 68, "end": 76}]}}, "schema": []}
{"input": "In conclusion, our findings suggest melamine increased inflammation and oxidative stress via activation of NF-kappa B/COX-2 and NOX/ROS pathway, and first revealed the critical role of NOX in melamine-induced ROS production, suggesting the potential of NOX inhibitor against melamine toxicity.", "output": {"entities": {"chemical": [{"text": "melamine", "start": 36, "end": 44}, {"text": "melamine", "start": 192, "end": 200}, {"text": "melamine", "start": 275, "end": 283}]}}, "schema": []}
{"input": "Genetic Polymorphism at Val (80) (rs700518) of the CYP19A1 Gene is Associated with Aromatase Inhibitor Associated Bone Loss in Women with ER (+) Breast Cancer.", "output": {"entities": {"chemical": [{"text": "Val", "start": 24, "end": 27}]}}, "schema": []}
{"input": "PURPOSE: Polymorphisms in the CYP19A1 (aromatase) gene have been reported to influence disease-free survival and the incidence of musculoskeletal complaints in patients taking aromatase inhibitors (AIs) for estrogen receptor positive (ER +) breast cancer.", "output": {"entities": {"chemical": [{"text": "estrogen", "start": 207, "end": 215}]}}, "schema": []}
{"input": "Bone loss and fractures are well-recognized complications from AI therapy.", "output": {"entities": {}}, "schema": []}
{"input": "The objective of this study is to determine the influence of polymorphisms in the CYP19A1 gene on bone loss among patients taking aromatase inhibitors for ER + breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "PATIENTS AND METHODS: The subjects consisted of 97 postmenopausal women with ER + breast cancer who were initiated on third-generation AIs.", "output": {"entities": {}}, "schema": []}
{"input": "Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at baseline and at 6 and 12 months.", "output": {"entities": {}}, "schema": []}
{"input": "Twenty-four hour urine N-telopeptide (NTX) was measured by Elisa and serum estradiol was measured by ultrasensitive radioimmunoassay at baseline, and at 6 months.", "output": {"entities": {"chemical": [{"text": "N", "start": 23, "end": 24}, {"text": "estradiol", "start": 75, "end": 84}]}}, "schema": []}
{"input": "Genotyping was done by Taqman SNP allelic discrimination assay.", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: Women with the AA genotype for the rs700518 (G/A at Val (80)) developed significant bone loss at the lumbar spine and the total hip at 12 months relative to patients carrying the G allele (GA/GG); both p = 0. 03.", "output": {"entities": {"chemical": [{"text": "Val", "start": 61, "end": 64}]}}, "schema": []}
{"input": "There was a borderline greater increase in urinary NTX in those with the AA genotype compared to patients with the G allele, p = 0. 05; but no significant difference in changes in estradiol levels among the genotypes.", "output": {"entities": {"chemical": [{"text": "estradiol", "start": 180, "end": 189}]}}, "schema": []}
{"input": "CONCLUSION: Patients with the AA genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for AI-associated bone loss and deserve close follow-up during long-term AI therapy.", "output": {"entities": {}}, "schema": []}
{"input": "Epigenetic Mechanisms of Drug Addiction.", "output": {"entities": {}}, "schema": []}
{"input": "Drug addiction involves potentially life-long behavioral abnormalities that are caused in vulnerable individuals by repeated exposure to a drug of abuse.", "output": {"entities": {}}, "schema": []}
{"input": "The persistence of these behavioral changes suggests that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype.", "output": {"entities": {}}, "schema": []}
{"input": "Work over the past decade has demonstrated a crucial role for epigenetic mechanisms in driving lasting changes in gene expression in diverse tissues, including brain.", "output": {"entities": {}}, "schema": []}
{"input": "This has prompted recent research aimed at characterizing the influence of epigenetic regulatory events in mediating the lasting effects of drugs of abuse on the brain in animal models of drug addiction.", "output": {"entities": {}}, "schema": []}
{"input": "This review provides a progress report of this still early work in the field.", "output": {"entities": {}}, "schema": []}
{"input": "As will be seen, there is robust evidence that repeated exposure to drugs of abuse induces changes within the brain' s reward regions in three major modes of epigenetic regulation-histone modifications such as acetylation and methylation, DNA methylation, and non-coding RNAs.", "output": {"entities": {}}, "schema": []}
{"input": "In several instances, it has been possible to demonstrate directly the contribution of such epigenetic changes to addiction-related behavioral abnormalities.", "output": {"entities": {}}, "schema": []}
{"input": "Studies of epigenetic mechanisms of addiction are also providing an unprecedented view of the range of genes and non-genic regions that are affected by repeated drug exposure and the precise molecular basis of that regulation.", "output": {"entities": {}}, "schema": []}
{"input": "Work is now needed to validate key aspects of this work in human addiction and evaluate the possibility of mining this information to develop new diagnostic tests and more effective treatments for addiction syndromes.", "output": {"entities": {}}, "schema": []}
{"input": "A new perspective on muscarinic receptor antagonism in obstructive airways diseases.", "output": {"entities": {}}, "schema": []}
{"input": "Acetylcholine has traditionally only been regarded as a neurotransmitter of the parasympathetic nervous system, causing bronchoconstriction and mucus secretion in asthma and COPD by muscarinic receptor activation on airway smooth muscle and mucus-producing cells.", "output": {"entities": {"chemical": [{"text": "Acetylcholine", "start": 0, "end": 13}]}}, "schema": []}
{"input": "Recent studies in experimental models indicate that muscarinic receptor stimulation in the airways also induces pro-inflammatory, pro-proliferative and pro-fibrotic effects, which may involve activation of airway structural and inflammatory cells by neuronal as well as non-neuronal acetylcholine.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 283, "end": 296}]}}, "schema": []}
{"input": "In addition, mechanical changes caused by muscarinic agonist-induced bronchoconstriction may be involved in airway remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "Crosstalk between muscarinic receptors and beta 2-adrenoceptors on airway smooth muscle causes a reduced bronchodilator response to beta 2-agonists, and a similar mechanism could possibly apply to the poor inhibition of inflammatory and remodeling processes by these drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Collectively, these findings provide novel perspectives for muscarinic receptor antagonists in asthma and COPD, since these drugs may not only acutely affect cholinergic airways obstruction, but also have important beneficial effects on beta 2-agonist responsiveness, airway inflammation and remodeling.", "output": {"entities": {}}, "schema": []}
{"input": "The clinical relevance of these findings is presently under investigation and starting to emerge.", "output": {"entities": {}}, "schema": []}
{"input": "Enhanced excitability in the infralimbic cortex produces anxiety-like behaviors.", "output": {"entities": {}}, "schema": []}
{"input": "The medial prefrontal cortex (mPFC) has been implicated in modulating anxiety.", "output": {"entities": {}}, "schema": []}
{"input": "However, it is unknown whether excitatory or inhibitory neurotransmission in the infralimbic (IL) subregion of the mPFC underlies the pathology of anxiety-related behavior.", "output": {"entities": {}}, "schema": []}
{"input": "To address this issue, we infused the GABAA receptor (GABAAR) antagonist bicuculline to temporarily activate the IL cortex.", "output": {"entities": {"chemical": [{"text": "bicuculline", "start": 73, "end": 84}]}}, "schema": []}
{"input": "IL cortex activation decreased the time spent in the center area in the open field test, decreased exploration of the open-arms in the elevated plus maze test, and increased the latency to bite food in the novelty-suppressed feeding test.", "output": {"entities": {}}, "schema": []}
{"input": "These findings substantiate the GABAergic system' s role in anxiety-related behaviors.", "output": {"entities": {"chemical": [{"text": "GABAergic", "start": 32, "end": 41}]}}, "schema": []}
{"input": "IL cortex inactivation with the AMPA receptor (AMPAR) antagonist CNQX produced opposite, anxiolytic effects.", "output": {"entities": {"chemical": [{"text": "AMPA", "start": 32, "end": 36}]}}, "schema": []}
{"input": "However, infusion of the NMDA receptor (NMDAR) antagonist AP5 into the IL cortex had no significant effect.", "output": {"entities": {"chemical": [{"text": "NMDA", "start": 25, "end": 29}]}}, "schema": []}
{"input": "Additionally, we did not observe motor activity deficits or appetite deficits following inhibition of GABAergic or glutamatergic neurotransmission.", "output": {"entities": {"chemical": [{"text": "GABAergic", "start": 102, "end": 111}]}}, "schema": []}
{"input": "Interestingly, we found parallel and corresponding electrophysiological changes in anxious mice; compared to mice with relatively low anxiety, the relatively high anxiety mice exhibited smaller evoked inhibitory postsynaptic currents (eIPSCs) and larger AMPA-mediated evoked excitatory postsynaptic currents (eEPSCs) in pyramidal neurons in the IL cortex.", "output": {"entities": {"chemical": [{"text": "AMPA", "start": 254, "end": 258}]}}, "schema": []}
{"input": "The changes of eIPSCs and eEPSCs were due to presynaptic mechanisms.", "output": {"entities": {}}, "schema": []}
{"input": "Our results suggest that imbalances of neurotransmission in the IL cortex may cause a net increase in excitatory inputs onto pyramidal neurons, which may underlie the pathogenic mechanism of anxiety disorders.", "output": {"entities": {}}, "schema": []}
{"input": "Haloperidol promotes mTORC1-dependent phosphorylation of ribosomal protein S6 via dopamine-and cAMP-regulated phosphoprotein of 32 kDa and inhibition of protein phosphatase-1.", "output": {"entities": {"chemical": [{"text": "Haloperidol", "start": 0, "end": 11}, {"text": "dopamine", "start": 82, "end": 90}, {"text": "cAMP", "start": 95, "end": 99}]}}, "schema": []}
{"input": "The ribosomal protein S6 (rpS6) is a component of the small 40S ribosomal subunit, involved in multiple physiological functions.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we examined the effects produced by haloperidol, a typical antipsychotic drug, on the phosphorylation of rpS6 at Ser240/244 in the striatum, a brain region involved in neurodegenerative and neuropsychiatric disorders.", "output": {"entities": {"chemical": [{"text": "haloperidol", "start": 42, "end": 53}, {"text": "Ser240", "start": 119, "end": 125}]}}, "schema": []}
{"input": "Administration of haloperidol increased Ser240/244 phosphorylation in a subpopulation of GABA-ergic medium spiny neurons (MSNs), which express dopamine D2 receptors (D2Rs).", "output": {"entities": {"chemical": [{"text": "haloperidol", "start": 18, "end": 29}, {"text": "Ser240", "start": 40, "end": 46}, {"text": "GABA", "start": 89, "end": 93}, {"text": "dopamine", "start": 143, "end": 151}]}}, "schema": []}
{"input": "This effect was prevented by rapamycin, an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1), or by PF470867, a selective inhibitor of the p70 ribosomal S6 kinase 1 (S6K1).", "output": {"entities": {"chemical": [{"text": "rapamycin", "start": 29, "end": 38}, {"text": "rapamycin", "start": 80, "end": 89}, {"text": "PF470867", "start": 116, "end": 124}]}}, "schema": []}
{"input": "We also found that the effect of haloperidol on Ser240/244 phosphorylation was prevented by functional inactivation of dopamine-and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), an endogenous inhibitor of protein phosphatase-1 (PP-1).", "output": {"entities": {"chemical": [{"text": "haloperidol", "start": 33, "end": 44}, {"text": "Ser240", "start": 48, "end": 54}, {"text": "dopamine", "start": 119, "end": 127}, {"text": "cAMP", "start": 132, "end": 136}]}}, "schema": []}
{"input": "In line with this observation, incubation of striatal slices with okadaic acid and calyculin A, two inhibitors of PP-1, increased Ser240/244 phosphorylation.", "output": {"entities": {"chemical": [{"text": "okadaic acid", "start": 66, "end": 78}, {"text": "calyculin A", "start": 83, "end": 94}, {"text": "Ser240", "start": 130, "end": 136}]}}, "schema": []}
{"input": "These results show that haloperidol promotes mTORC1-and S6K1-dependent phosphorylation of rpS6 at Ser240/244, in a subpopulation of striatal MSNs expressing D2Rs.", "output": {"entities": {"chemical": [{"text": "haloperidol", "start": 24, "end": 35}, {"text": "Ser240", "start": 98, "end": 104}]}}, "schema": []}
{"input": "They also indicate that this effect is exerted by suppressing dephosphorylation at Ser240/244, through PKA-dependent activation of DARPP-32 and inhibition of PP-1.", "output": {"entities": {"chemical": [{"text": "Ser240", "start": 83, "end": 89}]}}, "schema": []}
{"input": "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death.", "output": {"entities": {"chemical": [{"text": "Arylpiperazine", "start": 0, "end": 14}, {"text": "6-hydroxydopamine", "start": 84, "end": 101}]}}, "schema": []}
{"input": "We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SH-SY5Y neuroblastoma cells from the neurotoxin 6-hydroxydopamine (6-OHDA).", "output": {"entities": {"chemical": [{"text": "arylpiperazine", "start": 55, "end": 69}, {"text": "6-hydroxydopamine", "start": 145, "end": 162}, {"text": "6-OHDA", "start": 164, "end": 170}]}}, "schema": []}
{"input": "The compound with the most potent neuroprotective action was N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), which reduced 6-OHDA-induced apoptotic death through stabilization of mitochondrial membrane and subsequent prevention of superoxide production, caspase activation and DNA fragmentation.", "output": {"entities": {"chemical": [{"text": "N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide", "start": 61, "end": 122}, {"text": "6-OHDA", "start": 143, "end": 149}, {"text": "superoxide", "start": 251, "end": 261}]}}, "schema": []}
{"input": "6-OHDA-triggered autophagic response was also reduced by 6b, which prevented inactivation of the main autophagy repressor mTOR, upregulation of pro-autophagic beclin-1, conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to autophagosome-associated LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 0, "end": 6}, {"text": "6-OHDA", "start": 327, "end": 333}]}}, "schema": []}
{"input": "The inhibition of autophagy using LC3 beta gene silencing or pharmacological autophagy blockers 3-methyladenine or bafilomycin A1, mimicked the cytoprotective effect of 6b.", "output": {"entities": {"chemical": [{"text": "3-methyladenine", "start": 96, "end": 111}, {"text": "bafilomycin A1", "start": 115, "end": 129}]}}, "schema": []}
{"input": "While the treatment with 6b had no effect on the phosphorylation of proapoptotic MAP kinases ERK and JNK, it markedly increased the phosphorylation of the prosurvival kinase Akt in 6-OHDA-treated cells.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 181, "end": 187}]}}, "schema": []}
{"input": "Akt inhibitor DEBC or RNA interference-mediated Akt silencing reduced the ability of 6b to block 6-OHDA-triggered apoptotic and autophagic responses, thus confirming their dependency on Akt activation.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 97, "end": 103}]}}, "schema": []}
{"input": "The cytoprotective effect of 6b was also observed in 6-OHDA-treated neuronal PC12 cells, but not in SH-SY5Y or PC12 cells exposed to 1-methyl-4-phenylpyridinium, indicating that the observed neuroprotection was dependent on the cytotoxic stimulus.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 53, "end": 59}, {"text": "1-methyl-4-phenylpyridinium", "start": 133, "end": 160}]}}, "schema": []}
{"input": "Because of the ability to prevent 6-OHDA induced apoptotic/autophagic cell death through activation of Akt, the investigated arylpiperazines could be potential candidates for treatment of neurodegenerative diseases.", "output": {"entities": {"chemical": [{"text": "6-OHDA", "start": 34, "end": 40}, {"text": "arylpiperazines", "start": 125, "end": 140}]}}, "schema": []}
{"input": "The fatty acid amide hydrolase inhibitor, URB597, promotes retinal ganglion cell neuroprotection in a rat model of optic nerve axotomy.", "output": {"entities": {"chemical": [{"text": "fatty acid amide", "start": 4, "end": 20}, {"text": "URB597", "start": 42, "end": 48}, {"text": "retinal", "start": 59, "end": 66}]}}, "schema": []}
{"input": "The endocannabinoid, N-arachidonoylethanolamine (AEA), is degraded by the enzyme fatty acid amide hydrolase (FAAH).", "output": {"entities": {"chemical": [{"text": "N-arachidonoylethanolamine", "start": 21, "end": 47}, {"text": "AEA", "start": 49, "end": 52}, {"text": "fatty acid amide", "start": 81, "end": 97}]}}, "schema": []}
{"input": "This study examined whether the FAAH inhibitor, URB597, increases retinal ganglion cell (RGC) survival following optic nerve axotomy in young and aged animals.", "output": {"entities": {"chemical": [{"text": "retinal", "start": 66, "end": 73}]}}, "schema": []}
{"input": "URB597 alone, or together with either a CB1 or CB2 receptor antagonist, was administered daily for 1 or 2 weeks post-axotomy.", "output": {"entities": {"chemical": [{"text": "URB597", "start": 0, "end": 6}]}}, "schema": []}
{"input": "Histological assessment of retinas indicated that URB597 increased RGC survival in young retina at 1 and 2 weeks post-axotomy.", "output": {"entities": {"chemical": [{"text": "URB597", "start": 50, "end": 56}]}}, "schema": []}
{"input": "The increase in RGC survival at 2 weeks was accompanied by a reduction in phagocytic microglia.", "output": {"entities": {}}, "schema": []}
{"input": "The CB1 antagonist, AM281, but not the CB2 antagonist, AM630, ablated URB597-mediated RGC neuroprotection.", "output": {"entities": {"chemical": [{"text": "AM281", "start": 20, "end": 25}, {"text": "AM630", "start": 55, "end": 60}, {"text": "URB597", "start": 70, "end": 76}]}}, "schema": []}
{"input": "CB1 or CB2 antagonism increased phagocytic microglia in URB597 and vehicle-treated animals.", "output": {"entities": {"chemical": [{"text": "URB597", "start": 56, "end": 62}]}}, "schema": []}
{"input": "In aged animals, URB597 increased RGC survival at 1 week, but not at 2 weeks post-axotomy and had no effect on microglia.", "output": {"entities": {"chemical": [{"text": "URB597", "start": 17, "end": 23}]}}, "schema": []}
{"input": "Retinal Iba-1 positive microglia were also decreased in URB597-treated axotomized young animals and this decrease was mitigated by CB1 but not CB2 antagonism.", "output": {"entities": {"chemical": [{"text": "Retinal", "start": 0, "end": 7}, {"text": "URB597", "start": 56, "end": 62}]}}, "schema": []}
{"input": "As seen with phagocytotic microglia, the CB2 antagonist, AM630, increased Iba-1 positive microglia in the absence of URB597 treatment.", "output": {"entities": {"chemical": [{"text": "AM630", "start": 57, "end": 62}, {"text": "URB597", "start": 117, "end": 123}]}}, "schema": []}
{"input": "Measurement of retinal endocannabinoid levels in URB597-treated animals at 2 weeks post-axotomy revealed a significant increase in AEA levels, accompanied by a decrease by a decrease in the AEA metabolite, N-arachidonoylglycine, in young animals but not aged animals.", "output": {"entities": {"chemical": [{"text": "retinal", "start": 15, "end": 22}, {"text": "URB597", "start": 49, "end": 55}, {"text": "AEA", "start": 131, "end": 134}, {"text": "AEA", "start": 190, "end": 193}, {"text": "N-arachidonoylglycine", "start": 206, "end": 227}]}}, "schema": []}
{"input": "2-arachidonoylglycerol levels were similar across all experimental groups.", "output": {"entities": {"chemical": [{"text": "2-arachidonoylglycerol", "start": 0, "end": 22}]}}, "schema": []}
{"input": "These data demonstrate that URB597-mediated retinal neuroprotective effects are mediated primarily through CB1 receptors and that URB597 neuroprotective efficacy declines with age.", "output": {"entities": {"chemical": [{"text": "URB597", "start": 28, "end": 34}, {"text": "retinal", "start": 44, "end": 51}, {"text": "URB597", "start": 130, "end": 136}]}}, "schema": []}
{"input": "Differential Effects of Cholinergic and Noradrenergic Neuromodulation on Spontaneous Cortical Network Dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "Cholinergic and noradrenergic neuromodulation play a key role in determining overall behavioral state by shaping the underlying cortical network dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "The effects of these systems on synaptic and intrinsic cellular targets are quite diverse and a comprehensive understanding of how these neuromodulators regulate (spontaneous) cortical network activity has remained elusive.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we used multielectrode electrophysiology in vitro to investigate the effect of these neuromodulators on spontaneous network dynamics in acute slices of mouse visual cortex.", "output": {"entities": {}}, "schema": []}
{"input": "We found that application of Carbachol (CCh) and Norepinephrine (NE) both enhanced the spontaneous network dynamics by increasing (1) the activity levels, (2) the temporal complexity of the network activity, and (3) the spatial complexity by decorrelating the network activity over a wide range of neuromodulator concentrations (1 mu M, 10 mu M, 50 mu M, and 100 mu M).", "output": {"entities": {"chemical": [{"text": "Carbachol", "start": 29, "end": 38}, {"text": "CCh", "start": 40, "end": 43}, {"text": "Norepinephrine", "start": 49, "end": 63}]}}, "schema": []}
{"input": "Interestingly, we found that cholinergic neuromodulation was limited to the presence of CCh in the bath whereas the effects of NE, in particular for higher concentrations, induced plasticity that caused outlasting effects most prominently in the deep cortical layers.", "output": {"entities": {"chemical": [{"text": "CCh", "start": 88, "end": 91}]}}, "schema": []}
{"input": "Together, these results provide a comprehensive network-level understanding of the similarities and differences of cholinergic and noradrenergic modulation of spontaneous network dynamics.", "output": {"entities": {}}, "schema": []}
{"input": "Assessment of subjective cognitive and emotional effects of antipsychotic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Effect by defect?", "output": {"entities": {}}, "schema": []}
{"input": "Antipsychotic medication represents the first-line treatment of schizophrenia.", "output": {"entities": {}}, "schema": []}
{"input": "While it is undisputed that antipsychotics ameliorate positive symptoms, the exact cognitive and emotional pathways through which its effect is exerted has remained unclear.", "output": {"entities": {}}, "schema": []}
{"input": "The present study investigated the subjective effects of antipsychotics across various domains of cognition and emotion in both patients with psychotic symptoms and patients with other psychiatric diagnoses.", "output": {"entities": {}}, "schema": []}
{"input": "A total of 69 patients with a probable history of psychosis or psychotic symptoms and 26 patients with psychiatric diagnoses other than psychosis participated in a survey conducted over the Internet.", "output": {"entities": {}}, "schema": []}
{"input": "Multiple control measures aimed to secure response validity.", "output": {"entities": {}}, "schema": []}
{"input": "All patients were currently or had previously been treated with antipsychotic agents.", "output": {"entities": {}}, "schema": []}
{"input": "A questionnaire comprising 49 items and measuring possible effects of antipsychotics on cognition and emotion was administered.", "output": {"entities": {}}, "schema": []}
{"input": "For 30 out of 49 items a clear response pattern emerged, which was similar for patients with psychotic disorders and patients with other diagnoses.", "output": {"entities": {}}, "schema": []}
{"input": "Factor analysis of these items revealed three main effects of antipsychotic medication related to doubt and self-doubt, cognitive and emotional numbing, and social withdrawal.", "output": {"entities": {}}, "schema": []}
{"input": "Antipsychotic treatment appears to be connected to a number of negative subjective effects on cognition and emotion.", "output": {"entities": {}}, "schema": []}
{"input": "Further studies are warranted to assess how these effects impact on the patients' subjective well-being and quality of life, as well as their association with antipsychotic efficacy on the one hand, and adherence rates on the other.", "output": {"entities": {}}, "schema": []}
{"input": "The induction of doubt and the dampening of emotion may be one reason why antipsychotics work and at the same time offer an explanation why they are experienced as rather unpleasant and are eventually discontinued by many patients.", "output": {"entities": {}}, "schema": []}
{"input": "Controlling the Physical form of Mannitol in Freeze-Dried Systems.", "output": {"entities": {"chemical": [{"text": "Mannitol", "start": 33, "end": 41}]}}, "schema": []}
{"input": "A potential drawback with the use of mannitol as a bulking agent is its existence as mannitol hemihydrate (MHH; C6H14O6 (.) 0. 5H2O) in the lyophile.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 37, "end": 45}, {"text": "mannitol hemihydrate", "start": 85, "end": 105}, {"text": "MHH", "start": 107, "end": 110}, {"text": "C6H14O6 (.) 0. 5H2O", "start": 112, "end": 131}]}}, "schema": []}
{"input": "Once formed during freeze-drying, MHH dehydration may require secondary drying under aggressive conditions which can be detrimental to the stability of thermolabile components.", "output": {"entities": {"chemical": [{"text": "MHH", "start": 34, "end": 37}]}}, "schema": []}
{"input": "If MHH is retained in the lyophile, the water released by MHH dehydration during storage has the potential to cause product instability.", "output": {"entities": {"chemical": [{"text": "MHH", "start": 3, "end": 6}, {"text": "MHH", "start": 58, "end": 61}]}}, "schema": []}
{"input": "We systematically identified the conditions under which anhydrous mannitol and MHH crystallized in frozen systems with the goal of preventing MHH formation during freeze-drying.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 66, "end": 74}, {"text": "MHH", "start": 79, "end": 82}, {"text": "MHH", "start": 142, "end": 145}]}}, "schema": []}
{"input": "When mannitol solutions were cooled, the temperature of solute crystallization was the determinant of the physical form of mannitol.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 5, "end": 13}, {"text": "mannitol", "start": 123, "end": 131}]}}, "schema": []}
{"input": "Based on low temperature X-ray diffractometry (using both laboratory and synchrotron sources), MHH formation was observed when solute crystallization occurred at temperatures >=-20 degrees C while anhydrous mannitol crystallized at temperatures <=-10 degrees C.", "output": {"entities": {"chemical": [{"text": "MHH", "start": 95, "end": 98}, {"text": "mannitol", "start": 207, "end": 215}]}}, "schema": []}
{"input": "The transition temperature (anhydrate-MHH) appears to be ~-15 degrees C.", "output": {"entities": {"chemical": [{"text": "MHH", "start": 38, "end": 41}]}}, "schema": []}
{"input": "The use of a freeze-dryer with controlled ice nucleation technology enabled anhydrous mannitol crystallization at ~-5 degrees C.", "output": {"entities": {"chemical": [{"text": "mannitol", "start": 86, "end": 94}]}}, "schema": []}
{"input": "Thus, ice crystallization followed by annealing at temperatures <=-10 degrees C can be an effective strategy to prevent MHH formation.", "output": {"entities": {"chemical": [{"text": "MHH", "start": 120, "end": 123}]}}, "schema": []}
{"input": "Investigation on the interaction of the toxicant, gentian violet, with bovine hemoglobin.", "output": {"entities": {"chemical": [{"text": "gentian violet", "start": 50, "end": 64}]}}, "schema": []}
{"input": "Gentian violet (GV) is a well-known triarylmethane dye that is used in aquacultural, industrial and medicinal fields.", "output": {"entities": {"chemical": [{"text": "Gentian violet", "start": 0, "end": 14}, {"text": "triarylmethane", "start": 36, "end": 50}]}}, "schema": []}
{"input": "But concerns in growing number have been paid to its potential health problems to human beings and its hazardous effects to environment.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, the toxic interaction of GV with bovine hemoglobin (BHb) was investigated by a series of spectroscopic methods and molecular modeling method.", "output": {"entities": {}}, "schema": []}
{"input": "The fluorescence emission profile exhibited a remarkable quenching upon addition of GV to the buffered aqueous solution of BHb and the analysis of results revealed the dominant role of static quenching mechanism in GV-BHb interaction.", "output": {"entities": {}}, "schema": []}
{"input": "The negative Delta H and positive Delta S values demonstrated that the electrostatic interactions mainly stabilized this toxicant-protein complex.", "output": {"entities": {}}, "schema": []}
{"input": "Synchronous fluorescence, UV-vis absorption and CD spectroscopic studies proved that the conformational change of BHb was induced by GV' s combination.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular modeling studies exhibited the binding mode of GV-BHb complex and the detailed information of related driving forces.", "output": {"entities": {}}, "schema": []}
{"input": "During the 1H nuclear magnetic resonance spectra (1H NMR) study, the chemical shift perturbation and spin-lattice relaxation times of different protons were further used to investigate the interaction of GV with BHb and the results indicated that GV bound orientationally to BHb.", "output": {"entities": {"chemical": [{"text": "1H", "start": 11, "end": 13}, {"text": "1H", "start": 50, "end": 52}]}}, "schema": []}
{"input": "Alteration of prolyl oligopeptidase and activated alpha-2-macroglobulin in multiple sclerosis subtypes and in the clinically isolated syndrome.", "output": {"entities": {"chemical": [{"text": "prolyl", "start": 14, "end": 20}]}}, "schema": []}
{"input": "Prolyl oligopeptidase (PREP) has been considered as a drug target for the treatment of neurodegenerative diseases.", "output": {"entities": {"chemical": [{"text": "Prolyl", "start": 0, "end": 6}]}}, "schema": []}
{"input": "In plasma, PREP has been found altered in several disorders of the central nervous system including multiple sclerosis (MS).", "output": {"entities": {}}, "schema": []}
{"input": "Oxidative stress and the levels of an endogenous plasma PREP inhibitor have been proposed to decrease PREP activity in MS.", "output": {"entities": {}}, "schema": []}
{"input": "In this work, we measured the circulating levels of PREP in patients suffering of relapsing remitting (RR), secondary progressive (SP), primary progressive (PP) MS, and in subjects with clinically isolated syndrome (CIS).", "output": {"entities": {}}, "schema": []}
{"input": "We found a significantly lower PREP activity in plasma of RRMS as well as in PPMS patients and a trend to reduced activity in subjects diagnosed with CIS, compared to controls.", "output": {"entities": {}}, "schema": []}
{"input": "No signs of oxidative inactivation of PREP, and no correlation with the endogenous PREP inhibitor, identified as activated alpha-2-macroglobulin (alpha 2M *), were observed in any of the patients studied.", "output": {"entities": {}}, "schema": []}
{"input": "However, a significant decrease of alpha 2M * was recorded in MS.", "output": {"entities": {}}, "schema": []}
{"input": "In cell cultures, we found that PREP specifically stimulates immune active cells possibly by modifying the levels of fibrinogen beta, thymosin beta 4, and collagen.", "output": {"entities": {}}, "schema": []}
{"input": "Our results open new lines of research on the role of PREP and alpha 2M * in MS, aiming to relate them to the diagnosis and prognosis of this devastating disease.", "output": {"entities": {}}, "schema": []}
{"input": "The C1 domain-targeted isophthalate derivative HMI-1b11 promotes neurite outgrowth and GAP-43 expression through PKC alpha activation in SH-SY5Y cells.", "output": {"entities": {"chemical": [{"text": "isophthalate", "start": 23, "end": 35}]}}, "schema": []}
{"input": "Protein kinase C (PKC) is a family of serine/threonine phosphotransferases ubiquitously expressed and involved in multiple cellular functions, such as proliferation, apoptosis and differentiation.", "output": {"entities": {"chemical": [{"text": "serine", "start": 38, "end": 44}, {"text": "threonine", "start": 45, "end": 54}]}}, "schema": []}
{"input": "The C1 domain of PKC represents an attractive drug target, especially for developing PKC activators.", "output": {"entities": {}}, "schema": []}
{"input": "Dialkyl 5-(hydroxymethyl) isophthalates are a novel group of synthetic C1 domain ligands that exhibit antiproliferative effect in HeLa cervical carcinoma cells.", "output": {"entities": {"chemical": [{"text": "Dialkyl 5-(hydroxymethyl) isophthalates", "start": 0, "end": 39}]}}, "schema": []}
{"input": "Here we selected two isophthalates, HMI-1a3 and HMI-1b11, and characterized their effects in the human neuroblastoma cell line SH-SY5Y.", "output": {"entities": {"chemical": [{"text": "isophthalates", "start": 21, "end": 34}]}}, "schema": []}
{"input": "Both of the active isophthalates exhibited significant antiproliferative and differentiation-inducing effects.", "output": {"entities": {"chemical": [{"text": "isophthalates", "start": 19, "end": 32}]}}, "schema": []}
{"input": "Since HMI-1b11 did not impair cell survival even at the highest concentration tested (20 mu M), and supported neurite growth and differentiation of SH-SY5Y cells, we focused on studying its downstream signaling cascades and effects on gene expression.", "output": {"entities": {}}, "schema": []}
{"input": "Consistently, genome-wide gene expression microarray and gene set enrichment analysis indicated that HMI-1b11 (10 mu M) induced changes in genes mainly related to cell differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "In particular, further studies revealed that HMI-1b11 exposure induced up-regulation of GAP-43, a marker for neurite sprouting and neuronal differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "These effects were induced by a 7-minute HMI-1b11 treatment and specifically depended on PKC alpha activation, since pretreatment with the selective inhibitor G o 6976 abolished the up-regulation of GAP-43 protein observed at 12hours In parallel, we found that a 7-minute exposure to HMI-1b11 induced PKC alpha accumulation to the cytoskeleton, an effect that was again prevented by pretreatment with G o 6976.", "output": {"entities": {"chemical": [{"text": "G o 6976", "start": 159, "end": 167}, {"text": "G o 6976", "start": 401, "end": 409}]}}, "schema": []}
{"input": "Despite similar binding affinities to PKC, the isophthalates had different effects on PKC-dependent ERK1/2 signaling: HMI-1a3-induced ERK1/2 phosphorylation was transient, while HMI-1b11 induced a rapid but prolonged ERK1/2 phosphorylation.", "output": {"entities": {}}, "schema": []}
{"input": "Overall our data are in accordance with previous studies showing that activation of the PKC alpha and ERK1/2 pathways participate in regulating neuronal differentiation.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, since PKC has been classified as one of the cognitive kinases, and activation of PKC is considered a potential therapeutic strategy for the treatment of cognitive disorders, our findings suggest that HMI-1b11 represents a promising lead compound in research aimed to prevent or counteract memory impairment.", "output": {"entities": {}}, "schema": []}
{"input": "Discovery of highly potent triazole antifungal derivatives by heterocycle-benzene bioisosteric replacement.", "output": {"entities": {"chemical": [{"text": "triazole", "start": 27, "end": 35}, {"text": "benzene", "start": 74, "end": 81}]}}, "schema": []}
{"input": "On the basis of our previously discovered triazole antifungal lead compounds, heterocycle-benzene bioisosteric replacement was used to improve their pharmacokinetic profile.", "output": {"entities": {"chemical": [{"text": "triazole", "start": 42, "end": 50}, {"text": "benzene", "start": 90, "end": 97}]}}, "schema": []}
{"input": "The designed new triazole derivatives have good antifungal activity toward a wide range of pathogenic fungi.", "output": {"entities": {"chemical": [{"text": "triazole", "start": 17, "end": 25}]}}, "schema": []}
{"input": "Their binding mode with the target enzyme was clarified by molecular docking.", "output": {"entities": {}}, "schema": []}
{"input": "The MIC value of the highly potent compound 8f against Candida albicans, Candida tropicalis, and Cryptococcus neoformans is 0. 016 mu g/mL, 0. 004 mu g/mL, and 0. 016 mu g/mL, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, preliminary pharmacokinetic studies revealed that it showed improved oral absorption as compared to the lead compound iodiconazole and deserved for further evaluations.", "output": {"entities": {"chemical": [{"text": "iodiconazole", "start": 128, "end": 140}]}}, "schema": []}
{"input": "Metabolic Regulation of Brain Response to Food Cues.", "output": {"entities": {}}, "schema": []}
{"input": "Identification of energy sources depends upon the ability to form associations between food cues and nutritional value.", "output": {"entities": {}}, "schema": []}
{"input": "As such, cues previously paired with calories elicit neuronal activation in the nucleus accumbens (NAcc), which reflects the reinforcing value of food [1-4].", "output": {"entities": {}}, "schema": []}
{"input": "The identity of the physiological signals regulating this response remains elusive.", "output": {"entities": {}}, "schema": []}
{"input": "Using fMRI, we examined brain response to noncaloric versions of flavors that had been consumed in previous days with either 0 or 112. 5 calories from undetected maltodextrin.", "output": {"entities": {}}, "schema": []}
{"input": "We report a small but perceptually meaningful increase in liking for the flavor that had been paired with calories and find that change in liking was associated with changes in insular responses to this beverage.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, NAcc and hypothalamic response to the calorie-paired flavor was unrelated to liking but was strongly associated with the changes in plasma glucose levels produced by ingestion of the beverage when consumed previously with calories.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 152, "end": 159}]}}, "schema": []}
{"input": "Importantly, because each participant ingested the same caloric dose, the change in plasma glucose depended upon individual differences in glucose metabolism.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 91, "end": 98}, {"text": "glucose", "start": 139, "end": 146}]}}, "schema": []}
{"input": "We conclude that glucose metabolism is a critical signal regulating NAcc and hypothalamic response to food cues, and that this process operates independently from the ability of calories to condition liking.", "output": {"entities": {"chemical": [{"text": "glucose", "start": 17, "end": 24}]}}, "schema": []}
{"input": "Architecture of Cortical Bone Determines in Part its Remodelling and Structural Decay.", "output": {"entities": {}}, "schema": []}
{"input": "Bone remodelling accelerates and becomes unbalanced after menopause; less bone is deposited than resorbed from the surface of canals traversing the cortex.", "output": {"entities": {}}, "schema": []}
{"input": "The canals enlarge so the intracortical surface area enlarges.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that cortical bone with a larger internal surface area, due to more or larger canals, is more liable to being remodelled, further enlarging the internal surface area and facilitating more remodelling and structural deterioration.", "output": {"entities": {}}, "schema": []}
{"input": "For 95 monozygotic twin pairs aged 40-61 years, we measured internal cortical surface areas and structure of the distal tibia using high resolution peripheral computed tomography, and three circulating bone remodelling markers.", "output": {"entities": {}}, "schema": []}
{"input": "Using principal components (PC) analyses, we identified one summary measure of intracortical and endocortical bone surface areas, cortical porosity and volumetric bone mineral density (structure PC), and one summary measure of bone remodelling markers (remodelling PC).", "output": {"entities": {}}, "schema": []}
{"input": "We applied a twin regression analysis (Inference on Causation by Examination of Familial Confounding; ICE FALCON) to assess consistency with a causal component in the association between a predictor (X) and an outcome (Y) by testing if the regression coefficient for the X value of the co-twin decreases after adjusting for the X value of the twin herself.", "output": {"entities": {}}, "schema": []}
{"input": "With Y = remodelling PC, the regression coefficient for structure PC in the co-twin was 0. 29 (p < 0. 001) before, and 0. 18 (p = 0. 03) after, adjusting for her own structure PC (40% lower; p = 0. 06).", "output": {"entities": {}}, "schema": []}
{"input": "With Y = structure PC, the regression coefficient for remodelling PC in the co-twin was 0. 17 (p = 0. 01) before, and 0. 20 (p < 0. 001) after, adjusting for her own remodelling PC (22% higher; p = 0. 7).", "output": {"entities": {}}, "schema": []}
{"input": "The structure of bone, its surface area to bone matrix volume configuration, contributes in part to its own remodelling and deterioration, but not vice versa.", "output": {"entities": {}}, "schema": []}
{"input": "Streptococcus pneumoniae ClpP protease induces apoptosis via caspase-independent pathway in human neuroblastoma cells: cytoplasmic relocalization of p53.", "output": {"entities": {}}, "schema": []}
{"input": "Streptococcus pneumoniae causes the most severe form of the bacterial meningitis which is the major cause of bacterial meningitis.", "output": {"entities": {}}, "schema": []}
{"input": "Virulence factors produced by S. pneumoniae have been known to contribute significantly to the disease process.", "output": {"entities": {}}, "schema": []}
{"input": "ClpP protease (ClpP) which is essential for virulence and survival under stress conditions in S. pneumonia was examined for the ability to induce apoptosis and the mechanism of the induction of apoptosis in human neuron-like cells, SK-N-SH neuroblastoma cells.", "output": {"entities": {}}, "schema": []}
{"input": "ClpP inhibited cell growth and induced apoptosis in SK-N-SH cells.", "output": {"entities": {}}, "schema": []}
{"input": "Treatment with ClpP resulted in hypodiploid DNA contents, increased Bax/Bcl-2 ratio and induction of reactive oxygen species (ROS) production.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 110, "end": 116}]}}, "schema": []}
{"input": "The release of cytochrome c from mitochondria into the cytosol, which is an initiator of the activation of caspase cascades, was not observed in ClpP-treated cells.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, pretreatment with Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk), a broad spectrum of caspase inhibitor, could not rescue apoptotic cells from ClpP toxicity.", "output": {"entities": {"chemical": [{"text": "Z-Val-Ala-Asp-fluoromethylketone", "start": 31, "end": 63}, {"text": "Z-VAD-fmk", "start": 65, "end": 74}]}}, "schema": []}
{"input": "Coincidently, caspase-3 and-8 activation and cleavage of PARP were not detected.", "output": {"entities": {}}, "schema": []}
{"input": "Moreover, caspase independent apoptosis-inducing factor (AIF) was released from mitochondria and translocated to the nucleus in response to ClpP.", "output": {"entities": {}}, "schema": []}
{"input": "We also found that ClpP treatment resulted in the increase of p53 activity and cytoplasmic p53 levels were increased by ClpP, suggesting that functional activation of p53 is intact despite increased cytoplasmic accumulation.", "output": {"entities": {}}, "schema": []}
{"input": "Taken together, these data suggest that ClpP contributes to neuronal damage in meningitis and provide further insight into the mechanisms underlying action of pneumococcal virulence factors during bacterial pathogenesis.", "output": {"entities": {}}, "schema": []}
{"input": "Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A4.", "output": {"entities": {"chemical": [{"text": "formyl", "start": 25, "end": 31}, {"text": "lipoxin A4", "start": 82, "end": 92}]}}, "schema": []}
{"input": "Lipoxin A4 (LXA4) has been described as an anti-inflammatory mediator, which exerts its effects through the formyl peptide receptor FPR2, also known as ALX.", "output": {"entities": {"chemical": [{"text": "Lipoxin A4", "start": 0, "end": 10}, {"text": "LXA4", "start": 12, "end": 16}]}}, "schema": []}
{"input": "However, there has been a controversy whether or not cells expressing FPR2/ALX, such as neutrophils, respond to LXA4.", "output": {"entities": {"chemical": [{"text": "LXA4", "start": 112, "end": 116}]}}, "schema": []}
{"input": "We, therefore, systematically examined the ability of the human and murine forms of the receptor to respond to LXA4.", "output": {"entities": {"chemical": [{"text": "LXA4", "start": 111, "end": 115}]}}, "schema": []}
{"input": "We show that both receptor orthologues responded to the FPR2/ALX peptide agonist WKYMVM when expressed heterologously.", "output": {"entities": {}}, "schema": []}
{"input": "In contrast, LXA4 from different sources neither increased [Ca (2 +)] i and extracellular-signal-regulated kinase (ERK) phosphorylation, nor did it induce a decrease in cAMP levels or a translocation of beta-arrestin.", "output": {"entities": {"chemical": [{"text": "LXA4", "start": 13, "end": 17}, {"text": "Ca (2 +)", "start": 60, "end": 68}, {"text": "cAMP", "start": 169, "end": 173}]}}, "schema": []}
{"input": "Also, several LXA4 analogues were found to be unable to signal through FPR2/ALX.", "output": {"entities": {"chemical": [{"text": "LXA4", "start": 14, "end": 18}]}}, "schema": []}
{"input": "We conclude that FPR2/ALX is not activated by LXA4 and that the molecular mechanism by which LXA4 functions still needs to be identified.", "output": {"entities": {"chemical": [{"text": "LXA4", "start": 46, "end": 50}, {"text": "LXA4", "start": 93, "end": 97}]}}, "schema": []}
{"input": "Design, synthesis and antiproliferative activity studies of novel 1, 2, 3-triazole-dithiocarbamate-urea hybrids.", "output": {"entities": {"chemical": [{"text": "1, 2, 3-triazole-dithiocarbamate-urea", "start": 66, "end": 103}]}}, "schema": []}
{"input": "A series of novel 1, 2, 3-triazole-dithiocarbamate-urea hybrids were designed, synthesized and their antiproliferative activities against four selected human cancer cell lines were evaluated.", "output": {"entities": {"chemical": [{"text": "1, 2, 3-triazole-dithiocarbamate-urea", "start": 18, "end": 55}]}}, "schema": []}
{"input": "The results showed that a number of the hybrids exhibited potent activity in selected human cancer cell lines.", "output": {"entities": {}}, "schema": []}
{"input": "Among them, compounds 27 and 34 showed broad spectrum anticancer activity with IC50 values ranging from 1. 62 to 20. 84 mu M and 0. 76 to 13. 55 mu M, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Interestingly, compounds 27 and 34, being very potent against MGC-803 cells, exhibited no significant cytotoxicity against normal human embryonic kidney cells at up to 55 mu M and 70 mu M, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "Evidences of cell cycle arrest and apoptosis induction were obtained for the most effective compounds 27 and 34 by means of flow cytometry and microscopic techniques.", "output": {"entities": {}}, "schema": []}
{"input": "Elucidation of the pharmacophore of echinocystic acid, a new lead for blocking HCV entry.", "output": {"entities": {"chemical": [{"text": "echinocystic acid", "start": 36, "end": 53}]}}, "schema": []}
{"input": "To elucidate the pharmacophore of echinocystic acid (EA), an oleanane-type triterpene displaying substantial inhibitory activity on HCV entry, two microbial strains, Rhizopus chinensis CICC 3043 and Alternaria alternata AS 3. 4578, were utilized to modify the chemical structure of EA.", "output": {"entities": {"chemical": [{"text": "echinocystic acid", "start": 34, "end": 51}, {"text": "oleanane", "start": 61, "end": 69}, {"text": "triterpene", "start": 75, "end": 85}]}}, "schema": []}
{"input": "Eight new metabolites with regio-and stereo-selective introduction of hydroxyl and lactone groups at various inert carbon positions were obtained.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 70, "end": 78}, {"text": "lactone", "start": 83, "end": 90}, {"text": "carbon", "start": 115, "end": 121}]}}, "schema": []}
{"input": "The anti-HCV entry activity of the metabolites 2-13, along with their parental compound EA and other analogs 14-15, were evaluated.", "output": {"entities": {}}, "schema": []}
{"input": "Most of the metabolites showed no improvement but detrimental effect on potency except compound 5 and 6, which showed similar and even a litter higher anti-HCV entry activity than that of EA.", "output": {"entities": {}}, "schema": []}
{"input": "The results demonstrated that ring A, B, C and the left side of ring E of EA are highly conserved, while ring D and the right side of ring E of EA are flexible.", "output": {"entities": {}}, "schema": []}
{"input": "Introduction of a hydroxyl group at C-16 enhanced the triterpene potency.", "output": {"entities": {"chemical": [{"text": "hydroxyl", "start": 18, "end": 26}, {"text": "triterpene", "start": 54, "end": 64}]}}, "schema": []}
{"input": "Further analysis indicated that the hemolytic effect of EA disappeared upon such modifications.", "output": {"entities": {}}, "schema": []}
{"input": "Ligand-based design, synthesis, and experimental evaluation of novel benzofuroxan derivatives as anti-Trypanosoma cruzi agents.", "output": {"entities": {"chemical": [{"text": "benzofuroxan", "start": 69, "end": 81}]}}, "schema": []}
{"input": "A set of substituted-[N'-(benzofuroxan-5-yl) methylene] benzohydrazides (4a-t), previously designed and synthesized, was experimentally assayed against Trypanosoma cruzi, the etiological agent of Chagas' disease, one of the most neglected tropical diseases.", "output": {"entities": {"chemical": [{"text": "N'-(benzofuroxan-5-yl) methylene] benzohydrazides", "start": 22, "end": 71}]}}, "schema": []}
{"input": "Exploratory data analysis, Hansch approach and VolSurf formalism were applied to aid the ligand-based design of novel anti-T. cruzi agents.", "output": {"entities": {}}, "schema": []}
{"input": "The best 2D-QSAR model showed suitable statistical measures [n = 18; s = 0. 11; F = 42. 19; R (2) = 0. 90 and Q (2) = 0. 77 (SDEP = 0. 15)], and according to the optimum 3D-QSAR model [R (2) = 0. 98, Q (2) = 0. 93 (SDEP = 0. 08)], three latent variables explained 62% of the total variance from original data.", "output": {"entities": {}}, "schema": []}
{"input": "Steric and hydrophobic properties were pointed out as the key for biological activity.", "output": {"entities": {}}, "schema": []}
{"input": "Based upon the findings, six novel benzofuroxan derivatives (4u-z) were designed, synthesized, and in vitro assayed to perform the QSAR external prediction.", "output": {"entities": {"chemical": [{"text": "benzofuroxan", "start": 35, "end": 47}]}}, "schema": []}
{"input": "Then, the predictability for the both models, 2D-QSAR (Rpred (2) = 0. 91) and 3D-QSAR (Rpred (2) = 0. 77), was experimentally validated, and compound 4u was identified as the most active anti-T. cruzi hit (IC50 = 3. 04 mu M).", "output": {"entities": {}}, "schema": []}
{"input": "N-Alkylated 2, 3, 3-trimethylindolenines and 2-methylbenzothiazoles.", "output": {"entities": {"chemical": [{"text": "N-Alkylated 2, 3, 3-trimethylindolenines", "start": 0, "end": 40}, {"text": "2-methylbenzothiazoles", "start": 45, "end": 67}]}}, "schema": []}
{"input": "Potential lead compounds in the fight against Saccharomyces cerevisiae infections.", "output": {"entities": {}}, "schema": []}
{"input": "The synthesis of a variety of N-alkylated 2, 3, 3-trimethylindolenines and 2-methylbenzothiazoles is reported herein.", "output": {"entities": {"chemical": [{"text": "N-alkylated 2, 3, 3-trimethylindolenines", "start": 30, "end": 70}, {"text": "2-methylbenzothiazoles", "start": 75, "end": 97}]}}, "schema": []}
{"input": "Their potential as antifungal agents is evaluated by preliminary screening against Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe), and Candida albicans (C. albicans).", "output": {"entities": {}}, "schema": []}
{"input": "Statistical analyses illustrate a strong relationship between chain length and growth inhibition for S. cerevisiae and S. pombe (p < 0. 0001 in every case).", "output": {"entities": {}}, "schema": []}
{"input": "Of particular interest is the activity of both sets of compounds against S. cerevisiae, as this is emerging as an opportunistic pathogen, especially in immunosuppressed and immunocompromised patients.", "output": {"entities": {}}, "schema": []}
{"input": "Bioassays were set up to compare the efficacy of our range of N-alkylated compounds against classic antifungal agents; Amphotericin B and Thiabendazole.", "output": {"entities": {"chemical": [{"text": "N", "start": 62, "end": 63}, {"text": "Amphotericin B", "start": 119, "end": 133}, {"text": "Thiabendazole", "start": 138, "end": 151}]}}, "schema": []}
{"input": "Synthesis and biological characterization of spiro [2H-(1, 3)-benzoxazine-2, 4'-piperidine] based histone deacetylase inhibitors.", "output": {"entities": {"chemical": [{"text": "spiro [2H-(1, 3)-benzoxazine-2, 4'-piperidine]", "start": 45, "end": 91}]}}, "schema": []}
{"input": "Histone Deacetylases (HDACs) have become important targets for the treatment of cancer and other diseases.", "output": {"entities": {}}, "schema": []}
{"input": "In previous studies we described the development of novel spirocyclic HDAC inhibitors based on the combination of privileged structures with hydroxamic acid moieties as zinc binding group.", "output": {"entities": {"chemical": [{"text": "hydroxamic acid", "start": 141, "end": 156}, {"text": "zinc", "start": 169, "end": 173}]}}, "schema": []}
{"input": "Herein, we report further explorations, which resulted in the discovery of a new class of spiro [2H-(1, 3)-benzoxazine-2, 4'-piperidine] derivatives.", "output": {"entities": {"chemical": [{"text": "spiro [2H-(1, 3)-benzoxazine-2, 4'-piperidine]", "start": 90, "end": 136}]}}, "schema": []}
{"input": "Several compounds showed good potency of around 100 nM and less in the HDAC inhibition assays, submicromolar IC50 values when tested against tumour cell lines and a remarkable stability in human and mouse microsomes.", "output": {"entities": {}}, "schema": []}
{"input": "Two representative examples exhibited a good pharmacokinetic profile with an oral bioavailability equal or higher than 35% and one of them studied in an HCT116 murine xenograft model showing a robust tumour growth inhibition.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, the two benzoxazines were found to have a minor affinity for the hERG potassium channel compared to their corresponding ketone analogues.", "output": {"entities": {"chemical": [{"text": "benzoxazines", "start": 21, "end": 33}, {"text": "potassium", "start": 83, "end": 92}, {"text": "ketone", "start": 133, "end": 139}]}}, "schema": []}
{"input": "Synthesis and in vitro anticancer studies of novel C-2 arylidene congeners of lantadenes.", "output": {"entities": {"chemical": [{"text": "lantadenes", "start": 78, "end": 88}]}}, "schema": []}
{"input": "The antitumor pentacyclic triterpenoids, Lantadene A (1) and B (2) were isolated from the leaves of weed Lantana camara L.", "output": {"entities": {"chemical": [{"text": "Lantadene A (1) and B", "start": 41, "end": 62}]}}, "schema": []}
{"input": "(Verbenaceae) and were structurally transformed to bioactive intermediates 3-6.", "output": {"entities": {}}, "schema": []}
{"input": "The Claisen-Schmidt reaction of 22 beta-hydroxy-3-oxoolean-12-en-28-oic acid (5) with requisite aldehydes afforded 2-arylidene-22 beta-hydroxy-3-oxoolean-12-en-28-oic acids (7-16).", "output": {"entities": {"chemical": [{"text": "22 beta-hydroxy-3-oxoolean-12-en-28-oic acid", "start": 32, "end": 76}, {"text": "aldehydes", "start": 96, "end": 105}, {"text": "2-arylidene-22 beta-hydroxy-3-oxoolean-12-en-28-oic acids", "start": 115, "end": 172}]}}, "schema": []}
{"input": "The compounds were evaluated for their in-vitro anticancer activity by National Cancer Institute (NCI), USA and some of these compounds showed marked cytotoxicity in micromolar range.", "output": {"entities": {}}, "schema": []}
{"input": "The mean graph midpoint (MG _ MID) value of compound 3 (MG _ MID-5. 69) was higher than standard drug cisplatin (MG _ MID-5. 66) while comparable in case of compound 12 (MG _ MID-5. 52).", "output": {"entities": {"chemical": [{"text": "cisplatin", "start": 102, "end": 111}]}}, "schema": []}
{"input": "The NCI' s COMPARE molecular mechanistic analysis showed that these compounds were in significant correlations with activity patterns of mechanistic set of compounds (PCC >= 0. 60).", "output": {"entities": {}}, "schema": []}
{"input": "Low molecular weight dual inhibitors of factor Xa and fibrinogen binding to GPIIb/IIIa with highly overlapped pharmacophores.", "output": {"entities": {}}, "schema": []}
{"input": "Dual antithrombotic agents acting as anticoagulants and aggregation inhibitors could have substantial advantages over currently prescribed combinations of antithrombotic drugs.", "output": {"entities": {}}, "schema": []}
{"input": "Herein, we report compounds with moderate inhibitory activity for factor Xa and fibrinogen GPIIb/IIIa binding (both in the micromolar range).", "output": {"entities": {}}, "schema": []}
{"input": "These compounds resulted from our efforts to merge the pharmacophores of selective factor Xa inhibitor rivaroxaban with a mimic of the Arg-Gly-Asp (RGD) sequence of fibrinogen to obtain designed multiple ligands with potential antithrombotic activity.", "output": {"entities": {"chemical": [{"text": "rivaroxaban", "start": 103, "end": 114}, {"text": "Arg-Gly-Asp", "start": 135, "end": 146}]}}, "schema": []}
{"input": "Resulting from this study, a structurally novel class of submicromolar fibrinogen GPIIb/IIIa binding inhibitor bearing 1, 2, 4-oxadiazol-5 (4H)-one moiety is also described.", "output": {"entities": {"chemical": [{"text": "1, 2, 4-oxadiazol-5 (4H)-one", "start": 119, "end": 147}]}}, "schema": []}
{"input": "Synthesis and biological evaluation of N-(4-hydroxy-3-mercaptonaphthalen-1-yl) amides as inhibitors of angiogenesis and tumor growth.", "output": {"entities": {"chemical": [{"text": "N-(4-hydroxy-3-mercaptonaphthalen-1-yl) amides", "start": 39, "end": 85}]}}, "schema": []}
{"input": "A series of N-(4-hydroxy-3-mercaptonaphthalen-1-yl) amides were synthesized and investigated for their in vitro antiangiogenic activity.", "output": {"entities": {"chemical": [{"text": "N-(4-hydroxy-3-mercaptonaphthalen-1-yl) amides", "start": 12, "end": 58}]}}, "schema": []}
{"input": "Among these compounds, 6d, which possesses an ortho-nitro group at the benzene ring, exhibited potent inhibitory effect on the proliferation of HUVECs, A549, K562, PC-3, HCT116, MDA-MB-231 and MCF-7 cells (IC50 = 5. 34, 40. 53, 10. 81, 52. 52, 10. 19, 21. 37 and 2. 81 mu M, respectively).", "output": {"entities": {"chemical": [{"text": "ortho-nitro", "start": 46, "end": 57}, {"text": "benzene", "start": 71, "end": 78}]}}, "schema": []}
{"input": "Meanwhile, compound 6d inhibited in vitro angiogenesis markedly in both HUVECs tube formation assay and the rat thoracic aorta rings test.", "output": {"entities": {}}, "schema": []}
{"input": "Further kinase assay study showed that compound 6d had good VEGFR2, ALK, AKT1 and ABL inhibitory activities and moderate EGFR and PDGFR-beta inhibitory activities.", "output": {"entities": {}}, "schema": []}
{"input": "The data supports the further investigation of this class of compounds as potential antiangiogenic and anticancer agents.", "output": {"entities": {}}, "schema": []}
{"input": "Steroidal glycosides from the bulbs of Easter lily (Lilium longiflorum Thunb.) promote dermal fibroblast migration in vitro.", "output": {"entities": {"chemical": [{"text": "Steroidal glycosides", "start": 0, "end": 20}]}}, "schema": []}
{"input": "ETHNOPHARMACOLOGICAL RELEVANCE: Preparations derived from bulbs of various Lilium species have been used to promote the healing of skin abrasions, sores and burns and to aid in healing wounds in Traditional Chinese and Greco-Roman Medicine.", "output": {"entities": {}}, "schema": []}
{"input": "AIM OF THE STUDY: To evaluate fractionated Easter lily bulb extracts and their steroidal glycosides (1-5) for the promotion of dermal fibroblast migration in vitro, as a model for the early events in wound healing.", "output": {"entities": {"chemical": [{"text": "steroidal glycosides", "start": 79, "end": 99}]}}, "schema": []}
{"input": "MATERIALS AND METHODS: An activity-guided screening approach was used by coupling sequential solvent extraction, gel permeation chromatography (GPC), and semi-preparative reverse-phase high performance liquid chromatography (RP-HPLC) with an in vitro dermal fibroblast migration assay.", "output": {"entities": {}}, "schema": []}
{"input": "Cytotoxicity was evaluated with methyl thiazole tetrazolium (MTT).", "output": {"entities": {"chemical": [{"text": "methyl thiazole tetrazolium", "start": 32, "end": 59}, {"text": "MTT", "start": 61, "end": 64}]}}, "schema": []}
{"input": "To gain insight into the mode of action of the steroidal glycosides, nitric oxide (NO) production, and expression of genes for transforming growth factor beta-1 (TGF-beta) and its receptors were evaluated.", "output": {"entities": {"chemical": [{"text": "steroidal glycosides", "start": 47, "end": 67}, {"text": "nitric oxide", "start": 69, "end": 81}, {"text": "NO", "start": 83, "end": 85}]}}, "schema": []}
{"input": "RESULTS: Fractionated bulb extracts and the two isolated steroidal glycoalkaloids (1) and (2) induced NO production and TGF-beta receptor I mRNA expression in fibroblast cell culture.", "output": {"entities": {"chemical": [{"text": "steroidal glycoalkaloids", "start": 57, "end": 81}, {"text": "NO", "start": 102, "end": 104}]}}, "schema": []}
{"input": "In a cytotoxicity assay, steroidal glycosides (1) and (3) had IC50 values of 8. 2 and 8. 7 micro M, but the natural acetylation of the C-6''' hydroxy of the terminal glucose unit in (2) resulted in a 3-fold decrease in cell cytotoxicity when compared with (1).", "output": {"entities": {"chemical": [{"text": "steroidal glycosides", "start": 25, "end": 45}, {"text": "hydroxy", "start": 142, "end": 149}, {"text": "glucose", "start": 166, "end": 173}]}}, "schema": []}
{"input": "Results from the dermal fibroblast migration assay revealed that the steroidal glycoalkaloids (1) and (2), and the furostanol saponin (3) promoted fibroblast migration from the range of 23. 7 +/- 5. 7 to 37. 7 +/- 5. 1%, as compared with the control.", "output": {"entities": {"chemical": [{"text": "steroidal glycoalkaloids", "start": 69, "end": 93}, {"text": "furostanol saponin", "start": 115, "end": 133}]}}, "schema": []}
{"input": "CONCLUSION: Collectively, our data demonstrate that the steroidal glycosides present in Easter lily bulbs induce, at least in part, the observed dermal fibroblast migration activity of the bulb extracts.", "output": {"entities": {"chemical": [{"text": "steroidal glycosides", "start": 56, "end": 76}]}}, "schema": []}
{"input": "This is the first evidence that steroidal glycosides from L. longiflorum may potentially play a role in the wound healing process and may provide a scientific basis for the historical use of lily bulbs for this purpose.", "output": {"entities": {"chemical": [{"text": "steroidal glycosides", "start": 32, "end": 52}]}}, "schema": []}
{"input": "CENP-A confers a reduction in height on octameric nucleosomes.", "output": {"entities": {}}, "schema": []}
{"input": "Nucleosomes with histone H3 replaced by CENP-A direct kinetochore assembly.", "output": {"entities": {}}, "schema": []}
{"input": "CENP-A nucleosomes from human and Drosophila have been reported to have reduced heights as compared to canonical octameric H3 nucleosomes, thus suggesting a unique tetrameric hemisomal composition.", "output": {"entities": {}}, "schema": []}
{"input": "We demonstrate that octameric CENP-A nucleosomes assembled in vitro exhibit reduced heights, indicating that they are physically distinct from H3 nucleosomes and negating the need to invoke the presence of hemisomes.", "output": {"entities": {}}, "schema": []}
{"input": "Correction: Wiedmann, M., et al.", "output": {"entities": {}}, "schema": []}
{"input": "Exploration of the Role of the Non-Coding RNA SbrE in L. monocytogenes Stress Response.", "output": {"entities": {}}, "schema": []}
{"input": "Int.", "output": {"entities": {}}, "schema": []}
{"input": "J.", "output": {"entities": {}}, "schema": []}
{"input": "Mol.", "output": {"entities": {}}, "schema": []}
{"input": "Sci.", "output": {"entities": {}}, "schema": []}
{"input": "2013, 14, 378-393.", "output": {"entities": {}}, "schema": []}
{"input": "The original version of the paper in Section 3. 8 reports that \" The peptide mass tolerance and fragment mass tolerance values were 10 ppm and 30 mDa, respectively \" [1] (p. 387).", "output": {"entities": {}}, "schema": []}
{"input": "To help others who may want to use the same methods in the future, the authors would like to correct the wording to: \" The peptide mass tolerance and fragment mass tolerance values were 30 ppm and 0. 15 Da, respectively.", "output": {"entities": {}}, "schema": []}
{"input": "In order to decrease the probability of false peptide identification, only peptides with significance scores above the identity threshold (at the 95% confidence interval), defined by Mascot probability analysis (www. matrixscience. com/help/scoring _ help. html #PBM), were considered to be confidently identified and used for protein identification. Furthermore, only proteins identified in all four iTRAQ samples through at least two peptides with a p-value of < 0. 05 (expectation value) were further analyzed \".", "output": {"entities": {}}, "schema": []}
{"input": "The authors would like to apologize for any inconvenience this may have caused to the readers of this journal.", "output": {"entities": {}}, "schema": []}
{"input": "Cortical excitability in smoking and not smoking individuals with and without nicotine.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 78, "end": 86}]}}, "schema": []}
{"input": "RATIONAL: Activation of nicotinic acetylcholine receptors has a major neuromodulatory impact on central nervous system function.", "output": {"entities": {"chemical": [{"text": "acetylcholine", "start": 34, "end": 47}]}}, "schema": []}
{"input": "Beyond acute activation, chronic nicotine intake has long-lasting effects on cortical excitability in animal experiments, caused by receptor up-or down-regulation.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 33, "end": 41}]}}, "schema": []}
{"input": "Knowledge about the impact of nicotine on cortical excitability in humans, however, is limited.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 30, "end": 38}]}}, "schema": []}
{"input": "OBJECTIVES: We therefore aimed to explore the effect of nicotine intake on cortical excitability in healthy human smokers and non-smokers.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 56, "end": 64}]}}, "schema": []}
{"input": "METHODS: The primary motor cortex served as model, and cortical excitability was monitored via transcranial magnetic stimulation (TMS).", "output": {"entities": {}}, "schema": []}
{"input": "Corticospinal excitability and intracortical excitability were recorded before and after application of nicotine patch in both groups.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 104, "end": 112}]}}, "schema": []}
{"input": "Corticospinal excitability was explored by motor threshold and input/output curve (I/O curve), and intracortical excitability was explored by means of paired-pulse TMS techniques (intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), I-wave facilitation and short-latency afferent inhibition (SAI)).", "output": {"entities": {}}, "schema": []}
{"input": "RESULTS: The results show that smokers during nicotine withdrawal display increased corticospinal excitability with regard to the I/O curve (TMS intensity 150% of resting motor threshold) compared to non-smokers and furthermore enhanced SAI and diminished ICF at the intracortical circuit level.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 46, "end": 54}]}}, "schema": []}
{"input": "After administration of nicotine, intracortical facilitation in smokers increased, while in non-smokers, inhibition (SICI, SAI) was enhanced.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 24, "end": 32}]}}, "schema": []}
{"input": "CONCLUSION: Our results show that chronic nicotine consumption in smokers alters cortical excitability independent from acute nicotine consumption and that acute nicotine has different effects on motor cortical excitability in both groups.", "output": {"entities": {"chemical": [{"text": "nicotine", "start": 42, "end": 50}, {"text": "nicotine", "start": 126, "end": 134}, {"text": "nicotine", "start": 162, "end": 170}]}}, "schema": []}
{"input": "Neuritogenic and Neuroprotective Effects of Polar Steroids from the Far East Starfishes Patiria pectinifera and Distolasterias nipon.", "output": {"entities": {"chemical": [{"text": "Steroids", "start": 50, "end": 58}]}}, "schema": []}
{"input": "The neuritogenic and neuroprotective activities of six starfish polar steroids, asterosaponin P 1, (25S)-5 alpha-cholestane-3 beta, 4 beta, 6 alpha, 7 alpha, 8, 15 alpha, 16 beta, 26-octaol, and (25S)-5 alpha-cholestane-3 beta, 6 alpha, 7 alpha, 8, 15 alpha, 16 beta, 26-heptaol (1-3) from the starfish Patiria pectinifera and distolasterosides D1-D3 (4-6) from the starfish Distolasterias nipon were analyzed using the mouse neuroblastoma (NB) C-1300 cell line and an organotypic rat hippocampal slice culture (OHSC).", "output": {"entities": {"chemical": [{"text": "steroids", "start": 70, "end": 78}, {"text": "asterosaponin P 1", "start": 80, "end": 97}, {"text": "(25S)-5 alpha-cholestane-3 beta, 4 beta, 6 alpha, 7 alpha, 8, 15 alpha, 16 beta, 26-octaol", "start": 99, "end": 189}, {"text": "(25S)-5 alpha-cholestane-3 beta, 6 alpha, 7 alpha, 8, 15 alpha, 16 beta, 26-heptaol", "start": 195, "end": 278}, {"text": "distolasterosides D1-D3", "start": 327, "end": 350}]}}, "schema": []}
{"input": "All of these compounds enhanced neurite outgrowth in NB cells.", "output": {"entities": {}}, "schema": []}
{"input": "Dose-dependent responses to compounds 1-3 were observed within the concentration range of 10-100 nM, and dose-dependent responses to glycosides 4-6 were observed at concentrations of 1-50 nM.", "output": {"entities": {}}, "schema": []}
{"input": "All the tested substances exhibited notable synergistic effects with trace amounts of nerve growth factor (NGF, 1 ng/mL) or brain-derived neurotrophic factor (BDNF, 0. 1 ng/mL).", "output": {"entities": {}}, "schema": []}
{"input": "Using NB cells and OHSCs, it was shown for the first time that starfish steroids 1-6 act as neuroprotectors against oxygen-glucose deprivation (OGD) by increasing the number of surviving cells.", "output": {"entities": {"chemical": [{"text": "steroids", "start": 72, "end": 80}, {"text": "oxygen", "start": 116, "end": 122}, {"text": "glucose", "start": 123, "end": 130}]}}, "schema": []}
{"input": "Altogether, these results suggest that neurotrophin-like neuritogenic and neuroprotective activities are most likely common properties of starfish polyhydroxysteroids and the related glycosides, although the magnitude of the effect depended on the particular compound structure.", "output": {"entities": {"chemical": [{"text": "polyhydroxysteroids", "start": 147, "end": 166}]}}, "schema": []}
{"input": "Amylin Acts in the Central Nervous System to Increase Sympathetic Nerve Activity.", "output": {"entities": {}}, "schema": []}
{"input": "The pancreatic hormone amylin acts in the central nervous system (CNS) to decrease food intake and body weight.", "output": {"entities": {}}, "schema": []}
{"input": "We hypothesized that amylin action in the CNS promotes energy expenditure by increasing the activity of the sympathetic nervous system.", "output": {"entities": {}}, "schema": []}
{"input": "In mice, ip administration of amylin significantly increased c-Fos immunoreactivity in hypothalamic and brainstem nuclei.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, mice treated with intracerebroventricular (icv) amylin (0. 1 and 0. 2 nmol) exhibited a dose-related decrease in food intake and body weight, measured 4 and 24 hours after treatment.", "output": {"entities": {}}, "schema": []}
{"input": "The icv injection of amylin also increased body temperature in mice.", "output": {"entities": {}}, "schema": []}
{"input": "Using direct multifiber sympathetic nerve recording, we found that icv amylin elicited a significant and dose-dependent increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT).", "output": {"entities": {}}, "schema": []}
{"input": "Of note, icv injection of amylin also evoked a significant and dose-related increase in lumbar and renal SNA.", "output": {"entities": {}}, "schema": []}
{"input": "Importantly, icv pretreatment with the amylin receptor antagonist AC187 (20 nmol) abolished the BAT SNA response induced by icv amylin, indicating that the sympathetic effects of amylin are receptor-mediated.", "output": {"entities": {}}, "schema": []}
{"input": "Conversely, icv amylin-induced BAT SNA response was enhanced in mice overexpressing the amylin receptor subunit, RAMP1, in the CNS.", "output": {"entities": {}}, "schema": []}
{"input": "Our data demonstrate that CNS action of amylin regulates sympathetic nerve outflow to peripheral tissues involved in energy balance and cardiovascular function.", "output": {"entities": {}}, "schema": []}
{"input": "Antagonistic Basic Helix-Loop-Helix/bZIP Transcription Factors Form Transcriptional Modules That Integrate Light and Reactive Oxygen Species Signaling in Arabidopsis.", "output": {"entities": {"chemical": [{"text": "Oxygen", "start": 126, "end": 132}]}}, "schema": []}
{"input": "The critical developmental switch from heterotrophic to autotrophic growth of plants involves light signaling transduction and the production of reactive oxygen species (ROS).", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 154, "end": 160}]}}, "schema": []}
{"input": "ROS function as signaling molecules that regulate multiple developmental processes, including cell death.", "output": {"entities": {}}, "schema": []}
{"input": "However, the relationship between light and ROS signaling remains unclear.", "output": {"entities": {}}, "schema": []}
{"input": "Here, we identify transcriptional modules composed of the basic helix-loop-helix and bZIP transcription factors PHYTOCHROME-INTERACTING FACTOR1 (PIF1), PIF3, ELONGATED HYPOCOTYL5 (HY5), and HY5 HOMOLOGY (HYH) that bridge light and ROS signaling to regulate cell death and photooxidative response.", "output": {"entities": {}}, "schema": []}
{"input": "We show that pif mutants release more singlet oxygen and exhibit more extensive cell death than the wild type during Arabidopsis thaliana deetiolation.", "output": {"entities": {"chemical": [{"text": "oxygen", "start": 46, "end": 52}]}}, "schema": []}
{"input": "Genome-wide expression profiling indicates that PIF1 represses numerous ROS and stress-related genes.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular and biochemical analyses reveal that PIF1/PIF3 and HY5/HYH physically interact and coordinately regulate the expression of five ROS-responsive genes by directly binding to their promoters.", "output": {"entities": {}}, "schema": []}
{"input": "Furthermore, PIF1/PIF3 and HY5/HYH function antagonistically during the seedling greening process.", "output": {"entities": {}}, "schema": []}
{"input": "In addition, phytochromes, cryptochromes, and CONSTITUTIVE PHOTOMORPHOGENIC1 act upstream to regulate ROS signaling.", "output": {"entities": {}}, "schema": []}
{"input": "Together, this study reveals that the PIF1/PIF3-HY5/HYH transcriptional modules mediate crosstalk between light and ROS signaling and sheds light on a new mechanism by which plants adapt to the light environments.", "output": {"entities": {}}, "schema": []}
{"input": "Self-assembling doxorubicin silk hydrogels for the focal treatment of primary breast cancer.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 16, "end": 27}]}}, "schema": []}
{"input": "Standard care for early stage breast cancer includes tumor resection and local radiotherapy to achieve long-term remission.", "output": {"entities": {}}, "schema": []}
{"input": "Systemic chemotherapy provides only low locoregional control of the disease; therefore, we describe self-assembling silk hydrogels that can retain and then deliver doxorubicin locally.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 164, "end": 175}]}}, "schema": []}
{"input": "Self-assembling silk hydrogels show no swelling, are readily loaded with doxorubicin under aqueous conditions and release drug over 4 weeks in amounts that can be fine-tuned by varying the silk content.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 73, "end": 84}]}}, "schema": []}
{"input": "Following successful in vitro studies, locally injected silk hydrogels loaded with doxorubicin show excellent antitumor response in mice, outperforming the equivalent amount of doxorubicin delivered intravenously.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 83, "end": 94}, {"text": "doxorubicin", "start": 177, "end": 188}]}}, "schema": []}
{"input": "In addition to reducing primary tumor growth, doxorubicin-loaded silk hydrogels reduce metastatic spread and are well tolerated in vivo.", "output": {"entities": {"chemical": [{"text": "doxorubicin", "start": 46, "end": 57}]}}, "schema": []}
{"input": "Thus, silk hydrogels are well suited for the local delivery of chemotherapy and provide a promising approach to improve locoregional control of breast cancer.", "output": {"entities": {}}, "schema": []}
{"input": "Molecular spectroscopy and dynamics: a polyad-based perspective.", "output": {"entities": {}}, "schema": []}
{"input": "The efficiency and insight of global, polyad-based modeling in overtone spectroscopy and dynamics is demonstrated.", "output": {"entities": {}}, "schema": []}
{"input": "Both vibration and vibration-rotation polyads are considered.", "output": {"entities": {}}, "schema": []}
{"input": "The spectroscopic implications of polyad Hamiltonians derive from their ability to account for the detailed line positions and intensities of spectral features and their unique predictive power.", "output": {"entities": {}}, "schema": []}
{"input": "The dynamical implications of polyad Hamiltonians include classical bifurcations that lead to the birth of new vibrational modes and intramolecular vibrational-rotational energy redistribution over multiple timescales.", "output": {"entities": {}}, "schema": []}
{"input": "The literature is reviewed, with emphasis on acetylene results.", "output": {"entities": {"chemical": [{"text": "acetylene", "start": 45, "end": 54}]}}, "schema": []}
{"input": "Can mitochondrial dysfunction be initiated by dissociative electron attachment to xenobiotics?", "output": {"entities": {}}, "schema": []}
{"input": "Resonance attachment of low-energy electrons to xenobiotic molecules, 2, 4-dichlorophenoxyacetic acid (), dichlorodiphenyltrichloroethane () and dichlorodiphenyldichloroethylene (), was investigated under gas-phase conditions by means of complementary experimental techniques.", "output": {"entities": {"chemical": [{"text": "2, 4-dichlorophenoxyacetic acid", "start": 70, "end": 101}, {"text": "dichlorodiphenyltrichloroethane", "start": 106, "end": 137}, {"text": "dichlorodiphenyldichloroethylene", "start": 145, "end": 177}]}}, "schema": []}
{"input": "Electron transmission spectroscopy (ETS) and dissociative electron attachment spectroscopy (DEAS), in the 0-6 eV and 0-15 eV energy range, respectively, were applied with the aim of modeling the behavior of these pesticide molecules under reductive conditions in vivo.", "output": {"entities": {}}, "schema": []}
{"input": "Formation of long-lived parent molecular anions and fragment negative ions was observed at incident electron energies very close to zero, in agreement with the results of density functional theory calculations.", "output": {"entities": {}}, "schema": []}
{"input": "The gas-phase DEA process, analogous to dissociative electron transfer in solution, was considered as a model for the initial step which occurs in the intermembrane space of mitochondria when a xenobiotic molecule captures an electron \" leaked \" from the respiratory chain.", "output": {"entities": {}}, "schema": []}
{"input": "A possible involvement of the fragments produced by DEA to the pesticides under investigation into cellular processes is discussed.", "output": {"entities": {}}, "schema": []}
{"input": "It is concluded that the free radicals and potential DNA adducts formed by DEA are expected to be dangerous for mitochondrial functionalities, while several of the products observed could act as messenger molecules, thus interfering with the normal cellular signaling pathways.", "output": {"entities": {}}, "schema": []}